BioSpectrum Asia April 2023

A World Sans Malaria Volume 18 | Issue 4 | April 2023

The Most Sought-After & Much Talked About Annual Awards Night To Felicitate The Stalwarts Of Indian Biotechnology & Health Science Industry Hear from the Experts Search for a New Molecule: Shift from Generics to Novel Drugs To Know More Mail at: [email protected] or visit: www.biospectrumindia.com/bsiawards2023 30th June 2023 The Lalit, New Delhi

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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 4; April 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 | APRIL 2023 | www.biospectrumasia.com Acknowledgement I read your ‘The New Pandemic of Layoff’s article in the March edition. Layoffs are considered a massive problem in the tech industry but I agree with you, these things happen and the only way to move forward is to nourish your knowledge and skills. Great post! - Kelly Wilson, US We at Fermata appreciate being credited for our findings and including us in the write-up ‘APAC FemTech Space Gains Momentum’. We are more than happy to extend our knowledge and insights in the industry and region. - Francesca Geary-Stingl, Singapore The article by Qure.ai has come out very well in the March edition. Thank you! - Amrutha Joseph, India

Letter from Publisher Ravindra Boratkar Publisher & Managing Editor, MD, MM Activ Sci-Tech Communications Pvt. Ltd. Dear Readers, Over 600,000 people, mostly children, die of malaria each year. The fight against Malaria has been discouraging over the past decade as the drugs used against it have been losing its effectiveness. Malaria has long been a major public health concern in the Asia Pacific region, affecting millions of people. The latest World Health Organisation’s (WHO) report on malaria indicates that the region had 5.4 million estimated cases and 8900 estimated deaths in 2021. There are nine malaria-endemic countries in the South-East Asia Region in 2021, contributing to 2 per cent of the global burden of malaria cases. Three countries accounted for 99.7 per cent of the estimated cases in the region, with India being the largest contributor (79 per cent), followed by Indonesia (15.6 per cent) and Myanmar (1.6 per cent). Nonetheless, governments, healthcare organisations and communities are working together to implement innovative strategies, technologies and programmes that can help curb the spread of malaria. However, these efforts were hampered because of COVID-19. As a part of the Sustainable Development Goal (SDGs) targets, the UN set a goal to end the Malaria epidemic by 2030. In 2022, the WHO South-East Asia Region renewed its commitment to eliminate malaria by 2030, with countries pledging accelerated action and greater efforts at the sub-national and community levels. Other parts of Asia also fared well. China was declared malaria free in June 2021, after 70 years of fighting. Malaysia is on its way to become malaria-free as well. In this issue our edit team explores the current status of Asia’s malaria elimination efforts, highlighting the progress made, and strategies needed for a malaria-free future. ‘Even though precision medicine has many advantages when compared with the traditional healthcare system, the Asia region is currently witnessing limited adoption of the same due to various underlying reasons.’ This was the beginning of the article BioSpectrum Asia published in June 2021. Once again, our content team has turned to precision medicines in Asia to find out what has changed (or not). Asia’s multi-ethnic population presents challenges and opportunities for precision medicine. The article explains how collaborative management and analysis of patient data are helping researchers in the Asia Pacific region to spearhead improvements in disease diagnosis, treatment and prevention.. The impact of Rare Diseases, although prevalent, hasn’t been tackled effectively enough due to various reasons, some related to availability and affordability of drugs and also lack of innovations in this sphere. I am sure you will find both these primary articles interesting to read. Thanks & Regards, Ravindra Boratkar Publisher & Managing Editor 5 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Looking for a job? See open roles at www.biospectrumjobs.com premier source of pharma healthcare & bio jobs n Find Talent n Post Jobs n Attract Candidates Find the right people no matter what your hiring needs are... TALENT SOLUTIONS

Malaria has long been a major public health concern in the Asia Pacific region, particularly in South East Asia (SEA) affecting millions of people. According to a latest report on malaria from the World Health Organisation (WHO), there were approximately 5.4 million cases and 9000 deaths in the region in 2021. The SEA region has nine countries where malaria is prevalent, and their contribution to the global burden of malaria cases is two per cent. India is the main contributor to the malaria cases in the region, accounting for 82.5 per cent of them, followed by Indonesia with 15.6 per cent, and Myanmar with 1.6 per cent. These three countries were responsible for almost all of the malaria cases in the region, making up 99.7 per cent of the total estimated cases. Governments, healthcare organisations, and communities are implementing innovative strategies, technologies, and programmes that can help curb the spread of malaria. Though these efforts were hampered because of COVID-19, in 2022, the WHO South-East Asia Region renewed its commitment to eliminate malaria by 2030, with countries pledging accelerated action and greater efforts at the sub-national and community levels. Other parts of Asia also progressed well. China was declared Malaria free in June 2021, after 70 years of fighting. In its fights against malaria, Asian countries have recently announced significant investment including a $1.9 million investment in February 2023 by Japan’s GHIT Fund for the research and development of a new malaria drug, and a $1 million contribution by Singapore’s Ministry of Health to the Global Fund to fight AIDS, TB, and Malaria, announced in December 2022. While observing World Malaria day on April 25, let’s explore the current status of Asia’s malaria elimination efforts, highlighting the progress made and strategies needed for a malaria-free future. COVER STORY 20 6 BIO CONTENT BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com MALARIA A World Sans

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 People News.............................................................44 R&D News .................................................................46 Supplier News ..........................................................48 Lets Talk Health .......................................................50 PRECISION MEDICINE How Equitable Data Sharing is key to realising precision medicine in APAC Nino da Silva, Deputy Managing Director, BC Platforms The Key to a Precision Medicine Future: AI Plus Human Ingenuity Dr Alex Aliper, President, Insilico Medicine 41 42 BIO CONTENT 7 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com RARE DISEASES Rare Diseases Needn’t Be Neglected Anymore 28 Addressing ‘Orphaning’ of Rare Diseases Ravi Shet, Clinical Data Management Professional 31 SPEAKING WITH “Immutep has started exploring the potential of the first ever triple combination therapy with Eftilagimod” Marc Voigt, CEO, Immutep 32 “APAC continues to be a global hub for clinical trials” Dr John Moller, CEO, Novotech “There’s strong commercial growth potential in the Asia Pacific markets” Steve Mason, CEO, Medical Segment, Cardinal Health “Diagnostic market in the Asia Pacific region is currently in a critical period” Seungman Han, CEO, Bertis, South Korea 33 35 37 EVENT REPORT One World TB Summit “India is now working on the target of ending TB by 2025” 39

8 BIO EDIT BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Dr Milind Kokje Chief Editor [email protected] ERA OF AI-AUGMENTED DRUG DISCOVERY Two developments of a similar type – one in Silicon Valley and another in Japan – are expected to dramatically change the pace of artificial intelligence (AI) in the pharmaceutical sector in general and drug discovery in particular. A leading healthcare company from Palo Alto, huma.ai launched its ‘industry first AI platform for life sciences’ last month. It is designed to accelerate the development of life-saving drugs through better usage of data. In the far east, one of the largest Japanese business conglomerates, Mitsui & Co. is collaborating with NVIDIA for a technology named Tokyo-1. It is an initiative to supercharge Japan’s pharma leaders with technology for drug discovery. It includes high-resolution molecular dynamics simulations and generative AI models. AI in drug discovery was not merely an idea as pharmaceutical companies started using machine learning in late 2020. In 2018 itself, Pfizer started using IBM Watson, a system that uses machine learning, to strengthen its search for immune-oncology drugs. At around the same time, Sanofi deployed UK startup Exscientia’s AI platform, seeking out new metabolic disease therapies. Roche’s subsidiary Genentech also began using AI for cancer treatments. Still, the awareness about the use of AI, machine learning in drug discovery was low back then. A survey published in Canada then revealed that 41 per cent of 330 drug discovery researchers were unfamiliar with AI. The situation has changed a lot since then. AI and machine learning were then expected to usher in an era of quicker, cheaper and more-effective drug discovery. That seems to have begun now. In its report released last month, InsightAce Analytic has estimated global AI in the biopharma development market to grow at a phenomenal 49.3 per cent CAGR from 2022 to 2030. The market, which was valued at $452.33 million in 2021 is expected to reach $16441.32 million by 2030. Maybe the two new developments – and similar ones in near future – will help push the pace of the growth to achieve the estimated market size. Currently, the industry primarily depends on manual curation of data, which comes at a major cost of time and money, still leaving some critical questions unanswered. Moreover, 80 per cent of healthcare data is still text based. Huma.ai claims that its generative AI platform leverages existing large language models to surface previously unknown intelligence. Its natural language processing (NLP) replaces and automates manual curation. It connects and searches multiple, disparate, unstructured data sources, answering questions in seconds. It leverages existing large language models to surface previously unknown intelligence. In Japan, the Tokyo-1 project will make the NVIDIA DGX AI supercomputer accessible to Japan’s $100 billion pharma industry and startups to accelerate its efforts of drug development. With Tokyo-1, Mitsui is creating an innovation hub enabling the pharma industry to transform the landscape with the state of the art tools for AI-accelerated drug discovery. This will provide the pharma industry access to molecular dynamics simulations, quantum chemistry, large language models, generative AI models creating novel molecular structures for potential drugs. Mitsui claims that Tokyo-1 is designed to address some of the barriers to implementing data-driven, AI-accelerated drug discovery. Experts point out that the Japanese pharma sector has not yet taken advantage of highperformance computing and AI on a large scale and that has delayed drug development in Japan. They are of the opinion that Tokyo-1 will provide an opportunity to the Japanese pharma to transform itself and go to the next level in drug research to remain competitive. McKinsey estimates that the new technologies may considerably reduce the time for drug discovery as scientists may be able to move at a pace at which one person can do what it would have taken 100 to do before. As a result, we may get new drugs in one tenth of the current time of nearly a decade. Additionally, it will also help in having therapies for the diseases which have no treatments available now. How fast such facilities spread in other countries in the Asia Pacific region is important and worth watching for the future development of pharmaceuticals in the APAC region.

The Department of Pharmaceuticals (DoP) under the Ministry of Chemicals and Fertilizers, Government of India has released the first tranche of incentives under the Product Linked Incentive (PLI) scheme for pharmaceuticals amounting to Rs 166 crore to four selected applicants- Dr. Reddy’s Laboratories, Biocon, Strides Pharma Science, Premier Medical Corporation. The DoP has received an incentive claim of about Rs 544 crore from 15 applicants. Based on the evaluation, Rs 221 crore of claims of incentives from the selected four applicants were found to be eligible and 75 per cent of this amount i.e., Rs 165.74 crore have been released. DoP launched the PLI scheme for pharmaceuticals in 2021. The financial outlay under this PLI scheme is Rs 15,000 crore over a period of six years. So far, 55 applicants have been selected under the scheme, including 20 Micro, Small & Medium Enterprises (MSMEs). The financial year of 2022-2023 being the first year of production for the PLI Scheme, DoP has ear-marked Rs 690 crore as the budget outlay. As of January 31, 2023, sales of about Rs 36,000 crore have been reported by the select 55 applicants. Hong Kong injects additional $500M into Chinese Medicine Development Fund During the Budget speech of 2023-24, the Hong Kong government has announced plans to inject an additional amount of $500 million into the Chinese Medicine Development Fund starting from this financial year to support the commissioning of large-scale training, research and publicity projects on strategic themes and to take forward more capacity building programmes for the sector, which include making preparations for Hong Kong’s first Chinese medicine hospital which is expected to commence services in 2025 and strengthening the role of Chinese medicine in the primary healthcare system. Since the official launch of the Chinese Medicine Development Fund in 2019, more than 10 funding schemes have been rolled out to benefit various practitioners and organisations in the Chinese medicine sector. The government put forward the Primary Healthcare Blueprint at the end of last year, under which a series of key reform initiatives for enhancing Hong Kong’s primary healthcare services are set out, and prevention-oriented, community-based, family centric, and early detection and intervention strategies are adopted. The Australian Government is investing $382 million in nearly 200 medical research projects, including $32 million to improve First Nations health. Funding is from the Medical Research Future Fund (MRFF). Of these, 19 grants worth more than $32.3 million are related to First Nations health. There are13 grants worth more than $16.9 million for mental health research. The projects will help Australia’s outstanding medical researchers, including clinician researchers, discover new ways to diagnose, treat and care for people with a variety of health conditions. They will also support early and mid-career researchers and give more Australians access to clinical trials.Research projects on cardiovascular disease, primary and preventive health care, respiratory diseases, maternal health, mental health and First Nations health, will receive funding to progress important work. Australia invests $382M in nearly 200 groundbreaking medical research projects India releases Rs 166 Cr incentives under PLI scheme for pharma REGULATORY NEWS 9 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com

In a significant achievement towards recognising efforts in the health sector and especially COVID management, Ministry of Health and Family Welfare (MoHFW), Government of India received the Porter Prize 2023. The prize was announced at “The India Dialog” organised by Institute for Competitiveness (IFC) and US Asia Technology Management Center (USATMC) at Stanford University, on February 23 & 24, 2023. The prize recognises the strategy followed by the Government of India in managing COVID-19, the approach, and involvement of various stakeholders especially involvement of ASHA workers in the industry to create PPE Kits. It was also noted that the idea of vaccine development and vaccine manufacturing and the scale that India achieved, was tremendous. India has delivered more than 2.5 billion doses, which has just been amazing. The ministry took all the necessary steps to combat the COVID situation in the country. Porter Prize is named after Michael E. Porter, an economist, researcher, author, advisor, speaker and teacher. He has brought economic theory and strategy concepts to bear on many of the most challenging problems facing corporations, economies and societies, including market competition and company strategy, economic development, the environment and healthcare. His research has received numerous awards, and he is the most cited scholar today in economics and business. India receives Porter Prize 2023 10 REGULATORY NEWS BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com On March 2, the Ministry of Health and Welfare, led by Minister Cho KyooHong, announced the New BioHealth Industry Regulation Innovation Plan at the Third Regulatory Innovation Strategy Meeting. The Plan comes on the heels of the strategies for creating new bio-health markets announced at the interdepartmental meeting held on February 28. The government is seeking innovation of biohealth regulation to create the foundation needed for South Korea to grow into a global digital and bio healthcare leader. The bio-health industry is a promising new industry owing to its potential for rapid growth, given the aging population trend worldwide and a rising global need for good healthcare. Its importance also prioritizes the health security domain which involves vaccines and other treatments needed to protect people’s lives, health, and safety. Korea’s bio-health industry has made significant achievements over the years, including developing the world’s second-largest capacity to produce bio-pharmaceuticals, but the global bio-health market is so vast that there is still massive room for growth of the domestic bio-health industry. Singapore increases MediShield Life claim limit for cancer drug services Korea announces New Bio-Health Industry Regulation Innovation Plan The Ministry of Health (MOH), Government of Singapore will increase the MediShield Life claim limit for cancer drug services from $1,200 per calendar year to $3,600 per calendar year from April 1, 2023. There is no change to the MediSave withdrawal limit of $600 per calendar year. To ensure the affordability of cancer drug treatments and sustainability of insurance premiums in the long term, MOH regularly reviews the financing schemes for cancer drug treatments. Since September 1, 2022, only treatments that are listed on the Cancer Drug List are covered under MediShield Life and MediSave.

