A Personalized Revolution

No treatment can yet guarantee a cure for cancer, but two Israeli companies are offering groundbreaking approaches. One uses targeted heat to destroy tumors while the other deploys a precision-guided “missile” that delivers radioactive material directly to cancer cells. Both companies leverage personalized medicine to exclusively attack tumors, leaving healthy organs unharmed

Every now and again, new technologies emerge that enable innovative cancer treatments and reshape the entire therapeutic approach to tackling the disease. It is exactly technologies such as these that are being developed by two Israeli startups, Starget Pharma and New Phase – the first, a biotech company, and the second, a medical device company. Despite different methodologies and development processes, they share a common vision: personalized, intelligent, selective medical treatments capable of combating disease without damaging healthy organs.

Starget Pharma develops a type of cancer treatment that sends tiny radioactive particles directly into cancer cells, like guided missiles, so they destroy only the tumor without harming the surrounding, healthy parts of the body. New Phase delivers targeted internal heat directly to tumors, avoiding surrounding tissue damage. Both companies are heading towards clinical trial phases and have ambitious long-term goals.

When Sigal Kalmanson Cusnir decided to establish a groundbreaking cancer treatment company with her brother, Ronen Kalmanson, she already had an impressive high-tech track record: extensive management experience, key roles in global companies, and profound expertise in innovation and development processes. They knew their company would straddle the intersection of advanced science, medical technology, and Artificial Intelligence.

For an entire year, they searched Israel for a mature technology capable of triggering a true revolution and met with leading researchers at the Technion, the Weizmann Institute, hospitals, and universities. At the Sheba Medical Center, they encountered a team that had spent 15 years developing peptide molecules capable of delivering targeted therapies directly into cancer cells. Realizing that they had found exactly what they were looking for, they founded Starget Pharma, a company that realizes the potential of developing precise, safer, innovative cancer therapies.

In one of the innovative approaches in this area, known as radio theranostics (diagnostic & therapy), patients initially receive a low-dose radioactive agent for imaging – a kind of biological scan confirming that the molecule indeed reaches the cancer cells. Only if strong uptake is confirmed does the treatment proceed to the next step, involving the introduction of the same molecular compound, combined with a potent isotope capable of destroying the tumor.

To achieve this, the company has developed what Kalmanson Cusnir calls “the world’s first AI-driven platform for engineering radioactive molecules.” “Our system identifies unique receptors in cancer cells and matches them with smart molecules that precisely bind to their targets without breaking down,” she explains. “This requires integration of chemistry, molecular engineering, nuclear medicine, AI & computational biology, and oncology, all at a development pace that allows us to move forward quickly.”

Starget’s platform takes the innovative targeted treatment concept further. Firstly, the patient receives only a harmless imaging agent that ensures precise localization within cancer cells. “The patient will only receive the actual treatment if the imaging shows clear uptake in the cancer cells,” says Kalmanson Cusnir. “This completely changes the therapeutic approach because instead of guessing whether the treatment is effective, we can confirm its suitability for each specific patient in advance, significantly saving costs and time, and dramatically increasing the chances of success.”

“Our vision revolves around creating smart treatments that deliver the active substance exactly where it is needed,” Kalmanson Cusnir adds. “We’ve developed a groundbreaking platform delivering radioactive substances directly into cancer cells, thereby dramatically reducing side effects and ensuring that treatment is given only to those who can truly benefit from it. We call it a “precision-guided missile” – the molecule carries radioactive material solely to cancer cells. Through this, treatment becomes much safer and far more focused and accurate compared to chemotherapy or external radiation.”

Kalmanson Cusnir describes it as “personalized medicine on steroids,” promising effective, safe, and efficient treatment for patients, while simultaneously acknowledging the challenges and risks inherent in radioactive treatment. Although it significantly reduces the risk to healthy organs, meticulous dosage precision is required, as mild kidney damage or other side effects are still possible, even though these effects are minimal compared to traditional treatments.

Starget’s innovative platform is based on a complex integration of technologies that enables the company to rapidly and efficiently develop new molecules tailored specifically to different types of cancer. “The business potential is immense, and our platform can serve as the basis for numerous collaborations with global pharma companies in order to develop a wide array of targeted drugs for various cancers,” says Kalmanson Cusnir.

