A gene therapy developer emerging from stealth mode said today it could generate more than $2 billion through collaborations launched with Novartis and Sarepta Therapeutics to develop treatments based on a delivery platform developed in the lab of George Church, PhD, of Harvard Medical School.

Dyno Therapeutics said it will partner with Novartis on research, development, and commercialization of new gene therapies for eye diseases incorporating improved adeno-associated virus (AAV) vectors. Separately, Dyno will collaborate with Sarepta on gene therapies for muscle diseases.

Both collaborations will apply Dyno’s CapsidMap™ platform, which uses artificial intelligence (AI) to design novel capsids that confer improved functional properties to AAV vectors.  At the core of CapsidMap, according to Dyno, are advanced search algorithms applying machine learning and the company’s large quantities of experimental data.

CapsidMap is designed to integrate DNA library synthesis and next generation DNA sequencing to measure in vivo gene delivery properties in high throughput. The capsid platform is designed to expand the universe of diseases treatable via gene therapy by improving upon present-day AAV vectors, which are limited by delivery, immunity, packaging size, and manufacturing challenges.

“Our portfolio of R&D programs and newly-announced collaborations with leading gene therapy developers reflect the applicability of our AI-powered approach to improve treatments for patients and expand the number of treatable diseases with gene therapies,” Eric Kelsic, PhD, a former postdoc of Church who is Dyno’s CEO and Co-founder, said in a statement. “We see a vast opportunity to expand the treatment landscape for gene therapies.”

Dyno has an exclusive option to enter into a license agreement with Harvard University for the CapsidMap technology, which was developed in the lab of Church, a co-founder of Dyno and chairman of its scientific advisory board. Church is the Robert Winthrop Professor of Genetics at Harvard Medical School and a Core Faculty member at Harvard’s Wyss Institute for Biologically Inspired Engineering.

Church and other co-founders and members of his lab at HMS and the Wyss Institute carried out work that underpin Dyno’s approach to AAV capsid engineering, described in “Comprehensive AAV capsid fitness landscape reveals a viral gene and enables machine-guided design,” a paper published November 29, 2019, in the journal Science.

200,000-Variant library

In that paper, Church, Kelsic, and two co-authors detailed how they mutated one-by-one each of the 735 amino acids within the AAV2 capsid, including all possible codon substitutions, insertions and deletions at each position. They generated a virus library containing about 200,000 variants and identified capsid changes that both maintained AAV2’s viability and improved its “homing” potential (tropism) to specific organs in mice.

Unexpectedly, the team also discovered a new accessory protein hidden within the capsid-encoding DNA sequence that binds to the membrane of target cells, playing a significant role in viral production.

“Our comprehensive, machine-guided design strategy generated viable mutants in a principled and high-throughput manner and is generalizable to other proteins and engineering challenges,” the researchers reported. “Applied to AAV, such methods now enable the systematic optimization of natural capsids into synthetic variants with enhanced properties for emerging gene therapies.”

Under its partnership with Novartis, Dyno will be responsible for using AI technology and its suite of machine learning and experimental tools for the design and discovery of novel AAV capsids. Novartis agreed to conduct preclinical, clinical, and commercialization activities for the gene therapy product candidates created with the novel AAV capsids.

Dyno and Novartis did not disclose specific financial terms of their collaboration. They did say, however, that Novartis agreed to pay Dyno an upfront fee plus committed research funding and license fees. Dyno will be eligible to receive clinical, regulatory and sales milestone payments. Dyno will also receive royalties on worldwide net sales of any commercial products developed through the partnership.

Opening opportunities

“Many eye diseases are ideally suited to being treated with gene therapies, and more opportunities can be opened with new and improved AAV vectors,” Kelsic added. “With their extensive ophthalmologic expertise, Novartis is an ideal partner to leverage Dyno’s platform to design AI-powered vectors to expand the impact of gene therapies for ocular diseases.”

Under its collaboration with Sarepta, Dyno agreed to oversee the design and discovery of novel AAV capsids with improved functional properties for gene therapy, while Sarepta agreed to take responsibility for conducting preclinical, clinical and commercialization activities for gene therapy product candidates using the novel capsids.

“Our agreement with Dyno provides us with another valuable tool to develop next-generation capsids for gene therapies to treat rare diseases,” stated Doug Ingram, Sarepta’s president and CEO. “By leveraging Dyno’s AI platform and Sarepta’s deep expertise in gene therapy development, our goal is to advance next-generation treatments with improved muscle-targeting capabilities.”

Sarepta agreed to pay Dyno a total $40 million in in upfront, option, and license payments during the research phase of their collaboration. Should Sarepta develop and commercialize “multiple” candidates for multiple muscle diseases, Dyno said, it will be eligible for additional significant future milestone payments. Dyno will also receive royalties on worldwide net sales of any commercial products developed through the collaboration.

Dyno was launched in late 2018 with a $9 million financing co-led by Polaris Partners and CRV. Alan Crane, a co-founder of Dyno and entrepreneur partner at Polaris Partners, and Dylan Morris, general partner at CRV, have joined Dyno’s board, with Crane serving as Dyno’s executive chairman.

Dyno said it did not anticipate the need for additional fundraising, based on the “significant” financial resources made available through its collaborations.

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