SHP2

KRAS stands out as the most commonly altered among the trio of RAS genes, with NRAS and HRAS following suit. The human KRAS gene resides on chromosome 12p12.1 and comprises six exons, primarily positioned in exon 1 at sites 12 and 13, though occasionally found in codons 61, 63, 117, 119, and 146. The emergence of KRAS inhibitors marks a notable advancement in the rapidly progressing field of oncology, instilling hope in combating formidable solid tumors. The landscape of treatment for KRAS-mutant cancers is undergoing rapid evolution, marked by several promising advancements in recent years. Forecasts anticipate significant growth in the KRAS inhibitors market in the coming years, propelled by rising cancer incidence rates and the escalating demand for personalized cancer therapies. Ongoing research and clinical trials continue to unveil potential treatment strategies, fostering optimism for improved patient outcomes. According to DelveInsight’s analysis, the market size for KRAS inhibitors across the 7MM and is expected to grow with a tremendous 36% CAGR to reach USD 10 billion by 2032. As per the estimates, the US is set to be the largest market for KRAS inhibitors, with ~70% of the market share among the seven major markets. The KRAS inhibitor market is expected to grow significantly in the coming years, driven by the increasing incidence of cancer and the growing demand for personalized cancer treatments; ongoing research and clinical trials have identified potential treatment strategies. Key players, including Mirati, Novartis Pharmaceuticals, Amgen, Eli Lilly, Verastem, and others, are involved in developing drugs for KRAS mutation for various indications such as NSCLC, colorectal cancer, pancreatic cancer, and others. The treatment landscape for KRAS-mutant cancers has rapidly evolved, with several promising advancements in recent years. Keen to know how the KRAS inhibitors market will evolve by 2032? Find out @ KRAS Inhibitors Market Forecast Amgen and Mirati Therapeutics are at the forefront of the race to develop KRAS inhibitors for cancer treatment. However, their current candidates are focused solely on targeting G12C-mutant tumors, leaving a significant gap in addressing other KRAS variants. This represents a major unmet need in the field, as no approved treatments are currently available for other variants. Recognizing this challenge, numerous key players actively explore alternative KRAS variants and expand their research to include other types of cancers beyond NSCLC. This shift in focus holds promising potential for developing effective therapies that can address a wider range of KRAS mutations and target multiple cancer types. Many companies are focusing on developing their candidates in pan-KRAS, like Cardiff Oncology (onvansertib), Gritstone bio (SLATE KRAS), Hookipa Pharma (HB-700), and others. Now, let’s examine the emerging KRAS inhibitor therapies JDQ443: Novartis Pharmaceuticals Phase III JDQ443 represents an experimental KRASG12C inhibitor that is selective, covalent, and can be taken orally. Initial findings from the Phase Ib stage of the KontRASt-01 trial (NCT04699188) indicate a confirmed overall response rate (ORR) of 57% at the recommended dosage of 200 mg twice daily in individuals with advanced non-small cell lung cancer (NSCLC). Presently, JDQ443 is undergoing Phase III evaluation, aiming to compare its effectiveness as a standalone treatment against docetaxel in patients with advanced NSCLC carrying a KRASG12C mutation who have previously undergone platinum-based chemotherapy and immune checkpoint inhibitor therapy, either sequentially or in combination. Novartis intends to New Drug Application (NDA) for NSCLC by 2024 and for colorectal cancer (CRC) post-2026. Avutometinib (VS-6766): Verastem Oncology Phase II Avutometinib (VS-6766) functions as an RAF/MEK clamp, prompting the formation of inactive complexes involving MEK and ARAF, BRAF, and CRAF. This mechanism potentially enhances the anti-tumor response by thoroughly inhibiting the RAS pathway, possibly leading to more sustained effects. Currently, avutometinib is in advanced stages of development. Unlike other MEK inhibitors, it not only blocks MEK kinase activity but also prevents RAF from phosphorylating MEK. This distinctive mode of action enables avutometinib to inhibit MEK signaling effectively without triggering compensatory activation, a limitation observed in other inhibitors. The FDA has recognized the potential of avutometinib in combination with defactinib (a FAK inhibitor) by granting it Breakthrough Therapy designation for treating all patients with recurrent low-grade serous ovarian cancer (LGSOC), irrespective of their KRAS status, after one or more prior lines of therapy, including platinum-based chemotherapy. RAMP 201 is a trial aimed at registering avutometinib, either alone or combined with defactinib, in patients with recurrent LGSOC. RMC-4630 (SAR442720): Revolution Medicines Phase II RMC-4630 (also known as SAR442720) is a highly effective small compound intended for oral use, engineered to specifically hinder the function of SHP2. This essential cellular protein regulates cell survival and proliferation by transmitting signals from receptor tyrosine kinases to RAS. Currently, the company is in the Phase II trial stage, investigating the combination of RMC-4630 with sotorasib for individuals with non-small cell lung cancer harboring a KRAS G12C mutation. These patients have not responded to standard therapies and have not previously undergone treatment with an RAS inhibitor. Discover which therapies are expected to grab major KRAS inhibitors market share @ KRAS Inhibitors Market Report BI 1701963: Boehringer Ingelheim Phase I BI 1701963 is a compound designed to inhibit the activity of KRAS across various oncogenic variants, particularly targeting major G12 and G13 oncoproteins. Its mechanism involves binding to SOS1, a crucial component in activating KRAS by facilitating the exchange of RAS-bound GDP for GTP. This selective inhibition of SOS1 presents a promising therapeutic approach, enabling KRAS suppression regardless of mutation type. Preclinical studies demonstrate the efficacy of this pan-KRAS inhibitor in impeding tumor growth across numerous tested G12 and G13 KRAS mutations, which are commonly observed in the protein. Additionally, the compound exhibits selectivity towards cancer cell lines bearing mutations in the KRAS gene. Currently undergoing Phase I trials, BI 1701963 is being assessed both as a standalone treatment and in combination with trametinib for patients with advanced or metastatic solid tumors carrying KRAS mutations. Boehringer Ingelheim has initiated a clinical collaboration with Amgen to explore the potential of BI 1701963 in combination with LUMAKRAS. Divarasib/GDC-6036: Roche Phase I Divarasib/GDC-6036, an orally administered small molecule, exhibited strong and specific inhibition of the KRAS G12C protein in preclinical trials. Engineered to target the switch II pocket of the KRASG12C protein, it interacts specifically with the cysteine at position 12, effectively locking it in an inactive GDP-bound state irreversibly. Results from a Phase Ib study presented at AACR 2023 showed that combining GDC-6036 with cetuximab effectively treated colorectal cancer (CRC), displaying notable clinical efficacy and tolerable safety levels. LY353798: Eli Lilly Phase I LY353798 is a specific covalent blocker of KRASG12C, exhibiting efficacy both alone and when paired with other anti-cancer treatments in preliminary studies. Its pharmacokinetic pro well, prompting its progression to clinical trials. In laboratory settings, LY3537982 has displayed the ability to target the KRAS G12C mutation, hindering mutant KRAS-driven signaling. Phase I clinical trials are underway, focusing on patients with non-small cell lung cancer, colorectal cancer, or other advanced solid tumors. For further information on the most promising KRAS inhibitors, reach out @ KRAS Inhibitors Treatment Pipeline Related Reports PD-1 and PD-L1 Inhibitors Competitive Landscape PD-1 and PD-L1 Inhibitors Competitive Landscape – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug pro including clinical and non-clinical stage products, and the key PD-1 and PD-L1 inhibitors companies, including Merck, Laekna Therapeutics, Genentech, Tracon Pharmaceuticals Inc., Celgene, MedImmune, Hangzhou Sumgen Biotech, among others. Non-Small Cell Lung Cancer Market Non-Small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key NSCLC companies, including EMD Serono, Merck, Cellular Biomedicine Group, Inc., Celgene, CellSight Technologies, Inc., BeyondSpring Pharmaceuticals Inc., J Ints Bio, Forward Pharmaceuticals Co., Ltd., AstraZeneca, Bristol-Myers Squibb, Teligene US, Rain Oncology Inc, ReHeva Biosciences, Inc., Amgen, Novartis, RedCloud Bio, Parexel, Vitrac Therapeutics, LLC, Mythic Therapeutics, Instil Bio, Mirati Therapeutics Inc., Daiichi Sankyo, Inc., AstraZeneca, Precision Biologics, Inc, Promontory Therapeutics Inc., Palobiofarma SL, Regeneron Pharmaceuticals, Revolution Medicines, Inc., Cullinan Oncology, LLC, Iovance Biotherapeutics, Inc., Innate Pharma, among others. Multiple Myeloma Market Multiple Myeloma Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key multiple myeloma companies, including Johnson & Johnson (Janssen), Pfizer, AbbVie and Roche (Genentech), Regeneron Pharmaceuticals, Bristol-Myers Squibb, Celgene, Roche (Genentech), Arcellx, Novartis, Regeneron Pharmaceuticals, BeiGene, CARsgen Therapeutics, Cartesian Therapeutics, C4 Therapeutics, Heidelberg Pharma, Bristol-Myers Squibb, RAPA Therapeutics, AbbVie (TeneoOne), Takeda, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve. Conference Coverage Solutions: DelveInsight’s Conference Coverage Solutions delivers a comprehensive examination of conference outcomes from a range of prominent events, such as ASCO, ESMO, ASH, AACR, ATS, ERS, EULAR, ELCC, and IPF Summit 2023. This in-depth analysis equips businesses with the insights they need for effective competitive intelligence and forecasting market trends, aiding in the development of future strategies. Contact Us Shruti Thakur info@delveinsight.com +14699457679

BEIJING and SHANGHAI and BOSTON, Feb. 18, 2024 /PRNewswire/ -- Jacobio Pharma (1167.HK), a clinical-stage oncology company drugging the undruggable targets, today announced it received approval of registrational phase III clinical trial of the combination therapy between its novel KRAS G12C inhibitor glecirasib and novel SHP2 inhibitor JAB-3312. JAB-3312 is the first SHP2 inhibitor entered into phase III study globally in combination with KRAS G12C inhibitor. This approved study in China is a randomized active controlled phase III trial design to evaluate the efficacy and safety of JAB-3312 in combination with glecirasib for first-line non-small cell lung cancer patients with KRAS G12C mutations. The control arm is the current standard treatment for first-line non-small cell lung cancer, which is the combination therapy of PD-1 antibody and chemotherapy. Jacobio initiated clinical trials of SHP2 inhibitors in 2018. Data presented by Jacobio in an oral presentation at the 2023 European Society for Medical Oncology Annual Meeting (ESMO 2023) showed that among 129 patients with non-small cell lung cancer, 58 patients were first-line treatment patients (including 7 dose groups), ORR (objective response rate) was 65.5% (38/58), and the DCR (disease control rate) was 100%. Among them, in the dose group of 800 mg (once daily) glecirasib and 2 mg JAB-3312 (once daily for 1 week on, then 1 week off), the ORR was 86.7% (13/15). This clinical study is continuing to enroll patients. The KRAS G12C inhibitors currently on the market have not been approved as first-line non-small cell lung cancer treatments for KRAS G12C mutations. Jacobio's JAB-3312 and glecirasib are both oral formulations, and the combination therapy is also the first approved Phase III registration clinical trial for dual oral inhibitors in the first-line treatment of non-small cell lung cancer worldwide. About JAB-3312 JAB-3312 is a highly selective SHP2 allosteric inhibitor with best-in-class potential. Jacobio is currently conducting clinical trials of JAB-3312 in monotherapy and combination therapies with glecirasib and other agents in China, the United States and Europe. The phase III study in combination with KRAS G12C inhibitor Glecirasib has been approved by China CDE in Feb 2024. About Glecirasib Glecirasib is a KRAS G12C inhibitor developed by Jacobio. A number of Phase I/II clinical trials of glecirasib are currently ongoing in China, the United States and Europe for patients with advanced solid tumors harboring KRAS G12C mutation. These include a pivotal clinical trial in NSCLC in China; a monotherapy study for STK11 co-mutated NSCLC in the front-line setting, and combination therapy trials with SHP2 inhibitor JAB-3312 in NSCLC and with Cetuximab in colorectal cancer. About Jacobio Jacobio Pharma (1167.HK) is committed to developing and providing new and innovative products and solutions to improve people's health. Our pipeline revolves around novel molecular targets on six major signaling pathways: KRAS, immune checkpoints, tumor metabolism, P53, RB and MYC. We aim for our key projects to be among the top three in the world. Our vision is to become a global leader recognized for our impact in drug R&D together with our partners. Jacobio has R&D centers in Beijing, Shanghai and Boston with our Induced Allosteric Drug Discovery Platform (IADDP) and our iADC Platform. SOURCE Jacobio Pharma

