Off the Beaten Path

Research evidence excerpt

Off the Beaten Path

Idea

June 22, 2026 03:00 AM GMT

Morgan Stanley & Co. International plc+MPharmaceuticals | Europe Sarita Kapila

Equity Analyst

Off the Beaten Path Sarita.Kapila@morganstanley.comThibault Boutherin +44 20 7425-1320

Thibault.Boutherin@morganstanley.com +44 20 7425-9688

In this note we examine three underappreciated read-throughs: Adithya Venkat

what Roche’s persevERA miss really means for AZN’s SERENA-4, ResearchAdithya.Venkat@morganstanley.comAssociate +44 20 7425-2216

how OptiTROP and EVOKE-3 reshape the AVANZAR debate, and Gizel Askin

Research Associate

why Saphnelo SC/Gazyva could pressure long-term Benlysta Gizel.Askin@morganstanley.com +44 20 7425-3286

estimates. Pharmaceuticals

Europe

Key Takeaways Industry View In-Line

Read from ROP's persevERA: 1. De novo patients may dilute SERD benefit, a HR

0.93 suggests many are AI-sensitive, where AI + CDK4/6 is already a high bar

2. Later relapse looks more attractive, with >12m post adjuvant therapy HR of

0.86, suggesting later relapse as a cleaner endocrine sensitive population

SERENA-4 targets the >24m sweet spot, but de novo inclusion caps upside.

SERENA-4 is likely powered for a HR 0.87–0.88, an overall HR 0.86–0.87 looks

realistic

Merck's sac-TMT supports TROP2 ADC + IO in lung cancer, but Trodelvy’s

EVOKE-3 failure makes AVANZAR dependent on QCS selection against a tougher

chemo-IO bar

Benlysta’s £2.2bn FY30 consensus looks exposed, with Saphnelo SC targeting ~

£700m SC sales and Gazyva raising the SLE/LN efficacy bar

1. [ROP, AZN] Roche’s persevERA miss resets expectations for AZN’s SERENA-4.

Roche’s Phase 3 persevERA trial, evaluating giredestrant + palbociclib vs letrozole +

palbociclib in 1L HR+/HER2 advanced breast cancer, failed to meet its primary PFS