Repare Therapeutics Unveils Two Programs Expected to Enter Clinical Trials in 2024: RP-1664, an Oral PLK4 Inhibitor, and RP-3467, an Oral Polθ Inhibitor
November 15 2023 - 7:00AM
Business Wire
RP-1664 demonstrated potent and selective
inhibition of PLK4 and synthetic lethality in TRIM37-high tumor
cells in preclinical studies
RP-3467 demonstrated complete, sustained
regressions preclinically in combination with PARPi, and compelling
anti-tumor activity in combination with radioligand therapy (RLT)
and chemotherapy
Company expects to initiate clinical trials of
RP-1664 in 1H 2024 and RP-3467 in 2H 2024
Repare to host conference call and webcast
today at 8:00 a.m. ET
Repare Therapeutics Inc. (“Repare” or the “Company”) (Nasdaq:
RPTX), a leading clinical-stage precision oncology company, today
disclosed polo-like kinase 4 (PLK4) as the target of its RP-1664
development program and reported comprehensive preclinical data for
both RP-1664 and the Company’s Polθ inhibitor, RP-3467.
RP-1664 is a potential first-in-class, selective, oral PLK4
inhibitor that is synthetic lethal with TRIM37 amplification or
overexpression in solid tumors. Tumors rely on PLK4 for survival in
the presence of high levels of TRIM37. Preclinical studies
demonstrate RP-1664 drives potent synthetic lethality in
TRIM37-high tumor models, both in vitro and in vivo. Elevated
TRIM37 is a feature found across a range of solid tumors and in
nearly all high-grade neuroblastomas.
RP-3467 is a potential best-in-class inhibitor of DNA polymerase
theta, or Polθ. Polθ is a synthetic lethal target associated with
homologous recombination deficiency (HRD) tumors, including those
with BRCA1/2 mutations or other genomic alterations. Data suggest
that RP-3467 works synergistically with therapies that result in
double stranded DNA breaks, such as PARP inhibition, radioligand
therapy and multiple chemotherapies and antibody-drug conjugates
(ADCs). Additionally, initial data suggest that Polθ inhibition may
interfere with mechanisms central to the development of PARPi
resistance.
"We are excited to announce the initial clinical approach for
RP-1664 based on highly compelling preclinical data supporting its
potential for treating TRIM37-high tumors,” said Lloyd M. Segal,
President and CEO of Repare. "We are also pleased to share
preclinical data from our RP-3467 program supporting its
significant potential across multiple high-value therapeutic
opportunities. These programs represent our third and fourth
internally developed clinical candidates and provide further
confirmation of Repare’s powerful discovery platform. We look
forward to advancing both RP-1664 and RP-3467 into Phase 1 clinical
trials in 2024."
RP-1664 Highlights
- RP-1664 is a highly potent, selective and bioavailable PLK4
inhibitor that is synthetic lethal with TRIM37 gain of
function.
- RP-1664 demonstrated robust and dose-dependent monotherapy
activity in multiple TRIM37-high preclinical models across a
variety of tumor types, including breast cancer, non-small cell
lung cancer (NSCLC) and neuroblastoma.
- The Company plans to initiate a Phase 1 dose escalation study
of RP-1664 in adult and adolescent patients with TRIM37-high solid
tumors in the first half of 2024.
RP-3467 Data Highlights
- RP-3467 is a highly potent and selective inhibitor of the Polθ
helicase domain.
- RP-3467 demonstrates synergy with PARP inhibitor activity,
resulting in durable, complete tumor regressions in multiple
preclinical models.
- Preclinical studies also show combination potential with
multiple other modalities, including RLT, chemotherapy and
ADCs.
- The Company plans to initiate a Phase 1 dosing finding clinical
trial of RP-3467 in the second half of 2024.
“Preclinical data for RP-1664 demonstrate early and promising
activity in TRIM37-high tumors, including breast cancer, NSCLC and
neuroblastoma,” said Michael Zinda, Ph.D., EVP, Chief Scientific
Officer of Repare. “The durable, complete regressions observed in
the preclinical RP-3467 and PARPi combination studies are also
extremely exciting and demonstrate the broad combination potential
of our potent and selective Polθ helicase inhibitor. Repare plans
to investigate RP-3467 with a focus on its potential as a
combination partner across agents that induce double stranded DNA
breaks, including RLT, ADCs, and a range of chemotherapies.”
Conference Call and Webcast Repare will host a conference
call and webcast today, November 15, 2023, at 8:00 a.m. ET. To
access the call, please dial (877) 870-4263 (U.S. and Canada) or
(412) 317-0790 (international) at least 10 minutes prior to the
start time and ask to be joined to the Repare Therapeutics call. A
live webcast will be available in the Investor section of the
Company’s website at
https://ir.reparerx.com/events-and-presentations/events. A webcast
replay will also be archived for at least 30 days.
