New Progress -- XellSmart Unveiled Phase I Results of Off-the-Shelf Parkinson's Disease Cell Therapy at MDS & Completed Blinded Phase II Enrollment

SEOUL, South Korea and SHANGHAI, Oct. 18, 2026 /PRNewswire/ -- New clinical data for XellSmart's off-the-shelf cell therapy for Parkinson's Disease was presented at the International Congress of Parkinson's Disease and Movement Disorders (MDS), one of the world's most prestigious gatherings for Parkinson's and movement disorder research. During the session Parkinson's Disease: Clinical Trial, Pharmacology, and Medical Management, an investigator shared landmark Phase I results for XS411, XellSmart's proprietary off-the-shelf cell injection, alongside a major milestone: full enrollment in its multicenter, randomized, parallel-group Phase II trial in China, which uses an open-label design with blinded endpoint assessment. The findings captured widespread interest among the global movement disorders community.

XS411 is an allogeneic cell therapy candidate comprising induced pluripotent stem cell (iPSC)-derived dopaminergic neural progenitor cells. It is designed for use without patient-specific human leukocyte antigen (HLA) matching and is administered with a standardized immunosuppressive regimen. Following transplantation into the putamen, the cells are intended to differentiate into functional dopaminergic neurons. These cells restore dopamine synthesis and metabolism, delivering meaningful improvements in Parkinsonian symptoms while maintaining a favorable safety profile.

Phase I Findings: Sustained Improvements in Motor Function, QoL and Molecular Imaging Biomarkers

This Phase I single‑arm, open‑label trial enrolled nine participants with moderate‑to‑advanced Parkinson's disease into three dose cohorts using a 3+3 dose‑escalation design. Mean disease duration was approximately 10 years. All had end‑of‑dose wearing‑off and OFF‑state Hoehn–Yahr stages of 3 to 4. Symptoms remained inadequately controlled with standard‑of‑care treatment, causing marked impairment in occupational and daily function.

Following standardized screening and assessments, participants received XS411 stem cell transplantation into the bilateral posterior putamen. The trial met its primary safety and tolerability objectives, and XS411 was generally well tolerated. No dose-limiting toxicities, serious adverse events or adverse events considered related to XS411 were reported during the follow-up period. Serial MRI monitoring showed no aberrant cellular overgrowth or tumor formation, and no graft-induced dyskinesia was observed.

All nine participants achieved robust clinical improvements during the follow-up period, with response magnitudes surpassing published minimal clinically important difference (MCID) thresholds — showing that the motor benefits potentially carry clinical significance.

For motor function, participants' OFF-state MDS-UPDRS Part III scores improved by an average of more than 30 points from baseline at six months post-transplant. Therapeutic gains continued to deepen per available longer-term follow-up data, with a trend toward greater efficacy in the higher-dose group compared with the lower-dose cohort.

Patient diaries captured real-world motor fluctuations，a major burden for people with moderate-to-advanced Parkinson's disease. At six months post-transplant, participants gained an average of over five hours of good ON time per day— defined as ON time without troublesome dyskinesia. Treatment benefits were sustained throughout the available follow-up, with a trend favoring the higher-dose arm.

Patient-reported outcomes from the 39-item Parkinson's Disease Questionnaire (PDQ-39) mirrored these positive trends. The results corroborate clinician-rated motor function and patient diaries, confirming concordance between measurable motor improvements and participants' self-perceived gains in daily living.

Notably, however, open-label trials carry inherent risk of bias in clinician ratings and patient-reported outcomes. To mitigate this limitation, this Phase I study integrated ¹⁸F-DOPA PET molecular imaging — a globally accepted objective biomarker to assess dopamine synthesis and metabolic capacity.

Post-transplant ¹⁸F-DOPA PET scans revealed elevated specific binding ratios in the putamen compared with baseline. Areas of increased tracer signal were anatomically consistent with the injection sites. These data demonstrate that transplanted XS411 cells survive, engraft and differentiate at the target site to establish functional dopamine synthesis and metabolic capacity. The graft replaces degenerated dopaminergic neurons with healthy, functionally active cells, creating a new endogenous source of dopamine.

Phase II Full Enrollment Achieved for World's First PROBE-Designed Stem Cell Trial in Parkinson's Disease

Building on the promising Phase I clinical outcomes, the registrational Phase II study of XS411 has successfully completed enrollment. This multicenter trial investigates the efficacy and safety of off-the-shelf XS411 cell injection for the treatment of primary Parkinson's disease. Led by Beijing Tiantan Hospital, a flagship National Center for Neurological Disorders, the trial includes multiple top-tier Parkinson's treatment centers across China as participating sub-centers, namely Peking Union Medical College Hospital, the Second Affiliated Hospital of Soochow University, and Jiangsu Province Hospital.

