The Fight Against Alzheimer’s Goes Beyond Plaque. Tangles Are a Target, Too.

But another important feature of Alzheimer’s-damaged cells—tangles of protein called tau—is a focus as well. Eliminating amyloid plaques seems to reduce the spread of tau, but drug developers are also investigating the benefit of directly targeting tau. Some reported progress at the Amsterdam conference, including Biogen (ticker: BIIB), Eisai (ESAIY),
Prothena
(PRTA) and some still-private start-ups.

With decades of research behind it—but no drug sales yet—Prothena probably has the most riding on its development efforts. The company’s neuroscience work started in the 1980s at Athena Neurosciences, a start-up later acquired by Ireland’s
Elan
Pharmaceuticals. After Elan ran into trouble, Prothena was spun off in 2012 to pursue treatments for Alzheimer’s and other neurological disorders.

Prothena shares leapt in May, when
Bristol Myers Squibb
(BMS) paid $55 million to exercise an option to invest in an experimental antibody designed to head off tau’s spread through the brain. At a recent $71, Prothena stock is up nearly 140% in the past 12 months, compared with a 26% rise for the
Nasdaq Composite.
The Dublin-domiciled company now valued at $3.7 billion.

Antibodies targeting tau have disappointed in previous trials, but Prothena and others in the industry are now testing some that latch onto the part of the protein that causes tau to spread from brain cell to brain cell. Top-line results from administering a single dose of Prothena’s PRX005 antibody in a Phase 1 study were released in January, suggesting it was safe.

At this week’s Alzheimer’s conference, more details on the 19 patients dosed in that study showed that PRX005 safely reached concentrations comparable to those that prevented the damaging spread of tau tangles in lab mice. A study examining multiple doses of the tau-blocker is now being funded by Bristol Myers.

Analysts including Oppenheimer’s Jay Olsen suspect that Bristol’s $55 million bet on the tau treatment may have been informed by a glimpse of the multidose trial. He has a Buy rating on Prothena and a target of $120 for the price.

Prothena has other irons in the fire, in its Alzheimer’s program. It is in Phase 1 trials for an antibody that targets amyloid-beta plaques, like the recently approved Leqembi from Biogen and Eisai, as well as Lilly’s promising donanemab. In the lab, Prothena’s PRX012 seemed more potent than other anti-amyloid drugs, and it can be dosed by injection instead of a hospital infusion.

At the Amsterdam conference, Prothena researchers also showed data for a vaccine that caused mice to generate their own antibodies against both amyloid and tau. The shots cleared amyloid in the mice. Around the end of this year, the company hopes to ask U.S. regulators for permission to start human trials of the double-barreled PRX123 vaccine.

The little company had $700 million in cash and was burning through it at a $200 million annual rate in the March quarter. It faces big rivals in targeting tau.

An anti-tau antibody was detailed by Japan’s Eisai at this week’s Alzheimer’s conference. Like Prothena’s, the E2814 antibody blocks the tau protein from spreading from cell to cell. Eisai says that in a Phase 1 trial with several dozen patients, it reduced tau-related measures in some people.

Biogen discussed a different line of attack on tau. It told meeting attendees about a so-called antisense drug that Biogen is developing in partnership with
Ionis Pharmaceuticals
(IONS), which blocks the genetic instructions that lead brain cells to make tau. Biogen has advanced to Phase 2 trials, after a Phase 1 study that showed the drug reduced tau levels in the brain and blood, in Alzheimer’s patients.

Write to Bill Alpert at [email protected]