Presented positive initial data from ongoing Phase 1 MYTHIC clinical trial evaluating lunresertib alone and in combination with camonsertib, including an overall RECIST response rate of 50% in patients with heavily pre-treated gynecological tumors
Repare to host conference call and webcast to discuss latest data from its preclinical programs and overall pipeline,
“We substantially advanced our pipeline during the third quarter, particularly our Phase 1 MYTHIC trial evaluating lunresertib as a monotherapy and in combination with camonsertib. The initial data that was presented in a plenary session at the
Third Quarter 2023 Review and Operational Updates:
-
Advancing lunresertib (
RP-6306 ), a first-in-class, oral PKMYT1 inhibitor, for the treatment of molecularly selected advanced solid tumors. -
Presented initial positive data from Modules 1 and 2 of its ongoing Phase 1 MYTHIC trial evaluating lunresertib alone and in combination with camonsertib in patients with advanced solid tumors harboring CCNE1 amplification or FBXW7 or PPP2R1A deleterious alternations (NCT04855656) at the 2023
AACR-NCI-EORTC International Conference and additional data from a later cut-off date in a virtual webcast event hosted by Repare.-
As of the
September 5, 2023 data cut-off date as presented during the company virtual webcast event, the Company reported that 67 patients were enrolled in Module 1 (monotherapy) and 59 patients in Module 2 (combination therapy). - In the Module 2 cohort at the combination preliminary recommended Phase 2 dose (RP2D):
-
As of the
- Protocol-defined overall response (OR) (RECIST or GCIG CA-125 responses) was observed to be 33.3% (N=18). Clinical benefit rate (CBR) (overall response or stable disease of at least 16 weeks without tumor progression) was 50.0%.
-
In the cohort of patients with gynecologic tumors, the RECIST response was 50%, OR was 60%, and CBR was 70%. These patients also had a median of 3 and up to 9 prior lines of therapy, before administration of lunresertib.
- In all evaluable patients in the trial, across all doses (N=55), OR was 23.6% and CBR was 41.8%.
- RECIST responses in this ongoing combination trial included 8 confirmed and 3 unconfirmed partial responses (PR). Additionally, 3 patients with ovarian tumors had cancer antigen 125 (CA-125) responses.
- Encouraging and highly manageable safety and tolerability was observed for the combination therapy arm of the trial (N=59). The most common treatment-related adverse event (TRAE) was anemia, with Grade 3 occurring in 42% of patients enrolled in the trial:
- 35% of patients did not develop anemia at the preliminary RP2D. Generally, those with Grade 3 anemia had the lowest hemoglobin values at the time of trial enrollment, were intensely pretreated with greater than 4 prior therapies and were of advanced age.
- The anemia reported by patients in the trial usually improved after a one-week treatment interruption and standard supportive care, and did not lead to any therapy discontinuations for patients who received treatment at the preliminary RP2D.
- There were no Grade 4 or Grade 5 TRAEs reported at the preliminary RP2D.
-
This data indicates that anemia management can be individualized and alleviated with simple patient monitoring. This approach is now being tested in the expansion cohorts of the MYTHIC trial.
- Repare expects to report additional combination therapy data from the expansion cohorts of the MYTHIC trial in the second half of 2024.
- Repare expects to report initial data from its ongoing Phase 1 MINOTAUR trial evaluating lunresertib in combination with FOLFIRI (NCT05147350) in the first half of 2024. Additionally, the Company expects to report initial updated data from its ongoing Phase 1 MAGNETIC trial evaluating lunresertib in combination with gemcitabine (NCT05147272) in the second half of 2024.
-
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 to take place by the end of 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 trial that will evaluate lunresertib in combination with gemcitabine in patients with CDK4/6 inhibitor treated ER+/HER2- metastatic breast cancer (NCT05601440). -
Advancing camonsertib (
RP-3500 / RG6526), 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 trial (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 enrollment of the first patient with camonsertib in the TAPISTRY trial, which is expected by year-end, and could be eligible for an additional$15 million milestone payment if this study becomes registrational. - Repare is continuing to conduct dose optimization and efficacy assessments in tumor specific expansions in the ATTACC clinical trial in collaboration with Roche to support future clinical development plans for camonsertib combinations with PARP inhibitors.
- Repare also presented clinical and preclinical data from its ongoing Phase 1b TRESR clinical trial evaluating camonsertib in combination with gemcitabine in patients with solid tumors with ATR inhibitor sensitizing mutations at the AACR-NCI-EROTC conference. The latest data cut from the trial continues to show the benefits of combination therapy, which has led to anti-tumor activity in heavily pretreated patients, including 7 patients (N=28) with confirmed or unconfirmed PRs per RECIST, or GCIG CA-125 responses (N=28), with responses observed primarily in patients with gynecologic cancers. Overall molecular response rate (MRR) of 57%, along with 82% decrease in circulating tumor DNA (ctDNA). The combination therapy was found to be safe and well-tolerated to date, with no drug-drug interactions observed. Efficacy assessment is ongoing at the proposed RP2D in patients with ovarian cancer.
