BioSpectrum Asia Feb 2023

For queries, please contact : [email protected] TO SUBSCRIBE SCAN THE QR CODE FROM YOUR MOBILE www.mmactiv.com An publication Comprehensive Ecosystem Coverage Spiraling Growth TRUSTED B2B MEDIA IN BIOTECH, HEALTHCARE & AGRO SECTOR Policy Business Science Technology The only B2B Media for the complete ecosystem of: Nutraceuticals, Dietary Supplements, Functional Foods, Ingredients, Food Processing www.nuffoodsspectrum.in www.biospectrumasia.com Trusted across APAC by Biotech & Healthcare sectors for over a decade BioSpectrum India NuFFooDs Spectrum BioSpectrum Asia AgroSpectrum India Trusted by Biotech & Healthcare sectors in India for over a decade www.biospectrumindia.com Trusted by Agro Sector in India www.agrospectrumindia.com

PARTNER WITH BIOSPECTRUM INDIA TO TELL YOUR STORY Get a 360 degree exposure to the universe of Biotechnology and Health Sciences industries. PARTNER VOICES ARE AN EXCELLENT WAY TO ENGAGE WITH OUR AUDIENCE AND TELL YOUR STORY FROM A TRUSTED THIRD PARTY PERSPECTIVE. Each Partner Voice is produced in cooperation between our clients and our editorial team and includes several design elements to support your messaging. The Partner Voices remain evergreen on www.biospectrumindia.com for maximum ROI. PARTNER VOICE www.biospectrumindia.com Deliverables • Your story professionally edited by Biospectrum editorial staff (1,000 - 1,500 words).* • Up to two (2) relevant embedded links • Up to two (2) relevant embedded images • One (1) relevant embedded video • Multiple “Road Block” Banners: • A 728x90 or 970x60 banner ad. • A 300x250 or 300x600 banner ad. • A 88x31 or 120x60 logo. Distribution • Evergreen placement on www.biospectrumindia.com • Up to three (3) placements in www.biospectrumindia.com inBOX eNewsletter. • Social channel distribution • Additional market segment distribution is available through our other brands. * Biospectrum editorial staff is available to develop the content asset. The cost is based on the individual requirements (single source, multi-source, word-count, etc.) and will be priced accordingly. To know more on Partner Voice please contact: [email protected] | [email protected]

Go Digital: To request subscription email: [email protected] Taiwan Media Representative: Ms Christine Wu Image Media Services Company 2F-2, No. 35, Sec. 2, Flushing South Road, Taipei 10665, Taiwan Tel: +886-2-87734199 Fax:+886-2-87734200 Mobile: 886-937890533 E-mail: [email protected] website: www.imagemediatw.com China Erika Cheng RFCOMMS E101, East Lake Villas, 35 Dongzhimenwai Main Street, Dongcheng District, Beijing 100027, P. R. China Mobile: +86 17375668063 E-mail: [email protected] India Apoorva Mahajan Key Account Executive “NITON”, Block B, First Floor, 11/3, Palace Road, Bangalore 560052 Tel: +91-80-41131912/13 Mobile: +91-7724025888 [email protected] Photo: Shutterstock Vol 18; Issue 2; February 2023 Publisher & Managing Editor: Ravindra Boratkar Editorial: Chief Editor: Dr Milind Kokje [email protected] Advisor - Content: Vijay Thombre Editor: Narayan Kulkarni [email protected] Executive Editor: Dr Manbeena Chawla [email protected] Assistant Editor: Nitesh Pillai [email protected] Assistant Editor (Digital): Sanjiv Das [email protected] Asst. Manager Content Creation and Coordination- APAC Region: Hithaishi C. Bhaskar [email protected] Social Media Communications: Ankit Kankar [email protected] CFO & Special Correspondent: Manasee Kurlekar [email protected] Operations and HR: Asmita Thakar [email protected] Production & Design: MM Activ Sci-Tech Communications Anil Walunj Cover Design: Dominix Strategic Design Pvt. Ltd. Business Enquiry: Ankit Kankar [email protected] Subscription Services Print Edition: Saradha Mani [email protected] Digital Edition: Ankit Kankar [email protected] News Letter : Sudam Walekar [email protected] Database Executive: Sudam Walekar Subscription Services: Apoorva Mahajan [email protected] Bio Spectrum Jobs: Poonam Bhosale [email protected] MM Activ Singapore Pte. Ltd. Singapore MM Activ Singapore Pte. Ltd. Saradha Mani General Manager #08-08, High Street Centre, 1 North Bridge Road, Singapore - 179094 Tel: +65-63369142 / Fax:+65-63369145 Mobile: +65-90681202 [email protected] Asia Pacific & South East Asia Ankit Kankar DY. General Manager Digital Intell. & Growth 1st Floor, CIDCO Convention Center, Sector 30A, Vashi, Navi Mumbai, Maharashtra-400703. Mobile: +91-9579069369 [email protected] USA BioSpectrum Bureau MM Activ Sci-Tech Communications Mobile: +91-9579069369 [email protected] Europe BioSpectrum Bureau MM Activ Sci-Tech Communications Mobile: +91-9579069369 [email protected] Printed and published by Ravindra Boratkar on behalf of MM ACTIV Singapore Pte Ltd. Printed at Times Printers Private Limited 16 Tuas Avenue 5, Singapore 639340 Tel : +65-63112888 Reprinted in India for private Circulation Chief Editor: Dr Milind Kokje MCI (P) 020/06/2022 Copyright: MMActiv Singapore Pte Ltd. Acknowledgements/ Feedback What a great article as the cover story for January edition! Thank you so much for including Juniper Biologics in it. - Victoria, Singapore One of the major trends for 2023 is the rising impact of Chinese biotech companies in global markets. The Chinese players are also looking at emerging markets where the price points may help make newer therapies available to local patients for the first time. - Jeff Weisel, Singapore Excellent cover story for the January 2023 edition! Many thanks for including me. - Jane Lowe, Australia Artificial Intelligence (AI) is indeed a rising star with tremendous potential to transform bioprocessing efficiencies. Thank you for featuring the article by Frost & Sullivan. - Aishwarya Venugopal Nair, India 4 BIO MAIL BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com

Letter from Publisher Ravindra Boratkar Publisher & Managing Editor, MD, MM Activ Sci-Tech Communications Pvt. Ltd. Dear Readers, Among the various diseases that are spreading fast in Asia, Cancer occupies the top slot as the number of cancer cases and also mortality caused by it is very high. An estimated 8.7 million Asians were afflicted by cancer in 2020, with nearly half of all new global cancer cases reported the same year. That accounts for 169.1 cases per 100,000 people, as per the trend analysis published in a research article in National Library of Medicine. The Republic of Korea has the highest number of cases followed by China. The most commonly occurring cancers include lung cancer, accounting for 13.8 per cent, breast cancer, 10.8 per cent and colorectal cancer, 10.6 per cent. Mortality stood at 101.6 per 100,000 people, 58.3 per cent of the global cancer deaths. One important response to this growing problem can be early screening and detection. Knowing early signs of the disease and precancerous conditions through screening improves the chances of treatment and survival. This is also one disease wherein new technologies are developed for early detection. No wonder, oncology draws a major chunk of the R&D investments by pharma companies. Global oncology spending in 2020 was $167 billion, compared to $74 billion in 2014, according to Statista. The focus of cancer treatment is rapidly shifting from a traditional one-size-fits-all approach to precision medicine, tailored treatments for individual patients, which is a critical change in focus. In Europe, diagnostic companies are identifying the defective genes that are causing cancer and building a huge database. February 4 is observed as World Cancer Day to draw attention to the problem. Coinciding with this important day,our content team takes a deep dive into the status of cancer drugs research and development in Asia Pacific. The next wave of innovations making headlines in the cancer space include immunotherapies, vaccines, CAR-T therapies, PD-1/L1 inhibitors, light-activated drugs, etc. Venture capital and private equity funding in the Asia Pacific biosciences and healthcare arena witnessed some fluctuations last year. In healthcare, the number of deals in private equity in 2022 are expected to fall by 20 to 30 per cent compared to 2021. The issue provides a comprehensive overview of venture capital and private equity funding in the Asia Pacific bioscience arena. I am sure that this will provide you a lot of insight from the financial perspective of the bioscience sector and may help you in varied ways. Happy reading. Thanks & Regards, Ravindra Boratkar Publisher & Managing Editor 5 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com Looking for a job? See open roles at www.biospectrumjobs.com premier source of pharma healthcare & bio jobs n Find Talent n Post Jobs n Attract Candidates Find the right people no matter what your hiring needs are... TALENT SOLUTIONS

CANCER THERAPEUTICS GAINING GROUND IN APAC COVER STORY 19 6 BIO CONTENT BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com Cancer, the leading cause of death in most parts of the world, is a veritable Achilles heel for the pharma industry. Not surprising that pharma companies continue to dedicate a significant part of their R&D budget for Oncology. Cancer medicine spending rose to $185 billion globally in 2021 and is expected to reach more than $300 billion by 2026, as per IQVIA. China’s oncology spending now exceeds the rest of emerging countries and is driven by expanded access to new therapies and offset by lower prices. Chinese and other Asian cancer drug developers are at the forefront of driving innovation in this space. The focus of cancer treatment is rapidly shifting from a traditional one-size-fits-all approach to precision medicine, tailored treatments for individual patients. The next wave of innovations making headlines in the cancer space include immunotherapies, vaccines, CAR-T therapies, PD-1/L1 inhibitors, light-activated drugs etc. Many drug makers in Asia are investing in new science and hope to develop the next holy grail in oncology. Let’s take a deep dive into the status of cancer drug research and development in the Asia Pacific (APAC). Advances in the Oncology Drug Development 22 Rachel Webster, Head of Oncology & Biosimilars, Market Assessment Singapore is beginning to see benefits of investing in technological aspect of cancer treatment 24 Chew Huat Seng, Managing Director, Hitachi Asia, Singapore A Stitch in Time to Save Lives 26 Dr Robert W. Carlson, Chief Executive Officer, National Comprehensive Cancer Network (NCCN)

Scan QR code to access BioSpectrum Asia Digizine BIO CONTENT 7 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com REGULARS BioMail............................................................................04 BioEdit.............................................................................08 Policy and Regulatory News.......................................09 Finance News................................................................11 Company News ............................................................12 Start-Up News...............................................................14 Academics News..........................................................43 People News..................................................................44 R&D News ......................................................................46 Supplier News ...............................................................48 Lets Talk Health ............................................................50 SPEAKING WITH “We’re dedicated to Multiple Sclerosis with two approved therapies and Evobrutinib currently in phase 3 trial” Liz Henderson, Senior Vice President APAC, Merck Healthcare 37 “Australia is poised to establish itself as a global life sciences hub” Santosh Nambiar, Founder and MD, Assay Matrtix 39 29 “Technology will play a significant role in reducing numbers of new cases and deaths” Raja Sekhar Kommu, Co-Founder and CTO, Karkinos Healthcare “We need to foster risky projects that can have large rewards” Dr Jing Zhang, Co-Founder, Vice President, High Throughput and High Content Screening, Anticancer Bioscience “Global investors can leverage our deep immunomics platform to develop TCR Cell therapies for solid tumours” capabilities” Ng Choon Peng, Founder & CEO, Immunoscape 33 How imaging tech and liquid biopsy will play pivotal role in cancer care Dr Dario Heymann, Chief Research Officer, Galen Growth 35 AMR VALUE is the Trending Word of 2023 Steve Peretz, Group Director (Health Experience and Product Strategy), Appnovation, AMER 41 31

8 BIO EDIT BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com Dr Milind Kokje Chief Editor [email protected] CHINESE VAX DEBACLE The recent surge of COVID-19 in China has baffled the world. Although the Chinese authorities claimed 70 to 80 per cent reduction in infections in the last week of January, before that, the media carried detailed reports of a sharp surge, one of the world’s largest, in the number of new cases as well as in deaths, emergence of new variants, infection, moving from urban centres to rural areas, etc. The World Health Organisation (WHO) was issuing warnings and the media was busy publishing estimates of the tsunami of fresh cases and the number of deaths, with cases probably running into millions. In one of its reports, the BBC narrated how coffin makers in rural areas were busy almost round the clock to meet the growing demand, indicating the increase in deaths. Since a few months back, the world was (and probably still is) watching the developments in China with bated breath as remnants of the beginning of the COVID-19 pandemic around the same time (October-November) two years back and from the same country is probably giving nightmares. This fresh wave of cases in China is apparently caused by abrupt removal of pandemic restrictions with very little preparations in early December 2022. The extent of the surge in cases following the celebration of Chinese new year was not known till the time this article was being written. But, even before that, various estimates of the number of cases were being presented and published. Leading epidemiologist Wu Zunyou was quoted as saying that 80 per cent of the Chinese population, over a billion people, have been infected in December. The same figure was quoted by a doctor from a rural clinic in a BBC report. The surge in cases in the last two months was baffling because elsewhere in the world, the pandemic was receding. In India itself, the number of new cases were reducing drastically. In two populous cities, New Delhi and Mumbai, no new cases were reported by the end of the last month. This was mostly due to the vaccination of the people. Not only India, several countries in Asia and the world are now enjoying COVID-19 free life due to a sharp reduction in cases and deaths, thanks to effective vaccination. The question is, where exactly did China fail? When it comes to vaccines, CoronaVac and Sinopharm, both developed and produced in China, were administered to the people. Over 90 per cent of the Chinese population has reportedly received two doses of either of the vaccines. It includes 86 per cent of adults over 60 who have gotten at least two doses of the primary series and around 68 per cent who have received the booster. Among people over 80, 65.8 per cent are fully vaccinated and just 40 per cent have got a booster shot. Even after that, if the country is witnessing a major surge in cases, then it’s safe to conclude that the Chinese vaccines are not efficacious. Both these vaccines have not used any new technology like mRNA. They both are inactivated vaccines, that is, based on conventional but well proven technology of using inactivated or killed viruses. In initial clinical trials, CoronaVac and Sinopharm had shown 51 per cent and 79 per cent efficacy, respectively. Though it was low compared to Pfizer’s and Moderna’s mRNA vaccines’ 90 per cent efficacy at the time of approval, the comparison has become meaningless now with Pfizer’s vaccine embroiled in controversy regarding its real-world efficacy and adverse effects. The point is, although some experts claimed that inactivated vaccines ‘don’t give a broad immune response’, it probably was not true. The Chinese vaccines showed strong efficacy in a study done in Hong Kong. China has now approved six more vaccines. Maybe, it considers using more effective vaccines or increasing the dose of the two vaccines. But the waves of surge need to be stopped as the world cannot afford another ‘pandemic’.

REGULATORY NEWS 9 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com Indonesia’s TB response programme gets $300 M World Bank loan The World Bank’s Board of Executive Directors has approved a $300 million loan to the Indonesian government to improve coverage, quality and efficiency of tuberculosis (TB) response in Indonesia. Indonesia’s health system has seen increasing challenges to find and treat TB cases, especially since the beginning of the COVID-19 pandemic. Even before the pandemic, Indonesia was the third largest contributor to the global TB cases. In 2021, the country contributed around 9 per cent of the total 10.6 million new TB cases worldwide. It had a TB incidence of over 969,000 people and lost more than 150,000 people annually because of this communicable disease. The financing uses a results-based approach that will focus on three areas. The first area is strengthening Indonesia’s subnational TB response, such as case finding, treatment coverage, and timely response, and the performance in this area will be linked to a fiscal transfer. The second is strengthening TB response among primary health providers, including private healthcare providers. The financing will help better connect private sector providers with the national programme, and making it easier for them to notify, diagnose, and treat TB by improving their access to diagnostics and medicines provided by the NTP. Genexine, a clinical-staged Korean biopharma company committed to the discovery & development of novel biologics for the treatment of unmet medical needs, has received Fast Track Designation (FTD) from the Korean Ministry of Food and Drug Safety (MFDS) for GX-188E (tirvalimogene teraplasmid), its firstin-class proprietary therapeutic DNA vaccine. Following an evaluation of the full set of Phase 2 data from the recently completed clinical trial in advanced cervical cancer, Korea’s Health Authority (MFDS) concluded that GX-188E met the criteria for fast-track designation. Under MFDS regulations, FTD is given to a drug that is intended to treat a serious condition and the nonclinical or clinical data demonstrate the potential to address an unmet medical need. Having such a designation can mean that a drug can move more quickly through the development & regulatory process in an expedited manner. The company is in the process of designing the optimal Phase 3 study with GX-188E and expects to initiate that study this year. Korea gives fast track approval to promising DNA vaccine for advanced cervical cancer Specialised Therapeutics Asia (ST), based in Singapore, has announced that a new therapy to treat rare gastrointestinal stromal tumour (GIST) shown to improve survival has now been approved in New Zealand. The therapy, QINLOCK (ripretinib) has been approved for use by the country’s regulatory agency Medsafe for the treatment of adult patients with GIST who have received prior treatment with three or more kinase inhibitors, including imatinib. It is currently being made available to eligible patients in New Zealand via a co-pay Access Programme while it is considered by PHARMAC for reimbursement. QINLOCK belongs to a class of drugs known as tyrosine kinase inhibitors, or TKIs. It is designed to inhibit key enzymes linked to tumour growth. In Australia it has been fully reimbursed on the Pharmaceutical Benefits Scheme since 2021. QINLOCK is made available in New Zealand by independent pharmaceutical company Specialised Therapeutics (ST) under an exclusive distribution agreement from US based Deciphera Pharmaceuticals. New Zealand approves new therapy to treat rare gastrointestinal stromal tumour

Millions of adolescents and youth in Bangladesh will be able to access health information and services through two online portals launched recently at The National Adolescent Health Conference held in Dhaka. The Adolescent Health website and mobile application, launched by the Ministry of Health and Family Welfare with support from UNICEF and the Embassy of Sweden, aims to increase awareness and ensure easy access to physical and mental health information and services for adolescents. Adolescents in Bangladesh, accounting for over 36 million of the country’s population, face multiple social barriers to accessing information and health services that are essential for them to grow and thrive. The Adolescent Health platforms include educational and gender-adapted guides and courses on sexual and reproductive health and rights, nutrition, violence, and physical and mental health as well as information on how and where to access adolescent-friendly health services. The Ministry of Women and Children Affairs and Ministry of Education will engage with adolescent clubs, youth peer groups and teachers in all secondary schools in the country. Mobile app to help adolescents access public health services in Bangladesh 10 REGULATORY NEWS BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com South Korea-headquartered SK bioscience, a global innovative vaccine and biotech company, has received a biologics license application approval of the SKYZoster from the National Pharmaceutical Regulatory Agency (NPRA) in Malaysia. The vaccine was approved in South Korea from the Ministry of Food and Drug Safety (KMFDS) in September 2017. This is the second overseas approval of SKYZoster after Thailand in May 2020. SKYZoster is the world’s second developed shingles vaccine. It is a live vaccine that attenuates varicella zoster virus. SKYZoster is shown clinically acceptable immunogenicity and safety at Phase III clinical trial. SK bioscience plans to submit for the Pre-Qualification(PQ) to the WHO next year to further accelerate the vaccine’s approval for overseas emerging markets, such as Southeast Asia and developing countries. Ministry of Ayush inks MoU with ITDC for promotion of medical value travel in India SK bioscience’s shingles vaccine receives biologics license application approval in Malaysia India’s Ministry of Ayush has signed a Memorandum of Understanding (MoU) with India Tourism Development Corporation (ITDC), Ministry of Tourism, Government of India to work together for the promotion of Medical Value Travel in Ayurveda and other traditional systems of medicine. According to the MoU, the Ministry of Ayush will provide training to the officials of ITDC to sensitise them about the medical value of travel in Ayurveda and other traditional systems of medicine. It will identify tourist circuits, where there is immense scope to promote medical value travel in Ayurveda and other traditional systems of medicine and provide all the technical knowhow from time to time to ITDC. The implementation and progress of the MoU will be monitored by a Joint Working Group (JWG) co-chaired by representatives from Ayush Ministry and ITDC. The JWG will also identify the best practices adopted by Malaysia, Singapore and Thailand etc. to promote themselves as a preferred destination for medical value travel.

