On October 4, 2024 Immatics N.V. (NASDAQ: IMTX, "Immatics" or the "Company"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, reported upcoming oral and poster presentations at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in Houston, Texas from November 6 – 10, 2024 (Press release, Immatics, OCT 4, 2024, View Source [SID1234647028]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Full abstracts will be available on November 5, 2024, at 9:00 am EST in the JITC Supplement.

Oral Presentations

Date / Time: November 8, 2024 / 3:50 – 5:25 pm Central Standard Time
Session: Oral Abstract Session 1
Abstract Number: 687
Title: ACTengine IMA203 TCR-T targeting PRAME shows deep and durable anti-tumor activity in heavily pretreated solid cancer patients
Presenter: Martin Wermke, M.D. (University Hospital Dresden, Germany)

Date / Time: November 9, 2024 / 12:30 PM – 1:30 pm Central Standard Time
Session: Rapid Oral – Clinical 2
Abstract Number: 661
Title: Enhanced pharmacology data of next-generation IMA203CD8 TCR-T monotherapy targeting PRAME
Presenter: Dejka M. Araujo, M.D. (MD Anderson Cancer Center, Houston, Texas, USA)

Poster Presentations

Date: November 8, 2024
Poster Number: 355
Title: An approach to bridging starting materials to monitor T cell persistence in adoptive T cell therapy
Presenter: Jourdan Andersson, Ph.D. (Immatics)

Date: November 9, 2024
Poster Number: 226
Title: An effective donor screening program for manufacturing of allogeneic γδ T cell products
Presenter: Inbar Azoulay Alfaguter, Ph.D. (Immatics)

Date: November 9, 2024
Poster Number: 228
Title: Optimizing and streamlining the manufacturing of Vγ9Vδ2 γδ T cells for allogeneic therapy
Presenter: Pooja Mehta, Ph.D. (Immatics)

Date: November 9, 2024
Abstract Number: 360
Title: Combination of a TCR-engineered autologous PRAME-targeting T cell therapy with a PRAME-encoding mRNA for the treatment of solid tumors
Presenter: Fabian Brunk, Ph.D. (Immatics)

Date: November 9, 2024
Poster Number: 372
Title: TCR-engineered T cells exhibit enhanced persistence and serial killing ability when armored with membrane-bound IL-15
Presenter: Justin Gunesch, Ph.D. (Immatics)

About IMA203 and Target PRAME
ACTengine IMA203 T cells are directed against an HLA-A*02-presented peptide derived from preferentially expressed antigen in melanoma (PRAME), a protein frequently expressed in a large variety of solid cancers, thereby supporting the program’s potential to address a broad cancer patient population. Immatics’ PRAME peptide is present at a high copy number per tumor cell and is homogeneously and specifically expressed in tumor tissue. The peptide has been identified and characterized by Immatics’ proprietary mass spectrometry-based target discovery platform, XPRESIDENT. Through its proprietary TCR discovery and engineering platform XCEPTOR, Immatics has generated a highly specific T cell receptor (TCR) against this target for its TCR-based cell therapy approach, ACTengine IMA203.

ACTengine IMA203 TCR-T is currently being evaluated in Phase 1 IMA203 monotherapy, and IMA203CD8 (GEN2) monotherapy, where IMA203 engineered T cells are co-transduced with a CD8αβ co-receptor.

On October 4, 2024 TheraVectys, a biotechnology company that designs and develops lentiviral vector-based vaccines and immunotherapies against infectious agents and cancers, reported that the first patient has been enrolled in the Phase I/IIa clinical trial evaluating the onco-therapeutic vaccine Lenti-HPV-07 for the treatment of human papillomavirus (HPV)-induced cancers (Press release, Theravectys, OCT 4, 2024, View Source;induced-Cancers-First-Patient-Enrolled-in-Phase-IIIa-Clinical-Trial-for-Lenti-HPV-07-the-TheraVectys%E2%80%99-Therapeutic-Vaccine-Candidate-Against-Oropharyngeal-and-Cervical-Cancers [SID1234647044]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This study will include 36 patients in a dose-escalation protocol conducted at several cancer centers in the United States. Selection and inclusion of these patients are already underway.

