On November 10, 2022 Intensity Therapeutics, Inc. ("Intensity"), a clinical-stage biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, along with The Ottawa Hospital and Ontario Institute of Cancer Research ("OICR"), reported that it will present updated data from the INVINCIBLE study, a randomized, phase 2 presurgical window of opportunity trial for Intensity’s intratumoral INT230-6 comprising SHAO (dispersion enhancer), vinblastine (VIN) and cisplatin (CIS), that is evaluating clinical and biological effects in patients with early-stage operable breast cancer (Press release, Intensity Therapeutics, NOV 10, 2022, View Source [SID1234623873]). The study, to be presented today at the 2022 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting being held in Boston and virtually from November 8-12, 2022, will report data demonstrating efficacy and tolerability of INT230-6.

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Abstract Number: 545
Title: A Phase II Randomized Window of Opportunity Trial Evaluating Cytotoxic and Immunomodulatory effects of Intratumoral INT230-6 (Cisplatin, Vinblastine) in Early Stage Breast Cancer: the INVINCIBLE Trial
First Author: Angel Arnaout, M.D., FACS
Session Date and Time: Thursday, November 10, 2022, 9:00 am – 9:00 pm EST
Location: Hall C; In-Person & On Demand

Copies of the presentation materials will be available on the Intensity Therapeutics website on the publications and posters page.

"For a breast cancer patient, the typical waiting period of 2-6 weeks from diagnosis to surgery is a very anxious time. Surgeons and patients feel helpless, as there are currently no therapeutic options for the patient during this time," said Angel Arnaout, M.D., Scientist and Surgical Oncologist at the Ottawa Hospital, and Professor of Surgery at the University of Ottawa and Co-lead of OICR’s Window-of-Opportunity Network. "INT230-6 remains in the tumor following injection and can cause tumor cell death and high levels of necrosis in multiple breast cancer subtypes including triple negative breast cancer, as demonstrated by Part 1 of this study. Interestingly, we also saw immune activation with a relative increase in the abundance of CD4 T naïve, B and NK cells, post treatment, and, within the tumor microenvironment, a relative increase in abundance of CD8 memory T, CD4 naïve and B cells, post treatment, when comparing drug treated with control samples. The ability to use just one or two doses of this agent to elicit a rapid and marked cytotoxic and immune induction response within the tumor during the surgical waiting period, all without an increase in postoperative complications, is very novel and highly attractive to patients. We are excited about how this may shift the paradigm on how we treat cancer patients awaiting surgery, in general. We look forward to future studies to demonstrate how this intratumoral agent can have systemic benefit and long-term impact in patients with breast cancer."

"INT230-6’s ability to rapidly cause high levels of tumor necrosis combined with immune activation in early stage breast cancer patients with only low grade adverse events is unprecedented and quite exciting," said Lewis H. Bender, President and Chief Executive Officer of Intensity Therapeutics. "The results from the INVINCIBLE study, coupled with our data in metastatic patients, provide strong evidence and support for the potential of our drug in treating cancer patients from before surgery to late stage disease. We look forward to the full data set from the INVINCIBLE study and further development of our pioneering new medicine."

About the INVINCIBLE Study
The INVINCIBLE study (NCT 04781725), a phase 2, randomized, open label study, has enrolled 91 women with newly diagnosed, operable early-stage intermediate or high-grade T1-T2 invasive breast cancers 2 to 5 weeks prior to surgery (lumpectomy or mastectomy). Dose was set by the diameter of the tumor. Subjects were randomly allocated (2:1) prior to resection to 1 to 3 IT injections of INT230-6 versus no treatment (part 1 n=29) or saline sham injection (part 2 n=58). Part 1 evaluated safety, feasibility, and dose amounts. Part 2 was a double-blind, randomized arm. The objective of using saline will be to rule out the potential confounding effect of hydrostatic pressure on tumor necrosis. The results of Part 2 will further evaluate the potential cytotoxic, immunomodulatory and other biologic effects of INT230-6 and its role as a potential cancer therapy in breast cancer patients awaiting surgery. The INVINCIBLE study is being conducted under a Health Canada (HC) approved Clinical Trial Application (CTA), under the direction and supervision of Principal Investigator, Dr. Angel Arnaout. The Ottawa Hospital Research Institute conducted subject enrollment and treatment and will evaluate clinical responses. OICR will analyze subject immune responses and conduct biomarker analyses such as Ki67 and T-cell repertoire.

