Inovio SynCon avian influenza vaccine demonstrates broad coverage

Inovio Pharmaceuticals, Inc. (NYSE MKT: INO) announced today that its SynCon® avian influenza vaccine generated protective HAI titers against six different unmatched strains of H5N1 in a phase I clinical trial - a distinct clinical achievement on Inovio's path to develop universal influenza vaccines. By design, Inovio's SynCon® flu vaccine is not matched to any single virus. Importantly, the vaccine generated a hemagglutination inhibition (HAI) titer of 1:40 or higher against at least one of the six tested H5N1 strains in 8 of 17 (47%) immunized subjects, demonstrating the vaccine's broad coverage; 12 of 17 (71%) vaccines generated an HAI titer of 1:20 or higher, indicating a positive vaccine response, against at least one H5N1 strain.

Dr. J. Joseph Kim, Inovio's president and CEO, said: "Our goal has been to develop a truly universal influenza vaccine capable of providing years of protection across subtypes and strains. The protective levels of antibody responses generated by our universal H5N1 vaccine against diverse unmatched strains of this dangerous subtype provides proof of principle for our SynCon universal flu program and our other antibody-based vaccine products. We are planning further development initiatives for this program and look forward to forthcoming data from INO-3510, our universal vaccine for the influenza H5N1 and H1N1."

The major challenge to developing broadly effective vaccines against influenza is that within subtypes there are hundreds of strains that may vary slightly and which naturally and frequently mutate to create new strains. Today's vaccines only provide protection by matching targeted virus strains, which are those predicted to be of concern in the next flu season; however, they often fail to be protective because the predicted strain(s) changes as the next flu season emerges. Of even greater concern, subtypes can reassort, i.e. strains from different subtypes combine with one another, which is usually the cause of pandemic influenza outbreaks. As one example of concern, a strain of the deadly influenza subtype H5N1, which has killed about 60% of everyone infected by this virus but does not currently pass easily from person to person, may combine with a strain of H1N1 or other subtype that has a high infection rate to create a more virulent new strain. In addition, several recent, controversial published studies have shown that current H5N1 viruses can be manipulated to become more infectious. There is consequently a clear need for universal influenza vaccines capable of protecting against multiple, changing strains of influenza.

Inovio's novel SynCon® vaccine design process creates a single consensus gene sequence from one or more selected antigens (e.g. HA, NA, NP) of multiple existing virus strains within each targeted influenza subtype. The vaccine based on one or more of these new gene sequences is designed to achieve cross-strain or universal protection against the natural and frequent mutations of influenza strains that will inevitably emerge within each targeted subtype. In this study, a total of 17 patients completed a full H5N1 immunization regimen consisting of two intramuscular (IM) vaccinations with a synthetic DNA vaccine encoding three flu antigens (HA, NA, NP) followed by two intradermal (ID) vaccinations of only the HA antigen using Inovio's novel skin electroporation device. The vaccine was found to be well tolerated at each immunization. Reported adverse events and injection site reactions were mild to moderate and required no treatment.

We had previously reported that two IM immunizations alone generated strong T cell immune responses against 72% of the vaccinated subjects. The T cell responses from this study mirrored the best-in-class T cell responses generated from Inovio's other Phase I SynCon® vaccine trials for HIV and cervical cancer/dysplasia.

In this final data, 100% and 89% of vaccinated subjects demonstrated high-titered binding antibody responses against the more common Clade 1 A/Vietnam/1203/04 and Clade 2 A/Indo/5/05 strains, respectively, demonstrating vaccine-specific immune activation.

We also tested the vaccine's ability to generate protective HAI responses against six distinct H5N1 virus strains (Clades 0, 1, 2.1, 2.2, 2.3.2 and 2.3.4), representing all major genetic branches of the H5N1 genetic tree. Of the 17 subjects who completed the full immunization regimen:

• Eight of 17 (47%) immunized subjects had an HAI titer of 1:40 or higher against at least one of the tested H5N1 viruses.
• Twelve of 17 (71%) vaccinated subjects had an HAI titer of 1:20 or higher against at least one H5N1 strain.
• Seven of 17 (41%) had an HAI titer of 1:40 or higher against the Clade 2.2 A/Turkey/1/05 strain.
• Five of 17 vaccinated subjects (29%) displayed an HAI titer of 1:20 or higher against at least three different H5N1 viruses tested.
• In an unprecedented result, two vaccinated subjects demonstrated an HAI titer of 1:20 or higher against all six strains tested.

Hemagglutination inhibition (HAI) measurements from the blood of a vaccinated subject are used to assess the generation of protective HA antibody responses generated by a vaccine. All HAI titer data are presented in geometric mean titers (GMT). Generating an HAI titer of 1:20 is generally regarded as a positive response to the vaccine; a titer of 1:40 or higher in the blood of vaccinated subjects is generally associated with protection against seasonal influenza viruses and has been observed in multiple subtypes.

Inovio is advancing its universal influenza vaccine strategy with a second Phase I influenza vaccine study. This trial is assessing Inovio's INO-3510 multi-subtype SynCon® vaccine consisting of the H5N1 and H1N1 subtypes, delivered exclusively using intradermal electroporation, with a goal to provide cross-strain protection against H1N1 and H5N1 viruses. Inovio is also advancing its H3N2 and Type B SynCon vaccines through preclinical development. Inovio's plan is to combine these components into a single universal flu vaccine which could protect against multiple divergent strains of seasonal and pandemic flu viruses.