Ascentage's Bet on a Rare Cancer Drug Pays Off with Novel Science

ROCKVILLE, MD – November 24, 2025 – In the high-stakes world of biopharmaceutical development, a calculated bet on a niche market can yield outsized returns. Ascentage Pharma (NASDAQ: AAPG; HKEX: 6855) provided a masterclass in this strategy today, announcing the publication of promising clinical data for its drug, olverembatinib, in a rare and notoriously difficult-to-treat cancer. The results, featured in the prestigious Nature journal Signal Transduction and Targeted Therapy, not only offer a potential lifeline to a young patient population with no standard treatment options but also unveil a novel scientific mechanism that could reshape cancer metabolism research.

For investors and industry watchers, the news is a significant validation of Ascentage's pipeline and its strategic pivot into solid tumors. The data provides a powerful one-two punch: robust clinical efficacy in a setting of high unmet need, combined with a groundbreaking biological discovery that differentiates olverembatinib from a crowded field of cancer drugs.

A Breakthrough in a Neglected Cancer

Gastrointestinal stromal tumors (GIST) are rare, but the development of tyrosine kinase inhibitors (TKIs) like Novartis's Gleevec revolutionized their treatment over two decades ago. However, a small but significant subset of these tumors, known as succinate dehydrogenase (SDH)-deficient GIST, remained an enigma. This subtype, which disproportionately affects children and young adults, lacks the common mutations targeted by standard TKIs, rendering them largely ineffective.

For these patients, the prognosis is often grim, with limited benefit from existing therapies. Clinical studies of drugs like Pfizer's Sutent in similar patient groups have shown a median progression-free survival (mPFS) of less than six months. Against this bleak backdrop, Ascentage's Phase Ib study of olverembatinib stands out dramatically. In the largest prospective trial ever conducted for this rare disease, the drug achieved a clinical benefit rate of 84.6% among 26 patients who had already failed prior treatments. Most impressively, the median time before the disease progressed was 25.7 months—a more than four-fold improvement over previously studied options.

“SDH-deficient GIST is an extremely rare tumor type that lacks high-quality, prospective clinical data; and in Chinese and international clinical guidelines, there are currently no recommended treatments for unresectable SDH-deficient GIST,” said Prof. Ruihua Xu, Academician of the Chinese Academy of Engineering and a lead investigator of the study. “This Phase I study has yielded encouraging efficacy and safety results, suggesting that olverembatinib may offer a new treatment option for this indication.”

The publication of these findings in a journal with an impact factor north of 50 provides a powerful external validation, signaling that the data has withstood the scrutiny of leading independent scientists.

Starving the Tumor: A Novel Attack on Cancer Metabolism

Perhaps more compelling than the clinical numbers is the underlying science. The research accompanying the trial revealed how olverembatinib works in these specific tumors, and it's not just another kinase inhibitor. The translational study discovered that SDH-deficient tumors have a unique metabolic vulnerability: they are addicted to absorbing external fats, or lipids, to fuel their survival and growth.

This dependency is driven by the abnormal overexpression of a protein called CD36, which acts as a transporter on the cell's surface, pulling in lipids from the surrounding environment. The study established, for the first time, a direct mechanistic link between the SDH-deficiency that defines the cancer and this reliance on external fat.

Olverembatinib exploits this weakness. The research confirmed the drug effectively inhibits CD36 expression, shutting down the tumor's primary fuel line—an effect not seen with other TKIs. In essence, the drug starves the cancer cells. This dual-action approach, combining the modulation of lipid metabolism with the inhibition of other known cancer-driving pathways (like FGFR and VEGFR), likely explains its potent antitumor effect.

“Our pioneering translational research identified a putative mechanism of action,” commented Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. “We are very encouraged by these results, as they signal a potential breakthrough in addressing an indication with urgent unmet clinical need.” This discovery opens a new therapeutic paradigm, suggesting that targeting metabolic dependencies could be a powerful strategy for cancers that have proven resistant to conventional treatments.

The Business of Hope: Ascentage's Orphan Drug Strategy

For Ascentage Pharma, a commercial-stage but still unprofitable biotech, this success is a major strategic victory. The company's lead asset, olverembatinib, is already approved and generating revenue in China for treating specific types of chronic myeloid leukemia (CML). However, demonstrating its efficacy in a solid tumor significantly de-risks the asset and broadens its long-term potential.

The company is pursuing a classic and often lucrative orphan drug strategy. By targeting a rare disease with no approved treatments, Ascentage navigates a less crowded competitive landscape and can benefit from a more streamlined regulatory path. The company has already received a Breakthrough Therapy Designation from China’s NMPA for this indication, which can accelerate the review process.

This approach allows for smaller, faster, and less expensive pivotal trials. The ongoing international Phase III study, POLARIS-3, is a single-arm trial, meaning all participants receive olverembatinib. If the results from this study mirror the impressive Phase Ib data, it could pave the way for global regulatory filings with the FDA and EMA. Success in this niche market would not only provide a new revenue stream but also enhance the valuation of Ascentage’s entire kinase inhibitor platform, proving its technology can be applied beyond hematologic cancers.

From Bench to Bedside: The Path to Approval

The journey from a promising trial to an approved therapy is long, but Ascentage has a clear path forward. The POLARIS-3 pivotal trial is now actively recruiting patients across international sites. Its design as a registration-enabling study means its results will form the core of marketing applications submitted to health authorities worldwide.

The high level of unmet need and the engagement of patient advocacy organizations like The Life Raft Group, which is actively publicizing the trial to its community, create a favorable environment for recruitment and regulatory consideration. For a patient population of mostly children and young adults who have exhausted all other options, the 25.7-month progression-free survival seen in the early trial represents a tangible measure of hope—years of life that current medicine cannot offer.

As the POLARIS-3 trial progresses, both the investment community and the medical world will be watching closely. Ascentage Pharma has successfully translated a deep scientific insight into a potent clinical response, positioning a single asset to become a standard of care in two distinct areas of oncology. The company’s bet on a rare tumor may soon prove to be a defining moment in its evolution from a promising biotech to a significant player in the new economy of cancer therapeutics.