ISB 1442

Results: As of July 18, 2023, based on preliminary data from ongoing clinical database, 10 subjects had received once weekly SC injections of ISB 1442 in 4 dose-escalation groups from 6 mg to 150 mg. The majority were male (60%) and white (90%). The median age was 67 years (range 57-79). The median number of prior anti-myeloma lines of therapy was 6 (range 3-7); 70% were exposed to 5 drugs (2PIs, 2IMiDs, and CD38). The median number of ISB 1442 cycles was 1(range 1-2). Eight subjects (80%) experienced treatment-related adverse events (TRAEs), all were grade 1 or 2: cytokine release syndrome (CRS) (50%), injection site reactions (injection site erythema 20%, injection site bruising 10%), anemia (10%, 1 subject, grade 2) (Table 1). No grade 5 TRAE was observed. Following QW SC injection, ISB 1442 was slowly absorbed into the systemic circulation with Tmax generally occurring on day 2 of dosing. The ISB 1442 serum concentrations generally remained quantifiable over the entire dosing duration from 20 mg and above. The available PK data suggest an approximately dose-linear increase in serum concentration up to DL 3 (60 mg), followed by a supra-proportional increase in serum levels in subjects treated at DL 4 (150 mg). To date, 5 subjects treated at DL4 (150 mg) have experienced clinical symptoms of CRS (Grade 1-2) following the first dose of ISB 1442. Assessment of a panel of 63 soluble factors (including multiple cytokines, chemokines and growth factors) in the peripheral blood revealed that several subjects at DL3-4 exhibited transient increases (>10-fold) in macrophage inflammatory protein-1b (MIP-1b/CCL4) within 24h after treatment with ISB 1442, consistent with a macrophage-associated mechanism of action.

Conclusions: Treatment with ISB 1442 was well tolerated at the dose levels evaluated. The observed clinical CRS events were moderate and potentially related to macrophage activation following ISB 1442 administration. Updated clinical, biomarker and PK data will be presented for this ongoing study.