Alpelisib

Presented compelling new preclinical data demonstrating anti-tumor activity for OP-3136, a novel KAT6 inhibitor, with enhanced activity of palazestrant combinations at EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (ENA 2024) New clinical data for palazestrant (OP-1250) in combination with ribociclib to be presented at the San Antonio Breast Cancer Symposium (SABCS) in DecemberIND submission for OP-3136 expected before year end; clinical study to initiate early 2025Cash, cash equivalents, and marketable securities of $214.8 million as of September 30, 2024 SAN FRANCISCO, Nov. 12, 2024 (GLOBE NEWSWIRE) -- Olema Pharmaceuticals, Inc. (“Olema”, “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 reported financial results for the third quarter ended September 30, 2024, and provided a corporate update. “We look forward to presenting updated data from our ongoing Phase 2 clinical study of palazestrant in combination with ribociclib in frontline metastatic breast cancer patients at SABCS in December. The OPERA-01 Phase 3 clinical trial of palazestrant as a monotherapy in second/third-line patients continues to advance and we remain on track for top-line readout in 2026,” said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. “At ENA 2024, we presented three new, robust preclinical data sets. Palazestrant demonstrated combinability and enhanced tumor suppression with both everolimus and capivasertib. OP-3136, our potent and selective KAT6 inhibitor, demonstrated robust anti-tumor activity as a single agent, as well as synergy and enhanced anti-tumor activity in combination with palazestrant. These data reinforce our belief in the potential of OP-3136 as an exciting new therapy for breast and other cancers, and we remain on track to submit the IND application before year end.” Recent Progress Continued enrollment of patients in OPERA-01, the pivotal Phase 3 clinical trial of palazestrant as a monotherapy in second/third-line ER+/HER2- metastatic breast cancer.Presented preclinical data for OP-3136 and palazestrant at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (ENA 2024) in Barcelona, Spain.Initiated Phase 1b/2 clinical study of palazestrant in combination with everolimus.Successfully completed Investigational New Drug (IND)-enabling studies for OP-3136. Anticipated Upcoming Milestones Present updated Phase 2 data showing palazestrant in combination with ribociclib at the San Antonio Breast Cancer Symposium (SABCS) in December 2024.Submit the IND application for OP-3136 to the U.S. Food and Drug Administration (FDA) before year-end; initiate the Phase 1 clinical study for OP-3136 in early 2025. Third Quarter 2024 Financial ResultsCash, cash equivalents, and marketable securities as of September 30, 2024, were $214.8 million. Net loss for the quarter ended September 30, 2024, was $34.6 million, as compared to $21.5 million for the quarter ended September 30, 2023. The increase in net loss for the third quarter was primarily related to increased spending on clinical development and research activities as a result of late-stage clinical trials for palazestrant and the advancement of our KAT6 inhibitor program, as well as general and administrative (G&A) activities. The increase was partially offset by higher interest income earned from marketable securities. GAAP research and development (R&D) expenses were $33.2 million for the quarter ended September 30, 2024, as compared to $19.5 million for the quarter ended September 30, 2023. The increase in R&D expenses was primarily related to increased spending on clinical operations and development-related activities as we continue to advance palazestrant through late-stage clinical trials, research-related activities associated with the advancement of our KAT6 inhibitor program, and personnel related costs, including an increase in non-cash stock-based compensation expense of $1.5 million. Non-GAAP R&D expenses were $28.9 million for the quarter ended September 30, 2024, which excluded $4.3 million non-cash stock-based compensation expense. Non-GAAP R&D expenses were $16.7 million for the quarter ended September 30, 2023, excluding $2.8 million non-cash stock-based compensation expense. A reconciliation of GAAP to non-GAAP financial measures used in this press release can be found at the end of this press release. GAAP G&A expenses were $4.4 million for the quarter ended September 30, 2024, as compared to $3.9 million for the quarter ended September 30, 2023. The increase in G&A expenses was primarily due to increased spending on corporate-related costs and an increase in non-cash stock-based compensation expense of less than $0.1 million. Non-GAAP G&A expenses were $3.0 million for the quarter ended September 30, 2024, excluding $1.3 million non-cash stock-based compensation expense. Non-GAAP G&A expenses were $2.6 million for the quarter ended September 30, 2023, excluding $1.3 million non-cash stock-based compensation expense. A reconciliation of GAAP to non-GAAP financial measures used in this press release can be found at the end of this press release. 