The Lenti-HPV-07 vaccine is based on the lentiviral vector technology platform developed by Pasteur-TheraVectys Joint Laboratory and pioneered by TheraVectysfor for nearly 20 years. The highly promising preclinical studies results on the Lenti-HPV-07 vaccine candidate, published in September 2023 in EMBO Molecular Medicine (1) and in June 2024 in NPJ Vaccines (2), showed that after a single intramuscular injection the vaccine was able to induce a strong cellular immune response against the E6 and E7 antigens of HPV16 and HPV18, resulting in:

complete elimination of HPV-induced tumors in 100% of individuals, regardless of tumor size,
a very long-lasting immune memory, notably based on anti-tumor cytotoxic CD8+ T cells, essential for avoiding relapses, which are responsible for a large proportion of deaths,
profound remodeling of the tumor microenvironment,
elimination of metastases in 100% of individuals, and
a strong synergy of Lenti-HPV-07, even at a sub-optimal dose, with treatments such as anti-PD11 antibodies.
Aims and methodology of the human trial
The open-label Phase I/IIa trial will evaluate the safety of ascending doses of Lenti-HPV-07, determine its immunogenicity profile and assess the preliminary efficacy through the Objective Response Rate. It will include two groups of patients with oropharyngeal or cervical cancers induced by HPV-16 or HPV-18, all of whom will be clinically and immunologically followed for one year. Group A will consist of patients with recurrent/metastatic cancers who have not responded to multiple lines of treatment, including immunotherapies. These patients will receive two intramuscular injections of Lenti-HPV-07, one month apart. Group B will be composed of patients with newly diagnosed, treatment-naïve, locally advanced cancers. Patients in Group B will receive a single intramuscular injection of Lenti-HPV-07.

The trial comprises 2 parts: a dose escalation and dose expansion.
In the dose escalation portion participants are enrolled successively to receive increasing doses of Lenti-HPV-07. Safety will be carefully monitored after each dose and before proceeding to enrolment at a higher dose. Enrolment and dose escalation in each arm A and B will be conducted independently.
In each arm, when 18 participants will have received Lenti-HPV-07 treatment in the dose-escalation portion and the safety results will be satisfying, a dose-expansion portion of the trial will be open to treat 18 additional patients at the Optimal Biological Dose. In total, 72 patients with HPV+ cancer will be enrolled in this Phase I/IIa clinical trial.

In terms of safety, TheraVectys has already completed a Phase I clinical trial on a therapeutic HIV-1 vaccine based on an integrative lentiviral vector. Over a 5-year follow-up, this clinical trial revealed no notable side effects or genotoxicity. The ongoing Lenti-HPV-07 clinical trial uses a non-integrative lentiviral vector, which reinforces the safety of the approach.

It should be noted that since group B patients are newly diagnosed and untreated, their immune systems will not have been affected by other chemo- or radiotherapy treatments. These patients will receive standard care, often including anti-PD1 treatments, one month after treatment with Lenti-HPV-07. TheraVectys has shown in animal models that the Lenti-HPV-07 vaccine acts synergistically with treatments such as anti-PD1, increasing the efficacy of anti-PD1 immunotherapy alone by a factor of 4 (1, 2).

Professor Christian Bréchot, Medical Director of TheraVectys commented: "The inclusion of the first patient in the Phase I/IIa trial represents a key milestone for TheraVectys. It is the achievement of more than 2.5 years of preparation, from first interaction with the FDA, production of the vaccine, performance of the preclinical studies, review and approval by the regulatory authorities till sites preparation. The careful selection of adequate partners and the development of a cooperative relationship have been key in successfully building the project."

