mTORC2

– New preclinical data to be presented at EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics – Oct. 23, 2024 -- Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today announced the upcoming presentation of new preclinical data supporting the combination of its next-generation farnesyl transferase inhibitor (FTI) KO-2806 with targeted therapies, including KRASG12C inhibitors and pan-RAS inhibitors, at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain. “We look forward to presenting an update to our growing body of preclinical and clinical data that demonstrate the potential of KO-2806 as a companion therapeutic to augment the antitumor activities of KRASG12C and pan-RAS inhibitors,” said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. “These findings support the promising therapeutic strategy of blunting the effects of innate and adaptive resistance to targeted agents to treat cancers driven by KRAS mutations, including KRASG12C non-small cell lung cancer (NSCLC) and KRAS-mutant colorectal cancers. If successful, we believe KO-2806 could drive enhanced antitumor activity and become a combination partner to multiple targeted therapies in large solid tumor indications.” Details for the session titles and information for the two abstracts are listed below. Copies of the presentations will be available in the Posters and Presentations section on Kura’s website following presentation at the conference. KO-2806, a next-generation farnesyl transferase inhibitor, re-sensitizes KRAS G12C NSCLC tumors to KRAS G12C mutant-specific inhibitors through mTOR signaling inhibition Session Date and Time: Friday, October 25, 2024; 9:00 AM - 3:00 PM ET Session and Location: Drug Resistance and Modifiers, Exhibition Hall Poster Number: PB376 The next-generation farnesyl transferase inhibitor KO-2806 sensitizes colorectal cancers to pan-RAS inhibition Session Date and Time: Friday, October 25, 2024; 9:00 AM - 3:00 PM ET Session and Location: Drug Resistance and Modifiers, Exhibition Hall Poster Number: PB378 KO-2806 is a next-generation inhibitor of farnesyl transferase designed to improve upon the potency, pharmacokinetic and physicochemical properties of earlier FTI drug candidates. At the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Kura presented preclinical data supporting the rationale for combining KO-2806 with distinct classes of targeted therapies, including tyrosine kinase inhibitors, KRASG12C inhibitors and KRASG12D inhibitors. Kura is evaluating KO-2806 in a Phase 1 dose-escalation trial (FIT-001) as a monotherapy, in combination with cabozantinib in clear cell renal cell carcinoma and in combination with adagrasib in KRASG12C NSCLC. Additional information about clinical trials for KO-2806 can be found at https://kuraoncology.com/clinical-trials/#farnesyl-transferase-inhibitor. Kura Oncology is a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. The Company’s pipeline consists of small molecule drug candidates that target cancer signaling pathways. Ziftomenib, a once-daily, oral drug candidate targeting the menin-KMT2A protein-protein interaction, has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration for the treatment of relapsed/refractory (R/R) NPM1-mutant AML. Kura has completed enrollment in a Phase 2 registration-directed trial of ziftomenib in R/R NPM1-mutant AML (KOMET-001). The Company is also conducting a series of clinical trials to evaluate ziftomenib in combination with current standards of care in newly diagnosed and R/R NPM1-mutant and KMT2A-rearranged AML. Kura is evaluating KO-2806, a next-generation FTI, in a Phase 1 dose-escalation trial as a monotherapy and in combination with targeted therapies (FIT-001). Tipifarnib, a potent and selective FTI, is currently in a Phase 1/2 trial in combination with alpelisib for patients with PIK3CA-dependent head and neck squamous cell carcinoma (KURRENT-HN). For additional information, please visit Kura’s website at www.kuraoncology.com and follow us on Twitter and LinkedIn. The content above comes from the network. if any infringement, please contact us to modify.

