- First clinical study to evaluate novel combination blocking KRAS G12C and its activator SOS1 to potentially increase the therapeutic benefit for lung and colorectal cancer patients
- Study is based on preclinical evidence suggesting synergistic effect of KRAS G12C and SOS1 inhibition
INGELHEIM, Germany AND SAN DIEGO, CA, USA I September 17, 2020 I Boehringer Ingelheim and Mirati Therapeutics, Inc. (NASDAQ: MRTX) today announced a clinical collaboration to evaluate the combination of BI 1701963, a SOS1::pan-KRAS inhibitor blocking KRAS independent of mutation type, and MRTX849, a KRAS G12C selective inhibitor in patients with solid tumors that harbor the KRAS G12C mutation. The collaboration will investigate the potential of this combination to provide more effective and durable responses for patients with lung and colorectal cancers who currently have limited treatment options.
Preclinical data suggest that the combination of a KRAS G12C inhibitor with a SOS1::pan-KRAS inhibitor results in increased anti-tumor activity based on the complementary mechanisms of these targeted oncology agents. By shifting the equilibrium from active KRAS(ON) towards the inactive KRAS(OFF) form, SOS1::pan-KRAS inhibitors have the potential to sensitize KRAS G12C mutant tumors to covalent KRAS G12C inhibitors that bind to KRAS(OFF).
“We look forward to collaborating with Boehringer Ingelheim to test this combination in clinical trials,” said Joseph Leveque, M.D., Executive Vice President and Chief Medical Officer of Mirati Therapeutics, Inc. “This collaboration is aligned with the broad and aggressive development strategy we have for MRTX849 and brings the potential for another therapeutic option to patients with KRAS G12C mutations.”
“We are excited to partner with Mirati in our ambition to make a difference for people living with KRAS-driven cancers. Combining our SOS1::pan-KRAS inhibitor with the mutation specific G12C inhibitor could be a win-win approach enhancing the response to therapy,” said Victoria Zazulina, M.D., Global Medical Head for Oncology at Boehringer Ingelheim. “We have a comprehensive KRAS program including the first SOS1::pan-KRAS inhibitor in the clinic, BI 1701963, for which we are exploring several combinations to optimize its therapeutic benefit in broad patient populations.”
Under the terms of the non-exclusive collaboration, Mirati will be the sponsor of the trial and Boehringer Ingelheim and Mirati will jointly share the costs of and oversee clinical development for the combined therapy.
About MRTX849
MRTX849 is an investigational, orally available small molecule that is designed to potently and selectively inhibit a form of KRAS, which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 14% of non-small cell lung cancer (NSCLC) adenocarcinoma patients, in 3-4% of colorectal cancer patients, and in subsets of other types of cancer. Tumors characterized by KRAS G12C mutations are commonly associated with poor prognosis and resistance to therapy, and patients with these mutations have few treatment options. MRTX849 is being evaluated in a Phase 1/2 trial treating patients with molecularly identified, KRAS G12C-positive advanced solid tumors and in the first quarter of 2020, enrollment began in the registration enabling cohort in monotherapy NSCLC, colorectal cancer and pancreatic cancer.
About BI 1701963
BI 1701963 is an investigational, orally available small molecule, that is designed to bind to the catalytic domain of SOS1 preventing the interaction with KRAS(OFF) and simultaneously blocking SOS1 driven feedback. This reduces the formation of KRAS(ON) and in consequence inhibits MAPK pathway signaling in KRAS-dependent cancers. The selective inhibition of SOS1 is a therapeutic concept that could allow KRAS blockade irrespective of KRAS mutation type (pan-KRAS approach). SOS1::KRAS inhibitors exhibit activity on a broad spectrum of KRAS alleles, including all major G12D/V/C and G13D oncoproteins, as recently published by Hofmann MH, et al. in Cancer Discovery, a journal of the American Association of Cancer Research (AACR). BI 1701963 is currently being evaluated in a Phase I clinical trial in patients with advanced KRAS-mutated cancers to evaluate safety, tolerability, pharmacokinetic and pharmacodynamic properties, and preliminary efficacy of BI 1701963 alone and in combination with MEK inhibitors.
About Mirati Therapeutics
Mirati Therapeutics, Inc. (NASDAQ: MRTX) is a San Diego-based clinical-stage biotechnology company dedicated to advancing novel therapeutics that extend the lives of patients by directly addressing the genetic and immunological drivers of cancer. Mirati is developing sitravatinib, designed to selectively target a spectrum of tyrosine kinases implicated in both tumor growth and the suppression of immune responses to tumors. Sitravatinib is being evaluated in multiple clinical trials to treat patients who are refractory to prior immune checkpoint inhibitor therapy, including a potentially registration-enabling Phase 3 trial of sitravatinib in combination with a checkpoint inhibitor in non-small cell lung cancer (NSCLC).