FINANCE NEWS 11 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com Lotte Biologics CEO Richard Wonjik Lee has announced a blueprint to leap forward as a global contract development and manufacturing organisation (CDMO). The company plans to invest a total of $3 billion (approximately KRW 3 trillion) by 2030 to construct three mega plants with a total production capacity of 360,000 litres of antibody drugs in Korea. Each plant will be capable of producing 120,000 litres of antibody drugs, with additional expansion plans calling for a small-scale incubator for clinical drug substance production as well as a commercial drug product production facility. Construction of the first mega plant will begin in the second half of 2023, with completion scheduled for the second half of 2025, GMP approval for the second half of 2026, and commercial production for 2027. Lotte aims to have all three mega plants fully operational by 2034 and expects to generate revenue of $3 billion while maintaining an operating profit margin of 35 per cent. Sun Pharma buys US-based Concert Pharma for $576 M Sun Pharmaceutical and Concert Pharmaceuticals have executed a definitive agreement under which Sun Pharma will acquire all outstanding shares of Concert through a tender offer for an upfront payment of $8 per share of common stock in cash, or $576 million in equity value. Concert is a late-stage biotechnology company pioneering the use of deuterium in medicinal chemistry. The company has an extensive patent portfolio, including its lead product candidate deuruxolitinib – an oral inhibitor of Janus kinases JAK1 and JAK2 for the treatment of Alopecia Areata, an autoimmune dermatological disease – which is in late-stage development. Concert has completed the evaluation of the efficacy and safety of deuruxolitinib in adult patients with moderate to severe Alopecia Areata in its THRIVE-AA Phase 3 clinical programme and two open label, long-term extension studies are ongoing in North America and Europe. Sun Pharma’s immediate focus would be to follow Concert’s plan to submit a New Drug Application (NDA) to the US Food and Drug Administration (FDA) in the first half of 2023. Japanese pharmaceutical firm Takeda has entered into an exclusive licensing agreement with Hutchmed (China) for the further development and commercialisation of fruquintinib outside of mainland China, Hong Kong and Macau. Fruquintinib is orally administered and has the potential to be used across subtypes of refractory metastatic colorectal cancer (CRC), regardless of biomarker status. The US Food and Drug Administration (FDA) granted Fast Track Designation for the development of fruquintinib for the treatment of patients with metastatic CRC in 2020. In December 2022, Hutchmed initiated a rolling submission of a New Drug Application (NDA) for fruquintinib with the US FDA, which is planned to be completed in the first half of 2023. Under the terms of the agreement, Takeda will receive an exclusive worldwide license to develop and commercialise fruquintinib in all indications and territories outside of mainland China, Hong Kong and Macau. Subject to the terms of the agreement, Takeda will pay Hutchmed $400 million upfront, up to $730 million in additional potential payments relating to regulatory, development and commercial sales milestones, as well as royalties on net sales. Takeda inks $730 M oncology deal with Hutchmed to improve cancer treatment Lotte Biologics announces $3 B investment plan to leap forward as global CDMO

12 COMPANY NEWS BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com Hong Kong Science and Technology Parks Corp inks strategic collaboration with Roche Hong Kong Science and Technology Parks (HKSTP) Corporation has announced a strategic collaboration with Roche, one of the world’s largest pharmaceutical companies, with an aim of leading HK and the Greater Bay Area (GBA) in becoming a pioneer in life science innovation and to be an example for the region. This collaboration is the first agreement between HKSTP and a life science corporation for multidimensional collaboration (including technology and data sharing). HKSTP and Roche are dedicated in their support for advancing life science innovation and healthcare policy. Both parties are hoping to provide a greater platform and support to startups based in HK and mainland China, and create an ecosystem for healthcare startups. The long-term goal is to turn the GBA into a national leader in life science and healthcare innovation, and setting an example the rest of the country might follow in technology application and registration. It is also hoped the GBA will be a hub for talent and for corporates in the Asia Pacific region. Terumo and Siemens Healthineers collaborate to strengthen cardiac care in India Terumo India, a part of Japan-based medical technology firm Terumo Corporation, and Siemens Healthineers India are partnering to strengthen cardiac care in India through collaborative interventions in the areas of physician training and development, access to advanced medical technologies, and improved penetration of Tier-II and III cities. The collaboration will flag off its efforts with a customised training programme for Cathlab professionals, being developed in partnership with an eminent academic institute in India. Currently, there is a need for more structured courses to enhance operational efficiency and patient experience in Cathlabs. This first-of-its-kind Cathlab Director programme will aim to fulfill this need and help raise the overall standards of care and efficiency in Cathlabs. The programme will include topics on Operations Excellence, Digital Transformation, and Patient Centricity. Other initiatives planned as a part of the collaboration include training programmes for Intervention Cardiologists and joint go-to-market initiatives for Tier 2 and 3 cities. Aculys Pharma, a company focussed on the development and commercialisation of new innovative drugs in the fields of neurology and psychiatry and Four H, have announced an exploratory research collaboration in Japan, using wearable devices to help patients with narcolepsy and excessive daytime sleepiness (EDS) associated with obstructive sleep apnea syndrome (OSAS). In its quest to establish a new pharmaceutical model, Aculys is promoting DX (digital transformation) in clinical trials and medicine. In this collaborative exploratory study to be launched with Four H, Aculys will collect trial participants’ subjective assessments of their sleep as well as data on their sleep, activities, and heart rate acquired from wearable devices to be worn each night during the clinical trial period. This exploratory research will allow a further accurate understanding of each patient’s sleep and lifestyle patterns, which had been difficult to measure previously. Aculys Pharma, Four H initiate collaboration using wearable devices to study sleep disorders in Japan

COMPANY NEWS 13 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com Seno Medical, based in the US, has entered into an exclusive distributor agreement with Genetik, to market, sell and service the company’s groundbreaking Imagio Opto-Acoustic/ Ultrasound (OA/US) Breast Imaging System. This distributor agreement, a first for Seno, will enable Genetik to regionally distribute the Imagio System in Singapore, where the distributor is headquartered. Seno’s groundbreaking diagnostic breast cancer imaging system helps the physicians to differentiate between benign and malignant breast lesions using non-invasive optoacoustic/ultrasound (OA/US) technology to provide information on breast lesions in real time, helping providers to characterise masses that may or may not require more invasive diagnostic evaluation. In addition to the novel imaging provided by the ImagioSystem, Seno includes an artificial intelligence (AI) decision-support tool (SenoGram) to help physicians interpret the new images. This AI tool, along with training and certification, helps radiologists transition from ultrasound alone to OA/ US imaging to more precisely assign the likelihood of malignancy. Seno Medical enters exclusive distributor agreement with Genetik Malaysian Genomics explores R&D collaboration with SIRIM Malaysian Genomics Resource Centre Berhad, a leading genomics and biopharmaceutical specialist, has announced a strategic cooperation with SIRIM Berhad, to explore the commercialisation of joint research and development (R&D) projects in the medical and biotechnology fields. SIRIM Berhad is wholly owned by the Malaysian Government, and is focussed on R&D, standardisation and quality. The organisation acts as a catalyst for industrial development through programmes involving technology and standardisation. Under the strategic cooperation, both parties will evaluate the potential commercial value of a range of genomicsdriven biotechnology R&D projects. These include developing biofuels and biopharmaceuticals, companion diagnostic tests for cancer treatment, and bioactive cosmeceuticals. This two-year strategic collaboration will also jointly source for suitable private and public institutional partners for the funding and commercialisation of these projects. According to Encik Sasha Nordin, CEO, Malaysian Genomics, SIRIM and Malaysian Genomics have complementary experiences, resources, and technology assets. Aurisco, an innovative pharmaceutical company and CDMO (contract development and manufacturing organisation) in China, is cooperating with Cytiva, a global science leader, to build its first Oligo FlexFactory platform for commercial production. The Oligo FlexFactory platform is the first of the three planned commercial manufacturing lines of Aurisco in Yangzhou of East China. And this whole manufacturing site is expected to produce 200 kgs of oligonucleotides every year. Oligonucleotides are synthetic strands of DNA or RNA that can be used as therapies, diagnostics by binding to a target gene or protein sequence. Oligonucleotide therapeutics, including siRNA (small interfering RNA) and ASO (antisense oligonucleotide), hold promise in treating cancers, Parkinson’s diseases, and various other conditions. During this cooperation, Cytiva will offer a comprehensive enterprise solution to Aurisco. It includes an Oligo FlexFactory GMP platform and various technical and service support, such as talent training, process design of the manufacturing site, as well as life-cycle project management. Aurisco collaborates with Cytiva to build first Oligo FlexFactory in China

The New South Wales (NSW) Government has launched a $40 million Biosciences Fund (BioSF) to support startups developing and commercialising problemsolving products, devices and systems in the biological sciences space. Minister for Science, Innovation and Technology Alister Henskens said the BioSF provides a platform for NSW’s best minds and most agile new businesses to solve pressing issues in areas such as health and the environment. According to Henskens, the $40 million fund will boost the NSW Government’s support of innovative researchers, startups and entrepreneurs in the biological sciences space over the next four years, and is modelled on its highly successful Physical Sciences Fund. The BioSF will consider applications that target one of the three priority industries identified in the NSW Industry Development Framework – agriculture/ agrifoods, medical and life sciences, and clean energy and waste – while also aligning with specific technology applications outlined in the 20-Year R&D Roadmap. China’s ReLive Biotechnologies strengthens presence in regenerative therapy market New South Wales launches $40M biosciences fund for innovative startups 14 START-UP NEWS BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com China-based startup ReLive Biotechnologies has completed the acquisition of all operating assets of Germany-listed biotech company Co.Don, taking over the global patent rights of its flagship products Spherox and Chondrosphere. “Spherox” is one of the only two authorised cell therapy for the regenerative treatment of articular cartilage defects globally. It was authorised by the European Medicines Agency (EMA) for distribution across Europe in 2017. Simultaneously with the acquisition, ReLive also completed its Series A financing of $36 million to fund the company’s global ambition. ReLive plans to use the fund for R&D, licensing, manufacturing, distributions, and other operational needs in China, US and Europe. Series A was led by Shanghai Healthcare Capital (SHC), with contributions from two existing angel investors, Indaco Capital and Jiuyo Capital, and a new joiner Watson Capital. G&G Capital serves as the exclusive financial advisor. Moderna buys Japanese startup OriCiro for $85M Moderna, a US-based biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, and OriCiro Genomics K.K., a pioneer in cell-free DNA synthesis and amplification technologies, have entered into a definitive agreement through which Moderna will acquire OriCiro for $85 million. According to Stéphane Bancel, CEO, Moderna, OriCiro’s technology strategically complements the manufacturing expertise and further accelerates the research and development engine. OriCiro Genomics, founded in December 2018, is focussed on the development and commercialisation of cellfree synthesis and amplification of plasmid DNAs for applications in gene/cell-based therapies and synthetic biology. OriCiro’s proprietary technologies are positioned to unlock and expedite the possibilities of advanced therapeutics and synthetic biology by providing a powerful tool to be used for research, development and manufacturing of plasmid DNA.

DeepTek introduces new AI powered lumbar spine quantification automation tool India-based health tech startup DeepTek has announced the global launch of DeepSpine - an artificial intelligence (AI) powered lumbar spine quantification and metrics tool designed to analyse MRI lumbar spine images. The tool was launched at the Radiological Society of North America (RSNA) annual meeting in Chicago, USA. DeepTek’s new innovation DeepSpine provides AI powered quantification and analysis tool for lumbar spine MRI studies and can assist radiologists, technologists, orthopaedic surgeons and physio experts to get objective automated quantification and other document of lumbar spine, adding value to the radiology reports and decongesting the radiology workflow. DeepTek has been instrumental in transforming the radiology workflow by leveraging the power of AI. Its AI-powered radiology orchestration solution Augmento has already created waves across the Asia Pacific (APAC) and is also getting deployed in a progressive Singapore health system. Another flagship product by DeepTek is Genki - the AI-powered public health screening solution which is helping medical professionals across India, Philippines, Mongolia, and several other countries in the APAC region to eradicate tuberculosis (TB) by identifying suspected cases promptly and precisely, leading to earlier treatment and better patient care. START-UP NEWS 15 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com South Korea-based startup Lunit has signed a software license agreement with the Hospital Israelita Albert Einstein in São Paulo, Brazil. Under the agreement, Lunit will supply its artificial intelligence (AI) solution for chest x-ray image analysis, Lunit INSIGHT CXR, to the Hospital Israelita Albert Einstein for three years until 2025. The hospital plans to operate Lunit’s AI solution in screening chest X-ray images in its intensive care unit and emergency room as well as in-patient examinations. Lunit INSIGHT CXR detects suspicious lesions in chest x-ray images, helping radiologists distinguish disease areas by providing the location of the lesion with an abnormality score that reflects the AI’s confidence level. The AI solution can detect 10 of the most common chest abnormalities with 97-99 per cent accuracy, including pulmonary nodules, pulmonary fibrosis, and pneumothorax, as well as supporting tuberculosis screening. Lunit provides AI-based chest X-Ray solution to Latin America’s largest hospital US-based Veradigm has announced an investment in Holmusk, a global behavioural health real-world evidence and data analytics company in Singapore, as part of Holmusk’s $45 million series B financing round. The round was led by Veradigm, with participation from current investors including Heritas Capital, Health Catalyst Capital, Novartis (dRx Capital), and Northwell Holdings, the venture investment arm of Northwell Health, as well as other previous investors. Holmusk will leverage this investment to continue its rapid expansion of its flagship offering, the NeuroBlu Database, a leading source of real-world clinical data for the behavioural health industry. Now that the financing has been completed, Veradigm and Holmusk intend to enter into a data partnership to bring cohorts of behavioural health and related de-identified patient data from Veradigm to the NeuroBlu Database, significantly adding to Holmusk’s real-world clinical data asset. Veradigm announces strategic investment in Holmusk from Singapore

What are the barriers to access that are impacting patient outcomes in managing antimicrobial resistance? Why do they exist? Mr Luongo: In line with the World Health Organisation’s (WHO)’s objective to tackle the emerging threat of antimicrobial resistance (AMR), Menarini is striving to reduce morbidity and mortality rates by supporting both the responsible use of antibiotics through global antimicrobial stewardship programmes and providing access to novel antibiotics targeting multidrug-resistant infections. However, new treatments alone are insufficient to combat AMR. The urgent need to accelerate research and development on AMR prevention and care is hampered by the weak pipeline of antibiotic medicines and dearth of anti-infectives that can effectively treat multidrug-resistant infections. Although 60 products1 are currently in development, the unpredictable, costly and long R&D timelines for antibiotic development impact the availability of new antibiotics. This issue is further exacerbated by the pharmaceutical industry’s shift away from antibiotic discovery in favour of medicines targeted towards chronic disease management (e.g., depression and cancer) as they guarantee higher returns on investment. In Asia, inadequate infrastructure and funding, multiple regulatory and administrative barriers, the high cost of AMR diagnostic test consumables and limited pool of qualified clinicians and scientists deter Addressing Unmet Patient Needs in Antimicrobial Resistance (AMR): The Vital Role of Industry Partnerships « Mr Zhao Hong, President and Chief Executive Officer, SciClone Pharmaceuticals « Mr Maurizio Luongo, Chief Executive Officer, Menarini Asia-Pacific the development of AMR solutions for patients in the region. All of these interrelated circumstances hinder the roll-out of effective AMR surveillance platforms and the inclusion of anti-infective drugs in international or national antimicrobial guidelines, which often mean patients in Asia are not prescribed with appropriate antibiotics. We foresee an urgent need to foster strategic partnerships between industry, healthcare professionals and regulators to address the future of AMR as one ecosystem, with authorities needing to look much more at both the existing data and the actual needs of patients so they can choose the right medicines for the right patients at the right time. Mr Zhao: AMR is a complex problem that requires a united multi-sectoral approach. For instance, action is needed on targeted fronts to strengthen our approach to human medicine, animal medicine, the pharmaceutical industry and educating the general public on AMR. China is already doing many of these things and has attained some invaluable achievements. In August 2016, China issued a National Action Plan to Contain Antimicrobial Resistance (2016-2020) with 14 ministries to ensure a clear multi-sectoral approach to tackling this growing issue2 . In October 2022, China issued the National Action Plan to Contain Antimicrobial Resistance (2022-2025), aiming to further curb AMR and better protect people’s health. 16 PARTNER CONTENT BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com 1 Lack of new antibiotics threatens global efforts to contain drug-resistant infections, News, World Health Organisation. 16 January 2020. Link: https://www.who.int/news/ item/17-01-2020-lack-of-new-antibiotics-threatens-global-efforts-to-contain-drug-resistant-infections 2 China: National action plan to contain antimicrobial resistance 2016-2020 (Chinese & English). World Health Organization (WHO). 14 July 2014. Link: https://www.who.int/ publications/m/item/china-national-action-plan-to-contain-antimicrobial-resistance-(2016-2020)

