On December 11, 2021 Ichnos Sciences Inc., a global biotechnology company developing innovative biologics in oncology, reported that preclinical data that support the potential for ISB 1442, a first-in-class 2+1 biparatopic bispecific antibody that targets both CD38 and CD47, as a treatment for relapsed/refractory multiple myeloma and other CD38+ hematological malignancies (Press release, Ichnos Sciences, DEC 11, 2021, View Source [SID1234596808]). The data were presented today by Stefano Sammicheli, Ph.D., Director of Innate Cell Engagers, during an oral session at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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ISB 1442 includes three arms in a 2+1 biparatopic BEAT 2.0 bispecific[1] format:

Two proprietary high-affinity anti-CD38 binding arms, each targeting different CD38 epitopes, neither of which competes functionally with daratumumab, drive the binding of this molecule to CD38 expressing tumor cells.
A third, lower affinity arm masks CD47 and disrupts binding to SIRPα on macrophages, blocking the "do not eat me signal."
Engineering of the fragment crystallizable (Fc) region enhances antibody dependent cell phagocytosis (ADCP), antibody dependent cell cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC).
Ichnos’ proprietary BEAT 2.0 platform is among the most innovative multispecific platforms: it mimics the natural full length antibody format, the BEAT interface enables high yield for heavy chain pairing, and light chains are assembled via common light chain Fab technique.
The data presented today demonstrate the potency and anti-tumor activity of ISB 1442 in multiple in vitro and in vivo tumor models relative to daratumumab and magrolimab. Specifically, the results show that:

ISB 1442 induces comparable blockade of CD47/SIRPα interactions to the clinical benchmark magrolimab, an antibody that targets CD47.
ISB 1442 enables a significant increase in phagocytosis in CD38 low tumor cells relative to that of daratumumab, an antibody that targets CD38.
ISB 1442 shows higher ADCC relative to daratumumab.
ISB 1442 improved tumor growth inhibition in an in vivo preclinical model compared to daratumumab.
"We are excited to present data on Ichnos’ first-in-class biparatopic CD38 x CD47 bispecific antibody at ASH (Free ASH Whitepaper)," said Mario Perro, Ph.D., Vice President Oncology, Interim Head of Discovery at Ichnos. "ISB 1442 has demonstrated high potency in multiple in vitro tumor models, including one that assessed multiple antibody-dependent mechanisms of actions simultaneously, and higher tumor growth inhibition in vivo. We believe that this asset has the potential to effectively treat patients with multiple myeloma who have relapsed or are refractory to daratumumab as well as other CD38 expressing hematological malignancies."

"Today’s presentation represents another step forward as Ichnos works to bring this novel multispecific approach that co-targets CD38 and CD47 to patients with hematologic malignancies," said Cyril Konto, M.D., President and Chief Executive Officer of Ichnos. "With its unique design and mechanisms of action, data suggest that ISB 1442 may enhance anti-tumor activity relative to approved anti-CD38 targeted therapies by overcoming primary and acquired tumor mechanisms of resistance. We look forward to submitting the IND to FDA in early 2022 and initiating our first-in-human clinical study in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia and T-cell acute lymphoblastic leukemia in the middle of 2022."

The video presentation is available to registered meeting attendees on the ASH (Free ASH Whitepaper) platform. Additional details are also included in the abstract.

Ichnos continues to advance its pipeline of agents based on the proprietary BEAT technology platform. Using this platform, Ichnos is exploring the full design space for treating cancer and engineering multispecific antibodies capable of simultaneously engaging tumor and immune cells.