On May 13, 2024 Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), reported its financial results for the first quarter of 2024, its recent business highlights, and a preview of select anticipated milestones (Press release, Sutro Biopharma, MAY 13, 2024, View Source [SID1234643156]).

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"The Sutro team executed on multiple fronts in the first quarter of 2024, advancing luvelta through the clinic in multiple indications of high unmet need, continuing to progress our pipeline and collaboration programs, and establishing a new licensing relationship with Ipsen. The upfront funding from the Ipsen deal and our recent financing also augmented our strong cash position," said Bill Newell, Sutro’s Chief Executive Officer. "We plan to deliver on important catalysts throughout 2024, reporting on expanded patient data with luvelta in combination with bevacizumab, the initiation of a registrational trial for pediatric patients with a rare form of acute myeloid leukemia (AML), and a Phase 2 trial in non-small cell lung cancer (NSCLC). We continue to build upon our momentum and are well positioned on our goal to rapidly deliver precisely designed ADCs to patients in need."

Recent Business Highlights and Select Anticipated Milestones

Luveltamab Tazevibulin (luvelta), FolRα-Targeting ADC Franchise:

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Part 1 (dose-optimization) of the registration-directed trial, REFRαME-O1, for treatment of platinum-resistant ovarian cancer (PROC), has completed enrollment. Part 2 (randomized portion) is now enrolling, with an anticipated ~140 sites in ~20 countries planned to be opened by the end of 2024.
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Enrollment of REFRαME-P1, a registration-enabling trial for pediatric patients with CBFA2T3::GLIS2 (CBF/GLIS; RAM phenotype) AML, is expected to be initiated in the second half of 2024.
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An Investigational New Drug (IND) application for the treatment of NSCLC has been cleared by U.S. Food and Drug Administration (FDA). The Phase 2 trial is expected to begin enrolling patients in the second half of 2024. Initial data is expected in the first half of 2025.
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A Phase 2 expansion study in combination with bevacizumab is well underway. Enrollment is expected to be complete in the first half of 2024.

Additional Pipeline Development and Collaboration Updates:

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In April 2024, Sutro announced a global licensing agreement for STRO-003, a ROR1-targeting ADC, with Ipsen. Sutro is eligible to receive up to $899 million in upfront and potential milestone payments, including up to $92 million in near-term payments, of which $75 million, including an equity investment, have been received in April. Sutro is also eligible to receive tiered royalties ranging from low double-digit to mid-teen digit percentages on annual global sales of STRO-003.
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Sutro plans to submit an IND for STRO-004, a tissue factor-targeting ADC, in 2025.
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Sutro continues to seek to maximize the value of its proprietary cell-free platform by working with partners on programs in multiple disease spaces and geographies and has generated from collaborators an aggregate of approximately $864 million in payments through March 31, 2024, including equity investments.
Corporate Updates:

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Additionally, Sutro strengthened its cash position with an underwritten offering of 14,478,764 shares of its common stock at a price of $5.18 per share, resulting in gross proceeds of $75.0 million. The offering was led by a high-quality group of new and existing healthcare-focused institutional investors.
Upcoming Events: Sutro will participate in two upcoming investor conferences. Webcasts of the presentations will be accessible through the News & Events page of the Investor Relations section of the Company’s website at www.sutrobio.com. Archived replays will be available for at least 30 days after the events.

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The Citizens JMP Life Sciences Conference in New York, May 13-14, 2024
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Jefferies Healthcare Conference in New York, June 5-6, 2024
First Quarter 2024 Financial Highlights

Cash, Cash Equivalents and Marketable Securities

As of March 31, 2024, Sutro had cash, cash equivalents and marketable securities of $267.6 million, and approximately 0.7 million shares of Vaxcyte common stock with a fair value of $45.6 million.

