polyGenomics Inc.

PolyGenomics was spun-out of Yale University to develop a genetic amplification technology in the search for genes implicated in psychiatric illnesses.

Rolling Out of Yale and Into the Genomics Competition

• c/o Collinson, Howe & Lennox

• 1055 Washington Blvd., 5th Fl.

• Stamford, CT 06901

• Tel.: [phone]

• Contact: Ronald Lennox, Acting Chairman

• Business: Positional cloning, gene discovery

• Founded: February 1997

• Founders: Jeffrey Gruen, PhD; David Ward, PhD; Myrna Weissman, PhD; Sherman Weissman, PhD

• Employees: 5

• Financing to date: $5 million

• Scientific Advisory Board: David Ward, PhD (Yale University ); Myrna Weissman, PhD (Columbia University Medical Center); Sherman Weissman, PhD (Yale University)

Recently, two genomics companies have been spun-out of Yale University , founded, in part, on the same genetic amplification technology: rolling circle amplification. These companies are polyGenomics Inc. , a start-up so new, they are naming scientific advisory board members as you read this, and Molecular Staging Inc. (MSI) of Allendale, NJ.

David Ward, PhD, chair of Yale School of Medicine's genetics department developed both firms' basic technology. Ward is a founder of both firms and sits on the Scientific Advisory Boards of both. Domain Associates and Collinson, Howe & Lennox fund both firms. But beyond that, they differ. PolyGenomics is focusing on identifying multiple genes involved in psychiatric illness, while MSI focuses on prostate, urogenital, and infectious diseases. And both companies are using additional, but different, technologies out of Yale.

PolyGenomics is applying three sets of technologies to produce a very rapid technique that is a variation on positional cloning, according to John Soderstrom of Yale's Office of Cooperative Research. Using small amounts of DNA—much smaller than are usually necessary for gene amplification—rolling circle amplification is able to isothermally amplify DNA without denaturing or renaturing, making this a faster amplification step than usual. This technique was developed in the laboratory of Paul Lizardi, from Yale School of Medicine's department of pathology. But this is only one part of polyGenomics' technology. The second is called allele frequency distortion, a biochemical and statistical method that can be used to search for mutations in the DNA after it has undergone amplification and is separated and cut with restriction enzymes. The restriction enzymes they are using are proprietary and were developed in Sherman Weissman's laboratory at Yale. Weissman is one of the founders of the company and is a member of the Scientific Advisory Board.

There are many well established positional cloning companies, among them Affymetrix Inc. ; Millennium Pharmaceuticals Inc. ; Myriad Genetics Inc. ; and Hyseq Inc. So what makes polyGenomics unique? According to James C. Blair, general partner at Domain Associates, "We think we will be able to discover genetic disorders in probably one-tenth the time it has taken people who are using traditional positional cloning methodologies."

Because one of the founders and members of the Scientific Advisory Board, Myrna Weissman, of Columbia University Medical Center, has access to populations with psychiatric disorders, polyGenomics will initially focus on identifying genes in individuals with such disorders: anxiety, depression, schizophrenia, manic-depressive psychosis, and autism, for example. And they are stressing diseases where multiple genes may be responsible for the condition. The focus will not just be on identifying the genes that cause the disorder, but also in discovering drugs that can be used to treat these disorders.

But, in fact, as it is a very new start-up—founded in February 1997—polyGenomics has a way to go to demonstrate the utility of its systems for identifying disease genes in a population. "We've been able to demonstrate utility of each one of the individual components of the technology," says Soderstrom. They have not, as yet, built this into a system where each technology meshes with the next. "We're trying to develop the alpha version of this system…. Now we want to pull it together more specifically, with more sensitivity and faster."

They foresee their positional cloning technology as attractive to genomics companies, biotechnology companies, and the pharmaceutical industry, and they are hoping to attract partners or clients within these groups. "We see our near-term market as actually being genomics companies. We're looking at groups like Incyte Pharmaceuticals Inc. and Human Genome Sciences Inc. , and others that have large databases for which they want to identify genes that would be of interest to the pharmaceutical industry," explains Soderstrom.

But in the long-term, polyGenomics is looking to enter the field of pharmacogenomics. Here, they hope to supply the pharmaceutical industry with technology to aid in determining what populations are most likely to benefit from a particular treatment, says Soderstrom. They wish to answer the question, as far as it can be genetically determined: Who responds to specific pharmaceutical treatments and who does not? They see this as a service to pharmaceutical companies.

Yale, which is a co-founder and partner in the company, has applied for both U.S. and foreign patents on all of the technology, a total of between eight and 10 patent filings.

According to Soderstrom, polyGenomics is putting an entire package together—following the infusion of $5 million in funding from Collinson, Howe & Lennox and Domain in early January 1998 [See Deal]—that will include executives and staff, boards, collaborations (both with clinical researchers and industry), and facilities. They're also looking for partners to supply them with the hardware systems they will need for genomics discoveries. Right now, the company has a staff of five and is hiring additional people; it is being run out of Lennox's offices at Collinson, Howe & Lennox, and the research is being carried out at Sherman Weissman's laboratory at Yale. They are looking for facilities, preferably in the New Haven area.

They expect their first round of partnerships to be completed by the end of the year at the latest.

Why is Domain willing to risk money on polyGenomics' success? Blair says, "It's a hot area and there are a lot of people out there; but I think this meets the test of faster, better, cheaper." —MW