Biomarker Data from Oncology Trial for Adicet Bio’s Gamma Delta T-cell Therapy ADI-001 Indicates Potential for Use in Autoimmune Disease
In lymph node biopsies from patients treated in the study, a mean exposure of 236,701 CAR T-cells per million across all dose levels was observed.
Biomarker data collected in the phase 1 GLEAN clinical trial (NCT04735471) evaluating Adicet Bio’s ADI-001, an investigational allogeneic chimeric antigen receptor (CAR)-engineered gamma delta T-cell therapy, for the treatment of B-cell malignancies, indicates the therapy’s potential to treat autoimmune disease, according to the company.1
In lymph node biopsies from patients treated in the study, a mean exposure of 236,701 CAR T-cells per million across all dose levels was observed. Furthermore, CAR T-cells comprised 27% to 64% of total cellular material as measured by ddPCR in evaluable biopsies from patients treated at the 1x109 dose level. In situ detection of granzyme B also indicated a “robust” activation profile. Analysis of secondary lymphoid tissue also revealed complete depletion of CD19+ B-cells alongside ADI-001 tissue trafficking and activation.
“These results clearly support the potential of ADI-001 and Adicet’s off-the-shelf gamma delta CAR T-cell platform, by demonstrating robust trafficking and complete B-cell depletion in tissue, while providing superior exposure of ADI-001 in secondary lymphoid tissue compared to published third-party data reported for alpha-beta CAR T therapies,” Blake Aftab, PhD, the chief scientific officer of Adicet Bio, said in a statement.1 “Together, the totality of our findings provide multiple levels of evidence highlighting the significant advantages of our approach and present a compelling opportunity for ADI-001 to extend B-cell targeting into tissues, as we look to address a range of autoimmune diseases in the clinic.”
Adicet currently has programs for ADI-001 in lupus nephritis (LN), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and antineutrophil cytoplasmic autoantibody associated vasculitis (AAV). Clearance of investigational new drug applications have been obtained from the FDA for each of these indications.2 The company expects to begin clinical trial enrollment activities for SLE, SSc, and AAV before the end of 2024. Based on expectations for site initiation and patient enrollment, initial clinical results may be announced in the first half of next year.
In a United States Securities and Exchange Commission (SEC) filing from September 10, 2024, Adicet stated its intention to strategically shift its focus for the development of ADI-001 to autoimmune diseases, including the aforementioned indications.3 The company also stated its intent to explore additional autoimmune disease indications for ADI-001 in the near-term future. As a result of the strategic reprioritization, the company noted that it would be discontinuing enrollment activities for patients with mantle cell lymphoma (MCL) in GLEAN. Although, the company has separately stated that it did not view the results in MCL as disappointing, according to FirstWord Pharma.4
“Across all doses, 10 evaluable patients with MCL that were treated with ADI-001 demonstrated an overall response rate of 80%, a complete response rate of 60%, with a median duration of complete response of 17.5 months as of August 22, 2024,” the company pointed out in the SEC filing.3 “Patients were heavily pretreated with a median of 3 prior lines of therapy and 30% of patients had progressed on prior CAR-T.”
A phase 1 clinical trial (NCT06375993) for ADI-001 in LN is currently active, but not yet recruiting, according to its clinicaltrials.gov page, which was most recently updated on June 5, 2024. Notably, in June 2024, the FDA granted fast track designation to ADI-001 for treating relapsed/refractory class III or class IV LN.5
“We believe ADI-001 has best-in-class potential for autoimmune diseases and we are excited about the opportunity to expand ADI-001 clinical development beyond LN to include patients with SLE, SSc and AAV,” Chen Schor, the president and chief executive officer of Adicet Bio, said in an August 2024 statement.2 “We have initiated startup activities at multiple clinical sites and expect to begin enrolling patients with LN in our phase 1 study in the third quarter of 2024.”
REFERENCES
1. ADI-001 clinical biomarker data demonstrate robust tissue trafficking and complete B-cell depletion in secondary lymphoid tissue. News release. Adicet Bio, Inc. September 19, 2024. Accessed September 24, 2024. https://investor.adicetbio.com/news-releases/news-release-details/adi-001-clinical-biomarker-data-demonstrate-robust-tissue
2. Adicet reports second quarter 2024 financial results and provides business updates. News release. Adicet Bio, Inc. August 13, 2024. Accessed September 24, 2024. https://investor.adicetbio.com/news-releases/news-release-details/adicet-reports-second-quarter-2024-financial-results-and
3. United States Securities and Exchange Commission Form 8-K. Adicet Bio, Inc. September 10, 2024. Accessed September 24, 2024. https://investor.adicetbio.com/static-files/45f3f5de-47ac-41cb-b2c7-2a59784e9e4c
4. Adicet joins industry trend by redirecting cell therapy to autoimmune diseases. News article. Anna Bratulic, FirstWord Pharma. September 11, 2024. Accessed September 24, 2024. https://firstwordpharma.com/story/5894359
5. Adicet Bio Receives FDA Fast Track Designation for ADI-001 in Lupus Nephritis. News release. Adicet Bio, Inc. June 5, 2024. Accessed September 24, 2024. https://www.businesswire.com/news/home/20240605481965/en/Adicet-Bio-Receives-FDA-Fast-Track-Designation-for-ADI-001-in-Lupus-Nephritis
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