Olema Oncology Presents Compelling New Preclinical Data Demonstrating Anti-Tumor Activity for OP-3136 with Enhanced Activity of Palazestrant Combinations at ENA 2024
Olema Oncology presented preclinical data at ENA 2024 showcasing anti-tumor activity of their drug candidates. OP-3136, a KAT6 inhibitor, demonstrated strong anti-tumor activity alone and enhanced effects when combined with palazestrant. The company plans to submit an IND application for OP-3136 by year-end. Additionally, palazestrant showed improved tumor suppression when combined with everolimus and capivasertib in ER+/HER2- breast cancer models. The studies revealed synergistic effects and significant tumor regression, particularly when palazestrant was combined with these agents, showing superior results compared to fulvestrant combinations.
Olema Oncology ha presentato dati preclinici all'ENA 2024, evidenziando l'attività anti-tumorale dei loro candidati farmaci. OP-3136, un inibitore di KAT6, ha dimostrato una forte attività anti-tumorale da solo e effetti potenziati quando combinato con palazestrant. L'azienda prevede di presentare una domanda IND per OP-3136 entro la fine dell'anno. Inoltre, il palazestrant ha mostrato un miglioramento della soppressione tumorale quando combinato con everolimus e capivasertib in modelli di cancro al seno ER+/HER2-. Gli studi hanno rivelato effetti sinergici e una significativa regressione tumorale, in particolare quando il palazestrant è stato combinato con questi agenti, mostrando risultati superiori rispetto alle combinazioni con fulvestrant.
Olema Oncology presentó datos preclínicos en ENA 2024 que muestran la actividad antitumoral de sus candidatos a medicamentos. OP-3136, un inhibidor de KAT6, demostró una fuerte actividad antitumoral por sí solo y efectos mejorados cuando se combinó con palazestrant. La compañía planea presentar una solicitud IND para OP-3136 a finales de año. Además, el palazestrant mostró una mejor supresión tumoral cuando se combinó con everolimus y capivasertib en modelos de cáncer de mama ER+/HER2-. Los estudios revelaron efectos sinérgicos y una regresión tumoral significativa, particularmente cuando el palazestrant se combinó con estos agentes, mostrando resultados superiores en comparación con las combinaciones de fulvestrant.
올레마 온콜로지는 ENA 2024에서 자사 약물 후보들에 대한 전임상 데이터를 발표하며 항종양 활성을 보여주었습니다. OP-3136는 KAT6 억제제로 단독으로 강력한 항종양 활성을 나타냈고, 팔라제스트란트와 결합했을 때 효과가 증가했습니다. 회사는 연말까지 OP-3136에 대한 IND 신청서를 제출할 계획입니다. 또한, 팔라제스트란트는 ER+/HER2- 유방암 모델에서 에버롤리무스 및 카피바세르티브와 결합했을 때 종양 억제 효과가 개선되었습니다. 연구는 이러한 요인들과 결합했을 때 특히 시너지 효과와 유의미한 종양 퇴행을 보여주었으며, 팔라제스트란트를 사용한 경우 풀베스트란트 조합에 비해 우수한 결과를 나타냈습니다.
Olema Oncology a présenté des données précliniques lors de ENA 2024, mettant en avant l'activité anti-tumorale de ses candidats médicaments. OP-3136, un inhibiteur de KAT6, a démontré une forte activité anti-tumorale seul et des effets amplifiés lorsqu'il est combiné avec le palazestrant. L'entreprise prévoit de soumettre une demande IND pour OP-3136 d'ici la fin de l'année. De plus, le palazestrant a montré une amélioration de la suppression tumorale lorsqu'il est combiné avec l'évérolimus et le capivasertib dans des modèles de cancer du sein ER+/HER2-. Les études ont révélé des effets synergiques et une régression tumorale significative, notamment lorsque le palazestrant était associé à ces agents, montrant des résultats supérieurs par rapport aux combinaisons avec le fulvestrant.
Olema Oncology präsentierte präklinische Daten auf ENA 2024, die die antitumorale Aktivität ihrer Arzneimittelkandidaten zeigen. OP-3136, ein KAT6-Inhibitor, zeigte starke antitumorale Aktivität alleine und verbesserte Wirkungen in Kombination mit Palazestrant. Das Unternehmen plant, bis Ende des Jahres einen IND-Antrag für OP-3136 einzureichen. Darüber hinaus zeigte Palazestrant eine verbesserte Tumorsuppression in Kombination mit Everolimus und Capivasertib in ER+/HER2- Brustkrebsmodellen. Die Studien zeigten synergistische Effekte und eine signifikante Tumorreduktion, insbesondere wenn Palazestrant mit diesen Wirkstoffen kombiniert wurde, was bessere Ergebnisse im Vergleich zu Fulvestrant-Kombinationen zeigte.
