BioSpectrum Asia May 2023

A World Sans Malaria Volume 18 | Issue 4 | April 2023 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: istockphoto Vol 18; Issue 5; May 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. 4 BIO MAIL BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Acknowledgement/ Feedback I appreciate your support for the 90 million rare disease patients in India. It is their voice reflected in your BioSprectrum. Thank you so much for giving attention to this rare disease’s cause in India. Your article is well received in India and abroad. - Ramaiah Muthyala, US Thank you BioSpectrum for featuring the article- Addressing ‘Orphaning’ of Rare Diseases in both India and Asia editions. - Ravi Shet, India BC Platforms is very pleased with the opinion piece published in the April issue of BioSpectrum Asia on ‘How Equitable Data Sharing is key to realising precision medicine in APAC’. - Daniel, UK

Letter from Publisher Ravindra Boratkar Publisher & Managing Editor, MD, MM Activ Sci-Tech Communications Pvt. Ltd. Dear Readers, From a generic power house to an important hub for pharma R&D, the Asia Pacific region has transformed when it comes to pharmaceuticals. What is the total gross spending on R&D in the Asia Pacific region in 2021? Which country from APAC is spending highest on R&D? R&D in drug and therapy development for which diseases are the prime focus of companies? What are the budget allocations of pharma companies for R&D and what are the focus areas of the research? There are several important questions. You will have to go through the cover package of this issue to know the answers to these and several other questions. Our content team has gone deep into the sector to unearth the answers for these questions. I am sure this will give a good insight into Pharma R&D in the APAC region to arrive at key business decisions. Within R&D, radiopharmaceuticals are rapidly catching on for cancer treatment. They offer several advantages over traditional chemotherapy and radiation therapy, including increased specificity and fewer side effects. We delve into the rising interest in radiopharmaceuticals and what it could turn out for treating cancer. We have also carried an article examining the emergence of Non-invasive prenatal testing (NIPT). Since its debut in the United States and China/Hong Kong in 2011, the molecular screening test used to detect foetal congenital anomalies is the fastestgrowing prenatal genetic technology globally, accounting for 38 per cent of the prenatal genetic testing market. We have put the spotlight on Aevice Health, a Singapore-based MedTech company that develops patient management solutions for patients with chronic respiratory disease and how its flagship product, the AeviceMD Monitoring System, powered by the smart wearable stethoscope can provide an overview of lung health anytime and anywhere. We also have Dr Josephine (Pina Cardarelli, Chief Scientific Officer of South Korea-based GPCR Therapeutics, telling us about G protein-coupled receptors (GPCR) therapies for cancer and how it is set to change the cancer treatment landscape. I believe this edition’s exhaustive coverage of various therapeutics and emerging tech will keep you wanting for more on similar topics. Thanks & Regards, Ravindra Boratkar Publisher & Managing Editor 5 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Looking for a job? See open roles at www.biospectrumjobs.com n Find Talent n Post Jobs n Attract Candidates Find the right people no matter what your hiring needs are... BIOSPECTRUM TALENT SOLUTIONS premier source of pharma healthcare & bio jobs

COVER STORY 19 6 BIO CONTENT BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com $15B Pharma R&D Spends ROCKS APAC Earlier seen as a generic powerhouse, Asia is now an important hub for pharma R&D innovation. The total gross expenditure by major companies on R&D across the Asia Pacific region crossed the $15 billion mark (approx) in 2022. Oncology, neurology, and immunology continue to draw a significant chunk of this investment. BioSpectrum Asia examines how top pharma companies in the region are allocating their R&D budgets and the impact of the ensuing R&D endeavours on the industry. Accelerating R&D in Biosciences Startups with AI and mRNA Therapeutics Wally Wang, Founding Partner, Scale Asia Ventures Why talent and collaboration is crucial for biotech startups to sustain R&D Francis van Parys, Vice President Commercial, Asia Pacific, Cytiva Investment in deeptech companies soars to propel APAC pharma R&D Ruplekha Choudhurie, Senior Industry Analyst - Health & Wellness, Frost & Sullivan China Emerges as New APAC Pharma R&D Engine Ian Haydock, Editor-in-Chief, Insights, Asia Pacific, Citeline 25 28 26 29

Scan QR code to access BioSpectrum Asia Digizine REGULARS BioMail..................................................................................04 BioEdit...................................................................................08 Policy and Regulatory News.............................................09 Finance News......................................................................11 Company News ..................................................................13 Start-Up News.....................................................................15 WHO NEWS .........................................................................17 World NEWS ........................................................................18 Academics News................................................................43 People News........................................................................44 R&D News ............................................................................46 Supplier News .....................................................................48 Lets Talk Health ..................................................................50 SINGLE-CELL TECH Understanding Single-Cell Technology in clinical research applications Dr Irene Whitney, Director of Applications and Collaborations, Honeycomb Biotechnologies, United States 41 PRENATAL TESTING Non-invasive Prenatal Testing Runs Global Amartya Bose, Healthcare & Life Sciences Industry Analyst, Frost & Sullivan 39 BIO CONTENT 7 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com RADIOPHARMA How Radiopharmaceuticals Are Transforming Cancer Treatment 30 SPEAKING WITH “As Precision Medicine is critical, we cannot think about one size fits all” Dr Pina Cardarelli, Chief Scientific Officer, GPCR Therapeutics 33 “EBPs are leveraging digitalisation to drive innovation and improve patient outcomes” Jerome Armellini, Asia Head of Clinical Development & Operations Strategy, R&D Solutions Asia, IQVIA Asia Pacific 35 “Protecting patient information is essential for building trust with both patients and healthcare providers” Adrian Ang, CEO, Aevice Health 37

8 BIO EDIT BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Dr Milind Kokje Chief Editor [email protected] RECLAIMING INDIA’S IMAGE I n view of linking the children’s death in Gambia and Uzbekistan to cough syrups produced by Indian pharma companies a few months back, the Indian government has launched a major confidence building exercise abroad. Diplomatic efforts are ongoing to prevent any adverse impact on Indian drug exports due to the purported syrup-linked-deaths. Trade officials in Indian missions abroad are interacting with regulatory authorities to maintain desired confidence levels on quality of Indian drugs. On the other hand, the Pharmaceutical Export Promotion Council (Pharmexcil) had sent delegations abroad. Pharmexcil sends delegation abroad regularly to crack new markets, to boost exports of drugs & to expand the scope of business. But, the purpose of this delegation was to increase the confidence in Indian medicines. The delegation was to have industry level interactions with pharma trade associations and also with regulators. Pharmexcil is also conducting workshops on international standards and compliances. The Indian Pharmaceutical Association (IPA) has been doing similar efforts locally for the last few years to introduce its member companies to international norms, standards and compliances so that these companies will ensure that their products comply with them. Even after five months since the cough syrup ‘incident’, the assessment has not yet been completed and various agencies are still looking into it. It is also imperative to unearth the underlying reasons why regulators in these countries have levelled baseless allegations against Indian manufacturing standards. The World Health Organisation (WHO) had, thus, rightly issued a warning to the regulators when government laboratories did not find toxins in the syrups, in subsequent testing. Pharmexcil’s efforts bring us to the issue of general upskilling for maintaining quality parameters, which is crucial for exports. Indian drug exports are key to our economy with exports soaring tremendously. From 2014 to 2022 pharma exports doubled to $24.6 billion. To maintain this pace and even improve upon it, along with the quality, innovating new products, that too non-generic, is also pivotal. With that vision, the pharma sector is now focusing more on R&D. The government has also revealed its detailed plan in the recent Union Budget to encourage research for developing original medicines. Just prior to the budget presentation, the US pharma industry, through Boston-based USA-India Chamber of Commerce (USAIC), suggested that India formulate a R&D policy for the pharma sector. Policies should aim to move up the value chain driven by R&D which would make India R&D hub, emphasised the USAIC. Indian pharma’s vision is to grow to $130 billion by 2030. For targeted growth and moving up the value chain, research and innovation is vital for a knowledge-driven sector like pharma as it lends a competitive edge. To be competitive in the world market, Indian pharma will have to focus on R&D, which it is doing now. That will require human resources with the right skills for research. The government has already been encouraging skill development required in different sectors, including pharmaceuticals. Even the World Bank’s collaboration has been sought and the programme ‘Skill Acquisition and Knowledge Awareness for Livelihood Promotion’ (SANKALP) has been launched to improve short term skill training through strengthening institutions. Skill development is particularly more important now in view of the new technologies of artificial intelligence, data analytics and machine learning that will play a key role in drug development. They are expected to significantly reduce the time and costs involved for new drug development. Another area where skilling is required is quality control. Although Indian labs ruled out the presence of any toxins in the cough syrups, a strict vigil on quality control will help maintain India’s image as the Pharmacy of the World with Impeccable Quality Standards. While promoting research and exports, the government will have to initiate various other steps and only then will it prove to be a real confidence building exercise.

The Ministry of Health and AstraZeneca Vietnam Company have recently signed a Memorandum of Understanding (MoU) to deepen their long-term partnership and strengthen their collaboration to comprehensively enhance healthcare for the people of Vietnam. The expanded partnership, to take place from 2023 to 2028, will see comprehensive cooperation between the two parties in the areas of disease prevention and control, pharmaceutical research, development and manufacturing, and sustainable health system development. Following the MoU, AstraZeneca will advance both ongoing and new programmes, in collaboration with the Ministry of Health and healthcare partners, to promote disease awareness, prevention, and early detection. These include the Health Lung Programme to improve the diagnosis and management of asthma, chronic obstructive pulmonary disease (COPD), and lung cancer; the Young Health Programme to help youths build a healthy lifestyle and prevent non-communicable diseases; and the CAREME programme to transform the cardiovascularrenal-metabolic care ecosystem. In addition, AstraZeneca’s VNĐ7 trillion ($310 million) investment from 2020 to 2030, which includes VNĐ2 trillion ($103 million) for technology transfer and local contract manufacturing of medicines, as well as partnerships with various hospitals on clinical research. India exempts full customs duty on all drugs used in rare diseases treatment The Government of India has given full exemption from basic customs duty on all drugs and food for special medical purposes imported for personal use for treatment of all rare diseases listed under the National Policy for Rare Diseases 2021 through a general exemption notification. In order to avail this exemption, the individual importer has to produce a certificate from Central or State Director Health Services or District Medical Officer/Civil Surgeon of the district. Drugs/Medicines generally attract basic customs duty of 10 per cent, while some categories of lifesaving drugs/vaccines attract concessional rate of 5 per cent or Nil. While exemptions have already been provided to specified drugs for treatment of Spinal Muscular Atrophy or Duchenne Muscular Dystrophy, the government has been receiving many representations seeking customs duty relief for drugs and medicines used in treatment of other Rare Diseases. Drugs or Special Foods required for the treatment of these diseases are expensive and need to be imported. It is estimated that for a child weighing 10 kg, the annual cost of treatment for some rare diseases, may vary from Rs 10 lakh to more than Rs 1 crore per year with treatment being lifelong and drug dose and cost, increasing with age and weight. The Central Epidemic Command Center (CECC) in Taiwan has reported that the Advisory Committee on Immunisation Practices (ACIP) at the Ministry of Health and Welfare recently held an expert meeting and issued its recommendations on the use of Moderna’s BA.4/BA.5 bivalent COVID-19 vaccine as a booster for children. Moderna’s BA.4/BA.5 bivalent COVID-19 vaccine can be given as a booster to children 6 months through 5 years of age who have completed their primary series vaccination. The bivalent COVID-19 vaccine is not suitable for use in children 6 months through 5 years of age who have completed their primary series vaccination with the PfizerBioNTech vaccine for children. These children are recommended to follow the current recommendations to receive three primary series doses of the PfizerBioNTech vaccine for children. Taiwan allows Moderna’s bivalent COVID-19 vaccine as booster for children Vietnam deepens long-term partnership with AstraZeneca REGULATORY NEWS 9 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com

A world first guide addressing the unique demands and challenges for Registered Nurses in rural and regional Australia has been released. Communities across Australia rely on Registered Nurses to provide primary care, acute care and aged care. They are skilled, capable and trusted healthcare practitioners often working in some of the most rural and remote parts of the country. The National Rural and Remote Nursing Generalist Framework 2023-2027 is a guide for Registered Nurses working outside urban areas, as well as employers, mentors, and educators. As well as describing skills and capabilities, the Framework emphasises the importance of clinical decisionmaking judgement of the patient’s situation, culturally safe practice, collaboration, and partnerships with clients, families and communities. The Framework was developed by the Office of the National Rural Health Commissioner, Adjunct Professor Ruth Stewart, and Adjunct Professor Shelley Nowlan, with guidance and contributions from members of a national steering committee. Australia announces world first framework for rural and remote nursing 10 REGULATORY NEWS BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Aevice Health, a Singapore-based medtech startup that specialises in developing remote respiratory monitoring solutions, has announced that its flagship medical device, the AeviceMD Monitoring System, has received approval from the Health Sciences Authority of Singapore (HSA). The award-winning patient management platform, powered by a smart wearable stethoscope, is the first of its kind to be made available in Singapore. The AeviceMD Monitoring System’s wearable stethoscope is one of the smallest globally that can detect abnormal breath sounds, such as wheezing, and monitor vital signs including heart rate and respiratory rate. The device, which is approved for use in patients three years and above, has a unique form factor that allows for continuous and comfortable monitoring across a wide spectrum of ages from young children to the elderly, where respiratory diseases are more prevalent. The AeviceMD Monitoring System continuously monitors digital biomarkers of interest, providing healthcare professionals with an overview of the patient’s lung health to track progress over time. Patients, who are at risk of exacerbations, can be identified early to prevent readmissions or emergency department (ED) visits. See-Mode Technologies gets approval for AI-based ultrasound solution in ANZ Singapore gives nod to first smart wearable stethoscope See-Mode Technologies, a leading provider of artificial intelligence (AI)-powered medical imaging solutions, has received regulatory approvals for its AI-powered breast and thyroid ultrasound solution in Australia and New Zealand (ANZ). These approvals represent a significant milestone for the company, as it expands its presence in the region and brings its innovative technology to market. Australia-based See-Mode uses AI to detect lesions in ultrasound images, then assigns feature classifications to each lesion, in line with the American College of Radiology’s BI-RADS and TI-RADS rating systems. Sonographer worksheets, complete with lesion classifications and diagrams are instantly generated and sent to picture archive and communication system (PACS), while preliminary impressions are sent to radiology reporting systems. In follow-up scans, See-Mode allows for fast comparison between old and new images, and will automatically highlight changes in lesion characteristics.

FINANCE NEWS 11 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com SingHealth and the Agency for Science, Technology and Research (A*STAR) entered a Healthcare Translation Partnership (HTP) to accelerate the translation, deployment and commercialisation of healthcare research and innovation projects for better patient care. The partnership, which will provide S$8 million in funding support for projects, focuses on three healthcare innovation areas, which include (i) Medical Technology (ii) Data Science, Artificial Intelligence (AI) and Digital Health; and (iii) Health Services Innovation. The HTP aims to address this by establishing a framework and consolidating resources and support systems to facilitate joint projects between the SingHealth Duke-NUS Academic Medical Centre (AMC) and A*STAR. For example, there will be a dedicated partnership office which will coordinate and address the translation challenges holistically. It will also build important bridges between experts in the three healthcare innovation focus areas, enabling clinicians, healthcare innovators, researchers and industry partners to collaborate and accelerate the research translation process. Temasek picks additional 41% stake in India’s Manipal Health Enterprises Singapore headquartered Temasek, an investment company with a net portfolio value of S$403 billion (as of March 31, 2022), has signed definitive agreements to acquire an additional 41 per cent stake in Manipal Health Enterprises (MHE), based in India. Following the closing of the transaction, Manipal Group will hold about 30 per cent of MHE. Sheares Healthcare Group, a wholly owned subsidiary and independently managed portfolio company of Temasek, will retain its existing 18 per cent stake. Leading global alternative asset management firm TPG, which first invested in MHE through TPG Asia VI in 2015, will fully exit, but it will hold an interest of 11 per cent in MHE, through its new Asia fund - TPG Asia VIII. National Investment & Infrastructure Fund (NIIF) will exit its holding from MHE. Manipal Hospitals, headquartered in Bengaluru, Karnataka, has a pan-India presence. The hospital chain currently serves over 5 million patients a year through its network of 29 hospitals. Japanese pharmaceutical firm Eisai Co. has announced the completion of a major renovation of its Tsukuba Research Laboratories, which is a part of strategic investment to execute Eisai’s mediumterm business plan ‘EWAY Future & Beyond’. Eisai implements research and development activities under the DHBL (Deep Human Biology Learning) drug discovery and development system in its efforts to create new drugs based on innovative and efficient next-generation drug discovery concepts. Tsukuba Research Laboratories is positioned as a core facility in the DHBL drug discovery and development system. This renovation seeks to accelerate knowledge circulation by connecting each researcher with patients, other members within the laboratories, other research sites across the world, and external researchers based on its key concept ‘Human Connected Laboratories: Laboratories Connecting Human and Human, and Data, and the World’. Eisai invests ¥8.5B in ‘Human Connected Laboratories’ for accelerated knowledge exchange SingHealth and A*STAR establish S$8 million partnership to co-develop healthcare innovations

