Adicet Bio Announces Positive Interim Clinical Data From First-Ever Allogeneic, Off-The-Shelf, Gamma Delta CAR T Investigational Cell Therapy

Rhea-AI Summary

Adicet Bio announced promising interim results from its Phase 1 study of ADI-001, a gamma delta CAR T cell therapy targeting B-cell Non-Hodgkin's Lymphoma. As of November 22, 2021, six patients received ADI-001, with an overall response rate (ORR) of 75% and a complete response (CR) rate of 50%. Notably, no serious adverse events were reported. The findings support the therapy's safety and potential effectiveness, highlighting its ability to offer an off-the-shelf treatment option. Further data is anticipated in the first half of 2022, showcasing the ongoing progress of Adicet's innovative platform.

Positive

• Overall response rate (ORR) of 75% and complete response (CR) rate of 50% observed in evaluable patients.
• No serious adverse events related to ADI-001 reported, indicating a favorable safety profile.
• Promising interim data suggests high clinical activity, especially in heavily pre-treated patients.

Negative

• None.

• Complete and near complete responses observed with ADI-001 starting at lowest dose level in Phase 1 study for the treatment of B-cell Non-Hodgkin’s Lymphoma (ORR=75%, CR=50%)
• No ADI-001-related serious adverse events, including GvHD, neurotoxicity or high-grade CRS have been reported to date
• Evidence of in vivo expansion and circulating pharmacodynamic biomarkers consistent with ADI-001 activation
• Favorable safety and clinical activity reinforces the potential of Adicet’s first-in-class allogeneic, off-the-shelf gamma delta CAR T cell platform
• Company to hold webcast today at 5:30am PT / 8:30am ET

MENLO PARK, Calif. and BOSTON, Dec. 06, 2021 (GLOBE NEWSWIRE) -- Adicet Bio, Inc. (Nasdaq: ACET), a biotechnology company discovering and developing first-in-class allogeneic gamma delta CAR T cell therapies for cancer and other diseases, today announced positive interim data from its dose escalation Phase 1 study evaluating the safety and tolerability of ADI-001, Adicet’s investigational therapy targeting CD20 for the potential treatment of B-cell Non-Hodgkin’s Lymphoma. 

As of the November 22, 2021 data cutoff, six patients had been enrolled and received ADI-001. The first two patients enrolled in the lowest dose level tested did not reach the day 28 assessment and were not evaluable for efficacy per protocol. Three of the four evaluable patients achieved responses, including two complete responses (CR) and one partial response (PR) that investigators characterized as near complete response. Patients were heavily pre-treated, with a median of five lines of prior systemic therapy, including a patient who had received prior autologous CD19 CAR T,​ and achieved complete response following a single infusion of ADI-001 administered at the lowest dose level.

“We are extremely excited to see such profound early complete responses in our Phase 1 dose-finding study evaluating ADI-001 as monotherapy among patients with very advanced cancer starting at our first dose level of 30 million CAR+ cells," said Chen Schor, President and Chief Executive Officer of Adicet Bio. "Data to-date suggest that ADI-001 is highly clinically active. We look forward to reporting additional data in the first half of 2022 and to rapidly progressing our pipeline to realize the full potential of our gamma delta CAR T cell platform for patients.”

“The unequivocal responses to ADI-001 in this heavily pre-treated patient population at such low dose levels are highly promising," said Sattva Neelapu M.D., Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. “These data suggest that ADI-001 has the potential to be an effective treatment option for B cell malignancies if confirmed in further clinical testing. ADI-001 does not require gene editing and provides complementary innate, adaptive, and CAR mediated antitumor effects which may improve durability and minimize emergence of tumor resistance.”

Of the four efficacy evaluable patients, three received ADI-001 at dose level one (30 million CAR+ cells) and one received ADI-001 at dose level two (100 million CAR+ cells). In dose level one, one patient achieved a CR, one patient achieved a PR that was characterized as near CR and one patient had progressive disease (PD). In dose level two, the first patient achieved a CR.

All evaluable patients had been heavily pre-treated with a median of five lines of prior systemic therapies. Of the three patients who achieved PR or better under Lugano 2014 criteria (ORR=75%, CR=50%), one had diffuse large B-cell lymphoma (DLBCL) with five prior lines of therapy including two cycles of anti-CD19 CAR T cell therapy, one had follicular lymphoma transformed into a large B-cell tumor with four prior lines of therapy, and the third had mantle cell lymphoma with five prior lines of therapy. These patients achieved two CRs and a near CR.

Overall, ADI-001 infusions were generally well-tolerated. No dose-limiting toxicities, graft vs host disease (GvHD), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) or grade 3 or higher Cytokine Release Syndrome (CRS) have been reported to-date, suggesting a potentially wide therapeutic window for ADI-001.

A significant increase in circulating IL-15 was observed during the 28-day window following lymphodepletion, potentially providing cytokine support for the proliferation of ADI-001​. Emergence of circulating ADI-001 in the blood was observed by quantitative polymerase chain reaction and by flow cytometry, demonstrating expansion of ADI-001 in patients​. Elevations in additional circulating cytokines, primarily IL-2 and IL-8 were observed during the first 14 days from dosing, consistent with the activation profile of ADI-001 and similar to the observed time-to-peak for cytokines previously reported in association with autologous alpha-beta CAR T cells. Importantly, no meaningful increases in IL-6 were seen in association with ADI-001, except for one patient who experienced COVID-19 infection, suggesting reduced likelihood for ICANS and high-grade CRS.

