BMS-986258

Novartis is also stopping development of a BTK inhibitor in Sjögren’s syndrome. Novartis’ anti-TIM-3 antibody has flunked a phase 3 blood cancer trial, prompting the Swiss drugmaker to pull the drug candidate from its pipeline. The failed study was the biggest test to date of an immuno-oncology target into which a who’s who of leading drug developers have pumped money. In Novartis’ phase 3 trial, patients with intermediate or worse risk myelodysplastic syndrome or chronic myelomonocytic leukemia-2 received the chemotherapy drug azacitidine plus either the TIM-3 candidate MBG453 or placebo. MBG453, also known as sabatolimab, was designed to address the unmet needs of patients who are unfit for hematopoietic stem cell transplantation. TIM-3 is expressed by immune effector cells, where it acts as an immune checkpoint, and leukemic stem cells, leading Novartis to identify the receptor as a way to simultaneously activate the immune system and suppress the proliferation of cancer cells. That theory failed to translate into efficacy in phase 3. Novartis broke the news that the late-stage study missed its primary endpoint, overall survival, as part of its fourth-quarter results (PDF) on Wednesday. The Swiss drugmaker responded to the setback by stopping development of sabatolimab, which was in phase 1 and 2 trials in acute myeloid leukemia and low-risk myelodysplastic syndrome at the time of the pivotal flop. Novartis’ retreat from TIM-3 makes GSK’s cobolimab the most advanced candidate against the receptor. While Novartis focused on blood cancers, GSK and other big names with TIM-3 candidates have largely looked at solid tumors. GSK, which acquired its TIM-3 candidate in the $5.1 billion Tesaro takeover, is running a phase 2/3 clinical trial in non-small cell lung cancer patients.  The list of other active TIM-3 programs has thinned in recent years. Roche removed (PDF) a PD-1xTIM-3 bispecific from its pipeline in 2022. AstraZeneca is continuing to study its rival bispecific in phase 1 and 2 trials, and Incyte is enrolling a phase 2 endometrial cancer trial to assess its monoclonal antibody. Bristol Myers Squibb terminated a phase 1 trial of one TIM-3 candidate, BMS-986299, in 2022 because its “business objectives” had changed. A phase 1/2 clinical trial of a second TIM-3 asset, the Five Prime Therapeutics-partnered BMS-986258, is still active but BMS stopped enrollment at around one-third of its original target around the time the other study was terminated. Eli Lilly has also axed a TIM-3 drug. Sabatolimab was the big pipeline news in Novartis’ results but the Swiss drugmaker also shared smaller updates. Novartis is stopping development of the BTK inhibitor remibrutinib in Sjögren’s syndrome but is continuing to advance toward phase 3 data in three other indications. And a HIF2A inhibitor disappeared from Novartis’ pipeline, one month after the company stopped enrollment in a phase 1/1b trial early.

DUBLIN, Aug. 5, 2022 /PRNewswire/ -- The "TIM3 Inhibitors Drug Clinical Trials & Market Opportunity Insight 2028" report has been added to ResearchAndMarkets.com's offering. The global TIM-3 inhibitor market is expected to surpass US$ 1 Billion by 2028 driven by the first drug approval expected to be launched by 2024. The surge in prevalence of cancer across geographies, high demand for targeted therapeutics for cancer management, development of favorable reimbursement policies, and rise in awareness of TIM-3 immune checkpoint inhibitors for the management of cancer due to positive results in combination therapy are the major factors boosting the growth of the market. In addition, the surge in the geriatric population and the increase in technological advancements in screening and diagnosing cancer will supplement the market growth during the forecast period. Cancer immunotherapy is a novel approach that harnesses the potential of the immune system to target tumor cells. Subsequently, the entrance of immune checkpoints including cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death-1 (PD-1) and its ligand (PD-L1) have shown huge potential in the treatment of cancer. However, despite these promising long-term responses, the majority of patients failed to respond to immune checkpoint blockade, demonstrating primary resistance. Additionally, many of these patients who initially respond to treatment eventually experience relapse secondary to acquired resistance. Recent studies have identified several new immune checkpoint targets, like lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), T cell immunoglobulin, and ITIM domain (TIGIT), V-domain Ig suppressor of T cell activation (VISTA), and so on. More recently TIM3 has emerged as a potential immune checkpoint inhibitor in the