UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): |
(Exact name of Registrant as Specified in Its Charter)
(State or Other Jurisdiction |
(Commission File Number) |
(IRS Employer |
||
|
|
|
|
|
|
||||
|
||||
(Address of Principal Executive Offices) |
|
(Zip Code) |
||
Registrant’s Telephone Number, Including Area Code: |
|
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Securities registered pursuant to Section 12(b) of the Act:
|
|
Trading |
|
|
|
|
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 2.02 Results of Operations and Financial Condition.
On May 7, 2024, Repare Therapeutics Inc. (the "Company") issued a press release announcing its recent business highlights and financial results for the three months ended March 31, 2024. A copy of the press release is furnished hereto as Exhibit 99.1 and is incorporated herein by reference.
Additionally, on May 7, 2024, the Company posted an updated corporate presentation to its website. The corporate presentation is available under the “Events & Presentations” tab in the “Investors & Media” section of the Company’s website, located at www.reparerx.com. The Company intends to use this presentation in meetings with analysts, investors and others from time to time. A copy of the presentation is furnished as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.
The information in this Current Report on Form 8-K, including Exhibits 99.1 and 99.2 attached hereto, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section. The information contained herein and in the accompanying exhibits is not incorporated by reference in any filing of the Company under the Securities Act of 1933, as amended, or the Exchange Act, whether made before or after the date hereof, regardless of any general incorporation language in such filing, except as shall be expressly set forth by specific reference in such filing.
The Company’s website and any information contained on the Company’s website are not incorporated into this Current Report on Form 8-K.
Item 9.01 Financial Statements and Exhibits.
Exhibit |
|
|
No. |
|
Description |
99.1 |
|
|
99.2 |
|
|
104 |
|
Cover Page Interactive Data File (embedded within the Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
|
|
|
REPARE THERAPEUTICS INC. |
|
|
|
|
Date: |
May 7, 2024 |
By: |
/s/ Lloyd M. Segal |
|
|
|
Lloyd M. Segal |
Exhibit 99.1
Repare Therapeutics Provides Business and Clinical Update and Reports First Quarter 2024 Financial Results
Phase 1 MYTHIC clinical trial of lunresertib in combination with camonsertib demonstrated a significant reduction in Grade 3 anemia and continued trends of patient response and benefit; FDA agrees with RP2D
First patient dosed in Phase 1 MYTHIC clinical trial of lunresertib in combination with the WEE1 inhibitor, Debio 0123; first clinical trial inhibiting both PKMYT1 and WEE1
Initiating Phase 2 TRESR expansion in ~20 patients evaluating monotherapy camonsertib in NSCLC; initial data expected in 2025
First patient dosed in Phase 1 LIONS monotherapy trial for PLK4 inhibitor RP-1664
Announced the appointment of Steven H. Stein, M.D. to Repare’s Board of Directors, effective in June 2024
$237.0 million in cash and cash equivalents and marketable securities to advance clinical programs and portfolio to mid-2026
CAMBRIDGE, Mass. & MONTREAL (BUSINESS WIRE)—May 7, 2024— Repare Therapeutics Inc. (“Repare” or the “Company”) (Nasdaq: RPTX), a leading clinical-stage precision oncology company, today reported financial results for the first quarter ended March 31, 2024.
“This was a quarter of clinical progress as we await key, near-term data on a rich set of distinctive clinical approaches for our four wholly-owned compounds in 2024,” said Lloyd M. Segal, President and Chief Executive Officer of Repare. “We have agreement with the FDA regarding our recommended Phase 2 dose (RP2D) for our lunresertib plus camonsertib combination, with significantly improved tolerability at the RP2D with our updated dosing schedule. We are seeing continuing trends of patient response and benefit, and we are on track to report the updated dataset in the fourth quarter of 2024. Our objective is to determine the best opportunity for a registrational trial, to start in 2025. Additionally, we are initiating a small clinical trial to rapidly confirm a camonsertib monotherapy signal in non-small cell lung cancer (NSCLC) and expect that readout to be available in 2025. Our clinical portfolio also includes the LIONS trial of our RP-1664 PLK4 inhibitor, the PKMYT1 and WEE1 inhibitor combination in MYTHIC, and the upcoming clinical start of our Polθ inhibitor program, RP-3467, in the second half of 2024.”
First Quarter 2024 and Recent Portfolio Highlights:
Summary of Expected Milestones:
First Quarter 2024 Financial Results:
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 1/2 clinical development; camonsertib (also known
as RP-3500), a potential leading ATR inhibitor currently in Phase 1/2 clinical development; RP-1664, a Phase 1 PLK4 inhibitor; RP-3467, a preclinical Polθ ATPase inhibitor program; as well as 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 current and future preclinical studies and clinical trials of the Company’s product candidates, including the expansion of its Phase 1 MYTHIC trial evaluating lunresertib alone and in combination with camonsertib, its Phase 1 MINOTAUR trial evaluating lunresertib in combination with FOLFIRI, the Module of the Company’s Phase 1/1b MYTHIC trial of, its Phase 1/1b trial of Debio 0123 and lunresertib in partnership with Debiopharm, the expansion of its Phase 2 TRESR trial of camonsertib in patients with ATMm, its Phase 1 LIONS trial of RP-1664, its Phase 1 trial of RP-3467; its planned expansion of development of lunresertib plus camonsertib combination; a potential registrational trial in 2025; the tolerability, efficacy and clinical progress of camonsertib, lunresertib, RP-1664 and RP-3467; the potential of RP-3467 as a best-in-class Polθ ATPase inhibitor; the potential synergies of Debio 0123 in combination with lunresertib, lunresertib in combination with camonsertib and lunresertib in combination with FOLFIRI; the Company’s anticipated cash runway; 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: the potential that 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 conflict in Ukraine and the conflict in the Middle East, heightened 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; the Company’s ability to realize the benefits of its collaboration and license agreements; 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 Quarterly Report on Form 10-Q for the quarter ended March 31, 2024 filed with the Securities and Exchange Commission (“SEC”) and the Québec Autorité des Marchés Financiers ("AMF") on May 7, 2024. 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.