We are also aware of the fact that AMR still remains a public health concern in China. Surveillance results showed that the detection rate of carbapenem-resistant Klebsiella pneumoniae (CRKP) in China increased from 0.7% in 2007 to 19.9% in 20183 . Efforts to eliminate AMR in the country continue to be impeded by limited reliable clinical therapeutic regimens and listing processes implemented in some of the hospitals, causing delays to patients’ access to new products in some cases. At SciClone, we recognise the importance of leveraging collective industry expertise to exercise all possible options for addressing AMR. The WHO’s Strategic Priorities on Antimicrobial Resistance, published earlier this year, recommended that stakeholders must concentrate their resources into multisectoral coordination to develop strong sectorspecific responses, otherwise AMR will render common diseases untreatable and undermine modern life-saving procedures4 . As “partners-in-arms” in the fight against AMR, Menarini and SciClone hope that our strategic partnership and collective commitment in the antiinfectives space will catalyze the need to prioritize investment in antimicrobials and facilitate policy reforms to uplift accessibility of antibiotics for patients in Asia. What are your plans for anti-infectives in Asia that are particularly focused on AMR? Mr Luongo: By 2050, the APAC region is forecast to account for 47% of the AMR-related deaths worldwide, with the incidence of AMR much higher than the rest of the world5 . A study of 50 countries concluded that India and China have the highest resistance to top-priority antibiotics-pathogen pairs, including common strains like Staphylococcus aureus, E-coli and Carbapenemresistant Enterobacterales (CRE)6 . Menarini takes our commitment to fighting AMR in the Asia Pacific region very seriously and intentionally focus our efforts on where patients are most in need. To strengthen an Asia-specific antiinfective pipeline and solution, we continuously seek to bolster the lean antibiotic pipeline in the region by leveraging our key strengths (in-licensing, selfmarketing and out-licensing) to provide faster and easier access to antibiotics. Given the pressing statistics indicating the prevalence of AMR, there is an intrinsic need to partner with innovators across our value chain to offer solutions to AMR in areas of high unmet need. This is why we recently entered into a strategic collaboration with SciClone Pharmaceuticals to bring to market a novel meropenem/vaborbactam treatment originally discovered and developed by Melinta Therapeutics. This initiative will serve to expand options to address unmet therapeutic needs in AMR infections, specifically CRE in Asia. Mr Zhao: There are strong unmet medical needs for CRE treatment in China but limited therapeutic choices in clinical application. This is evident from the report by the China Antimicrobial Surveillance Network (CHINET), which showed the rising incidence of CRKP infections in China over the last 10 years7 . To expand options to address the public health threat of AMR infections in China, particularly CRE, we will utilize our in-depth knowledge of the regulatory and access procedures to move forward quickly with China-based clinical trials and ultimately facilitate the approval of meropenem/vaborbactam. We are hopeful that this will help provide greater access to anti-infective treatments for patients with severe multidrug-resistant infections in China and other parts of the world and play an important part in global efforts in the fight against AMR. What initiatives are being taken by Menarini to raise more awareness about AMR globally? Mr Luongo: As a founding investor of the USD$1 billion AMR Action Fund, Menarini is working alongside more than 20 other strategic and innovative biopharmaceutical companies to facilitate the necessary policy reforms to make antibiotics more accessible and allow collaboration with governments to develop a PARTNER CONTENT 17 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com 3 Analysis of the Drug Resistance of Carbapenem-Resistant Klebsiella pneumoniae in the China Antimicrobial Resistance Surveillance Trial Program, 2007–2018. Research Gate. Feb 2020. Link: https://www.researchgate.net/publication/339198400_Analysis_of_the_Drug_Resistance_of_Carbapenem-Resistant_Klebsiella_pneumoniae_in_the_ China_Antimicrobial_Resistance_Surveillance_Trial_Program_2007-2018 4 WHO Strategic Priorities on Antimicrobial Resistance: Preserving antimicrobials for today and tomorrow. World Health Organization (WHO). 18 May 2022. Link: https:// www.who.int/publications/i/item/9789240041387 5 Asia-Pacific in the Eye of AMR Storm: Nurturing Innovation To Fight Antimicrobial Resistance. L.E.K. Consulting, Strategy Consulting Firm. 28 May 2021. Link: https://www. lek.com/insights/sr/asia-pacific-eye-amr-storm 6 Asia-Pacific in the Eye of AMR Storm: Nurturing Innovation To Fight Antimicrobial Resistance. L.E.K. Consulting, Strategy Consulting Firm. 28 May 2021. Link: https://www. lek.com/insights/sr/asia-pacific-eye-amr-storm 7 Virulence evolution, molecular mechanisms of resistance and prevalence of ST11 carbapenem-resistant Klebsiella pneumoniae in China: A review over the last 10 years. Science Direct.com, Science, health and medical journals, full text articles and books. Dec 2020. Link: https://www.sciencedirect.com/science/article/pii/S2213716520302356

18 PARTNER CONTENT BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com 8 The AMR Action Fund announces its first non-industry investments, raising an additional US$140 million toward addressing antimicrobial resistance (AMR). Antimicrobial Resistance Research & Development – AMR Action Fund. 18 Feb 2021. Link: https://www.amractionfund.com/blog-2022/the-amr-action-fund-announces-its-first-non-industryinvestments-raising-an-additional-us140-million-toward-addressing-antimicrobial-resistance-amr#:~:text=The%20AMR%20Action%20Fund%20is%20an%20initiative%20 from%20over%2020,antibiotics%20to%20patients%20by%202030. 9 Drug-Resistant Infections: A Threat to Our Economic Future. World Bank, World Bank Group. 1 Mar 2017. Link: https://www.worldbank.org/en/topic/health/publication/ drug-resistant-infections-a-threat-to-our-economic-future sustainable pipeline of new antibiotics by 20308 . Menarini also contributes to further scientific understanding and education at international meetings on AMR, such as the World AMR Congress and we continue to support the International Federation of Pharmaceutical Manufacturers and Associations’ (IFPMA) AMR Data Generation and Endorsement Project. This important initiative is looking at alternatives to the broken volume-driven drug reimbursement model that is holding back research and development in this area. How do you foresee the growth of the antiinfectives space and approaches to managing AMR in the next 5 years? Mr Luongo: Beyond its devastating impact on public health, the threat of AMR also poses a profound economic burden with research showing that in Thailand alone, it incurs US$0.5 billion-$2.3 billion additional treatment costs annually due to drugresistant nosocomial infections. Extrapolating the Thailand experience to the wider APAC region suggests AMR could cost the region in the range of US$50 billion-$150 billion in annual healthcare expenditure. Left unaddressed, this equates to 0.8%-1% of regional GDP9 . Therefore, it is critical to invest human and financial resources to addressing AMR as a public health threat before the health and economic costs escalate to unmanageable levels. Beyond strengthening the antibiotic pipeline, we also need to build patient and public trust to untangle the decades of overuse and misuse of antibiotics. This requires a clear focus on patients who are suffering from AMR infections. Often, such patients are not ‘owned’ by a particular infectious disease doctor and as a result, health systems are not fully aware of the causal factors behind sepsis deaths – i.e., specific drug resistant infections. More companies need to pay attention to the unmet needs of patients and this is why Menarini places importance on selecting partners who share this view and are willing to form strong patientcentric partnerships built on strong compliance and governance principles that can help us move the needle on AMR. Our strong presence, established reputation, and breadth of experience in the region together with our long-term vision and commitment to ensuring patient access to high-quality, highvalue medicines can ultimately be leveraged for the collective benefit of our patients and partners. In the coming year, we will focus on expanding access to the treatment (meropenem/vaborbactam) with Melinta Therapeutics and SciClone Pharmaceuticals while continuing to look at other novel approaches and pipelines needed for effective antibacterial therapies to sustainably combat AMR. Mr Zhao: SciClone is keen to work with global partners to introduce internationally developed and advanced treatment options to China and to provide patients around the world with our own high-quality innovative drugs to cure severe AMR infections. Companies should not do it alone – partnerships are vital, especially with those that already have the commercial infrastructure in place so we avoid reinventing the wheel. More companies need to be allied with a common goal to shine a spotlight on the unmet needs of patients as this will make a difference. As innovative biopharmaceutical companies, we should give full play to our professional expertise to meet unmet clinical needs. We are grateful that in our path to excellence in healthcare, we have Menarini Asia-Pacific and Melinta Therapeutics as partners in tackling AMR. We need to see more partnerships like the collaboration between Menarini, Melinta, and SciClone, as I am sure this will be a successful model for the future. n

Cancer, the leading cause of death in most parts of the world, is a veritable Achilles heel for the pharma industry. Not surprising that pharma companies continue to dedicate a significant part of their R&D budget for Oncology. Cancer medicine spending rose to $185 billion globally in 2021 and is expected to reach more than $300 billion by 2026, as per IQVIA. China’s oncology spending now exceeds the rest of emerging countries and is driven by expanded access to new therapies and offset by lower prices. Chinese and other Asian cancer drug developers are at the forefront of driving innovation in this space. The focus of cancer treatment is rapidly shifting from a traditional one-size-fits-all approach to precision medicine, tailored treatments for individual patients. The next wave of innovations making headlines in the cancer space include immunotherapies, vaccines, CAR-T therapies, PD-1/L1 inhibitors, light-activated drugs etc. Many drug makers in Asia are investing in new science and hope to develop the next holy grail in oncology. Let’s take a deep dive into the status of cancer drug research and development in the Asia Pacific (APAC). COVER STORY 19 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com CANCER THERAPEUTICS GAINING GROUND IN APAC

20 COVER STORY BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com An estimated 8.7 million Asians were afflicted with cancer in 2020. That’s nearly half of all new global cancer cases. It’s no wonder then that the Asia-Pacific region has seen a 138 per cent increase in the number of oncology trials taking place over the past decade, the largest increase for any region worldwide, according to GlobalData. “Cancer research in Asia Pacific is contributing significantly to the global knowledge base. Based on the data from ClinicalTrials.gov, the largest public clinical research database in the world, more than a quarter of the global cancer research is taking place in APAC. In addition, there are specific cancer types that are more prevalent in Asia. For instance, the frequency of epidermal growth factor receptor (EGFR) mutations was 50 per cent or higher for patients of East Asian ethnicities. While nasopharyngeal cancer (NPC) is rare in other parts of the world, it is quite commonly found in the southern region of China and many parts of Southeast Asia,” said Choon-Peng Ng, Co-Founder and Chief Executive Officer, ImmunoScape, Singapore. ImmunoScape, is developing T Cell Receptor-based (TCR) cell therapies across multiple HLA types, including A24 and A11 HLA types that are more prevalent in Asia, against solid tumours. Immuno-oncology therapeutics Immuno-oncology therapeutics have become the cornerstone of cancer treatment. They are classified into six broad drug categories, including Checkpoint Modulators, Cell therapies, Cancer vaccines, Cytokines, Bispecific antibodies and Oncolytic viruses. Currently, the Immuno-Checkpoint Modulators (ICMs) are the leading drug category and have been a mainstay of treatment for many different tumour types. Asia Pacific has shown significant increase in Immuno-oncology (IO) trials between 2017 and 2021 and contributes to about 35 per cent of clinical development in IO globally. APAC has been the fastest growing region globally in IO trials. Phase II trials were the majority followed by phase I indicating a robust early and mid-stage IO drug development pipeline in the APAC region, according to a report from Novotech. A plethora of companies, including Akeso Therapeutics, Junshi Biosciences, LG Chem and Noxopharm and others in the region are developing immune checkpoint inhibitors to improve the cancer treatment landscape. Akeso Biopharma’s Ivonescimab is a first-inclass and the first to enter phase III clinical trial PD-1/VEGF bi-specific antibody. Currently, the firm is conducting a phase III clinical trial of AK112 monotherapy versus Pembrolizumab monotherapy as the first-line treatment for NSCLC patients with positive PD-L1 expression. In addition, a phase III clinical trial of AK112 plus chemotherapy versus chemotherapy in EGFR mutated advanced nonsquamous NSCLC that failed in prior EGFR-TKI therapy is ongoing. The Chinese regulator granted Breakthrough Therapy Designation (BTD) for Ivonescimab, in October 2022. Tifcemalimab is the world’s first-in-human recombinant humanised anti-BTLA (B- and T-lymphocyte attenuator) monoclonal antibody independently developed by Junshi Biosciences. So far, tifcemalimab has entered phase Ib/II study, and several trials of tifcemalimab in combination with toripalimab in patients with different types of tumours are ongoing in China and the United States. IBI110 is an IgG4κ recombinant human antiLAG-3 monoclonal antibody independently developed by Innovent Biologics, China. The firm presented positive phase 1b results in December 2022. Korea’s LGChem is developing CUE-101/LR19127 in collaboration with US-based Cue Biopharma for the treatment of HPV+ recurrent or metastatic head and neck cancer. This drug is currently in phase II development, and LGChem owns the Asia rights to this checkpoint inhibitor drug. Noxopharm’s Veyonda is a first-in-class, dual-acting oncotoxic and immuno-oncology molecule known as idronoxil. Veyonda is currently being investigated in a phase 1 CEP-2 trial USA in combination with the chemotherapy drug doxorubicin, for first-line treatment of soft tissue sarcoma. Veyonda received Orphan Drug Designation (ODD) from the USFDA in March 2022. CAR-T Therapies Chimeric antigen receptor therapy (CAR-T) is developing at a significant pace and is all set to revolutionise oncology. With Chinese companies undertaking the highest number of CAR-T cell therapy trials, GlobalData anticipates the country is likely to dominate the treatment landscape in coming years. According to GlobalData, there are nearly 60 CAR-T therapies in the overall clinical pipeline in China which are being developed by domestic pharma companies. Of which, there are 25 CAR-T therapies in phase II pipeline. So far, eight CAR-T cell products have been approved worldwide, including six US FDA-approved and two NMPA (National Medical Products Administration) approved CAR-T cell products.

COVER STORY 21 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com One of the trailblazers in this space in China is Legend Biotech. Its lead product candidate CiltaCel was the first Chinese CAR-T therapy to be approved by the US FDA in February 2022. Then the European Commission and Japan’s Ministry of Health, Labour and Welfare granted conditional marketing authorisation of Cilta-Cel. In January 2023, NMPA formally accepted its NDA for Cilta-Cel. It is the first Chinese company to achieve the overseas commercialisation of self-developed CAR-T products. Another leading company in China is CARsgen Therapeutics, which received NDA (New Drug Application) acceptance of their BCMA (B-cell maturation antigen CAR-T products, making them the first company in this sub-category. Apart from these, Singapore-based UTC Therapeutics and Tessa Therapeutics are also developing CAR-T therapies. Australian firm Carina Biotech is also at the forefront of CAR-T therapy development in the region. On January 24, 2023, the firm received a green signal to conduct a firstin-human phase 1/2a clinical trial of CNA3103, its LGR5-targeted CAR-T therapy candidate, in patients with advanced colorectal cancer (CRC) in the US. Antibody Drug Conjugate Another promising cancer therapy is Antibody Drug Conjugate (ADC). One of the leading ADC companies in Asia is China’s RemeGen. Its lead product Disitamab Vedotin (RC48), is the first Chinese ADC drug created and developed by to receive breakthrough designations in both the United States and China, the treatment of gastric cancer had been granted approval by NMPA in 2021 and also been included in the National Reimbursement Drug List (NRDL), the indication of urothelial carcinoma had been granted approval by NMPA in the same year. The drug is currently awaiting US FDA approval. The firm’s other ADCs are in various stages of development. Another Chinese firm, Kelun Pharmaceutical, has three ADCs in pipeline, out of which two are currently in phase 2 trials and the other one is in phase 1 trial. Singapore is also catching up in this space. The country’s drug discovery efforts reached a new milestone as EBC-129, the first made-in- Singapore antibody-drug conjugate, was cleared by the US FDA to progress into first-in-human studies, in January 2023. Also, Singapore-based Hummingbird Bioscience has two ADCs in pipeline both in phase 1 studies. Over the last few years, antibody-drug conjugates have continued to deliver a steady flow of positive news and the market is set to reflect that. The APAC “Cancer research in Asia Pacific is contributing significantly to the global knowledge base. Based on the data from ClinicalTrials. gov, the largest public clinical research database in the world, more than a quarter of the global cancer research is taking place in APAC. In addition, there are specific cancer types that are more prevalent in Asia.” - Choon-Peng Ng, Co-Founder and Chief Executive Officer, ImmunoScape, Singapore “Asia offers huge opportunities in research, development and marketing of cancer drugs. There are some substantial hurdles for regulatory authorities but with this aside, it’s a desirable region for development of cancer therapeutics.” - Leslie Chong, CEO, Imugene, Australia “The Asian region is very active in cancer drug therapy. China has the greatest number of immune therapies under trial including many CAR-T clinical trials and very active research in immune therapies including cell therapies. Having patents awarded in the Asia region is sound business and could lead to partnering and rights sales for developments for cancer therapies.” - Prof Alan Trounson, CEO, Cartherics, Australia