BEIJING and SAN FRANCISCO, Jan. 19, 2024 /PRNewswire/ -- Jacobio Pharmaceuticals (1167.HK), a clinical-stage oncology company focusing on undruggable targets, announced data of glecirasib in patients with pancreatic cancer and other solid tumors in the oral abstract session at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium (" 2024 ASCO GI"). As of December 6, 2023, the monotherapy global study of glecirasib enrolled 52 patients with pancreatic cancer and other solid tumors harboring KRAS G12C mutation in China, the United States, Europe, Israel and other regions, including 31 patients with pancreatic cancer, and 21 patients with other solid tumors (8 with biliary tract tumors, 3 with gastric cancer, 3 with small bowel cancer, 2 with appendix cancer, and 5 with other solid tumors). Among 50 patients with evaluable solid tumors, the confirmed objective response rate (cORR) was 48% (24/50) and the disease control rate (DCR) was 90% (45/50). For second-line and above KRAS G12C mutated pancreatic cancer patients, the cORR was 41.9% (13/31) and the DCR was 93.5% (29/31). The median progression-free survival (mPFS) was 5.6 months, and the median overall survival (mOS) was 10.7 months. In other solid tumor patients, the cORR was 57.9% (11/19), DCR was 84.2% (16/19), the mPFS was 7.0 months, and the mOS has not yet matured. The above safety and efficacy data are better than the published data of similar studies. Glecirasib has good tolerability and safety characteristics, the majority of treatment-related adverse events (TRAEs)are grades 1-2, and grade 3 or above TRAEs occurred in 25% of patients. No patient has permanently withdrawn from the study due to TRAE. Professor Lin Shen, director of Peking University Cancer Hospital gastroenterology department, is the principal investigator for this trial. She introduced at the conference, "Pancreatic cancer is a highly malignant tumor, and current patients lack effective standardized treatment methods, with a five-year overall survival rate of only 5%. Every year in China, nearly 1-2% of pancreatic cancer patients carry a KRAS G12C mutation, and the mutation rate in other solid tumors is also around 1%. The clinical data of glecirasib have preliminarily confirmed the efficacy in patients with pancreatic cancer and other solid tumors. Compared with the standard chemotherapy treatment, the ORR of glecirasib is higher, and the safety and tolerance is better. It is expected that glecirasib will accelerate the clinical development in pancreatic cancer and other solid tumors, bringing a better treatment option beyond chemotherapy for patients." Jacobio continues to explore the application of glecirasib in pancreatic cancer. Glecirasib's registrational pivotal study for pancreatic cancer was approved by CDE in July 2023, which became the first global pancreatic cancer KRAS G12C registrational clinical study. The study results will be used to submit NDA (New Drug Application) for pancreatic cancer. Based on the clinical efficacy and safety data from ongoing clinical trials, glecirasib was granted breakthrough therapy designation (BTD) by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) for the pancreatic cancer patients with a KRAS G12C mutation who have progressed after frontline standard care treatment. Pancreatic cancer is a malignant tumor and there is a lack of effective treatment currently. The five-year overall survival rate is only 5%-10%. The BTD will expedite the clinical development of glecirasib and accelerate its early access to the patients. For more information, please visit the official website of the ASCO GI: Conference Call Information Jacobio will host a live conference call on Jan. 23, 2024, at 9:30-10:30 (UTC+8). Participants must register in advance of the conference call. Registration Link: About Glecirasib Glecirasib is a KRAS G12C inhibitor developed by Jacobio. A number of Phase I/II clinical trials of glecirasib are currently ongoing in China, the United States and Europe for patients with advanced solid tumors harboring KRAS G12C mutation. This includes a pivotal clinical trial in NSCLC in China (patients enrollment has been completed); a monotherapy study for STK11 co-mutated NSCLC in the front-line setting, combination therapy trials with SHP2 inhibitor JAB-3312 in NSCLC and with Cetuximab in colorectal cancer, and a registrational pivotal clinical trial in pancreatic cancer. About Jacobio Pharma Jacobio Pharma (1167.HK) is committed to developing and providing new and innovative products and solutions to improve people's health. Our pipeline revolves around novel molecular targets on six major signalling pathways: KRAS, immune checkpoints, tumor metabolism, P53, RB and MYC. We aim for our key projects to be among the top three in the world. Our vision is to become a global leader recognized for our impact in drug R&D together with our partners. Jacobio has R&D centers in Beijing, Shanghai and Boston with our Induced Allosteric Drug Discovery Platform (IADDP) and our iADC Platform. SOURCE Jacobio Pharma