For decades, neurological diseases such as Parkinson’s disease, spinal cord injury, MSA and ALS have remained among the most difficult conditions to treat, with available therapies largely focused on managing symptoms rather than restoring lost function. XellSmart is pioneering a paradigm shift, leveraging allogeneic, off-the-shelf iPSC-derived cell therapies designed to replace damaged neural cells and potentially alter the course of disease itself. Founder and CEO Dr. Xiang Li (Micheal Lee) discusses the scientific rationale behind this approach, the progress of the company’s clinical programmes, and why he believes regenerative medicine is approaching a pivotal moment in the treatment of central nervous system disorders.
Our vision is to build a robust and compelling body of clinical evidence that establishes the therapeutic potential of iPSC-derived cell therapies. Step by step, our goal is to generate rigorous clinical data demonstrating that these therapies can deliver meaningful and lasting benefits for patients.
What led you to found XellSmart, and where does the company stand today in its development journey?
My commitment to regenerative medicine was born from a deeply personal experience that revealed how few effective treatment options exist for PD patients living with devastating neurological diseases. That experience ultimately inspired me to found XellSmart with a singular mission: to develop transformative stem cell therapies that restore hope and improve the lives of millions of patients and their families. Today, our primary focus is Parkinson’s disease, while advancing a broader pipeline for spinal cord injury (SCI), amyotrophic lateral sclerosis (ALS), and multiple system atrophy–parkinsonian type (MSA-P).
From the outset, we made a conscious decision to focus on allogeneic, off-the-shelf therapies rather than personalised or autologous approaches because we believe regenerative medicine must be scalable if it is to benefit large patient populations. The scientific rationale begins with the unique properties of induced pluripotent stem cells (iPSCs). Because these cells can self-renew and differentiate into a wide range of specialised cell types, they provide a powerful foundation for regenerative medicine and enable us to generate subtype-specific neural progenitor cells for different diseases. In Parkinson’s disease, for example, we develop dopaminergic neural progenitor cells, while in SCI and ALS we focus on spinal cord neuron progenitor cells. Importantly, a single well-characterised clinical-grade iPSC line can be expanded to support large-scale manufacturing and consistent production of therapeutic cells, ensuring ultimate product consistency and standardizability that is difficult to achieve with personalised approaches.
The second consideration is the scale of the diseases we are targeting. Parkinson’s disease alone affects more than 10 million people worldwide and remains the second most common neurodegenerative disease after Alzheimer’s disease. When treating patient populations of that size, it is difficult to see how personalised cell therapies can reach enough patients to make widespread clinical impact. We therefore believe that allogeneic iPSC-derived therapies represent the most practical path forward, combining the biological potential of regenerative medicine with a manufacturing model capable of delivering these therapies to patients on a far larger scale.
What differentiates XellSmart’s allogeneic, off-the-shelf iPSC-derived cell therapy platform, and why do you believe this approach is particularly well suited to CNS diseases?
For patients with early to mid-stage Parkinson’s disease, treatment typically relies on dopaminergic medications such as levodopa. While these therapies can be effective for a number of years, their ability to control symptoms often becomes less predictable as the disease progresses, leading to motor fluctuations and off-periods when symptoms return despite ongoing treatment. For some patients, deep brain stimulation (DBS) can provide additional benefit, but both medication and DBS remain symptomatic approaches. They can help manage the consequences of the disease, but neither can restore the dopaminergic neurons lost over time.
XellSmart operates on a fundamentally differentiated principle: cell replacement as a disease-modifying modality. Parkinson’s disease is driven in large part by the progressive degeneration of dopaminergic neurons, which diminishes dopamine production and impairs motor function. We are therefore using iPSC-derived dopaminergic neural progenitor cells as a regenerative therapy engineered to restore that lost cellular function. Rather than solely managing symptoms, we aim to address the underlying biological deficit through cell replacement. This is also the broader concept behind our work in other CNS disorders where specific neuronal populations are damaged or lost.
Initially, we target patients with moderate to advanced Parkinson’s disease who no longer gain sufficient relief from standard therapies. The cells are delivered through a stereotactic neurosurgical procedure, similar to DBS in terms of surgical precision, but without the need for permanent implanted hardware. The goal is to place the cells into the putamen, where they can potentially restore dopaminergic input to affected motor circuits and, over time, provide longer-lasting therapeutic effects.
What progress has XS411 made in clinical development, and how is XellSmart preparing the programme for global expansion?
