SynCon universal H1N1 influenza vaccine generates protective antibody levels in phase 1 study

Inovio Pharmaceuticals, Inc. (NYSE MKT: INO) announced today that its SynCon® universal H1N1 influenza vaccine generated protective antibody levels comparable to a current FDA-approved seasonal influenza vaccine against a currently circulating influenza strain. The SynCon® vaccine is designed to protect against a spectrum of viral strains and is not matched to the currently circulating H1N1 strain targeted by the current "conventional" vaccine. This is the first demonstration of a broadly-targeted SynCon® influenza vaccine achieving a protective immune response rate comparable to a conventional seasonal vaccine that is matched to a circulating influenza strain. The data generated in a phase 1 study of healthy volunteers (18 – 55 years) using Inovio's skin-targeted electroporation device was presented today at the World Vaccine Congress in Washington, DC, by Dr. Niranjan Sardesai , Inovio's Chief Operating Officer.

The current FDA-approved trivalent influenza vaccines are designed to protect against only the three strains included in their formulation and are therefore incapable of addressing the inevitable and frequent shift and drift of influenza viral strains that can occur from season to season. However, scientists have questioned whether an influenza vaccine designed to be broadly protective against multiple, unmatched influenza virus strains could provide the same level of protection as the currently licensed trivalent vaccines that are typically matched to two different influenza A strains and a single influenza B strain. In this 100 patient phase I study assessing multiple SynCon® DNA constructs and dose levels, 6 of 10 (60%) volunteers that received the highest (1.8 mg) dose at least two times achieved a protective HAI titer of at least 1:40 with at least a four-fold increase in titer over pre-vaccination levels (i.e. levels considered protective in humans or "seroconverted") against the currently circulating H1N1 A/California/07/09 strain. This response rate was comparable to that seen in volunteers who received the matched seasonal influenza vaccine, where 6 of 10 (60%) seroconverted against H1N1 A/California/07/09.

"We couldn't be more pleased with the results from this proof-of-principle and dose-finding study of our H1N1 universal influenza vaccine," said Dr. J. Joseph Kim , Inovio's President and CEO. "We have already demonstrated that we can generate protective antibodies against the important H1N1 strains of the last century using our H1N1 universal vaccine. The new data shows that our universal approach can achieve protection rates comparable to the current seasonal vaccines, which require annual changes to try to match the predicted circulating strains. Collectively, these results further support our mission to develop a universal influenza vaccine capable of providing years of true preemptive protection across subtypes and strains. These results add significantly to the advancement of our seasonal universal flu vaccine program. They will also help fine-tune dosing for our pandemic avian H5N1 program and support our research for the new H7N9 subtype that has emerged even more rapidly than H5N1."

Inovio previously reported interim results from this phase I study showing that its SynCon® universal H1N1 influenza vaccine generated protective HAI titers against some of the most prevalent strains of H1N1 influenza from the past 100 years. The vaccine recipients from this study generated protective HAI responses against the H1N1 A/South Carolina/1/18 strain (so-called 1918 Spanish flu) as well as all the H1N1 strains that were part of the seasonal trivalent inactivated flu vaccines (TIV) since 1986, including: A/Taiwan/1/86, A/Texas/36/91, A/Bayern/07/95, A/Beijing/262/95, A/New Caledonia/20/99, A/Solomon Islands/03/06, A/Brisbane/59/07, and A/California/07/09.

Demonstrating Inovio's synthetic vaccine's broad protective coverage against unmatched strains, a significant percentage of subjects immunized with lower doses of Inovio's SynCon® vaccine had an HAI titer of 1:40 or higher against each of the nine H1N1 strains tested, ranging from a 30% protective rate to the A/Solomon Islands/03/06 strain to a 70% protective rate to the A/Beijing/262/95 strain. Overall, those immunized with Inovio's vaccine at lower doses ranging from 0.3 mg to 0.9 mg generated a higher seroconversion rate (HAI titer levels associated with protection) against all of the strains except for A/California/07/09 compared to the seasonal TIV (trivalent influenza vaccine)-immunized control group.

This open label phase I study evaluated two synthetic H1N1 hemagglutinin (HA) plasmids designed to broadly protect against unmatched influenza strains within different branches of the H1N1 subtype. These plasmids were delivered in ~90 healthy adults with Inovio's CELLECTRA® intradermal electroporation device with doses of 0.3, 0.45, 0.9 and 1.8 mg separately and in combination up to three times over six months. A ten subject control group was vaccinated with a single injection of the licensed seasonal trivalent influenza vaccine targeting the matched HA antigen sequence of the currently circulating H1N1 strain, A/California/07/09.

Inovio's H1N1 DNA vaccine delivered with electroporation was well tolerated. All reported adverse events and injection site reactions were mild to moderate and required no treatment. The favorable safety profile is consistent with multiple studies in different disease areas in which Inovio DNA vaccines delivered with Inovio electroporation delivery devices have been administered to over several hundred subjects.