Adicet Bio Presents Clinical Biomarker Data for Off-the-Shelf CAR T Cell Therapy in an Oral Session at the American College of Rheumatology (ACR) Convergence 2024

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-Data demonstrate characteristics essential for treatment of autoimmune diseases, including robust tissue homing and complete CD19+ B cell depletion in secondary lymphoid tissue

-Results highlight the potential benefits unique to gamma delta 1 CAR T cell therapy and ADI-001’s potential as a best-in-class off-the-shelf cell therapy for autoimmune diseases

-The company is pursuing ADI-001 in a basket study across six indications including lupus nephritis (LN), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), idiopathic inflammatory myopathy (IIM), stiff person syndrome (SPS) and anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV)

REDWOOD CITY, Calif. & BOSTON–(BUSINESS WIRE)–Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic, gamma delta T cell therapies for autoimmune diseases and cancer, today announced that clinical biomarker data from the ADI-001 Phase 1 GLEAN trial which demonstrates robust tissue homing, significant CAR T cell activation, and complete CD19+ B cell depletion in secondary lymphoid tissue will be featured in an oral session at ACR Convergence 2024 in Washington, D.C., November 14-19.

“We believe the key to advancing care for autoimmune patients is to develop a therapeutic candidate that demonstrates robust tissue homing, complete CD19+ B cell depletion in tissue, and superior drug exposure in secondary lymphoid tissue with a positive safety profile. We are proud to share data and analyses, including clinical biomarker data, at ACR that support the potential of ADI-001 in autoimmune diseases,” said Francesco Galimi, M.D., Ph.D., Chief Medical Officer. “After activating clinical trial sites for LN and receiving investigational new drug application (IND) clearances to pursue additional autoimmune indications, we are committed to advancing ADI-001 in a basket study across six autoimmune indications. This strategy highlights our focus on addressing the significant unmet medical needs of patients who urgently require innovative and effective new treatment options.”

A summary of the results is reported below:

ADI-001 demonstrated significant levels of CAR T cell activation and tissue exposure in lymph node biopsies in the GLEAN trial, representing a range of 27-64% of total cellular material detected by ddPCR in evaluable biopsies at the 1E9 dose, and exceeding levels previously reported for patients who received autologous alpha-beta CAR T therapies. CAR T cells detected in tissues also demonstrated a robust activation profile, based on in situ levels of granzyme B.
- Recently published studies have demonstrated depletion of CD19+ plasmablasts, memory B cells and naïve B cells in peripheral blood using anti-CD20 targeted antibodies, however, these CD20-targeted antibody modalities failed to fully deplete B cells within secondary lymphoid tissue.
Concurrent with ADI-001 tissue trafficking and activation, complete depletion of CD19+ B cells within analyzed lymph node tissue was also observed. These results support ADI-001’s potential for achieving complete B-cell depletion in peripheral blood and within tissues.

Details of the oral presentation

Title: ADI-001: An Allogeneic CD20-targeted γδ CAR T Cell Therapy with Potential for Improved Tissue Homing in Autoimmune Indications

Session Name: Abstracts: Miscellaneous Rheumatic & Inflammatory Diseases II

Abstract Number: 1866169

Presenting Author: Monica Moreno, Ph.D.

Date and Time: November 19, 2024; 12:00 p.m. – 12:15 p.m. ET

About ADI-001 in Autoimmune Diseases

ADI-001 is an investigational allogeneic gamma delta CAR T cell therapy targeting B-cells via an anti-CD20 CAR. ADI-001 was granted Fast Track Designation by the FDA for the potential treatment of relapsed/refractory class III or class IV lupus nephritis (LN). Adicet is exploring the potential of ADI-001 in a basket study across six indications including lupus nephritis (LN), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), idiopathic inflammatory myopathy (IIM), stiff person syndrome (SPS) and anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV).

For more information about becoming a study site, please email clinicaltrials@adicetbio.com or visit https://www.adicetbio.com/hcp/autoimmune/.

About the Phase 1 Clinical Trial

The Phase 1 study has four separate arms, enrolling LN and SLE patients into one arm, SSc patients into a second arm, IIM and SPS patients in a third arm and AAV patients into a fourth arm. Enrolled patients will receive a single dose of ADI-001. The dose-limiting toxicity window is 28 days with response and safety assessments conducted on Day 28 and during the follow-up period on months 3, 6, 9, 12, 18 and 24. The primary objectives of the study are to evaluate the safety and tolerability of ADI-001. Secondary objectives include measuring cellular kinetics, pharmacodynamics, changes in autoantibody titers, and appropriate disease activity scores in each indication.

About Adicet Bio, Inc.

Adicet Bio, Inc. is a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer. Adicet is advancing a pipeline of “off-the-shelf” gamma delta T cells, engineered with chimeric antigen receptors (CARs), to facilitate durable activity in patients. For more information, please visit our website at https://www.adicetbio.com.

