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Item 2. Management’s Discussion and Analysis

2026-05-12 compared with 2025-11-10 · 100 added, 137 removed, 170 unchanged (58% of the section changed)

Management’s Discussion and Analysis of Financial Condition and Results of Operations.

You should read the following discussion and analysis of our financial condition and results of operations together with the unaudited condensed consolidated financial statements and related notes that are included elsewhere in this Quarterly Report on Form 10‑Q and the audited financial statements and related notes that are included in our Annual Report on Form 10‑K for the fiscal year ended December 31, 2024, filed with the U.S.

Securities and Exchange Commission, or the SEC, on March 18, 2025, or our Annual Report on Form 10‑K.

This Quarterly Report on Form 10-Q contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, or the Securities Act, and Section 21E of the Securities Exchange Act of 1934, as amended, or the Exchange Act.

You should read the following discussion and analysis of our financial condition and results of operations together with the unaudited condensed consolidated financial statements and related notes that are included elsewhere in this Quarterly Report on Form 10‑Q, or Quarterly Report, and the audited financial statements and related notes that are included in our Annual Report on Form 10‑K for the fiscal year ended December 31, 2025, filed with the U.S.

Securities and Exchange Commission, or the SEC, on March 16, 2026, or our Annual Report.

This Quarterly Report contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, or the Securities Act, and Section 21E of the Securities Exchange Act of 1934, as amended, or the Exchange Act.

Forward-looking statements are identified by words such as “believe,” “will,” “may,” “estimate,” “continue,” “anticipate,” “intend,” “should,” “plan,” “expect,” “predict,” “could,” “potentially” or the negative of these terms or similar expressions.

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We caution investors that our business and financial performance are subject to substantial risks and uncertainties.

In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject, and these statements are based on information available to us as of the date of this Quarterly Report on Form 10-Q.

While we believe that such information provides a reasonable basis for these statements, that information may be limited or incomplete.

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We are advancing our pipeline of novel therapies by leveraging our deep understanding of endocrine-driven cancers, nuclear receptors, and mechanisms of acquired resistance.

We aspire to transform the treatment paradigm for metastatic breast cancer (MBC).

Our lead product candidate, 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), 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 non-clinical models, palazestrant binds and completely blocks ER-driven transcriptional activity in both wild-type and mutant forms of ER+ MBC.

In clinical studies across more than 400 patients, palazestrant has demonstrated strong anti-tumor activity, attractive pharmacokinetics and prolonged drug exposure, favorable tolerability, and combinability with CDK4/6 inhibitors with no significant drug-drug interaction.

Our lead product candidate, palazestrant, is a novel, orally-available small molecule with dual activity as both a complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD), 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 pre-clinical models, palazestrant binds and completely blocks ER-driven transcriptional activity in both wild-type and mutant forms of ER+ metastatic breast cancer (MBC).

In clinical studies across more than 400 patients, palazestrant has demonstrated strong anti-tumor activity, attractive pharmacokinetics and prolonged drug exposure, favorable tolerability, and combinability with cyclin dependent kinase 4/6 (CDK4/6) inhibitors with no significant drug-drug interaction.

Based on the clinical results we have achieved to date, we are advancing palazestrant through late-stage clinical development both as a monotherapy and in combination with other targeted agents.

Our pivotal Phase 3 clinical trial of palazestrant as a monotherapy in second/third-line ER+/HER2- MBC, OPERA-01, is ongoing.

90mg of once-daily palazestrant has been selected as the dose for Part 2 of OPERA-01.

We anticipate top-line results for this trial in the second half of 2026, expect to submit the New Drug

Application in 2027, and anticipate U.S.

In November 2023, we initiated OPERA-01, our pivotal Phase 3 clinical trial of palazestrant as a monotherapy in second/third-line ER+/HER2- MBC.

We anticipate top-line results for this trial in the fall of 2026, expect to submit the new drug application (NDA) in 2027, and, if successful, anticipate potential U.S.

Food and Drug Administration (FDA) approval and commercial launch in late 2027.

In combination, we are investigating palazestrant in multiple Phase 1/2 studies with CDK4/6 inhibitors (palbociclib or ribociclib), a phosphatidylinositol-3-kinase alpha (PI3Ka) inhibitor (alpelisib), with an mTOR inhibitor (everolimus).

We have also entered into a clinical trial collaboration and supply agreement with Pfizer Inc.

(Pfizer) to evaluate the safety and combinability of palazestrant and atirmociclib, Pfizer's investigative selective CDK4 inhibitor, in patients with ER+/HER2- MBC.

We expect to initiate this Phase 1b/2 study in the fourth quarter of 2025.

We presented updated results from the ongoing Phase 1b/2 study of palazestrant in combination with ribociclib in patients with ER+/HER2- advanced or MBC at the San Antonio Breast Cancer Symposium (SABCS) in December 2024.

In March 2025, we disclosed updated median progression-free survival (mPFS) from this study at the TD Cowen 45th Annual Health Care Conference.

As of a data cutoff date of February 18, 2025, the mPFS was 13.8 months in 56 patients treated with 120 mg of palazestrant and 600 mg of ribociclib daily.

40 of the 56 patients had received prior treatment of a CDK4/6i plus an endocrine therapy;

the mPFS in this population was 13.1 months.

In October 2025, we presented updated data from this study at the European Society for Medical Oncology (ESMO) Congress.

