On November 8, 2024 Eisai reported Second Quarter Financial Results for Fiscal Year Ending March 31, 2025 (Presentation, Eisai, NOV 8, 2024, View Source [SID1234648888]).

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On November 8, 2024 BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW) (TSX: BCT) ("BriaCell" or the "Company"), a clinical-stage biotechnology company that develops novel immunotherapies to transform cancer care, reported preclinical data showing strong anti-cancer activity of its next generation, personalized, off-the-shelf, cell-based breast and prostate cancer immunotherapies, Bria-BRES+ and Bria-PROS+, respectively, during a poster session at the 2024 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting, held November 6-10, 2024, in Houston, TX (Press release, BriaCell Therapeutics, NOV 8, 2024, View Source [SID1234648541]).

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Bria-OTS+ is an Off-The-Shelf (i.e. pre-manufactured and ready for use) cell-based personalized immunotherapy platform for cancer. First generation Bria-OTS immunotherapy is HLA matched to individual patients and expresses a variety of cancer-related antigens, including Tumor-Associated Antigens (TAAs) and Post-Translational Modifications (PTMs). Bria-OTS+ further expresses multiple immune activating cytokines and co-stimulatory molecules in addition to immune boosting granulocyte-macrophage colony-stimulating factor (GM-CSF). The Bria-OTS+ platform technology includes both Bria-BRES+ and Bria-PROS+, expansions of the Bria-OTS program.

"Bria-OTS+ represents a significant advancement in the fight against cancer, leveraging gene-modified allogeneic tumor cells as a comprehensive immunotherapeutic platform. This innovative approach is set to address major challenges in cancer therapy, including effective antigen selection, T-cell immune escape, and manufacturing complexities. The development of Bria-OTS+ builds on the success of BriaCell’s initial platform, Bria-IMT, which has shown promising clinical results in metastatic breast cancer," commented Miguel A. Lopez-Lago, PhD, BriaCell’s Chief Scientific Officer.

"We are thrilled with our pre-clinical data confirming the expected high potency and potential for long-lasting anti-tumor activity of our novel next-generation immunotherapy in multiple cancer models," commented Dr. William V. Williams, BriaCell’s President and CEO. "We believe that activating both adaptive and innate immune systems is a novel and highly effective approach for cancer treatment and look forward to generating proof of concept data in our ongoing Phase 1/2 study of Bria-OTS in metastatic breast cancer, and other cancers."

The poster is summarized below and linked here: View Source

Title: Bria-OTS+: A Cellular Cancer Vaccine Platform Targeting Innate and Adaptive Immunity
Location: Exhibit Halls A B George R. Brown Convention Center, Houston, TX
Date and Time: Friday, Nov. 8, 2024, 9:00 am -7:00 pm CST

Results:

Both Bria-BRES+ (clinical candidate for breast cancer) and Bria-PROS+ (clinical candidate for prostate cancer) activated key components of the innate immune system, the body’s first line of defense against cancer, including Natural Killer (NK) cells and NKT cells in preclinical cancer models.
Activation of the innate immune system by Bria-BRES+ and Bria-PROS+ was mediated by CD86, IL-12, NKG2D and inhibited by HLA class I molecules
Bria-BRES+ and Bria-PROS+ both effectively activated immune cells to destroy breast cancer and prostate cancer cells in a pre-clinical cancer model
Both Bria-BRES+ and Bria-PROS+ activated key adaptive immune responses demonstrating immunological memory and suggesting potent and durable anti-cancer effects in cancer patients
Conclusion:
The characteristics of the next generation Bria-OTS+ immunotherapy platform include the following:

Engages multiple facets of the adaptive immune response
Activates components of the innate immune system
Specifically activates Natural Killer (NK) cells to offset cancer immune escape caused by the loss of human leukocyte antigens (HLA)
Designed for both personalized and ready-to-use therapy with long-term stability
Simplified intradermal administration (injection into the skin)
Targeted mechanism of action expected drive high efficacy with a favorable side effect profile
"The preclinical data demonstrating targeted activation of both the innate and adaptive immune systems suggest potential efficacy and safety across multiple cancer indications," stated Adam M. Brufsky, MD, PhD, FACP, Professor of Medicine at the University of Pittsburgh School of Medicine and Medical Director of the Magee-Women’s Cancer Program. "Personalized off-the-shelf cancer immunotherapy is an especially exciting treatment modality that would benefit many cancer patients."