- OP-3136 demonstrated robust anti-tumor activity both as single agent and in combinations
- Palazestrant showed superior anti-tumor efficacy compared to fulvestrant in combinations
- Synergistic effects observed in combinations with everolimus and capivasertib
- IND submission for OP-3136 planned before year end
- Phase 3 OPERA-01 trial for palazestrant progressing as planned
- None.
Insights
The preclinical data for OP-3136 and palazestrant combinations shows significant promise in breast cancer treatment. The key developments demonstrate:
- OP-3136 exhibits synergistic effects with both anti-estrogens and CDK4/6 inhibitors, achieving superior tumor regression when combined with palazestrant versus fulvestrant
- Palazestrant shows enhanced efficacy in combinations with everolimus and capivasertib, displaying stronger anti-tumor activity than current standard treatments
- The planned IND submission for OP-3136 by year-end marks a important regulatory milestone
These results suggest potential therapeutic advantages over existing treatments, particularly in ER+/HER2- breast cancer. The synergistic effects and improved tumor suppression could translate to better clinical outcomes, though this needs validation in human trials. The multiple successful combination studies indicate a versatile treatment approach that could address resistance mechanisms in breast cancer therapy.
This preclinical data strengthens Olema's pipeline value proposition. The three key investment considerations are:
- The dual advancement of OP-3136 (approaching IND stage) and palazestrant (in Phase 3) provides multiple shots on goal
- Palazestrant's superior combinability with various agents suggests potential for broader market penetration and multiple revenue streams
- The upcoming Phase 2 combination data with ribociclib at SABCS could be a near-term catalyst
The robust preclinical results across multiple combinations position Olema competitively in the breast cancer market. The progression toward clinical development of OP-3136 and ongoing Phase 3 trial of palazestrant represent significant value-creating milestones for investors to monitor.
- OP-3136, a potent KAT6 inhibitor, demonstrated robust anti-tumor activity as a single agent, as well as synergy and enhanced anti-tumor activity in combination with palazestrant; IND submission expected before year end
- Palazestrant demonstrated combinability and enhanced tumor suppression with both everolimus and capivasertib
SAN FRANCISCO, Oct. 23, 2024 (GLOBE NEWSWIRE) -- Olema Pharmaceuticals, Inc. (“Olema” or “Olema Oncology”, Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, today announced results from three preclinical studies that will be presented during poster sessions at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (ENA 2024) in Barcelona, Spain.
“Building on our earlier studies that showed compelling single agent activity for OP-3136, this new data demonstrates the potential for OP-3136 in combination with palazestrant, with strong tumor growth inhibition and regression relative to combinations with fulvestrant,” said David C. Myles, Ph.D., Chief Discovery and Non-Clinical Development Officer of Olema Oncology. “Taken together, these data reinforce our belief in the potential of OP-3136 as an exciting new therapy for breast and other cancers. We look forward to submitting our Investigational New Drug (IND) application for OP-3136 to the US Food and Drug Administration before the end of this year.”
Title: “Combining OP-3136, a KAT6 inhibitor, with endocrine therapy and CDK4/6 inhibitor enhances anti-tumor activity in ER+/HER2- breast cancer models”
Abstract: 230
Session: 300
Date: Thursday, October 24, 2024
Time: 9:00 to 17:30 CEST
Key findings include:
- OP-3136 inhibited cell proliferation and synergized with anti-estrogens (fulvestrant and palazestrant) and a CDK4/6 inhibitor (ribociclib) in a breast cancer cell line.
- OP-3136 led to either tumor growth inhibition or tumor regression in vivo in xenograft models across all treatment groups.
- In combination with OP-3136, palazestrant was consistently superior to fulvestrant and led to improved anti-tumor activity and tumor regression.
- OP-3136 showed robust synergistic anti‑tumor activity when combined with fulvestrant or palazestrant as doublet therapy in breast cancer models.
