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Alpheus Medical Treats First Patients in First-In-Human Clinical Trial for Novel High-Grade Glioma Brain Cancer Treatment

On November 10, 2022 Alpheus Medical, Inc, a privately held company developing a novel sonodynamic therapy (SDT) platform targeting solid body cancers, reported the treatment of the first three patients in the U.S.-based multi-center Phase 1 clinical trial evaluating the safety and optimal dosage of the company’s proprietary platform (Press release, Alpheus Medical, NOV 10, 2022, View Source [SID1234623870]).

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The milestone coincides with the announcement that the company nearly doubled their recent Series A investment and closed a $14 million follow-on round with existing investor participation from OrbiMed Advisors, Action Potential Venture Capital, the Medtech Convergence Fund, an SV Health Investors venture fund, and BrightEdge, the impact investment and venture capital arm of the American Cancer Society. Driven by a successful pre-clinical program, the new investment will be used to expand cohorts in the first-in-human (FIH) clinical trial, initiate an additional clinical trial internationally, and pursue indications for other non-brain, solid body cancers.

"Conventional therapy options for patients with high-grade glioma, including glioblastoma, are limited and innovation in the field has too long been stagnant, leaving patients with poor outcomes and significant tradeoffs in quality of life. By non-invasively targeting and eradicating tumor through the entire brain hemisphere, Alpheus’ novel SDT platform represents a potential paradigm shift in the fight against this disease," stated Michael Schulder, MD, Director of the Brain Tumor Center at Northwell Health’s Institute for Neurology and Neurosurgery. "We are excited to be part of this important clinical trial and look forward to following these patients as we evaluate the therapy."

"The heterogeneous, diffuse nature of gliomas behind the blood-brain-barrier (BBB) is preferably treated with a repeatable, large-field therapy that can extend beyond the borders of the visible tumor to eradicate the highly invasive cancer cells," remarked Tanner M. Johanns, MD, Assistant Professor of Medical Oncology at Washington University School of Medicine in St. Louis. "Alpheus’ non-invasive SDT therapy aims to overcome both challenges with a safe, repeatable therapy that targets only cancer cells." Dr. Johanns and Dr. Schulder are primary investigators in the Alpheus trial.

Alpheus Medical’s investigational SDT treatment includes an innovative, non-invasive drug-device combination that targets cancer cells throughout the entire brain hemisphere using low-intensity, large-field ultrasound. The treatment can be done in an outpatient setting, allows for repeat treatment, and does not require the use of imaging, such as MRI.

The FIH Phase 1 multi-center trial (NCT05362409) is designed to study the safety and optimal dosage of Alpheus’ SDT treatment and is planned to enroll up to 33 patients. The trial is currently enrolling patients with high-grade gliomas, including glioblastomas, across three sites, including Northwell Health’s North Shore University Hospital (greater New York City, NY), Washington University in St. Louis (St. Louis, MO), and Dent Neurologic Institute (Buffalo, NY).

"Thanks to our clinical and investor partners, we are building a company that is poised to revolutionize the treatment of brain cancer with our non-invasive, repeatable SDT platform," stated Dr. Vijay Agarwal, CEO and founder of Alpheus Medical and a practicing brain tumor surgeon in New York City. "These milestones follow our recent Orphan Drug and Fast Track Designations from the FDA and build momentum as we work towards advancing this novel technology to market for the treatment of high-grade gliomas and other solid body tumors."

NCCN Announces Funding for Bladder Cancer Research Projects, in Collaboration with Pfizer and EMD Serono

On November 10, 2022 The National Comprehensive Cancer Network (NCCN) Oncology Research Program (ORP) reported awards and funding for projects focused on improving quality of patient care and outcomes for locally advanced or metastatic bladder cancer (Press release, NCCN, NOV 10, 2022, View Source [SID1234623869]). Funding and oversight will be provided through support from Pfizer and EMD Serono.

Surgically unresectable metastatic bladder cancer remains largely incurable, with few patients surviving more than two years. Real-world studies suggest that only about half of bladder cancer patients receive appropriate front-line therapy and, of those, many are not offered second-line or subsequent therapies despite the benefits of survival with these treatments. The goal of these projects is to address barriers, challenges, and opportunities for improving care, through navigation, expert care review, shared-decision making, care planning workflows, and patient reported outcomes.