Consolidated Balance Sheets
(Unaudited)
(Amounts in thousands of U.S. dollars, except share data)
|
|
As of |
|
|
As of |
|
||
|
|
2024 |
|
|
2023 |
|
||
ASSETS |
|
|
|
|
|
|
||
CURRENT ASSETS: |
|
|
|
|
|
|
||
Cash and cash equivalents |
|
$ |
103,217 |
|
|
$ |
111,268 |
|
Marketable securities |
|
|
133,784 |
|
|
|
112,359 |
|
Income tax receivable |
|
|
10,829 |
|
|
|
10,813 |
|
Other current receivables |
|
|
3,377 |
|
|
|
4,499 |
|
Prepaid expenses |
|
|
3,463 |
|
|
|
4,749 |
|
Total current assets |
|
|
254,670 |
|
|
|
243,688 |
|
Property and equipment, net |
|
|
3,714 |
|
|
|
4,215 |
|
Operating lease right-of-use assets |
|
|
2,763 |
|
|
|
3,326 |
|
Income tax receivable |
|
|
1,630 |
|
|
|
2,276 |
|
Other assets |
|
|
307 |
|
|
|
396 |
|
TOTAL ASSETS |
|
$ |
263,084 |
|
|
$ |
253,901 |
|
LIABILITIES AND SHAREHOLDERS’ EQUITY |
|
|
|
|
|
|
||
CURRENT LIABILITIES: |
|
|
|
|
|
|
||
Accounts payable |
|
$ |
6,825 |
|
|
$ |
2,400 |
|
Accrued expenses and other current liabilities |
|
|
20,454 |
|
|
|
24,057 |
|
Operating lease liability, current portion |
|
|
2,218 |
|
|
|
2,400 |
|
Deferred revenue, current portion |
|
|
1,073 |
|
|
|
10,222 |
|
Total current liabilities |
|
|
30,570 |
|
|
|
39,079 |
|
Operating lease liability, net of current portion |
|
|
561 |
|
|
|
1,010 |
|
Deferred revenue, net of current portion |
|
|
— |
|
|
|
1,730 |
|
TOTAL LIABILITIES |
|
|
31,131 |
|
|
|
41,819 |
|
SHAREHOLDERS’ EQUITY |
|
|
|
|
|
|
||
Preferred shares, no par value per share; unlimited shares authorized |
|
|
— |
|
|
|
— |
|
Common shares, no par value per share; unlimited shares authorized as of |
|
|
486,375 |
|
|
|
483,350 |
|
Additional paid-in capital |
|
|
65,638 |
|
|
|
61,813 |
|
Accumulated other comprehensive (loss) income |
|
|
(113 |
) |
|
|
28 |
|
Accumulated deficit |
|
|
(319,947 |
) |
|
|
(333,109 |
) |
Total shareholders’ equity |
|
|
231,953 |
|
|
|
212,082 |
|
TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY |
|
$ |
263,084 |
|
|
$ |
253,901 |
|
Repare Therapeutics Inc.
Consolidated Statements of Operations and Comprehensive Loss
(Unaudited)
(Amounts in thousands of U.S. dollars, except share and per share data)
|
|
Three Months Ended |
|
|||||
|
|
2024 |
|
|
2023 |
|
||
Revenue: |
|
|
|
|
|
|
||
Collaboration agreements |
|
$ |
52,404 |
|
|
$ |
5,678 |
|
Operating expenses: |
|
|
|
|
|
|
||
Research and development, net of tax credits |
|
|
32,970 |
|
|
|
31,830 |
|
General and administrative |
|
|
8,618 |
|
|
|
8,529 |
|
Total operating expenses |
|
|
41,588 |
|
|
|
40,359 |
|
Income (loss) from operations |
|
|
10,816 |
|
|
|
(34,681 |
) |
Other income (expense), net |
|
|
|
|
|
|
||
Realized and unrealized gain (loss) on foreign exchange |
|
|
31 |
|
|
|
(56 |
) |
Interest income |
|
|
2,968 |
|
|
|
3,427 |
|
Other expense |
|
|
(24 |
) |
|
|
(15 |
) |
Total other income, net |
|
|
2,975 |
|
|
|
3,356 |
|
Income (loss) before income taxes |
|
|
13,791 |
|
|
|
(31,325 |
) |
Income tax expense |
|
|
(629 |
) |
|
|
(3,616 |
) |
Net income (loss) |
|
$ |
13,162 |
|
|
$ |
(34,941 |
) |
Other comprehensive (loss) income: |
|
|
|
|
|
|
||
Unrealized (loss) gain on available-for-sale marketable securities |
|
$ |
(141 |
) |
|
$ |
193 |
|
Total other comprehensive (loss) income |
|
|
(141 |
) |
|
|
193 |
|
Comprehensive income (loss) |
|
$ |
13,021 |
|
|
$ |
(34,748 |
) |
Net income (loss) per share attributable to common shareholders: |
|
|
|
|
|
|
||
Basic |
|
$ |
0.31 |
|
|
$ |
(0.83 |
) |
Diluted |
|
$ |
0.30 |
|
|
$ |
(0.83 |
) |
Weighted-average common shares outstanding: |
|
|
|
|
|
|
||
Basic |
|
|
42,234,001 |
|
|
|
42,040,674 |
|
Diluted |
|
|
44,024,198 |
|
|
|
42,040,674 |
|
Investor Relations & Media Contact:
Robin Garner
Vice President and Head of Investor Relations
Repare Therapeutics Inc.
