Alnylam Pharmaceuticals (ALNY): Straight from the CSO and Chief R&D officer "we want both labels, but we will protect mono"

Research evidence excerpt

10 August 2026

Jeffrey Walch, MD, Ph.D.

US Biotechnology

Alnylam Pharmaceuticals Inc

Wen Jiang, Ph.D., CFA

Rating

Outperform

Specialist Sales

Price Target

Christian Moore

ALNY

376.00 USD

Alnylam Pharmaceuticals (ALNY): Straight from the CSO and

Chief R&D officer “we want both labels, but we will protect

mono”

We caught up with ALNY’s Chief Scientific Officer (CSO) and Chief Research & Development

Officer (CRDO) after our note last week. The company let us know they replicated our

published (Link) outside-in statistical analysis of the chance that HELIOS-B combo results

were a “fluke” given AZN’s (Smith, O) CARDIO-TTRansform. We met to compare notes.

Based on our conversation with the CSO & CRDO, we are convinced that ALNY is not going

to make the same costly mistake as AZN: clinical trial design failure to protect the label in the

monotherapy population. In addition, we think the statistical analyses in our last two notes

(pending announced CARDIO-TTRansform HR) signify that Wainua’s distinct mechanism vs

Amvuttra/Nucresiran more likely than not translates to differentiated clinical outcomes.

Therefore, CARDIO-TTRansform’s more recent results do not nullify HELIOS-B or the

potential for Nucresiran to add significant benefit to patients on a background stabilizer

(71% POS based on our analysis).

Four key takeaways from our conversation with ALNY’s CSO & CRDO include:

1. ALNY replicated our outside-in statistical analysis. They note that their results were

broadly in-line with ours: Low chance for HELIOS-B combo HR= 0.79 to be a fluke,

especially if CARDIO-TTRansform combo HR is greater than 0.9. ALNY noted small

differences in final chance results given they have more robust data set available for

HELIOS-B. Bernstein view: I’m sure their analysis is more accurate- but the general

answer still applies. Reminder that our DCF & PT reflects ALNY’s worst-case reported

HR= 0.9 for CARDIO-TTRansform in patients with a background stabilizer. However,

our base-case is that AZN will report HR ~1.0, which translates to a 16% chance that if

repeated HELIOS-B would replicate the recent negative CARDIO-TTRansform results in

patients on a background stabilizer.

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