Takeda Pharmaceutical will invest approximately 100 billion yen (¥) to build a new manufacturing facility for plasma-derived therapies (PDTs) in Osaka, Japan. The new state-of-theart facility will be the largest of its kind in the country and is expected to be operational by around 2030. The new site increases the capacity of Takeda’s current plasma manufacturing site in Narita, Japan almost five-fold and will enable Takeda to serve more patients in Japan sustainably, as well as add incremental capacity to its global manufacturing network. The facility will be built to the highest global manufacturing standards, including the latest automation and advanced digital technologies. It will be a fully integrated plant, consisting of teardown, fractionation, purification, filling, finishing capabilities as well as a cold storage warehouse. The design will be environmentally friendly to support Takeda’s goal of achieving net-zero greenhouse gas emissions related to operations including scopes 1 and 2 before 2035. Takeda’s existing Narita plasma manufacturing site will continue day-to-day operations until at least the end of the decade, with continued necessary investments for maintenance. Takeda to invest ¥100 B in new facility for plasma-derived therapies in Japan 12 FINANCE NEWS BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Israel-based Sisram Medical, a global leading innovator and provider of medical aesthetic devices, has announced that Alma Lasers, a wholly-owned company by Sisram, has entered an agreement to acquire the energy-based devices distributor, PhotonMed International. As part of the acquisition, Alma paid 270 million RMB (¥) to secure 60 per cent of the business, becoming the major shareholder in the new joint venture. The acquisition will strengthen Alma’s distribution channels and increase its profits by enabling direct sales of energybased devices in the Chinese market. PhotonMed, an important long-term strategic partner of Alma and a leader in the Chinese market, has been distributing Alma’s energybased devices since 2003. The acquisition represents a major step in Sisram’s direct sales expansion and direct-to-consumer strategic layout, aimed at strengthening the group’s positioning, brand recognition, and advancing its deep cultivation and penetration in the Chinese market. Earlier this month, Sisram released its annual results for 2022, posting record revenue for the second consecutive year in a row. Samsung Biologics invests over KRW 1.9 T in new facility Sisram Medical expands footprint in China, acquires PhotonMed for ¥270M Samsung Biologics, a leading contract development and manufacturing organisation (CDMO) based in South Korea, has announced that the company will commence the construction of a fifth plant as part of its strategic expansion in response to increased market demand. The company will invest over KRW 1.9 trillion in the new facility and break ground in the first half of this year with the aim to commence operations in 2025. Located near its current Songdo site, Plant 5 will be the first facility of the company’s second Bio Campus, encompassing an area of 96,000 square metres and holding a capacity of 180,000 liters. Upon Plant 5’s full completion, Samsung Biologics will maintain its global biomanufacturing capacity leadership with a total of 784,000 liters. The plant is expected to further maximise operational efficiency, allowing the company to leverage existing capabilities, expertise and technologies acquired through its experience with Plants 1 through 4, while introducing advanced digitalisation and sustainability features.

COMPANY NEWS 13 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Serum Institute of India gets Ghana FDA’s clearance for malaria vaccine The University of Oxford-developed and Serum Institute of India (SII) manufactured and scaled up R21/Matrix-M malaria vaccine, leveraging Novavax’s adjuvant technology, has been licensed for use in Ghana by the country’s Food and Drugs Authority (FDA). This marks the first regulatory clearance for the R21/Matrix-M malaria vaccine for use in any country. The successful registration was notified to SII by the FDA Ghana. SII is the manufacturing and commercialisation license holder for the vaccine. The vaccine has been approved for use in children aged 5 to 36 months, the age group at highest risk of death from malaria. It is hoped that this first crucial step will enable the vaccine to help Ghanaian and African children to effectively combat malaria. The R21/Matrix-M vaccine has demonstrated high levels of efficacy and safety in Phase II trials, including amongst children who received a booster dose of R21/Matrix-M at one year following a primary three-dose regime. Taiwan-based Bora Pharmaceuticals Co. and Celltrion Asia Pacific, a subsidiary of South Korea-based Celltrion Group Inc, have announced their partnership to contract manufacture and commercialise a range of oral dosage form drugs (OSD) across the Asia Pacific (APAC) region. The range of oral dosage form products will be manufactured at Bora’s Zhunan site, which is one of the largest US FDA and MHRA-approved pharmaceutical production facilities in Taiwan. The site has an outstanding compliance record across global regulatory authorities. The manufactured batches will be used to support Celltrion’s regulatory filings for approval in seven countries, and Bora will further support Celltrion to commercialise the products immediately upon approval by utilising its cutting-edge manufacturing capabilities in complex oral dosage form and superior total-solution services. Bora and Celltrion partner to expand OSD capabilities in APAC Smith+Nephew, the global medical technology company, has announced an agreement with NAVBIT to exclusively distribute the NAVBIT SPRINT disposable navigation device for use in primary hip arthroplasty in Japan. NAVBIT SPRINT delivers a fast and reliable alternative to capital investment improving efficiencies for hospitals. Postoperative dislocation is the number two most common reason for revision of a total hip replacement around the world and remains a serious concern for surgeons when performing total hip arthroplasty. Studies have shown reduced risk of dislocation when using navigation. The NAVBIT SPRINT device has been shown to be accurate to within an average error of 2.13° in cup inclination and 2.36° in cup anteversion. NAVBIT’s SPRINT System is available through Smith+Nephew in Japan for either supine and lateral approaches to primary hip arthroplasty. Smith+Nephew brings disposable navigation device NAVBIT SPRINT to Japan

HKSTP strengthens collaboration with AstraZeneca Hong Kong Science and Technology Parks Corporation (HKSTP) continues to strengthen the strategic partnership with AstraZeneca, one of the world’s leading pharmaceutical companies. The goal of this collaboration is to position Hong Kong and the Greater Bay Area as a trailblazer in life science innovation and serve as a model for the region. This marks a milestone that HKSTP has entered into a multidimensional collaboration, which includes technology and data sharing, with a life science corporation. Since 2021, AstraZeneca and HKSTP have been collaborating, and this partnership will not only continue but also be upgraded. The extended collaboration involves AstraZeneca and HKSTP supporting and providing services to startup companies under the HKSTP co-incubation programme. Additionally, the collaboration includes attracting more companies from overseas and mainland China to the HKSTP community, with the aim of connecting them with hospitals, key opinion leaders in the Greater Bay Area, and universities in Hong Kong. 14 COMPANY NEWS BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com CSL unveils new vaccine R&D facility in US Australian biotech firm CSL recently celebrated the official opening of the company’s new state-of-the-art research and development (R&D) centre in Waltham, Massachusetts, US. The custom-built facility is approximately 140,000 square feet with 54,000 square feet of lab space, including the first biosafety level 3 laboratory (BSL-3) in Waltham. The site will serve as CSL’s central hub for current and future vaccine design. CSL’s global Research and Development organisation has more than 2,000 employees in ten countries around the world, contributing to a robust and promising pipeline of novel therapeutic candidates. In addition to Waltham, Massachusetts, the company has an R&D presence in King of Prussia, Pennsylvania; Pasadena, California; Melbourne, Australia; Bern, Switzerland; Amsterdam, Netherlands; and Marburg, Germany – helping to create an integrated global organisation that can conveniently collaborate with institutions everywhere and offer access to professional development opportunities and enhancing external innovation. Fujitsu has announced the launch of a new cloud-based platform that allows users to securely collect and leverage health-related data to promote digital transformation in the medical field. Fujitsu will offer the new platform to medical institutions and pharmaceutical companies in Japan starting March 28, 2023. The new platform enables the automatic conversion of medical data from medical institutions’ electronic medical records to conform with the next generation standards framework HL7 FHIR and secure aggregation of health-related data. Based on their consent, patients can securely store personal health information such as vital data, step counts, and calorie consumption - converted into non-personally identifiable information on the platform - this in turn supports medical institutions and pharmaceutical companies in performing data analysis and R&D activities to accelerate the development of individualised healthcare and the discovery of new drugs. Fujitsu launches new cloud-based platform for healthcare in Japan

US startup Nymbl Science brings app-based mobility programme to NZ seniors US-based digital health startup Nymbl Science has announced a significant expansion of its partnership with New Zealand’s Accident Compensation Corporation (ACC), making Nymbl’s award-winning balance training programme available to all older adult residents of New Zealand. In August 2020, Nymbl started a pilot study in New Zealand with 15,000 participants, making it the world’s largest fall prevention study completed outside of a clinical setting. This nationwide pilot programme with the country of New Zealand was made possible by an association with ACC and its Live Stronger for Longer programme. The study results demonstrated that Nymbl delivers a positive ROI that can be scaled to impact the entire population of older adults in New Zealand. After a rigorous evaluation process, ACC selected Nymbl to be the long-term provider of fall prevention services as part of their continued commitment to empowering older adults to lead thriving, independent lives. ACC chose Nymbl as a partner so that all older adults in New Zealand could have access to an in-home programme to improve their strength and balance. START-UP NEWS 15 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com BestDoc, an Indian health-tech provider offering a suite of omni-channel end-toend patient relationship management products, has expanded its operations to the city of Dubai. The startup established its regional headquarters in Dubai last year and the move was supported and facilitated by Dubai International Chamber. Within a short period of time, the company has already acquired association with some of the most sought-after names in UAE such as Burjeel Royal Hospital, Al Ain, and Emirates International Hospital and they are currently working on a pilot project with the Saudi German Hospital, Dubai. BestDoc has invested over $0.5 million in Dubai with primary focus on establishing a robust brand presence, setting up a local entity, and building dedicated sales and support teams to better serve their customers in the region. The company is ambitiously planning to increase their investments in the Gulf Cooperation Council (GCC) region by three to four times over the next 3 to 5 years with a significant share earmarked for Dubai. Indian startup BestDoc sets shop in Dubai Taiwan’s Health2Sync has announced that its latest version of the Health2Sync App integrates insulin data from Mallya Cap, the connected device dedicated to insulin pens developed by Biocorp and marketed in Japan by Novo Nordisk. This partnership realises the first data integration of its kind in the world and is expected to help patients on insulin treatment manage their health by capturing multiple data points, including insulin injection logs. The population of diabetes and prediabetes exceeds 20 million in Japan. Owing to the advances in insulin and non-insulin drugs during the past two decades, the combined use of those drugs in Japan increased, and the glycemic control leveled off after 2014 in patients with type 2 diabetes. However, according to a 2017 study, 44 per cent of Japanese diabetes patients still reported omission or non-adherence to insulin, a greater value than that reported in other countries. Mallya is a non-medical smart sensor that attaches directly to the FlexTouch insulin pen, saving time and effort from manually inputting or recording injection data. After attaching the Mallya cap to a FlexTouch pen, the smart cap enables automatic data collection and sends the injection dosage, date, and time to the Health2Sync App wirelessly in real-time. Health2Sync adds more data points to Japan’s personal health record initiative

Standigm, a South Korea-based startup using artificial intelligence (AI) technology for drug discovery and development, and Korean non profit research institute Institut Pasteur Korea have jointly developed new lead compounds effective in treating resistant tuberculosis (TB). The two organisations conducted a technology acceleration grant project supported by the Right Foundation from 2021 to 2022. They achieved encouraging results by combining their core competencies of AI platforms, infectious disease research capabilities and drug discovery technologies. This breakthrough demonstrates that AI technology can effectively address unmet medical needs for low and middle-income countries that tend to have higher than normal rates of resistant TB. Standigm utilised its drug design AI platform, Standigm BEST, with a scaffold-based molecular generation model and a deep learning prediction model that learned the features of three-dimensional molecular structures. Standigm, Institut Pasteur Korea identify drug candidates for resistant TB In a boost to regenerative therapies for damaged hearts and eyes, Duke-NUS in Singapore has licensed two laminin-related patents to Sweden-based biotech startup Alder Therapeutics to enhance the development of Alder’s retinal and cardiac cell therapeutic products. Both licenses originated from discoveries made by Prof. Karl Tryggvason from Duke-NUS’ Cardiovascular and Metabolic Disorders Programme, who discovered that this family of proteins can direct stem cell differentiation. One of the two inventions being advanced to clinical application by Alder is based on the retinal cell research led by Assistant Professor Tay Hwee Goon from Duke-NUS’ Centre for Vision Research. With the ability to produce two previously unavailable retina-specific laminins—LN523 and LN-323—the team has developed a method to influence human embryonic stem cells to differentiate into photoreceptors, presenting an effective treatment option that may benefit patients who have lost their vision due to retinal degeneration. Duke-NUS in Singapore partners with Swedish startup Alder Therapeutics 16 START-UP NEWS BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Japanese startup Jolly Good, Harvard University Hospital codevelop emergency care VR content Japan-based startup Jolly Good, in collaboration with Brigham and Women’s Hospital, a hospital affiliated with Harvard University, develops emergency care virtual reality (VR) content. At the same time, Dr Kei Ouchi, Associate Professor of Medicine at Harvard Medical School, will become a medical advisor to Jolly Good and Jolly Good begins full-scale entry into the US medical market. In the future, Jolly Good will develop live-action medical VR in various medical departments under the guidance and supervision of medical advisor Dr Kei Ouchi and will collaborate with him to verify the educational effects. The size of the medical augmented reality (AR)/VR market is expanding every year and is expected to reach 3.9 trillion yen by 2027. The four main categories are medical education, treatment, diagnosis, and rehabilitation. In the US, VR technology is implemented in medical education, but most of the VR content is produced using computer graphics, which not only lacks reality, but also requires an enormous amount of time and cost to produce.

WHO NEWS 17 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Yale University and WHO to scale up behavioural sciences for better health initiative WHO to enhance access to novel COVID-19 treatments The World Health Organisation (WHO) together with Unitaid and with the support of Medicines Law & Policy, have published a briefing document to support country access to affordable COVID-19 treatments. This briefing document is a factual explanation of some of the legal instruments that WHO Member States can use to promote public health and access to COVID-19 therapeutics in the framework of their multilateral trade obligations and rights, and according to their national legislation and level of development. It is intended to support countries dealing with challenges at the intersection of public health and intellectual property, to increase access to novel COVID-19 therapeutics and to facilitate alternative and more affordable sourcing of such treatments, where possible. The briefing document contains background information and resources on the therapeutics landscape and WHO recommendations; an overview of the Medicines Patent Pool licenses for oral antivirals and the implications for country access; the WHO COVID-19 Technology Access Pool; other licenses relevant to COVID-19 therapeutics; and guidance on the use of Trade-Related Aspects of Intellectual Property Rights (TRIPS) flexibilities. WHO certifies Azerbaijan and Tajikistan as malaria-free The World Health Organisation (WHO) has certified Azerbaijan and Tajikistan for achieving elimination of malaria in their territories. The certification follows a sustained, century-long effort to stamp out the disease by the two countries. Certification of malaria elimination is the official recognition by WHO of a country’s malaria-free status. The certification is granted when a country has shown – with rigorous, credible evidence – that the chain of indigenous malaria transmission by Anopheles mosquitoes has been interrupted nationwide for at least the past three consecutive years. A country must also demonstrate the capacity to prevent the re-establishment of transmission. Azerbaijan detected its last case of locally transmitted Plasmodium vivax (P.vivax) malaria in 2012 and Tajikistan in 2014. With this announcement, a total of 41 countries and 1 territory have been certified as malaria-free by WHO, including 21 countries in the European Region. The Yale Research Initiative on Innovation and Scale (Y-RISE) and the World Health Organisation’s (WHO) Behavioural Insights Unit (BI-Unit) have signed a Memorandum of Understanding (MoU) agreeing to work together over the next two years to contribute to the shared goals of promoting and enabling systematic use of the behavioural and social sciences in public health, designing, and scaling up evidence-based behavioural interventions. Behavioural insights can help improve understanding on how and why people behave in ways that affect their health, and help design policies and services that address behavioural factors for improved physical and mental well-being. WHO and Y-RISE will work together to respond to requests for technical support for the planning and design stage of pilot behavioural interventions as well as requests for examining complexities of scaling up behavioural interventions. They will also give strategic advice in the area of application of behavioural sciences to public health and capacity building.

