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.

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]).

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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 4, 2024 Johnson & Johnson (NYSE: JNJ) reported that it will participate in the Guggenheim Global Healthcare Conference on Tuesday, November 12th, at the InterContinental Boston in Boston, MA (Press release, Johnson & Johnson, OCT 4, 2024, View Source [SID1234647043]). Biljana Naumovic, President, Solid Tumor, U.S. Oncology and Mark Wildgust, Vice President, Global Medical Affairs Oncology, will represent the Company in a session scheduled at 10:30 a.m. (Eastern Time).

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This live audio webcast will be available to investors and other interested parties by accessing the Johnson & Johnson website at www.investor.jnj.com.

The audio webcast replay will be available approximately 48 hours after the webcast.

On October 4, 2024 TiumBio Co., Ltd. (Kosdaq: 321550), a clinical-stage biopharmaceutical company focused on discovering and developing innovative therapeutics for patients with rare and incurable diseases, reported that the first patient has been dosed in its Phase 2 clinical trial of TU2218 (Press release, TiumBio, OCT 4, 2024, View Source [SID1234647042]).

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TU2218 is a novel oral dual inhibitor targeting TGFR1 and VEGFR2. TGF-ß and VEGF pathways are known to suppress the activity of immune checkpoint inhibitors (ICIs), so TU2218 is expected to improve the efficacy of ICIs by blocking the two pathways.

In Phase 1a and 1b clinical trials, TiumBio evaluated the safety, pharmacokinetics, and pharmacodynamics of TU2218 as a monotherapy and in combination with Keytruda (pembrolizumab) in 41 patients with advanced solid tumors. These profiles were used to determine the dose levels for Phase 2 trials. The Phase 2a trial is designed to assess the safety and efficacy of TU2218 in combination with Keytruda in patients with head and neck squamous cell carcinoma (HNSCC), biliary tract cancer (BTC), and colorectal cancer (CRC).

The Phase 2 trial begins at Seoul National University Hospital and Asan Medical Center in South Korea, which is planned to expand to hospitals in the United States. The first dose was administered to an HNSCC patient.

HNSCC refers to malignant tumors that occur in the oral cavity, throat, larynx, or salivary glands. The standard treatment typically involves surgery and radiation therapy. According to Global Data, as of 2023, the number of HNSCC patients worldwide is estimated to be around 610,000, and it is expected to exceed 670,000 by 2030.

"HNSCC is a disease with a high unmet medical need, as the average survival rate for first-line treatments is known to be only about one year," said Hun-taek Kim, Ph.D., MBA, CEO of TiumBio. "We have selected cancer types for the Phase 2 clinical trial based on other trials that demonstrated strong anti-cancer effects from targeting TGF- ß or VEGF pathways. Our goal is to develop TU2218 as a first-line treatment for HNSCC," he added.

In the Phase 1b trial, among 10 patients with advanced solid tumors who received a 195mg daily dose (the determined dose for Phase 2) of TU2218 with Keytruda, three patients achieved partial response (PR) and five patients had stable disease (SD), yielding an 80% disease control rate (DCR).

On October 4, 2024 HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting regulatory sites on proteins referred to as "natural hotspots," reported it will present additional Phase 1 clinical biomarker data for HST-1011, an investigational oral, selective inhibitor of Casitas B-lineage lymphoma proto-oncogene (CBL-B), in a poster presentation at the 2024 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, taking place November 6-10, 2024, in Houston, Texas. The poster will showcase exploration of potential clinical biomarkers that correlate with signs of clinical activity in patients from the ongoing Phase 1 monotherapy dose-escalation study of HST-1011.

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Presentation details are as follows:

Title: Peripheral Blood and Tumor Gene Expression as Biomarkers and Potential Predictors of Clinical Outcome with HST-1011, an Oral CBL-B Inhibitor
Session Date and Time: Sat., Nov. 9, 2024, 9:00 AM-8:30 PM CT
Location: Exhibit Halls A & B, George R. Brown Convention Center
Abstract Number: 1310