ORIC® Pharmaceuticals Presents Data Further Supporting Potential Best-In-Class Profile of ORIC-114 to Treat EGFR Exon 20 Insertions and Other Atypical Mutations at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics
ORIC Pharmaceuticals presented data highlighting ORIC-114's potential as a best-in-class EGFR/HER2 inhibitor for treating EGFR exon 20 insertions and other atypical mutations. The brain-penetrant, orally bioavailable treatment demonstrated superior potency across EGFR mutational classes compared to other inhibitors. Key findings showed tumor regressions in all tested EGFR mutant models, with 100% tumor regressions in complex atypical mutant EGFR models. The drug displayed superior kinome selectivity and complete molecular responses in ctDNA from patients. Updated data from Phase 1b expansion cohorts is expected in H1 2025.
ORIC Pharmaceuticals ha presentato dati che evidenziano il potenziale di ORIC-114 come un inibitore EGFR/HER2 di classe superiore per il trattamento delle inserzioni dell'esone 20 dell'EGFR e di altre mutazioni atipiche. Il trattamento, che penetra nel cervello e può essere assunto per via orale, ha dimostrato una potenza superiore rispetto ad altri inibitori tra le classi di mutazioni dell'EGFR. Risultati chiave hanno mostrato regressioni tumorali in tutti i modelli mutazionali EGFR testati, con regressioni tumorali del 100% nei modelli di EGFR mutante atipico complesso. Il farmaco ha mostrato una selettività kinomica superiore e risposte molecolari complete nel ctDNA dei pazienti. Sono attesi dati aggiornati dai coorti di espansione di Fase 1b nel primo semestre del 2025.
ORIC Pharmaceuticals presentó datos que destacan el potencial de ORIC-114 como un inhibidor EGFR/HER2 de clase mundial para tratar inserciones en el exón 20 de EGFR y otras mutaciones atípicas. El tratamiento, que penetra en el cerebro y es biodisponible por vía oral, demostró una potencia superior en todas las clases de mutaciones de EGFR en comparación con otros inhibidores. Hallazgos clave mostraron regresiones tumorales en todos los modelos mutantes de EGFR probados, con un 100% de regresiones tumorales en modelos de EGFR mutantes atípicos complejos. El fármaco mostró una selectividad kinómica superior y respuestas moleculares completas en ctDNA de los pacientes. Se esperan datos actualizados de los cohortes de expansión de Fase 1b en el primer semestre de 2025.
ORIC Pharmaceuticals는 EGFR 엑손 20 삽입 및 기타 비정형 변이를 치료하기 위해 ORIC-114의 잠재력을 강조하는 데이터를 발표했습니다. 뇌 침투가 가능하고 경구 생체 이용 가능한 이 치료법은 다른 억제제와 비교하여 EGFR 변이 클래스 전반에 걸쳐 우수한 효능을 보여줍니다. 핵심 발견은 테스트한 모든 EGFR 돌연변이 모델에서 종양 퇴축을 보여주었으며, 복잡한 비정형 돌연변이 EGFR 모델에서 100% 종양 퇴축이 있었습니다. 이 약물은 우수한 키노믹 선택성과 환자의 ctDNA에서 완전한 분자 반응을 나타냈습니다. 2025년 상반기에는 1b상 확장 집단의 업데이트된 데이터가 예상됩니다.
ORIC Pharmaceuticals a présenté des données soulignant le potentiel d'ORIC-114 en tant qu'inhibiteur EGFR/HER2 de classe mondiale pour le traitement des insertions de l'exon 20 d'EGFR et d'autres mutations atypiques. Ce traitement, qui pénètre dans le cerveau et est biodisponible par voie orale, a démontré une puissance supérieure dans toutes les classes de mutations d'EGFR par rapport à d'autres inhibiteurs. Les résultats clés ont montré des régressions tumorales dans tous les modèles mutés d'EGFR testés, avec 100 % de régressions tumorales dans des modèles complexes de mutants atypiques d'EGFR. Le médicament a affiché une sélectivité kinomique supérieure et des réponses moléculaires complètes dans le ctDNA des patients. Des données mises à jour des cohortes d'expansion de la phase 1b sont attendues au premier semestre 2025.
