Catalyst: ATTR-CM AstraZeneca+Ionis. Combo at 20.3% odds. Good for IONS ALNY. Unclear on BBIO

Research evidence excerpt

Catalyst: ATTR-CM AstraZeneca+Ionis. Combo at 20.3% odds. Good for IONS ALNY. Unclear on BBIO

Biotechnology - Immunology

Genetic Medicines - Market Weight

Catalyst: ATTR-CM AstraZeneca+Ionis. Combo at 20.3% May 26, 2026

odds. Good for IONS ALNY. Unclear on BBIO

The Wolfe Byte

Cumulatively, 20.3% odds of achieving stat sig on the combo. Low odds of best case scenario, but the overall

risk-reward here suggest the following tactical stock calls for this event (likely Sep-Oct?): long IONS, long ALNY,

uncertain-or-short BBIO

Setup. Ph3 from the AstraZeneca-Ionis collaboration will likely read out in the ~Sep-Oct timeframe, and Ionis would

benefit from seeing a result of eplontersen+tafamidis > tafamidis alone (i.e. combo better than mono), because Alnylam

failed a similar endpoint at HR 0.78 p = 0.28. We were previously worried about optics of a worse HR compared to

Alnylam, but buyside appears to be singularly focused on 'stat sig-ness' as an end-all be-all metric. While both Astra

+Ionis communicate that the trial size is not designed to see a successful combo endpoint, bulls are still hopeful due to

the larger trial size. Detailed baseline characteristics on May 9 showed 819 (57%) patients were on a stabilizer, allowing

us to more accurately calculate odds.

Method. Eplontersen is a slower-acting and shallower-acting drug vs vutrisiran, and could realize a slightly worse

HR especially given slightly less time for a full separation. We assume placebo rate at 0.112 recurrent CV events per

patient/year and 0.057 CV deaths per patient/year because placebo event rates may be sliding as ATTR-CM patients

become healthier. Further, the CV mortality-exclusive endpoint should accrue fewer events than the all-cause mortality

endpoint.