"NCCN Guidelines already contain evidence-based recommendations for improving outcomes in bladder cancer; now we need to address the many factors that keep patients from receiving optimal treatment. These quality improvement projects will explore potential methods to address some of the barriers, including patient age, socioeconomic status, and location," said Crystal S. Denlinger, MD, FACP, Senior Vice President, Chief Scientific Officer, NCCN. "Congratulations to all of these inspiring investigators. We hope their work can supply real-world insights and answers, to guide improvement in the quality of patient care."

The selected projects are:

Joaquim Bellmunt, MD, PhD, Dana-Farber Cancer Institute
Management of Cisplatin-Ineligible Patients with Metastatic Bladder Cancer and The Role of Geriatric Assessments
Adam Gadzinski, MD, Beaumont Health
Metastatic Bladder Cancer ECHO
Dharmesh Gopalakrishnan, MD, Roswell Park Comprehensive Cancer Center
A Comprehensive Education and Navigational Support Program for Advanced Bladder Cancer
Sumati Gupta, MD, Huntsman Cancer Institute at the University of Utah
Integrating Geriatric and Oncology Care Principles in Advanced Urothelial Cancer Care
Anoop Meraney, MD, Hartford HealthCare
Use of Patient-Provided Data to Improve Care for Advanced Bladder Cancer Patients
Nihal Mohamed, PhD, Icahn School of Medicine at Mount Sinai
Assessment of Supportive Care and Educational Needs to Guide Quality Care Improvements for Patients with Locally Advanced and Metastatic Bladder Cancer (ACCESS)
Proposals were peer reviewed by a Scientific Review Committee, which consisted of leading expert oncologists from NCCN Member Institutions. The selected projects are set to be completed within two years. Approximately $1.2 million in funding will be provided across all grants.

The NCCN ORP fosters innovation and knowledge discovery that improve the lives of people with cancer and supports preclinical, translational, and clinical research and quality improvement projects in oncology at NCCN Member Institutions. In an effort to improve collaboration in cancer research, the NCCN ORP also maintains a shared resources website, an informed consent database, and points to consider on the best practices for biorepositories, registries, and databases. For more information, visit NCCN.org/orp.

Myeloid Therapeutics Presents Update On Myeloid Cell Programming Technologies, Including Non-Human Primate Proof-Of-Concept Data Delivering in vivo mRNA TROP-2 Targeting CAR (MT-302) at Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting

On November 10, 2022 Myeloid Therapeutics, Inc. ("Myeloid"), a clinical stage mRNA-immunotherapy company, reported that multiple posters on its therapeutics platforms, ATAK CAR receptors and in vivo mRNA programming, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting, being held in Boston, MA, November 8-12, 2022 (Press release, Myeloid Therapeutics, NOV 10, 2022, View Source [SID1234623868]).

"The data presented at SITC (Free SITC Whitepaper) further highlight the power of Myeloid’s platform to enable broad immune responses and attack cancer cells, supporting the accelerated development of our deep clinical and preclinical pipeline," said Daniel Getts, Ph.D., CEO of Myeloid. "In particular, we are really excited about the progress we’ve made with in vivo programming with MT-302, our TROP2-FcA-LNP, that has shown confirmed tumor killing activity and strong expression in myeloid cells in non-human primates. We are planning to advance this program into the clinic and expect to file an IND in 2023."

Myeloid has combined the power of mRNA with proprietary ATAK CAR receptors, to program myeloid cells to target and kill cancer through direct mechanisms and the elicitation of a broad anti-tumor responses, including the activation of T cells. Myeloid cells are a primary orchestrator of immune response and accumulate naturally within solid tumors, in some cases representing up to seventy-five percent of the tumor mass. Myeloid’s adaptations of mRNA for the myeloid compartment have enabled the evolution to deliver these receptors directly to the patient without any ex-vivo cell engineering.