The company is expected to begin advanced clinical trials in collaboration with MD Anderson, one of the world’s leading oncology centers. “Our clinical trial involves patients dealing with challenging types of cancer, such as sarcoma, liver cancer, skin cancer, and neuroendocrine cancer,” says Kalmanson Cusnir. Additional trials in drugs targeting breast, prostate, and lung cancers are planned for the coming year.

Kalmanson Cusnir attributes significant importance to the collaboration with the Israel Innovation Authority. “We aspire to be an Israeli pioneer in the highly promising but also very complex field of bio-convergence, which requires integrating multiple disciplines. The Innovation Authority plays a critical role not only in investments but also by enabling us to form significant collaborations, develop essential infrastructure, and advance technologies that will truly change reality.”

Kalmanson Cusnir also places great importance on the composition of the company’s team. Most managers in the company are women, and the staff features a unique blend of scientists and researchers from diverse fields, ranging from chemistry, pharmacology, and biology to nuclear medicine, software engineering, and Artificial Intelligence, spanning a wide range of ages. “We have senior scientists with 40 years of experience in drug development working alongside young researchers aged 25 who have just completed their PhD,” she says proudly. “I believe that this combination of wisdom and experience from senior scientists, together with the innovation and freshness of younger researchers,  is a significant part of our ability to break new ground and tackle complex challenges.”

Targeting Cancer with Precision

New Phase is an Israeli deep-tech company that has developed a groundbreaking technology to destroy cancerous tumors using magnetic hyperthermia. The treatment involves the injection of magnetic nanoparticles that accumulate within tumors and are heated within the body to a temperature of 50°C using an external electromagnetic field, resulting in the targeted and selective destruction of cancer cells without damaging healthy tissue. This is a precise technology that attacks cancer’s vulnerabilities, which is changing reality.

The company is currently in its first clinical trial phase, in collaboration with hospitals in Israel and the United States and is attracting growing interest from the FDA and leading global medical centers.

Ofer Shalev, the company’s CEO and co-founder, established New Phase in 2013, together with Dr. Raphael Hof, following Dr. Hof’s personal experience with his mother’s lung cancer. “That was the trigger to explore a different approach,” he recalls. “We looked for an alternative solution – not another attempt to invent a new biology, but rather, to understand the weaknesses of cancer cells and destroy them via physical means, by leveraging their sensitivity to temperatures above 45°C. Seeing the patients we’re already helping today is a dream come true.”

Shalev, who previously managed other companies in the life sciences field, emphasizes that New Phase’s approach is based on two core assumptions. The first is that there is currently no definitive cure for cancer, making it essential to develop a tool to manage the disease, i.e., prevent its spread; the second assumption is that this must be achieved without the harsh side effects of existing treatments, and in a way that bypasses the tumor’s drug resistance. Indeed, the patients who enrolled in the trial did so after exhausting all other existing therapies.

“Instead of developing a new drug, we turned to physics, out of an understanding that physics-based assumptions work,” he explains. “Cancer cells are significantly more sensitive to heat than healthy cells. They lack the heat dissipation capacity of healthy tissue, and their membranes cannot develop heat resistance, unlike their typical response to drugs. That’s how the concept was born: we will generate precise internal heat that only targets the cancer cells and will destroy them without harming surrounding healthy tissue.”

New Phase’s technology is based on electromagnetic hyperthermia using superparamagnetic nanoparticles. These are tiny particles containing iron oxide, coated with a biocompatible polymer, injected into the bloodstream, and designed to exploit the unique biological properties of cancer cells to accumulate precisely at tumor sites. “Cancer cells’ blood vessels have a different, more permeable structure and an inefficient lymphatic system that fails to vacate the particles. This almost guarantees their accumulation in tumors,” Shalev explains.

Following the injection, the body is exposed to an alternating magnetic field, which is non-ionizing but penetrates deep into the body. This radiation heats the nanoparticles that have accumulated in the cancer cells, and from there, physics begins to exert its delicate effect.

The particles are engineered to prevent them from heating beyond 50°C. A phenomenon known as latent heat allows them to absorb energy without rising in temperature. This is important because cancer cells are destroyed in the range of 41-45°C, whereas healthy cells can withstand temperatures of up to 55°C. “This means that only the tumor is damaged, while the surrounding healthy tissue remains intact,” says Shalev.

