Nventa Announces Positive Data From Cervical Dysplasia Trial
Nventa Biopharmaceuticals Corporation announced interim immunological data from the first two cohorts of its ongoing Phase 1 clinical trial of its lead product candidate, HspE7, in patients with cervical intraepithelial neoplasia, or CIN, a precursor to cervical cancer. Preliminary evaluation of biological samples collected from the study's first and second cohorts indicates that administration of HspE7 results in an E7-specific T-cell immune response.
Independent research findings recently published in the journal Gynecologic Oncology by Jeffrey Weber, M.D., Ph.D., associate director for clinical research at the University of Southern California's Norris Comprehensive Cancer Center, demonstrated that such an immune response may be associated with objective clinical responses in patients with CIN. Accordingly, Nventa believes that HspE7 may successfully treat CIN by activating and enhancing the body's natural immune system.
As previously reported, doses administered in both study cohorts were found to be safe and well tolerated, with no serious adverse events being reported in either group. Cohort 1 was designed to establish a baseline for the study with patients in this group being administered 500 mcg of HspE7 and 50 mcg of Poly-ICLC, a potent toll-like receptor 3 (TLR-3) adjuvant. Consistent with previous preclinical studies conducted by Nventa, this dose level demonstrated anti-HspE7 antibody responses but limited T-cell responses. In cohort 2, patients were administered 500 mcg of HspE7 and 500 mcg of Poly-ICLC. In this group, 3 out of 4 patients showed anti-HspE7 antibody responses and HPV16 E7-specific T-cell responses. These findings verify the company's predicted mechanism-of-action of HspE7 as demonstrated by early preclinical models and support the compound's potential to treat HPV-16 induced CIN. HPV-16 is the most common subtype of the HPV virus and is responsible for a significant percentage of cases of CIN.
"We are very encouraged with the interim immunological results from our Phase 1 HspE7 trial as they demonstrate the anticipated immune response improvement from cohort 1 to cohort 2. We believe that these results may correlate to the activity of the drug in future clinical trials," said Gregory M. McKee, president and chief executive officer at Nventa. "We look forward to reviewing the immunological data from the remaining two cohorts of this study to determine if yet higher doses of HspE7 will improve the drug's immunological activity."
The company recently announced positive safety and tolerability findings from cohort 3 in this Phase 1 study, as well as the completion of enrollment and initiation of dosing for the study's fourth and final cohort. Safety and tolerability results from cohort 4 are expected in mid-April. In addition to safety findings, immunological samples for the study's third and fourth cohorts are presently being collected and evaluated, and such findings will be released in the next several months.
Nventa is currently working with the FDA to finalize trial design for the company's Phase 2 clinical study for HspE7, and expects to initiate this trial in patients in CIN in mid-2008. In addition to CIN, Nventa is currently evaluating HspE7 as a potential treaent for a broad range of HPV-related pre-cancerous and cancerous diseases, and has a platform to generate other compounds that may treat a variety of other viral associated diseases.
About Cervical Intraepithelial Neoplasia (CIN)
CIN, also known as cervical dysplasia, is characterized by the presence in the cervix of abnormal cells that precede and can develop into cervical cancer. The primary cause of such abnormalities is infection with certain HPV types, of which HPV-16 is the most common. In the U.S., these infections are typically discovered through nearly 60 million Pap screens completed each year, at a cost of up to $6 billion. Each year in the U.S., an estimated 1.2 million women are diagnosed with low grade cervical dysplasia, (CIN 1), 300,000 with high grade dysplasia (CIN 2/3) and 2.4 million with atypical squamous cells of undetermined significance (ASCUS). No therapies other than surgery are currently approved by the U.S. Food and Drug Administration (FDA) for the treaent of any type of CIN.
The company's lead candidate, HspE7, is a novel therapeutic candidate intended for the treaent of precancerous and cancerous lesions caused by the human papillomavirus (HPV), one of the most common sexually transmitted diseases in the world. HspE7 incorporates the proprietary adjuvant, Poly-ICLC, a toll-like receptor-3 (TLR3) agonist. An adjuvant is a substance added to vaccines to improve immune responses against target antigens. HspE7 is derived from Nventa's proprietary CoVal fusion platform, which uses recombinant DNA technology to covalently fuse stress proteins to target antigens, thereby stimulating cellular immune system responses. Nventa is developing HspE7 for multiple indications.