“It is remarkable to see our early preclinical studies translate to the clinic. The preliminary safety and efficacy data from low-dose ADI-001 collected to date indicate the potential for a broad therapeutic window. Without the need for gene editing and its associated safety concerns, our platform is designed to preserve the natural innate and adaptive anti-tumor activity of gamma delta CAR T cells, which we believe may lead to better durability,” said Francesco Galimi, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Adicet Bio. "As we look to expand into additional cohorts, we plan to leverage our scalable off-the-shelf manufacturing process to meet future needs. We look forward to advancing our novel allogeneic gamma delta T cell pipeline for cancer patients.”

Table 1: Summary of ADI-001 interim data from two dosing cohorts*:

Dose Level	Age/Sex	B-cell lymphoma subtypes	# Prior lines of therapies	Prior CAR T?	Best Response (BOR) by Lugano Criteria (2014)
30 million CAR+ cells	62/F	Transformed DLBCL​ (from chronic lymphocytic leukemia)	5 prior lines	No	PD
	66/F	Transformed high grade​ B cell tumor (from follicular lymphoma)	4 prior lines	No	PR (Near CR)
	75M	DLBCL	5 prior lines	Yes (liso-cel)	CR
100 million CAR+ cells	62/M	Mantle cell lymphoma	5 prior lines	No	CR

*Efficacy evaluable patients as of November 22, 2021 database entry. Data are subject to further review and verification.

Webcast/Conference Call Information 
Adicet will host a live presentation on Monday, December 6 at 8:30am EST to discuss the results. Dr. Sattva Neelapu from the University of Texas MD Anderson Cancer Center will participate in the event.

The live webcast of the presentation can be accessed under “Presentations & Events” in the investors section of the Company’s website at www.adicetbio.com or by dialing (877) 800-3802 (domestic) or (615) 622-8057 (international) and reference the conference ID 6952318. The archived webcast will be available on the Company's website beginning approximately two hours after the event.

About ADI-001
ADI-001 is an investigational allogeneic gamma delta CAR T cell therapy being developed as a treatment for B-cell non-Hodgkin's lymphoma. ADI-001 targets malignant B-cells via an anti-CD20 CAR and via the gamma delta innate and T cell endogenous cytotoxicity receptors. Gamma delta T cells engineered with an anti-CD20 CAR have demonstrated potent antitumor activity in preclinical models, leading to long-term control of tumor growth.

About the GLEAN Study 
This Phase I study is an open-label, multi-center study of ADI-001 enrolling adults diagnosed with B cell malignancies who have either relapsed, or are refractory to at least two prior regimens. The primary objectives of the study are to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ADI-001, and to determine optimal dosing as a monotherapy. The study is expected to enroll approximately 75 patients. For more information about the clinical study design, please visit: www.clinicaltrials.gov (NCT04735471).

About Adicet Bio, Inc. 
Adicet Bio, Inc. is a biotechnology company discovering and developing allogeneic gamma delta T cell therapies for cancer and other diseases. Adicet is advancing a pipeline of “off-the-shelf” gamma delta T cells, engineered with chimeric antigen receptors and T cell receptor-like targeting moieties to enhance selective tumor targeting, facilitate innate and adaptive anti-tumor immune response, and improve persistence for durable activity in patients. For more information, please visit our website at http://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 business and operations of Adicet. These forward-looking statements include, but are not limited to, express or implied statements regarding Adicet’s beliefs and expectations regarding: the interim clinical data resulting from its Phase 1 study of ADI-001, including the expected potential therapeutic effects, safety and tolerability profile, design, implementation, timing, and success of ADI-001; and expectations regarding the potential of its other CAR gamma delta T cell therapy development activities.

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 COVID-19 on our business and financial results, including with respect to disruptions to our clinical trials, business operations, and ability to raise additional capital; Adicet's ability to execute on its strategy; that positive results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; future clinical studies may fail to demonstrate adequate safety and efficacy of our product candidates, which would prevent, delay, or limit the scope of regulatory approval and commercialization; regulatory approval processes of the FDA and comparable foreign regulatory authorities are lengthy, time–consuming, and inherently unpredictable; regulatory developments in the United States and foreign countries; and the company's estimates regarding expenses, future revenue, and capital requirements. 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-K and our periodic reports on Form 10-Q and Form 8-K filed with the 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.

Adicet Bio, Inc.
Investor and Media Contacts
Anne Bowdidge
abowdidge@adicetbio.com

Janhavi Mohite
Stern Investor Relations, Inc.
212-362-1200
janhavi.mohite@sternir.com

Photos accompanying this announcement are available at

https://www.adicetbio.com/images/adicet-1

https://www.adicetbio.com/images/adicet-2

https://www.adicetbio.com/images/adicet-3

FAQ

What are the results of the Phase 1 study for ACET?

The interim results show an overall response rate of 75% and a complete response rate of 50% among evaluable patients treated with ADI-001.

How safe is ADI-001 based on the latest data for ACET?

ADI-001 demonstrated a favorable safety profile, with no reported serious adverse events, including graft vs host disease or high-grade cytokine release syndrome.

What is the next step for ADI-001 for ACET investors?

Adicet plans to report additional data in the first half of 2022, focusing on further development of the ADI-001 therapy.

What is ADI-001 and its target population for ACET?

ADI-001 is an investigational gamma delta CAR T cell therapy targeting B-cell Non-Hodgkin's Lymphoma, developed for patients who are relapsed or refractory to prior treatments.