As of the data cutoff date of July 8, 2025, in the 120 mg palazestrant dose cohort, with a median follow-up of more than 19 months, mPFS are mature.

mPFS was 15.5 months for all patients and 12.2 months for those who received prior treatment with CDK4/6i, including 9.2 months for patients with estrogen receptor 1 (ESR1) wild-type tumors and 13.8 months for patients with tumors with ESR1 mutations.

In the 90 mg palazestrant dose cohort, with a median follow-up of 10.8 months, mPFS was not reached.

Further, we have initiated patient enrollment in the pivotal Phase 3 clinical trial of 90 mg of once-daily palazestrant in combination with 600 mg of ribociclib daily in front-line ER+/HER2- MBC, called OPERA-02.

The execution of OPERA-02 is supported by our clinical trial collaboration and supply agreement with Novartis Pharma AG (collectively, with affiliated entities, Novartis), entered into in November 2024 (Novartis Pharma Agreement).

Under the terms of the Novartis Pharma Agreement, Novartis will provide Olema with ribociclib drug supply for OPERA-02.

We anticipate top-line data in 2028 and anticipate potential FDA approval and commercial launch in the frontline MBC setting in the U.S.

In addition, we are investigating palazestrant in multiple Phase 1/2 studies in combination with CDK4/6 inhibitors (palbociclib or ribociclib), a phosphatidylinositol-3-kinase alpha (PI3Ka) inhibitor (alpelisib), with an mTOR inhibitor (everolimus), and a CDK4 inhibitor (atirmociclib).

In October 2025, at the European Society for

Medical Oncology, we presented updated results from the ongoing Phase 1b/2 clinical trial of palazestrant in combination with ribociclib in patients with ER+/HER2- advanced or MBC.

This data further support our thesis that palazestrant possesses key characteristics to make it a potential backbone endocrine therapy of preference for ER+/HER2- breast cancer, while also supporting the ongoing pivotal Phase 3 clinical trial of palazestrant in combination with ribociclib in front-line ER+/HER2- MBC, called OPERA-02.

The execution of OPERA-02 is supported by our clinical trial collaboration and supply agreement with Novartis Pharma AG (Novartis), which was also announced in December 2024.

Under the terms of the agreement, Novartis is providing Olema with ribociclib drug supply for the OPERA-02 trial, which we initiated in 2025.

We anticipate top-line data from this trial in 2028 and, if successful, anticipate potential FDA approval and commercial launch in the frontline MBC setting in the United States in 2029.

Our second product candidate in clinical development, called OP-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.

The IND application for OP-3136 was cleared by the FDA in late 2024 and the Phase 1 study is now enrolling patients.

In April 2025, we presented new preclinical data at the AACR Annual Meeting demonstrating the anti-tumor activity of OP-3136 in prostate, ovarian, and non-small cell lung cancer models.

We expect initial clinical results from the OP-3136 Phase 1 study in mid-2026, potential additional data readout in 2027, and potential initiation of a Phase 3 clinical trial in 2028.

Based on our internal estimates, we believe that the current global market potential for OP-3136 in the second/third-line ER+/HER2- MBC market is approximately $5 billion.

The Investigational New Drug (IND) application for OP-3136 was cleared by the FDA in late 2024 and the Phase 1 study is enrolling patients.

In April 2025, we presented preclinical data at the AACR Annual Meeting demonstrating the anti-tumor activity of OP-3136 in prostate, ovarian, and non-small cell lung cancer models.

In April 2026, at the AACR Annual Meeting, we presented preclinical data demonstrating that OP-3136, in combination with palazestrant, exhibited synergistic anti-tumor activity in ER+/HER2- breast cancer models driven by suppression of cell-cycle and estrogen receptor-driven oncogenic signaling.

We expect to present initial clinical results from the OP-3136 Phase 1 study at the 2026 American Society of Clinical Oncology Annual Meeting in May.

Since our inception, we have devoted substantially all of our resources to organizing and staffing our company, research and development activities, business planning, raising capital, establishing and maintaining our intellectual property portfolio, conducting non-clinical studies and clinical trials and providing general and administrative support for these operations.

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We have incurred significant operating losses since the commencement of our operations.

Our net losses were $42.2 million and $34.6 million for the three months ended September 30, 2025 and 2024, respectively, and $116.4 million and $95.9 million for the nine months ended September 30, 2025 and 2024, respectively.

Our net losses were $53.1 million and $30.4 million for the three months ended March 31, 2026 and 2025, respectively.

We expect to incur significant and increasing losses for the foreseeable future as we continue to advance our product candidates, make potential milestone payments to our licensors, and as we continue to operate as a public company.

Our net losses may fluctuate significantly from period to period, depending on the timing of expenditures on our research and development activities.

As of September 30, 2025, we had an accumulated deficit of $551.5 million.

As of March 31, 2026, we had an accumulated deficit of $650.6 million.

Our primary use of cash is to fund operating expenses, which consist primarily of research and development expenditures and general and administrative expenditures.

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• add clinical, operational, financial and management information systems and personnel, including personnel to support our product development and planned future commercialization efforts;

• expand our operations in the United States and to other geographies;

• expand our operations in the United States and in other geographies;

• incur additional legal, accounting, investor relations and other expenses associated with operating as a public company.

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We may be unable to raise additional funds or to enter into such agreements or arrangements on favorable terms, or at all.

