On March 5, 2024 MaaT Pharma (EURONEXT: MAAT – the "Company"), a clinical-stage biotech company and a leader in the development of Microbiome Ecosystem TherapiesTM (MET) dedicated to improving survival outcomes for patients with cancer, reported the completion of patient recruitment for the Phase 2a clinical trial[1] sponsored by AP-HP[2] and in collaboration with INRAE and Institut Gustave Roussy, evaluating MaaT013, the Company’s lead product candidate, in combination with immune checkpoint inhibitors (ICI), ipilimumab (Yervoy) and nivolumab (Opdivo) (Press release, MaaT Pharma, MAR 5, 2024, View Source [SID1234640784]).

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A total of 70 patients have been enrolled in 5 different centers in France in the randomized controlled Phase 2a PICASSO trial, which started in April 2022. The Company provided MaaT013 drug candidate and placebo and will contribute to the microbiome profiling of patients using its proprietary gutPrint research engine. The unblinding will be done at Week 27 (W27) to assess the primary endpoint which is safety. In parallel, the first efficacy data will be made available, assessed by the best overall response rate, rated by immunological Response Evaluation Criteria in Solid Tumors (iRECIST; 19).

Having reached this key recruitment milestone, the first publication will be submitted at the end of 2024 or in the first quarter of 2025.

The PICASSO trial is funded by the Directorate of Health Care Supply (DGOS: Direction Générale de l’Offre de Soins) and operated by the French National Cancer Institute (INCa: Institut National du Cancer) as part of a call for projects (project PHRC-K19-183).

[1] NCT04988841: Prospective randomIzed clinical trial assessing the tolerance and clinical benefit of feCAl tranSplantation in patientS with melanOma treated with CTLA-4 and PD-1 inhibitors.

[2] AP-HP: Assistance Publique – Hôpitaux de Paris

About MaaT013

MaaT013 is a full-ecosystem, off-the-shelf, standardized, pooled-donor, enema Microbiome Ecosystem TherapyTM for acute, hospital use. It is characterized by a consistently high diversity and richness of microbial species and the presence of ButycoreTM (group of bacterial species known to produce anti-inflammatory metabolites). MaaT013 aims to restore the symbiotic relationship between the patient’s functional gut microbiome and their immune system to correct the responsiveness and tolerance of immune functions and thus reduce steroid-resistant, gastrointestinal (GI)-predominant aGvHD. MaaT013 has been granted Orphan Drug Designation by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

On March 5, 2024 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors, reported that three abstracts of new nonclinical data have been accepted for presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 taking place in San Diego, CA, April 5-10 (Press release, Lyell Immunopharma, MAR 5, 2024, View Source [SID1234640783]).

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One oral and two poster presentations will highlight data from Lyell’s product pipeline and research programs, including:

An oral presentation on Lyell’s rejuvenation technology which has shown the potential to turn back the epigenetic clock to generate more stem-like T cells with reduced epigenetic age and enhanced proliferation ability
A poster presentation of nonclinical data on LYL119, Lyell’s second-generation ROR1-targeted CAR T-cell product candidate
A poster presentation on technology being advanced through a collaboration between Lyell and Outpace to enable tumor-restricted IL-12 activity to enhance solid tumor T cell therapies
Details on the presentations are below.

An oral presentation titled "Rejuvenation of Tumor Infiltrating Lymphocytes: A novel strategy to revitalize TIL antitumor function for cell therapy" will highlight Lyell’s rejuvenation technology which has shown the potential to generate T cells with reduced epigenetic age, more stem-like properties and enhanced proliferation ability. Previously published studies have demonstrated the decline in T-cell function as a person ages. These new nonclinical data show tumor infiltrating lympyocytes (TIL) rejuvenated with Lyell’s technology retain a broad T-cell receptor repertoire and demonstrate sustained proliferation and improved antitumor activities in vivo.