Unrealized Gain from Increase in Value of Vaxcyte Common Stock

The non-operating, unrealized gain of $3.7 million for the quarter ended March 31, 2024 was due to the increase since December 31, 2023 in the estimated fair value of Sutro’s holdings of Vaxcyte common stock. Vaxcyte common stock held by Sutro will be remeasured at fair value based on the closing price of Vaxcyte’s common stock on the last trading day of each reporting period, with any non-operating, unrealized gains and losses recorded in Sutro’s statements of operations.

Revenue

Revenue was $13.0 million for the quarter ended March 31, 2024, as compared to $12.7 million for the same period in 2023, with the 2024 amount related principally to the Astellas collaboration, and the Tasly and Vaxcyte agreements. Future collaboration and license revenue under existing agreements, and from any additional collaboration and license partners, will fluctuate as a result of the amount and timing of revenue recognition of upfront, milestones, and other agreement payments.

Operating Expenses

Total operating expenses for the quarter ended March 31, 2024 were $69.6 million, as compared to $54.9 million for the same period in 2023. The 2024 quarter includes non-cash expenses for stock-based compensation of $6.1 million and depreciation and amortization of $1.8 million, as compared to $6.0 million and $1.6 million, respectively, in the comparable 2023 period. Total operating expenses for the quarter ended March 31, 2024 were comprised of research and development expenses of $56.9 million and general and administrative expenses of $12.7 million.

On May 13, 2024 Cartesian Therapeutics, Inc. (NASDAQ:RNAC) (the "Company), a clinical-stage biotechnology company pioneering mRNA cell therapy for autoimmune diseases, reported that management will participate in a fireside chat at the H.C. Wainwright 2nd Annual BioConnect Investor Conference on Monday, May 20, 2024, at 3:00 p.m. ET (Press release, Cartesian Therapeutics, MAY 13, 2024, View Source [SID1234643155]).

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A live webcast of the fireside chat is expected to be accessible in the Events section of the Company’s website at www.cartesiantherapeutics.com, where an archived replay of the event will be accessible for a limited time.

On May 13, 2024 Quince Therapeutics, Inc. (Nasdaq: QNCX), a late-stage biotechnology company developing an innovative drug delivery technology designed to leverage a patient’s own biology to deliver rare disease therapeutics, reported an update on the company’s development pipeline and announced financial results for the first quarter ended March 31, 2024 (Press release, Quince Therapeutics, MAY 13, 2024, View Source [SID1234643154]).

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Dirk Thye, M.D., Quince’s Chief Executive Officer and Chief Medical Officer, said, "Our primary corporate objective is the advancement of our lead asset, EryDex, for the treatment of patients with ataxia-telangiectasia. We remain on track to begin enrollment of our pivotal Phase 3 study in the second quarter of 2024 and will diligently pursue enrollment at U.S. and European study sites to provide an opportunity for patients living with this rare, devastating disease to participate in research to identify a beneficial therapeutic solution.

"We are pleased to report the selection of Duchenne muscular dystrophy (DMD) as Quince’s second development program for EryDex. We consider DMD a promising indication for EryDex as corticosteroids are the standard of care for this rare disease, but its utility is limited by significant chronic toxicity due to adrenal suppression. We believe EryDex has the potential to provide the therapeutic benefit of corticosteroids without this chronic toxicity. Physicians caring for patients with DMD, along with DMD advocacy groups, also have encouraged the development of EryDex for DMD as a potentially safer alternative to conventional corticosteroids for their patients," concluded Dr. Thye.

Pivotal Phase 3 NEAT Clinical Trial

Secured regulatory approvals in the U.S. and European Union related to the company’s pivotal Phase 3 NEAT (Neurologic Effects of EryDex on Subjects with A-T; IEDAT-04-2022/NCT06193200) clinical trial.
Commenced NEAT study site initiation and activation activities throughout the U.S., U.K., and European Union as NEAT enrollment remains on track to begin in the second quarter of 2024.
NEAT is an international, multi-center, randomized, double-blind, placebo-controlled study to evaluate the neurological effects of the company’s lead asset, EryDex (dexamethasone sodium phosphate [DSP] encapsulated in autologous red blood cells), in patients with A-T.