To strengthen the robustness of evidence, the trial employs a Prospective Randomized Open-label Blinded Endpoint (PROBE) design. Its core methodological features—randomized grouping, parallel-arm comparison, and blinded endpoint evaluation—effectively mitigate research bias, enabling more rigorous assessment of therapeutic efficacy and providing solid evidence to support subsequent confirmatory clinical trials. Specifically, under the study's blinded endpoint framework, independent outcome assessments eliminate subjective investigator bias, delivering a more precise and reliable reflection of genuine disease progression and treatment effects.

Notably, this is the world's first stem cell therapy trial for Parkinson's disease built around the PROBE design. To date, all 30 planned participants have been enrolled, cell transplantation has been completed in the treatment group, and follow-up is ongoing. The data generated from this study is expected to lay solid clinical and methodological groundwork for the pivotal Phase III registrational trial and provide high-grade evidence to support clinical translation of this novel cell therapy.

Delving into XS411: an HLA-Independent Off-the-Shelf Cell Therapy for Parkinson's Disease

Recent landmark studies published in Nature (2025), Cell (2025), and Nature Medicine (2026) have demonstrated the transformative potential of iPSC-derived dopaminergic neural progenitor cells for Parkinson's disease (PD) treatment. Among the four pioneering international trials, three adopted embryonic stem cell-based approaches, which face inherent ethical limitations that restrict broad clinical application. Kyoto University's iPSC therapy, the only conditionally approved PD cell product to date, relies on HLA "super-donor" lines and encounters technical, cost-related and regulatory barriers hindering worldwide deployment.

Conversely, XellSmart's XS411 is an off-the-shelf cell injection eliminating patient-specific HLA matching. Engineered for broad accessibility, XS411 avoids personalized cell production and large HLA cell banks. Combined with standardized immunosuppression, it has exhibited preliminary safety and promising efficacy for PD cell replacement in the Phase I trial.

But this is not enough. Off-the-shelf neural cell therapies demand reproducible manufacturing and accumulating clinical evidence. This design, only when combined with standardized cell sources, GMP-grade manufacturing and robust QC, could enable stable multicenter supply for future widespread clinical use. XS411 offers preliminary validation of this technical toute: Phase I dose-escalation is complete, and a multicenter randomized Phase II trial is underway, supporting a feasible route toward large-scale translation.

Further, two key milestones in 2026 bolster XS411's standardized global development.

First, XS411 has secured funding under China's National Major Innovative Drug Program. The XellSmart-led consortium includes Tongji University, NIFDC, Beijing Tiantan Hospital and Peking Union Medical College Hospital. Kicked off in June 2026, this industry-academia-clinic collaboration will speed breakthroughs and translation of universal neural cell drugs.

Second, in July 2026, after clinical trial clearance in China and the US, XS411 obtained FDA Fast Track Designation. This milestone enables efficient FDA communication on clinical strategy and trial design, and may qualify the program for expedited pathways including rolling review.

Leveraging these milestones and robust China clinical progress, XS411 maintains global competitiveness as an innovative, widely accessible cell therapy candidate through parallel progress across three workstreams: clinical evidence generation, pharmaceutical quality system optimization, and cross-border registration capacity building.

From Bench to Bedside: Full‑stack R&D and Manufacturing Sustain Global Rollout

The competitiveness of cell therapeutics spans the entire value chain, from cell source to clinical administration. Built around XS411, XellSmart has established an integrated R&D system covering iPSC reprogramming, directed differentiation, product characterization, quality control and preclinical safety assessment to manufacture clinical-grade cell products. Analytical tools including single-cell transcriptomics and systematic safety evaluations jointly support product characterization and quality research.

This capability is being validated within multicenter clinical settings. Enrolment has finished for the 30-participant Phase II trial, marking entry into a more rigorous phase. This stage hinges on robust clinical supply, cross-site alignment and standardized follow-up. Mastery of these operational elements will also build clinical process and quality know‑how to enable further trial expansion and industrial translation.

Collectively, the presentation at MDS brings XS411's clinical progress to the attention of the global Parkinson's research community. Its HLA-Independent product strategy, ongoing follow-up from the nine-participant dose-escalation study, multicenter randomized Phase II trial, Sino-US registrational roadmap and support from the National Major Innovative Drug Program exemplify the competitive strengths of pioneering Chinese biotechs including XellSmart in the global iPSC-derived cell therapy space.

SOURCE XellSmart Biopharmaceutical Co., Ltd.