Roche Terminates Collaboration with 4DMT on Ocular Gene Therapy 4D-110 Prior to Early-Stage Trial Completion

Compiled and translated by | Fan Dongdong

Recently, Roche announced it will terminate its collaboration with 4D Molecular Therapeutics, cease development support for the ophthalmic gene therapy 4D-110, and return the rights to the therapy to the small biotechnology company. Following Roche's review of early data and its subsequent concerns regarding the risk-benefit profile, 4DMT stated that it will continue to develop the therapy.

Previously, Roche had been funding an early-stage trial of 4D-110 in patients with advanced choroideremia, a blinding disease with no approved therapies. The collaboration will now be terminated this September, with full rights to the therapy reverting to 4DMT. Following the major pharmaceutical company's withdrawal, shareholder confidence in 4DMT has been shaken. Hit by this negative news, the stock fell nearly 13% to $21.61 per share.

In a report, Evercore analysts stated, "Overall, we are not discouraged by this collaboration update," noting that with the rights reverting, the choroideremia program is "generally back on track." Evercore indicated that Roche likely terminated the collaboration based on early preclinical data, which showed poor payload delivery and that 4DMT's gene therapy utilized a known vector capable of stimulating an immune response.

Roche noted that other studies conducted by 4DMT have demonstrated more favorable immune responses and clinical benefits. Another potential reason for Roche's withdrawal may be the concerning safety data from a recent study by Adverum Biotechnologies, along with Biogen's trial failure earlier this month. These events have hindered progress across the broader ocular gene therapy sector. Following the termination of the collaboration, Roche's portfolio will retain only the commercialization rights for the smaller choroideremia indication, while 4DMT secures a position in the significantly larger potential markets for X-linked retinitis pigmentosa and wet age-related macular degeneration.

Additionally, 4DMT disclosed a series of adverse events associated with the gene therapy, with half of the patients treated with 4D-110 reporting ocular inflammation. Compared to the Adverum trial, the side effects appear less concerning. Evercore stated, “Given the unmet clinical need in these diseases, such adverse reactions are entirely acceptable.” 4DMT noted that the decision to advance 4D-110 was “based on the totality of data generated to date.” The company is eager to initiate the next clinical trial, which will include patients with early-stage disease.

But first, 4DMT must review the Phase I data alongside the investigators and the FDA, with Roche apparently dissatisfied with the results. Patients who have already received the gene therapy will be transitioned to a long-term follow-up study to further monitor their biological activity endpoints, safety, and tolerability. Preliminary biological activity data for 4D-110 are expected to be released in the fourth quarter of this year; however, preliminary safety and toxicity data indicate that the therapy is well-tolerated, with no dose-limiting toxicities observed in any of the six enrolled patients.

This Thursday, 4D Molecular Therapeutics (4DMT) also provided updates on four other pipeline programs. These include 4DMT’s plan to report initial biological activity data in the fourth quarter from the Phase 1/2 clinical trial of 4D-125, another ophthalmic therapy targeting patients with X-linked retinitis pigmentosa. Preliminary clinical data from the Phase 1/2 trial of 4D-310 in patients with Fabry disease are expected in the second half of the year. Additionally, 4DMT plans to initiate two clinical trials in the fourth quarter: one for patients with diabetic macular edema and another for patients with cystic fibrosis lung disease.

Source: Roche walks away from 4DMT's eye gene therapy before early-stage trial finishes