Inovio Pharmaceuticals Inc (NASDAQ:INO) announced that The Lancet, one of the world’s leading medical journals, published a peer-reviewed article detailing the successful results of its phase 2b trial with VGX-3100 in treating women with high grade cervical neoplasia. Previously, medical researchers have tried to stimulate therapeutic immune responses against the human papillomavirus (HPV) and cervical lesions with little success. This publication details that VGX-3100, a first-in-class product for treating high grade cervical neoplasia associated with HPV, is the first therapy to demonstrate that activated killer T cells induced in the body have the power to clear neoplastic lesions as well as the virus which caused the disease.
Dr. J. Joseph Kim, Inovio’s President and CEO, said, “Inovio’s SynCon® products have overcome the elusive and difficult challenge of generating activated killer T cells in the body which clear established disease as well as eradicate cancer-causing HPV virus.”
“Building on this proof-of-concept phase 2b study, Inovio is mobilizing to initiate our phase 3 trial for VGX-3100 next year. We are also advancing our two major immunotherapy partnerships, one with MedImmune and another with Roche, as well as driving forward multiple clinical and preclinical cancer products based on our core SynCon®platform.”
Commenting on Inovio’s HPV results, two senior investigators at the U.S. National Cancer Institute Division of Cancer Epidemiology & Genetics (Dr. Mark Schiffman and Dr. Nicolas Wentzensen) wrote in The Lancet: “The current trial represents a major breakthrough and proof-of-principle that therapeutic HPV vaccination is feasible. More broadly, the trial shows that it is possible to boost immune clearance of HPV among women who initially failed to control infection.”
Dr. Mark L. Bagarazzi, Inovio’s Chief Medical Officer and the senior author of The Lancet article, said, “For women with cervical dysplasia there is no alternative treatment except for surgery – a procedure that can bring side effects such as bleeding and fertility complications. Our study of VGX-3100 provides hope for women that a safe, non-surgical option will be available to them.”
Results of the trial were reported in the article entitled, “Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomized, double-blind, placebo-controlled phase 2b trial,” by C. Trimble, et al. Dr. Cornelia Trimble, Professor of Gynecology and Obstetrics, Oncology, and Pathology at Johns Hopkins School of Medicine, was the principal investigator for the study.
Specifically, the phase 2b trial showed that histopathological regression of high grade cervical neoplasia (CIN2/3) to low grade neoplasia (CIN 1) or no disease occurred in a significantly higher percentage of VGX-3100 recipients compared with placebo recipients. Furthermore, concomitant histopathological regression and clearance of HPV occurred in a significantly higher percentage of VGX-3100 recipients compared with placebo recipients. HPV-specific CD8+ “killer T cells” were also generated in the blood as well as a substantial infiltration of CD8+ cells in the cervical tissue of VGX-3100 recipients, underscoring the role played by Inovio’s best-in-class T-cell responses. VGX-3100 was safe and generally well-tolerated.
In VGX-3100-treated women who regressed their lesion, most (43 out of 53) completely cleared their lesions to normal (complete response). Moreover, eighty percent of VGX-3100-treated women who regressed their lesion also eradicated the infecting HPV genotype (i.e. 16 or 18) in the cervix. This is an important outcome as persistence of the virus is associated with recurrence of the disease. All data analyzed per protocol or modified intent to treat were similar with equal statistical significance.
Analyses of patient immune responses showed that overall antigen-specific T cell levels in women treated with VGX-3100 were greater than those treated by placebo at all observation periods. At week 14, T cell levels in women treated with VGX-3100 were ten times greater than those in the placebo group.
Patients who regressed their lesions had higher frequencies of HPV-specific CD8+T cells which co-expressed key molecules important in T cell killing cascade and directly correlated with clinical efficacy. Specifically, we determined that higher levels of CD8+ killer T cells which co-expressed checkpoint molecule CD137 on their surface as well as the cytolytic protein perforin could be a predictive tool for efficacy. As a strong activation marker for CD8+ T cells, stimulation through CD137 has been shown in some systems to confer resistance of CD8+ T cells to the suppressive activity of regulatory T cells and its presence can identify tumor reactive T cells. Perforin is a pore-forming protein deployed by killer T cells to bore holes into the target cell’s plasma membrane and destroy the cell. In fact, the difference in frequencies of CD8+ cells expressing CD137 and perforin was greatest in patients who had both regressed their lesions and cleared HPV compared to patients who did not.
This is the first publication to our knowledge that demonstrates the correlation of antigen-specific CD8 T cells directly to clinical efficacy. Inovio has successfully identified several key biomarkers of killer T cells which can be used to predict the clinical efficacy of VGX-3100 as well as other immunotherapies in future clinical studies. (Original Source)
Shares of Inovio Pharmaceuticals closed yesterday at $7.47. INO has a 1-year high of $13.04 and a 1-year low of $6.19. The stock’s 50-day moving average is $7.25 and its 200-day moving average is $8.15.
On the ratings front, Inovio has been the subject of a number of recent research reports. In a report issued on September 9, Maxim Group analyst Jason Kolbert reiterated a Buy rating on INO, with a price target of $23, which implies an upside of 207.9% from current levels. Separately, on August 10, Brean Murray Carret’s Jonathan Aschoff reiterated a Buy rating on the stock and has a price target of $20.
According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Jason Kolbert and Jonathan Aschoff have a total average return of -9.2% and 7.4% respectively. Kolbert has a success rate of 34.2% and is ranked #3743 out of 3765 analysts, while Aschoff has a success rate of 47.6% and is ranked #388.
The street is mostly Bullish on INO stock. Out of 4 analysts who cover the stock, 4 suggest a Buy rating . The 12-month average price target assigned to the stock is $20.00, which implies an upside of 167.7% from current levels.
Inovio Pharmaceuticals Inc is a clinical stage biopharmaceutical company. The Company develops active DNA immunotherapies and vaccines in combination with proprietary electroporation delivery devices to prevent and treat cancers and infectious diseases.