Plan to enroll approximately 86 patients with A-T ages six to nine years old (primary analysis population) and approximately 20 patients with A-T ages 10 years or older.

Pivotal Phase 3 NEAT clinical trial is being conducted under a Special Protocol Assessment (SPA) agreement with the U.S. Food & Drug Administration (FDA).

Participants will be randomized (1:1) between EryDex or placebo and treatment will consist of six infusions scheduled once every 21 to 30 days. The primary efficacy endpoint will be measured by the change from baseline to last visit completion in rescored modified International Cooperative Ataxia Rating Scale (RmICARS) compared to placebo.
Participants who complete the full treatment period, complete study assessments, and provide informed consent will be eligible to transition to an open label extension study.
Expect to report Phase 3 NEAT topline results in the second half of 2025 with a potential NDA submission in 2026, assuming positive study results.
Pipeline and Corporate Updates

Completed initial patient sizing project with third-party analysis from IQVIA Medical Claims (Dx), IQVIA Analytics confirming approximately 3,400 diagnosed patients with A-T in the U.S., which aligns with an estimated U.S. prevalence of approximately 5,000 patients with A-T in the U.S. There are currently no approved therapeutic treatments for A-T, and the market represents a $1+ billion peak commercial opportunity globally, based on the company’s internal estimates and assumptions.
Advanced evaluation of other potential indications for EryDex with the selection of Duchenne muscular dystrophy (DMD) as the company’s second development program. DMD is an ideal indication for EryDex as corticosteroids are the standard of care for this rare disease, but its utility is limited by significant chronic toxicity due to adrenal suppression. Corticosteroid treatment in patients with DMD is commonly interrupted during adolescence due to interference with sexual maturation and delayed puberty.
Targeting EryDex for the potential treatment of patients with DMD would leverage the company’s AIDE technology designed to encapsulate the corticosteroid DSP in a patient’s own red blood cells, which have several characteristics that make them an ideal vehicle for drug delivery. EryDex is designed to alter the biodistribution, pharmacokinetics, and pharmacodynamics of the DSP, allowing for potentially safe and effective treatment for patients with DMD.
Focused on generating proof-of-concept clinical trial study designs to evaluate EryDex for the potential treatment of patients with DMD, including corticosteroid intolerant populations, in addition to evaluating optimal capital efficient study approaches such as investigator initiated trials and Phase 2/3 options.
Investigating other potential indications for EryDex where chronic corticosteroid treatment is – or has the potential to become – a standard of care, if there were not corticosteroid-related safety concerns. This evaluation process is expected to span across ataxias, neuromuscular indications, hematology, cancer, and autoimmune diseases, with a focus on rare diseases.
Plan to evaluate additional potential applications of Quince’s proprietary AIDE technology platform using drugs and biologics targeted at rare and debilitating diseases to further expand the company’s drug development pipeline.
Evaluate potential strategic partnerships to out-license ex-U.S. rights to extend operational runway to support potential NDA approval of EryDex in the U.S., as well as further advance other potential indications and programs using the AIDE platform.
Participation at The Citizens JMP Life Sciences Conference on Monday, May 13, 2024 beginning at 1:30 p.m. Eastern Time. A live webcast and archive of the presentation will be accessible here.
First Quarter 2024 Financial Results

Reported cash, cash equivalents, and short-term investments of $67.8 million for the first quarter ended March 31, 2024. Quince expects its existing cash runway to be sufficient to fund the company’s capital efficient development plan into 2026.

Expect to fully fund lead asset, EryDex, through Phase 3 NEAT topline results and prepare for a potential NDA submission in 2026, assuming positive study results. This includes approximately $20 million for the NEAT clinical trial and approximately $15 million in direct trial costs for the open label extension study.
Reported research and development (R&D) expenses of $3.7 million for the quarter ended March 31, 2024. R&D expenses for the quarter primarily reflected costs related to the advancement of lead asset EryDex, the startup of related Phase 3 NEAT clinical trial activities, and stock-based compensation expense.
Reported general and administrative (G&A) expenses of $5.0 million for the quarter ended March 31, 2024. G&A expenses for the quarter primarily included personnel-related expenses, insurance, professional and legal fees, and stock-based compensation.

