Astellas Pharma and 4D Molecular Therapeutics (4DMT) just announced a license agreement giving Astellas rights to 4DMT’s intravitreal retinotropic R100 vector for use in gene therapy for a rare monogenic ophthalmic disease, with options to add up to two additional targets after paying additional option exercise fees.

4DMT will receive $20 million upfront, and potential future option fees and milestones of up to $942.5 million including potential near-term development milestones of $15 million for the initial target. In addition, 4DMT is entitled to receive mid-single digit to double-digit, sub-teen royalties on net sales of all licensed products.

Most vectors cannot reach the retina due to the inner limiting membrane. Therefore, in many cases, genetic medicines require subretinal injection via vitrectomy surgery. R100 is an adeno-associated virus (AAV) vector that can penetrate the internal limiting membrane barrier and transduce the entire retina.

All three 4DMT clinical-stage ophthalmic product candidates use the R100 vector, including 4D-150 for wet age-related macular degeneration and diabetic macular edema.

Under the terms of the agreement, 4DMT will provide R100 vector technology to deliver Astellas’ unique genetic payloads for the treatment of rare monogenic diseases. Astellas will conduct all subsequent research, development, manufacturing, and commercialization activities.

“This collaboration with Astellas, a leader in AAV gene therapy, continues to validate R100 for routine intravitreal low dose delivery of genetic payloads for the treatment of retinal diseases,” said David Kirn, MD, co-founder and chief executive officer of 4DMT.

“With over 70 patients dosed to-date with R100-based product candidates in wet age-related macular degeneration and rare ophthalmic diseases, this collaboration also demonstrates the modularity of the Therapeutic Vector Evolution platform resulting in efficient design and development of new intravitreal products. 4DMT retains rights to large market non-hereditary ophthalmic diseases,” he added.

Adam Pearson, Chief Strategy Officer (CStO) at Astellas said, “At Astellas, we have a strong commitment to developing novel treatments for ophthalmic diseases, and have positioned Blindness & Regeneration as one of the Primary Focuses of our R&D strategy. Staying at the forefront of gene therapy technology is a key part of our strategy. We believe that this collaboration will bring synergies between the two companies’ cutting-edge research, and will ultimately lead to the development of new therapeutics for patients with ophthalmic diseases at high risk of blindness.”

4DMT aims to use directed evolution for genetic medicines targeting large market diseases. Its proprietary platform–Therapeutic Vector Evolution–combines directed evolution with approximately one billion synthetic AAV capsid-derived sequences to invent customized and evolved vectors for use in our product candidates.

The company’s vectors include R100, A101, and C102, which are currently being tested in three therapeutic areas for both rare and large market diseases: ophthalmology, pulmonology, and cardiology. 4DMT says its vectors were “Invented with the goal of being delivered at relatively low doses through clinically routine, well-tolerated, and minimally invasive routes of administration, transducing diseased cells in target tissues efficiently, having reduced immunogenicity and, where relevant, having resistance to pre-existing antibodies.”

4DMT is currently advancing five product candidates in clinical development: 4D-150 for wet AMD and DME, 4D-710 for cystic fibrosis lung disease, 4D-310 for Fabry disease cardiomyopathy, 4D-125 for XLRP, and 4D-110 for choroideremia.

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