On December 8, 2023 Intensity Therapeutics, Inc. (Nasdaq: INTS), 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, reported that safety, tolerability, efficacy and immune activation data from the company’s Phase 2 INVINCIBLE trial of INT230-6 in patients with early-stage breast cancer without chemotherapy was presented at a Podium Poster Spotlight discussion session today during the 2023 San Antonio Breast Cancer Symposium (SABCS) (Press release, Intensity Therapeutics, DEC 8, 2023, View Source [SID1234638352]). Information on the presentation is below.

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Concurrent Poster Spotlight Session Block #6
PS16 Enhancing Immunotherapy for Triple Negative Breast Cancer: Novel Therapies and Biomarkers
Moderator: Hope S. Rugo, MD, FASCO, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California
Title: Intra-tumoral dosing of INT230-6 in early-stage breast cancer patients induces tumor cell necrosis and immunomodulatory effects: A phase II randomized window-of-opportunity study – the INVINCIBLE trial
Presentation #: PS16-03
Date and Time: Friday, December 8, 7:00 – 8:00 a.m. CT
Location: Stars at Night Ballroom 3 & 4
Presenter: Angel Arnaout, M.D., MSc, Ottawa Hospital Research Institute, Ontario Institute for Cancer Research
Discussant: Sangeetha Reddy, M.D., M.S.C.I., UT Southwestern Medical Center, Dallas, Texas

Copies of the presentation materials are available on Intensity’s website on the publications, papers and posters page.

"A large unmet need in the treatment of breast cancer is that the majority of breast cancers are immune quiescent; resulting in minimal response to immunotherapies. INT230-6 has the potential to fill this unmet need for multiple subtypes, including triple negative breast cancer, through its unique multiple anti-cancer mechanisms of action that cause tumor cell necrosis, ignition of an anti-cancer immune-based activation, increasing the diversity of the T-cell repertoire systemically that can enter into the tumor and its microenvironment," said Angel Arnaout, M.D.,MSc., Breast Surgical Oncologist at the Ottawa Hospital, Scientist at the Ottawa Hospital Research Institute, Professor of Surgery at the University of Ottawa and Co-Lead of the Ontario Institute for Cancer Research’s Window-of-Opportunity Network. "The ability for INT230-6 to induce necrosis and noted immune effects prior to a patient’s surgery, while maintaining a favorable safety profile, would be a major move forward for the treatment paradigm of breast cancer and potentially many other cancers."

"I am encouraged by the immune-related data being reported and the potential of INT230-6 as a presurgical treatment for women suffering from early-stage breast cancer," said Melanie Spears, Ph.D., Co-Director of Diagnostic Development and Co-Lead of the Window-of-Opportunity Network at the Ontario Institute for Cancer Research. "The localized effect of increased CD4 T-cells and NK cells within injected tumors and systemically increased T-cell diversity from baseline in these patients is quite interesting and remarkable for a locally-delivered therapy."

The INVINCIBLE Trial is a Phase 2, randomized study that enrolled 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). Drug dose was set by the diameter of the tumor. Subjects were randomly allocated (2:1) prior to resection to 1-3 IT injections of INT230-6 versus either no treatment (part 1 N=29) or saline sham injection (part 2 N=58). Several markers normally associated with systemic treatment were evaluated.

Efficacy Data:
The INVINCIBLE Phase 2 trial of INT230-6 demonstrated a high order of necrosis in presurgical breast cancer tumors in the period from diagnosis to surgery, with some patients in the Phase 2 study experiencing greater than 95% necrosis of the tumor. A functional pathway enrichment analysis was conducted and confirmed positive changes in T-cell activation, lymphocyte activation and inflammatory response. Further, INT230-6 treated patients experienced differential gene expression with an increase in median clonal diversity compared to baseline as well as significant changes in the immune cell composition, including CD4 T-cell and NK cells.

Safety Data:
Data show that INT230-6 has a favorable safety profile and is well tolerated. Over 95% of treatment-emergent adverse events (TEAEs) were low grade 1 or 2 primarily localized pain, fatigue, and nausea.

"We continue to be impressed with the safety and efficacy of INT230-6. Today’s news about the increase in mean systemic T-cell clonal diversity is truly exciting because it is a signal of the strength of adaptive immune response systemically. We believe that the ability to cause large levels of necrosis on a single dose of our locally-delivered drug with immune effects in a relatively cold cancer type such as breast cancer prior to surgery shortly after diagnosis is truly a new weapon in the war on cancer," said Lewis H. Bender, President and Chief Executive Officer of Intensity. "In addition to our anticipated Phase 3 program in metastatic sarcoma using INT230-6 as a monotherapy, we are underway in our preparations for a Phase 2/3 clinical program to test INT230-6 in combination with standard of care neoadjuvant therapy. We see the potential opportunity for our technology and drug products in both the metastatic and presurgical settings for many types of cancers."

About T-Cell Repertoire
The adaptive immune system is one of the body’s most powerful defenses. By being able to adapt, the body’s immune cells can be trained to attack undesirable cells or viruses anywhere in the body. T-cells are an important systemic component of the adaptive immune system that aid in the destruction of invaders. Immune repertoire refers to all the unique T-cell receptor (TCR) and B-cell receptor (BCR) genetic rearrangements. Only lymphocytes that encounter an antigen with the right receptor to bind to it will be activated and proliferate during an immune response, forming a clone of cells with identical antigen receptors for attack. A greater diversity of T-cell repertoire means there is higher likelihood for a T-cell to bind to the foreign entity (e.g. cancer cells) and increase the specific T-cell clonal population to destroy the invader.

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 immunosuppression that so often occurs with systemic chemotherapy.