Multiple myeloma is a blood cancer that develops in plasma cells in the bone marrow. Although researchers have developed a better understanding of how multiple myeloma develops over the years, the exact cause has not yet been identified.
According to American Cancer Society, multiple myeloma is most common in older people. Less than 1 percent of these cancers are diagnosed in people younger than 35. Most people diagnosed with multiple myeloma are at least 65 years old. The average age of people diagnosed is 69. As per the Global Cancer Observatory (GLOBOCAN) 2020, the worldwide 5-year prevalence of multiple myeloma was 5.78 per 1,00,000, and in India, it was 2.2 per 1,00,000.
Even though the overall survival of multiple myeloma has been consistently improving over the past several years, it is still considered an incurable disease. Ichnos Glenmark Innovation (IGI), a key player in the oncology treatment landscape, recently released the preclinical development of ISB 2001, a first-in-class trispecific antibody targeting BCMA and CD38 on myeloma cells and CD3 on T cells. ISB 2001 is currently being investigated in a Phase 1 clinical study in relapsed/refractory multiple myeloma (r/r MM). IGI will be also presenting the Phase 1 study of ISB 2001 at the 66th ASH Annual Meeting.
In a recent email interaction with Financial Express.com, Cyril Konto, President, Executive Director and Chief Executive Officer at Ichnos Glenmark Innovation (IGI) talked about the unique mechanism of ISB 2001, challenges in the multiple myeloma treatment landscape, clinical breakthroughs, market potential and more. Edited Excerpts:
Can you explain the unique mechanism of ISB 2001 and how it is different from existing multiple myeloma treatments?
ISB 2001 is a BCMA x CD38 x CD3 TREAT trispecific antibody, the first T-cell engaging trispecific antibody based on IGI proprietary BEAT technology platform. In ISB 2001, three proprietary Fab antigen-binding arms bind to the CD3 epsilon chain on T cells, as well as BCMA and CD38 on multiple myeloma cells. ISB 2001 redirects CD3+ T lymphocytes to kill tumor cells expressing low to high levels of both BCMA and CD38.
Bispecific and monoclonal antibodies have revolutionized cancer care. However, in too many cases, low response rates and treatment resistance have persisted.
In terms of a multispecific antibody approach, ISB 2001 has the potential to afford greater safety and efficacy. More specifically, a trispecific approach can augment immune cell activation or activate specifically certain immune cells, achieve more precise tumor targeting and killing, and reduce the cost of production compared to earlier-generation CAR T or mAb combination therapy.
How Ichnos Glenmark Innovation (IGI) is working towards developing multi-specific antibodies for cancer treatment?
Our biologics platform, BEAT goes well beyond the standard mAb or bispecific approaches to solve engineering bottlenecks that previously prevented making bispecifics on a large scale. BEAT, coupled with proprietary universal light chain, enables IGI to develop cutting-edge immune cell engagers with great potential in oncology. Multispecific antibodies, like those developed by IGI, have more than two binders, potentially overcoming resistance mechanisms and enhancing immune cell activity.
We have both the internal knowledge and the platform for discovery and creation of new multispecific antibodies combined with sophisticated in vitro pharmacology assays for rapid functional assessment in final format and are fully enabled to evaluate lead molecules in a range of in vivo models. This includes T cell, NK and myeloid effector cell formats.
IGI is fully enabled in cell and protein sciences to generate the complete antigen toolbox required for discovery, small, mid and large-scale production and stable pool generation to enable the production of hundreds of mg of purified TREAT molecules required for Non-Human Primate studies.
IGI is focused on continuous optimization of multispecific technologies and is a leader and innovator in this space. We are now also employing structural biology and modelling with the Schrödinger platform to further enhance Lead Optimization and leverage Machine Learning and Artificial Intelligence approaches.
Could you share more insights into the Phase 1 trial for ISB 2001?
IGI has submitted initial data from the early dose-escalation phase of an ongoing, multi-center, single-agent Phase 1 study of ISB 2001 to the 2024 ASH annual meeting. We are encouraged by the early data from our Phase 1 study of ISB 2001, which shows a remarkable response rate. The data also demonstrates the potential of ISB 2001 to address the challenge of treatment resistance among heavily pre-treated multiple myeloma patients. Issues with treatment resistance can necessitate multiple lines of treatment for many patients.
The study continues to enroll patients in US, Australia and now India, and an expanded clinical dataset with longer follow-up for patients already submitted in the abstract, as well as new patients treated at higher doses, will be presented in an oral session at the ASH 2024 Annual Meeting on December 9.
