On October 13, 2023 Scorpion Therapeutics, Inc. ("Scorpion"), a pioneering clinical-stage oncology company redefining the frontier of precision medicine through its Precision Oncology 2.0 strategy, reported preclinical data for STX-241, an orally bioavailable, highly selective, central nervous system ("CNS")-penetrant and potentially best-in-class fourth generation epidermal growth factor receptor ("EGFR") tyrosine kinase inhibitor ("TKI") designed to inhibit C797S mutations with a co-occurring EGFR exon 19 deletion or exon 21 mutation ("double mutant") in non-small cell lung cancer ("NSCLC") (Press release, Scorpion Therapeutics, OCT 13, 2023, View Source [SID1234635964]). Discovered by Scorpion, STX-241 is currently being developed in collaboration with Pierre Fabre Laboratories, a leading French medical and beauty care company with 4 decades of experience in innovation, development, manufacturing, and commercialization in oncology. The data will be presented today in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper), the National Cancer Institute, and the European Organisation for Research and Treatment of Cancer ("AACR-NCI-EORTC") Symposium 2023 in Boston, Massachusetts.
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"We are pleased to share the first preclinical data for STX-241, the second highly selective development candidate from our franchise of next-generation EGFR inhibitors for the treatment of NSCLC that we are developing with our partner, Pierre Fabre Laboratories," said Axel Hoos, M.D., Ph.D., Chief Executive Officer of Scorpion. "These data bolster our belief that STX-241 can overcome the challenges of currently approved EGFR-targeting medicines that are limited in their impact by the emergence of acquired resistance mutations. We look forward to building on these encouraging findings and submitting an investigational new drug ("IND") application in the first half of next year, as we work to deliver better outcomes for people with ‘double mutant’ NSCLC."
NSCLC is the most common form of lung cancer and EGFR mutations are one of its most common disease drivers, occurring in up to 38 percent of tumors1,2,3. The current standard-of-care therapy for NSCLC patients with EGFR exon 19 or 21 mutations is osimertinib; however, co-occurring L858R/C797x or ex19del/C797x mutations ("double mutants") are emerging as an on-target resistance mechanism in a subset of these patients, with the most recent data analyses suggesting mutation frequencies of approximately 12.5%4,5,6,7,8. There are currently no approved therapeutic options for patients that develop "double mutant" EGFR NSCLC. In addition, the relative lack of CNS penetrance with first-generation inhibitors may limit durable clinical responses to treatment, further underscoring the need for new therapies, particularly in patients with CNS metastases.
"The strong pre-clinical profile of STX-241 is a primary reason we believe in its potential to play a meaningful role in treating patients with NSCLC who have limited options," said Francesco Hofmann, Head of Research and Development for Medical Care at Pierre Fabre Laboratories. "We look forward to working with Scorpion to advance it into the clinic."
In the poster presented at AACR (Free AACR Whitepaper)-NCI-EORTC, Scorpion scientists will share data from preclinical studies characterizing the potency and selectivity of STX-241, as well as its ability to penetrate the CNS. In these studies, STX-241 demonstrated strong biochemical inhibition of EGFR double mutant kinase activity, as well as strong C797S double mutant potency and selectivity across both proliferation and target engagement assays, exceeding clinical-stage competitor benchmarks in each of these model systems.
In addition, STX-241 demonstrated strong in vivo antitumor activity across a variety of single and double-mutant cell line-derived xenograft ("CDX") models, effectively retaining activity in the presence of the C797 mutation, and CNS penetrance on-par with osimertinib, supporting its potential to address CNS metastases.
"We designed STX-241 as a potentially best-in-class small molecule for NSCLC patients who progress following first-line therapy," said Darrin Stuart, Ph.D., Chief Scientific Officer of Scorpion Therapeutics. "Together, the data presented at AACR (Free AACR Whitepaper)-NCI-EORTC underscore STX-241’s potential to provide a better option for patients who develop ‘double mutant’ disease, for which there is currently no approved treatment, as well as address the CNS metastases that occur in patients who progress on osimertinib."
STX-241 is the third development candidate nominated by Scorpion in less than three years, and the second highly selective EGFR development candidate from the Company’s franchise of next-generation mutant EGFR inhibitors for the treatment of NSCLC. Scorpion is also developing STX-721, a potentially best-in-class exon 20 mutant EGFR inhibitor, which entered the clinic earlier this month.
The poster can be viewed in the Publications & Presentations section of Scorpion’s website: View Source
About STX-241
STX-241 is a fourth generation, orally delivered, CNS-penetrant small molecule designed with potentially best-in-class selectivity to target resistance mutations at C797S. Scorpion estimates that up to 3,000 patients per year in the United States, or up to 12.5 percent of NSCLC patients with Exon 19 or 21 mutations, develop resistance mutations at C797S. STX-241 is currently advancing through preclinical studies, and Scorpion expects to submit an IND to the U.S. FDA in the first half of 2024.