Myeloid’s novel in vivo engineering platform specifically targets and activates myeloid cells to elicit broader anti-tumor adaptive immunity. Through this approach, Myeloid demonstrates that delivery of lipid-nanoparticles (LNPs) encapsulating mRNA results in selective uptake and expression by myeloid cells in vivo, leading to potent tumor killing in multiple cold tumor models. These data demonstrate the potential for Myeloid’s technology to program cells directly in vivo.

Myeloid’s lead program from this platform, MT-302, is a TROP2-FcA-LNP currently in IND-enabling studies for the treatment of multiple indications including colon, lung and breast cancer. MT-302 has demonstrated strong expression and favorable safety in myeloid cells in two species, rodents and non-human primates. In addition, treatment with MT-302 demonstrates monotherapy activity in a TROP2/TNBC model, confirming the potency of programmed myeloid cells in the absence of T cells. Myeloid believes that MT-302 has significant advantages over TROP2-ADC approaches through its ability to engage the full immune response.

Myeloid’s novel class of CARs, known as ATAK Receptors, combine tumor recognition with multiple proprietary innate-immune signaling domains. Myeloid scientists have screened multiple unexplored combinations of innate-immune signals and uncovered optimal multi-signal pathways. The combination of cancer recognition binders with these novel intracellular signaling domains allows myeloid cells to be reprogrammed with previously unexplored combinations of immune signals, leading to tumor killing and broad systemic anti-tumor responses that support their clinical development in cell therapies.

Marengo Therapeutics Presents Preclinical Data Supporting Clinical Investigation of its Lead Asset, STAR0602, at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting

On November 10, 2022 Marengo Therapeutics, Inc., a company pioneering novel therapeutics targeting the T cell receptor Vβ chain (TCR Vβ) to selectively activate the right T cell subsets to fight cancer, reported that it will be presenting preclinical data that characterizes the mechanism of action and confirms robust anti-tumor activity for its novel T cell-activating antibody STAR0602 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting in Boston (Press release, Marengo Therapeutics, NOV 10, 2022, View Source [SID1234623867]). The data disclosed also includes extensive characterization pharmacokinetic (PK) and pharmacodynamic (PD) relationships of STAR0602 in NHP studies. These data support the modelling of human pharmacology and inform the design of START-001, a Phase 1/2 clinical trial of STAR0602 monotherapy in a biomarker enriched, tissue agnostic, PD-1 refractory cancer patient population.

"STAR0602 has been shown to promote potent anti-tumor activity through a PD-1 independent mechanism and leads a new IO category of selective immune activators, potentially offering another important treatment option to reach more patients," said Zhen Su, M.D., MBA, Chief Executive Officer of Marengo. "We are pleased to present a compelling body of preclinical data that builds on the initial proof-of-concept data shared during our Plenary Oral presentation at the recent 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium last month."

The data presented at SITC (Free SITC Whitepaper) by Marengo scientists and its academic collaborators highlight Marengo’s novel TCR Vβ repertoire-targeting antibody platform, which promotes the expansion of polyclonal Vβ T cells with a novel effector memory phenotype.

Presentation details are outlined below.

Title: A novel class of T cell-activating antibody that selectively targets the TCR β chain to promote antitumor activity through activation and expansion of a novel, polyclonal effector memory T cell subset
Abstract Number: 1316
Presenter: Andrew Bayliffe, Ph.D. (Marengo Therapeutics, Cambridge, Massachusetts USA)
Research Highlights: STAR0602 is a first-in-class bifunctional fusion molecule that selectively binds and activates subsets of the germline TCR repertoire. In vitro, STAR0602 promotes a novel T cell phenotype with hallmarks of both effector and central memory cells, and in vivo mSTAR0602 demonstrates potent and durable single-agent anti-tumor activity in several solid tumor models that is dependent on expanded Vβ T cells. The modulation of the tumor microenvironment (TME), striking increase in TCR diversity, and functional immune memory observed in murine models suggests that STAR0602 could remodel the adaptive immune response to solid tumors that are refractory to checkpoint inhibitor therapy, and thus represents a novel therapeutic strategy for patients.