XS411 is our lead Parkinson’s disease programme. The name reflects World Parkinson’’s Day on 11 April and stands as a tribute toserves as a reminder of the patient community that inspired our work in this area. In 2025, the programme secured regulatory clearance from both the US FDA and China’s NMPA, and it has since advanced into a multicentre Phase II registrational study in China. In parallel, we are evaluating the same product in early-onset Parkinson’s disease through a separate clinical programme led by Huashan Hospital of Fudan University, allowing us to explore its potential across different patient populations.
To date, we have enrolled more than 30 Parkinson’s disease participants across our studies and have not observed any serious safety issues related to XS411 itself. The adverse events reported so far have been associated primarily with the neurosurgical procedure or immunosuppressive agents and have been manageable. At the same time, we have seen encouraging signals across both clinical and imaging endpoints, including improvements in MDS-UPDRS Part III motor scores, increased ON time, and higher dopamine uptake on 18F-DOPA PET-CT scans. While it remains too early to draw definitive conclusions, these findings support our belief that XS411 has the potential to become a disease-modifying therapy rather than simply another symptomatic treatment.
Supporting this clinical development is a fully integrated manufacturing and quality platform that we have built in-house. The entire process, from iPSC reprogramming and cell banking through differentiation, cryopreservation, batch release, and clinical delivery, is conducted within our own GMP facility. Our strategy has always been to develop products in China with global standards in mind, which is why our manufacturing, CMC, and quality systems have been designed to align with both NMPA and FDA expectations. This foundation provides a clear pathway for international development and supports our long-term ambition to deliver our regenerative therapies to patients worldwide.
Why has XellSmart prioritised spinal cord injury as a key area of focus, and what have you learned from the early development of XS228?
Spinal cord injury is one of the most devastating neurological conditions and remains an area of profound unmet medical need. More than 15 million people are estimated to be living with spinal cord injury worldwide, including millions in China, with many cases resulting from traumatic events such as road traffic accidents. What makes this indication particularly important is that many patients are relatively young, yet a single injury can permanently alter the course of their lives, leading to the loss of mobility, independence, and employment, while creating a significant burden for their families.
From a scientific standpoint, spinal cord injury shares an important characteristic with Parkinson’s disease. In Parkinson’s disease, dopaminergic neurons are progressively lost, while in spinal cord injury, spinal-cord specified neurons are damaged or destroyed. In both cases, the central nervous system has only a limited ability to regenerate these cells naturally. Existing treatments, including surgery, rehabilitation, and physiotherapy, can help patients recover a degree of function, but they do not repair the underlying neural damage. This is where we believe regenerative medicine can make a meaningful difference by focusing on the cells themselves rather than simply managing the consequences of the disease or injury.
Our programme is built around XS228, an allogeneic, off-the-shelf iPSC-derived spinal neural progenitor cell therapy that is distinct from our Parkinson’s disease programme, XS411. We are developing XS228 for both spinal cord injury and ALS, applying the same underlying principle of restoring damaged motor neuron pathways via cell replacement. Across these programmes, we have already treated more than 20 patients in clinical studies and are working to advance both indications into the next stage of development as more clinical data matures.
How are your programmes in spinal cord injury and ALS evolving, and is there general interest in partnering or licensing your pipeline assets, as iPSC technology has till now not been truly attractive for MNCs?
We have been encouraged by the early clinical experience with XS228, particularly in spinal cord injury. One of the first participants treated in our programme had suffered a severe cervical spinal cord injury following a road traffic accident and initially had almost no meaningful motor function. Over the months following the XS228 transplantation, we observed progressive improvements across multiple muscle groups and functional measures. Approximately six months after cell administration, the patient was able to stand independently, by nine months had regained the ability to perform simple but important daily activities such as lifting a cup and drinking water, and by twelve months fine motor control had further improved, enabling relatively precise finger movements. While these findings come from an early-stage study and await confirmation in larger controlled trials, they have provided important encouragement for both our team and the clinicians involved in the programme.
The spinal cord injury study is being led by the Third Affiliated Hospital of Sun Yat-sen University in Guangzhou, one of China’s leading centres in this field. As with our Parkinson’s disease programmes, our strategy is to develop these therapies in China while building towards global clinical development, including future studies in the United States. The level of interest has already extended well beyond China, with enquiries from patients and families internationally who are closely following progress in the field and looking for opportunities to participate in future studies.