18 WORLD NEWS BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com The World Bank Board has approved a EUR92.30 million ($100 million equivalent) Health Sectors Programmatic Development Policy Loan for Bosnia and Herzegovina (BiH). The programme will provide budget support to underpin policy efforts by BiH authorities to improve the financial sustainability of the healthcare systems and quality of health services its citizens receive. This programme aims to improve the financial sustainability of health institutions, by helping clear arrears in the health sector and introduce measures that would prevent the generation of new arrears. It also aims to introduce incentives for improved service delivery and stronger primary healthcare, as well as reforms to improve environmental management and strengthen tobacco control. The design of this programme was informed and supported by a complementary World Bank programme, the Health Systems Improvement Project, and technical assistance, including a functional review of the sector’s performance and ongoing activities to strengthen the transparency and accountability of health systems in BiH. The World Bank portfolio of active projects in BiH comprises 12 operations totaling around $720 million. World Bank grants $100M to Bosnia and Herzegovina to enhance healthcare systems USAID funds MATRIX to innovate HIV prevention products for women in Sub-Saharan Africa Gavi to identify and vaccinate millions of unjabbed children Gavi, the Vaccine Alliance has launched the Zero-Dose Learning Hub (ZDLH), a new mechanism to improve how data and evidence are leveraged to successfully identify and reach the millions of children who have not yet received a single routine vaccine shot – “zerodose” children – and the missed communities in which they live. The goal of the ZDLH collaboration is to supplement existing and ongoing monitoring efforts by building deeper understanding and sharing learning on the complex array of factors that impact efforts to reach zero-dose children, particularly in lower-income Gavi implementing countries. Funded and coordinated by Gavi, ZDLH is composed of Country Learning Hubs in Bangladesh, Mali, Nigeria and Uganda, as well as a global hub led by JSI Research and Training Institute, Inc. (JSI), with support from the Indian Institute of Health Management Research (IIHMR) and The Geneva Learning Foundation (TGLF). The global hub will provide technical and operational support to countries; and disseminate learning across immunisation stakeholders at the community, national, regional and global levels. In cooperation with Oak Crest Institute of Science based in California, the H3D Foundation has announced the award of $721,209 in funding from the United States Agency for International Development (USAID) through MATRIX, a USAID project to advance the research and development of innovative HIV prevention products for women. The awarded Integrated Special Project (ISP) will support a pilot project aimed at evaluating an innovative continuous flow technology for cost-effective manufacturing of active pharmaceutical ingredients (APIs) in South Africa. MATRIX initiated the ISP programme to support projects that will add value to and strengthen the capacity of research and development to be conducted in the Global South. The pilot project consists of technology transfer and capacity building, facilitated by Oak Crest, to University of Cape Town (UCT) scientists who will deploy a Synthetron system at UCT for the rapid and efficient synthesis of antiretroviral agents used to prevent and treat HIV.

COVER 19 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com E arlier seen as a generic powerhouse, Asia is now an important hub for pharma R&D innovation. The total gross expenditure by major companies on R&D across the Asia Pacific region crossed the $15 billion mark (approx) in 2022. Oncology, neurology, and immunology continue to draw a significant chunk of this investment. With Asia’s growing importance in R&D, the region is poised to play a significant role in shaping the future of pharmaceutical innovation globally. According to Pharmaprojects, as of January 2022, the top four countries in the region with the most drugs in their pipelines are China, South Korea, Japan and Australia. China leads with 20.8 per cent of the global pipeline, representing 4,189 drugs. South Korea follows closely behind with 13.1 per cent of the pipeline or 2,627 drugs. Japan and Australia have around 10 per cent of the pipeline, with 1,931 and 2,010 drugs, respectively. These four countries demonstrate a strong focus on research and development in the pharmaceutical industry, and their contributions to drug development and innovation are likely to have a significant impact on the future of healthcare. 2022 was a crucial year for many countries as many R&D projects which were halted during the COVID-19-induced slowdown resumed. The region saw an increase in immuno-oncology drugs and many of the top companies expanded their manufacturing footprint with the expansion of new facilities. The average R&D investment was 6-10 per cent of the revenue. We have featured the top-performing publicly listed companies with more than a billion in revenue from developed markets such as China, Australia, Japan and South Korea. As for Taiwan and Indonesia, we have covered the largest companies in their country. Ayesha Siddiqui $15B Pharma R&D Spends S.No Company Revenue (in $ ) R&D Investment (in $) 1 CSL (Australia)# 10.562 billion 1.15 billion 2 Takeda (Japan)+ 30.09 billion 4.44 billion 3 Fosun Pharma (China)@ 5.64 billion 719 million 4 Shanghai Pharmaceuticals (China)@ 31 billion 362.1 million 5 CSPC Pharmaceuticals Group (China)@ 4.03 billion 496.13 million 6 Daiichi Sankyo (Japan)+ 9.42 billion 2.18 billion 7 Hanmi Pharmaceuticals (South Korea)** 1.07 billion 147.4 million 8 Daewoong Pharmaceuticals (South Korea) 861.63 million 95 million 9 Lotus Pharma (Taiwan)* 410 million 19.38 million 10 Kalbe Farma (Indonesia)* 1.79 billion 20 million 11 SK bioscience (South Korea)* 390 million 96.6 million Asian Pharma Firms R&D Investment in 2021 * FY21 - January 1, 2021- December 31, 2021 # FY 21- July 1, 2021-June 30, 2022 + FY 21 - April 1, 2021-March 31, 2022 @ FY 21- January1, 2021- December 31, 2021 ** FY 22- January 1, 2022- December 31, 2022 ROCKS APAC

20 COVER BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com CSL (Australia) Revenue: $10.562 billion R&D Budget: $1.15 billion T he year 2021-22 was a good year for the Australian behemoth. During the year, revenue was up 2 per cent to $10.562 billion and the firm increased its investment into research and development by 17 per cent. The firm completed a $156 million expansion of its US manufacturing facility and is on track to finish an $800+ million vaccine production facility, the only one of its kind in the Southern Hemisphere. Nearly completed, their new R&D campus in Marburg, Germany, will accommodate around 500 R&D employees, fostering strong collaborative relationships with their other global R&D campuses. In addition, CSL’s state-of-the-art global R&D campus and new corporate headquarters in Parkville’s biomedical precinct in Melbourne, Australia, are well advanced in construction and slated for completion in early 2023. Recognising the pivotal role that plasma donors play in their business, CSL is implementing a new plasmapheresis platform that utilises technology to improve the donor experience and streamline processes for CSL Plasma employees. This initiative will be introduced across their 300 US centres from late 2022 to early 2023, promising a safer, more efficient, and superior experience for all stakeholders. In a move to diversify its business, in August 2022, Australian biopharma CSL agreed to acquire Vifor Pharma for $11.7 billion. The deal would give CSL—heavily dependent on vaccines and blood plasma products— a leading portfolio of therapies in nephrology, dialysis and iron deficiency. New late-stage assets to the pipeline include Sparsentan for IgA nephropathy and focal segmental glomerulosclerosis (FSGS) and SNF472 for calciphylaxis and calcific uremic arteriolopathy (CUA). Our R&D budget is typically between 10 and 11 per cent of revenue. For FY22, this was around $1.15 billion. This is focused on 6 key areas: Immunology, Hematology, Cardiovascular & Metabolic, Respiratory, Preventative vaccines and Transplant,” said a company representative. CSPC Pharmaceuticals Group (China) Revenue: $4.03 billion R&D Expense: $496.13 million According to the FY 2021 (January 1, 2021 - December 31, 2021) results, the revenue of the group grew by 11.7 per cent to RMB 27,867 million or $4.03 billion. In line with its innovation-focused development strategy, the group continued to increase its investment in R&D. R&D expenses for the year 2021 amounted to RMB 3,433 million or $496.13 million, representing an increase of 18.8 per cent and accounting for approximately 15.1 per cent of the revenue of the finished drug business. There are currently around 300 projects under development, of which over 40 are innovative smallmolecule drugs, over 40 are innovative large-molecule drugs and over 30 are new-formulation drugs, mainly focusing on the therapeutic areas of oncology, immunology and respiratory, psychiatry and neurology, cardio-cerebrovascular, metabolism and anti-infectives. During the period, 4 innovative drug candidates have filed applications for marketing approval, while more than 50 others are in the clinical trial stage. The Group has built an internationalised R&D team, eight innovative R&D platforms and five major innovative R&D centres located in China and the US. The Group’s nanotechnology platform has developed several core delivery technologies encompassing liposomes, albuminbound nanoparticles and polymeric micelles, with a pipeline layout occupying a leading position in the international arena. For large molecule drugs, the focus is on the development of multifunctional proteins and antibody drugs, such as bispecific, trispecific and novel antibody-drug conjugate (ADC) drugs. For small molecule drugs, the focus is on the development of PROTAC, LYTAC and AI-based screening platforms to develop small molecule targeted drugs with multiple functions such as anti-tumour and immune modulation, and small molecule drugs based on epigenetics. For the mRNA technology platform, in addition to the COVID-19 mRNA vaccine, the Group has also initiated the development of rabies vaccine, shingles vaccine, respiratory syncytial virus vaccine, and therapeutic tumour vaccine (including HPV vaccine). For the siRNA technology platform, the Group has been developing many genetically related products for major chronic diseases. It has also established CAR-T, CAR-NK and CAR-M cell therapy platforms based on LNP transient transfection of CAR mRNA/DNA for the treatment of tumours and chronic diseases. These leading technology platforms and R&D pipeline candidates will provide continuous momentum for the Group’s sustainable development.

COVER 21 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Takeda Pharmaceutical Company (Japan) Revenue: $30.09 billion R&D: $4.44 billion J apanese leading pharmaceutical company Takeda Pharmaceutical has recorded a sales revenue of $30.09 billion in FY21 (April 1, 2021- March 31, 2022) with an investment of $4.44 billion in R&D. Takeda strives to advance a steady stream of potential first-in-class or bestin-class therapies through a pipeline of approximately 40 molecules in clinical development – 90 per cent of which did not exist six years ago. In FY21, Takeda further demonstrated its ability to bring new therapies to patients, receiving its highest total number of approvals in a fiscal year across Japan (4 NMEs), China (3 NMEs), the U.S. (2 NMEs), and Europe (1 NME) and leading the industry in drug approvals in Japan. Our R&D spending model is disciplined in terms of prioritisation and flexibility to allow for agile funding across programmes as data emerges. In FY22, our R&D operating budget was ~620 billion Yen (~ $4.6 billion as of April 2023) which is about 16 per cent of total revenue. The majority of our R&D spend is focused on our Innovative Biopharma portfolio across three therapeutic area units (TAUs: Gastrointestinal and Immunology, Neuroscience, Oncology plus Cell Therapy) and a late-stage development organisation focused on Rare Genetics and Hematology. Over 60 per cent of our pipeline addresses a rare disease or rare subset of a broader disease class. Our scientific strategy is to explore targeted patient populations in which we often find larger effect sizes in the clinic, which translate into smaller trials and may offer faster clinical development. R&D funding also supports Plasma-Derived Therapies and Vaccines,” said a company representative. Lotus Pharma (Taiwan) Revenue:$410 million R&D: $19.38 million L otus reported total net sales at NT$12,649 million or $410 million, compared to NT$10,729 million for the prior year, representing an increase of 17.9 per cent supported by consistent growth from both Asian Business and Export Business. R&D expenses were NT$596 million or $19.38 million in 2021, a 17.9 per cent increase compared to a year before as a result of the impairment of discontinued R&D projects due to the market dynamics. During 2021, Lotus had been aggressively expanding the addressable markets with a more diversified portfolio, especially oncology products, both in Asian countries and for global markets. 121 submissions were made around the world either by its own regulatory team or through its strategic partners, including 2 biosimilar products to enhance the overall portfolio. In addition, the Company received 100 approvals from its Asian footprints as well as additional 42 countries outside Asia by working with its global partners to boost the worldwide potentials for its leading portfolio. In addition to its internal R&D projects continuously building up, the Company has signed 28 business development deals to bring in additional drivers to accelerate the substantial growth for both top line and bottom line. Among these 28 deals, the Company acquired Evista (Raloxifene) in Taiwan and successfully re-launched the product within 2 months from the contract execution and got its first NCE cancer drug, Zepzelca (lurbinectedin), licensed-in from the originator for the territory of Taiwan aiming to further penetrate the lung cancer market along with its existing portfolio.

22 COVER BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com SK bioscience (South Korea) Revenue: $390 million R&D: $96.6 million S K bioscience increased its R&D investment to 113 billion KRW or $390 million which represents 24.7 per cent of its total revenue of 456.7 billion or $96.6 million KRW. This significant increase in R&D investment demonstrates the company’s commitment to innovation and developing new products or services “During the pandemic, SK bioscience’s R&D investment greatly jumped to 113 billion won in 2022 from 30.3 billion won in 2019 by 273 per cent increase.Thanks to such investment, SK bioscience has achieved outstanding results in FY22,” said a company representative. The company’s launch of South Korea’s first COVID-19 vaccine, SKYCovion, is a significant accomplishment and demonstrates its ability to address critical healthcare needs. Additionally, SK bioscience’s SKYZoster vaccine secured a record market share for four consecutive quarters in 2022, indicating the company’s success in developing effective vaccines. Furthermore, the company’s win of the bid to supply its chickenpox vaccine SKYVaricella to PAHO for $31.27 million highlights its growing reputation in the global healthcare market. The export licence obtained for the typhoid conjugate vaccine, SKYTyphoid, demonstrates the company’s growing reach beyond the domestic market. The new partnerships with CEPI and Hilleman Laboratories for vaccine development and technology platforms signify SK bioscience’s commitment to research and development. Finally, the planned establishment of the ‘Songdo Global Research & Process Development Center’ shows the company’s ambition to expand its capabilities and innovate. Overall, SK bioscience’s achievements in FY22 indicate a bright future for the company and its contributions to the healthcare industry. Kalbe Farma (Indonesia) Revenue: $1.79 billion R&D: $20 million F or the full year ended December 31, 2021, PT Kalbe Farma Tbk reported sales was IDR 26.26 trillion ($1.79 billion) with net income at IDR 3.18 trillion. For Indonesia and PT Kalbe Farma Tbk, it was a year of increased solidarity and collaboration with all stakeholders to accelerate the journey towards a stronger and healthier nation. Fortunately, the company achieved its strategic targets and sustained its financial performance. Net profit after tax (NPAT) grew by 6.3 per cent to IDR 3.4 trillion or $ 233.72 million, in 2022. Kalbe Farma Tbk’s Prescription Pharmaceuticals Division maintained its position as the leading player in Indonesia, accounting for 21.3 per cent of Kalbe’s total net sales, with a sales growth of 7.5 per cent to IDR 6.2 trillion or $420 million. R&D remained a crucial part of the company’s strategy in supporting new product development initiatives in 2022. Kalbe also invested IDR 292.1 billion, $20 million in cutting-edge research centres to perform breakthrough research in cancer treatment, stem cells, genomic tests, and biotechnology. Kalbe International continued to perform well, with IDR 1.7 trillion export value and a double-digit growth rate compared to the previous year. In addition, a new joint company was established with a consumer goods distribution firm in the Philippines to broaden market coverage and anticipate future growth. Innovative marketing and customer engagement campaigns were also introduced in the ASEAN region and the African continent to drive customer loyalty and sales performance.

COVER 23 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Daiichi Sankyo (Japan) Revenues: $9.42 billion R&D: $2.18 billion Daiichi’s revenue was 1,044.9 billion yen or approximately $9.42 billion, of which the firm spent 24 per cent, approximately 54.1 billion Japanese yen or $2.18 billion on R&D during FY21 (April 1, 2021- March 31, 2022). The firm mainly focuses on oncology, central nervous system (CNS) and rare disease areas. Daiichi Sankyo provided support for antibody manufacturing technologies in the manufacturing division to prepare for a future increase in demand for antibodies used in 3ADCs. They also established antibody production methods for Dxd-ADCs following 3ADCs and supplied the antibodies for clinical trials as planned. As for proprietary technology development, they developed manufacturing technology in collaboration with Daiichi Sankyo RD Novare and external global partners. Daiichi Sankyo achieved outstanding results with their 3ADCs and made great progress with the ‘Rising Stars’ in the DXd-ADC family. They also strengthened the modality technology and research intended to support further growth of the pipeline and progressed in the development of DS5670, a COVID-19 vaccine. Additionally, it launched products such as Edoxaban, achieved important milestones in the Alpha oncology and specialty medicine projects and advanced research programs, and implemented organisational and capability enhancements to realise the Global RD One Team approach. Enhertu achieved blockbuster status in 2022, with global sales exceeding $1.2 billion driven by breast cancer and gastric and gastroesophageal cancer, and to a lesser extent, NSCLC. GlobalData’s consensus forecast projects global sales for Enhertu to reach $9.9 billion by 2028, with this driven by increased uptake for already approved indications across markets and expansion into new indications. The company is currently conducting clinical trials for Nilemdo and Nustendi, which were launched in Europe last year. The trials aim to expand the indications of the drugs to include the suppression of cardiac events in Europe, with the company expressing optimism for positive results. Additionally, the company aims to quickly expand sales of its Emgality prophylaxis for migraine attacks and Reyvow migraine treatment in Japan by leveraging their respective product strengths. These efforts aim to support continuous growth in the company’s new drugs business outside of oncology. Hanmi Pharmaceuticals (South Korea) Revenue: $1.07 billion R&D: $147.4 million Hanmi Pharmaceuticals posted 1.33 trillion won or $1.07 billion in revenue in 2022, a 10.7 per cent increase from a year earlier. Operating profit rose 25.2 per cent year-on-year to 157 billion won, and net profit, 17.4 per cent to 95.7 billion won, the largest ever in the company’s history. Hanmi attributed the robust sales growth to its self-developed medicines. In 2022, Hanmi raised 789.1 billion won in outpatient prescription sales. Sales of Rosuzet, a dyslipidemia combination drug mixing ezetimibe and rosuvastatin calcium, reached 140.3 billion won alone. Hypertension drug Amosartan products sold 130.5 billion won, Hanmi spent about 177.9 billion won or $147.4 million on R&D,13.4 per cent of the revenue. Daewoong Pharmaceuticals (South Korea) Revenue: $861.63. million R&D: $95 million Daewoong Pharmaceutical consolidated annual sales in 2021 was KRW 1.153 trillion or $861.63 million rose by 9.2 per cent y-o-y and the firm invested KRW 127.3 billion or $95 million, which exceeds 10 per cent of its annual sales revenue, in R&D, and created the business cycle that the R&D outcome leads the growth of sales and operating profit and assures new growth engine. The company saw business upturns and made key achievements in FY21; it received new drug approval of Fexuclue tablets and generated more than KRW 1 trillion profits from overseas technology transfer, and this year is expected to introduce Nabota to the world’s second and third largest botulinum toxin markets, Europe and China. In China, Daewoong has already submitted a biologics licence application. Furthermore, the phase-3 trial of Enavogliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor for diabetes first developed by a Korean pharmaceutical company, was successfully completed earlier this year and showed a strong possibility that Daewoong will successively introduce new drug, following Fexuclue tablets.