Presentation details:

Session Date/Time: Tuesday Apr 9, 2024 2:30 PM – 4:30 PM
Abstract Number: 6593
Session Category: Immunology
Session Title: New Insights for Therapies Modulating Antitumor T-Cell Responses
New nonclinical data on LYL119, Lyell’s second-generation ROR1-targeted CAR T-cell therapy, will be presented in a poster titled "LYL119, a Preclinical ROR1-Targeted CAR T-Cell Product Incorporating Four Novel Reprogramming Technologies Designed for Effective Cell Therapy for Solid Tumors." LYL119 incorporates four of Lyell’s complementary, stackable T-cell reprogramming technologies and is designed to create potent ROR1-targeted CAR T cells with durable function. In this study, LYL119 demonstrated superior in vivo antitumor efficacy in a mouse xenograft tumor model across a 10-fold dose range, including at very low cell doses. In addition, following repeated rounds of tumor cell killing, LYL119, displayed reduced expression of exhaustion-related gene signatures and retained unique cell subsets characterized by upregulation of memory and effector-associated gene signatures.

Presentation details:

Session Date and Time: Sunday Apr 7, 2024 1:30 PM – 5:00 PM
Abstract Number: 49
Session Category: Immunology
Session Title: Adoptive Cell Therapies 2: CAR-T Cells
A poster presentation titled "Development of Tumor-restricted IL-12 With Antigen-dependent Expression and Localized IL-12 Activity" highlights an innovative tumor-restricted IL-12 (trIL-12) technology that delivers potent IL-12 stimulation at the tumor site while avoiding systemic exposure. IL-12 is an immune-stimulatory cytokine that can induce potent anti-tumor activity, but unregulated systemic delivery of IL-12 has been shown to have a limited therapeutic window. trIL-12 was designed leveraging Outpace’s OUTSMART technology to rapidly auto-inactivate IL-12 after inducible secretion from engineered T cells with the aim of achieving safe, local delivery of IL-12 activity in the tumor microenvironment. trIL-12 is being advanced under a collaboration between Lyell and Outpace with the goal of improving efficacy for T-cell therapies by harnessing the therapeutic potential of IL-12.

Presentation details:

Session Date and Time: Tuesday Apr 9, 2024 9:00 AM – 12:30 PM
Abstract Number: 4067
Session Category: Immunology
Session Title: Immune Modulation with Cytokines

On March 5, 2024 Kronos Bio, Inc. (the "Company") reported that it has amended its protocol for its clinical trial of KB-0742, an oral CDK9 inhibitor in a phase 1/2 dose escalation and expansion trial in solid tumors (Press release, Kronos Bio, MAR 5, 2024, View Source [SID1234640782]).

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To date, anti-tumor activity has been observed without grade 3/4 neutropenia in patients treated with KB-0742 at doses ranging from 10 mg to 80 mg using the current three-days-on, four-days-off dosing schedule. The Company has seen target engagement, tumor regressions and an acceptable safety profile at 60 mg dosed three-days-on, four-days-off, and have subsequently cleared 80 mg three-days-on, four-days-off.

Moving forward, the Company is pursuing a four-days-on, three-days-off dosing schedule to further increase patient time on KB-0742 at or above a therapeutic threshold. In a 3+3 design, the Company plans to dose escalate through doses of 60 mg, four-days-on, three-days-off, and 80 mg, four-days-on, three-days-off, before enrolling expansion cohorts at the latter dose and schedule (80 mg, four-days-on, three-days-off). KB-0742 clinical data from existing dose escalation and ongoing expansion cohorts are still expected in mid-2024. In the third quarter of 2024, the Company expects to provide an update from the new four-days-on, three-days-off dosing schedule and announce its plans for the dose expansion phase of the Phase 1/2 clinical trial of KB-0742. The Company currently contemplates the expansion cohort will include patients with either small cell or non-small cell lung cancer, ovarian cancer, or triple negative breast cancer and expects to announce topline data from the expansion phase in the first half of 2025.