– Combination of ziftomenib and imatinib shows robust and durable antitumor activity in imatinib-sensitive (1L) and imatinib-resistant (2L/3L) GIST models – – Proof-of-concept study of ziftomenib plus imatinib in patients with advanced GIST after imatinib failure to begin in 1H 2025 – SAN DIEGO, Oct. 24, 2024 (GLOBE NEWSWIRE) -- Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today reported preclinical data supporting the development of the Company’s menin inhibitor, ziftomenib, for the treatment of advanced gastrointestinal stromal tumors (GIST). The new findings are being presented at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona. A copy of the poster, entitled “Menin Inhibitor Ziftomenib Synergizes with Imatinib in Tyrosine Kinase Inhibitor (TKI)-Resistant Gastrointestinal Stromal Tumor Models,” is available in the Posters and Presentations section on Kura’s website. “Kura has generated a substantial body of preclinical data that support potential for ziftomenib in combination with KIT inhibitors for the treatment of patients with advanced GIST,” said Francis Burrows, Ph.D., Senior Vice President, Translational Research. “Our results indicate that the combination of ziftomenib and imatinib acts via a synthetic lethal mechanism through which ziftomenib targets an epigenetic vulnerability of GIST tumors, creating potent synergy even with KIT inhibitors that are otherwise inactive as monotherapy. Indeed, the activity of ziftomenib appears to be agnostic to the mutational status of KIT in GIST, suggesting an opportunity to explore the combination for all patients, even in the frontline setting.” The combination of ziftomenib and imatinib unexpectedly showed robust and durable antitumor activity in both imatinib-sensitive and imatinib-resistant GIST patient-derived xenograft models, and in all cases was significantly superior to imatinib monotherapy. Mechanistically, the data reveal a KIT-dependent mechanism, with ziftomenib and imatinib combining to sharply reduce KIT expression and/or activity, effectively silencing both the ERK and AKT/mTOR signaling pathways and driving robust cell cycle arrest and apoptosis. Given that imatinib is well established as the frontline standard of care in patients with GIST, and that generic versions are available, imatinib represents a promising combination partner for ziftomenib. In August 2024, Kura announced clearance by the U.S. Food and Drug Administration (FDA) of the Investigational New Drug (IND) application for ziftomenib for the treatment of advanced GIST. The Company is now preparing to initiate a proof-of-concept study evaluating ziftomenib and imatinib in patients with advanced GIST after imatinib failure in the first half of 2025. For more information regarding the study, please visit www.clinicaltrials.gov (identifier: NCT06026410). About GIST Gastrointestinal stromal tumors (GIST) are the most common form of sarcoma, characterized as KIT-dependent solid tumors. Despite the successful disease control achieved with imatinib in advanced GIST patients, most patients eventually progress due to acquired secondary KIT mutations. TKIs such as sunitinib can target imatinib-resistant genotypes and are approved in later lines, but response rates and long-term outcomes are modest, so new therapeutic options are needed. Previously published data show that the menin-MLL complex regulates KIT expression in GIST cells, and menin inhibitors display additive therapeutic activity in combination with imatinib in imatinib-sensitive GIST models1. About Ziftomenib Ziftomenib is a potent, selective and oral menin inhibitor currently in development for the treatment of genetically defined AML patients with high unmet need. In April 2024, ziftomenib received Breakthrough Therapy Designation (BTD) by the FDA for the treatment of relapsed/refractory (R/R) NPM1-mutant acute myeloid leukemia (AML) based on data from Kura’s ongoing KOMET-001 clinical trial. Additional information about clinical trials for ziftomenib can be found at kuraoncology.com/clinical-trials/#ziftomenib. About Kura Oncology Kura Oncology is a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. The Company’s pipeline consists of small molecule drug candidates that target cancer signaling pathways. Ziftomenib, a once-daily, oral drug candidate targeting the menin-KMT2A protein-protein interaction, has received BTD for the treatment of R/R NPM1-mutant AML. Kura has completed enrollment in a Phase 2 registration-directed trial of ziftomenib in R/R NPM1-mutant AML (KOMET-001). The Company is also conducting a series of clinical trials to evaluate ziftomenib in combination with current standards of care in newly diagnosed and R/R NPM1-mutant and KMT2A-rearranged AML. Kura is evaluating KO-2806, a next-generation farnesyl transferase inhibitor (FTI), in a Phase 1 dose-escalation trial as a monotherapy and in combination with targeted therapies (FIT-001). Tipifarnib, a potent and selective FTI, is currently in a Phase 1/2 trial in combination with alpelisib for patients with PIK3CA-dependent head and neck squamous cell carcinoma (KURRENT-HN). For additional information, please visit Kura’s website at www.kuraoncology.com and follow us on X and LinkedIn. Forward-Looking Statements This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and therapeutic potential of ziftomenib, potential benefits of combining ziftomenib with appropriate standards of care, and progress and expected timing of the ziftomenib program and clinical trials. Factors that may cause actual results to differ materially include the risk that compounds that appeared promising in early research or clinical trials do not demonstrate safety and/or efficacy in later preclinical studies or clinical trials, the risk that Kura may not obtain approval to market its product candidates, uncertainties associated with performing clinical trials, regulatory filings, applications and other interactions with regulatory bodies, risks associated with reliance on third parties to successfully conduct clinical trials, the risks associated with reliance on outside financing to meet capital requirements, and other risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. You are urged to consider statements that include the words “may,” “will,” “would,” “could,” “should,” “believes,” “estimates,” “projects,” “promise,” “potential,” “expects,” “plans,” “anticipates,” “intends,” “continues,” “designed,” “goal,” or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to the Company’s periodic and other filings with the Securities and Exchange Commission (SEC), including the Company’s Form 10-Q for the quarter ended June 30, 2024 filed with the SEC on August 8, 2024, which are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and Kura assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Contacts Investors:Pete De SpainExecutive Vice President, Investor Relations &Corporate Communications(858) 500-8833pete@kuraoncology.com Media:Cassidy McClainVice PresidentInizio Evoke Comms(619) 849-6009cassidy.mcclain@inizioevoke.com 1 Hemming ML et al., Cancer Discov. 2022;12:1804-1823.

