Inovio is going after the ‘impossible tumor’ left in the dust of new cancer meds

Patients with difficult cancers have seen a massive influx of new treatment options in recent years and are hoping for extended survival – except for those with the aggressive brain cancer glioblastoma.

Inovio hopes to change that with a new DNA drug combination of INO-5401, INO-9012 and Regeneron-Sanofi’s PD-1 inhibitor Libtayo. The Plymouth Meeting, Pennsylvania biotech is conducting a phase 1 clinical trial called GBM-001 that will provide early data in a quest to extend the lives of newly diagnosed patients beyond the three to five years that are currently the norm is.

Jeff Skolnik, MD (Inovio)

“This is still such an impossible tumor to treat,” said Jeff Skolnik, MD, Inovio’s senior vice president of clinical development. Although immune checkpoint inhibitors have boomed in metastatic lung cancer and other indications, boosting survival and prolonging progression, “GBM has seen none of these benefits.”

Globlastoma has long thwarted the pharmaceutical world, even as breakthrough therapies changed the landscape in other cancers. Skolnik, who is still a practicing physician at the Children’s Hospital of Philadelphia despite his role with Inovio, said this type of brain cancer has typically spread through the brain by the time it is diagnosed.

Treatment options include surgery, chemotherapy, and radiation, but they can only go so far for obvious, if not sobering reasons: “You can go for breast cancer, you can go for a prophylactic mastectomy, and completely prevent breast cancer from recurring by simply going 100 % of breast tissue. You can’t do that with the brain. That’s incompatible with life, “said Skolnik.

Once the surgery is complete, oncologists have to treat what’s left, and glioblastoma is an uphill battle. The tumor has a notoriously hostile microenvironment that likes to wipe out immune cells.

Inovio is certainly not alone in trying to finally break the code for glioblastoma, but the pipeline isn’t as rich as some of the other cancers that have become the intensive target of immunology research. And Inovio has never had any therapy across the finish line and become a marketed drug. The company – classified as a late-stage biotech – has a COVID-19 vaccine product that is likely the farthest, but that program recently hit a wall when the FDA halted a government-sponsored study over vaccine proliferation in The United States. Inovio has several other hopeful cancer patients, including a program with AstraZeneca in head and neck cancer and HPV.

So why Inovio? Skolnik said the glioblastoma program “builds on the totality of data we have in the immune space specifically,” and is expected to become part of a much larger oncology portfolio one day.

RELATED: Inovio’s COVID-19 Vaccine Funding Cut As US Says Thanks, But No Thanks

Upsides are hard to come by in the ongoing pandemic, but for a company like Inovio, the approval of mRNA vaccines has brought the technology to the forefront.

“For better or worse, since the COVID pandemic, that concept of nucleic acid therapies and the validation of those therapies has become kind of household terminology,” Skolnik said. “We really build and use exactly the same type of technology.”

Inovio’s technology uses synthetic DNA to build antigen-specific T cells in the body. But instead of attacking a virus as in the vaccine programs, the Inovio combination is designed to attack common tumor-associated antigens that are overexpressed in glioblastoma.

‘The idea is … Inovio is building a T-cell army that is antigen-specific. It goes after the tumor cell, the PD-1 inhibitor stimulates those cells, activates them and causes that combination to potentially benefit the patient, ”Skolnik explains.

RELATED: Glioblastoma and Other Solid Tumors With CAR-Ts Targeting Multiple Antigens

There are some genetic differences in glioblastoma patients. Skolnik explained that patients are cleaved by a biomarker called MGMT promoter methylation status. Patients whose tumors are not methylated generally have a worse prognosis. Inovio’s treatment could potentially be used for both types of patients, but the clinical trial may provide some clues as to who will benefit most from it.

“Ultimately, the question is: why do some patients do better than others? Who are the patients who can best benefit from this? Will it be everyone at the end of the story? Skolnik said.

At the discontinuation of the one-year data in the trial, 85% of the patients were still alive, which Skolnik said was very encouraging. At 18 months, 70% of the methylated and 55% of the non-methylated patients were alive. Inovio will release two-year data later this summer, following the June close. The trial now provides data other than survival rates that Skolnik says could help in future studies.

Inovio, which fully sponsored the glioblastoma study, is currently in talks about the next clinical step for the INO-5401 and INO-9012 combination. While the company has not formally partnered with Regeneron, Skolnik said the two companies worked well together on the trial, with Regeneron offering Libtayo. He hopes this will continue as the combination moves into later development.

As for when the combo can be submitted to regulators, Skolnik said the FDA wants to see randomized data for studies like this one, which Inovio hasn’t done yet. The company’s next step will likely try to compare the combination to the standard of care.

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