OLMA Olema Pharmaceuticals Inc

 

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): December 09, 2024

 

 

Olema Pharmaceuticals, Inc.

(Exact name of Registrant as Specified in Its Charter)

 

 

Delaware			001-39712	30-0409740
(State or Other Jurisdiction of Incorporation)			(Commission File Number)	(IRS Employer Identification No.)
780 Brannan Street
San Francisco, California				94103
(Address of Principal Executive Offices)				(Zip Code)

 

Registrant’s Telephone Number, Including Area Code: 415 651-3316

 

N/A

(Former Name or Former Address, if Changed Since Last Report)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

Securities registered pursuant to Section 12(b) of the Act:

Title of each class		Trading Symbol(s)		Name of each exchange on which registered
Common Stock, par value $0.0001 per share		OLMA		The Nasdaq Global Select Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

 

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Item 7.01 Regulation FD Disclosure.

On December 9, 2024, Olema Pharmaceuticals, Inc. (the “Company”) announced that the U.S. Food and Drug Administration (“FDA”) has cleared its Investigational New Drug (“IND”) application for OP-3136, a novel small molecule that potently and selectively inhibits KAT6, a validated epigenetic target that is dysregulated in breast and other cancers. A copy of the press release issued in connection with the announcement is being furnished as Exhibit 99.1 to this Current Report on Form 8-K.

 

On December 10, 2024, the Company announced updated clinical results from its ongoing Phase 1b/2 study of palazestrant in combination with CDK4/6 inhibitor (“CDK4/6i”), ribociclib in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (“ER+/HER2-”) advanced or metastatic breast cancer. A copy of the press release issued in connection with the announcement is being furnished as Exhibit 99.2 to this Current Report on Form 8-K.

On December 10, 2024, the Company made available on its website a presentation to be shared with investors and others from time to time. A copy of this presentation is being furnished as Exhibit 99.3 to this Current Report on Form 8-K.

The information in Exhibits 99.1, 99.2, and 99.3 attached hereto is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended or the Exchange Act, except as expressly set forth by specific reference in such filing.

Item 8.01 Other Events.

FDA Clearance of Investigational New Drug Application for OP-3136

 

On December 9, 2024, the Company announced that the FDA has cleared its IND application for OP-3136.

 

The Company expects to initiate the Phase 1 clinical trial in early 2025.

 

Interim Results from the Phase 1b/2 Study of Palazestrant in Combination with Ribociclib

 

On December 10, 2024, the Company announced updated clinical results from its ongoing Phase 1b/2 study of palazestrant in combination with CDK4/6 inhibitor, ribociclib in patients with ER+/HER2- advanced or metastatic breast cancer. Results as of a data cutoff date of September 25, 2024 will be presented at the San Antonio Breast Cancer Symposium (“SABCS”) being held December 10-13, 2024. Updated results as of a data cutoff date of November 11, 2024 are detailed below.

Enrollment

62 patients with advanced or metastatic ER+/HER2- breast cancer were treated with palazestrant (n=56 at the recommended Phase 2 dose of 120 mg once daily continuously) plus ribociclib (600 mg once daily, three weeks on treatment followed by one week off treatment).

 

Efficacy

Palazestrant combined with ribociclib showed promising clinical activity including tumor responses, prolonged disease stabilization, and progression-free survival (“PFS”) in patients with ESR1wild-type and ESR1 activating mutations at baseline and in those previously treated with one or two lines of CDK4/6i. Efficacy data continue to mature; 30 (48%) patients remained on treatment as of the November 11, 2024 data cutoff date, and the longest duration on treatment was approximately 18 months (79 weeks) and was ongoing as of the data cutoff date of November 11, 2024.

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1 CBR is the proportion of patients who remained on treatment through at least 24 weeks with a confirmed complete response or partial response, or stable disease.

 

Safety and Tolerability

Across 62 treated patients, the combination of up to 120 mg of palazestrant with the approved dose for metastatic disease of 600 mg of ribociclib daily was well tolerated with no new safety signals or increase in toxicity. The overall safety profile was consistent with the established safety profile of ribociclib 600 mg plus an endocrine therapy.

 

Pharmacokinetics

Palazestrant did not affect ribociclib drug exposure when compared with published exposure data for single-agent ribociclib. Steady-state trough values showed no clinically significant difference between the combination and single-agent palazestrant.

Conclusions

Findings from this study support the advancement of palazestrant in combination with ribociclib into clinical development for the first-line treatment of ER+/HER2- advanced or metastatic breast cancer.

