On November 8, 2024 Oncolys BioPharma reported non-consolidated Financial Results for the Nine Months Ended September 30, 2024 (Press release, Oncolys BioPharma, NOV 8, 2024, View Source [SID1234649625]).

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On November 8, 2024 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, reported initial preclinical data for FT836, a multiplexed-engineered, chimeric antigen receptor (CAR) T-cell product candidate targeting major histocompatibility complex (MHC) proteins A (MICA) and B (MICB) at the 2024 Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting being held in Houston, TX on November 6-10, 2024 (Press release, Fate Therapeutics, NOV 8, 2024, View Source [SID1234648037]). The expression of MICA/B cell-surface proteins is induced by cellular stress or malignant transformation, and is detectable across many types of cancer cells with limited expression on healthy tissue. FT836 incorporates multiple next-generation synthetic controls of CAR T-cell function including the Company’s novel Sword & Shield technology, which is comprised of a constellation of genetic edits that both target and evade host alloreactive immune cells and is designed to promote functional persistence of off-the-shelf CAR T-cell therapies without conditioning chemotherapy.

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"The novel suite of synthetic controls incorporated into FT836 is intended to address critical challenges that have limited CAR T-cell safety and efficacy in treating solid tumors including on-target, off-tumor toxicity, effector cell suppression in the tumor microenvironment, tumor heterogeneity, and limited functional persistence," said Bob Valamehr, Ph.D., President of Research & Development of Fate Therapeutics. "Our FT836 preclinical data presented today at SITC (Free SITC Whitepaper) support the pan-cancer activity of MICA/B targeting, and indicate that our next-generation, iPSC-derived CAR T-cell platform has the potential to drive potent and durable anti-tumor activity without the need for administration of conditioning chemotherapy to deplete host immune cells."

Preclinical Data

MICA/B targeting is emerging as a novel cancer-specific strategy to attack a wide range of solid tumors, however, proteolytic cleavage and shedding of MICA/B at the membrane-proximal α3 domain is a common mechanism of cancer resistance and escape from canonical NKG2D-mediated recognition. FT836 is designed to uniquely target and bind the α3 domain, which has been shown to stabilize MICA/B expression and induce robust cytolytic killing of tumor cells. At an oral presentation today at SITC (Free SITC Whitepaper) entitled "Development of an Off-the-Shelf, MICA/B Targeting CAR T Cell to Overcome Pan-tumor Escape Mechanism for Solid Tumors", scientists from the Company highlighted that FT836 exerted potent and durable anti-tumor activity in vivo across a broad array of solid tumors. In addition, treatment of tumor cells with chemotherapy or radiation therapy in vitro elicited an increase in MICA/B expression and further enhanced the cytolytic activity of FT836, indicating the potential for combination with standard-of-care regimens used for the treatment of solid tumors.

Novel Sword & Shield Technology

FT836 is also the Company’s first product candidate to incorporate its novel Sword & Shield technology, which utilizes a 4-1BB-targeted CAR (ADR) alongside the complete knock-out of CD58 (CD58KO), to both target and evade host alloreactive immune cells. In preclinical studies presented at SITC (Free SITC Whitepaper), iPSC-derived Sword & Shield CAR T cells demonstrated functional persistence and durable anti-tumor activity in vivo that was uniquely maintained upon supraphysiological challenge with alloreactive T cells, indicating the potential of Sword & Shield CAR T cells to thrive without administration of conditioning chemotherapy to deplete host immune cells. The Company’s novel Sword & Shield technology was also featured in a poster presentation at SITC (Free SITC Whitepaper) entitled "Alloimmune Defense Receptor Combined with Genetic Ablation of Adhesion Ligand CD58 is a Comprehensive Approach to Promote Functional Persistence of Allogeneic Cell Therapies without Conditioning Chemotherapy".

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.

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 Amgen reported the company will present at the 2024 UBS Global Healthcare Conference at 10:15 a.m. PT on Wednesday, Nov. 13, 2024 (Press release, Amgen, NOV 8, 2024, View Source [SID1234648018]). Peter Griffith, executive vice president and chief financial officer at Amgen, will present at the conference. The webcast will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

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The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.