Reported a net loss of $11.1 million, or a loss of $0.26 per basic and diluted share, for the quarter ended March 31, 2024. Weighted average shares outstanding for the quarter were 43.0 million.
Reported net cash used in operating activities of $8.4 million for the quarter ended March 31, 2024, which included adjustments for $3.6 million of non-cash items: a $2.5 million change in the fair value of contingent consideration liabilities due to passage of time, $1.3 million in stock-based compensation, and $0.4 million change in the fair value of long-term debt due to passage of time, offset by a $0.6 million amortization of discount on the company’s investments.

On May 13, 2024 Precision BioSciences, Inc. (Nasdaq: DTIL), an advanced gene editing company utilizing its novel proprietary ARCUS platform to develop in vivo gene editing therapies for sophisticated gene edits, including gene elimination, insertion, and excision, reported financial results for the first quarter ended March 31, 2024, and provided a business update (Press release, Precision Biosciences, MAY 13, 2024, View Source [SID1234643153]).

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"In 2024, Precision is focused on strong execution as we advance our wholly owned Hepatitis B virus (HBV) and primary mitochondrial myopathy (PMM) in vivo gene editing programs towards the clinic as soon as possible," said Michael Amoroso, Chief Executive Officer at Precision BioSciences. "In parallel, our partner, iECURE has already advanced the first ARCUS in vivo gene editing program for OTC deficiency into the clinic. We believe this not only validates ARCUS novel editing approach for gene insertion, but also sets key regulatory precedence for in vivo ARCUS gene editing programs across global markets including the US."

"We were pleased to regain control of three exciting development opportunities from our work with Prevail Therapeutics, which take advantage of ARCUS’ unique cut, size, and simplicity. Strong in vivo proof-of-concept data generated to date have yielded three advanced preclinical programs that we believe have first-in-class and best-in-class potential across multiple therapeutic areas. We are currently assessing which programs Precision will advance internally and seek to re-partner and expect to provide an update once plans have been finalized," added Mr. Amoroso.

"In addition to the important operational progress we continue to make with our wholly owned and partnered programs, we added cash to our balance sheet by monetizing our CAR T assets and completing a $40 million equity offering to extend our cash runway into the second half of 2026 to fund continued development of our programs."

Wholly Owned Portfolio – Lead Programs

PBGENE-HBV (Viral Elimination Program): Precision is developing PBGENE-HBV for the treatment of patients with chronic hepatitis B. Currently, it is estimated that approximately 300 million people worldwide are afflicted with chronic Hepatitis B. PBGENE-HBV is expected to be the first and only potentially curative gene editing program to enter the clinic that is specifically designed to eliminate cccDNA and inactivate integrated HBV DNA.

In February 2024, Precision announced that the company had received pre-IND regulatory feedback from the US Food and Drug Administration (FDA) in addition to regulatory feedback from agencies outside the US providing clarity and alignment on PBGENE-HBV investigational new drug (IND)/clinical trial application (CTA)-enabling preclinical plans and clinical strategy. PBGENE-HBV is advancing through final toxicology studies and Precision expects to submit an IND and/or CTA for this program in 2024.

PBGENE-PMM (Mutant Mitochondrial DNA Elimination Program): PBGENE-PMM is a first of its kind potential treatment for m.3243-associated PMM by targeting mutant mitochondrial DNA. Mitochondrial diseases are the most common hereditary metabolic disorder in the world. The m.3243 associated PMM that our program intends to address is sizable, affecting up to 25,000 people in the US alone. Precision scientists published new preclinical data in Nature Metabolism highlighting the high specificity of ARCUS nucleases designed to edit and eliminate mutant mitochondrial DNA while allowing wild-type (normal) mitochondrial DNA to repopulate in the mitochondria, thus improving cellular function. This is a differentiated program because unlike CRISPR/Cas, base editors, and prime editors, ARCUS nucleases are able to penetrate the mitochondrial membranes because they are single-component editors that do not require a guide RNA. The Company expects to submit an IND and/or CTA for PBGENE-PMM in 2025 for this program.