OP-3136, a potent KAT6 inhibitor, demonstrated robust anti-tumor activity as a single agent, as well as synergy and enhanced anti-tumor activity in combination with palazestrant; IND submission expected before year endPalazestrant demonstrated combinability and enhanced tumor suppression with both everolimus and capivasertib SAN FRANCISCO, Oct. 23, 2024 (GLOBE NEWSWIRE) -- Olema Pharmaceuticals, Inc. (“Olema” or “Olema Oncology”, Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, today announced results from three preclinical studies that will be presented during poster sessions at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (ENA 2024) in Barcelona, Spain. “Building on our earlier studies that showed compelling single agent activity for OP-3136, this new data demonstrates the potential for OP-3136 in combination with palazestrant, with strong tumor growth inhibition and regression relative to combinations with fulvestrant,” said David C. Myles, Ph.D., Chief Discovery and Non-Clinical Development Officer of Olema Oncology. “Taken together, these data reinforce our belief in the potential of OP-3136 as an exciting new therapy for breast and other cancers. We look forward to submitting our Investigational New Drug (IND) application for OP-3136 to the US Food and Drug Administration before the end of this year.” Title: “Combining OP-3136, a KAT6 inhibitor, with endocrine therapy and CDK4/6 inhibitor enhances anti-tumor activity in ER+/HER2- breast cancer models”Abstract: 230Session: 300Date: Thursday, October 24, 2024Time: 9:00 to 17:30 CEST Key findings include: OP-3136 inhibited cell proliferation and synergized with anti-estrogens (fulvestrant and palazestrant) and a CDK4/6 inhibitor (ribociclib) in a breast cancer cell line.OP-3136 led to either tumor growth inhibition or tumor regression in vivo in xenograft models across all treatment groups.In combination with OP-3136, palazestrant was consistently superior to fulvestrant and led to improved anti-tumor activity and tumor regression.OP-3136 showed robust synergistic anti‑tumor activity when combined with fulvestrant or palazestrant as doublet therapy in breast cancer models. Dr. Myles continued, “With the potential to become a best-in-class endocrine therapy and improve upon current standard of care treatments for women living with metastatic breast cancer, our lead product candidate, palazestrant, continues to move through the clinic as a monotherapy in our pivotal Phase 3 OPERA-01 trial while also demonstrating combinability with multiple targeted agents, including CDK 4/6 inhibitors, in Phase 1/2 studies. Our preclinical posters at ENA show that the combination of palazestrant with both everolimus and capivasertib are synergistic and result in significant tumor regression. We look forward to advancing the development of palazestrant in combination with everolimus, ribociclib, and other agents and expect to present updated Phase 2 data for palazestrant in combination with ribociclib at the San Antonio Breast Cancer Symposium (SABCS) this December.” Title: “Combining palazestrant, a CERAN, and everolimus, an mTOR inhibitor, enhances tumor suppression in ER+/HER2- breast cancer models”Abstract: 211Session: 300Date: Thursday, October 24, 2024Time: 9:00 to 17:30 CEST Key findings include: Palazestrant and everolimus demonstrate synergy in vitro and in vivo and resulted in greater anti-proliferative activity than either agent alone.Combining palazestrant with everolimus causes gene signature transcriptional changes, downregulating cell cycle progression and upregulating apoptosis.These data support clinical investigation of the combination of palazestrant and everolimus. Title: “Combining palazestrant, a CERAN, and capivasertib, a pan-AKT inhibitor, enhances tumor suppression in ER+/HER2- breast cancer models”Abstract: 212Session: 300Date: Thursday, October 24, 2024Time: 9:00 to 17:30 CEST Key findings include: Palazestrant and capivasertib work synergistically to inhibit proliferation of multiple ER+ breast cancer models, both in vitro and in vivo.Palazestrant demonstrates superior anti-tumor efficacy over fulvestrant in combination with capivasertib, significantly inhibiting and repressing tumor growth.Combining palazestrant and capivasertib increases downregulation of genes associated with cell cycle progression.These data support clinical investigation of the combination of palazestrant and capivasertib. Copies of these posters are available on the Publications page of Olema’s website. About