Pierre Charneau, head of the Pasteur-TheraVectys Joint Laboratory and founder of TheraVectys, said: "With the launch of this study, we are proud to bring our product to a new phase of its development. We expect the preliminary results on safety and immunogenicity a couple of months after all patients in one group will have received their last injection."

HPV causes almost all cervical cancers, as well as many oropharyngeal and anogenital cancers. The preventive HPV vaccines currently available essentially induce HPV-neutralizing antibodies and thus prevent infection, but have no effect on chronic HPV infections or established tumors.

In comparison to Lenti-HPV-07, the immunotherapeutic potential of mRNA-based vaccine technology has only been shown to be effective against very small HPV-related tumors, with early relapse in almost 50% of treated animals (3). In contrast, in the preclinical study conducted by Pasteur-TheraVectys Joint Laboratory, Lenti-HPV-07 immunotherapy was active against large tumors, which are notoriously more difficult to control, demonstrating the superior efficacy of the lentiviral vector-based vaccine platform.

A recent publication of a cross-sectional comparison of the most relevant vaccine strategies tested to date in preclinical anti-HPV immuno-oncotherapy showed that lentiviral vector-based approaches were the most effective at eliminating tumors, while providing the longest-lasting memory (4).

About lentiviral vector technology
TheraVectys is Institut Pasteur’s exclusive licensee for all human and animal vaccine applications of lentiviral vectors worldwide. Thanks to its interaction with dendritic cells, this technology stimulates the body’s natural immune defenses, particularly T cells, more effectively than other vaccine strategies.
The technology is based on the natural attraction of lentiviral vectors for dendritic cells and on their ability to induce directly in these cells a sufficiently long-lasting and highly effective endogenous antigenic presentation of the antigens encoded by the vector. Dendritic cells programmed in this way play a key and unique role in the development of T cell responses, the main effectors against tumor cells.

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".

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

On October 4, 2024 IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported a late-breaking oral presentation of the Phase 1 expansion results of IDE397, a first-in-class, oral, MAT2A inhibitor in methylthioadenosine phosphorylase (MTAP)-deletion urothelial and non-small cell lung cancer (NSCLC) patients at the 36th edition of the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics taking place on October 23 to 25, 2024, in Barcelona, Spain (Press release, Ideaya Biosciences, OCT 4, 2024, View Source [SID1234647030]). In addition, IDEAYA will also have additional poster presentations at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium highlighting preclinical data for the MAT2A and PARG programs.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Details for the oral presentation are as follows:

Presenter: Dr. Benjamin Herzberg, MD, Assistant Professor, Columbia University

Title: Phase 1 expansion results of IDE397, a first-in-class, oral, MAT2A inhibitor (MAT2Ai) in MTAP deleted(del) non-small cell lung cancer (NSCLC) and urothelial cancer (UC)

Abstract #: 501 LBA

Session: Plenary Session 7, Late Breaking Abstracts and Proffered Papers: Novel discoveries in drug development

Date and Time: Friday, October 25, 2024 at 3:00pm CEST

Poster presentation details are below:

Author: Garbett, D. et al.

Title: The mechanistic basis of both deep and durable antitumor activity by combinatorial inhibition of MAT2A and PRMT5 in MTAP-deleted tumors

Poster Number: PB204

Session Title: Combination Therapies

Date and Time: Thursday, October 24, 2024, 9:00am – 5:30pm CEST, Exhibition Hall

Author: Munoz, D. et al.

Title: IDE161, a potential first-in-class clinical candidate PARG inhibitor, selectively targets solid tumors with replication stress and DNA repair vulnerabilities

Poster Number: PB337

Session Title: DNA Repair Modulation (e.g. PARP, CHK, ATR, ATM)

Date and Time: Friday, October 25, 2024, 9:00am – 3:00pm CEST, Exhibition Hall

The oral presentation and posters will be available online at View Source following the presentations.

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.