Capstone Therapeutics Corp. (the “Company” or “we”), is traded on the OTCQB under the ticker symbol “CAPS”. We are a biotechnology company committed to developing a pipeline of novel peptides and other molecules aimed at helping patients with underserved medical conditions.
Our primary asset is ownership in a joint venture development company, called LipimetiX Development, Inc. (“LipimetiX” or “JV”) based in Natick, Massachusetts. In 2012, Capstone invested $6 million in the joint venture for 60% ownership. Our partners in the venture include three PhD drug developers, The University of Alabama at Birmingham Research Foundation (“UABRF”) and scientists at The University of Alabama at Birmingham (“UAB”). Both Capstone (with two full time employees) and the joint venture (managed under consulting contract by Benu Biopharma) operate virtual business models to maintain capital efficiency for our shareholders.
Through funding provided by Capstone, LipimetiX developed its first candidate peptide molecule, AEM-28, through pre-clinical and human clinical Phase 1a, 1b and 2a studies. 51 patients were enrolled in double-blinded, placebo-controlled studies at a clinical site in Perth, Australia. AEM-28 was delivered in single ascending dose and multiple ascending dose formats to test safety, tolerability and efficacy. The Medical Safety Committee, reviewing all safety-related aspects of the clinical trial, observed a generally acceptable safety profile. Of the first-in-man study, the primary endpoint was safety; yet, efficacy measurements analyzing pharmacodynamics yielded statistical significance in the pooled data set favoring AEM-28 vs. placebo in multiple lipid biomarker endpoints, especially VLDL cholesterol and triglycerides. Please see www.lipimetix.com
Based upon AEM-28’s clinically proven ability to rapidly reduce triglycerides and other lipoproteins, we are targeting various clinical indications including acute pancreatitis with high triglycerides (“TGs”), Homozygous Familial Hypercholesterolemia or HoFH, genetic hypertriglyceridemia and other orphan dyslipidemic disease states.
Acute Pancreatitis with High Triglycerides. In 2015, we retained a consultancy to conduct a market assessment study for AEM-28 in acute pancreatitis (“AP”) with high triglycerides. The consultancy’s report concluded that the AP indication represents a significant unmet clinical need for a therapeutic that could rapidly reduce TGs. Our consultant and market research literature cite an estimated 74,000 hospitalizations for all types of AP in the U.S. each year, with approximately 45,000 presenting with severe levels of TG equal to or greater than 1,000 mg/dL. Reducing TGs early in the onset of acute pancreatitis is a factor in shortening hospital stays and improving clinical outcomes, according to pancreatologists and lipidologists who serve these patients. AEM-28 and its analogs may be an ideal therapeutic agent for this extremely-ill patient population.
Homozygous Familial Hypercholesterolemia (HoFH). In 2012, AEM-28 received orphan designation from FDA for a rare disease indication, called Homozygous Familial Hypercholesterolemia or HoFH. This is a very small global population of individuals who are born with no LDL receptors in the liver and are unable to clear LDL (the “bad” cholesterol) through a natural pathway. Historically, these patients have experienced cardiovascular complications in their teens and twenties often leading to early death. Standard of care therapy was a process called apheresis, which is a mechanical filtering of the lipid fat from the patient’s entire blood volume, akin to the kidney dialysis process. In 2013, two pharmaceutical therapies were approved in the U.S., Aegerion’s Juxtapid and Sanofi-Genzyme’s Kynamro. Juxtapid has proven the market with an impressive revenue ramp while revenue data for Kynamro is not publicly available. We believe that AEM-28, or the new analogs, if approved, could compete favorably with these other drugs due to potentially equivalent efficacy and an expectation of fewer and less severe side effects.
Chimeric Apolipoprotein E Mimetic Peptides. Apolipoprotein E (Apo E) is in a class of protein that occurs throughout the body. Apo E is essential for the normal metabolism of cholesterol and triglycerides. After a meal, the postprandial (or post-meal) lipid load is packaged in lipoproteins and secreted into the blood stream. Apo E targets cholesterol and triglyceride rich lipoproteins to specific receptors in the liver, decreasing the levels in the blood. Elevated plasma cholesterol and triglycerides are independent risk factors for atherosclerosis, the buildup of cholesterol rich lesions and plaques in the arteries. Atherosclerosis is the major cause of cardiovascular disease, peripheral artery disease and cerebral artery disease, and can cause heart attack, loss of limbs and stroke. Defective lipid metabolism also plays an important role in the development of adult onset diabetes mellitus (Type 2 diabetes), and diabetics are particularly vulnerable to atherosclerosis, heart and peripheral artery diseases.
The UAB scientists patented the first chimeric Apo E mimetic peptide in 1999, reducing the 299 amino acid native Apo E into a smaller 28 amino acid, dual domain peptide that can be delivered therapeutically. One domain inserts into a lipoprotein surface and the second domain binds to the Apo E receptors in the liver. In 2010, our JV’s founding scientist, Dr. Dennis Goldberg, obtained worldwide right to patents for Apo E mimetic peptides from UABRF. The JV has an Exclusive License Agreement with UABRF for AEM-28 and its analogs.
Concurrent with the development activities with AEM-28, the JV has performed limited pre-clinical studies that have identified an analog of AEM-28, referred to as AEM-28-14 and a formulation, that has the potential of higher efficacy and higher dose toleration (in pre-clinical models). A fresh composition of matter patent application was filed in July 2015 with the U.S. Patent and Trademark Office for AEM-28-14 and a broad domain of analogs.
Previously, we were focused on the development and commercialization of two product platforms: AZX100 and Chrysalin (TP508). Since March 2012, we no longer have any interest in or rights to Chrysalin. In 2014, we terminated the License Agreement for AZX100 intellectual property and returned all interest in and rights to the AZX100 intellectual property to the Licensor (AzTE).
The JV and Company intend to explore fundraising, partnering or licensing to obtain additional funding to continue development activities of new leading candidate AEM-28-14. The JV and the Company do not have sufficient funding at this time to continue additional material development activities of AEM-28 and its analogs or other operations. The JV may conduct future clinical trials in Australia, the USA, and other regulatory jurisdictions if regulatory approvals, additional funding, and other conditions permit.
The Company intends, funding permitting, to continue limiting its internal operations to a virtual operating model while monitoring and participating in the management of LipimetiX’s development activities and maintaining the required level of corporate governance and reporting required to comply with Securities and Exchange Commission rules and regulations.