-- Decision follows two dose-limiting
toxicities related to hand-foot skin reaction observed in Cohort 7
(27 mg) --
-- Company prioritizing THE-349, a
potentially best-in-class fourth-generation EGFR inhibitor for EGFR
mutant non-small cell lung cancer; IND on track for submission in
Q4 2023 --
-- Theseus announces new program targeting KIT
for patients with early-line GIST; development candidate nomination
expected in the H1 2024 --
-- Development candidate nomination from
BCR-ABL program also expected in H1 2024 --
-- $234 million
in cash, cash equivalents, and marketable securities as of
June 30, 2023; runway extended into
2026 --
CAMBRIDGE, Mass., July 13,
2023 /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 is
discontinuing enrollment in the ongoing phase 1/2 study and
terminating development of THE-630 in patients with
gastrointestinal stromal tumors (GIST).
Theseus previously released initial dose escalation data from
the ongoing phase 1/2 trial, which employs a standard 3 + 3 dose
escalation design, on May 25, 2023.
As of the April 21, 2023 data cutoff
date, 23 patients had been dosed through Cohort 6 (18 mg) and 2
patients had been enrolled in Cohort 7 (27 mg). As of May 25, those 2 patients in Cohort 7 had cleared
the dose–limiting toxicity (DLT) observation period without
experiencing a DLT.
Following the data release on May
25, the third patient enrolled in Cohort 7 experienced grade
3 hand-foot skin reaction (HFSR), which required an expansion of
the cohort to 6 patients. Subsequently, one of the patients
enrolled in the Cohort 7 expansion group experienced grade 2 HFSR,
which required a dose interruption of ≥7 days. Both the grade 3
HFSR and the grade 2 HFSR necessitating ≥7 days dose interruption
were determined to be DLTs according to the study protocol.
Therefore, with 2 out of 6 patients experiencing a DLT, the 27 mg
dose exceeds the maximum tolerated dose (MTD). The Company does not
believe that THE-630 has a differentiated profile at doses below 27
mg, which would provide exposure well below the target level of 100
nanomolar average concentration. As a result, the Company has made
the decision to terminate the development of THE-630 in GIST.
Patients currently enrolled in the trial will continue to receive
THE-630 until a treatment discontinuation criterion is met.
As of July 10, 2023, 32 patients
have been treated with THE-630 across 7 dose levels (3 mg to 27
mg). Six patients developed grade 1 to 3 HFSR (3 patients in the 27
mg cohort, 2 patients in the 18 mg cohort, and 1 patient originally
in the 9 mg cohort after intra-patient dose escalation to 18 mg).
Grade 3 HFSR was only observed in a patient who started treatment
at 27 mg. HFSR was not observed at doses of 12 mg or lower. No
significant skin toxicity was observed in preclinical toxicology
studies. The Company is analyzing trial data to inform the
feasibility of developing low dose THE-630 for KIT-associated mast
cell-driven inflammatory indications, given its potent inhibition
of wild-type KIT observed in preclinical assays.
Theseus has continued an extensive medicinal chemistry effort to
target KIT, which has led to the discovery of a series of
chemically distinct, highly selective, pan-variant KIT inhibitors
for the treatment of early-line GIST. Theseus plans to nominate a
development candidate from this series in the first half of
2024.
"We are disappointed that we will not be able to achieve the
target exposure for pan-variant inhibition with THE-630, as we
continue to believe a therapy with potent activity against all
major classes of activating and resistance mutations in KIT has the
potential to confer significant clinical benefit, given the unmet
need in GIST," said Tim Clackson,
Ph.D., President and Chief
Executive Officer of Theseus. "On behalf of the entire Theseus
team, I would like to thank the patients, their caregivers, and the
investigators and site staff who participated in this study. We
remain committed to helping GIST patients with plans to nominate a
new, highly selective pan-variant KIT inhibitor candidate for GIST
in the first half of 2024. Moving forward, we are excited to have
THE-349 as our next near-term clinical program, with its potential
best-in-class profile as a fourth generation EGFR inhibitor
appropriate for both monotherapy and combination approaches."
Strategic Priorities:
- Advance THE-349 into clinical studies: THE-349 is a potentially
best-in-class fourth-generation epidermal growth factor receptor
(EGFR) tyrosine kinase inhibitor (TKI) for the treatment of EGFR
mutant non-small cell lung cancer.
-
- Preclinical data demonstrate THE-349 can potently
inhibit all major classes of EGFR activating and
resistance mutations observed in a post-first- or later-line
osimertinib setting, possesses kinome and wild-type EGFR
selectivity, and has central nervous system (CNS) activity.
- IND-enabling toxicology studies have been completed, and
Theseus remains on track to submit an Investigational New Drug
Application (IND) for THE-349 in the fourth quarter of 2023, and
commence its clinical program as soon as possible thereafter,
subject to clearance of the IND by the U.S. Food and Drug
Administration.
- Advance BCR-ABL Program: Theseus aims to develop a potent
and selective, next-generation, pan-variant BCR-ABL TKI candidate
that optimizes the balance of safety and efficacy for patients with
relapsed/refractory chronic myelogenous leukemia (CML) and patients
with newly diagnosed Philadelphia
chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).
-
- Theseus plans to pursue clinical development in patients with
CML who have been previously treated with a second-generation TKI
or have the T315I mutation, and in newly diagnosed patients with
Ph+ ALL.
- Theseus plans to nominate a development candidate for this
program in the first half of 2024.
- Advance KIT program for GIST: KIT mutant GIST remains an area
of major unmet medical need, requiring a pan-variant molecule to
target all major activating and resistance mutations in KIT, with
high selectivity, for use in early-line patients.
-
- Theseus has continued an extensive medicinal chemistry effort
to target KIT which has led to the discovery of a series of
chemically distinct, highly selective, pan-variant KIT inhibitors
for the treatment of early-line GIST.
- Theseus plans to nominate a development candidate from this
series in the first half of 2024.
- As of June 30, 2023, the Company
had approximately $234 million in
cash, cash equivalents, and marketable securities. Theseus
expects its current cash, cash equivalents, and marketable
securities to fund operations and capital expenditures into 2026
based on its current operating plan.
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 classes of cancer-causing and resistance mutations that lead to
clinically relevant variants in a particular protein in a given
type of cancer. Theseus is 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), a
pan-variant BCR-ABL inhibitor for the treatment of
relapsed/refractory chronic myeloid leukemia (CML) and newly
diagnosed Philadelphia
chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), and a
next-generation, highly selective, pan-variant KIT inhibitor for
the treatment of early-line GIST. 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," "project," "anticipate," "expect,"
"plan," "predict," "potential," "on track", "seem," "outlook,"
"continue," "intend," 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:
the discontinuation of the THE–630 phase 1/2 clinical trial;
Theseus' plans with respect to its BCR-ABL and next generation KIT
programs, including the intention to nominate a development
candidate for such programs in the first half of 2024; the timing
for filing an Investigational New Drug Application for THE–349; and
the Company's expectations regarding its cash runway.
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 and clinical
trials; risks and uncertainties regarding whether results from
preclinical studies and clinical trials will be predictive of the
results of future trials; risks related to the expected timing of
submissions to regulatory authorities and timing for review by such
regulatory authorities; risks related to market volatility and
global economic conditions; 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, 2022 and subsequent Quarterly
Reports on Form 10-Q which will be 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.
Investor and Media Contact
Josh Rappaport
Stern Investor Relations
212-362-1200
josh.rappaport@sternir.com
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SOURCE Theseus Pharmaceuticals