ONM-400-IL-2

The company’s founder and chief executive officer, Ravi Srinivasan, took time to speak with BioSpace to discuss the company and its technology platform. There are many approaches to cancer treatment, with the most common being surgery, chemotherapy, radiation and now immuno-therapy. There are other variations, such as hormone therapy, bone marrow transplant, cryoablation, radiofrequency ablation and some variation of targeted drug therapy. In terms of chemotherapy, immuno-therapy and various targeted drug therapies, a variety of methods are used to deliver a therapy directly to the cancer cells, whether it’s with antibodies that target antigens on the cancer cells or DNA or RNA from the tumors. It has been understood since at least the 1930s that cancer metabolism releases lactic acid, which decreases the pH. This has been difficult to exploit, but OncoNano Medicine, which spun out of the University of Texas Southwestern and is headquartered in Southlake, Texas, has a technology platform based on ultra-sensitivity to pH in the tumor microenvironment. As such, the company’s technology uses pH as a biomarker for cancer immunotherapy, therapeutic use and intra-operative imaging. The company’s founder and chief executive officer, Ravi Srinivasan, took time to speak with BioSpace to discuss the company and its technology platform. Srinivasan notes that changes in the acidity or pH values in the tumor environment can be quite small, where most probes can’t differentiate the differences. “Which is where ours is different. We’ve developed micelles based on that chemistry that the pH transition are 0.2 to .25 pH units, which from a proton concentration perspective is about 100 times more sensitive than off-the-shelf molecular probes.” This heightened sensitivity allows the company to basically load different types of payloads into the small micelles—small molecules, cytokines, antibodies—and deliver it with a high degree of specificity and selectivity to the tumor. They are pH-activated, so the micelles open up and release the payload to a very specific tumor marker. The company’s lead product, ONM-100, is a conjugated micelle that, Srinivasan says, “upon an intravenous injection, goes to the tumor and lights it up intraoperatively for the cancer surgeon to visualize. It ensures complete dissection of the tumor.” In a Phase I trial, 30 different patients across four different tumor types, breast, head-and-neck, colorectal and esophageal, were tested and all the tumors were illuminated comparable to the gold standards. “And more exciting,” Srinivasan said, “in 30% of patients we tested, we found tumors completely missed by standard care—by the surgeon, antibodies, etc., and this restaged the patients for potentially changed treatments.” hbspt.cta.load(4413123, '4e87abe9-779b-4c65-98dd-ea451779faa9', {}); Srinivasan says they view this as validation of the platform. “We’ve shown the agents are able to identify and light up tumors across multiple species, tumors, and this conserved marker species,” Srinivasan said. “And our platform is able to take advantage of it by specifically delineating the tumors.” ONM-100 is currently in Phase II studies. Another lead product, ONM-500, now called Mi-Vax, leverages the same micelle platform. An HPV tumor-specific antigen is loaded into the micelles. When subcutaneously injected, they accumulate in the lymph nodes and are endocytosed (engulfed) by dendritic cells. The lower pH of intracellular endosomes causes the micelles to dissociate, which releases the intracellular antigen and activates STING (STimulator of INterferon Genes), which activates the body’s T-cells directed to the tumor. This platform is dubbed Mi-Vax. In late-August, OncoNano received a $15.4 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT) to advance ONM-500. This was on top of a 2014 grant from CPRIT to advance ONM-100. “We have one more platform, our onboard platform,” Srinivasan said. “The same micelles validated for the imaging agent are used but are loading cytokines and small molecules.” He indicates they are in discussions with various companies on partnering on the technology to deliver the tumor markers. The next couple years will likely be busy ones for the company. OncoNano expects to complete the Phase II trial of ONM-100 in late 2020. Another program is ONM-400, called ONBOARD, with ONM-400 and ONM-401 being two different programs within ONBOARD that loads cytokines or small molecules into a similar micelle platform. “We also will advance our Mi-Vax platform product into the clinic by early 2021,” Srinivasan said. “And that program has now been funded by CPRIT.” The company hopes to make regulatory filings for both in mid-2021. In July 2019, the company completed a $23.7 million second tranche of its Series A financing, bringing the total Series A round to $35.4 million. The proceeds from the private financing, along with the grant from CPRIT, will be used to advance the imaging program through Phase II and bring the other programs forward. As said at the beginning of the article, there are many different approaches to delivering therapeutics to tumor cells, but OncoNano’s approach has some distinct advantages. “Antibody engineering has been trying to minimize the toxic side effects of potent molecules like cytokines, but there are toxicity issues in the clinic,” Srinivasan said. “Our approach offers complete encapsulation of these agents straight to the tumor, which increases the therapeutic window with fewer toxic side effects.”