RS Oncology's PRX3 Inhibitor (RSO-021) Shows Promise in Fight Against Deadly Mesothelioma, Rooted in Discovery Science from the University of Vermont

RS Oncology's PRX3 Inhibitor (RSO-021) Shows Promise in Fight Against Deadly Mesothelioma, Rooted in Discovery Science from the University of Vermont

Phase 1 Clinical Trial Shows 67% Disease Control

BOSTON — RS Oncology, LLC (“RSO” or the “Company”), a Boston-based clinical-stage biotechnology company, today highlighted results from a Phase 1 clinical trial of its lead candidate, RSO-021, published July 14 in Nature Communications. The study, led by Brian Cunniff, Associate Professor at the University of Vermont (UVM) and Chief Science Officer for RSO, together with an international team of collaborators, reports on a first-in-human trial of a novel therapeutic approach discovered at UVM and advanced into the clinic by RS Oncology.

About RS Oncology

RS Oncology was founded on a scientific discovery to treat pleural mesothelioma. RSO's mission is to address the significant unmet needs of patients with mesothelioma, a rare and aggressive cancer. The Company has built its scientific strategy around a novel biological vulnerability in the mitochondria that selectively kills mesothelioma tumor cells. RSO has developed a therapy around this mechanism, RSO-021, and is the first to enter clinical testing for treating patients with Mesothelioma.

About RSO-021

RSO-021 is RS Oncology's lead clinical candidate and the first small molecule therapeutic designed to covalently inhibit PRX3 in cancer cells. By inhibiting PRX3, RSO-021 overwhelms tumor cells with oxidative stress, leading to selective cancer cell death while minimizing effects on healthy tissue. As a locally delivered therapy with selective tumor cell elimination, RSO-021 offers a substantially improved safety profile relative to alternatives such as chemotherapy and immunotherapy. The program has successfully completed a first-in-human clinical trial and is currently finishing the Phase 2 portion of the MITOPE study in patients with malignant pleural mesothelioma.

An Urgent Need

Mesothelioma is a rare but aggressive cancer, usually caused by asbestos exposure. Inhaled asbestos fibers lodge in the lungs, triggering inflammation that can lead to tumor formation decades later. Approximately 30,000 people are diagnosed with mesothelioma worldwide each year. Existing treatments —immunotherapy and chemotherapy—offer limited benefit. Patients, often men who worked in shipbuilding, oil refining, and asbestos manufacturing, face a median survival of approximately 12 months and a five-year survival rate of barely 10 percent.

“It's a disease of significant unmet medical need,” said Cunniff.

Promising Phase 1 Results

In the Phase 1 trial, RSO-021 controlled disease progression in 67 percent of patients, with tumor shrinkage observed in some cases. The drug was well tolerated, and patients receiving RSO-021 lived longer than those on standard-of-care treatments. The trial met its safety and tolerability endpoints at a 90-milligram dose, with no patient deaths attributed to the drug. The team also confirmed on-target engagement in patient tissue samples, demonstrating that the mechanism observed in laboratory and animal studies also holds in human tumors. Progression-free survival averaged 4.2 months, comparable to current therapies, while overall survival exceeded what is typically seen with existing treatments — a result Cunniff called a potential “game changer.” “Our overall survival data is very promising and will hopefully persist with additional patients,” he said.

The Science: Turning Cancer's Own Defenses Against It

RSO-021's mechanism grew out of research at UVM's Larner College of Medicine that flipped the conventional logic of cancer treatment. Like many cancers, mesothelioma tumors generate elevated levels of “reactive oxygen species." To survive under these conditions, tumor cells ramp up production of antioxidant enzymes, including one called peroxiredoxin 3, or PRX3, in the mitochondria. For years, clinical trials attempted to increase antioxidants to combat cancer, reasoning that lowering reactive oxygen species would slow tumor growth. Those trials largely failed, and some showed that increasing antioxidants promoted tumor growth. The UVM team took the opposite approach: inhibit PRX3, overwhelm the tumor cell with oxidative stress, and kill the cancer cells.

RSO-021 is administered directly into the chest through a catheter already in place for patients with pleural effusions — a buildup of fluid between the lung and chest wall that affects roughly 90 percent of mesothelioma patients. This local delivery concentrates the drug at the tumor site while limiting systemic exposure. Beyond its cytotoxic activity, early data suggest RSO-021 may also help engage the immune system against the tumor. “Our drug has both cytotoxic activity — it can kill the tumor cells — but it also has immunomodulatory capacity, where it can modulate the immune system to now manage the tumor,” said Cunniff.

What Comes Next

The Phase 2 portion of the MITOPE study is now complete, and results are expected to be presented at an international oncology conference later this year. RSO is also advancing a second-generation PRX3 inhibitor with potential for systemic oral or IV delivery, an advance that could simplify the path to market and broaden the approach to other cancer types. Separately, the research team is exploring RSO-021’s potential in other pleural diseases and peritoneal malignancies, including mesothelioma, lung/ovarian cancers, urothelial carcinoma, and gastrointestinal cancers. “We believe this mechanism could be applicable to other cancers,” Cunniff said.

What matters most to us is what these results could mean for patients. Delivering a novel therapy directly to the pleural cavity and seeing this kind of tolerability and survival benefit is deeply encouraging, and it's a testament to the extraordinary collaboration with our international investigators, especially our colleagues in the UK. We're excited for the Phase 2 readout and for continuing this work to bring novel therapies to the patients who need them most.

“What matters most to us is the effect these results could have on patients. Delivering a novel therapy directly to the pleural cavity and seeing this kind of tolerability and survival benefit is deeply encouraging, and it's a testament to the extraordinary collaboration with our international investigators, especially our colleagues in the UK. We're excited for the Phase 2 readout and for continuing this work to bring novel therapies to the patients who need them most.” – Jarrett Duncan, CEO of RS Oncology