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. Non-GAAP Financial InformationThe results presented in this press release include both GAAP information and non-GAAP information. As used in this release, non-GAAP R&D expense is defined by Olema as GAAP R&D expense excluding stock-based compensation expense, and non-GAAP G&A expense is defined by Olema as GAAP G&A expense excluding stock-based compensation expense. We use these non-GAAP financial measures to evaluate our ongoing operations and for internal planning and forecasting purposes. We believe that non-GAAP financial information, when taken collectively, may be helpful to investors because it provides consistency and comparability with past financial performance. However, non-GAAP financial information is presented for supplemental informational purposes only, has limitations as an analytical tool, and should not be considered in isolation or as a substitute for financial information presented in accordance with GAAP. Other companies, including companies in our industry, may calculate similarly titled non-GAAP measures differently or may use other measures to evaluate their performance, all of which could reduce the usefulness of our non-GAAP financial measures as tools for comparison. Investors are encouraged to review the related GAAP financial measures and the reconciliation of these non-GAAP financial measures to their most directly comparable GAAP financial measures and not rely on any single financial measure to evaluate our business. 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) and OP-3136, each as a monotherapy and in combination trials, Olema’s financial condition and resources, results of operations, cash position, 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, combinability with other drugs, palazestrant, or OP-3136, 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 September 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. Olema Pharmaceuticals, Inc. Condensed Consolidated Balance Sheets Data (in thousands) September 30,December 31, 2024 2023 Cash, cash equivalents and marketable securities $214,763$261,807 Total assets 230,173 276,945 Total current liabilities 30,700 21,621 Total liabilities 31,262 23,050 Total stockholders’ equity 198,911 253,895 Total liabilities and stockholders’ equity $ 230,173$ 276,945 Olema Pharmaceuticals, Inc. Condensed Consolidated Statements of Operations (In thousands, except share and per share data) Three Months Ended September 30, Nine Months Ended June 30, 2024 2023 2024 2023 Operating expenses: Research and development (1)$33,226 $19,453 $92,218 $60,268 General and administrative (2) 4,395 3,889 13,272 14,277 Total operating expenses 37,621 23,342 105,490 74,545 Loss from operations (37,621) (23,342) (105,490) (74,545) Other income: Interest income 2,928 1,919 9,388 4,774 Other income (expense) 138 (79) 195 (112) Total other income 3,066 1,840 9,583 4,662 Net loss$ (34,555)$ (21,502) $ (95,907)$ (69,883) Net loss per share, basic and diluted$(0.60)$(0.48) $(1.80)$(1.66) Weighted average shares used to compute net loss per share, basic and diluted 57,262,803 44,977,161 53,194,081 41,999,978 Reconciliation of GAAP to Non-GAAP Information (In thousands) Three Months Ended September 30, Nine Months Ended June 30, 2024 2023 2024 2023 (1) Research and development reconciliation GAAP research and development (3)$33,226 $19,453 $92,218 $60,268 Less: share-based compensation expense 4,280 2,801 11,925 8,858 Non-GAAP research and development$ 28,946 $ 16,652 $ 80,293 $ 51,410 (2) General and administrative reconciliation GAAP general and administrative$4,395 $3,889 $13,272 $14,277 Less: share-based compensation expense 1,346 1,304 4,334 4,047 Non-GAAP general and administrative$ 3,049 $ 2,585 $ 8,938 $ 10,230 (3) Research and development expenses for the nine-months ended September 30, 2024 include a $5.0 million milestone payment in connection to the Aurigene Agreement. IR and Media ContactCourtney O’Konek, Vice President, Corporate Communicationsmedia@olema.com

