PERTH, Australia – Sydney-based Kazia Therapeutics Ltd. reported interim data showing that lead candidate paxalisib (formerly GDC-0084) saw a positive overall survival signal in its phase II glioblastoma trial, and the company raised AU$7.2 million (US$4.4 million) days after the data were released.

Data from the first nine patients of the escalation cohort showed median overall survival (OS) of 17.7 months compared to 12.7 months associated with the standard of care, temozolomide.

Progression-free survival (PFS) of all 30 patients was 8.5 months compared to 5.3 months for temozolomide. In November 2019, Kazia reported interim data that showed a PFS rate of 8.4 months.

The longest-treated patients remain progression free 19 months after diagnosis, Kazia CEO James Garner told BioWorld.

Roughly half of the enrolled patients remain on the drug, and both the OS and PFS figures may improve as the trial progresses, Garner said. The group of patients being treated in the phase II study are newly diagnosed with glioblastoma, the most common and most aggressive form of brain cancer.

“This is a single-arm phase II study so there’s a little bit of a journey ahead for this drug, but all the data are very consistently pointing in the same direction, which is that the drug works,” Garner said.

Thirty patients were enrolled in the study, comprising nine in part A and 21 in part B. The study is being conducted in six centers in the U.S., including the Dana Farber Cancer Institute in Boston, and the MD Anderson Cancer Center in Houston.

“We’re really pleased with the data. If this difference between what we’re seeing in our study and the historical benchmark of temozolomide is replicated in a pivotal study, we feel confident this will be a very viable commercial product,” Garner said.

“There has been little progress in treating the disease in almost 20 years,” he added. The standard of care is surgery followed by radiotherapy and treatment with temozolomide, which the FDA approved in 1999. It is the only FDA-approved drug to treat newly diagnosed glioblastoma.

Temozolomide, however, is ineffective in two-thirds of patients, and Kazia is targeting those nonresponders, “For this group of patients, there is really nothing else working,” the CEO said.

All patients in the phase II study had unmethylated MGMT promoter status, a genetic switch that makes them resistant to temozolomide.

Paxalisib was designed specifically for brain cancer because it crosses the blood-brain barrier. It inhibits the phosphoinositide 3-kinase (PI3K) signaling pathway, which is implicated in roughly 85% of glioblastoma tumors, Garner said.

Licensed from Roche Holding AG unit Genentech in late 2016, paxalisib is a small-molecule inhibitor of the PI3K/AKT/mTOR pathway. It entered phase II trials in 2018.

“The PI3K class has been well-researched. It’s one we know and understand quite well – there’s been evidence of proof of concept in a range of tumor types. A lot of the PI3K inhibitors only target certain types of PI3K isotopes, whereas our drug is differentiated because it is a pan-PI3K inhibitor and hits all four main isoforms,” Garner said.

“Although there are other PI3K inhibitors on the market, and it is becoming a very interesting class of drugs; none of those drugs cross the blood-brain barrier and are not being studied in brain cancer.”

Final data are expected in the first quarter of 2021.

The phase II data had been accepted for presentation at the annual meeting of the American Association of Cancer Research (AACR) in San Diego, April 24-29, 2020. However, the meeting was cancelled due to the COVID-19 outbreak.

“We usually try to put out data at these international conferences because we get more bang for our buck. It’s a terrific way to get out in front of investors and clinicians, so it’s obviously disappointing that we can’t do that in person. But hopefully the second half of the year will show some normalcy,” Garner said.

On the heels of the data announcement, Kazia completed a AU$7.2 million (US$4.4 million) placement consisting of 18 million new fully paid ordinary shares priced at AU40 cents per share, representing a discount of 2.6% to the five-day volume-weighted average price. Alongside the placement, Kazia will launch a share purchase plan (SPP) to existing shareholders at the same price point.

Led by Bell Potter Securities Ltd., the placement is expected to close on April 16.

Next steps

“Our next step is a pivotal study for paxalisib, and we would very much like to include Australia in that,” Garner said. “The challenge we come up against is that Australia is a smaller commercial market with a small number of patients, especially working in a smaller space like glioblastoma.

“As much as we would love to do more work in our home country, we have to go where the economics and practicalities take us. We have applied for a grant for the Medical Research Futures Fund, and if successful, we would be able do a lot more work in Australia and would make a huge difference.”

The next step is to participate in GBM AGILE, a platform study that is the biggest global collaboration in the history of brain cancer and is backed by more than 200 collaborators around the world.

“The study runs independently of any one pharmaceutical company and it runs over a long period of time. It doesn’t have a definitive beginning or end, and drug companies can put their drug into it for a couple of years at a time,” Garner said. The study is an adaptive trial platform that tests treatments tailored to patients’ genomic profiles.

The pivotal study is expected to begin recruiting in the second half of 2020.

With a market cap of roughly AU$32 million, Kazia’s shares on Australia’s Securities Exchange (ASX:KZA) stayed relatively flat at AU44 cents per share on market close April 9. Its shares on Nasdaq (KZIA) were trading at $2.98 per share on market close April 9.

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