From a basement-born idea to a publicly traded biotech advancing late-stage clinical trials, Lew Bender’s journey reflects both scientific persistence and entrepreneurial conviction. With more than three decades of experience spanning drug delivery, regulatory strategy, and biopharmaceutical leadership, Bender has built Intensity Therapeutics around a bold premise: that directly targeting tumors with engineered chemistry can fundamentally reshape how cancer is treated. At the center of this vision is INT230-6, a novel intratumoral therapy designed to penetrate dense tumor microenvironments, induce rapid tumor cell death, and activate a systemic immune response. In this interview with Biopharma Boardroom, Lew Bender shares the scientific rationale behind the platform, its clinical positioning, and the broader implications for the future of oncology.

Intensity Therapeutics’ approach with INT230-6 introduces a fundamentally different mechanism of action through direct intratumoral delivery and tumor saturation. Could you elaborate on the scientific rationale behind this engineered chemistry platform, particularly how it overcomes the physical and biological barriers of dense, high-pressure tumor microenvironments that have historically limited drug penetration and efficacy?

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. After intratumoral injection, the cytotoxic agents disperse throughout the tumor and diffuse into the cancer cells. The agents remain in the tumor, the tumor dies in a manor that releases chemicals to attract and train certain immune cells to attack the cancer.  Side effects are minimal. Our approach is a new way to kill cancer, unlike any current therapy. 

One of the most intriguing aspects of your clinical findings is the rapid induction of both tumor cell death and adaptive immune response within days of administration. How does INT230-6 mechanistically bridge cytotoxic activity with immune activation, and what differentiates this response from conventional immunotherapies that often struggle in “cold” or non-immunogenic tumors?

For decades, the standard of care for metastatic cancer has been systemic, delivering drugs through the bloodstream to reach every corner of the body. While this is effective for blood cancers, solid tumors like those found in the lung, pancreas, or breast are essentially biological fortresses. They create an environment characterized by high internal pressure, a low amount of blood vessels, high fat content and dense structural barriers. Furthermore, many of these tumors are cold, as you’ve mentioned, meaning they have evolved to be immune deserts especially in cancer with lower mutation burden. There is also a lack of the inflammatory signals needed to attract immune cells, allowing the cancer to grow undetected. When we give potent immunotherapies intravenously, we often face a common Catch-22: we must increase the dose to force the drug to bind to more immune cells, but those high concentrations of activated immune cells circulate through the entire body, causing off-target toxicities that damage healthy organs without the cancer being attacked sufficiently. Millions across the country who unfortunately develop cancer face an untenable dilemma: face the complications from cancer or face the incredibly toxic treatment that could leave their bodies permanently damaged. The result is very similar to the story of Christine Handy, somebody I’ve had the privilege of working with these past few years, whose story is all too common in this realm, where breast cancer treatment has left her with permanent cardiac damage.

The true magic of our product isn't just the delivery, it’s the biological "reprogramming" that follows. After direct injection, the drug saturates the cancer cells with the potent agents and causes tumors to die. Then, the immune system begins to recognize the cancer. Cisplatin and vinblastine have dual killing and immune-activating mechanisms of action. With the proper dose into the tumor, these drugs can cause the majority of cancer cells to die in an immunologically activating manner. The debulking process of our drug then creates a more precise T-cell attack on the injected and uninjected tumors. When we inject a combination of cancer-killing agents directly into a tumor, we are essentially creating a personalized antigen that are chemicals that can be used to train immune cells to fight the cancer. These signals act as a flare gun for the immune system, teaching local dendritic cells and T cells exactly what the cancer looks like. Once educated, these immune cells enter the bloodstream to seek and destroy cancer cells in the injected tumor and distant, untreated parts of the body. This allows a local treatment to have a truly systemic impact and hopefully can limit the amount of toxic treatment the patient will have to endure.

As you advance through late-stage clinical development, how are you positioning INT230-6 within the broader oncology treatment landscape? Specifically, do you see it as a standalone therapeutic modality, a combination backbone, or a platform that could be tailored across multiple tumor types and stages? Additionally, how are you thinking about patient selection and biomarkers in this context?

We are using INT230-6 in all three ways you noted above as a standalone therapeutic modality, a combination with current therapies, and a platform across multiple tumor types and stages. So far, we have targeted advanced soft tissue sarcoma for the use of our drug as a standalone product randomized to standard of care systemic therapies.  In neoadjuvant triple-negative breast cancer, we are using INT230-6 just prior to the start of the standard of care regimen, randomized to the SOC alone. 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. Finally, since our drug uses a diffusion process, the type of solid tumor becomes less important, so the drug potentially can be used in a variety of different solid tumor types. Triple-negative breast cancer is a very aggressive form of 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 (i.e., a delay in the return of the cancer). Unfortunately, only a fraction of women achieve a pCR, and up to 0.5 percent 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. These 3 approaches are how we see intratumoral injection fitting into the oncology treatment paradigm. 

We hope that this delivery technology will be a valuable tool across various cancer indications, but it is not a cure for every type of cancer. There will be some tumors that you can’t get a needle into for the intratumoral injection, and there will be some instances where it just won’t be a feasible treatment, such as when the tumors are too diffuse or blood cancers, which are not amenable to injection, etc. But there are enough cancers that I think can be injected where this new drug may have a real impact and make a difference for patients. The other thing to consider is that 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 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.  Patient selection will be dependent on having the appropriate amount of tumor burden; many small sub-centimeter single tumors, such as in some types of ovarian cancers, would be challenging. Patients with several large tumors greater than 20 cm in diameter would also be challenging for us (or any therapy) to treat.  

