JointStem Nears U.S. Entry with 2025 IND and 20,000-Dose Production
Interview with Jeong-chan Ra, Chairman of Nature Cell JointStem aims for Phase 3 finish in 2027, BLA in 2028 U.S. entry accelerates with expanded trial plans Distribution routes forming in Cancún and Florida
Nature Cell, which recently announced plans to enter the U.S. stem-cell market, has unveiled a roadmap for its transition into a global biotech company.
On November 20, the company held a press conference in Washington, D.C., to outline its U.S. stem-cell business strategy and future plans. During the event, Nature Cell shared details from its End of Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA) held on November 18, as well as five-year follow-up data from the Phase 3 clinical trial in Korea for its knee osteoarthritis stem-cell therapy, JointStem.
At the EOP2 meeting, the company discussed the design of the planned global Phase 3 trial and clarified the list of upcoming Chemistry, Manufacturing, and Controls (CMC) submissions required by the FDA.
Nature Cell also provided an update on the construction of the BioStar Stem Cell Campus, a GMP-certified manufacturing facility currently being built in Baltimore, Maryland.
Hit News spoke with Nature Cell Chairman Jeong-Chan Ra to discuss JointStem’s development and commercialization goals, the company’s vision for its U.S. expansion, and other topics not fully covered during the press conference.
You recently held an investor briefing in the United States to announce your entry into the stem-cell market. It must have been a meaningful moment. How would you describe your reflections on the event?
“Our U.S. operations will be centered in Baltimore, Maryland. Historically, Baltimore served as one of the most important ports during every major era of American expansion.
The new stem-cell campus is set to be established in a building originally constructed in 1883. Interestingly, 1883 is also the year when American missionaries began their work in Korea—at a time when Korea borrowed significant funds from them to begin initiatives in education and medicine.
This press conference symbolized a reversal of that history: Korean medical and stem-cell technology is now entering the United States to help save American lives. To convey that sentiment, we opened the event with a video of the Mugunghwa, the national flower of South Korea.
It reinforced our commitment. The idea that Korean technology could become a foundation for protecting the lives of people in the United States carries deep significance.”
Officials from the State of Maryland and the City of Baltimore also attended the event. How did they respond, and what kind of support can be expected going forward?
“Maryland is a major hub for biotechnology in the United States. Both the FDA and the National Institutes of Health (NIH) are located there.
Perhaps because of the high expectations for JointStem, the Maryland Lieutenant Governor reached out on the morning of the press conference requesting a meeting. They expressed strong interest in the project and said they would provide all possible support.
As part of that support, Maryland agreed to relocate the Public Safety and Correctional Services facility currently leased inside the Baltimore plant building we are acquiring, so that the space can be used to build the JointStem GMP center. Thanks to this cooperation, the GMP center has already moved into the design phase.
In addition to administrative assistance, Maryland will also provide legal support to ensure that we can complete the facility next year using our own internal capabilities. The state has committed more than $63 million in tax benefits, along with a $4 million conditional loan that does not need to be repaid if certain conditions are met.
Given the level of support we are receiving, we believe the timing of our expansion into the United States could not be better.”
You recently completed your EOP2 meeting with the FDA. You mentioned that the discussions were very positive. Could you elaborate on what was covered?
“Calling it ‘positive’ is actually an understatement. Put simply, an End of Phase 2 (EOP2) meeting is where all requirements for advancing a product into Phase 3 are agreed upon.
Once agreement is reached at this stage, it means that as long as those conditions are met, approval to proceed is essentially guaranteed. That is a crucial point.
As we also felt during our previous RMET (Regenerative Medicine Advanced Therapy) meeting, the FDA expressed complete satisfaction with the Phase 3 design and clinical components already conducted in Korea. They raised no objections or points of disagreement.
This means that the clinical pathway is now extremely clear, with no remaining differences of opinion. The only remaining area to finalize is the CMC section, which is especially important for biologics.
To be clear, this is not because there were issues with our current CMC plan. Rather, we aim to update certain test methods to ensure more efficient and reliable quality control in the future. Once Phase 3 begins, manufacturing processes and quality-control methods cannot be modified without jeopardizing approval.
Given the outcomes of the EOP2 meeting, the approval of our Phase 3 clinical trial plan is effectively assured. This meeting served as a preparatory step to ensure that the Phase 3 trial proceeds smoothly, and we are very grateful for that.
Another important achievement is that the FDA agreed to recognize the Korean Phase 3 study. Normally, companies must conduct at least two Phase 3 trials in the United States to obtain approval, but this recognition allows us to save more than $67.9 million in costs and years of development time.
