Data Show INT230-6 is Well Tolerated and Elicits Both Direct Tumor Killing and Immune Activating Effects in a Variety of Sarcomas

In a Heavily Pre-Treated, Mixed, Advanced Sarcoma Population, the Median Overall Survival (mOS) of INT230-6 Alone was 649 Days (n=15)

When Combined with Ipilimumab, the mOS has not Been Reached with 297 Days of Median Follow-Up (n=12)

Full Set of Results to be Presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting in Both Poster and Oral Discussion Sessions

WESTPORT, Conn., June 2, 2022 /PRNewswire/ -- 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, announced that data from its ongoing phase 1/2 clinical trial in refractory patients demonstrating the efficacy and tolerability of INT230-6, either as monotherapy or in combination with ipilimumab in patients with relapsed, refractory and metastatic sarcomas, will be presented on June 5, at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting being held in Chicago and virtually from June 3-7, 2022.

Abstract Title: INT230-6 monotherapy and in combination with ipilimumab (IPI) across a broad spectrum of refractory soft tissue sarcomas (STS) [Intensity IT-01; BMS#CA184-592].
Presenter/First Author: Matthew Ingham, MD
Session Type/Title: Poster Discussion Session/Sarcoma
Poster Discussion Session Date and Time: Sunday, June 5, 2022, 12:30 PM – 2:00 PM EDT
Location: In-Person & On Demand | S404
Abstract Number: 11515
Poster: 420 (9:00 am to 12:00 am EDT)

Copies of the presentation materials will also be available on the Intensity Therapeutics website on the publications and posters page, following completion of the live presentation.

"Sarcoma has been a very challenging cancer to treat and has proven resistant to checkpoint blockade. Novel immunotherapy-based approaches are needed, and sarcoma is an attractive cancer for intratumoral injection," stated Matthew Ingham, M.D., assistant professor of medicine in the Division of Hematology and Oncology, Columbia University Vagelos College of Physicians and Surgeons, and a principal investigator for the trial. "The results from this ongoing study are maturing and showing compelling early signs of efficacy with this intratumoral approach as monotherapy. Preliminary data from this study also show immune cell infiltration with INT230-6 alone, in sarcoma, which is normally a non-immunogenic cancer type, that may be enhanced by combination with ipilimumab."

We are excited to have had our abstract, 11515, selected for both a poster and a podium discussion at ASCO this year," stated Lewis H. Bender, President and Chief Executive Officer of Intensity Therapeutics. "The biomarker and clinical data generated in sarcoma patients provide strong proof-of-concept evidence for our approach and underscore the potential of this new, potential treatment. As recent data readout events in the field of oncology have shown, there remains a high unmet need for novel therapeutic approaches in this deadly disease. With the strength of this data and following a meeting with FDA, we are in the process of designing a phase 3 clinical study."

The presentations report the mOS and disease control rate (DCR: CR + PD + SD per the Response Evaluation Criteria in Solid Tumors (RECIST)).  However, RECIST metrics (sum of longest diameters) to gauge efficacy are only validated for use with systemically delivered therapies. Data generated in the study suggests that RECIST is inadequate with intratumorally (IT) administered INT230-6. In this study, RECIST response is complicated by the amount of INT230-6 repeatedly injected and retained in the tumors prior to the first radiographic scan. Biomarker findings suggest immune infiltration into the tumor microenvironment is occurring that could also increase tumor size. Additionally, results in a neoadjuvant setting (see ASCO 2022 Abstract Number: 605, Poster: 376) show a single injection of INT230-6 can cause near complete necrosis of the tumor without change in diameter. Finally, data reported shows that tumor volume, when calculated using all three dimensions, can be decreasing while the longest diameter of the corresponding tumor is increasing or stable. The lack of correlation between longest diameter and actual volume illustrates that RECIST may be unreliable for use as an efficacy endpoint for IT INT230-6.

As of the April 21, 2022 cutoff, the phase 1/2 clinical trial evaluated 27 patients with a heterogenous mix of several sarcoma subtypes including leiomyosarcoma, liposarcoma, pleomorphic sarcoma, chondrosarcoma, sacral chordoma, undifferentiated, connective tissue, osteosarcoma (chondroid syringoma), myofibroblastic, Kaposi, myxoid spindle cell, Langerhans  and fibrosarcoma. The preliminary efficacy and safety of either INT230-6 alone (n=15) or in combination with the anti-CTLA-4 antibody, ipilimumab (n=12) were evaluated. Patients were treated with and progressed following a median of three prior therapies in the monotherapy group and five prior treatments receiving the combination. INT230-6 was administered intratumorally every two weeks for five doses either alone or with 3 mg/kg of ipilimumab dosed every three weeks for four doses. Preliminary efficacy measured DCR and mOS. Additional outcome measures included safety/tolerability, response in the injected tumor and the pharmacokinetic profile. The DCR rate >50 days for monotherapy in sarcoma (excluding chordoma) was 56% and the DCR for INT230-6+IPI was 57%.