On March 5, 2024 Keros Therapeutics, Inc. ("Keros") (Nasdaq: KROS), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapeutics to treat a wide range of patients with disorders that are linked to dysfunctional signaling of the transforming growth factor-beta ("TGF-ß") family of proteins, reported that Keros’ President and Chief Executive Officer Jasbir S. Seehra, Ph.D., will participate in a fireside chat presentation at the Leerink Partners 2024 Global Biopharma Conference on Tuesday, March 12, 2024 at 3:00 p.m. Eastern time (Press release, Keros Therapeutics, MAR 5, 2024, View Source [SID1234640781]).

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A live audio webcast of the fireside chat presentation will be available at View Source and an archived replay will be accessible in the Investors section of the Keros website at View Source for up to 90 days following the conclusion of the event.

On March 5, 2024 IO Biotech (Nasdaq: IOBT), a clinical-stage biopharmaceutical company developing novel, immune-modulating therapeutic cancer vaccines based on its T-win platform, reported financial results for the fourth quarter and year-ended December 31, 2023 (Press release, IO Biotech, MAR 5, 2024, View Source [SID1234640780]).

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"In 2023, we reached a significant milestone in our pivotal Phase 3 trial evaluating our lead therapeutic cancer vaccine, IO102-IO103, in combination with KEYTRUDA, completing enrollment in this trial in mid-November," said Mai-Britt Zocca, Ph.D., President and CEO of IO Biotech. "The acceleration in enrollment observed in this study in the second half of 2023 is a testament to the need that exists today for more efficacious and better tolerated first-line treatment options for patients with advanced melanoma."

Dr. Zocca continued, "The coming months will prove to be a critical period in the development of IO Biotech, with the outcome of the pivotal Phase 3 interim analysis expected in the third quarter of 2024, and, more importantly, the primary endpoint of progression free survival estimated to follow in the second half of 2025. Our team is dedicated to continuing our diligent work to efficiently bring IO102-IO103 to patients in need, potentially as early as 2025."

Fourth Quarter 2023 and other Recent Highlights

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In November 2023, the company completed enrollment of 380 patients in its pivotal Phase 3 trial (IOB-013/KN-D18) of IO102-IO103 in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in advanced melanoma. The primary endpoint of the pivotal Phase 3 trial is progression free survival (PFS). The PFS analysis is event-driven and will be conducted when 226 events have occurred in the trial, which the company estimates will take place in the second half of 2025. Additionally, a planned interim analysis of overall response rate (ORR) will be conducted when the first 225 randomized patients reach one year of treatment in June 2024. The outcome of this analysis is expected in the third quarter of 2024.

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In December 2023, the first patient was dosed in the company’s Phase 2 solid tumor basket trial (IOB-032/PN-E40) studying treatment with IO102-IO103 in combination with pembrolizumab given before (neo-adjuvant) and after (adjuvant) surgery with curative intent in patients with resectable melanoma or squamous cell carcinoma of the head and neck (SCCHN).

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The company’s Phase 2 basket trial (IOB-022/KN-D38) evaluating IO102-IO103 in combination with pembrolizumab in patients with metastatic non-small cell lung cancer (NSCLC) or recurrent or metastatic SCCHN is ongoing. Encouraging preliminary data that support the potential of IO102-IO103 in combination with pembrolizumab as first-line treatment in NSCLC and SCCHN were presented at the IASLC 2023 World Conference on Lung Cancer (WCLC) in September 2023 and at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) annual meeting in October 2023.

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Progress continued in several investigator-initiated trials the company is supporting including dosing of the first patient in the Phase 2 trial evaluating its lead therapeutic cancer vaccine candidate, IO102-IO103, and pembrolizumab as neoadjuvant followed by adjuvant treatment of patients with SCCHN (NCT05977907), as well as continuing enrollment in both the Phase 2 trial of IO102-IO103 given in combination with nivolumab-relatlimab in patients with untreated, unresectable Stage III/IV melanoma (NCT05912244) and the Phase 1 study of the IO102-IO103 vaccine in combination with pembrolizumab for patients with BCG-unresponsive or intolerant high-risk non-muscle invasive bladder cancer (NCT05843448).