24 COVER BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Shanghai Pharmaceuticals (China) Revenue: $31 billion R&D: $362.1 million As per the FY21 (January 1, 2021 - December 31, 2021) annual report, the company achieved operating income of RMB 215.824 billion or approximately $31 billion, representing a year-onyear increase of 12.46 per cent. The company further increased its R&D investment, totalling RMB 2.503 billion, approximately $362.1 million representing a year-on-year increase of 26.94 per cent and accounting for 9.97 per cent of sales revenue from manufacturing. There have been 47 new drug pipelines for clinical application acceptance and entering the clinical study stage, including 39 innovative drugs and 8 improved new drugs. Among the innovative drug pipeline, six are in pivotal studies or clinical Phase III. In recent years, China has paid more and more attention to the field of rare diseases and continuously issued a number of encouragement policies, involving multiple aspects such as drug guarantee for rare diseases, drug R&D and tax reduction and exemption. In response to the national call, Shanghai Pharmaceuticals established a rare disease business unit and operating entity, SPH Ruier, in 2020 to carry out the physical operation of the rare disease platform and invested over RMB 100 million in rare disease R&D in 2021. Shanghai Fosun Pharmaceutical (China) Revenue: $5.64 billion R&D Expense: $719 million F osun Pharma’s revenue and recurring income have continued to grow steadily during the reported period, thanks to the contribution of new and sub-new products and effective control over marketing expenses. The company achieved a revenue of RMB 39,005 million or $5.64 billion in FY 21 (January 1, 2021 - December 31, 2021), representing an increase of 28.70 per cent year-on-year (YOY). Revenue from regions outside Mainland China and countries overseas accounts for 34.86 per cent of the total revenue. The annual R&D expenditure was RMB 4,975 million or $719 million, representing an increase of 24.28 per cent YOY. By the end of 2021, the Group had over 240 pipeline projects, including innovative candidates, biosimilars, generic candidates and consistent evaluation of generic candidates. After over a decade of continuous investment, innovative products including Han Li Kang (Rituximab Injection), Han Qu You (Trastuzumab Injection), Su Ke Xin (Avatrombopag Maleate Tablets) and COMIRNATY (mRNA COVID-19 vaccine) have been approved and sold in large quantities in the past three years, accelerating the implementation of innovative R&D and driving sustainable growth of the Group. In 2021, the revenue from new and sub-new products accounted for more than 25 per cent of revenue in the pharmaceutical manufacturing segment. Sales from in-house developed product Han Li Kang (Rituximab Injection) reached RMB1,690 million, representing an increase of 125.33 per cent YOY. Han Qu You (Trastuzumab Injection) and Su Ke Xin (Avatrombopag Maleate Tablets), both launched in 2H 2020, recorded revenue of RMB 930 million and RMB 426 million respectively in 2021. COMIRNATY (mRNA COVID-19 vaccine) jointly developed by Fosun Pharma and BioNTech, was included in the government vaccination programs in Hong Kong SAR and Macau SAR in March 2021 and supplied to the Taiwan region in September 2021. By the end of February 2022, over 20 million doses of BNT162b2 have been administered in Hong Kong SAR, Macau SAR, and Taiwan region, helping to establish the local COVID-19 immune barrier. In June 2021, Yi Kai Da (Axicabtagene Ciloleucel Injection) of Fosun Kite, a joint venture, became the first CAR-T cell therapy product approved for launch in China, offering the possibility of sustained remission for patients with lymphoma after two or more lines of systemic therapy. Since the launch of Yi Kai Da, Fosun Kite has been exploring diversified and innovative payment methods to increase product accessibility to benefit more patients. As of the end of February 2022, Yi Kai Da has been included in the urban inclusive supplementary medical insurance and over 40 commercial insurance in 23 provinces and cities, and the number of registered treatment centres has reached 75. In addition, around one hundred patients have entered into the treatment process.

COVER 25 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Wally Wang, Founding Partner, Scale Asia Ventures Accelerating R&D in Biosciences Startups with AI and mRNA Therapeutics The pharmaceutical industry has long been plagued by high R&D costs and long development timelines, often taking more than a decade and billions of dollars to bring a new drug to market. In recent years, artificial intelligence (AI) has emerged as a powerful tool that can address these challenges, transforming drug discovery and development processes. In this article, we will discuss the reasons why pharma companies should leverage AI to reduce R&D costs and accelerate innovation. As the biotechnology and health science industries continue to evolve, the significance of research and development (R&D) spent in bioscience startups is increasingly evident. At Scale Asia Ventures, a Silicon Valley-based VC fund, we have been actively monitoring the trends and emerging technologies in the biotech space. In this article, we focus on two crucial aspects driving the growth of biosciences startups: artificial intelligence (AI) and the rapid advancements in mRNA therapeutics. Investing in R&D is critical for biotech startups, as it drives innovation and enables the adoption of cutting-edge technologies. On average, biotech startups allocate 15-20 per cent of their total budget to R&D efforts. However, this percentage can be higher for startups focused on AI and mRNA therapeutics, given the potential for rapid advancements and returns on investment in these areas. Artificial Intelligence (AI): Artificial intelligence is playing a pivotal role in revolutionising drug discovery, development, and clinical trials, enabling a faster, more efficient, and cost-effective approach to R&D. With the vast amounts of data generated from genomics, proteomics, and other omics approaches, AI has the potential to analyse and interpret these complex datasets, accelerating the identification of novel drug targets and biomarkers. In drug development, AI-driven approaches like machine learning (ML) and deep learning (DL) can

Ruplekha Choudhurie, Senior Industry Analyst - Health & Wellness, Frost & Sullivan Investment in deeptech companies soars to propel APAC pharma R&D The pandemic put severe pressure on many healthcare systems and pharma companies, indirectly providing impetus for large pharma and startups to focus on R&D and innovation and development of sustainable business models. Despite the general slowdown in investments globally, biopharma and life sciences companies continue to witness a steady influx of investments, though many pharma and biotech companies have been forced to realign their research priorities and business strategies. Pharma investments in the Asia Pacific (APAC) region continued to surge in 2022, bolstered by several factors, including an evolving R&D ecosystem, a growing number of innovative startups, partnerships with large pharma/biopharma companies, favourable regulatory policies, and growing unmet healthcare needs in the region. The APAC biopharma ecosystem is brimming with activity since 2020 - pharma, biotech, diagnostics, biomanufacturing, life sciences, and deep technology startups playing a pivotal role in early-stage R&D, product development, and translation to clinic. Many countries in the APAC region are a crucial but often undermined component of the global pharma ecosystem. However, the landscape is changing, with several global pharma companies such as GSK, Sanofi, Pfizer, Merck, Roche investing in companies in the region and VC investors also turning their heads towards innovative R&D-focused biosciences companies. Several companies in the APAC region are repositioning themselves from CROs and generic developers to innovation-driven biopharma and deep technology-focused companies. For instance, Indian pharma 26 COVER BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com streamline the drug design process, optimising the selection of lead compounds and predicting their pharmacokinetics and pharmacodynamics. This allows for the development of more effective and safe drugs with fewer side effects. Furthermore, AI is making a substantial impact on clinical trials. It can enhance patient recruitment by identifying suitable candidates based on genomic data and medical histories, reducing the time and cost of patient enrollment. Additionally, AI can analyse real-time data during trials, ensuring better monitoring of patient safety and enabling datadriven decision-making to optimise trial designs. mRNA Therapeutics: The rapid advancements in mRNA therapeutics have made headlines globally, thanks to the success of mRNA-based COVID-19 vaccines. This technology holds immense potential to transform medicine by offering a flexible, scalable, and rapid approach to developing new treatments. AI-Driven Drug Discovery: One notable case study is the collaboration between Silicon Valley-based startup Atomwise and pharmaceutical company Merck. Atomwise utilises AI-driven technology for drug discovery, focusing on deep learning to predict the bioactivity of small molecules. Their platform, AtomNet, has facilitated the identification of several drug candidates across various therapeutic areas. As a VC fund, Scale Asia Ventures is excited by the potential of both AI and mRNA therapeutics to disrupt the biotech landscape. We believe that startups leveraging these technologies can significantly accelerate R&D efforts, translating to faster time-to-market and improved patient outcomes. We are committed to supporting such startups, ensuring they have the resources and guidance needed to bring their innovative solutions to the forefront of healthcare. To capitalise on the opportunities offered by AI and mRNA therapeutics, it is crucial for biosciences startups to invest in R&D. This investment will drive innovation, enable the adoption of cutting-edge technologies, and ultimately contribute to the growth of the biotech industry in the Asia Pacific region. In conclusion, AI and mRNA therapeutics represent transformative technologies that can propel biosciences startups to the forefront of innovation. By investing in R&D and embracing these advancements, startups can accelerate the development of life-saving treatments and drive the growth of the biotechnology and health science industries in the Asia Pacific region. We are excited to be part of this journey and look forward to fostering the success of these startups and the positive impact they will have on global health.

companies such as Dr. Reddy’s Laboratories, Piramal, and Reliance Biosciences are investing heavily in R&D for new biologics and NCEs. Steady Flow of Investments to Accelerate Advanced Therapeutics R&D A steady influx of capital from both domestic and global players is enabling APAC companies to drive innovation. Cell and gene therapy developers and RNA therapeutics-focused startups in the region received sizable investments from big pharma and VC to advance their R&D and progress clinical pipelines in the last two years. Companies with innovative immuno-oncology candidates (cellular therapies, ADCs, and antibodies) attracted the highest funding in the region in the last one year, with novel biologics and NCEs for neurology, metabolic and rare diseases emerging as active areas of R&D and therapeutic development in the region. Astellas and Takeda have made rapid strides in terms of R&D for advanced therapeutic modalities and expanding their portfolio and capabilities by making strategic investments in other companies across the globe. For instance, Astellas invested $50 million in Cell and Gene Therapy company Tayesha Gene Therapies, while Takeda Ventures invested in the Norway-based Zelluna Immunotherapy to advance development of the ‘off the shelf’ allogeneic TCR-NK cell therapy. Chinese RNA therapeutics developers, Therorna (circRNA), and Stemirna Therapeutics (mRNA) have also raised more than $250 million in the last two years to advance their platform and pipelines. In October 2022, Pfizer/BioNTech established the first Asia Pacific R&D center in Australia, which will be key for the company to collaborate with local researchers and provide research capabilities in the region. Some of the other notable VC deals around advanced modalities were Singapore-based Tessa Therapeutics and RVAC Medicines securing $126 million Series A funding and $140 million Series B, respectively, to advance their cell therapy and mRNA platforms. Fostering a Startup Ecosystem While Singapore is known as the hub of biosciences innovation, countries such as Japan, Taiwan, and India have also indicated innovation in R&D as a priority, with both federal and private investments pouring in for novel drug development, vaccines, and platform technologies. Biosciences accelerators such as ClavystBio were launched in Singapore in late 2022 to support innovations from early-stage biotech companies in the country. It has invested more than $220 million in investment commitments to six early-stage companies - Allay Therapeutics, CoV Biotechnology, Engine Biosciences, Hummingbird Bioscience, Medisix Therapeutics, and Sunbird Bio. In 2023, federal budget announcements in India and Japan have promised to foster an innovative biosciences environment where collaboration and R&D-focused incentives will drive growth. India is expected to broaden its focus from generics and vaccine manufacture to innovative biologics and vaccine development and is the first country to launch a DNA vaccine for COVID-19. Japan aims to nurture its startup ecosystem with major funding announcements in its 2023 budget - 100 billion yen towards DeepTech companies and 300 billion yen for drug discovery. On similar lines, the Indian budget has also emphasised investing in R&D and promoting PPPs. The Kansai area of Japan has emerged as a deeptech hotspot in Japan and recently formed its startup ecosystem. Interestingly, some of the notable R&D startups from the Kansai region were biosciences companies such as Luxna Biotech, Bio Palette Co. Ltd, PeptiStar Inc., among others. Indigenous cash-rich pharma companies such as Astellas and Eisai are investing in startups via their corporate ventures arm. Pharma companies from the region are also collaborating beyond drug development R&D. In December 2022, Astellas Pharma, Eisai Co, Daiichi Sankyo, and Takeda Pharmaceutical announced that the four companies would collaborate to develop sustainable pharma packaging technologies. In the APAC, there is a growing trend in investing in deeptech companies, and AI, data analytics, and digital platforms to drive pharma R&D and workflow management are garnering traction from both pharma and VC investors. Deeptech biosciences startups such as Engine Biosciences, Insilico Medicine, Xtalpi, Iktos, and others are focused on developing cuttingedge technologies to drive innovation in the industry and have attracted large amounts of VC funding and strategic collaborations with big pharma over the last two years. COVER 27 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com

Francis van Parys, Vice President Commercial, Asia Pacific, Cytiva Why talent and collaboration is crucial for biotech startups to sustain R&D The power of biotech startups has proven to be enormous by BioNTech, during the pandemic, when its mRNA vaccines saved lives around the world. Since then, the biotechnology industry and its investors have been searching eagerly for ‘the next BioNTech’” Many startups had good days between 2019 and 2021 when $35 billion venture capital flooded into the companies. However, we have seen the fever cooling down since 2022. Biotech startups need more flexible solutions to secure their cash flow and talents, which are keys to their surviving and thriving. Since 2018, Cytiva has provided flexible access to bioprocess development, technology verification, and opportunities to collaborate alongside industry experts and institutional investors to biotech startups’ to accelerate and advance their projects from molecule to market. This initiative is called BioChallenge, and it’s now expanding its impact across China, Korea, the Southeast Asia region, and Australia and New Zealand. BioChallenge is also exploring and fostering cooperation among governments, industry associates and academia institutions to mitigate the talent, resources and scalability constraints faced by earlystage biotechs. In South Korea for example, BioChallenge engaged the Korean Ministry of Health and Welfare and the Ministry of Food and Drug Safety which then joined as co-sponsors. Two participants of the first season of BioChallenge, GI Innovation and Yuhan Corporation, have since gone on to sign a million USD deal to jointly develop and commercialise a treatment of allergic diseases. Another BioChallenge winner, Genexine, has risen to become the face of K-bio. In China, BioChallenge goes one step further to bridge startups and investors. In 2022, we attracted over 110 submissions, and thousands of investors. As a result, the winner, GENHOUSE, received $14 million in funding to develop a small molecule anti-tumor drug. Another flexible offer from Cytiva to meet biotech startups’ demands is the talent training and development system, which is taking a high stake in their R&D budget. Compared with the well-established institutions in big biopharma companies, startups are struggling to compete for mature talents, and to train the fresh hands. Cytiva has established the Fast Trak Education and Training Programme, available at six centres globally – three of which are based in Asia Pacific region -- Korea, China, and India. For example, both Songdo and Shanghai centres have the capability to train more than 300 people every year for the biotechnology industry. The India centre collaborates with Bangalore BioInnovation Centre to set up a world class incubation centre to provide bioprocessing training programmes to support the startup ecosystem in India. To nurture talent in ASEAN, Cytiva established the Experience Learning Lab (CELL) in Singapore in 2021. CELL, a learning facility that provides education and training on the latest bioprocessing and production techniques to develop advanced therapeutics, has delivered over 70 training sessions to tertiary academic and research institutes. I firmly believe that we must continue the kind of collaboration in the R&D ecosystem that has brought us safe and effective COVID-19 vaccines. With the reset of the biotech industry after the pandemic, emerging biotech startups developing innovative, high-impact therapeutics for patients must also be supported. And this should be the joint responsibility of industry, governments, think tanks and academia institutions. Besides money, biotech startups need talent and collaboration to sustain their R&D investment, in an accessible, affordable, and flexible way. 28 COVER BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com

