The Cardiology Renaissance: Post CARDIO-TTransform, two top-of-mind catalysts remain for 3Q

Research evidence excerpt

The Cardiology Renaissance: Post CARDIO-TTransform, two top-of-mind catalysts remain for 3Q

Goldman Sachs Global Healthcare: Pharmaceuticals

Framing two top-of-mind cardiology catalysts

Recall, AZN and IONS announced that the Phase 3 CARDIO-TTRansform study (n= 1,432)

of antisense oligonucleotide Wainua in ATTR-cardiomyopathy (CM) missed its primary

endpoint of the composite outcome of cardiovascular (CV) mortality and recurrent CV

clinical events assessed up to week 140 - while there was a nominally significant hazard

ratio of 0.71 in the monotherapy arm, there was no evidence of benefit in combination

with stabilizer therapy (e.g., PFE’s tafamidis), and tafamidis-treated patients performed

better-than-expected in the milder population.

The update was a negative surprise, as success on the primary endpoint was expected

per our investor discussions and the key debate centered on whether the stabilizer

combination group - 57% of patients with an additional 24% drop-in rate - would

achieve significance. We await full results at the European Society of Cardiology (ESC)

Congress in August.

After the CARDIO-TTRansform news, significant stock moves transpired for AZN (-10%),

IONS (-33%), and affected companies ALNY (-11%) and BBIO (+6%). On the forward, we

look to two other Phase 3 cardiovascular catalysts this quarter that could result in

volatility for the subject companies as well as wide-reaching effects for the field: (1)

NVS/IONS’ HORIZON trial of Lp(a)-targeting pelacarsen; and (2) NVO’s ZEUS assessing

ziltivekimab (IL-6). Below, we provide the set-up into the catalysts, including

benchmarks for success, readthrough to other affected companies, our implied up/down

moves, and options commentary.

Exhibit 1: Key cardiology catalysts in 2026 and 2027