Advances in the Oncology Drug Development Rachel Webster, Head of Oncology & Biosimilars, Market Assessment Oncology is the growth engine of the pharma industry. The oncology drug market totaled $193 billion in sales in 2021 and is estimated to reach $300 billion by 2028. Fueling the growth of this dynamic marketplace is the unrelenting pace of drug development, especially in the immunooncology arena and combinatorial approaches comprising immune checkpoint inhibitors in particular. In 2022, the FDA approved 10 new oncology drugs – and countless label expansions, broadening the indications of many marketed novel therapies – including acclaimed antibody-drug conjugates (ADC), bispecific therapies, and therapies targeted to specific molecular markers. The diversity and sophisticated nature of 2022-approved oncology drugs exemplifies the exciting period of discovery and advancement we are in. We witnessed three first-in-class bispecific therapy approvals: most recently, Lunsumio (mosunetuzumab; Genentech), a first-in-class CD20xCD3 T-cell engaging antibody for follicular lymphoma; Kimmtrak (tebentafusp; Immunocore), a gp100xCD3 protein for uveal melanoma; and Tecvayli (teclistamab; Janssen), a BCMAxCD3 antibody for multiple myeloma. In addition, Elahere (mirvetuximab soravtansine; ImmunoGen), a novel antifolate receptor ADC, is the first FDA-approved treatment for platinum-resistant ovarian cancer. Another much-awaited biologic to reach the market is Imjudo (tremelimumab; AstraZeneca), a CTLA4 inhibitor in combination with PD-L1 inhibitor Imfinzi (durvalumab) for hepatocellular carcinoma. Other noteworthy ‘firsts’ include Pluvicto (lutetium Lu177 vipivotide tetraxetan; Novartis), a radioligand therapy for PSMA-positive metastatic castrateresistant prostate cancer and Opdualag (a fixed 22 COVER STORY BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com dose combination of nivolumab and relatlimab; Bristol Myers Squibb), a dual-targeted PD-1 and LAG-3 inhibitor for malignant melanoma. In addition, several novel therapies targeted to niche patient segments received the FDA nod: Krazati (adagrasib; Mirati) for KRAS G12C-mutated non-small-cell lung cancer (NSCLC), Rezlidhia (olutasidenib; Rigel) for acute myeloid leukemia patients with a susceptible IDH1 mutation, and Lytgobi (futibatinib; Taiho) for intrahepatic cholangiocarcinoma patients harboring FGFR2 gene fusions or other rearrangements. So, what can we expect for 2023? Likely another long list of new oncology drug approvals comprising biologic and small-molecule therapies with an array of novel mechanisms and combination approaches, plus numerous label expansions. Despite the oncology landscape being characterised by increased fragmentation and narrower patient populations, driven by the development and selective use of therapies targeted to molecular markers (e.g., ROS1, ALK, KRAS G12C in NSCLC), the era of the blockbuster is not over. Several drugs in development could achieve blockbuster status over the next decade. Drugs to watch are capivasertib (AstraZeneca), an oral small-molecule pan-AKT inhibitor therapy that has the potential to secure 2023 approval in HR-positive, HER2-negative breast cancer irrespective of biomarker status. For 2022-approved Tecvayli, success in ongoing Phase III trials could propel it to achieve sales of more than $1.5 billion through use in combination with other treatments and in earlier disease settings. With the promise of continued oncology drug development in 2023 and beyond, if one thing is certain, it is that this development will drive rapid evolution of the oncology treatment landscape and dynamic markets.

COVER STORY 23 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com CANCER DRUGS AUNCHED IN 2022 No Company Drug Drug Type Indication Approval 1 Immunocore, UK KIMMTRAK T cell receptor (TCR) therapy Unresectable or metastatic uveal melanoma Jan 26, 2023 2 Janssen, USA CARVYKTI CAR-T therapy Relapsed or refractory multiple myeloma Febraury 28 3 Bristol Myers Squibb, USA Opdualag Combination therapy, PD-1/ LAG-3 Unresectable or metastatic melanoma March 18 4 Novartis, Switzerland Locametz Radioactive therapy Metastatic prostate cancer March 23 5 Taiho Oncology, USA LYTGOBI Targeted therapy Unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma September 30 6 AstraZeneca, UK Imjudo Anti-PD1 Liver cancer October 24 7 Janssen, USA Tecvayli Bispecific antibody Relapsed or refractory multiple myeloma October 25 8 ImmunoGen, USA ELAHERE Antibody-drug conjugates (ADCs) Ovarion cancer November 14 9 Rigel Pharmaceuticals, USA REZLIDHIA Targeted therapy Relapsed or refractory acute myeloid leukemia December 1 10 Mirati Therapeutics, USA KRAZATI Targeted therapy Non-small cell lung cancer (NSCLC) December 12 11 Ferring Pharmaceuticals, Switzerland Adstiladrin Gene therapy Bladder cancer December 16 12 Genentech, USA Lunsumio Bispecific antibody Relapsed or refractory follicular lymphoma December 22 ADC market, which was valued at $1.96 billion in 2022, is set to swell to $6.86 billion by 2027, according to Market Data Forecast. Vaccines Cancer vaccines can be categorised as either therapeutic or preventative. The stupendous success of COVID-19 vaccines has spurred the development of mRNA vaccines for cancer. On January 20, 2023, Korea’s Genexine, received Fast Track Designation (FTD) from the Korean Ministry of Food and Drug Safety (MFDS) for GX-188E (tirvalimogene teraplasmid), its first-in-class proprietary therapeutic DNA vaccine for advanced cervical cancer. China’s Stemirna is also developing mRNAbased personalised cancer vaccines. On January 24, 2023, the Serum Institute of India launched the first indigenously developed human papillomavirus vaccine (HPV)-- CERVAVAC, against cervical cancer in women. Chinese firm YS biopharma, currently has two cancer vaccines in development, YS-ON-001, which received US FDA orphan drug designation and category I in China is expected to start phase 1 trial in 2023. The other candidate is still in preclinical evaluation. Synthetic lethality Synthetic lethality is a promising new area of cancer therapy. A couple of firms in Asia are exploiting this approach to develop new anti-cancer drugs. Leading among them is China’s Insilico Medicine which has built a strong portfolio of synthetic lethality assets. The company announced its first synthetic lethality preclinical candidate, a potent and selective MAT2A inhibitor. Insilico is progressing the candidate in IND-enabling studies and anticipates IND filing in early 2023.

Chew Huat Seng, Managing Director, Hitachi Asia, Singapore Medicine and technology have made tremendous strides toward defeating one of the deadliest diseases of the world, despite the world’s continued search for a cure for cancer. Although there are a wide variety of cancer treatments available today, the difficult truth is that these treatments usually come with side effects worse than cancer itself. Soaring cancer cases in Singapore According to the Singapore Cancer Registry Report 2019, Singapore had 189 cancer cases per 100,000 of the population, between 1968 and 1972. That average increased to 235 cancer cases per 100,000 individuals between 2015 and 2019. It is a sobering fact that one in three Singaporeans will be diagnosed with cancer in their lifetime, making cancer the number one killer in Singapore. This has triggered an urgency in Singapore’s fight against cancer. In response to the exponential increase of cancer cases, Singapore is fast becoming a leader in cancer treatment within Southeast Asia. This is especially evident in the reduced number of cancer deaths, despite the exponential increase in cancer cases – with an average of 93 deaths per 100,000 individuals between 1968 and 1972 and 78 deaths per 100,000 individuals between 2015 and 2019. To date, the republic has made significant investments in cancer research, more recently with a sum of SG$ 25 million being dedicated to liver cancer research. These investments have nurtured more opportunities for collaboration across various research and medical institutions. In the field of medicine, Singapore has been seeing a number of successful outcomes, including the newly developed ETC-159 drug targeted at solid tumours including colorectal, endometrial, ovarian and pancreatic cancers. But even with all the treatment options available today, cancer still has far-reaching consequences, even for those who may eventually recover. The journey to recovery itself is not an easy feat. Most of the time it comes with severe side effects that will drastically impact the lives of cancer patients. This is where technology has shifted the needle, providing a more holistic approach to cancer treatment. Beyond medicine, Singapore is beginning to see the benefits of investing in the technological aspect of cancer treatment. 24 COVER STORY BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com Singapore is beginning to see benefits of investing in technological aspect of cancer treatment

Company Drug Drug Type Indication Gamida Omidubicel Stem cell therapy Blood cancer Vertex Pharmaceuticals, USA/CRISPR Therapeutics, Switzerland Exa-cel CRISPR/ Cas 9 sickle cell disease (SCD) and transfusion dependent beta thalassemia (TDT) AstraZeneca, UK Capivasertib AKT inhibitor Breast cancer Genentech, USA Glofitamab Bispecific antibody Relapsed or refractory large B-Cell lymphoma Gilead Sciences, USA Trodelvy Antibody drug conjugate (ADC) Breast cancer COVER STORY 25 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com China-based Anticancer Biosciences is another leading firm in this space. China’s IMPACT Therapeutic, the leading clinical programme, PARP inhibitor (senaparib/ IMP4297), is in phase II/III studies for ovarian cancer, prostate cancer, small cell lung cancer and other indications worldwide, including China. Senaparib’s preliminary clinical data demonstrated superior tolerability and wider therapeutic window compared with other PARPi. Another innovative firm in this space is Korea’s Avelos Therapeutics. It is currently developing a synthetic lethality platform called SMILOG (Small Molecules Inducing Lethality in OncoGenic cells) to find new and more reliable synthetic lethal targets. In August 2022, the firm raised $8 million in Series A funding round. Though still in its infancy, Avelos Therapeutics has established meaningful research partnerships, including a collaboration for a first-ofits-kind drug programme with the Research Institute of England. The company plans to select preclinical candidates in the first half of 2023. Oncolytic viruses In November 2021, Japan approved the world’s first oncolytic virus therapy for brain cancer. Daiichi Sankyo’s, DELYTACT (teserpaturev/G47∆), an oncolytic virus developed by the company in collaboration with Professor Tomoki Todo of the Institute of Medical Science, The University of Tokyo. A less abrasive approach Early cancer detection needs to be accompanied by less abrasive approaches to treatment so that they are able to carry on with their responsibilities and continue to enjoy their quality of life. The good news is that there are such options available in the market today. One such revolutionary tech-enabled treatment is Proton Therapy – a cutting-edge cancer treatment that reduces side effects commonly found in conventional radiotherapy. With conventional radiotherapy, photon beams are used. These are essentially light particles which are very small and have the ability to pass through many tissues. While they are used to target cancerous tumours, these photons tend to also affect surrounding tissues behind the tumour. Conversely, protons are larger particles that can be hurled at incredible speeds with the help of magnets, to focus solely on where the tumour is located, without compromising surrounding healthy tissue. Proton Therapy works by sending protons to the site of the tumour, where they release their energy. The healthy cells in front of the tumour get a low dose of radiation, and the ones behind it are not exposed at all. With Proton Therapy, patient’s side effects that are commonly associated with conventional radiotherapy are minimised. While this technology has already been in use in Japan and the USA, it is now available in Singapore – a first in Southeast Asia. This will offer more treatment options for Singaporeans affected by cancer. The new NCCS building houses a comprehensive therapy centre, named the Goh Cheng Liang Proton Therapy Centre, which will start operations in 2023. The centre will be fully integrated with a Proton Therapy system produced by Hitachi Asia. Cure for cancer in sight? The fight against cancer is tough, and the road to recovery is often long. Collaboration between medical professionals, research institutions and technology providers will be pivotal to providing cancer patients a sustained quality of life, whilst seeking treatment. For all we know, with continued efforts and collaboration in cancer research, we might very well see the cure for cancer available within our lifetime. CANCER DRUGS AWAITING APPROVAL IN 2023

26 COVER STORY BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com A Stitch in Time to Save Lives When United States President Joseph R. Biden introduced the relaunch of the Cancer Moonshot Initiative in 2022, NCCN was among many leading cancer organisations to strongly advocate for the new focus on increasing cancer screening and prevention. Much more needs to be done in the U.S. and around the world to expand the use of life-saving cancer screening and detection tools such as mammograms, colonoscopies, pap smears, and low-dose CT scans. There have been remarkable improvements made in cancer management in recent years; incredible achievements of research and innovation that continue to accelerate every day. In the U.S., the death rates for most cancer types have been going down steadily over the past 20 years or so, even as the number of new cases go up. But cancer mortality rates are still way too high worldwide. To truly reduce the devastating impact of the second leading cause of death globally—we need to look beyond new cures and do everything we can to enact equitable prevention and early detection. The earlier the cancer is detected the more treatment options are available and the better chances for survival. Sometimes screening can even prevent cancer entirely by identifying abnormalities that can be treated before they develop into a cancer. However, too many people are not currently participating in screening on a recommended schedule, as determined by evidence-based expert consensus guidelines. This is due to many factors, including accessibility, public knowledge, and lingering impact from the COVID-19 pandemic. All of us, including healthcare professionals and the general public, should seek out trustworthy, vetted information on when and how to get screened. Care providers can help by making sure their patients are aware of recommended timing for when they should receive screenings and how they should be screened. Health centers can and should facilitate better screening access through flexible hours, versatile locations, and other accommodations to meet people where they are. Those in the life sciences industry can also do their part to share this important message. It is particularly important that education and resources are directed to underserved communities in order to make sure evidence-based cancer preventive services are accessible to and accessed by people regardless of individual social or economic circumstances. There is a strong risk that scientific progress will lead to widening disparities in outcomes across race, ethnicity, region, sexual orientation and gender identity, socioeconomomic status, and other factors—if equity is not considered at every step of the way. This shared social responsibility, added to personal responsibility, can save lives. Australian firm Imugene is also developing oncolytic virotherapy. In January 2023, the firm received green signal to commence a phase I clinical trial of its oncolytic virotherapy candidate, VAXINIA in Australia. There has been a flurry of activities and partnership in this space in Asia Pacific. In March 2020, Kissei Pharmaceutical (Japan) signed a licensing agreement with CG Oncology (US) to gain development and commercialisation rights to the US company’s oncolytic viral therapy candidate CG0070 in 20 markets in Asia. In August 2020, Chinese firms ImmVira and Shanghai Pharmaceuticals signed a clinical collaboration and exclusive licence agreement for ImmVira’s MVR-T3011 intratumoral oncolytic virus programme. “Asia offers huge opportunities in research, Dr Robert W. Carlson, Chief Executive Officer, National Comprehensive Cancer Network (NCCN)

COVER STORY 27 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com No Partners Details 1 Synaffix, the Netherlands and Hummingbird Bioscience, Singapore Hummingbird Bio to develop a next generation ADC program using Synaffix technology 2 AdAlta, Australia and GPCR Therapeutics, South Korea “to evaluate AdAlta’s CXCR4 inhibiting i-bodies as cancer therapeutics, using GPCR Therapeutics’ proprietary combination inhibition approach.” 3 Eucure Biopharma, China and ISU ABXIS, South Korea ISU ABXIS will utilize the sequence of YH003, Biocytogen’s humanized agonistic anti-CD40 antibody currently in phase II clinical trials, to construct a few groups of tri-specific antibodies and develop cancer drugs for multiple indications using its technology platform 4 XtalPi, China and Experimental Drug Development Centre (EDDC), Singapore To discover novel treatment candidates for non-small cell lung cancer (NSCLC) 5 Merck,USA and Kelun-Biotech, China To develop seven investigational preclinical antibody-drug conjugates (ADC) for the treatment of cancer 6 Charles River Laboratories, USA and Rznomics, South Korea Rznomics will leverage Charles River’s viral vector CDMO experience to initiate clinical development of its RNA-based anticancer gene therapy in liver cancer patients. 7 Takeda, Japan and Hutchmed, China Takeda to acqiuire rights of ruquintinib, a colorectal cancer drug 8 Qurient, South Korea and Merck, USA For clinical study of Q901, a selective CDK7 inhibitor in combination with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) 9 EpiAxis Therapeutics, Asutralia and University Health Network, Canada “To study a new approach to prostate cancer treatment.“ 10 Bora Pharma and TaiRx, Taiwan to manufacture a novel anticancer drug, CVM-1118 11 Harbour BioMed and CSPC NBP Pharmaceutical, China The deal grants NBP Pharma the exclusive rights to develop and commercialize batoclimab in Greater China including mainland of China, Hong Kong, Macau, and Taiwan. 12 Jacobio Pharma, China and Merck, USA To study combination therapy between Jacobio’s KRAS G12C inhibitor JAB-21822 and Merck’s epidermal growth factor receptor (EGFR) inhibitor Erbitux (cetuximab) 13 Eucure Biopharma, China and Syncromune, USA For the development and commercialization of intratumoral immunotherapies 14 CellOrigin and Qilu Pharma, China “To develop “”Off-the-Shelf”” CAR-iMAC cell therapy” 15 Ono Pharma, Japan and Memo Therapeutics, Switzerland To discover and develop antibody drugs in the immuno-oncology field 16 EpiAxis Therapeutics, Asutralia and Seatle’s Children Hospital, USA The partnership is study a new approach to treating paediatric brain cancer 17 NextCure, USA and LegoChem Biosciences, South Korea The partnership is focused on generating a B7-H4 antibody drug conjugate (ADC) and options for two additional targets 18 Immutep, Australia and Merck, Pfizer, USA “Clinical trial collaboration for new combination study of its first-in-class LAG-3 candidate, Eftilagimod Alpha, and Avelumab to treat urothelial Cancer” 19 Ajinomoto and Exelixis, Japan To develop ADCs for cancer 20 Innovent Biologics, China and Sanofi, France Clinical trial programs combining two of Sanofi’s prioritized oncology assets with sintilimab, the leading checkpoint inhibitor in China, to address some of the most prevalent solid tumors in China 21 Ascentage Pharma, China and Tanner Pharma, USA They have jointly launched an innovative Named Patient Program (NPP) for olverembatinib 22 Cancer Research, UK and Sosei Heptares, Japan “The agreement is to bring Sosei Heptares’ cancer immunotherapy drug candidate into a firstin-human trial“ 23 Guardant Health, Singapore and Adicon, China Guardant Health will license to Adicon its industry-leading liquid biopsy technology, for patients with any solid cancerous tumor. 24 “GE Healthcare, USA and National Cancer Centre, Singapore“ The firms to collaborate on AI-driven research to improve cancer care 25 Boehringer Ingelheim, Germany and A*STAR, SIngapore Boehringer Ingelheim gains exclusive global rights to a panel of cancer-specific antibodies to enable the development of targeted cancer therapies 26 AUM Biosciences, Singapore and Roche, USA To evaluate AUM001, the Company’s novel, highly selective MNK1/2 inhibitor, in combination with atezolizumab (Tecentriq), Roche’s anti-PD-L1 therapy, across multiple solid tumor indications, leading with Non-Small Cell Lung Cancer (NSCLC) and Urothelial Cancer (UC) 27 “NiKang Therapeutics, USA and Hansoh Pharma, China“ To develop and commercialise NKT2152, for the treatment of cancer in Greater China, including Mainland China, Hong Kong, Macau and Taiwan 28 ImmVira, China and Roche, USA To conduct clinical studies in the US on the combination therapy of ImmVira’s MVR-T3011 IT and Roche’s MEK inhibitor cobimetinib, to evaluate the safety and efficacy of this combo strategy 29 Genome and Company, Korea and Merck, USA Genome and Company will conduct a phase 2 clinical trial to evaluate the safety and efficacy of its immuno-oncology microbiome therapeutic, ‘GEN-001’, in combination with MSD’s antiPD-1 therapy, KEYTRUDA (pembrolizumab), in patients with biliary tract cancer. Cancer collaborations

