Adicet Bio, Inc. (NASDAQ:ACET) is a clinical-stage biotechnology company that is pioneering the development of allogeneic gamma delta T cell therapies for the treatment of autoimmune diseases and cancer. The company's lead product candidate, ADI-001, is currently in a Phase 1 clinical trial for the treatment of relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma (NHL), and the company recently received FDA clearance to initiate a Phase 1 trial of ADI-001 in lupus nephritis (LN).

Adicet's Gamma Delta T Cell Platform: A Unique Approach

Adicet's approach to activating, engineering, and manufacturing allogeneic gamma delta T cell product candidates derived from the peripheral blood cells of unrelated donors allows the company to generate new product candidates in a rapid and cost-efficient manner. This "off-the-shelf" manufacturing process is designed to allow product from unrelated donors to be stored and sold on demand to treat patients without inducing a graft versus host immune response.

In contrast to therapies based on alpha beta T cells, Adicet's gamma delta T cell approach may lessen the likelihood of graft versus host disease. Additionally, gamma delta T cells exhibit both innate and adaptive immune properties, allowing them to specifically target cancer and infected cells regardless of MHC presentation.

ADI-001: Promising Results in Relapsed/Refractory NHL

Adicet's lead product candidate, ADI-001, is a first-in-class allogeneic gamma delta T cell therapy expressing a CAR targeting CD20. In the ongoing Phase 1 GLEAN trial, ADI-001 has demonstrated promising results in patients with relapsed or refractory aggressive B-cell NHL.

As of the May 4, 2023 cutoff date, of the 24 evaluable subjects in the GLEAN trial, 18 had large B-cell lymphoma (LBCL), five had mantle cell lymphoma (MCL), and one patient had follicular lymphoma. Most patients were heavily pre-treated, with a median four lines of prior therapy, and 12 patients (50%) had previously progressed following CAR T cell therapy.

Despite the advanced nature of patients at baseline, Adicet observed a high complete response (CR) rate and favorable durability in MCL patients. Across all doses of MCL patients, the company observed an 80% (4/5 patients) overall response rate (ORR), an 80% CR rate (4/5 patients) and a 60% CR rate (3/5 patients) at six months. As of May 4, 2023, the safety profile of ADI-001 was generally favorable, with no significant risk of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or T cell malignancy observed.

Expansion into Autoimmune Indications: ADI-001 in Lupus Nephritis

In December 2023, the FDA cleared Adicet's IND application for ADI-001 in lupus nephritis. Lupus nephritis is a serious complication of systemic lupus erythematosus (SLE) which affects approximately 40% of the estimated 322,000 patients with SLE in the U.S. Adicet expects to initiate a Phase 1 clinical trial of ADI-001 for the treatment of lupus nephritis in the second quarter of 2024 and expand development efforts into one to two additional autoimmune indications in the second and third quarters of 2024, subject to clearance of INDs in those indications.

ADI-270: Targeting CD70+ Solid Tumors

Adicet's pipeline also includes ADI-270, an investigational allogeneic gamma delta CAR T cell therapy targeting CD70 for the treatment of renal cell carcinoma (RCC) and other CD70+ solid tumor indications. ADI-270 is designed to home to solid tumors, with a highly specific targeting moiety for CD70 and an armoring technology to address immunosuppressive factors in the tumor microenvironment. Adicet plans to file an IND application for ADI-270 in RCC in the second quarter of 2024 and provide clinical data in the first half of 2025, subject to regulatory clearance and study initiation activities.

Financials

Adicet reported a net loss of $28.0 million for the first quarter of 2023, compared to a net loss of $30.9 million in the same period of the prior year. The company's operating expenses for the quarter were $30.9 million, down from $33.3 million in the prior year period. As of March 31, 2023, Adicet had $247.6 million in cash and cash equivalents, which the company believes will be sufficient to fund its operations into the second half of 2026.

In January 2023, Adicet raised approximately $91.7 million in net proceeds from an underwritten public offering of common stock and pre-funded warrants. Additionally, the company sold $19.3 million in shares through its at-the-market (ATM) offering program in the first quarter of 2023. Adicet has no outstanding debt and remains well-capitalized to advance its pipeline of gamma delta T cell therapies.

For the full year 2022, Adicet reported a net loss of $142.7 million and had no revenue. The company's annual operating cash flow was negative $93.7 million, and its annual free cash flow was negative $98.2 million.

Risks and Challenges

As a clinical-stage biotechnology company, Adicet faces several risks and challenges common to the industry, including the inherent uncertainty of clinical development, the potential for regulatory delays or setbacks, and the need to continuously raise capital to fund its operations.

The success of Adicet's lead product candidate, ADI-001, will be critical to the company's future. While the early data in relapsed/refractory NHL are promising, there is no guarantee that the positive results will be replicated in larger, later-stage trials. Additionally, the company's expansion into autoimmune indications with ADI-001 and its development of ADI-270 for solid tumors will require successful execution of their clinical programs.

Adicet also relies on its proprietary gamma delta T cell platform, and any setbacks in the company's ability to manufacture or scale this technology could have a significant impact on its pipeline. Furthermore, the competitive landscape in the cell therapy space is rapidly evolving, and Adicet will need to continue to innovate and differentiate its approach to maintain a competitive edge.

Outlook

Despite the risks, Adicet's pipeline of gamma delta T cell therapies for autoimmune diseases and cancer represents a compelling investment opportunity. The company's strong cash position, coupled with several upcoming clinical milestones, position Adicet well to execute on its strategic priorities.

In the near-term, investors will be closely watching for updates from the ongoing Phase 1 GLEAN trial of ADI-001 in NHL, including the six-month complete response rate in MCL patients and the safety profile of the therapy. Additionally, the initiation of the Phase 1 trial of ADI-001 in lupus nephritis and the filing of the IND for ADI-270 in RCC will be important catalysts to monitor.

Longer-term, Adicet's ability to expand its pipeline of gamma delta T cell therapies and demonstrate the versatility of its platform across multiple disease indications will be key to the company's success. The potential market opportunity for Adicet's therapies in autoimmune diseases and cancer is substantial, and the company's innovative approach could position it as a leader in the rapidly evolving cell therapy landscape.

Conclusion

In conclusion, Adicet Bio is a promising biotechnology company with a unique gamma delta T cell therapy platform and a pipeline of product candidates addressing significant unmet needs in autoimmune diseases and cancer. While the company faces the typical risks associated with clinical-stage biotechnology companies, Adicet's strong financial position, upcoming catalysts, and innovative approach make it a compelling investment opportunity for those willing to take on the inherent risks of the sector.