management of cancer. TIM-3 is regulatory of both innate and adaptive immune responses and is expressed on multiple tumor types including effector T cells, monocytes, natural killer cells, and dendritic cells. Apart from this, TIM-3 has been shown to promote immune tolerance, and overexpression of TIM-3 is associated with more advanced stages and poor prognosis of the disease. Owing to this, pharmaceutical companies have designed novel TIM-3 inhibitors across a wide range of cancers. The promising preclinical data has encouraged pharmaceutical companies to develop a clinical pipeline of monoclonal antibodies targeting TIM-3 as an alternative to target cancers. Currently, several anti-TIM-3 monoclonal antibodies have been developed which have shown encouraging responses in clinical trials. However, studies have supported the fact that combined blockade of PD-1 and TIM-3 pathways synergistically improved the CD8 T cell response and viral control. The advancement in the field of biotechnology and their encouraging response in combination therapy have led to the development of bispecific antibodies. Currently, only a few bispecific antibodies have been developed, however with the advancement in the field of genetic engineering, it is expected that bispecific antibodies will emerge as a shining star in TIM-3 therapy owing to several benefits associated with them. The pipeline for novel TIM-3 inhibitors is highly concentrated and is expected to flourish in the market during the forthcoming years. Cobolimab developed by Tesaro Therapeutics is one of the advanced stage TIM-3 inhibitors which are currently being evaluated in phase-II clinical trial. Recent data has shown that anti-TIM-3 antibody cobolimab is well-tolerated as monotherapy and in combination with the PD-1 inhibitor dostarlimab. Based on this encouraging data, the company is translating the drug into late-stage clinical trials for the management of solid tumors. Apart from this, several other drugs are under development including MBG453, Sym-023, BMS-986258, AZD7789, INCAGN02390, and others which are also present in the initial stages of clinical development. US is currently dominating the global market development for TIM3 Drugs driven by a large number of ongoing clinical trials and the presence of pharmaceutical companies which actively invest in this segment. The US FDA also grants several special designations to expedite the drug development and approval process. For instance, in 2021, US FDA granted fast-track designation for sabatolimab (MBG453) for the treatment of adult patients with myelodysplastic syndromes (MDS) in combination with hypomethylating agents. Report Highlights: Insight on Emerging TIM3 Inhibitors in Development As Monotherapy & combination Therapy Future Market Opportunity Insight From First Drug Approval: 2024 - 2028 Insight On TIM3 Inhibitors Drug In clinical Trials: > 15 Drugs TIM3 Inhibitors Drug In Clinical Trials Insight By Country, Company, Indication Comprehensive Clinical Insight On Biomarker Identified During Clinical Trials TIM3 Targeted Therapy Application By Various Cancers Key Topics Covered: 1. TIM3 - Emerging Immune Checkpoint 1.1 Introduction to TIM3 Inhibitor 1.2 Structure & Biology of TIM3 2. TIM3 as Cancer Combination Immunotherapy Target 3. Emerging TIM3 Inhibitors in Development 4. TIM3 Inhibitor Mechanism of Action 4.1 General Mechanism 4.2 Sabatolimab Proposed Mechanism of Action 5. Potential of TIM3 as Cancer Biomarker 5.1 TIM3 as Diagnostic Biomarker 5.2 TIM3 as Prognostic Biomarker 6. TIM3 Therapy Targeted Therapeutic Approach 6.1 Small Molecule Immunotherapy 6.2 Monoclonal Antibodies 6.3 Bispecific Antibodies 7. Global TIM3 Inhibitors Drugs Clinical Trials Overview 7.1 By Company 7.2 By Country 7.3 By Patient Segment/Disease Stage 7.4 By Phase 8. Global TIM3 Inhibitors Drugs Clinical Trials by Company, Indication & Phase 8.1 Preclinical 8.2 Phase-I 8.3 Phase-I/Ii 8.4 Phase-Ii 8.5 Phase-Ii/Iii 8.6 Phase-Iii 9. Application of TIM3 Targeted Therapy in Cancer 9.1 Myeloid Leukemia 9.2 Melanoma 9.3 Lung Cancer 9.4 Head & Neck Cancer 10. TIM3 Therapy Future Perspective 10.1 Clinical Forecast 10.2 Future Market Opportunity 11. Competitive Landscape 11.1 Agenus 11.2 Astrazeneca 11.3 Aurigene 11.4 Beigene 11.5 Brightpath Therapeutics 11.6 Bristol Myers Squibb 11.7 Chia Tai Tianqing Pharmaceutical Group 11.8 Curis 11.9 Eli Lilly 11.10 GlaxoSmithKline 11.11 Hanall Biopharma 11.12 Incyte Corporation 11.13 Ligand Pharmaceuticals 11.14 Neologics Bio 11.15 Novartis 11.16 Roche 11.17 Sutro Biopharma 11.18 Symphogen 11.19 Truebinding For more information about this report visit Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1904 Fax (outside U.S.): +353-1-481-1716 Logo: SOURCE Research and Markets