Estrogen receptor positive breast cancer

Presented compelling clinical results for palazestrant both as a monotherapy and in combination with CDK4/6 inhibitors, ribociclib and palbociclib, in Q4 2023 Initiated OPERA-01 pivotal Phase 3 monotherapy trial in Q4 2023; top-line results expected in 2026 60-patient Phase 2 studies in combination with each of ribociclib and palbociclib are fully enrolled; palazestrant-ribociclib clinical update to be presented at ESMO Breast Cancer Annual Congress 2024, May 15-17, 2024, in Berlin Cash, cash equivalents and marketable securities of $261.8 million as of December 31, 2023 SAN FRANCISCO, March 11, 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 women’s cancers, today reported financial results for the fourth quarter and full year ended December 31, 2023, and provided a corporate update. “In 2023 we demonstrated the unique opportunity ahead for palazestrant to make a meaningful impact on improving treatment options for women with ER+/HER2- breast cancer. We believe palazestrant’s activity on both wild-type and ESR1-mutant breast cancer, and its ability to safely combine with ribociclib, result in a highly differentiated pro this emerging new class of estrogen receptor-targeting therapies,” said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. “We have recently completed enrollment in our 60-patient Phase 2 study of 120 mg palazestrant in combination with 600 mg ribociclib, and we are looking forward to sharing an update on this study at the 2024 ESMO Breast Cancer Annual Congress. Beyond palazestrant, we recently declared a development candidate for our KAT6 program, OP-3136, and we are advancing towards an IND filing by the end of this year. Our mission at Olema is to improve the lives of women living with cancer and we are very pleased with the progress we are making.” Recent Corporate Highlights Presented interim clinical results of palazestrant in combination with CDK4/6 inhibitors ribociclib and palbociclib at the 2023 San Antonio Breast Cancer Symposium (SABCS), showing no significant drug-drug interaction, no dose-limiting toxicities and a tolerability pro with the FDA-approved labels of ribociclib or palbociclib plus an endocrine therapy. Presented palazestrant monotherapy Phase 2 clinical results at the European Society for Medical Oncology (ESMO) Congress 2023 in Madrid, Spain, as an oral presentation demonstrating compelling activity in both wild-type and ESR1-mutant tumor types. Initiated OPERA-01, our pivotal Phase 3 monotherapy clinical trial in the second- and third-line setting of ER+/HER2- advanced or metastatic breast cancer, including dosing first patients and activating multiple trial sites globally. Nominated OP-3136, an orally bioavailable KAT6 inhibitor, as a development candidate. OP-3136 demonstrated potent anti-tumor activity alone and in combination with both palazestrant and CDK4/6 inhibitors in preclinical ER+ breast cancer models. Announced the expansion of Olema's clinical collaboration with Novartis Institutes for BioMedical Research, Inc. (Novartis), increasing the size of the ongoing Phase 1/2 clinical study testing palazestrant in combination with ribociclib to approximately 60 patients. This study is fully enrolled. Completed a combined financing for up to $180 million including an equity private placement of approximately $130 million of common stock as well as a new senior secured credit facility with an aggregate principal amount of up to $50 million with Silicon Valley Bank (SVB), $25 million of which is currently available. Upcoming Milestones Present interim Phase 2 clinical results of palazestrant in combination with ribociclib at ESMO Breast Cancer Annual Congress 2024, May 15-17, 2024, in Berlin, Germany. Initiate Phase 1b/2 clinical study of palazestrant in combination with mTOR inhibitor, everolimus, in Q3 2024. File an Investigational New Drug, or IND, application with the FDA for OP-3136, a KAT6 inhibitor, in late 2024, and advance clinical development. Prepare for pivotal Phase 3 first-line trial in combination with CDK4/6 inhibitor, ribociclib. Fourth Quarter and Full-Year 2023 Financial Results Cash, cash equivalents and marketable securities as of December 31, 2023, were $261.8 million. Net loss was $26.8 million and $96.7 million for the quarter and year ended December 31, 2023, respectively, as compared to $26.2 million and $104.8 million for the quarter and year ended December 31, 2022, respectively. The increase in net loss for the fourth quarter was primarily related to increased spending on clinical operations and development-related activities, including personnel-related expenses, as Olema continues to advance palazestrant into late-stage clinical trials. This increase was offset by decreased spending on general and administrative activities and higher interest income earned from marketable securities. The decrease in net loss for the full year 2023 was primarily due to higher interest income earned from marketable securities. GAAP research and development (R&D) expenses were $25.9 million and $86.1 million for the quarter and year ended December 31, 2023, respectively, as compared to $21.6 million and $82.3 million for the quarter and year ended December 31, 2022, respectively. The increase in R&D expenses was primarily a result of increased spending on clinical operations and development-related activities including personnel-related costs as Olema continues to advance palazestrant into late-stage clinical development, which were offset by decreased spending on research-related activities. Non-GAAP R&D expenses were $23.0 million and $74.4 million for the quarter and year ended December 31, 2023, respectively, excluding $2.9 million and $11.8 million non-cash stock-based compensation expense, respectively. Non-GAAP R&D expenses were $18.2 million and $69.8 million for the quarter and year ended December 31, 2022, respectively, excluding $3.4 million and $12.5 million non-cash stock-based compensation expense, respectively. 