Forward-Looking Statements

This press release contains “forward-looking statements” of Adicet within the meaning of the Private Securities Litigation Reform Act of 1995 relating to the business and operations of Adicet. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements include, but are not limited to, express or implied statements regarding: the potential safety, tolerability and efficacy of ADI- 001 in multiple autoimmune indications; the potential for ADI-001 to be best-in-class allogenic cell therapy for autoimmune diseases; and the clinical development of ADI-001 in LN, SLE, SSc, IIM, SPS and AAV.

Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events, and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including without limitation, the effect of global economic conditions and public health emergencies on Adicet’s business and financial results, including with respect to disruptions to our preclinical and clinical studies, business operations, employee hiring and retention, and ability to raise additional capital; Adicet’s ability to execute on its strategy including obtaining the requisite regulatory approvals on the expected timeline, if at all; that positive results, including interim results, from a preclinical or clinical study may not necessarily be predictive of the results of future or ongoing studies; clinical studies may fail to demonstrate adequate safety and efficacy of Adicet’s product candidates, which would prevent, delay, or limit the scope of regulatory approval and commercialization; and regulatory approval processes of the U.S. Food and Drug Administration and comparable foreign regulatory authorities are lengthy, time-consuming, and inherently unpredictable; and Adicet’s ability to meet production and product release expectations. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Adicet’s actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in Adicet’s most recent annual report on Form 10-Q and subsequent filings with the U.S. Securities and Exchange Commission (SEC), as well as discussions of potential risks, uncertainties, and other important factors in Adicet’s other filings with the SEC. All information in this press release is as of the date of the release, and Adicet undertakes no duty to update this information unless required by law.

Contacts

Adicet Bio, Inc.
Investor and Media Contacts

Investors:
Anne Bowdidge

abowdidge@adicetbio.com

Janhavi Mohite

Precision AQ

212-362-1200

janhavi.mohite@precisionaq.com

Media:
Kerry Beth Daly

kbdaly@adicetbio.com

iCell Gene Therapeutics Announces Positive Clinical Data from Investigator Initiated Phase 1 Trial Evaluating BCMA-CD19 Compound CAR in Patients with Systemic Lupus Erythematosus/Lupus Nephritis Published in Annals of the Rheumatic Diseases

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– BCMA-CD19 compound CAR (cCAR) therapy was safe and well tolerated and achieved proof of concept of complete humoral reset delivering long-term medication-free remission –

– iCell’s BCMA-CD19 cCAR was the first CAR T evaluated in autoimmune disease with first SLE patient treated September 2019 –

– Based on successful IIT study, iCell plans to file INDs in U.S. and China –

STONY BROOK, N.Y.–(BUSINESS WIRE)–iCell Gene Therapeutics, a clinical stage biopharmaceutical company focused on immunotherapies for autoimmune disorders and cancer, today announced the publication in Annals of the Rheumatic Diseases of positive results of an investigator initiated clinical trial (IIT) for its BCMA-CD19 compound chimeric antigen receptor (cCAR) T cell immunotherapy.

The clinical trial evaluated the safety and efficacy of a complete humoral reset of both long-lived plasma cells and B cells in 13 systemic lupus erythematosus (SLE) patients treated with iCell’s cCAR, including 11 patients with SLE and lupus nephritis (LN). All patients (12/13) who received an initial dose of 3×10⁶ cCAR cells/kg were negative for all autoantibodies, including those derived from long-lived plasma cells, 3-months post-cCAR, and the complement returned to normal levels. These patients achieved symptom-free and medication-free remission (MFR), with post-cCAR follow-up to 46 months. cCAR therapy was well tolerated with mild cytokine-release syndrome (no CRS >1). iCell considers this IIT to be a successful proof of concept; the Company plans to file an investigational new drug application (IND) for its BCMA-CD19 cCAR in the United States and China.

iCell’s cCAR, with two independently functioning CARs in a single construct targeting the B cell CD19 and the plasma cell BCMA surface antigens, is uniquely designed to completely reset humoral immunity and address the underlying cause of SLE/LN through the elimination of all elevated autoantibodies including those produced by long-lived plasma cells.

Unique armoring of iCell’s cCAR allows for safe pretreatment conditioning with cyclophosphamide only (no fludarabine was used in LN patients), and patients in the study discontinued all lupus medications, including glucocorticoids and immunosuppressants, prior to cCAR treatment and remained lupus medication-free post-infusion. There are currently no approved therapies that deliver MFR in SLE/LN patients who are at high risk of long-term organ damage and kidney transplant.

