With the 2024 Olympics now in full swing, we thought to recognize lead EpicentRx therapy, and torchbearer, AdAPT-001. This is an oncolytic adenovirus that encodes and expresses a transforming growth factor beta (TGFβ) trap. On injection, the AdAPT-001 TGFβ trap, which neutralizes the potently immunosuppressive cytokine, TGFβ, ignites the “cold” microenvironments of local and distant tumors and sensitizes them to subsequent treatment with an already tried, and failed, checkpoint inhibitor. Tumors are “hot” when they show signs of inflammation with infiltrating immune cells that mobilize to fight the cancerous cells, whereas “cold” tumors lack infiltrating immune cells, and this makes it a real challenge to treat them with immunotherapies.
The fact is that for all the success of checkpoint inhibitors like Yervoy, Opdivo, Keytruda in select tumor types such as melanoma and non-small cell lung cancer (NSCLC) and their potential to durably control or even cure the disease, most patients treated with them either fail to see improvement or only benefit for a short time. An intensive search is on in academia and pharmaceutical companies to develop the next generation of immune-based therapies that boost the activity but, most importantly, not the toxicity of checkpoint inhibitors. For example, the strategy to combine two checkpoint inhibitors, while often effective, comes at a steep price — a high rate of immune-related serious adverse events (irSAEs), which forces a significant ∼30-40% percent of patients to discontinue therapy.
By contrast, in preclinical and clinical studies, the AdAPT-001 torchbearer stimulates inflammation in cold, non-immune cell infiltrated tumors like sarcoma without severe toxicities. In this way, AdAPT-001 preconditions and primes resistant tumors for effective checkpoint inhibitor therapy, and dramatic antitumor responses are often the result, as has been repeatedly observed in the Phase 2 clinical trial called BETA PRIME.
For Paris 2024, the Olympic torch traveled via the Mediterranean from Olympia, Greece, where it was first lit, to Marseilles, France. Analogously, we hope and expect that AdAPT-001, having begun its anticancer journey in the United States, will soon traverse the seas and oceans to light the way for the millions of cancer patients across the world.