Ichnos Glenmark Innovation Presents Preclinical Data for its Oncology Asset ISB 2001 at AACR 2024 Annual Meeting

-  ISB 2001 is a first-in-class T cell-engaging (TCE) trispecific antibody based on Ichnos' proprietary BEAT^® platform that targets BCMA and CD38 on multiple myeloma (MM) cells.

-  ISB 2001 exhibited superior cytotoxicity over teclistamab in bone marrow aspirates from patients with either newly diagnosed or relapsed/refractory (r/r) MM (as well as smoldering MM and Plasma Cell Leukemia patients).

-  Remarkably, ISB 2001 maintained strong cytotoxicity against tumor cells in bone marrow aspirates from patients relapsing after CD38- or BCMA-targeted therapies, suggesting that the dual targeting TCE ISB 2001 can overcome the escape mechanisms. 

NEW YORK, April 8, 2024 /PRNewswire/ -- Ichnos Glenmark Innovation (IGI), an alliance between Ichnos Sciences Inc., a global fully-integrated clinical-stage biotech company developing multispecifics™ in oncology, and Glenmark Pharmaceuticals Ltd., shared preclinical data for its oncology asset ISB 2001 during the oral presentation at the annual American Association for Cancer Research (AACR) 2024. ISB 2001 is currently being tested in a Phase I clinical trial in r/r MM.

The oral presentation showcased the results of ISB 2001 anti-myeloma activity in bone marrow aspirates from patients who were either newly diagnosed or suffer from r/r MM following multiples lines of treatment, including patients relapsing after CD38 and BCMA targeted therapies. This pre-clinical study shows the promise of ISB 2001 trispecific antibody targeting BCMA and CD38 against multiple myeloma, and CD3 on T cells. It illustrates IGI's support in the fight against r/r MM.

"We are thrilled to present our preclinical findings for ISB 2001 at AACR," said Lida Pacaud, MD, Chief Medical Officer of Ichnos Glenmark Innovation. "The development of ISB 2001 holds special significance for us as it is crafted utilizing our cutting-edge BEAT^® antibody engineering platform, a cornerstone of our pioneering approach to create innovative multispecific treatments for blood cancers and solid tumors."

ISB 2001 – Mechanism of Action

ISB 2001 is the first T cell-engaging antibody that simultaneously targets BCMA and CD38 on MM cells. It is a trispecific antibody based on BEAT^® (Bispecific Engagement by Antibodies based on the TCR) technology, a proprietary platform allowing maximal flexibility and manufacturability of full length multispecific antibodies. ISB 2001 combines three proprietary antigen-binding arms, each targeting a different antigen, with one arm binding to the epsilon chain of CD3 on T cells, and the other two binding BCMA and CD38 on MM cells. Its fragment crystallizable (Fc) domain was fully silenced to suppress Fc effector functions. ISB 2001 redirects CD3+ T lymphocytes to kill tumor cells expressing low to high levels of both BCMA and CD38. With two different tumor-associated antigens instead of one, ISB 2001 has increased binding specificity to MM cells due to enhanced avidity-based binding.

Other Impactful Preclinical Results

The oral presentation summarized the preclinical characterization of ISB 2001, while focusing on the features that enable ISB 2001 to overcome escape mechanisms.

1. ISB 2001 showed superior cytotoxicity in comparison with teclistamab, alnuctamab and EM-801 across cell lines with variable expression levels of both BCMA and CD38.
2. ISB 2001 showed minimal cytotoxicity reduction by soluble factors (sCD38, sBCMA, APRIL) compared to teclistamab, alnuctamab and EM-801, which exhibited cytotoxicity reduction to a much eater degree.
3. Superior tumor growth inhibition in MM xenograft models relative to teclistamab + daratumumab combination.
4. Maintained cytotoxicity against MM cell in bone marrow aspirates from two patients relapsing from CD38 or BCMA targeted therapies as well as demonstrated superior cytotoxicity against MM cells over teclistamab in newly diagnosed or r/r patients (as well as smoldering MM and Plasma Cell Leukemia patients).

In relapsed/refractory (r/r) MM patients, who received CD38 targeted therapy, daratumumab cytotoxicity was substantially reduced due to low CD38 expression, while ISB 2001 was still effective.

Teclistamab is considered the next line of treatment in such patients. However, ISB 2001 consistently demonstrated increased cytotoxicity compared to teclistamab in bone marrow aspirates from both newly diagnosed and r/r patients, as well as in two patients with smoldering MM and plasma cell leukemia. Remarkably, ISB 2001 also induced stronger cytotoxic response in one patient relapsing after BCMA targeted therapy, suggesting that the dual targeting by ISB 2001 TCE can overcome the escape mechanisms. 

The oral presentation and corresponding data are available for review here. More information about ISB 2001, and the rest of Ichnos' pipeline can be found here.

About Ichnos Glenmark Innovation

Ichnos Glenmark Innovation (IGI) is an alliance between Ichnos Sciences Inc., a global fully-integrated clinical-stage biotech company developing multispecifics™ in oncology, and its parent, Glenmark Pharmaceuticals Ltd. (Glenmark), with the aim to accelerate new drug discovery in cancer treatment. IGI combines Ichnos' research and development proficiencies in novel biologics with those of Glenmark's in new small molecules to continue developing cutting-edge therapy solutions that treat hematological malignancies and solid tumors. Harnessing the combined proficiency of over 150 scientists and a robust pipeline of novel molecules, this collaboration will leverage the capabilities of its three global centers of innovation spread across the USA, Switzerland and India to propel Innovation. For more information, visit www.iginnovate.com.

Photo: https://mma.prnewswire.com/media/2381266/ISB_2001_KEY_ATTRIBUTES.jpg
Photo: https://mma.prnewswire.com/media/2381264/MODES_OF_ACTION.jpg

SOURCE Ichnos Glenmark Innovation