Leveraging its immune modulatory oligonucleotide (IMO) technology platform, Hybridon Inc. entered a collaboration with Novartis Pharma AG to find Toll-like receptor 9 drug candidates for asthma and allergy.
During the research phase, the companies will evaluate IMOs and Novartis will select candidates for development through clinical proof-of-concept studies. At that point, Basel, Switzerland-based Novartis can choose to exercise an option to continue development and commercialize the candidates.
"We were looking for a partner that had experience and deep pockets to forward this program," said Sudhir Agrawal, Hybridon's president, CEO and chief scientific officer. "We had not been able to forward this program internally."
The deal is worth up to $136 million, making it Hybridon's largest immune modulation deal to date. Toll-like receptors have generated a large amount of interest from pharmaceutical companies in recent months. In March, 3M Pharmaceuticals Inc., of St. Paul, Minn., announced an agreement with Osaka, Japan-based Takeda Pharmaceutical Co. Ltd. for a topical treatment that is part of 3M's family of immune response modifier molecules for cervical high-risk human papillomavirus infection and cervical dysplasia. And Wellesley, Mass.-based Coley Pharmaceutical Group Inc. recently signed a potential $505 million deal giving New York-based Pfizer Inc. exclusive worldwide rights to develop, manufacture and commercialize the TLR9 agonist ProMune to treat, control and prevent certain cancers. (See BioWorld Today, March 25, 2005.)
Agrawal declined to break down the $136 million that Hybridon could receive, but the money includes funding of all research activities, up-front license fees and milestone payments, assuming Novartis elects to develop and commercialize IMO candidates. Cambridge, Mass.-based Hybridon also is entitled to royalties.
"Looking at the market potential of these compounds, we have a decent royalty rate," Agrawal told BioWorld Today. The asthma and allergy market worldwide is about $10 billion, he said.
Hybridon's IMO technology is used to develop immune modulatory compounds to address the underlying conditions of asthma and allergy. Scientists now recognize Toll-like receptors as the gateways to immune modulation, and Hybridon has developed IMO compounds that are designed to act as agonists of TLR9.
"The asthmatic and allergic populations have an immune response, which is dominated by Th-2, and these agents, TLR9 agonists, are strong stimulators of the Th-1 immune activity," said Tim Sullivan, Hybridon's vice president of development programs. "So they in essence recalibrate the patient's immune system so that they would be less reactive to and less sensitive to an allergen."
The agents are designed not as acute response therapeutics, but as long-term maintenance drugs. Such agonists are useful not only in treating asthma and allergy, but also in treating cancer and infectious disease.
Hybridon's lead IMO, called IMOxine, is in a Phase II trial for renal-cell cancer. Phase I data reported a year ago showed the compound was safe and produced immunological activity in patients with advanced metastatic solid tumors. All patients in the Phase II trial should be enrolled by the end of this year, and Hybridon plans to start a trial in an additional cancer type in the third quarter.
Founded in 1989, Hybridon spent its early years focused on antisense technology, which uses synthetic DNA to block the production of disease-causing proteins at the cellular level. That platform led to partnerships like the one with Montreal-based Aegera Therapeutics Inc. and another with Vancouver, British Columbia-based Micrologix Biotech Inc. for antisense compounds in cancer and human papillomavirus, respectively. Internally, the company has completed Phase I trials of GEM231 for cancer, and also has been developing other products for cancer and macular degeneration.
But Hybridon's main focus for now is on the IMO platform, and all antisense programs are being placed on hold, Agrawal said.
"We will move these programs forward only with a partner," he said.
Hybridon's stock (AMEX:HBY) dipped 2 cents Wednesday to close at 72 cents.