development and marketing of cancer drugs. There are some substantial hurdles for regulatory authorities but with this aside, it’s a desirable region for development of cancer therapeutics,” said Leslie Chong, CEO, Imugene, Australia. Light activated drugs Photoimmunotherapy is also being explored as a treatment for cancer. Japan’s Rakuten Medical, is a pioneer in this space. The company’s first drug developed on its Alluminox platform, ASP-1929, has received approval from the Japanese Ministry of Health, Labour, and Welfare, and is currently the subject of a global phase 3 clinical trial for recurrent head and neck cancer. In September 2022, the firm opened its India office. In April 2022, Kansai Medical University established a new centre for research on photoimmunotherapy. The research centre in the western Japan city of Hirakata, Osaka Prefecture, is headed by Prof. Hisataka Kobayashi, who developed the treatment method. Drugs launched in 2022 The US FDA approved 12 new therapeutics in 2022. It was the year of landmark approvals, the regulator approved the first T cell receptor (TCR) therapy, Immunocore’s KIMMTRAK; the first radioligand therapy, Novartis’ Locametz. The year also saw the first approval of a LAG3 therapy, BMS’ Opdualag. Janssen marked first approval worldwide for Tecvayli, the first T-cellengaging bispecific antibody for multiple myeloma. Ferring’s Adstiladrin is the first gene therapy approved to treat bladder cancer. Drugs in the pipeline In June 2022, Gamida Cell completed its submission to the US FDA for omidubicel’s biologics licence application, with a final decision expected in June 2023. Omidubicel is the first stem cell transplant donor source to receive breakthrough therapy designation from the FDA and has also received ODD in the US and EU. If approved, omidubicel will be the first and only advanced cell therapy for patients with blood cancer in need of an allogeneic stem cell transplant. In November 2022, Vertex and CRISPR therapeutics submitted regulatory filings for exa-cel (CTX001) in transfusion-dependent beta-thalassemia (TDT) and sickle cell disease. If successful, it will become the first CRISPR/Cas 9 based product ever approved, an important boost for gene editing technology. xa-cel has been granted multiple important regulatory designations, including Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease Designations from the FDA for both SCD and TDT. Exa-cel has also been granted Orphan Drug Designation (ODD) from the European Commission, as well as Priority Medicines (PRIME) designation from the EMA, for both SCD and TDT. AstraZeneca’s breast cancer drug Capivasertib, a potential first-in-class AKT inhibitor, if approved, will become a new option for patients in this setting regardless of biomarker status. Another breast cancer drug awaiting approval is Gilead Trodelvy, an ADC. On January 5, 2023, the US FDA granted priority review to Genentech’s bispecific antibody Glofitamab for people with relapsed or refractory large B-Cell lymphoma. If approved, glofitamab would be the first fixed-duration CD20xCD3 T-cell engaging bispecific antibody approved to treat the most aggressive type of non-Hodgkin’s lymphoma. Crucial collaborations There are 29 partnerships at present (from January 2022- 2023) between various pharma firms, research institutes and governments in Asia Pacific in a race to develop a cure for the deadly disease. China leads the way followed by Japan and South Korea. Collaborations between pharmaceutical companies have varying focuses ranging from drug discovery and development, clinical trials, licensing and study combination therapies. Majority of the partnerships in the region is to develop immunooncology therapeutics. Almost all the big pharma firms have tied up with smaller firms in the region. “The Asian region is very active in cancer drug therapy. China has the greatest number of immune therapies under trial including many CAR-T clinical trials and very active research in immune therapies including cell therapies. Having patents awarded in the Asia region is sound business and could lead to partnering and rights sales for developments for cancer therapies,” said Professor Alan Trounson, CEO, Cartherics, Australia. Cartherics is developing allogeneic and autologous CAR-T cell therapies. On January 9, 2023, Cartherics granted first patent in China for multiple development candidates Asia Pacific is at the forefront of modern oncology drug development and the market is on the verge of a paradigm shift, with gene and cell therapy, targeted therapies and vaccines gaining much more ground. In the future, we may have an indigenously developed cure for this dreaded disease. Ayesha Siddiqui 28 COVER STORY BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com

COVER 29 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com ‘Close the care gaps’ – a bold theme set for 2022-2024 World Cancer Day campaigns that fall on February 4 each year – intends to make a huge difference in delivering cancer care to the people. For 2023, an extended theme ‘Uniting our voices and taking action’ exhorts that meaningful steps must be taken to reduce cancer incidence and make early diagnosis more accessible. Bearing the theme in mind, BioSpectrum India connected with Raja Sekhar Kommu, Co-Founder and CTO, Karkinos Healthcare, whose company is leveraging new-age technologies to take evidence-based action in democratising cancer care. Edited excerpts; The 2020 International Agency for Research on Cancer (IARC) GLOBOCAN’s cancer statistics reports that there were an estimated 19.3 million new cases of cancer and almost 10 million deaths from cancer. How can intervention by new age technologies make a difference to these numbers? We have to pay attention to both the numbers here - number of new cases and number of deaths. The reason for such alarming numbers is because of the lack of awareness about cancer, lack of accessibility of cancer care and poor affordability of treatment. In most cases, cancer gets detected in the late stage making it very difficult for oncologists to save lives. Technology, therefore, has a significant role to play to improve both the numbers. With the help of technology, one can leverage existing distribution networks to increase the awareness about cancer, thereby nudging the population to go for periodic checks for assessing their individual risk for common cancers. In addition, with advances in technologies the diagnosis for cancer is moving from invasive to non-invasive techniques such as liquid biopsy. It is possible to screen and diagnose large populations at a fraction of cost. Both these result in improving the overall new cases and helps move the needle from illness construct to wellness construct. In addition, with advances in immunotherapy and reducing sequencing costs - it is just a matter of time for molecular testing to become a first line of companion diagnosis, ensuring the right treatment is given the first time to an individual who needs to be treated. The large amounts of data that gets generated as part of molecular testing, coupled with existing imaging and electronic health records of an individual, can be easily analysed now with machine learning algorithms. This creates the perfect feedback loop back to improve the accuracy of diagnosis and to identify early warning signs of cancer. We are anyway aware of how machine learning helps in the development of new cancer vaccines, cancer immunotherapies and cancer cell therapies. Karkinos Platform is meant to change the way cancer care is delivered, i.e., made more accessible and affordable. Can you elaborate about its Platform’s purpose and the technology involved? Karkinos platform was developed with the primary purpose as an oncology platform that binds the widely prevalent fragmented cancer care infrastructure in India into an efficient and highly functional network. To accomplish this, Karkinos’ 4D model of Detection, Diagnosis, Delivery, and Discovery has been designed. Karkinos Platform acts like the glue that integrates varied and fragmented treatment touchpoints – creating a Distributed Cancer Care Network (DCCN). The platform can connect an NGO personnel doing a cancer risk assessment at doorstep of a citizen; a trained technician doing a mammogram in a mobile camp unit; a molecular biologist doing genome sequencing in a lab; a physician administering chemotherapy at a day care centre; a medical physicist doing radiation therapy planning; an oncologist prescribing the next step of treatment; an expert participating in a molecular tumour board remotely and most importantly the patient themselves, thus, giving everyone a one single, and relevant view of the information that enables them to effectively do their respective tasks. “Technology will play a significant role in reducing numbers of new cases and deaths” « Raja Sekhar Kommu, Co-Founder and CTO, Karkinos Healthcare

30 COVER BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com Karkinos Platform is conceived to enable interoperability by design, evolve an integration ecosystem, to execute at population scale, to separate data from application and further separate application from user experience, which caters to both clinical and research – ultimately helping to achieve better outcomes for patients and making the journey accessible and affordable. The platform integrates and analyses data from multiple sources, combines data from different modalities and makes it easily accessible and actionable for Karkinos’ Care Professionals and Partners. The platform is designed as a cloud native construct hosted on Google Cloud, leveraging multitude of cloud technologies. The platform primarily uses openEHR, an open data standard to store clinical data in the Clinical Data Repository and uses FHIR for exchanging information with systems outside Karkinos. We strongly believe in Open Source and leverage many open-source tools & products from Cloud Native Computing Foundation. We also intend to make contributions to Open Source in due course. Additionally, the platform is built with security and privacy considerations in mind, as it will be handling sensitive patient data. Technologies like AI, ML, NLP are all being explored for their applications in oncology - ranging from early diagnosis to advanced cancer research. How, according to you, are these technologies supporting the oncology vertical? AI, ML, and NLP are all being used in oncology to support various aspects of cancer care, including early diagnosis, treatment planning and advanced cancer research. For instance, Karakinos’ Cancer Risk Assessment App is an ML-driven questionnaire chatbot that presents procedurally generated questions as per the respondent’s inputs to generate a risk score immediately. In terms of early diagnosis, AI and ML are being extensively used to analyse imaging data, such as CT and MRI scans, to identify signs of cancer in the early stages. This includes using deep learning algorithms to analyse images and identify patterns that indicate the presence of cancer. Additionally, AI and NLP can be used to analyse patient data from electronic health records, such as lab results and medical history, to identify patients at high risk for cancer and to help triage patients for further evaluation. Karkinos’ Oncology specific NLP model OncoKEEN derives structured intelligent longitudinal insights from vast troves of historical treatment data to drive better, faster analysis of the patient care continuum - supporting research and identifying gaps in care. In terms of treatment planning and cancer research, AI and ML are being used to analyse large amounts of data, such as genomic data and patient outcomes, to: Identify the most effective treatments for individual patients. This includes using ML algorithms to predict which patients will respond best to a particular treatment and to identify new drug targets. Understand the underlying biology of cancer and to identify new targets for drug development. Additionally, AI and ML can be used to identify patterns in patient data that may indicate new cancer subtypes or to discover new biomarkers for cancer diagnosis. On these lines, Karkinos has partnered with prestigious academic institutes in the country such as IIT Madras for the National Centre for Precision Medicine in Cancer and IIT Guwahati for the Centre of Advanced Research on Diagnostics in Cancer (C-CARD) to drive data driven cancer research. It is the age of preventive and precision medicine. Unless technology is implemented, preventive or precision medicine in cancer care cannot be achieved. How do you support this statement? Modern cancer care is characterised by three important facets: 1. State-of-the-art clinical medicine, which may include evidence-based and sophisticated therapies targeted to patients’ tumour and biological characteristics. 2. An approach to care that is attentive to the spectrum of patients’ needs (i.e., physical, psychosocial, functional, spiritual). 3. Use of systems solutions, both human and machine, that support organisations in achieving their clinical medicine and patient-centred care delivery goals. Optimising these delivery features for a disease as complicated and heterogeneous as cancer often entails complex decision making, multiple handoffs between primary and specialty care providers, and coordination among cancer care team members. Preventive and precision medicine are both centred around the idea of using individualised information, such as genetic and molecular data, to tailor treatment and prevention strategies to each patient. In order to achieve this, large amounts of data need to be analysed and interpreted. Technologies like AI, ML, and NLP are particularly well-suited for this task, as they can process and analyse large amounts of data quickly and accurately. Anusha Ashwin

COVER 31 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com “We need to foster risky projects that can have large rewards” « Dr Jing Zhang, Co-Founder, Vice President, High Throughput and High Content Screening, Anticancer Bioscience Synthetic lethality is a promising area of cancer therapy. Anticancer Bioscience (ACB) is a precision oncology company, applying synthetic lethal approaches to develop targeted cancer therapies. Dr Jing Zhang, Co-Founder, Vice President, High Throughput and High Content Screening, ACB highlights the main advantages of synthetic lethality, drug programmes at ACB and trends in cancer research. Edited excerpts; What is Anticancer Bioscience’s competitive edge and what is unique about the pipeline you are developing? Anticancer Bioscience (ACB) specialises in the development of synthetic lethal therapies. A synthetic lethal drug interaction occurs when the very same genetic and epigenetic changes that promote cancer, confer unique vulnerabilities to cancer cells. These can include apoptotic, metabolic or mitotic vulnerabilities, among others. Identifying and developing drugs that target these vulnerabilities is extremely difficult, and that is what ACB has fostered expertise in accomplishing. We have several synthetic lethal drug programmes at ACB, but the most advanced programme aims to produce small molecule therapeutics that are synthetic lethal with hyperactivity of the oncoprotein MYC. Accomplishing this goal has required the development of novel screening methods, new sources of small molecule diversity, and unique synthetic lethality validation assays. ACB’s novel, mechanisminformed phenotypic screening system is capable of guiding the identification and optimisation of lead compounds, and uncovering drug targets and predictive biomarkers. Together, our effort has culminated in the identification of multiple classes of highly potent MYC synthetic lethal compounds that are highly efficacious in vivo and readily orally bioavailable. Biomarker studies are a vital component of any targeted drug development programme, and this is especially true for synthetic lethal therapies. ACB has uncovered markers that alongside MYC expression predict which tumours will be hyperresponsive to our synthetic lethal compounds. Bringing our drugs to the clinic alongside this screening strategy to stratify patients will enable focused and effective targeting of patient tumours. A final edge for the compounds we are developing lies in the MYC synthetic lethal target that our drugs bind and inhibit. Our lead compounds bind a novel synthetic lethal target. Our studies suggest its inhibition confers lethality in MYC-overexpressing cells, not normal cells. This means that while tumour cells succumb to our drugs, normal tissues will be left relatively healthy. Another unique programme in the pipeline is contact inhibition restoration, a promising approach that has not yet been fully explored. Loss of contact inhibition is a hallmark of cancer cells. As an innovative cancer therapy, CIR drugs do not necessarily aim to kill dividing tumour cells as most current cancer therapies do. Instead, they can enable cancer cells to re-establish contact inhibition. ACB has established a unique

32 COVER BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com image-based high-throughput screening assay to identify agents that restore contact inhibition and has developed a combination treatment with two drugs identified from the screening. ACB is exploring nanoformulation of this drug combination for selective accumulation and controlled release of active pharmaceutical ingredients into tumour tissues. What potential do you see for this class of targets? We see enormous potential for synthetic lethal therapies. The ultimate goal for synthetic lethal therapy is to be able to target indirectly, the oncogenes and tumour suppressor losses that we know are drivers of carcinogenesis, but have until now proven difficult to drug using traditional means. One thing to keep in mind is that we are developing synthetic lethal therapies as stand-alone therapies, but once proven in the clinic they may prove especially potent alongside other therapeutic modalities as components of combination therapies. At ACB we have deliberately focused on the development of compounds that can be used in a wide variety of cancer indications. MYC, for example, is arguably the most widely expressed cancer protein, as it is overexpressed in more than 70 per cent of human malignancies. It is mutated in some types of lymphomas but genetically amplified in about 28 per cent of solid cancers. In many more cases, however, the overexpression of MYC is due to the loss of transcriptional or post-translational control mechanisms. With our lead MYC synthetic lethal compounds, we observe anticancer activity against cancers derived from a large variety of indications including lymphoma and solid cancers such as stomach, colon, and non-small cell lung cancer. A second programme at ACB, which is currently in an early preclinical stage, aims to target cancer cells that have lost activity of the p53 tumour suppressor protein. Like MYC, loss of p53 is found in a wide array of human cancers, and developing drugs that attack vulnerabilities enabled by p53 genetic loss-of-function will have a large impact. We aim to make a large difference for patients at ACB, not an incremental one. What are the latest trends and challenges in cancer drugs development? There are lots of great ideas and truly brilliant people working in the areas of both basic cancer research and cancer drug development. However, despite the large VC-driven funding rounds that some companies are able to achieve, most ideas do not move forward. We fear that with an ailing economy, this may become an even deeper problem. For Innovation to be the driver of the next generation of drug development, we need to foster risky projects that can have large rewards. We are grateful to our funding partners for seeing this potential in Anticancer Bioscience and are grateful to the talented people that choose to work at ACB. Oncology has been the primary focus of precision medicine in the past decade. The latest trends in cancer drug development include targeted immunotherapies like immune checkpoint therapies, CAR-T, and mRNA vaccines, and synthetic lethal cancer therapies. ACB, as the pioneer in synthetic lethal approaches to precision oncology, has developed its unique and innovative pipeline based on over 20 years of collaborative research between the founder Dr Dun Yang and his Nobel laureate mentor Dr J. Michael Bishop. The lack of biomarkers to guide treatments has been a challenge in the field and remains so. Apart from traditional molecular or biochemical biomarkers, new types of biomarkers are arising. Signatures detected in genomic, transcriptomic, proteomic, and metabolomics data can be used as a prediction for treatment response and prognosis. With this knowledge, the next challenge would be how to effectively apply it to provide new avenues for therapeutic strategies. At least, understanding the treatment resistance and developing a rationale combination is certainly needed for durable efficacy. Ayesha Siddiqui The lack of biomarkers to guide treatments has been a challenge in the field and remains so. Apart from traditional molecular or biochemical biomarkers, new types of biomarkers are arising. Signatures detected in genomic, transcriptomic, proteomic, and metabolomics data can be used as a prediction for treatment response and prognosis. With this knowledge, the next challenge would be how to effectively apply it to provide new avenues for therapeutic strategies.

