As of 25 July 2023, 22 patients have been enrolled in the doublet (MDS n=5; MDS HMA failed n=5; r/r AML n=12). Baseline characteristics are shown in Table 1. 8/10 MDS/MDS HMA-failed patients were of high to very high risk based on rIPSS; of the r/r AML 7/12 patients had adverse risk based on ELN 2017. The median number of prior therapies for the MDS HMA-failed patients was 1 (range 1-2). The median number of prior therapies for the r/r AML patients was 2 (range 1-4) with all patients having failed prior HMA-containing therapies and 7/12 having received prior HMA plus venetoclax.

The majority of observed adverse events (AE) were Grade 1-2 and no dose limiting toxicities have been reported. As of 25 July 2023, a total of 10 BEX related AEs have been reported (8% of all treatment emergent AEs) with four of these events of ≥ Grade 3, two being immune related (capillary leak syndrome and hemophagocytic lymphohistiocytosis).

Sustained target engagement of soluble Clever-1 of up to 75% compared to baseline was seen at all tested dose levels in patient blood. Activity of BEX in patient BM was demonstrated using receptor binding assays with BEX treatment resulting in decreased blast Clever-1 expression at all dose levels of the doublet cohort. Increased immune activation as measured using HLA expression and T/NK cell numbers in patient BM was observed after BEX treatment across indications. Up to 2-3-fold increase of CD8 T and NK cells in the BM of BEX treated patients was observed.

Preliminary efficacy shows objective responses in 8/15 evaluable patients across all tested BEX doses. Four were observed in patients with prior HMA-failure and four patients stayed on treatment > 6 months. Clinical activity for frontline MDS was seen as one complete remission (CR), marrow CR (mCR) and hematologic improvement for platelets (HI-P); for MDS with HMA failure as one CR, mCR and partial remission (PR); for r/r AML as two incomplete CRs (CRi). Based on accumulating data, responses are observed between end Cycle 1 and end Cycle 4 for all BEX doses.

Conclusion

Combining BEX plus azacitidine is well-tolerated and shows efficacy across indications. Additional clinical and pharmacodynamic data of the completed Ph1 of the study will be presented during the meeting. Ph2 of BEX plus azacitidine will open in the 2 nd half of 2023 in HMA-failed r/r AML and/or higher risk MDS patients.

Bexmarilimab