FINANCE NEWS 11 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Biocytogen Pharmaceuticals (Beijing) has announced that its wholly owned subsidiary, Eucure (Beijing) Biopharma has reached an exclusive licensing agreement with Chipscreen NewWay Biosciences, a holding subsidiary of Shenzhen Chipscreen Biosciences for the clinical development and commercialisation of bispecific antibody YH008 in Greater China (including Mainland China, Hong Kong, Macau and Taiwan). Eucure Biopharma retains YH008’s global rights to develop and commercialise YH008 outside Greater China. Under the agreement, Chipscreen NewWay will pay Eucure Biopharma an upfront payment of 40 million RMB (¥), a potential development milestone payment of up to 360 million RMB, a potential sales milestone payment of up to 196 million RMB, as well as tiered royalties on net sales. YH008 is Biocytogen’s independently developed proprietary bispecific antibody for tumour immunotherapy. Teijin Pharma, Novartis sign $230M deal for kidney disease treatment Teijin Pharma, based in Japan, has entered into an exclusive global license agreement with Swiss firm Novartis to research, develop, manufacture and commercialise an investigational preclinical candidate for proteinuric kidney diseases. The investigational small molecule candidate was discovered at the Teijin Institute for Bio-medical Research, Teijin Pharma’s drug development base in Tokyo. The candidate acts in a genetically validated pathway and is believed to impact the pathogenesis of multiple kidney diseases. Under the terms of the license agreement, Teijin Pharma will grant Novartis exclusive worldwide rights to research, develop, manufacture and commercialise the candidate for all potential indications. Teijin Pharma will receive an upfront cash payment of $30 million from Novartis and is eligible to receive potential development and commercial milestone payments of up to $200 million. Teijin Pharma is further eligible to receive additional sales milestones and tiered annual net sales royalties. Dr. Reddy’s Laboratories SA, a whollyowned subsidiary of Indian pharmaceutical company Dr. Reddy’s Laboratories, has entered into a definitive agreement to acquire the US generic prescription product portfolio of Salisbury, Australiabased Mayne Pharma Group. The portfolio includes approximately 45 commercial products, four pipeline products and 40 approved non-marketed products, including a number of generic products focused on women’s health. Under the terms of the agreement, Dr. Reddy’s will acquire the portfolio for an upfront payment of approximately $90 million in cash, contingent payments of up to $15 million, consideration towards inventory and credits for certain accrued channel liabilities to be determined on the closing date. The acquisition will complement Dr. Reddy’s US retail prescription pharmaceutical business with limited competition products. It also supports Dr. Reddy’s efforts to accelerate and expand affordable medications for patients. Dr. Reddy’s acquires Mayne Pharma’s US generic prescription product portfolio for $90M Biocytogen inks ¥596M cancer immunotherapy deal with Chipscreen Biosciences in China

Olympus Corporation, a global medtech company headquartered in Japan, has agreed to acquire Taewoong Medical Co., a Koreabased manufacturer of medical devices such as gastrointestinal (GI) metallic stents to strengthen its GI endotherapy product portfolio capabilities, and in turn, contributing to improving patient outcome through comprehensive solutions. Taewoong will receive approximately $370 million in cash, of which $255.5 million will be paid at the closing and up to $114.5 million will be paid if future milestones are achieved. The company expects to complete the transaction on June 30, 2023, subject to customary closing conditions. Olympus is targeting GI as one of its key disease states, as outlined in its medical business strategy announced in December 2021. The addition of Taewoong Medical’s medical devices to its product portfolio will enable Olympus to become a comprehensive solutions provider in the GI market with varied solutions in GI, contributing to improved patient outcomes and elevating the standard of care. Olympus acquires Korean gastrointestinal stent firm Taewoong Medical for $370M 12 FINANCE NEWS BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Taiwan’s AnnJi Pharmaceutical Co. has entered into an exclusive license agreement with American firm Avenue Therapeutics Inc. for the development and commercialisation of AJ201 for spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s Disease. Under the terms of the license agreement, AnnJi will receive upfront payments of $3 million and is entitled to receive future development, regulatory and commercialisation milestone payments amounting up to $250 million, as well as up to 2-digit percentage royalty of the net sales. This agreement is one of the largest license deals for a small molecule drug in early Phase 1b/2a clinical development in the past 24 months. Greenberg Traurig served as AnnJi’s legal advisor in this transaction. AJ201 is a novel small molecule new drug and a first-in-class treatment, which has the potential to treat Kennedy’s Disease through multiple mechanisms including degradation of the abnormal androgen receptor (AR) protein, which is believed to be the cause of the disease, as well as suppression of proinflammatory cytokines and protection of cells from oxidative stress. Phase 1 clinical trial in healthy subjects has demonstrated the safety of AJ201 in humans. World Bank signs $1B programme to support India’s health sector AnnJi Pharma inks $250M deal for muscular atrophy treatment The Government of India and the World Bank have signed two complementary loans of $500 million each to support and enhance India’s health sector development. Through this combined financing of $1 billion, the bank will support India’s flagship Pradhan Mantri-Ayushman Bharat Health Infrastructure Mission (PM-ABHIM), launched in October 2021, to improve the public healthcare infrastructure across the country. In addition to the national level interventions, one of the loans will prioritise health service delivery in seven states including Andhra Pradesh, Kerala, Meghalaya, Odisha, Punjab, Tamil Nadu, and Uttar Pradesh. The agreement was signed by Rajat Kumar Mishra, Additional Secretary, Department of Economic Affairs, Ministry of Finance on behalf of the Government of India and Auguste Tano Kouamé, Country Director, India, World Bank.

COMPANY NEWS 13 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Kyorin, Sumitomo to introduce drug for overactive bladder in Taiwan & other Asian countries Kyorin Pharmaceutical, a subsidiary of Kyorin Holdings, Inc. and Sumitomo Pharma, in Japan, have entered into a license agreement for development, manufacturing, and commercialisation of a therapeutic agent for overactive bladder (OAB) called Vibegron as international nonproprietary name (INN), in Taiwan, Hong Kong, Singapore, Indonesia, and Vietnam. Based on the agreement, Kyorin will grant Sumitomo Pharma the exclusive rights to develop, manufacture, and commercialise the compound in these five countries and regions. Kyorin will receive an upfront payment and is eligible to receive development and sales milestone payments from Sumitomo Pharma. Following the launch of the compound, Kyorin is eligible to receive royalties based on net sales of the compound by Sumitomo Pharma. The compound is a once-daily oral selective β3- adrenergic receptor agonist. GenScript Biotech Corporation has announced the expansion of its Singapore facility to provide a premium gene synthesis service. The move adds an additional 976 square meters to the facility, bringing the total production footprint in Singapore to 3,500 square meters, and making it the third-largest GenScript facility worldwide. The expansion will also increase the total headcount at the Singapore facility to 150. In February 2022, GenScript Asia-Pacific announced the opening of a new recombinant protein production facility; now, that same facility will offer an advanced gene-synthesis service. This marks a significant expansion of the company’s advanced gene-synthesis capability and enables GenScript to provide the premium service levels required for novel vaccine and therapeutics development in life sciences. The Singapore facility houses state-of-the art automated workstations capable of synthesising more than 400 genes per day. GenScript expands footprint in Singapore The Indian Institute of Technology, Kanpur (IIT-K) has licensed a pioneering technology to Reliance Life Sciences, India that has the potential to revolutionise the field of gene therapy, especially for many genetic eye diseases. This marks the first time that a gene therapy related technology has been developed and transferred from an academic institution to a company in India. The gene therapy technology from IIT-K will be further developed as an indigenous product by Reliance Life Sciences. Developed by Prof. Jayandharan Giridhara Rao and Shubham Maurya from the Department of Biological Sciences and Bioengineering (BSBE), IIT-K, the patented technology modifies the gene of an organism to treat a hereditary disorder. In this case, the site refers to a specific location on an Adenoassociated virus (AAV) (viral vector) used for gene therapy. The technology modifies this location to optimise its ability to deliver genes to the affected cells and improve its effectiveness. IIT-K, Reliance Life Sciences to revolutionise gene therapy for hereditary eye diseases

Clover Biopharma to commercialise quadrivalent seasonal influenza vaccine in China Clover Biopharmaceuticals has entered into an exclusive agreement with Adimmune Corporation for Clover to distribute AdimFlu-S (QIS) in mainland China, the only imported quadrivalent seasonal influenza vaccine which is approved. AdimFlu-S (QIS) is a quadrivalent split inactivated vaccine for prevention of influenza. The quadrivalent vaccine contains hemagglutinin from four influenza virus strains (two A and two B), which increases its chances of achieving high vaccine effectiveness regardless of which influenza B strain becomes seasonally prevalent relative to trivalent options. AdimFlu-S (QIS) was approved by the China National Medical Products Administration in January 2022 for individuals aged three years and older. In the near term with commercial launch in H2 2023, Clover will be responsible for the distribution of AdimFlu-S (QIS) throughout mainland China, where the vaccine is already approved and where Clover can leverage its existing commercial infrastructure and growing sales organisation. 14 COMPANY NEWS BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Malaysian Genomics offers world’s first DNA-driven fertility test Malaysian Genomics Resource Centre Berhad, a leading genomics and biopharmaceutical specialist, has announced that the Group has signed a strategic collaboration agreement with Divine Genes Sdn Bhd to collaborate on business opportunities in relation to the improvement and international distribution of genetic tests for reproductive health. Divine Genes is an investment holding company with businesses in pharmaceutical product distribution, financial consultancy services as well as general merchandise and trading. Under the strategic collaboration, Divine Genes’ genetic test for reproductive health will be added to Malaysian Genomics’ genetic test portfolio, which will market and distribute these tests in Malaysia and overseas. Both parties will also cooperate in improving the product. According to Sasha Nordin, CEO, Malaysian Genomics, decreasing fertility and birth rates are common across the world, and demand for reproductive medicine is growing in many countries. South Korea-based Medit, a leading provider of 3D intraoral scanners and digital dentistry solutions, has announced the release of its new app, the Medit Occlusion Analyser. It is a powerful tool that allows dental professionals to perform occlusion analysis quickly and easily without the need to return to the Medit Scan for Clinics or reprocess data. With the app’s automatic detection and analysis of occlusal interferences, users can explore the occlusal relationship and review results through annotations and colour maps. The app’s section view feature enables users to create section planes to examine specific areas of interest and use multi-view to compare sections of multiple planes. Additionally, the app allows users to measure distances by one or two points for greater accuracy. The Medit Occlusion Analyser also includes a colour map, available in both opened and closed states, to provide a visual representation of the occlusal relationship. With alignment and edit modes, users can realign jaw data to occlusal bite based on selected areas or points and edit data by trimming, sculpting, or filling holes. Medit launches occlusion analyser app for dental professionals

Metanoia Sensing unveils breath analyser to monitor fat burning status Singapore-based tech startup Metanoia Sensing has announced the launch of a new breath analyser ‘MetaNose’ to help people monitor their fat (lipid) burning status. The device also provides insights into the users’ metabolic health risk such as diabetic related conditions. The MetaNose device has been launched on Indiegogo and has reached its funding goal within the first hour. MetaNose is made of environmentally sustainable materials, including those for assembly and packaging. Recyclable materials are used to reduce the overall production cost while achieving high quality and producing less emission that is harmful to the planet. MetaNose determines the metabolic condition of the user from a single breath, by utilising a state-of-the-art Micro-Electro-Mechanical System (MEMS) acetone sensor and a signal processing algorithm, which measure the volatile organic compounds (VOCs) in exhaled breath and analyse the oxidative stress of lipid metabolism. START-UP NEWS 15 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com India-based startup Mylab Discovery Solutions, and DnaNudge, a UK-based pioneer of consumer genetics testing and medical diagnostics, have announced a strategic partnership to develop nextgeneration molecular diagnostic solutions for diabetic foot ulcer detection and other key health conditions. The Memorandum of Understanding (MoU) was signed between the two companies in the presence of Dr Thaksin Shinawatra, Former Prime Minister of Thailand, Yingluck Shinawatra, Former Prime Minister of Thailand, Regius Professor Chris Toumazou, Cofounder of DnaNudge and Founder of the Institute of Biomedical Engineering at Imperial College London and Hasmukh Rawal, MD of Mylab. The novel diabetic foot ulcer detection kit will be the first of the many testing kits to be co-developed by the companies. Together, DnaNudge and Mylab will introduce transformative point-of-decision testing kits for health conditions which are of major public health concern in India. Mylab partners with UK-based DnaNudge for point-of-decision diagnostic solutions Australian startup Provectus Algae has secured an undisclosed strategic investment from CJ BIO, a division of CJ CheilJedang, a South Koreabased food & bio company within CJ Group. Provectus Algae is a biotechnology company developing the future of biomanufacturing with carboncapturing microbes. Using its proprietary technologies, Provectus programmes microalgae to produce valuable biochemicals using both natural and synthetic biology approaches. This strategic investment provides Provectus Algae with additional funds to accelerate commercialisation efforts that bring innovative specialty ingredients to market, and Provectus Algae expects to gain access to the experience and expertise CJ BIO has built in the biomanufacturing sector. CJ BIO is a world leader in sustainable biotechnologies and biomanufacturing, recognised for its work on large-scale biomolecule production, scale-up technologies, process automation, and beyond. CJ BIO owns the largest share of the global lysine, tryptophan, nucleic acid, valine, and soy protein concentrate (SPC) markets, manufacturing goods at 13 plants across 6 countries. In addition, CJ BIO has continued to innovate and expand its offerings, including its PHACT, a biodegradable, biobased polyester. CJ BIO invests in Australian biotech startup Provectus Algae

US-headquartered startup C2i Genomics has announced a collaboration with Riken Genesis (RG) Co. to bring minimal residual disease (MRD) cancer monitoring to Japan for pharmaceutical and clinical research. Under this agreement, RG will work with C2i Genomics to commercialise its C2intelligence cloud-based platform and the C2inform MRD test for pharmaceutical and clinical research and eventually for commercial clinical testing in Japan. C2i’s technology allows cancer tumor burden monitoring using ultra-sensitive whole genome sequencing (WGS) for personalised medicine and accelerated drug development. This collaboration will build on RG’s current capabilities to provide MRD detection for haematology by expanding its MRD capabilities across all solid tumors. RG provides lab-assay services and products for genetic testing based on cutting-edge gene analysis technologies and bioinformatics. The company engages in four businesses: pharmaceutical development support, gene contract analysis, and reagents and diagnostic reagents. C2i Genomics, Riken Genesis expand AIpowered cancer detection technology across Japan 16 START-UP NEWS BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Microba unveils next-gen human gut microbiome tests Microba Life Sciences, a startup based in Australia, has announced that its next generation testing product range, MetaXplore, has been launched to healthcare professionals in Australia under a new brand, Co-Biome. The new MetaXplore range provides diagnostic gastrointestinal health testing together with metagenomic-driven gut microbiome analysis to deliver comprehensive gastrointestinal testing solutions for Healthcare Professionals. The MetaXplore test range has been developed together with healthcare professionals and brought to market under a new brand called Co-Biome. The range consists of 3 products: MetaXplore, MetaXplore GI and MetaXplore GI Plus. It has an easy to interpret report format designed specifically for healthcare professionals to support efficient patient consultation. It provides scientifically graded clinical insights using National Health and Medical Research Council guidelines. SiYi Intelligence secures $15M to build digital rehabilitation service platform Chinese startup SiYi Intelligence, an intelligent rehabilitation solution provider, has completed nearly $15 million in Series A financing. This round was led by Chengdu Bio-town Equity Investment Fund with participation from existing investor Tao Capital. The company plans to use the funding to accelerate the R&D of integration solutions for neurorehabilitation and build the digital rehabilitation service platform. The SiYi intelligence leadership team is composed of doctors and masters from Top universities such as Shanghai Jiao Tong University, Harbin Institute of Technology, and Jilin University; most of them have over 10 years of experience in the robotics, healthcare and rehabilitation industry. With industrial system thinking and multidisciplinary know-how, SiYi has innovated a series of professional rehabilitation robots for scientific research and clinical and family use. They have released worldwide hit products- SYREBO soft robotic hand rehabilitation glove, EasyWalk exoskeleton walking suit for lower extremity augmentation, EEG-based assistive BCIs and SYREBO upper limb rehabilitation robot A2 for both clinical and home use.

WHO NEWS 17 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com WHO promotes access to ear and hearing care The World Health Organisation (WHO) has released a new primary ear and hearing care training manual to assist countries in building the capacity of their health workforce to provide ear and hearing care at the community level. The manual is a practical guide on the prevention, identification and management of hearing loss and common ear diseases and can be used to train health workers and doctors who work at community level primary healthcare facilities. It contains modules on the mechanism of hearing, conducting ear examination and hearing assessment, guidance on prevention, management, and referral of common ear diseases, as well as rehabilitation of hearing loss. It includes hands-on practical activities for skill development. In most places, services for ear and hearing problems remain mainly limited to the tertiary or secondary levels of care, and are provided by highly skilled professionals such as ear, nose and throat (ENT) specialists and audiologists. A new practical guide released by the World Health Organisation (WHO) supports non-governmental organisations to more effectively advocate for life-saving emergency care. Around the world, acutely ill and injured people seek care every day for medical, surgical and obstetric emergencies, including injuries resulting from road traffic crashes. The guide clearly defines the role that non-governmental organisations can have and offers concrete actions for more effective and impactful advocacy. Developed collaboratively by WHO, including the WHO Global Alliance for Care of the Injured, and the Global Alliance of NGOs for Road Safety, Advocating for emergency care: a guide for non-governmental organisations is especially targeted towards non-governmental organisations that operate with limited resources. It proposes a step-bystep advocacy framework that encourages its users to assess the terrain, prepare to act, take action and review progress. A series of case studies from around the world and links to useful resources are also included. New WHO guide to enhance advocacy for life-saving emergency care WHO, ESCEO sign pact to develop a strategic roadmap on bone health and ageing The World Health Organisation (WHO) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) have signed an agreement to develop a strategic roadmap on bone health and ageing and advocate for a public health strategy to prevent fractures among older people. The agreement includes the development of a public health strategy and action plan to prevent fractures among older people as well as to improve the coverage of health services for fractures which are critical for achieving the triple billion targets of WHO’s Thirteen General Programme of Work (GPW13). As part of the agreement, WHO and ESCEO will collaborate to develop global estimates on fracture and osteoporosis; review evidence-based interventions to prevent fractures; create an economic model for an investment case in fracture prevention and care; provide guidance to countries on strengthening national health information systems by integrating osteoporosis and fractures in routine data monitoring; and provide guidance to countries on using data to design evidence-informed policies and programmes to reduce the risk of fractures in older people.

