Theseus Pharmaceuticals Announces Preclinical Data Characterizing Next-Generation Epidermal Growth Factor Receptor (EGFR) Inhibitors at the 2022 American Association for Cancer Research (AACR) Annual Meeting

Poster presentation details lead compounds demonstrating activity against EGFR variants that are resistant to all approved EGFR inhibitors

Nomination of development candidate expected in Q3 2022; IND expected in 2023

CAMBRIDGE, Mass., April 8, 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 preclinical data characterizing next-generation pan-variant EGFR inhibitors that will be detailed in a live poster presentation at the American Association for Cancer Research (AACR) 2022 Annual Meeting, being held April 8-13, 2022 in New Orleans, Louisiana. The poster highlights advanced lead compounds for use in non-small cell lung cancer (NSCLC) that have been observed to potently inhibit the kinase activity, both in vitro and in vivo, of all major single-, double-, and triple-mutant EGFR variants, including T790M and C797S, with selectivity over wild-type EGFR and the ability to penetrate the central nervous system (CNS). 

"Up to half of all non-small cell lung cancer tumors are driven by activating mutations (single-mutants) in EGFR and up to 90 percent of those mutations are found in exons 19 and 21. Furthermore, as patients progress through lines of treatment, a substantial percentage of patients' tumors may develop one or more additional EGFR mutations (double- and triple-mutants) that cause resistance to treatment," said William Shakespeare, Ph.D., President of Research and Development at Theseus. "At Theseus, we have developed a series of potent and selective, single molecule, fourth-generation EGFR inhibitors that are designed to inhibit all major classes of EGFR activating and resistance mutations that contribute to later-line clonal heterogeneity in patients who have been failed by current approved therapies. We are finalizing preclinical studies to characterize our lead compounds and look forward to designating a development candidate in the third quarter of this year."

The preclinical data presented at AACR demonstrates that pan-variant EGFR inhibition of all major single-, double-, and triple-mutants, including T790M and C797S, with selectivity over wild-type, is achievable with a single molecule. Detailed findings show that:

• Theseus' lead compounds potently inhibited all major single-, double-, and triple-mutant EGFR variants in vitro, demonstrating cellular IC₅₀ values between 2-12 nM.
• Lead compounds displayed favorable selectivity over wild-type EGFR, with ratios between 11- to 88-fold.
• An advanced lead compound demonstrated tumor regressions in mice against variants associated with both 1^st and 2^nd line osimertinib clinical failure – i.e., C797S double- and triple-mutants – at well-tolerated doses.
• This lead compound also demonstrated a brain:plasma ratio consistent with predicted activity against CNS metastatic disease.

Studies to further characterize lead compounds are under way, with additional data expected to be presented at a scientific conference in the second half of 2022.

Presentation details:

Poster Title: Discovery of potent and selective next-generation EGFR inhibitors with activity against single, double, and triple mutant EGFR variants including T790M and C797S

Poster Number: 3342

Presenter: Wei-Sheng Huang, Ph.D., Vice President of Chemistry

Session Date and Time: Live presentation on Tuesday, April 12^TH, 1:30pm - 5pm CT

About NSCLC
Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85 percent of the estimated 2.2 million cases of lung cancer diagnosed in 2020. Up to half of NSCLC patients have tumors that are driven by activating mutations in the epidermal growth factor receptor (EGFR) and up to 90 percent of those mutations are found in exons 19 and 21. [Most] patients' tumors, in response to treatment, develop one or more additional EGFR mutations, causing resistance and rendering current therapies ineffective.

About Theseus Pharmaceuticals, Inc.
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 a fourth-generation, selective epidermal growth factor receptor (EGFR) inhibitor for C797S-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.

Cautionary Statement Regarding Forward Looking Statements
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," "continue," "anticipate," "intend," "expect," "should," "would," "plan," "predict," "potential," "seem," "seek," "future," "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 planned preclinical studies and clinical trials, expected milestones, market opportunity and sizing and objectives of management, including in relation to the EGFR inhibitor program and the conclusions derived from preclinical data and the expected designation of a development candidate in respect thereof.

Actual results may differ materially from those indicated by such forward-looking statements as a result of various important 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 filed with the SEC on March 10, 2022. However, new risk factors and uncertainties may emerge from time to time, 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.

Media Contact
Amy Jobe, Ph.D.
LifeSci Communications
315-879-8192
[email protected]

Investor Contact
Christen Baglaneas
Theseus Pharmaceuticals
857-706-4993
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SOURCE Theseus Pharmaceuticals