Coiled Therapeutics (AIM:COIL) executive chair, Dr Sotirios Stergiopoulos, talked with Proactive about promising clinical results for its lead oncology candidate AO-252, alongside CEO Sridhar Vempati. The discussion highlights a significant improvement in clinical outcomes, with the company reporting an increase in clinical benefit rate from 40% to 80% following a shift to twice-daily dosing.
Vempati explained that the enhanced efficacy appears linked to sustained drug exposure, noting that maintaining therapeutic levels for longer durations helps drive stronger results. He also emphasised AO-252’s multimodal mechanism, targeting mitosis, DNA damage repair, and immune activation. This approach not only attacks tumours directly but may also help the immune system recognise and respond to cancer more effectively.
Dr Stergiopoulos highlighted the importance of these findings in heavily pre-treated patients, many of whom had exhausted available treatment options. He said, “The fact that we’re seeing effect is really astounding… and it gives us every confidence that we are on the right path.” The ability to generate responses in such late-stage cases suggests potential for even greater efficacy in earlier treatment lines.
The company is now advancing plans for combination trials and new formulations, with multiple data readouts expected throughout 2026. AO-252’s favourable safety profile and synergy with existing therapies could expand its use across a wide range of cancer indications.
Proactive: Sotirios, Sridhar, very good to speak with you. I'll start with you Sridhar — you've gone from a 40% to an 80% clinical benefit rate just by switching to twice daily dosing. How significant is that jump? And what does it tell you about how this drug actually works?
Sridhar Vempati: It's a very good question. What we see is that doubling the clinical benefit rate from 40% to 80% is a profound shift. It tells us that AO-252 is likely concentration-dependent rather than peak-dependent. With once-daily dosing, drug levels may drop below the efficacy threshold during the day. With twice-daily dosing, we maintain therapeutic levels for longer, which drives efficacy.
This has also been validated preclinically, where we saw more cures in mice with twice-daily dosing. Clinically, we’re now seeing that confirmed. Additionally, because AO-252 activates the immune system through mitosis and DNA damage repair pathways, sustained exposure helps maintain immune activation. Importantly, switching to twice-daily dosing has not increased toxicity — the safety profile remains benign, and we have not yet reached the maximum tolerated dose.
Proactive: Sotirios, some of these patients had already tried nine different treatments before AO-252. What does it mean to see results in people who have essentially run out of options?
Dr Sotirios Stergiopoulos: This is exactly what you look for in a drug. As a physician, you never want to run out of options. The fact that we’ve seen clinical effects in heavily pre-treated patients gives us confidence that this drug can work even in very difficult situations.
These patients had undergone multiple lines of therapy, and many were being considered for hospice care. Seeing reductions in such cases is very encouraging. It suggests that if the drug is used earlier, it could be even more effective.
Proactive: You’re talking about AO-252 potentially activating the immune system as well as attacking tumors directly. If that holds up, how could this broaden long-term market potential, particularly in combination therapies?
Sridhar Vempati: Most oncology drugs are either cytotoxic or immunotherapies. AO-252 is multimodal — it targets mitosis, DNA damage repair, and the immune system.
This allows it to work across multiple pathways and makes it highly suitable for combination therapies. Its safety profile supports combining with chemotherapy, targeted therapies, or immunotherapies.
Importantly, AO-252 can convert “cold” tumors into “hot” ones, making them visible to the immune system. That opens up combinations with major immunotherapies like KEYTRUDA. Preclinical data also shows synergy with chemotherapy and antibody-drug conjugates, significantly expanding the market opportunity.
Proactive: Sotirios, you’ve got a packed calendar for 2026. What’s the single data readout you're most excited about?
Dr Sotirios Stergiopoulos: There are multiple areas of focus in 2026. We’re starting with a new formulation aimed at improving on the 80% clinical benefit rate. We expect to have a significant number of patients enrolled by mid-year.
We’re also exploring multiple indications and planning combination trials, including one in Australia. Additionally, we’re working with the FDA to define dosing for expansion cohorts. It’s a very data-rich year with multiple catalysts expected in the second half.
Proactive: Final thoughts?
Sridhar Vempati: We believe Coiled Therapeutics is poised for its next step. We have the team and strategy to execute on key milestones and bring AO-252 to market faster.
Dr Sotirios Stergiopoulos: We’re extremely excited and look forward to continuing to develop this treatment and potentially changing the treatment landscape.