CAEL-101

CAEL-101 is a fibril-reactive monoclonal antibody (mAb) that is currently in Phase 3 clinical development for the treatment of patients with amyloid light chain (“AL”) amyloidosis. The Cardiac Amyloid Reaching for Extended Survival (CARES) clinical program includes two parallel Phase 3 studies – one in patients with Mayo stage IIIa disease and one in patients with Mayo stage IIIb disease – and will collectively enroll approximately 370 patients globally. Enrollment is underway in both studies. The primary objective of the clinical program is to assess overall survival.

The Phase 2 open-label dose escalation study was conducted to investigate higher doses of CAEL-101 than had been evaluated in Phase 1 studies with a primary objective to identify the best dose to advance into Phase 3 development. The study evaluated the safety and tolerability of CAEL-101 in 13 AL amyloidosis patients at three study sites who received up to 1000 mg/m2 of CAEL-101 (two times the Phase 1 dose) administered in combination with SoC treatment. The study met its primary objectives, supporting the safety and tolerability of CAEL-101 and the selection of the 1000 mg/m2 dose for the Phase 3 study.

Phase 1a/1b data presented at the American Society of Hematology’s 59th Annual Meeting in December 2017, the 16th International Symposium on Amyloidosis in March 2018, the American Society of Echocardiography 29th Annual Scientific Sessions in June 2018 and the American Society of Hematology’s 60th Annual Meeting in December 2018 support CAEL-101’s potential to be a safe and well-tolerated therapy that promotes amyloid resolution. The data also demonstrated a correlation between a sustained decrease in N-terminal pro-brain natriuretic peptide (“NT-proBNP”) levels and an improvement in global longitudinal strain (“GLS”) following CAEL-101 treatment in patients with cardiac AL amyloidosis.

Twenty-seven patients were treated with CAEL-101 in this open-label, dose-escalation trial. In the Phase 1a trial, CAEL-101 was administered to eight patients via a single IV infusion at week one. In the Phase 1b trial, CAEL-101 was administered to 19 patients via one weekly IV infusion for four weeks. Trial investigators at Columbia determined the study achieved its primary objective of establishing maximum tolerated dose of up to 500mg/m2 of CAEL-101.

Trial investigators presented organ response rates in the Phase 1a and the Phase 1b, with 63 percent (14 of 24) overall organ response rate, 67 percent (8 of 12) overall cardiac response rate and 50 percent (5 of 10) overall renal response rate.[1] Early organ response was demonstrated in a high-mortality population (21 days median time to cardiac response in Phase 1b; 28 days median time to renal response in Phase 1b[2]).

Trial investigators found that CAEL-101 achieved and demonstrated organ response at multiple points in time throughout the duration of treatment; all patients either showed an organ response or were stable, and no patients showed organ progression. Organ response independent of a chemotherapy-free light chain response was demonstrated. No drug-related grade 4 or 5 adverse events or dose-limiting toxicities were seen in the trial. There was no mortality during the study. The investigators followed patients beyond the study and reported an overall survival rate of 93 percent (median follow-up period of 18.6 months).

As previously reported, the Phase 1a/1b study of CAEL-101 was the first clinical trial to demonstrate improvement in cardiac function via GLS after treatment with an amyloid fibril targeted therapy in AL amyloidosis patients with amyloid cardiac involvement. Long-term follow-up data from the Phase 1a/1b study were presented at the virtual International Symposium on Amyloidosis (ISA). These data demonstrate 78 percent survival (15/19) at a median follow-up of more than three years (37 months) in AL amyloidosis patients treated with CAEL-101 as well as durable organ response among evaluable patients, further supporting the advancement of CAEL-101 into Phase 3 development.

CAEL-101 has received Orphan Drug Designation from both the U.S. Food and Drug Administration and European Medicine Agency as a therapy for patients with AL amyloidosis.

[1] Response rates are based on the number of evaluable patients.

[2] First renal response evaluation point was 28 days for all but one patient, who was evaluated at 21 days.