Pepducin Therapeutics

Inventors of the pepducin technology

The pepducin technology—discovered in the Tufts Medical Center laboratories of Athan Kuliopulos and Lidija Covic—has launched the start-up company Anchor Therapeutics and a $10 million NIH grant to Tufts Medical Center to test a new blood clot prevention drug.

Kuliopulos, director of the Hemostasis & Thrombosis Laboratory at Tufts Medical Center and professor of medicine at Tufts University, and Covic, assistant professor of medicine at Tufts University, established a new way of activating or inhibiting signaling between receptors and G proteins based on cell-penetrating peptides known as pepducins. These new peptides are powerful tools for evaluating protease-activated receptors, chemokines, and other receptors for their potential as therapeutic targets.

The pepducin technology has been the subject of publications in journals that include Nature Medicine, Circulation, Journal of Biological Chemistry, and Proceedings of the National Academy of Sciences. In 2006, the pepducin technology won the TechConnect Emerging Technology Award in the Life Sciences Category based on strength of the intellectual property portfolio, value proposition, and potential market impact. In 2008, the Tufts Tech Transfer office negotiated a worldwide exclusive license to the technology to Anchor Therapeutics. Since then Anchor has achieved significant success in developing pepducin drugs, partnering with large pharmaceutical companies, and raising capital.

An “inside-the-cell” therapeutic solution

Anchor Therapeutics was founded to address serious human diseases by advancing the pepducin technology. Pepducins are new modulators of G protein–coupled receptors (GPCRs), familiar targets in the drug development world. Although these cell-membrane molecules are involved in almost all signaling pathways in the human body—and nearly one-third of commercialized therapeutics target GPCRs—only about 10% of GPCRs have been drugged through traditional small molecule–drug and antibody–drug approaches.

Undruggable GPCR targets have enormous untapped potential. Anchor believes that the pepducin approach—using short peptides to penetrate to the receptor on the inner cell membrane—is much more effective than the extracellular approach that characterizes traditional GPCR drugs.

The pepducin technology platform represents an entirely new paradigm for modulating GPCR signal transduction and may transform the scope of GPCR therapeutics to treat a much wider range of illnesses. In addition to providing an exciting option for first-in-class therapeutics, pepducins are versatile pharmacologic tools that can be used to accelerate small molecule GPCR programs.

Anchor has established a portfolio of first-in-class pepducin drug candidates for 15 different GPCRs. The pepducin candidates are being optimized through traditional peptide medicinal chemistry methods and they are geared toward metabolic disease, inflammation, cardiovascular disease, and regenerative medicine.

Pepducins either agonize or antagonize their targets: Anchor is one of the few companies developing agonists of GPCRs. One leading drug candidate under development by Anchor is an agonist pepducin for CXCR4, a GPCR found on progenitor cells of the immune system that directs these cells to areas of injury. A natural ligand of CXCR4, Anchor’s agonist pepducin draws hematopoietic stem cells to the bone marrow. A CXCR4 agonist is more difficult to manufacture than an antagonist. If the company is successful, Anchor’s candidate CXCR4 agonist would be the first to market.

Athan Kuliopulos and Lidija Covic credit Tufts Tech Transfer for helping them launch Anchor Therapeutics. John Cosmopoulos, senior associate director, directed them in identifying investors and marketing the pepducin technology. With the assistance of Tufts Tech Transfer, Anchor has brought in some key venture backers. Anchor successfully secured $18 million in Series A financing from HealthCare Ventures, Novartis BioVentures, and TVM Capital and an additional $3 million from Novartis Option Fund. Anchor also raised a $10 million Series B financing. Says Athan Kuliopulos, “The marketing expertise and guidance from Tufts Tech Transfer was essential in developing pepducins into a viable start-up opportunity. John continues to provide valuable advice and assistance in bringing this important technology to the market.”

Tufts Tech Transfer also helped Kuliopulos and Covic navigate the patent protection process. Today Anchor has filed multiple patent applications related to the pepducin technology throughout the world. Anchor continues to expand intellectual property protection for the technology, with broad patent claims for composition of matter, methods of use, formulations, and combination uses for a variety of GPCR targets.

$10 million NIH grant to develop pepducin-based drug

Athan Kuliopulos and Lidija Covic’s success is a great example of the academic entrepreneurialism and drug development capabilities that are found at Tufts. Kuliopulos and Covic continue to discover new applications for pepducins, and in July 2012 they were awarded a $10 million grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) to begin testing a novel blood clot-prevention drug based on the pepducin technology.

This first-of-its-kind drug is designed to prevent deadly blood clots in heart disease patients without incurring the risk of serious bleeding that is associated with current blood-thinning medications. Heart disease is the leading cause of death in the United States, and this new drug could benefit patients who have had heart attacks or who need cardiac catheterization procedures to prop open clogged arteries with a stent. If successful, this innovative blood clot-prevention drug would be game-changing and could become part of the standard of care for patients being treated for coronary artery blockages.

The hoped-for effectiveness of this clot-prevention drug is based on the ability of pepducins to travel inside cells to block receptors and inhibit molecular pathways that stimulate clot formation. This approach differs from that of most drugs, which block receptors on the outside of cells. Details were published in the June 2012 edition of Circulation.

Over the next five years, the NIH grant will fund the drug’s early-stage development, wherein the safety and effectiveness of a pepducin in humans will be evaluated. Tufts researchers will first conduct a Phase I clinical trial in healthy volunteers to determine whether the drug is safe in humans and, if this is successful, then use the grant to cover a multi-center Phase II clinical trial in 800 patients.

Kuliopulos and Covic recently shared their experiences in advancing the pepducin technology at Tufts Tech Transfer’s Drug Development Day, which was held in June 2012. Their presentation can be viewed at the Tufts Tech Transfer YouTube channel.

“Athan Kuliopulos and Lidija Covic bring tremendous drug development experience and expertise to Tufts,” says John Cosmopoulos. “They conduct first-rate research which is readily translatable to real world applications.”