-S.BIOMEDICS revealed promising one-year post-transplant data from their Phase 1/2a clinical trial of the TED-A9 cell therapy for Parkinson's disease. The data demonstrate efficacy profile of TED-A9 in 6 participants in the trial’s low and high dosing cohorts in a one-year follow-up.

• TED-A9 is high-purity ventral midbrain dopaminergic progenitor cells derived from human embryonic stem cells (hESCs) under rigorous GMP conditions
• All 12 participants in Phase 1/2a were administered with TED-A9, with the last participant receiving treatment in February 2024
• 6 participants from first group showed clinical improvement with cell survival and engraftment after 12 months
• TED-A9 transplantation demonstrated an enhancement of dopamine transporters by FP-CIT PET, which was correlated to the observed behavioral recovery.

Utilizing the Hoehn and Yahr scale which is a key parameter for assessing the severity of motor symptoms in Parkinson’s disease, 3 low-dose recipients demonstrated an average improvement of 19.4% (from stage 3.7 to 3.0), while 3 high-dose patients experienced a more significant improvement of 44.4% (from stage 3.7 to 2.0), indicating a notable shift from severe to milder disease states.

Another positive trend was observed through the MDS-Unified Parkinson’s Disease Rating Scale Part III (off) (MDS-UPDRS Part III (off)), which demonstrated notable behavioral recovery in participants confirming the treatment's efficacy. Low-dose patients showed a 22.7% improvement (12.7-point decrease), while high-dose patients experienced a 25.3% improvement (13-point decrease). Notably, freezing of gait, a side effect that causes temporary movement cessation, was completely resolved in 1 of 2 low-dose patients (50% improvement) and in all 3 high-dose patients (100% improvement), suggesting a return to normalcy. In addition, wearing-off in patients has also improved.

The mechanism of behavioral recovery was evaluated using FP-CIT PET, a neuroimaging technique that assesses dopaminergic graft and synapse formation. It detects increase of dopamine transporters (DAT) in synapses formed by transplanted cells. TED-A9 showed an overall increase in FP-CIT PET with higher increase in high-dose group compared to low-dose group, further confirming underlying mechanisms.

TED-A9 also demonstrated positive outcomes in non-motor assessments including the Non-Motor Symptoms Scale (NMS), Parkinson’s Disease Questionnaire-39 (PDQ-39), MDS-UPDRS Part II, and the Schwab and England Activities of Daily Living Scale (SEADL).

In terms of safety, no issues have been observed related to the transplanted cells. One of the 12 participants experienced mild hemorrhaging in an area unrelated to the transplant site, but no specific neurological abnormalities or other side effects were observed.

“We are excited by our data package, which shows a positive trend throughout the study period. The results demonstrate that we have developed a cell therapy that not only promotes behavioral recovery but also confirms the mechanism through neuroimaging,” said Prof. Dong-Wook Kim from Yonsei University College of Medicine and CTO of S.BIOMEDICS. “We will continue to unveil new data through our ongoing study.”

TED-A9 and Phase 1/2a clinical trial

TED-A9 is an investigational cell therapy designed to replace ventral midbrain-specific dopaminergic cells lost in patients with Parkinson's disease. These ventral midbrain-specific dopaminergic cells are derived from hESCs (human embryonic stem cells) by exclusively utilizing small molecules only. TED-A9 represents a significant advancement in the field, offering highly purified dopamine cells derived from hESCs. Through surgical procedure, these hESC-derived dopaminergic progenitor (precursor) cells are transplanted to three segments of the putamen; the anterior, middle, and posterior sections, with three tracks per each putamen. Bilateral putamina received cell transplantation in a single surgical procedure, with cells injected at three points within each track. After transplantation, the expectation is that the transplanted dopaminergic progenitor cells will mature into dopaminergic neurons which will enhance the neural link of Parkinson’s patient, restoring the motor function of patient.

The Phase 1/2a clinical trial was conducted on 12 participants who have been diagnosed with Parkinson's disease for more than 5 years and exhibited motor complications such as wearing-off, freezing of gait or dyskinesia. Participants were aged 50 to 75 years. TED-A9 was administered to 6 participants in the low-dose group (3.15 million cells) and to another 6 participants in the high-dose group (6.30 million cells).

An initial cohort of three patients was enrolled at a low-dose to assess initial safety, including dose-limiting toxicity (DLT) evaluation, over a period of up to 3 months post-transplantation. There were no safety concerns within this timeframe. Thus, an additional 3 patients were enrolled at a high-dose for evaluation over another 3-month period post-transplantation. As no safety issues arose during this extended period, the clinical trial continued by adding three further patients to each of the low-dose and high-dose groups, totaling 12 patients. The final participant was administered with TED-A9 on February 2024.

The primary objective of the Phase 1/2a trial is to assess the safety and exploratory efficacy of TED-A9 transplantation for 2 years post-transplant. Safety will be monitored for additional 3 years, making it a total 5 years.