RESTEM, a clinical-stage biotechnology company, presented positive Phase 1 trial data for its umbilical cord outer lining-derived stem cells (ULSCs) program in adult patients with Polymyositis (PM) and Dermatomyositis (DM), also known as Idiopathic Inflammatory Myopathy (IIM). The data, presented at the American College of Rheumatology's ACR Convergence 2024, demonstrated the safety and potential efficacy of ULSCs in treating this orphan disease with high unmet medical needs.
The open-label, dose-escalation Phase 1 trial (NCT04723303) involved nine participants, with three receiving single intravenous infusions of 50, 100, or 200 million ULSCs, respectively, followed by 12 months of observation. The primary endpoint was to determine dose-limiting toxicity (DLT) and the recommended Phase 2 dose.
Key Phase 1 Findings
Efficacy data revealed that six out of nine patients (66.7%) met the criteria for moderate improvement, achieving a Total Improvement Score (TIS) of ≥40% within six months of infusion. A clinically significant improvement, defined as a TIS of ≥20%, was observed in seven out of nine subjects (77.8%). The average TIS was sustained in the 30-35% range over the 12-month study period.
Manual Muscle Testing (MMT8) scores showed a significant improvement in muscle strength, increasing by nearly 10 points from baseline (59 ± 4) to Month 6 (68 ± 4) (mean ± SEM, p<0.001).
Importantly, the average prednisone dosage decreased by 35% at 6 months, excluding data from one non-responder who experienced a flare treated with corticosteroids. Among the seven participants who were daily prednisone users, six (86%) experienced an average reduction of nearly 50% in their prednisone dosage.
The treatment was generally well-tolerated, with only one adverse event (flushing reaction) occurring during the infusion in the first patient. The infusion was temporarily paused, hydrocortisone was administered, and the infusion was successfully re-initiated without recurrence.
Clinical Perspective
"We are extremely encouraged by the data presented at this year’s ACR which validates our ULSC approach to targeting the symptoms of PM/DM while reducing detrimental steroid use," said Andres Isaias, Chief Executive Officer of RESTEM. "The treatment was well tolerated and led to clinically meaningful and durable improvements in the TIS in 78% of patients. Based on the promising results from Phase 1 we look forward to advancing the study to Phase 2/3 in 1Q 2025."
Rafael Gonzalez, PhD, Chief Development and Science Officer, added, "Phase 1 data are highly promising, demonstrating the safety and tolerability of ULSCs, along with encouraging initial clinical outcomes. Notably, treatment with ULSCs resulted in a 35% reduction in steroid dosage within 6 months, indicating its potential to modulate inflammation in the immune system. These results serve as a testament to the significant progress we are making in advancing cell therapies, and we believe that our ULSC therapy has the potential to become a transformative treatment option for PM/DM."
Dr. Jonathan Krant, Chairman of Rheumatology for Monadnock Health Systems, commented, "These are remarkable clinical data. If validated, a 35% reduction in steroid use has broad implications for PM/DM patients currently treated with standard induction and maintenance regimens".
About Polymyositis and Dermatomyositis
Polymyositis and dermatomyositis are debilitating inflammatory myopathies characterized by muscle weakness and inflammation. Current treatments primarily involve immunosuppressive drugs, which can have significant side effects. The need for safer and more effective therapies is substantial.