About Repare Therapeutics’ SNIPRx® Platform Repare’s
SNIPRx® platform is a genome-wide CRISPR-based screening approach
that utilizes proprietary isogenic cell lines to identify novel and
known synthetic lethal gene pairs and the corresponding patients
who are most likely to benefit from the Company’s therapies based
on the genetic profile of their tumors. Repare’s platform enables
the development of precision therapeutics in patients whose tumors
contain one or more genomic alterations identified by SNIPRx®
screening, in order to selectively target those tumors in patients
most likely to achieve clinical benefit from resulting product
candidates.
About Repare Therapeutics Inc. Repare Therapeutics is a
leading clinical-stage precision oncology company enabled by its
proprietary synthetic lethality approach to the discovery and
development of novel therapeutics. The Company utilizes its
genome-wide, CRISPR-enabled SNIPRx® platform to systematically
discover and develop highly targeted cancer therapies focused on
genomic instability, including DNA damage repair. The Company’s
pipeline includes lunresertib (also known as RP-6306), a PKMYT1
inhibitor currently in Phase 1 clinical development; camonsertib
(also known as RP-3500 or RG6526), a potential leading ATR
inhibitor currently in Phase 1/2 clinical development and partnered
with Roche; RP-3467, a preclinical Polθ inhibitor program; RP-1664,
a preclinical PLK4 inhibitor; as well as several additional,
undisclosed preclinical programs. For more information, please
visit www.reparerx.com and follow @Reparerx on X (formerly Twitter)
and LinkedIn.
SNIPRx® is a registered trademark of Repare Therapeutics
Inc.
Forward-Looking Statements This press release contains
“forward-looking statements” within the meaning of the Private
Securities Litigation Reform Act of 1995 and securities laws in
Canada. All statements in this press release other than statements
of historical facts are “forward-looking statements. These
statements may be identified by words such as “aims,”
“anticipates,” “believes,” “could,” “estimates,” “expects,”
“forecasts,” “goal,” “intends,” “may,” “plans,” “possible,”
“potential,” “seeks,” “will” and variations of these words or
similar expressions that are intended to identify forward-looking
statements, although not all forward-looking statements contain
these words. Forward-looking statements in this press release
include, but are not limited to, statements regarding: the design,
objectives, initiation, timing, progress and results of the
Company’s current and future preclinical studies and clinical
trials, including specifically the clinical development of RP-1664
and RP-3467 programs; the tolerability, efficacy and clinical
progress of RP-1664 and RP-3467; the potential of RP-1664 as a
first-in-class oral PLK4 inhibitor and RP-3467 as a best-in-class
Polθ inhibitor; and the benefits and ability to discover further
targets and clinical candidates from the Company’s discovery
platform. These forward-looking statements are based on the
Company’s expectations and assumptions as of the date of this press
release. Each of these forward-looking statements involves risks
and uncertainties that could cause the Company’s clinical
development programs, future results or performance to differ
materially from those expressed or implied by the forward-looking
statements. Many factors may cause differences between current
expectations and actual results, including: success in preclinical
testing and earlier clinical trials does not ensure that later
clinical trials will generate the same results or otherwise provide
adequate data to demonstrate the efficacy and safety of a product
candidate; the impacts of macroeconomic conditions, including the
COVID-19 pandemic, the conflict in Ukraine and the conflict between
Israel and Hamas, rising inflation, and uncertain credit and
financial markets on the Company’s business, clinical trials and
financial position; unexpected safety or efficacy data observed
during preclinical studies or clinical trials; clinical trial site
activation or enrollment rates that are lower than expected;
changes in expected or existing competition; changes in the
regulatory environment; the uncertainties and timing of the
regulatory approval process; and unexpected litigation or other
disputes. Other factors that may cause the Company’s actual results
to differ from those expressed or implied in the forward-looking
statements in this press release are identified in the section
titled "Risk Factors" in the Company’s Annual Report on Form 10-K
for the year ended December 31, 2022 filed with the Securities and
Exchange Commission (“SEC”) and the Québec Autorité des Marchés
Financiers ("AMF") on February 28, 2023, and its other documents
subsequently filed with or furnished to the SEC and AMF including
the Company’s Quarterly Report on Form 10-Q for the quarter ended
September 30, 2023 filed with the SEC on November 9, 2023. The
Company expressly disclaims any obligation to update any
forward-looking statements contained herein, whether as a result of
any new information, future events, changed circumstances or
otherwise, except as otherwise required by law. For more
information, please visit reparerx.com and follow Repare on Twitter
at @RepareRx and on LinkedIn at
https://www.linkedin.com/company/repare-therapeutics/.
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version on businesswire.com: https://www.businesswire.com/news/home/20231115912777/en/
Repare Contact: Steve Forte Executive Vice-President and
Chief Financial Officer Repare Therapeutics Inc.
investor@reparerx.com
Investors: Matthew DeYoung Argot Partners
repare@argotpartners.com
Media: David Rosen Argot Partners
david.rosen@argotpartners.com 212-600-1902
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