With the continued emergence of China as a global hub for biopharma innovation, companies from the country are now looking to take some of their principal original products to the smaller global markets of Southeast Asia, as they seek to diversify commercialisation of their expanding pipelines. The engine driving this change continues to become more powerful. According to Citeline’s latest annual R&D report, 24 per cent of global R&D into new drugs and vaccines in development was taking place in China as of early January this year (comprising more than 5,000 products), up from 21 per cent in 2022. Meanwhile, the US was down slightly at 51 per cent of the total, from 53 per cent in 2022. The global R&D pipeline continued to grow by around 6 per cent during the course of the preceding year, and now comprises more than 21,000 drugs and vaccines – but the balance of innovation is gradually shifting and Asia is becoming increasingly important. In terms of therapeutic focus, oncology remained dominant overall, accounting for 41 per cent of all R&D projects worldwide, but rare diseases together now account for a significant 20 per cent. Chinese firms have so far focused on the US as their main target market outside China, but a series of setbacks over the past few years with immunooncology drug approvals in the US, linked mainly to a lack of diverse clinical data, appears to be prompting a new consideration of opportunities within Asia Pacific. As a result, it seems likely that some major Chinabased innovators will increasingly target markets in Southeast Asia and Japan over the next few years, given the likely lower challenges around clinical data given their more ethnically similar patient populations, Ian Haydock, Editor-in-Chief, Insights, Asia Pacific, Citeline along with ongoing moves to harmonise global regulatory requirements. There have already been some clear steps by Chinese firms to develop their business in Asia Pacific, with Shanghai Junshi Biosciences Co., Ltd. for example partnering with China Medical System Holdings Limited subsidiary Rxilient Biotech Pte. Ltd. to develop and commercialise the anti-PD-1 antibody toripalimab in nine Southeast Asian nations. Shanghai Henlius Biotech Co. Ltd. has also licensed its antiPD-1/L1 antibody serplulimab to Indonesia-based PT Kalbe Genexine Biologics for Southeast Asia. Another Indonesian firm, Etana Biotechnologies, has teamed up with several other Chinese pharma companies, including Walvax Biotechnology Co., Ltd., a vaccine maker, and ABOGEN INC, a messenger RNA-focused biotech, for the development and manufacturing of various types of vaccines in Indonesia. A notable factor for biopharma R&D in Asia Pacific is that innovation is tending to come from smaller companies with fewer products compared to the US and Europe, where activity is more concentrated in large companies with diverse pipelines. Reflecting the wider trends, companies in the region are also active in the rare disease space, led by Japan’s Takeda, which had 90 such projects in its pipeline, making up about half the total and ranking sixth overall worldwide. Here again, China is also building up its presence – BeiGene for instance had 34 rare disease projects in development, the Citeline annual R&D report shows, accounting for 61 per cent of its pipeline and ranking 19th worldwide. According to Scrip’s Outlook 2023, Japanese pharma companies still remain the biggest spenders on R&D within Asia Pacific in absolute terms. China Emerges as New APAC Pharma R&D Engine COVER 29 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com

30 RADIOPHARMA BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com A key goal for any innovative cancer treatment is the ability to deliver an anti-cancer agent directly to the tumour and avoid a negative impact on healthy tissue. This concept is central to the development of Targeted Radionuclide Therapy (TRT), which is an emerging class of cancer therapeutics that uses the power of radiation in a targeted way to destroy tumour tissue. Several TRT therapies have demonstrated positive outcomes in clinical evaluation and have reached the market, providing new hope for patients suffering from hard-to-treat cancers. This sparked the interest of big pharma that’s betting big on radiopharmaceuticals. Novartis is clearly the trailblazer focusing on radiopharmaceuticals, spending $6 billion in 2017 and 2018 to buy Advanced Accelerator Applications and Endocyte. In March 2022, the Swiss drugmaker won U.S. approval for Pluvicto to treat an advanced form of prostate cancer. In March 2023, the firm inked a deal worth $1.75 billion with Bicycle Therapeutics to develop, manufacture and commercialise Bicycle radio-conjugates (BRCs) for multiple agreed-upon oncology targets. In August 2022, American drugmaker Merck participated in an $84 million funding round of USbased startup Aktis Oncology. Novartis and Bristol Myers Squibb are other investors in Atkis. German drugmaker Bayer was an early entrant in the field, its Xofigo (radium 223) won US approval back in 2013 for prostate cancer. In 2021, the firm acquired Noria Therapeutics Inc. (Noria) and PSMA Therapeutics Inc. to expand its radiopharmaceutical pipeline. Not to be left behind, the British drugmaker AstraZeneca jumped on the field, by partnering with Fusion Pharmaceuticals in 2020. Not only big pharma, but smaller biotech firms have also cropped up looking to cash-in on the hot field. In October 2022, Eclipse and Mayo Clinic created Nucleus RadioPharma to better serve cancer How Radiopharmaceuticals Are Transforming Cancer Treatment A new class of drugs, radiopharmaceuticals, are gaining traction with several regulatory approvals and investments in recent years. Big pharma firms are taking an active interest and have propelled the developments in the sector. Chief among them is Swiss firm Novartis whose $6 billion investment paid off with the approval of Pluvicto in March 2022. Almost every pharma firm is trying to get a foot in the door by investing in or acquiring radiopharmaceutical developers. BioSpectrum Asia explores the growing interest in radiopharmaceuticals and the recent advances in the field. patients. In September 2022, The University of Texas MD Anderson Cancer Center and Australian firm Radiopharm Theranostics launched Radiopharm Ventures, LLC, a joint venture company created to develop novel radiopharmaceutical therapeutic products for cancer. “There is clearly a rising interest in radiopharmaceutical products from both drug development companies and investors. This is likely to be driven by the commercial success of recently approved products such as Lutathera (AAA/ Novartis) and Pluvicto (Endocyte/Novartis) and by recent significant investments in biotech over the 12 months. This is exemplified by the Series A round of $75 million announced by Aktis in March 2021 and the Series D of $160 million announced by Rayzebio in September 2022. Ariceum is another example of growing interest from European as well as VCs in the field. More than 30 companies are actively developing theranostic pairs across US and Europe, and there is growing interest in Asia as illustrated by the involvement of the company Grand Pharmaceutical in China,” said Serge Sagodira, Chief Business Officer, Ariceum Therapeutics, Germany. The firm recently raised EUR 22.75 million in extended Series A funding. Current landscape The potential of radiopharmaceuticals has been known for decades, ever since the use of Radioactive iodine-131 in the 1940s to treat thyroid cancer. New technologies for targeting other cancer biomarkers are greatly expanding the use of radiopharmaceuticals beyond thyroid cancer into areas of unmet need, such as prostate cancer. With indications expanding rapidly, radiopharmaceuticals could soon become a new pillar of cancer treatment. “Although these new anti-cancer drugs have been in development for years, recent innovations and market launches have brought a lot of attention to the

RADIOPHARMA 31 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com therapeutic principle of TRT and its potential. The interest in the space can also be seen in the increasing number of financings and deals for companies that are focused on radiopharmaceutical development and TRT. It is exciting to see the progress in this area of medical science and be a part of the growing awareness of how it can potentially improve clinical outcomes and quality of life for cancer patients. We are truly seeing the rise of a powerful new drug class for cancer treatment. There will be further advances in the selection of targeting molecules and the continual improvement of radioisotope manufacturing and supply chain that will allow the field to broaden the scope of patients it can serve,” said Steffen Schuster, CEO of ITM Isotope Technologies Munich SE (ITM). ITM is a leading player in this space. The firm has several products in the pipeline including two in late-stage trials. There are currently 671 clinical trials underway as of April 20, 2023 on clincialtrials.gov investigating the use of radiopharmaceuticals for a wide range of cancer indications, including breast, prostate cancer, lung, and lymphoma, among others. It’s not just big pharma and western counterparts that are fascinated with radiopharmaceuticals. Closer home in Asia Pacific, a lot of companies are tapping into the potential of radiopharmaceuticals. Leading among them is Australian firm Telix Pharma who’s Extensive, late-stage radiopharmaceutical pipeline. In the first quarter of 2023, the firm reported $100 million revenue. Another Australian firm, Radiopharm Theranostics has also focused on developing radiopharmaceuticals for diagnosing and treating diseases with high unmet medical needs. In September 2022, the US FDA granted an orphan drug designation (ODD) to its lead asset LRRC15 antibody DUNP19 for the treatment of patients with osteosarcoma. Clarity Pharma is another leading Australian firm in the space. Japanese biotech Perseus Proteomics and PeptiDream are also leading the radiopharmaceuticals development. In September 2021,PeptiDream acquired the radiopharmaceutical business of FUJIFILM Toyama Chemical Co., Ltd. from Fujifilm Corporation for ¥22.1 billion. Gland Pharma, China’s largest drugmaker, has invested $28 million in ITM, a leading player in the field. China’s CASI Pharmaceuticals is another leading player in this space. Challenges remain Radiopharmaceutical development poses unique challenges. They are difficult to manufacture and “Recent innovations and market launches have brought a lot of attention to the therapeutic principle of TRT and its potential. The interest in the space can also be seen in the increasing number of financings and deals for companies that are focused on radiopharmaceutical development and TRT. It is exciting to see the progress in this area of medical science and be a part of the growing awareness of how it can potentially improve clinical outcomes and quality of life for cancer patients.” - Steffen Schuster, CEO of ITM Isotope Technologies Munich SE (ITM) “There is clearly a rising interest in radiopharmaceutical products from both drug development companies and investors. This is likely to be driven by the commercial success of recently approved products such as Lutathera (AAA/Novartis) and Pluvicto (Endocyte/Novartis) and by recent significant investments in biotech over the 12 months.” - Serge Sagodira, Chief Business Officer, Ariceum Therapeutics, Germany require specialised facilities. Novartis’ Pluvicto has been plagued with manufacturing woes since its approval in March 2022. The firm had to halt its production owing to potential quality issues in May 2022. As of March 2023, the drug is facing production shortage. “One of the specific challenges of TRT is the nature of radioisotopes and the need to provide the therapy to patients in a timely way, with the right dose at the right time and place for each patient. Based on the breadth of the potential of TRT, this requires a worldwide production and supply network as well as a sophisticated process to ensure radioisotopes are delivered to clinics and patients before they decay. A great deal of specialised knowledge is needed to support the on-time delivery and dosing. The demand for TRT treatments has

32 RADIOPHARMA BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com grown exponentially and ITM continues to expand its leading global production and supply network to meet the needs of patients now and in the future,” said Steffen. A couple of radiopharmaceutical contract development and manufacturing organisations (CDMO) have come up that could help in addressing these woes. In March 2023, AtomVie announced plans to build a new contract manufacturing facility specifically for radiopharmaceuticals. In November 2022, NorthStar Medical Radioisotopes established a new CDMO services unit. “In addition to logistical challenges, one would add isotopes supply as one the main challenges as the use of radiopharmaceuticals gets expanded. In addition, the requirement for a multidisciplinary team including nuclear medicine, radiation oncology and general oncology could be seen as a constraint but this might disappear with the increasing number of drugs that could reach the market in the future,” added Sagodira. Road map Data Bridge Market Research analyses that the radiopharmaceuticals market, which was worth $5.32 billion in 2022, would rise to $12.18 billion by 2030. No wonder, big pharma and smaller biotech firms are scrambling to get the bigger piece of the pie. The increasing prevalence of cancerous diseases on account of the rising ageing population and unhealthy dietary patterns represent the key factors contributing to the growing use of radiopharmaceuticals across the globe. Apart from this, the escalating number of diagnostic centres is also supporting the market. Moreover, the rising number of oncologists that are suggesting diseasetargeted cancer therapy, which utilises drugs to target specific proteins and genes involved in the development of cancer cells, are positively influencing the overall sales. Furthermore, the use of radiolabeled peptides and monoclonal antibodies for the diagnosis and treatment of cancerous tumours, along with rising healthcare expenditures, is strengthening the market growth. According to the IMARC report the increasing use of radiopharmaceuticals by oncologists to track radioactivity throughout the body and determine the presence of cancer cells and the increasing shift towards positron emission tomography (PET) and single-photon emission computerised tomography (SPECT) scans will drive the growth of the market. Ayesha Siddiqui Recent developments in APAC ● On April 3, 2023, China’s Ablaze Pharmaceuticals, announced the development plans of a first-in-class novel peptide drug candidate against GPC3. The proprietary GPC3 targeting peptide is being licensed from US-based RayzeBio pursuant to an existing licence agreement. ● On March 3, 2023, Australian firms Radiopharm Theranostics, a clinical-stage radiotherapeutics company, and GenesisCare, a leading global provider of integrated cancer care and theranostics research, announced a new two-year strategic research collaboration to develop novel radiopharmaceuticals for some complex, hard-to-treat cancers ● On March 8, 2023, Japan-based Sumitomo Heavy Industries (SHI) announced the decision to invest in Alpha Fusion Inc. (AF), a developer of Astatine based radiopharmaceuticals for Targeted Alpha Therapy (TAT) ● In August 2022, Australia’s Advancell closes AU$18M series B round to take alpha-emitting radiotherapy to the clinic ● In February 2022, China’s Gland Pharmaceutical Group announced a EUR 25 million ($28 million) equity investment in Germany’s ITM. The agreement to further deepen the strategic collaboration between the two companies and support ITM to further expand its broad pipeline of precision oncology treatments and diagnostics in Greater China Key global radiopharmaceuticals players ● Advanced Accelerator Applications (Novartis AG) ● Bayer AG ● Bracco S.p.A. ● Cardinal Health Inc. ● Curium Pharma ● General Electric Company ● IBA RadioPharma Solutions ● Jubilant Pharma Limited ● Lantheus Medical Imaging Inc ● Nordion Inc. (Sotera Health) ● NTP Radioisotopes SOC Ltd ● PharmaLogic Holdings Corp. ● Siemens AG Source: IMARC Group

SPEAKING WITH 33 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com South Korea-based GPCR Therapeutics is a venture-backed, clinical-stage international biopharmaceutical company with an innovative approach to developing therapeutics built on its proprietary G protein-coupled receptors (GPCRs) data. The company’s proprietary datadriven approach has identified over 1,000 GPCR pairs upon which drug screening campaigns can be pursued. In an email interview with BioSpectrum Asia, Dr Pina Cardarelli, Chief Scientific Officer, GPCR Therapeutics explains more about their unique approach and how GPCR-targeted therapies may change the cancer treatment landscape. Edited excerpts; Can you explain what GPCR heteromers are and why they are a promising target for cancer therapeutics? Before I answer your question about heteromers, let me explain what GPCRs are first. GPCRs represent the largest protein family that consists of 7 transmembrane proteins located on the cell membrane. They transmit chemical signals from extracellular stimuli resulting in key physiological effects. Their endogenous ligands include hormones, neurotransmitters and chemokines. GPCRs have been implicated in many diseases, such as type 2 diabetes mellitus (T2DM), Alzheimer’s disease, and cancer as well as many others. As of 2020, 142 compounds were in clinical trials targeting 83 different GPCRs (19 are novel GPCRs with no previous FDA-approved drugs). Based on technology from Seoul National University that has been pursued at GPCR Therapeutics, Inc. we know distinct GPCRs can associate with other GPCRs forming heteromers. When both ligands are present, they amplify the signal induced by each ligand-receptor pair alone. Using a bimolecular fluorescence complementation (BiFC) technique, the team discovered over 1000 interactors of two distinct GPCRs coming together to form a heteromer. The team then focused on one GPCR called CXCR4, which plays a critical role in cancer progression. CXCR4 drives cell migration, metastasis, angiogenesis, proliferation and survival. Multiple CXCR4 inhibitors have failed in the clinic; however, we believe a blockade of multiple pathways could be the key to getting a sustained therapeutic benefit. “As Precision Medicine is critical, we cannot think about one size fits all” « Dr Pina Cardarelli, Chief Scientific Officer, GPCR Therapeutics Can you walk us through your drug discovery and development process, from identifying potential targets to clinical trials? We identified over 40 GPCRs that associate with CXCR4. We then prioritised the list to GPCRs where the ligand was known. This allowed us to perform functional assays like calcium flux assay to determine if we see additive or synergistic effects. The top selected GPCR that was selected was the beta 2 adrenergic receptor (β2AR). So why β2AR? Many similar qualities are shared with CXCR4. Interestingly, this target also plays an important role in cancer. Firstly, the ligands for this target, Epinephrine (Epi) and Norepinephrine (NE) are induced under stress. Patients diagnosed with cancer experience significant stress, and this stress promotes tumorigenesis, proliferation, angiogenesis and immunosuppression. For their immunosuppressive role, Epi and NE induce suppressive immune cells, such as M2 or MDSCs in tumour microenvironments. In addition, a number of studies have shown that cancer patients on nonselective beta-blockers, such as propranolol, have improved PFS and OS. While propranolol was commercially available, it was critical that we acquire a CXCR4 inhibitor and preferably one that had been tested clinically. We acquired Burixafor, now known as GPC-100, from a company called Taigen. A review of their clinical data showed exciting safety and efficacy in stem cell mobilisation. From our in vivo stem cell mobilisation studies, we found the addition of propranolol improved the mobilisation of cells driven by GPC-100. Concurrently, we embarked on the synthesis of a GMP-grade new drug product, identified a clinical CRO and initiated a clinical trial design.

