Carolus Therapeutics, Inc., a biopharmaceutical company, and The Alpha-1 Project, Inc. (TAP), a wholly-owned subsidiary of the Alpha-1 Foundation, have collaborated to characterize human biological samples for the presence of the novel target, RANTES:PF4 heterodimer (the heteromer), a soluble protein complex that is secreted by activated platelets and implicated in many inflammation-related diseases, including genetic emphysema and COPD (chronic obstructive pulmonary disease).
As a part of the collaboration, TAP is making an equity investment in Carolus. Terms of the collaboration and equity investment were not disclosed.
"COPD is a major and growing cause of death in the United States, and treatment approaches are generally limited to bronchodilators and anti-inflammatory agents," said John Walsh, co-founder, president and CEO of the Alpha-1 Foundation and Co-founder and President of the COPD Foundation. "Those of us with Alpha-1 are among a small minority with a specific treatment. But clearly, all patients need more and better ways to manage these diseases. Creatively investing in potential new therapies is exactly the reason TAP was created. Carolus is approaching COPD treatment from a completely novel mechanism, which we hope will open up new ways to help patients, and we are committed to supporting their work."
Genetic emphysema is caused by a deficiency in alpha-1 antitrypsin (AAT), a protein that protects tissues such as lung from the destructive enzymes of inflammatory cells. In people who have AAT deficiencies, these inflammatory enzymes cause excessive breakdown of lung tissue, resulting in emphysema – also a key feature of a syndrome known as COPD (chronic obstructive pulmonary disease).
"I've been working on the pathological processes leading to COPD for over 35 years, and based on the data available thus far, I see great potential in this 'anti-platelet' approach," said Robert A. Stockley, MD, DSc, Professor of Medicine at the University Hospital Birmingham and one of the scientists who will study the samples in collaboration with the Carolus team. "If we are successful in our efforts to link the heteromer to AAT 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."
Carolus' lead compound, CT-2009, selectively targets the heteromer, which has been shown in preclinical efforts to be present and elevated in AAT and COPD patient samples. The goals of the collaborative effort between Carolus and TAP will be to understand, among other things, whether the concentration of the heteromer is related to the severity and progression of disease, and eventually whether heteromer levels can be successfully modulated by CT-2009 in patients.
"Novel targets for disease present significant opportunities for more effective and safer treatments for patients. However, they may represent risky, unproven territory," noted Court R. Turner, CEO of Carolus Therapeutics. "Validating such targets in humans is a significant milestone to building value in the compounds. With this collaboration, we will have the opportunity to validate the heteromer as a target for AATD COPD specifically, and, perhaps, COPD in general."
CT-2009, is an IND-ready molecule that selectively disrupts the RANTES:PF4 heteromer with potential therapeutic utility in respiratory, pulmonary, cardiovascular and other indications. Initial focus with CT-2009 has been on Alpha-1 Antitrypsin Deficiency (and COPD) and Cystic Fibrosis. CT-2009 has demonstrated robust preclinical efficacy in relevant animals models of these diseases.
Carolus Therapeutics, Inc. is a San Diego biopharmaceutical company developing innovative new drugs that will provide relief to patients suffering from a host of disorders triggered by acute and chronic inflammation.