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Replies to post #2498 on Lisata Therapeutics Inc (LSTA)
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MANUFACTURING & SCALE-UP WORKSHOP
7:00am – 9:00am | CONCURRENT WORKSHOPS
7:15am – 8:45am | Learning Theater
Sponsored by PCT, a Caladrius Company
As practitioners in the development of the regenerative medicine industry, we are often compared to those that came before us in the biologics industry. In fact, whilst the challenges to commercial success in this industry are real, just as in the industries that we are being compared to, solutions are forming along the lines of the unique challenges presented. That being said, are we really that different than our biologics industry predecessors? What lessons can we learn from how they solved the challenges of developing novel and game changing therapeutics that didn’t quite fit their predecessors in the small molecule drug development industry? As we contend with the key issues including dose finding, optimal route of administration and frequency of administration for our therapeutics, it is often said that, in regenerative medicine, traditional drug and then biologic paradigms of pharmacokinetic (PK) and pharmacodynamics (PD) modelling are difficult, if at all possible to directly apply. This session is intended to bring experts on the topic of how PK/PD models have been adapted to biologics to describe the relation between dosing, concentration and efficacy, in an attempt to inform the practices and approaches of today’s regenerative medicine development professionals.
Chair:
Robert Preti, Ph.D., Co-Founder & President, PCT, a Caladrius company; SVP, Development & Technical Operations & Chief Technology Officer, Caladrius Biosciences
Speakers:
Frank Borriello, M.D., Ph.D., VP, Head of Search & Evaluation, Baxalta
Andrew Weber, Investigator, Modeling & Translational Biology Group, GlaxoSmithKline"
"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."
