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 Tempus AI, Inc. (NASDAQ: TEM), a technology company leading the adoption of AI to advance precision medicine and patient care, reported nine abstracts were accepted for presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 39th Annual Meeting, which convenes in Houston, Texas, from November 6-10, 2024 (Press release, Tempus, NOV 8, 2024, View Source [SID1234648052]).

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"Presenting our latest research is a vital opportunity to showcase the advancements Tempus is making in harnessing the power of data and AI to drive immunotherapy innovation," said Ezra Cohen, MD, Chief Medical Officer of Oncology at Tempus. "We are committed to working with the oncology community to share insights that can accelerate the development of more effective, personalized therapies and contribute to the improvement of outcomes for patients."

This year, highlights of Tempus’ poster presentations include:

Poster Presentation (#188): Clinical validation of a novel multi-omic algorithm for stratifying outcomes in a real-world cohort of metastatic solid cancer patients treated with immune checkpoint inhibitors
Session Date & Time: Saturday, November 9, 2024; 9:00 a.m. – 8:30 p.m. CT
Location: George R. Brown Convention Center; Exhibit Halls AB

Overview: This study aimed to predict patient outcomes to immune checkpoint inhibitors (ICI) by developing an integrated DNA/RNA ICI biomarker. A de-identified pan-cancer cohort from the Tempus multimodal real-world database was utilized to develop and validate the Immune Profile Score (IPS) algorithm that leverages Tempus xT (DNA sequencing) and xR (RNA sequencing). The researchers found that IPS status can be used to stratify patient cohorts and prognosticate ICI-treatment response.

Poster Presentation (#1352): Impact of timing of real-world CT imaging on cost-effectiveness of a molecular biomarker for treatment response monitoring of immunotherapy
Session Date & Time: Saturday, November 9, 2024; 9:00 a.m. – 8:30 p.m. CT
Location: George R. Brown Convention Center; Exhibit Halls AB

Overview: The research team sought to model the impact of Computed Tomography (CT) imaging patterns on the clinical utility and cost-effectiveness of a molecular biomarker for treatment response monitoring (TRM) compared to imaging. The team analyzed real-world imaging patterns from a cohort of 4,147 advanced cancer patients treated with immune checkpoint inhibitors (ICI) across five solid tumor types. The study found significant variability in CT scan intervals between cancer types and treatments. Incorporating these patterns into a microsimulation model, the team demonstrated that using the molecular biomarker in conjunction with CT imaging provided substantial cost savings and reduced inappropriate therapy compared to imaging alone, with the most benefit observed in small cell lung cancer (SCLC) treated with ICI-chemotherapy.

On November 8, 2024 Palleon Pharmaceuticals, a clinical-stage company pioneering glyco-immunology drug development to treat autoimmune diseases and cancer, reported results from the Phase 1/2 GLIMMER-01 trial of E-602, its first-in-class human sialidase enzyme therapeutic, in combination with PD-1 inhibitor cemiplimab (Libtayo) in patients with PD-(L)1-resistant solid tumors (Press release, Palleon Pharmaceuticals, NOV 8, 2024, View Source [SID1234648051]). The results will be shared in both rapid oral and poster presentations on Saturday, November 9 at the 2024 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Houston, Texas.

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In the Phase 1/2 study, 21 patients with anti-PD(L)-1-resistant melanoma, non-small cell lung cancer and esophagogastric junction cancer, defined according to the SITC (Free SITC Whitepaper) consensus definition for resistance to immunotherapy, were treated with E-602 in combination with cemiplimab. All patients were assessed for tumor sialoglycan levels and characterized as having hypersialylation or not. The combination was generally well-tolerated, with no dose-limiting toxicities observed. Patients with tumor hypersialylation trended toward better clinical outcomes compared to those lacking hypersialylation, including a confirmed partial response achieved in one anti-PD-1 resistant melanoma patient, and disease stabilization achieved in another six patients. All patients lacking hypersialylation showed disease progression. In addition, paired tumor biopsies from patients with hypersialylation showed tumor desialylation and immune modulation in tumors, however, tumor desialylation only lasted 2-3 days with weekly dosing. These findings provide the first proof of mechanism for glycan editing as a novel therapeutic approach to modulating the immune system.

"The proof of mechanism and antitumor responses observed with E-602 as a combination therapy for patients with solid tumors further validate the therapeutic potential of targeting glyco-immunology to regulate the immune response in treating cancer and autoimmune diseases," said Li Peng, Ph.D., Chief Scientific Officer of Palleon Pharmaceuticals. "We look forward to applying E-602 to treat diseases that align with its pharmacological characteristics, and advancing our next-generation EAGLE molecules that have a longer half-life sialidase and a tumor-targeting moiety to address the unmet needs of cancer patients."

"E602 is the first candidate in a brand new class of therapeutics designed to modulate the immune system by targeting glyco-immunology. Palleon is building a rich pipeline of first-in-class drug candidates with the potential to improve and extend the lives of patients with diseases characterized by immune dysfunction, including cancer and autoimmunity," added Jim Broderick, M.D., CEO and Founder of Palleon.

The study results will be available for viewing on the Palleon Publications section of the Education Hub page of Palleon’s website following the official presentation on November 9.

On November 8, 2024 SystImmune, Inc (SystImmune), a clinical-stage biotechnology company, reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for BL-M17D1, an antibody-drug conjugate (ADC) with a novel linker and payload technology (Press release, SystImmune, NOV 8, 2024, View Source [SID1234648050]). The IND supports the initiation of a Phase 1 clinical trial, BL‑M17D1-ST-101, to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of BL-M17D1 for the treatment of patients with advanced or metastatic solid tumors in the United States.

