ADP-600

The Phase I/II clinical trial will investigate the T cell therapy in patients with haematological malignancies. Credit: Yomal2233 via Shutterstock. Genome writing company Replay Bio has had its investigational new drug (IND) application cleared by the US Food and Drug Administration (FDA) to initiate a clinical trial of its T cell therapy for haematological malignancies. PRAME TCR/IL-15 NK (SY-307) is an engineered T cell receptor natural killer (TCR-NK) cell therapy, targeting preferentially expressed antigens in melanoma (PRAME). The candidate is being developed by Syena, a company launched by Replay and MD Anderson. Syena is working alongside the University of Texas MD Anderson Cancer Center to fund the Phase I/II clinical trial in patients with relapsed/refractory acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). In the study, 44 patients will be administered the TCR therapy following lymphodepletion. This is a process that uses chemotherapy to reduce or deplete lymphocytes. Standard doses of fludarabine/cyclophosphamide (Flu/Cy) and decitabine chemotherapies will be used for lymphodepletion in this trial, which is anticipated to begin in Q3 2024. The PRAME-directed cell therapy is Syena’s second programme to enter the clinic following NY-ESO-1 TCR/IL-15 NK, a first-in-class cell therapy for relapsed or refractory multiple myeloma. The candidate is currently being investigated in a Phase I/II study (NCT06066359), which started in November. An additional study in patients with synovial sarcoma and myxoid/round cell liposarcoma that tests the same therapy is expected to begin, following IND clearance from the FDA in June 2023. See Also: Xyphos and Poseida to develop allogeneic cell therapies for cancer Pfizer and Genmab’s Tivdak wins full FDA approval for cervical cancer Since then, Syena has also entered a research collaboration with JURA Bio for the development of TCR-based therapies. PRAME is a highly immunogenic antigen that is expressed on lots of different cancer cell types, making it an attractive target for cell therapy-mediated cancer immunotherapy. In February 2024, Immunocore and BMS teamed up to investigate the PRAME-targeting candidate IMC-F106C as a first-line treatment for melanoma. At the same time, other projects involving PRAME-directed therapies have been in development for a while. After a nine-year cell therapy-related collaboration between GSK and Adaptimmune , GSK returned the rights to its preclinical PRAME-targeted programme to Adaptimmune last year, which received £30m ($37.5m) in the process. Despite this, Adaptimmune announced plans to advance the therapy, ADP-600, into clinic this year following positive preclinical safety and potency data. Replay launched into the cell therapy scene with $55m in seed financing in July 2022, backed by global investment company KKR and fund OMX Ventures. Artis Ventures, Lansdowne Partners, SALT, DeciBio Ventures, and Axial also participated in that round. In the announcement accompanying the IND clearance, professor of stem cell transplantation and cellular therapy at MD Anderson Katy Rezvani said: “This is an exciting milestone in the development of ‘off-the-shelf’ engineered TCR-NK cell therapies to address significant unmet medical needs. “Our hope is the PRAME studies, initially in haematological malignancies and then in solid tumours, will further advance our understanding of the potential for engineered TCR-modified NK cells to benefit patients with relapsed/refractory myeloid malignancies.”

Candidate is 10x more sensitive to target peptide than competitor candidates Entry into the clinic in 2024 Selection of approaches from next-gen toolbox in development Philadelphia, Pennsylvania and Oxford, United Kingdom--(News - November 8, 2023) - Adaptimmune Therapeutics plc (NASDAQ: ADAP), a leader in cell therapy to treat cancer, provides a progress update on its PRAME program (ADP-600). Jo Brewer Adaptimmune Chief Scientific Officer: "We have taken everything we know about design and development of TCRs to make a potent engineered TCR targeting PRAME with 10-fold greater peptide sensitivity than other competitor candidates. ADP-600 exhibits excellent potency and safety in preclinical assessments, and we plan to move this TCR into the clinic in 2024. We anticipate that combining this TCR with our next-gen approaches will create a best-in-class product." The PRAME antigen is highly expressed in many tumor types including endometrial carcinoma, ovarian carcinoma, melanoma, and synovial sarcoma and is validated as a target by other clinical candidates. Adaptimmune's PRAME program presents a considerable opportunity to bring a best-in-class engineered TCR T-cell therapy to a wide range of people with solid tumor cancers. The first-generation clinical candidate, designated ADP-600, was identified through Adaptimmune's proprietary preclinical testing program to investigate the safety, specificity and potency of T-cells expressing engineered T-cell receptors (TCRs). This will support an IND submission to progress the Company's PRAME program to an initial Phase 1 clinical trial to evaluate the safety of ADP-600 in multiple tumor types. ADP-600 TCR demonstrates 10-fold greater peptide sensitivity than competitor clinical candidates. TCR sensitivity to its target is a key driver of TCR signaling and ability to respond to 10-fold lower target concentration indicates that T-cells expressing ADP-600 have the potential to be more effective in vivo. T-cells expressing ADP-600 proliferate robustly in the presence of PRAME positive target cell lines and demonstrate cytotoxicity in in-vitro assays towards PRAME positive tumor cell lines, patient derived xenograft and primary tumor tissue. The Company is evaluating multiple next-gen approaches using the same TCR. The next-gen approaches are intended to improve persistence and T-cell effectiveness (e.g., CD8α and membrane-bound IL-15) or help overcome the tumor microenvironment (e.g., PD-1 Switch technology). The PRAME program will benefit from the application of Adaptimmune's established vector and cell manufacturing facilities and clinical footprint. This program complements the Company's existing validated clinical programs with MAGE-A4 and more information will be available on the program in 2024. About Adaptimmune Adaptimmune is a clinical-stage biopharmaceutical company focused on designing, developing, and delivering cell therapies to transform the lives of people with cancer. The Company's unique engineered T-cell receptor (TCR) platform enables the engineering of T-cells to target and destroy cancers across multiple solid tumor types. Forward-Looking Statements This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 (PSLRA). These forward-looking statements involve certain risks and uncertainties. Such risks and uncertainties could cause our actual results to differ materially from those indicated by such forward-looking statements, and include, without limitation: the success, cost and timing of our product development activities and clinical trials and our ability to successfully advance our TCR therapeutic candidates through the regulatory and commercialization processes. For a further description of the risks and uncertainties that could cause our actual results to differ materially from those expressed in these forward-looking statements, as well as risks relating to our business in general, we refer you to our Annual Report on Form 10-K filed with the Securities and Exchange Commission for the year ended December 31, 2022, our Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and other filings with the Securities and Exchange Commission. The forward-looking statements contained in this press release speak only as of the date the statements were made and we do not undertake any obligation to update such forward-looking statements to reflect subsequent events or circumstances. Adaptimmune Contact Investor Relations Juli P. Miller, Ph.D. - VP, Corporate Affairs and Investor Relations T : +1 215 825 9310 M : +1 215 460 8920 Juli.Miller@adaptimmune.com Media Relations Dana Lynch, Senior Director of Corporate Communications M: +1 267 990 1217 Dana.Lynch@adaptimmune.com To view the source version of this press release, please visit