The follow-up period after JointStem administration was also shortened. While similar products require two years of follow-up, we agreed on a six-month period for JointStem. In terms of reducing development time and cost, this is extremely significant—and I consider the meeting a major success.”
What is the detailed development timeline for JointStem?
“JointStem has received Breakthrough Therapy designation, which allows us to consult with the FDA in writing at any time.
Using these support mechanisms, we expect to finalize the remaining procedures and discussions by the end of January next year. The FDA recommended that we begin the clinical trial only after all CMC matters have been fully clarified.
Once that is completed, we plan to submit our Phase 3 clinical trial application to the FDA in February. This will initiate a 90-day IND review period. If no additional information is requested, we expect approval around May. Should the IND be approved, it would mark the first time in Korean history that a stem-cell therapy receives authorization to conduct a Phase 3 trial in the United States.
The Phase 3 study will be a global trial involving patients from the United States, Korea, Japan, and Europe. The benefit of this approach is that, once U.S. approval is secured, the data can also support submissions in Europe, Japan, and other regions. However, because the U.S. GMP center will not be completed by May, the initial clinical supply will be manufactured at our GMP facility in Korea.
We expect all patients in the study to receive JointStem injections and complete their six-month follow-up by the end of 2027. That would allow us to submit the Biologics License Application (BLA) in 2028.
We are aiming for final approval within the same year, and we are advancing construction of our U.S. GMP plant to ensure that we can meet market demand as soon as the product is authorized.”
There is also strong interest in the possibility of accelerated approval. How are you preparing for that pathway?
“We discussed accelerated approval during the EOP2 meeting, and I consider that a very meaningful outcome. At our IR session in Korea this past September, we stated that if the FDA agreed during our pre-meeting in January, we would pursue accelerated approval.
The EOP2 meeting provided an early opportunity to gauge the FDA’s stance. Importantly, the FDA did not say ‘no.’ When the FDA believes something is not feasible, they are very clear in saying so. The fact that they did not reject the idea outright is significant.
However, the FDA noted that, at this stage, the materials supporting accelerated approval are still ‘premature.’ This is because accelerated approval depends on establishing a surrogate marker, and that marker must be clearly defined and justified. The FDA asked us to propose how we plan to set this marker.
On the other hand, the FDA responded positively to the five-year long-term follow-up results from the Korean Phase 3 study. We expect to receive the Clinical Study Report (CSR) for that dataset next week.
Because the original study did not include a control arm, the FDA asked us to scientifically demonstrate whether JointStem reduces the rate of total knee replacement compared with patients who did not receive the treatment.
To address this, we plan to use pharmacoepidemiologic analysis—leveraging real-world claims data from the Korean Health Insurance Review and Assessment Service—to generate comparative evidence.
We aim to complete the accelerated approval briefing materials by February. In February or March, we plan to request a Type-C or Type-D meeting with the FDA to discuss the accelerated approval strategy. If the FDA agrees at that meeting, then pursuing accelerated approval becomes fully viable.
At this point, we cannot say definitively whether accelerated approval is ‘possible’ or ‘not possible.’ Just as with the full approval pathway, pursuing accelerated approval is one of our key goals for next year.”
The five-year follow-up data show that only about 5.8% of patients who received JointStem ultimately underwent total knee replacement. What is the significance of this result?
“For patients with severe knee osteoarthritis, surgery has essentially been the only option. These results demonstrate that a single injection of JointStem can deliver sustained benefit for five years. In other words, it presents a new treatment option.
With the aging population in the United States, the number of osteoarthritis patients is rising rapidly. It is estimated at roughly 70 million people, with about 30 million classified as severe cases. For these individuals, there has historically been no alternative to surgery.
Some ask how JointStem differs from steroids or hyaluronic acid, but JointStem targets a completely different population—patients who typically do not respond to those treatments. In that sense, it represents an entirely new market.
As demand in the United States grows, how do you plan to scale up production capacity and ensure supply?
“Our wholly owned U.S. subsidiary, Nature Cell America, will oversee the operation. We expect to finalize agreements related to the building and land in Baltimore around mid-month, which will transfer ownership to us.
Beginning in January next year, we plan to operate the site as a pilot plant capable of producing 20,000 doses annually—enough to treat 20,000 patients. Since we will be installing GMP facilities within an existing building, the project can be fully funded with our internal resources. We expect construction to be completed by October.
While supplying JointStem for the U.S. Phase 3 trial is one of the goals, the facility will also significantly strengthen the company’s visibility and credibility in the United States.