34 SPEAKING WITH BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com What specific types of cancers are you currently targeting with your therapeutics, and what progress have you made in these areas? Because the US clinical study previously conducted in stem cell mobilisation in a number of hematologic malignancies showed promising data, we decided to focus on Multiple Myeloma. Currently, the trial is a two-arm study with each arm having 20 patients. In the first arm, patients will be treated with a low dose of propranolol and GPC-100. The second arm is a triple combination which includes GPC-100, propranolol and G-CSF. We are excited to report that our first clinical site was activated on February 14, 2023. With respect to future trials, GPC-100 plus propranolol can be extended to stem cell mobilisation in NHL or used as a chemosensitiser in AML. Finally, if our arm that omits G-CSF is successful, this gives us an opportunity to work on diseases where G-CSF is contraindicated, like Sickle Cell Disease. How does your company plan to address potential challenges or roadblocks in bringing GPCR heteromer-targeted therapeutics to market? We have recently published a paper in scientific reports, meaning that our co-targeting drug development strategy has been peer-reviewed and validated in academia. We plan to continue our work and expand our pipeline by targeting the interaction of CXCR4 and other GPCRs as well. If our Phase 2 study is successful, it will increase the likelihood of finding a partner to collaborate with us in further developing this programme and bringing our therapeutics to market. With whom have you partnered to further your mission and research? A recent partnership between AdAlta and GPCR Therapeutics was established to evaluate a new cancer treatment approach combining beta blockers plus AdAlta’s CXCR4-inhibiting i-bodies. AdAlta is a clinical-stage drug discovery company developing novel therapeutic products from its i-body platform and we will evaluate AdAlta’s CXCR4 inhibiting i-bodies as cancer therapeutics, using GPCR Therapeutics’ proprietary combination inhibition approach. Can you speak to any recent milestones or successes that your company has achieved in its mission to develop cancer therapeutics targeting GPCR heteromers? In the past seven months, we have opened up our own independent US laboratory site in the San Francisco Bay area. As mentioned above, we have recently published one paper which supports our heteromer hypothesis with another GPCR known as histamine receptor H1 (HRH1). HRH1 is widely expressed in various cancers, and, like ADRB2, the level of co-expression of CXCR4 and HRH1 is related to poor prognosis, in this case, in breast cancer patients. The simultaneous expression of both receptors leads to the formation of the CXCR4- HRH1 heteromer, and this complex demonstrates enhanced signalling and migration capabilities. We have also submitted an additional manuscript that provides evidence for ADRB2 and heteromer formation in cancer cell lines endogenously expressing each receptor using a time-resolved fluorescence spectroscopy technique. Of course, our biggest milestone was conducting the numerous steps that are required to initiate a clinical trial. The tremendous work that ultimately led to proceeding into the clinic with our first site activation in February, was incredibly rewarding. How do you envision the future of cancer treatment and the role that GPCR-targeted therapies may play in this landscape? As we progress forward, we cannot think about one size fits all. Precision medicine is critical. With the developments in AI, I believe that we will be able to genetically determine the profile of the tumour, and integrate that information with multiple databases leading to more precisely treating the patients with the correct drugs. What is also critical is to determine what combinations are appropriate. Since I was intimately involved in the rise of checkpoint inhibitors, I see their success but also am clear that not all tumours respond so we need to determine what is the best approach for these patients. I also suspect that CAR-T will make great advances eventually leading to more cures. Currently, there is a long delay to produce the cells and the side effect profile is not ideal. Hopefully, we will see advancement in allogeneic CAR-T or CAR-NK. Because I have spent most of my career working on biologics, one area that I am particularly interested in is leading the company into this space. We only have one approved antibody drug targeting GPCR for cancer treatment. I see significant opportunities for us to consider bispecific antibodies that target two GPCRs or one antibody that can block the formation of the two GPCRs and thereby block signal crosstalk. To demonstrate our commitment to this area, we have recently hired an expert antibody engineer to move us quickly into this space. Ayesha Siddiqui

SPEAKING WITH 35 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Streamlining laboratory processes accelerates the development of therapies. Digitalisation is transforming the execution practices of biopharmacology and clinical research. In an age of digital innovation, researchers can simplify clinical trials and research and development by integrating lab data, resources, and processes into unified environments. Adopting Decentralised Clinical Trials (DCT) models can improve research outcomes, and productivity, with better compliance. Stakeholders (drug, vaccine, and medical device developers) and CROs must redefine end-to-end approaches to increase the efficiency, security, and accessibility of clinical trials. Digitalised clinical trials and R&D practices in pharmacovigilance can address operational constraints and development challenges. In an interaction with BioSpectrum, Jerome Armellini, Asia Head of Clinical Development & Operations Strategy and R&D Solutions (Asia) at IQVIA, Asia Pacific delves deeper into the decentralised drug discovery landscape. Edited excerpts; How do you define the essentials of a decentralised approach in the current drug discovery landscape? It is essential that such an approach is considered as early as the study design stage. Indeed, successfully executing DCTs is about more than selecting a technology platform or digital components. Every study will require a different combination of technologies, support services, and training to optimise results. This process is based on a thorough review of the targeted patient population, the trials’ inclusion/exclusion criteria, duration, patient expectations, protocols, endpoints, and other study requirements. Decentralised trials leverage technology, including connected devices, and specialised services to engage participants in the community and facilitate patient-centric care through remote pre-screening, tele-visits, at-home treatment and the increasing role of mobile research nurses and staff. While catering to a fast-moving drug discovery landscape, a decentralised approach aims to bring the patient voice to the trial, reduce the burden on “EBPs are leveraging digitalisation to drive innovation and improve patient outcomes” « Jerome Armellini, Asia Head of Clinical Development & Operations Strategy, R&D Solutions Asia, IQVIA Asia Pacific sites and patients, and increase trial awareness, diversity inclusion as well as reach to patients living further away from sites by expanding traditional site boundaries to deliver a more personalised trial experience. Finally, to ensure a successful decentralised trial, it is also essential for trial sponsors to address the unique concerns and motivations among different populations and demographics to effectively translate patients’ interest to trial participation, through the help of an end-to-end digital patient journey solution. How well are emerging biotechs and biopharmas leveraging digitalisation? Emerging biotechs and biopharmas (EBPs) have been increasingly leveraging digitalisation throughout the drug discovery process, from drug development strategies to decentralised trials. In designing more efficient and effective clinical trials, EBPs are increasingly using Artificial Intelligence (AI) and Machine Learning (ML) to leverage multi-omic data and algorithms that are based on historical clinical trials, real-world data and molecular data, to observe the responses of digital patients and improve trial outcomes. AI/ML can also be used to hone the clinical development plan by tailoring the trial to a specific population as algorithms can predict and gauge the trial’s effectiveness in the subpopulation and proposed indication. Overall, EBPs are leveraging digitalisation to drive innovation and improve patient outcomes, both globally and in APAC. However, the extent of digitalisation varies across regions and countries, depending on factors such as a regulatory

36 SPEAKING WITH BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com environment, infrastructure and many others. In their journey towards digitalisation, EBPs sometimes face challenges such as regulatory limitations and getting the right stakeholder support. However, with the help of an experienced CRO, they can successfully leverage digitisation by ensuring that stakeholders understand the benefits of digital adoption through education, training and support, and monitor regulatory developments closely. How do you describe the development and operational aspect of DCTs in the Japan and Asia Pacific region? The adoption of DCTs has rapidly soared in the last three years due to the rush to conduct clinical trials during and after the pandemic, and the increased competition among biotech companies. Additionally, the highest quarterly utilisation of decentralised methods shown in Q4 2022 suggests that the industry continues to push into new territory with this set of innovations. In Asia Pacific, the increase in DCT adoption has inevitably brought about regulatory considerations to ensure patient safety and secure data sharing between patients and investigators. China has imposed strict data privacy laws for the use of AI/ ML when targeting and engaging patients, such as the Personal Information Protection Law (PIPL) and Personal Data Security Specification (PDSS). EBPs and biotech companies in the Asia Pacific need to examine regulations in the areas of data privacy, data residency, and data stewardship before embarking on digital adoption. Several regulators in the Asia Pacific and in the rest of the world, are also developing recommendations for sponsors on DCT deployment (such as, but not limited to, the EMA Recommendation Paper On Decentralised Elements published in December 2022). In Japan, the Pharmaceuticals and Medical Devices Agency is planning to provide DCT guidelines. With this, DCT adoption in Japan will increase. It is therefore helpful to engage a CRO that knows the best practices across different countries and has the global regulatory landscape understanding, operations support and technology to support digital activities of sites, patients, and sponsors, to accelerate digital adoption in the region. What should clinical and biopharma operations consider when adopting DCTs? How do companies weigh elements at risk? Clinical and biopharma operations can consider these aspects when adopting DCTs. First, the trial endpoints must be measurable through a DCT approach and appropriate trial support tools can be adopted based on the clinical trial phase. Second, the regulatory environment in chosen countries must support the required DCT elements such as tele- or home visits, direct-to-patient investigational medicinal product (IMP) shipment, etc. Third, operations must ensure a convenient end-to-end patient experience throughout the DCT process. Decentralised trials are more than just a technology, there is still the need to include a strong human touch to support patients and sites. Companies can weigh all those critical elements by finding a partner with the expertise to run such trials globally and understand the local compliance and restrictions. Sponsors that partner with mature providers, for a managed service or full-service, will benefit from a successful DCT experience. An experienced partner that is very familiar with the General Data Protection Regulation (GDPR) and data privacy laws, will have the resources to support the needed compliance. How do you summarise the benefits of adopting DCTs? What is the current status of DCTs in the APAC region? A key benefit of DCTs is the patient-centricity of the trial design. DCTs provide a convenient endto-end patient experience that reduces the patient burden, e.g., cutting down travel times and costs, and improving patient engagement and satisfaction. This leads to new patient access, compliance and retention, faster enrolment and trial completion with measurable benefits for sponsors. Many EBPs who develop medicines for rare diseases are also able to enrol patients that would not have participated in a study under the traditional model. DCTs can also decrease site burden by using a technology platform that acts as a better engagement channel and allows EBPs to gain access to real-time patient progress on demand. A whitepaper that compared DCTs to traditional study models showed that DCTs delivered time and cost efficiencies at virtually every point in the clinical research journey. However, there will always be a role for in-person trials as some patients feel more comfortable being examined by a clinician. Hybrid models, a mix of faceto-face interactions and technology access, are now a permanent fixture of the clinical trial landscape. The adoption of DCTs is gaining momentum in APAC, such as, but not limited to Australia, China, South Korea, Taiwan, Japan and Malaysia, with many countries starting to implement or develop regulations and/or guidelines for these trials. Hithaishi C Bhaskar [email protected]

SPEAKING WITH 37 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com I n March 2023, Singapore-based Aevice Health, a MedTech company that focuses on developing patient management solutions for chronic respiratory diseases, announced that its flagship product, AeviceMD Monitoring System, was granted approval by Health Sciences Authority (HSA) in Singapore. Now the firm is seeking US FDA clearance. In an interview with BioSpectrum Asia, Adrian Ang, CEO of Aevice Health, shared some insights about the distinctive features and privacy concerns surrounding wearable devices. Edited excerpts; How does the AeviceMD Monitoring System work? The AeviceMD Monitoring System is like a virtual doctor with a stethoscope — it is a patient management platform that is powered by a smart wearable stethoscope to detect abnormal lung sounds in diseases like asthma and COPD so that exacerbations can be intervened in time. The lightweight sensor continuously and passively analyses chest sounds and logs the measurements (respiratory rate, heart rate, and wheeze) onto a userfriendly app to track clinical deterioration over time. Patients have the choice to share this information with their healthcare professionals. Alongside its ability to record and playback chest sounds like a digital stethoscope, the solution paints an overview of the patient’s lung health in-between consultations, empowering doctors to make expedited and informed clinical decisions anytime and anywhere. How do you envisage that the technology would be typically used? Is this something that is primarily for home use or for use by clinicians? Currently, the focus of the AeviceMD Monitoring System is on home monitoring, where it is used as an at-home solution for patients with asthma and COPD. Our system offers continuous monitoring of patient’s respiratory health, with a focus on tracking overall progress and early detection of exacerbations before they escalate. By providing patients with personalised insights, the AeviceMD Monitoring System empowers them to manage their conditions more effectively and “Protecting patient information is essential for building trust with both patients and healthcare providers” « Adrian Ang, CEO, Aevice Health proactively, ultimately leading to an improved quality of life. The convenience of using the AeviceMD Monitoring System at home allows patients to receive long-term care without the need for frequent hospital visits. Our goal is to not only reduce the burden on healthcare systems but also help patients feel more in control of their own health. Furthermore, patients can easily share their data with clinicians, enabling healthcare professionals to remotely track their progress and make informed decisions about their treatment plans without patients leaving the comfort of their homes. What were some of the challenges in developing this? Developing the AeviceMD Monitoring System presented a unique set of challenges. One of the primary obstacles we encountered was creating a compact stethoscope and sensor that can accurately capture and analyse respiratory sounds. For the device to be comfortable and usable across a wide range of ages from paediatrics to geriatrics, it has to be lightweight and highly miniaturised without compromising on the quality of acoustic signals the sensor collects. After much R&D, we have managed to develop one of the world’s smallest wearable stethoscopes for continuous monitoring of breath sounds with high accuracy for chronic respiratory disease. Another challenge we faced involved adhering to various regulatory requirements and standards to ensure the safety and effectiveness of the AeviceMD Monitoring System. Apart from clinical studies, we have also conducted extensive user testing to validate

38 SPEAKING WITH BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com the accuracy and usability of our product. This process required a significant investment of time and resources to meet regulatory standards and deliver accurate, reliable results for our end users. However, while the development of the AeviceMD Monitoring System was challenging, it is a rewarding journey at the same time. We believe it holds the potential to improve the way respiratory care is delivered, ultimately improving the lives of those living with asthma and COPD. Where do you currently see the most significant gaps in respiratory care? Is there room for innovation? Respiratory conditions like asthma and COPD are often underdiagnosed or diagnosed at later stages. Developing enhanced screening and diagnostic tools to identify respiratory issues early can lead to more effective interventions and improved patient outcomes. The COVID-19 pandemic has underscored the importance of remote monitoring and telehealth services for managing chronic conditions, including respiratory diseases. By expanding telehealth solutions and remote monitoring devices, such as the AeviceMD Monitoring System, patients and healthcare providers can manage respiratory infections more effectively and conveniently, reducing hospital visits and readmissions. In many regions, access to quality healthcare services, equipment, and medications for respiratory conditions is limited. Innovations in affordable, portable devices and telemedicine can help bridge this gap, offering better care for underserved populations. Could stringent regulations enhance the perception of wearables from being perceived as merely fashionable gadgets with some diagnostic features to being regarded as more credible medical devices? We believe that stringent regulations could indeed enhance the perception of wearables like the AeviceMD Monitoring System, transforming their image from fashionable gadgets with some diagnostic features to credible medical devices. This is because strict regulations and standards help ensure that these wearables meet essential criteria for safety, accuracy and reliability. For instance, when wearable devices like the AeviceMD Monitoring System undergo rigorous regulatory oversight and adhere to established medical device guidelines, we believe this bolsters the device’s credibility in the eyes of both healthcare professionals and patients. As a result, such wearables are more likely to be accepted and integrated into healthcare practices, with companies demonstrating a commitment to providing accurate, reliable data and genuinely addressing healthcare needs. Moreover, this regulatory compliance fosters trust and confidence among patients and healthcare providers, encouraging them to use and recommend these devices as part of a comprehensive care plan. In this way, stringent regulations can play a pivotal role in elevating the status of wearables like the AeviceMD Monitoring System, shifting their perception from mere gadgets to legitimate, valuable tools for managing and improving health outcomes. It is impossible to have a comprehensive discussion about the intersection of technology & healthcare without addressing privacy concerns. What is your perspective on this matter, & how does Aevice Health ensure the security of its devices? We acknowledge that privacy concerns are of utmost importance when discussing the intersection of technology and healthcare. As a provider of healthcare technology solutions, Aevice Health is committed to ensuring the security and privacy of patient data collected and transmitted by our devices. We believe that protecting patient information is essential for building trust with both patients and healthcare providers. To ensure the security of our platform, we ensure that the communication channels in which data is transmitted between the devices to healthcare professionals are highly encrypted. We also implement strong access controls to ensure only authorised users are allowed access to the patient data. These are just some of the many steps we have taken to ensure data integrity and patient privacy. Lastly, we adhere to relevant healthcare data protection regulations, such as Health Information Privacy and Portability Act (HIPPA) in the United States. By maintaining compliance with these regulations, we ensure that our data handling practices meet the rigorous requirements set forth by the respective authorities, further emphasising our commitment to the privacy and security of patient information. What’s ahead for Aevice Health? In the near future, we plan to improve the integration of our devices with telehealth platforms, facilitating seamless communication between patients and healthcare providers. This will enable more efficient remote consultations and expedited adjustments to treatment plans when required. Additionally, we are dedicated to broadening our global reach, making our solutions accessible to underserved populations worldwide. Ayesha Siddiqui