Wholly Owned Portfolio – Under Assessment

As previously announced, Precision’s collaboration with Prevail Therapeutics Inc., has concluded, and Precision exercised its option to regain rights for the three programs developed under the collaboration. The Company is in the process of conducting a portfolio assessment for the newly returned programs for internal development and/or development through new partners and expects to provide an update as decisions are finalized. These programs include:

PBGENE-DMD – novel gene excision approach for treatment of Duchenne Muscular Dystrophy utilizing a pair of ARCUS nucleases, delivered by a single adeno-associated virus (AAV), that are designed to excise an approximately 500,000 base pair mutation "hot spot" region from the dystrophin gene to generate a functionally competent variant of the dystrophin protein.
PBGENE-LIVER – liver target for gene insertion with data demonstrating that ARCUS is capable of 40% to 45% high efficiency gene insertion at 1- and 3-months in nondividing cells, the most challenging context for gene insertion, in adult nonhuman primates.
PBGENE-CNS – gene editing program targeting neurons to address a disease of the central nervous system.
Partnered Programs – In Vivo Gene Editing

iECURE-OTC (Gene Insertion Program): Led by iECURE, ECUR-506 is the first ARCUS-mediated in vivo gene editing program to advance into the clinic following regulatory approvals in the US, the United Kingdom, and Australia for initiation of the OTC-HOPE study. The OTC-HOPE study is a first-in-human Phase 1/2 trial evaluating ECUR-506 as a potential treatment for neonatal onset ornithine transcarbamylase (OTC) deficiency and has begun screening patients. iECURE has recently communicated that one site in the United Kingdom is open and recruiting patients for the OTC-HOPE study. Non-human primate (NHP) data presented by researchers from the University of Pennsylvania’s Gene Therapy Program demonstrated sustained gene insertion of a therapeutic OTC transgene one-year post-dosing in newborn and infant NHP’s with high efficiency. iECURE has received Fast Track designation from the FDA for ECUR-506 and expects initial data from this trial to be available in late 2024 or in 2025.

PBGENE-NVS (Gene Insertion Program): Precision continues to advance its gene editing program with Novartis to develop a custom ARCUS nuclease for patients with hemoglobinopathies, such as sickle cell disease and beta thalassemia. The collaborative intent is to insert, in vivo, a therapeutic transgene as a potential one-time transformative treatment administered directly to the patient to overcome disparities in patient access to treatment with other therapeutic technologies, including those that are targeting an ex vivo gene editing approach.

Business Updates – Monetization of CAR T Investments:

Completed Licensing Deal with TG Therapeutics for Cell Therapy Azer-Cel in Autoimmune Diseases, and Other Indications Outside of Cancer:

In January 2024, Precision announced the completion of a transaction with TG Therapeutics (Nasdaq: TGTX) for certain exclusive and non-exclusive license rights to develop Azercabtagene Zapreleucel (azer-cel) for autoimmune diseases and other indications outside of cancer. In exchange for these rights, Precision received upfront and potential near-term economics valued at $17.5 million. Precision is eligible to receive up to $288 million in additional milestone payments based on the achievement of certain clinical, regulatory, and commercial milestones, in addition to high-single-digit to low-double-digit royalties on net sales of the licensed product.

Completed Non-Exclusive Patent License Agreement with Caribou Biosciences:

In February 2024, Precision announced that it had granted Caribou Biosciences (Nasdaq: CRBU) a non-exclusive, worldwide license, with the right to sublicense, to one of Precision’s foundational cell therapy patent families for use with CRISPR-based therapies in the field of human therapeutics. The licensed patents and applications include method and composition of matter claims that relate to Precision’s approach for targeted insertion of a sequence encoding an exogenous antigen binding receptor, such as a CAR, into the T cell receptor alpha constant (TRAC) gene locus of human T cells via a single gene edit. The licensed family, which includes more than 20 granted US and international patents, expires in October 2036.

