PI3Kα

-- OnKure is focused on advancing a pipeline of candidates targeting oncogenic mutations in phosphoinositide 3-kinase alpha (PI3Kα), initially in breast cancer -- On track to announce early clinical data for its lead program, OKI-219, in Q4-2024 -- Post-transaction cash, cash equivalents, and short-term investments of approximately $139 million expected to provide funding through multiple clinical readouts and runway into Q4-2026 -- Shares to trade on Nasdaq under the new ticker symbol “OKUR” commencing on October 7, 2024 BOULDER, Colo., Oct. 04, 2024 (GLOBE NEWSWIRE) -- OnKure Therapeutics, Inc. (Nasdaq: OKUR) (“OnKure”), a clinical-stage biopharmaceutical company focused on the development of novel precision medicines in oncology, today announced the completion of its previously announced merger of OnKure, Inc. and Reneo Pharmaceuticals, Inc. (“Reneo”). The combined company will operate under the name OnKure Therapeutics, Inc., and its shares are expected to begin trading on the Nasdaq Global Market on October 7, 2024 under the ticker symbol "OKUR". Concurrent with the closing of the merger, the company completed a $65 million private placement with a group of new and existing investors, including Acorn Bioventures, Cormorant Asset Management, Deep Track Capital, Perceptive Advisors, Samsara BioCapital, Surveyor Capital (a Citadel company), Vestal Point Capital, and other undisclosed investors. Following the transactions, OnKure is expected to have a cash runway through multiple clinical readouts and into Q4-2026. “We are ecstatic to finalize this merger, and move to accelerate the development of our mutant-specific PI3Kα inhibitor portfolio. Combined with our unique expertise in PI3K-mutated cancers, we aim to fully target and exploit the vulnerabilities of this oncogenic menace for the benefit of patients suffering needlessly,” said Nicholas Saccomano, Ph.D., President and Chief Executive Officer of OnKure. “Our lead program OKI-219, a highly selective inhibitor of PI3KαH1047R, has the potential to provide benefit to breast cancer patients. With the PIKture-01 trial of OKI-219 well underway, we look forward to releasing early clinical data in the fourth quarter of 2024 and initiating planned combination arms of the PIKture-01 trial.” Transaction Details In connection with the closing of the merger, Reneo effected a 1-for-10 reverse stock split of its common stock. Following the reverse stock split and based on the final exchange ratios of 0.0236 shares of Reneo common stock for each share of OnKure common stock and 0.1448 shares of Reneo common stock for each share of OnKure preferred stock, at the closing of the merger there were approximately 13.3 million shares of common stock outstanding, with prior Reneo stockholders owning approximately 31.8% and prior OnKure, Inc. stockholders holding approximately 68.2% of the combined company's outstanding common stock before the concurrent financing. Following the consummation of the private placement of $65.0 million of newly issued common stock, prior OnKure, Inc. stockholders own approximately 53.6%, prior Reneo stockholders own approximately 25.1%, and the private placement investors own approximately 21.3% of the combined company’s outstanding stock. Leerink Partners served as exclusive financial advisor for Reneo. Jones Day and Cooley LLP served as legal counsel for Reneo for the transactions. Leerink Partners, Evercore ISI and LifeSci Capital served as the placement agents for the private placement financing. Covington & Burling LLP served as legal counsel to the placement agents in connection with the private placement financing. Oppenheimer & Co. served as capital markets advisor to OnKure, Inc., and Wilson Sonsini Goodrich & Rosati, P.C. served as legal counsel to OnKure, Inc. Leadership Team and Board of Directors Updates The combined company will be led by Nicholas A. Saccomano, Ph.D. as President and Chief Executive Officer of OnKure. In addition to Dr. Saccomano, the OnKure leadership team includes Samuel Agresta, M.D., as Chief Medical Officer, Dylan Hartley, Ph.D., as Chief Scientific Officer, and Jason Leverone, as Chief Financial Officer. The Board of Directors of OnKure will be composed of Dr. Saccomano, Isaac Manke, Ph.D., R. Michael Carruthers, Andrew Philips, Ph.D., who join from OnKure, Inc.’s Board of Directors, Michael Grey and Edward T. Mathers, who continue from Reneo’s Board of Directors, and Valerie M. Jansen, who joined the Board at the closing of the merger. About PI3Kα and OKI-219 PI3Kα is the most frequently mutated oncogene in cancers, and PI3KαH1047R is the most common mutation in this gene, being found in 15% of breast cancer and 4% of cancers overall. While novel drugs targeting PI3Kα have been approved for treatment, the lack of mutant selectivity of these therapeutics drives considerable on-target toxicity by inhibiting the normal version of this protein in various