From a strategic perspective, the discussions we have had with potential partners reflect the different stages of maturity across the field. In Parkinson’s disease, the concept of cell replacement is supported by decades of scientific research, beginning with early fetal tissue transplantation studies that demonstrated the potential of replenishing lost dopaminergic neurons. What iPSC technology brings is a scalable, standardised, and commercially viable source of those cells. In spinal cord injury, by contrast, regenerative cell therapy remains a much newer clinical field. As a result, there is considerable interest from pharmaceutical and biotechnology companies. Our focus today is therefore on continuing to generate robust clinical data that can validate the approach and support the next phase of clinical development.
What do you see as the next catalysts for XellSmart, and how are you positioning the company to achieve them?
XellSmart is entering an important phase of its development. Following encouraging Phase I clinical results demonstrating a favorable safety profile and consistent signals of clinical benefit, XellSmart has advanced its lead product, XS411 Cell Injection, into a multicenter Phase II clinical trial in China. The study is led by Beijing Tiantan Hospital, the National Center for Neurological Disorders, in collaboration with Peking Union Medical College Hospital and other leading clinical centers nationwide.
The Phase II study employs the internationally recognized PROBE (Prospective, Randomized, Open-label, Blinded Endpoint) design. Given the chronic and progressive nature of Parkinson’s disease, clinical benefit must be evaluated across multiple dimensions, including motor function, activities of daily living, medication requirements, and long-term safety. The PROBE design provides both methodological rigor and a close reflection of routine clinical practice, enabling a comprehensive assessment of the efficacy, safety, and tolerability of XS411 while generating high-quality evidence to support its continued clinical development. Looking further ahead, our objective is to move our lead assets into Phase III pivotal studies, initiate broader clinical development in the United States, and ultimately progress towards BLA submissions and commercialisation.
In the next 6-12 months, we expect our other programmes across Parkinson’s disease, early-onset Parkinson’s disease, ALS, spinal cord injury, and MSA-P to be in Phase II clinical development. We aim to build a sustainable development model that enables consistent, streamlined registration pathways for novel therapeutics as our pipeline matures further.
As these programmes advance, we are seeing increasing interest from potential partners. While many pharmaceutical companies recognise the promise of regenerative medicine, iPSC-derived cell therapies remain a relatively new field, and discussions often extend beyond the clinical data to the underlying science, manufacturing platform, quality systems, and development capabilities required to bring these products to patients. We view this dynamic as a natural stage in the industry’s maturation. The unmet need in diseases such as Parkinson’s disease, spinal cord injury, and ALS is clear, and as more clinical evidence emerges, we believe the value of regenerative approaches will become increasingly evident.
Financially, we are in a strong position to continue executing our strategy. Since founding XellSmart, we have completed multiple financing rounds alongside key development milestones, supported by long-term investors including Qiming Venture Partners, Lilly Asia Ventures, HongShan, and others. Our most recent financing provides sufficient runway to complete our ongoing studies and support the transition of our lead programmes into late-stage development. At the same time, we continue to engage with international investors and remain open to structures such as a US-focused NewCo. This vehicle would pool incremental funding, local U.S. industry know-how and specialized management to accelerate clinical development for targeted pipeline assets in the United States.
What message would you like to leave with potential partners, investors, and the broader life sciences community about XellSmart?
At XellSmart,we remain focused on a long-term mission: developing allogeneic, off-the-shelf cell therapies for central nervous system diseases with significant unmet medical needs. We believe regenerative medicine represents a fundamentally different treatment strategy from standard pharmaceuticals and surgery, and that is what continues to generate interest across the industry. While I cannot disclose the names of potential collaborators, we are actively engaged in discussions with several organisations. There is rising consensus that regenerative cell therapy may offer a new way to address diseases such as Parkinson’s disease, spinal cord injury, ALS, and MSA-P, where treatment options remain limited and the burden on patients and families is substantial. Our goal is to continue building the clinical evidence, step by step, and demonstrate that these therapies can deliver tangible, meaningful benefits to patients.
Developing iPSC-derived therapies requires expertise across research, CMC, GMP manufacturing, quality systems, clinical development, and regulatory affairs, and we have built those capabilities within XellSmart. More importantly, there is a strong shared belief in what we are doing and in the potential impact these therapies could have on patients. As we continue to advance our pipeline, our ambition is to establish XellSmart as a recognised leader in central nervous system regenerative medicine and to build a distinctive position through scientific excellence, clinical execution, and a continued focus on addressing some of the most challenging neurological diseases.