Forward Looking Statements

Statements contained in this Current Report on Form 8-K, including the exhibits furnished herewith, 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,” “will,” “may,” “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 forward-looking statements include, without limitation, statements regarding the advancement of OP-3136 into clinical development, including timelines for initiation and enrollment for potential clinical studies, the combinability of OP-3136 with other drugs and potential beneficial characteristics, including but not limited to safety, tolerability, activity, efficacy and therapeutic effects of OP-3136 as a monotherapy and in combination with other drugs, potential beneficial characteristics, safety, tolerability, efficacy, and therapeutic effects of palazestrant, and the development of palazestrant, in each case, including in combination with other drugs, the potential of palazestrant to work in combination with ribociclib to suppress tumor growth or extend PFS, palazestrant in combination with ribociclib advancing into clinical development for the first-line treatment of ER+/HER2- advanced or metastatic breast cancer, the timing and likelihood of initiating clinical trials, and the timing of generating and announcing trial results, the timing and content of potential New Drug Application submissions, and commercial launch of product candidates, including the timing thereof. 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 other 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 set forth in the forward-looking statements.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits

 

Exhibit No.	Description
99.1	Press Release, dated December 9, 2024, of Olema Pharmaceuticals, Inc.
99.2	Press Release, dated December 10, 2024, of Olema Pharmaceuticals, Inc.
99.3	Investor Presentation, dated December 10, 2024, of Olema Pharmaceuticals, Inc.

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Exhibit No.	Description
104	Cover Page Interactive Data File (embedded within the Inline XBRL document).

 

 

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SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

			OLEMA PHARMACEUTICALS, INC.
Date:	December 10, 2024	By:	/s/ Shane Kovacs
			Shane Kovacs Chief Operating and Financial Officer

 

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EXHIBIT 99.1

Olema Oncology Announces FDA Clearance of Investigational New Drug Application for OP-3136, a Potent KAT6 Inhibitor

 

 

SAN FRANCISCO, CA - (GLOBE NEWSWIRE) - December 9, 2024 - 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 that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for OP-3136, a novel small molecule that potently and selectively inhibits KAT6, a validated epigenetic target that is dysregulated in breast and other cancers.

 

"We are very pleased to have received notification from the FDA that OP-3136 may proceed into the clinic,” said David C. Myles, Ph.D., Chief Discovery and Non-Clinical Development Officer of Olema Oncology. “The compelling activity demonstrated by OP-3136 in preclinical models both as a single agent and in combination with palazestrant has generated strong investigator interest in OP-3136. We expect to initiate the Phase 1 clinical trial early next year and are excited by OP-3136’s potential in breast cancer and beyond.”

 

About Olema Oncology

Olema Oncology is a clinical-stage biopharmaceutical company committed to transforming the standard of care and improving outcomes for patients living with breast cancer and beyond. 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 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,” “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 advancement of OP-3136 into clinical development, including timelines for initiation and enrollment, the combinability of OP-3136 with other drugs and potential beneficial characteristics of OP-3136 as a monotherapy and in combination with other drugs. Because such statements deal with future events and are based on Olema’s current expectations, they are subject to various risks

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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 other 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.

 

Media and Investor Relations Contact

Courtney O’Konek

Vice President, Corporate Communications

Olema Oncology

media@olema.com

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EXHIBIT 99.2

Olema Oncology Presents Updated Clinical Results for Palazestrant in Combination with Ribociclib at the San Antonio Breast Cancer Symposium

 

SAN FRANCISCO - December 10, 2024 - (GLOBENEWSWIRE) - 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 updated clinical results from the ongoing Phase 1b/2 study of palazestrant in combination with CDK4/6 inhibitor, ribociclib, in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic breast cancer. Results as of September 25, 2024, will be presented in a poster session at the San Antonio Breast Cancer Symposium (SABCS 2024) being held December 10-13 at the Henry B. Gonzalez Convention Center in San Antonio, Texas. Updated results as of November 11, 2024, are detailed below.

 

“We believe these data, while still maturing, are compelling and highly differentiated, with robust clinical activity shown across both ESR1 wild-type and mutant patient populations after prior treatment with a CDK4/6 inhibitor in combination with endocrine therapy. Mutations in the ESR1 gene are one of the most common resistance mechanisms arising during current front-line standard of care treatment, leading to progression. Palazestrant has demonstrated its potential to work in combination with ribociclib by completely blocking estrogen receptor signaling and suppressing tumor growth to extend progression-free survival after prior progression on the current standard of care, regardless of ESR1 status,” said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. “These data provide the foundation to initiate OPERA-02, our planned pivotal Phase 3 trial of palazestrant in combination with ribociclib in front-line metastatic breast cancer next year. We look forward to sharing mature data from this combination in 2025 and continuing the development of palazestrant as we work to advance our goal of creating innovative therapies to improve the lives of breast cancer patients.”