tissues. OnKure is discovering and developing a portfolio of highly mutant-selective PI3Kα inhibitors with the goal of improving efficacy and safety with molecules that fully inhibit the mutant oncogene while sparing the wild-type enzyme in normal tissues. OnKure’s lead product candidate, OKI-219, is an orally bioavailable, highly selective inhibitor of PI3KαH1047R with approximately 80-fold selectivity for the mutated form of the enzyme compared to wild-type. OnKure believes that the wild-type-sparing properties of OKI-219 should significantly improve the activity and safety relative to currently approved PI3Kα inhibitors. Currently, OKI-219 is being evaluated in a Phase 1 clinical trial in solid tumor patients with PI3KαH1047R mutations, including breast cancer. About OnKure OnKure is a clinical-stage biopharmaceutical company focused on the discovery and development of best-in-class precision medicines that target biologically validated drivers of cancers that are underserved by available therapies. Using a structure-based drug design platform, OnKure is building a robust pipeline of tumor-agnostic candidates that are designed to achieve optimal efficacy and tolerability. OnKure is currently developing OKI-219, a selective PI3KαH1047R inhibitor, as its lead program. OnKure aims to become a leader in targeting oncogenic PI3Kα and has multiple programs designed to enable best-in-class targeting of this key oncogene. For more information about OnKure, visit us at www.onkure.com and follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this press release, including statements regarding our future financial condition, results of operations, business strategy and plans, and objectives of management for future operations, as well as statements regarding industry trends, are forward-looking statements. Such forward-looking statements include, among other things, statements regarding the potential of, and expectations regarding, OnKure’s product candidates and programs, including OKI-219; OnKure’s ability to advance additional programs; the expected milestones and timing of such milestones, including for OKI-219 and its discovery programs; and statements regarding OnKure’s financial position, including its liquidity, cash runway and the sufficiency of its cash resources. In some cases, you can identify forward-looking statements by terminology such as “estimate,” “intend,” “may,” “plan,” “potentially” “will” or the negative of these terms or other similar expressions. The company based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things, those risks described in the section entitled “Risk Factors” in documents that OnKure files from time to time with the Securities and Exchange Commission (“SEC”), including Reneo’s Quarterly Report on Form 10-Q filed with the SEC on August 13, 2024 and the final 424B3 proxy statement/prospectus filed with the SEC on August 26, 2024. These risks are not exhaustive. New risk factors emerge from time to time, and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this press release. Contact: Dan FerryLifeSci Advisorsdaniel@lifesciadvisors.com

Relay Therapeutics is laying off 10% of its staff, or about 30 employees, in an additional round of job cuts after a smaller downsizing in July. A spokesperson for the biotech confirmed the layoffs in a statement to Endpoints News Thursday, saying the decision centered on “rationalizing the tools and on streamlining the teams to enable them to be more efficient.” There have been no new program discontinuations that precipitated the move, a spokesperson said. The new layoffs come less than a month after Relay brought in $200 million in new capital through a public offering. The raise was tied to encouraging data from its pan-mutant PI3Kα inhibitor, RLY-2608, showing that the treatment had a “clinically meaningful” improvement in progression-free survival for patients with breast cancer when combined with fulvestrant. Following the Sept. 9 readout, Relay’s shares $RLAY jumped more than 50%. But those gains have since vanished. It hinted at the coming cuts with that announcement, saying there was “ongoing streamlining of the research organization.” Earlier this summer, Genentech announced that it was handing back an SHP2 program to Relay after investing $120 million in the asset, which Relay said it would not continue to develop. Relay laid off about 5% of the team shortly after, though they were not a result of the axed collaboration, according to a Relay spokesperson. The reductions come as the company is widening its pipeline outside of cancer, a move that will largely take shape next year. One such decision is aiming RLY-2608 at vascular malformations, defined by abnormal blood vessel development, with a clinical trial set to start in the first quarter of 2025. Relay also launched a preclinical program for Fabry disease and plans to launch a human trial in the second half of 2025.

