Intensity Therapeutics Provides Business Update Reflecting Progress in Phase 3 Sarcoma Program

Intensity Therapeutics, Inc. recently announced a business update reflecting progress in its Phase 3 sarcoma clinical program.

In the fourth quarter of 2023, the company submitted a new Investigational New Drug (IND) to the US FDA. The submission included the Phase 3 protocol for a superiority trial of the company’s lead product INT230-6 used as monotherapy compared to the standard of care drugs in second and third line treatment for certain soft tissue sarcoma subtypes. The FDA provided the company a Study May Proceed letter for Phase 3 within the 30-day period following the IND submission.  The study is an open-label, randomized Phase 3 trial expected to enroll 333 patients. For every three patients enrolled, two will receive INT230-6 and one will receive standard of care drug(s) chosen by the investigators depending on the type of sarcoma.  The company is working with its contracted vendors  to initiate the Phase 3 trial in the first half of 2024.

In the fourth quarter of 2023, the company successfully developed the Phase 3 quality analytical methods for measurement of the key INT230-6 components, validated those methods and manufactured a clinical batch of the drug product that met specifications. During the fourth quarter, the company requested and was granted a meeting that was held with the FDA to review the INT230-6 chemical manufacturing and controls (CMC) for INT230-6. The CMC discussion focused on the tasks necessary to initiate the Phase 3 study and future product registration as part of a potential New Drug Application (NDA). During the meeting, the company and FDA agreed upon a plan for the CMC set of activities for the active pharmaceutical ingredients and the drug product (INT230-6) necessary for the NDA.

“The FDA’s Study May Proceed letter is another important milestone toward achieving our mission to develop a new, safer, and more effective way to treat cancer patients especially in the difficult to treat types such as sarcoma.  A head-to-head comparison of INT230-6 as monotherapy locally delivered in metastatic sarcoma against the active, systemically delivered standard-of-care drugs may be a first-of-its kind clinical trial,” said Lewis H. Bender, President and Chief Executive Officer of Intensity. “Current standard-of-care drugs used for sarcoma after progression of the first line therapies require extensive safety monitoring. The standard of care drugs cause severe toxicities and provide median overall survival of only between 12 and 15 months depending on the drug and sarcoma subtype used.  New and more effective ways to treat these patients are desperately needed.”

In November of 2023 at the annual Connective Tissue Oncology meeting held in Dublin, Christian Frederick Meyer, MD, PhD, MS, an Assistant Professor of Oncology at the Sidney Kimmel Cancer Center at Johns Hopkins University and an investigator for Intensity’s Phase 1/2 clinical trial of INT230-6, presented that when compared to a synthetic control, INT230-6 alone extended survival in refractory soft tissue sarcoma subjects by approximately 14.9 months. Dosing higher amounts of INT230-6 relative to a patient’s presenting total tumor burden showed a potential further increase in survival when compared to the synthetic control.

• Median survival of the synthetic control for subjects failing a median of 3 lines of prior therapy was about 6.8 months.
• Median overall survival of INT230-6 monotherapy (n=15) was 21.5 months.
• The INT230-6 Disease Control Rate was 93% in subjects who received at least one dose of INT230-6 as monotherapy.

Data on INT230-6 generated in metastatic patients indicated that INT230-6 has a favorable safety profile and is well tolerated with the majority of treatment-emergent adverse events (TEAEs) being grade 1 or 2 primarily localized pain, fatigue, and nausea.

In September of 2023, the company announced the FDA’s Office of Orphan Products Development granted orphan-drug designation for the treatment of soft tissue sarcoma (STS) to the three active moieties comprising INT230-6, cisplatin, vinblastine sulfate, and the diffusion enhancer SHAO-FA (8-((2-hydroxybenzoyl) amino) octanoate).

Soft tissue sarcoma is a broad term for cancers that start in soft tissues (muscle, tendons, fat, lymph and blood vessels, and nerves). These cancers can develop anywhere in the body but are found mostly in the arms, legs, chest, and abdomen. There are many types of sarcoma; however, the four most common are bone sarcoma (referred to as osteosarcoma), leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS) and liposarcoma. When sarcoma is metastatic prognosis is poor, even with chemotherapy. Each year, 12,000 people in the US and 1,150 in Canada are diagnosed with soft tissue sarcomas. About 3,000 patients have bone sarcomas.

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 sulfate, 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 i.e. direct killing of the tumor by INT230-6, the dying tumor 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 systemically delivered chemotherapy.

Intensity Therapeutics is a late-stage clinical biotechnology company that applies novel engineered chemistry to turn “cold” tumors “hot” by enabling its aqueous cytotoxic-containing drug product, INT230-6, to mix and saturate the dense, high-fat pressurized environment of the tumor. As a result of the saturation, Intensity’s clinical trials have demonstrated the ability of INT230-6 to kill tumors and elicit an adaptive immune response within days of injection, representing a truly novel approach to cancer cell death that holds the potential to shift the treatment paradigm and turn many deadly cancers into chronic diseases. INT230-6 has completed enrollment of over 200 patients in two Phase 2 and Phase 1 dose escalation clinical trials (NCT03058289 and NCT04781725) with various advanced solid tumors; IT-01 in metastatic disease, and IT-02 (the INVINCIBLE study) in presurgical breast cancer. The company partnered 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 malignancies. The Company also partnered with Bristol-Myers Squibb to evaluate the combination of INT230-6 with Bristol-Myers Squibb’s anti-CTLA-4 antibody, ipilimumab, in patients with advanced cancers. The company also executed agreements with the Ottawa Hospital Research Institute (OHRI) and the Ontario Institute of Cancer Research (OICR) to study INT230-6 in the INVINCIBLE study, a randomized controlled neoadjuvant phase 2 study in women with early stage breast cancer. For more information, visit www.intensitytherapeutics.com.