About Potential INT230-6 Approval Pathways in the Presurgical Setting
The U.S Food and Drug Administration (FDA) instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint. Pathological complete response (pCR) is an accepted FDA accelerated approval criterion for approval in high-risk breast cancer, such as triple negative breast cancer (TNBC) subtype. pCR is defined as the absence of residual invasive and in situ cancer after evaluation of the complete resected breast specimen and lymph nodes following completion of neoadjuvant systemic therapy.

Data from the INVINCIBLE study will provide an understanding of the effect of INT230-6 on cancer cell proliferation and tumor necrosis. If INT230-6 causes increased tumor necrosis with good safety, then the addition of INT230-6 to the existing or a modified neoadjuvant (presurgical) systemic standard-of-care treatment regimen may increase pCR rates in TNBC. In November of 2020, Intensity Therapeutics met with FDA and discussed the potential use of INT230-6 in the presurgical neoadjuvant breast cancer setting in an accelerated approval program.

About INT230-6
INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug is composed of two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor resulting in a favorable safety profile. In addition to local disease control, direct killing of the tumor by INT230-6 releases a bolus of neoantigens specific to the patient’s malignancy, leading to engagement of the immune system and systemic anti-tumor effects. Importantly, these effects are mediated without the immunosuppression of concomitant systemic chemotherapy.

On November 10, 2022 Galvanize Therapeutics, Inc., a commercial-stage biomedical platform company operating at the convergence of engineering, biology and healthcare delivery, reported promising clinical data using its Aliya Pulsed Electric Field (PEF) system in patients with non-small cell lung cancer (NSCLC) (Press release, Galvanize Therapeutics, NOV 10, 2022, View Source [SID1234623872]).

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Initial results from the INCITE-ES clinical study conducted outside of the U.S., presented at this week’s Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting, indicate that the Aliya PEF system has the potential to stimulate an immune response in NSCLC patients.

INCITE-ES is a prospective, two-arm, non-randomized, concurrently controlled, multi-center treat-and-resect study in patients with suspected or confirmed NSCLC stage IA2-IB. In 30 patients PEF energy was delivered to a solitary tumor either percutaneously or endoscopically at the time of biopsy, prior to surgical resection. Eight additional patients were enrolled in the non-treated control group. Data presented previously demonstrated safety and feasibility to deliver PEF with no device or procedure-related adverse events. In an initial cohort of 10 PEF treated patients, tertiary lymphoid structures (TLS) [average 43.1 ± 41.0, (range 5-113)] were observed within tumors post-PEF, whereas none were identified on pre-PEF biopsy. TLS accumulation was greater in the PEF treated group as compared to the non-treated control group. TLS formation, shown in other studies to generate anti-tumor immunity¹, is emerging as a strong prognostic and predictive biomarker2 associated with patient survival benefits in NSCLC3,4.

"The five-year survival rate for NSCLC has only modestly improved from 13% in the 1970s to 21.7% in 20195, despite advances in surgery, radiation and advanced therapeutics," explained Marcelo Jimenez, MD, PhD, Professor of Surgery, Thoracic Surgery Department, Salamanca University Hospital, Spain, investigator in the INCITE ES clinical study. "New treatment approaches are critically needed in NSCLC, and early indications of the potential for pulsed- electric field energy to activate the patient’s immune system are very encouraging. I look forward to future studies assessing this novel immuno-oncology approach in more patients."

"These early clinical data build upon the recent U.S. Food and Drug Administration (FDA) 510(k) clearance for the Aliya system for soft tissue ablation and add to our confidence that PEF has the potential to mutually kill target cells and create immunogenic molecules," said Jonathan Waldstreicher, M.D., Founder and CEO of Galvanize Therapeutics. "We are eager to expand our clinical program to further understand the opportunity for PEF to stimulate the immune system to activate against NSCLC and other solid tumors."

About Aliya PEF System
The Aliya PEF system delivers non-thermal, high-voltage, high-frequency electrical currents through a single monopolar electrode placed in the target tissue. The PEF energy destabilizes the cells, resulting in cell death.

The non-thermal modality of the Aliya PEF system preserves surrounding healthy tissue, enabling ablation near critical structures, such as nerves and blood vessels. The Aliya waveform and electrode are designed to maximize the potential for releasing tumor antigens and may stimulate an immune response, potentially disrupting the immunosuppressive tumor microenvironment.

The Aliya System is 510(k) cleared in the United States for the surgical ablation of soft tissue. It is not currently commercially available in any other geography.

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."

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.

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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.

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]).

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"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.