Source: Repare Therapeutics Inc.
Insight that enriches. Precision that empowers. Corporate Presentation May 2024
Disclaimer Statements contained in this presentation regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as "anticipates," "believes," "expects," "intends," “plans,” “potential,” "projects,” “would” and "future" or similar expressions are intended to identify forward-looking statements. Each of these forward-looking statements involves substantial risks and uncertainties that could cause actual results to differ significantly from those expressed or implied by such forward-looking statements. Forward-looking statements contained in this presentation include, but are not limited to, statements regarding the initiation, timing, progress and results of our current and future preclinical studies and clinical trials, including specifically our clinical trials of lunresertib, camonsertib, RP-1664, and preclinical studies of RP-3467; the expected timing of program updates and data disclosures; the timing of filing INDs and other regulatory documents; the timing and likelihood of seeking regulatory approval for our product candidates; the competitive landscape for our product candidates; our ability to identify and develop additional product candidates using our SNIPRx platform; and our estimates regarding expenses, future revenue, capital requirements, cash runway and needs for additional financing. These forward-looking statements reflect our current beliefs and expectations. Many factors may cause differences between current expectations and actual results, including the duration and impact of the COVID-19 pandemic on our business and market volatility, unexpected safety or efficacy data observed during preclinical or clinical studies, clinical site activation rates or clinical trial enrollment rates that are lower than expected, changes in expected or existing competition, changes in the regulatory environment, and unexpected litigation or other disputes. These and other risks are described more fully in our filings with the Securities and Exchange Commission (“SEC”), including the “Risk Factors” section of our Annual Report on Form 10-Q filed with the SEC on May 7, 2024, and other documents we subsequently filed with or furnished to the SEC. All forward-looking statements contained in this presentation speak only as of the date on which they were made. Except as required by law, we assume no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. Neither we nor any other person makes any representation as to the accuracy or completeness of such data or undertakes any obligation to update such data after the date of this presentation. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. Solely for convenience, the trademarks and trade names in this presentation may be referred to without the ® and ™ symbols, but such references should not be construed as any indicator that their respective owners will not assert their rights thereto.
3 3 Differentiated, proprietary clinical pipeline Lunresertib: First-in-class oral PKMYT1 inhibitor (Phase 1/2) Camonsertib: ATR inhibitor (Phase 1/2) RP-1664: First-in-class selective PLK4 inhibitor (Phase 1) Developing Next-Generation Precision Oncology Medicines Multiple clinical catalysts expected in 2024 Key readouts from ongoing trials New clinical entries (PLK4 and Pol ATPase inhibitors) Proprietary CRISPR- enabled SNIPRx platform Focused on genomic instability and DNA damage repair Clinical trials enriched for patients with tumors carrying a network of synthetic lethal alterations (STEP2) Strong balance sheet Cash and investments of ~$237M1 fund operations to mid-2026 Multiple clinical catalysts in that timeframe 1 As of March 31, 2024.
Targeting the untargetable through synthetic lethality Specifically targeting and disrupting genes essential for cancer cell survival SNIPRx identifies and targets necessary genes to induce synthetic lethality Highly targeted & tumor-type agnostic approach Exploiting cancer cell genomic instability, including DNA damage repair Platform validated with established and expanding clinical-stage pipeline Precision oncology last 20 years: Targetable gain of function (e.g., EGFR) Focused on 71% untapped target space, conventionally untargetable Gain of function (e.g., CCNE1, 17%) Loss of function (no known driver; e.g., BRCA1, 54%)
Expanding pipeline of precision oncology therapeutics PROGRAM TUMOR LESION DRUG TARGET PRECLINICAL PHASE 1 PHASE 2 PHASE 3 RIGHTS Lunresertib (RP-6306) CCNE1, FBXW7 + others PKMYT1 Camonsertib (RP-3500) ATM + 16 STEP2 lesions ATR RP-1664 TRIM37-high PLK4 RP-3467 BRCA1/2 Polθ ATPase SNIPRx® Platform Additional SL targets in advanced stages of development Discovery and validation of new SL precision oncology targets Monotherapy NSCLC Expansion Monotherapy + PARP (Talazoparib) Combination PARP (olaparib/niraparib) Combination Gemcitabine Combination Camonsertib Combination Gemcitabine Combination FOLFIRI Combination 2 Combination ISTs Debio 0123 Wee1i Combination Monotherapy
Proven experience in drug discovery and development Leadership Team Scientific Founders Steve Forte, CPA Chief Financial Officer Michael Zinda, PhD Chief Scientific Officer Maria Koehler MD, PhD Chief Medical Officer Cameron Black, PhD Head of Discovery Philip Herman Chief Commercial, Portfolio Development Officer Daniel Bélanger Head of Human Resources Lloyd M. Segal President & CEO Kim A. Seth, PhD Chief Business Officer Daniel Durocher, PhD Developed CRISPR SL platform Deep DNA repair knowledge Lunenfeld-Tanenbaum Research Institute (LTRI) & professor at University of Toronto Agnel Sfeir, PhD DDR and cancer pathway investigator Pioneer in Polθ, genome instability Professor, MSKCC Frank Sicheri, PhD Globally recognized structural biologist, expert in eukaryotic cell signaling, drug mechanism of action LTRI & professor at University of Toronto
Lunresertib (RP-6306)
Lunresertib: First-in-class, oral, small molecule, PKMYT1 inhibitor Large, genomically defined potential addressable patient population of ~90k 50% RECIST response in camonsertib combination in gynecological tumors Repare discovered synthetic lethality of PKMYT1 inhibition Initially identified CCNE1 amplification STEP2 screen identified additional genes – FBXW7 and PPP2R1A First and currently the only PKMYT1 inhibitor in clinical trials Anti-tumor activity observed Across multiple tumor types and genotypes POC in patients established FDA agreed with RP2D; safe and well tolerated Supported preclinical synergy hypothesis and patient selection approach from proprietary SNIPRx platform 8 POC, proof of concept; RP2D, recommended Phase 2 dose.