Next year, we also plan to establish a system that allows U.S. patients to receive JointStem treatment at our partner hospitals in locations such as Cancun, Mexico, ahead of formal FDA approval. In that scenario, the 20,000 doses produced in the United States would be utilized very quickly.
Although we are building distribution channels that can be used before full approval, we intend to maintain a direct-sales model rather than licensing our rights to another company. Reducing distribution layers will maximize revenue and margin. While the U.S. is a large country, the number of physicians who will actually administer JointStem is relatively concentrated—around 1,000. We plan to bring those key physicians into our network.
After the 2029 launch, our goal is to expand to a full capacity of 200,000 doses within three years. We estimate the associated costs at around $80 million.
Of this, we plan to invest roughly $30 million internally and raise $50 million from U.S. investors. Once this portion is secured, we expect to begin construction in October next year. After 2031, we plan to invest an additional $200 million to build an expanded GMP facility capable of producing 800,000 more doses.
In total, the required investment will be about $300 million. However, we will not raise this all at once—it will be carried out step by step, aligned with each development milestone.
We will fund the portions we can manage internally, and secure investment for the remaining phases. By 2031, we intend to grow into a facility with a production capacity of one million doses.”
How do you plan to secure the necessary investment?
“We already operate an active and growing stem-cell business. Because of that, we can cover roughly $30 million internally within our group. Even now, about 12,000 Korean patients travel to Japan each year to receive JointStem treatment, and that number continues to increase.
This business is operated by the Biostar Stem Cell Research Institute, and the revenue flowing in will be used to support both the initial 20,000-dose facility and the subsequent expansion to 200,000 doses.
For the remaining $50 million, we plan to raise external investment. In October, we were invited to the Florida headquarters of Raymond James Capital, where we were introduced to potential investors.
We cannot say we are in discussions with only one party, but we have identified several investors offering favorable terms. We are currently reviewing business plans together to determine the most advantageous structure.
Once the selection of investors is finalized, we aim to secure $50 million in funding by May next year. Since Nature Cell America is a U.S. corporation, we expect U.S. investors to participate through equity investment. We are reviewing these various options with guidance from experts.”
Are there any challenges anticipated regarding staffing for the U.S. GMP facility?
“Even though we plan to expand from 200 employees in 2028 to around 500 by 2031, we are not particularly concerned. That confidence comes from the experience we have already accumulated in Korea and Japan.
We have standardized processes for recruiting staff, dispatching them, and training them. Even employees without a science background or a four-year degree can complete job-specific training within about six months. Our plan is to train new hires in Korea and then send them to the U.S. facility.
However, to oversee and manage these teams, we will dispatch Korean personnel at the mid-management level or higher.”
What level of sales do you expect for JointStem in the U.S. market?
“Since there are no comparable drugs in this category, it is more appropriate to think in terms of how many patients we can treat, rather than estimating revenue based on the size of the severe osteoarthritis market.
We expect the factory price of JointStem to be at least $15,000 per dose, with the final physician-administered price exceeding $20,000. When you consider the number of patients who can afford this treatment, the potential population is in the millions.
Our plan is to treat around 50,000 patients in the first year after launch, 100,000 in the following year, and 200,000 thereafter.
In addition, many upper-middle-class patients who have not yet progressed to severe disease may seek out JointStem as an off-label preventive treatment. This would create an entirely new market.
Off-label use is also expected to grow for conditions such as rheumatoid arthritis or rotator cuff tears. To capture this demand, it is critical that we commercialize JointStem for osteoarthritis as quickly as possible—and that is where we are focusing our efforts.”
For which additional indications do you plan to seek approval for JointStem?
“The first new indication we have decided to pursue is autism. JointStem is more effective the younger the patient is, and we have already confirmed this in Japan. We expect to submit the clinical trial application no later than February next year.
We are currently in discussions for Johns Hopkins Hospital to serve as the lead clinical site. A major advantage is that our research institute is only about a 15-minute drive from Johns Hopkins.
Over the past decade in Japan, the area where we observed the strongest results has been autoimmune diseases. JointStem has shown promising effects not only on lupus itself, but also in dramatically reducing associated pain.
We have also seen strong results in Parkinson’s disease. Many Korean patients have already received the treatment and reported high satisfaction. We also believe JointStem may help reduce aggression in patients with Alzheimer’s disease, as we have consistently observed a decrease in aggressive behavior following treatment.
We plan to sequentially expand indications into areas with significant unmet medical needs—such as these conditions and rotator cuff tears—where patients currently have few effective treatment options.”