This approach enabled New Phase to register its solution as a medical device rather than a pharmaceutical drug – a significant distinction in terms of clinical trials, development timelines, and costs. “We knew that adopting the drug route would require hundreds of millions of dollars, which is simply not realistic. As a technology, we’re talking about a sustainable sum of tens of millions,” Shalev explains.

The technology they developed can also reach deep tissues, including the abdominal region, liver, and lungs, and selectively heat only the targeted areas without causing systemic harm. “We don’t need radiation or chemotherapy that affect the body’s healthy systems, but rather, only the particles that have already reached the cancer cells – and that’s exactly what we do,” Shalev emphasizes.

One of technology’s most substantial advantages is its high selectivity. “The particles we inject travel through the bloodstream,” Shalev explains, “but in areas without tumors, they simply flow on by without penetrating tissues. They accumulate in the liver and spleen, which are also responsible for vacating the particles, but this is temporary as these organs efficiently dissipate heat before any damage occurs.”

According to Shalev, the nanoparticles themselves are highly stable. They are vacated by the body naturally and do not break down in the body due to heat, radiation, or exposure to enzymes or bodily fluids. The treatment itself only lasts about 30 minutes, and the only documented side effect to date is a brief sensation of heat in the lower back, a reaction anticipated by the team but which typically disappears within minutes.

Still Learning the New Language

To date, the technology has been successfully tested on hundreds of mice and pigs and has already been used to treat 24 patients with nine different types of cancer. “No toxicity was observed, and in some cases the disease was classified as stable with no new metastases detected,” says Shalev. “Although we don’t yet have statistically significant data – the groups are small, with just a few patients per indication – the direction is promising and will allow us to focus on the second phase that will have a defined number of cancer cases.”

New Phase currently has regulatory approval to treat stage 4 cancer patients – individuals who have exhausted all other therapeutic options and are left with no hope in the form of conventional treatment. “This is a very complex target group,” Shalev emphasizes, “and that’s precisely why it was important for us to develop a solution that offers quality of life alongside a longer life – and without the side effects.”

While there are other heat-based treatments worldwide, most require precise tumor identification via MRI or CT, followed by localized heating using focused ultrasound or radiofrequency (RF) energy. “That works when the tumor is visible,” says Shalev, “but what if the tumor is too small to detect? These technologies cannot be used systemically in the metastatic stage.”

This is where New Phase’s systemic approach comes in: the particles are injected into the bloodstream, reach the tumors via the enhanced permeability effect, and are heated by the electromagnetic field to a controlled temperature of 50°C, which only kills the cancer cells that are inherently heat-sensitive.

“The breakthrough in systemic treatment is that we don’t need to know exactly where the tumor is,” says Shalev. “We simply heat the patient’s torso – not by aiming the electromagnetic field at a specific tumor, but at the general area where the metastases are located.”

Over the next six months, the company plans to narrow its focus to three or four types of cancer and conduct a broader trial, part of it in Israel and the remainder in the US. “We’ll soon commence work with hospitals in the US and test groups of 15-20 patients per cancer type. Some patients have already undergone six or seven treatments, and the disease remains stable, with no side effects.”

Alongside the clinical optimism, Shalev voices criticism of the local investment ecosystem. “The Innovation Authority supported us – and that’s important – but it’s not enough,” he says candidly. “There are no tools to support companies in advanced stages. Israeli venture capital funds are largely absent from the medical sector, despite the lofty sentiments they express. They focus on software, digital health, and invest only very sparsely in companies performing clinical trials. Drug development and medical technologies have been largely abandoned. Deep-tech investment is insufficient, and from many conversations with foreign investors, it’s clear that the right path for growth is often to turn an Israeli company into an American one.”

New Phase’s technology is entirely novel and, as such, requires both clinical validation and ongoing learning across the ecosystem. “This is a technology that didn’t exist before – so it’s natural, especially in Phase I, that both regulators and clinical teams are still learning its language,” says Shalev. “There are very few clinical trials of this kind, so even at the international level, there’s limited accumulated knowledge.” This is also reflected in the number of scientific publications the company has released to date.

New Phase presently employs 23 people across various disciplines, including chemistry, biology, physics, and engineering, with balanced representation across gender and social groups. This inclusive and diverse approach is part of the company’s medical vision. “What keeps our people going is passion,” he says. “In the beginning, it was the excitement of the technology. Today, it’s the interaction with patients and the clinical trials that drive us forward.”