9/11. Veterans. Mesothelioma.

The health legacy of September 11 has not closed. The CDC's World Trade Center Health Program estimates that approximately 400,000 people were exposed to toxic contaminants, physical injury risk, and the stressful conditions that followed the attacks. That population includes responders, area workers, residents, students, and others who lived or worked in Lower Manhattan in the days and months afterward.

In 2024, investigators at the WTC Environmental Health Center reported four mesothelioma cases among survivors in their care: two pleural and two peritoneal. None of these patients had any identifiable asbestos exposure other than the WTC dust. Two of these patients were diagnosed at unusually young ages, and the latencies in the cohort were short relative to the typical asbestos-to-mesothelioma window. The authors called for continued surveillance, noting that further cases are expected as more time passes since the original exposure.

Asbestos was widely used throughout U.S. military operations during much of the 20th century. The VA documents potential exposure across shipyard work, insulation, demolition of older buildings, carpentry and construction, and the manufacture or installation of flooring and roofing materials, among other settings. Because asbestos-related disease can take decades to surface, a veteran who served in the 1960s, 1970s, or 1980s may receive a mesothelioma diagnosis only now.

That timeline is the reason mesothelioma is a long-term veterans' health concern rather than a closed historical issue. The VA continues to provide registry evaluations and benefits information for veterans who suspect prior asbestos exposure.

First-line therapy for mesothelioma has improved over the past decade. The FDA approved nivolumab plus ipilimumab for unresectable malignant pleural mesothelioma in 2020, and pembrolizumab in combination with pemetrexed and platinum chemotherapy in 2024 for unresectable advanced or metastatic disease. These approvals have expanded the choices clinicians have at the front line.

Even so, mesothelioma remains difficult to treat. The American Cancer Society reports a 5-year relative survival of approximately 15% for pleural mesothelioma across all SEER stages, with the figure falling to 11% in patients with distant disease. Patients who progress after initial therapy continue to face a meaningful gap in available options, especially those with advanced or unresectable disease. That gap is what drives the need for new, scientifically grounded approaches.

Cyncado Therapeutics is advancing TT-4, an investigational selective A2B adenosine receptor antagonist, as part of a focused effort on mesothelioma. The program is built around the rationale that adenosine signaling contributes to immune suppression in the tumor microenvironment, and that selective blockade of the A2B receptor may help restore anti-tumor immune activity.

We are also evaluating coordinated A2B/A2A receptor blockade through co-administration of TT-4 with TT-10, our investigational A2A receptor antagonist. For patients whose disease is driven in part by adenosine-mediated resistance to existing therapies, this combined approach may offer something the current standard of care does not.