18 WORLD NEWS BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Australian biotechnology leader CSL has announced that the European Commission has granted conditional marketing authorisation (CMA) for HEMGENIX (etranacogene dezaparvovec), the first and only one-time gene therapy for the treatment of severe and moderately severe hemophilia B (congenital Factor IX deficiency) in adults without a history of Factor IX inhibitors. It is the first approved gene therapy for hemophilia B in the European Union (EU) and European Economic Area (EEA). The European Commission’s decision follows the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP)’s positive opinion in December 2022, based on findings from the pivotal HOPE-B trial, the largest gene therapy trial in hemophilia B to date. HEMGENIX is an adeno-associated virus five (AAV5)-based gene therapy given as a one-time treatment for moderately severe to severe hemophilia B patients. This approval marks an important step forward in the treatment of hemophilia B, which changes the lives of people weakened by bleeding in the muscles, joints and internal organs, alleviating the burden of lifelong intravenous infusions of Factor IX products. European Union approves first gene therapy for hemophilia B The US Food and Drug Administration amended the emergency use authorisation (EUA) of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent to provide for a single booster dose of the vaccine in children six months through four years of age at least two months after completion of primary vaccination with three doses of the monovalent (single strain) Pfizer-BioNTech COVID-19 Vaccine. The FDA evaluated immune response data from 60 children in this age group who had completed primary vaccination with three doses of monovalent Pfizer-BioNTech COVID-19 Vaccine and received a booster dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent in a clinical study. One month after receiving the PfizerBioNTech COVID-19 Vaccine, Bivalent, the study participants demonstrated an immune response to both the original SARS-CoV-2 virus strain and to omicron BA.4/BA.5. According to Peter Marks, Director of the FDA’s Center for Biologics Evaluation and Research, currently available data show that vaccination remains the best defense against severe disease, hospitalisation and death caused by COVID-19 across all age groups, and encourage all eligible individuals to make sure that their vaccinations are up to date with a bivalent COVID-19 vaccine. US finds temperaturestable TB vaccine safe, with prompt immune response FDA authorises Bivalent Pfizer-BioNTech COVID-19 Vaccine as booster dose for children A clinical trial testing a freeze-dried, temperature-stable experimental tuberculosis (TB) vaccine in healthy adults found that it was safe and stimulated both antibodies and responses from the cellular arm of the immune system. The Phase 1 trial was supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health in the US. A non-temperature stable form of the candidate previously had been tested in several clinical trials. However, this was the first clinical trial of any subunit TB vaccine candidate in a temperature-stable (thermostable) form. The investigators note some limitations in this small trial. For example, no established correlates of protection define what immune responses are required for vaccine-induced protection from TB disease. Therefore, it is not possible to say whether the enhanced immune responses seen in the thermostable vaccine formulation would translate to improved protective vaccine efficacy.

New grant to improve management of healthcare waste in Egypt The World Bank has announced a $9.13 million grant from the Global Environment Facility (GEF) to expand the scope of the Greater Cairo Air Pollution Management and Climate Change Project in Egypt. This grant will reinforce the environmental benefits of the original project, both at the local and global levels, by improving the management of electronic and healthcare waste. The original project - approved in 2021- supports Egypt’s efforts to reduce pollution in Greater Cairo, with a focus on reducing vehicle emissions, improving the management of solid waste, and strengthening the air and climate decision-making system. The generation of healthcare waste is rapidly increasing in Egypt, as in other countries, as a result of COVID-19, expanding healthcare systems, increased utilisation of single-use items, and poor waste segregation practices. The current treatment and disposal practices of healthcare and electronic waste need to be improved in order to reduce the release of more uPOPs (unintentional persistent organic pollutants). WORLD NEWS 19 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Africa CDC launches Public Health Emergency Management Fellowship for health professionals South Sudan to address zoonotic diseases and other public health threats The Africa Centres for Disease Control and Prevention (Africa CDC) has launched the Africa CDC Public Health Emergency Management Fellowship (Africa CDC PHEM Fellowship), as part of its strategic commitment to broader workforce development under the New Public Health Order. This fellowship will foster the development of a cadre of African public health workforce highly skilled to coordinate and lead preparedness and response to public health emergencies in Africa. According to its design and rollout plan, the fellowship will target mid-career African public health professionals in the public sector, with proven experience of managing PHEOCs and/or leading emergency preparedness and response programs drawn from the public sector across African Union Member States. Africa CDC acting Director, Dr Ahmed Ogwell Ouma emphasized that combating several public health threats across the continent requires an adequately trained and equipped workforce. South Sudan has operationalised and launched its One Health Multi Sectoral Coordination Mechanism. The first ever One Health Mechanism was launched in Juba by Dr Martin Elia Lomoro, Minister of Cabinet Affairs alongside his counterparts from the Ministry of Health, the Ministry of Livestock and Fisheries and the Ministry of Environment with participation of other stakeholders. The establishment of the One Health platform will foster multi sectoral coordination, administrative and technical collaboration among animal, human and environmental health sectors to address potential zoonotic diseases and other health threats. In his remarks on the importance of One Health approach for better health outcome of both human and animal health, Dr Lomoro said that the establishment of the One Health platform will enhance the implementation of the South Sudan National Action Plan for Health Security.

A World Sans MALARIA Malaria has long been a major public health concern in the Asia Pacific region, particularly in South East Asia (SEA) affecting millions of people. According to a latest report on malaria from the World Health Organisation (WHO), there were approximately 5.4 million cases and 9000 deaths in the region in 2021. The SEA region has nine countries where malaria is prevalent, and their contribution to the global burden of malaria cases is two per cent. India is the main contributor to the malaria cases in the region, accounting for 82.5 per cent of them, followed by Indonesia with 15.6 per cent, and Myanmar with 1.6 per cent. These three countries were responsible for almost all of the malaria cases in the region, making up 99.7 per cent of the total estimated cases. Governments, healthcare organisations, and communities are implementing innovative strategies, technologies, and programmes that can help curb the spread of malaria. Though these efforts were hampered because of COVID-19, in 2022, the WHO South-East Asia Region renewed its commitment to eliminate malaria by 2030, with countries pledging accelerated action and greater efforts at the sub-national and community levels. Other parts of Asia also progressed well. China was declared Malaria free in June 2021, after 70 years of fighting. In its fights against malaria, Asian countries have recently announced significant investment including a $1.9 million investment in February 2023 by Japan’s GHIT Fund for the research and development of a new malaria drug, and a $1 million contribution by Singapore’s Ministry of Health to the Global Fund to fight AIDS, TB, and Malaria, announced in December 2022. While observing World Malaria day on April 25, let’s explore the current status of Asia’s malaria elimination efforts, highlighting the progress made and strategies needed for a malaria-free future. 20 COVER STORY BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com

COVER STORY 21 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Malaria, the oldest and most complex disease affecting mankind, is prevalent in the Asia Pacific (APAC) region, which houses 60 per cent of the world’s population and is second only to Africa in the number of malaria cases. Despite this, most APAC countries have made impressive strides in combating malaria, reducing malaria cases by 82 per cent from approximately 18 cases per 1000 at-risk population in 2000 to about three cases per 1000 at-risk population in 2021. The 2022 World Malaria Report by WHO states that South East Asia is progressing towards achieving its 2030 malaria targets. Seven of the nine countries in the region that are endemic to malaria recorded a reduction of over 40 per cent in malaria cases, with Timor-Leste reporting zero cases. While Indonesia recorded less than a 40 per cent reduction, Myanmar reported no change. Bhutan, DPR Korea, Thailand, and TimorLeste recorded zero malaria deaths. Most countries in the region achieved over a 40 per cent reduction in mortality rates, with the exception of Indonesia, which achieved less than a 25 per cent reduction. Despite the gains, malaria elimination remains challenging owing to drug resistance, new strains and accessibility issues. Let’s take a deep dive into the elimination strategies of high-burden countries in the region. India In the WHO South-East Asia Region, India bears a significant burden of malaria, accounting for 79 per cent of cases and approximately 83 per cent of all malaria-related deaths. The Indian government has made ending malaria a top priority, introducing its first National Framework for Malaria Elimination (2016-2030) and taking various initiatives to achieve its target. In 2019, the government increased funding for the National Vector Borne Disease Control Programme by more than 25 cent, demonstrating its commitment to the cause. Additionally, India contributed $22 million to the Global Fund for AIDS, TB, and Malaria for the 6th replenishment cycle (2020-22), an increase of 10 per cent over the previous cycle. To coordinate and prioritise research efforts, Malaria Elimination Research Alliance (MERA) India was launched in

22 COVER STORY BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com 2019, bringing together researchers from the Indian Council of Medical Research (ICMR) non-ICMR research institutions, universities, and national programmes. The alliance fosters multicentric studies in thematic areas to provide a platform for pan-India data, supporting the goal of eliminating malaria from India by 2030. The government claims that at least 124 districts reported zero malaria cases in 2021. It also shows that India’s e-Sanjeevani has shown the pathway for tele-consultation and tele-referencing which are being widely used at the round levels for diagnosis and treatment of various healthcare problems including malaria. Odisha has played a significant role in India’s successful fight against malaria in recent years, particularly in high-burden states. The state government has implemented innovative strategies and scaled up the distribution of long-lasting insecticide nets and rapid diagnostic tests to reduce malaria cases and deaths. In 2017, the government launched the ‘Durgama Anchalare Malaria Nirakaran’ (DAMaN) programme, which provided populationwide malaria testing and treatment services to the state’s most inaccessible people at the highest risk of malaria. These efforts have been successful, and since 2017-2018, Odisha has reduced malaria cases and deaths by over 90 per cent. Malaria No More, along with its network of advisers and partners such as UNICEF and Abbott, is now working with the governments of Odisha and India to replicate Odisha’s success nationwide by supporting local strategies that have already shown positive results. “We have made significant progress in reducing the incidence of malaria, and are on track to eliminate it by 2030. However, there are some remote forest areas in states like Odisha, Chhattisgarh, and the North Eastern states, where marginalised tribal communities reside, which pose a challenge in achieving the last mile elimination. To overcome this challenge, it is necessary to intensify surveillance, testing, and vector control measures in these areas,” said Dr Ambarish Dutta, Additional Professor, Epidemiology at Public Health Foundation of India (PHFI). Pratik Kumar, Country Director, Malaria No More, has a different stance. He said, “India has set forth an ambitious goal of eliminating malaria from the country by 2030, in line with the Prime Minister’s vision. While the country has made tremendous progress in controlling the spread of malaria, the road to elimination is still far and has some key challenges along the way. The private health sector, responsible for treating and diagnosing a major proportion of malaria patients, is a key stakeholder for ascertaining and addressing the true disease burden of malaria in India - ensuring each case is detected and treated. Furthermore, the country also contains hidden or asymptomatic burden of malaria - where the disease manifests without the presence of detectable symptoms - further adding to the problem. Finally, while innovative tools and inventive solutions exist or are in the pipeline, the prompt uptake of such solutions into our malaria elimination programme has been lacking. Addressing these and other key challenges will remain critical to achieving malaria elimination. Eliminating malaria is not the responsibility of the government alone. All sections of the society must come together and do their bit to help us achieve a Malaria Mukt Bharat.” Two of India’s largest pharmaceutical companies, Serum Institute of India (SII) and Bharat Biotech, are working (separately) on developing malaria vaccines. SII has licensed the R21 malaria vaccine from the Jenner Institute at Oxford University and will be using Novavax’s proprietary Matrix-M vaccine adjuvant in conjunction with it. Meanwhile, Bharat Biotech has signed a technology transfer agreement with GlaxoSmithKline (GSK) and PATH for the malaria vaccine, RTS,S/AS01. The agreement includes the transfer of manufacturing of the RTS,S antigen part of the vaccine and the grant of a licence on all rights pertaining to the RTS,S/AS01 malaria vaccine to Bharat Biotech. Additionally, Hyderabadbased startup Sapigen Biologix has received Rs 200 crore from the Indian government and Bharat Biotech to develop and commercialise two vaccines - an intranasal COVID-19 vaccine and an RTS,S malaria vaccine. Indian drugmakers and researchers are also working on developing novel antimalarial drugs. In 2021, Zydus Cadila’s antimalarial compound ZY19489 (MMV253) received Orphan Drug Designation from the US FDA. The drug has completed phase 1 clinical trial. CSIR-Central Drug Research Institute (CDRI), scientists are looking for alternative drug targets by probing into mitochondrial dynamics and interorganelle communication of malarial parasites during environmental stress and drug-induced toxicity. Indonesia Indonesia had an estimated 800,000 malaria cases in 2021, the second highest number in Southeast Asia after India. Indonesia is aiming to achieve malaria elimination by 2030 by adopting a regionwise subnational elimination plan in a phased manner.

COVER STORY 23 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com “We have made significant progress in reducing the incidence of malaria, and are on track to eliminate it by 2030. However, there are some remote forest areas in states like Odisha, Chhattisgarh, and the North Eastern states, where marginalised tribal communities reside, which pose a challenge in achieving the last mile elimination. To overcome this challenge, it is necessary to intensify surveillance, testing, and vector control measures in these areas.” - Dr Ambarish Dutta, Additional Professor, Epidemiology at Public Health Foundation of India (PHFI) “While India has made tremendous progress in controlling the spread of malaria, the road to elimination is still far and has some key challenges along the way. The private health sector, responsible for treating and diagnosing a major proportion of malaria patients, is a key stakeholder for ascertaining and addressing the true disease burden of malaria in India - ensuring each case is detected and treated. All sections of the society must come together and do their bit to help us achieve a Malaria Mukt Bharat.” - Pratik Kumar, Country Director, Malaria No More The country has adopted four key strategies to ensure universal access to malaria case management and prevention; transform malaria surveillance as the core intervention of malaria elimination; improve enabling environment to ensure malaria elimination achievement including through community engagement; and strengthen health systems to deliver the malaria elimination programme. Improving malaria surveillance through the electronic malaria surveillance information system (SISMAL) have led to improvement in case-finding and reporting, response and data analysis. In addition to health facilities, private-sector hospitals and clinics as well as military hospitals are reporting to SISMAL. “Indonesia is implementing sub-national elimination towards national elimination in 2030. Currently 372 out of 514 districts/cities have achieved malaria elimination. Indonesia is in the hard rock level, where 90 per cent of cases come from Papua, which is mostly a hard to reach area and for low endemic and stagnant areas, most of them have problems with MMP (migrant mobile population). So in an effort to achieve 2030 elimination, we must reduce the burden of cases in Papua as fast as possible and also focus on the MMP problem, innovations that we will try to do such as MDA (mass drugs administration), IPTp (intermittent preventive treatment of malaria during pregnancy), IPTf (intermittent preventive treatment for forest goers). In addition, intensive and sustainable vector control must also be carried out,” said Dr Hellen Dewi Prameswari, Head of Malaria Prevention and Control Working Team, Ministry of Health, Republic of Indonesia. Myanmar In 2021, Myanmar saw an increase in numbers of both Plasmodium falciparum (Pf) and Plasmodium vivax cases because of the continued political instability in the area. In 2021, Myanmar continued to account for most of the indigenous malaria cases (87.7 per cent) and indigenous P. falciparum malaria cases (80.9 per cent). Myanmar adopted the goal of eliminating malaria by 2030. Also in Myanmar, the new USAID/PMI Eliminate Malaria Activity (PMIEM), started programme implementation in October 2021 in collaboration with Myanmar’s National Malaria Control Programme and other implementing partners, including PATH and Alight. Building on Defeat Malaria’s impact, this 5-year activity works in regions with high malaria incidence and with hard-to-reach migrant groups, scaling up proven interventions to ensure treatment compliance and identify cases of drug-resistant malaria. PMI-EM ● Sri Lanka (2016) ● China (2021) ● Malaysia ● Bhutan ● Thailand ● Vietnam Malaria free countries Countries on path to eliminate malaria