This patent family is potentially also available for non-exclusive license to other high-quality partners in the cell therapy space.

Business Updates – $40 Million Offering:

On March 1, 2024, Precision completed a $40 million public underwritten offering consisting of 2,500,000 shares of its common stock and accompanying warrants to purchase up to 2,500,000 shares of common stock at a combined offering price of $16.00 price per share, for total gross proceeds of $40 million, before deducting underwriting discounts and commissions. The financing included participation from leading life sciences investors, including Perceptive Advisors, Janus Henderson Investors, Aquilo Capital Management, LLC and LYFE Capital.

Quarter Ended March 31, 2024 Financial Results:

Cash and Cash Equivalents: As of March 31, 2024, Precision had approximately $137.8 million in cash and cash equivalents. Existing cash and cash equivalents, upfront and potential near-term cash from CAR T transactions, along with expected operational receipts, continued fiscal and operating discipline, availability of Precision’s at-the-market (ATM) facility, and available credit are expected to extend Precision’s cash runway into the second half of 2026. The company’s cash runway is expected to enable funding the development of our PBGENE-HBV and PBGENE-PMM in vivo gene editing programs through Phase 1 read out while enabling commencement of a new third wholly owned gene editing program.

Revenues: Total revenues for the quarter ended March 31, 2024, were $17.6 million, as compared to $8.8 million for the same period in 2023. The increase of $8.8 million was primarily driven by upfront investments from cell therapy transactions with TG Therapeutics and Caribou Biosciences.

Research and Development Expenses: Research and development expenses were $13.3 million for the quarter ended March 31, 2024, as compared to $11.0 million for the same period in 2023. The increase of $2.3 million was primarily due to increasing investment in our wholly owned in vivo gene editing programs, PBGENE-HBV and PBGENE-PMM, as the programs advance toward IND/CTA filing. The increases in program spending were partially offset by lower employee-related costs and lab supplies.

General and Administrative Expenses: General and administrative expenses were $8.4 million for the quarter ended March 31, 2024, as compared to $11.1 million for the same period in 2023. The decrease of $2.7 million was primarily related to lower employee-related costs and a reduction of external operational expenses.

Net Income/Loss from Continuing Operations: Net income from continuing operations was $8.6 million for the quarter ended March 31, 2024, inclusive of a $10.4 million non-cash gain on the fair value of our warrant liability which does not impact our cash runway, as compared to a net loss from continuing operations of $14.0 million, for the same period in 2023. The improvement was primarily related to the revenue growth compared to the prior period as well as the non-cash gain related to the fair value adjustments of our warrant liability and Elo equity investment.

Net Loss: Net income was $8.6 million, or $1.70 per share (basic and diluted), for the quarter ended March 31, 2024, as compared to a net loss of $25.1 million, or $(6.75) per share (basic and diluted), for the same period in 2023. The net loss in the first quarter of 2023 includes a $11.1 million loss from discontinued operations related to the decision to exit CAR T in August 2023.

Shares: Basic weighted-average common shares outstanding for the first quarter of 2024 were 5,060,978 compared to 3,709,894 for the same period in 2023. Following the common stock offering, we had 6,916,239 shares outstanding as of March 31, 2024.

On May 13, 2024 Reneo Pharmaceuticals, Inc. (Nasdaq: RPHM) and OnKure, Inc., a privately-held, clinical-stage biopharmaceutical company focused on the development of novel precision medicines in oncology, reported that they have entered into a definitive merger agreement to combine the companies in an all-stock transaction (Press release, OnKure, MAY 13, 2024, View Source [SID1234643151]). 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. Upon completion of the transaction, the combined company is expected to operate under the name OnKure Therapeutics, Inc., and trade on the Nasdaq Global Market under the ticker symbol "OKUR".