Study IT-01 is a single arm study; however, published clinical phase 1/2 basket trials in sarcoma report mOS, ranging from 7.6 to 9.6 months (Jones et. al., Cancer Chemother Pharmacol (2011) 68:423–429; Cassier et. al., Annals of Oncology 25: 1222–1228, 201; vi. Subbiah et. al., Scientific Reports | 6:35448 2016,).  Using the Subbiah study data set and the RMHI scores from the IT-01 study sarcoma patients, a synthetic control group Kaplan Meier (KM) survival curve was generated.  The overall survival of the control, all INT230-6 patients in sarcoma and those receiving a cumulative dose of greater than 40% of their total tumor burden (TTB), are shown in the below table. Subjects receiving combination with ipilimumab have not yet reached median survival with 297 days median follow-up. There has been only 1 death reported in the combination group as of data cut-off. The Hazard Ratio (HR) for monotherapy patients to the control was 0.290 CI (0.173, 0.494), whereas the HR for monotherapy patients receiving INT230-6 at a dose great than or equal to 40% of the TTB was 0.236 CI (0.130, 0.423). Data is encouraging though the sample size is small. Sarcoma subtypes may differ between groups and data is still early. 

The pharmacokinetic profile for the individual drug components of INT230-6 (cisplatin and vinblastine sulfate) was measured and ~95% of the active agents remaining in the tumor. Additional outcome measures included overall safety. INT230-6, either as monotherapy or in combination with ipilimumab, was well tolerated. The most common treatment related adverse events (TRAEs) were localized tumor-related pain, nausea, fatigue, decreased appetite and vomiting in the monotherapy group. TRAEs were mild to moderate, with 20% grade 3 in the monotherapy group and 11% in combination with ipilimumab. There were no Grade 4 or 5 AEs.

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 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.

INT230-6 is currently being evaluated in several phase 2 cohorts (NCT03058289) in patients with various advanced solid tumors as part of Study IT-01. In 2019, the Company signed a clinical collaboration agreement with Merck Sharpe & Dohme (Merck) to evaluate the combination of INT230-6, Intensity's lead product candidate, and KEYTRUDA® (pembrolizumab), Merck's anti-PD-1 (programmed death receptor-1) therapy, in patients with advanced pancreatic, colon, squamous cell and bile duct malignancies. In 2020, the Company executed a clinical collaboration agreement with Bristol-Myers Squibb to evaluate the combination INT230-6 with Bristol-Myers Squibb's anti-CTLA-4 antibody, Yervoy® (ipilimumab), in patients with advanced liver, breast and sarcoma cancers. Intensity is managing the individual combination arms separately with each respective partner via a joint development committee. In 2021, the Company executed agreements with the Ottawa Hospital Research Institute (OHRI) and the Ontario Institute of Cancer Research (OICR) to study INT230-6 in a randomized controlled neoadjuvant phase 2 study in women with early stage breast cancer (the INVINCIBLE study) (NCT04781725).

Intensity Therapeutics, Inc. is a clinical-stage biotechnology company pioneering a new immune-based approach to treat solid tumor cancers. Intensity leverages its DfuseRx℠ technology platform to create new, proprietary drug formulations that, following direct injection, rapidly disperse throughout a tumor and diffuse therapeutic agents into cancer cells. Intensity's product candidates have the potential to induce an adaptive immune response that not only attacks the injected tumor, but also non-injected tumors. In addition to the clinical collaborations, the Company executed a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute's (NCI) Vaccine Branch in 2014. For more information, please visit www.intensitytherapeutics.com and follow the Company on Twitter @IntensityInc.

This press release contains forward-looking statements regarding Intensity Therapeutics' plans, future operations and objectives. Such statements involve known and unknown risks, uncertainties and other factors that may cause actual performance or achievements to be materially different from those currently anticipated. These forward-looking statements include, among other things, statements about the initiation and timing of future clinical trials.

YERVOY® is a trademark of Bristol-Myers Squibb Company.

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