 

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Interim Results from the Phase 1b/2 Study of Palazestrant in Combination with Ribociclib

Enrollment

62 patients with advanced or metastatic ER+/HER2- breast cancer were treated with palazestrant (n=56 at the recommended Phase 2 dose (RP2D) of 120 mg once daily) plus ribociclib (600 mg once daily; three weeks on treatment followed by one week off treatment).

Efficacy

Palazestrant combined with ribociclib showed promising clinical activity including tumor responses, prolonged disease stabilization, and progression-free survival in patients with ESR1 wild-type and ESR1 activating mutations at baseline and in those previously treated with one or two lines of CDK4/6i. Efficacy data continue to mature; 30 (48%) patients remain on treatment, and the longest duration on treatment is approximately 18 months (79 weeks) and was ongoing as of the data cutoff date of November 11, 2024.

 

Safety and Tolerability

Across 62 treated patients, the combination of up to 120 mg of palazestrant with the approved dose for metastatic disease of 600 mg of ribociclib daily was well tolerated with no new safety signals or increase in toxicity. The overall safety profile was consistent with the established safety profile of ribociclib 600 mg plus an endocrine therapy.

 

Pharmacokinetics

Palazestrant did not affect ribociclib drug exposure when compared with published exposure data for single-agent ribociclib. Steady-state trough values showed no clinically significant difference between the combination and single-agent palazestrant.

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Conclusions

Findings from this study support the advancement of palazestrant in combination with ribociclib into clinical development for the first-line treatment of ER+/HER2- advanced or metastatic breast cancer.

 

“Palazestrant is not an endocrine therapy where you need to wait six months to see a patient derive benefit. We have seen impressive responses quickly and a significant reduction of disease burden. The patients I have seen feel much better than they have on other treatments available in the armamentarium today,” said Virginia Borges, M.D., Professor, Medicine-Medical Oncology at the University of Colorado, and Principal Investigator for the palazestrant plus ribociclib combination study. “The findings presented at SABCS show that the combination of palazestrant and ribociclib is well-tolerated with meaningful preliminary efficacy that I believe has the potential to outperform the current standard of care and change how metastatic breast cancer is treated. I look forward to the continued development of palazestrant.”

 

A copy of the poster presented at SABCS reflecting a September 25, 2024 data cutoff date will be made available on the Publications page of Olema’s website in alignment with the Symposium’s embargo policy.

 

1CBR is the proportion of patients who remained on treatment through at least 24 weeks with a confirmed complete response or partial response, or stable disease.

 

Conference Call Information

Olema will hold a conference call to discuss these results today with the investment community at 8:00 a.m. ET (7:00 a.m. CT). Register to join the webcast by visiting the Events and Presentations page on the Investors section 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 preclinical studies, palazestrant completely blocks ER-driven transcriptional activity in both ESR1 wild-type and mutant forms of breast cancer cell. In Olema’s ongoing clinical trials for advanced or metastatic ER+/HER2- breast cancer, palazestrant has demonstrated anti-tumor activity along with attractive pharmacokinetics and exposure, favorable tolerability, 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 Olema Oncology

Olema Oncology is a clinical-stage biopharmaceutical company committed to transforming the standard of care and improving outcomes for patients living with breast cancer and beyond. 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

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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 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,” “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 potential beneficial characteristics, safety, tolerability, efficacy, and therapeutic effects of palazestrant and the development of palazestrant, in each case, including in combination with other drugs, the potential of palazestrant to work in combination with ribociclib to suppress tumor growth or extend progression-free survival, the initiation and timing of clinical trials, and Olema’s potential to transform the endocrine therapy standard of care treatments for patients living with ER+/HER2- metastatic breast 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, 2024, and other 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.

 

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Media and Investor Relations Contact
Courtney O’Konek

Vice President, Corporate Communications

Olema Oncology

media@olema.com

 

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Palazestrant in Combination with Ribociclib Clinical Update SABCS 2024 December 10, 2024 EXHIBIT 99.3

