Caladrius announces $12.2 million grant to pursue cell therapy for recent-onset type 1 diabetes – March 24, 2017

Caladrius Biosciences recently announced that it received a $12.2 million grant from the California Institute for Regenerative Medicine (CIRM) for the continued development of CLBS03, a regulatory T-cell (T-reg) based therapy being studied as a treatment for type 1 diabetes.  The grant will be used to fund the remaining costs of the ongoing phase 2 T-Rex study, which Caladrius is pursuing in partnership with Sanford Health. The T-Rex study launched in 1Q16 and will evaluate the effect of two doses (2.5  and 20 million cells/kg) of the T-reg therapy on C-peptide preservation after 52 weeks in adolescents (n=111) with recent onset type 1 diabetes (i.e. diagnosis of type 1 diabetes within 100 days of initiation of CLBS03 therapy). Primary completion is expected in March 2019 and full completion in March 2020; according to Caladrius’ press release, an interim analysis of early therapeutic effects will be completed by the end of 2017. Notably, CLBS03 has been granted both an Orphan Drug designation and a Fast Track designation by the FDA (the first of its kind for a type 1 diabetes therapy!), and an accompanying Advanced Therapeutic Medicinal Product (ATMP) classification from the EMA. We are encouraged to see the increasing momentum behind CLBS03, both in terms of funding and its position with major regulatory bodies, and we imagine that the recently passed 21^st Century Cures Act will also prove advantageous in shortening the candidate’s development timeline, should the T-Rex phase 2 results prove positive. There is longstanding need for new therapies in type 1 diabetes, and we will be keeping a close eye on Caladrius’ innovative approach.

• In an interview with us, Caladrius’ CMO, Dr. Doug Losordo, underscored the uniqueness of CLBS03 in comparison to other immune therapies in development for type 1 diabetes. Whereas most type 1 immunotherapies come in the form of immunosuppressive drugs or antibodies (view our the immune therapies section of our type 1 diabetes prevention competitive landscape for an overview of this), CLBS03 involves T-regs that constitute part of the body’s natural immune response. “T-regs are part of nature’s toolkit and spent four billion years being perfected – that’s a lot of drug development!” remarked Dr. Losordo, “Caladrius is trying to leverage that natural biology, and that’s a very distinguishing feature.”
• Although the ongoing T-Rex study is testing the efficacy of CLBS03 in recent onset type 1 diabetes, Dr. Losordo explained that CLBS03 may also be a viable option for people with longstanding diabetes. As a regulatory T-cell based therapy intended to protect and restore beta cell function, CLBS03 has the greatest potential for success in individuals with recent-onset type 1 diabetes, particularly in light of the steep decline in pancreatic function that follows initial diagnosis. However, this is not to say that CLBS03’s efficacy is limited to early onset cases. Dr. Losordo pointed to mounting evidence that individuals with longstanding type 1 diabetes may have more residual beta cell activity than previously believed: autopsy studies have shown that people with decades of type 1 diabetes still possess beta cell progenitors in the pancreas, and a study published in Cell just last month points out that a subpopulation of beta cells can survive immune attack in the progression of type 1 diabetes. If CLBS03 proves effective in the newly-diagnosed participants in the T-Rex study, there is reason to believe that a more aggressive version of the therapy could be helpful in improving beta cell function in individuals who have had type 1 diabetes for years.

-- by Hae-Lin Cho, Abigail Dove, and Kelly Close