Title: Preclinical evaluation of STAR0602, a novel, first-in-class anti-TCR Vβ targeted bispecific antibody with potent anti-tumor activity for PD-1 refractory solid tumors
Abstract Number: 1337
Presenter: James Gulley, M.D., Ph.D. (National Cancer Institute, Bethesda, Maryland USA)
Research Highlights: STAR0602 is a first-in-class T cell activator that targets subsets of the germline TCR repertoire that are enriched in TILs. STAR0602 potently expands both naive and antigen-specific human T cells. In PD1 refractory human organoid models with a high TMB, STAR0602 induced potent anti-tumor activity as monotherapy, mediated by selective expansion of Vβ CD8+ memory T cells. This pharmacology was translated into monkeys with IV dosed STAR0602 and supports the design of a novel Phase 1/2 precision-oncology trial with STAR0602 planned to commence in 2022.

Title: An atypical central-memory like phenotype can be induced in human T cells by Innate TCRαβ engagement
Abstract Number: 1392
Presenter: Pierre Vantourout, Ph.D. (Kings College London, London, UK)
Research Highlights: Engaging germline-encoded regions of human TCRVβ consistently activate primary human T cells toward an atypical central memory (TCM)-like phenotype distinct from those most commonly described for anti-CD3 antibody stimulation. The cells show myriad surface markers of chronic stimulation, but are not exhausted, being highly proliferative and strongly expressing cytolytic mediators and IFN-γ. This phenotype can be induced in cells previously driven toward effector memory (TEM) and TEMRA states. The use of TCRβ chain as an innate receptor offers new insight into T cell biology and ways in which such cells might be clinically manipulated.

HotSpot Therapeutics Presents Preclinical Data from CBL-B Program at 2022 Society for Immunotherapy of Cancer Annual Meeting

On November 10, 2022 HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of orally delivered, small molecule allosteric therapies for the treatment of cancer and autoimmune diseases, reported the presentation of additional preclinical data on the Company’s Casitas B-lineage lymphoma proto-oncogene (CBL-B) program in two poster presentations at the 2022 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, HotSpot Therapeutics, NOV 10, 2022, View Source [SID1234623866]).Due to its role as a gatekeeper in immune cell activation, CBL-B inhibition holds the potential to address several key mechanisms important in immuno-modulation. Translational data supports a role for CBL-B inhibition to address suboptimal response to current immunotherapies in certain cancers. Targeting CBL-B represents a novel therapeutic approach because inhibition of CBL-B has been shown to lower the threshold for T cell and NK cell activation, even in the absence of co-stimulatory signals, potentially bringing benefit to patients with suboptimal conditions in the tumor microenvironment.

"At HotSpot, we are generating preclinical data elucidating the central role of CBL-B inhibition to immune cell activation, providing strong biological rationale for this mechanism’s potential as a promising immuno-oncology treatment option," said Geraldine Harriman, Ph.D., Co-Founder and Chief Scientific Officer of HotSpot Therapeutics. "Our data in syngeneic mouse models underscore the broad range of immunostimulatory activity of CBL-B inhibition which, coupled with compelling data from the mixed lymphocyte reaction (MLR) assay, a clinical correlate for I-O agents, as well as clear synergistic activity with anti-PD-1, support the continued advancement of our CBL-B inhibitor program. We look forward to continuing to work toward advancing HST-1011, our lead CBL-B inhibitor development candidate, into the clinic."

The presentations describe compelling data for HotSpot compounds designed as novel, allosteric, small molecule inhibitors of CBL-B E3 ubiquitin ligase activity:

A HotSpot CBL-B inhibitor demonstrated immune-mediated tumor growth inhibition in multiple syngeneic mouse models. Gene expression profiling of the tumor microenvironment demonstrated upregulation of pro-inflammatory pathways in vivo. These effects were notable with CBL-B inhibition alone and further enhanced when combined with a PD-1 inhibitor.
In the MLR assay, a predictive correlate of the clinical activity of I-O therapies, the HotSpot CBL-B inhibitor demonstrated robust effects on cytokine release and T cell proliferation as monotherapy. Additionally, CBL-B inhibition demonstrated synergistic activity in the MLR assay when combined with anti-PD1.