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‍The clearance of this IND application marks an important milestone for SystImmune as the company continues to advance its pipeline of novel therapeutic candidates into clinical development. Dr. Jie D’Elia, Chief Executive Officer of SystImmune, commented, "Our mission at SystImmune is to bring therapies that can provide transformative clinical benefit to patients. As BL-M17D1 is developed using our next generation linker and payload technology, the initiation of clinical development for BL-M17D1 demonstrates our ability to continue to innovate in the ADC space and bring potentially best-in-class products to patients."

On November 8, 2024 Myeloid Therapeutics, Inc. ("Myeloid"), a clinical-stage immunology company advancing RNA therapeutics to conquer cancer, reported an oral presentation at the Society for Immunotherapy in Cancer (SITC) (Free SITC Whitepaper) 2024 annual meeting, occurring November 6 – 10, 2024, in Houston, Texas (Press release, Myeloid Therapeutics, NOV 8, 2024, View Source [SID1234648049]). Dr. Matthew Maurer, Myeloid’s Chief Medical Officer, will present on Myeloid’s discovery and development of MT-303. MT-303 is the Company’s second in vivo mRNA CAR program to enter the clinic from its pipeline of in vivo immune cell programming therapies.

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MT-303 is a first-in-class Glypican-3 (GPC3) targeting CAR encoded from mRNA and encapsulated in lipid nanoparticles. It is currently in a first-in-human Phase 1 clinical trial of advanced hepatocellular carcinoma (HCC). There are limited treatment options to combat HCC.

GPC3 is a target of growing therapeutic interest given its overexpression in many cancers, including the majority of hepatocellular carcinomas, coupled with limited expression in normal tissues. GPC3 expression has been linked to aggressive tumor behavior and poor prognosis.

Myeloid’s treatment approach focuses on selective in vivo programming of immune cell subsets with innovative off-the-shelf mRNA-encoded CAR technologies. These candidates are administered without the need for preconditioning. MT-303 arms myeloid cells with a proprietary chimeric antigen receptor that expresses specifically within myeloid cells. This approach directs and enables myeloid cells to kill GPC3 expressing cancers while orchestrating a coordinated adaptive immune anti-tumor response marked by expansion of new T cell clones.

"Myeloid has rapidly advanced MT-303 into first-in-human testing as our second in vivo CAR clinical program. Dose escalation of MT-303 and MT-302 continues, and we are encouraged by the ongoing biologic indications of proof-of-mechanism, as well as the early observed safety and efficacy experience," said Dr. Matthew Maurer, Chief Medical Officer of Myeloid. "The clinical observations extend the earlier preclinical results, that also demonstrated selective activation of CAR myeloid cells and robust anti-tumor activity in mouse hepatocellular tumor models."

Oral presentation details are as follows:

Abstract #: 1125
Title: "Preclinical Development of MT-303, a Novel LNP-Formulated GPC3-Specific CAR mRNA, for in vivo Programming of Monocytes to Treat Hepatocellular Carcinoma"
Session Title: Protein and Cellular Engineering Strategies
Session Date and Time: Friday, November 8, 2024, 5:10 pm
Presenting Author: Matthew Maurer – Myeloid Therapeutics

For more information, please visit the SITC (Free SITC Whitepaper) 2024 website.

Myeloid’s in vivo programming candidates are designed with proprietary insights to deliver personalized therapy, providing benefits to patients while reducing time and costs through the elimination of ex vivo handling of patient cells and complex neoantigen sequencing. The Myeloid platform integrates validated antibody/antigen binding with novel combinations of myeloid signaling domains, coded within a simple mRNA that can be delivered repeatedly using lipid nanoparticles (LNPs). The platform’s versatility provides a range of signaling domains and immune cell types useful for combination approaches.

About Liver Cancer

With limited treatment options, and over 850,000 new cases diagnosed globally each year, liver cancer has become the third leading cause of cancer death. After initial treatment success with small molecule therapies, the development of new treatment approaches in the field of liver cancer has been limited. Today, patients with liver cancer who are refractory to first line treatment are left with few treatment options, creating a substantial unmet medical need. Myeloid sees an opportunity to make a significant contribution to address this need, by providing a new CAR for these patients who are living with liver cancer. The CARs are capable of providing a coordinated and durable immune response to counter advanced disease. The CARs are combinable and will expand the treatment options for physicians.

About the Phase 1 Study of MT-303

The MT-303 Phase 1 study (NCT06478693) is an open-label dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of MT-303 in adults with advanced or metastatic hepatocellular carcinoma that overexpresses GPC3. This study will also define the recommended Phase 2 dose (RP2D) of MT-303.

About MT-303

MT-303 represents the first candidate in a new therapeutic modality targeting hepatocellular carcinoma (HCC). This clinical candidate is a first-in-class, GPC3-FcA-LNP, with a strong preclinical profile supporting its advance into this first-in-human trial. GPC3 is overexpressed in most human hepatocellular carcinomas, with limited expression in corresponding normal tissues. Increased GPC3 expression has been linked to tumor growth.

Treatment with MT-303 as a monotherapy demonstrates activity in a GPC3/HCC preclinical model, confirming the tumor-fighting potency of programmed myeloid cells even in the model’s absence of T cells. MT-303 has demonstrated strong expression in myeloid cells and a favorable safety profile in rodents and non-human primates. Unlike other therapies, MT-303 brings the potential advantages of eliciting a full immune response by also presenting tumor neoantigen to stimulate T cells.

MT-303 represents Myeloid’s second in vivo CAR clinical program, building on the company’s innovative approach to cancer treatment through immune cell programming.