Adicet Bio’s Prula-Cel Delivers 54% Lupus Remission Rate at 12 Months

Key Points

• Prula-cel showed promising 12-month efficacy in lupus: 54% of evaluable patients achieved DORIS remission, while 50% of lupus nephritis patients achieved a complete renal response. Remissions generally occurred without immunosuppressants and with minimal steroid use.
• The therapy demonstrated a manageable safety profile in 24 patients, with no dose-limiting toxicities, ICANS, IEC-HS, or graft-versus-host disease; 25% experienced only Grade 1 or 2 cytokine release syndrome.
• Adicet plans an FDA-aligned pivotal study in refractory lupus nephritis, with start-up expected by year-end, interim data in 2028, and a readout in 2029. The company is also exploring expansion to non-renal lupus.

Adicet Bio NASDAQ: ACET reported positive clinical data for prula-cel, its investigational allogeneic gamma delta CAR-T cell therapy, in patients with systemic lupus erythematosus, or SLE, including patients with lupus nephritis.

The company said that, among evaluable lupus nephritis patients, 50% achieved complete renal response at 12 months. Across the overall lupus population, including patients with and without nephritis, 54% achieved Definition of Remission in SLE, or DORIS, remission at 12 months. The reported remissions occurred while patients were off immunosuppressants and taking no more than 5 milligrams of prednisone equivalent, according to the company.

“A one-time therapy that achieves high rates of immunosuppressant-free clinical remissions would be transformative,” Interim Chief Medical Officer Lloyd Klickstein said during the webcast.

Study Population and Clinical Results

The lupus cohort enrolled 24 patients: 16 with lupus nephritis and eight with lupus without nephritis. Participants were primarily women, had a mean age of 35, and had received at least three prior therapies. Adicet said 71% of patients had received four or more prior immunosuppressants in addition to glucocorticoids.

Among lupus nephritis patients at the 12-month mark, the company reported that five patients had achieved complete renal response. Two had reached that response by month six, two additional patients achieved it by month nine, and another reached it by month 12. Adicet also said an additional 20% of nephritis patients achieved at least a 50% decline in proteinuria from baseline, meeting the protocol definition for partial renal response.

All 12-month complete renal and DORIS remissions remained ongoing over follow-up periods ranging from 12 to 21 months, except for one patient whose urine protein-creatinine ratio rose to 0.65 grams per gram after month 12. The company said that patient remained off immunosuppressants.

Adicet reported that 21 of 22 efficacy-evaluable patients remained off immunosuppressant therapy during the study. All but one patient reduced background steroid use to 5 milligrams or less of prednisone equivalent. The company also said prula-cel produced rapid and sustained reductions in SLEDAI disease activity scores and Physician Global Assessment scores.

Safety Profile and Immune Reset Findings

Across 24 safety-evaluable patients, Adicet reported no dose-limiting toxicities, no immune effector cell-associated HLH-like syndrome, or IEC-HS, no immune effector cell-associated neurotoxicity syndrome, or ICANS, and no cytokine release syndrome events above Grade 2.

Grade 1 or Grade 2 cytokine release syndrome occurred in 25% of patients, while two of 24 patients experienced Grade 3 infections. There were no cases of graft-versus-host disease, according to the company.

Chief Executive Officer Chen Schor said the company had aligned with the Food and Drug Administration to enable outpatient enrollment for prula-cel going forward. Adicet attributed the observed safety profile to the biology of gamma delta T cells, which it said produce lower levels of cytokines associated with hyperproliferation and severe inflammatory toxicities seen with alpha-beta CAR-T approaches.

Chief Scientific Officer Blake Aftab said every efficacy-evaluable patient experienced deep and complete depletion of CD19-positive B cells during the first month after treatment. B-cell recovery generally occurred within one to four months and was driven primarily by naïve and non-class-switched B-cell populations, which the company characterized as evidence of immune reset.

Adicet also reported that, among patients with evaluable quantitative data, at least 91% had reductions in anti-double-stranded DNA antibody titers and increases in complement measures. Approximately 70% returned to the normal range, Aftab said.

Pivotal Study Plans

Adicet said it has aligned with the FDA on a proposed single-arm pivotal study in patients with active lupus nephritis who have had inadequate responses to at least two immunosuppressants. The planned primary endpoint is complete renal response at 12 months.

The company expects the nephritis study to enroll a double-digit number of patients with biopsy-proven proliferative Class III or IV lupus nephritis, with or without Class V involvement. Management also plans to discuss expanding the study to include SLE patients without nephritis, using DORIS remission as a primary endpoint. The potential combined study size would be about 90 patients.

• Study start-up activities are expected by the end of the year.
• Adicet expects interim pivotal data in 2028.
• A pivotal study readout is anticipated in 2029.

For the pivotal trial, the company plans to propose a 3E8-cell dose after observing no efficacy dose-response across tested doses, while noting a trend toward more safety events at the highest 1E9-cell dose.

Adicet said it estimates that approximately 70,000 U.S. patients have refractory organ- or life-threatening lupus disease, including roughly 35,000 with lupus nephritis and 35,000 with non-renal lupus.

About Adicet Bio (NASDAQ:ACET)

Adicet Bio, Inc is a clinical-stage biotechnology company developing allogeneic T-cell therapies for the treatment of cancer. Its platform is based on gamma delta T cells, a type of immune cell that may be engineered to recognize and attack tumor cells while potentially offering advantages associated with off-the-shelf cell therapies.

The company's pipeline has included investigational CAR T-cell products designed to target specific cancer antigens, including ADI-001, an anti-CD19 therapy developed for B-cell malignancies.

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