OnKure Announces Closing of Merger with Reneo Pharmaceuticals and Concurrent Private Placement of $65 Million

On October 7, 2024 OnKure Therapeutics, Inc. (Nasdaq: OKUR) ("OnKure"), a clinical-stage biopharmaceutical company focused on the development of novel precision medicines in oncology, reported the completion of its previously announced merger of OnKure, Inc. and Reneo Pharmaceuticals, Inc. ("Reneo") (Press release, OnKure Therapeutics, OCT 4, 2024, View Source [SID1234647061]). 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".

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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.

Avistone Announces Updates on ANS014004

On October 4, 2024 Beijing Avistone Biotechnology Co., Ltd (also referred to as "Avistone Biotechnology" or "Avistone"), an innovative biotechnology company focused on precision oncology therapeutics, reported that the Phase I dose escalation study evaluating ANS014004 ("ANS01"), a novel small-molecule type II c-Met tyrosine kinase inhibitor (TKI) was recently cleared to proceed with enrollment of patients in Canada by Health Canada (Press release, Avistone Pharmaceuticals, OCT 4, 2024, View Source [SID1234647048]). The U.S. Food and Drug Administration (FDA) cleared ANS01’s Investigational New Drug (IND) Application last year and the trial is currently enrolling US patients in the dose escalation portion of the phase 1 study. Detailed information on the trial can be found at View Source

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There is also a concurrent, ongoing Phase I study operating in China and detailed information on this study can be found at: View Source

Both Phase I studies are enrolling patients diagnosed with locally advanced or metastatic solid tumors harboring a pathogenetic MET alteration (including MET mutation, MET amplification, MET overexpression, or MET fusion) and the primary objectives are (1) to evaluate the tolerability and safety of ANS014004 and (2) to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of ANS014004.

Mesenchymal epithelial transition (MET) proto-oncogene receptor tyrosine kinase (RTK) is a cell surface receptor selective for hepatocyte growth factor (HGF), and is involved in embryogenesis regulation, wound healing, organ regeneration, angiogenesis, and immunomodulation. Aberrant MET oncogenic alterations include MET exon 14 skipping (MET∆ex14) mutations; activating mutations in the kinase domain; MET gene amplification; MET fusions; and MET protein overexpression. These oncogenic alterations occur in a wide range of human solid cancers.

Presently, type I c-Met inhibitors are used as monotherapies in patients with locally advanced or metastatic NSCLC with MET∆ex14 mutations. However, development of post-treatment resistance to type I c-Met inhibitors occurs clinically, including through acquired mutations in codons D1228 and Y1230. No drugs have been approved globally for MET alteration indications other than MET∆ex14 mutations. Next generation MET inhibitors are thus needed to treat patients harboring various MET oncogenic alterations beyond MET∆ex14, including post-treatment acquired mutations.

AbCellera Announces Presentation on T-cell Engager Platform at the Society for Immunotherapy of Cancer (SITC) Annual Meeting 2024

On October 4, 2024 AbCellera (Nasdaq: ABCL) reported an upcoming poster presentation on its T-cell engager platform at the SITC (Free SITC Whitepaper) 39th Annual Meeting, to be held November 6 to 10 at the George R. Brown Convention Center in Houston, Texas (Press release, AbCellera, OCT 4, 2024, View Source [SID1234647047]).

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Details on AbCellera’s poster presentation at SITC (Free SITC Whitepaper) are as follows:

Title: Profiling bispecific T-cell engagers: Strategies for enhancing potency while minimizing cytokine release
Abstract Number: 1291
Date and Time: Friday, November 8 from 9:00 a.m. to 7:00 p.m. CST
Location: Exhibit Halls A B George R. Brown Convention Center or online at View Source

About AbCellera’s T-Cell Engager Platform

CD3 T-cell engagers have the potential to be a cornerstone of cancer treatment. They guide the immune system to find and eliminate cancer cells by binding tumor targets and the CD3 protein on cancer-killing T cells at the same time. However, the development of T-cell engagers has been limited due to challenges with efficacy and safety. To address these challenges, AbCellera developed a T-cell engager platform that includes novel CD3-binding antibodies to expand the therapeutic window for this modality, costimulatory building blocks to enhance efficacy for difficult-to-treat cancers, and discovery capabilities to broaden the range of T-cell engagers to complex peptide-MHC tumor targets. AbCellera is leveraging its platform to unlock the full potential of this modality and bring potential new cancer medicines to patients.

Clasp Therapeutics to Present Preclinical Data Evaluating Novel T Cell Engager Targeting p53 Mutant Solid Tumors

On October 4, 2024 Clasp Therapeutics, a biotechnology company bringing unparalleled precision to immuno-oncology using next-generation T cell engagers (TCEs), reported it will present comprehensive preclinical data demonstrating the selectivity and activity of CLSP-1025, a TCE targeting a common p53 mutation, at the 2024 Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), being held November 8 – 10, 2024 in Houston, Texas and virtually (Press release, Clasp Therapeutics, OCT 4, 2024, View Source [SID1234647046]).