Our ability to raise additional funds may be adversely impacted by potential worsening global economic conditions and volatility in, the credit and financial markets in the United States and worldwide resulting from geopolitical and macroeconomic conditions.

Our ability to raise additional funds may be adversely impacted by potential worsening global economic conditions, geopolitical uncertainty, and volatility in, the credit and financial markets in the United States and worldwide resulting from geopolitical and macroeconomic conditions.

Our failure to obtain sufficient funds on acceptable terms when needed could have a material adverse effect on our business, results of operations or financial condition, including requiring us to have to delay, reduce or eliminate our product development or future commercialization efforts.

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The amount and timing of our future funding requirements will depend on many factors, including the pace and results of our development efforts.

We cannot provide assurance that we will ever be profitable or generate positive cash flow from operating activities.

Global economic and business activities continue to face widespread uncertainty due to the geopolitical and macroeconomic environment, generally, including economic uncertainty, market volatility, labor shortages, recent and changing tariff policy announcements, tariffs, trade tensions and retaliatory measures by other countries, supply chain disruptions, the ongoing conflicts between Ukraine and Russia and in the Middle East, as well as any related political or economic responses and counter-responses or otherwise by various global actors, inflationary pressures, monetary supply shifts, increased recession risk, and related financial instability.

The extent of the impact of these factors on our operational and financial performance, including our ability to execute our business strategies and initiatives in the expected time frame, will depend on future developments, which are uncertain and cannot be predicted.

We cannot provide assurance that we will ever be profitable or generate revenue or positive cash flow from operating activities.

Global economic and business activities continue to face widespread uncertainty due to the geopolitical and macroeconomic environment, generally, including economic and geopolitical uncertainty, market volatility, labor shortages, evolving trade and tariffs policies, including related legal challenges, trade tensions, and retaliatory measures by other countries, supply chain disruptions, military conflicts, as well as any related political or economic responses or counter-responses by various global actors, inflationary pressures, monetary supply shifts, increased recession risk, and related financial instability.

The extent of the impact of these factors on our

operational and financial performance, including our ability to execute our business strategies and initiatives in the expected time frame, will depend on future developments, which are uncertain and cannot be predicted.

Any continued or renewed disruption resulting from these factors could negatively impact our business.

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We track outsourced development costs by product candidate or non-clinical program, but we do not allocate personnel costs, other internal costs or external consultant costs to specific product candidates or non-clinical programs.

While our research and development expenses may fluctuate from period to period, we generally expect our research and development expenses to increase substantially in absolute dollars for the foreseeable future as we advance palazestrant, OP-3136 or any other future product candidates we may develop into and through non-clinical studies and clinical trials and pursue regulatory approval of our product candidates.

While our research and development expenses may fluctuate from period to period, we generally expect our research and development expenses to increase substantially in absolute dollars for the foreseeable future as we advance palazestrant, OP-3136, or any future product candidates we may develop into and through non-clinical studies and clinical trials and pursue regulatory approval of our product candidates.

The process of conducting the necessary clinical research to obtain regulatory approval is costly and time-consuming.

The actual probability of success for palazestrant, OP-3136 or any other future product candidates we may develop may be affected by a variety of factors including but not limited to:

The actual probability of success for palazestrant, OP-3136, or any future product candidates we may develop may be affected by a variety of factors including but not limited to:

the safety and efficacy of our product candidates, early clinical data, investment in our clinical program, the ability of collaborators to successfully develop our licensed product candidates, competition, manufacturing capability, and commercial viability.

We may never succeed in achieving regulatory approval for our product candidates.

As a result of the uncertainties discussed above, we are unable to determine the duration and completion costs of our research and development projects or when and to what extent we will generate revenue from the commercialization and sale of palazestrant, OP-3136 or any other future product candidates we may develop.

Clinical and non-clinical development timelines, the probability of success and development costs can differ materially from expectations.

We anticipate that we will make determinations as to which product candidates to pursue and how much funding to direct to each product candidate on an ongoing basis in response to the results of ongoing and future non-clinical studies and clinical trials, regulatory developments and our ongoing assessments as to each product candidate’s commercial potential.

In addition, we cannot forecast whether palazestrant, OP-3136 or any other future product candidates we may develop may be subject to future collaborations, when such arrangements will be secured, if at all, and to what degree such arrangements would affect our development plans and capital requirements.

We are also unable to predict when, if ever, we will generate revenue from our

product candidates to offset these expenses.

In addition, we cannot forecast whether palazestrant, OP-3136, or any future product candidates we may develop may be subject to future collaborations, when such arrangements will be secured, if at all, and to what degree such arrangements would affect our development plans and capital requirements.

We are also unable to predict when, if ever, we will generate revenue from our product candidates to offset these expenses.

Our expenditures on current and future non-clinical and clinical development programs are subject to numerous uncertainties in timing and cost to completion.

The duration, costs and timing of non-clinical studies and clinical trials and development of our product candidates will depend on a variety of factors, including:

The duration, costs, and timing of non-clinical studies, clinical trials, and development of our product candidates will depend on a variety of factors, including:

• the timing and progress of non-clinical and clinical development activities;

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General and administrative

General and administrative expenses consist primarily of personnel expenses, including salaries, benefits and stock-based compensation expense, for personnel in executive, finance, accounting, business development, communications, legal, human resources, information technology (IT), and administrative functions.

