When Cassava Sciences Inc.’s president and CEO, Remi Barbier, opened up the interim analysis of the company’s open-label study for Alzheimer’s disease (AD) candidate simufilam, he was more than pleased with the results but found himself an audience of one. His researchers had been confident about the results before the data were tallied.

“I was ecstatic,” he told Bioworld. “No one’s seen this type of improvement in Alzheimer’s. But our scientists said, ‘See, I told you so.’ It was not my expectation.”

Barbier said he would have been very happy, given simufilam’s mechanism of action and the cerebrospinal fluid biomarkers, just to see AD patients stabilized over the six-month study period.

The new data showed six months’ treatment with the oral, small molecule not just stabilized but improved cognition and behavior scores in AD patients. Cognition scores for the same patients rose 10% from baseline to the sixth month of treatment, 1.6 points on the Alzheimer's Disease Assessment Scale-cog11 scale. Anxiety, delusions and agitation, all dementia-related behavior, showed a 29% mean improvement in the same period, improving by 1.3 points on the Neuropsychiatric Inventory.

Cassava said the positive data are enough to propel simufilam into a phase III study sometime in the second half of 2021.

The ongoing, multicenter study reflects data at the halfway mark for the first 50 patients with mild to moderate AD receiving 100 mg twice daily or placebo. The study began in March and is about 80% enrolled. After racking up solid data, Barbier said as many as 50 more patients will join the study, bringing the total to 150.

Remi Barbier, president and CEO, Cassava

“We’re getting a lot of calls from clinical sites, from caregivers, that say Aricept no longer works or it never worked, saying please take my patients,” he said. “It’s humanitarian and it’s the right thing to do. Unfortunately, as a small company we can’t increase it to 1,000 or 2,000.”

Barbier said the company has been working on the science of simufilam for more than 10 years with plenty of scientific and financial support from the U.S. NIH.

“They’ve been our strongest believers since the beginning,” he added. “The NIH is the one government program that is top notch. It works.”

Simufilam is designed to restore the normal shape and function of altered filamin A (FLNA), a scaffolding protein, in the brain. The scaffolding protein physically holds up the brain, Barbier said, giving it structure and integrity. It’s also a nexus of communication, so FLNA supports the brain and acts as an air traffic controller.

“In Alzheimer’s, the filament misfolds and it’s the altered shape that allows downstream pathologies such as inflammation, the characteristics of Alzheimer’s,” he said. “Once we had that insight, we developed a small molecule.”

Phase IIb data of simufilam released in November showed treatment significantly reduced levels of HMGB1 protein in cerebrospinal fluid (CSF), at -33% for 50 mg and -32% for 100 mg (p<0.001 for both). The data showed it significantly improved the integrity of the blood-brain barrier, with CSF IgG decrease of 30% for both dose groups (p<0.05) and CSF albumin decrease of 15% and 28% for 50-mg and 100-mg doses (p<0.05 for both). The data also showed the albumin ratio improved by about 5 and 7 points for patients treated with 50 mg and 100 mg, respectively, over 28 days while the ratio was unchanged for patients on placebo.

“We believe the results have positioned the company with compelling rationale to advance sumifilam into a pivotal study in Alzheimer’s,” wrote H.C. Wainwright analyst Vernon Bernardino on Nov. 10. “FLNA-binding molecules are new to Alzheimer’s research, and in our opinion, represent important advances in targets for AD drug development. Thus, with the AD drug development landscape littered by continued setbacks in targeting β-amyloid, we believe the emergence of Cassava’s sumifilam as a new targeted approach remains underappreciated.”

Share prices of company stock (NASDAQ:SAVA) have languished in the single digits during the past 12 months but the new data put an end to that. On Feb. 2, shares rose a staggering 141.15% to $55.44, up $32.45. In the past year, the shares had dropped to as low as $2.12 in May.

Barbier said he knows the company is fighting a tough indication, one pharma companies large and small have struggled with for decades.

“They call it the graveyard of drug development,” he said. “But cancer was like that for about 30 years. Until it wasn’t.”