8-K: Adicet Bio Presents Promising Preclinical Data for ADI-270, a Novel CAR T-Cell Therapy

Adicet Bio's ADI-270, an armored allogeneic anti-CD70 CAR T-cell therapy, shows strong preclinical results for multiple solid and hematological cancers.

Summary

• Adicet Bio presented preclinical data for ADI-270, a novel CAR T-cell therapy, at the 27th Annual Meeting of the American Society of Gene and Cell Therapy.
• ADI-270 is designed to target CD70, a protein highly expressed in various solid and hematological cancers, while minimizing expression on normal tissues.
• The therapy utilizes a CD27 binding domain and includes CD27 and 4-1BB costimulatory domains, plus CD3, making it a 3rd generation CAR T-cell.
• ADI-270 incorporates an inactive form of the TGF receptor II to counteract the immunosuppressive effects of TGF in the tumor microenvironment.
• It also features host vs graft armoring to increase persistence by protecting against alloreactive activated CD70+ T cells.
• Preclinical studies demonstrated that ADI-270 is highly enriched for Vd1 T cells and is resilient to the inhibitory effects of TGF.
• ADI-270 showed potent in vitro cytotoxicity against a range of CD70 levels in diverse solid and heme malignancies.
• The therapy exhibited higher innate cytolytic activity against CD70 negative tumor cells compared to CAR-T cell references.
• ADI-270 was associated with a lower potential for macrophage activation syndrome and cytokine release syndrome (CRS) compared to CAR T-cell benchmarks.
• In ccRCC xenograft models, a single dose of ADI-270 showed potent regression and sustained systemic anti-tumor activity.
• The therapy demonstrated rapid homing, activation, and killing kinetics, leading to tumor and target eradication.
• ADI-270's anti-tumor activity extended to multiple hematologic tumor xenografts with lower CD70 expression.

Sentiment

Score: 8

Explanation: The document presents very positive preclinical data for a novel cancer therapy, with strong efficacy and safety profiles compared to benchmarks. The expectation of an IND submission in Q2 2024 is also a positive sign.

Positives

• ADI-270 targets CD70, which is highly expressed in multiple cancers but has limited expression on normal tissues.
• The therapy's design includes features to enhance persistence and overcome immunosuppression.
• ADI-270 showed strong in vitro and in vivo efficacy against various cancer types.
• The therapy demonstrated a lower potential for severe side effects like macrophage activation syndrome and CRS compared to other CAR T-cell therapies.
• ADI-270 exhibited rapid tumor eradication and sustained anti-tumor activity in preclinical models.

Risks

• The data presented is preclinical, and clinical trials are needed to confirm the safety and efficacy of ADI-270 in humans.
• The therapy's effectiveness in patients with varying levels of CD70 expression needs to be further evaluated.
• Potential for off-target effects and other toxicities, although preclinical data suggests a lower risk, cannot be completely ruled out.

Future Outlook

Adicet Bio expects to submit an IND application for ADI-270 in ccRCC in Q2 2024.

Industry Context

The development of ADI-270 aligns with the growing interest in CAR T-cell therapies for cancer treatment, particularly in addressing solid tumors and overcoming challenges such as immunosuppression and off-target effects. The focus on allogeneic therapies also addresses the limitations of autologous CAR T-cell therapies.

Comparison to Industry Standards

• ADI-270 is compared to clinically relevant CD70-targeting CAR T-cell benchmarks, showing superior performance in several areas.
• The therapy demonstrated higher innate cytolytic activity against CD70 negative tumor cells compared to CAR-T cell references.
• ADI-270 showed a lower potential for macrophage activation syndrome and CRS compared to CAR T-cell benchmarks.
• The presentation references several publications (Shaffer et al., Blood 2011; Acharya et al., Blood 2023; Leick et al., Cancer Cell 2022; Kasap et al., BioRxiv 2024) which are likely to be industry benchmarks for CAR T-cell development.

Stakeholder Impact

• Positive results could lead to increased shareholder value.
• Successful development of ADI-270 could provide a new treatment option for cancer patients.
• The company's employees may benefit from the success of the therapy.

Next Steps

• Adicet Bio plans to submit an IND application for ADI-270 in ccRCC in Q2 2024.

Key Dates

Keywords

CAR T-cell therapy, ADI-270, CD70, cancer, immunotherapy, allogeneic, preclinical, hematological malignancies, solid tumors, TGF, cytotoxicity, xenograft, ccRCC, Vd1 T cells