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Legal disclaimer This presentation contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Statements in this presentation that are not statements of historical fact are forward-looking statements. Words such as “anticipate,” “believe,” “estimate,” “expect,” “goal,” “intend,” “may,” “plan,” “potential,” “project,” “will,” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements necessarily contain these identifying words. Such forward-looking statements include, without limitation, statements regarding our research and clinical development plans, the scope, progress, results and costs of developing our product candidates or any other future product candidates, strategy, market size and opportunity, clinical trial designs, regulatory matters, including the timing and likelihood of success of obtaining drug approvals, the timelines for the potential initiation of clinical trials and the results of any such clinical trials of palazestrant (OP-1250) as a monotherapy and in combination trials, including OPERA-01, the Company’s pivotal Phase 3 monotherapy clinical trial, and OPERA-02, the Company's potential pivotal Phase 3 clinical trial of palazestrant in combination with ribociclib, the timelines for potential commercial launch and related preparatory work, the sufficiency and potential beneficial characteristics,  profile, safety, tolerability, efficacy and therapeutic effects of palazestrant as a monotherapy and in combination trials, the progression-free survival rate under palazestrant in combination trials, the potential of palazestrant to become a therapeutic leader and a best-in-class treatment option for ER+/HER2- metastatic breast cancer and a backbone therapy for women living with breast cancer and beyond, the combinability of palazestrant with other drugs, the timelines for initiation of potential clinical trials for and the results of any such clinical trials in connection with our KAT6 inhibitor program, including OP-3136, the potential value and impact of a KAT6 inhibitor program, the best-in-class potential for OP-3136, the potential beneficial characteristics, profile, safety, efficacy, tolerability, and therapeutic effects of OP-3136, our ability to complete certain milestones, our financial condition, our opportunity in breast cancer and beyond, our ability to impact treatment for endocrine-driven cancers, cash position and runway and sufficiency of our financial resources, and the sufficiency and expertise of our management team. These forward-looking statements are based on the beliefs of the Company’s management as well as assumptions made by and information currently available to the Company. Such statements reflect the current views of the Company with respect to future events and are subject to known and unknown risks, including business, regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about the Company, including, without limitation, risks inherent in developing products and technologies, future results from the Company’s ongoing and planned clinical trials, the Company’s ability to obtain adequate financing to fund its planned clinical trials and other expenses, trends in the industry, the legal and regulatory framework for the industry and future expenditures, and other risks and uncertainties affecting the Company, including those described under the caption "Risk Factors" and elsewhere in the Company‘s Quarterly Reports on Form 10-Q, Annual Report on Form 10-K, and other filings and reports the Company files with the Securities and Exchange Commission from time to time. In light of these risks and uncertainties, the events or circumstances referred to in the forward-looking statements may not occur. The actual results may vary from the anticipated results and the variations may be material. These forward-looking statements should not be taken as forecasts or promises nor should they be taken as implying any indication, assurance or guarantee that the assumptions on which such forward-looking statements have been made are correct or exhaustive or, in the case of the assumptions, fully stated in this presentation. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date this presentation is given. This presentation discusses product candidates that are under clinical study and which have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of these product candidates for the use for which such product candidates are being studied. This presentation incorporates publicly-available third-party data that we have not independently verified. There are risks inherent in conducting cross-trial comparisons and the results should be interpreted with caution. The presentation of such third-party data does not represent a head-to-head comparison of how palazestrant, in monotherapy or in combination, or OP-3136 performed against any other third-party drug candidate or study. Rather, such third-party data has been pulled by us from publicly-available sources for supplemental informational purposes, only. We caution you that any comparisons against third-party data set forth herein should not be viewed as a side-by-side comparison, and you should not rely on the completeness or accuracy of our presentation of the results of any third-party drug candidate in these slides, due to differences in study design, how other companies quantify or qualify eligibility criteria, and how results are recorded, among other distinguishing factors and uncertainties. Because we may be unaware of or may not adequately present various distinguishing factors and uncertainties, the comparisons set forth herein may not properly present such third-party data, which may differ materially from the data as presented here. Investors are encouraged to independently review third party data and should not rely on our presentation of such data (including any such data placed in comparison with the performance of palazestrant) as a single measure to evaluate our business. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products.

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— We are on a mission to elevate patient care in breast cancer and beyond Expertise in endocrine-driven cancers with mechanistically superior scientific approach that fully inactivates estrogen receptors OP-1250, a promising potential backbone therapy for ER+/HER2- breast cancer in late-stage clinical development, forms basis of breast cancer program Exciting new and potent KAT6 inhibitor with potential to significantly impact breast cancer treatment; IND cleared by FDA and initiation of Phase 1 clinical trial anticipated early 2025 Management and Board with deep expertise developing and commercializing oncology medicines Molecular Advantage Lead Asset – Palazestrant OP-3136 Expands Pipeline Proven Leadership