24 COVER STORY BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Following a 70-year effort, on June 30, 2021, China was awarded a malaria-free certification from World Health Orgnisation (WHO) – a notable feat for a country that reported 30 million cases of the disease annually in the 1940s. China is the first country in the WHO Western Pacific Region to be awarded a malaria-free certification in more than three decades. Other countries in the region that have achieved this status include Australia (1981), Singapore (1982) and Brunei Darussalam (1987). Globally, 40 countries and territories have been granted a malaria-free certification from WHO – including, most recently, El Salvador (2021), Algeria (2019), Argentina (2019), Paraguay (2018) and Uzbekistan (2018). Elimination journey Beginning in the 1950s, health authorities in China worked to locate and stop the spread of malaria by providing preventive antimalarial medicines for people at risk of the disease as well as treatment for those who had fallen ill. The country also made a major effort to reduce mosquito breeding grounds and stepped up the use of insecticide spraying in homes in some areas. In 1967, the Chinese Government launched the “523 Project” – a nation-wide research programme aimed at finding new treatments for malaria. This effort, involving more than 500 scientists from 60 institutions, led to the discovery in the 1970s of artemisinin – the core compound of artemisininbased combination therapies (ACTs), the most From 30 million to zero: China’s success in eliminating malaria effective antimalarial drugs available today. In the 1980s, China was one of the first countries in the world to extensively test the use of insecticidetreated nets (ITNs) for the prevention of malaria, well before nets were recommended by WHO for malaria control. By 1988, more than 2.4 million nets had been distributed nation-wide. The use of such nets led to substantial reductions in malaria incidence in the areas where they were deployed. By the end of 1990, the number of malaria cases in China had plummeted to 117,000, and deaths were reduced by 95 per cent. With support from the Global Fund to Fight AIDS, Tuberculosis and Malaria, beginning in 2003, China stepped up training, staffing, laboratory equipment, medicines and mosquito control, an effort that led to a further reduction in cases; within 10 years, the number of cases had fallen to about 5000 annually. In 2020, after reporting four consecutive years of zero indigenous cases, China applied for an official WHO certification of malaria elimination. Members of the independent Malaria Elimination Certification Panel travelled to China in May 2021 to verify the country’s malaria-free status as well as its programme to prevent re-establishment of the disease. Keys to success China provides a basic public health service package for its residents free of charge. As part of this package, all people in China have access to affordable services for the diagnosis and treatment of malaria, regardless of legal or financial status. Effective multi-sector collaboration was also key to success. In 2010, 13 ministries in China – including is contributing to the elimination of the indigenous transmission of Pf malaria by 2025 and helping to put Myanmar on the path to eliminate all human malaria by 2030. What’s next in drug developments The approval of the malaria vaccine in 2021 was a significant milestone in the fight against this disease. Developed by PATH Malaria Vaccine Initiative and GlaxoSmithKline, UK, the TRS,S vaccine is the first and only vaccine recommended to prevent malaria in children, protecting over 1.2 million children in Ghana, Kenya, and Malawi. The vaccine will soon be expanded to several other countries, while other vaccines such as BioNTech’s BNT165b1 and Sanaria Inc. malaria vaccine are also in development, with phase 1 and phase 2 trials underway. Apart from vaccines, a couple of antimalarial drugs to combat drug resistant malaria are also in the pipeline. Novartis and Medicines for Malaria Venture (MMV) have decided to progress their novel non-artemisinin combination treatment for uncomplicated malaria into phase 3 trials. Australian researchers from Monash University have identified an antimalarial compound, ML901, which inhibits the malaria parasite but does not harm mammalian – human or other mammals’ – cells. Japanese pharma behemoth Shionogi has entered into a comprehensive cooperation agreement with Nagasaki University, pursuing research for the prevention and treatment of malaria. Early and accurate detection is a mainstay when

COVER STORY 25 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com “The malaria situation in Asia varies from country to country. In a big place like India, as you can imagine, there is a wide variation in vegetation, rainfall, resources for control, etc. So we have very predictable malaria in some places, and lack of malaria in other places.” - Dr Pradip Rathod, Professor of Chemistry and a joint Professor of Global Health, University of Washington “Indonesia is implementing sub-national elimination towards national elimination in 2030. Currently 372 out of 514 districts/cities have achieved malaria elimination. In an effort to achieve 2030 elimination, we must reduce the burden of cases in Papua, which is mostly a hard to reach area as fast as possible and also focus on the MMP problem, innovations that we will try to do such as MDA, IPTp, IPTf.” - Dr Hellen Dewi Prameswari, Head of Malaria Prevention and Control Working Team, Ministry of Health, Republic of Indonesia “As PV malaria can remain dormant in the liver for years, and can reactivate later, the burden of PV malaria is persistent and challenging. The regular antimalarials cannot kill the liver stage, and thus requires special medication that belongs to the group ‘8-aminoquinolines’ that can cause bleeding among specific populations who have deficiency of a specific enzyme - G6PD.” - Bipin Adhikari, Researcher, Mahidol-Oxford Tropical Medicine Research Unit (MORU), Bangkok, Thailand those representing health, education, finance, research and science, development, public security, the army, police, commerce, industry and information technology, customs, media and tourism – joined forces to end malaria nationwide. In recent years, the country further reduced its malaria caseload through a strict adherence to the timelines of the “1-3-7” strategy. The “1” signifies the one-day deadline for health facilities to report a malaria diagnosis; by the end of day 3, health authorities are required to confirm a case and determine the risk of spread; and, within 7 days, appropriate measures must be taken to prevent further spread of the disease. Keeping malaria at bay The risk of imported cases of malaria remains a key concern, particularly in southern Yunnan Province, which borders 3 malaria-endemic countries: Lao People’s Democratic Republic, Myanmar and Viet Nam. China also faces the challenge of imported cases among Chinese nationals returning from sub-Saharan Africa and other malaria-endemic regions. To prevent re-establishment of the disease, the country has stepped up its malaria surveillance in at-risk zones and has engaged actively in regional malaria control initiatives. Throughout the COVID-19 pandemic, China has maintained trainings for health providers through an online platform and held virtual meetings for the exchange of information on malaria case investigations, among other topics. Source: WHO it comes to fighting against an endemic disease. To that effect, researchers in the regions are working to develop a sensitive point of care diagnostics, In February 2023, two WEHI (Walter and Eliza Hall Institute of Medical Research) projects received $1.3 million from Australian government funding to clinically translate a test that can detect people with ‘hidden’ Plasmodium vivax (Pv) – considered the most widespread and resilient malaria parasite for its ability to remain dormant in the liver for years. A handheld, smartphone-operated, nearinfrared spectrometer has also been developed by the University of Queensland and Brazil’s Instituto Oswaldo Cruz to detect changes in blood caused by malaria. Meanwhile, researchers from the Indian Institute of Technology Bombay have created a panel

26 COVER STORY BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com of proteins that can differentiate between malaria parasite species and gauge the severity of infection. Although there have been some sporadic developments in creating new tools to combat malaria, there is still an urgent need to invest in newer tools to address the increasing challenges of drug-resistant malaria.WHO’s world malaria report also sheds light on the continued investments in this space to make the malaria free world a reality. According to the report, in 2021, the global funding for malaria basic research and product development was reduced by $54 million from 2020, totaling $626 million. This is below the estimated amount of $851 million needed to achieve the targets and marks the third consecutive year of funding decline since 2018. The total annual resources required to achieve the 2025 and 2030 milestones are estimated at $6.8 billion in 2020, increasing to $9.3 billion in 2025 and $10.3 billion by 2030. Additionally, an extra $0.85 billion annually is estimated to be necessary for global malaria research and development from 2021 to 2030. The way forward Though there has been remarkable progress in tackling malaria, much more needs to be done to actually eradicate malaria for good. Scaling up proven implementation strategies, and adopting The World Health Organisation (WHO) global malaria strategy for malaria urges all malariaendemic countries to accelerate progress towards the goal of elimination. In settings approaching elimination, interventions will be most effective at reducing transmission if they are tailored to the distribution of the reservoir of malaria infection. The new recommendations for the final phase of elimination available in the WHO Guidelines for malaria. Some of these recommendations are also relevant to areas that have achieved elimination and are working to prevent re-establishment of transmission. The recommendations are divided into 3 categories of possible interventions: “mass” strategies, “targeted” strategies and “reactive” strategies. Mass Strategies: In areas where malaria transmission is generalised across the population of a defined geographical area (for example, in a district or village), strategies that cover the whole population may be needed to reduce transmission. These strategies could include mass drug administration, mass testing and treatment or mass relapse prevention. Mass strategies are generally not recommended for post-elimination settings unless there is a resumption of local transmission of malaria. Targeted Strategies: At very low and low levels of transmission, malaria cases are often concentrated among people with shared risk factors. The premise behind targeted strategies is that interventions applied to a small subset of the population that is believed to encompass the reservoir of infection could reduce transmission overall. In many low-transmission settings, populations at higher risk of malaria infection WHO recommendations on malaria elimination are engaged in outdoor activities such as mining, rubber tapping, forestry and cattle herding. People who participate in night-time sports, socialise outdoors or sleep outside are also at higher risk of contracting the disease. Targeted strategies for reaching such populations could include targeted drug administration and targeted testing and treatment. Reactive Strategies: As malaria transmission declines and approaches zero, cases tend to cluster geographically (in small areas such as households and neighbourhoods) or socially, among people exposed to the disease at the same time and place (such as through a common occupation or shared travel to endemic areas). If clusters can be identified and targeted with effective interventions, malaria transmission at the community level may be reduced. “Reactive” strategies are triggered “in reaction” to the identification of a confirmed case of malaria. They include: reactive drug administration, reactive case detection and treatment, and reactive indoor residual spraying. The success of these 3 interventions depends on a strong surveillance system that is capable of detecting suspected malaria cases and investigating all confirmed cases at their place of origin. When used, these interventions should be one of several components of a programme to eliminate or prevent re-establishment of malaria, including intensive surveillance, as described in the Framework for malaria elimination. As cases of malaria may be identified in post-elimination settings, reactive strategies are also relevant to areas working to prevent re-establishment of malaria. Source: WHO

COVER STORY 27 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com malaria is persistent and challenging. The regular antimalarials cannot kill the liver stage, and thus requires special medication that belongs to the group ‘8-aminoquinolines’. Antimalarial regimen consisting of 8-aminoquinolines is called radical cure regimen. The challenge with 8-aminoquinolines is that it can cause bleeding among specific populations who have deficiency of a specific enzyme called ‘Glucose 6 Phosphate Dehydrogenase (G6PD). Identifying the risk population with inadequate G6PD enzymes is the major challenge. Although G6PD can be accurately measured in advanced labs, the optimal point of care (POC) tests are only becoming available recently. Deploying these POC tests and treating with radical cure regimen are not yet (fully) rolled out in the region. The next step is to explore implementation possibilities of the POC tests available so far and adding further interventions to this regular treatment such as mass antimalarial and vaccine administration.” No strategy will help if it doesn’t reach the people who need it the most. As countries in the Asia Pacific region aim to eliminate malaria by 2030, it is necessary to expand currently available preventive measures and prompt diagnosis and treatment to populations that are difficult to reach. One way to achieve this is by implementing mobile malaria clinics, village volunteer malaria workers, and screening posts. Since eliminating Malaria in Asia is a formidable challenge, we need an all-hands-on-deck approach. Learning from the countries who have successfully eradicated the diseases, adopting effective strategies and utilising innovative genetic tools for surveillance and control, along with cross-collaboration among countries in the region, can make malaria free Asia a reality. It is crucial to continue investing in research, funding and public health initiatives to eliminate malaria and improve the health and well-being of millions of people in the region. Ayesha Siddiqui newer, innovative strategies such as new investments, vector control approaches, diagnostics, antimalarial medicines, and other tools will speed up the pace of progress against malaria. “The malaria situation in Asia varies from country to country. In a big place like India, as you can imagine, there is a wide variation in vegetation, rainfall, resources for control, etc. So we have very predictable malaria in some places, and lack of malaria in other places,” Dr Pradip Rathod, Professor of Chemistry and a joint Professor of Global Health at University of Washington. He also directs a large US NIH (National Institute of Health) programme project on malaria, with many partners in India, and some in the US. This is where technology can come in handy. Israel based Zzapp malaria uses artificial intelligence to identify malaria hotspots and optimise interventions for maximum impact. Zzapp’s mapbased mobile app conveys the AI strategies to field workers as simple instructions, ensuring thorough implementation. The firm has successfully deployed this in Africa where compared to a control community, the operation reduced the mosquito population by over 60 per cent in as little as three and a half months. Tried and tested tools such as bed nets, other vector control products, diagnostics, drugs, a functional surveillance system, and a supply chain all built upon sound sub-national public health management has yielded remarkable results — leading to elimination in places like Sri Lanka and, most recently, China. Other Asian countries can emulate these practices. The Lancet study suggests that malaria elimination in South-East Asia can be achieved by adopting Sri Lanka’s 1-2-3 strategy of case reporting, investigation, and follow-up. Cross-collaboration among countries in the region, such as collaborative research for a new malaria vaccine targeting P vivax, would be beneficial. Bhutan and Timor-Leste are already attempting to develop action plans to counter cross-border transmission by collaborating with neighbouring countries like India and Indonesia. China’s use of innovative genetic tools to monitor drug resistance, identify local versus imported cases, and track the sources of infections in malaria control and elimination could offer game-changing results when applied to settings with ongoing transmission. Bipin Adhikari, a researcher at Mahidol-Oxford Tropical Medicine Research Unit (MORU), Bangkok, Thailand suggests the following strategies. He said, “Since PV malaria can remain dormant in the liver for years, and can reactivate later, the burden of PV

28 RARE DISEASES BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com The death of a 13-year-old Ghaziabad boy suffering from Hunter Syndrome or MPS-II due to the non-availability of medicine and the right treatment is something to be pondered on. The boy was suffering from what is known as a rare disease or an orphan disease. Rare diseases are nothing new to us and according to the Ministry of Health and Family Welfare, there are about 450 diseases recorded so far in India. If we go by the estimates, 50 per cent of new cases are in children and are responsible for 35 per cent of deaths before the age of one year, 10 per cent between the ages of one and five years and 12 per cent between five and 15 years. Rare Diseases Needn’t Be Neglected Anymore India has over 450 types of rare diseases. Lack of awareness and stigma attached to rare diseases have added to the woes of patients suffering from them. The exorbitant cost of therapies makes many patients opt out altogether. Experts opine that the road ahead to make notable progress in this area of healthcare is long and the right policy measures will determine how this neglected space fares. The commonly reported rare diseases in India are Haemophilia, Thalassemia, Sickle-cell Anaemia and Primary Immuno Deficiency in children, auto-immune diseases, Lysosomal storage disorders such as Pompe disease, Hirschsprung disease, Gaucher’s disease, Cystic Fibrosis, Hemangiomas and certain forms of muscular dystrophies. According to the World Health Organisation (WHO), these diseases are debilitating, lifelong disorders whose prevalence is less than one per 1,000 persons. They include autoimmune disorders, congenital malformations, inherited cancers, and certain endemic infectious diseases that have very low prevalence. Hurdles Lack of awareness and the stigma attached are the two major concerns for rare disease patients and their families. Though the Ministry of Health and Family Welfare formulated a National Policy for Treatment of Rare Diseases (NPTRD) in 2017, the implementation was faced with a lot of challenges. Lack of clarity on the exact number of patients, cost-effectiveness of interventions for rare diseases vis-a-vis other health priorities etc. took a toll on those who suffered from the disease. Poor awareness among the healthcare staff and lack of proper diagnostic facilities also compound the woes of the patients. The other major concern is the cost of treatment. The exorbitant cost of therapies prevents many patients from going in for the right treatment and many leave halfway. Ramaiah Muthyala, President and CEO, Indian Organisation for Rare Diseases opines, “Rare diseases are genetic disorders; for them, there are no cures, only treatments. Generic orphan drugs, about 350 APIs are manufactured by Indian pharma and all are being exported. They are formulated elsewhere and come back into India at an exorbitant price and import license requirement. As a result, none of them is easily accessible for Indian rare disease patients. Pulled up In December 2022, the Government of india was directed by the Delhi High Court (HC) to release Rs 5.35 crore to enable clinical trials for medicines that can treat rare diseases such as Duchenne Muscular Dystrophy (DMD). The HC observed that the “magnitude of the problem suffered by children with rare diseases leaves no doubt in the mind of the court that the creation of treatment therapeutics for children with rare diseases would be considered as a nationally important project.” It also observed that the efforts for crowdfunding for treatment of DMD and other rare diseases had not yielded much results as the issue does not appear to have gained enough importance in the society in general. The Biotechnology Industry Research Assistance Council (BIRAC) with Hanugen Therapeutics was to conduct clinical trials, however, things were delayed due to lack of funds. The HC also directed BIRAC to release the above-mentioned fund to Hanugen Therapeutics to begin the trial.

