Leading CAR T Development in Solid Tumors The past year we’ve continued to advance our lead allogeneic program CYAD-101 for the treatment of metastatic colorectal cancer (mCRC), a devastating disease and historically, a difficult indication for immunotherapies. Colorectal cancer is the third most diagnosed cancer worldwide and has the fourth highest mortality rate of cancer deaths. There is a high unmet need for novel therapies for those with mCRC and we are working hard to address these late-stage patients who have no other options. In December 2020, we started dosing patients in the expansion cohort of the alloSHRINK trial which evaluates CYAD-101 following FOLFIRI preconditioning chemotherapy at the recommended dose of one billion cells per infusion. This clinical program was the first to generate evidence of clinical activity for an allogeneic CAR T investigational therapy in any solid tumor indication, a major challenge for the industry. To date, we’ve seen encouraging data showing an improvement in median overall survival and median progression free survival, the gold standards for assessing treatments of mCRC, as compared to historical treatments. We look forward to potentially building upon these positive clinical data for CYAD-101 in patients with mCRC and
expect to announce preliminary data from the expansion cohort during the first half of 2021.
In addition, later this year, in collaboration with MSD, a subsidiary of Merck & Co., we plan to initiate the Phase 1b KEYNOTE-B79 trial which will evaluate CYAD-101 with MSD’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in refractory mCRC patients with microsatellite stable (MSS) / mismatch-repair proficient (pMMR) disease. We believe the mechanism of actions of CYAD-101 and KEYTRUDA® may be highly complementary and could help to drive meaningful clinical benefit in patients. We also believe there are other opportunities to further assess CYAD-101’s potential clinical activity in mCRC, as well as with other challenging indications. shRNA Packs Single Punch for Multiple Knockdowns Over the past few quarters, we’ve made great progress with our proprietary short hairpin RNA (shRNA) technology platform, which we moved from concept to clinic in just two years. In November 2020, we dosed the first patient in the Phase 1 IMMUNICY-1 trial evaluating the safety and efficacy of our first shRNA-based CAR T candidate CYAD-211, an anti-BCMA allogeneic cell therapy for the treatment of relapsed/refractory multiple myeloma (r/r MM). We expect this trial to establish that allogeneic CAR T cells using shRNA technology can generate clinical benefit without inducing graft-versus-host disease (GvHD). Preclinical data generated to date for CYAD-211 supports its further development. Early evidence of anti-tumor activity has been observed with no demonstrable evidence of GvHD. We’ve also demonstrated the ability to multiplex with the shRNA technology platform, which allows us to knockdown multiple targets of interest simultaneously. Preclinical data for the program has been encouraging and we hope to see this translate in the clinic.
Initial proofof-concept data from the IMMUNICY-1 trial are expected to be announced in the first half of 2021.