– Combined company to trade on Nasdaq under ticker “OKUR” – Reneo announces 1-for-10 reverse split of common stock IRVINE, Calif., Oct. 02, 2024 (GLOBE NEWSWIRE) -- Reneo Pharmaceuticals, Inc. (Nasdaq: RPHM) (“Reneo”) today announced the results of the special meeting of its stockholders held on September 26, 2024. At the special meeting, Reneo’s stockholders voted in favor of all proposals, including the proposals required to complete the proposed merger of Reneo and OnKure, Inc. (“OnKure”). The closing of the merger is anticipated to take place on or around Friday, October 4, 2024. Following the closing of the merger, the combined company plans to change its name from “Reneo Pharmaceuticals, Inc.” to “OnKure Therapeutics, Inc.” and trade on The Nasdaq Global Market under the ticker symbol “OKUR.” The combined company will be led by OnKure’s existing management team. The combined company will focus on advancing OnKure’s pipeline candidates targeting oncogenic mutations in phosphoinositide 3-kinase alpha (PI3Kα), including its lead program OKI-219, which is currently in a Phase 1 clinical trial for the treatment of solid tumors. In addition, Reneo also announced that it will effect a 1-for-10 reverse split of its common stock that is expected to be effective immediately prior to the closing of the merger. The combined company’s common stock is expected to be reclassified as Class A common stock immediately prior to the closing of the merger. It is expected that the combined company's common stock will commence trading on a split-adjusted basis, and after giving effect to the merger, under the ticker symbol “OKUR” at the open of trading on October 7, 2024, under a new CUSIP number (68277Q 105). On September 26, 2024, Reneo stockholders approved the reverse stock split and gave Reneo’s board of directors discretionary authority to select a ratio for the reverse stock split ranging from 1-for-7 to 1-for-15. Reneo’s board of directors approved the reverse stock split at a ratio of 1-for-10 on September 27, 2024. Upon effectiveness of the reverse stock split, every 10 shares of Reneo’s common stock issued and outstanding or held as treasury shares as of such date will be automatically combined into one share of Reneo common stock. The reverse stock split will have no effect on the number of shares of Reneo common stock authorized for issuance or on the par value of Reneo’s common stock. Outstanding Reneo equity-based awards under Reneo’s equity plans will be proportionately adjusted. No fractional shares will be issued in connection with the reverse stock split and following the effective time of the reverse stock split, and upon the surrender of any Reneo stockholders’ certificate(s) (if any), Reneo will pay cash to any such holder(s) of fractional shares of Reneo’s common stock an amount equal to such fractional shares multiplied by the fair value of Reneo’s common stock on the date of the reverse split, as determined by Reneo’s board of directors. Reneo’s transfer agent, Equiniti Trust Company, LLC, will maintain the book-entry records for Reneo’s common stock. Registered stockholders holding pre-split shares of Reneo’s common stock electronically in book-entry form are not required to take any action to receive post-split shares or payment for fractional shares. Stockholders owning shares via a broker, bank, custodian or other nominee will have their positions automatically adjusted to reflect the reverse stock split, subject to such broker’s particular processes, and will not be required to take any action in connection with the reverse stock split. Such beneficial holders are encouraged to contact their broker, bank or custodian with any procedural questions. About OnKure OnKure, Inc. is a clinical-stage biopharmaceutical company focused on the discovery and development of best-in-class precision medicines that target biologically validated drivers of cancers that are underserved by available therapies. Using structure-based drug design portfolio, OnKure is building a pipeline of tumor-agnostic candidates that are designed to achieve optimal efficacy and tolerability. OnKure is currently developing OKI-219, a selective PI3KαH1047R inhibitor, as its lead program. OnKure aims to become a leader in targeting oncogenic PI3Kα and has multiple programs designed to enable best-in-class targeting of this key oncogene. About Reneo Pharmaceuticals Reneo is a pharmaceutical company historically focused on the development and commercialization of therapies for patients with rare genetic mitochondrial diseases, which are often associated with the inability of mitochondria to produce adenosine triphosphate. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including but not limited to, express or implied statements regarding the timing, completion and impacts of the proposed merger between Reneo and OnKure, the expected management of the combined company, the development of the combined company’s current and future product candidates, the future operations of the combined company, the timing and completion of the reverse stock split and other statements that are not historical fact. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements generally are accompanied by words such as “anticipate,” “believe,” “continue,” “estimate,” “expect,” “future,” “goal,” “intend,” “may,” “outlook,” “plan,” “potential,” “predict,” “project,” “seem,” “seek,” “should,” “target,” “will,” “would,” and similar expressions that indicate future events or trends or that are not statements of historical matters. There can be no assurance that future developments affecting Reneo, OnKure or the proposed merger will be those that have been anticipated. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of Reneo’s management and are not assurances as to actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on by any investor as, a guarantee, an assurance, a prediction or a definitive statement of fact or probability. Actual events and circumstances, many of which are outside of the control of Reneo, are difficult or impossible to predict and will differ from assumptions underlying forward-looking statements. These forward-looking statements are subject to a number of risks and uncertainties, including, among other things: the risk that the conditions to the closing of the proposed merger are not satisfied; uncertainties as to the timing of the closing of the proposed merger and the ability of each of Reneo and OnKure to consummate the proposed merger; risks related to the ability of Reneo and OnKure to correctly estimate and manage their respective operating expenses and expenses associated with the proposed merger pending the closing of the proposed merger; risks associated with the possible failure to realize certain anticipated benefits of the proposed merger, including with respect to future financial and operating results; the potential for the occurrence of any event, change or other circumstance or condition that could give rise to the termination of the proposed merger and any agreements entered into in connection therewith; the possible effect of the announcement, pendency or completion of the proposed merger on Reneo’s or OnKure’s business relationships, operating results and business generally; risks related to the market price of Reneo’s common stock relative to the value suggested by the exchange ratio; unexpected costs, charges or expenses resulting from the proposed merger; the potential for, and uncertainty associated with the outcome of, legal proceedings instituted against Reneo or OnKure or any of their respective directors or officers related to the proposed merger; risks related to OnKure’s early stage of development; the uncertainties associated with OnKure’s product candidates, as well as risks associated with the clinical development and regulatory approval of product candidates, including potential delays in the completion of clinical trials; the significant net losses each of Reneo and OnKure has incurred since inception; the combined company’s ability to initiate and complete ongoing and planned preclinical studies and clinical trials and advance its product candidates through clinical development; the timing of the availability of data from the combined company’s clinical trials; the outcome of preclinical testing and clinical trials of the combined company’s product candidates, including the ability of those trials to satisfy relevant governmental or regulatory requirements; the combined company’s plans to research, develop and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of the combined company’s product candidates; the requirement for additional capital to continue to advance these product candidates, which may not be available on favorable terms or at all; the combined company’s ability to attract, hire, and retain skilled executive officers and employees; the combined company’s ability to protect its intellectual property and proprietary technologies; the combined company’s reliance on third parties, contract manufacturers, and contract research organizations; the possibility that Reneo, OnKure or the combined company may be adversely affected by other economic, business, or competitive factors; risks associated with changes in applicable laws or regulations; those risks and uncertainties more fully described in periodic filings with the U.S. Securities and Exchange Commission (“SEC”), including the factors described in the section titled “Risk Factors” in Reneo’s Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent Quarterly Reports on Form 10-Q, as well as the final proxy statement/prospectus on Form 424(b)(3) filed with the SEC on August 26, 2024; and other risks. This press release also concerns product candidates that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration. Such product candidates are currently limited by federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated. No Offer or Solicitation This press release is for informational purposes only and is neither an offer to sell, nor a solicitation of an offer to buy or subscribe for, any securities of Reneo or OnKure, nor is it a solicitation of any vote in any jurisdiction with respect to the proposed merger or otherwise. Contacts: Investor RelationsReneo Pharmaceuticals, Inc.investors@reneopharma.com Investor RelationsOnKure, Inc.Dan FerryLifeSci Advisorsdaniel@lifesciadvisors.com