RARE DISEASES 29 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Rare diseases are genetic disorders for which there are no cures, only treatments. Generic orphan drugs, about 350 APIs, are manufactured by Indian pharma and all are being exported. They are formulated elsewhere and come back into India at an exorbitant price and import license requirement. As a result, none of them are easily accessible for Indian rare disease patients. - Ramaiah Muthyala, President and CEO, Indian Organisation for Rare Diseases It is really important if we are starting treatment from a very early stage. Hence, it is extremely important to have such medical treatment facilities to be made available in India. - Dr Sheela Nampoothiri, Clinical Professor, Department of Pediatric Genetics, Amrita Hospital It will be instrumental to build innovative access initiatives and strategic partnerships across the rare disease landscape to bring customised solutions for patients with targeted education, awareness, diagnosis, and treatment for effective disease management. - Ruchi Sogarwal, Head, Public Affairs and Patient Advocacy, Takeda Biopharmaceuticals Modern therapies for rare diseases, including gene editing, gene therapy, ASOs, RNAi, mRNA, and ERT are highly promising but unaffordable and inaccessible to the Indian patient community. Although a small percentage of rare disease patients need expensive drugs, others can be managed by alternate therapies such as diet, medical foods, the Indian system of medicines (AYUSH), social support, and medical devices, which improves the quality of life.” Indian Organisation for Rare Diseases has been promoting collaborations with patient organisations, e.g., Rare Disease International (RDI), European Organization for Rare Diseases (EURORDIS), National Organization for Rare Diseases (NORD), the International Rare Diseases Research Consortium (IRDiRC), the International Collaborations on Rare Diseases and Orphan Drugs (ICORD). Creating awareness Advancements in medical research and technology will be the key drivers for the development of innovative drugs for the treatment of rare diseases. AI is also being used to improve the diagnostic process. Apart from this, developments in the precision of genetic testing and the clinical use of genome sequencing are now also accelerating the diagnosis of rare diseases. The Department of Biotechnology has set up Nidan Kendras under the Unique Methods of Management and Treatment of Inherited Disorders (UMMID) project for genetic testing and counselling services. These Nidan Kendras perform screening, genetic testing and counselling for rare diseases. Recently, the Government of Karnataka launched a research and training unit for rare diseases. The unit will strengthen diagnosis, counselling and treatment, including developing the service facility for prenatal diagnosis for early identification of genetic disorders in pregnancy. The activities to be undertaken at the Research and Training Unit for Rare Diseases include comprehensive genetic counselling facilities for around 2,500 families with rare disorders, to be evaluated annually; increasing the capacity of diagnostic testing, including exome sequencing; and developing training and service facility for prenatal diagnosis for early identification of genetic disorders in pregnancy. It will also provide hands-on training in laboratory genetics and incubate startups in developing low-cost therapies for rare disorders along with conducting regular educational modules in Kannada, English and Hindi for raising awareness of human genetic disorders, their early recognition, and treatments available, among pre-university college students in the state. The unit will be around 40,000 sq ft with three floors. Dr Sheela Nampoothiri, Clinical Professor, Department of Pediatric Genetics, Amrita Hospital, who recently joined ICMR’s Rare Diseases National Consortium’s expert committee as co-chair says, “It is really important if we are starting treatment from a very early stage. Hence, it is extremely important to have such medical treatment facilities to be made available in India. Regarding the rare disease policy, as the cost of therapy is exorbitant, the policy statement

30 RARE DISEASES BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Centres of Excellence in India Treating Rare Diseases ● All India Institute of Medical Sciences, New Delhi ● Maulana Azad Medical College, New Delhi ● Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow ● Post Graduate Institute of Medical Education and Research, Chandigarh ● CDFD with Nizam Institute of Medical Sciences, Secunderabad ● King Edward Memorial Hospital, Mumbai ● Institute of Post- Graduate Medical Education and Research, Kolkata ● Center For Human Genetics (CHG) with Indira Gandhi Hospital, Bengaluru ● All India Institute of Medical Sciences, Jodhpur ● Institute of Child Health and Hospital for Children, Chennai is suggesting crowdfunding as the model to raise funds for patients.” Amrita Institute is currently treating seven patients with Pompe disease apart from treating 17 patients with five types of treatable Lysosomal Storage Disorders and these patients are being treated through a charitable access programme. Recently, the institute has started enzyme replacement therapy (ERT) for a patient with Niemann Pick B disease and this is the first patient to be started with ERT from India. According to the institute, before 2008, there was no availability of treatment and these babies were all dying before the age of one year. ERT needs to be started at the earliest in the newborn period itself and treatment is given as an intravenous infusion once every two weeks. The therapy should be given for life because they lack the enzyme alpha-glucosidase in their body. The SAT Hospital in Thiruvananthapuram Medical College has started the registration process for treating diseases as part of the centre of excellence programme. All rare disease cases will be registered with SAT hospital even if the disease was diagnosed in other hospitals. The registered patients will be provided the benefits of the centre of excellence programme at the treating hospital. In partnership with the All India Institute of Medical Sciences (AIIMS) Jodhpur and the Dystrophy Annihilation Research Trust (DART), the Indian Institute of Technology (IIT), Jodhpur has established a research centre for Duchenne Muscular Dystrophy (DMD). It is characterised by advancing muscle weakness and degeneration as a result of changes to a protein called dystrophin. Exploring treatment methods Pfizer is exploring options for some early-stage treatments for rare diseases in a bid to focus on highimpact medicines. According to the company, there are plans to focus on internally developing rare disease treatments using technologies such as gene editing, while exploring external opportunities for early-stage gene therapy programmes. The Subject Expert Committee functional under Central Drug Standard Control Organisation (CDSCO) has given a waiver to Cipla to conduct Phase IV study of Tocilizumab Injection for giant cell arteritis, a form of rare disease. Takeda Biopharmaceuticals has launched two medicines namely Adynovate, an extended half product for the treatment of haemophilia patients and Cinryze to treat hereditary angioedema (HAE) in India. Ruchi Sogarwal, Head, Public Affairs and Patient Advocacy, Takeda Biopharmaceuticals, says, “It will be instrumental to build innovative access initiatives and strategic partnerships across the rare disease landscape to bring customised solutions for patients with targeted education, awareness, diagnosis, and treatment for effective disease management. Takeda is committed to introducing medicines in focus areas that have a huge unmet need. With this aim in mind, we launched two of our innovative medicines.” Researchers at the Indian Institute of Technology (IIT), Madras, Tel Aviv University & Columbia University are working on developing a drug to treat a rare genetic brain disease known as GNB1 Encephalopathy, which affects individuals at the foetal stage. The research is supported by an Indo-Israel Binational grant offered by Israel Science Foundation (ISF) & India’s University Grants Commission (UGC). The way forward Affordable medicines are the need of the hour. Epidemiological data needs to be in place with proper policy measures. Awareness among the ASHA workers who can go to the interiors to update on the exact number of rare disease patients across the country will help to create a database which will eventually help to come up with certain policies needed. Pharma companies need to re-look at strategies to do more clinical research for rare diseases. On a good note, the Government of Tamil Nadu offered to treat a girl diagnosed with Systemic Lupus Erythematosus free of cost. Sanjiv Das [email protected]

RARE DISEASES 31 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Addressing ‘Orphaning’ of Rare Diseases « Ravi Shet, Clinical Data Management Professional To tackle any disease requires sustained research and development (R&D), to help us learn more about it and to create effective treatments. However, when it comes to R&D around rare diseases, there are few key challenges which ultimately impact patient outcomes. The most important challenge is how unevenly spread rare diseases are among populations. We don’t have a complete picture of how many people are affected by rare diseases in India, because most of the time these are not reported properly from the patient or their relatives. It becomes more difficult for the pharmaceutical companies to prioritise, since most of the rare diseases are clinically dissimilar and require unique treatments. Another big challenge is funding to develop drugs for treating these rare diseases. Since it affects a small number of people in comparison with cancer, cardiovascular disease and diabetes, they are often considered low priority when it comes to allocating funds. Drugs needed to treat rare diseases are known as Orphan Drugs which essentially means that they treat medical conditions so rare that it would not be profitable to produce and develop them. Conducting clinical trials for rare diseases can be equally challenging in terms of recruiting patients for the particular rare disease as well as time taken to complete the trial for the same, which in turn costs millions of dollars. Post approval follow-up process takes on an even greater role to ensure that the drugs work effectively on the patients. To promote more efficient & effective research into rare diseases, new epidemiological & clinical trial methods have also been developed. This could benefit and make it much easier & affordable to run clinical trials for rare diseases. Game Plan Advancements in medical research and technology will be the key drivers for development of innovative drugs for the treatment of rare diseases. AI is also being used to improve the diagnostic process. Developments in the precision of genetic testing and the clinical use of genome sequencing are now also accelerating the diagnosis of rare diseases. With lower costs, they are becoming more widely available, and this is leading to a paradigm shift in public health which is termed as ‘precision public health.’ This is enabling screening for rare diseases much earlier and leading to better outcomes overall, which eventually reduces the lengthy journey to an accurate diagnosis. India Roadmap The Government of India has launched National Policy for Rare Diseases (NPRD), 2021 in March 2021 for the treatment of rare disease patients. As per the NPRD, rare diseases have been identified and categorised into 3 groups namely Group 1, Group 2 and Group 3. ● Group 1: Disorders amenable to one-time curative treatment ● Group 2: Diseases requiring long term/lifelong treatment having relatively lower cost of treatment and benefit has been documented in literature and annual or more frequent surveillance is required ● Group 3: Diseases for which definitive treatment is available but challenges are to make optimal patient selection for benefit, very high cost and lifelong therapy The NPRD, 2021 has provisions for promotion of R&D for diagnosis and treatment of rare diseases; promotion of local development and manufacture of drugs and creation of a conducive environment for indigenous manufacturing of drugs for rare diseases at affordable prices. In addition to these, financial incentives for the patients as well as set-up of testing and counselling centres are part of the policy. Conclusion No doubt, India has the potential as well as the talent pool to cater the demand for more innovations in producing drugs to treat rare diseases. Also, the policies set by the Government of India will be a game changer for companies going for more R&D in this domain that might benefit patients with rare diseases. At the same time, we should continue to support the improvements and innovations with proper cross collaboration towards the common goal of attacking rare diseases for patient’s better health and longevity.

32 SPEAKING WITH BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Australian firm Immutep has partnered with Merck and Pfizer for a new Phase I clinical study in patients with urothelial cancer for its lead product candidate -eftilagimod, in combination with avelumab (BAVENCIO). In an email interaction with BioSpectrum Asia, Immutep, CEO, Marc Voigt highlights the pioneering work that the company is undertaking in the immuno-oncology field and the trends and developments in the sector. Edited excerpts; Please describe your immunotherapy research. Immutep is the global pioneer and leader in the development of LAG-3 therapeutics. LAG-3 was discovered by Immutep’s Chief Medical Officer and Chief Scientific Officer, Prof. Frederic Triebel. It is a naturally occurring protein that activates the antigen presenting cells (APCs) of the immune system by binding to the Major Histocompatibility Complex (MHC II). The interaction between the LAG-3 protein and the MHC II can be influenced or changed to help the body fight cancer by activating or inhibiting the immune system. Today, LAG-3 is considered the promising new immune checkpoint in immuno-oncology since the success of PD-1 related treatments. LAG-3 drugs have the potential to overcome many of the limitations of other oncology drugs, such as chemotherapy and even established immuno-oncology treatments such as anti-PD-1 monotherapy, a common immune checkpoint therapy where unfortunately 70-80 per cent of patients fail to respond. Immutep is developing four candidates based on LAG-3, including our lead product candidate, efti which is advancing in late-stage clinical trials. It is an “immune booster” with a broad immune “Immutep has started exploring the potential of the first ever triple combination therapy with Eftilagimod” « Marc Voigt, CEO, Immutep activation and the versatility to be paired with existing standard of care treatments such as PD-1 (or PD-L1) antagonists in combination therapies. Efti also has a strong safety profile and a unique mode of action, differentiated from anti-LAG-3 products. Acting as an APC activator, efti complements the effect of immune checkpoint inhibitor (ICI) drugs, such as the blockbuster drug Keytruda, also known as pembrolizumab. Efti is the only MHC II agonist (APC activator) product candidate currently in clinical development and has shown encouraging clinical results in multiple cancer settings, including nonsmall cell lung cancer, head and neck squamous cell carcinoma, metastatic breast cancer and melanoma. How do you see the cancer immunotherapy field evolving? In general, we believe cancer immunotherapy will continue to play a key role in treating many different carcinomas. Interest and investment in LAG-3 therapeutics has accelerated significantly over the last year since LAG-3 was validated via the approval of BMS’s Relatlimab by the US FDA, and is expected to rise even more. There is still work to do to fully realise the significance of the LAG-3 / MHCII interaction in cancer; however, many therapies are advancing rapidly through late-stage trials towards approval, including efti. Overall, we will continue to see a high number of clinical trials testing different combinations of therapies in order to get the best outcome for as many patients as possible. This may imply we will see a more fragmented treatment landscape and that the role of biomarkers will continue to increase. Also, I’m excited by the opportunity ahead to explore LAG-3 related treatments in autoimmunity. What are the latest trends and challenges in cancer immunotherapy? Combination therapies, where we pair an immunooncology drug with, for example, a chemotherapy or radiotherapy, are a relatively new paradigm. The idea is to get the immune system functioning well enough to fight the cancer alongside another treatment. In some cases, there can be advantages beyond improved efficacy, such as the ability to give lower doses of chemo which are more tolerable for patients. We’re hopeful this approach will provide a new option to many cancer patients. Ayesha Siddiqui

SPEAKING WITH 33 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com The Asia Pacific (APAC) represents more than a third of all cell and gene therapy in global trials. In line with the trend, Sydney-based contract research organisation (CRO), Novotech has conducted a statistical analysis which indicates that, between 2017 and 2021, over 70,000 new clinical trials were registered in the APAC region, the US, and the EU5 (France, Germany, Italy, Spain, UK). During the forecast period, the APAC region reportedly accounted for 50 per cent of the trials, followed by the US (29 per cent) and the EU5 (17 per cent). China recorded the largest number of new trials, followed by the US and India. Dr John Moller, CEO Novotech, provides his views on the APAC CRO market. Edited excerpts; What is your outlook for the Asia Pacific CRO market in 2023? The latest Novotech research with GlobalData shows that APAC continues to be a global hub for clinical trials. Our current data shows it had the highest growth rate globally with 9 per cent CAGR in 2022. In addition, the APAC is well positioned with 7,600 clinical sites, more than any other region, combined with higher urban density which translates to expedited patient access. We expect the APAC to continue this exceptional growth through 2023 and beyond, fueled by access to patient populations, quality medical and site facilities, site capacity and the ability to deliver accelerated timelines with globally accepted data. What do Novotech’s Cell & Gene Therapy clinical trial statistical analyses for APAC indicate? Which country is the leading hub for trial activities? The APAC is certainly the global hub for cell and gene therapy research. The region’s cell and gene sector is currently growing almost 50 per cent faster than the rest of the world (ROW) and we expect to see this sector continuing to grow at record speed, especially in oncology, vaccine, and cardiovascular research. In addition, China has an exceptional growth profile which is currently 15 per cent faster growth rate than ROW. The latest research from GlobalData data shows “APAC continues to be a global hub for clinical trials” « Dr John Moller, CEO, Novotech APAC is involved in more than a third of all cell and gene studies. From 2017 to August 2022, there were close to 1,800 trials initiated in cell and gene therapy, with APAC involved in ~40 per cent of trials. In addition, the APAC is the leading location globally for CAR-T trials, with China attracting ~60 per cent of all CAR-T trials between 2015 and 2022. We know the region is a proven destination for quality clinical data, exceptional medical facilities, and access to vast patient populations. Indeed, due to its large population and lower volume of studies, the APAC region has a trial density about 6 times lower than the US and 5 times lower than Europe. China has the lowest trial density. The majority of cell and gene clinical trials are in oncology, specifically for blood cancers, viral infections, and solid tumors. After oncology, the majority are in infectious diseases, CNS, and cardiovascular diseases. The region also has a favorable research and development landscape for early and mid-phase cell and gene therapy studies with Phase I and Phase II trials accounting for the majority (>90 per cent) of trials conducted in the APAC region. Which are the leading therapeutic areas for clinical trials in APAC? APAC countries undertake trials across the therapeutic spectrum and the main underlying driver is sheer population, with lower trial density than the rest of the world. They have also experienced an increase in some cancers, infectious diseases and lifestyle and metabolic conditions. For example, one in three of the approximately 400 million hepatitis B-infected global population resides in China. In comparison to the United States and Europe,