Dr. Myles continued, “With the potential to become a best-in-class endocrine therapy and improve upon current standard of care treatments for women living with metastatic breast cancer, our lead product candidate, palazestrant, continues to move through the clinic as a monotherapy in our pivotal Phase 3 OPERA-01 trial while also demonstrating combinability with multiple targeted agents, including CDK 4/6 inhibitors, in Phase 1/2 studies. Our preclinical posters at ENA show that the combination of palazestrant with both everolimus and capivasertib are synergistic and result in significant tumor regression. We look forward to advancing the development of palazestrant in combination with everolimus, ribociclib, and other agents and expect to present updated Phase 2 data for palazestrant in combination with ribociclib at the San Antonio Breast Cancer Symposium (SABCS) this December.”
Title: “Combining palazestrant, a CERAN, and everolimus, an mTOR inhibitor, enhances tumor suppression in ER+/HER2- breast cancer models”
Abstract: 211
Session: 300
Date: Thursday, October 24, 2024
Time: 9:00 to 17:30 CEST
Key findings include:
- Palazestrant and everolimus demonstrate synergy in vitro and in vivo and resulted in greater anti-proliferative activity than either agent alone.
- Combining palazestrant with everolimus causes gene signature transcriptional changes, downregulating cell cycle progression and upregulating apoptosis.
- These data support clinical investigation of the combination of palazestrant and everolimus.
Title: “Combining palazestrant, a CERAN, and capivasertib, a pan-AKT inhibitor, enhances tumor suppression in ER+/HER2- breast cancer models”
Abstract: 212
Session: 300
Date: Thursday, October 24, 2024
Time: 9:00 to 17:30 CEST
Key findings include:
- Palazestrant and capivasertib work synergistically to inhibit proliferation of multiple ER+ breast cancer models, both in vitro and in vivo.
- Palazestrant demonstrates superior anti-tumor efficacy over fulvestrant in combination with capivasertib, significantly inhibiting and repressing tumor growth.
- Combining palazestrant and capivasertib increases downregulation of genes associated with cell cycle progression.
- These data support clinical investigation of the combination of palazestrant and capivasertib.
Copies of these posters are available on the Publications page 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 clinical studies, palazestrant completely blocks ER-driven transcriptional activity in both wild-type and mutant forms of metastatic ER+ breast cancer and has demonstrated anti-tumor efficacy along with attractive pharmacokinetics and exposure, favorable tolerability, CNS penetration, and combinability with CDK4/6 inhibitors. Palazestrant has been granted U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of ER+/HER2- metastatic breast cancer that has progressed following one or more lines of endocrine therapy with at least one line given in combination with a CDK4/6 inhibitor. It is being evaluated both as a single agent in an ongoing Phase 3 clinical trial, OPERA-01, and in Phase 1/2 combination studies with CDK4/6 inhibitors (palbociclib and ribociclib), a PI3Ka inhibitor (alpelisib), and an mTOR inhibitor (everolimus). For more information on OPERA-01, please visit www.opera01study.com.
About OP-3136
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. In preclinical studies, OP-3136 has demonstrated significant anti-proliferative activity in ER+ breast cancer models and is combinable and synergistic with endocrine therapies including palazestrant and CDK4/6 inhibitors. Olema has successfully completed IND-enabling studies in support of a potential Investigational New Drug (IND) application with the FDA and expects to initiate Phase 1 clinical trials for OP-3136 in early 2025.
About Olema Oncology
Olema Oncology is a clinical-stage biopharmaceutical company committed to transforming the standard of care and improving outcomes for women living with cancer. Olema is advancing a pipeline of novel therapies by leveraging our deep understanding of endocrine-driven cancers, nuclear receptors, and mechanisms of acquired resistance. 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 timelines for initiation and enrollment for potential clinical studies and for results of clinical trials of palazestrant (OP-1250) as a monotherapy and in combination trials, potential beneficial characteristics, including but not limited to safety, tolerability, activity, efficacy and therapeutic effects of palazestrant, the potential of palazestrant to advance the standard of care for women living with cancer, palazestrant’s combinability with other drugs, the initiation of a phase 1b/2 clinical study of palazestrant in combination with everolimus and timing thereof, and the sufficiency and timing of Olema’s preclinical program, including the potential beneficial characteristics of its KAT6 inhibitor compounds and the timing of a potential IND application and advancement into clinical development for OP-3136. Because such statements deal with future events and are based on Olema’s current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of Olema could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including, without limitation, those discussed in the section titled “Risk Factors” in Olema’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, and future filings and reports that Olema makes from time to time with the U.S. Securities and Exchange Commission. Except as required by law, Olema assumes no obligation to update these forward-looking statements, including in the event that actual results differ materially from those anticipated in the forward-looking statements.
Contact
Courtney O’Konek, Vice President, Corporate Communications
media@olema.com
FAQ
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