General and administrative expenses also include costs not otherwise included in research and development expenses, including corporate facility costs, depreciation and other expenses, which include direct or allocated expenses for rent and maintenance of facilities and insurance, and professional fees for legal, patent and consulting services.

While our general and administrative expenses may fluctuate from period to period, we generally expect that our general and administrative expenses will increase in the foreseeable future as we increase our headcount to support the continued research and development of our programs and the growth of our business.

We also anticipate incurring additional expenses associated with operating as a public company, including increased expenses related to the building and improving of our IT infrastructure, including cyber security monitoring, legal, other regulatory and compliance, director and officer insurance, investor and public relations and tax-related services associated with maintaining compliance with the rules and regulations of the SEC and standards applicable to companies listed on a national securities exchange, additional insurance expenses, investor relations activities and other administrative and professional services.

General and administrative expenses consist primarily of personnel expenses, including salaries, benefits and stock-based compensation expense, for personnel in executive, finance, accounting, business development, communications and investor relations, commercialization, legal, human resources, information technology (IT), and administrative functions.

General and administrative expenses also include costs not otherwise included in research and development expenses, including corporate facility costs, depreciation and other expenses, which include rent and maintenance of facilities and insurance, and professional fees for legal, patent and consulting services.

We also anticipate incurring additional expenses associated with operating as a public company, including increased expenses related to the building and improving of our IT infrastructure, such as cybersecurity monitoring, legal, regulatory and compliance, director and officer insurance, investor and public relations, and tax-related services associated with maintaining compliance with the rules and regulations of the SEC and the standards applicable to companies listed on a national securities exchange, as well as additional insurance expenses and other administrative and professional services.

Total other income

Total other income consists of interest income and other income (expense).

Total other income consists of interest income and other income.

Interest income primarily consists of interest earned from our cash equivalents and marketable securities.

Other income (expense) primarily consists of unrealized foreign currency remeasurement gain (loss), interest expense, and other miscellaneous income (expense) not related to operating activities.

Other income primarily consists of realized and unrealized foreign currency remeasurement gain (loss), interest expense, and other miscellaneous income (expense) not related to operating activities.

Results of operations

Comparison of the three months ended September 30, 2025 and 2024

The following table summarizes our results of operations for the three months ended September 30, 2025 and 2024:

Three Months Ended September 30,

(in thousands)

Operating expenses:

Research and development

General and administrative

Total operating expenses

Loss from operations

Other income:

Interest income

Total other income

Research and development expenses

The following table summarizes our research and development expenses by functional area for the three months ended September 30, 2025 and 2024:

Three Months Ended September 30,

(in thousands)

CROs, CMOs and other clinical development related third-party vendor expenses

Compensation and related benefits

Other research and development expenses

Stock-based compensation

Total research and development expenses

Research and development expenses for the three months ended September 30, 2025 were $40.0 million, compared to $33.2 million for the three months ended September 30, 2024.

The increase of $6.7 million was primarily related to (i) increased spending on clinical development-related activities as we continue to advance palazestrant through late-stage clinical trials, (ii) increased spending related to the advancement of OP-3136, and (iii) increased personnel-related costs due to higher headcount, partially offset by a decrease in non-cash stock-based compensation expense of $1.7 million mainly due to lower fair value of options granted in 2025.

General and administrative expenses

General and administrative expenses for the three months ended September 30, 2025 were $5.9 million compared to $4.4 million for the three months ended September 30, 2024.

The increase of $1.5 million was primarily attributable to higher corporate-related costs and an increase in non-cash stock-based compensation expense of $0.3 million due to higher headcount, partially offset by lower fair value of options granted in 2025.

Other income for the three months ended September 30, 2025 was $3.7 million, compared to $3.1 million for the three months ended September 30, 2024.

The increase of $0.6 million was primarily due to an increase in interest income from our investments in interest-bearing money market funds and marketable securities.

Comparison of the nine months ended September 30, 2025 and 2024

The following table summarizes our results of operations for the nine months ended September 30, 2025 and 2024:

Nine Months Ended September 30,

Comparison of the three months ended March 31, 2026 and 2025

The following table summarizes our results of operations for the three months ended March 31, 2026 and 2025:

Three Months Ended March 31,

(in thousands)

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Interest income

Other income (loss)

Total other income

¹The amounts for the nine months ended September 30, 2025 and 2024 include one-time milestone payments to Aurigene of $10,000 and $5,000, respectively.

Research and development expenses

The following table summarizes our research and development expenses by functional area for the nine months ended September 30, 2025 and 2024:

Nine Months Ended September 30,

The following table summarizes our research and development expenses by functional area for the three months ended March 31, 2026 and 2025:

Three Months Ended March 31,

(in thousands)

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Other research and development expenses

Milestone payment made to Aurigene

Stock-based compensation

Total research and development expenses

Research and development expenses for the nine months ended September 30, 2025 were $114.5 million, compared to $92.2 million for the nine months ended September 30, 2024.

The increase of $22.3 million was primarily related to (i) increased spending on clinical development-related activities as we continue to advance palazestrant through late-stage clinical trials, (ii) increased spending related to the advancement of OP-3136, (iii) $5.0 million higher milestone payment to Aurigene, and (iv) increased personnel-related costs due to higher headcount, partially offset by a decrease in non-cash stock-based compensation expense of $2.3 million mainly due to lower fair value of options granted in 2025.

