Ankyra Therapeutics presented encouraging preliminary data from its first-in-human Phase 1 ANCHOR study of tolododekin alfa (ANK-101), an anchored interleukin-12 drug conjugate, at the 2025 American Association for Cancer Research (AACR) Annual Meeting. The study enrolled 15 patients with metastatic solid tumors who had progressed on standard therapy, demonstrating the potential to overcome historical limitations of IL-12 therapy through innovative anchoring technology.
Overcoming Historical IL-12 Limitations
The development represents a significant advancement in IL-12 delivery, addressing toxicity concerns that previously limited therapeutic potential. "The study demonstrates for the first time that IL-12 can be delivered to tumors at therapeutic doses higher than previously achievable without systemic toxicity," stated Dr. Howard Kaufman, Ankyra's President and CEO. Historical attempts at systemic IL-12 delivery were halted after reaching a maximum tolerated dose of 500 ng/kg, preventing further dose escalation in cancer patients.
Dr. Joe Elassal, Chief Medical Officer, highlighted the enhanced delivery efficiency: "IL-12 anchoring has resulted in 6-fold higher local IL-12 delivery to established cancers compared with what has been achieved with systemic administration." The anchored approach maintains highly efficient tumor retention while keeping systemic IL-12 exposure generally below 1%.
Phase 1 Study Design and Patient Population
The ANCHOR study enrolled patients across four sites in the United States and Canada, focusing on individuals with accessible lesions suitable for direct injection. The patient cohort included diverse tumor types: melanoma (n=7), head and neck cancer (n=4), breast cancer (n=2), bladder cancer (n=1), and apocrine adenocarcinoma (n=1).
The dose escalation portion evaluated safety and tolerability, with ANK-101 monotherapy well-tolerated at doses up to 250 µg/mL. Notably, the study reported no dose-limiting toxicities (DLTs) or Grade 3 or greater treatment-related adverse events, supporting the safety profile of the anchored delivery approach.
Biomarker Evidence and Immune Activation
Biomarker analysis of tumor-treated biopsies provided compelling evidence of immune activation. The treatment induced CD8+ T cell recruitment, local PD-L1 expression, and inflammatory gene signatures consistent with biologic IL-12 activity. "The high levels of PD-L1 seen provide strong justification for our expansion cohort combining tolododekin alfa with immune checkpoint blockade," noted Dr. Elassal.
These biomarker findings align with preclinical data showing recruitment and retention of CD8+ T cells, NK cells, and M1 macrophages, activating both innate and adaptive anti-tumor immunity.
Early Efficacy Signals
Initial efficacy results showed promising clinical activity with two partial responses and a disease control rate of 80% by modified RECIST v1.1 criteria. While preliminary, these results suggest meaningful therapeutic potential for the anchored IL-12 approach in heavily pretreated patients with advanced solid tumors.
Combination Therapy Expansion
Building on the monotherapy data, Ankyra has initiated combination therapy with Regeneron's PD-1 inhibitor cemiplimab (Libtayo). On March 25, 2025, the first patient with advanced cutaneous squamous cell carcinoma received the combination treatment in an expansion cohort of the ongoing Phase 1 trial. This strategic combination leverages the observed PD-L1 upregulation to potentially enhance therapeutic efficacy.
Technology Platform and Mechanism
Tolododekin alfa consists of interleukin-12 linked to aluminum hydroxide, creating a stable depot after local administration. The anchoring technology enables prolonged IL-12 activity in the tumor microenvironment for several weeks while preventing systemic diffusion and associated toxicity. This approach expands the therapeutic window by maintaining local immune activation without systemic adverse effects.
The company's broader platform technology aims to enhance various therapeutic agents through similar anchoring approaches, potentially addressing delivery challenges across multiple drug classes.
Future Development Plans
Ankyra plans additional clinical trials across different cancer types, building on the Phase 1 safety and activity data. The current study includes dose expansion cohorts following the completed dose escalation portion, with the combination therapy expansion representing the next phase of clinical development.
The company, founded in 2019 and headquartered in Cambridge, Massachusetts, continues to advance its anchored drug conjugate platform with tolododekin alfa as the lead asset. The technology's potential extends beyond IL-12, offering a platform approach for improving the therapeutic index of various cancer treatments.