PRENATAL TESTING 39 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Non-invasive Prenatal Testing Runs Global 2023 is the year of the growing preference for early disease detection and prevention, minimally invasive testing methods, and consumerization in diagnostic testing. Non-invasive prenatal testing (NIPT) is a powerful tool empowering clinicians and prospective parents with valuable clinical insights to make informed decisions regarding pregnancy management. With guidelines for NIPT expanding and payers reimbursing for screening procedures, clinically validated virtual care platforms will open the aperture to a larger addressable NIPT market. Non-invasive prenatal testing (NIPT) requires the evaluation of foetal cells or cell-free DNA obtained from a maternal blood sample during pregnancy. Since its debut in the United States and China/Hong Kong in 2011, the molecular screening test used to detect foetal congenital anomalies is the fastest-spreading prenatal genetic technology globally, accounting for 38 per cent of the prenatal genetic testing market. Technological innovations shaped by commercial interests Although Next Generation Sequencing (NGS)- based methods have been majorly used, technology evolutions encompassing qPCR, dPCR, and amplification technologies aim to further drive the quality of tests and reduce costs. The commercial sector is broadening its scope to include sex chromosome aneuploidies, rare autosomal trisomies, and sub-microscopic copy-number variants. Automated in-lab workflows and remote patient monitoring in pregnancy are enabling providers to better manage pregnancies and risks. A new generation of screening tests is promising to enhance pregnancy management by providing information about placental development acquired in real-time with trophoblast cells, implying a focus on targeted management of at-risk pregnancies. As the technology evolves, debates surrounding the expansion of NIPT beyond chromosomal abnormalities will increase. Hence for test developers, the role of private clinics and biomedical professionals is key to spearheading access, especially in underpenetrated regions. Another strategy central to « Amartya Bose, Healthcare & Life Sciences Industry Analyst, Frost & Sullivan attracting customers includes validation studies. While clear guidelines and services to address potential medical and ethical issues are critical for the responsible future use of NIPT, leveraging complementary informatics technologies that enhance data analysis and reporting capabilities will be vital in accelerating new product development, in addition to expanding core intellectual property portfolio and sample preparation technology. Commercial potential across geographies With 140 million babies born globally, NIPT represents an exciting opportunity, with many geographies still in the nascent stages of adoption. A large US market offers significant potential. There are about 4 million babies born in the United States each year, and 97 per cent of high-risk pregnancies and 56 per cent of average-risk pregnancies are covered. NIPT is widely adopted throughout Europe, though only a few countries have a national policy that regulates its use. NIPT for all pregnancies is covered in the Netherlands and Belgium as a first-tier screening test. Within Asia-Pacific, the rising number of women postponing pregnancy until later in life across China, Australia, India, and Japan is favouring adoption. Thailand and Vietnam are other markets with sizable populations offering significant opportunities. Expanded clinical applications, such as autosomes and microdeletions, spur innovation in the sector, making it a viable industry in the long term. Growing competitiveness with substantial new entry The market is in the growth phase. The dominance of large-scale companies in the industry, including

40 PRENATAL TESTING BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Natera, Illumina, LabCorp, Roche Molecular Systems/ BioReference Laboratories, and BGI Genomics, is challenged by new entrants in the field embracing non-PCR, non-NGS-based methods to enable broader adoption, like the Vanadis NIPT system from PerkinElmer. To further reduce implementation costs, companies like Atila Biosystems are harnessing the power of digital PCR to detect targets that indicate possible chromosomal anomalies—trisomy 21 associated with Down Syndrome, trisomy 18 associated with Edwards Syndrome, and trisomy 13 associated with Patau Syndrome and foetal fractions. As NIPT marches toward becoming the standard screening tool for pregnancies worldwide, companies like Bionano Genomics emerge as game changers, with optical genome mapping (OGM) analysis providing high-throughput, comprehensive follow-up genome analysis in case of a positive NIPT screen or for highrisk pregnancies following an abnormal ultrasound. OGM can be developed as the basis of a new standard of care in prenatal genetic analysis because of its ability to identify all types of structural variants. Other notable new participants encompass Dutch biotech VyCAP, Danish ARCEDI Biotech, and US-based RareCyte, which developed methods for separating circulating trophoblast cells from maternal blood samples. Rapid advancements in novel techniques imply an enriching product matrix for decentralised NIPT. Growth strategy to address the surge in test volume 2023 is the year of the growing preference for early disease detection and prevention, minimally invasive testing methods, and consumerization in diagnostic testing. The three macro trends imply volume growth and improved test economics for NIPT, driven by growing awareness of preventing chromosomal anomalies such as Downs Syndrome. With guidelines for NIPT expanding and payers reimbursing for screening procedures, clinically validated virtual care platforms that enable obstetrician-gynaecologists to deliver prenatal care offer risk-specific experiences, detect risk more quickly, and automate critical elements of care, driving the adoption of guidelinerecommended NIPT. As adoptions surge, workflow improvements via artificial intelligence-based technologies (deep neural networks and probabilistic modelling) learning from millions of processed samples are poised to improve positive predictive value, lower the cost of goods sold, and reduce the no-call rate. Cell-based NIPTs represent another promising field in research, addressing the challenges associated with whole-foetal-cell isolation from the maternal blood draw. However, evidence will decide the success of this next-generation approach in bringing tests from screening to diagnostics. The path of foetal cells might be long, but the rewards are promising. New technologies must undergo validation for responsible clinical implementation. Increasing public awareness of testing is critical to prepare prospective parents for crucial decision-making. Remote pregnancy monitoring platforms delivering medical-grade foetal wellness checks will empower providers and patients to expand care delivery. Due to the advanced nature of technology, achieving economies of scale is key to incremental growth. Hence, techniques should enable providers to support expectant parents with more accurate, timely, and personalised pregnancy management options. NIPT is a powerful tool empowering clinicians and prospective parents with valuable clinical insights to make informed decisions regarding pregnancy management. Technological advances and responsible innovation make it a promising screening avenue for the detection of additional genetic conditions. Industry participants carving distribution and marketing agreements to expand access and coverage, in addition to product development and commercialization agreements, will effectively navigate the coming age of distributable kits, offering new solutions to expand testing to all autosomes and microdeletions. Empowering laboratories with computational frameworks for sequencing-based NIPT analysis to enable the characterisation of disease transitions and their reflection in the blood will open the aperture to a larger addressable NIPT market. NIPT is a powerful tool empowering clinicians and prospective parents with valuable clinical insights to make informed decisions regarding pregnancy management. Technological advances and responsible innovation make it a promising screening avenue for the detection of additional genetic conditions. Industry participants carving distribution and marketing agreements to expand access and coverage, in addition to product development and commercialization agreements, will effectively navigate the coming age of distributable kits, offering new solutions to expand testing to all autosomes and microdeletions.

SINGLE-CELL TECH 41 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Single-cell analysis technology has contributed significantly to medical research. In the past few years, single-cell RNA sequencing technologies have been widely used for analysing cancer constituent cells, identifying cells causing therapeutic resistance, and analysing gene signatures of resistant cells. The single-cell applications will continue moving “from bench to bedside,” especially with further innovation in related technologies. Since the publication of the first single-cell RNA-sequencing (scRNA-seq) study nearly 15 years ago, a “cellular resolution revolution” has propelled single-cell technologies from academic labs into more mainstream discovery, development and clinical research applications. Understandably, the swift uptake and rapid pace of technological innovation in this field since then can seem overwhelming. Would-be single-cell researchers have myriad options and opportunities to choose from when organising their studies. To begin to make sense of this burgeoning field of study, a better understanding of the origins of these technologies, common challenges associated with single-cell studies and specific capabilities to look for in tools for single-cell isolation and analysis is an ideal starting point. The origins To begin to understand current applications and future opportunities for single-cell technology, it can be helpful to first understand the technologies that preceded scRNA seq. One of these is bulk RNA sequencing – a method for transcriptomic analysis that measures the average expression of pooled cell populations, tissue sections or biopsies. This approach offers researchers a comprehensive look at a given sample, but it lacks the ability to drill down to the single-cell level. Flow cytometry is another early technology used for single-cell research and is the basis for fluorescence-activated cell sorting (FACS). This technique is used to isolate individual cells from a sample into cell populations, labelling each with fluorescent markers and sorting them based on the colour of the marker. This method allows researchers to analyse the properties of each population individually. While this approach offers Understanding Single-Cell Technology in clinical research applications « Dr Irene Whitney, Director of Applications and Collaborations, Honeycomb Biotechnologies, United States a more granular look at cell properties, it is not as comprehensive as others. In contrast to the aforementioned methods, scRNA-seq is both comprehensive and highresolution. It allows for the transcriptomic analysis of heterogeneous tissue or dynamic processes in one single experiment – offering researchers the expression profiles of individual cells. Challenges Building on this foundational knowledge of technologies used for single-cell research, awareness of the potential pitfalls in these studies is also helpful to know. Inherently, there are technical complexities involved in working at the single-cell level. Across all applications, two factors are of the utmost importance: sample quality and sample preparation. In terms of sample quality, fresh samples are considered the gold standard for single-cell research. Because RNA and protein expression changes rapidly in cells once they are removed from a host, efficient sample processing as soon as possible after collection is ideal. This is particularly challenging in multi-site studies where samples are being collected at multiple, sometimes remote locations, which will then require careful storage and shipping to maintain sample quality. Even still, fresh samples may not be available in all cases. In these instances, lower quality samples will suffice, but may end up hindering the final data outputs being analysed. A second key challenge is sample preparation. Once a sample has been collected and processed, sample preparation can become an unintended source of technical variation and batch effects due to cell dissociation. Any enrichment required by rare cell types could also skew data and results yielded. Fortunately, these risks can be reduced or avoided

42 SINGLE-CELL TECH BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com altogether with sample prep best practices. For example, having an automated cell counter that is accurate and has two colour fluorescence for live/ dead markers (such as acridine orange/propidium iodide) is essential for rapid quality control and optimisation of sample preparation to create a protocol that provides the best possible viability. Innovative solutions In addition to following best practices for sample collection and preparation, scRNA-seq technology developers are innovating where research efficiencies are needed most. Sample preservation is one of these areas. In many cases, researchers will store single-cell samples via cryopreservation – the process of collecting and storing cells, tissues, or organs at freezing temperatures for later use. While it’s a commonly used method, it may also cause undue stress and damage the sample. This is especially true for more fragile sample types such as clinical biopsies, or cell-types such as granulocytes, hepatocytes, and neurons. For instance, Honeycomb Biotechnologies is helping researchers circumvent these limitations with its flagship offering, the HIVE scRNAseq Solution, through the gentle isolation and capture of single cells combined with stable singlecell storage after capture. Single cells can be pipetted directly into handheld HIVE devices and the RNA of captured cells is preserved to lock in molecular signals. Cell-loaded HIVEs can then be stored until ready for Honeycomb’s scalable workflow for making single-cell RNAseq libraries. By preserving the sample at time of collection, the HIVE solution maintains the full diversity of cells in a sample, who’s transcriptomes can then be extracted, amplified and analysed at a later date. Transportation is another key challenge for single-cell researchers and one that Honeycomb Biotechnologies has also aimed to solve. Different sample types, storage times and variable shipping protocols add complexity to how and when single-cell samples are moved from collection site to the lab for processing. Stable storage and shipping of cell-loaded HIVEs enables time-courses, sporadic or end-of-day samples, distributed collection sites with centralised processing, and multi-site collaborations. Without the need for specialised equipment, meaning the workflow can be run in most labs. This alone expands opportunities for researchers pursuing broader studies, especially those in lower resource settings. Future opportunities Despite some of the challenges involved, innovation in scRNA-seq technologies continue to make vast and varied applications of single-cell research possible. One field seeing increased interest and activity is innate immunology. These studies involve the capture of fragile cell types, such as neutrophils – the white blood cells playing a central role in inflammatory responses. Another booming area of single-cell research is in the field of infectious diseases, where the careful handling and storage of samples is of the utmost importance. Additionally, meaningful single-cell discoveries are being made in the arena of clinical research using human samples and minimally invasive biopsies. Looking ahead, we can expect single-cell applications to continue moving “from bench to bedside,” especially with further innovation in related technologies. The development of these tools – whether they’re in industry or academia – will continue to find ways to optimise research efficiencies and reduce the cost of performing these studies. Ultimately, the deeper understanding and democratisation of tools used to complete them will result in new discoveries that improve human health. Innovation in scRNA-seq technologies continue to make vast and varied applications of single-cell research possible. One field seeing increased interest and activity is innate immunology. These studies involve the capture of fragile cell types, such as neutrophils – the white blood cells playing a central role in inflammatory responses. Another booming area of single-cell research is in the field of infectious diseases, where the careful handling and storage of samples is of the utmost importance.

Tanoto Foundation and Tsinghua University Education Foundation have signed a Memorandum of Understanding (MoU) in Beijing, heralding a greater level of strategic cooperation in the medical field, including the setting up of the first-ever bilateral medical scholarship between National University of Singapore (NUS) and China’s Tsinghua University. The MoU covers three key programmes including the bilateral scholarship programme between NUS and Tsinghua, the Tanoto Foundation Chair Professorship, and the Tanoto Foundation Clinician-Investigator Award tied to the Centre for Physician Scientist Development at Tsinghua. Across all programmes, the collaboration will focus on talent development and training, as well as medical research, development, and application. Under the bilateral scholarship between NUS and Tsinghua, two students from each university will undertake various medical and health related courses in exchange, offered respectively at the Tsinghua University School of Medicine and NUS, under both the NUS Yong Loo Lin School of Medicine and the Duke-NUS Medical School. National University of Singapore, Tsinghua University announce bilateral medical scholarship The Hong Kong Polytechnic University (PolyU) has joined hands with China-based startup Hai Robotics, to officially launch the cutting-edge Smart Delivery System in its new Artificial Intelligence and Robotics Lab (AIR Lab) at the University’s Industrial Centre. The Smart Delivery System aims to strengthen PolyU’s robotics education and encourage co-creation and innovation among students and researchers. The AIR Lab is an innovative teaching and research platform, with a total area of 1,800 square metres. It is equipped with advanced robotic arms, robots, automatic guided vehicles, drones, as well as machine learning kits related to AI robotics and Industry 4.0. The Laboratory allows educators, students and researchers to explore various aspects of the emerging field of collaborative robotics, including application development, component fabrication, control system design, autonomous system development, and intelligent and AI algorithm design for robots. PolyU lays focus on robotics education in healthcare New international opportunities are open to Sydney researchers and students as the University expands partnership agreements with the University of Glasgow, Scotland and the University of California San Diego, US. The University of Sydney (also known as Sydney University), in Australia and University of Glasgow’s joint PhD agreement will see PhD candidates given the opportunity to undertake research and to be supervised by leading researchers across both institutions. This will provide candidates from multiple disciplines with access to a wider range of expertise and resources, allowing them to develop a more comprehensive understanding of their research area. To support joint PhD students participating in the programme, the University of Sydney will provide outbound students with a one-off $5000 scholarship to support their travel and accommodation at the University of Glasgow. Sydney University strengthens international ties in research and innovation ACADEMICS NEWS 43 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com

Intas Pharma appoints Dr Narahari Chittoor Rao as Associate VP- Cell & Gene Therapy Norway-based Coalition for Epidemic Preparedness Innovations (CEPI) has announced a new board member- Dr Yasuhiro Suzuki. Dr Suzuki has been appointed to the Board where he will sit as a representative of the CEPI Investors Council. This appointment was made following an election by CEPI’s investors’ representatives. He will replace Dr Ichiro Kurane whose term as Investor Board member has concluded. Dr Suzuki served as Vice-Minister for Health and Chief Medical and Global Health Officer for the Government of Japan’s Ministry of Health, Labour and Welfare. He served as Executive Director for Social Change & Mental Health and Executive Director of Health Technology and Pharmaceuticals at the World Health Organisation (WHO). His expertise covers infectious diseases, mental health, environmental health, and health research policy. CEPI appoints Dr Yasuhiro Suzuki to the Board Intas Pharmaceuticals from India has announced the appointment of Dr Narahari Chittoor Rao as Associate Vice President- Cell & Gene Therapy. Dr Rao has over two decades of experience in the biotech industry having worked for both large multinational companies and startups. In addition to traditional biologicals such as recombinant proteins and antibody based projects, he has also worked with newly emerging modalities such as mRNA and viral vectors. His experience spans process and product development from preclinical stage to commercially manufactured products. He was previously serving as the Head of Global Process Development at Pune-based Enzene Biosciences. He has also worked with companies like Ultragenyx Pharmaceutical Inc., Moderna Therapeutics, Bristol-Myers Squibb, GlaxoSmithKline, Amgen, to name a few. 44 PEOPLE NEWS BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Prof. Alan Wong takes charge as President of AHPC in Singapore Professor Alan Wong Wai Pong will assume the role of President of the Allied Health Professions Council (AHPC) from April 1, 2023, taking over Dr Lau Hong Choon who has helmed the Council for 10 years from 2013 to 2023. Prof. Wong, a physiotherapist by training, has represented AHPC in various national professional committees. He was a member of the pro tem AHPC under the Ministry of Health (MOH) from 2010 to 2012. He led the Physiotherapy Implementation Committee from 2011 to 2012 to implement the first phase of the AHP Act after it was passed in Parliament in 2011. Since 2013, Prof. Wong has been a member of AHPC and chief trainer of supervisors in the five Allied Health professions, namely diagnostic radiographers, occupational therapists, physiotherapists, radiation therapists and speech therapists. He was also the chairperson of the AHPC’s Complaints Panel between 2014 and 2022. On the professional front, he worked in Singapore General Hospital from 1996 to 2012 before assuming the role of Cluster Director, Health and Social Sciences (HSS) Cluster, Singapore Institute of Technology (SIT) from 2015 to 2022, where he was involved in setting up allied health programmes. He is currently a Professor at SIT.

