Roche has told 4D Molecular Therapeutics that it's time to wind down a sponsored trial for an eye disease gene therapy and send the rights for the therapy back to the small biotech.
4DMT vowed to roll on with developing the therapy, even if Roche is questioning the risk-benefit profile after reviewing early data.
The Swiss Big Pharma had been funding an early stage trial for 4D-110 in patients with advanced choroideremia, a blinding disease with no approved therapies. That deal will now terminate in September, with the full rights for the therapy transferring back to 4DMT.
With the Big Pharma dropping out, shareholders' confidence was shaken, sending the stock sliding nearly 13% to $21.61 per share as of 3:04 p.m. ET Thursday.
"[O]verall, we’re not discouraged by this update," Evercore analysts said in a note. With the rights returned, the analysts said the choroideremia program is "generally on track."
Roche may have cut the cord based on early preclinical data that showed poor delivery of the payload and the fact that 4DMT's gene therapy uses a vector known to spur immune responses, Evercore said. Other studies conducted by 4DMT have shown a better immune response and benefit, the firm noted.
Another reason for Roche's exit may have been Adverum Biotechnologies' recent shaky safety results and a Biogen trial failure earlier this month. Those events have put a damper on the entire gene therapy field in eye diseases.
Finally, Roche had rights for just the small choroideremia indication, whereas 4DMT has held tight to the larger potential markets in X-linked retinitis pigmentosa and wet age-related macular degeneration.
All that together, and Roche was ready to cut its losses.
4DMT also disclosed its own set of adverse events, although not nearly as concerning as the blinding event seen in the Adverum trial. Half of the patients who received 4D-110 reported eye inflammation.
"Given the unmet need in these settings, that’s entirely acceptable," Evercore said.
4DMT said the decision to move forward with 4D-110 is "based on the totality of the data generated to date." The company is raring to go on the next clinical trial, which will include earlier-stage patients. But first, they must review the phase 1 data—which Roche clearly balked at—with the investigators and the FDA.
Patients who have already been treated with the gene therapy will be transferred to a long-term follow-up study to further monitor their biologic activity endpoints, safety and tolerability.
Initial biologic activity data for 4D-110 is expected in the fourth quarter, but preliminary safety and toxicity data suggest the therapy has been well-tolerated and did not lead to dose-limiting toxicity in all six enrolled patients.
"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,” said 4DMT CEO David Kirn, M.D., in a statement. “We would like to thank our Roche colleagues for a highly productive collaboration and funding support for the 4D-110 choroideremia program."
The California biotech provided updates on four other programs Thursday, as well.
4DMT is slated to provide initial biologic activity data in the fourth quarter for a phase 1/2 clinical trial of another ophthalmologic treatment, 4D-125, which is aimed at patients with X-linked retinitis pigmentosa.
Initial clinical data for a phase 1/2 trial of 4D-310 for patients with Fabry disease are expected in the second half. 4DMT is also planning to start two clinical trials in the fourth quarter: one for patients with diabetic macular edema and another for patients with cystic fibrosis lung disease.
The news comes six months after 4DMT raised $222 million in an IPO and added a clinical leader for ophthalmology.