– Topline results from registration-directed trial of ziftomenib in R/R NPM1-mutant AML expected in early 2025; Phase 1 results published in The Lancet Oncology – – Data from 100 patients in Phase 1a dose-escalation study of ziftomenib combined with ven/aza in R/R AML and 7+3 in 1L adverse risk AML to be presented at ASH – – Phase 1b expansion study of ziftomenib in combination with standards of care now enrolling at 600 mg in all cohorts – – Preclinical data support opportunity for ziftomenib in GIST; proof-of-concept study expected to begin in 1H 2025 – – First patient dosed in study of KO-2806 and adagrasib in KRASG12C-mutated NSCLC – – $455.3 million in cash, cash equivalents and investments provide runway into 2027 – – Management to host webcast and conference call today at 4:30 p.m. ET – SAN DIEGO, Nov. 07, 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 third quarter 2024 financial results and provided a corporate update. “We approach the end of 2024 in a strong position, with a series of important catalysts ahead,” said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. “First, we look forward to sharing a robust dataset from more than 100 patients in our Phase 1a dose-escalation study of ziftomenib in combination with standards of care in acute myeloid leukemia (AML) at the upcoming American Society of Hematology (ASH) Annual Meeting, followed by topline results from our registration-directed trial of ziftomenib in relapsed/refractory (R/R) NPM1-mutant (NPM1-m) AML early next year. In the meantime, we continue to enroll rapidly across all our ziftomenib studies, further supporting the broad development of our menin inhibitor programs.” Recent Highlights Topline results from registration-directed trial of ziftomenib in early 2025 – In May 2024, Kura completed enrollment of 85 patients in the Phase 2 portion of KOMET-001, a registration-directed clinical trial of its menin inhibitor, ziftomenib, in patients with R/R NPM1-m AML. Ziftomenib is the first and only investigational therapy to be granted Breakthrough Therapy Designation (BTD) for the treatment of R/R NPM1-m AML, which accounts for approximately 30% of new AML cases annually and represents a disease of significant unmet need for which no approved targeted therapy exists. Results from the Phase 1 portion of KOMET-001 were recently published in the leading clinical oncology journal, The Lancet Oncology.Data from Phase 1a dose-escalation study of ziftomenib at ASH – Two abstracts reporting preliminary data from the Phase 1a dose-escalation study of ziftomenib in combination with standards of care in patients with NPM1-m and KMT2A-rearranged (KMT2A-r) AML have been accepted for presentation at the ASH Annual Meeting in December. As of the June 21, 2024 data cutoff, the abstracts continue to support a potential best-in-class safety and tolerability profile for ziftomenib, as well as robust and durable activity in combination with standards of care, including venetoclax plus azacitidine (ven/aza) as well as cytarabine plus daunorubicin (7+3). Kura expects to present a more mature dataset from more than 100 patients in the Phase 1a dose-escalation study in the presentations at ASH.Phase 1b expansion study of ziftomenib now enrolling in all cohorts – All four cohorts in the Phase 1a dose-escalation study have cleared the highest dose and advanced into the Phase 1b expansion study at 600 mg. The Phase 1b expansion study includes multiple combination cohorts, including ziftomenib plus ven/aza in newly diagnosed NPM1-m or KMT2A-r AML and ziftomenib plus 7+3 in newly diagnosed NPM1-m or KMT2A-r AML without qualification for high-risk disease. Each of the seven combination cohorts is expected to enroll at least 20 patients. A total of 45 patients have already enrolled in the study since the first dose-expansion cohort opened in August 2024. The Company anticipates sharing preliminary data from the Phase 1b expansion study at a medical meeting in 2025.Preclinical data support opportunity for ziftomenib in GIST – Last month, at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Kura reported preclinical data supporting the combination of ziftomenib and imatinib for the treatment of advanced gastrointestinal stromal tumors (GIST). The combination showed unexpectedly 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. The Company received FDA clearance of its Investigational New Drug application for ziftomenib for the treatment of advanced GIST in August and expects to initiate a proof-of-concept study in the first half of 2025 evaluating ziftomenib and imatinib in patients with advanced GIST who have failed imatinib.First patient dosed in study of KO-2806 and adagrasib in KRASG12C-mutated NSCLC – In August 2024, Kura began dosing patients in its study of KO-2806, a next-generation farnesyl transferase inhibitor (FTI), in combination with adagrasib in KRASG12C-mutated non-small cell lung cancer (NSCLC). The Company’s findings suggest that combining KO-2806 with adagrasib may drive tumor regressions and enhance both duration and depth of antitumor response in preclinical models of KRASG12C-mutated NSCLC. The study of KO-2806 and adagrasib is supported by a clinical collaboration and supply agreement with Mirati, now a Bristol Myers Squibb company.Preclinical data support potential for menin inhibitor in diabetes – In June 2024, Kura reported data showing that ziftomenib induces insulin production, improves insulin