Our Science

Therapeutic Molecular Clusters (TMC's) are an entirely novel class of therapeutic. These are small, extremely stable molecules consisting of covalently bonded atoms. TMC’s are not traditional biologics, recombinant proteins or monoclonal antibodies, which were the genesis of the biotech industry. TMC's are not nano-particles, yet they are very small molecules, much like traditional pharmaceuticals. And most importantly, our small molecules act as a catalyst in cell biology. The electron orbitals of our engineered covalently bonded atoms bring a specific therapeutic action and catalyze cells in the body with beneficial biological actions.

TMC's are stable at extreme temperatures and pH and will likely be orally bioavailable. The small size allows our molecules to diffuse freely throughout the body, across the blood-brain barrier into areas with low vascularity and into cells. We have three TMC molecules in development, with Ag5 as our lead molecule.

Intracellular reactive oxygen species (ROS) are required for all cells to function. However, if ROS levels are elevated sufficiently, cancer apoptosis will occur. Levels of ROS are therefore tightly regulated in cells, and perturbations in this delicate balance are thought to be a cause of many types of disease, including cancer. The subgroup of cancer that exhibits the highest levels of ROS are those caused by mutations in KRas. Indeed, KRas mutant-driven cancers are dependent on high levels of ROS to drive cancer cell metabolism and cell division. A large body of research in the cancer field shows that levels of ROS in KRas mutant cells are very close to being fatal for the cell. Furthermore, experimental inhibition of ROS production in KRas mutant cells prevents cancer-like behavior in KRas mutant cells, meaning that high ROS is obligatory for KRas cancers. Therefore, there is a potential therapeutic opportunity to either kill KRas mutant cells by boosting ROS levels beyond toxic levels or inhibiting ROS production to prevent cancer development. So far, exploitation of both of these strategies has proved unsuccessful in patients, because the treatments to either induce or inhibit ROS production are also active in non-cancer cells, leading to unacceptable side effects.

Ag5 selectively kills cancer cells already exhibiting high levels of reactive oxygen species (ROS), while having no effect on non-cancer cells, via a novel mechanism that has been thoroughly investigated and defined by our academic team and founders (multiple academic publications and patents filed). Ag5 acts as a catalyst inside cells to increase the oxidation of proteins by ROS leading to cell death. A crucial advantage of this over previous ROS-dependent cancer killing therapies is that Ag5 does not induce ROS production, only amplifying the effect of tumor-produced ROS, meaning that non-tumor cells are unaffected. Ag5 is therefore non-toxic when administered long-term to rats, and we therefore expect a benign toxicology profile in humans. Preclinical testing of Ag5, in animal models, shows significant tumor killing efficacy in KRas mutant cancers. We are investigating biomarkers that allow us to identify cancers with the highest levels of ROS, and therefore the most sensitivity to Ag5. We have compelling evidence that these biomarkers will allow us to identify cancers for treatment with Ag5 beyond those with mutant KRas genes. We therefore believe that eventually, the patient population that is addressable by Ag5 treatment will go beyond KRas mutant cancers.

We built Arjuna Therapeutics on the guiding premise that if TMC’s work as a medicine for one disease, they should work for many diseases. Moreover, since our first two compounds have a catalytic effect on cancer cells – it could meaningfully improve how medicines are discovered, developed, and manufactured in other disease states with unmet medical needs. We have a 27 additional TMC’s in our pipeline to explore. Using TMC’s to create medicine is a complex undertaking and required Arjuna Therapeutics to overcome novel scientific and technical challenges. Our multidisciplinary team has worked together closely to address these scientific and technical challenges. This intensive cross-functional collaboration has enabled us to advance key aspects of our platform and make significant strides to deliver TMC medicines for patients.

