SUBSPECIALTY NEWS

OPKO's SiRNA Drug for AMD Shows Promise

Company CEO Also Founded IVAX and Key.

JERRY HELZNER, SENIOR EDITOR

■ Philip Frost, MD, the Miami dermatologist who started 2 highly successful drug companies, IVAX and Key Pharmaceutical, has given up the leisurely lifestyle befitting a 70-year-old billionaire to see if he can replicate his earlier successes, this time in eye care.

Over the past 9 months, Dr. Frost has been instrumental in putting together the first pieces of OPKO Health, Inc. The plan is for Miamibased OPKO to eventually be a fully integrated eyecare company. OPKO has already acquired a wound-healing device that is designed to prevent endophthalmitis associated with retinal procedures, an investigational dry eye treatment that can be administered as a nasal spray, as well as Ophthalmic Technologies, Inc., a company that makes SLO/OCT imaging equipment.

However, the true centerpiece of the company is bevasiranib, an injectable drug for the treatment of wet AMD and diabetic macular edema. Bevasiranib is the first drug based on the gene-silencing SiRNA (small interfering RNA) concept to ever reach a phase 3 clinical trial. The discovery of SiRNAs won the Nobel Prize for Medicine in 2006. The mechanism of action of bevasiranib is to shut down the gene that produces the VEGF that leads to proliferative blood vessels in the macula. Looking longer term, the drug may also have the potential of being effective in stopping the progression of dry AMD to wet AMD.

The drug demonstrated an impressive duration of response during its phase 2 trial and is now in a 330-patient phase 3 trial called COBALT. It is intended to be used to maintain vision after initial treatment with an anti-VEGF agent such as Lucentis or Avastin. Bevasiranib was recently named amng the 5 most promising drugs entering phase 3 trials by Thomson Scientific, which tracks drug development pipelines.

"We see bevasiranib as a sequential therapy," says Sam Reich, PhD, the 32-year-old executive vice president of ophthalmologics at OPKO and a codeveloper of bevasiranib. "Our endpoint in phase 3 is to demonstrate at least a 12-week duration of response for the drug. We're comfortable and confident with that endpoint as we already achieved that in the phase 2 study."

Actually, bevasiranib achieved more than that in phase 2. The average "time-to-rescue" (need for another injection) in patients given the lowest dose (0.2 mg) was 153 days. Patients who received higher doses (1.5 and 3 mg) had an average time-to-rescue that was much longer, though the company has not provided specific timeframes as yet. Lucentis injections are usually given every 4 to 8 weeks.

There were no systemic adverse effects observed in the phase 2 study.

Bevasiranib was initially developed at the University of Pennsylvania by Dr. Reich and Michael Tolentino, MD, who was a professor of ophthalmology at the university's medical school. The pair formed Acuity Pharmaceuticals in 2002, attracting venture capital to finance the company. In 2006, Dr. Frost read about Acuity in a Wall Street Journal article that discussed the potential of the SiRNA concept and contacted Dr. Reich about the possibility of working together. The 2 entrepreneurs immediately hit it off.

In March 2007, Dr. Frost folded Acuity into newly formed OPKO Health, which now trades on the American Stock Exchange under the symbol OPK. The combination of Dr. Frost's track record of success and the potential of bevasiranib has already led investors to give OPKO a $450 million market cap. This could be considered a high valuation for a company that has yet to produce any significant revenue, but it should be noted that Merck recently paid $1.1 billion for SIRNA Corp, whose SiRNA-based treatment for wet AMD is still in phase 1/2 trials. In addition, Dr. Frost has demonstrated his confidence in OPKO by consistently buying company shares on the open market and by leading a group that recently provided $20 million in additional funding for the company.

