Theseus Pharmaceuticals Nominates THE-349, a Fourth-Generation EGFR Inhibitor Development Candidate in Non-Small Cell Lung Cancer

 THE-349 is a fourth-generation, potent and selective, small molecule designed to inhibit all major classes of EGFR activating and resistance mutations

Preclinical data to be presented at the 34^th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics

IND submission anticipated in H2 2023

CAMBRIDGE, Mass., Oct. 3, 2022 /PRNewswire/ --  Theseus Pharmaceuticals, Inc. (NASDAQ: THRX) (Theseus or the Company), a clinical-stage biopharmaceutical company focused on improving the lives of cancer patients through the discovery, development, and commercialization of transformative targeted therapies, today announced that it has nominated THE-349 as the development candidate for its epidermal growth factor receptor (EGFR) inhibitor program in non-small cell lung cancer (NSCLC). THE-349 is designed to address treatment resistance to existing EGFR inhibitors by targeting the common activating mutations in exons 19 and 21 alone or in combination with the most frequently observed resistance mutations, T790M and C797X. In preclinical models, THE-349 potently inhibits single-, double-, and triple-mutant EGFR variants with these mutations that are observed in a post-first- or later-line osimertinib setting.

Preclinical characterization of THE-349 as a fourth-generation EGFR, central nervous system- (CNS) active, and mutant-selective inhibitor with potent activity against single-, double-, and triple-mutant EGFR variants, including T790M and C797X, will be shared in a poster presentation at the 34^th EORTC-NCI-AACR (ENA) Symposium taking place in Barcelona on October 26-28, 2022.

"We are delighted to announce THE-349 as the Company's second development candidate and we look forward to evaluating its potential in patients with EGFR-mutant NSCLC," said William Shakespeare, Ph.D., President of Research and Development at Theseus. "Clonal heterogeneity in patients who develop resistance to osimertinib is complex, and we believe a single EGFR inhibitor capable of targeting all major mutant forms of EGFR activating and resistance mutations is the optimal way to address this urgent medical need."

NSCLC is the most common form of lung cancer. Activating mutations in EGFR occur in 10-15% of Caucasian and up to 50% of Asian NSCLC patients, with up to 90% of those mutations found in exons 19 and 21. Although patients may initially respond to treatment with a first-, second- or third-generation EGFR tyrosine kinase inhibitor (TKI), their tumors eventually develop resistance to therapy. In patients whose tumors progress on osimertinib, point mutations at the C797 position (C797X) in EGFR have been observed at a frequency of up to approximately 12% after first-line osimertinib and 20% after second-line osimertinib. Patients presenting with these mutations have no available targeted therapy options due to current therapies lacking the necessary activity that can address both activating and resistance mutations.

Details for the presentation are as follows:

Title: Preclinical characterization of CNS-active, mutant-selective fourth-generation EGFR inhibitors with potent activity against single, double, and triple mutant EGFR variants including T790M and C797S
Abstract Number: 236
Session: Molecular Targeted Agents 2
Session Date and Time: Thursday, October 27, 2022: 10:00am-5:00pm (CEST)
Presenter: Sen Zhang, Ph.D. (Theseus Pharmaceuticals, Cambridge, USA)

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85% of the estimated 2.2 million cases of lung cancer diagnosed globally in 2020. Activating mutations in EGFR occur in 10-15% of Caucasian and up to 50% of Asian NSCLC patients, with up to 90% of those mutations found in exons 19 and 21. In response to treatment, patients' tumors can develop one or more additional EGFR mutations, causing resistance and rendering current therapies ineffective.

Theseus is a clinical-stage biopharmaceutical company focused on improving the lives of cancer patients through the discovery, development and commercialization of transformative targeted therapies. Theseus is working to outsmart cancer resistance by developing pan-variant tyrosine kinase inhibitors (TKIs) to target all known classes of cancer-causing and resistance mutations that lead to variants in a particular protein in a given type of cancer. Theseus' lead product candidate, THE-630, is a pan-variant KIT inhibitor for the treatment of patients with advanced gastrointestinal stromal tumors (GIST), whose cancer has developed resistance to earlier lines of kinase inhibitor therapy. Theseus is also developing THE-349, a fourth-generation, selective epidermal growth factor receptor (EGFR) inhibitor for C797X-mediated resistance to first- or later-line osimertinib treatment in patients with non-small cell lung cancer (NSCLC). For more information, visit www.theseusrx.com.

Certain statements included in this press release are not historical facts but are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements generally are accompanied by words such as "believe," "may," "will," "estimate," "anticipate," "expect," "plan," "predict," "potential," "seem," "outlook," and similar expressions that predict or indicate future events or trends or that are not statements of historical matters, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements include, but are not limited to, statements regarding: Theseus' strategy, future operations, prospects and plans; the structure and timing of its preclinical studies and clinical trials, expected milestones, market opportunity and sizing and objectives of management;  the significance of results of preclinical studies of THE-349, including the ability of the development candidate to potentially inhibit EGFR variants and the outlook of the EGFR inhibitor program; the Phase 1/2 dose escalation and expansion clinical trial for THE-630, and other programs and development candidates; and expectations regarding the submission of an IND for THE-349.

Actual results may differ materially from those indicated by such forward-looking statements as a result of various important risks, uncertainties and other factors, including, but not limited to: uncertainties inherent in preclinical studies; uncertainties regarding whether results from preclinical studies will be predictive of the results of future trials; risks related to the expected timing of submissions to regulatory authorities, and other risks, uncertainties and other factors  such as those described from time to time in the reports Theseus files with the Securities and Exchange Commission (SEC), including Theseus' Form 10-K for the year ended December 31, 2021,  and Quarterly Reports on Form 10-Q for the quarters ended March 31, 2022 and June 30, 2022,  which are on file with the SEC and available on the SEC's website at https://www.sec.gov/. However, new risk factors and uncertainties may emerge from time to time which may cause actual results to differ materially from those anticipated or implied by the forward looking statements in this press release, and it is not possible to predict all risk factors and uncertainties. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. Any forward-looking statements contained in this press release are based on the current expectations of Theseus' management team and speak only as of the date hereof, and Theseus specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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SOURCE Theseus Pharmaceuticals