Large, genomically defined potential patient population Top New Advanced Tumor Cases (US+UK/EU4) Top Tumors (New Advanced Cases, US+UK/EU4) Tumor Type Prevalence of Genes of Interest Eligible Patients Uterine 7,000 Ovarian 6,300 Stomach 9,000 Colorectal 24,500 Bladder 6,200 Cervical 1,300 Esophageal 4,500 Sarcoma1 1,200 Lung Squamous2 5,300 * Based on estimated number of pts US+UK/EU4 treated in 1st line, advanced setting for diagnosed and new recurrent patients (CancerMPact®, Treatment Architecture, United States, 2021; accessed 5/19/23) and lesion prevalence (TCGA). 1 Soft Tissue Sarcoma only; 2 Squamous subtype of Non-Small Cell Lung Cancer only CCNE1 FBXW7 PPP2R1A Multiple ~90K addressable patients including ~65K among top tumors with genetic alterations largely mutually exclusive
Evolving broad trial program: sponsored and collaborative PPP2R1A FBXW7 Recurrent solid tumors Key inclusion criteria: CCNE1 amplification or inactivating mutations Determine RP2D dose / schedule Progress to late-stage trials MAGNETIC: + Gemcitabine MYTHIC: + Camonsertib; + Debio 0123 (Wee1 inhibitor) MINOTAUR: + FOLFIRI Multiple Investigator Sponsored Trials (CCTG1, Carbo/paclitaxel2) Lunresertib Combination Therapy Selected tumors with FBXW7 loss Tumors with high rate of sensitivity genes Basket trial 1 Canadian Clinical Trial Group (CCTG) collaborations include NCT05605509 and NCT05601440. 2 Standard of care (“SOC”) for 1st line ovarian cancer is carbo/paclitaxel (6 cycles) + PARPi maintenance therapy or carbo/paclitaxel with bevacizumab + bev maintenance therapy; this IST supports future potential 1st line combination studies as triplet therapy in patients with CCNE1 amplified tumors. Selected tumors with amplified CCNE1 Ovarian, Lung, Esophageal / Gastric Future Opportunities CRC, Other GI, Pan Tumor Endometrial, Bladder Breast, Sarcoma, Bile Duct
Lunresertib: MYTHIC Preliminary Phase 1 Trial Results (M1: Monotherapy) (M2: Camonsertib Combination Therapy) OR, overall response; CBR, clinical benefit rate. MONOTHERAPY Safe, well tolerated and anti-tumor activity observed (N=67) Recommended Phase 2 dose: 80 mg twice daily in intermittent schedule CAMONSERTIB COMBINATION THERAPY Safe, well tolerated and promising anti-tumor activity observed across tumors and all lunresertib-sensitizing genomic alterations (N=59) 23.6% OR; 41.8% CBR in efficacy-evaluable patients (N=55) 33.3% OR; 50.0% CBR at preliminary RP2D range, across all tumors (N=18) 38.5% OR; 57.7% CBR in patients with heavily pre-treated gynecologic cancers (N=26); 50% RECIST response at preliminary RP2D (N=10) Dose/schedule optimization complete; RP2D of lunresertib 80mg twice daily and camonsertib 80mg once daily
Key updates since ENA 2023; registrational decision on track Registrational decision on track in gyn expansions in Q4 2024 Continuing trends of patient response and benefit Grade 3 anemia reduced from 45% to 25% at RP2D with updated dosing 2 weeks on / 1 week off for patients with low Hg, otherwise weekly FDA agreed with RP2D Efficacy assessment is ongoing, continues to be promising and on track to be shared by end of Q4 2024 Data is expected to include ~20-30 patients per histology (ovarian and endometrial) at RP2D
Lun + cam responses across tumor types and genotypes * One response evaluable patient became uPR and four patients had responses confirmed after the Sept. 5, 2023 cutoff, data as of Oct. 6, 2023. Relevant patient tumor co-mutations †BRCA1 rearrangement and ‡BRCA2 biallelic loss. +Treatment ongoing. BL, baseline; cPR, confirmed partial response; RECIST, Response Evaluation Criteria in Solid Tumors; TL, target lesion; Tx, treatment; uPR, unconfirmed partial response. RECIST and tumor marker responses occurred early despite heavily pre-treated, relapsed/refractory patient population Tumor type Genotype Response Best % change in TL from BL Therapy (weeks) Lines of prior Tx/ prior platinum Endometrial PPP2R1A/FBXW7 cPR -55.9 30.4 3/Y PPP2R1A/CCNE1 cPR -53.0 18.1 2/Y FBXW7 cPR* -100.0 11.1+ 3/Y FBXW7 uPR -39.6 16.0 3/Y FBXW7 uPR* -44.7 11.4+ 3/Y Ovarian CCNE1 cPR* -70.2 21.4+ 2/Y CCNE1† cPR* -30.8 12.6+ 3/Y CCNE1 CA-125 -16.9 29.0+ 9/Y CCNE1 CA-125 -23.1 37.0+ 2/Y CCNE1 CA-125 13.6 12.9+ 5/Y Cervical PPP2R1A cPR* -44.4 11.0+ 1/Y Colorectal FBXW7 cPR -43.3 27.6 3/Y Bile duct CCNE1 cPR -35.0 28.1 2/Y Breast FBXW7‡ uPR -43.8 18.1 2/N
