Affinia Therapeutics Files for IPO Following $110 Million Series B to Build World’s Largest Functional AAV Capsid Library
Affinia Therapeutics
Gene Therapy Developer
Following large-scale public health measures, the adoption of anesthesia in surgery, and the use of vaccines and antibiotics,Gene therapy is regarded as the fourth revolution in the history of human medicine. This ongoing revolutionary saga has, to date, developed intoA History Spanning Over 50 Years. What Kind of Journey Has It Been?
Throughout this journey, gene therapy has experienced both surges and periods of stagnation. Today, it has become one of the brightest stars in the biomedical field. Driven by investor interest and entrepreneurial enthusiasm, an increasing number of gene therapy companies and clinical projects are gradually emerging.
Recently,Genetic Technology CompanyAffinia Therapeutics Announces Completion of $110 Million Series B FinancingThe proceeds from this financing will be allocated for three primary purposes: first, to further develop the company’s gene therapy platform; second, to advance its programs into clinical trials; and third, to cover general corporate expenses.
The Series B financing round was co-led by EcoR1 Capital and Farallon Capital Management.Existing InvestorsAtlas Venture, F-Prime Capital, Lonza, Mass General Brigham Ventures, and New Enterprise Associates participated in this financing round.
On this basis, Affinia has also attracted a new group of investors,IncludingAvidity Partners, Casdin Capital, GV, Octagon Capital, Perceptive Advisors, RA Capital Management, TCG Crossover, and Woodline Partners LP.
In March 2020, Affinia completed a $60 million Series A financing round. The proceeds were used to advance Affinia’s AAV platform and develop therapies for hereditary muscle diseases.and the central nervous system (CNS) diseases gene therapy.
This financing round was led bySeed Venture InvestorF-Prime Capital, New Enterprise Associates, andNew InvestorsAtlas Venture co-led the round, with follow-on investments from Alexandria Venture Investments, Lonza, and Partners Innovation Fund.
As a financing agreementa part of,Dr. Dave Grayzel (of Atlas Venture)Partner),Ed Mathers (General Partner at NEA) and Dr. Robert Weisskoff (Partner at F-Prime Capital) have joined the Board of Directors of Affinia Therapeutics. The Chairman of the Board isIndustry Veteran and Gene Therapy LeaderSean Nolan serves as the chair.
What Is AAV Gene Therapy?
When patients receive gene therapy drugs, AAV vectors carrying the payload attach to cells and enter them. Once inside the cells, the AAV undergoes in vivo tracking.
PendingAfter escaping the endosomal compartment and entering the nucleus, the AAV sheds its capsid and releases its payload. At this point,VirusDNA forms an episome within the nucleus, and the therapeutic gene begins to be expressed from this episome. This marks the formal commencement of gene therapy.
In this process, the greatest challenge encountered by scientists is:Exceeding50% of patientsPre-existing neutralizing antibodies in the body can prevent the vector from entering cells, thereby compromising its therapeutic efficacy.
AffiniaBy leveraging its proprietaryAAV libraries and technologies for engineering viral capsid proteins to modulate immunogenicity and enable tissue-specific targeting, with the aim of treating hereditary central nervous system and muscular disorders.
Dr. Luk, Co-Founder and Chief Scientific Officer of Affinia Therapeutics, stated, “Affinia is bringing together complementary expertise to enable the rational design of AAV vectors, promoters, and other components of gene therapies. This represents a novel paradigm in medicine. By leveraging synthetic and systems biology, high-throughput screening, and single-cell isolation technologies, we aim to develop urgently needed therapies for patients.”
Dr. Luk and his team have successfully developedtitled“AAV Smart Libraries” carrier library, which contains severalA Thousand Functional Novel TypesAAV vectors. Affinia stated that the library has the potential to becomeThe World's Largest FunctionalAAV Vector Library.
AAV Smart Librarieseach vector in theUniquely Identified。This library canScreening across different speciesInterestedparameters of，including tissue compatibility, manufacturing yield, and pre-existing immunity.Screening results from the library will provide scientists with unique insights into the structure and function of vectors, enabling them to design novel vectors and gene therapies with significantly improved characteristics.
