Immunomodulatory oligonucleotides demonstrate response

Hybridon has presented preclinical results illustrating that its second generation immunomodulatory oligonucleotide (IMO) compounds demonstrated potent adjuvant activity, inducing Th1-type mucosal immune responses in mice following oral administration.

Th1-type immune responses are important in protecting against infectious diseases and boosting antibody formation.

'These results indicate the improved stability of our novel IMO structures in the gut facilitates increased immune responses,' said Dr Tim Sullivan, senior director of development programs for Hybridon. 'The data support the potential use of IMO compounds as Th1 adjuvants with vaccines and antigens through oral or intragastric administration.'

In the preclinical studies, second generation IMO compounds were shown to be more stable in mouse gastrointestinal contents following oral administration than was a conventional CpG oligonucleotide. Hybridon's IMO compounds induced selected Th1 cytokines and chemokines in stomach/intestinal tissues and in serum in mice. Intragastric immunisation of mice with ovalbumin plus IMO produced significantly increased ovalbumin-specific IgG2a antibodies. Second-generation IMO compounds contain novel DNA structures and synthetic immunostimulatory motifs.

Hybridon recently evaluated its lead IMO product candidate in a phase I clinical trial in healthy volunteers. The trial demonstrated that the IMO was well tolerated and immunopharmacologically active. The adjuvant application of Hybridon's lead IMO compound is referred to as Amplivax.

Hybridon

Hybridon is a leader in the discovery and development of novel therapeutics based on synthetic DNA. The Company's focus is to develop therapeutics based on two proprietary technology platforms: i) Synthetic immunomodulatory oligonucleotide (IMO) motifs that act to modulate responses of the immune system; and ii) Antisense technology that uses synthetic DNA to block the production of disease-causing proteins at the cellular level. The Company is conducting clinical trials in oncology patients with HYB2055 (IMOxine), a second-generation IMO, and with GEM 231 (a second-generation antisense oligonucleotide targeted to protein kinase A) in combination with irinotecan. Hybridon also is collaborating on development of additional second-generation antisense oligonucleotides for the treatment of cancer and viral infections, and has completed a Phase I trial of HYB2055 in healthy volunteers. Hybridon has licensed Amplivax (an adjuvant application of HYB2055) as an adjuvant for IR103, a potential therapeutic and prophylactic vaccine for HIV infection being developed by The Immune Response Corporation.