*Efficacy evaluable patients only (≥1 post-baseline tumor assessment). Other tumor types include cervical (n=1), esophageal (n=1), GI (n=1), liver (n=1), lung (n=3), melanoma (n=1), osteosarcoma (n=1), pancreatic (n=2), and upper GI (n=1). CBR: overall response or time on treatment ≥ 16 wk w/o progression; CRC, colorectal cancer; RECIST, Response Evaluation Criteria in Solid Tumors (RECIST) Gynecologic Cancer InterGroup (GCIG); MRR, molecular response rate; OR, overall response based on RECIST or GCIG CA-125 response; RP2D, recommended phase 2 dose; lun, lunresertib. Frequent and deep tumor reductions observed with lun + cam In evaluable patients*, across all tumors/doses: OR: 23.6% (n=55) CBR: 41.8% (n=55) MRR: 50.0% (n=24) At preliminary RP2D, across all tumors: OR: 33.3% (n=18) CBR: 50.0% (n=18) CA-125 response Treatment ongoing + Tumor type: Ovarian Endometrial CRC Bile Duct Breast Other Best change from baseline in tumor size (%) 100 −80 80 60 40 20 0 −20 −40 −60 −100
* Gynecologic cancers: ovarian, endometrial, and cervical cancers. Data represent the efficacy evaluable population (≥1 post-baseline tumor assessment). CBR, clinical benefit rate; OR, overall response based on RECIST or GCIG CA-125 response; MRR, molecular response rate; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors ; Gynecological Cancer InterGroup (GCIG); RP2D, recommended phase 2 dose. Across all doses (n=26): Overall response: 38.5%; RECIST Response: 26.9% CBR: 57.7%; MRR: 8/10 (80%) At preliminary RP2D (n=10): Overall response: 60%; RECIST Response: 50% CBR: 70% Patients had 1-9 prior therapies (median=3); treatment ongoing in 11 patients; enrollment in expansion cohorts at RP2D continues Meaningful tumor reductions, durable clinical benefit observed in heavily pre-treated patients to date PR Tumor marker response Treatment ongoing Gynecologic cancers* Efficacy evaluable patients Weeks of treatment 0 4 8 12 16 20 24 28 32 36 40 Best change from baseline in tumor size (%) CA-125 response Treatment ongoing + 60 40 20 0 −20 −40 −60 −80 −100 At preliminary RP2D Combination treatment effective in gynecologic tumors
Significant improvement in anemia observed with updated dosing Selected hematologic TRAEs, n (%) All Grades Gr3 Gr4 All Grades Gr3 Gr4 Anemia 13 (65.0) 9 (45.0) 0 29 (65.9) 11 (25.0) 0 Leukopenia 3 (15.0) 0 0 9 (20.5) 3 (6.8) 0 Neutropenia 3 (15.0) 2 (10.0) 0 7 (15.9) 5 (11.4) 0 Thrombocytopenia 0 0 0 0 0 0 RP2D (ENA Cutoff)a N=20 RP2D (Cohort Post ENA) N=44 RP2D: lunresertib 80mg BID + camonsertib 80mg QD 3d/4d Updated dosing strategy reduced Grade 3 anemia by ~half Hematologic safety profile similar to commercial SL agents No thrombocytopenia observed a ENA data cutoff of September 2023. TRAEs, treatment-related adverse events.
TRAEs in ≥10% of patients, n (%) All Grades Gr3 Gr4 Nausea/Vomiting 34 (52.3) 0 0 Rasha 26 (40.0) 1 (1.5) 0 Fatigue 18 (27.7) 1 (1.5) 0 Stomatitis 18 (27.7) 4 (6.2) 0 Decreased appetite 13 (20.0) 0 0 Diarrhea 10 (15.4) 0 0 Headache 7 (10.8) 0 0 Constipation 5 (7.7) 0 0 a Data as of March 2024; all patients treated at exposures consistent with RP2D at any time of the trial. DOT, duration of treatment. Lun+Cam RP2D N=65a FDA agreement on RP2D No FDA comments raised about safety profile observed in lun + cam combination Continued favorable safety profile observed to date Patient demographics remain comparable: Entry Hg Gender and age Prior lines and therapies ECOG Histologies and DOT Differences in anemia rates likely a result of the updated dosing strategy
Lun + FOLFIRI combination promising Source: Clarivate-Decision Resources Group, No added heme tox observed to FOLFIRI alone MINOTAUR demonstrating overall favorable tolerability and early signal in CRC and other GI tumors Favorable tolerability: lunresertib given continuously daily (QD), demonstrating promising tolerability profile vs. other FOLFIRI combinations No new toxicities observed; no treatment withdrawals at RP2D Focus on potential for duration of treatment advantage in both FOLFIRI-naïve and experienced patients 20%* 5-10%** * FOLFIRI ; ** TAS-102/regorafenib Full data to be shared at ESMO GI in June 2024
First clinical trial inhibiting both PKMYT1 and WEE1 Combination synergistically eradicates ovarian cancer cells and organoid models at a low doses… Strong preclinical evidence of PKMYT1 + WEE1 inhibitor combination potential; Ph1/1b now enrolling Benada et al., NAR Cancer, 2023. …drives tumor regressions on intermittent schedule at doses below monotherapy EC50 … Gallo et al., ANE 2023, Poster #A023. … and overcomes resistance to MK-1775 (adavosertib) mediated by tet-induced Myt1 upregulation Sokhi et al., AACR 2023, Poster #5511.