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Three posters were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 38th Annual Meeting in November 2023 with data providing further evidence of the differential biological impact of therapeutic vaccines IO102, IO103 and IO112.

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The company expanded its Board of Directors with the appointment of Helen Collins, MD in November 2023.

Fourth Quarter 2023 Financial Results

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Net loss for the three months ended December 31, 2023, was $26.2 million, compared to $20.1 million for the three months ended December 31, 2022.

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Research and development expenses were $21.8 million for the three months ended December 31, 2023, compared to $14.4 million for the three months ended December 31, 2022. The increase was primarily related to clinical trial-related activities for the company’s IO102-IO103 therapeutic cancer vaccine candidate, including the continued execution of the company’s Phase 3 clinical trial. The company recognized $0.5 million in research and development equity-based compensation for the three months ended December 31, 2023, compared to $0.6 million for the three months ended December 31, 2022.

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General and administrative expenses were $6.4 million for the three months ended December 31, 2023, compared to $6.0 million for the three months ended December 31, 2022. The increase was primarily related to personnel costs due to an increase in head count that was offset by a decrease in professional services, consultant and other costs. The company recognized $1.0 million in general and administrative equity-based compensation for the three months ended December 31, 2023, compared to $1.1 million for the three months ended December 31, 2022.

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Cash and cash equivalents as of December 31, 2023 were $143.2 million, compared to $142.6 million at December 31, 2022. During the three months ended December 31, 2023, the company used cash, cash equivalents and restricted cash of $22.9 million from operating and investing activities.

About IO102-IO103

IO102-IO103 is an investigational off-the-shelf therapeutic cancer vaccine designed to kill both tumor cells and immune-suppressive cells in the tumor microenvironment (TME) by stimulating activation and expansion of T cells against indoleamine 2,3-dioxygenase (IDO) and/or programmed death-ligand 1 (PD-L1) cells. The company is currently conducting a pivotal Phase 3 trial (IOB-013/KN-D18; NCT05155254) investigating IO102-IO103 in combination with pembrolizumab versus pembrolizumab alone in patients with advanced melanoma, a Phase 2 basket trial (IOB-022/KN-D38; NCT05077709) investigating IO102-IO103 in combination with pembrolizumab as first line treatment in patients with solid tumors, and a Phase 2 basket trial (IOB-032/PN-E40; NCT05280314) investigating IO102-IO103 in combination with pembrolizumab as neo-adjuvant/adjuvant treatment of patients with solid tumors.

The clinical trials are sponsored by IO Biotech and conducted in collaboration with Merck and Merck is supplying pembrolizumab. IO Biotech maintains global commercial rights to IO102-IO103.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About the IOB-013/KN-D18 Pivotal Phase 3 Clinical Trial

IOB-013/KN-D18 (Clinical Trials.gov: NCT05155254) is an open label, randomized Phase 3 clinical trial of IO102-IO103 in combination with pembrolizumab versus pembrolizumab alone in patients with previously untreated, unresectable or metastatic (advanced) melanoma, being conducted in collaboration with Merck. Patients have been enrolled from centers across the United States, Europe, Australia, Turkey, Israel and South Africa. The primary endpoint of the study is progression free survival. Biomarker analyses will also be conducted. IO Biotech is sponsoring the Phase 3 trial and Merck is supplying pembrolizumab. IO Biotech maintains global commercial rights to IO102-IO103.

About the IOB-013/KN-D18 Clinical Trial Endpoints

The primary endpoint of the IOB-013/KN-D18 trial is progression free survival (PFS). The PFS analysis is event-driven and will be conducted when 226 events have occurred in the trial, which the company estimates will take place in the second half of 2025. Additionally, there is a planned per-protocol interim analysis of overall response rate when the first 225 randomized patients reach one year of treatment in mid-2024. The outcome of this analysis is expected in the third quarter of 2024. There is a high statistical bar for the Phase 3 interim analysis (p≤0.005), which was set to preserve most of the alpha for the primary endpoint of PFS. Regardless of the outcome of the interim analysis, the trial is designed to continue to the primary PFS endpoint.