Shares of Inovio Pharmaceuticals Inc. enjoyed a nice boost Wednesday after the Plymouth Meeting, Pa.-based firm reported immune response rates approaching 100 percent in the first clinical study for its Pennvax-GP HIV vaccine. Though early, the data readout "represents to us very clearly" that there is a path forward, said Niranjan Sardesai, chief operating officer.

"What we showed in the study was that almost everybody who got vaccinated, the vast majority of subjects, were able to drive an antigen-specific T-cell response as well as an antibody response," he told BioWorld Today. Inducing both a cellular and a humoral response has been one of the biggest challenges in the area of vaccine development, he added. "And what this opens up is that we can look [to develop Pennvax-GP] for prevention of HIV as well as for treatment of HIV."

The 94-patient study, supported by the HIV Vaccine Trials Network (HVTN) and the National Institute of Allergy and Infectious Diseases (NIAID), in collaboration with Inovio, tested a four-dose regimen of Pennvax-GP DNA vaccine, given either via intradermal or intramuscular administration, in combination with a DNA-encoded immune activator IL-12 dubbed INO-9012. Preliminary data, presented at a plenary session at the HVTN's Spring Full Group meeting in Washington this week, showed that 71 of 76 evaluable vaccinated subjects had a CD4-positive or CD8-positive cellular immune response to at least one of the vaccine antigens. Sixty-two of 66 patients (94 percent) demonstrated an env-specific antibody response.

That compared to none of the nine placebo patients (0 percent) demonstrating either a cellular or an antibody response.

"What's most striking is that the response rate was almost 100 percent," Sardesai said. "That has not been seen previously, and not just with HIV vaccines."

The news caught Wall Street's attention. Inovio's stock (NASDAQ:INO) gained $1.55, or 21.7 percent, to close Wednesday at $8.68, with shares changing hands at more than 37 times the normal trading volume.

More good news showed that intradermal administration was as effective as intramuscular, with 96 percent (27 of 28) patients demonstrating a cellular response and 96 percent (27 of 28) demonstrating an HIV env-specific antibody response in the Pennvax-GP plus IL-12 intradermal group vs. 100 percent (27 of 27) showing a cellular response and 90 percent (19 of 21) demonstrating an env-specific antibody response in the Pennvax-GP plus IL-12 intramuscular group. That's notable because the intradermal vaccination requires one-fifth of the dose of vaccine compared to intramuscular injection.

"Both approaches led to very high levels of response rates so both of them are viable approaches," Sardesai said. "But for a prophylactic scenario, the intradermal data was particularly striking." Intradermal administration would be more ideal for a prophylactic vaccine, given the lower volume required and ease of use.

Inovio has shown similar efficacy with its other infectious disease programs. A 40-subject phase I trial testing Zika vaccine GLS-5700 demonstrated high levels of binding antibodies in 100 percent of 39 evaluated subjects after three doses, as well as safety and tolerability. A second phase I study, enrolling 160 subjects in Puerto Rico randomized to either GSL-5700 or placebo, is ongoing and will assess Zika infection rates between the two arms as an exploratory signal of vaccine efficacy.

GLS-5300, a vaccine for Middle East respiratory syndrome, has produced high levels of binding antibodies in 92 percent (57 of 62) evaluated subjects after three vaccinations in a phase I trial. And preliminary results from an expanded stage of a phase I trial testing Ebola vaccine showed that 95 percent (170 of 179) of evaluable subjects generated an Ebola-specific antibody immune response.

Designed for global coverage, Pennvax-GP comprises a combination of four HIV antigens – envA, envC, gag and pol – to cover HIV strains prevalent in North America, Europe, Africa and Asia. It's a similar strategy employed by Inovio in the developing of vaccines targeting influenza, Ebola and Zika, other viruses that require a breadth of immune responses to cover rapidly mutating strains. "HIV has multiple clades and regional presence of these clades – though these days, the geographical limitation is narrowing," Sardesai noted.

According to Inovio, the most prevalent clades are B (found largely in North America and Europe), A and D (both of which are mainly found in Africa) and C (largely found in Africa and Asia).

MORE ANALYSIS TO BE DONE

Data presented at the HVTN meeting are top-line results, based on samples taken two weeks after the fourth and final dose was administered, Sardesai explained. "Study participants continue to be followed for about a year, so there's a lot more analysis that remains to be done."

One part of that analysis will involve characterizing the immune responses to see if the vaccine is driving responses to the various HIV antigens.

The NIH's NIAID has supported much of the work on Pennvax-GP, awarding a $25 million contract in 2009 and a five-year, $16 million Integrated Preclinical/Clinical AIDS Vaccine Development grant in 2015.

"We're getting the team together to plan out the next studies," Sardesai said.

As it moves into later-stage trials, Inovio will look to engage partners, both from big pharma as well as government and non-government collaborations. As a global problem, HIV vaccine development "is going to be a global effort," he said.

In addition to positioning Pennvax-GP as a prophylactic vaccine, Inovio continues to advance its use in treatment. Earlier this year, it launched a study to test whether a vaccination approach can address viral reservoirs.

Those pools of latently infected cells are the reason antiretroviral therapy falls short of a cure, even if treatment reduces viral loads to undetectable levels. Tackling those viral reservoirs, however, hasn't proved easy, though earlier this month preliminary phase IIa data from Abivax SA pointed to the potential of its HIV maturation inhibitor, ABX-464, in reducing viral reservoirs in HIV patients who already have undetectable plasma viral load. (See BioWorld Today, May 3, 2017.)

A $6.95 million grant from NIAID will be used by Inovio and its collaborators to test the ability of Pennvax-GP, either alone or in combination with a PD-1 inhibitor, to produce long-term HIV remission without antiviral drug therapy. The hope is that enhancing anti-HIV-specific CD8 killer T-cell immune responses can affect the viral reservoir pool, potentially reducing – or even eradicating – the virus.

The company, which ended the first quarter with $89.7 million on its balance sheet, has plenty of other immunotherapy programs underway, including a recently started phase II study of VGX-3100 in human papillomavirus (HPV)-related vulvar neoplasia. VGX-3100 is a DNA immunotherapy targeting cancers and precancers caused by HPV, specifically plasmids targeting the E6 and E7 proteins of HPV types 16 and 18. The start of a phase III trial for cervical dysplasia caused by HPV was delayed last year on FDA questions regarding the Cellectra intramuscular delivery device.

Inovio said in its first-quarter earnings that it had submitted a response to the agency. Should the FDA lift the clinical hold, a pivotal study in high-grade cervical dysplasia could start in the second quarter, H.C. Wainwright analyst Raghuram Selvaraju wrote in a May 11 research note, adding, "We expect this pivotal study to enroll approximately 400 subjects and to complete in roughly two years."

Inovio also has a deal with Regeneron Pharmaceuticals Inc., of Tarrytown, N.Y., in which it is combining its T-cell activator INO-5401 with REGN-2810, a PD-1 inhibitor, in a phase I/II study in newly diagnosed glioblastoma, set to start in the second half of this year.