Research and development expenses for the three months ended March 31, 2026 were $49.2 million, compared to $30.6 million for the three months ended March 31, 2025.

The increase of $18.6 million was primarily related to (i) increased spending on clinical development-related activities as we continue to advance palazestrant through late-stage clinical trials and OP-3136 in early-stage clinical studies, and (ii) increased personnel-related costs, including an increase in non-cash stock-based compensation expense of $3.3 million mainly due to higher grant price in 2026, and higher headcount.

General and administrative expenses

General and administrative expenses for the nine months ended September 30, 2025 were $14.1 million compared to $13.3 million for the nine months ended September 30, 2024.

The increase of $0.8 million was primarily related to higher corporate-related costs, partially offset by a decrease in non-cash stock-based compensation expense of $0.6 million due to lower fair value options granted in 2025.

Other income for the nine months ended September 30, 2025 was $12.2 million, compared to $9.6 million for the nine months ended September 30, 2024.

The increase of $2.6 million was primarily due to an increase in interest income from our investments in interest-bearing money market funds and marketable securities.

General and administrative expenses for the three months ended March 31, 2026 were $8.8 million compared to $4.2 million for the three months ended March 31, 2025.

The increase of $4.6 million was primarily attributable to higher corporate-related costs, increased personnel-related costs, including an increase in non-cash stock-based compensation expense of $2.5 million mainly due to higher grant price in 2026.

Other income for the three months ended March 31, 2026 was $4.9 million, compared to $4.5 million for the three months ended March 31, 2025.

The increase of $0.4 million was primarily due to an increase in interest income from our investments in interest-bearing money market funds and marketable securities mainly due to higher investment balance.

Liquidity and capital resources

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Since our inception, we have not generated any revenue from product sales and have incurred significant operating losses and negative cash flows from our operations.

Through September 30, 2025, we had received aggregate gross proceeds of $793.2 million from sales of our common stock, convertible preferred stock and issuance of convertible promissory notes, stock option exercises, sale of stock through the Company’s 2020 Employee Stock Purchase Plan (ESPP) and borrowings under our Credit Facility, as defined below.

As of September 30, 2025, we had $329.0 million in cash, cash equivalents and marketable securities and accumulated deficit of $551.5 million.

On September 5, 2023, we entered into a loan and security agreement (the Original Loan Agreement) with Silicon Valley Bank, a division of First Citizens Bank & Trust Company (the Bank), which provided us with an aggregate principal amount of up to $50.0 million (the Original Credit Facility), of which $25.0 million became available in September 2023 (Term Loan A) upon the closing of a private placement and issuance of our common stock to selected institutional and accredited investors pursuant to a securities purchase agreement, and the remaining $25.0 million could have been made available upon approval of the Bank in its discretion.

The Original Credit Facility was to mature on August 1, 2027.

On June 28, 2024, we entered into the First Amendment to Loan and Security Agreement (the First Amendment) with the Bank, which, among other things, (i) increased the aggregate principal amount of the Original Credit Facility from up to $50.0 million to up to $100.0 million of which the Term Loan A of $25.0 million was immediately available, an additional $25.0 million will become available upon achieving certain milestones related to execution of a first-line pivotal Phase 3 clinical trial of palazestrant in combination with ribociclib, and an additional $50.0 million which may be made available upon approval of the Bank in its discretion, and (ii) extended the maturity date to July 1, 2028 (Maturity Date).

On June 27, 2025, we entered into a Second Amendment to Loan and Security Agreement (the Second Amendment, and the Original Loan Agreement, as amended by the First Amendment, the Credit Facility) with the Bank, which, among other things, (i) decreased the interest rate to a floating rate equal to the greater of 6.0% or the prime rate, and (ii) extended the draw period of Term Loan A to January 15, 2026.

As of September 30, 2025, we had an outstanding liability of $3.0 million under our Credit Facility, representing the full amount drawn to date.

Our net losses were $53.1 million and $30.4 million for the three months ended March 31, 2026 and 2025, respectively.

From our inception through March 31, 2026, we had received aggregate net proceeds of $1.1 billion from sales of our common stock, convertible preferred stock and issuance of convertible promissory notes, stock option exercises, sale of stock through the Company’s 2020 Employee Stock Purchase Plan (ESPP), and borrowings under our Credit Facility, as defined below.

As of March 31, 2026, we had $505.3 million in cash, cash equivalents and marketable securities and accumulated deficit of $650.6 million.

On September 5, 2023, we entered into a loan and security agreement (the Original Loan Agreement) with Silicon Valley Bank, a division of First Citizens Bank & Trust Company (the Bank), which provided us with an aggregate principal amount of up to $50.0 million (the Original Credit Facility), of which $25.0 million became available in September 2023 (Term Loan A) upon the closing of a private placement and the issuance of our common stock to selected institutional and accredited investors pursuant to a securities purchase agreement, and the remaining $25.0 million could have been made available upon approval of the Bank in its discretion.

The Original Credit Facility was scheduled to mature on August 1, 2027.