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Rapidly advancing clinical pipeline Palazestrant second/third-line and first-line clinical trials in metastatic breast cancer Discovery Non-Clinical Phase 1 Phase 2 Phase 3 2nd/3rd line monotherapy Combo therapy with PI3Kαi alpelisib with PIK3CA mutated Combo therapy with mTOR inhibitor everolimus Indication Palazestrant (OP-1250) - ER+/HER2- Metastatic Breast Cancer Combo therapy with CDK4/6i ribociclib Combo therapy with CDK4/6i palbociclib OP-3136 KAT6 Inhibitor - Oncology ER+/HER2- metastatic breast cancer/castrate-resistant prostate cancer/lung cancer KAT6 = lysine acetyltransferase 6; ER = estrogen receptor; HER2 = human epidermal growth factor receptor 2; CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; PI3Kαi = phosphatidylinositol 3-kinase alpha inhibitor; mTORi = mammalian target of rapamycin inhibitor; PI3Kαi = phosphoinositide-3 kinase alpha-specific inhibitors; PI3KCA = phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha 1st line combo with CDK4/6i ribociclib Initiation expected mid-2025in collaboration with In collaboration with In collaboration with In collaboration with Phase 1 clinical trial initiation expected early 2025 NEW! On track for top-line data in 2026

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“A Phase 1b/2 study of palazestrant (OP-1250) in combination with ribociclib, in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-), advanced or metastatic breast cancer” SABCS 2024 Poster #P2-09-16

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Phase 1b/2 combination study design Key eligibility criteria Women or men with ER+/HER2– advanced or metastatic breast cancer Up to 2 prior endocrine therapies ± a CDK4/6i for locally advanced or metastatic disease; up to 1 prior line of chemotherapy for advanced or metastatic breast cancer was allowed Evaluable disease (measurable by RECIST v1.1 or bone only) Screening QTcF <450 ms, resting heart rate 50-90 beats/min ER+/HER2- advanced or metastatic breast cancer (CDK4/6i-naïve or previously treated) Part 1: Dose escalation Part 2: Dose expansion Primary endpoints: DLTs, MTD and/or RP2D of palazestrant when administered in combination with ribociclib, incidence and severity of adverse events, PK Secondary endpoints: ORR (CR + PR), CBR (CR + PR + SD ≥ 24 weeks), DOR Primary endpoints: incidence and severity of adverse events, PK Secondary endpoints: ORR (CR + PR), CBR (CR + PR + SD ≥ 24 weeks), DOR, time to progression, PFS + Palazestrant 120 mg+ Ribociclib 600 mg Ribociclib 600 mg Palazestrant 120 mg 60 mg 30 mg CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; CBR = clinical benefit rate; CR = complete response; ctDNA = circulating tumor DNA; DLT = dose-limiting toxicity; DOR = duration of response; MTD = maximum tolerated dose;ORR = objective response rate; PK = pharmacokinetics; PR = partial response; QTcF = QT corrected for heart rate using Fridericia's formula RECIST = response evaluation criteria in solid tumors; RP2D = recommended Phase 2 dose; SD = stable disease

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Demographics N=62; N=56 at 120 mg 58% with visceral disease 68% with measurable disease 77% received prior endocrine therapy in advanced setting 74% received prior CDK4/6i + ET 34 (55%) patients received 1 prior line of CDK4/6i Palbociclib, n=23; abemaciclib n=7 ribociclib, n=4      12 patients (19%) received 2 prior lines of CDK4/6i Palbociclib → abemaciclib, n=3 Palbociclib → palbociclib, n=3 Palbociclib → ribociclib, n=3   Ribociclib → ribociclib, n=1 Abemaciclib → palbociclib, n=1   Palbociclib → experimental CDK4/6i, n=1 28% with ESR1 mutation Data cutoff date: November 11, 2024. a ESR1 mutations in ctDNA at baseline were determined centrally using SafeSEQ Breast Cancer Panel (Sysmex Inostics, Baltimore, MD). Two samples were not evaluable. CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; ctDNA = circulating tumor DNA; ECOG = Eastern Cooperative Oncology Group; ESR1 = estrogen receptor 1 gene Patient Characteristics Total (N=62) Median age (years) 61 Range 28–85 Female sex 62 (100%) Premenopausal 9 (15%) ECOG performance status, n (%) 0 38 (61%) 1 24 (39%) Measurable disease at baseline, n (%) 42 (68%) Visceral disease, n (%) 36 (58%) Prior lines of therapy in advanced setting, n (%) 0 14 (23%) 1 29 (47%) 2 14 (23%) 3 5 (8%) Prior lines of endocrine therapy in advanced setting, n (%) 0 14 (23%) 1 35 (56%) 2 13 (21%) Types of prior therapy in advanced setting, n (%) CDK4/6 inhibitor 46 (74%) Aromatase inhibitor (AI) 33 (53%) Fulvestrant 25 (40%) Chemotherapy 11 (18%) ESR1 mutations at baseline (ctDNA), n/N (%) 17/60a evaluated (28%)