“This study demonstrates that the complete reset of humoral immunity results in elimination of all elevated autoantibodies, that long term medication free remission is achievable, and that treatment with a BCMA-CD19 compound CAR is well-tolerated in patients suffering from lupus nephritis. The data show humoral immunity recovering, a low rate of infections, no CRS greater than 1, and no ICANS observed to date,” said Yupo Ma, M.D., Ph.D., Chief Scientific Officer and Founder of iCell. “iCell now has the largest clinical dataset of autoimmune patients receiving CAR therapy, and we are excited to continue the advancement of our BCMA-CD19 cCAR.”

“iCell first envisioned the potential for CAR treatments in autoimmune diseases more than 10 years ago and subsequently became the first to patent a BCMA-CD19 compound CAR. Nearly five years ago, we were the first company worldwide to treat an autoimmune patient with a CAR, and we are delighted to see that this patient continues to do well,” said Greg Deener, Chief Executive Officer of iCell. “We look forward to receiving further follow up data confirming the promising results to date, and we plan to present this data on June 12^th at the European Alliance of Associations for Rheumatology (EULAR) 2024 Congress.”

Study Details:

iCell designed its cCAR T Cell immunotherapy to express two distinct and fully functional CAR molecules in a single construct, one that targets the molecule CD19 present on B cells and one that targets BCMA present on plasma cells. Targeting both B cells and long-lived plasma cells is needed to eliminate all elevated autoantibodies, given they have separate and redundant memory. iCell’s cCAR is armored to safely promote T cell survival and function and to allow for cyclophosphamide-only conditioning.

The single arm IIT evaluating iCell’s BCMA-CD19 cCAR was conducted in two leading centers in China, Zhongshan People’s Hospital and Peking University Shenzhen Hospital. Initially two patients with SLE and comorbid localized lymphoma were treated with the BCMA-CD19 cCAR (the first in September 2019); 11 patients with LN with biopsy-confirmed active disease (Class III-V) and inadequate response to at least two lines of therapies were subsequently enrolled into the study and treated between June 2022 and February 2023. Ten LN patients received the target single cCAR dose of 3×10⁶/kg.

Overall, the cCAR therapy was found to be generally safe and well-tolerated. The 10 LN patients receiving the target dose achieved depletion of B cells from peripheral blood within 10 days post-cCAR treatment and depletion of immunoglobulin within 42 days, and complete recovery of B cells and IgM was seen within 2-6 months post-cCAR. Excluding COVID-19, the only infection reported was a grade 1 urinary tract infection. In iCell’s overall cCAR safety database of 18 patients with autoimmune diseases (including the 13 patients with SLE or LN), there have been no CRS >1 and no ICANS or CRES.

All lupus patients (12/13) who received the target dose were negative for all autoantibodies, including those derived from long-lived plasma cells, 3-months post-cCAR, and the complement returned to normal levels. Patients achieved symptom-free and medication-free remission (MFR), with post-cCAR follow-up to 46-months. Mean Systemic Lupus Erythematosus SLE Disease Activity Index 2000 (SLEDAI-2K) reduced from 9.9 (baseline) to 2.3 (3 months), and mean renal function significantly improved in the 10 LN patients ≤90 days post-cCAR. The data suggest that cCAR therapy was safe and effective in inducing MFR and depleting disease-causing autoantibodies in SLE and LN patients.

About SLE/LN

Systemic lupus erythematosus is an antibody-mediated autoimmune disease, in which autoantibodies attack the body’s own tissues, resulting in widespread damage in affected organs including kidneys, lungs, joints, brain and blood vessels. According to the Lupus Foundation of America, an estimated 1.5 million Americans, and at least five million people worldwide, have SLE/LN. Lupus nephritis affects ~40% of SLE patients and disproportionately burdens nonwhite women from lower socioeconomic groups. LN patients have a 6-fold higher risk of mortality with 1 in 4 progressing to end stage renal disease There are currently no treatments targeting the underlying causes of the disease delivering MFR. Standard of care LN treatments have substantial side effects. Prolonged immunosuppression increases the risk of serious infections and cancers. Glucocorticoid associated adverse effects include osteoporotic fractures, avascular necrosis, diabetes mellitus, cataracts, glaucoma, and premature mortality.

About iCell Gene Therapeutics

iCell Gene Therapeutics is a clinical-stage biopharmaceutical company developing chimeric antigen receptor (CAR) immunotherapies designed to be innovative, first-in-class and lifesaving. iCell is focused on developing treatments for diseases where no treatment options exist and where dramatic improvements in quality and duration of life are needed, including autoimmune disorders, AML, and T-cell malignancies. The company is currently conducting clinical trials in the U.S. and China utilizing its CARvac, T-cell targeted CARs, compound CARs and non-gene edited universal CARs engineered as treatments for autoimmune diseases, cancer, and organ rejections. For more information, please visit http://icellgene.com/

Contacts

Investor Contact:

Greg Deener, CEO

greg.deener@icellgene.com

Media Contact:

Argot Partners

icellgene@argotpartners.com