On March 8, 2024 Ichnos Glenmark Innovation (IGI), an alliance between Ichnos Sciences Inc., a global fully-integrated clinical-stage biotech company, reported that Nature Communications – peer-reviewed, open access, scientific journal – published a manuscript describing the pre-clinical development of ISB 1442, a CD38 and CD47 Bispecific Biparatopic Antibody Innate Cell Modulator (online manuscript available here) (Press release, Ichnos Sciences, MAR 8, 2024, View Source;utm_medium=rss&utm_campaign=ichnos-glenmark-innovation-reports-the-publication-in-nature-communications-of-the-preclinical-development-of-isb-1442-bispecific-antibody-for-treatment-of-relapsed-refractory-multiple-myeloma [SID1234642877]). ISB 1442 is currently being tested in a Phase I clinical trial in relapsed refractory multiple myeloma.
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"The acceptance of our manuscript by Nature Communications signifies the high quality of research conducted at Ichnos Glenmark Innovation, particularly in the challenging field of multiple myeloma. Our ongoing Phase I trial is a testament to our commitment to advancing care for patients battling this complex disease. We are eager to present further data to the medical community before the end of this year, highlighting our continuous efforts to innovate and improve patient outcomes," said Cyril Konto, President, CEO and Board Member of Ichnos Glenmark Innovation.
ISB 1442 is a multispecific antibody, rationally designed to harness innate immunity to treat CD38+ hematologic malignancies. ISB 1442 antibody is unique due to three features: (i) it uses two distinct Fab arms to target the CD38 tumor associated antigen (biparatopic approach), allowing for improved Complement Dependent Cytotoxicity (CDC) and improved binding to tumor cells when an antigen is downregulated; (ii) it blocks the CD47 ‘don’t eat me’ signal to counteract tumor escape from phagocytosis, leveraging selective avidity-induced binding to CD38+ tumor cells, thereby avoiding off-tumor targeting; and (iii) it is equipped with the Fc mutations enhancing effector mechanisms (CDC, Antibody Dependent Cell Cytotoxicity and Antibody Dependent Cell Phagocytosis).
The flexibility of the BEAT(Bispecific Engagement by Antibodies based on the TCR) platform enabled straightforward integration of all these features into a single antibody molecule.
Impactful pre – clinical study outcome
On cell lines, ISB 1442 showed superior tumor cell killing against daratumumab or to the combination of daratumumab with an anti-CD47 mAb (hu5F9). This implies that the engineering and architecture of ISB 1442 possesses improved effector functions compared to standard anti-CD38 monoclonal antibodies as well as their combination with CD47 blocking agents.
ISB 1442 consistently demonstrated superior tumor growth inhibition compared to daratumumab in preclinical mouse models in vivo and higher killing of tumor cells in primary multiple myeloma patient’s samples ex vivo, including in patients that relapsed from anti-CD38 therapies. This suggests that ISB 1442 could be effective as monotherapy as well as salvage therapy. Altogether, ISB 1442 may represent an improved therapeutic option available for the treatment of multiple myeloma patients relative to other monospecific anti-CD38 antibodies.