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Well tolerated with no DLTs; safety profile consistent with ribociclib + ET Treatment-emergent AEs TEAEs in ≥25% of patients Palazestrant + Ribociclib** MONALEESA-2*Letrozole + Ribociclib† (n = 62) (n = 334) All grades‡ Grade 3 Grade 4 All grades Grade 3 Grade 4 Neutropenia§ 51 (82%) 28 (45%) 6 (10%) 93%‖ 49% 11% Nausea 49 (79%) 2 (3%) 0% 52% 2% 0% Fatigue 37 (60%) 2 (3%) 0% 37% 2% <1% Diarrhea 31 (50%) 2 (3%) 0% 35% 1% 0% Anemia 27 (44%) 1 (2%) 0% 57%‖ 2% 0% WBC decrease 26 (42%) 10 (16%) 1 (2%) 93%‖ 31% 3% Constipation 24 (39%) 0% 0% 25% 1% 0% Creatinine increased 20 (32%) 0% 0% 20% 1% 0% Vomiting 20 (32%) 1 (2%) 0% 29% 4% 0% ECG QT prolonged 19 (31%) 3 (5%) 0% 43%¶ 8%¶ NR Arthralgia 18 (29%) 0% 0% 27% 1% NR Lymphocyte count decreased 16 (26%) 5 (8%) 1 (2%) 51%‖ 12% 2% Cough 16 (26%) 0% 0% 20% 0% 0% LDH increased 16 (26%) 0% 0% NR NR NR Data cutoff date: November 11, 2024. Data shown are n or n (%). * NOTE: This analysis is the aggregation of results across independent studies. There are risks inherent in conducting cross-trial comparisons and results should be interpreted with caution. Refer to further disclaimers on slide 2. **Includes 3 patients at each of 30 mg and 60 mg palazestrant and 56 patients at 120 mg palazestrant in combination with 600 mg ribociclib. †Adverse reactions reported in ≥10% of patients who received ribociclib plus letrozole in the MONALEESA-2 study.(KISQALI (ribociclib). Prescribing information. Novartis; 2022; Hortobagyi, 2016) ‡Two subjects experienced Grade 5 AEs, heart failure and depressed level of consciousness not related to study drugs but disease progression. §Combined term includes neutropenia, decreased neutrophil count and febrile neutropenia. ‖These values were taken from MONALEESA-2 lab abnormalities data; source: KISQALI (ribociclib). Prescribing information. Novartis; 2022. ¶Ribociclib + fulvestrant in MONALEESA-3 per the Ribociclib Approval Package (NUMBER:209092Orig1s001, June 2018); ribociclib + non-steroidal aromatase inhibitors in MONALEESA-7: all grade QTcF prolongation was 46.5% (Grade 2, 5.3%; Grade 3, 9%). Aggregate analysis (n=1054 patients) . AE = adverse event; DLTs = dose-limiting toxicity; ET = endocrine therapy; NR = not reported; TEAEs = treatment-emergent adverse events; WBC = white blood cell No patients discontinued only palazestrant due to a treatment-emergent AE; 4 patients discontinued both treatments due to a TEAE; 2 patients discontinued ribociclib but stayed on palazestrant 30 (48%) patients still on treatment at the data cut-off Overall safety and tolerability profile consistent with ribociclib + endocrine therapy No DLTs were observed during dose escalation and the maximum tolerated dose was not reached

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Six-month PFS rate of 73% in all patients, 68% in those with prior CDK4/6i​ Median follow-up of 12 months; median PFS not yet reached; 48% of patients remain on study​ Data cutoff date: November 11, 2024 * Follow up was calculated from first dose date to data cutoff date regardless of disease progression status.CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; PFS = progression-free survival Patients with prior CDK4/6i plus ET (N=46)​ All patients (N=62) Median follow-up: 12 months Median PFS not reached 6-month PFS rate = 73% Median follow-up: 12 months Median PFS not reached 6-month PFS rate = 68%

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Six-month PFS rate of 81% in ESR1-mutant patients, 70% in ESR1 wild-type Median follow-up of 12 months; median PFS not yet reached; sustained efficacy regardless of ESR1 status​ Data cutoff date: November 11, 2024 * Follow up was calculated from first dose date to data cutoff date regardless of disease progression status. ESR1 = estrogen receptor 1 gene; PFS = progression-free survival ESR1-mutant (n=17) ESR1 wild-type (n=43) Median follow-up: 12 months Median PFS not reached 6-month PFS rate = 70% Median follow-up: 12 months Median PFS not reached 6-month PFS rate = 81%

