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Bioneex Story with the CEO of ARJUNA Therapeutics
Ross Breckenridge

ARJUNA Therapeutics Develops An Innovative Approach to Cancer Treatments

ARJUNA Therapeutics has a novel approach to developing highly targeted molecules to fight cancer, and after spending four years developing a GMP manufacturing process, is now ready for scale-up and clinical trials. 

Specifically, its proprietary molecules hold promise as single agents and combinatorial therapies for solid tumors and as adjunct therapies to radiation to improve efficacy and limit side effects. 

The molecules the company is developing had been studied for many years but in tiny quantities making it difficult to run studies with them.  But a team at the University of Santiago in Spain, where ARJUNA was launched, figured out a way to make the molecules in solution so they could be made in the quantities needed to run biological experiments. 

Arturo López Quintela, scientific founder of ARJUNA, and professor of chemistry at the University of Santiago in Spain, found three classes of these “therapeutic molecular clusters” as ARJUNA calls them, and then his colleague Professor Fernando Dominguez worked out their mechanism of action.

“In some ways, this is the opposite way to modern targeted drug discovery, but it harks back to the previous model of drug discovery, in a way,” says Ross Breckenridge, CEO of ARJUNA. “It turns out that our molecules are actually incredibly targeted. It's just that we've arrived in a slightly circuitous route.”

Platinum therapy is still a widely used and successful cancer treatment, but not all metals are equal. ARJUNA’s lead molecule, Ag5, is the first of a new therapeutic modality and represents a novel form of metal. Five silver atoms are covalently bonded together using quantum chemistry to make a very small molecule capable of crossing the blood-brain barrier. 

“It’s a form of silver that does not exist in nature,” says Breckenridge. “These are absolutely unique molecules that nobody else has in their hands. They're not available in drug libraries.”

Ag5 acts as a catalyst. If it is put into cells that don’t have high levels of mitochondrial activity, it is inert. “Most cancer drugs are pharmacological inhibitors and they act equally well on a molecule if it's in a cancer cell or a non-cancer cell,” says Breckenridge. “This is a big side effect problem. Because our molecule is activated by a reaction that is only occurring at a significant rate in the cancer cell, this gives it differential activity. Killing cells selectively so you only kill cells that you want is what cancer therapy is.”

Ag5 is essentially inert unless it encounters very high levels of chemicals that are only generated at the threshold concentration in the energy-generating part of cancer cells. So, the company is targeting cancers that have the highest abnormal energy generation, which turns out to be the cancers that are the most resistant to therapies and the most aggressive—cancer metastasis cells that break off from a primary tumor and spread. 

“It's not the primary tumor, it's when it spreads to the brain, the bones, and other organs that the cancer kills you. Metastatic cells have much higher rates of mitochondrial respiration than the primary tumor,” Breckenridge notes. 

ARJUNA thinks Ag5 may be a drug eventually to specifically target metastasis in solid tumors of all types. It’s a big goal and the company still has to take a number of de-risking steps to get there. The company has conducted a number of studies in different types of cancer that all essentially have the same phenotype, the high mitochondrial activity it is targeting, and has data from animal studies done in collaboration with academic partners in several cancers including brain cancer, lung cancer, and myeloma. While most of this work was done at low doses because at the time the company could only make a low concentration of Ag5, the company saw very considerable single-agent efficacy in animal models without any side effects. Animal model work is now underway to define Ag5 doses that can be translated to human clinical trials.

ARJUNA’s studies also show that dosing with Ag5 can improve radiation treatment because it amplifies one of its main effects. Worldwide, 50% of cancers are treated with external beam radiotherapy. Radiation kills cells by cutting up the DNA and inducing a pulse of reactive oxygen species in the mitochondria of cells. Ag5 catalyzes the reactive oxygen species in mitochondria, making that pulse of reactive oxygen species more likely to kill the cell because it amplifies the effect. Ag5 also indirectly induces a small increase in antioxidants in non-cancer cells, raising their resistance to radiation, and increasing the safety margin of the radiation treatment.

“This is a big deal because we've got data from in vitro work showing that Ag5 will actually restore radiation sensitivity in cell lines taken from patients with brain cancer that have become resistant to radiation,” Breckenridge says. “But it also potentially will allow us to give a lower dose of radiation for the same amount of cancer-killing. That’s particularly important for children with brain cancer who have radiotherapy.” 

ARJUNA is in the midst of raising $10 million in a series A financing round, which it believes will get it to an Investigational New Drug application and into the clinic for its first trial in lung cancer, which it will conduct in Spain. 

Breckenridge sees huge potential for ARJUNA’s molecules in solid tumors like KRAS mutant lung cancer, which is currently treated with combination therapies and leads to combinatorial side effects. “The KRAS combination therapies have really been really difficult for patients to take. And the problem is with something like lung cancer, you're probably going to have to stay on treatment forever if you're going to treat it,” he says. “We think that actually there's a huge opportunity for our drug because it works so differently. It works at 90 degrees to everything else.”

The company is also aiming for grants to pay for its brain cancer program in parallel. It is also talking to partners about collaborations. 

ARJUNA recently won the prize at the recent MATWIN partnering conference in France where the company pitched to pharma oncology business development people and got specific feedback from them. “At the stage that we're at, at the moment, we're interested in finding an R&D partner, a partner that will have our drug in their hands and put it in their systems, and figure out what they think,” said Breckenridge.

ARJUNA also joined the Bioneex drug marketplace as a Provider for just that reason. Breckenridge has already started conversations through the platform.  “Our aim is to get into the clinic, hopefully by the end of 2025. We have a pipeline of molecules that come after Ag5, some of which we're talking about, others we're not yet because we haven't filed the patent. In the end, we're aiming to have a platform of these molecules that we think will be of widespread use. Of course, we're trying to be absolutely focused, but at the same time not leaving any opportunities.”

By Marie Daghlian, Chief Editor at Bioneex

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