🔒Lipid Genomics searches for therapeutic cure to genetic heart defect

1 of 5

Dr. Annabelle Rodriguez is driven to find a therapeutic cure for people with good levels of the healthy HDL cholesterol but who are still at risk for heart disease and heart attacks — even if it means waiting another 10 years to get medication in people's hands.

It was more than a decade ago, when she worked at Johns Hopkins University School of Medicine in Baltimore, that she discovered genetic variations in the HDL cholesterol gene, SCARB1, among patients who had good levels of HDL but, paradoxically, had heart disease or were at risk for it. She set out not only to create a reliable test for the genetic variation, which she did, but also a way to treat it, eventually forming in 2010 a company, Lipid Genomics Inc., to develop that therapeutic remedy.

Rodriguez, a physician-scientist at UConn Health, is at the point now where the Farmington startup needs investors to take a proposed therapeutic through the expensive and time consuming drug-trial process.

“I know that when we're starting to look at therapeutics, it also takes about a decade,” Rodriguez said. “So I've just learned to be patient again and think, 'Well, I'm 59, I think I can do it until 69,' ” she said with a laugh, “that we'll find that therapeutic — that would be wonderful.”

Currently, patients with the gene variation are treated with statins, but Rodriguez, an endocrinologist who's studied cholesterol disorders her entire career, isn't sure that's the best option. She calls it the still-unanswered question.

The market potential for a treatment is a multi-billion-dollar one, according to Gerry Smith, who became CEO of Lipid Genomics last fall and also splits his time as CEO of Hershey, Pa.-based Targepeutics Inc., which is developing targeted therapeutics for cancer treatment.

“The prevalence of the genetic variations that Annabelle's identified is very, very large, so it applies to a lot of patients,” Smith said from his office near Harrisburg, Pa.

Smith has been talking with potential investors to help fund the company through Phase 1 clinical trials of a drug, probucol, that was used in the U.S. from 1977 to 1995, then licensed in Japan, where it's used to treat the bad cholesterol, LDL, but not for the same issues Rodriguez identified.

She'd like to see if it would help people in the U.S. with the HDL problem she identified. It works well in mice, she said.

She proposed a repurposing of the drug for treating the issues she discovered related to good levels of HDL and received an Investigational New Drug approval from the Food and Drug Administration in 2013, but Lipid Genomics needs funding to proceed with Phase 1 trials in humans in the U.S.

The company has all its intellectual property and other groundwork in place and Smith hopes the quality of Rodriguez's science woos investors.

Rodriguez's science is applicable to a broader market than people with healthy levels of HDL with genetic cholesterol disorders who are at risk of heart disease, Smith said.

“If it's successful in that market, it can be meaningful in other markets as well, so the science that she's putting out, we're having a lot of dialog with big pharma and we're looking for a quality syndicate of venture capitalists,” Smith said.

Rodriguez's research also has explored the link to inflammation and changes in one's immune system that can be linked to cholesterol and heart attacks. At UConn, she's developed a blood test to identify protein markers for the inflammation, which can lead to heart disease and heart attacks, and is studying ways to treat it, hypothesizing that probucol could be helpful.

Discussions with potential investors are occurring on both the repurposed probucol and commercializing the protein-marker diagnostic test, she said.

There seems to be momentum, she said, noting some investors are doing due diligence.

Breaking down the science

Smith said Rodriguez's research provides a radically new understanding of how the body works, backed by tests on about 6,000 blood samples from people on the genetic test she developed at Johns Hopkins and the protein marker test she developed at UConn, the latter of which shows people with healthy HDL levels who are deficient in a certain protein marker had demonstrated inflammation and almost a 50 percent greater risk of heart attack.

“It's a huge sample size that she's done and this is where we get to the quality of the preclinical science,” Smith said. “When you're testing 6,000 different people for these qualities, the science, the odds go up that you're much more accurate.”

Rodriguez would like to see the proteinmarker test, like the genetic test she developed at Johns Hopkins, be a standard test among doctors.

Smith said Connecticut, with large health insurers in the area, can take a leading role influencing the repurposing and development of drugs like Lipid Genomics proposes.

“We often focus on what patients need and leave what patients can afford as an afterthought,” Smith said. “Connecticut … can provide leadership in this discussion. They represent what the patients can afford.”

Insurer participation, guidance and support at an early stage of drug development is a missing piece of how to dramatically improve and streamline the drug-development process, he continued.

Lipid Genomics' novel research using probucol for targeted heart-disease treatment is an example, he said.

“Because [Lipid Genomics] would be repurposing an existing drug, neither big pharma or VCs are interested in supporting development,” Smith said. “Given the amount of time, resources and risk involved, it doesn't make sense for them to. Especially since pricing for this drug, if developed and approved by the FDA for this purpose, would have a shorter time being exclusive in the marketplace.

“But developing probucol for heart disease would be a great deal for both patients and the people and institutions that pay for health care,” he wrote. “Better targeted personalized treatment at lower costs. Health insurers have a large role to play in recognizing this type of innovation and working with the FDA and the [National Institutes of Health]to develop these types of drugs.”

UConn connection

UConn, which recruited Rodriguez in 2012 from Johns Hopkins, owns some of Rodriguez's protein-marker technology, which UConn licensed to her. Lipid Genomics was accepted into UConn's Technology Incubation Program, or TIP, in mid-2015, to assist the fledgling company's diagnostic and therapeutic efforts.

When Rodriguez commercializes her technology through Lipid Genomics, there will be a royalty stream back to UConn, “so that's good for Connecticut, the jobs are good for Connecticut and the royalty stream is good for UConn,” said Rita Zangari, director of innovation programs and external relations in the Office of the Vice President for Research at UConn.

Rodriguez was drawn to Connecticut by the state's desire to support and grow bioscience companies, the link to The Jackson Laboratory for Genomic Medicine and support for personalized medicine and commercializing academic research for the greater public good. She sees tremendous opportunity for the bioscience industry in Connecticut.

Lipid Genomics is one of 38 companies already in or coming to UConn's incubator program, which includes UConn sites in Farmington, Storrs and Avery Point. The 400 Farmington Ave. location was expanded by 20,000 square feet in January, giving the incubator about 40,000 square feet total among the three locations.

The new space is state of the art, with a great entrepreneurial environment, programs and resources only offered at a research institution and often unattainable for small startups, Zangari said, adding it's already half-occupied.

“It's a perfect environment for commercialization,” she said.

That's what Rodriguez aims for as she seeks to better help millions of potential patients through Lipid Genomics, a small, four-person company of her; Smith; her son, Eric Oquendo, business manager; and Ryan Smith, business development manager. Ryan Smith is Gerry Smith's son and Rodriguez's son-in-law. None is an employee or paid.

“Everybody's doing it through sweat equity, believing in the mission,” Rodriguez said.

See related story: CT's bioscience investment lured Rodriguez to UConn