34 SPEAKING WITH BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Asia also has a significantly higher prevalence of nonHodgkin’s lymphoma, non-small cell lung cancer, and certain genetic disorders. These disease rates translate to a larger patient population, enabling rapid enrollment. Additionally, China and Japan are the second and third biggest pharmaceutical markets in the world, respectively. Further, the region has a lower trial density due to its vast patient population and lower study volumes, which means there is less competition for eligible patients. In addition, the multiethnic populations in the APAC region enables sponsors to gather a wide range of data on patients who have historically been underrepresented in clinical research. This has recently been emphasized by regulatory authorities to ensure the broadest access to novel medications. For a CRO, which are the strategically significant locations in Asia? What is Novotech’s approach to aligning its strategies with the market? While the region as a whole is experiencing significant growth, the strategically significant regions in APAC are Greater China, South Korea, Taiwan, Australia and New Zealand. Novotech serves specific and unique requirements including study phase, protocol, timelines and of course, therapeutic areas. The market dynamics that shape our clinical programmes include disease prevalence, access to standard of care, regulatory environments, access to patients, and our long-term relationships with sites and investigators across the region. While our company has deep expertise in the APAC and the data shows a significant number of studies globally are conducted in the region, Novotech’s European and US operations offer expanded services for global clinical development for biotech clients. How do you perceive the complexity and regulatory process involved in cell and gene therapy research? Cell and gene therapy research typically presents another level of complexity and regulatory processes which means an experienced CRO partner is vital. There are often additional regulatory agencies and complex definitions around the nature and risk of a cell and gene therapies that need to be complied with. We are pleased to have been recently recognised with the Gene & Cell Therapy Excellence Award 2022 which is a real credit to our Novotech team and their expertise in this rapidly growing sector. How would you describe Novotech’s perspectives on global expansion? How would you describe investigator relationships? Novotech has been executing a global expansion strategy over the last 12 months. This has been driven by the demand of our larger biotech clients, many of which are undertaking global Phase 3 projects. We acquired a US CRO last year, and the recent acquisition of EastHORN completes the European part of this strategy giving us access to around 30 European countries. We’ve been close partners with EastHORN for well over a decade and we take a similar approach to client service and we know each other well. While EastHORN operates throughout Europe it has a long history in Central and Eastern Europe, which has some of the attractive patient recruitment characteristics that Novotech enjoys in Asia, as well as some similarities in disease prevalence. We have also recently acquired CBR International, a global product development, clinical oversight and strategic regulatory operations group. Our US regulatory acquisition gives us additional FDA-focused regulatory expertise and services including regulatory strategy development and writing, FDA representation, e-submissions, and GMP support amongst those services. The acquisition will strengthen Novotech’s capabilities in regulatory strategy and US FDA interactions and submissions including IND, IDE, NDA, BLA, Fast-Track, Break-through and Orphan Drug Applications. This will be particularly important for many of our Asia-based clients who are moving into the clinic at an incredibly fast pace and often need external regulatory support. The CBR acquisition, together with Novotech’s existing regulatory affairs capability, creates a large global group of experts in toxicology, drug development, and global regulatory submissions support. Novotech has decades of drug development and clinical trial experience with biotech clients, exceptional site and investigator relationships, access to vast patient populations, and a project management approach focused on problem-solving, ownership, and flexibility. We continue to invest heavily in our training and development as well as state-of-the-art systems which will be of enormous benefit to our newly acquired companies and our clients. Hithaishi C Bhaskar [email protected]

SPEAKING WITH 35 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Cardinal Health (Hq: Ohio), a global manufacturer and distributor of medical and laboratory products has steadily expanded its operations in the Asia Pacific (APAC) over the years, with Singapore as its APAC commercial hub. Steve Mason, CEO of Cardinal Health’s Medical Segment recently visited Singapore and shared his vision for the APAC medical device market in an exclusive tête-à-tête interview. Edited excerpts; What is your outlook for the APAC medical device market in 2023? The global market for elective surgical procedures continues to lag behind that of pre-COVID levels. The lower number of procedures has slowed demand for medical devices. We expect these numbers to begin to normalise as COVID-19 becomes less of a critical healthcare concern. From a macro perspective, raw material shortages and limited shipping capacity have led to a rise in the cost of goods, and reinforce two continuing market challenges that need to be addressed: inflation and supply chain constraints. The APAC market faces these same issues. We have worked to mitigate these cost challenges by expanding our global transportation network and collaborating with our suppliers to address shortages by creating greater operational efficiencies. Our international business, which includes APAC, continues to perform well despite these challenges. We expect to maintain our momentum and to grow market share in our focused medical product categories. What will Cardinal Health’s strategic roadmap look like in 2023? How significant and conducive is the APAC region for medical products and distribution? We employ two operating models in Asia Pacific markets. The first is a Direct Markets approach where we have in-market commercial operations supported by cross-functional teams. These teams focus on developing the capabilities required to exceed customer expectations and drive profitable growth through direct customer engagement. In Asia Pacific, we adopt this approach in markets like Australia, “There’s strong commercial growth potential for medical devices in APAC markets” « Steve Mason, CEO, Medical Segment, Cardinal Health China, Korea and Singapore. The second is a Channel Partnerships approach where we work in close association with distributors in countries like India, Vietnam, and Thailand. Japan is our second largest International market, and we operate that as a standalone operation that is more vertically integrated than others. Our Asia Pacific operations are critical to the company. We have an extensive manufacturing and sourcing footprint in the region, and there is strong commercial growth potential in the Asia Pacific markets. Singapore is our Asia Pacific hub, which was established in 2004. Apart from being a key product distribution centre, our global sourcing and Asia commercial teams are based in Singapore. We also have a global R&D centre here, the only one outside of the US. Furthermore, our long-standing partnership with Singapore’s Economic Development Board (EDB) in the areas of innovation and technical excellence, as well as the availability of highly skilled local talent have led to our Singapore operations contributing significantly to our growth in APAC and beyond. By understanding customer needs in the region, and leveraging the depth and breadth of our capabilities in Asia Pacific, we hope to continue to grow market share in the medical product categories that align with our international commercial strategy. These include surgical gloves, nutrition delivery, and pneumatic compression products. We are also exploring how we can further tap into Japan’s broader growth potential by leveraging our Japan design and manufacturing capabilities. We have products developed solely for the Japanese market such as neonatal catheters

36 SPEAKING WITH BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com that we believe may benefit patients in other markets. This opens a new avenue of growth for our Japan business, and also creates new revenue opportunities for us. In what ways is Cardinal Health staying relevant in an ever-evolving market? How competitive is the APAC marketplace? At Cardinal Health, our growth strategy focuses on having the right commercial resources in the right markets with the right products. We seek to offer our customers around the world high-quality, clinically differentiated products that support better patient outcomes. We are leading in surgical gloves, pneumatic compression devices, and nutritional delivery. We have also been investing to enhance technical capabilities across our supply chain, especially in data and resource management. The Asia Pacific region is a competitive one. Apart from large multinational healthcare companies, there are a number of local market companies that are producing quality medical products. That is why we have deployed a focused growth strategy in APAC. We’ve implemented this strategy to keep pace with rapidly shifting global marketplace dynamics. This strategy allows us to better tap into growth opportunities, and identify commercial synergies. For example, we have a strategic agreement with Medika Medical Technology (Zhejiang) Co. Ltd to distribute the company’s EZ Pump enteral feeding system in China. Through this collaboration, Medika leverages Cardinal Health’s broad distribution network in China, and taps into our global enteral nutrition expertise to promote and market Medika’s EZ Pump across the country. These sorts of partnerships combined with Cardinal Health’s broad range of market-leading medical products will help us to grow by leveraging our expertise in our core health care focus areas. How do you envision commercialisation strategies evolving towards novel product pipelines? Is the APAC market amenable to partnerships and collaborations? The best way to deliver innovation that matters is to address both customer and patient challenges. New product development centres on improving patient outcomes and product functionality for healthcare professionals. We do this within Cardinal Health as well as in collaboration with strategic partners to improve the customer experience and end-user well-being. Our Fukuroi R&D team in Japan recently partnered with DIC Corporation and Osaka University to develop a first-of-its-kind Fluorescent Ureteral Near Infrared Ray (NIR) catheter. Typically, a standard (non-fluorescent) catheter is used in ureteral surgeries. However, the level of risk increases in complex ureteral procedures, where physicians sometimes face difficulties in seeing where to place the catheter. Our Fluorescent Ureteral Near Infrared Ray catheter allows a physician to monitor the exact location of the catheter in the ureters when using an NIR endoscope. This greatly reduces the risk of complications and improves patient outcomes. How would you summarise your objectives for long-term growth and profitability around APAC medtech markets? We see immense opportunities in the Asia Pacific. Cardinal Health has a diverse range of medically differentiated General Medical, Specialty and Operating Room products and we believe that we are uniquely positioned to meet the evolving needs of healthcare professionals and patients in the region. APAC comprises different cultures and market types at various stages of development. That’s why we’ve moved away from the typical regional business model that groups markets by geographic proximity, to one that enables us to provide targeted, strategic support to customers in markets with similar growth profiles regardless of location. This model allows us to collaborate more easily, quickly, and effectively. It also helps us to tap into synergies across markets, and sharpen our product focus. We believe that with these changes we are well positioned to tap into growth opportunities across Asia Pacific. This is an exciting time for us in Asia Pacific. The combination of our Japan business’s deep history in the APAC market, and the reputation we’re building among our customers in maturing markets like Australia, China, Korea and Southeast Asia, provide us with an excellent foundation for future growth. The key to unlocking this growth potential is understanding what customers and patients require in addressing changing health care needs. Developing and distributing products that are geared towards our Asian patients like our Japan made Argyle neonatal catheter or our next generation Kangaroo enteral feeding pump will enable us to meet these evolving needs, and drive long-term sustainable, profitable growth in APAC. Hithaishi C Bhaskar [email protected]

SPEAKING WITH 37 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com As a leader in the precision medicine diagnostic platform solutions, a Seoul (South Korea) based Bertis has ventured into developing unique biomarkers for cancer and other major ailments, providing diagnostic and analysis solutions powered by proteomics, bioinformatics, and Artificial Intelligence (AI). Besides developing companion diagnostic markers for precision medicine, Bertis is at the forefront of advanced quantitative proteomics research, as well as companion diagnostics for oncology drug development and personalised treatment. Seungman Han, CEO of Bertis’ shares further insights on the current trends and innovations in the Asian proteomics diagnosis platform. Edited excerpts; How robust is the proteomics diagnosis platform as predictors of disease status? What’s Bertis’ role in developing target treatments? Proteins provide clinically useful information by reflecting the actual expression of the functional as a phenotype, thus allowing real-time data representation of the disease state. However, both the upside and the downside of protein are that it is far more diverse, and dynamic compared to genomes. Historically, proteomics was regarded as challenging for disease prediction because of the diverse results that were obtained depending on the conditions of the sample and the situations during analysis and research, in addition to the processing of vast amounts of data. However, as informatic technology has advanced in conjunction with protein analysis technology, the quality of protein data has improved considerably and proteomics-based diagnostic techniques have also advanced. With our unrivaled proteomics technology, Bertis’ mission is to combat deadly diseases. Our goal is to develop products for the early detection of diseases such as breast cancer, pancreatic cancer, and ovarian cancer. We also contribute to the development of precision medicine and targeted treatments, as well as in analysis services such as PASS (Panomics Analysis Service & Solution), a platform for integrative analysis of pan-omics (multi-omics) data, which is being developed to assist with the discovery of new drug targets substances. “Diagnostic market in the Asia Pacific region is currently in a critical period” « Seungman Han, CEO, Bertis, South Korea Our flagship solutions include Mastocheck, the world’s first proteomics-based blood test solution for early breast cancer detection, and PASS. How competitive is the proteomics-based screening and diagnostic tests market? How is the momentum of the market? Proteomics is expected to provide solutions to the next trend in healthcare innovations such as precision medicine and the conquering of cancer. The importance of proteomics in the healthcare field is growing to the extent that proteomics data must be used in new drug development and patient treatment in the US FDA guidelines. Furthermore, Cancer Moonshot, a US government initiative launched in 2016, accelerates cancer research and improves cancer prevention, detection, and treatment, highlighting the need for proteomics-based diagnosis. As a promising next-generation technology followed by genomics worldwide, proteomicsfocused companies, including US-based films, were driving their efforts in research and development. Many NASDAQ-listed companies such as Seer, SomaLogic, and Olink, specialise in protein profiling, a technology for detecting more proteins in samples. These companies are diverging their interests to proteomics diagnosis with protein profiling capabilities. Bertis has experience and expertise in developing and commercialising protein biomarkers in the blood to diagnose early breast cancer, which was the first to receive approval from the South Korean authority. Using proteomics technology, we have successfully commercialised diagnostic solutions. Thus, we expect to contribute greatly with the launching of useful diagnostics, aligned with the expansion of the proteomics market.

38 SPEAKING WITH BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com What is Bertis’ stake in stabilising the industry through its unrivaled proteomics expertise? In addition to utilising diagnosis solutions in a real clinical setting, Bertis has more than 10 years of experience working with proteomics R&D expertise in clinical, experimental development, and data analysis. With the world’s leading capability in protein profiling, Bertis can identify phosphopeptides in tissue samples by analysing over 50,000 proteoforms. A key focus of Bertis is also in developing an innovative health information interpretation AI model called “SAN (Spectrum is All You Need)” to overcome the limitations of existing mass spectrometry proteomics data interpretation and to maximise its utilisation. A preliminary study of SAN revealed that patients with ovarian cancer or pancreatic cancer could be classified with 95 per cent accuracy. Its first achievements were announced at ‘Human Proteome Organisation 2022 (HUPO 2022)’, the world’s largest academic event in the field of proteomics. Additionally, HUPO 2023 will be held in Korea in 2023. The academic event, HUPO encourages international collaboration and cooperation in proteomics through training and development of new technologies. The event brings together leading global and APAC regional entities to share research and attract new investments in proteomics. By exchanging and collaborating with companies and research institutions, Bertis hopes to maximise the potential of proteomics. How has the funding and investment process been so far? A total of $35 million has already been raised by Bertis, with SK Planet, part of the SK Group, the third-largest multinational corporation in South Korea, and Hyosung being the biggest investors. Our research and business will be supported by a funding round targeting over $30 million in the next few months. How do you perceive the complexity and regulatory process involved with commercialisation and expansion into diverse markets? Medical device commercialisation and market entry require complicated processes and customised strategies for each region and often require cooperation with local partners such as research and medical institutions. Although it acts as a safeguard, sometimes it acts as a barrier to innovative, pioneering products like proteomics diagnosis. Bertis’ strategy is to launch proteomics diagnostic assays in Korea first and then we are looking to enter other geographical regions such as US middle east and Asia markets with possession of commercialisation experience in Korea. Since Korea is also a very competitive market for easier diagnosis access with an established advanced medical system, experience and know-how in the Korean market will provide insight into the most appropriate strategies in individual markets. Could you share your expansion plans? Bertis has established a long-term plan to enter major Asian countries for several years and as result, we recently introduced Mastocheck in Singapore in 2022, making it the first entry to an international market. We plan to accelerate the expansion of our product in other Asian countries, as one of the key milestones this year. Based on our success in South Korea and our experience in entering the Singapore market, we expect to produce a positive result. How do you foresee the proteomics market potential within Asia Pacific? How will the market dynamics evolve in 2023? I believe the diagnostic market in the Asia Pacific region is currently in a critical period. To determine the future direction of the market, it is important to establish which technologies and methods are initially implemented. As a rapidly developing technology, proteomics-based biomarker diagnostics can provide convenient, accurate and cost-effective opportunities, which allows more people to be benefited from medical advantages. Based on these strengths, Bertis plans to focus on contacting and collaborating with various partners in Asia in 2023 to introduce proteomics-based diagnostic technologies to more countries. While exploring the potential trends in proteomics technology in Asian countries during a recent discussion on Mastocheck’s business development, we discovered a huge demand among APAC companies and institutions. Currently, Bertis is primarily entering Asian markets with Mastocheck as its early diagnostic solution. We are working towards advancing our proteomics technology platforms and upgrading diagnostic pipelines in order to make a positive impact on the Asian proteomics market. Hithaishi C Bhaskar [email protected]

EVENT REPORT 39 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com One World TB Summit “India is now working on the target of ending TB by 2025” Noting the declining number of Tuberculosis (TB) patients, India resolved to eliminate TB by 2025 as against the global target of 2030. Referring to the capacity and health infrastructure enhancement during the pandemic, the Prime Minister of India, Narendra Modi underlined the high use of 5Ts namely Trace, Test, Track, Treat and Technology, in the fight against the disease. Addressing the One World TB Summit in Varanasi (India) held on the occasion of World Tuberculosis Day on March 24, the Prime Minister said that the commitment and determination with which India dedicated itself to tackling TB after 2014 is unprecedented. India’s efforts are important, as this is a new model for the global war on TB. Elaborating on a multi-pronged approach against TB in the last nine years, he listed out many measures such as people’s participation, enhancing nutrition, treatment innovation, tech integration and wellness and prevention such as Fit India, Yoga, and Khelo India type of interventions. Regarding people’s participation, the Prime Minister talked about the Ni-kshay Mitra Campaign in helping TB patients. He informed that about 10 lakh TB patients have been adopted by citizens and even children aged 10-12 years have came forward. Financial help to the TB patient under the programme has reached up to Rs 1000 crore. He termed the movement ‘inspirational’ and expressed happiness that even Pravasi Indians are participating in this. Noting the major challenge of nutrition for TB patients, the Prime Minister highlighted the contributions of Ni-kshay Mitra Campaign in helping TB patients. He underlined that the government had announced a Direct Benefit Transfer scheme for TB patients in 2018 and as a result, approximately Rs 2000 crore have been directly transferred into their bank accounts for their treatment, where more roughly 75 lakh TB patients have benefitted from this. “Ni-kshay Mitras have now become a new source of energy for all TB patients”, the Prime Minister said. Noting that it is extremely difficult to arrive at new solutions by practicing outdated ways, the Prime Minister said that the government has The Prime Minister of India, Narendra Modi addressing the ‘One World TB Summit’ at Varanasi, in India on March 24, 2023 The commitment and determination with which India dedicated itself to tackling TB after 2014 is unprecedented. India’s efforts are important, as this is a new model for the global war on TB. India has taken a multi-pronged approach against TB in the last nine years and some of the measures include people’s participation, enhancing nutrition, treatment innovation, tech integration and wellness and prevention such as Fit India, Yoga, and Khelo India type of interventions.