Regulatory discussions for regenerative stem-cell medicine are currently underway in the State of Florida. Are you planning to offer JointStem prior to formal FDA approval?
“Yes. After Florida’s announcement, we engaged a U.S. law firm to conduct a legal review. Their conclusion was that if we establish a GMP facility within the State of Florida, we would be able to supply JointStem with minimal legal risk.
In other words, products manufactured in another state—or in Korea—could raise regulatory concerns. For that reason, we are currently searching for property in Florida and plan to build a center with separate floors for GMP manufacturing, a clinic, and administrative offices.
Because constructing a GMP facility takes time, we also intend to maintain a parallel treatment pathway through Mexico. Our goal is to begin offering treatment in Florida as early as next November. However, since nothing is finalized, the program may ultimately run in both Florida and Mexico, or in only one of the two locations.”
You are currently in an administrative lawsuit regarding the MFDS’s rejection of JointStem’s approval. What is the status of the case?
“Personally, I respect the authority and decisions of our national regulatory agencies. However, when a decision is clearly mistaken, it should be corrected.
This lawsuit is not an act of defiance or protest against the regulator. It is about establishing proper standards so that Korea’s biotech industry can advance.
We are currently waiting for the MFDS to submit its response for the administrative hearing. They have not yet filed their statement. We expect the trial to begin around March next year.
We firmly believe that the decision will be corrected. Our recent discussions with the U.S. FDA have strengthened that conviction.
The FDA confirmed that there is no objective guideline for determining clinical significance specifically for treatments targeting severe knee osteoarthritis. Historically, for therapies in this situation, the FDA has granted approval when statistical significance is demonstrated, and has accepted that as evidence of clinical relevance.
Because the conversation often focuses solely on statistical significance, some have argued that JointStem lacks clinical significance. But academic societies—such as orthopedic associations—do have standards for evaluating clinical relevance. Their approach is based on patient-reported improvement: whether patients feel the treatment worked or not. The key question is whether the response rate is statistically higher than that of the control group.
By this measure, JointStem demonstrates clear clinical significance. The proportion of patients who reported meaningful improvement was far higher among those who received JointStem than among those who did not.
For that reason, we believe the MFDS’s rejection was influenced by subjective factors—even intentional bias—and that this must be brought to light.
The FDA stated that it does not have its own criteria for judging clinical relevance in this context, and will rely solely on statistical significance measured by the WOMAC osteoarthritis index and the VAS pain scale.
In this sense, correcting the MFDS decision is important not just for JointStem but for the broader advancement of Korea’s biotech innovation.”
Will the outcome of the administrative lawsuit affect your plans for a future launch in Korea?
“At this stage, we do not have plans to launch in Korea. Our focus is entirely on the United States.
The Korean market represents a very small share globally—about 1%, compared with more than 30% for the U.S. Given this difference, concentrating on the U.S. market is the right strategy. Once approval is obtained in the United States, we expect approval in Korea to follow naturally.”
You continue to pursue approval for JointStem. What guiding mindset and goals are driving this effort?
“Our entry into the U.S. market is not meaningful only for our company. We see it as a mission—an opportunity for Korean biotechnology to become a symbol of saving American lives.
We believe that the path we are taking in the United States represents the role of a ‘new way maker.’ Our efforts can serve as a model for other Korean biotech companies, allowing them to follow the same path. We are moving forward with a sense of responsibility and purpose, knowing that the work we do can help open doors for the entire industry.”
What kind of turning point will entry into the U.S. market represent for Nature Cell?
“It will mark the moment when Nature Cell evolves from a South Korean biotech company into a global major player. Once JointStem is approved in the United States, we are not looking at hundreds of billions of won in revenue—we are looking at sales in the multi-trillion-won range. After 2031, we estimate annual revenue of around $10 billion.
Beyond financial performance, this will also be a turning point in becoming a respected global biotech company—one that fulfills its responsibility to help save the lives of patients with difficult-to-treat diseases.”
Many patients and investors in Korea are closely following Nature Cell’s progress. Is there a message you would like to share with them?
“February 14 next year marks our 25th anniversary. It has been a long journey with many challenges, but we see this moment as the start of a new chapter—one where we move forward boldly in the U.S. market with a future-focused mindset.
For that reason, we do not dwell on the past. We are focused on the future we are about to create.
What matters most is trust. Not short-term, but trust sustained over years. I hope you will continue to believe in us, support us, and stay with us through this journey. If you continue to stand with us, I believe that in time, Nature Cell will become a company worthy of applause."