What is a Therapeutic Molecular Cluster?
Therapeutic Molecular Clusters are an entirely novel class of therapeutic. They 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.