40 EVENT REPORT BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com worked with new strategies so that TB patients do not fall out of their treatment. He gave examples of initiating the Ayushman Bharat Scheme for the screening and treatment of TB, increasing the number of testing labs in the country and formulating region-specific work policies by targeting cities where the number of TB patients is high. On similar lines, the Prime Minister launched a new campaign called ‘TB Mukt Panchayat Abhiyan’ on the day. As part of the campaign the government is starting a three months treatment programme for the prevention of TB instead of a 6-month course. He informed that earlier, the patients had to take medicines for six months every day but now, in the new system, the patient will have to take medicine only once a week. The Prime Minister informed about the tech integration in the TB Free India campaign. He said that Ni-kshay Portal and the use of data science are going a long way in this regard. He said that the Health Ministry- Indian Council of Medical Research (ICMR) developed a new method for subnational disease surveillance that has made India, apart from World Health Organisation (WHO), the only country to have this kind of model. “There is a massive global potential in this local approach of India”, he said emphasizing the need to collectively use that potential. He informed that 80 per cent of TB medicines are made in India. “I would like that more and more countries get the benefit of all such campaigns, innovations and modern technology of India. All of the countries involved in this summit can develop a mechanism for this. I am sure, this resolution of ours will definitely be fulfilled - Yes, We can End TB”, the Prime Minister added. He also highlighted the role of social organisations and public participation in this and expressed confidence about India’s success against TB. “Today’s New India is known for achieving its goals”, the Prime Minister said and gave examples of achieving the pledge to be Open Defecation Free, achieving the target of solar power generation capacity as well as the target of ethanol blending of fixed percentage in petrol ahead of schedule. “The power of public participation is boosting the confidence of the whole world”, he remarked and credited the success of India’s fight against TB to public participation. India is engaged in the campaign to eradicate TB by making use of the nation’s experience, expertise and willpower. He noted that India is constantly ready to help every country in need. “Our campaign against TB will be successful only with Sabka Prayas (everyone’s efforts). I believe, our efforts today will strengthen the foundation of our secure future, and we will be in a position to hand over a better world to our future generations”, the Prime Minister concluded. During the event, the Prime Minister launched various initiatives including the official pan-India rollout of a shorter TB Preventive Treatment (TPT); the Family-centric care model for TB and the release of India’s Annual TB Report 2023. In March 2018, during the End TB summit held in New Delhi, the Prime Minister called on India to achieve TB-related Sustainable Development Goals (SDGs) targets by 2025, five years ahead of the stipulated time. One World TB Summit provided an opportunity to showcase learnings from National TB Elimination Programmes and to further deliberate upon the targets as the country moves forward to meet its TB elimination objectives. International delegates from over 30 countries participated in the summit. Stop TB urges Modi to lead and inspire other world leaders in the fight against TB The UN high-level meeting on Tuberculosis (TB) is taking place on September 22, during the UN General Assembly in New York. Stop TB Partnership, a hosted entity of the United Nations Office for Project Services (UNOPS), with its Secretariat based in Geneva, Switzerland has requested the Prime Minister Narendra Modi’s presence in the meeting. Speaking at the One World TB Summit held in one of the oldest cities of the world, Varanasi to discuss a thousand-year-old disease in the world i.e TB, Dr Lucica Ditiu, Executive Director of Stop TB Partnership urged the Prime Minister Modi to lead and inspire other world leaders in this fight against TB. India has a very high burden of TB but with the best plan, ambition and great implementation of activities India can end TB by 2025. Dr Lucica said that India is on the road to ending TB by 2025 under the leadership of the Prime Minister. Due to the efforts of countries like India, she said that the number of people who are not getting diagnosis and treatment for TB has gone below three million for the first time in history. She praised India’s scale in tackling TB and the TB Free India initiative and expressed the belief that India will end TB by 2025.

PRECISION MEDICINE 41 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Asia’s multi-ethnic population presents challenges and opportunities for precision medicine. Collaborative management and analysis of patient data are helping researchers in the Asia Pacific region to spearhead improvements in disease diagnosis, treatment and prevention. Hence there is a good scope for collaboration that will put Asian haplotypes at the heart of global precision medicine. Targeting treatments to individuals is the panacea for precision and personalised medicine. It depends on a detailed understanding of the genetic profiles and molecular signatures that can be linked to disease. But to achieve this goal and ensure all patients can benefit from therapeutic innovations and novel prevention measures, researchers and drug hunters must test their hypotheses and findings on diverse populations that include all relevant genetic haplotypes. Historically, Asian haplotypes have been underrepresented in patient biobanks and datasets used by researchers, mainly in the US and Europe, to develop novel therapies and treatments. Yet, in many parts of the APAC region, comprehensive datasets exist, and new ambitious population level programs are underway, including the SG100K programme in Singapore and the National Orphan Disease Programme in Japan. These studies involve thousands of people representing the diverse population of the region, including Chinese, Malay, and Indian ethnicities. It is these population level cohort studies, devised and led by local experts that will help redress the lack of Asian real-world data in global life science research. Such studies should enable researchers to identify the interplay between environmental, lifestyle and genetic factors that increase the risk of heart disease, diabetes, cancer and other chronic diseases prevalent in the APAC region. To ensure the data can be used to benefit people across the region, leading Asian healthcare institutions are partnering with organisations which can provide the infrastructure to manage this copious and complex genomic data and make it accessible to researchers in a controlled, secure and equitable way. For example, in Singapore, where efforts are underway to implement a National Precision Medicine programme, the Health for Life in How Equitable Data Sharing is key to realising precision medicine in APAC « Nino da Silva, Deputy Managing Director, BC Platforms Singapore (HELIOS) study has been established and led by the Lee Kong Chan School of Medicine at Nanyang Technological University. The study, which is part of the wider SG100K project to sequence the genomes of 100,000 Singaporeans, uses BC Platforms’ TCE (Trusted Collaboration Environment) with BC/INSIGHT and BC/RQUEST to manage the genotypic and phenotypic data. This new data infrastructure enables multiple data partners to securely share real-world data. It is paving the way for sustainable collaborations between partners at local and international levels and will accelerate innovations in research and development that transcend geographical and economic boundaries, improving healthcare outcomes for people across the region. Creating virtual patient cohorts in this way will transform the way rare diseases, such as rare cancers, autoimmune diseases & neurodegenerative conditions, can be studied. Such innovations in data management also mean that researchers can robustly and repeatedly test findings on diverse populations expressing different haplotypes, accelerating the translation of research into clinical practice through rapid generation of translatable, actionable, research insights. The scope for collaborative research is now almost limitless. With appropriate regulations in place, state-of-the-art data management infrastructure brings together diverse datasets, from low and higheconomic regions, country-wide and international cohorts and facilitates equitable data sharing. This trusted data infrastructure provides immediate value by creating a secure and sustainable environment to investigate pathways underlying health and disease in Asian populations, locally and globally. Such collaborations will put Asian haplotypes at the heart of global precision medicine.

42 PRECISION MEDICINE BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Artificial intelligence (AI) is being used to find new promising targets and design new molecules to treat diseases. It is also being applied in the optimisation of the clinical trial process – analysing data to predict outcomes to help prevent timely and costly late-stage failures, and producing health digital twins to speed up trials, and precision public health. It’s very possible to imagine a data-driven, streamlined, precision medicine future merging the best of human and machine intelligence to manage our individual health in ways we never previously imagined. Artificial intelligence (AI) is accelerating precision medicine, giving us the ability to analyse complex data sets and find patterns that can tell us how genes are linked to diseases, and how diseases are linked to biological processes. AI can process reams of existing scientific data and uncover new biomarkers for disease, new targets for therapeutics, and even design new drug-like molecules to treat disease. And we’re still in the early stages of what this technology can do. Generative Adversarial Networks (GANs) – machine learning models that create new images, video, and text from existing data – were first proposed in 2014 by a young scientist named Ian Goodfellow, currently with DeepMind. He and other scientists discovered that technology can be utilised to generate new images based on specific generation conditions. Now, this technology has exploded, bringing with it breakthroughs that have lately dominated headlines – from Microsoft’s new Copilot for Office, to Bing’s AI chatbot, to image- and artgenerating tools like DALL-E and Midjourney. The Key to a Precision Medicine Future: AI Plus Human Ingenuity « Dr Alex Aliper, President, Insilico Medicine Generative AI is an amazing tool that is quickly evolving to transform the way we create, work, and discover. What is often misunderstood, however, is the essential role that humans play in advancing these technologies. That’s particularly true in AI drug discovery, where we are working with diverse and complex datasets and an untold number of potential interactions and biological responses. Back in 2016, Insilico Medicine’s founder and CEO, Alex Zhavoronkov, PhD, was one of a few pioneers to realise the potential of generative AI in drug discovery. He published the first peer-reviewed paper in the emerging field of “generative chemistry” on applying GANs to generate novel small molecules against cancer. In order to continue to evolve generative AI to a place where it can accurately assess, diagnose, and provide individualised treatments for patients, there are three essential elements that are needed: highly sophisticated AI and machine learning algorithms; robust and accurate data; and human scientific expertise. Too often, discussions around AI focus on how machines will be used to replace humans, when in fact the technology serves as a tool to automate and accelerate key parts of the process in order to improve speed, cost, and accuracy. AI is very good at finding hidden connections in large quantities of data around diseases, genes, and clinical trials that human scientists might miss. Once those connections are discovered, however, it’s up to human scientists to produce and test the compounds and provide the feedback that improves the data and ultimately strengthens the predictive accuracy of these AI systems which are themselves designed by computer scientists. Insilico Medicine’s Chemistry42 generative AI drug design system, for instance, relies on a library of millions of small molecules, many of which have known properties, combined with in vitro and in vivo data. Over 40 generative AI algorithms embedded in the platform were trained on this data to design completely novel molecules. Through the process of active learning, these molecules are optimised for key features such as novelty, diversity, affinity, metabolic stability, synthetic accessibility and ADME features, among others. Think of it as launching over 40 intelligent Voyager probes into the chemical

PRECISION MEDICINE 43 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com space in order to find new previously unexplored chemical galaxies – and the most promising small molecule “stars” within them. Ultimately, generated individual molecules need to be synthesised and further assessed and tested, and this work is done by medicinal chemists. This ongoing human-to-machine feedback loop is essential as we move toward a precision medicine future. We will need to build on the expertise of scientists from both big pharma and small biotech companies with their research and development capabilities and on rapidly evolving tech innovation happening in AI drug discovery biotechs which are continually improving and adapting their platforms. This even includes incorporating conversational large language model functionality into the platform, as Insilico Medicine has recently done by introducing ChatPandaGPT. AI is already being used to find new promising targets and design new molecules to treat diseases, as has been shown by a number of AI-driven biotech companies in the field, including Insilico Medicine, with our programmes in idiopathic pulmonary fibrosis, cancer, and COVID-19. By advancing the field of AI-powered drug discovery, Insilico Medicine is aiming to extend healthy productive longevity for everyone, Alex Zhavoronkov has even pledged his entire wealth into this field. AI is also being applied in the optimisation of the clinical trial process – analysing data to predict outcomes to help prevent timely and costly latestage failures, and producing health digital twins to speed up trials, reduce costs, provide additional patient insights, and precision public health. It’s very possible to imagine a data-driven, streamlined, precision medicine future merging the best of human and machine intelligence to manage our individual health in ways we never previously imagined. Chemistry42 platform Deep Learning (DL) has proven to be very effective in speech and image recognition. This is because DL-based architectures are uniquely suited for the automatic identification of patterns within complex, nonlinear data sets without the need for manual feature engineering. DL methods have recently been adapted to successfully overcome limitations inherent in the standard techniques used for small molecule design. These adaptations offer exciting possibilities for the development of new methods that efficiently explore uncharted chemical space. Insilico Medicine was one of the first groups to publish a method that uses a deep adversarial model for new compound generation. Since then, deep learning (DL)-based architectures that combine generative algorithms with reinforcement learning (RL) have been developed and applied in chemistry and pharmacology to generate novel molecular structures with predefined properties. Especially encouraging is the recent progress in the de novo design of active molecules that have been validated in both in vitro and in vivo assays. Generative chemistry is now one of the fastest-growing areas in drug discovery. The Chemistry42 platform has been routinely and successfully used at Insilico Medicine to drive the drug discovery process in several therapeutic areas and has evolved significantly during the past years. The Chemistry42 platform is a customisable working environment that offers state-of-the-art AI technologies developed for de novo molecular design. The flexible, user-friendly interface makes it accessible to medicinal and computational chemists, AI experts, and other scientists working in the field of drug discovery. The collaborative nature of Chemistry42 enables and fosters relationships between different scientific communities and facilitates the decision-making process-a process which is exceptionally demanding in the field of drug design.

Starpharma names Justin Cahill as CFO and Company secretary ChemPartner has announced the appointment of Lilly Xu, PhD as President of Shanghai ChemPartner. Lilly is a seasoned manager with a strong portfolio of success. She joined ChemPartner in 2017 to lead the strategic drug discovery services as Senior Vice President and Head of DMPK and Exploratory Toxicology. Prior to joining ChemPartner, she held various positions in US biotech and pharmaceutical companies including Amgen and Sanofi US. Additionally, she was the Head of the Center for Predictive ADMET at Sanofi US, and she holds a green belt in Lean 6 Sigma. Lilly earned a PhD in molecular and cellular biology from Saint Louis University in St Louis, Missouri. During her time in academia, she pioneered the use of human and animal hepatocytes in drug metabolism and drug-drug interactions. Dr Lilly Xu takes charge as President of Shanghai ChemPartner Australian firm Starpharma Holdings has announced the appointment of Justin Cahill as Chief Financial Officer (CFO) and Company Secretary, following an extensive executive search process. Cahill has extensive corporate finance and leadership experience in the biopharmaceutical, food, and agricultural sectors for both ASX-listed and private companies. He is currently CFO at Paradigm Biopharmaceuticals having joined the company in 2020. During his time at Paradigm he has also worked closely with, and provided support to, the company secretarial function. He also worked at CSL for over nine years where he held a number of senior financial and leadership roles, including five years as Divisional CFO at CSL Plasma in the United States (US). As Divisional CFO, Cahill provided financial and strategic support to the organisation during a period of significant business expansion where the number of collection centres in the US increased from 65 to 130. 44 PEOPLE NEWS BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Amplify Health Asia appoints new CEO Singapore-headquartered Amplify Health Asia, the pan-Asian integrated health technology solutions joint venture (JV) between AIA Group Limited and Discovery Limited, has announced the planned succession of Deputy Chief Executive Officer Dr Axel Baur to the role of Chief Executive Officer (CEO), effective immediately. Dr Baur joined Amplify Health in March 2022 following a 26-year career at management consultancy McKinsey & Company where he was a leader of the firm’s Asia Healthcare practice and a Senior Partner in the Hong Kong office. A global expert in innovative care delivery models, he has extensive experience working with organisations and governments across Asia to deliver sustainable impacts to healthcare systems and healthcare companies throughout the value chain. Prior to joining McKinsey, Dr Baur co-founded a researchbased biotech company. He succeeds Dr Jonathan Broomberg, who joined Amplify Health from Discovery Limited, which is the JV partner to AIA in Amplify Health. Dr Broomberg will continue to serve as a non-executive director of Amplify Health and will resume his role as CEO of Vitality Health International and Global Head of Health Insurance for Discovery Limited.