On June 28, 2024, we entered into the First Amendment to Loan and Security Agreement (the First Amendment) with the Bank, which, among other things, (i) increased the aggregate principal amount of the Original Credit Facility from up to $50.0 million to up to $100.0 million (the Credit Facility) of which the Term Loan A of $25.0 million was immediately available, an additional $25.0 million became available upon achieving certain milestones related to the execution of a first-line pivotal Phase 3 clinical trial of palazestrant in combination with ribociclib (Term Loan B), and an additional $50.0 million which may be made available upon the approval of the Bank in its discretion (Term Loan C), and (ii) extended the maturity date to July 1, 2028.

On June 27, 2025, we entered into a Second Amendment to Loan and Security Agreement (the Second Amendment) with the Bank, which, among other things, (i) decreased the interest rate to a floating rate equal to the greater of 6.0% or the prime rate, and (ii) extended the draw period of Term Loan A to January 15, 2026.

As of March 31, 2026, we had an outstanding liability of $3.0 million under the Credit Facility, representing the full amount drawn to date.

On January 11, 2026, we entered into the Third Amendment to Loan and Security Agreement (the Third Amendment, together with the Original Loan Agreement, as amended by the First Amendment and the Second Amendment, the Loan Agreement), which, among other things, (i) extended the draw period of Term Loan A to January 31, 2027, (ii) extended the draw period of Term Loan B to January 31, 2027, (iii) extended the draw period of Term Loan C to January 31, 2027, and (iv) extended the Maturity Date to January 1, 2029 (Maturity Date).

Based on the occurrence of specified (a) development milestones related to the pivotal Phase 3 OPERA-01 clinical trial of palazestrant or (b) receipt of proceeds from capital financing, the draw period of Term Loan B and Term Loan C may be further extended to July 31, 2027, and the Maturity Date may be further extended to July 1, 2029.

On November 29, 2024, we entered into a securities purchase agreement for a private placement of (i) 19,928,875 shares of our common stock at a price of $9.08 per share and (ii) pre-funded warrants to purchase up to an aggregate of 7,604,163 shares of our common stock at a price of $9.0799 per pre-funded warrant, which represents the per share purchase price of the common stock sold in the private placement less the $0.0001 per share exercise price for each pre-funded warrant to selected institutional and accredited investors (the 2024 Private Placement).

The aggregate gross proceeds for the 2024 Private Placement were approximately $250.0 million.

After deducting offering expenses related to the 2024 Private Placement of approximately $13.0 million, the net proceeds to us from the 2024 Private Placement were approximately $237.0 million.

After deducting offering expenses related to the 2024 Private Placement of approximately $13.0 million, the net proceeds to us from the 2024 Private Placement were approximately

$237.0 million.

Of the $13.0 million issuance costs, $6.5 million was paid in the fourth quarter of 2024 and $6.5 million was paid in the first quarter of 2025.

Concurrently, on November 29, 2024, we entered in an exchange agreement with an investor and issued to such investor pre-funded warrants to purchase up to 3,420,000 shares of our common stock at an exercise price of $0.0001 per share, in exchange for 3,420,000 shares of our common stock previously outstanding and held by such investor.

Thereafter, on January 10, 2025, we entered into exchange agreements with certain investors pursuant to which we issued pre-funded warrants to purchase up to 6,070,000 shares of our common stock at an exercise price of $0.0001 per share, in exchange for 6,070,000 shares of our common stock previously outstanding and held by such investors.

Certain holders of pre-funded warrants (together with such holder’s affiliates and other attribution parties) may not exercise pre-funded warrants held by them to the extent that immediately prior to or after giving effect to such exercise such holder would own more than 9.99% of our outstanding common stock immediately after exercise, which percentage may be changed at the holder’s election to a lower or higher percentage not in excess of 19.99% upon 61 days’ notice to us, subject to the terms of the pre-funded warrants.

Refer to Note 12 of our notes to the condensed consolidated financial statements contained in this Quarterly Report on Form 10-Q for further information regarding the exchange transactions.

On January 5, 2024, we entered into a sales agreement (the 2024 Sales Agreement), with Cowen and Company, LLC (Cowen and Company), as sales agent, pursuant to which we were permitted to offer and sell, from time to time, shares of our common stock, having an aggregate offering price of up to $150.0 million (the 2024 ATM Shares).

The sales of the 2024 ATM Shares were made as an “at-the-market” (ATM) equity offering as defined in Rule 415(a)(4) promulgated under the Securities Act.

We agreed to pay Cowen and Company a commission of up to 3.0% of the aggregate gross proceeds from any 2024 ATM Shares sold by Cowen and Company.

During the year ended December 31, 2024, we issued 1,772,278 shares of our common stock under the 2024 Sales Agreement at a weighted-average price of $13.19 for net proceeds of $22.8 million after deducting related issuance costs.

On January 6, 2025, we entered into a sales agreement (the 2025 Sales Agreement) with TD Securities (USA) LLC, (TD Cowen) as sales agent, pursuant to which the Company may offer and sell, from time to time, shares of the Company's common stock, having an aggregate offering price of up to $150.0 million (the 2025 ATM

The 2025 Sales Agreement replaced our 2024 Sales Agreement, and no further sales may be made pursuant to the 2024 Sales Agreement.

The sales of the 2025 ATM Shares will be made by any method permitted that is deemed to be an ATM equity offering as defined in Rule 415(a)(4) promulgated under the Securities Act, including sales made directly on or through the Nasdaq Global Select Market.

We have agreed to pay TD Cowen a commission of up to 3.0% of the aggregate gross proceeds from any 2025 ATM Shares sold by TD Cowen.