The journey from founding Intensity Therapeutics in your basement to achieving a public listing is both unconventional and inspiring. Could you share key inflection points in this journey—scientific, financial, and strategic—that were critical in transforming an early-stage concept into a clinically validated and publicly traded company? What lessons might this hold for emerging biotech founders navigating today’s capital and innovation environment?

I would say the first major important inflection point for the company was when Dr. Jay Berzofsky from the National Cancer Institute helped be awarded a collaborative research and development agreement (CRADA) with the NCI. This research set us off on the right research path and helped us to understand the mechanism by which our drug functioned. Another Key milestone occurred when a VC group in Chicago lead a Series A financial round that helped us to raise over $11 million. That funding allowed us to complete our nonclinical safety studies and conduct our first clinical study. I will also never forget the patients whom I have had the honor to meet from our prior studies.  Seeing the positive results that of our drug has had on patients and their caregivers is the experience of a lifetime. 

A big event was when bankers brought us public during a challenging market back in 2023.  My family, early investors, staff, bankers, and lawyers celebrated at Nasdaq when we rang the bell. The achievement of becoming a public company on the Nasdaq was a proud moment for all who worked hard to make that day happen. That capital allowed the company to initiate our two ongoing late-stage randomized controlled clinical trials in multiple countries, both of which are now ongoing. I will also never forget the days when the FDA, Health Canada, and EMA sent us notifications that the Phase 3 study could begin to enroll. Other notable inflection points along the path were receiving our first US and international patents, hiring staff, and the publication of our peer-reviewed papers in nonclinical research, including a paper jointly published with the NCI. Another major inflection point was when our first clinical paper was published in the Lancet’s eBioMedicine journal. The first paper to show a local therapy with the potential to treat metastatic disease. These were all wonderful events and inflection points; however, to me, until the safety and efficacy of this new approach is proven and the drug receives marketing approval in the US and other counrties the job remains unfinished.

Recent clinical updates appear to reinforce the potential of INT230-6 to shift cancer treatment toward a model where even aggressive malignancies could be managed as chronic conditions. From your perspective, what are the most important clinical endpoints and real-world outcomes that will define success for this approach, and what challenges remain in translating early promise into durable, long-term patient benefit?

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 treatment that works, helping them live longer without the fear of serious harm to their bodies or other side effects from their treatment. Our technology has the potential to help people stay alive longer, and I think we can take the pain out of the disease. Current treatments are just horrible for the patients, but they’re the best we’ve got. In my opinion, society must do better.  This kind of story, where cancer treatment has left permanent scars, is one that many patients worldwide can identify with. Treatment can be almost as bad as the cancer. Doctors know that the toxic cocktail of drugs given to their patients offers the best chance of keeping the cancer from returning after surgery. It’s an untenable situation, but one that too many patients face. A lot of cancer patients in remission will face permanent health issues. We want patients to have cancer treatment without the fear of complications from the treatment itself. We don’t want our patients to come out the other side of cancer therapy damaged. We've created something that will potentially take care of the patients in a way that could both save their lives and not torture them or cause them to have permanent harm. There are still many challenges ahead before we reach full-fledged approval, but our data to date is extremely promising for these patients, and we’ve had a number of compassionate care use cases that showcase the same. In our INVINCIBLE-4 triple metastatic breast cancer study, the primary endpoint is to determine the change in the pathological complete response rate for the combination and the standard of care alone, while the INVINCIBLE-3 study in three specific soft tissue sarcoma subtypes has a primary endpoint of overall survival. 

Looking ahead, how do you envision the evolution of intratumoral therapies and localized treatment strategies within oncology over the next decade? In a landscape increasingly dominated by precision medicine, cell and gene therapies, and systemic immunotherapies, where does Intensity Therapeutics see its role in shaping a more integrated and effective cancer care paradigm?

From a clinical perspective, the transition to intratumoral delivery based on a new diffusion delivery technology that activates a systemic immune response is transformative because it solves the therapeutic window problem—the narrow margin between a dose that kills cancer and a dose that harms the patient. By delivering therapy directly to the source, we can achieve drug concentrations at the tumor site that are often 100 times higher than what is possible via IV, yet with only a fraction of the systemic circulation. The systemic treatment comes from providing personalized, high-quality antigen. This means we can use more aggressive, multi-drug killing agents in the IT product while significantly reducing the risk of organ stress and chronic fatigue for the patient. Thinking back to the example of my colleague Christine Handy, intratumoral injection prior to any further treatment could have led to a much better outcome without the toxic cardiac side effects. 

A common misconception in this field is that intratumoral injection is limited to visible skin lesions like melanoma. In reality, the field of interventional oncology has turned deep-seated tumors into accessible targets. Using real-time, high-definition imaging, clinicians can now navigate needles into internal organs with millimeter precision. This precision is particularly revolutionary for neoadjuvant care, which is treatment given before a primary tumor is surgically removed. By injecting a tumor while it is still in the body, we essentially use the tumor as a classroom for the immune system. The T cells learn to recognize the specific mutations of that patient's cancer. When the surgeon eventually removes the physical mass, the patient is left with a primed immune system and an internal security force already trained to seek out and mop up any microscopic cancer cells that may have escaped into the bloodstream, potentially preventing a recurrence in the future.

Intratumoral injection is not a panacea for every cancer. However, there are many cancers that will be amenable to this and can have a real impact and make a significant difference for patients. That is and should be the main goal of cancer researchers today: allowing patients to live longer, with a high quality of life, and without the fear of being harmed by the treatment.