Carigent Therapeutics Inc.

Carigent Therapeutics' novel nanoparticle targeted drug delivery technology allows for controlled release of therapeutic agents, targeting drugs to a particular physiological site, tethering of surface ligands, and the ability to combine multiple agents--like imaging agents and drugs--into one vehicle. The foundation of the platform is an FDA-approved biocompatible and biodegradable polymer material, PLGA, which is made into particles at the nano- or micro-scale depending on the application.

Nano-based targeted drug delivery

5 Science Park

Suite 13

New Haven, CT 06520

Phone: [phone]

Fax: [phone]

Web Site: www.carigent.com

Contact: Seth Feuerstein, MD, President

Industry Segment: Drug Delivery

Business: Nano-based biodegradable polymers for drug delivery

Founded: May 2007

Founders: Seth Feuerstein; Peter Fong, PhD, VP & CSO; Tarek Fahmy, PhD, Consultant (Yale University); W. Mark Saltzman, PhD, Consultant (Yale University)

Employees: 7

Financing to date: $2 million

Investors: Saint Simeon Marketing

Scientific Advisory Board: W. Mark Saltzman; Tarek Fahmy

Board of Directors: Founders; Undisclosed representatives from Yale University and Saint Simeon Marketing

Not often do things come together in business and academia as they did for Carigent Therapeutics Inc. at the time of its founding last May. In the preceding months, its founders had made what they describe as a real leap forward in the development of their novel nanoparticle targeted drug delivery technology.

That technology allows for controlled release of therapeutic agents, targeting drugs to a particular physiological site, tethering of surface ligands, and the ability to combine multiple agents--like imaging agents and drugs--into one vehicle.

It is the outcome of some three years of work by Tarek Fahmy and Peter Fong, who at the time were postdoctoral researchers in the laboratory of W. Mark Salzman, chair of Yale University’s biomedical engineering department.

Following discussions with Yale University Office of Cooperative Research (OCR), the three scientists determined that the technology was viable for commercialization and that a company could be founded based on the invention and its potential application to pharmaceutical therapeutics, diagnostics, and vaccines.

The inventors invited Seth Feuerstein, a Yale School of Medicine physician with a law degree and background in life sciences start-ups and venture capital, to join the enterprise. The group worked closely with Yale’s OCR to structure a licensing agreement for exclusive worldwide rights to the suite of patents covering general concepts, manufacturing, and applications of the technology. Concurrently, the company secured $2 million in financing from Saint Simeon Marketing.

The company’s founders claim that Carigent’s platform is unprecedented in its ability to tether multiple targeting and imaging agents to the nanoparticle surface at previously unattainable densities, and to combine multiple therapeutic and/or diagnostic agents within the miniature carriers.

Carigent’s engineered nanoparticles incorporate an FDA-approved biocompatible and biodegradable polymer material, PLGA (polylactic-co-glycolic acid), which can be made into particles for controlled release at the nano- or micro-scale, depending on the application.

PLGA is a biomaterial used in a number of FDA-approved products that arinjected into muscles and sustain the release of drugs in the body over several weeks, e.g., Janssen Pharmaceuticals Inc.’s (a division of Johnson & Johnson) risperidone (Risperdal; developed with Alkermes PLC [See Deal]) and TAP Pharmaceutical Products Inc.’s leuprolide acetate (Lupron depot). "Their approval sets a precedent and heightens the likelihood of success for other products using PLGA," notes Feuerstein.

In contrast to these products, Carigent says its technology enables exceptionally high-density surface attachment of a variety of molecular ligands—including targeting ligands, diagnostic imaging agents, and/or polyethylene glycol, or PEG, which help increase the circulation time of the particles—to drug-loaded PLGA particles. In addition, Carigent believes this increased circulation time provides advantages for delivering drugs that have short half-lives (and the potential for toxicity after systemic delivery) and for treating diseases that require longer exposure to therapeutic levels of a drug.

Carigent says this capability to coat the nanoparticles with an exceptionally dense and long-lasting layer of targeting ligands allows for cell-specific and time-controlled delivery of small- and large-molecule drugs for a variety of clinical indications, including cancer, cardiovascular, and autoimmune and alloimmune diseases. The company believes that its technology is particularly well-suited to delivering drugs known to be effective but that were in the past limited by toxicities, and drugs that have formulation problems due to insolubility, such as siRNA therapeutics. Carigent reports that its studies have demonstrated that its targeted, drug-loaded PLGA nanoparticles have the potential for highly effective, low-toxicity delivery of chemotherapy drugs and a variety of other agents.