BriaCell is currently conducting its Phase 1/2 Study of Bria-OTS (first generation product), also known as Bria-BRES, in metastatic breast cancer (listed on ClinicalTrials.gov as NCT06471673).This is a bucket trial with other cancer indications expected to be added soon. The next generation (Bria-OTS+) is expected to enter the clinic in 1H2025 starting with Bria-PROS+ for prostate cancer.

Bria-OTS+ leverages advanced biomanufacturing techniques, ensuring scalability and cost-effectiveness, crucial for rapid global deployment. It is designed to target a range of cancer types and strong intellectual property strategy protects Bria-OTS+ innovations and strengthens BriaCell’s competitive position. Bria-OTS+ is designed as an open-ended, modular platform, allowing for continuous refinement and the addition of new components. This flexibility enables BriaCell to rapidly adapt to emerging scientific insights and therapeutic needs, ensuring long-term relevance and effectiveness.

On November 8, 2024 HUYABIO International reported it will present the final analysis of data from a phase 2 study evaluating HBI-8000 in combination with nivolumab (anti-PD1 therapy), a novel combination for the treatment of advanced and metastatic melanoma (Press release, HUYA Bioscience, NOV 8, 2024, View Source [SID1234648449]).

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The results will be presented by Study Chair, Dr. Nikhil Khushalani, Senior Member and Vice Chair, Department of Cutaneous Oncology from Moffitt Cancer Center, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2024 Annual Meeting on Saturday, November 9.

HBI-8000, an oral drug, when combined with nivolumab has shown encouraging efficacy signals in treating patients with advanced and metastatic melanoma. This innovative therapy has clinically meaningful advantages over traditional double immune checkpoint inhibitor combinations, offering patients an oral treatment in combination with nivolumab that has enhanced efficacy and reduced toxicities.

"The promising results from the HBI-8000 and nivolumab combination represent a significant advancement in treating advanced melanoma," said Dr. Mireille Gillings, President, CEO & Executive Chair at HUYABIO. "Coupling oral convenience with a reduction in immune-related toxicities will give clinicians new tools to improve patient outcomes. We are proud to contribute to this new era of immunotherapy that prioritizes both efficacy and patient well-being."

"We are pleased to share the final Phase 2 results of the HBI-8000 and nivolumab combination in patients with advanced melanoma at this year’s SITC (Free SITC Whitepaper) conference," said Dr Nikhil Khushalani. "The combination appears safe and effective in this Phase 2 study, which may show great promise in this patient population. HBI-8000 plus nivolumab could be an important addition to the armamentarium of oncologists treating this disease and is currently being investigated in a Phase 3 study."

Title: HBI-8000, a class I histone deacetylase (HDAC) inhibitor, in combination with nivolumab for treatment of anti-PD(L)1-naive advanced melanoma: final analysis of Study HBI-8000-302

Abstract Number: 620

Authors: Nikhil I. Khushalani1 (Presenter), Andrew Brohl1, Joseph Markowitz1, Heather Yeckes-Rodin2, Lori McCormick1, Charlie Liu3, Mireille Gillings3, Gloria Lee3, and Zeynep Eroglu1 1H. Lee Moffitt Cancer Center, Tampa FL, 2Hematology-Oncology Associates of the Treasure Coast, Port. St. Lucie, FL, 3HUYABIO International, San Diego, CA, USA

Oral Presentation Date and Time: Saturday, November 9th at 3:44 PM CST

Addressing the Unmet Need for Innovative Melanoma Therapies

The combination of HBI-8000 and nivolumab represents a significant advancement in melanoma treatment. As the first combination therapy that does not rely on dual immune checkpoint inhibitors, it presents a desirable option for community practices and specialty cancer centers, particularly in regions with limited technical support. This therapy can potentially expand combination therapy for melanoma containing nivolumab-backbone beyond established markets in the U.S. and EU, providing access to more patients worldwide.