- Advancing preclinical programs into clinical development.
-
RP-1664 IND-enabling studies, which began in the first quarter of 2023, are nearing completion and Repare expects to initiate a clinical trial in the first half of 2024. -
RP-3467 is Repare’s wholly-owned Polθ inhibitor, currently in IND-enabling studies, which began in the second quarter of 2023 and remain ongoing. Repare expects to initiate a clinical trial in the second half of 2024.
Third Quarter 2023 Financial Results:
-
Cash and cash equivalents and marketable securities: Cash and cash equivalents and marketable securities as of
September 30, 2023 were$250.1 million , which Repare believes will be sufficient to fund its planned operations into 2026. -
Revenue from collaboration agreements: Revenue from collaboration agreements were
$2.2 million and$38.1 million for the three and nine months endedSeptember 30, 2023 , respectively, as compared to$112.5 million and$113.6 million for the three and nine months endedSeptember 30, 2022 . The decrease in revenue for the three- and nine-month periods were primarily due to a decrease in revenue recognized under the Roche collaboration mainly as a result of the$108.0 million revenue recognized in the third quarter of 2022 pursuant to the satisfaction of our performance obligations for the issuance of the combined licenses and the clinical trial materials transferred. The decrease in the nine-month period was partially offset by higher deferred revenue recognized from the Roche collaboration, the BMS collaboration and the Ono collaboration. -
Research and development expenses, net of tax credits (Net R&D): Net R&D expenses were
$32.7 million and$98.3 million for the three and nine months endedSeptember 30, 2023 , respectively, as compared to$31.2 million and$89.2 million for the three and nine months endedSeptember 30, 2022 . The increase in Net R&D expenses for the three- and nine-month periods were primarily due to higher personnel-related costs and direct external costs related to the progress of our lunresertib clinical program, as well as the advancement of preclinical programs into IND-enabling studies. -
General and administrative (G&A) expenses: G&A expenses were
$7.9 million and$25.1 million for the three and nine months endedSeptember 30, 2023 , respectively, compared to$7.9 million and$24.6 million for the three and nine months endedSeptember 30, 2022 . The increase in G&A was primarily due to higher personnel related costs, offset by lower D&O insurance premiums and lower professional fees. -
Net income (loss): Net loss was
$18.9 million , or$0.45 per share, and$65.8 million , or$1.56 per share, in the three and nine months endedSeptember 30, 2023 , respectively, and net income was$75.5 million , or$1.71 per share, and$2.6 million , or$0.06 per share, in the three and nine months endedSeptember 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
SNIPRx® is a registered trademark of
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
|
Condensed Consolidated Balance Sheets (Unaudited)
(Amounts in thousands of |
||||||||
|
|
|
As of
|
|
|
As of
|
|
||
|
|
|
2023 |
|
|
2022 |
|
||
|
ASSETS |
|
|
|
|
|
|
||
|
CURRENT ASSETS: |
|
|
|
|
|
|
||
|
Cash and cash equivalents |
|
$ |
107,369 |
|
|
$ |
159,521 |
|
|
Marketable securities |
|
|
142,703 |
|
|
|
184,420 |
|
|
Income tax receivable |
|
|
15,739 |
|
|
|
— |
|
|
Other current receivables |
|
|
3,731 |
|
|
|
4,323 |
|
|
Prepaid expenses |
|
|
5,551 |
|
|
|
5,715 |
|
|
Total current assets |
|
|
275,093 |
|
|
|
353,979 |
|
|
Property and equipment, net |
|
|
4,722 |
|
|
|
4,228 |
|
|
Operating lease right-of-use assets |
|
|
3,883 |
|
|
|
5,371 |
|
|
Income tax receivable |
|
|
2,312 |
|
|
|
— |
|
|
Other assets |
|
|
397 |
|
|
|
497 |
|
|
TOTAL ASSETS |
|
$ |
286,407 |
|
|
$ |
364,075 |
|
|
LIABILITIES AND SHAREHOLDERS’ EQUITY |
|
|
|
|
|
|
||
|
CURRENT LIABILITIES: |
|
|
|
|
|
|
