AskBio, Founded by the Pioneer of AAV Genome Cloning, Files IPO Prospectus Highlighting Its Leadership in Gene Therapy for Previously 'Incurable' Diseases

In 2019, lamentations over the “capital winter” grew increasingly loud. The overall environment for investment and financing was unfavorable, making it difficult for institutions to raise funds and prompting them to exercise greater caution when deploying capital. Many institutions and companies braced themselves for a “tight winter.” Yet there were exceptions.

For Asklepios BioPharmaceutical (AskBio), 2019 was a game-changing year. In April, two of the most prominent U.S. investment firms, TPG Capital and Vida Ventures, invested $225 million in AskBio. The company’s founders and board members also contributed $10 million. This funding provided the necessary support to accelerate its broad technology portfolio, promising clinical studies, high-yield manufacturing, and groundbreaking research collaborations.

AskBio is a privately held, clinical-stage gene therapy platform company focused on developing adeno-associated virus (AAV) gene therapies. Gene therapy involves delivering therapeutic genes to diseased cells in the human body via viral vectors to directly correct genetic defects. AskBio’s core technology, AAV gene therapy, is a gene therapy approach that uses adeno-associated virus as the vector.

When the company was founded in 2001, gene therapy was widely regarded by the financial community as an unfeasible and unworthy investment. Over two tumultuous decades, AskBio withstood skepticism and achieved remarkable success. As a gene research company, what are its standout features? Why has capital shifted its stance and extended olive branches to it?

Jude (Richard Jude Samulski) is the Chief Scientific Officer of AskBio. He co-founded AskBio in 2001 with Sheila Mikhail, a seasoned life sciences expert focused on treating Duchenne muscular dystrophy, and Dr. Xiao Xiao, who specializes in developing miniaturized dystrophin genes.

AskBio’s name is inspired by Asclepius, a figure from Greek mythology who cured a series of incurable diseases and has become a symbol of modern medicine. Like Asclepius, AskBio focuses on rare genetic disorders that lack treatment options, such as Duchenne muscular dystrophy (DMD), Pompe disease, limb-girdle muscular dystrophy, and giant axonal neuropathy (GAN).

In 1978, Jude, who earned a Bachelor of Science degree in Microbiology from Clemson University, began his doctoral research in molecular biology at the University of Florida. Jude focused on how to use viruses to safely deliver corrected genes into the body. He discovered how to clone adeno-associated virus (AAV), an unprecedented achievement that was reflected in his paper published in 1982. This groundbreaking research laid the foundation for gene therapy and made it possible to cure previously “incurable” diseases.

Dr. Xiao Xiao was Jude’s first doctoral student, and together they published numerous significant and influential studies, such as those demonstrating long-term AAV-mediated gene expression in the brain and muscle, as well as AAV production without adenoviral helper functions. He also served as the scientist for Avigen’s inaugural project and later held the position of Chief Scientific Officer (CSO) at Merlin, with a particular interest in muscular dystrophy. Subsequently, he designed and invented a series of mini- and micro-dystrophin genes that effectively ameliorated the pathological symptoms of muscular dystrophy in mice.

Sheila Mikhail is a successful serial entrepreneur who has founded and operated three biotechnology companies. A graduate of Northwestern University’s law program, she established her own law firm, providing intellectual property (IP) consulting services to global pharmaceutical companies such as Bayer and Aventis.

In 1993, Jude was appointed as the Director of the Center for Gene Therapy at the School of Medicine, University of North Carolina at Chapel Hill. Over the past few decades, Jude has spearheaded the advancement of gene therapy technologies through countless pioneering studies and scientific discoveries. His work in AAV development, therapeutic design, and the application of gene technology has evolved into a critical body of intellectual property and extensive compendia essential to the industry. Jude is dedicated to developing effective gene therapies and addressing challenges in clinical processes and manufacturing.

In the early years of its founding, AskBio faced a challenging survival environment amid widespread skepticism toward gene therapy in the financial sector. It was not until 2004 that the Muscular Dystrophy Association (MDA) agreed to invest $1.6 million in Jude’s vision and AskBio. This investment marked the MDA’s first and largest-ever investment in a commercial entity, serving as a catalyst for research into Duchenne muscular dystrophy (DMD).

