<div id="readability-page-1"><p>Olema Pharmaceuticals <span>NASDAQ: OLMA<span></span></span> President and CEO Sean Bohen said the company believes the emerging oral selective estrogen receptor degrader (SERD) class has proven its value over the past year, even as many earlier candidates fell away due to molecular, pharmacologic, or combination limitations. Speaking at a healthcare conference in a discussion moderated by analyst Matt Biegler, Bohen said the central issue in ER-positive, HER2-negative breast cancer has long been “not adequately suppressing the estrogen receptor-mediated growth and proliferation signals,” and that prior endocrine therapies each have meaningful shortcomings.</p><div><p><span></span><span>Get <strong>Olema Pharmaceuticals</strong> alerts:</span></p></div><h2>SERDs and what has become clearer over the past year</h2> <p>Bohen outlined why he believes a large development effort was warranted: tamoxifen is a partial agonist, aromatase inhibitors reduce but do not eliminate peripheral estrogen and do not interact with the receptor directly, and fulvestrant has “really flawed” clinical pharmacology despite its molecular appeal. He described estrogen receptor targeting as difficult because it is a ligand-regulated transcription factor requiring both a complete antagonist profile and “exposure all the time” to keep the receptor occupied. </p><p>According to Bohen, the field started with roughly ten drugs in the space, and it was “fairly predictable” that many would be flawed. He said the attrition contributed to skepticism about the class, but that recent results have made it “very clear it does work… if you do it well.”  </p><h2>How palazestrant is positioned versus other agents</h2> <p>Bohen distinguished between drugs he described as complete estrogen receptor antagonists (CERAs) and those he characterized as SERMs. He said palazestrant is among the complete antagonists, along with giredestrant and camizestrant, while elacestrant and fabtuzastrant are not. </p><p>Beyond molecular mechanism, Bohen emphasized pharmacokinetics and combination feasibility. He said palazestrant has “superior exposure” versus giredestrant and other agents, and argued that being able to maintain full-dose exposure while combining with other therapies is critical. In discussing combination use, he cited the need to avoid both overlapping toxicity and drug-drug interactions that could alter exposure.  </p><h2>Watching Roche’s persevERA readout and implications for OPERA-02</h2> <p>The conversation turned to Roche’s metastatic first-line persevERA trial (giredestrant plus palbociclib). Bohen said Roche had guided to a near-term top-line press release and noted that, while the top-line result will be binary, the data could contain more nuance—ranging from a lack of treatment effect, to a trend that misses statistical significance, to a clear positive outcome. </p><p>Bohen discussed a key operational detail: giredestrant was dose-reduced historically, and he said the dose used in persevERA is 30 mg, the same as in the adjuvant lidERA trial. He added that while he still believes the dose reduction may limit the ability to maximize efficacy, lidERA’s result was “not subtle” and demonstrated clear activity. </p><p>On biology, Bohen framed uncertainty around endocrine sensitivity and prior endocrine exposure. He said lidERA enrolled endocrine-sensitive, ESR1 wild-type patients in an adjuvant, endocrine-naïve setting, while in first-line metastatic persevERA the majority of patients—he estimated roughly 70–75%—will have received prior adjuvant therapy and be “endocrine experienced.” He said the remaining 25–30% may be de novo metastatic and endocrine naïve. </p><p>Importantly, Bohen said Olema is “not beholden to persevERA at all,” though he views the palbociclib plus aromatase inhibitor control arm as particularly informative for understanding how contemporary control arms perform versus older historical benchmarks. He said Olema may adjust assumptions or design elements in its ongoing Phase 3 OPERA-02 trial (ribociclib plus aromatase inhibitor versus ribociclib plus palazestrant) if control-arm performance in persevERA and potentially SERENA-4 suggests revisions are appropriate.  </p><h2>Combination strategy and second-line data context</h2> <p>Biegler and Bohen also discussed combination feasibility with ribociclib and broader “combinability.” Bohen said Olema has combined palazestrant at full doses with multiple agents, including palbociclib, ribociclib, alpelisib, and everolimus, and noted ongoing work with atirmociclib (a Pfizer CDK4-selective molecule) as well as Olema’s KAT6 inhibitor, OP-3136. </p><p>He attributed combination flexibility to tolerability and lack of meaningful pharmacokinetic interference, contrasting this with giredestrant’s dose reduction driven by tolerability issues, including bradycardia. He said Olema has not observed overlapping toxicity or significant PK alterations in combination. </p><p>In discussing second-line outcomes in a post-CDK4/6-treated population, Bohen said other combination datasets have shown median progression-free survival (PFS) “around eight months,” while Olema observed “one year” median PFS. He said, within that, Olema saw “nicely over nine months” in ESR1 wild-type patients and “almost 14 months” in ESR1-mutant patients, describing the effect as preserved regardless of whether ESR1 mutation is the resistance mechanism. </p><p>Bohen said Olema is evaluating whether it is worthwhile to run another second-line trial involving a CDK4/6 backbone, acknowledging that physicians often keep a CDK4/6 inhibitor and change the endocrine partner in practice, even though post-CDK4/6 data have not been “wildly encouraging.”  </p><h2>OPERA-01 goals, commercial planning, and the KAT6 program</h2> <p>Looking to OPERA-01, Bohen described expectations for the control arm (fulvestrant or exemestane, “mostly… fulvestrant”), citing repeatedly observed median PFS of roughly 2–3 months and a goal of achieving about two additional months. He also noted potential patient convenience from an oral daily pill compared with fulvestrant injections. </p><p>On commercialization, Bohen said Olema has begun hiring commercial expertise and is developing a U.S.-only launch strategy, assuming a positive trial. He said the company intends to seek a partner with global capabilities, describing building a global commercial operation as a “terrible distraction.” In market terms, he characterized ESR1-mutant disease as a “$2 billion a year market,” and said addressing wild-type disease would be “a $5 billion plus market,” adding that longer duration from combinations could expand the opportunity further. </p><p>Bohen also previewed the company’s KAT6 inhibitor program, saying OP-3136 targets KAT6A, KAT6B, and KAT7 while dialing back inhibition of KAT5 and KAT8. He cited published mouse knockout data supporting the need to inhibit both KAT6A and KAT6B, noting compensatory behavior by KAT6B. He said dysgeusia and cytopenias are the primary adverse events for the class, with cytopenias being the key dose-limiting concern. Bohen said Olema expects to present first data in the second quarter of the year, “mostly monotherapy data,” including tolerability and exposure, and added that preclinical work suggests potential beyond breast cancer, including castration-resistant prostate cancer and non-small cell lung cancer. </p><p>When asked about acquisition interest, Bohen said he does not spend time on it day to day, emphasizing a focus on developing better therapies and noting existing collaborations with Novartis and Pfizer. He added that if a party preferred ownership over collaboration, the company would consider it, but said it is not the operational focus.</p><h2>About Olema Pharmaceuticals <span>NASDAQ: OLMA<span></span></span></h2><p>Olema Pharmaceuticals, Inc, a clinical-stage biopharmaceutical company, focuses on the discovery, development, and commercialization of therapies for women's cancers. Its lead product candidate is OP-1250, an estrogen receptor (ER) antagonist and a selective ER degrader, which is in Phase 3 clinical trial for the treatment of recurrent, locally advanced, or metastatic estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer; and OP-1250 combine with CDK4/6 inhibitors palbociclib, ribociclib, and alpelisib in Phase 1/2 clinical trial for the treatment of recurrent, locally advanced, or metastatic estrogen receptor-positive human epidermal growth factor receptor 2-negative breast cancer, as well as develops OPERA-01 for the of ER+/HER2- advanced or metastatic breast cancer.</p><h2>Read More</h2><ul><li>Five stocks we like better than Olema Pharmaceuticals</li><li>The gold chart Wall Street is terrified of…</li><li>This makes me furious</li><li>America’s 1776 happening again</li><li>Buy this Gold Stock Before May 2026</li><li>“Fed Proof” Your Bank Account with THESE 4 Simple Steps</li></ul><p><em>This instant news alert was generated by narrative science technology and financial data from MarketBeat in order to provide readers with the fastest reporting and unbiased coverage. Please send any questions or comments about this story to contact@marketbeat.com.</em></p><h2>Should You Invest $1,000 in Olema Pharmaceuticals Right Now?</h2><p>Before you consider Olema Pharmaceuticals, you'll want to hear this.</p><p>MarketBeat keeps track of Wall Street's top-rated and best performing research analysts and the stocks they recommend to their clients on a daily basis. MarketBeat has identified the five stocks that top analysts are quietly whispering to their clients to buy now before the broader market catches on... and Olema Pharmaceuticals wasn't on the list.</p><p>While Olema Pharmaceuticals currently has a Moderate Buy rating among analysts, top-rated analysts believe these five stocks are better buys.</p><p>View The Five Stocks Here</p>                  </div>

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<p>Olema Pharmaceuticals CEO Sean Bohen highlighted the value of the emerging oral selective estrogen receptor degrader (SERD) class at a healthcare conference. He noted that while many earlier candidates faced limitations, palazestrant stands out as a complete estrogen receptor antagonist with superior pharmacokinetics. Bohen discussed the importance of maintaining full-dose exposure in combination therapies and the implications of Roche's persevERA trial on Olema's ongoing Phase 3 OPERA-02 trial. He emphasized the promising median progression-free survival rates observed with palazestrant in various patient populations.</p>

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Olema Pharmaceuticals CEO Touts Palazestrant Edge as Oral SERDs Shake Out at Conference