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Efficacy comparison in 2/3L patients vs. competitive landscape MAINTAIN study of ribociclib plus ET after CDK4/6i progression serves as best clinical benchmark* Six-Month PFS Rate* in CDK4/6i pre-treated patients MAINTAIN1:ET + Placebo(n = 59) Olema: Palazestrant + Ribociclib(n = 46) Interim efficacy signals for palazestrant in combination with ribociclib MORPHEUS2:Giredestrant+ Ribociclib(n = 15) * NOTE: This analysis is the aggregation of results across independent studies. There are risks inherent in conducting cross-trial comparisons and results should be interpreted with caution. Refer to further disclaimers on slide 2. Data cutoff date: November 11, 2024.  CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; ESR1-mut = ESR1-mutant; ESR1-wt = ESR1 wild-type; ET = endocrine therapy 1 ASCO 2022 MAINTAIN data; 2 ASCO 2023 MORPHEUS data MAINTAIN1:ET + Ribociclib (n = 60) Median PFS (months)* in CDK4/6i pre-treated patients MAINTAIN1:ET + Placebo(n = 59) Olema: Palazestrant + Ribociclib(n = 46) MORPHEUS2:Giredestrant+ Ribociclib(n = 15) MAINTAIN1:ET + Ribociclib (n = 60) Not Reached

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Compelling anti-tumor activity in both wild-type and ESR1 mutant tumors 60% of patients showed tumor reduction 30 mg Treatment group (palazestrant dose): 60 mg 120 mg Treatment ongoing ESR1 mutation Prior AI Prior CDK4/6i Prior chemotherapy Prior fulvestrant Patients of efficacy population 40 20 0 -20 -40 -60 Best change from baseline (%) ESR1 mutant ESR1 wild-type cPR cPR cPR uPR cPR cPR cPR cPR SD 0 PD 0 SD 0 SD 0 SD 0 SD -3 SD -12 SD -13 -19 -24 -32 -39 -53 -57 -100 Data cutoff date: November 11, 2024.  Waterfall plot n=37. 2 = 2 prior CDK4/6 inhibitors in metastatic setting. SD = stable disease; PD = progressive disease; AI = aromatase inhibitor; PR = partial response; cPR = confirmed PR; uPR = unconfirmed PR; uCR = unconfirmed complete response; cCR = confirmed complete response; CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; ESR1 = estrogen receptor 1 gene Best percent change from baseline in target lesions and best overall response 60% of patients (n=22) had a reduction in target lesion size -19 -22 -61 -60 -4 SD -5 SD SD SD 2 SD 19 SD 4 PD 17 SD 10 SD 9 PD 20 PD 21 PD 32 80 cPR cCR -100 -64 SD 46 PD 61 60 -80 SD -2 2 2 2 -24 -29 -41 -42 SD SD SD SD 2 2 2 2

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Safety and Tolerability Palazestrant (120 mg) in combination with full dose ribociclib was well tolerated Safety was consistent with combinations of ribociclib (600 mg) with endocrine therapy Pharmacokinetics No clinically meaningful drug-drug interaction Efficacy Median follow-up of 12 months with mPFS not yet reached 6-month progression-free survival rate was: 73% across all patients 68% in patients with prior CDK4/6i exposure 70% in patients with ESR1-wt disease 81% in those with ESR1-mut disease 11 responses to date (2 confirmed CRs*, 8 confirmed PRs, and 1 unconfirmed PR) 27% (10/37) ORR among response-evaluable patients with measurable disease Clinical benefit rate (CBR)^: 76% in all patients (37/49 CBR-eligible)  81% in ESR1-mut (13/16 CBR-eligible) 74% in ESR1-wt (23/31 CBR-eligible) CBR in patients who received prior CDK4/6i: 71% in all patients (25/35 CBR-eligible)  81% in ESR1-mut (13/16 CBR-eligible) 65% in ESR1-wt (11/17 CBR-eligible) Longest duration of treatment 79 weeks and ongoing Efficacy data are maturing; 30 (48%) patients remain on treatment Highly encouraging preliminary efficacy from the combined agents, including in patients with prior CDK4/6i treatment *1 cCR in patient with non-measurable but evaluable disease. ^ CBR is the proportion of patients who remained on treatment through at least 24 weeks with a confirmed complete response or partial response, or stable disease. Abbreviations: CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; ESR1 = estrogen receptor 1 gene; PR = partial response; CR = complete response.