There were no sales under the 2025 Sales Agreement during the nine months ended September 30, 2025 and as of September 30, 2025, $150.0 million remained available for issuance under the 2025 Sales Agreement.

Refer to Note 12 of our notes to the condensed consolidated financial statements contained in this Quarterly Report for further information regarding the Exchange Transactions.

On January 6, 2025, we entered into a sales agreement (the Original 2025 Sales Agreement) with TD Securities (USA) LLC, (TD Cowen) as sales agent, pursuant to which the Company may offer and sell, from time to time, shares of the Company's common stock, having an aggregate offering price of up to $150.0 million (the Original 2025 ATM Shares).

The sales of the Original 2025 ATM Shares could be made by any method permitted that is deemed to be an ATM equity offering as defined in Rule 415(a)(4) promulgated under the Securities Act, including sales made directly on or through the Nasdaq Global Select Market.

We agreed to pay TD Cowen a commission of up to 3.0% of the aggregate gross proceeds from any 2025 ATM Shares sold by TD Cowen.

On December 11, 2025, we entered into amendment no.

1 to the sales agreement (together with the Original 2025 Sales Agreement, the 2025 Sales Agreement), which increased the maximum aggregate offering price under the ATM program to $200.0 million (the 2025 ATM Shares).

During the three months ended March 31, 2026, we issued 1,712,739 shares of our common stock under the 2025 Sales Agreement at a weighted-average price of $24.92 for net proceeds of $41.9 million after deducting related issuance costs.

On November 19, 2025, we completed a follow-on public offering pursuant to which we sold 11,500,000 shares of common stock at a public offering price of $19.00 per share, including 1,500,000 shares sold pursuant to the underwriters’ full exercise of their option to purchase additional shares, resulting in aggregate net proceeds of $204.8 million, after deducting underwriting discounts and commissions and estimated offering costs.

Sales of our common stock were made under our shelf registration on Form S-3, which we initially filed with the SEC on January 6, 2025 and that was declared effective by the SEC on January 15, 2025.

We expect to incur significant expenses and operating losses for the foreseeable future as we advance the clinical development of palazestrant, OP-3136, and non-clinical studies.

We expect that our research and development and general and administrative costs will increase in connection with conducting additional non-clinical studies and clinical trials for our current and future research programs and product candidates, contracting with CMOs to support non-clinical studies and clinical trials, expanding our intellectual property portfolio, and providing general and administrative support for our operations.

We expect that our research and development and general and administrative costs will increase in connection with conducting additional non-clinical studies and clinical trials for our current and future research programs and product candidates, contracting with CMOs to support non-clinical studies and clinical trials, expanding our intellectual property portfolio, developing our commercialization capabilities, and providing general and administrative support for our operations.

As a result, we will need additional capital to fund our operations, which we may obtain from additional equity or debt financings, collaborations, licensing arrangements or other sources.

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The amount and timing of our future funding requirements will depend on many factors, including the pace and results of our development efforts.

We expect our cash, cash equivalents, and marketable securities as of September 30, 2025, as well as the available balance under the Credit Facility, will enable us to fund our current operating plan for at least the next 12 months from the filing date of these condensed consolidated financial statements.

Refer to Notes 9, 10 and 11 of our notes to the condensed consolidated financial statements contained in this Quarterly Report on Form 10-Q for further information regarding our material cash requirements;

other than as set forth therein, there have been no material changes outside the ordinary course of business during the three and nine months ended September 30, 2025 to our commitments and contingencies disclosed in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” included in our Annual Report on Form 10-K.

We expect our cash, cash equivalents, and marketable securities as of March 31, 2026, as well as the available balance under the Credit Facility, will enable us to fund our current operating plan through mid-2028.

We have based this estimate of cash runway on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we expect.

Refer to Notes 9, 10 and 11 of our notes to the condensed consolidated financial statements contained in this Quarterly Report for further information regarding our material cash requirements.

Other than as set forth therein, there have been no material changes outside the ordinary course of business during the three months ended March 31, 2026 to our commitments and contingencies disclosed in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” included in our Annual Report.

If we are unable to raise capital when needed or on attractive terms, we would be forced to delay, reduce or eliminate our research and development programs or future commercialization efforts.

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Debt financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends.

If we raise funds through collaborations, strategic alliances or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to us.

For example, our Loan Agreement includes covenants limiting our ability to, among other things, fund future acquisitions, make dividend payments, or obtain additional financing.

If we raise funds through collaborations, strategic alliances, or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs, or product candidates or to grant licenses on terms that may not be favorable to us.

If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce, or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

The following table shows a summary of our cash flows for each of the periods presented:

Nine Months Ended September 30,

Three Months Ended March 31,

(in thousands)

Net cash used in operating activities

Net cash provided by investing activities

Net cash (used in) provided by financing activities

Net decrease in cash and cash equivalents

Net cash provided by (used in) investing activities

Net cash provided by financing activities

Net increase (decrease) in cash and cash equivalents

Operating activities

Net cash used in operating activities during the nine months ended September 30, 2025 consisted primarily of our net loss of $116.4 million, non-cash interest income on our marketable securities of $5.1 million and net decrease in operating assets and liabilities of $0.4 million, offset by non-cash charges of $13.6 million.

The net loss consisted primarily of $114.5 million in research and development expenses and $14.1 million in general and administrative expenses.

