Presented initial camonsertib-PARPi combination
Phase 1/2 clinical data at AACR 2023 demonstrating durable clinical
benefit across tumor types, genomic alterations, PARPi choice or
platinum resistance
Roche has included a camonsertib-based arm in
its Phase 2 TAPISTRY study and its Phase 1/2 Morpheus Lung study of
multiple combinations in metastatic non-small cell lung cancer
Reported clinical proof of concept for
lunresertib (RP-6306) in June 2023 including achievement of
monotherapy safety and tolerability primary endpoints and
identification of two proposed dose/schedules
Presented early lunresertib combination
response data in June 2023, and expects to present further Phase 1
MYTHIC Module 2 data at a medical conference in the fourth quarter
of this year
Granted FDA Fast Track designation for
lunresertib in combination with camonsertib for the treatment of
adult patients with CCNE1 amplified, or FBXW7 or PPP2R1A mutated
endometrial cancer in August
Initiated IND-enabling studies for newly
designated Polθ inhibitor RP-3467
Repare Therapeutics Inc. (“Repare” or the “Company”) (Nasdaq:
RPTX), a leading clinical-stage precision oncology company, today
reported financial results for the second quarter ended June 30,
2023.
“During the second quarter we made great progress advancing our
clinical programs and presenting novel findings from our ongoing
clinical trials, including reporting on camonsertib’s combination
with three PARP inhibitors and initial clinical proof of concept
for lunresertib,” said Lloyd M. Segal, President and Chief
Executive Officer of Repare. “While these clinical programs move
towards Phase 2 studies, we continue to support our preclinical
pipeline, for example with the designation of our Polθ inhibitor,
RP-3467. We look forward to reporting initial combination data of
lunresertib with camonsertib in the fourth quarter of this year as
we continue advancing our differentiated, synthetic lethal-based
oncology pipeline.”
Second Quarter 2023 Review and Operational Updates:
- Advancing camonsertib, a potent and selective oral small
molecule inhibitor of ATR (Ataxia-Telangiectasia and Rad3-related
protein kinase) for the treatment of tumors with specific synthetic
lethal genomic alterations in partnership with Roche.
- Roche has included a camonsertib-based arm in its Phase 2,
global, multicenter, open-label, multi-cohort TAPISTRY study
(NCT04589845) and its Phase 1/2 study of multiple
immunotherapy-based treatment combinations in participants with
metastatic non-small cell lung cancer (Morpheus Lung; NCT03337698).
Repare is eligible to receive a milestone payment of $40 million
upon dosing of the first patient with camonsertib in the TAPISTRY
study and could be eligible for an additional $15 million milestone
if this study becomes registrational.
- Repare is continuing to conduct dose optimization and efficacy
assessments in tumor specific expansions in the ATTACC study in
collaboration with Roche to support future clinical development
plans for camonsertib combinations with PARP inhibitors. In April
2023, we received a payment of $4 million from Roche for additional
revisions to the clinical development plan under the Roche
Agreement. Repare is eligible to receive further milestone payments
upon the initiation of registrational trials or the transition of
existing trials to become registrational for camonsertib in
specific tumor types.
- Published data in Nature Medicine from the ongoing Phase 1/2
TRESR clinical trial evaluating camonsertib monotherapy in 120
patients (NCT04497116). The article, entitled “Camonsertib in DNA
damage response-deficient advanced solid tumors: phase 1 trial
results” can be accessed here.
- Announced initial clinical data from the Phase 1/2 TRESR and
ATTACC trials evaluating camonsertib in combination with three poly
(ADP-ribose) polymerase (PARP) inhibitors in a Clinical Trials
Plenary Session at the 2023 American Association for Cancer
Research (AACR) Annual Meeting.
- Camonsertib-PARP inhibitor combinations appeared to be well
tolerated and resulted in durable clinical benefit across tumor
types and genomic alterations, regardless of choice of PARP
inhibitor and presence of platinum resistance. Overall clinical
benefit rate (CBR) for all patients was 48%. Patients with
platinum-resistant tumors had an overall response rate (ORR) of 12%
and CBR of 49% and benefited similarly to non-platinum-resistant
tumors (ORR 13%, CBR 46%). Compelling results were observed
particularly in patients with advanced ovarian cancer (n = 19),
including overall response of 32%, CBR of 58% and median
progression-free survival of approximately 7 months with treatment
greater than 16 weeks and ongoing in 9 patients, as of the 2023
AACR Annual Meeting data cutoff of February 27, 2023. The molecular
response rate (MRR) of circulating tumor DNA was significantly
higher in patients with clinical benefit (83%) compared to those
without (48%; p=0.015) and significantly higher than seen in the
camonsertib monotherapy trial in which camonsertib was administered
at higher doses (66% vs. 43%; p=0.02). Molecular responses were
also observed in patients with prior PARP inhibitor exposure (57%)
and platinum resistance (64%).
- Advancing lunresertib (RP-6306), a first-in-class,
oral PKMYT1 inhibitor, for the treatment of molecularly select
advanced solid tumors as a monotherapy and in combinations in
multiple clinical studies.