COVER 33 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com “Global investors can leverage our deep immunomics platform to develop TCR Cell therapies for solid tumours” « Ng Choon Peng, Founder & CEO, Immunoscape The global biotech ecosystem continues to fluctuate and pose fresh challenges but many emerging enterprises and technologies are keen to collaborate with other stakeholders to solve healthcare challenges. Singapore is a leading startup hub in Asia having the expertise and network to be the launch pad to the region and beyond. Singapore’s A*STAR spin-off ImmunoScape, a pre-clinical biotechnology company focused on the discovery and development of next-generation T-cell receptor (TCR) cell therapies in the field of oncology has been thriving in the regional and global space. In an interaction with BioSpectrum Asia, Ng Choon Peng, Founder & CEO at Immunoscape discussed the opportunities and challenges in commercialising technology spin-outs from biomedical research amidst Singapore’s fast-growing ecosystem for bioscience ventures. Edited excerpts; How crucial is the adaptation of nextgeneration TCR cell therapies for diagnostic and prophylactic purposes? TCR cell therapies have evolved from their initial ventures around the isolation, expansion and re-infusion of T-cells to the patient, to newer and exciting ways of devising novel TCR cell therapies. As cell therapies are designed to be highly specific to a patient’s tumour these are built using cuttingedge, in-silico Machine Learning approaches that can improve efficacy and patient safety. While current TCR technologies primarily address unmet treatment options, next-generation TCR cell technologies could potentially include the following: ● Diagnostic use cases such as the development of patient stratification tools, i.e., by identifying variations in antigen-specific T-cells within patient groups for a deeper understanding of the pathology. This ensures that the right drugs reach the right patients at specified times ● Prognostic use cases such as monitoring patient responses to alter treatment regimens and take positive responders off therapies, thereby reducing the economic burden ● Prophylactic use cases such as the development of TCR cell therapies for the prevention of opportunistic infections in patients on immunosuppressants for organ transplants Although ImmunoScape’s technology stack has the potential to address many of the above scenarios, we are very focused on our TCR discovery and development of TCR-based therapeutics. How would you describe ImmunoScape’s investor relationships globally and especially in Singapore? ImmunoScape was spun out of A*STAR (by in-licensing key A*STAR technology) in 2017. ImmunoScape is dedicated to discovering and developing a diverse, risk-balanced portfolio of novel TCRs against solid tumours. ImmunoScape’s focus has been to partner with life science investors both in Singapore and globally. The value-add from these investors goes beyond just the financing, into business development, follow-on investments, and governance. Singapore’s Economic Development Board Investments (EDBI) has helped introduce us to their global partners since ImmunoScape became a portfolio company. Based on their interactions with other portfolio companies across the globe, they have also offered us advice on best practices. In addition, we received support from three more venture capitalists, namely; “Anzu Partners” who helped us set up and expand in San Diego from our headquarters in Singapore, “Amgen Ventures”, who created rigorous due diligence on our cuttingedge science validates the technology. We are always grateful to our first institutional investor, the University of Tokyo Edge Capital (UTEC), who

34 COVER BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com believed in us even when our technology was deemed early by many. Global investors can join our journey in leveraging our deep immunomics and machine learning platforms, to discover and develop a diverse, riskbalanced portfolio of novel T Cell Receptors (TCR) to treat solid tumours. What is your approach towards commercialising technology spin-outs from biomedical research? ImmunoScape, a spin-out of A*STAR, focuses on novel TCRs against solid tumours. We keep an eye on what the market needs are and the other eye on how our technology can meet those needs. The way to create value is to identify the pain points and solve them, leveraging on the uniqueness of our technology. In our case, it is the unmet need of cancer, especially against solid tumours. Our unique deep immunomics and machine learning platforms can uncover novel TCRs against a diverse range of tumour antigens. We continue to build on the strengths of our highly skilled immunologists and computation biologists, many of whom are from A*STAR or local universities, to optimise our wet lab approaches and train predictive algorithms for our machine learning in predicting antigen specificities. The data from the wet lab feeds the unique database for machine learning and the wet lab in turn validates the predictions - creating this feedback loop that increases the accuracy for the next prediction. Thus, ImmunoScape is working to generate a wealth of data that lead to the speedy discovery of many novel TCRs which have commercial potential. Some of these include lead therapeutic products that ImmunoScape can accelerate through clinical trials and bring to the market. Our own proprietary pipeline comprises novel TCRs against both validated and novel targets that are linked to solid tumour indications. With the in vitro and in vivo data that we are gathering now, we hope to file for an Investigational New Drug (IND) soon. Other disease signatures that biopharma companies might be interested in licensing from ImmunoScape are also in the running. Harnessing the power of collaboration and diversity in the workplace is also crucial for us. Our discovery science teams comprise both local and global talents so we have a diversified set of skills and perspectives as we tackle various challenges. Active collaboration with academic labs and clinician-scientists for access to patient samples for the discovery and validation of novel TCRs is also crucial for us. For example, we have an ongoing collaboration with the National Cancer Centre of Singapore to obtain patient-derived blood samples to identify novel TCRs. At present, we are also looking towards working with other biopharma companies with capabilities that can be synergised with that of ImmunoScape’s to enable faster pre-clinical and clinical development of novel TCRs. This synergistic approach is intended to maximise the utilisation of ImmunoScape’s proprietary technology and resources to bring multiple therapies (and modalities) that will target solid tumour cancer patients suffering in a much shorter time frame. How would you describe the strategic approaches adopted by ImmunoScape to capitalise on the opportunities in the global market? How does Singapore’s enterprise ecosystem foster startups? The Singapore startup ecosystem has grown from strength to strength over the last few years. Enterprise Singapore provided significant support for ImmunoScape in multiple areas, including funding and manpower. In 2019 and 2020, we received two funding awards from Enterprise Singapore. The first was the Startup SG Tech Grant (2019-2020) and the latter was the Enterprise Development Grant (2020-2021). This funding went a long way as we expanded ImmunoScape in the US, as well as our executive and scientific teams. We were also provided with manpower support through A*STAR’s “T-Up program”, with Enterprise Singapore covering a significant portion of ImmunoScape’s hiring costs. In addition, Enterprise Singapore connected ImmunoScape with other potential investors to get additional funding and provided us access to networking opportunities with other successful start-ups, venture capitalists, and ecosystem partners. When we first started ImmunoScape, we were faced with challenges such as the lack of early-stage funders, appropriate lab spaces, and talent with the right skill sets. Entrepreneurs who want to start a bioscience business today will also have better access to shared lab spaces, incubation centres, and a larger pool of skilled talents as compared to 5-10 years ago. Connection to and facilitation of all these different resources play a big role in any startup’s success, particularly during the early stages of growth. Hithaishi C Bhaskar [email protected]

How imaging tech and liquid biopsy will play pivotal role in cancer care A core tenet of precision medicine is to simplify the delivery of the right treatment to the right patient at the right dose and at the right time. Precision Oncology is rapidly developing and currently includes molecular profiling of tumours to identify targetable alterations. At the core of Precision Oncology is a patientcentric approach. 2023 marks the year of the 20th anniversary of the conclusion of the Human Genome Project. Today, the use of genotyping and genomics have become essentials in standards and researchers and the industry is looking into expanding to include big data, proteomics, transcriptomics, molecular imaging, and more, to translate that ideal into meaningful and equitable healthcare for patients. Recent rapid developments within the liquid biopsy and medical imaging technologies should encourage radiologists to view it as an opportunity to find synergistic ways of combinational techniques to improve personalised medicine and optimise patient care. Biomarkers and Digital Biomarkers Biomarkers are molecules that have different expressions in tumour cells than in normal body cells, and can be used for diagnosis, prediction of sensitivity to treatment, and prognosis. Especially ctDNA (Circulating tumour DNA) which can be found in fluids has gained significant attention. This is especially because ctDNA can easily be obtained through a simple blood draw – a liquid biopsy – and is used as a non-invasive biomarker to identify tumour-specific abnormalities. As a less invasive technique as compared to solid biopsy, liquid biopsy has the potential to be used to detect and monitor the presence and progression of cancer. In the first week of January, AstraZeneca and US-based C2i Genomics announced a partnership to utilise the C2i Genomics’ whole-genome minimal residual disease assay and cancer-monitoring platform for use in clinical research and drug development efforts. This announcement comes just a month after AstraZeneca and Guardant360 announced a collaboration for the Guardant360 CDx blood-based liquid biopsy assay as a companion diagnostic for a breast cancer drug being developed by AstraZeneca. Based on data provided by Digital Health venture analytics platform HealthTech Alpha, « Dr Dario Heymann, Chief Research Officer, Galen Growth there were 146 partnerships announced between Digital Health omics-related solution providers and corporations and institutions in 2022, up 2.4x from the previous year. Immuno-oncology Immunotherapy is a formidable weapon against cancer as it has shown the potential to use the body’s natural immune response against the infection. Compared to conventional therapy, immunotherapies have demonstrated long-lasting and significantly better responses for cancer patients. For the immune context, biomarker discovery plays a pivotal role in the assessment of potential Immuno-oncology (I-O) therapies and therapy combinations. The appropriate identification of Biomarkers enables the adaptation of individual treatment approaches for each patient and can be used to monitor a therapy response. The efficient and successful development of I-O biomarkers requires utilisation of appropriate tools and, several aspiring studies have used artificial intelligence (AI) to facilitate the transitions from preclinical evaluation through clinical development. Immune checkpoint inhibitors (ICIs) have shown a promising response for several cancer types with lung, bladder and head and neck as well as melanoma. In 2011, Bristol Myers Squibb (BMS) received the first FDA clearance of ipilimumab, an ICI employed against CTLA-4, for the treatment of metastatic melanoma. Thereafter, another checkpoint protein, PD1, and its ligand PD-L1 have been found to have a higher response and lower side effects relative to anti-CTLA-4. While anti-CTLA-4 drugs are limited, at least six drugs are available against PD1 and PD-L1. These include Imfinzi (AstraZeneca), Bavencio (Pfizer), COVER 35 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com

36 COVER BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com Tecentriq (Genentech / Roche), Libtayo (Sanofi / Genzyme), Opdivo (BMS) and Keytruda (Merck). Keytruda was initially approved by the FDA in 2014 exclusively for the treatment of Advanced Melanoma. In the following years its application was extended to include a number of head and neck, lung, bladder, cervical, skin, kidney, colorectal, esophageal and breast cancers. In 2017, Keytruda was the first cancer drug to receive approval based on a common biomarker rather than the location in the body where the tumour originated which was extended in 2020 to include a second biomarker-based indication. Innovative solutions in Digital Health and biotechnology are a key driver behind the continuous development of drugs like Keytruda. Functional Imaging Medical images have long been used to guarantee satisfying treatment planning and outcome management of radiation therapy. Recently, the use of functional images to extract quantifiable radiologic biomarkers has arisen. The application of functional images is used to strengthen and improve prognostication response to radiation therapies and to facilitate personalised treatment and clinical trial designs. Moreover, quantitative functional imaging can also be applied for heterogeneous dose painting, whereby radiation is delivered within the tumour volume by targeting radioresistant areas. According to HealthTech Alpha, there are more than 220 Digital Health ventures active in the field of cancer medical imaging. Many of these ventures are employing artificial intelligence and machine learning capabilities to their product offerings. One example of how Digital Health is impacting the development of biomarkers is PathAI, a Cambridge, MA, based provider of AI-powered research tools and services for pathology. PathAI has developed AISight, a web-based digital pathology slide viewing platform that enables the management and review of whole slide images and will accelerate access to AIpowered algorithms’ quantitative and visual outputs. In August 2022, the company received their FDA and the CE Mark from the EU for their AISight Dx digital pathology platform for primary diagnosis in clinical settings. According to HealthTech Alpha PathAI has closed partnerships with numerous leading pharmaceutical companies, including BMS, GSK (both in 2022), Novo Nordisk, Roche, Merck, and Gilead Sciences. Since 2021, more than 20 partnerships have been disclosed between medical imaging Digital Health ventures and leading pharmaceutical companies. Such partnerships are not entirely based on the latest developments in treatment options and personalised medicine but also due to the advancements in the application of artificial intelligence in image processing. Its use in quantitative imaging is crucial to improve the quality of the images because of its traditionally worst signal-to-noise-ratio compared to other imaging techniques. Artificial intelligence also helps to construct image-based biomarkers which can provide a comprehensive view of the tumour and its heterogeneity. And, because medical imaging techniques are largely non-invasive, its application for tumour phenotyping related to prognosis and monitoring the development and progression are favoured. Moving Forward Combining medical imaging technologies and liquid biopsy as complementary tools in cancer care at each step will play a pivotal role in the cancer care continuum. As an example, a recent imaging study suggested correlations between a higher disease burden measurement on CT correlated with plasma ctDNA burden. Other results of a study on the detection of rising ctDNA levels also indicate that its monitoring may also prove to be helpful in detecting tumour progression in settings in which subtle imaging changes can be difficult to detect. Through findings like this, radiologists should feel encouraged to better understand the potential of liquid biopsy and the development of new imaging algorithms for screening, diagnosis and prognosis, and cancer management. Through further collaborations all stakeholders, including radiologists, oncologists, researchers and big data scientists are needed to optimise combined technologies and improve the early cancer detection in real-world settings.

SPEAKING WITH 37 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com Rare diseases remain untreatable globally despite major advances in research that have enabled us to understand their molecular basis, as well as legislation that provides regulatory and economic incentives to encourage their development. Rare diseases often lack treatment options and are decades behind in R&D. An important component of addressing this translational gap is the selection of the optimal therapeutic modality to translate advances in rare disease knowledge into potential medicines, such as small molecules, monoclonal antibodies, protein replacement therapies, oligonucleotides, gene and cell therapies, as well as drug repurposing. Global pharma firm, Merck is into development of therapies for one such rare disease, Multiple sclerosis (MS), a chronic inflammatory condition of the central nervous system prevalent in Asia-Pacific. It is the most common non-traumatic, disabling neurological disease in young adults. Like many other rare diseases, MS has received less attention from drug developers because of the smaller market opportunity in this group of patients. In an interaction with BioSpectrum Asia Liz Henderson, Senior Vice President APAC, Merck Healthcare explains the therapeutic prospects around this rare disease. Edited excerpts; Why does multiple sclerosis (MS) deserve attention and investment in APAC for the development of novel treatments? In my opinion, there can never be too many treatment options for someone with a serious autoimmune disease like MS, because not every treatment works for every patient. Merck believes that a healthier future deserves a sizable investment. In 2018 our Healthcare business devoted roughly 20 per cent of total sales to R&D activities aimed at discovering and developing new therapies. All of these are integrated in four strategically located and highly connected hubs on three continents: Darmstadt, Boston, Beijing and Tokyo. “We’re dedicated to Multiple Sclerosis with two approved therapies and Evobrutinib currently in phase 3 trial” « Liz Henderson, Senior Vice President APAC, Merck Healthcare What are the latest developments and investments at Merck around MS? Merck has a long history with MS – we’ve been developing drugs to treat this disease for over 20 years and we continue to invest heavily in this area of unmet need. The main goal of our drug development programme for MS patients is to help improve their quality of life and delay the progression of the disease. The goal is to reduce the treatment burden, improve adherence, improve care outcomes and make administration easier. We are also fostering debate among the MS community. In 2017, we received EMA approval for Mavenclad, an oral therapy to treat relapsing MS. This was followed by FDA approval in 2019 for the therapy. Our first product to receive approval was Rebif, 20 years ago, and we have an active neurology and immunology pipeline in lupus and MS with assets in stages 2 and 3 of development. In addition, we partner with companies with interesting drug candidates which can provide us with strategic additions to our portfolio. Our recent acquisition of Chord Therapeutics allows us to explore the potential of Cladribine in indications beyond MS to generalised myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). We primarily focus on the molecules we know well and strive to develop their full potential for the benefit of patients. Furthermore, an earlier initiative called the Grant for Multiple Sclerosis Innovation (GMSI) which supports the advancement of science and medical research in the field of MS. Funding is

awarded to early stage research projects, enabling talented and inspiring researchers to advance our understanding of how we predict, diagnose, treat and monitor the progression of this disabling disease. How do you foresee the opportunities and challenges in the MS treatment sphere? MS is a complex disease that is difficult to treat. The greatest challenge is around the medical community’s understanding of the disease itself – MS symptoms present differently from patient to patient, and responses to therapies vary greatly, making clinical trials challenging. Therefore, research into biomarkers will open up a lot of possibilities in terms of treatments and response rates. There has been significant progress made in the last decade in the identification of MS biomarkers, and we can now diagnose patients faster, and ensure safe and personalised treatment. Are there any new pathways that can modulate the immune system in a more targeted way than traditional immunosuppressant therapies to tackle rare diseases? For immune mediated disease, our focus is on targeting the innate and adaptive components of the immune system, which means we develop products that aim to inhibit inappropriate immune activation that contributes to the disorder, as well as enhancing immune tolerance, training the body not to react to certain triggers. In the immune system, there are many complex pathways that can go wrong, which is why so many drugs are being developed by pharmaceutical companies targeting various complex pathways involved in immune dysfunction. For patients with autoimmune diseases, disease-modifying therapies have greatly evolved. Drug discoveries usually start by identifying a specific target, such as inhibiting the Bruton’s Tyrosine Kinase (BTK) receptor. Evobrutinib is a BTK inhibitor, developed by Merck and is currently in phase 3 trials for MS. From a mechanistic perspective, what excites me about this drug is that it is the first and only BTK inhibitor to show a reduction in levels of a key biomarker called blood neurofilament light chain (NfL) levels, indicating neuronal damage and inflammation in patients with MS. Measurement of this biomarker, especially early on in the disease, can capture the extent of neuroaxonal damage. While monoclonal antibodies are viewed as a mainstay of treatment for MS because they bind very specifically to large proteins called antigens that can then mediate their effects on specific pathways, BTK inhibitors are much smaller molecules, and are able to enter the central nervous system, which is a property that monoclonal antibodies do not have and thus might have an impact on the disease evolution over time. Which drugs are in the pipeline for immune-mediated rare diseases? What are Merck’s development plans for FY 2023? In collaboration with Global Business Development, we scout and evaluate external opportunities in immunology, including technologies, preclinical and early clinical assets. In January 2022, we entered an out-licensing agreement for a drug called sprifermin with Trial Spark and High Line Bio, based in New York. Sprifermin is a disease modifying treatment for osteoarthritis (OA) that improves cartilage thickness. The drug is a recombinant form of human fibroblast growth factor 18 and could be the first disease modifying therapy for people with OA. Across our Neurology and Immunology portfolio, we are also developing drugs to treat lupus, another autoimmune disease that occurs when the body attacks its own cells. Enpatoran is a novel, investigational immune checkpoint inhibitor in development for two different types of lupus, systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). Lupus is a multifactorial autoimmune disease compromising various processes and cell types, including the loss of tolerance to self-nuclear antigens and is driven by Toll Like Receptor (TLR) 7/8 overactivation. TLR’s are a relatively new discovery (1985). They are an important part of our innate immune system and defend us against pathogens. Inhibiting the overactivation of these proteins has recently been identified as a potential target for lupus. Enpatoran is currently in phase 2 trials and we expect to generate preliminary data soon. In Neurology and Immunology, we remain dedicated to MS with two approved therapies, and we are focusing on our ongoing phase 3 study of Evobrutinib, which will be out by the end of 2023. Hithaishi C Bhaskar [email protected] 38 SPEAKING WITH BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com