Platinum-resistant ovarian cancer (PROC) market opportunity 1 Chemo+Bevacizumab vs Chemo (AURELIA); Source: Bevacizumab FDA Label 2 Mirvetuximab vs Chemo (MIRASOL); Source: Mirvetuximab FDA Label, ASCO 2023. Mirvetuximab is approved for ~1/3 of PROC patients who are folate receptor positive. 3 Eligible Patients in US and EU4/UK Based On Company Estimates from TCGA and GENIE, 2L+ (2L - 5L) PFI, progression-free interval. Chemo + Bevacizumab1 28% ORR 6.8 mo. PFS 16.6 mo. OS Platinum Sensitive ~2,900 2L+ Patients with CCNE13 Platinum Chemo 1st Line Therapy 1st Line Maintenance PARP and/or Bevacizumab 2nd Line Therapy Platinum Chemo PFI > 6 mo. PFI ≤ 6 mo. PFI ≤ 6 mo. ~70% Single Agent Chemo +/- Bev ~30% Mirvetuximab (FR-alpha +) Unmet Need Single Agent Chemo1,2 13 - 16% ORR 3.4 - 4.0 mo. PFS 12.8 - 13.3 mo. OS Mirvetuximab2 42% ORR 5.6 mo. PFS 16.5 mo. OS Platinum Resistant Unmet need remains significant for platinum resistant patients
Endometrial cancer market opportunity 1 Lenvatinib/Pembrolizumab vs Single Agent Chemo (KEYNOTE-775); Source: Lenvatinib FDA Label 2 Ixabepilone vs Paclitaxel or Doxorubicin; McMeekin S. Gynecologic Oncology 2015 https://doi.org/10.1016/j.ygyno.2015.04.026 3 Eligible Patients in US and EU4/UK Based On Company Estimates from TCGA and GENIE, 2L+ (2L - 5L) Single Agent Chemo1,2 15 - 16% ORR 3.8 - 4.0 mo. PFS 12.0 - 12.3 mo. OS Chemo +/- Immune Checkpoint Inhibitor (“ICI”) 1st Line Therapy ICI or Single Agent Chemo No SOC (various chemotherapies) Unmet Need 2nd Line+ Therapy Prior ICI No Prior ICI ~3,600 2L+ Patients with CCNE1, FBXW7, or PPP2R1A3 Evolving 1L SOC towards Chemo + ICI creating large unmet need in future 2L+ setting
Metastatic CRC is a large market opportunity for MINOTAUR 1 FOLFIRI+Aflibercept vs FOLFIRI (VELOUR); Source: Aflibercept FDA Label 2 FOLFIRI+Ramucirumab vs FOLFIRI (RAISE); Source: Ramucirumab FDA Label, Lancet 2015 3 Napabucasin+FOLFIRI vs FOLFIRI+Bevacizumab (CanStem303C); Source: Shah M. Clinical Colorectal Cancer 2022 4 Panitumumab+FOLFIRI vs FOLFIRI+Bevacizumab (SPIRITT); Source: Hecht JR. Clinical Colorectal Cancer 2015 5 Eligible Patients in US and EU4/UK Based On Company Estimates from TCGA and GENIE, 2L+ (2L - 5L) 1st Line Therapy 2nd Line+ Therapy FOLFIRI+ VEGF1,2,4 13 - 20% ORR 5.7 - 9.2 mo. PFS 13.3 - 21.4 mo. OS Irinotecan-based Chemotherapy +/- VEGF KRAS Inhibitors (KRAS G12C) Encorafenib + Cetuximab (BRAF V600) ~11,300 2L+ Patients with FBXW75 (~13% of CRC) G7 Colorectal Cancer market: >$8B today (>$10B by 2032) Oxaliplatin-based Chemotherapy +/- VEGF Unmet Need FOLFIRI1,2,3 11 - 15% ORR 4.5 - 5.6 mo. PFS 11.7 - 13.8 mo. OS Unmet need in 2L+ oxaliplatin-treated mCRC patients
Camonsertib (RP-3500)
Camonsertib: Potential best-in-class ATR inhibitor Durable antitumor activity in combination with PARPi; meaningful clinical benefit observed in ovarian cancer Global development and commercialization rights wholly-owned by Repare - Rapid monotherapy signal confirmation in NSCLC Proof of concept established in Phase 1/2 monotherapy trial Demonstrated synthetic lethal interaction of ATR and a network of genes identified by SNIPRx and STEP2 process 24 NSCLC, non-small cell lung cancer.
Potential across significant additional patient populations Top 10 Tumor Types* with Highest Prevalence of ATM Deficiency Top 10 Tumor Types* with Highest Prevalence of ATM Deficiency or STEP2 Genomic Alterations * TCGA; Not weighted for tumor prevalence
Updated camonsertib monotherapy data in ATMm tumors Updated data continues to support ATR-ATM synthetic lethality thesis across various tumor types and genotypes 114 total efficacy evaluable patients treated at 3 efficacious dose levels 36 patients enrolled with ATM alterations 4 with responses and treatment durations 41-112+ weeks 9/36 (25%) total with Tx duration >6 months
Camonsertib: rapid monotherapy signal confirmation in NSCLC >12 months durability observed in >20% of patients with ATMm tumors treated with camonsertib monotherapy ATMm NSCLC (~4% of NSCLC) an attractive opportunity Camonsertib monotherapy signal potentially offers rapid and cost-efficient path to PoC with ~15-20 more patients within TRESR 11 NSCLC patients (4 with ATMm) highlight improved mPFS in ATMm NSCLC vs non-ATMm AstraZeneca HUDSON Ph2 data subset (ATR + PD-L1 post IO) further supports ATMm hypothesis in NSCLC ATMm tumors do not have better outcomes in NSCLC TRESR open to enrollment; data expected in 2025, with potential for expansion IO collaborations beyond monotherapy an obvious, substantial opportunity unselected mPFS (mo.) SOC benchmark > 10 mo 3.4mo 8.4mo 4.6mo 4mo * mPFS of 4.6 months reported for both primary resistance and acquired resistance cohorts in the biomarker non-matched group, as reported in Besse, B. et al. Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial. Nature Medicine. 13 February 2024 (HUDSON trial). Promising Camonsertib mPFS in NSCLC