Palazestrant (OP-1250)Palazestrant (OP-1250) is a novel, orally-available small molecule with dual activity as both a complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD). It is currently being investigated in patients with recurrent, locally advanced or metastatic ER-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. In clinical studies, palazestrant completely blocks ER-driven transcriptional activity in both wild-type and mutant forms of metastatic ER+ breast cancer and has demonstrated anti-tumor efficacy along with attractive pharmacokinetics and exposure, favorable tolerability, CNS penetration, and combinability with CDK4/6 inhibitors. Palazestrant has been granted U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of ER+/HER2- metastatic breast cancer that has progressed following one or more lines of endocrine therapy with at least one line given in combination with a CDK4/6 inhibitor. It is being evaluated both as a single agent in an ongoing Phase 3 clinical trial, OPERA-01, and in Phase 1/2 combination studies with CDK4/6 inhibitors (palbociclib and ribociclib), a PI3Ka inhibitor (alpelisib), and an mTOR inhibitor (everolimus). For more information on OPERA-01, please visit www.opera01study.com. About OP-3136OP-3136 is a novel, orally-available small molecule that potently and selectively inhibits KAT6, an epigenetic target that is dysregulated in breast and other cancers. In preclinical studies, OP-3136 has demonstrated significant anti-proliferative activity in ER+ breast cancer models and is combinable and synergistic with endocrine therapies including palazestrant and CDK4/6 inhibitors. Olema has successfully completed IND-enabling studies in support of a potential Investigational New Drug (IND) application with the FDA and expects to initiate Phase 1 clinical trials for OP-3136 in early 2025. About Olema OncologyOlema Oncology is a clinical-stage biopharmaceutical company committed to transforming the standard of care and improving outcomes for women living with cancer. Olema is advancing a pipeline of novel therapies by leveraging our deep understanding of endocrine-driven cancers, nuclear receptors, and mechanisms of acquired resistance. Our lead product candidate, palazestrant (OP-1250), is a proprietary, orally-available complete estrogen receptor (ER) antagonist (CERAN) and a selective ER degrader (SERD), currently in a Phase 3 clinical trial called OPERA-01. In addition, Olema is developing a potent KAT6 inhibitor (OP-3136). Olema is headquartered in San Francisco and has operations in Cambridge, Massachusetts. For more information, please visit us at www.olema.com. Forward Looking StatementsStatements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Words such as “anticipate,” “believe,” “could,” “expect,” “goal,” “may,” “potential,” “upcoming,” “will” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These statements include those related to the timelines for initiation and enrollment for potential clinical studies and for results of clinical trials of palazestrant (OP-1250) as a monotherapy and in combination trials, potential beneficial characteristics, including but not limited to safety, tolerability, activity, efficacy and therapeutic effects of palazestrant, the potential of palazestrant to advance the standard of care for women living with cancer, palazestrant’s combinability with other drugs, the initiation of a phase 1b/2 clinical study of palazestrant in combination with everolimus and timing thereof, and the sufficiency and timing of Olema’s preclinical program, including the potential beneficial characteristics of its KAT6 inhibitor compounds and the timing of a potential IND application and advancement into clinical development for OP-3136. Because such statements deal with future events and are based on Olema’s current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of Olema could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including, without limitation, those discussed in the section titled “Risk Factors” in Olema’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, and future filings and reports that Olema makes from time to time with the U.S. Securities and Exchange Commission. Except as required by law, Olema assumes no obligation to update these forward-looking statements, including in the event that actual results differ materially from those anticipated in the forward-looking statements. ContactCourtney O’Konek, Vice President, Corporate Communicationsmedia@olema.com