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The Alzheimer's debate may not seem positive, but AC Immune's CEO promises it's been a breakthrough year

It’s all about the biomarkers for AC Immune CEO Andrea Pfeifer, Ph.D.

After earlier this year showing for the first time the potential of an anti-tau therapy in Alzheimer’s disease, the small Roche-partnered biotech is capitalizing on the massive moment underway in research for the neurodegenerative disease.

That moment, of course, began with the June approval of Biogen’s Aduhelm under the accelerated pathway based on biomarker data, i.e., data that suggest the drug can address an underlying cause of the disease rather than on efficacy. This move by the FDA opened up a new regulatory path for Alzheimer’s treatments, which have long struggled through the clinic even with some of the largest pharmas behind them.

“This, for me, is the biggest breakthrough in the field,” Pfeifer told Fierce Biotech in an interview. She points to cancer research, where biomarkers were identified as crucial to drug development 35 years ago.

RELATED: ‘What it takes’: Beyond the headlines, women are pushing groundbreaking new Alzheimer’s treatments forward

With that said, Pfeifer does not dismiss the work to come. She knows that her company, and the many others with aspiring Alzheimer’s therapeutics, must back up the biomarker data with clinical development to establish clinical benefit. But she believes that absent the FDA’s decision, Alzheimer’s drug development would have continued to plug along without a spark to keep going.

“It’s an important year. It doesn’t necessarily look so positive, maybe for everybody, but for the people inside the field, it’s a breakthrough year,” she said, with a nod toward the controversy that has followed Biogen since the approval.

Now, Pfeifer believes the field needs to develop new and better endpoints for clinical trials in Alzheimer’s with the biomarker idea in mind. She thinks studies today are not sensitive or objective enough to pick up on a treatment’s benefit.

Backing up tau

AC Immune and Roche’s Genentech unit reported in August that their monoclonal antibody semorinemab had demonstrated the first clinical evidence of a tau-targeting therapeutic in a phase 2 trial. Semorinemab met one of the co-primary endpoints of reducing cognitive decline but failed to lower the rate of functional decline, which was the second co-primary goal. The study failed on all of its secondary measures.

RELATED: Roche-backed AC Immune finds even mixed-bag Alzheimer’s data are enough to make shares explode

Nevertheless, in Alzheimer’s, few data go a long way. Pfeifer said the partners are now looking to an open-label expansion of the trial to better understand what happened with the secondary endpoints. The teams are looking at biomarker data that Pfeifer hopes will correlate to the full memory effect.

But demonstrating that reducing tau can have an effect on Alzheimer’s was a pretty big deal. The most recent semorinemab data release came a few months after Biogen reported the failure of a tau candidate in phase 2. Semorinemab itself has seen plenty of setbacks, including a phase 2 failure in early Alzheimer’s back in September 2020. 

Tau is a protein that helps stabilize the brain’s nerve cells. In patients with Alzheimer’s, these proteins fall apart and clump together to form tangles. These tangles, along with beta-amyloid plaques that are another clumped-up group of abnormally functioning proteins, are hallmarks of Alzheimer’s. The prevailing theory is that tau accumulates in parts of the brain responsible for memory. As beta-amyloid plaques increase, the abnormal tau is eventually pushed throughout the brain.

Pfeifer thinks tau may play a role in the disease at different stages.

“Obviously, there’s a lot to learn, but without this first clinical data, we wouldn’t even know where to start, so now we have a very good starting point,” Pfeifer said. 

With the lessons from the phase 2 study in hand, AC Immune is plowing on with a number of studies and partnerships with Big Pharma. In addition to the Genentech collaboration on semorinemab, the biotech is working with Johnson & Johnson and Eli Lilly.

RELATED: Eli Lilly, Roche’s Alzheimer’s prospects, including flops, boosted in light of FDA’s Aduhelm approval: analysts

Big Pharma partnerships have always been a part of AC Immune’s DNA, from the first antibody it developed. Pfeifer said the company had a strong candidate and was able to hand-pick the company to work with.

“For me coming from oncology, there was only one company with all the knowledge in antibodies. This was Genentech. It was absolutely no question,” said Pfeifer, who co-founded AC Immune in 2003.

That first tie-up ended up setting the course for a second deal: “To have two deals in a row with Genentech, you have to do well, your science has to be top otherwise there is no second deal,” the CEO said.

And then came the others. 

“First of all, antibodies: Genentech. Second, we wanted vaccines: Johnson & Johnson. Third, we were in small molecules,” Pfeifer explained, which led the company to Lilly. “On one hand, we wanted to learn from the partners to get the best of class. At the same time, we wanted to really build on their development experience and validate our platform.”

‘Why should I worry?’

Pfeifer herself brought plenty of experience to her leadership role when she founded AC Immune 18 years ago, joining an unfortunately small group of women running major biotechs or pharmas in Europe. She was previously head of the Nestlé Research Centre in Switzerland with a background in oncology. Pfeifer spent time as an executive in the U.S., so she didn’t exactly realize that she was breaking ground at first.

“Being a professional woman, where you sort of develop your professional scientific career in America has helped me a lot to say, ‘Okay, it’s normal. Why should I worry?’” she said.

RELATED: How a distinct type of tau protein could offer a new target for treating Alzheimer’s disease

But when she looked around, Pfeifer realized she was a “rare disease,” she said with a laugh. Now, she leads a biotech that is 60% women, which she says has come pretty naturally, as women see what’s possible. 

Pfeifer said young women want to work at a place where they can see a woman in charge and “a boss who makes it,” adding “it has a huge influence.”

Under Pfeifer’s leadership, AC Immune has tallied Big Pharma partnerships that could net a combined 3.3 billion Swiss francs ($3.5 billion) in milestone payments, with $34 million already banked. That’s allowed the biotech to bulk up its pipeline for Pfeifer’s ultimate goal: a vaccine for Alzheimer’s that could prevent damage from ever occurring in patients’ brains. For that, a diagnostic is needed, and the biotech has four of those in development, too.

For 2022, AC Immune is shooting to get three vaccine trials off the ground, including one for Parkinson’s disease and a tau vaccine. Pfeifer said the company also wants to have more data on the tau candidate to “know how this thing works.” The biotech will also narrow down the lead candidate in the Lilly collaboration.

Annalee Armstrong

https://www.fiercebiotech.com/biotech/alzheimer-s-debate-may-not-seem-positive-but-ac-immune-s-ceo-promises-it-s-been-a

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