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Presentation Details:

Title: CLSP-1025, a novel bispecific T cell engager targeting a p53 R175H mutant peptide presented by HLA-A*02:01
Presentation Type: Poster
Abstract Number: 1061
Date and Time: Friday, November 8, 2024, at 9 a.m. CT – 7 p.m. CT
Location: Exhibit Halls AB, George R. Brown Convention Center in Houston, TX
Presenters: Justina X Caushi, Alec R Andrews, James Bingham, Lenore Cullen, Anthony S Gizzi, Gillian A Kingsbury, Kaleigh Krapfl, Madison Curtis Siok, Catherine Souza, Kate Stokes and Michael F Maloney

A2 Bio to Present Safety and Biomarker Data from EVEREST-1 Trial during 2024 Annual Meeting of the Society for Immunotherapy of Cancer

On October 4, 2024 A2 Biotherapeutics, Inc. (A2 Bio), a clinical-stage cell therapy company developing first-in-class logic-gated cell therapies to selectively target tumor cells and protect normal cells, reported the acceptance of six abstracts for presentation during the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) taking place November 8-10, 2024, in Houston (Press release, A2 Biotherapeutics, OCT 4, 2024, View Source [SID1234647045]).

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The company will share an oral presentation that details continued progress to enhance the diversity of patients enrolled in its BASECAMP-1 prescreening trial. Additional posters will present safety and biomarker data in the EVEREST-1 trial; continued progress in the ongoing EVEREST-2 clinical trial; and adaptations to boost potency and preserve selectivity of TmodTM-based cell therapies.

The accepted abstracts are available online on the SITC (Free SITC Whitepaper) website.

Oral Presentation Details

Presentation Title:

"BASECAMP-1 is an efficient pre-screening study that identifies patients with HLA LOH and provides mutational, RNA-Seq, and microbiome data for precision logic-gated CAR T therapeutic trials"

Session Title:

Cellular Therapies – Financial Toxicities, Access to Care

Session Date/Time:

Saturday, Nov. 9, 5:15-6:35pm CDT

Session Room:

George R. Brown Convention Center – Level 3 – Grand Ballroom B

Final Abstract Number:

589

Presenting Author:

Julian Molina, M.D., Ph.D., Mayo Clinic

Poster Presentation Details

Abstract Title

Author

Abstract
Number

Poster
Presentation
Date

Poster
Presentation
Location

EVEREST-1: Initial safety data from a seamless phase 1/2 study of A2B530, a logic-gated Tmod CAR T-cell therapy, in patients with solid tumors associated with CEA expression also exhibiting HLA-LOH

Patrick Grierson

Washington University

588

Saturday,
November 9,
9am-8:30pm

Exhibit Halls A B
George R. Brown Convention Center

BASECAMP-1 is an efficient pre-screening study that identifies patients with HLA LOH and provides mutational, RNA-Seq, and microbiome data for precision logic-gated CAR T therapeutic trials

Julian Molina

Mayo Clinic

589

Friday,
November 8,
9am-7pm

EVEREST-2: A seamless phase 1/2 study of A2B694, a logic-gated Tmod CAR T-cell therapy, in patients with solid tumors with human leukocyte antigen-A*02 loss of heterozygosity

Julian Molina

Mayo Clinic

627

Onboard, tethered cytokines boost potency and maintain selectivity of a Tmod NOT gate

Jingli Zhang

A2 Biotherapeutics

341

Functional screen to optimize logic gate potency and selectivity

Sara Martire

A2 Biotherapeutics

292

Saturday,
November 9,
9am-8:30pm

Signal 1 boosters for Tmod: addressing the next obstacle in cell therapy for solid tumors

Julie Oh

A2 Biotherapeutics

302

About EVEREST-1

EVEREST-1 (NCT05736731) is a seamless Phase 1/2 study for A2B530, an autologous logic-gated investigational cell therapy developed from the A2 Bio proprietary Tmod platform. The Tmod platform provides selective killing of tumor cells and protection of normal cells via a dual-receptor design consisting of an activator that targets tumor cells and a blocker that protects normal cells. A2B530 consists of an activator that targets carcinoembryonic antigen (CEA) and a blocker that targets HLA-A*02. HLA-A*02 is lost in tumor cells and present in normal cells in the eligible patient population. The study is recruiting participants with non-small cell lung, colorectal and pancreatic cancers.

About EVEREST-2

EVEREST-2 (NCT06051695) is a seamless Phase 1/2 study for A2B694, an autologous logic-gated investigational cell therapy developed from the A2 Bio proprietary Tmod platform. The Tmod platform provides selective killing of tumor cells and protection of normal cells via a dual-receptor design consisting of an activator that targets tumor cells and a blocker that protects normal cells. A2B694 consists of an activator that targets mesothelin (MSLN) and a blocker that targets HLA-A*02. HLA-A*02 is lost in tumor cells and present in normal cells in the eligible patient population. The study is recruiting participants with non-small cell lung, colorectal, pancreatic, ovarian and mesothelioma cancers.

About BASECAMP-1

BASECAMP-1 (NCT04981119) is a prescreening study to identify patients for potential treatment in A2 Bio clinical trials. It is a novel approach to help optimize patient treatment outcomes by enabling patients’ immune cells to be banked in their healthiest state earlier in their course of cancer treatment. Next-generation sequencing is used to identify patients who have lost HLA-A*02, the biomarker of interest for the A2 Bio studies. Patients then undergo leukapheresis to collect, process, and store patient T cells for future Tmod CAR T cell therapy. BASECAMP-1 is currently enrolling participants with non-small cell lung, colorectal, pancreatic, ovarian and mesothelioma cancers.

About the Tmod Platform

A2 Bio has pioneered a precision-targeting cellular system – the Tmod platform – that incorporates two receptors, an activator and a blocker, to aim the powerful armaments of immune cells directly at tumors to unequivocally differentiate tumors from normal tissues. The activator recognizes antigens on tumor cells that trigger their destruction, while the blocker recognizes antigens on normal cells that protect them. This novel blocker technology enables precise, personalized and effective T cell targeting. The blocker component equips Tmod cells with the capacity to identify tumors as distinct from normal cells.