sensitivity and reduces insulin resistance in a preclinical in vivo model of type 2 diabetes. Ziftomenib demonstrated meaningful levels of glycemic control, including reduced fasting blood glucose levels and %HbA1C within 27 days, as well as consistent improvement in both insulin sensitivity and insulin production. The data were presented at the American Diabetes Association Scientific Sessions in Orlando. The Company expects to nominate a next generation menin inhibitor candidate targeting diabetes in the first half of 2025. Financial Results Research and development expenses for the third quarter of 2024 were $41.7 million, compared to $29.3 million for the third quarter of 2023.General and administrative expenses for the third quarter of 2024 were $18.2 million, compared to $13.1 million for the third quarter of 2023.Net loss for the third quarter of 2024 was $54.4 million, compared to a net loss of $38.6 million for the third quarter of 2023. This included non-cash share-based compensation expense of $8.3 million, compared to $7.1 million for the same period in 2023.As of September 30, 2024, Kura had cash, cash equivalents and short-term investments of $455.3 million, compared to $424.0 million as of December 31, 2023.Based on its operating plan, management expects that cash, cash equivalents and short-term investments will fund current operations into 2027. Forecasted Milestones Present updated data from the KOMET-007 trial of ziftomenib in combination with ven/aza and 7+3 at ASH in December 2024.Report topline results from the KOMET-001 registration-directed trial of ziftomenib in NPM1-mutant R/R AML in early 2025.Present preliminary data from the Phase 1b expansion portion of KOMET-007 at a medical meeting in 2025.Initiate proof-of-concept study evaluating ziftomenib and imatinib in patients with advanced GIST in the first half of 2025.Nominate a next generation menin inhibitor development candidate targeting diabetes in the first half of 2025.Identify the maximum tolerated dose for KO-2806 as a monotherapy in the second half of 2024.Initiate one or more expansion cohorts for the combination of KO-2806 and cabozantinib in renal cell carcinoma in the first half of 2025.Present data from the KURRENT-HN trial of tipifarnib in combination with alpelisib in PIK3CA-dependent head and neck squamous cell carcinoma (HNSCC) in the first half of 2025. Conference Call and Webcast Kura’s management will host a webcast and conference call at 4:30 p.m. ET / 1:30 p.m. PT today, November 7, 2024, to discuss the financial results for the third quarter 2024 and to provide a corporate update. The live call may be accessed by dialing (800) 225-9448 for domestic callers and (203) 518-9708 for international callers and entering the conference ID: KURAQ3. A live webcast and archive of the call will be available online from the investor relations section of the company website at www.kuraoncology.com. 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-m AML. Kura has completed enrollment in a Phase 2 registration-directed trial of ziftomenib in R/R NPM1-m 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-m and KMT2A-r 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 HNSCC (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 Kura’s product candidates, ziftomenib, KO-2806 and tipifarnib, progress and expected timing of Kura’s drug development programs and clinical trials and submission of regulatory filings, the presentation of data from clinical trials, plans regarding regulatory filings and future clinical trials, the strength of Kura’s balance sheet and the sufficiency of cash, cash equivalents and short-term investments to fund its current operating plan into 2027. 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, 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. KURA ONCOLOGY, INC. Statements of Operations Data (unaudited) (in thousands, except per share data) Three Months Ended Nine Months Ended September 30, September 30, 2024 2023 2024 2023 Operating Expenses: Research and development $41,705 $29,328 $117,700 $82,702 General and administrative 18,179 13,145 53,040 36,340 Total operating expenses 59,884 42,473 170,740 119,042 Other income, net 5,480 3,871 15,974 9,197 Net loss $(54,404) $(38,602) $(154,766) $(109,845)Net loss per share, basic and diluted $(0.63) $(0.50) $(1.80) $(1.53)Weighted average number of shares used in computing net loss per share, basic and diluted 86,950 77,241 85,834 71,845 KURA ONCOLOGY, INC. Balance Sheet Data (unaudited) (in thousands) September 30, December 31, 2024 2023 Cash, cash equivalents and short-term investments $455,297 $423,957 Working capital 422,817 397,218 Total assets 478,837 448,935 Long-term liabilities 14,694 16,399 Accumulated deficit (876,205) (721,439)Stockholders’ equity 423,771 397,273 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