On November 8, 2023 Adaptimmune Therapeutics plc (NASDAQ: ADAP), a leader in cell therapy to treat cancer, reported a progress update on its PRAME program (ADP-600) (Press release, Adaptimmune, NOV 8, 2023, View Source [SID1234637286]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
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.