HYBRIDON PUBLISHES CLINICAL SAFETY DATA ON gem^®231, A 2^ndGENERATION ANTISENSE oligonucleotide

Cambridge, MA, October 2, 2003 – Hybridon, Inc. (OTC Bulletin Board: HYBN.OB) announced the publication of the results from a clinical safety study of GEM^®231, a 2nd‑generation antisense oligonucleotide targeted to the RIa regulatory subunit of protein kinase A (PKA).  The article, entitled “A Safety Study of a Mixed-Backbone Oligonucleotide (GEM231) Targeting the Type I Regulatory Subunit a of Protein Kinase A Using a Continuous Infusion Schedule in Patients with Refractory Solid Tumors,” appears in the current issue of Clinical Cancer Research (Vol. 9, Number 11, pages 4069-4076, September 15, 2003). 

In the clinical safety study, fourteen cancer patients received escalating doses of GEM^®231 as a 3-day (1 patient) or 5-day (13 patients) continuous intravenous infusion at 80 to 180 mg/m²/day.  The dose of 120 mg/m²/day was evaluated in 8 patients and was established as the dose to be recommended for phase 2 studies.  There was low-grade fatigue in 57% of patients that was cumulative over 4-6 weeks of repeated 5-day infusions and that rapidly reversed at the end of treatment.  Medically insignificant, but dose-related, reversible increases in serum transaminases and activated partial thromboplastin times were also observed. 

“With this study and other clinical studies conducted by us, we now have given GEM^®231 safely by infusions ranging from 2 hours to 5 days in duration.  This flexibility is important for combination trials with various anticancer agents,” said R. Russell Martin, M.D., Hybridon’s Senior Vice President of Drug Development.  “Our ongoing Phase 1/2 clinical trial combining GEM^®231 and irinotecan is using the 5-day infusion schedule.”

The authors of the present publication are Sanjay Goel, M.D., Kavita Desai, M.D., Anca Bulgaru, M.D., Abbie Fields, M.D., Gary Goldberg, M.D., and Sridhar Mani, M.D., (Albert Einstein College of Medicine), and Sudhir Agrawal, D. Phil., Russell Martin, M.D., and Michael Grindel Ph.D. (Hybridon). 

About GEM^®231

The clinical safety of GEM^®231 administered to cancer patients by 2-h intravenous infusion has been described previously (Clin. Cancer Res., 6, 1259-1266, 2000).  In preclinical studies, GEM^®231 has been shown to down-regulate its target PKA RIa gene product and to increase the proapoptotic proteins bax, bak, and bad in prostate cancer cells in vitro (Clin. Cancer Res. 8, 607-614, 2002).  In addition, as studied by DNA microarray, GEM^®231 down-regulated proliferation-transformation gene clusters and up-regulated differentiation and reverse-transformation gene clusters in prostate cancer cells in vitro and in tumor xenografts implanted in athymic mice (Proc. Natl. Acad. Sci. USA 98, 9819-9823, 2001).  In tumor xenograft animal models, GEM^®231 has been shown to potentiate antitumor activity of various chemotherapeutic agents including irinotecan (Int. J. Oncol. 18, 1061-1069, 2001; Int. J. Oncol. 21, 65-72, 2002; Int. J. Oncol. 21, 73-80, 2002) and targeted anticancer agents such as C225, a monoclonal antibody to epidermal growth factor receptor (Clin. Cancer Res. 5, 875-881, 1999; Clin. Cancer Res. 6, 4343-4350, 2000).  GEM^®231 has also shown antitumor potentiation in preclinical models by oral administration in combination with paclitaxel (Clin. Cancer Res. 6, 2506-2512, 2000), bcl-2 targeted antisense compound (Clin. Cancer Res. 7, 2537-2544, 2001), and Iressa^® (gefitinib) (Clin. Cancer Res. 7, 4156-4163, 2001). Moreover, the three-way combination of GEM^®231 administered orally with Iressa^® and a cyclooxygenase-2 inhibitor to xenograft-bearing mice had a dramatic cooperative antitumor effect (Clin. Cancer Res. 9, 1566-1572, 2003). 

PKA as a target for cancer therapy has been highlighted in a recently published editorial (Clin. Cancer Res. 8, 303-304, 2002).

About Hybridon

Hybridon, Inc. is a leader in the discovery and development of novel therapeutics and Hybridon, Inc. is a leader in the discovery and development of novel therapeutics and diagnostics, based on synthetic DNA. The Company now has four technology platforms: 1) Synthetic immunomodulatory oligonucleotide (IMO^TM) motifs that act to modulate responses of the immune system; 2) Antisense technology which uses synthetic DNA to block the production of disease-causing proteins at the cellular level; 3) Synthetic DNA drug candidates that enhance the antitumor activity of certain marketed anticancer drugs, thereby increasing their effectiveness; and 4) Cyclicon™ probes, novel synthetic DNA structures for identifying gene function, which can be used for target validation and drug discovery as well as for PCR-based gene amplification.

This press release contains forward-looking statements concerning Hybridon that involve a number of risks and uncertainties. For this purpose, any statements contained herein that are not statements of historical fact may be deemed to be forward-looking statements. Without limiting the foregoing, the words, "believes," "anticipates," "plans," "expects," "estimates," "intends," "should," "could," "will," "may," and similar expressions are intended to identify forward- looking statements. There are a number of important factors that could cause Hybridon’s actual results to differ materially from those indicated by such forward-looking statements including risks as to whether results obtained in preclinical studies or early clinical trials will be indicative of results obtained in future preclinical studies or clinical trials, or warrant further clinical trials and product development; whether products based on Hybridon’s technology will advance through the clinical trial process and receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether, if such products receive approval, they will be successfully distributed and marketed; whether the patent and patent applications owned or licensed by Hybridon will protect the Company’s technology and prevent others from infringing it; whether Hybridon’s cash resources will be sufficient to fund product development and such other important factors as are set forth under the caption "Risk Factors" in Hybridon’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2003, which important factors are incorporated herein by reference.  Hybridon disclaims any intention or obligation to update any forward-looking statements.

IRESSA is a registered trademark of the AstraZeneca group of companies.

GEM is a registered trademark of Hybridon, Inc.

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Contacts:

Hybridon, Inc.                              Euro RSCG Life NRP

617-679-5500, x5593                    212-845-4269

R. Russell Martin, M.D.                  Brian Ritchie (media and investors)

Sr. Vice President, Drug Development