In an approach that taps the resources of a patient advocacy group, San Diego’s Carolus Therapeutics says it is now working with The Alpha-1 Project (TAP) of Miami to accelerate pre-clinical research focused on diseases associated with alpha-1 antitrypsin deficiency.
Alpha-1 antitrypsin is a protein that protects the lungs and other tissue from destructive enzymes produced by an inflammatory response. In patients with a deficiency of alpha-1 antitrypsin, inflammatory enzymes run amok, causing an excessive breakdown of tissue in the lungs and elsewhere.
TAP is both making an equity investment in Carolus and collaborating in research to validate a new drug target implicated in alpha-1 diseases, such as chronic obstructive pulmonary disease (COPD) and genetic emphysema. Terms of the funding and collaboration with TAP, a subsidiary of the Alpha-1 Foundation, were not disclosed.
Carolus is a virtual startup founded by San Diego’s Avalon Ventures. It is currently using proprietary diagnostic technologies to identify the soluble protein complex designated RANTES:PPF4 heterodimer in human disease samples. The heteromer, which is secreted by platelets and implicated in many inflammation-related diseases, represents a potential new drug target for the company, according to Avalon partner Court Turner, who is serving as Carolus president and CEO.
Preclinical studies have shown that the heteromer is present in COPD patients with alpha-1 antitrypsin deficiency, but Turner says it is unclear whether the heteromer is the right target for COPD in general.
The collaborative effort between Carolus and TAP is intended to understand whether the concentration of the heteromer is related to the severity and progression of disease. Among other things, the collaborators also want to determine whether the drug compound, an IND-ready molecule designated CT-2009, can successfully modulate heteromer levels in patients. The startup sees potential therapeutic use for CT-2009 in COPD and cystic fibrosis, and eventually in other respiratory, pulmonary, and cardiovascular disorders.
Through its collaboration with TAP, Turner said the Carolus diagnostic assay can be used to test hundreds of samples from COPD patients for elevated levels of the heteromer. The collaboration also should provide an opportunity to determine if the heteromer is the right drug target. “We’re looking for ways to validate our target,” he added. “Our drug breaks up this particular protein complex.”
Carolus plans to work under its TAP collaboration with Robert Stockley, a professor of medicine specializing in COPD and related respiratory disorders at England’s University Hospital Birmingham.
In a statement from the company, Stockley says he sees great potential in the focus Carolus has taken on aberrant platelet expression. “If we are successful in our efforts to link the heteromer to [alpha-1 antitrypsin deficiency] COPD, we could open up a completely new way to treat both the rare, genetic form of COPD as well as the more common type, which is the fourth-leading cause of death worldwide,” Stockley says.