About the HBI-8000 Phase 2 Trial

The trial was a Phase 1b/2 trial evaluating the combination of HBI 8000 with nivolumab (an anti-PD1 immune checkpoint inhibitor) in advanced melanoma, kidney cancer and non-small cell lung cancer. The recommended Phase 2 dose of HBI-8000 was determined to be 30mg orally twice weekly (BIW) combined with intravenous nivolumab administered at the manufacturer’s approved dosing schedule. Patients with metastatic melanoma not previously treated with anti-PD(L)-1 inhibitor, with measurable disease, ECOG performance status 0-1, and adequate hematologic and biochemical parameters were enrolled. Previously treated stable brain metastases not requiring steroids were permitted. Disease status was assessed by standard imaging using RECIST v1.1 every 8 weeks. Treatment was continued until disease progression, unacceptable toxicity or completion of 24 months of therapy. View Source

On November 8, 2024 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported that new preclinical data supporting the clinical development of its proprietary next generation antibody-drug conjugate (ADC) and innovative tetra-specific ANKET will be presented at the SITC (Free SITC Whitepaper) Annual Meeting 2024 (Press release, Innate Pharma, NOV 8, 2024, View Source [SID1234648054]).

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"We are thrilled to share our latest preclinical data at the SITC (Free SITC Whitepaper) Annual Meeting, highlighting the potential of IPH6501, our tetra-specific NK cell engager and IPH4502, our innovative ADC targeting Nectin-4. These findings underscore our commitment to advancing next-generation immunotherapies and reflect significant progress in the development of our drug candidates. We look forward to engaging with the scientific community as we continue to push the boundaries of next generation immunotherapies," commented Pr. Eric Vivier, Chief Scientific Officer of Innate Pharma.

Details of the presentations

Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting | 6-10 November, Houston, Texas and Virtual

Harnessing NK Cells in Cancer Therapies
Session 107d: NK Cells and Innate Immunity
Presentation Type: Oral Presentation
Session Date and Time: Friday, Nov. 8, 2024, 3:50-5:25pm CST
Presentation Time: 4:35pm CST
Speaker: Eric Vivier, Chief Scientific Officer, Innate Pharma (co-chair of the session)
Preclinical Characterization of IPH6501: A Novel IL2v-Armed Tetraspecific NK Cell Engager Targeting CD20 in Relapsed or Refractory B cell Non-Hodgkin Lymphoma Subtypes and Post-CAR-T Therapy.
Abstract Number: 1083
Presentation Type: Poster Presentation
Primary Category: Immuno-Conjugates and Chimeric Molecules
Poster Presentation Day: Friday, Nov. 8, 2024
IPH45, a next-generation antibody-drug conjugate (ADC) targeting Nectin-4
Abstract Number: 1056
Presentation Type: Poster Presentation
Primary Category: Immuno-Conjugates and Chimeric Molecules
Poster Presentation Day: Saturday, Nov. 9, 2024
More information can be found on the JITC website.

Protein & Antibody Engineering Summit (PEGS) Europe | November 5-7, Barcelona, Spain and virtual

In addition, the presentation entitled « A Next-Generation ADC for Nectin-4 Expressing Tumours: Preclinical Characterisation of IPH45, a Novel and Differentiated Exatecan-Based ADC Targeting Nectin-4 » was presented at the PEGS Europe Summit. The presentation is available on the Company website, in the publications section.

About IPH4502

IPH4502 is a novel topoisomerase I inhibitor Antibody Drug Conjugate (ADC) conjugated to exatecan targeting Nectin-4.

Nectin-4 is a cell membrane adhesion protein overexpressed in several solid tumors, including urothelial, breast, lung, ovarian, and pancreatic cancers, with limited expression in normal tissues.

In non-clinical models, IPH4502 is well tolerated and shows anti-tumor efficacy in vitro and in vivo.

In September 2024, the U.S Food and Drug Administration cleared Innate’s investigational new drug (IND) application to initiate a Phase 1 clinical study of IPH4502 in Nectin-4 expressing solid tumor indications.

About IPH6501

IPH6501 is the first Antibody-based NK cell Engager Therapeutic to co-engage activating receptors on NK cells (NKp46 and CD16), IL-2R (but not a subunit) through a variant of human IL-2, and a tumor antigen (CD20) via a single molecule, hence providing proliferation and activation signals targeted to NK cells and promoting their cytotoxic activity against CD20 expressing malignant cells.

IPH6501 has shown better anti-tumor efficacy than approved benchmark antibodies in preclinical tumor models (Demaria, EHA (Free EHA Whitepaper) 2023).

IPH6501 is currently being evaluated in a Phase 1/2 multicenter trial (NCT06088654), investigating the safety and tolerability of IPH6501 in patients with Relapsed and/or Refractory CD20-expressing B-cell Non-Hodgkin’s Lymphoma.

