Richard Silverman was left in the dark for the last five years of clinical development of the drug he discovered. The Northwestern University professor found out about the first approval of Lyrica, in the last few days of 2004, like most other people: in the newspaper.
What became one of Pfizer’s top-selling meds, at $5 billion in 2017 global sales before losing patent protection in 2019, started slipping out of his hands when Northwestern licensed it out to Parke-Davis, one of two biotechs that showed interest in developing the drug in the pre-email days, when the university’s two-person tech transfer team had to ship out letters to garner industry appetite.
So after years of complaining to his two sons about the Pfizer experience, he decided to go a different route. His answer: forming his own biotech, Akava Therapeutics. Silverman is holding off on venture capital funding until the Chicago startup’s lead ALS drug gets to Phase II, likely in early 2024, should a healthy volunteer Phase I study in 2023 pan out.
“It wasn’t a great experience, and that was one of the reasons why I wanted to start my own company because I just wanted to feel connected to discoveries from my lab,” Silverman told Endpoints News, referring to being left out of conversations in Lyrica’s clinical development post-Pfizer’s acquisition of Parke-Davis. “That and we had other issues with licensing compounds that then didn’t go further because a company ran out of money or change of direction, or whatever it is, so that’s why we decided to try and bring this along ourselves.”
The story behind Akava’s lead asset, AKV9, dates close to a dozen years. Having gone from an initial screen of more than 50,000 compounds to just a few molecules after half a decade of optimization in his Northwestern cohort’s lab, Silverman and team landed on AKV9, formerly known as NU9 under the university’s wings.
After initially testing the drug in mouse models for extending lifespan — which ended up showing the drug worked “about as well” as approved ALS med riluzole — Silverman ran into “an expert in ALS biology” at Northwestern’s downtown Chicago campus, medical school professor Hande Ozdinler.
Hande Ozdinler
“[T]he field was looking for extension of mouse lifespan as a potential solution moving from mice to human, but they [experienced] failure after failure after failure. There were like 32 clinical trials that failed,” Ozdinler said in a joint interview with Silverman.
So, she looked at tackling the tough-to-treat disease from a different angle: the brain component.
“This shouldn’t be a surprise to people because the movement starts in the brain. The brain gives the order for the movement,” Ozdinler said.
In mouse models of the disease, giving 100 mg/kg daily for 60 days showed that, at a cellular level, the neurons “were pretty much comparable to the healthy controls,” she explained. In the animal models, the drug has shown multiple key results: improving the health of the cell’s powerhouse (mitochondria) and protein producers (endoplasmic reticulum), protein aggregation and axonal growth.
“ALS is a very heterogenous disease. There are many underlying causes that lead to ALS, and one of the challenges for drug discovery was to find one compound that hits multiple birds all at the same time because there are so many different avenues to improve,” Ozdinler said.
While the drug is now licensed to Silverman’s Akava, Ozdinler is still able to conduct scientific investigations of its mode of action, biomarkers, etc, so that there’s a better overall understanding heading into potential Phase II and Phase III studies, she noted.
The drug is undergoing IND-enabling studies right now, including GLP ones anticipated for next month. At the same time, Akava is searching for a new CEO — the previous one returned to his old biotech after the company was able to revive itself by pivoting to a Covid-19 therapeutic — to help bring in donations to bankroll its first clinical trial. Venture funding will come later; it’s not time yet to let others control the drug’s fate, Silverman said.
Currently leading Akava’s operations is Olga Jasinsky, an industry veteran who’s worked across Abbott, Astellas, Horizon, Cour and others since the ’80s. Philip Silverman and Matthew Simon — Silverman’s two sons and the people who convinced him to launch Akava in 2020 — are also providing their business and legal know-how alongside six consultants. Ozdinler and other ALS-focused experts sit on the biotech’s scientific advisory board.
Further down the line, Akava will look to use various assets to treat Alzheimer’s, Parkinson’s, epilepsy, cerebral palsy, neuropathic pain, melanoma and hepatocellular carcinoma, Silverman said.
As for the name, Akava comes from the Hebrew word for inhibition. “Being Jewish, I wanted to have a Hebrew name,” he said, explaining the biotech’s drugs inhibit enzymes, cancer and protein aggregation.
And this time around, Silverman doesn’t want his lab’s discoveries to be inhibited by a Big Pharma.
Click here to read the original story by Kyle LaHucik that appeared in EndPoints News and May 26, 2022.