SPEAKING WITH 39 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com Synthetic biology markets are experiencing a surge in demand for molecular diagnostics and technological advances in molecular biology, spurring growth in the Assay and Reagent market in Asia Pacific. A shift towards molecular diagnostics and personalised medicine has further motivated bioscience entrepreneurs to develop new assay methodologies. The Australia and New Zealand biotech commercial space is also stimulated by increasing demands for reagents in the clinical trials and diagnostics arena over the rapid growth of molecular biology applications in the region. A Melbourne-based biotech company, Assay Matrix Pty Ltd was founded by Santosh Nambiar, who supports Australia and New Zealand biomedical research. Nambiar shares his insights about the Assay and Reagent market with Biospectrum Asia. Edited excerpts; How would you describe the assay and bioreagents market in Australia and New Zealand? What impact does the Assay Matrix have on the region? The biotech industry in Australia experiences a gap in the industry for the reliable supply of antibodies, assay kits and reagents. Assay Matrix was set up to close this gap. Australia and NZ being island nations separated from the world by ocean, often face difficulties obtaining these products (Assay Kits, antibodies, and reagents, including recombinant proteins) for research, especially as we lack local manufacturing. Not only are these products temperature and time sensitive, but the strict customs in Australia and NZ can also make the importation of these products challenging. Therefore, researchers may have to wait for weeks and months to get their products from overseas. Unfortunately, this does not promote a level playing field for researchers in Australia and NZ. While a researcher in the US, UK or Europe can order their products and receive them on the same day or the following day and progress with their research, a researcher in Australia is at a disadvantage by having to wait weeks or even months to receive their product. Assay Matrix over the years has streamlined this process. At Assay Matrix, we make available a wide range “Australia is poised to establish itself as a global life sciences hub” « Santosh Nambiar, Founder and MD, Assay Matrtix of antibodies for research in Australia and New Zealand. Assay kits, particularly ELISA kits, are our primary focus of business, mostly used by universities and government-funded research organisations. Nevertheless, of late there are a lot of startup biotech companies creating significant demand for biotech research and resources in Australia. However, these products are not as highly sought after by the pharma market as they are in academia. Eventually, we also plan to expand into cell culture products, including primary cells. However, Customs delays are a constant challenge in Australia for transporting cell lines in liquid nitrogen or dry ice across the supply chain. How would you evaluate opportunities and challenges across the bioscience assay products market in Australia and NZ? What is your outlook for the market’s growth? In Australia and NZ, there’s a lot of emphasis on basic research, however, when it comes to patenting and commercialisation most of it happens outside of Australia. Although Australia and NZ foster a vibrant life-sciences ecosystem with a strong track record of basic research, it is ‘behind the world’ in commercialisation. My observation is that most startups are developed outside of Australia despite the initial basic research being developed by universities in Australia. Key challenges include difficulties in translating research intangible products, disruptions in the supply chain, inflexible regulatory and tax policies, difficulties in obtaining investments and support for skills development. However, with the rising demand for medical care and solutions, including developing

40 SPEAKING WITH BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com domestic and international vaccine production capacity, I strongly believe that the federal and state government will put a lot of emphasis in the future on providing a robust ecosystem for commercialisation within Australia. Especially with increasing local demand for ‘Australian-made’ biopharmaceuticals, Australia is demonstrating its interest and potential to expand its manufacturing and supply chain capabilities to establish itself as a global life sciences hub. The biotechnology sector relies on a highly skilled workforce that can respond to global development and changes in market trends. Building and maintaining a successful biotechnology sector in Australia requires the availability of a skilled workforce. The government is focusing on nurturing the required skills locally within Australia, while also considering the possibility of drawing in foreign talent. This will ensure that Australia develops self-sufficient capabilities within the biotechnological sector without depending on other nations, especially in situations of crisis and supplychain disruptions. What is driving the reagents and kits market in APAC? How large and conducive is the Australian market? According to market data, the global biotechnology reagents and kits market size was valued at $337.28 billion in 2020 and is forecast to grow at a compound annual growth rate (CAGR) of 16.5 per cent from 2021 to 2028. Increasing demand for reagents from academic and research institutions, rising R&D expenditure by biotech companies and technological advancement in the field are key factors driving market growth. Currently, the Asia Pacific is the fastest-growing market for bioreagents, with India and China providing the highest revenue contributions. Specifically, these regions offer significant opportunities for biotechnology companies in the global market due to the significant population base and rising investments in life science research. The life science research market in Australia, although small compared to the global market, predominantly uses assay kits and bio-reagents such as ELISA kits, detection kits, CLIA kits and metabolism kits. Australia is now a hub for leading life science R&D and manufacturing, where universities and private institutions are conducting ground-breaking research to prevent, diagnose and treat diseases. Specific research areas include cancer research, immunology, neuroscience, and neurology as well as cell and molecular biology. Internationally sourced Assay kits and bio-reagents are widely accepted and utilised for domestic research; however, it requires stringent protocols and documentation for the products to be used. What would bring in more bioscience entrepreneurs in Australia? Entrepreneurship, specifically in Australia is a new yet thriving area with a lot of future potential. After a successful career within the Indian biotech industry, I moved to NZ/Australia in 1996. Before starting Assay Matrix many years ago, I could see a widespread perception that starting a business requires a large team, huge investments, and minimal odds of succeeding. This notion has since been changed, with businesses in most industries being established with a minimal initial investment. The Australian government has helped by injecting millions to further propagate the initiation of new businesses by providing grants, investments and even tailored programmes allowing entrepreneurs to connect with experts. Local universities also support entrepreneurs by providing an atmosphere like incubators and accelerators to fast-track their ideas and connect with investors and launch their products within the market. Presently, entrepreneurial activity is booming in Australia. COVID-19 has also been a catalyst in creating more entrepreneurs, inspiring citizens to take risks and challenge themselves. Since 2020, the number of startups in Australia has risen significantly making it a hotspot. Hithaishi C Bhaskar [email protected]

TRENDS 41 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com The last two years saw a significant leap toward patient-centricity in the pharmaceutical space. In 2023, that trend will inevitably continue— although this next iteration will focus on leveraging the industry’s growing digital maturity to offer increased patient value while achieving measurable business goals. This shift will be driven by a host of factors. As we enter the digital age, most people—including patients, caregivers, physicians and other healthcare professionals—expect more from the brands they interact with. Gone are the days when a basic pharmaceutical website or simple app was enough to impress these external stakeholders—today, they want to see more advanced and useful user experiences. At the same time, the concept of value-based pricing has started to percolate in recent years. Essentially, a growing number of payers are challenging the traditional pricing structure of many pharmaceutical drugs and looking for proof that they warrant their associated price tag. Pharmaceutical companies, therefore, will be under increased pressure in 2023 to demonstrate that their products provide real value. These forces, and others, are inspiring many companies to rethink their traditional business model—and unlock new opportunities to provide patient value. In 2023, this will likely culminate in more value-based marketing strategies designed to forge a genuine connection with patients. Companies will uncover ways to bring new drugs to market faster and more cost effectively — and use the vast amount of data at their disposal to guide product decisions in a more tactical, and deliberate, manner. They may even strive to expand their offerings in the name of value — finding new ways to utilise technology, or content, to enhance the patient experience. To help envision what this may look like, below are four trends we expect to arise in the pharmaceutical space in 2023. 1. Data-informed decision making Data has been the key driver behind the pharmaceutical sector’s new product-focused business approach — and in 2023, we can expect companies to get even better at managing the vast amounts of data at their disposal. The focus, this year, will be to glean actionable insights from new and existing data — leading to even greater product VALUE is the Trending Word of 2023 « Steve Peretz, Group Director (Health Experience and Product Strategy), Appnovation, AMER and service innovations. Thanks to more advanced data management practices, pharmaceutical companies have become increasingly smarter in recent years — and in 2023, they’ll focus on getting faster as well. Specifically, we’re seeing increased investments in enterprise-wide platforms, processes and systems that will make it easier for all members across an organisation to access — and make sense of — pertinent data. Data Privacy will continue to figure prominently in the pharmaceutical space. To preserve patient trust, and make sure they’re onside of regional rules and regulations, organisations would be well-served to take a deliberate and tactical approach to the data management transition. 2. Value-added partnerships Digital therapeutics — technologies that deliver therapeutic interventions directly to patients, such as telehealth, mobile health, smart devices and wearable devices — have taken off in recent years. Although many digital health investments have begun to slow, the global digital therapeutics market — which was valued at $4.20 billion in 2021 — is expected to grow by a compound annual growth rate of 26.1 per cent from 2022 to 2040. To add value to their existing products, many pharmaceutical companies are looking to leverage these digital tools — either by launching their own or establishing companion partnerships. More companies are exploring the potential of wearable/hardware integrations, content partnerships, customer acquisition and data insights. Right now, the early winners appear to be focused on how to help patients with medication adherence. There are many reasons why a patient might stop taking a specific medication. For example, a company found that Multiple Sclerosis

42 TRENDS BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com (MS) patients were less likely to take their medication if they were in a poor mental state. In response, the company partnered with an app called Twill, which offers mindfulness and mental health support to ease depression and anxiety — conditions that are common with MS. By having access to the complimentary service, patients increased their medication adherence. If the pharmaceutical industry has learned one thing over the past few years, it’s that health startups operate differently than Big Pharma. When forging partnerships with tech startups, therefore, it’s important to set realistic goals and milestones. Many of the most ambitious ideas and partnerships have died because they failed to get off the ground — which is why it’s important to have clear contracts and resources in place to support the effort. 3. Silo breakdowns For customers and healthcare practitioners, there are few things more cumbersome than having to register for, or download, countless pharmaceutical programmes. In response, we can expect Pharma to make more advanced steps to seamlessly integrate their offerings — and ultimately provide a single online experience. This could be a single platform for CRM across brands, a single app platform, or a single website for all health conditions. In a recent study of pharma executives, 98 per cent of respondents said developing an omnichannel strategy is “very important” — and almost half reported optimising healthcare practitioner (HCP) engagement across touchpoints. At the same time, the adoption of electronic medical records (EMR) has rapidly increased over the last seven years — and now sits above 80 per cent. We’re also seeing a trend toward increased third-party data integrations — allowing the medical community to better leverage the power of data to analyse symptoms, identify treatment patterns, and uncover medical causes. Connecting all these different channels won’t be easy. Agencies are hired to put together tactical plans for the year, each of which have their own siloed ideas. Brands are structured to operate as their own mini company, without sharing resources across other brands that are often within the same disease state. Omni-channel efforts require more collaboration across agencies, brands, departments, payers and providers. To execute an omni-channel approach, therefore, organisations will have to find a way to break down silos and foster greater collaboration. 4. Mental health-focused content With the rise of remote health offerings and a clear gap in mental health support, most Pharma companies will begin to provide some degree of mental health information and resources to help their patients. Watch out for content designed to develop a meaningful partnership through advocacy; digestible and relevant mental health information; as well as digital programmes comprised of helpful mental health tools. According to the World Health Organisation, rates of depression and anxiety increased by more than 25 per cent in the first year of the pandemic — a trend many healthcare systems were poorly-positioned to address. At the same time, research shows that “adequate mental health resources are one of the foundations to improving medication adherence in patients with severe mental disorders.” Some current and future content will unfortunately fall short of offering real patient value. Things like link farms, which simply link patients to third party sites for mental health support, won’t achieve much. Rather, companies should focus on offering solutions that provide personalised, relevant benefits. Looking ahead These trends are a great sign of things to come. Better data management — combined with a push to break down silos, inside and outside of pharmaceutical organisations — will make it easier to integrate tools like Artificial Intelligence, which will allow for things like more targeted mental healthfocused content, personalised patient offerings and new opportunities to enhance drug adherence. This, ultimately, will lead to a reshaping of the healthcare industry — and even better patient outcomes. Data has been the key driver behind the pharmaceutical sector’s new product-focused business approach — and in 2023, we can expect companies to get even better at managing the vast amounts of data at their disposal. The focus, this year, will be to glean actionable insights from new and existing data — leading to even greater product and service innovations. Data Privacy will continue to figure prominently in the pharmaceutical space.

Gachon University, the Korea mRNA Vaccine Initiative (KmVAC), and the International Vaccine Institute (IVI) recently exchanged a memorandum of understanding (MoU) to expedite collaboration. The agreement calls for close cooperation in areas including exchange of technical information for infectious disease research and vaccine development; mutual cooperation in the entire vaccine development cycle including discovery of vaccine candidates, non-clinical and clinical trials; promotion of networking on research achievements and early vaccine utilisation; personnel exchange between related organisations; and joint hosting of vaccine R&D forums. Gachon University boasts of robust capabilities in medical service and education as it has the colleges of medicine, Asian medicine, pharmacology, and nursing. The university also operates the Intelligence Brain Science Research Center, the Lee Gil-ya Cancer and Diabetes Institute, and the Gachon Bionano Research Institute that excel in brain imaging and basic science. New partnerships in Korea to transform mRNA technology into more vaccines SGInnovate, a Deep Tech ecosystem builder and investor backed by the Singapore government, has launched Deep Tech Talent Central (DTTC), an integrated strategy for solving talent challenges across emerging tech sectors. In addition, it has launched Helix Immersion Programme, an industry training programme for academic and research professionals in the biotech sector. Heng Swee Keat, Deputy Prime Minister launched the programme along with Coordinating Minister for Economic Policies, and SGInnovate’s partners from across the Deep Tech community. Considering Singapore’s RIE2025 initiative, SGInnovate’s Helix Immersion Programme will support Singapore’s growing biomedical and biotech companies. Biomedical researchers and academic professionals will gain experience in both lab and non-lab settings at fast-growing companies through this one-year on-the-job training programme. With DTTC, organisations and talent can streamline their interactions to resolve demand- and supplyside issues in two major areas - “training and community building” and “building the Deep Tech job market”. Singapore unveils talent development strategy to boost Healthtech and Biotech ecosystem Goa Institute of Management (GIM) in India has launched a Professional Certificate Programme in Healthcare Management powered by Asia’s largest higher Edtech Company, upGrad. The 11-month course offers 300+ hours of learning experience and is designed by industry experts and academicians to integrate hands-on training within the curriculum seamlessly. A threeday on-campus immersion tour has also been embedded to make the learning more immersive and engaging through lectures, alumni connect, networking sessions, etc. Other value adds include 40+ hours of live sessions, 8+ case studies and assignments, and a capstone project along with 360-degree career support, 1:1 mentorship and job assistance to help learners build a stronger career in healthcare management. As per an industry report, healthcare jobs continue to rank high among the careers with the most job security. Individuals with an extensive understanding of the medical field and strong communication skills may find healthcare management to be an ideal career choice. The GIM Healthcare programme also provides ample career prospects that go beyond the fields of medicine, nursing, and therapy. Goa Institute of Management launches professional certificate programme in healthcare ACADEMICS NEWS 43 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com

Chaitanya Sarawate steps in as India MD for Wipro GE HealthCare Asieris Pharmaceuticals, a China-based biopharma company specialising in discovering, developing and commercialising innovative drugs for the treatment of genitourinary tumours and other related diseases, has announced that Linda Wu, PhD will join Asieris as Chief Development Officer. She will be a member of Asieris’ executive leadership team, with a key role in the strategy development and management of corporate’s product portfolio, and the development and execution of the global clinical pipeline. Dr Linda has over 20 years of industry experience and a successful track record in new drug R&D, commercialisation, and portfolio management, including extensive global experience in building and leading clinical R&D teams to successfully launch innovative oncology products in China and global markets. She joins Asieris from Janssen Pharmaceuticals, a Johnson & Johnson company, where she most recently served as a Group Medical Director of Oncology, US Medical Affairs. She has experience in drug R&D in China, serving as a Senior Director and the Head of Clinical Development of Oncology, and the Compound Development Team Leader at Janssen in China. Asieris Pharma appoints Dr Linda Wu as Chief Development Officer Rockwell appoints Mariya Prempeh as Singapore Country Manager Rockwell Automation, dedicated to industrial automation and digital transformation across sectors including pharma and healthcare, has appointed Mariya Prempeh as country manager for Singapore, effective immediately. Mariya will be responsible for the company’s business operations and direct sales in the country. She reports to Marcelo Tarkieltaub, regional director for Southeast Asia, Rockwell Automation. Mariya has more than 10 years experience in sales and marketing, working with enterprises across the globe in a variety of technology sectors. Prior to joining Rockwell Automation, she was the Singapore general manager for Leica Geosystems, part of Hexagon. At Leica Geosystems, she was responsible for creating a diverse high-performing team and helping the company achieve strong financial growth despite COVID-19. Mariya was also formerly with Hilti Corporation, a multinational company that develops, manufactures, and markets products for the construction, building maintenance, energy and manufacturing industries. Wipro GE HealthCare has announced the appointment of Chaitanya Sarawate as the Managing Director (MD), Wipro GE HealthCare and President & CEO, GE HealthCare South Asia. He succeeds Dr Shravan Subramanyam who is leaving to pursue an opportunity outside the company. Sarawate will work closely with Dr Shravan for a smooth transition as he integrates into his new role, effective February 13, 2023, and will be reporting to Elie Chaillot, President & CEO, GE HealthCare Intercontinental. Sarawate brings with him over two decades of corporate and healthcare experience and has been with GE HealthCare for over 12 years. In his new role, he will be responsible for strengthening the company’s market leadership position in South Asia by driving localisation strategy and delivering clinical excellence, access and precision care. 44 PEOPLE NEWS BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com