In 2005, AskBio spun off its pipeline projects to establish NanoCor Therapeutics, which was dedicated to the development of gene therapies for congestive heart failure. The subsidiary secured a $3.75 million investment from Medtronic in 2007.

As 2010 arrived, the feasibility of gene therapy gradually gained global recognition. From 2010 to 2018, AskBio made significant progress in gene therapy.

In 2010, Jude and Dr. Josh Grieger (AskBio’s current Chief Technology Officer) brought Pro10™ to life—a best-in-class cell line for producing novel AAV therapeutics. Pro10™ is a premier cell line for generating novel AAV therapies and represents the first AAV vector developed and sustained using human embryonic kidney (HEK) cells in serum-free suspension culture. Its scale and yield currently lead the industry, at a time when few in the AAV gene therapy field recognized the importance of manufacturing. With Pro10™, AskBio’s influence and value in the AAV therapeutic space have gained industry-wide recognition.

Subsequently, AskBio and its partners established Chatham Therapeutics, a subsidiary of AskBio focused on gene therapy solutions for hemophilia. In 2012, Baxter International collaborated with Chatham to develop BAX 335, a recombinant adeno-associated virus (rAAV) gene replacement therapy for hemophilia B. In April 2014, Shire announced the acquisition of Chatham and its hemophilia gene therapy technology for $70 million.

In 2014, AskBio spun off Bamboo Therapeutics, a company focused on neurological and neuromuscular diseases. Two years later, Bamboo secured $49.46 million in Series A financing to conduct multiple clinical trials. Six months thereafter, Bamboo attracted Pfizer’s interest and was acquired by the pharmaceutical giant. These two acquisition events provided AskBio with the capital needed to advance its end-to-end gene therapy platform.

In 2018, AskBio spun off its fourth subsidiary, Actus Therapeutics, to develop gene therapies for rare genetic diseases, including Pompe disease and epilepsy.

2019 was destined to write an important chapter in the history of AskBio’s development:

After securing $225 million in investment, AskBio established strategic partnerships with leading bioscience companies such as Selecta Biosciences, Editas Medicine, and SQZ Biotech to address challenges including neutralizing antibodies and in vivo delivery of gene therapies. With the approval of a second AAV gene therapy and based on extensive research by Jude, global bioscience companies and universities are expanding their gene therapy research portfolios. The company also acquired nanotechnology assets from Rovermed BioSciences and gene control technology from Synpromics; Synpromics’ office in Edinburgh, Scotland, now serves as AskBio’s European headquarters.

AskBio’s product pipeline focuses on advancing its gene therapy portfolio through rigorous clinical standards and research collaborations, concentrating on five core areas of clinical research: neuromuscular diseases, central nervous system disorders, cardiovascular diseases, cystic fibrosis, and acquired and rare genetic diseases. The company leverages its core adeno-associated virus (AAV) gene therapy technology and hundreds of gene vectors that have entered clinical testing.

Adeno-associated virus (AAV) is a non-enveloped DNA virus encased in a capsid protein. Based on differences in capsid protein antigens, AAV can be classified into multiple serotypes, each exhibiting distinct tissue and cellular tropism. AskBio’s core technology, AAV gene therapy, is a gene therapy approach that uses adeno-associated virus as a vector to deliver therapeutic genetic material to target cells. By providing new replacement genes that encode human therapeutic proteins, this approach aims to cure diseases.

AskBio’s proprietary Pro10™ is a universal AAV scalable production system based on an HEK293 cell line adapted for suspension growth. AAV viral vectors produced using Pro10™ can achieve titers of up to 10^17, providing manufacturing capacity sufficient to support long-term clinical development needs. Currently, AskBio is developing AAV gene therapies across multiple disease areas, including Carfostin and ACTUS-101, which are being developed by its first subsidiary, NanoCor Therapeutics, and its fourth subsidiary, Actus Therapeutics, respectively.

Carfostin：

Carfostin is an AAV gene therapy for congestive heart failure (CHF) developed by NanoCor Therapeutics.

