4D-150

4D Molecular Therapeutics\' gene therapy is currently in a phase 3 trial for its lead indication of wet age-related macular degeneration.\n 4D Molecular Therapeutics has sold the Asia-Pacific rights to its eye gene therapy to Otsuka Pharmaceutical, securing $85 million in upfront cash to fund the asset’s phase 3 development.In return for the rights to develop and commercialize the gene therapy, dubbed 4D-150, for retinal vascular diseases like wet age-related macular degeneration (AMD) and diabetic macular edema (DME) in Japan, China, Australia and other Asia-Pacific markets, Otuska is also expected to assist with cost-sharing at least $50 million over the next three years for global development activities.Further down the line, Otuska could also end up paying out up to $336 million in potential regulatory and commercial milestone payments, as well as tiered double-digit royalties should 4D-150 make it to market.4D-150 encodes aflibercept—an anti-VEGF drug Regeneron markets as Eylea—and a sequence that inhibits expression of VEGF-C. 4DMT designed 4D-150 to provide sustained delivery of anti-VEGF agents, freeing patients from burdensome injections and potentially improving outcomes.The deal comes three months after 4DMT posted 60-week data from a phase 2 trial of 4D-150 that demonstrated a 78% reduction in supplemental injections in people who received the phase 3 dose compared to projected on-label use of Eylea 2 mg.The gene therapy is currently in a phase 3 trial for wet AMD—its lead indication—with a further later-stage study for DME being lined up. The biotech said the upfront cash from the Otsuka deal would help fund this DME study as well as “pre-commercial activities.”“We are thrilled to announce this strategic partnership with Otsuka, a leading global pharmaceutical company with a strong presence in the APAC region, reflecting our shared long-term commitment to improving outcomes for patients with retinal vascular diseases,” 4DMT CEO David Kirn, M.D., said in the Oct. 30 release.“This partnership is a key pillar of our global strategy, with 4DMT continuing to lead phase 3 clinical trial and manufacturing activities globally, in addition to pre-commercial and commercial activities outside the APAC region,” Kirn added.4DMT Chief Commercial Officer Chris Simms said the Asia-Pacific region “represents a large and underserved retina market, with a high prevalence of wet AMD and DME.”“Navigating the region’s regulatory and patient-access complexities requires a strong local partner, and we expect Otsuka’s deep presence and expertise to accelerate both development of and access to 4D-150,” Simms added. It’s been a busy year for eye-related gene therapies. While Johnson & Johnson’s $130 million bet on an X-linked retinitis pigmentosa candidate suffered a phase 3 setback in May, the likes of Opus Genetics, MeiraGTx, Beacon Therapeutics and 4D Molecular Therapeutics have seen better news in the clinic.Meanwhile, the $135 million series B and Big Pharma backing secured by Stargardt disease-focused SpliceBio in June suggests investors can still be enthused, and Eli Lilly swooped in to buy Adverum last week.Otsuka has been on the lookout for opportunities to pad out its pipeline this year. The summer saw the Japanese company pay $33 million for a Swedish biotech’s IL1RAP antibodies designed to treat autoimmune and inflammatory diseases, as well as hand over $47 million for the ex-China rights to Harbour BioMed’s BCMAxCD3 bispecific candidate.

iStock, Enes Simsek Otsuka Pharmaceuticals could shell out over $400 million in total for the Asia-Pacific rights to 4D-150, which combines a VEGF-C inhibitory RNAi with Regeneron’s Eylea into a single ocular injection. 4D Molecular Therapeutics has signed an $85 million upfront deal with Japan’s Otsuka Pharmaceuticals to bring a genetic eye disease medicine to the Asia-Pacific region. Besides the upfront payment, 4DMT will also receive $50 million in cost sharing and will be eligible for up to $336 million in milestone payments, plus royalties, according to a Thursday press release . In return, Otsuka has secured rights to develop 4D-150 in wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME) in the greater Asia-Pacific (APAC) region including Japan. 4DMT will keep the rights to 4D-150 outside the APAC region. 4DMT will continue with Phase III activities for the candidate, including in the APAC region, according to the release. The biotech expects sites to open for the late-stage test in wet AMD by the end of the year. 4D-150 combines a VEGF-C inhibitory RNAi with Regeneron’s Eylea via a single, low-dose treatment that is injected into the eye. The therapy was developed by 4DMT via its Therapeutic Vector Evolution platform to provide a longer duration treatment for patients with wet AMD and DME. Regeneron’s blockbuster Eylea is an injectable medicine that must be administered by an eye specialist every one to two months. The company is working on Eylea HD, which would be a longer-lasting pre-filled syringe of the medicine, but the new formulation has been plagued by manufacturing delays stemming from a third-party manufacturer and was rejected by the FDA earlier this week. Sales of Eylea have been declining for Regeneron; it posted $1.11 billion for the third quarter, a 28% decline. 4DMT is not the only biotech coming after Regeneron’s Eylea crown. Ocular Therapeutix has an asset called Axpaxli that William Blair has heralded as “a significant advance” for the disease, however the therapy is still years away from the market. And Kalaris Therapeutics is in Phase I with TH103 for the condition, which is one of the leading causes of blindness. Meanwhile, Eli Lilly just offered up to $261.7 million to acquire Adverum Therapeutics, which has a gene therapy candidate called Ixo-vec for wet AMD.