||
|
Accounts payable |
|
$ |
5,438 |
|
|
$ |
461 |
|
|
Accrued expenses and other current liabilities |
|
|
20,729 |
|
|
|
21,645 |
|
|
Operating lease liability, current portion |
|
|
2,333 |
|
|
|
2,171 |
|
|
Deferred revenue, current portion |
|
|
20,472 |
|
|
|
53,102 |
|
|
Income tax payable |
|
|
— |
|
|
|
1,240 |
|
|
Total current liabilities |
|
|
48,972 |
|
|
|
78,619 |
|
|
Operating lease liability, net of current portion |
|
|
1,591 |
|
|
|
3,257 |
|
|
Deferred revenue, net of current portion |
|
|
2,476 |
|
|
|
2,682 |
|
|
TOTAL LIABILITIES |
|
|
53,039 |
|
|
|
84,558 |
|
|
SHAREHOLDERS’ EQUITY |
|
|
|
|
|
|
||
|
Preferred shares, no par value per share; unlimited shares authorized
|
|
|
— |
|
|
— |
|
|
|
Common shares, no par value per share; unlimited shares authorized as of
|
|
|
483,184 |
|
|
|
482,032 |
|
|
Additional paid-in capital |
|
|
55,515 |
|
|
|
37,226 |
|
|
Accumulated other comprehensive loss |
|
|
(252 |
) |
|
|
(428 |
) |
|
Accumulated deficit |
|
|
(305,079 |
) |
|
|
(239,313 |
) |
|
Total shareholders’ equity |
|
|
233,368 |
|
|
|
279,517 |
|
|
TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY |
|
$ |
286,407 |
|
|
$ |
364,075 |
|
|
Condensed Consolidated Statements of Operations and Comprehensive Loss (Unaudited)
(Amounts in thousands of |
||||||||||||||||
|
|
|
Three Months Ended
|
|
|
Nine Months Ended
|
|
||||||||||
|
|
|
2023 |
|
|
2022 |
|
|
2023 |
|
|
2022 |
|
||||
|
Revenue: |
|
|
|
|
|
|
|
|
|
|
|
|
||||
|
Collaboration agreements |
|
$ |
2,159 |
|
|
$ |
112,545 |
|
|
$ |
38,086 |
|
|
$ |
113,632 |
|
|
Operating expenses: |
|
|
|
|
|
|
|
|
|
|
|
|
||||
|
Research and development, net of tax credits |
|
|
32,709 |
|
|
|
31,242 |
|
|
|
98,327 |
|
|
|
89,175 |
|
|
General and administrative |
|
|
7,868 |
|
|
|
7,904 |
|
|
|
25,116 |
|
|
|
24,621 |
|
|
Total operating expenses |
|
|
40,577 |
|
|
|
39,146 |
|
|
|
123,443 |
|
|
|
113,796 |
|
|
(Loss) income from operations |
|
|
(38,418 |
) |
|
|
73,399 |
|
|
|
(85,357 |
) |
|
|
(164 |
) |
|
Other income (expense), net |
|
|
|
|
|
|
|
|
|
|
|
|
||||
|
Realized and unrealized (loss) gain on foreign exchange |
|
|
(40 |
) |
|
|
126 |
|
|
|
(137 |
) |
|
|
250 |
|
|
Interest income |
|
|
3,312 |
|
|
|
2,027 |
|
|
|
10,228 |
|
|
|
2,700 |
|
|
Other expense |
|
|
(32 |
) |
|
|
(37 |
) |
|
|
(73 |
) |
|
|
(56 |
) |
|
Total other income, net |
|
|
3,240 |
|
|
|
2,116 |
|
|
|
10,018 |
|
|
|
2,894 |
|
|
(Loss) income before income taxes |
|
|
(35,178 |
) |
|
|
75,515 |
|
|
|
(75,339 |
) |
|
|
2,730 |
|
|
Income tax recovery (expense) |
|
|
16,299 |
|
|
|
(54 |
) |
|
|
9,573 |
|
|
|
(119 |
) |
|
Net (loss) income |
|
$ |
(18,879 |
) |
|
$ |
75,461 |
|
|
$ |
(65,766 |
) |
|
$ |
2,611 |
|
|
Other comprehensive (loss) gain: |
|
|
|
|
|
|
|
|
|
|
|
|
||||
|
Unrealized gain (loss) on available-for-sale marketable
|
|
$ |
172 |
|
|
$ |
(524 |
) |
|
$ |
176 |
|
|
$ |
(524 |
) |
|
Total other comprehensive gain (loss) |
|
|
172 |
|
|
|
(524 |
) |
|
|
176 |
|
|
|
(524 |
) |
|
Comprehensive (loss) income |
|
$ |
(18,707 |
) |
|
$ |
74,937 |
|
|
$ |
(65,590 |
) |
|
$ |
2,087 |
|
|
Net (loss) income per share attributable to common shareholders: |
|
|
|
|
|
|
|
|
|
|
|
|
||||
|
Basic |
|
$ |
(0.45 |
) |
|
$ |
1.80 |
|
|
$ |
(1.56 |
) |
|
$ |
0.06 |
|
|
Diluted |
|
$ |
(0.45 |
) |
|
$ |
1.71 |
|
|
$ |
(1.56 |
) |
|
$ |
0.06 |
|
|
Weighted-average common shares outstanding: |
|
|
|
|
|
|
|
|
|
|
|
|
||||
|
Basic |
|
|
42,102,685 |
|
|
|
41,945,617 |
|
|
|
42,077,857 |
|
|
|
41,902,554 |
|
|
Diluted |
|
|
42,102,685 |
|
|
|
44,177,376 |
|
|
|
42,077,857 |
|
|
|
44,160,481 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
||||
View source version on businesswire.com: https://www.businesswire.com/news/home/20231109943377/en/
Repare Contact:
Executive Vice-President and Chief Financial Officer
[email protected]
Investors:
[email protected]
Media:
[email protected]
212-600-1902
Source: