On December 12, 2023 Ichnos Sciences, a global clinical-stage biotechnology company developing innovative multispecific immune cell engager antibodies in oncology, reported data during three poster presentations at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) 2023 Annual Meeting and Exposition in San Diego, California (Press release, Ichnos Sciences, DEC 12, 2023, View Source [SID1234638492]).

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The studies showcased encouraging safety profiles, dose-dependent pharmacokinetics, and efficacy signals, marking significant progress in the fight against relapsed or refractory multiple myeloma.

"The results of these studies are a validating mile marker for our proprietary BEAT1 multispecific platform’s innovative mechanism of action," said Eugene Zhukovsky, Ichnos’ Chief Scientific Officer. "Our platform shows promise to unleash a powerful combination that can specifically target multiple surface proteins of tumor cells. This novel approach means stronger and more specific binding of immune cells to tumor cells, offering a beacon of hope for patients in dire need of treatment options as they face challenging hematologic malignancies."

1. Dose Escalation of ISB 1342, a Novel CD38xCD3 Bispecific Antibody, in Patients with Relapsed / Refractory Multiple Myeloma (RRMM):

Safety and tolerance: Demonstrated treatment with ISB 1342 was manageable at higher dose levels evaluated, with mild to moderate CRS, no ICANS, and no increased risk of infection observed.
Dose-dependent pharmacokinetics and biomarkers: Following IV infusion, ISB 1342 showed dose-linear increase in serum exposures across the evaluated dose range. Increases in several T-cell activation-related biomarkers (CD69 by flow, and serum cytokines withing 24hrs, such as IFNg, TNFa, IL-2, IL-6 and IL-10), were consistently observed following ISB 1342 dosing supporting proof of mechanism.
Efficacy signals: Positive results in patient groups at higher dose levels (8 and 16 μg/kg cohorts) align with predicted effectiveness based on a sophisticated preclinical quantitative system pharmacology (QSP) model, supporting the drug’s potential success in treating multiple myeloma.
2. Initial Dose Escalation of ISB 1442, a Novel CD38 Biparatopic x CD47 Bispecific Antibody, in Patients with Relapsed / Refractory Multiple Myeloma (RRMM):

Safety and tolerance: Demonstrated treatment with ISB 1442 was well tolerated at the dose levels evaluated, with observed clinical cytokine release syndrome (CRS) events being low grade and potentially related to macrophage activation following ISB 1442 administration.
Dose-dependent pharmacokinetics: Showed dose-linear increase in serum concentration up to DL 3 (60 mg), followed by a super-proportional increase in serum exposure most evident between DL3 (60 mg) and DL4 (150 mg).
Mechanism of action: Increase in macrophage-associated markers are consistent with a potential mechanism of action involving macrophage activation enhanced by the effector function modifications incorporated into the design of ISB 1442.
3. A Phase 1, First-in-Human, Dose Escalation and Dose-Expansion Study of a BCMAxCD38xCD3 Targeting Trispecific Antibody ISB 2001 in Subjects with Relapsed / Refractory Multiple Myeloma (RRMM):

ISB 2001 debut: A BCMAxCD38xCD3 trispecific antibody1 based on Ichnos’ proprietary TREAT2 platform, which promotes strong avidity induction and enables efficient and potent killing of multiple myeloma (MM) cells. Dual TAA targeting with ISB 2001 may overcome escape mechanisms associated with BCMA and CD38 targeted therapies, including approved T cell engagers, ADC or cell therapies.
Study design: Phase 1 study (NCT05862012) employing a subcutaneous dosing strategy with a step-up dosing approach, aiming to confirm efficacy and tolerability in patients with RRMM. The first-in-human dose was derived using advanced preclinical modeling, emphasizing safety with a preemptive step-up dosing strategy.
Future direction: The study is currently open for enrollment. Part 2 aims to confirm safety, select the recommended Phase 2 dose (RP2D), and explore secondary and exploratory endpoints.
All three of Ichnos’ presentations and corresponding data are available for review on the Ichnos website. More information about the three oncology assets highlighted at the meeting, and the rest of Ichnos’ pipeline can be found at this link.