Current cancer treatments can be awful for the patients who are forced to undergo them. Sometimes treatment itself can be almost as bad as the cancer, but doctors are left with little choice but to provide their patients the best chance to keep the cancer from returning. Cancer patients want treatments that work, helping them live longer without the fear of serious harm to their bodies or other side effects from their treatment.

Intensity Therapeutics is on a mission to do just that. Intensity’s products focus on injecting drugs directly into tumors to kill them, instead of traditional cancer therapies that are typically delivered intravenously through the whole body, making it a struggle to target cancers directly. The company’s lead product candidate, INT230-6, is currently in human clinical studies to treat refractory solid tumors like localized triple-negative breast cancer and metastatic soft tissue sarcoma.

 Drug Development & Delivery recently interviewed Lew Bender, Founder and CEO of Intensity Therapeutics, to discuss the company’s science, clinical program, the drug development process, and more.

Q: Can you tell us about Intensity Therapeutics and how your intratumoral therapies work?

A: Intensity Therapeutics is a late-stage clinical biotechnology company with a mission to help patients live longer, higher-quality lives by discovering, developing, and commercializing first-in-class cancer drugs that attenuate tumors with minimal side effects while training the patient’s immune system to fight the cancer. Treatments, such as chemotherapy and immunotherapy, impact patients’ entire bodies, administering toxic side-effects throughout the system. Our technology is different, with our drug being injected directly into patients’ tumors, sparing healthy cells throughout the body. As the cancer cells die, the immune system begins to recognize the cancer. We debulk the live cancer and essentially convert a person’s tumor into their own personal anti-cancer vaccine, inducing a systemic adaptive immune response. Our lead product candidate, INT230-6, is currently in human clinical studies to treat refractory solid tumors like localized triple-negative breast cancer and metastatic soft tissue sarcoma. INT230-6 is a product comprising two potent commercial cytotoxic agents (cisplatin and vinblastine), which are typically given intravenously, along with a dispersion and diffusion enhancer. The new drug is designed explicitly for intratumoral delivery. After the direct injection, the drug saturates the cancer cells with the potent agents and causes tumors to die. Cisplatin and vinblastine each have dual killing and immune-activating mechanisms-of-action. With the proper amount of drug dosed into the tumor, our drug can cause the majority of cancer cells to die in an immunologically activating manner. Our drug creates a personal vaccine from a patient’s tumors that leads to a T-cell attack on the injected and uninjected tumors.

Q: Why did you decide to use intratumoral injection as your delivery method? How did you come up with this idea?

A: When immunotherapies began to gain traction, I learned that their immune-stimulating mechanisms are analogous to releasing the brakes (PD-1 antibodies) or stepping on the gas (CTLA-4 antibodies) in the immune system. I thought there needed to be a steering wheel to guide the immune cells to target the tumor more precisely. I’m a chemical engineer by trade and have worked for more than 20 years in drug delivery, focusing on delivering the precise amount of drug to the right place at the right time.

Intratumoral delivery has been a concept that others had previously explored, but unfortunately, they were unsuccessful in creating a viable product. Due to the high fat content found in tumors, water-soluble drugs are unlikely to be absorbed. We published data on this effect in 2020. To combat this water-fat incompatibility, I leveraged my previous training in drug delivery to develop INT230-6, which utilizes a dispersion and cell penetration enhancer molecule to facilitate the diffusion of therapeutic agents throughout the fatty, dense tumor and into cancer cells. Our proprietary chemistry enables the active agents to be soluble in both fat and water simultaneously. Almost all drugs are given intravenously or orally to fight metastatic disease systemically. Our local therapy kills tumors and stimulates the immune system to attack the tumors that we do not inject. After intratumoral injection, the cytotoxic agents disperse throughout the tumor and diffuse into the cancer cells. The agents remain in the tumor, and side effects are minimal; the tumor dies, and the immune system recognizes the cancer and attacks the injected and uninjected tumors. Our approach is a new way to kill cancer, unlike any current therapy.

