Update on Cassava Sciences (formerly Pain Therapeutics)

Cassava Sciences presented more detailed data from its phase IIa trial of PTI-125 on 13 patients with moderate Alzheimer’s disease (CTAD, https://www.cassavasciences.com/static-files/8fbb3e1b-528c-46d1-bbbd-d6ed7d9a6d9f). The results are well summarized on slide 30 of the presentation by Dr. Burns. It is amazing that every patient responded to treatment with improved biomarkers across the board. However, the most impressive piece of data is on slide 25: time-dependent restoration of cellular communication highway-native conformation of filamin A.

Alzheimer’s disease is like accumulated car wrecks on a thruway: debris everywhere, wrecked cars scattered around, and big holes all along the road due to years of neuron damage by inflammation, immune attacks, or chronic infection. Even if you clear all the debris and remove all wrecked cars (remove amyloid, soluble or deposit), still no vehicle can go through as the road is still not passable due to all the holes along the way. On the other hand, if you fix all the holes on the highway, some small cars can zigzag through. Indeed, the repaired road can have mails delivered and messages sent. In a similar way, signals between neurons can be delivered and retrieved. Scientists at Cassava Sciences have shown that accumulated neurodegeneration through the years alters the conformation of filamin A, blocking its ability to deliver signals from outside the neuron to the inside. PTI-125 restores the native conformation of the most important cellular network protein, filamin A, through its direct binding. As an added benefit, removal of debris (Amyloid load) becomes much easier due to the repaired roads.

The projection would be that the restoration of native conformation of filamin A by PTI-125 not only slows neurodegeneration, but also potentially could reverse the memory loss to a certain extent. 

I project that phase IIb will show improved cognition (secondary endpoints) even with only one month of treatment with 2 points improvement  of MMSE (100mg arm to control, p<0.05) as well as improvements on other executive functions.

My initial projection on price action still holds with increased confidence.