October 30, 2024

Calibr-Skaggs announces initial dosing of a first-in-class regenerative lung medicine in a phase 1 trial for idiopathic pulmonary fibrosis CMR316 is a once-weekly inhaled, lung-targeted drug designed to precisely expand lung stem cells and regenerate damaged lung tissue.

October 30, 2024

LA JOLLA, CA The Calibr-Skaggs Institute for Innovative Medicines, the nonprofit drug development division of Scripps Research, announced today that the first dose of a pioneering regenerative lung therapy, CMR316, has been given in a phase 1 trial assessing safety and tolerability in healthy volunteers and patients with idiopathic pulmonary fibrosis (IPF). This once-weekly, inhaled drug has potential to revolutionize treatment of lung diseases by stimulating stem cells to regenerate damaged lung tissue.

There are currently no regenerative treatments for any lung disease, including IPF, which is a deadly condition characterized by extensive tissue damage and permanent lung scarring, says Chan Beals, MD, chief medical officer of Calibr-Skaggs. Based on our encouraging preclinical data, CMR316 has the potential to halt or even reverse IPF, in addition to other severe lung conditions such as chronic obstructive pulmonary disease. This clinical milestone achieved through the collaborative bench to bedside' model of Scripps Research and Calibr-Skaggs scientists brings us closer to delivering a first-in-class medicine that could transform the lives of many people affected by debilitating lung diseases.

IPF is a severe, chronic, and progressive disease with no known cause and no cure. It affects roughly 100,000 people in the United States, drastically reducing their quality of life. With ever-increasing fibrosis in the lung over time, IPF progresses from mild shortness of breath and dry cough during activity to an inability to breathe even at rest. Difficulty breathing can lead to pulmonary hypertension and respiratory failure, preventing the brain and other organs from receiving adequate oxygen. There is no cure for IPF, aside from a lung transplant which is rarely an option, and tragically, patient survival after diagnosis is a mere 2 5 years. Available treatments, such as anti-fibrotics, can only slow disease progression and manage symptoms, highlighting the critical need for innovative new therapies. With an understanding that the lung's natural yet limited capacity to regenerate and repair is impaired in IPF, a new therapeutic strategy has emerged.

CMR316 is a first-in-class drug designed to precisely stimulate lung stem cells to regenerate lung tissue. Specifically, CMR316 targets type 2 alveolar epithelial cells (AEC2s) the stem cells in the lower airway of the lungs that are reduced in patients with IPF. Stimulating AEC2 stem cells causes them to differentiate into type 1 AEC (AEC1) cells that are crucial for gas exchange and maintaining lung stability and function. Thus, stimulating AEC2 stem cells with CMR316 has potential to repair damage caused by many lung conditions, including IPF. Furthermore, CMR316's regenerative mechanism is distinct yet complementary to that of approved anti-fibrotics, which could allow them to be combined for even greater effect.

CMR316 was discovered and developed through a partnership between Scripps Research and Calibr-Skaggs scientists, led by President and CEO Peter Schultz, PhD, and Associate Professor of Chemistry Michael Bollong, PhD, who is the Early Endowed Roon Chair for Cardiovascular Research. In April 2024, they published a study in the Proceedings of the National Academy of Sciences, which provided proof of concept for CMR316's ability to stimulate AEC2s to regenerate lung tissue in IPF and several other lung disease models.

From this foundational bench' research, the Calibr-Skaggs drug development team, led by Vice President of Pharmacology Sean Joseph, PhD, performed critical preclinical safety studies and received regulatory approval to reach the bedside' for testing CMR316 in humans.

Through careful testing of CMR316 over the last few years a huge team effort we are cautiously optimistic that the benefits and exceptional safety profile we observed preclinically will translate to patients with lung diseases, including those with IPF, says Joseph.

CMR316 is being tested at Fraunhofer ITEM in Hanover, Germany in an extensive phase 1 study in healthy volunteers (Parts 1 and 2) and patients with IPF (Part 3). The study title is A Phase 1/1b Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Nebulized CMR316 in Healthy Volunteers and Patients with Idiopathic Pulmonary Fibrosis (EU trial number: 2023-510456-23-00). The main objective of the trial is to assess the safety and tolerability of single (Part 1) and multiple inhaled doses of CMR316 in healthy volunteers (Part 2) and patients with IPF (Part 3).

This work was supported by funding from Calibr-Skaggs, with additional support from the Bachrach Family Foundation.

Calibr-Skaggs Schultz, Peter Bollong, Michael

LINK:	https://www.scripps.edu/news-and-events/press-room/2024/20241030-cmr31...
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