Rare Daily Staff

4D Molecular Therapeutics, a company using directed evolution for targeted gene therapies, reported updates on their rare disease ophthalmology experimental candidates targeting choroideremia and x-linked retinitis pigmentosa, and that the company received a notice of termination of the collaboration and license agreement by Roche resulting in full rights reverting to 4DMT.

Roche requested that 4DMT conclude the Roche-funded 4D-110 trial in advanced choroideremia patients due to Roche’s assessment of a change in the risk-benefit profile, effective as of September 16, 2021. As a result, 4DMT will regain full rights to 4D-110.

4DMT said it has not changed its position on the potential of 4D-110 for choroideremia, a blinding disease with no approved therapies. Based on the totality of the data generated to date, 4DMT intends to continue clinical development. The company plans to submit to FDA safety and efficacy data from the completed phase 1 clinical trial along with a new clinical study protocol as soon as possible. 4DMT will conclude the Roche-funded clinical trial under the collaboration and plans to subsequently transfer previously treated patients onto a 4DMT-sponsored long-term follow-up study to continue monitoring biologic activity endpoints, safety, and tolerability.

“We believe the initial clinical tolerability and adverse event profile data in twelve patients from our two intravitreal rare disease ophthalmology clinical trials, performed under 4DMT INDs, demonstrate the potential of our intravitreal product platform,” said David Kirn, CEO, president, and co-founder of 4D Molecular Therapeutics. “We expect to release initial 4D-110 biologic activity data in the fourth quarter of this year when at least six months of follow-up are available for all currently enrolled patients, and after the 90-day transition period with Roche is completed.”

Both clinical trials employed standard dose-escalation designed to assess the safety, tolerability and biologic activity of a single intravitreal injection of either 4D-110 for choroideremia or 4D-125 for XLRP at two dose levels (3E11 or 1E12 vg/eye). A total of twelve patients were enrolled across dose escalation cohorts, including six who received 4D-110 (three at each dose level) and six who received 4D-125 (three at each dose level). Patients received a standard immunosuppression regimen with taper; adjustments were determined by investigators.

For 4D-110, initial clinical safety data at the two dose levels in the phase 1 clinical trial indicate that 4D-110 was well-tolerated and did not result in any dose-limiting toxicity.

For 4D-125, initial clinical safety data at the two dose levels in the phase 1 portion of a phase 1/2 clinical trial indicate that 4D-125 was well-tolerated and did not result in any dose-limiting toxicity.

Photo: David Kirn, CEO, president, and co-founder of 4D Molecular Therapeutics

X