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 $4.5 million and $18.8 million for the quarter and year ended December 31, 2023, respectively, as compared to $5.6 million and $24.7 million for the quarter and year ended December 31, 2022, respectively. The decrease in G&A expenses was primarily due to decreased spending on corporate- and legal-related costs, and personnel-related expenses. Non-GAAP G&A expenses were $3.1 million and $13.3 million for the quarter and year ended December 31, 2023, respectively, excluding $1.4 million and $5.5 million non-cash stock-based compensation expense respectively. Non-GAAP G&A expenses were $4.1 million and $18.3 million for the quarter and year ended December 31, 2022, excluding $1.5 million and $6.4 million non-cash stock-based compensation expense, respectively. 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 activity 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 currently being evaluated both as a single agent in an ongoing Phase 3 clinical trial, OPERA-01, and in Phase 2 combination studies with CDK4/6 inhibitors (palbociclib and ribociclib) and a PI3Ka inhibitor (alpelisib). For more information, please visit . About Olema Oncology Olema 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. In addition to our lead product candidate, palazestrant (OP-1250), a proprietary, orally-available complete estrogen receptor (ER) antagonist (CERAN) and a selective ER degrader (SERD), Olema is developing a potent KAT6 inhibitor. Olema is headquartered in San Francisco and has operations in Cambridge, Massachusetts. For more information, please visit us at . Non-GAAP Financial Information The 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 Statements Statements 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,” “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 Olema’s financial condition and resources, results of operations, cash position, the timeline of Olema’s pivotal Phase 3 monotherapy clinical trial (OPERA-01), 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, efficacy and therapeutic effects of palazestrant, the potential of palazestrant to improve treatment options or outcomes for women living with ER+/HER2- breast cancer, palazestrant’s combinability with other drugs, and the sufficiency and timing of Olema’s preclinical program, including the potential beneficial characteristics of its KAT6 inhibitor compounds, its applicability to breast and other cancers and the timing of a potential IND application. 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 Annual Report on Form 10-K for the year ended December 31, 2023, 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) December 31, December 31, 2023 2022 Cash, cash equivalents and marketable securities $ 261,807 $ 204,421 Total assets 276,945 215,645 Total current liabilities 21,621 16,549 Total liabilities 23,050 18,099 Total stockholders’ equity 253,895 197,546 Total liabilities and stockholders’ equity $ 276,945 $ 215,645 Olema Pharmaceuticals, Inc. Condensed Consolidated Statements of Operations (In thousands, except share and per share data) Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 Operating expenses: Research and development (1) $ 25,872 $ 21,584 $ 86,140 $ 82,274 General and administrative (2) 4,544 5,635 18,821 24,714 Total operating expenses 30,416 27,219 104,961 106,988 Loss from operations (30,416 ) (27,219 ) (104,961 ) (106,988 ) Other income (expense): Interest income 3,551 973 8,325 2,228 Other income (expense): 93 67 (19 ) (27 ) Total other income 3,644 1,040 8,306 2,201 Net loss $ (26,772 ) $ (26,179 ) $ (96,655 ) $ (104,787 ) Net loss per share, basic and diluted $ (0.49 ) $ (0.65 ) $ (2.14 ) $ (2.62 ) Weighted average shares used to compute net loss per share, basic and diluted 54,783,945 40,188,466 45,247,098 39,995,460 Reconciliation of GAAP to Non-GAAP Information (In thousands) Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 (1) Research and development reconciliation GAAP research and development (3) $ 25,872 $ 21,584 $ 86,140 $ 82,274 Less: share-based compensation expense 2,911 3,374 11,769 12,462 Non-GAAP research and development $ 22,961 $ 18,210 $ 74,371 $ 69,812 (2) General and administrative reconciliation GAAP general and administrative $ 4,544 $ 5,635 $ 18,821 $ 24,714 Less: share-based compensation expense 1,440 1,487 5,487 6,367 Non-GAAP general and administrative $ 3,104 $ 4,148 $ 13,334 $ 18,347 (3) Research and development expenses for the twelve-months ended December 31, 2022 include an $8.0 million upfront payment in connection to the Aurigene Agreement. IR and Media Contact: Geoffrey Mogilner, Vice President, Investor Relations and Communications ir@olema.com

