CMR-316: An Investigational First-in-Class Regenerative Therapy for Pulmonary Disease

I. Executive Summary of CMR-316

A. Overview of CMR-316

CMR-316 is an innovative, first-in-class investigational small molecule drug candidate engineered for regenerative therapy of lung diseases.[1] Administered via inhalation, it is specifically designed to target and stimulate endogenous lung stem cells, particularly type 2 alveolar epithelial cells (AEC2s). The stimulation of these cells is intended to promote the regeneration of damaged lung tissue, offering a novel therapeutic paradigm.[1] The development of CMR-316 is being spearheaded by Calibr, the drug discovery and development division of Scripps Research, also known as the Calibr-Skaggs Institute for Innovative Medicines.[2]

The development trajectory of CMR-316, from initial screening of existing drug libraries to the creation of a highly specialized therapeutic agent, underscores a strategic shift in pharmaceutical research towards harnessing the body's intrinsic regenerative capabilities. This approach, centered on activating resident stem cell populations with small molecules, may offer advantages in scalability and cost-effectiveness compared to more complex cell-based therapies.[2] The progression from identifying a class of compounds through a repurposing library (ReFRAME) to engineering a novel, lung-targeted molecule like CMR-316 reflects an efficient and rational drug discovery process. This pathway strategically addressed the inherent limitations, such as high systemic exposure and potential for unsafe dosages, that would arise from attempting to directly repurpose existing Dipeptidyl Peptidase 4 (DPP4) inhibitors for lung regeneration.[5]

B. Lead Indication and Therapeutic Potential