Along the way, we have amassed a broad and deep patent estate. This includes foundational patents in TMC manufacturing technologies and TMC therapeutic applications for patients. While our platform is initially targeting the oncology space, we will be making a future announcement in additional disease areas. We continue to invest strategically in our science and technology to ensure Arjuna Therapeutics is in the strongest possible position to deliver on the promise of TMC’s to bring a new class of transformative medicines to patients in the decades to come.

Making cancer a manageable disease is undoubtedly one of the significant challenges of our century. The knowledge of the mechanisms behind cancer has dramatically improved. In recent years, several new platforms have arisen with the promise of improving the outcomes of cancer treatments.

Cancer Vaccines

Cancer is caused by mutations that turn healthy cells into tumor cells. Each tumor has unique mutations. Vaccines are given in the form of messenger RNA, a type of molecule that provides cells with the instructions to create a particular protein, and for oncology, a cancer antigen.

Cell Therapy

CAR-T cell therapy is about influencing immune cells to attack. Cell Therapy consists of taking immune T-cells from the patient, then manufactured individually using each patient's cells, guiding them to target a specific antigen, and injecting them back. The goal is to develop precise, targeted treatments that eradicate cancer while sparing healthy tissue.

Gene Editing

The technology could be used to improve cancer therapies such as CAR-T. This is where T cells are edited to target cancer cells better. Gene editing provides greater speed and efficiency than conventional CAR-T treatments.

Monoclonal Antibodies

These are crafted versions of immune system proteins. Antibodies are useful in treating cancer because they are designed to target a specific part of a cancer cell.

Immune Checkpoint Inhibitors

These drugs basically support the immune system, which helps it recognize and attack cancer cells.

Each of these platforms brings with it a new promise for the oncology market. Advances in drug design and precision medicine offer hope after a life-changing cancer diagnosis. However, there's a dark side to cancer-killing drugs designed to match distinct cancer mutations like a key into a lock. Some cancers that initially respond to targeted medicines become treatment-resistant.  We now know how hidden layers of regulation, epigenetics, can switch genes on and off to produce drug-resistant surviving cancer cells. A new study led by Cedars-Sinai illustrates the challenge of fighting cancer by identifying more than 2,000 genetic mutations in samples of esophageal tumors. Our platform will also be added into the mix as a new entrant in the fight against cancer, bringing with it hope for a solution immune to the mutating aspects of the disease. What differentiates our lead molecule is its ability to affect cancer cells downstream. Our method of action will be the first downstream catalyst of a cancer cell. 

Therapeutic Molecular Clusters 

TMC's are a new class of medicine that are catalysts within the cell structure. We influence a reaction without being permanently altered or consumed by the process. TMC's are very small molecules, allowing them to diffuse freely through the body, and across the blood-brain barrier.

To understand Therapeutic Molecular Clusters, you may need to think differently about drug development. We are taking a new approach to cancer treatments. Cancers cells are known for both complexity and adaptability and yet the most violent of cancers, after all their ability to adapt to treatments, will downstream express higher levels of reactive oxygen species (ROS), which our method of actions uses as a catalyst for creating cell apoptosis. Cancer will not be able to adapt to our Therapeutic Molecular Clusters catalytic effect. They won't be able to evolve and evade. Since we are targeting the endpoint of the cancers journey, we, in essence, are targeting the Achilles heel for multiple cancer indications. 

There are four important ways in which a new platform can impact patient care in the oncology market: 