Camonsertib NSCLC market opportunity 1 Atezolizumab vs Chemo (OAK); Source: Atezolizumab FDA Label 2 Ramucirumab+Chemo vs Chemo (REVEL); Source: Ramucirumab FDA Label 3 Eligible Patients in US and EU4/UK Based On Company Estimates from TCGA and GENIE, 2L+ (2L - 5L) 2nd Line+ Therapy Single Agent Chemotherapy +/- VEGF Immunotherapy (PD-L1) Chemoimmunotherapy Immunotherapy (PD-L1) Unmet Need Ramucirumab + Chemo2 23% ORR 4.5 mo. PFS 10.5 mo. OS Non-Biomarker Driven Patients 1st Line Therapy ~5,300 2L+ Patients with ATM3 Biomarker Driven Patients (EGFR, ALK, KRAS, ROS, etc.) 1+ Lines of Biomarker Driven Therapies Single Agent Chemo1,2 13 - 14% ORR 3.0 - 4.0 mo. PFS 9.1 - 9.6 mo. OS Significant unmet need for non-biomarker driven NSCLC patients
RP-1664
Actively enrolling in solid tumors and neuroblastoma RP-1664 First-in-class, oral PLK4 inhibitor ~63K addressable patient population with limited treatment options; potential across multiple tumor types Strong, dose-dependent anti-tumor activity observed as monotherapy across preclinical models Highly potent, selective and bioavailable PLK4 inhibitor synthetically lethal with TRIM37 gain of function 30
High prevalence in patient populations with limited treatment options *Based on estimated number of pts available for 1st line treatment in the advanced setting (CancerMPact®, Patient Metrics, 2022; accessed 8/18/23) and lesion prevalence (TCGA; GENIE-Neuroblastoma Only). 1 Represents only gene amplification for high risk Neuroblastoma; 2 Non-Squamous subtype of Non-Small Cell Lung Cancer only; 3 Squamous subtype of Non-Small Cell Lung Cancer only Top Tumors (New Advanced Cases, US+UK/EU4) Tumor type Prevalence of TRIM37 alterations Eligible patients* Neuroblastoma <1,000 Breast: HER2+ 5,900 Breast: HR+/HER2- 11,800 Breast: TNBC 2,200 Lung Non-Squamous 19,300 Bladder 4,100 Liver 2,200 Lung Squamous 4,700 Soft Tissue Sarcoma <1,000 Esophageal 2,000 Top TRIM37 Altered Tumors (New Advanced Cases, US+UK/EU4) 3 2 1 ~63K patients with TRIM37 amplification or overexpression, with ~53K among top tumors
Compelling synthetic lethal rationale for targeting PLK4 Biomarker-driven patient selection hypothesis for development of oral PLK4i for TRIM37-high tumors Centrosomes use centrioles and pericentriolar material (PCM) for mitotic spindle formation Polo-Like Kinase 4 (PLK4) required for centriole creation in S-phase TRIM37 (an E3 Ligase) reduces PCM stability; excess TRIM37 depletes PCM, increasing cell reliance on centrioles for spindle assembly Thus, PLK4 inhibition is harmful in cells with high TRIM37 and low PCM Validated in two 2020 Nature publications Chapman/Holland Nature volume 585, pages 447–452 (2020) Source: Holland AJ Nature 2020; Oegema K Nature 2020.
Potential first-in-class oral PLK4 inhibitor Key Parameter RP-1664 In vitro PLK4 Enzyme IC50 1 nM PLK4 cell binding IC50 3 nM Cell proliferation in MCF7 / T47D (TRIM37 amp) EC50 51 / 17 nM Cell-base selectivity vs AurA, AurB >2000-fold Kinome screen at 90x PLK4 IC50 8/280 kinases >50% inh ADME Human Hepatocyte Clearance (µL/min/106 cells) 2.2 Rat PK (%F, t1/2) 28%, 4h Monkey PK (%F, t1/2) 96%, 9h Highly potent, selective and orally bioavailable PLK4 inhibitor ~10x more potent than competitor molecules1 with vastly improved selectivity vs AurB Clean in PanLabs safety pharmacology screen 1 CFI-400945 and EXEL-7871. Source: internal data and Exelixis corporate presentation
Robust monotherapy efficacy across solid tumor PDX/CDX models Breast (Triple Negative) CDX Monotherapy drives tumor stasis to regression in TRIM37-high models Breast (ER positive) PDX NSCLC PDX
Highly efficacious as monotherapy in neuroblastoma models Neuroblastoma PDX and CDX models (all TRIM37-high) conducted at Children’s Hospital of Philadelphia demonstrate deep and prolonged monotherapy regressions in 5 of 6 evaluable models COG-N-424X Felix COG-N-421 COG-N-453x NBSD Ebc1 *J Maris and Y Mosse, CHOP
RP-1664 Phase 1/2 monotherapy clinical development plan Phase 1 Trial Adult solid tumors TRIM37-high High grade pediatric neuroblastoma Phase 1b Expansion Phase 1/2 Investigation Adult and adolescent patients with solid tumors TRIM37-high & additional biomarkers Goal: Recommended Phase 2 dose & safety Study started: Feb 2024 Efficient RP-1664 Phase 1 plan enables early start for pediatric dose finding study in neuroblastoma and clear view on adult solid tumor opportunity
RP-3467
RP-3467 capable of complete regressions and synergies in PARPi resistance preclinical models RP-3467 Potential best-in-class Polθ ATPase inhibitor FPI in 2H 2024 Global market segments comprise $16 billion in PARP inhibitors, RLT, and chemotherapy Demonstrates compelling potential for combination efficacy without added toxicity Highly potent, selective Polθ ATPase inhibitor; inhibits DNA repair and is synthetic lethal with BRCA loss 38