The non-cash charges consisted primarily of stock-based compensation expense of $13.3 million, depreciation and amortization expenses of $0.3 million, and non-cash lease expense of less than $0.1 million, net of cash payments of $0.9 million.

The net decrease in operating assets and liabilities was primarily due to (i) an increase of other assets and long-term deposits of $5.6 million due to project deposits paid to CROs as we advance OP-3136 and conduct initiation activities for OPERA-02, (ii) a decrease of $1.2 million in accounts payable, which is primarily related to timing of invoicing by vendors and related payments, and (iii) an increase in prepaid expenses and other current assets of $1.0 million.

These changes were partially offset by an increase of $7.4 million in other current liabilities, which is primarily related to increased spending on clinical development-related activities as we advanced palazestrant through late-stage clinical trials and OP-3136 program, as well as initiation activities for OPERA-02.

Net cash used in operating activities during the nine months ended September 30, 2024 consisted primarily of our net loss of $95.5 million and non-cash interest income on our marketable securities of $6.5 million, offset by non-cash charges of $16.5 million and net increase in operating assets and liabilities of $7.8 million.

Net cash used in operating activities during the three months ended March 31, 2026 consisted primarily of our net loss of $53.1 million, increased by cash outflows associated with working capital of $1.9 million and non-cash adjustments of $1.3 million related to interest income on our marketable securities.

These were partially offset by stock-based compensation expense of $10.1 million and depreciation and amortization expenses of $0.1 million.

The net decrease in operating assets and liabilities was primarily due to a $1.3 million increase in other current liabilities and a $5.7 million decrease in accounts payable, which is primarily reflecting the timing of vendor invoicing and related payments.

These were partially offset by a $2.6 million decrease in prepaid expenses and other current assets, including a non-cash reclassification impact of $0.5 million related to security deposits.

Net cash used in operating activities during the three months ended March 31, 2025 consisted primarily of our net loss of $30.4 million, non-cash interest income on our marketable securities of $2.1 million and net decrease in operating assets and liabilities of $16.0 million, offset by non-cash charges of $4.5 million.

The net loss consisted primarily of $30.6 million in research and development expenses and $4.2 million in general and administrative expenses.

The non-cash charges consisted primarily of stock-based compensation expense of $4.4 million, depreciation and amortization expenses of $0.1 million, and non-cash lease expense of less than $0.1 million, net of cash payments of $0.3 million.

The net increase in operating assets and liabilities was primarily due to (i) an increase of $9.0 million in accrued and other current liabilities and (ii) a decrease of $1.5 million in prepaid expenses and other current assets, which is primarily due to the reimbursable research and development costs received from a collaboration partner.

The net increases in operating liabilities were primarily offset by an increase of $2.6 million in other assets and long-term deposits.

The net decrease in operating assets and liabilities was

primarily due to (i) a decrease of $11.2 million in accrued and other current liabilities, (ii) a decrease of $4.3 million in accounts payable, which is primarily related to timing of invoicing by vendors and related payments, and (iii) an increase of other assets and long-term deposits of $1.0 million.

The changes are partially offset by an increase in prepaid expenses and other current assets of $0.5 million.

Investing activities

Net cash provided by investing activities during the nine months ended September 30, 2025 was predominantly due to maturities of marketable securities which were partially offset by purchases of marketable securities.

Net cash provided by investing activities during the nine months ended September 30, 2024 was predominantly due to maturities of marketable securities which were partially offset by purchases of marketable securities.

Net cash provided by investing activities during the three months ended March 31, 2026 was predominantly due to maturities of marketable securities which were partially offset by purchases of marketable securities.

Net cash used in investing activities during the three months ended March 31, 2025 was predominantly due to purchases of marketable securities which were partially offset by maturities of marketable securities.

Financing activities

Net cash used in financing activities during the nine months ended September 30, 2025 was predominately due to the $6.5 million payment of issuance costs related to the 2024 Private Placement, partially offset by $3.0 million draw down under our Credit Facility, $0.7 million from the sale of our common stock under the ESPP, and $0.5 million from the exercise of stock options.

Net cash provided by financing activities during the nine months ended September 30, 2024 consists of $22.8 million in net proceeds from the sale of 2024 ATM Shares, $1.1 million from the exercise of stock options, and $0.7 million from the sale of our common stock under the ESPP.

Net cash provided by financing activities during the three months ended March 31, 2026 consists primarily of $41.9 million of net proceeds from the issuance of shares under the at-the-market offering and $8.4 million of proceeds from stock option exercises, partially offset by payments of $4.4 million for tax withholdings associated with stock option exercises.

Net cash provided by financing activities during the three months ended March 31, 2025 was predominately due to $0.2 million from the exercise of stock options.

Critical accounting policies and significant judgments and estimates

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Our actual results may differ from these estimates under different assumptions or conditions.

During the three months ended September 30, 2025, there were no material changes to our critical accounting policies and estimates as reported in our Annual Report on Form 10-K.

During the three months ended March 31, 2026, there were no material changes to our critical accounting policies and estimates as reported in our Annual Report.

Quantitative and Qualitative Disclosures About Market Risk.

During the three months ended September 30, 2025, there were no material changes to our market risk disclosures reported in our Annual Report on Form 10-K.

During the three months ended March 31, 2026, there were no material changes to our market risk disclosures reported in our Annual Report.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-Q

Item 2. Management’s Discussion and Analysis