On November 9, 2024 Synthekine Inc., an engineered cytokine therapeutics company, reported positive translational results from the Phase 1a dose escalation portion of a Phase 1a/1b clinical trial of its first-in-class α/β-IL-2R biased partial agonist, STK-012, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting in Houston (Press release, Synthekine, NOV 8, 2024, View Source [SID1234648053]). STK-012 is engineered to selectively stimulate CD25+ antigen-activated T cells, which are associated with potent anti-tumor activity, and avoid broad stimulation of other lymphocytes, such as natural killer (NK) cells, which are associated with IL-2 toxicity. The Phase 1b dose expansion portion of the study in adults with advanced solid tumors remains ongoing (NCT05098132) and will include treating patients with STK-012 in combination with standard of care therapy in first line PD-L1 negative non-small cell lung cancer (NSCLC).

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Initial clinical findings for STK-012 monotherapy from the Phase 1a dose escalation portion of the study were presented at AACR (Free AACR Whitepaper) earlier this year, showing a favorable safety profile without Capillary Leak Syndrome (CLS) and with single agent efficacy, including multiple objective responses, in IO-refractory solid tumors. The findings shared at SITC (Free SITC Whitepaper) build on these monotherapy results from the same study population, further demonstrating the mechanism of action of STK-012 and its ability to selectively induce T cell activation and expansion.

Results presented in the STK-012 poster at SITC (Free SITC Whitepaper) include an analysis of key biomarkers, such as cytokine induction and memory CD8 T cell activation and expansion, both of which were found to correlate with best overall response (BOR). The poster also includes analysis of the TCR clonal expansion observed upon treatment with STK-012 monotherapy, which led to an 80-fold median increase in expanding TCR clones. TCR clonal expansion was found to correlate with both progression-free survival (PFS) and BOR in these patients.

"We are very encouraged by the translational data for STK-012 monotherapy as it represents a powerful advancement in cancer therapy, designed to realize the full efficacy potential of IL-2 while eliminating severe toxicities typically associated with IL-2 treatment," said Martin Oft, M.D., chief scientific officer of Synthekine. "Our data reinforces STK-012’s unique mechanism of action, as demonstrated by selective expansion of antigen activated T cells without broad expansion of other lymphocytes including NK cells. In addition, we see strong and sustained induction of interferon gamma (IFNγ) coupled with minimal increase of interleukin-6 (IL-6), supporting the efficacy and tolerability profile of STK-012. We look forward to advancing this promising candidate to the next stage of clinical development."

The company will also present two posters for STK-026, a biased IL-12 cytokine partial agonist. The preclinical data to be presented demonstrates STK-026 is engineered to retain the potent antitumor activity of IL-12 while avoiding its systemic toxicities. In addition, results of a GLP toxicology study in cynomolgus monkeys showed excellent tolerability of STK-026 and confirmed its preferential activity toward CD8 T cells. Relative to therapies based on unmodified IL-12, STK-026 is tuned to bias immune activation toward the adaptive and away from the innate immune systems, thus avoiding NK cell mediated dose-limiting toxicities that are the hallmark of IL-12 therapy, including cytokine release syndrome (CRS), hepatoxicity, and lymphopenia.

Details are as follows and available on the SITC (Free SITC Whitepaper) website:

Title: T cell and Immune Activation from a Phase 1 Study of STK -012, a First-in-class IL-2R α/ß Selective Partial Agonist in Advanced Solid Tumors
Session Name: Novel Single-Agent Immunotherapies
Session Date & Time: Friday, November 8, 2024, 9:00 AM – 7:00 PM CT
Format: Poster Presentation
Abstract Number: 1325

Title: STK -026, a detoxified IL-12 partial agonist is well-tolerated and sustains CD8+ T cell activity with repeat doses in cynomolgus macaques
Session Name: Immune-Stimulants and Immune Modulators
Session Date & Time: Friday, November 8, 2024, 9:00 AM – 7:00 PM CT
Format: Poster Presentation
Abstract Number: 941

Title: Gradual lymphocyte activation with IL-12 partial agonist STK-026 maintains anti-tumor efficacy but escapes acute NK-mediated cytokine release and toxicities associated with WT IL-12
Session Name: Immune-Stimulants and Immune Modulators
Session Date & Time: Saturday, November 9, 2024, 9:00 AM – 8:30 PM CT
Format: Poster Presentation
Abstract Number: 964

Copies of the posters will be available on Synthekine’s website following presentation at the meeting.