RP-3467 clinical plan: multiple potential Phase 1/2 trials Initiation expected in H2 2024 Goal: PK, safety and RP2D Phase 1 Trial PARPi combination – PARP1/2 or PARP1 Deep/durable complete responses preclinically, with no additional toxicity RLT combination Survival benefit preclinically in unselected tumor backgrounds, with no additional toxicity Chemotherapy / ADC Payloads Well tolerated preclinically in combination with carboplatin and irinotecan, including topoisomerase ADC payloads HCT116 BRCA2 -/- Global Market Segment Phase 1/2 Trials Combination Survival Benefit HCT116 BRCA2 -/- (Irinotecan combo) ~$3 Billion ~$8 Billion ~$5 Billion Preclinical Results
Profound, durable synergy observed with PARP inhibition HCT116 BRCA2 -/- Body Weight Deep/durable complete regressions observed across a wide dose range and well tolerated olaparib olaparib olaparib olaparib
Polθ: uniquely promising therapeutic target Polθ is a unique multifunctional DNA polymerase with ATP-dependent DNA helicase activity Required for microhomology-mediated end joining (MMEJ), a key mechanism of double-strand DNA break repair Uniquely active to repair double-strand DNA breaks during mitosis Minimally expressed in normal tissue and knockout animals have no significant phenotype [ ] S/G2 Recent evidence that MMEJ is the predominant repair pathway in mitosis
Target profile: potent, tolerable, capable of complete regressions Highly potent, selective and orally bioavailable Polθ ATPase inhibitor; clean PanLabs safety pharmacology screen RP-3467 demonstrated complete regressions in BRCA1/2 null PDX models, also synergy in a PARPi resistance model Parameter RP-3467 Potency Polθ ATPase Enzyme IC50 <0.25 nM CETSA cellular target engagement IC50 5 nM Cell proliferation DLD1 / HCT116 (BRCA2mt) EC50 4 / 7 nM Selectiv. Off-target ATPase (HELQ, WRN, BLM) IC50 > 10 µM Off-target Polθ polymerase domain IC50 > 100 µM ADME Human Hepatocyte Clearance (µL/min/106 cells) 2.1 Rat PK (%F, t1/2) 123%, 6h Monkey PK (%F, t1/2) 60%, 3h Complete regressions in PDX models at low doses HBCx-22 (BRCA2null) HBCx-10 (BRCA2null)
Addressing unmet need in critical patient populations PARP-naïve and PARP-treated (Treated Patients US+UK/EU4)* Top Tumors (New Advanced Cases, US+UK/EU4) Tumor type Prevalence of gene of interest PARP-naïve opportunity (1L) PARP-resistant opportunity (2L) Ovarian 7,700 3,500 Castrate-Resistant Prostate 5,100 2,400 HER2- Breast** 2,900 1,600 Pancreatic** 1,700 500 22.7% 8.2% 3.7% 2.6% Other HRD BRCA 2 BRCA 1 * Based on estimated number of drug treated pts in the advanced setting likely to be naïve to PARP inhibitor treatment or previously treated with a PARP inhibitor (CancerMPact®, Patient Metrics, 2022; accessed 9/25/23) and lesion prevalence (TCGA; Riaz, N. et al. Pan-cancer analysis of bi-allelic alterations in homologous recombination DNA repair genes. Nat Commun 8, 857 (2017)). Other HRD gene mutations include: BRIP1, ATM, RAD51B, RAD51C, RAD51D, PALB2, BARD1, CDK12, CHEK1, CHEK2, FANCL, RAD54L. ** Includes germline BRCA1/2 only ~26K among patients with PARP-naïve and PARP-treated tumors
Multiple potential market opportunities for near term milestones Expansion Opportunities to 1L Near Term Opportunity Lun + FOLFIRI 2L+ CRC (FBXW7) Camonsertib 2L+ NSCLC (ATM) Lun + Cam 2L+ Endometrial (CCNE1/FBXW7/PPP2R1A) Lun + Cam 2L+ PROC (CCNE1) Drug Treated Patients Per Year1 (2024 Estimate; US/EU4/UK) 1 Eligible Patients Based On Company Estimates from TCGA and GENIE; Source: Drug Treated patients from CernerEnviza/CancerMpact 40,490
Lunresertib + Debio 0123 combination data Camonsertib monotherapy data in NSCLC Initiate first pivotal trial for lun+cam in 2025 Camonsertib monotherapy expansion to NSCLC in TRESR RP-3467 Ph1 clinical trial initiation Lunresertib + camonsertib expansion cohort data in ovarian and endometrial in Q4 RP-1664 (PLK4i) clinical trial initiation Lunresertib + Debio 0123 combination Ph1/1b clinical trial initiation Regained camonsertib rights Initial lunresertib + FOLFIRI combination Ph1 data at ESMO GI in June Recent and expected milestones 1H 2024 2H 2024 2025
46 46 Differentiated, proprietary clinical pipeline Lunresertib: First-in-class oral PKMYT1 inhibitor (Phase 1/2) Camonsertib: ATR inhibitor (Phase 1/2) RP-1664: First-in-class selective PLK4 inhibitor (Phase 1) Developing Next-Generation Precision Oncology Medicines Multiple clinical catalysts expected in 2024 Key readouts from ongoing trials New clinical entries (PLK4 and Pol ATPase inhibitors) Proprietary CRISPR- enabled SNIPRx platform Focused on genomic instability and DNA damage repair Clinical trials enriched for patients with tumors carrying a network of synthetic lethal alterations (STEP2) Strong balance sheet Cash and investments of ~$237M1 fund operations to mid-2026 Multiple clinical catalysts in that timeframe 1 As of March 31, 2024.
Insight that enriches. Precision that empowers. Corporate Presentation May 2024