CAMBRIDGE, Mass., Nov. 22 /PRNewswire-FirstCall/ -- Hybridon, Inc. today provided updated Phase 1 results for IMOxine(TM), the Company's lead oncology drug candidate, following the completion of enrollment in the trial. Twenty-three patients with refractory solid tumors have enrolled in the study, which is being conducted at the Lombardi Comprehensive Cancer Center (LCCC) at Georgetown University Hospital. Based on these encouraging interim results, Hybridon recently announced initiation of a Phase 2 trial in renal cell carcinoma.
"Patients with a variety of cancer types have been studied in the Phase 1 trial, including patients with renal cell carcinoma, melanoma, colorectal cancer, sarcoma, breast cancer, non-small cell lung cancer, and other cancers," said John L. Marshall, M.D., Director, Developmental Therapeutics and Associate Professor of Medicine at LCCC. "Over 250 total doses have been administered to these refractory cancer patients. IMOxine was well tolerated with no dose-limiting toxicity observed in the study. Immunological markers have shown preliminary evidence of dose response effects."
"The clinical results to date of IMOxine safety, immune activity, and incidence of stable disease, including these interim results, have been extremely encouraging," said Tim Sullivan, Vice President of Development Programs at Hybridon. "We anticipate initiation of additional Phase 2 trials in 2005."
Hybridon had previously announced in May 2004 its intention to expand the Phase 1 trial with additional melanoma or renal cell carcinoma patients. Based on the interim results, the Company determined to move forward with a Phase 2 study instead of expanding the Phase 1 trial. Presentations of the complete Phase 1 data are expected to be made at scientific meetings in 2005.
About the Phase 1 Oncology Trial
The trial is designed to evaluate the safety and immunopharmacology of IMOxine as a monotherapy in patients with refractory solid tumors that had been classified as progressive disease in spite of multiple courses of prior therapies. IMOxine is administered as a monotherapy once a week by subcutaneous injection at dosages of 0.04, 0.16, 0.32, 0.48, or 0.64 mg/kg/week. Treatment duration is open-ended, based on safety and radiology assessment of tumor status at 8-week intervals. Immunopharmacological assessments performed after the first and third doses include ELISA measurement of serum cytokines (IL-6, IL-10, IL-12, tissue necrosis factor- alpha, interferon-alpha, and interferon-gamma) and flow cytometric analysis of surface markers on circulating leukocytes (total and activated populations), in addition to hematology.
Nineteen of the 23 patients completed at least four consecutive weeks of treatment to fulfill the safety evaluation requirements of the protocol. The four early withdrawals occurred due to disease progression. Seventeen patients were assessed for disease status by radiology and clinical evaluation after eight weeks of treatment, and nine of these patients were determined to have stable disease. Six of the nine stable-disease patients were re-assessed after 16 weeks of treatment, and 4 continued to maintain stable disease. Two patients continued treatment to the 32-week disease status assessment and both were stable radiologically, although one patient was withdrawn after 32 weeks due to symptomatic deterioration. One patient with metastatic renal cell carcinoma continues into the 11th month of treatment, with maintenance of stable disease at the Week 40 evaluation.
Adverse effects recognized to date have been consistent with the expected immune stimulation activity of IMOxine, and primarily have been mild to moderate injection site reactions of erythema and induration, pain, and "flu- like" symptoms (rigors/chills, fever, nausea, myalgia, headache, malaise, and fatigue). Observations that were considered serious adverse events and possibly related to IMOxine treatment have been: transient hypoxia, dyspnea, and rigors/chills 1 hour post-dose (1 patient); abdominal pain with nausea/vomiting (1 patient); and anemia requiring transfusion (2 patients). Monitoring of the database is not yet complete.
IMOxine is a 2nd-generation immunomodulatory oligonucleotide (IMO(TM)) that functions as an agonist of Toll-like Receptor 9 (TLR9), a specific protein receptor in certain cells of the immune system. Other receptors also may play a role in the immune system response to IMOxine. TLR9 is shown to recognize bacterial DNA and induce a defensive immune response, producing a Th1 type cytokine profile that allows modulation of host innate and adaptive immune responses.
TLR9 is expressed on human plasmacytoid dendritic cells and B lymphocytes. IMOxine and its murine analogue have been studied in a variety of preclinical tumor models, as monotherapy and in combinations with selected chemotherapeutic agents and monoclonal antibodies, and with radiation.
We also have studied IMOxine (also known as HYB2055 for Injection) in a Phase 1 trial in healthy subjects at weekly subcutaneous dosages of 0.005 to 0.16 mg/kg/week. The healthy volunteer trial evaluated safety and immunological activity by monitoring serum cytokines, leukocyte phenotyping, and various clinical laboratory parameters.
Hybridon, Inc. is a leader in the discovery and development of novel therapeutics based on synthetic DNA. The Company's focus is to develop therapeutics independently and with partners based on two proprietary technology platforms: i) Synthetic immunomodulatory oligonucleotide (IMO(TM)) 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(TM)), a 2nd-generation IMO, and with GEM(R)231, a 2nd- 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 1 trial of HYB2055 in healthy volunteers. Hybridon has licensed Amplivax(TM) (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.
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, such as the interim results referred to above, will be indicative of results obtained in future preclinical studies or clinical trials, or final clinical trial results, or warrant further clinical trials and product development; whether the Company will be able to enter into additional site agreements or recruit patients on a timely basis; 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 patents 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 filed on November 14, 2004, which important factors are incorporated herein by reference. Hybridon disclaims any intention or obligation to update any forward-looking statements.
Hybridon, Inc. Euro RSCG Life NRP
617-679-5500, x5526 212-845-4268
Tim Sullivan, Ph.D. Robert Stanislaro (media)
Brian Ritchie (investors)
Georgetown University Medical Center
Lindsey A. Spindle