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In connection with the transaction, Reneo Pharmaceuticals has entered into a subscription agreement for a $65 million private investment in public equity (PIPE) financing expected to close concurrently with the closing of the merger, with a group of institutional investors, including Acorn Bioventures, Cormorant Asset Management, Deep Track Capital, Perceptive Advisors, Samsara BioCapital, Surveyor Capital (a Citadel company), and Vestal Point Capital. The transactions are subject to stockholder approval by both companies, the effectiveness of a registration statement to be filed with the U.S. Securities and Exchange Commission, a condition that Reneo Pharmaceuticals have at least $55 million in net cash at the closing (excluding proceeds from the concurrent PIPE financing), the continued listing of the combined company on Nasdaq, and satisfaction of other customary closing conditions.

Including proceeds from the concurrent PIPE financing, the combined company is expected to have approximately $120 million of cash, cash equivalents, and short-term investments at closing. The merger and concurrent PIPE financing are expected to close in 2024.

In February 2024, OnKure initiated a first-in-human clinical trial to evaluate OKI-219, a mutant-selective PI3KαH1047R inhibitor. The PIKture-01 trial is a Phase 1 dose-escalation trial designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of OKI-219 as a monotherapy in patients with advanced solid tumors and in combination with endocrine therapy or HER-2 targeted therapy in patients with advanced breast cancer.

"Following a thorough evaluation of strategic alternatives, the Reneo board of directors and management team believe that this anticipated transaction represents a compelling opportunity to deliver shareholder value as the OnKure team advances their PI3Kα inhibitors," said Mike Grey, Executive Chairman and founder of Reneo Pharmaceuticals. "OnKure has an experienced team of drug developers, and we are excited about the potential for OKI-219 to become a meaningful treatment option for patients suffering from breast cancer."

"We are pleased to announce our proposed merger with Reneo Pharmaceuticals, allowing us to create a publicly traded company focused on advancing OnKure’s lead, mutant-specific programs targeting PI3Kα in breast cancer. This opportunity comes at an important time for OnKure as we recently initiated our PIKture-01 trial of OKI-219 and expect early clinical data in the fourth quarter of this year," said Nicholas Saccomano, President and Chief Executive Officer of OnKure.

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, the lack of mutant selectivity of these therapeutics drives considerable on-target toxicity by inhibiting the normal version of this protein in various tissues. To address this challenge, 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. OKI-219 is a potential best-in-class, 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 agents. OKI-219 is currently in Phase 1 of clinical development in solid tumor patients with PI3KαH1047R mutations, including breast cancer.

About the Proposed Merger

Pre-merger Reneo stockholders are expected to own approximately 31% of the combined company, and pre-merger OnKure stockholders are expected to own approximately 69% of the combined company, upon the closing of the merger, exclusive of the PIPE financing. The percentage of the combined company that each company’s former stockholders are expected to own may be adjusted based on Reneo’s net cash at closing.

The transaction has been unanimously approved by the board of directors of both companies and is expected to close in 2024, subject to customary closing conditions, including approval by the stockholders of each company.

Management and Organization

Following the merger, the combined company will be led by Nicholas Saccomano, Ph.D., President and Chief Executive Officer of OnKure, and other members of the OnKure management team. Reneo Pharmaceuticals will be renamed "OnKure Therapeutics, Inc." and the corporate headquarters will be located in Boulder, CO. The merger agreement provides that the board of directors of the combined company will be composed of eight members, including six board members chosen by OnKure and two members from the legacy Reneo board.

Advisors

Leerink Partners is acting as exclusive financial advisor to Reneo for the transaction. Jones Day and Cooley LLP are serving as legal counsel for Reneo. Leerink Partners, Evercore ISI and LifeSci Capital are serving as the placement agents for the PIPE financing. Covington & Burling LLP is serving as legal counsel to the placement agents in connection with the PIPE financing. Oppenheimer & Co. is serving as capital markets advisor to OnKure. Wilson Sonsini Goodrich & Rosati, P.C. is serving as legal counsel to OnKure.