4DTM Goes It Alone After Roche Pulls Out of Gene Therapy Trials

In 2018, 4D Molecular Therapeutics announced it was expanding its 2015 research agreement with Roche to develop and commercialize multiple ophthalmology products. This summer, things apparently went south.

In June, 4DMT said it had received a notice of termination of the collaboration and license agreement from Roche, resulting in full rights for the product 4D-110, an experimental gene therapy for choroideremia, reverting to 4DMT as of September 16. Choroideremia is an inherited disease marked by progressive vision loss; it has no treatments.

Moving on in Choroideremia
The company said it plans to submit safety and efficacy data from a completed Phase I clinical trial of 4D-110 to the Food and Drug Administration, along with a new clinical study protocol for treatment of earlier-stage patients, “as soon as possible.”

“Roche requested that 4DMT conclude the Roche-funded 4D-110 trial in advanced choroideremia patients as a result of Roche’s assessment of a change in the risk-benefit profile,” 4DMT said. There was no comment from Roche posted on its website or mentioned in news stories.

The announcement initially caused 4DMT stock price to fall 13% to $21.61 per share when the termination was announced, Fierce Biotech reported, but it has partly rebounded to around $23.50 a share early in the week.

“We are pleased to regain full rights to our 4D-110 product candidate for choroideremia, and to develop it further within our wholly owned ophthalmology product portfolio,” 4DMT CEO David Kirn, MD, said in a company press release. “We would like to thank our Roche colleagues for a highly productive collaboration and funding support for the 4D-110 choroideremia program.”

4DMT plans to conclude the Roche-funded clinical trial under the collaboration and subsequently transfer previously treated patients onto a long-term follow-up study to continue monitoring biological activity endpoints and safety, Robert Kim, MD, 4DMT’s senior vice president of clinical research and head of clinical ophthalmology, said in the June 24 announcement.

“We are committed to designing and initiating the next 4D-110 clinical trial, including treatment of earlier-stage patients, as soon as possible after reviewing the clinical data with our investigators and the FDA,” Dr. Kim said.

Trials Moving Along
In the June announcement, the company also shared initial clinical safety data for 4D-110 and its product 4D-125, which is being studied in X-linked retinitis pigmentosa. Both trials of six patients each employed standard 3+3 dose-escalation designed to assess safety, tolerability and biological activity of a single intravitreal injection, at two dose levels. Four of six patients (67%) treated with 4D-110 and two of six patients (33%) treated with 4D-125 developed grade 1 uveitis. There were no dose-limiting toxicities, or serious or retinal adverse events.

Initial biological activity data from the Phase I trial of 4D-110 and the Phase I/II clinical trial of 4D-125 are expected in the fourth quarter, the company said. 4DMT also plans to launch clinical trials for its candidate 4D-150 in wet age-related macular degeneration and diabetic macular edema, and for its candidate 4D-710 in cystic fibrosis lung disease, in the fourth quarter. And, it expects initial clinical data from a Phase I/II clinical trial of its product 4D-310 in Fabry disease in the second half of 2021.