ADI-001 Receives FDA Fast Track Designation to Treat Systemic Sclerosis

The FDA has granted a fast track designation (FTD) to ADI-001 (Adicet Bio), a genetically engineered T-cell therapy for the potential treatment of adult patients with systemic sclerosis (SSc).¹

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SSc, also known as scleroderma, is a chronic autoimmune disease that involves the hardening and tightening of the skin and internal organs. The disease occurs when the body produces too much collagen, causing it to build up in the body tissues. While the exact cause of SSc is unknown, experts believe it is most likely caused by immune system problems, genetics, and environmental triggers—including exposure to certain viruses, medicines, or drugs.²

Early symptoms of SSc usually include swelling and itchiness; however, signs can vary depending on which part of the body is impacted.¹

The first indication of skin-related symptoms includes skin thickening in the fingers, hands, feet, and face. Although, in some cases, the forearms, upper arms, chest, abdomen, lower legs, and thighs can also be affected. Small red bumps, known as telangiectasia, can also form on individuals’ hands and faces. Raynaud’s phenomenon is also common in SSc, stemming from a substantial contraction of the small blood vessels in the fingers and toes in response to cold temperatures or emotional distress. Additionally, SSc can affect any part of the digestive system, causing symptoms of heartburn, difficulty swallowing, bloating, diarrhea, constipation, and fecal incontinence. Other heart and lung-related symptoms include shortness of breath, decreased exercise tolerance, and dizziness.²

There is currently no cure for SSc, but treatments can decrease progression, ease symptoms, and improve the quality of life among individuals impacted.^1,2

As an investigational allogeneic gamma delta chimeric antigen receptor (CAR) T cell therapy, ADI-101 targets CD20 for the treatment of autoimmune diseases and is advancing across 6 autoimmune indications. The FTD for ADI-001 was granted for the treatment of relapsed/refractory class 3 or class 4 lupus nephritis (LN), systemic lupus erythematosus (SLE) with extrarenal involvement and systemic sclerosis (SSc). Various clinical trials assessing ADI-001’s autoimmune indications are ongoing.¹

Patient enrollment for a phase 1 study evaluating ADI-001 treatment for LN is ongoing, as patient enrollment for SLE, SSc, idiopathic inflammatory myopathy (IIM, or myositis), and stiff person syndrome (SPS) is expected to begin in the second quarter of 2025. Additionally, results from an open-label, multi-center phase 1 GLEAN trial highlighted ADI-001’s potential as a best-in-class allogeneic cell therapy for autoimmune disease.^1,3

In the GLEAN trial, ADI-001 achieved significant CAR T-cell activation and tissue exposure in lymph node biopsies. With a mean exposure of 236,701 CAR T-cells per million across all dose levels, ADI-001 reached 27% to 64% of total cellular material at the 1E9 dose, exceeding levels seen in prior autologous alpha-beta CAR T therapies. Furthermore, the detected CAR T-cells displayed a robust activation profile, as evidenced by in situ granzyme B detection.³

“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, chief scientific officer of Adicet Bio, said in a news release. “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.”³

REFERENCES

1. Adicet Bio Receives FDA Fast Track Designation for ADI-001 for the Treatment of Systemic Sclerosis (SSc). Adicet Bio. News release. Published February 27, 2025. Accessed March 3, 2025. https://investor.adicetbio.com/news-releases/news-release-details/adicet-bio-receives-fda-fast-track-designation-adi-001-0

2. Scleroderma. Mayo Clinic. News release. Published June 15, 2024. Accessed March 3, 2025. https://www.mayoclinic.org/diseases-conditions/scleroderma/symptoms-causes/syc-20351952

3. ADI-001 Clinical Biomarker Data Demonstrate Robust Tissue Trafficking and Complete B Cell Depletion in Secondary Lymphoid Tissue. Adicet Bio. News release. Published September 19, 2024. Accessed March 3, 2025. https://investor.adicetbio.com/news-releases/news-release-details/adi-001-clinical-biomarker-data-demonstrate-robust-tissue