Affinia’s technology isbyCo-licensed by Lonza and Massachusetts Eye and Ear. This technology was developed at the Gene Therapy Center of Massachusetts Eye and Ear by a team led by Dr. Luk Vandenberghe. Dr. Luk is the leader of this project and also one of the scientific co-founders of Affinia Therapeutics.
ExceptDr. Luk'soutside,Affinia’s scientific co-founders also include Aaron TwardandBotond Roska. These three scientists have collectively contributed to the field of gene therapyAuthoredPublished over 200 papers and filed more than 20 patent applications.
Dr. Luk holds a Master’s and a Ph.D. in Bioengineering, specializing in Cellular and Genetic Biotechnology, from KU Leuven in Belgium, and completed his postdoctoral training at the Perelman School of Medicine, University of Pennsylvania. Dr. Luk is the Director of the Gene Therapy Center at Massachusetts Eye and Ear and an Associate Professor at Harvard Medical School.
Dr. LukYesA renowned scientific leader in AAV gene therapy R&D, he is one of the inventors of the AAV9 vector. He has authored over 80 publications and holds more than ten patents.He is atIn 2018, he received the Outstanding New Investigator Award from the American Society of Gene & Cell Therapy. In addition to Affinia Therapeutics, Dr. LukStill a gene therapy companyCo-founder of Akouos, Odylia, and Albamunity.
Dr. Aaron is an Associate Professor at the University of California, San Francisco. He is aA surgeon who is also a pioneer in applying high-throughput sequencing technology to key biomedical challenges.Dr. Aaron has authored more than 30 publications, covering fields such as genomics, cancer biology, stem cell biology, and skull base surgery.
Dr. Aaron earned his Ph.D. in Biomedical Sciences and M.D. from the University of California, San Francisco, and completed his residency training in Otolaryngology–Head and Neck Surgery at Harvard Medical School. After obtaining these dual degrees, Dr. Aaron pursued further advanced training, completing his postdoctoral research at the Broad Institute of MIT and Harvard.
Dr. Botond holds multipleIn this role, he serves as the founding director of the Institute for Molecular and Clinical Ophthalmology Basel (IOB), a professor in the Faculty of Science and Medicine at the University of Basel, and an advisor to the Allen Institute.
Dr. Botond previously served as co-editor-in-chief of Annual Review of Neuroscience alongside Huda Zoghbi. He has authored more than 80 publications spanning multiple fields, including gene therapy, regulatory elements, and neuronal circuits.
Dr. Botond’s initial dream was not in the field of medicine. Born into a family of musicians, he studied cello at the Franz Liszt Academy of Music. Later, a hand injury ended his cello career, prompting him to switch to studying mathematics and medicine. He first attended Eötvös Loránd UniversityHe studied mathematics, then attended Semmelweis University School of Medicine and the University of California, Berkeley, earning an M.D. and a Ph.D. in Neurobiology, respectively.
Affinia Therapeutics focuses on disease areas involving debilitating disorders that affect the central nervous system and muscles.
Hereditary Central Nervous System Diseasesare among the most debilitating and difficult-to-treat conditions. This category encompasses a wide variety of disorders, characterized by their familial and lifelong nature. Gene therapy holds considerable promise for the treatment of genetic diseases; however, its full potential has yet to be realized due to the lack of viable vectors capable of delivering therapeutic agents to diseased cells.
AffiniaLeveraging its proprietary platform, systematically design novel agents with significant targeting propertiesAAV Vectors and Gene Therapy: These vectors will be able to penetrate the central nervous system more extensively and deeply, fundamentally improving the health and quality of life for patients with neurological disorders.
Hereditary Muscle DiseasesIt is a group of hereditary diseases primarily originating in muscle tissue.，The clinical hallmark is motor dysfunction. Gene therapy has demonstrated the potential to mitigate disease progression in this therapeutic area. In certain specific cases, gene therapy may offer a complete cure for hereditary muscle diseases, thereby restoring patients’ physical health.