What are the potential implications of these findings for the overall treatment landscape of multiple myeloma?
Despite there being numerous effective therapies marketed or in development, Multiple Myeloma remains an incurable disease and resistance mechanisms to approved T-cell engagers are emerging. There is no cure, and there remains an unmet need for new therapies for those who are relapsing or refractory. Among other potential indications, there is significant unmet medical need in triple refractory patients that have progressed following treatment with proteasome inhibitors, IMiD and antiCD38 monoclonal antibodies.
ISB 2001 is designed to surpass the various limitations of current therapies. If confirmed in clinical settings, this advantage could position ISB 2001 to leapfrog these approved therapies and expedite its path to frontline treatment for multiple myeloma.
Given the projected growth of the multiple myeloma treatment market, how does IGI plan to position itself to meet the increasing demand for innovative therapies?
To meet the growing demand in the multiple myeloma treatment market, IGI plans to strategically position itself through a robust pipeline of innovative therapies, including advanced multispecific biologics like ISB 2001. Our goal is to establish ISB 2001 as a frontrunner in myeloma treatment by demonstrating potentially superior response rates and longer duration of response in heavily pretreated and high-risk patient populations, relative to first-generation bispecifics.
IGI is committed to conducting targeted clinical trials to expedite development timelines in the relapsed/refractory setting following currently approved T-cell directed therapies by prioritizing mechanisms that target resistant myeloma populations and leveraging our scientific expertise.
IGI’s strategy includes building partnerships, securing regulatory support, and scaling manufacturing capabilities to meet anticipated demand as our products advance toward approval and commercialization.
By bringing together Ichnos Sciences Inc., with its extensive proficiencies in biologics, and the small molecule expertise and resources provided by Glenmark Pharmaceuticals Ltd., IGI has created a cutting-edge, clinical-stage pipeline in oncology. The company focuses on both liquid and solid tumors, advancing both next generation multispecifics that can engage multiple targets on the cell surface and small molecules modulating intracellular pathways in cancer or immune cells.
IGI’s three global centers of scientific innovation (USA, Switzerland, and India) synergize the expertise of more than 150 scientists across Ichnos’ biologics expertise and the small molecule resources of Glenmark.
Biologics research is in Switzerland, and small molecules research labs in Mumbai, with a focus on clinical development in the NYC headquarters. This approach will allow IGI to stay competitive in the rapidly expanding market and provide multiple myeloma patients with effective, next-generation treatment options.
What are the most significant challenges IGI faces in bringing novel treatments to market, and how does the company plan to address these while seizing new opportunities in precision oncology?
With IGI’s Protein Engineering, Research, and Process Development teams, the BEAT platform offers a competitive edge as a fully integrated end-to-end biotherapeutic engine. It enables IGI to deliver new IND-ready multispecific antibodies within three years from discovery, both for the company and in-licensing partners.
However, IGI faces several significant challenges in bringing innovative treatments like ISB 2001 to market, including clinical development complexities, competitive pressures, and regulatory hurdles. To address these challenges, IGI is pursuing a multi-faceted approach:
IGI is conducting carefully designed trials focused on high-risk and refractory patients. Conducting clinical trials in India provides IGI with the opportunity to reach a population that is less heavily pretreated while bringing innovative therapies to patients in emerging markets. This approach also allows IGI to leverage Glenmark’s established presence, achieving cost efficiencies in trial operations.
IGI is closely collaborating with regulatory authorities to proactively address safety and efficacy requirements. Ongoing data collection allows for adaptive trial protocols as needed. Additionally, IGI plans to engage with health authorities worldwide, leveraging available designations as data allows.
To harness opportunities in precision oncology, IGI is implementing extensive biomarker strategies in clinical trials to gain insights into in vivo mechanisms of efficacy and safety, with the goal of improving treatment precision and patient outcomes.
IGI is actively pursuing partnerships to enhance research capabilities, scale manufacturing, and expedite registration pathways. Collaborations with pharmaceutical companies help IGI broaden its expertise, expand its pipeline, and improve patient access to novel therapies. Specifically, for ISB 2001, IGI is seeking licensing partners to further extend the reach of this promising treatment.
Through these strategies, IGI is positioned to overcome challenges and seize new opportunities in bringing ISB 2001 to market, ensuring that innovative treatments reach patients in need while maintaining a competitive edge.
