Aeglea Cuts Majority of Staff Following Mixed Trial Results

Published: Apr 12, 2023 – Original Story

Wednesday, Aeglea Biotherapeutics announced it was reducing its headcount as part of a sweeping reorganization following mixed interim data from an ongoing Phase I/II study of its classical homocystinuria candidate pegtarviliase.

As part of its strategic review, Aeglea is laying off all but approximately 10 of its staff, who will remain with the company to see the realignment through and maintain “ongoing value-crating activities,” according to Aeglea’s announcement. In its 2022 annual report, the biotech declared 69 employees, primarily in the U.S.

The Texas-based biotech is also exploring strategic alternatives for its business, including an acquisition, merger, reverse merger or other business combination agreements. Aeglea could also sell off assets or engage in other transactions but has yet to confirm that the review will result in such deals.

Aeglea’s stocks dropped 24% in pre-market trading Wednesday following the news.

Michael Hanley, chief business officer, and Linda Neuman, chief medical officer, will also leave Aeglea.

The last few months have been difficult for Aeglea. In June 2022, the FDA handed the company a Refusal to File letter, asking for more efficacy data to support the Biologics License Application for pegzilarginase, Aeglea’s candidate for arginase 1 deficiency.

In its wake, the company cut off 25% of its workforce and lost its former CEO, Anthony Quinn. In January 2023, the company launched another corporate restructuring initiative that claimed 15% of its workforce and saw the discontinuation of its preclinical cystinuria asset and other unnamed early pipeline programs.

The strategic reassessment was triggered by mixed results from a Phase I/II trial, which had three cohorts, each corresponding to a specific dose of pegtarviliase. Patients treated with the 0.15-mg/kg and 0.45-mg/kg doses of Aeglea’s candidate showed consistent reductions in total homocysteine levels three and seven days after treatment.

However, at the highest dose level of 1.35 mg/kg, pegtarviliase could lower homocysteine concentrations over a three-day period. By seven days post-dose, total homocysteine had jumped 15% from baseline values.

In a statement, Jeffrey Goldberg, president and CEO at Aeglea, said these data suggest the company might need to conduct more studies of pegtarviliase, particularly regarding its dose level, duration and frequency.

As for safety, the study found pegtarviliase to be well-tolerated, inducing mild or moderate side effects. One serious adverse event occurred but was deemed unrelated to the candidate. No patient withdrew from the trial or needed a dose reduction due to toxicities.

Beyond pegtarviliase, Aeglea will continue to work on pegzilarginase. In the Phase III PEACE trial, the candidate induced a 76.7% drop in plasma arginine levels, leading to normalized arginine concentrations in 90.5% of treated patients. In turn, pegzilarginase improved patients’ gross motor function and exercise capacity.

The European Medicines Agency is reviewing pegzilarginase’s Marketing Authorization Application and is set to release a verdict in late 2023.

Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com