Lisata Therapeutics Inc (LSTA)

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Abstract: Type 1 diabetes mellitus (T1DM)...

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STEM CELL MEETING ON THE MESA
October 7-9, 2015
http://stemcellmeetingonthemesa.com/scientific-symposium/poster-session/
Poster Session

"32. Evaluation of the Safety & Efficacy of Autologous Ex Vivo Expanded TRegs (CLBS03) for the Treatment of New Onset Type 1 Diabetes Mellitus in an Adolescent Population

Presented by: Douglas Losordo, Caladrius Biosciences
Authors: Gitelman, Stephen (UC San Francisco); Herold, Kevan (Yale University); Bluestone, Jeffrey (UC San Francisco); Hsieh, Candace; Junge, Candice; Losordo, Douglas (Caladrius Biosciences)

Abstract:
Type 1 diabetes mellitus (T1DM) is one of the most common and costly pediatric diseases. Caladrius Biosciences is developing an autologous ex vivo expanded regulatory T cell (TRegs) therapy (CLBS03) as a potential treatment for new onset T1DM, aiming to attenuate the autoimmune destruction of beta-islet cells. A phase 1 study of ex vivo expanded polyclonal Tregs was performed at UCSF and Yale University under an investigator sponsored IND. Fourteen adult subjects were enrolled in an open label study of subjects (18-45 years old) with T1DM of at least 3 months duration, stimulated C-peptide on mixed meal tolerance test >0.1 pmol/ml, and no chronic active disease. 4 dosing cohorts of 3-4 subjects were enrolled, with the CLBS03 dose increasing from 5×10^6 to 2.6×10^9. Autologous Tregs (CD4+CD25+CD127lo) were isolated and expanded as described by Putnam et al., Diabetes 2009. The DNA in expanded Tregs was labeled with deuterated glucose in 2 cohorts to track their time in circulation and stability. Safety experience was the primary outcome, with secondary evaluation of metabolic changes and mechanistic studies. The mean subject age was 30, 10 months from diagnosis. Treg administration was well tolerated with no adverse safety signal observed. Accordingly, based on the acceptable safety profile in the phase 1 study, safety and efficacy will now be examined in the target T1DM adolescent population. In early 2015, the FDA approved a phase 2 randomized placebo-controlled, double-blind study evaluating CLBS03 in adolescents, aged 12-18, with recent onset. This will be a double-blinded, multi-center trial assessing two doses of CLBS03 (10×10^6 and 20×10^6 cells/kg BW) versus matching placebo. There will be initial randomization of 18 subjects to all treatment arms and to matching placebo at 1:1:1 ratio, followed by 3 months of safety follow-up. After the interim safety review, enrolled subjects will continue to be randomized to all treatment arms at a ratio of 1:1:1 to reach a final target sample size of approximately 111 subjects. Conclusion: Given the acceptable safety profile of CLBS03 observed in adults in the phase 1 study, the safety and efficacy of CLBS03 can now be examined in a phase 2 study focused on the target T1DM adolescent population."