1. Better efficacy than current treatments 

2. Better safety than current treatments 

3. Synergistic with existing treatments (e.g., consider a Chemo/IO/TMC combo) 

4. Better outcomes in certain patient subgroups

As any person with cancer knows, a cancer diagnosis also affects every family member and a broader network of relationships. Sometimes the complicated feelings and lifestyle changes caused by cancer and its treatment becomes as overwhelming for others as they are for the patient. Receiving a pediatric cancer diagnosis is one of the most devastating things a parent will ever hear. Cancer has a significant negative impact on being productive in all aspects of life and on every relationship. One in three people will have cancer in their lifetime. One of three cancer patients will be negatively affected by the Ras mutation. One out of every 9 people will be at the risk of the damaging effects of Ras. Some of the deadliest cancers with the shortest prognosis for survival are Ras driven. Cancer metastasis are the major cause of cancer mortality, and accounts for about 90% of all cancer deaths. Higher levels of reactive oxygen species (ROS), has been identified as involved in tumor metastasis. Cancer brings with it many significant fears. Can we get to it? Did we get all of it? Can we kill it? Will the treatment be worse than having the cancer? How will my family react? Will it be painful? Will it spread? Will it come back? 

The cellular mechanism of Ag5, our lead molecule, is novel, and it has proved effective in mouse models of KRas mutant cancer while exhibiting a low level of toxicity to the host animal.  To date, we have detected no significantly adverse toxicological signature of Ag5. We believe that Ag5 and our follow on TMC compounds can address many currently untreatable forms of cancer. We believe we can operationalize both our Ag5 and Ag3 molecules and we are hopeful we can provide patients with a powerful new class of medicine. Both Ag5 and Ag3 exhibit the potency, selectivity, pharmacokinetic, pharmacodynamic, and toxicity properties that can allow them to progress to IND-enabling studies for clinical candidate selection.

Our vision is to remove the fear of a cancer diagnosis for every patient and every family.

Cancer is a progressive disease. During the course of this disease, cancers generally become more diverse and dissimilar in cell expression over time. As a result of this ongoing dynamic change, the tumor will include a heterogeneous collection of cells with distinct molecular signatures and each with differential levels of susceptibility to treatment. 

These differences usually create subpopulations of genetic variations in the molecular makeup of cancer cells. This difference provides the fuel for resistance. More and more therapies are addressing the overall complex architecture of cancers by being more and more targeted. 

Our knowledge of the process behind cancer has improved in the last two decades. This has revealed a uniqueness that can be found between not only distinctive types of cancer, but also between different patients with the same kind of cancer.

The current trend of thought is their won’t be a single cure for cancer. Research is mainly headed toward treatment for each patient and their specific needs. Current investments are moving more towards personalized medicine; thus, we need a massive range of therapies that is wide enough to cover the whole spectrum of cancer.

We believe that Therapeutic Molecular Clusters, especially our Ag5 TMC, is headed in the exact opposite direction. We believe it has the potential to treat a wide variety of cancers, in a wide distribution of people.  TMCs are very small molecules, allowing them to diffuse freely through the body, and across the blood-brain barrier. The cellular mechanism of Ag5, our lead molecule, is novel, and it has proved effective in mouse models of KRas mutant cancer while exhibiting a low level of toxicity to the host animal.  To date, we have detected no significantly adverse toxicological signature of Ag5.

We are a catalyst. Catalysts are of immense importance in chemistry and biology. We expedite the biochemical reactions in a cancer cell in specific ways that accelerate cancer cell apoptosis. 

We believe that Therapeutic Molecular Clusters can be potential new pharmacological agents based on a number of factors.  We have shown that clusters of three atoms can augment chromatin accessibility. This effect only occurs during DNA replication. Administration of both our Therapeutic Molecular Cluster Ag3 with Cisplatin increases the cytotoxic effect of DNA-acting drugs on human lung carcinoma cells. In mice with orthotopic lung tumors, the coadministration of Ag3 increases the amount of Cisplatin (CDDP) bound to the tumor DNA by fivefold without modifying CDDP levels in normal tissues. 

As a result, CDDP coadministered with Ag3 more strongly reduces the tumor burden. Evidence of the significance of targeting chromatin compaction to increase the therapeutic index of chemotherapy is one of the future applications we are going to explore further in the new field of Therapeutic Molecular Clusters. 

We have developed TMCs, Therapeutic Molecular Clusters, as an entirely novel class of medicines to bring new solutions to unmet medical needs.