CHF is often the final stage of heart disease, characterized by myocardial stiffness and the heart's inability to supply sufficient blood and oxygen to the body. Carfostin directly delivers the protein phosphatase 1 inhibitor (I-1) protein into damaged cardiac cells and targets type 1 protein phosphatase (PP1), a key negative regulator of calcium cycling and cardiomyocyte contraction.

Carfostin leverages the company’s proprietary bio-nanoparticle (BNP®) and self-complementary vector technologies to specifically deliver therapeutic genes to cardiomyocytes. Derived from recombinant adeno-associated virus, BNP is a non-pathogenic virus naturally present in the human body, offering a favorable safety profile with minimal immunogenicity. Carfostin is a one-time therapy administered via the femoral artery to target damaged cardiomyocytes through the coronary arteries.

Dr. Roger Hajjar, scientific co-founder of NanoCor, stated in an interview: “CHF is characterized by multiple defects in calcium-handling proteins, and modulating the calcium-cycling protein PP1 represents a promising therapeutic approach. In preclinical studies, Carfostin inhibited PP1 and was shown to enhance cardiac contractility and halt the progression of CHF. Importantly, BNPs can target the heart; unlike agents that accumulate in the liver, they do not exhibit hepatic targeting, allowing for high-dose administration to ensure greater myocardial uptake.”

In 2016, the FDA accepted NanoCor’s Investigational New Drug (IND) application for Carfostin®. In the second half of 2016, NanoCor initiated a multicenter, open-label, dose-escalating Phase I clinical trial in patients with advanced chronic heart failure (CHF).

ACTUS-101：

In 2019, Actus Therapeutics initiated clinical trials of Actus-101, a gene therapy for Pompe disease. On January 22, 2019, the company announced that it had administered the first dose to a patient with Pompe disease in its Phase 1/2 clinical study of ACTUS-101.

Pompe disease is a hereditary enzyme deficiency disorder caused by a lack of acid alpha-glucosidase (GAA) in muscles, leading to glycogen accumulation in tissues and organs, particularly in muscle. Although GAA enzyme replacement therapy with alpha-glucosidase has shown benefits, many patients still experience persistent muscle weakness. Furthermore, some patients develop anti-GAA antibodies, which limit therapeutic efficacy, and there is currently no treatment for this issue.

ACTUS-101 is an AAV gene therapy for Pompe disease developed by Actus Therapeutics. It transduces liver cells via intravenous infusion, leading to continuous production of acid alpha-glucosidase (GAA), and has received FDA Fast Track designation.

In addition, AskBio is developing drugs for the treatment of heart failure, myotonic dystrophy, and several other muscular and neurological disorders.

PromPT™：

As mentioned earlier, AskBio acquired Synpromics in 2019, obtaining PromPT™, a proprietary data-driven promoter design and bioinformatics platform. Dr. Michael L. Roberts founded Synpromics in 2010 and developed PromPT™.

PromPT™ facilitates the generation of breakthrough cell-selective synthetic promoters and provides solutions for regulating and inducing gene expression. While naturally occurring promoters have limitations in industrial or therapeutic applications, Synpromics’ synthetic promoters are engineered to better modulate gene activity and precisely control protein production. This enables gene expression to be driven with uncompromising selectivity across any cell type, tissue, environment, or biological condition. In addition to enhancing the efficacy of current and next-generation cell and gene therapies, this technology offers advanced applications in bioprocessing.

David Venables, CEO of Synpromics, stated, “The significant potential represented by our two companies in the field of gene therapy cannot be overstated.” “Combining our company’s scientific expertise with the unparalleled vision of Dr. Samulski and AskBio’s AAV platform technology can transform the quality, efficacy, and safety of gene therapy vectors, ultimately expanding the range of diseases treatable with AAV therapeutics.”

The combination of AskBio’s AAV technology, capsid library, proprietary manufacturing systems, and multidimensional gene therapy platform with Synpromics’ promoters and bioinformatics technologies creates a powerful opportunity to more accurately target complex diseases and enhance the efficacy of AAV gene therapy vectors. The two companies will continue to operate as independent entities but will immediately share intellectual property to integrate Synpromics’ technologies with AskBio’s AAV platform ecosystem and its current pipeline of therapeutic products in development. This positions AskBio uniquely as the only company in the industry with a comprehensive, end-to-end AAV gene therapy platform.

