What was your biggest professional highlight of the past 12 months?
We’ve seen several notable highlights over the past 18 months, but if I had to name one, it would be the approval of lisaftoclax in China in July 2025 for patients with chronic lymphocytic leukemia and small lymphocytic lymphoma who have previously received at least one systemic therapy including Bruton’s tyrosine kinase (BTK) inhibitors, making it only the second B-cell lymphoma 2 (Bcl-2) inhibitor to be approved anywhere in the world since AbbVie’s venetoclax in 2016. The approval validated decades of work targeting apoptotic pathways. This approval brings a differentiated therapy to patients who urgently needed new options, including those who had already had their disease progress on venetoclax, which was the only other approved drug in this class.
In 2025, we also saw significant momentum across our pipeline. Our BTK protein degrader received investigational new drug clearance from the U.S. Food and Drug Administration, our first proteolysis-targeting chimera (PROTAC)-based asset to reach this milestone. Our flagship drug, olverembatinib, the first third-generation BCR-ABL tyrosine kinase inhibitor ever approved in China for patients with chronic myeloid leukemia, continued to reach more patients following its inclusion in China’s National Reimbursement Drug List. Taken together, 2025 confirmed that Ascentage Pharma has evolved from a single-product biotech to a global multi-product commercial biopharma.
Have small molecules been overshadowed by newer modalities – and where do they still hold a clear advantage?
The narrative that small molecules are being displaced is, I think, significantly overstated. The excitement around cell therapies, antibody-drug conjugates, and ribonucleic acid-based approaches is well-founded and these are genuinely important advances, but small molecules retain unique advantages that are often underappreciated.
Oral bioavailability remains a major advantage. Both of our approved drugs, olverembatinib for chronic myeloid leukemia and lisaftoclax for chronic lymphocytic leukemia and small lymphocytic lymphoma, are taken orally. For patients living with these conditions, many of whom may be on treatment for years or even decades, that matters enormously for quality of life and for sustained adherence in a way that infused biologics simply cannot match. The ability to cross the central nervous system, via the blood-brain barrier, is another area where small molecules have a real structural advantage, while remaining a major limitation for larger modalities. Perhaps most strikingly, the emergence of protein degraders like proteolysis-targeting chimeras is extending the reach of small molecules into targets previously considered undruggable. We are advancing our Bruton’s tyrosine kinase degrader, a drug designed to eliminate that protein entirely rather than simply inhibit it, into global Phase I trials. Unlike conventional inhibitors, it eliminates the target protein rather than simply inhibiting it, offering a potential way to overcome drug resistance. Far from being overshadowed, small molecules continue to evolve into increasingly sophisticated therapies. Small molecules also generally involve less complex manufacturing and regulatory requirements than biologics or cell therapies, supporting broader global commercialization.
What’s one area of drug development or manufacturing that is advancing faster than most people realize?
Targeted protein degradation is moving far faster than most people outside the field appreciate. The technology works by using specially engineered small molecules to hijack the cell's own protein disposal system to selectively destroy disease-causing proteins, including ones that have no site for a conventional drug to bind. When the first clinical trial in this field began in 2019, the technology was still largely a scientific curiosity with extraordinary theoretical promise. By mid-2025, at least 28 of these degrader candidates were in clinical trials globally, ten of which had already advanced to Phase II or Phase III. The first Phase III data showed a statistically significant clinical benefit, and the first regulatory submission followed shortly after. We are proud that our own degrader APG-3288, which targets a key protein involved in certain blood cancers, has now received clearance for clinical investigation from both the U.S. Food and Drug Administration and China’s drug regulatory authority. The pace of progress has yet to be fully appreciated, particularly for patients with diseases previously considered beyond the reach of small-molecule therapies.
What will look completely different about drug development in 10 years?
The boundary between small molecules and biologics will become obsolete so that the modality divide will no longer exist. Protein degraders, molecular glues, and other next-generation small molecule technologies are already reaching targets and mechanisms that were previously the exclusive domain of antibodies and cell therapies. We’re witnessing the dismantling of the assumption that the complexity of a disease target determines the complexity of the drug required to address it. That is no longer true. In ten years, I expect the choice of therapeutic modality to be dictated entirely by the biology of the problem rather than by historical convention or the limitations of prior technology. What will matter is whether a therapy reaches the right target, in the right cell, at the right time, with an acceptable safety profile. The patients who stand to benefit most from this shift are those whose diseases were previously considered beyond reach.
Dajun Yang is Chairman & CEO of Ascentage Pharma Group International
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