Q: What indications have you targeted for this type of treatment to date, and do you expect this to be applicable to more indications in the future?

A: So far, we have targeted advanced soft tissue sarcoma, as well as neoadjuvant and metastatic triple-negative breast cancer. We hope this delivery technology will be a valuable tool across various cancer indications. This is not a cure for every type of cancer, there will be some tumors you can’t get a needle to for the intratumoral injection and there will be some instances in which it just won’t be a feasible treatment, such as the tumors are too diffuse or blood cancers, which are not amenable to injection, etc. But there are enough cancers I believe can be injected in which this new drug may have a real impact and make a difference for patients.

The other thing to consider is cancers can develop resistance. Even if an initial drug is effective, the cancer could come back and then be resistant to the treatment. The idea is to use diffusion-based technologies like ours to overwhelm the tumor and delay or eliminate the onset of resistance. Also, there could be other active drugs that might be better than the cisplatin and vinblastine. There could be a whole host of other payloads that we could load into this intratumoral delivery technology that could be effective. We’re committed to seeing this drug delivery product through to the end and then sharing it with doctors who can determine the best path forward for their patients.

Q: Can you tell us about the progress of Intensity’s current clinical programs?

A: Currently, we have in-progress trials in both operable triple-negative breast cancer and advanced soft tissue sarcoma. The INVINCIBLE-4 study is a Phase 2 randomized, open-label, multicenter study to analyze the clinical activity, safety, and tolerability of INT230-6 administered before the standard-of-care treatment in patients with early stage, operable triple-negative breast cancer, compared to SOC alone. The primary endpoint is to determine the change in the pathological complete response rate for the combination and the SOC alone.

The study is recruiting patients in Switzerland and France and is expected to enroll 54 patients. The INVINCIBLE-3 study is a Phase 3, open-label, randomized study testing INT230-6 as monotherapy compared to standard of care (SOC) drugs in second- and third-line treatment for three specific soft tissue sarcoma subtypes. The study is expected to enroll 333 patients and initiate sites in eight countries. This study has been authorized by the US FDA, Health Canada, the European Medicines Authority (for France, Germany, Italy, Poland and Spain), and Australia’s Therapeutics Goods Administration. The primary endpoint in the INVINCIBLE-3 study is overall survival. We’ve had to pause new site activations and patient enrollments in the INVINCIBLE-3 study due to funding constraints, but we continue to treat all patients already enrolled, and the treatment has been effective and well-tolerated to date.

Q: Can you tell us more about triple-negative breast cancer, a target of your INVINCIBLE-4 Study, and why it’s important to find improved treatment options?

A: Triple negative is a very aggressive form of breast cancer. The negative refers to the absence of target protein receptors (estrogen, progesterone, and Herceptin) on the cancer cell. This status limits the amount of drugs available to treat the cancer. When women undergo chemotherapy prior to a lumpectomy or mastectomy, they are trying to eliminate all live cancer in the tumor and lymph nodes by the time of surgery. The absence of live cancer is referred to as a pathological complete response (pCR), which strongly correlates with a more prolonged event-free survival (ie, a delay in the return of the cancer). Unfortunately, only a fraction of women achieve a pCR, and up to 0.5% of women can die from the chemotherapy itself. By adding our drug upfront, before initiating the current standard treatment regimen, we hope to increase the percentage of women having a pCR without increasing toxicity and possibly even decreasing the toxicity.

One of the biggest trends we’re seeing is using drugs before surgery. Dosing before surgery is referred to as the neoadjuvant setting. The goal is to increase the chances of a patient delaying disease recurrence. Another trend is the earlier and earlier diagnosis of breast cancer using mammograms. Only a few years ago, women over 50 were the only ones recommended to get tested. Now, according to the United States Preventive Services Task Force (USPSTF), women should get their first mammogram at age 40 and continue to get screened every other year until they are 74.