DALLAS, March 6, 2024 /PRNewswire/ -- When patients and scientists come together to fuel scientific discovery, advancements are possible in breast cancer research that can ultimately improve patient treatment and outcomes. Susan G. Komen®, the world's leading breast cancer organization, plays a pivotal role as a convenor of researchers and patient advocates who can work together, share ideas and utilize big data approaches to address immediate needs or identify outstanding challenges in the fight against breast cancer. Continue Reading Susan G. Komen Breast Cancer Hackathon Challenge "We can impact care for all people and change the way we treat patients in the future by harnessing big data to identify potential new therapies to treat this disease," said Jerome Jourquin, senior director of Data Science at Susan G. Komen. "When people with unique skillsets and different backgrounds collaborate, we make discoveries that may not otherwise be possible, but these are novel discoveries that have the potential to make a long-lasting impact." Susan G. Komen, along with partners UT Southwestern and Lyda Hill Philanthropies, held its first Breast Cancer Hackathon Challenge in 2023 where 54 participants – representing 5 countries, 20 U.S. States and 34 institutions – had 48 hours to address one of three breast cancer challenges using publicly-available patient and/or pre-clinical data. The participants included students, oncologists, breast cancer researchers and data scientists, all bringing their own skillset to the fight against breast cancer. They worked alongside patient advocates who shared their personal perspectives and experiences with hackers so that their work could have the greatest impact on patient outcomes. The three compelling challenges addressed during the Hackathon were: Topic 1: Predict and visualize combined functional effects of germline (present at birth) and somatic (acquired in life) mutations in breast cancer. Topic 2: Define and compare metabolic states of cell types found in the breast tumor microenvironment. Topic 3: Identify and prioritize personal drug combinations based on the genomic landscape of breast cancer. Harikrishna Nakshatri, PhD, of Indiana University, led the winning Hackathon team and addressed Topic 1. His team developed a web-based application and identified two new molecules that are associated with a common genetic mutation that is found in 30% to 40% of all breast cancers and is known to increase breast cancer risk. These molecules are believed to work together to drive estrogen receptor-positive (ER+) breast cancer, which accounts for about 70% to 80% of all breast cancers. "Bringing these multidisciplinary teams together sparked new collaborations and a lot of creativity among the teams and was the first time many of the younger researchers and data scientists had worked with patient advocates," said Kimberly Sabelko, PhD, vice president of Scientific Strategy and Programs at Susan G. Komen. "The Hackathon was inspiring and impactful – the teams' work and the resulting two grants we're funding may help identify new potential drug targets and additional treatment options in the future." After the Hackathon, participants were invited to apply for grants from Susan G. Komen to build on the work they started at the event. Dr. Nakshatri's application was selected through a rigorous peer-review process led by a panel of scientists and patient advocates, and he will receive $200,000 over two years to continue his research. This work will build upon the computational approach taken at the Hackathon that identified these mutations from a large database of patient tumor samples, by using deep learning-based analytical tools to potentially identify even more mutations that may be targets for breast cancer therapies. Xin Lu, PhD, of University of Notre Dame, will also receive a $200,000 grant over two years to continue work his team started at the Hackathon while addressing Topic 2. His team used machine learning tools to analyze breast cancer datasets and identified a specific subpopulation of immune cells based on their unique metabolism, which are only expressed in tumors and are also known to drive disease progression. Based on their approach, they were honored with the Advocate Choice Award at the event for their efforts to incorporate the patient voice in their project. His research team will advance these initial findings by creating a novel metabolic model to identify molecules that inhibit these cells, and then they will validate the function of these molecules in laboratory experiments to determine their potential as new immunotherapeutic targets. "Tackling the intricate challenges in our understanding of breast cancer to enhance patient outcomes remains an ongoing journey," said Victoria Smart, senior vice president of Mission at Susan G. Komen. "Komen is profoundly appreciative of the unwavering dedication from the research and patient advocacy communities in addressing these challenges. By focusing on the most crucial needs within our communities and investing in groundbreaking research for the prevention, treatment and cure of breast cancer, we are saving more lives. Our progress is fueled by the exceptional leadership of researchers like Drs. Nakshatri and Lu, as well as the transformative efforts unfolding globally." About Susan G. Komen® Susan G. Komen® is the world's leading