- Announced clinical proof of concept for lunresertib, including
monotherapy data from the Phase 1 MYTHIC clinical trial and early
insights from ongoing combination trials in June 2023. Achieved
primary endpoints of safety and tolerability and proposed dose and
schedule. The tolerability profile of lunresertib monotherapy
appears favorable and differentiated from other clinical cell cycle
inhibitors, as lunresertib treatment does not result in significant
myelotoxicity nor diarrhea. No grade 4 toxicity was observed with
lunresertib, while grade 3 treatment emergent adverse events of
interest included rash (7.9%), anemia (6.3%) and nausea or vomiting
(1.6%). The dose limiting toxicity was reversible rash, alleviated
with dose modifications and simple supportive measures. Two
proposed dose/schedules were identified – 240mg daily continuously
and 80-100mg BID intermittent weekly – to offer maximum flexibility
in combination studies.
- Preliminary anti-tumor activity was observed for monotherapy,
including moderate tumor shrinkages and a confirmed partial
response per RECIST 1.1 criteria in a patient with metastatic
recurrent uterine carcinosarcoma.
- Early clinical responses per RECIST 1.1 criteria have been
observed with lunresertib and combinations with gemcitabine,
camonsertib, and FOLFIRI in multiple tumor types and
genotypes.
- Repare is collaborating with Princess Margaret Cancer Center to
initiate clinical testing, as part of an investigator-sponsored
trial (IST), of a fourth lunresertib combination with carboplatin
and paclitaxel for the treatment of recurrent gynecological
malignancies, with first patient dosing expected this year.
- Repare is also collaborating with the Canadian Cancer Trials
Group in an ongoing basket Phase 2 IST that is enrolling patients
with selected, advanced cancers receiving lunresertib as
combination with gemcitabine (NCT05605509), and in a second active
study that will evaluate lunresertib in combination with
gemcitabine in patients with CDK4/6 inhibitor treated ER+/HER2-
metastatic breast cancer (NCT05601440).
- In August 2023, the U.S. Food and Drug Administration (FDA)
granted Fast Track designation (FTD) to lunresertib in combination
with camonsertib for the treatment of adult patients with CCNE1
amplified, or FBXW7 or PPP2R1A mutated endometrial cancer
previously treated with a platinum-containing regimen and immune
checkpoint inhibitor when indicated. FTD is intended to facilitate
the development and expedite the review of drugs to treat serious
conditions and fulfill an unmet medical need, enabling drugs to
reach patients earlier.
- The Company expects to present further Phase 1 MYTHIC Module 2
combination data with camonsertib at a medical conference in the
fourth quarter of this year.
- Advancing preclinical programs into clinical
development.
- RP-1664 IND-enabling studies, which began in the first quarter
of 2023, remain ongoing with potential for the program to enter the
clinic in early 2024.
- Initiated IND-enabling studies for the newly designated Polθ
inhibitor RP-3467 in June 2023. RP-3467 has shown greater potency
in preclinical studies compared to RP-2119, our first Polθ
inhibitor designated in 2022, and has potential to enter the clinic
in 2024. The research term of our Polθ collaboration with Ono
Pharmaceutical Company Ltd., as previously extended, expired on
July 31, 2023. With the termination of the agreement with Ono
Pharmaceutical Company Ltd., Repare’s Polθ program, including
RP-3467, is wholly-owned by Repare.
- The Company intends to host an R&D day focused on its
ongoing pre-clinical programs and its overall pipeline in the
fourth quarter of this year.
- In May 2023, Bristol Myers Squibb exercised its option for a
third druggable target and separately triggered a $1 million
payment for a previously exercised druggable target
option.
Second Quarter 2023 Financial Results:
- Cash and cash equivalents and marketable securities:
Cash and cash equivalents and marketable securities as of June 30,
2023 were $280.7 million, which Repare believes will be sufficient
to fund its planned operations into 2026.
- Revenue from collaboration agreements: Revenue from
collaboration agreements were $30.2 million and $35.9 million for
the three and six months ended June 30, 2023, respectively, as
compared to $0.7 million and $1.1 million for the three and six
months ended June 30, 2022. The increase in revenue for the three-
and six-month periods were primarily due to revenue recognized from
our collaboration and license agreement with BMS and our
collaboration agreement with Ono.
- Research and development expenses, net of tax credits (Net
R&D): Net R&D expenses were $33.8 million and $65.6
million for the three and six months ended June 30, 2023,
respectively, as compared to $31.5 million and $57.9 million for
the three and six months ended June 30, 2022. The increase in Net
R&D expenses for the three- and six-month periods was primarily
due to higher personnel-related costs and direct external costs
related to the advancement of preclinical programs into
IND-enabling studies.
- General and administrative (G&A) expenses: G&A
expenses were $8.7 million and $17.2 million for the three and six
months ended June 30, 2023, respectively, compared to $7.9 million
and $16.7 million for the three and six months ended June 30, 2022.
The increase in G&A was primarily due higher personnel related
costs, offset by lower D&O insurance premiums.