The bottlenecks faced by gene therapy in the application to hereditary muscle diseases are consistent with those in hereditary central nervous system disorders. There is an urgent need in this field for evolved vectors that can safely and effectively deliver therapeutic agents into diseased cells to achieve therapeutic outcomes.
Currently, AffiniaDeveloping next-generation solutions by leveraging its proprietary platformAAV Vectors: Achieving the Goal of a Complete Cure for Hereditary Muscle Diseases
However, Affinia has yet to deliver tangible results for either hereditary central nervous system diseases or hereditary muscular diseases, with both programs remaining in the preclinical research stage.
In April 2020, Affinia Therapeutics and Vertex Pharmaceuticals established a strategic partnership. Affinia leveraged its proprietary AAVSmartLibrary vector library and itsNovel Design of Related TechnologiesAAV capsid,ForVertex’s Genetic Therapy Efforts Focus on Duchenne Muscular Dystrophy（DMD）、Type 1 Muscular Dystrophy（DM1) and cystic fibrosis(-izationCF）。
Under the terms of the agreement, Vertex has obtained an exclusive license to Affinia’s proprietary technology and intellectual property related to DMD and DM1, as well as exclusive option rights for CF and other undisclosed diseases. Vertex will be primarily responsible for funding the design and manufacturing of gene therapies, including selected capsids, preclinical and clinical development activities, and the commercialization of any approved products for the licensed indications.
According to the terms of the agreement, Affinia will receive VertexUpfront development, regulatory, and commercialization costs paid are expected to exceed$1.6 billion. This amount includes $80 million in upfront and research milestone payments, as well as tiered royalties on net product sales.
In June 2020, Affinia appointed Elliott Sigal, M.D., to its Board of Directors.。Dr. Sigal has over 25 years of leadership experience in the biopharmaceutical industry, having served as Chief Scientific Officer and President of Research and Development at Bristol Myers Squibb.
Rick Modi, CEO of AffiniaIndicates:“Dr. SigalAs a pioneer in the biopharmaceutical industry, we look forward to his constructive insights to advance the company’s platform and candidate products toward clinical development, ensuring they reach the most appropriate patients.”
May 2021, AffiniaAt thePreclinical study results of the AAV platform were presented at the 24th Annual Meeting of the American Society of Gene & Cell Therapy. The key points are as follows:
I. ANC80L65
ANC80L65 is AffiniaProprietary DevelopmentAAV Vectors. AffiniaStated at the conference that a single intrathecal injectionANC80L65 demonstrated superior efficacy to AAV9 in the central nervous system of non-human primates (NHPs).
During lumbar puncture administration, the RNA expression level of ANC80L65 was 32-fold higher than that of AAV9 administered via the intrathecal route. Furthermore, ANC80L65 exhibited higher expression levels than AAV9 in both the cerebral cortex and deep brain nuclei.
Charlie Albright, Chief Scientific Officer at Affinia Therapeutics, stated, “Affinia’s team of gene therapy experts has been focused on addressing some of the greatest challenges in the AAV field. We are striving to identify differentiated vectors, expand the therapeutic potential of AAV in areas such as central nervous system and neuromuscular disorders, and improve AAV manufacturing. ANC80L65 represents the first outcome of this effort, and we intend to incorporate it into the company’s initial clinical programs.”
II. Results of Screening Central Nervous System Vectors
In delivering AAVs to deep regions of the central nervous system (CNS), CNS vectors screened by Affinia Therapeutics demonstrate superior performance compared to AAV9. Through this intrathecal screening approach, Affinia has identified novel vectors that achieve vector copy numbers 256-fold higher than those of AAV9 in non-human primates (NHPs).
III. Novel Vectors to Address Concerns Over Hepatotoxicity
In neuromuscular diseases, traditional AAV vectors require systemic administration at high doses to achieve therapeutic efficacy, a approach that raises concerns about hepatotoxicity.
At the conference, Affinia stated that the company has identified a rational design strategy to address this issue. Compared with AAV9, Affinia’s vector incorporates one modification to reduce off-target liver uptake and another to enhance muscle expression in mice, thereby eliminating concerns about hepatotoxicity.