ORIC Pharmaceuticals hat Daten präsentiert, die das Potenzial von ORIC-114 als einen erstklassigen EGFR/HER2-Inhibitor zur Behandlung von EGFR-Exon-20-Insertionen und anderen atypischen Mutationen hervorheben. Die gehirngängige, oral bioverfügbare Therapie zeigte eine überlegene Potenz über alle EGFR-Mutationsklassen hinweg im Vergleich zu anderen Inhibitoren. Wichtige Ergebnisse zeigten Tumorrückgänge in allen getesteten EGFR-mutierten Modellen, mit 100% Tumorrückgängen in komplexen atypischen EGFR-mutierten Modellen. Das Medikament wies eine überlegene Kinomselektivität und vollständige molekulare Antworten in ctDNA von Patienten auf. Aktualisierte Daten aus den Phase 1b-Erweiterungsgruppen werden im ersten Halbjahr 2025 erwartet.
- Demonstrated superior potency across EGFR mutational classes compared to competitors
- Achieved 100% tumor regression rates in complex atypical mutant EGFR models
- Showed complete molecular responses in ctDNA from patients
- Demonstrated both systemic and intracranial clinical responses in heavily pre-treated patients
- None.
Insights
The preclinical data for ORIC-114 demonstrates compelling potential in treating EGFR/HER2 mutations in non-small cell lung cancer (NSCLC). Key strengths include superior potency across EGFR mutational classes and effective brain penetration, addressing a critical unmet need for patients with CNS metastases. The data shows 100% tumor regression in complex atypical mutant models and complete molecular responses in ctDNA from patients.
The drug's superior kinome selectivity profile and favorable safety data suggest reduced risk of off-target effects compared to competitors like firmonertinib and zipalertinib. Early clinical results showing both systemic and CNS responses in heavily pre-treated patients are particularly promising, though more extensive clinical validation is needed through the ongoing Phase 1b expansion cohorts.
SOUTH SAN FRANCISCO, Calif. and SAN DIEGO, Oct. 23, 2024 (GLOBE NEWSWIRE) -- ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, today announced the company presented a poster highlighting certain best-in-class properties of ORIC-114, a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor, to treat EGFR exon 20 insertions and other atypical mutations at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.
“Preclinical data presented today underscore ORIC-114’s superior potency and selectively across EGFR mutational classes compared to other EGFR inhibitors,” said Lori Friedman, PhD, chief scientific officer. “These results build on clinical findings that highlight ORIC-114’s potential best-in-class profile, showing notable systemic and CNS responses, along with a favorable safety profile, even in heavily pre-treated NSCLC patients. We are continuing to evaluate ORIC-114 in multiple Phase 1b expansion cohorts for NSCLC patients with EGFR exon 20, HER2 exon 20, and atypical EGFR mutations, with updated data expected in the first half of 2025.”
Poster presentation details:
ORIC-114 previously demonstrated systemic and intracranial clinical responses in heavily pre-treated patients with EGFR and HER2 exon 20 insertion mutations. Key findings of this poster presentation:
- Demonstrates regressions in all EGFR mutant in vivo models tested, including cell-derived xenografts, patient-derived xenografts and intracranial models that encompass exon 20 insertion and atypical mutant models. An in vivo model with complex atypical mutant EGFR dosed with ORIC-114 notably shows
100% tumor regressions and all tumors experienced a complete response. - In an expanded preclinical comparative analysis of exon 20 insertion, atypical PACC and other mutations, overall ORIC-114 is the most potent across EGFR mutational classes whilst displaying comparative wild-type selectivity in cell-based assays, relative to firmonertinib, zipalertinib, lazertinib and BDTX-1535.
