Advancing Precision Therapies Across High-Need Indications

When GBM inevitably returns following frontline standard-of-care, the disease is exceptionally aggressive and highly resistant to further conventional treatments. In this recurrent setting, clinical options are severely limited, and median survival drops drastically to approximately 6 to 9 months. This devastating cycle of relapse is driven by a highly resilient subpopulation of cancer stem cells (CSCs) that survive initial surgical and chemoradiation interventions. These residual CSCs rely heavily on the OLIG2 transcription factor to rebuild the tumor architecture and actively suppress the immune microenvironment. Because addressing this resistance is our most immediate clinical priority, Recurrent GBM is the foundational indication for the dose-escalation phase of our ongoing OPAL Trial. By utilizing CT-179 to precisely target OLIG2, we aim to dismantle the cellular engine of recurrence, reverse tumor-driven immune evasion, and offer a powerful new therapeutic avenue for patients who have exhausted standard therapies.

The most common and lethal primary adult brain tumor. There are approximately 30,000 to 40,000 new cases diagnosed annually across major global markets. Despite maximum surgical resection, radiation, and chemotherapy, recurrence is nearly universal. The median overall survival is approximately 14 to 16 months, with a 5-year survival rate of less than 10%. Furthermore, a significant portion of GBM patients have an MGMT-unmethylated status, rendering their tumors inherently resistant to standard chemotherapy. By targeting OLIG2, we aim to eliminate the cancer stem cells driving recurrence and sensitize tumors to radiation and immune attack.

Initially growing slowly, LGGs inevitably progress to lethal, high-grade tumors. Clinical outcomes vary significantly by grade. Grade 2 LGG generally responds well to newly developed targeted IDH inhibitors, which can dramatically extend progression-free survival (PFS) from roughly 11 months on standard care to over 27 months. However, Grade 3 LGG is far more aggressive and generally does not respond durably to IDH inhibitors alone, leading to rapid progression and sharply declining survival rates. The incidence of IDH-mutant astrocytoma and oligodendroglioma is estimated to be about 5,000 patients annually across the major markets. Curtana is exploring rational combinations to intervene at the cancer stem cell level and halt progression where standard IDH inhibition falls short.

Pediatric Diffuse Midline Gliomas (DMG, also known as DIPG) are devastating pediatric tumors located in critical, inoperable areas of the brainstem. Incidence across major markets is roughly 800 to 1,000 cases annually. Children have historically faced a severe lack of targeted therapies, resulting in a profoundly tragic prognosis: a median survival of merely 8 to 11 months, and a 5-year survival rate of less than 1%. While the recent emergence of targeted agents like dordaviprone has provided an encouraging clinical benefit for a subset of patients, tumors inevitably adapt and progress, underscoring the critical need for complementary therapies to overcome resistance. CT-179’s robust ability to successfully cross the blood-brain barrier offers highly targeted promise for these difficult-to-reach tumors, both as a monotherapy and as a rational combination to extend patient survival.

Medulloblastoma is the most common malignant pediatric brain tumor. Incidence across major markets is roughly 1,500 to 2,000 cases annually. While aggressive frontline treatments can achieve primary 5-year survival rates of 70-80%, roughly 30% of patients experience recurrence. Once the disease recurs, it becomes exceptionally difficult to treat. The median survival post-recurrence plummets to roughly 8 to 15 months, and the 5-year survival rate after relapse drops below 15%. This severe landscape demands novel combination approaches to bypass established treatment resistance.