The allure of gene therapy was proved yet again as Waltham, Mass.-based Affinia Therapeutics Inc. bagged an oversubscribed $60 million series A financing to boost the push for drugs to benefit people affected by muscle and central nervous system conditions.

Seed venture investors F-Prime Capital and New Enterprise Associates co-led the round alongside new investor Atlas Venture, with participation from seed investors Alexandria Venture Investments, Lonza and Partners Innovation Fund.

The company, founded in early 2019, is led by recently appointed CEO Rick Modi, formerly with Avexis Inc., a subsidiary of Basel, Switzerland-based Novartis AG, where he served as chief business officer for two and a half years. About 20 full-time employees are on board, and plans call for doubling that number by the end of the year, “with some gating to milestones,” Affinia’s scientific co-founder, Luk Vandenberghe, told BioWorld by email. He’s an associate professor at Boston’s Massachusetts Eye and Ear as well as Harvard Medical School.

“Both the scientific approach as well as the vectors are unique to Affinia,” Vandenberghe said. “The vectors are identified from rationally designed adeno-associated vector [AAV] libraries using the Smartlibrary approach.” The libraries are “subjected to a multiparametric screen to identify AAVs with a unique set of properties optimally matching the required target profile for each indication in terms of tissue tropism, pre-existing immunity and manufacturing yield.” At first, Affinia will aim at rendering “much-needed pharmacologic control to the next generation of gene therapies,” he said. Specifically, the series A cash will fuel “the company’s ambition to file the first IND within the next two years,” he added. Affinia has not disclosed the indications to be pursued within muscle and CNS spaces but will target those “with significant unmet need, and where [the company’s] technology and vector provide it a significant advantage over others.”

Advances lately “in translating vector and promoter biology into gene therapy medicines has made a difference in the lives of patients, and this is exciting,” said Vandenberghe, co-inventor of AAV9. “Having said that, we believe the field needs to evolve from the choice of serotypes by ‘instinct’ to one of better structure-function understanding, rational design and improved pharmacologic control.” He likened the times in gene therapy to the era of structure activity relationships in small molecules and biologics.

Joining the board as part of the financing are Atlas partner Dave Grayzel, NEA general partner Ed Mathers and F-Prime partner Robert Weisskoff. Industry veteran and gene therapy specialist Sean Nolan will chair the board.

The field has been steadily drawing more investors. Within the past week, Cambridge, Mass.-based Elevatebio LLC pulled down a $170 million series B round for manufacturing cell and gene therapies, enabling new technology platforms, and pursuing therapeutics. The firm deploys Basecamp to assemble single- and multiproduct enterprises in cell and gene therapies.

Ultragenyx Pharmaceutical Inc., of Novato, Calif., made public a partnership and nonexclusive license and technology access agreement with Tokyo-based Daiichi Sankyo Co. Ltd. for the former’s AAV-based gene therapy manufacturing technologies. Daiichi is paying $200 million up front, including $125 million in cash and a $75 million equity investment. J.P. Morgan analyst Cory Kasimov said in a report that the deal “extends Ultragenyx’s cash runway into 2022, taking any near-term dilutive financing off the table. Importantly (favorably, we might add), the nonexclusive nature of the deal does not pose a competitive risk to Ultragenyx’s current targets or any targets identified by the company in the future.” Given “little-to-no financing overhang in the near- to mid-term, investors focus will likely remain on the next datasets for the two lead gene therapies” in Ultragenyx’s hopper, plus the potential mid-2020 approval of UX-007 (triheptanoin), “pending no COVID-19-mediated delays,” in his view. In October 2019, the FDA accepted for review the company’s NDA for UX-007 for the treatment of long-chain fatty acid oxidation disorders (LC-FAOD), a group of genetic disorders in which the body is unable to convert long-chain fatty acids into energy. U.S. regulators set the PDUFA date for July 31, 2020.

Castle Creek Biosciences Inc., of Exton, Pa., bagged a new investment of $75 million to support the advancement of its gene therapy pipeline. The firm is a portfolio company of Paragon Biosciences, which led the $55 million equity investment from Fidelity Management & Research Co. and Valor Equity Partners, along with a $20 million venture loan from Horizon Technology Finance Corp.

Also recently, the FDA accepted an IND application from Novartis for OTQ-923, a CRISPR-based engineered cell therapy designed to treat sickle cell disease (SCD) by inducing expression of fetal hemoglobin in cells derived from hematopoietic stem cells. Novartis’ partner, Intellia Therapeutics Inc., of Cambridge, Mass., is eligible to collect a $5 million milestone payment from the filing of the IND, and could bank up to $230 million if development, regulatory and sales-based milestones are met, plus royalties in the mid-single digits. The IND “marks the entry of another ex-vivo gene therapy treatment into the increasingly competitive SCD space,” though the scientific rationale for the compound in SCD has been “thoroughly validated by data from competitors,” SVB Leerink analyst Mani Foroohar said in a March 31, 2020 report.

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