Abstract. Purpose: Inhibition of the cyclin D-cyclin dependent kinase (CDK)4/6-INK4-retinoblastoma pathway can overcome acquired or de novo treatment resistance to endocrine monotherapy. Responses to ...

Theriva Biologics (NYSE American: TOVX) reported significant progress in Q2 2025, highlighted by positive topline results from their VIRAGE Phase 2b trial of VCN-01 (zabilugene almadenorepvec) in metastatic pancreatic cancer. The drug, combined with standard chemotherapy, demonstrated improved overall survival, progression-free survival, and duration of response.The company also presented Phase 1 safety and clinical outcome data for VCN-01 in retinoblastoma at ASCO 2025. Financially, Theriva reported $12.1 million in cash as of June 30, 2025, with runway extending into Q1 2026. General and administrative expenses increased significantly to $11.2 million, while R&D expenses decreased 34% to $2.0 million.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the treatment landscape of hormone receptor-positive (HR + ) breast cancer.[1] Since their clinical introduction in 2015, the three CDK4/6i—ribociclib, palbociclib, and abemaciclib—have emerged as cornerstone therapies for HR+/HER2- metastatic breast cancer (mBC) in combination with endocrine therapy (ET). These agents exert their therapeutic activity by inhibiting CDK4/6-dependent phosphorylation of the retinoblastoma (Rb) protein, resulting in G1 cell cycle arrest and halting cancer cell proliferation.[2] All three agents have consistently demonstrated a significant improvement in progression-free survival (PFS) compared to ET alone,[3–6] while conflicting results have been yielded for overall survival (OS).[7–11] Beyond metastatic disease, CDK4/6i are currently being actively investigated in early-stage breast cancer, with early data suggesting a potential benefit in improving invasive disease-free survival (iDFS), leading to regulatory approval for select high-risk patient populations in adjuvant setting.[12,13] However, identifying the optimal patient population, determining the long-term benefits of these therapies, and evaluating their emerging role in neoadjuvant setting remain ongoing areas of investigation.