- In head-to-head comparisons with firmonertinib, zipalertinib, lazertinib and BDTX-1535, ORIC-114 has superior kinome selectivity with no off-target kinase liabilities identified.
- Shows complete molecular responses in ctDNA from patients with EGFR exon 20 insertion and PACC mutations from Phase 1 dose escalation study. Evidence of molecular responses observed across dose escalation cohorts supports broad therapeutic window for ORIC-114.
- ORIC-114 is a promising therapeutic candidate with best-in-class potential for patients with non-small cell lung cancer harboring exon 20 insertions and atypical mutations in EGFR, including those presenting with active CNS metastases, and is being evaluated in a global clinical trial (NCT05315700).
About ORIC-114
ORIC-114 is a highly selective, brain penetrant, orally bioavailable, irreversible inhibitor that selectively targets EGFR exon 20, HER2 exon 20 and EGFR atypical mutations, making it a promising therapeutic candidate to address the unmet medical need of having both meaningful systemic as well as CNS antitumor activity.
About ORIC Pharmaceuticals, Inc.
ORIC Pharmaceuticals is a clinical stage biopharmaceutical company dedicated to improving patients’ lives by Overcoming Resistance In Cancer. ORIC’s clinical stage product candidates include (1) ORIC-114, a brain penetrant inhibitor that selectively targets EGFR exon 20, HER2 exon 20 and EGFR atypical mutations, being developed across multiple genetically defined cancers, (2) ORIC-944, an allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via the EED subunit, being developed for prostate cancer, and (3) ORIC-533, an orally bioavailable small molecule inhibitor of CD73, a key node in the adenosine pathway believed to play a central role in resistance to chemotherapy- and immunotherapy-based treatment regimens, being developed for multiple myeloma. Beyond these three product candidates, ORIC® is also developing multiple precision medicines targeting other hallmark cancer resistance mechanisms. ORIC has offices in South San Francisco and San Diego, California. For more information, please go to www.oricpharma.com, and follow us on X or LinkedIn.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, statements regarding the best-in-class properties of ORIC-114; the continued clinical development of ORIC-114; the potential advantages of ORIC-114 and ORIC’s other product candidates and programs; timing of updated data from the clinical trial of ORIC-114; development plans for ORIC’s product candidates and programs; and statements by the company’s chief scientific officer. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. The forward-looking statements contained herein are based upon ORIC’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those projected in any forward-looking statements due to numerous risks and uncertainties, including but not limited to: risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early clinical stage company; ORIC’s ability to develop, initiate or complete preclinical studies and clinical trials for, obtain approvals for and commercialize any of its product candidates; changes in ORIC’s plans to develop and commercialize its product candidates; the potential for clinical trials of ORIC’s product candidates to differ from preclinical, initial, interim, preliminary or expected results; negative impacts of health emergencies, economic instability or international conflicts on ORIC’s operations, including clinical trials; the risk of the occurrence of any event, change or other circumstance that could give rise to the termination of ORIC’s license and collaboration agreements or its clinical trial collaboration and supply agreements; the potential market for ORIC’s product candidates, and the progress and success of competing therapeutics currently available or in development; ORIC’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; regulatory developments in the United States and foreign countries; ORIC’s reliance on third parties, including contract manufacturers and contract research organizations; ORIC’s ability to obtain and maintain intellectual property protection for its product candidates; the loss of key scientific or management personnel; competition in the industry in which ORIC operates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section titled “Risk Factors” in ORIC’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on August 12, 2024, and ORIC’s future reports to be filed with the SEC. These forward-looking statements are made as of the date of this press release, and ORIC assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law.
Contact:
Dominic Piscitelli, Chief Financial Officer
dominic.piscitelli@oricpharma.com
info@oricpharma.com
FAQ
What are the key findings of ORIC-114's latest clinical trial data presented at EORTC-NCI-AACR Symposium?
When will ORIC Pharmaceuticals (ORIC) release updated data from ORIC-114's Phase 1b expansion cohorts?
How does ORIC-114 compare to other EGFR inhibitors in preclinical studies?
