Kangstem Biotech(217730) is accelerating talks to out-license the osteoarthritis treatment "OSCA."
OSCA is a therapy that combines umbilical cord blood-derived mesenchymal stem cells with acellular cartilage matrix, and the company is developing it with the goal of the "world's first DMOAD (a disease-modifying osteoarthritis drug that slows disease progression)."
The key is "cartilage restoration." In the recently disclosed domestic phase 2a trial, pain and function improvement were consistently confirmed, but cartilage structure improvement achieved statistical significance only in some MRI indicators.
Kolon TissueGene(950160)'s "TG-C" also showed DMOAD potential in early trials but failed to reproduce it in later trials, so OSCA's MRI follow-up at 12 months after dosing is expected to be the first test. The company plans to secure those data in Nov.
◇ Pain and function improvement confirmed; "possibility" for cartilage restoration
A total of 113 patients with knee osteoarthritis participated in the trial. They were divided into a mid-dose group of 38, a high-dose group of 38, and a placebo group of 37, received a single administration of OSCA or placebo, and were followed for 24 weeks to compare pain, knee function, and cartilage status.
The effects on pain and function improvement were relatively clear.
In the VAS assessment, where patients mark perceived pain on a 100-mm line, the mid-dose group saw a decrease of 44.4 points and the high-dose group 37.7 points. Both were more than double the placebo reduction (14.9 points) and were statistically significant. Three other indicators assessing knee pain, daily living discomfort, joint stiffness, and physical function showed results in the same direction.
By contrast, the structural assessments using MRI were mixed.
In MOCART, which evaluates recovery in the most severely damaged area, only the mid-dose group achieved statistical significance versus placebo. The high-dose group showed a trend toward improvement but fell short of significance. In WORMS, which evaluates the overall knee joint structure, neither the mid- nor high-dose group showed a significant difference from placebo.
It showed a "possibility of cartilage restoration," but the evidence is still insufficient to conclude that structural improvement has been demonstrated.
Kangstem Biotech cited an insufficient number of patients as the reason the high-dose group did not reach significance in MOCART. The company said that in an exploratory trial with about 37 to 38 patients per group, individual response differences can greatly affect outcomes.
Assuming the currently observed between-group differences hold, the company also conducted internal simulations. It estimates that increasing the 36 patients in the placebo group and 35 in the high-dose group who completed 6-month follow-up to around 60 each could achieve statistical significance (p<0.05).
However, this is an analysis conducted after reviewing the trial results, not a sample size calculation pre-specified at the design stage. Whether the same effect is reproduced in actual follow-up trials must be confirmed in a larger study.
The company expects that the between-group difference in WORMS will become clearer as the observation period lengthens. Structural changes progress slowly, it said, making it difficult to confirm a significant difference across the entire joint in just 6 months.
◇ Preparing follow-up trials; reproducing and sustaining structural improvement is the task
Kangstem Biotech is preparing follow-up trials based on these results.
The company is considering setting pain improvement as the primary endpoint and structural improvement as a key secondary endpoint. Specific MRI assessment indicators and time points will be finalized in consultation with regulators, including the Ministery of Food and Drug Safety and the U.S. Food and Drug Administration (FDA), based on the 12-month analysis.
After completing the clinical study report (CSR) in the fourth quarter this year, the company plans to design the follow-up trials with its domestic partner, Yuyoung Pharmaceutical, and begin the trials next year after consultations with the Ministery of Food and Drug Safety. It then plans to submit an investigational new drug application (IND) to the FDA.
Founder Kang Gyeong-seon, a professor at Seoul National University's College of Veterinary Medicine, has taken on the role of scientific lead overseeing the follow-up development. Kangstem Biotech recently created the chief scientific officer (CSO) position and appointed Kang. As CSO, Kang will oversee scientific decisions in follow-up trial strategy, research and development, and the global technology transfer process.
The company is also pursuing technology transfer talks in parallel. It is prioritizing region-by-region transfer for North America, Europe, and Asia, while also leaving open the option of transferring global rights in a single deal, excluding Korea.
The company said, "We have begun full-fledged discussions with multiple corporations, and there is a global pharmaceutical company that is proceeding with a confidentiality disclosure agreement (CDA) at an unusually fast pace." A CDA is a contract signed before sharing technical data and is typically considered the first step in technology transfer negotiations.
The company is also presenting recently secured biomarker analysis results as grounds for the technology transfer talks. According to Kangstem Biotech, some biomarkers, including COMP related to cartilage damage, showed statistically significant differences compared with placebo.
The company said, "If the biomarker analysis results connect to OSCA's mechanisms of action for symptom and structural improvement, they could serve as grounds to enhance the consistency and reliability of the clinical results and lend momentum to our technology talks with global pharmaceutical companies."
However, global pharmaceutical companies' final judgment is expected to hinge on long-term follow-up data on structural improvement.
The basis for the company's expectations for the 12-month results is the long-term follow-up from the earlier phase 1 trial. According to the company, from about 6 months after dosing in phase 1, MRI signals of structural improvement or delayed structural worsening began to appear, centered on bone marrow lesions (BML), and these trends were maintained or strengthened at 12- and 24-month follow-ups.
Based on this, the company believes OSCA's structural changes may appear more clearly in longer-term follow-up than at 6 months.
The company said, "Global pharmaceutical companies review not only the efficacy of the therapy under development but also the reproducibility of the data, safety, and long-term durability. The 12-month data will be important materials to confirm the durability of the treatment effect and whether structural improvement is maintained."