- Net loss: Net loss was $11.9 million, or $0.28 per
share, and $46.9 million, or $1.11 per share, in the three and six
months ended June 30, 2023, respectively, and $38.1 million, or
$0.91 per share, and $72.9 million, or $1.74 per share, in the
three and six months ended June 30, 2022, respectively.
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; as well as several additional, undisclosed
preclinical programs, including RP-1664. For more information,
please visit reparerx.com.
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 safety,
efficacy and clinical progress of the Company’s clinical programs,
including lunresertib (RP-6306) and camonsertib; the clinical and
preclinical development of the Company’s pipeline and its research
and development programs, including the anticipated timing,
anticipated patient enrollment, trial outcomes or associated costs
of its clinical trials of lunresertib and camonsertib; and the
status of clinical trials (including, without limitation,
expectations regarding the data that is being presented, the
expected timing of data releases and development, as well as
completion of clinical trials) and development timelines for the
Company’s product candidates. 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: the
impacts of macroeconomic conditions, including the COVID-19
pandemic, the conflict in Ukraine, 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. 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/.
Repare Therapeutics
Inc.
Condensed Consolidated Balance
Sheets
(Unaudited)
(Amounts in thousands of U.S.
dollars, except share data)
As of June 30,
As of December 31,
2023
2022
ASSETS
CURRENT ASSETS:
Cash and cash equivalents
$
115,544
$
159,521
Marketable securities
165,148
184,420
Income tax receivable
1,751
—
Other current receivables
5,281
4,323
Prepaid expenses
4,201
5,715
Total current assets
291,925
353,979
Property and equipment, net
4,821
4,228
Operating lease right-of-use assets
4,434
5,371
Other assets
408
497
TOTAL ASSETS
$
301,588
$
364,075
LIABILITIES AND SHAREHOLDERS’
EQUITY
CURRENT LIABILITIES:
Accounts payable
$
4,893
$
461
Accrued expenses and other current
liabilities
21,628
21,645
Operating lease liability, current
portion
2,320
2,171
Deferred revenue, current portion
24,412
53,102
Income tax payable
—
1,240
Total current liabilities
53,253
78,619
Operating lease liability, net of current
portion
2,226
3,257
Deferred revenue, net of current
portion
695
2,682
TOTAL LIABILITIES
56,174
84,558
SHAREHOLDERS’ EQUITY
Preferred shares, no par value per share;
unlimited shares authorized as of June 30, 2023 and December 31,
2022, respectively; 0 shares issued and outstanding as of June 30,
2023, and December 31, 2022, respectively
—
—
Common shares, no par value per share;
unlimited shares authorized as of June 30, 2023 and December 31,
2022; 42,093,946 and 42,036,193 shares issued and outstanding as of
June 30, 2023 and December 31, 2022, respectively
482,739
482,032
Additional paid-in capital
49,299
37,226
Accumulated other comprehensive loss
(424
)
(428
)
Accumulated deficit
(286,200
)
(239,313
)
Total shareholders’ equity
245,414
279,517
TOTAL LIABILITIES AND SHAREHOLDERS’
EQUITY
$
301,588
$
364,075
Repare Therapeutics
Inc.
Condensed Consolidated
Statements of Operations and Comprehensive Loss
(Unaudited)
(Amounts in thousands of U.S.
dollars, except share and per share data)
Three Months Ended June
30,
Six Months Ended June
30,
2023
2022
2023
2022
Revenue:
Collaboration agreements
$
30,249
$
679
$
35,927
$
1,087
Operating expenses:
Research and development, net of tax
credits
33,788
31,475
65,618
57,933
General and administrative
8,719
7,938
17,248
16,717
Total operating expenses
42,507
39,413
82,866
74,650
Loss from operations
(12,258
)
(38,734
)
(46,939
)
(73,563
)
Other income (expense), net
Realized and unrealized (loss) gain on
foreign exchange
(41
)
141
(97
)
124
Interest income
3,489
544
6,916
673
Other expense
(26
)
(11
)
(41
)
(19
)
Total other income, net
3,422
674
6,778
778
Loss before income taxes
(8,836
)
(38,060
)
(40,161
)
(72,785
)
Income tax expense
(3,110
)
(33
)
(6,726
)
(65
)
Net loss
$
(11,946
)
$
(38,093
)
$
(46,887
)
$
(72,850
)
Other comprehensive (loss)
gain:
Unrealized (loss) gain on
available-for-sale marketable securities
$
(189
)
$
—
$
4
$
—
Total other comprehensive (loss) gain
(189
)
—
4
—
Comprehensive loss
$
(12,135
)
$
(38,093
)
$
(46,883
)
$
(72,850
)
Net loss per share attributable to common
shareholders - basic and diluted
$
(0.28
)
$
(0.91
)
$
(1.11
)
$
(1.74
)
Weighted-average common shares outstanding
- basic and diluted
42,089,530
41,899,509
42,065,237
41,880,666
View source
version on businesswire.com: https://www.businesswire.com/news/home/20230809252741/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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