Obsidian Therapeutics Inc., a clinical-stage biopharmaceutical company developing engineered Tumour-Infiltrating Lymphocyte cell therapies using its proprietary protein-regulation technology, has announced the enrolment of the first patient in the registration-enabling cohort of its phase 1/2 Agni-01 multicentre study.

The cohort is evaluating amsokigene autoleucel (amsoki-cel, formerly OBX-115), an investigational engineered TIL cell therapy in patients with Immune Checkpoint Inhibitor (ICI)-resistant advanced or metastatic melanoma.

Following discussions with the US Food and Drug Administration (FDA), Obsidian has opted for a single-arm trial design intended to support a future Biologics License Application (BLA) submission for amsoki-cel.

According to the company, the FDA has aligned with Obsidian on key aspects of the trial design and manufacturing programme, including considerations related to the drug potency assay. The registration-enabling cohort is designed to evaluate amsoki-cel at the Recommended Phase 2 Dose (RP2D) and generate data potentially supporting an accelerated approval pathway.

Parameswaran Hari, Chief Medical Officer, Obsidian Therapeutics, said, “The FDA alignment across key trial design and manufacturing considerations enables us to proceed with the registration-enabling cohort for amsoki-cel in advanced melanoma. The enrolment of the first patient represents an important milestone as we work towards developing a patient-focused TIL treatment option for people with difficult-to-treat ICI-resistant advanced melanoma.”

The ongoing Agni-01 study is a multicentre phase 1/2 clinical trial assessing the safety and efficacy of amsoki-cel across patients with advanced solid tumours. In the registration-enabling melanoma cohort, the primary endpoint is Objective Response Rate (ORR), assessed according to Response Evaluation Criteria in Solid Tumours (RECIST) through Blinded Independent Central Radiologist Review (BICR).

Enrolment in the registration-enabling cohort is expected to be completed by the end of the first quarter of 2027, with topline results anticipated by the end of 2027.

The decision to advance the programme follows encouraging data from the earlier phase 1/2 portion of Agni-01. At the RP2D, amsoki-cel achieved an objective response rate of 67 percent in 15 evaluable patients, with 10 patients achieving a response, including two complete responses.

The company also reported a favourable safety profile in the study. No dose-limiting toxicities, treatment-related deaths, immune effector cell-associated neurotoxicity syndrome or intensive care unit transfers were reported. The treatment regimen incorporates low-dose lymphodepletion and does not require interleukin-2 (IL-2), features that Obsidian believes could help simplify treatment administration.

Amsoki-cel is an autologous engineered TIL therapy designed with pharmacologically regulatable membrane-bound interleukin-15 (mbIL15). The approach is intended to enhance the persistence and antitumour activity of TILs while enabling regulation of IL15 activity using pharmacological control.

Obsidian's proprietary cytoDRiVE technology is designed to regulate the timing and level of protein activity through the use of US FDA-approved small-molecule drugs. The company is applying this platform to engineered cell therapies with the aim of improving therapeutic activity while maintaining greater control over safety and tolerability.

In addition to melanoma, Obsidian is evaluating amsoki-cel in patients with Non-Small Cell Lung Cancer (NSCLC) as part of the Agni-01 programme. Initial NSCLC phase 1 data are expected during the first half of 2027.

Amsoki-cel is an investigational therapy and has not been approved by the FDA or any other regulatory authority. Its development programme is focused on addressing the needs of patients with advanced melanoma and other solid tumours who have limited treatment options following disease progression on immune checkpoint inhibitors.