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Proposed OPERA-02 1L Phase 3 pivotal trial in combination with ribociclib ~1,000-patient trial vs. standard of care in preparation for 2025 initiation; in collaboration with Novartis CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; CBR = clinical benefit rate; DOR = duration of response; ER+ = estrogen receptor positive; HER2- = human epidermal growth factor receptor 2 negative; MBC = metastatic breast cancer; ORR = objective response rate; OS = overall survival; PFS = progression free survival; ESR1mut = ESR1-mutant; ET = endocrine therapy Study Endpoints Primary: PFS (BIRC) Secondary : OS (key) PFS (Investigator and by ESR1mut) ORR/CBR/DOR (BIRC, Investigator and by ESR1mut) Safety PK Health-related PROs STRATIFICATION: Menopausal status: post vs. pre/male Visceral metastasis: yes vs. no De novo metastatic disease vs. recurrent disease after adjuvant ET n ≈ 1,000 Palazestrant +ribociclib Letrozole +ribociclib Inclusion criteria: ER+/HER2- MBC Any menopausal status No prior systemic therapy for MBC No prior CDK4/6 inhibitor for MBC Evaluable disease (measurable or non-measurable) 1:1

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Preparing to initiate OPERA-02 in 2025 New clinical trial collaboration and supply agreement with Novartis combined with $250M private placement enables execution of Olema operating plan Novartis agreement enables pivotal Phase 3 OPERA-02 clinical trial of palazestrant in combination with ribociclib in frontline ER+/HER2- advanced or metastatic breast cancer Ribociclib drug supply expected to be sufficient to conduct the planned OPERA-02 trial; valued at ~$275M Olema responsible for the day-to-day operational activities for OPERA-02 Olema retains global commercial rights to palazestrant All clinical data from OPERA-02 will be jointly owned; each party retains rights to its background IP $250M equity private placement strengthens Olema’s balance sheet Participation by new and existing high-quality institutional and accredited investors Pro forma cash and cash equivalents expected to fund research and development activities including the execution of OPERA-01, OPERA-02, OP-3136 Phase 1/2, and for working capital and general corporate purposes

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Significant opportunity for palazestrant across the spectrum of care Estimated >$20B ER+/HER2- global metastatic breast cancer market1 1 2025 opportunity estimates for total endocrine therapy market (US and Europe). Olema internal data. 2 2025 incidence projection estimates. Olema internal data, Informa ER+/HER2- BC Prevalence Based Market Forecast. 3 Olema internal data. 4Olema internal data. 2L/3L+ER+/HER2- MBC 1L ER+/HER2- MBC Patients2 ~150K Duration of Therapy3 ~2-12+ months Global Market Potential4 $5B+ Patients2 ~115K Duration of Therapy3 ~6-36+ months Global Market Potential4 $10B+

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Olema: a compelling late-stage opportunity in breast cancer and beyond Changing the treatment paradigm for endocrine-driven cancers 1 Pro forma position includes the Company's cash, cash equivalents, and marketable securities as of September 30, 2024, plus net proceeds of approximately $237.5 million from equity private placement which closed on December 4, 2024. Palazestrant anchors Olema’s breast cancer program as a potential backbone therapy for metastatic breast cancer Highly differentiated as first oral CERAN/SERD endocrine agent Ongoing 2/3L OPERA-01 Phase 3 trial on track for top-line data in 2026 Planned 1L OPERA-02 Phase 3 trial in combination with ribociclib enabled; initiation expected in 2025 Go-to-market strategy for potential U.S. launch in 2027 OP-3136 expands pipeline with novel and validated KAT6 target IND cleared by FDA; first patient expected to enroll in Phase 1 clinical trial by early 2025 Well-capitalized with ~$452M of pro forma cash and cash equivalents as of September 30, 20241

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— Advancing medicines for breast cancer and beyond

v3.24.3

Document And Entity Information	Dec. 09, 2024
Cover [Abstract]
Document Type	8-K
Amendment Flag	false
Document Period End Date	Dec. 09, 2024
Entity Registrant Name	Olema Pharmaceuticals, Inc.
Entity Central Index Key	0001750284
Entity Emerging Growth Company	false
Entity File Number	001-39712
Entity Incorporation, State or Country Code	DE
Entity Tax Identification Number	30-0409740
Entity Address, Address Line One	780 Brannan Street
Entity Address, City or Town	San Francisco
Entity Address, State or Province	CA
Entity Address, Postal Zip Code	94103
City Area Code	415
Local Phone Number	651-3316
Entity Information, Former Legal or Registered Name	N/A
Written Communications	false
Soliciting Material	false
Pre-commencement Tender Offer	false
Pre-commencement Issuer Tender Offer	false
Title of 12(b) Security	Common Stock, par value $0.0001 per share
Trading Symbol	OLMA
Security Exchange Name	NASDAQ

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