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 1st and
2nd 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
12TH, 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
ajobe@lifescicomms.com
Investor Contact
Christen
Baglaneas
Theseus Pharmaceuticals
857-706-4993
christen.baglaneas@theseusrx.com
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SOURCE Theseus Pharmaceuticals