Dr. Frost is widely recognized as an innovative and successful entrepreneur. He co-founded Key Pharmaceuticals in 1972, focusing on creating new delivery systems for existing and underused drugs for asthma and other indications. After selling Key to Schering-Plough in 1986, Dr. Frost founded IVAX, which produced both generic and branded drugs. IVAX was purchased by Teva Pharmaceuticals for $7.4 billion in 2006. In recent years, Dr. Frost has also invested in a number of smaller healthcare companies, including SafeStich, an early-stage company specializing in endoscopic and minimally invasive surgery.

Dr. Frost is also known for his philanthropic activities in education and the arts. In 2003, he and his wife, Patricia, gave $33 million to the University of Miami to be used for furthering music education. The money has been used to create the Philip and Patricia Frost School of Music at the university. The Frosts have also been major benefactors of an art museum at Florida International University. RP

Optherion Obtains Funding for AMD Research

First Focus Is on Dry AMD.

■ Optherion, Inc., a recently formed company that intends to develop diagnostic tools and treatments for both the wet and dry forms of AMD, says it will first focus on developing diagnostic tests and disease-modifying therapies to prevent loss of vision in patients with dry AMD. To fund its research, the company has received a total of $37 million in start-up financing from a number of venture capital firms.

In a major step in pursuit of its goals, Optherion has licensed from the University of Pittsburgh the worldwide rights to develop diagnostic products for AMD associated with specific variations in genes on chromosome 10.

Scientists at the University of Pittsburgh in 2005 published their findings of a link between chromosome 10, specifically the LOC387715 and HTRA1 genes, and AMD. Genetic tests that can identify people at risk of developing AMD, or that can predict the likely rate of progression and end-stage outcome of patients already diagnosed, should enable medical professionals to intervene more aggressively at an earlier stage with lifestyle changes and available therapies, thereby changing the course of disease, says Optherion.

Optherion, which is headquartered in New Haven, CT, was founded following scientific discoveries linking the role of Complement Factor H (CFH) and Complement Factor B (CFB) to AMD. Both CFH and CFB are regulators of the alternative complement pathway. Researchers found that 3 gene loci have been strongly linked to AMD: CFH, CFB, and specific variations on chromosome 10. About half of patients with AMD suffer from variations in the CFH gene, while 74% of the disease can be explained by variations in the CFH and CFB genes combined. Variations associated with specific gene loci on chromosome 10 in combination with CFH are associated with about 79% of the disease.

Colin J. Foster, president and CEO of Optherion, said, "The licensing agreement with the University of Pittsburgh adds significantly to our portfolio. Optherion is now in position to develop diagnostic tests based upon the most recently discovered genetic associations of dry AMD. We are optimistic that the innovative discoveries we are licensing will lead to diagnostic tests that can help change the current paradigm of AMD risk assessment and patient care."

The finding that genetic variations on Chromosome 10 are implicated in AMD was first published in the American Journal of Human Genetics by scientists from the University of Pittsburgh under the direction of Michael B. Gorin, MD. Dr. Gorin is now professor of ophthalmology and Harold and Pauline Price Chair in Ophthalmology at the Jules Stein Eye Institute at UCLA in Los Angeles. Optherion says more recent research has substantiated and replicated the links of CFH, CFB, and chromosome 10 to AMD. Additional research published in 2007 found that people with homozygous risk profiles for CFH, CFB, and LOC387715/HTRA1 have as great as a 250 times increased risk of developing AMD.

Optherion's intellectual property estate is based on discoveries at the University of Iowa by Gregory Hageman, PhD, and at Yale University and Rockefeller University by Josephine Hoh, PhD, as well as work by investigators at other universities.

In related news, Optherion recently announced that it had completed a $37 million venture capital financing. Among the sources of capital for the financing are: Quaker BioVentures, Philadelphia; Domain Associates, Princeton, NJ, and San Diego; Johnson & Johnson Development Corporation, New Brunswick, NJ; Purdue Pharmaceutical Products L.P., Stamford, CT; Pappas Ventures, Research Triangle Park, NC; Biogen Idec New Ventures, Cambridge, MA and GE Healthcare Financial Services, Chicago.