Carigent’s platform combines the ability to control-release a therapeutic agent and to target its delivery directly to specific locations within the body and within tissues, resulting in enhanced drug efficacy while limiting toxicity and harmful effects on healthy tissues. In addition, in the case of anti-cancer therapeutics, the technology allows antibodies to be placed on the surface of the therapeutic and the particle to be delivered inside the cancer cell.

"One important feature of our technology is that we generally don’t alter the structure of what we deliver," Fong says. "So we can deliver lots of different kinds of therapeutics. This is important not just for small molecules but also for therapeutics such as peptides and siRNA, where if you alter the structure, you can affect their bioactivity."Unlike other controlled-release systems, which have limited density-attachment capabilities, "we can tether an incredible variety of ligands to the surface of the particle at exceptionally high densities," Fong notes. "People have been trying for years to give special traits to PLGA particles so they will go to where the disease is or avoid being cleared in the blood system."

In the eight months since its founding, Carigent has received two grants effective January 1, 2008. The first grant was awarded by the National Institutes of Health (NIH) for reformulating an improved version of doxorubicin for non-Hodgkin’s lymphoma. The second was from the National Science Foundation for reformulating chemotherapeutics used in ovarian cancer. Carigent has conducted studies with doxorubicin and other generic chemotherapy compounds and says it has demonstrated that its particles improve their biological activity.

"We’re taking drugs that already work and markedly improving their effect, which could be a decrease in toxicity, or an increase in efficacy, or even both," says Feuerstein, who expects both therapeutics to be in the clinic within the next couple of years.

The confluence of factors that Feuerstein observed in the firm’s initial formation also extends to the marketplace. A market push is "on" for advanced technology capable of targeted delivery of pharmaceutical and biological compounds. Biopharmaceutical firms are interested in niche products, with the pace of new molecular entity (NME) approvals slowing, and in ways to improve existing brands. Industry sources say that 30% of marketed products are improved formulations of existing compounds. More than half of all products could be reformulations by 2010 if current trends continue, experts forecast.

As to its target market, Feuerstein points to the sales volume of anti-cancer drugs and other therapeutic categories. "If the global market for oncology drugs is $35 billion, we’d be satisfied with a small piece of that market," Feuerstein says.

The growth in advanced drug delivery systems also has highly positive implications. US sales reached $64.1 billion in 2005, according to industry sources. A nearly 16% annual growth rate for advanced delivery systems is forecast through the end of the decade, while an even higher rate of 23% is expected for targeted drug delivery systems.

In the long term, Carigent seeks to branch out beyond development to commercialization by marketing its own products. "If there’s a generic agent already approved, it’s relatively easy to put it into our particles," says Feuerstein.

Its novel technology has also generated the interest of potential partners, he reports. The focus of its discussions has been primarily on oncology and on therapeutic profiles ranging from traditional small to large molecules.

Potential partners are interested in using Carigent’s platform to develop either second generations of their existing brands or improve developmental drugs with delivery problems, such as poor solubility, short half-lives, systemic toxicities, or low systemic drug levels.

These potential collaborators are "very excited" about the prospect of using Carigent’s platform for antibody therapeutics for cancer, Feuerstein notes. "We have the capability to take proven antibodies and use them to target our particles" and thus combine multiple therapeutic methods of action into one delivery vehicle, said Feuerstein.

In targeted delivery, Carigent was one of only a few companies to receive funding in 2007. The others, also start-ups, included recent Massachusetts Institute of Technology spin-out Bind Therapeutics Inc., which closed a $16 million Series B round in November, [See Deal] and Cerulean Pharma Inc., which raised $12.1 million in May. [See Deal] Although Feurstein says that Carigent has been recently contacted by additional potential investors, it currently has "no specific plans for additional equity financing."

As to its future, Carigent has been set up to be independent. "We plan to move forward and follow through on all our projects, but we have no mandate that says we can’t go public at some point," says Feuerstein. "And it’s obviously very common in this field that once you start generating exciting data you get approached to be acquired."

But for now, the company’s main challenge is to avoid distractions from the many potential applications of its technology. "We’ve got an extremely versatile and flexible platform with all kinds of applications, but for a small company like Carigent, it’s critical to focus on the right things," acknowledges Fong.--Ann Roberts Brice