After two decades of setbacks, gene therapy is rapidly emerging as a powerful tool for overcoming various genetic and acquired diseases. Even before AskBio made waves in the gene therapy sector in 2019, significant milestones had already been reached: on March 4, 2019, Nightstar, a clinical-stage gene therapy company specializing in AAV-based treatments for inherited retinal diseases, was fully acquired by the biotechnology firm Biogen; and on February 24, 2019, Regenxbio, a rising star in the AAV gene therapy field, licensed its NAV Technology Platform to numerous leading biotechnology companies. To date, at least 10 companies have obtained licenses for the NAV platform technology and developed more than 20 candidate products based on it.

The overseas market is booming, while the domestic market is also thriving.

In July 2019, PackGene (Guangzhou PackGene Biotechnology Co., Ltd.) completed its Pre-A financing round invested by Kaitai Capital, to promote the industrialization of new gene therapy drugs. PackGene is a gene drug industrialization platform that focuses on the production of gene therapy drugs and vector research and development.

Dr. Li Huapeng, founder of PackGene Biotech, completed his postdoctoral fellowship at the Gene Therapy Center of the University of Massachusetts Medical School. Together with his team of scientific advisors, he focuses on the innovation and production of AAV vectors and has secured multiple invention patents in AAV manufacturing. To date, the company has provided AAV packaging services to long-term clients comprising over 100 biopharmaceutical companies and research institutions across six countries and regions, including Biogen and AstraZeneca.

Four months later, Hedu Bio announced good news: it has completed a tens-of-millions-yuan angel financing round supported by Mifang Capital. Hedu Bio focuses on the research and development of bacterial vector-based gene therapy drugs, which offer unique advantages in safety and production costs compared with virus-mediated gene therapies.

Dr. Xiang Bin, the company’s founder, previously worked at the Novartis Institutes for BioMedical Research (NIBR) Shanghai R&D Center. He brings over 14 years of experience in oncology and metabolic disease research as well as new drug development, with extensive expertise in disease biology, preclinical drug discovery, gut microbiota, and gene therapy. Dr. Cheng Dachen, co-founder, has held positions at both AstraZeneca and the Novartis Institutes for BioMedical Research (NIBR) Shanghai R&D Center, and possesses rich experience in pharmaceutical CMC (Chemistry, Manufacturing, and Controls) and R&D operations.

Hedu Bio is the first biopharmaceutical company in China to engage in the development of bacterial vector-based gene therapy drugs. The company’s R&D center is located within the Shanghai Zhangjiang Pharma Valley platform and JLABS (Johnson & Johnson Innovation), and it is currently advancing multiple novel drug projects in the preclinical stage. Meanwhile, the company is collaborating with domestic and international synthetic biology enterprises through co-development models to promote the development of multiple bacterial gene therapy drugs.

The development of the gene therapy industry relies on the creation of novel viral vectors characterized by safety, high efficiency, and tissue or organ specificity. However, since gene therapy drug research and development are primarily conducted by research institutions and biotechnology companies, the establishment and optimization of large-scale manufacturing processes required throughout the entire R&D journey—from development to market launch—are largely outsourced.

Yuanxing Gene (Shenzhen Yuanxing Gene) is a leading domestic vertical CRO specializing in gene therapy, having delivered a diverse portfolio of clinical-grade viral vectors. Yuanxing Gene has long provided CRO services to gene therapy research institutions and enterprises, including preclinical pharmaceutical studies for gene therapy drugs and the preparation of clinical trial materials. Currently, leveraging its accumulated R&D and manufacturing processes for over 60 viral vector-based gene therapy products, Yuanxing Gene is expanding into full-industry-chain services such as CDMO and CMO.

The overseas gene therapy market is expanding rapidly, and emerging companies are beginning to appear in the domestic market. What does the future hold for the gene therapy market? It is believed that capital leverage will bring new dynamics to the market.

Source:

https://www.askbio.com/

https://mp.weixin.qq.com/s/wqsBnhuDyB65xVmOjYYQzw

https://mp.weixin.qq.com/s/ROZiEcQWLtbV0IU7pzXJMA