Aster DM Healthcare appoints Dr Nitish Shetty as India CEO Aster DM Healthcare, one of the largest integrated healthcare providers in the GCC and India, has announced the appointment of Dr Nitish Shetty as Chief Executive Officer (CEO) of its India business. In this capacity, Dr Shetty will oversee the company’s overall India operations and lead the growth of Aster DM Healthcare in India. Dr Shetty joined Aster DM Healthcare in 2014, taking charge as the CEO of Aster CMI Hospital in Bengaluru and then rose to become the Regional Director of Aster Hospitals in Karnataka and Maharashtra, alongside assuming responsibility as a Director for Aster Labs. His promotion to the role of CEO of Aster DM Healthcare India is in alignment with the Group’s strategy to further strengthen Aster DM Healthcare’s presence in the country. Before joining Aster, Dr Shetty worked for some of the reputed healthcare companies in India including BGS Global and Narayana Hrudayalaya. PEOPLE NEWS 45 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Dr Teo Ho Pin has assumed the role of the Chairperson of the Traditional Chinese Medicine Practitioners Board (TCMPB) from March 1, 2023, taking over Yu-Foo Yee Shoon who has helmed the Board for nine years. Under Yu-Foo’s leadership from 2014 to February 2023, the TCMPB introduced measures to further enhance the standards of Traditional Chinese Medicine (TCM) practitioners. The TCMPB convened a TCM Review Committee in March 2019 to review the development of TCM in Singapore, and also made recommendations on how TCM can better add value to Singapore’s healthcare landscape. Dr Teo has over 30 years of experience in Township Management in Singapore and has held various key positions in both the public and private sectors in the real estate and construction industry. He was a Member of Parliament from 1996 to 2020, and served as Mayor of North West District between 2001 and 2020. Dr Teo is currently an Adjunct Professor in the Department of the Built Environment at the National University of Singapore, a Visiting Professor to the Singapore University of Technology and Design, and an Adjunct Professor at the School of Science and Technology, Singapore University of Social Sciences. Dr Teo Ho Pin steps in as Chairperson of Traditional Chinese Medicine Practitioners Board in Singapore CTSI names Harish Trivedi as new CEO for South Asia Cancer Treatment Services International (CTSI), a wholly owned subsidiary of Varian Medical Systems Inc. (a Siemens Healthineers Company) has announced its new Chief Executive Officer (CEO)- Harish Trivedi for South Asia. Trivedi will be responsible for steering the operations of American Oncology Institute (Cancer Treatment Services Hyderabad), Citizens Specialty Hospital (Artmed Healthcare) and Ampath (American Institute of Pathology and Laboratory Sciences) in the Indian Subcontinent. He will be based out of Hyderabad Corporate Office and will be reporting to Dr Jagprag Singh Gujral, SVP MDO / Head of Emerging Markets, Group CEO, CTSI. With over 25+ years of rich healthcare experience, Trivedi will be responsible for driving and overseeing the development and execution of the hospital’s strategy, quality excellence, and patient relationship management.

A cash injection of $6 million into Auckland Bioengineering Institute (ABI) spin out Kitea is a major step towards scaling clinical trials and propelling the world’s first implantable long term brain pressure sensor into global markets. The long term brain pressure sensor is developed to be implanted into the brains of patients with hydrocephalus. It is based on several years of research by the Implantable Devices Group led by Simon Malpas, a professor of physiology and bioengineering at ABI, New Zealand. Hydrocephalus is a condition characterised by an increase in fluid around the brain which, unless treated, is fatal. Approximately 100 patients in New Zealand are diagnosed with hydrocephalus every year. Clinical trials will move the brain pressure sensor a huge leap closer to becoming the first New Zealand-designed fully implanted electronic medical device, akin to the complexity of a cochlear implant or pacemaker. The sensor, once FDA approved, would alleviate the considerable anxiety and suffering of parents of children with the disorder, as well as highlight the potential of remote monitoring of chronic conditions wherever a patient lives and ultimately, the means of providing more equitable healthcare. New Zealand to propel development of world-first brain micro implant Scientists in Japan have revealed a chemical compound that could be used for the treatment of various autoimmune diseases like multiple sclerosis and rheumatoid arthritis. These diseases occur when the body’s immune response goes wiry. The immune system, which normally attacks pathogens and infections, instead attacks healthy cells and tissues. For the millions of people who suffer from autoimmune diseases worldwide, the result can be debilitating—rheumatoid arthritis causes excessive joint pain, while multiple sclerosis can disable one’s brain and spinal cord function. The research focussed on T helper 17 cells, or Th17 cells. Th17 cells are a type of T cell—a group of cells, which form major parts of the immune system. The generation of Th17 cells requires glycolysis, a metabolic process in which glucose is broken down and converted to energy to support the metabolic needs of cells. The researchers found that treatment with phosphoenolpyruvate or PEP can inhibit the maturation of TH17 cells, leading to resolution of inflammatory response. PEP treatment inhibits the generation of Th17 cells by blocking JunB activity. Japan discovers potential treatment of autoimmune diseases Korea develops nanoparticle-based deep brain stimulation therapy to treat Parkinson’s Disease One of the various therapeutic approaches for neurodegenerative diseases such as Parkinson’s Disease, that is garnering attention is deep brain stimulation, a technique that employs electrical stimulation to directly trigger communication between nerve cells. Activation of nerve cells through electrode implantation is a treatment option for neuronal disorders, made possible by deep brain stimulation. However, this therapy necessitates a surgical procedure in which leads are deeply implanted into the brain, potentially leading to side effects that can make clinical application challenging. Recently, a research team at Pohang University of Science and Technology (POSTECH), in South Korea, has developed a new technique for administering electrical stimulation to the brain without the need for implanted electrodes. Researchers have created a nanomedicine material that uses piezoelectricity to produce electrical signals in response to non-invasive and biocompatible ultrasonic waves. 46 R&D NEWS BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com

In a recent study, researchers from the Department of Organic Chemistry (OC) and Materials Research Centre (MRC), at Bengaluru-based Indian Institute of Science (IISc), show that surface modifications of two-dimensional molybdenum disulphide (2D-MoS2) nanosheets can make them highly effective for applications like delivering drugs to diseased cells. Nanomaterials usually need to be modified or customised depending on the application to improve their efficiency. Typically, they are chemically modified through a process called functionalisation, which involves attaching ligands (small or large molecules) to the surface of the nanomaterial. In the new study, the researchers modified the surface of 2D-MoS2 nanosheets with thiol (sulphurcontaining) ligands. They found that these thiols can be exchanged with naturally-occurring thiols in biological systems, which could allow drugs attached to these nanosheets to be released. These chemically-modified nanosheets were also found to be safe to use inside living cells. Moving forward, the team plans to work on improving the stability of the nanomaterial in the presence of various thiol-containing liquids and exploring alternative surface modification approaches to customise the nanosheets for other applications. India explores use of nanosheets for better drug delivery A research team from the Faculty of Medicine and Faculty of Engineering, Chulalongkorn University, Thailand has jointly developed AICute, an innovative programme to assess the chance of stroke caused by heart disease (Ischemic Stroke), aimed at helping hospitals that lack cardiologists to enhance the effectiveness of stroke treatment, reduce congestion in hospitals and medical schools. Thailand has approximately 250,000 patients suffering from strokes each year, or one stroke for every 2 minutes. Of these, 30 per cent may die, and 30 per cent are severely disabled. AICute is a web application with artificial intelligence (AI) to analyse and evaluate patients for the risk of stroke from heart disease. It enables doctors in the community and small hospitals to make decisions and send patients to heart examinations more rapidly, making the treatment of stroke more effective. AICute’s accuracy is at 92-94 per cent according to the database of 40,000 high-resolution X-ray images. Thailand develops AI-based assessment tool for ischemic stroke Researchers from the Antimicrobial Resistance (AMR) Interdisciplinary Research Group (IRG) at SingaporeMIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, in collaboration with Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University (NTU), Massachusetts Institute of Technology (MIT), and University of Geneva, have developed a novel combination therapy using an anticancer agent, mitoxantrone (MTX), together with an antibiotic, vancomycin, for treating bacteria that are resistant to the vancomycin, which is also known as vancomycinresistant Enterococcus faecalis (VRE). The therapy uniquely targets both VRE and the host, stimulating the host immune system to more effectively clear bacterial infections and accelerate infected wound healing. AMR is a significant global health concern, causing 4.95 million deaths from infections associated with or attributed to AMR in 2019 alone. Singapore develops novel therapy for vancomycin-resistant bacterial infections R&D NEWS 47 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com

Sciex, US-based global leader in life science analytical technologies, has announced a new collaboration with HighRes Biosolutions, a leading global laboratory automation company, also based in the US. Complete automation solutions from HighRes Biosolutions, powered by Cellario software, adds automation benefits to the Echo MS system, built on Acoustic Ejection Mass Spectrometry technology from Sciex. This combined offering aims to provide comprehensive and customisable workflows for highthroughput screening, HT-ADME and synthetic biology studies. Cellario integrates all the devices and software within a laboratory, enabling scientists to customise and implement the best possible technologies to produce data and execute their work. It provides a single connection point for all data integration needs in a lab, meaning the lab’s asset base can grow without increasing in complexity. Customers with Cellario can connect to the Echo MS system and data collection software to help seamlessly manage large amounts of sample handling and analysis. Sciex collaborates with HighRes Biosolutions to deliver automated analytical solutions Agilent acquires ECD tech maker e-MSion Sophia Genetics, a Switzerland-based cloudnative software company in the healthcare space, has announced a new partnership with Qiagen that will pair QIAseq reagent technology with the SOPHiA DDM platform to enhance tumour analysis through next-generation sequencing (NGS). The partnership will allow customers to order QIAseq panels that can be processed through SOPHiA DDM, a cloud-based platform that analyses data from various sources to enable entirely new research perspectives. The partnership will initially support somatic variant detection (an alteration in DNA that occurs after birth) using QIAseq Targeted DNA Pro panels for homologous recombination repair (HRR), a special type of biomarker test to find tumors that have certain mutations that may make them sensitive to PARP inhibitors in oncology. The partnership with Sophia Genetics is planned to be expanded to other areas of analysis, including the use of QIAseq panels custommade solutions. It is the inaugural partnership in Qiagen’s QIAseq Platform Partnership. Qiagen forges partnership with Sophia Genetics to combine strengths in NGS Agilent Technologies has announced the acquisition of e-MSion, an early-stage company behind the innovative electron capture dissociation (ECD) technology known as the ExD cell. The ExD cell is a compact device for mass spectrometers that enables biological researchers to develop biotherapeutic products more quickly to treat disease. This is done by more comprehensively and precisely breaking the chemical bonds of complex biomolecules, enabling more complete, accurate, and detailed structural information to be obtained from them. The ExD cell is compatible with instruments common in many labs, such as Agilent’s 6500 LC/Q-TOF series, which will make this powerful characterisation technology, previously limited to only a few high-end mass spectrometers, more accessible to a larger share of labs and biopharma researchers worldwide. Agilent has worked closely with e-MSion for several years and has offered the company’s ExD cell technology with its 6500 series since 2019. e-MSion was founded by Oregon State University scientists, who developed the ExD cell. 48 SUPPLIER NEWS BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com

Thermo Fisher introduces new low-flow HPLC columns for proteomic research Thermo Fisher Scientific is providing proteomics and biopharmaceutical research laboratories with a new line of low-flow HPLC columns that improve separation performance and stability of biologically complex samples. Using a unique micro-pillar separation structure, the Thermo Scientific µPAC Neo HPLC Columns enable researchers to investigate proteomics samples in greater detail, from accurate identification of peptides to determination of protein quantities, discovery of disease biomarkers and post-translational modifications. The newest addition to the portfolio is the µPAC Neo low-load trapping column which is ideally suited for the smallest sample sizes in single-cell proteomics separations and features builtin nanoViper connections to the Vanquish Neo UHPLC systems for ease of use and reduced risk of errors. Users of all µPAC Neo columns benefit from excellent column reproducibility, allowing for more reliable data interpretation and confidence in their results. µPAC Neo columns are manufactured by micromachined etching of silicon wafers, resulting in highly reproducible separation paths. For proteomics researchers, this provides higher column-tocolumn consistency and longer column lifetimes compared to packed-bed columns, allowing for more robust development and validation of methods and easier study of larger sample batches. PerkinElmer, Inc., has launched the EnVision Nexus system, its fastest and most sensitive multimode plate reader to date, designed for demanding high-throughput screening (HTS) applications and to accelerate drug discovery efforts. The EnVision Nexus platform, with complementary microplates and optimised reagents from PerkinElmer’s drug discovery reagents portfolio, including proprietary HTRF and AlphaLISA technologies and latest reagent kits, provides researchers increased assay flexibility. The EnVision Nexus system features high-throughput, exceptionally fast dual detectors, enabling researchers to screen millions of samples with the increased accuracy, speed and sensitivity. For walkaway convenience, the system can be equipped with a plate stacker for 20 or 50 plates or can also be fully automated and integrated for 24/7 workflow-driven automation. The solution’s design draws on the company’s experience and success with its leading EnVision system, a workhorse in laboratories around the world for more than 20 years. PerkinElmer introduces EnVison Nexus Multimode Plate Reader Amar Equipment launches ‘NanoMake’, India’s first microfluidic platform Mumbai-based firm Amar Equipment launched ‘NanoMake’, India’s first microfluidic platform for fast-track preclinical development of mRNA vaccines and nano-formulations, at Institute of Chemical Technology’s “Biosimilar Workshop”, one of the largest gatherings of biopharmaceutical researchers in India, held on February 2-3, 2023, in Goa. Formulating nanomedicine is one of the major challenges towards translation. The in-vivo distribution, uptake, and clearance of nanoparticles are influenced by their size, making it a vital parameter to regulate. The formulation of nanomedicine normally possesses batch-to-batch variability by conventional methods, restricts translation and results in procedures that are difficult to scale from the discovery stage of a study through animal testing, clinical testing, and eventually commercial manufacturing. SUPPLIER NEWS 49 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com

50 BIOSPECTRUM | APRIL 2023 | www.biospectrumasia.com Neutralising Malaria Parasite with mAb I t is difficult to develop an effective vaccine against malaria, a mosquito-borne disease that infects around a quarter billion people worldwide each year. The University of New Mexico (UNM) researchers are working to engineer a vaccine capable of eliciting antibodies to attack a protein on the surface of the Plasmodium falciparum parasite that will prevent it from entering the liver and triggering a full-blown malaria infection. In March 2023, Dr Bryce Chackerian, principal investigator of a study at UNM to find ways of making vaccines do a better job of targeting the circumsporozoite protein (CSP), which sits on the parasite’s surface says, “The world’s first approved malaria vaccine known as RTS,S, being implemented primarily in Africa by the World Health Organisation (WHO), doesn’t work super well. It only has a 30-40 per cent efficacy in preventing children from getting infected and that protection only lasts for a very short time.” The UNM team wants to shut down the parasite as early as possible, before it enters the liver or infects red blood cells. Preliminary results show that this approach creates a potent antibody response. Dr Chackerian says, “But it is not yet perfect. That poses a problem because if the vaccine doesn’t work 100 per cent at blocking the parasite from the liver, it’s not going to be effective.” The researchers from the University of Oxford and their partners have reported new findings in September 2022 from their Phase 2b trial following the administration of a booster dose of the candidate malaria vaccine, R21/Matrix-M – which previously demonstrated high-level efficacy of 77 per cent over the following 12 months in young west African children in 2021. In their findings (reported in The Lancet Infectious Diseases), they found that a vaccine booster dose at one year following a primary threedose regime maintained high efficacy against malaria, and continued to meet the WHO’s Malaria Vaccine Technology Roadmap goal of a vaccine with at least 75 per cent efficacy. But the vaccine is only partially effective in preventing severe malaria. Researchers have been pursuing new approaches such as use of monoclonal antibodies (mAb) for the prevention and elimination of malaria. mAb represents a promising approach to reduce malaria morbidity and mortality, and they offer a new tool for use in preventing infection. Highly effective malaria vaccines have so far been elusive since they have not been shown to provide much protection in those who have already been infected with malaria earlier in life. Reported in January 2023, the Center for Vaccine Development and Global Health (CVD) at the University of Maryland School of Medicine (UMSOM) was the first centre in the world to develop controlled human malaria infection studies, providing proof of principle that live attenuated malaria vaccines protect against infection. The CVD researchers conducted genome-wide studies of antimalarial drug resistance and have tested mAb for treating malaria. This is the first time they have tested an experimental mAb in a challenge study in a CVD lab in Baltimore. The new research describes the final dose selection section of a three-part clinical trial. The mAb CIS43LS provided high levels of protection in the first two parts of the trial, in which researchers administered 20 or 40 mg/kg of the mAb via IV infusions. In the current study, 29 healthy study participants, between 18 and 50 years of age – who had no prior malaria infections or vaccinations – received a single dose of CIS43LS in doses of 1, 5, or 10 mg/kg via IV infusions, or by subcutaneous injection. Adverse events from the mAb were mild and included pain or redness at the infusion site, headache, abdominal pain, and hypertension, which resolved within a day. Phase 2 clinical trials are underway in Mali and Kenya. Scientists from the National Institutes of Health’s Vaccine Research Center also found that L9LS, a laboratory-made antibody fully protected 15 of 17 (88 per cent) participants from malaria infection during the 21-day challenge period. The technology of mAb may lend an important tool towards the eradication of human malaria as public health experts contend new strategies are urgently needed to achieve the United Nations sustainable development goal of 90 per cent reduction in malaria incidence and mortality by 2030. Narayan Kulkarni Editor [email protected]