Former FDA medical device officer joins Pulnovo Medical’s scientific advisory board China-based Pulnovo Medical has announced the appointment of Dr Mingdong Zhang to the company’s Scientific Advisory Board (SAB). Dr Zhang will provide guidance on Pulnovo Medical’s clinical development and registration strategy and support the company’s global development plan. Dr Zhang’s cutting-edge international outlook and research expertise in the field of medical science will greatly facilitate Pulnovo Medical’s development and exploration of novel technologies, and provide new insight for the expansion of Pulnovo Medical’s research and development pipeline. Dr Zhang is an expert in medical device regulatory and corporate medical affairs with extensive medical knowledge and international regulatory affairs experience. With over 20-years industry experience, Dr Zhang recently retired from Boston Scientific Corporation as Chief Medical Officer and Vice President of Medical Affairs and Health Economics for Asia Pacific. PEOPLE NEWS 45 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com South Korea-based SK bioscience has announced that Richard Kensinger, PhD, former Director and Head of Drug Substance Process Development in Sanofi Pasteur and former Executive Director of Process Development and Protein Sciences at Affinivax Inc. has joined in ‘SK bioscience USA Inc.’ as Vice President of R&D Project Management. Dr Kensinger is an expert who has been dedicated to biopharmaceutical R&D, working at global companies for more than 20 years. He received a Bachelor of Science in Health Sciences at Eastern University and a PhD in Biochemistry and Molecular Biology at the Pennsylvania State University. Dr Kensinger as an expert of R&D process, will take a role in strengthening the company’s global competitiveness mainly targeting the United States market by improving the manufacturing process to the cGMP (Good Manufacturing Practice) level, the US certification for manufacturing practice which is considered as the highest standard worldwide. SK bioscience has additionally recruited Kenneth Lee, former Head of Commercial Division, Americas of GenScript Probio, as Vice President of Biologic Business Development Department at R&D Centre in Pangyo, South Korea. SK Bioscience accelerates global growth strategy by picking talent from Big Pharma Dr David John Jeans steps in as HistoIndex’s Non-Executive Chairman HistoIndex, a Singapore-based medtech/healthcare company that specialises in its proprietary integrated stain-free artificial intelligence (AI) digital pathology platform, has announced that Sim Giok Lak has decided to step down as Non-Executive Chairman of the Board; and Dr David John Jeans has been appointed as the Non-Executive Chairman of the Board. Since the incorporation of the Company, Sim Giok Lak has guided HistoIndex with his wealth of industrial and corporate experiences. He will remain as a Non-Executive Director on the Board as well as Non-Executive Chairman of Choutu Technology, a wholly owned subsidiary of HistoIndex that is based in Hangzhou, China. Dr Jeans was first appointed to the Board as a non-executive director on May 17, 2022. He has helmed senior leadership positions in international healthcare corporations such as Bristol Myers Squibb and Johnson & Johnson. He was previously the Chairman of Cardiff University, Deputy Chief Executive of the UK Medical Research Council, chaired the Trustee Board of MRC Technology, involved in the Science Advisory Council for Wales, and served as Trustee of the Francis Crick Institute. He is currently the Chairman of the Digital Health & Care Innovation Centre in Scotland and in Singapore. Richard Kensinger Kenneth Lee

An international team of researchers, led by University of Sydney in Australia, has developed a method to reverse the loss of elasticity of damaged heart tissue following heart attacks. Preclinical studies in rats found a single injection of tropoelastin into the wall of the heart in the days following a heart attack could ‘turn back the clock’ on muscle damage, making the scars ‘stretchier’ and help improve the heart’s ability to contract. Tropoelastin is the protein building block that gives human tissue its elasticity and ability to stretch. The results are published in Circulation Research and is the first time this potential of tropoelastin in treating heart disease has been investigated. According to the lead researcher, Dr Robert Hume who conducted the research at the Westmead Institute for Medical Research, the research showcases the potential of tropoelastin in heart repair and suggest further work will show exciting possibilities of its role in future treatments and therapies. Australia turns back the clock on damaged heart tissue Singapore’s drug discovery efforts have reached a new milestone as EBC-129, the first made-in-Singapore antibodydrug conjugate, was cleared by the US FDA to progress into first-inhuman studies. As an antibody-drug conjugate (ADC), EBC-129 comprises a monoclonal antibody linked to a highly potent toxic drug, which serves as a cytotoxic (cell-killing) “payload”. This drug is similar to those used in chemotherapy. The ADC’s antibody has been designed to home in on, and bind to, specific sites known as epitopes. These are selectively expressed on the surface of cancer cells and not on normal, healthy cells. Moving forward, approvals will be sought from the Health Sciences Authority (HSA) and relevant ethics boards for the trial to open to patients in Singapore through the National Cancer Centre Singapore (NCCS) and National University Cancer Institute, Singapore (NCIS). Ethics board approvals will be obtained for trial sites in the US, which will include major cancer centres. First madein-Singapore antibody-drug conjugate to enter clinical trials Singapore demonstrates quantum recoil, paving way for precise X-ray imaging in healthcare For the first time since it was proposed over 80 years ago, scientists from Nanyang Technological University, Singapore (NTU Singapore) have demonstrated the phenomenon of “quantum recoil”, which describes how the particle nature of light has a major impact on electrons moving through materials. Making quantum recoil a practical reality should eventually allow businesses to more accurately produce X-rays of specific energy levels, leading to superior accuracy in healthcare and manufacturing applications such as medical imaging and flaw detection in semiconductor chips. The NTU scientists have filed a patent based on the recoil results and earlier research on producing X-rays by using inorganic compounds about the size of computer chips exposed to moving electrons. Singapore medical diagnostics equipment manufacturer CTmetrix has applied to use the NTU patent to develop more compact and precise tuneable X-ray machines for the biomedical imaging of human tissue samples. The company is aiming to have a prototype ready by the end of 2023. 46 R&D NEWS BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com

In two recent studies, researchers at the Indian Institute of Science (IISc), Bengaluru and Unilever have collaborated to develop computational models of bacterial cell walls that can speed up the screening of antimicrobials, molecules which can kill disease-causing bacteria. The research team at IISc is the first to propose a comprehensive molecular model of the cell wall for Staphylococcus aureus. In one study, the team created an ‘atomistic model’, a computer simulation that recreates the structure of the cell wall down to the level of individual atoms. In the other study, the team used their model to compare the movement of different surfactant molecules through the peptidoglycan layer in E. coli. Using the supercomputing facility at IISc, the team tested the effectiveness of their model with several known antimicrobials. One of these, melittin, a short peptide, binds with higher efficiency to the E. coli cell wall than that of S. aureus. IISc develops computational models to speed up screening of antimicrobials The US Food and Drug Administration (FDA) recommends indirect evaluation of drug interactions using a formula suggested in their guidance first published in 1997, revised in January of 2020, in order to evaluate drug interactions and minimise side effects of having to use more than one type of drugs at once. The formula relies on the 110-year-old Michaelis-Menten (MM) model which has a fundamental limit of making a very broad and groundless assumption on the part of the presence of the enzymes that metabolises the drug. Researchers at the Biomedical Mathematics Group within the Institute for Basic Science (IBS) and the Korea Advanced Institute of Science and Technology (KAIST) and pharmacological scientists from the Chungnam National University have identified the major causes of the FDA-recommended equation’s inaccuracies and presented a solution. The existing FDA formula predicted drug interactions within a 2-fold margin of error at the rate of 38 per cent, whereas the accuracy rate of the revised formula reached 80 per cent. Korea provides new equation to US FDA for improving drug interaction prediction A world-first Australian and New Zealand (NZ) study is set to change how clinicians treat children with acute respiratory problems, improving best care and potentially saving millions of healthcare dollars, particularly in remote, rural and indigenous communities. The PARI programme is led by Dr Andreas Schibler, a researcher at Queensland’s Wesley Research Institute and a member of the leading Paediatric Research in Emergency Departments International Collaborative (PREDICT) group. PARIS II is the world’s first large-scale clinical trial in children aged under five years presenting to hospital emergency departments with a respiratory illness requiring oxygen. It compared standard oxygen therapy with nasal highflow therapy, which is a simple method of providing increased oxygen via nasal cannula, but one that is rarely available in smaller hospitals. The results, based on 1500 children aged from one to five years presenting to 14 emergency departments across Australia and New Zealand, clearly identify the children who can be treated with standard oxygen and those who need additional respiratory support with nasal high-flow oxygen therapy. Study in NZ, Australia set to change treatment of children with acute respiratory problems R&D NEWS 47 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com

Japan-headquartered Shimadzu Corporation has announced the release of the world’s smallest MALDI-TOF imaging solution, available as an option on the successful benchtop MALDI-TOF mass spectrometry series: the MALDI-8020 for positive ion analysis and the MALDI-8030, which features a dual-polarity ion source. Suitable for users starting out in the world of biomolecular imaging, the compact format of the Shimadzu benchtop MALDI-TOF system provides a welcoming platform by combining the ease of MALDI analysis with extremely intuitive software in an all-inclusive imaging kit. The system can serve as an ideal teaching tool to introduce users to MALDI imaging. In addition, it offers a low-cost entry point to users who would like to see what MALDI imaging can offer for their workflow. Experienced users will also benefit from the Shimadzu benchtop MALDI imaging solution. Benchtop imaging is an ideal platform for method development and routine imaging analyses. The benchtop systems are equipped with a fast sample stage and quick-load technology, which enable a short time-toanalysis, while delivering low associated overhead costs with a long-life fast laser (200 Hz), the longer life AeonDetector and selfcleaning ion optics based on the Shimadzu TrueClean technology. Shimadzu opens door to biomolecular imaging with new compact MALDI-TOF solution Thermo Fisher Scientific has announced the launch of its CE-IVD marked Applied Biosystems TaqPath Seq HIV1 Genotyping Kit, a Sanger sequencing-based assay that examines positive samples of human immunodeficiency virus (HIV) to identify genetic variants that may resist common antiretroviral therapeutics. Data derived from the test can help to serve as a critical tool to monitor and help treat HIV1-infected individuals, as well as inform epidemiologic and genetic surveillance studies to track the ongoing evolution of the virus. Using HIV RNA extracted from plasma or dried blood spots, the assay is designed to analyse genomic mutations in the protease, reverse transcriptase and integrase regions of the HIV-1 pol gene across nine subtypes of global significance. Antiretroviral drug resistance testing is needed since greater than 10 per cent of treatment-naïve adults, and about half of newly diagnosed infants, show resistance to first-line drug classes. Resistance is also emerging to the newer class of integrase inhibitor-based drugs, risking diminished effectiveness of these life-saving therapies. 48 SUPPLIER NEWS BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com US-based Waters Corporation has announced that launch of waters_ connect System Monitoring, a new Software-as-a-Service (SaaS) application that enables laboratory managers and analysts to monitor the real-time status of any chromatography instruments, regardless of the manufacturer, running on Waters Empower Software. The waters_connect System Monitoring application was developed especially for high-volume quality assurance/ quality control (QA/QC) laboratories. It can reduce the turnaround time of product release samples and facilitate the planning and progress of critical analyses via live, at-a-glance dashboard views of the operational status of chromatography instruments. The cloud-native application also helps lab managers utilise capital resources better by providing an understanding of instrument history and usage levels and improve the productivity of their teams. Waters Corp launches SaaS for remote monitoring of QA/QC labs Thermo Fisher unveils CE-IVD marked assay to detect treatment-resistant HIV-1 strains

SUPPLIER NEWS 49 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com Qiagen launches EZ2 Connect MDx platform for automated sample processing in diagnostic labs Germany-headquartered Sartorius has extended a strategic collaboration partnership agreement with US-based RoosterBio to address purification challenges and establish scalable downstream manufacturing processes for exosomebased therapies. Through this collaboration, Sartorius and RoosterBio will provide best-in-class solutions and expertise for a human mesenchymal stem/stromal cell (hMSC) - based exosome production platform that delivers industryleading yield, purity, and potency. Additionally, this collaboration will focus on the development of comprehensive analytical techniques for the characterisation of exosomes and the entire spectrum of extracellular vesicles (EVs) to establish quantitative strategies for quality control of exosome purification intermediates and final drug products. Sartorius and RoosterBio will develop scalable platform purification processes using Sartorius’ comprehensive toolbox of solutions to maximise exosome productivity while maintaining therapeutic attributes. Sartorius’s Biostat STR manufacturing bioreactor platform, process analytical technologies (PAT) toolbox, along with RoosterBio’s hMSC banks, RoosterNourish hMSC cell growth medium, and RoosterCollect EV production medium will be used for upstream manufacture of exosomes at large scale. Sartorius & RoosterBio to advance downstream purification for exosomes manufacturing Agilent invests $725 M to expand production of nucleic acid-based therapeutics Agilent Technologies has announced that it is investing approximately $725 million to double manufacturing capacity of therapeutic nucleic acids in response to rapid growth of the $1 billion market and strong demand for the company’s highquality active pharmaceutical ingredients (API). Therapeutic nucleic acids, also called therapeutic oligonucleotides or oligos, are short DNA and RNA molecules that serve as the API for drugs targeting a growing number of diseases, including cancer, cardiovascular disease, and rare and infectious diseases. The new Train C and D manufacturing lines will be based in Agilent’s Frederick, Colorado facility in the US, where a Train B manufacturing line, announced in 2020, will go live later this year. Agilent’s therapeutic oligo facilities follow current good manufacturing practices (cGMP), and the expanded facility will employ advanced automation and engineering enhancements, including water reduction and solvent capturing and recycling. Qiagen has announced the launch of EZ2 Connect MDx for use in diagnostic laboratories, making the in vitro diagnostic (IVD) platform for automated sample processing available for wide scale use 18 months after being made available for research. With a high degree of automation, the EZ2 Connect MDx enables labs to purify DNA and RNA from 24 samples in parallel in as little as 30 minutes. The device now carries the EU’s CE-IVD compliance marking for IVD for the European Union and other countries that accept this designation. It is also available in the United States, Canada and other countries. EZ2 Connect MDx can extract nucleic acids from blood plasma, serum, stool and other sample types using magnetic-bead technology. High process safety is ensured with pre filled and sealed reagent cartridges, as well as load checking through integrated cameras. Other features include UV decontamination, onboard pipetting and heating as well as automated piercing of the sealed cartridge. The resulting analyte is compatible with a variety of downstream technologies such as real-time PCR, digital PCR and next-generation sequencing.

50 BIOSPECTRUM | FEBRUARY 2023 | www.biospectrumasia.com 3 Pillars of Action Against Breast Cancer The World Health Organisation (WHO) released a new Global Breast Cancer Initiative Framework on February 3, providing a roadmap to save 2.5 million lives from breast cancer by 2040. The newly published framework from WHO leverages proven strategies to design country-specific, resource-appropriate, health systems for the delivery of breast-cancer care in low- and middle-income settings. It outlines three pillars of action with specific key performance indicators: Recommending countries to focus on breast cancer early-detection programmes so that at least 60 per cent of the breast cancers are diagnosed and treated as earlystage disease; Diagnosing breast cancer within 60 days of initial presentation can improve breast cancer outcomes. Treatment should start within three months of first presentation and finally, Managing breast cancer so that at least 80 per cent of patients complete their recommended treatment. There are more than 2.3 million cases of breast cancer that occur each year, which make it the most common cancer among adults. In 95 per cent of countries, breast cancer is the first or second leading cause of female cancer deaths. Yet, survival from breast cancer is widely inequitable between and within countries; nearly 80 per cent of deaths from breast and cervical cancer occur in low- and middle-income countries (LMICs). To support LMICs, the WHO has the tools and the know-how to prevent breast cancer and save lives. It is supporting more than 70 countries, particularly LMICs, to detect breast cancer earlier, diagnose it faster, treat it better and give everyone with breast cancer the hope of a cancer-free future. Most of the developed and developing countries of Asia are increasingly adopting a westernised lifestyle, such as a diet high in fat and processed meat, low in fruits and vegetables and lack of (or low) physical activity leading to obesity, which is linked with breast cancer apart from several other health risks of obesity. On an average, obesity increases breast cancer-related mortality risk by 30–40 per cent. The high body mass index (BMI) and high fasting plasma glucose (FPG)-related breast cancer mortality rates were high in Asia and country-wise, these were the highest in Pakistan and Afghanistan, whereas alcohol-related mortality rate was highest in Japan, Mongolia, South Korea and Nepal. Breast cancer mortality is predicted to increase continuously. However, if effective control and prevention are not implemented, mortality is expected to continue to surge even more, in the coming decades because of substantial demographic changes, which may create considerable public health challenges for these Asian countries, according to a study published in PubMed Central. Previous studies have also found that breast cancer-related mortality has been increasing more rapidly in Asia than the global average. These increasing trends have many possible reasons apart from demographic changes, which includes risk factors such as smoking, alcohol consumption, physical inactivity, low fibre and high-fat diet, obesity, ambient air pollution and air pollution due to the burning of solid fuels in houses. The South Asian region demonstrated increasing mortality trends for all its countries with Pakistan, India, Nepal and Afghanistan demonstrating a steady upward trend in mortality in the next decade. The population aging is a non-modifiable risk factor for developing breast cancer leading to mortality in Asian women. Correspondingly, this study shows that mortality is predicted to increase with age, particularly among 80–84 year olds in all the East and South Asian countries. Among 10 countries of the region, six countries, China, Mongolia, South Korea, Pakistan, Afghanistan and Nepal, have shown a highpredicted mortality rate attributable to a diet high in red meat. Another study has shown that higher red meat consumption, especially processed red meat, is associated with an increased risk of breast cancer-related mortality. Accelerating the implementation of the WHO’s Global Breast Cancer Initiative has the potential to avert not only millions of avoidable female cancer deaths but also the associated, intergenerational consequences of these deaths. Narayan Kulkarni Editor [email protected]