nonprofit breast cancer organization, working to save lives and end breast cancer forever. Komen has an unmatched, comprehensive 360-degree approach to fighting this disease across all fronts and supporting millions of people in the U.S. and in countries worldwide. We advocate for patients, drive research breakthroughs, improve access to high-quality care, offer direct patient support and empower people with trustworthy information. Founded by Nancy G. Brinker, who promised her sister, Susan G. Komen, that she would end the disease that claimed Suzy's life, Komen remains committed to supporting those affected by breast cancer today, while tirelessly searching for tomorrow's cures. Visit komen.org or call 1-877 GO KOMEN. Connect with us on social at : Amanda DeBard Susan G. Komen (972) 701-2131 [email protected] SOURCE Susan G. Komen for the Cure

Data published in Molecular Cancer Therapeutics describes the scientific background underlying the design, discovery and optimization of palazestrant (OP-1250)Pre-clinical results demonstrate that palazestrant, as both a CERAN and a SERD, has a highly differentiated mechanism of action as a potential therapy for advanced ER+/HER2- breast cancer SAN FRANCISCO, March 06, 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 women’s cancers, today announced that Molecular Cancer Therapeutics, an American Association for Cancer Research journal, has selected as a featured article a data publication that describes the distinct properties of palazestrant (OP-1250). The paper, titled “Palazestrant (OP-1250), a Complete Estrogen Receptor Antagonist, Inhibits Wild-type and Mutant ER-positive Breast Cancer Models as Monotherapy and in Combination”, describes the scientific background underlying the design, discovery and optimization of palazestrant. “The research described in this paper reviews the deliberate design and processes used in discovering and optimizing palazestrant as a molecule purpose-built to address a crucial unmet need in the treatment of women’s cancers, and we are delighted that Molecular Cancer Therapeutics has featured our work,” said David C. Myles, Ph.D., Olema’s Chief Discovery and Non-Clinical Development Officer. “What’s even more exciting is to see how faithfully the pre-clinical research predicted the behavior of palazestrant now that it is in late-stage clinical development. We saw the potential then, as told in the paper, and we believe that every day brings us closer to having a real impact transforming the treatment paradigm for women with cancer.” As part of the discovery and optimization process, palazestrant was assessed across an extensive series of biochemical, cell culture, and in vivo assays comparing it with other antiestrogens and compounds that are either approved for use by the FDA or are currently in clinical development, including aromatase inhibitors, selective ER modulators (SERMs), traditional SERDs, and proteolysis-targeting chimeras (PROTACs). As a CERAN, palazestrant has a distinct mechanism of action (MOA), and though it actively degrades the ER, the paper shows that degradation alone is not a reliable mechanism to drive the efficacy of an endocrine agent. In mouse xenograft models, palazestrant demonstrated excellent pharmacokinetics, was well tolerated, showed synergy with CDK4/6 inhibitors, and was highly effective at reducing tumor growth in both wild-type and ESR1-mutant ER+ breast cancer. In addition, in an ESR1-mutant intercranial xenograft model, palazestrant inhibited tumor growth and improved survival of animals with CNS metastases, even after stopping drug treatment. The paper can be accessed in the latest print edition of Molecular Cancer Therapeutics or online at https://aacrjournals.org/mct/article/doi/10.1158/1535-7163.MCT-23-0351/731746/Palazestrant-OP-1250-a-Complete-Estrogen-Receptor. 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 currently being evaluated both as a single agent in an ongoing Phase 3 clinical trial, OPERA-01, and in Phase 2 combination studies with CDK4/6 inhibitors (palbociclib and ribociclib) and a PI3Ka inhibitor (alpelisib). For more information, please visit www.opera01study.com. About Olema Oncology Olema 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. In addition to our lead product candidate, palazestrant (OP-1250), a proprietary, orally-available complete estrogen receptor (ER) antagonist (CERAN) and a selective ER degrader (SERD), Olema is developing a potent KAT6 inhibitor. Olema is headquartered in San Francisco and has operations in Cambridge, Massachusetts. For more information, please visit us at www.olema.com. Forward Looking Statements Statements 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,” “expect,” “will,” “may,” “goal,” “potential” 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 Olema’s preclinical program, including the potential beneficial characteristics of palazestrant (OP-1250), both as a monotherapy and in combination with CDK4/6 inhibitors, palazestrant’s potential to address to address an unmet need in the treatment of women’s cancers, and palazestrant’s ability to transform the treatment paradigm for women with cancer. 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, 2023, 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. Contact:Geoffrey Mogilner, Vice President, Investor Relations and Communicationsir@olema.com