Mirati is also developing novel inhibitors of KRAS mutations including MRTX849, a potent and selective inhibitor of KRAS G12C. Our research in KRAS G12C has led to breakthroughs in targeting other KRAS mutations, including G12D, which drives tumor growth in more patients than G12C and includes pancreatic, colorectal and other types of cancer. Our lead clinical candidate for KRAS G12D, MRTX1133, is in IND-enabling studies. For more information, visit www.mirati.com (link is external).
About Boehringer Ingelheim
Making new and better medicines for humans and animals is at the heart of what we do. Our mission is to create breakthrough therapies that change lives. Since its founding in 1885, Boehringer Ingelheim is independent and family-owned. We have the freedom to pursue our long-term vision, looking ahead to identify the health challenges of the future and targeting those areas of need where we can do the most good.
As a world-leading, research-driven pharmaceutical company, more than 51,000 employees create value through innovation daily for our three business areas: Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. In 2019, Boehringer Ingelheim achieved net sales of 19 billion euros. Our significant investment of almost 3.5 billion euros in R&D drives innovation, enabling the next generation of medicines that save lives and improve quality of life.
We realize more scientific opportunities by embracing the power of partnership and diversity of experts across the life-science community. By working together, we accelerate the delivery of the next medical breakthrough that will transform the lives of patients now, and in generations to come.
More information about Boehringer Ingelheim can be found at www.boehringer-ingelheim.com or in our annual report http://annualreport.boehringer-ingelheim.com.
Boehringer Ingelheim in Oncology
Cancer takes. Takes away time. Takes away loved ones. At Boehringer Ingelheim Oncology, we are giving patients new hope, by taking cancer on. We are dedicated to collaborating with the oncology community on a shared journey to deliver leading science. Our primary focus is in lung and gastrointestinal cancers, with the goal of delivering breakthrough, first-in-class treatments that can help win the fight against cancer. Our commitment to innovation has resulted in pioneering treatments for lung cancer and we are advancing a unique pipeline of cancer cell directed agents, immuno-oncology therapies and intelligent combination approaches to help combat many cancers.
SOURCE: Boehringer Ingelheim
Post Views: 103
- First clinical study to evaluate novel combination blocking KRAS G12C and its activator SOS1 to potentially increase the therapeutic benefit for lung and colorectal cancer patients
- Study is based on preclinical evidence suggesting synergistic effect of KRAS G12C and SOS1 inhibition
INGELHEIM, Germany AND SAN DIEGO, CA, USA I September 17, 2020 I Boehringer Ingelheim and Mirati Therapeutics, Inc. (NASDAQ: MRTX) today announced a clinical collaboration to evaluate the combination of BI 1701963, a SOS1::pan-KRAS inhibitor blocking KRAS independent of mutation type, and MRTX849, a KRAS G12C selective inhibitor in patients with solid tumors that harbor the KRAS G12C mutation. The collaboration will investigate the potential of this combination to provide more effective and durable responses for patients with lung and colorectal cancers who currently have limited treatment options.
Preclinical data suggest that the combination of a KRAS G12C inhibitor with a SOS1::pan-KRAS inhibitor results in increased anti-tumor activity based on the complementary mechanisms of these targeted oncology agents. By shifting the equilibrium from active KRAS(ON) towards the inactive KRAS(OFF) form, SOS1::pan-KRAS inhibitors have the potential to sensitize KRAS G12C mutant tumors to covalent KRAS G12C inhibitors that bind to KRAS(OFF).
“We look forward to collaborating with Boehringer Ingelheim to test this combination in clinical trials,” said Joseph Leveque, M.D., Executive Vice President and Chief Medical Officer of Mirati Therapeutics, Inc. “This collaboration is aligned with the broad and aggressive development strategy we have for MRTX849 and brings the potential for another therapeutic option to patients with KRAS G12C mutations.”
“We are excited to partner with Mirati in our ambition to make a difference for people living with KRAS-driven cancers. Combining our SOS1::pan-KRAS inhibitor with the mutation specific G12C inhibitor could be a win-win approach enhancing the response to therapy,” said Victoria Zazulina, M.D., Global Medical Head for Oncology at Boehringer Ingelheim. “We have a comprehensive KRAS program including the first SOS1::pan-KRAS inhibitor in the clinic, BI 1701963, for which we are exploring several combinations to optimize its therapeutic benefit in broad patient populations.”
Under the terms of the non-exclusive collaboration, Mirati will be the sponsor of the trial and Boehringer Ingelheim and Mirati will jointly share the costs of and oversee clinical development for the combined therapy.
About MRTX849
MRTX849 is an investigational, orally available small molecule that is designed to potently and selectively inhibit a form of KRAS, which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 14% of non-small cell lung cancer (NSCLC) adenocarcinoma patients, in 3-4% of colorectal cancer patients, and in subsets of other types of cancer. Tumors characterized by KRAS G12C mutations are commonly associated with poor prognosis and resistance to therapy, and patients with these mutations have few treatment options. MRTX849 is being evaluated in a Phase 1/2 trial treating patients with molecularly identified, KRAS G12C-positive advanced solid tumors and in the first quarter of 2020, enrollment began in the registration enabling cohort in monotherapy NSCLC, colorectal cancer and pancreatic cancer.
About BI 1701963
BI 1701963 is an investigational, orally available small molecule, that is designed to bind to the catalytic domain of SOS1 preventing the interaction with KRAS(OFF) and simultaneously blocking SOS1 driven feedback. This reduces the formation of KRAS(ON) and in consequence inhibits MAPK pathway signaling in KRAS-dependent cancers. The selective inhibition of SOS1 is a therapeutic concept that could allow KRAS blockade irrespective of KRAS mutation type (pan-KRAS approach). SOS1::KRAS inhibitors exhibit activity on a broad spectrum of KRAS alleles, including all major G12D/V/C and G13D oncoproteins, as recently published by Hofmann MH, et al. in Cancer Discovery, a journal of the American Association of Cancer Research (AACR). BI 1701963 is currently being evaluated in a Phase I clinical trial in patients with advanced KRAS-mutated cancers to evaluate safety, tolerability, pharmacokinetic and pharmacodynamic properties, and preliminary efficacy of BI 1701963 alone and in combination with MEK inhibitors.
About Mirati Therapeutics
Mirati Therapeutics, Inc. (NASDAQ: MRTX) is a San Diego-based clinical-stage biotechnology company dedicated to advancing novel therapeutics that extend the lives of patients by directly addressing the genetic and immunological drivers of cancer. Mirati is developing sitravatinib, designed to selectively target a spectrum of tyrosine kinases implicated in both tumor growth and the suppression of immune responses to tumors. Sitravatinib is being evaluated in multiple clinical trials to treat patients who are refractory to prior immune checkpoint inhibitor therapy, including a potentially registration-enabling Phase 3 trial of sitravatinib in combination with a checkpoint inhibitor in non-small cell lung cancer (NSCLC).
Mirati is also developing novel inhibitors of KRAS mutations including MRTX849, a potent and selective inhibitor of KRAS G12C. Our research in KRAS G12C has led to breakthroughs in targeting other KRAS mutations, including G12D, which drives tumor growth in more patients than G12C and includes pancreatic, colorectal and other types of cancer. Our lead clinical candidate for KRAS G12D, MRTX1133, is in IND-enabling studies. For more information, visit www.mirati.com (link is external).
About Boehringer Ingelheim
Making new and better medicines for humans and animals is at the heart of what we do. Our mission is to create breakthrough therapies that change lives. Since its founding in 1885, Boehringer Ingelheim is independent and family-owned. We have the freedom to pursue our long-term vision, looking ahead to identify the health challenges of the future and targeting those areas of need where we can do the most good.
As a world-leading, research-driven pharmaceutical company, more than 51,000 employees create value through innovation daily for our three business areas: Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. In 2019, Boehringer Ingelheim achieved net sales of 19 billion euros. Our significant investment of almost 3.5 billion euros in R&D drives innovation, enabling the next generation of medicines that save lives and improve quality of life.
We realize more scientific opportunities by embracing the power of partnership and diversity of experts across the life-science community. By working together, we accelerate the delivery of the next medical breakthrough that will transform the lives of patients now, and in generations to come.
More information about Boehringer Ingelheim can be found at www.boehringer-ingelheim.com or in our annual report http://annualreport.boehringer-ingelheim.com.
Boehringer Ingelheim in Oncology
Cancer takes. Takes away time. Takes away loved ones. At Boehringer Ingelheim Oncology, we are giving patients new hope, by taking cancer on. We are dedicated to collaborating with the oncology community on a shared journey to deliver leading science. Our primary focus is in lung and gastrointestinal cancers, with the goal of delivering breakthrough, first-in-class treatments that can help win the fight against cancer. Our commitment to innovation has resulted in pioneering treatments for lung cancer and we are advancing a unique pipeline of cancer cell directed agents, immuno-oncology therapies and intelligent combination approaches to help combat many cancers.
SOURCE: Boehringer Ingelheim
Post Views: 103