HCmed Innovations appoints new CSO Taiwan’s HCmed Innovations Co., a contract development and manufacturing organisation (CDMO), has announced the appointment of Dr Gunilla Petersson, as the new Chief Scientific Officer (CSO). In her role as CSO, Dr Gunilla will contribute to the company’s strategic business development, while providing professional advice with regards to combination product development. Former Science and Innovation Director of Inhaled Drug Delivery at AstraZeneca, Dr Gunilla joins HCmed with more than 29 years of experience in the pharmaceutical industry. Affiliated to the Innovation Strategies & Internal Liaison segment, in most recent years, she dedicated herself to novel technology scouting, due diligence activities, and scientific marketing. During her extended and successful professional career, she has accumulated a vast number of connections with global pharmaceutical companies and renowned experts in the field. PEOPLE NEWS 45 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Hugel, a South Korea-based medical aesthetics company, has announced the appointment of Suk-yong Cha, former Vice chairman & CEO of LG Household & Health Care Co. (LG H&H), as Hugel’s new Executive Chairman and Chairman of the Board. Cha previously served as the CEO of LG H&H for 18 years from 2005 to 2022, while setting a record of 17 consecutive years of increasing sales and operating profits. In particular, he transformed LG H&H into the global beauty company by enhancing the portfolio of each business divisions through 28 important M&As and expanding the company’s reach into global markets, including North America, China, and Japan. In addition, Cha demonstrated his corporate management capabilities in various industries while serving as President & CEO of Procter & Gamble (P&G) Korea and President & CEO of Haitai Confectionery & Foods Co. The appointment of Cha is expected to aid Hugel in becoming a global top-tier company. Based on his know-how in the field of aesthetics and experience of expanding into global markets, Hugel plans to accelerate its growth by improving the global strategy for its botulinum toxin, HA filler, and cosmetics and strengthening the development of new businesses. Hugel appoints Suk-yong Cha as Executive Chairman Agilent announces Thought Leader Award for Dr Chenli Liu Agilent Technologies has announced that Dr Chenli Liu has been selected to receive an Agilent Thought Leader Award. The award will support his pioneering studies on synthetic biology, specifically research to develop a synthetic cell capable of reproducing by coordinating individual cell properties utilising a bottom-up approach to understand biological circuits. Dr Liu is the Vice President of the Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences in China. He is also the founder of iSynBio at SIAT, the largest research institute focused on synthetic biology, as well as the chief scientist of Shenzhen Infrastructure for Synthetic Biology. His lab at iSynBio is dedicated to the research of quantitative synthetic biology. Based on the research idea of quantitative analysis and synthetic reconstruction, it focuses on the basic principles of the formation process of complex biological systems, as well as the rational design principles of synthetic biological systems and other important scientific issues.

Three expert teams in Australia will share $1.5 million to undertake research into causes of dementia through projects funded by the National Health and Medical Research Council (NHMRC). NHMRC is partnering with the Japan Agency for Medical Research and Development (AMED) to increase the understanding of dementia and improve health outcomes for people living with the condition. Dr Chien-Hsiung (Alan) Yu, from the Florey Institute of Neuroscience and Mental Health at the University of Melbourne, will work with collaborators from the University of Tokyo and Niigata University to investigate how tau protein build-up triggers neuron death in the brain and develop therapies for preventing this damaging protein cascade. Dr Yijun Pan, also from the Florey Institute of Neuroscience and Mental Health at the University of Melbourne, will work with collaborators from Tohoku University and the National Center for Geriatrics and Gerontology to focus on accurate diagnosis, potential therapeutic targets and modifiable risk factors for patients living with vascular or frontotemporal dementia, with the goal to improve quality of life of people living with dementia. International dementia research collaboration to address key health challenge in Australia and Japan Brain tissue grown in a laboratory by University of Queensland (UQ) researchers in Australia will be used to test a treatment for a rare disease in children and help unlock therapies for a range of neurological disorders. Prof. Ernst Wolvetang and his team at UQ’s Australian Institute for Bioengineering and Nanotechnology (AIBN) have secured almost $1 million from the Medical Research Future Fund (MRFF) to test gene therapies for children with a specific type of Hereditary Spastic Paraplegia (HSP). HSP Type 56 (SPG56) is a degenerative brain disease that causes children to lose the ability to sit, stand, walk, or talk and there is currently no cure or treatment. Prof. Wolvetang hopes to find one, by testing gene therapies for the first time on patient-derived organoids - tiny, synthetic organs grown from a patient’s own cells. The SPG56 project will be the first time in Australia that brain organoids have been used to test the safety and efficacy of a gene therapy approach for HSP. Australian scientists grow brain tissue in lab to treat neurological disorders India develops screening device to assess blood vessel health A team of researchers at the Indian Institute of Technology Madras (IIT-M) has developed a novel, non-invasive device to assess the health and age of blood vessels and thereby provide early screening for cardiovascular diseases. Called ARTSENS, it is designed such that it can be used in routine medical examination by even non-experts, to assess and predict vascular health. It is powered by a proprietary non-imaging probe and an intelligent computing platform and is developed by the Healthcare Technology Innovation Centre (HTIC) at IIT-M. The device has been assessed on more than 5,000 human subjects. The technology already has five utility patents in the US, European Union and India, 10 design patents and awaits awarding of 28 patents in various jurisdictions. The product is ready for technology transfer and commercialisation after extensive testing. The IIT-M team intends to deploy this to conduct over a million vascular screenings per year. ARTSENS has been approved for clinical studies in India, US, and Europe. 46 R&D NEWS BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com

Victoria University of Wellington and University of Auckland, in New Zealand (NZ) have been named as co-hosts of a governmentfunded Ribonucleic Acid (RNA) Development Platform. The platform is supported by the Malaghan Institute of Medical Research and the University of Otago, with Dr Kjesten Wiig of the Malaghan Institute and Prof. John Fraser of the University of Auckland as the interim co-directors of the platform. Initial funding of $500,000 is being provided to the RNA Development Platform to prepare a seven-year research plan. This plan will be supported by a further $69.5 million over seven years to support capacity and capability-building in the sector. The platform will bring together RNA researchers from around the country. The results will come from a partnership approach that sees some of New Zealand’s leading research institutes and companies working to a shared goal of building this important technology in New Zealand. Interim co-director Dr Kjesten Wiig from the Malaghan Institute says RNA technology presents a significant opportunity for New Zealand to supercharge its thriving biotech sector and become a leader in the development of novel RNA therapeutics. New funding by NZ to boost RNA research in vaccines & healthcare A research team from Pohang University of Science and Technology (POSTECH), in South Korea, has engineered an artificial kidney that allows for the early detection of adverse drug reactions. The kidney plays a vital role in maintaining homeostasis within the body by eliminating toxic and superfluous substances in the bloodstream, including waste generated during metabolic processes, through urine. Nevertheless, toxicity can also be induced in the kidney from certain medications. Nephron is the fundamental structural and functional unit in the kidney. It encompasses a network of small blood vessels called the glomerulus, twisted into a convoluted thread-like shape, contributing to forming a kidney corpuscle along with glomerular capsules. It also plays a role in removing waste from the blood. When an excessive quantity of drugs is administered, the nephron is often the first organ to exhibit drug toxicity in the body. Korea designs artificial kidney for early detection of drug toxicity Tuberculosis (TB) patients can look forward to a much-shortened treatment period, compared to the current six-month treatment regimen used globally, based around the antibiotic rifampicin, or rifampin as it is called in the United States. In a groundbreaking study conducted across Asia and Uganda, Africa, the research team from the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), National University Hospital (NUH) and Singapore Clinical Research Institute (SCRI), led by Prof. Nicholas Paton from the Department of Medicine (NUS Medicine), found that a TB treatment strategy with an initial 8-week treatment period followed by retreatment of a small minority who were not cured, showed the same efficacy level as the standard 6-month treatment, but halved the average total time on treatment. The TRUNCATETB trial was designed and coordinated from Singapore across a network of 18 sites in Indonesia, Philippines, Thailand, India and Uganda, Africa. This multi-site trial was supported by SCRI, which provided support in patient randomisation, data management, pharmacovigilance, and statistical analysis. According to the researchers, this trial has the potential to transform the way people think about treating tuberculosis, and the way that clinical trials are done. Singapore conducts 8-week treatment trial for TB patients R&D NEWS 47 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com

Shimadzu Corporation, Kyushu University, and Kazusa DNA Research Institute, have recently opened the Auto Biomolecular analysis Systematisation Laboratory (ABiS Lab) on the first floor of the Healthcare R&D Centre, a research and development building at the Shimadzu Head Office in Japan. This lab will be a centre for collaborative research (Project name: Intelligent Biomolecular Screening Project for Advanced Healthcare), aimed at the development of an integrated platform for lipid analysis. Shimadzu high-performance liquid chromatograph mass spectrometers (LCMS) and supercritical fluid chromatography mass spectrometers (SFC-MS) are installed in ABiS Lab. Using ABiS Lab., the three parties will develop the analytical conditions, pretreatment procedures, standard samples, and measurement data analysis systems necessary for setting integrated standards in lipid data acquisition and analysis, aiming to complete the platform to integrate them. Triglycerides, cholesterol, and other lipids are now of interest because of their relationship to health promotion and various diseases, heightening the necessity for accurate measurement data. Shimadzu to develop integrated platform for lipid analysis BD introduces advanced ultrasound technology for optimal IV placement Germany-headquartered Sartorius Stedim Biotech, a leading international partner of the biopharmaceutical industry, has signed an agreement to acquire Polyplus for approximately 2.4 billion euros from private investors, including ARCHIMED and WP GG Holdings IV B.V., an affiliate of Warburg Pincus. Polyplus, with around 270 employees, develops and produces transfection as well as other DNA/RNA delivery reagents and plasmid DNA in high quality and GMP grade. These are key components in the production of viral vectors used in cell and gene therapies and other advanced medicinal therapeutic products. Recording significant growth rates, Polyplus is expected to generate sales revenue in the upper double-digit million-euro range and a very substantial EBITDA margin in 2023. The proposed transaction is subject to customary conditions, including completion of the information and consultation of the works’ council and approval by regulatory authorities and is expected to close during the third quarter of 2023. Founded in 2001, Polyplus is based in Strasbourg, France, and has offices in France, Belgium, the US, and China. Sartorius Stedim Biotech acquires Polyplus for €2.4B BD (Becton, Dickinson and Company), a leading global medical technology company based in the US, has launched a new, easy-to-use advanced ultrasound device with a specialised probe designed to provide clinicians with optimal IV placement. The BD Prevue II System addresses an unmet need in IV access through real-time needle depth markers. The system features the BD Cue Needle Tracking System, offering a highquality ultrasound image of the needle trajectory, and is compatible with BD Cue Needle Tracking-enabled catheters. Simulated studies show that pairing a needletracking system with ultrasound guidance may help reduce the number of attempts and time to successful vessel access which, according to the American Institute of Ultrasound in Medicine, may make vascular access procedures safer and easier for clinicians and patients. More than 90 per cent of hospitalised patients receive IV therapy through a peripheral IV catheter, representing hundreds of millions of patients a year. 48 SUPPLIER NEWS BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com

Agilent Technologies releases Cary 3500 Flexible UV-Vis system Becton Dickinson (BD) Holdings, a global leader in life science technologies, and the Agency for Science, Technology and Research (A*STAR), Singapore’s lead public sector R&D agency, have announced an extended research partnership that will focus on deep immunophenotyping of human tissues using spectral flow cytometry panels to bring forth discoveries that can be translated into positive healthcare outcomes. In a previous partnership between the A*STAR Singapore Immunology Network (A*STAR SIgN) and BD signed in 2016, a whole leukocyte panel comprising 35 markers with 26 fluorophores was generated using the sentinel approach. This partnership validated BD Biosciences’ prototype reagents and expanded the scope of biological data that could be acquired via flow cytometry. This successfully led to fast tracking of other highparameter flow cytometry panels that have been used to investigate responses to immuno-therapy, as well as the human immune response to COVID-19. With this previous partnership as a basis, the research team aims to expand the possible panel size up to 43 markers without using the sentinel approach by utilising specialised cell analyser equipment from BD. Waters Corporation has unveiled its next generation Xevo TQ Absolute IVD mass spectrometer, expanding its family of MassTrak IVD LC-MS/MS Systems for clinical diagnostic applications. The powerful analytical performance of the Xevo TQ Absolute IVD mass spectrometer is up to five times more sensitive for quantifying clinical analytes than similar commercial instruments on the market. This sensitivity enables clinical laboratories to detect and measure trace level analytes within a sample at the lowest detection levels than previously possible. It can extend the testing capabilities of the clinical laboratory to include lower volume samples obtained in less-invasive assays such as saliva, breath, and dried blood spots. The system also enables clinical laboratories to expand their test menu to include multiplex panels and large molecules. The Xevo TQ Absolute IVD System provides more consistent instrument-to-instrument performance, with a user-friendly design that maximises service uptime. Its innovative design is also 45 per cent smaller and uses 50 per cent less nitrogen gas and electricity than comparable tandem quadrupolemass spectrometry (TQ-MS) systems, making it ideal for hospital labs and independent commercial labs with both sustainability and business growth goals to meet. Waters Corp launches next generation Xevo TQ Absolute IVD mass spectrometer BD extends research partnership with A*STAR, Singapore SUPPLIER NEWS 49 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Becton Dickinson (BD) Holdings, a global leader in life science technologies, and the Agency for Science, Technology and Research (A*STAR), Singapore’s lead public sector R&D agency, have announced an extended research partnership that will focus on deep immunophenotyping of human tissues using spectral flow cytometry panels to bring forth discoveries that can be translated into positive healthcare outcomes. In a previous partnership between the A*STAR Singapore Immunology Network (A*STAR SIgN) and BD signed in 2016, a whole leukocyte panel comprising 35 markers with 26 fluorophores was generated using the sentinel approach. This partnership validated BD Biosciences’ prototype reagents & expanded the scope of biological data that could be acquired via flow cytometry. This successfully led to fast tracking of other high-parameter flow cytometry panels that have been used to investigate responses to immuno-therapy, as well as the human immune response to COVID-19.

50 BIOSPECTRUM | MAY 2023 | www.biospectrumasia.com Targeting Malaria Net Zero There were 247 million cases of malaria in 2021 compared to 245 million cases in 2020. The estimated number of malaria deaths stood at 619,000 in 2021 compared to 625,000 in 2020. Over the two peak years of the pandemic (2020–21), COVID-related disruptions led to about 13 million more malaria cases and 63,000 more malaria deaths, according to World Malaria Report 2022 by the World Health Organisation (WHO). The WHO South-East Asia (SEA) region continues to lead globally in controlling the disease. By the end of 2020, the SEA region was the only WHO region to achieve a 40 per cent reduction in malaria case incidence and mortality compared to 2015 – the first Global Technical Strategy (GTS) milestone. Amid the COVID-19 response, Maldives and Sri Lanka have maintained their malaria-free status, and five countries of the region – Bhutan, DPR Korea, Nepal, Thailand and Timor-Leste are among 25 countries and one territory globally identified as having the potential to eliminate malaria by 2025. In September 2023, Timor-Leste is likely to complete three consecutive years of reporting zero local malaria transmission. It would, therefore, be eligible to be certified malaria free. Asia Pacific is faced with a localised epidemic across the region, with more than 90 per cent malaria occurring in just five countries, namely India, Indonesia, Pakistan, Afghanistan and Papua New Guinea. According to Asia Pacific Leaders Malaria Alliance (APLMA) Afghanistan has 86,263 cases, India -161,753 cases, Indonesia - 304,579 cases, Pakistan - 399,097 cases, Papua New Guinea - 651,963 cases reported in 2021. It also noted that the number of cases in Pakistan, Indonesia, Solomon Islands (84,139) and Myanmar (79,000) were on the rise in 2021 as compared to other nations in the region. APLMA noted that 12 nations from the region namely Afghanistan, Bangladesh, Cambodia, India, Indonesia, Lao People’s Democratic Republic (LPDR), Myanmar, Pakistan, Papua New Guinea, Philippines, Solomon Islands and Vietnam are striving to eliminate malaria by 2030. APLMA unites 22 governments in Asia Pacific who have committed to eliminating malaria by 2030. APLMA translates evidence to advocate for policy change at the highest levels of government and supports leadership collaboration across the region. Besides APLMA, The Asia Pacific Malaria Elimination Network (APMEN), established in February 2009, a network of countries and stakeholders, has also committed to eliminate malaria in Asia Pacific by 2030. Since 2017, both APMEN and APLMA with a secretariat in Singapore, have been working closely to enhance and streamline the Asia Pacific’s regional response to malaria. Both support the region’s collective malaria response by guiding the implementation of the APLMA Leaders’ Malaria Elimination Roadmap – which prioritises research and innovation, financing and governance, policy and programme coordination, and regulatory cooperation for the malaria response. Progress against malaria is one of this century’s greatest public health successes. Over the past ten years, the countries of the Asia Pacific region have reduced cases of malaria by more than half, putting them on a positive course towards the 2030 goal. But 2.5 billion people in the region remain at risk. In some areas, malaria is staging a comeback. It is imperative that these threats get urgent attention and that the region’s gains aren’t wasted. APLMA pointed out that the domestic funding for malaria in Asia Pacific has doubled since 2012. There is a need to maintain this momentum and ensure financial and programmatic sustainability of malaria interventions in every country. At the same time, it observed that external grant funding is still critical for malaria elimination, and engage with partners and countries for it to be maintained, and/ or gradually transitioned. April 25, observed as World Malaria Day with this year’s theme ‘Time to Deliver Zero Malaria : Invest, Innovate, Implement’, the WHO has called for more effective implementation of available tools and strategies to prevent, diagnose and treat malaria, particularly among marginalised populations. The WHO reiterates its support to all countries of the region to accelerate and sustain malaria elimination and deliver its promise of zero malaria for everyone, everywhere. Narayan Kulkarni Editor [email protected]