赛诺菲-伊特佩奇单抗在呼吸道疾病的三期试验消息喜忧参半；但研发管线仍具潜力

F25EF26E10.59.316.613.92 Jun 202585.91124.0044%110.88/85.431,423.83Dec4.6%105,345114,1156M12M(6.4)(4.3)15.211.1(21.6)(15.4)05/2512001300140015001600 SanofiRatingOutperformPrice TargetSAN.FPAdjusted EPSSAN.FP (EUR)Source: Bloomberg, Bernstein estimates and analysis.the pipeline is not out of steamOn Friday, Sanofi announced a positive phase III trial (Exhibit 1)for itepekimab in COPD(smoker’s disease) but the product failed to show a benefit in moderate to severeexacerbations in the second trial (Exhibit 2).Approval unlikely as two positive trials are usually required.This was a surprise anddisappointing, as this product (collaboration with Regeneron, covered by Will Pickering,link to the report on this news) was supposed to complement the COPD franchise in anew population (former smokers). As a reminder, Dupixent was the first biological drug tobe approved last year for this difficult to treat indication. The company said these mixedresults may be explained by the difference between trials in the profiles of smokers andnon-smokers, potential problems with some sites, and the trial enrolled patients during thepandemic (further review of the detailed results needed according to SAN). However, wedon’t believe the FDA will accept pooled data (like GSK did in the past in respiratory and wasrejected by the regulatory authorities), as two positive trials are usually required. SAN maydecide to initiate a new trial, but it would delay the submission by at least three years. Sanofisaid it manages COPD as a franchise, and lunsekimig (IL-13/TSLP nanobody in phase II/III)should help (but not on the market before 2030).Still a broad pipeline in inflammation and diversified portfolio should more thanoffset the Dupixent patent expiry beyond 2030(35% of sales). We have removed ourestimates for itepekimab, which accounted for c.2% of 2030 sales (50/50 profit sharingwith Regeneron) and there is no impact on mid-term earnings. Sanofi has a broad late stagepipeline (Exhibit 9) of c.12 projects with limited market expectations (€1-3bn in 2030 or<5% of sales) with a diversified portfolio in vaccines (c.20% of sales) and rare diseases (14%of sales) that should drive growth beyond the Dupixent patent expiry (>2030). Moreover, bolton acquisitions such as Blueprint announced today (link) should help.Investment ImplicationsDespite the mixed news,we reiterate our Outperform rating(see p.4). Newsflow in 2H25:tolebrutinib (BTKi) in multiple sclerosis (we stand 50% above consensus for 2030e) andamlitelimab (OX40L) initial phase III in Atopic Dermatitis (more results in 2026).See the Disclosure Appendix of this report for required disclosures, analyst certifications and otherimportant information. Alternatively, visit our Global Research Disclosure Website.First Published: 02 Jun 2025 16:45 UTC Completion Date: 02 Jun 2025 16:45 UTC F24AF25EF26E7.128.209.28FinancialsF24AF25EF26ECAGRReported EPS4.445.176.18--Close DateEDMFYEDiv YieldEV (EUR) (M)PerformanceAbsolute (%)EDM (%)Relative (%)€120€115€110€105€100€95€90€8506/24 DETAILSEXHIBIT 1:Itepekimab (AERIFY-1) reductions in moderateto severe exacerbations*0%5%10%15%20%25%30%35%40%(*) placebo adjustedSource: SanofiEXHIBIT 3:Itepekimab tolerance profile (AERIFY-1)67%0%10%20%30%40%50%60%70%80%AEs: adverse eventsSource: SanofiCOPD: A DIFFICULT DISEASE TO TREATCOPD affects more than 200m people worldwide, of whom 5% are in the US, 70% are above 55 years of age, and two-thirdsare women. But this disease is massively undiagnosed, as up to 70% of patients don’t know they have the condition (mostly mildto moderate severity). It is projected that this disease could affect 600m people by 2050. This disease is responsible for 3mdeaths annually (vs 0.4m for asthma) and represents close to $40bn in healthcare costs. Approximately 15% of COPD patientsare frequent exacerbators and account for 50% of healthcare costs. COPD is a heterogeneous disease but, as is the case withasthma, doctors try to characterise the different phenotypes and use biomarkers. Mucus plugging is an important element interms of increased mortality risk.According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), COPD is characterised by persistent airflowlimitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and thelungs to noxious particles of gases. Exacerbations and comorbidities contribute to the overall severity in individual patients.Worldwide, the most commonly encountered risk factor is tobacco smoking, but air pollution is also a factor. As shown below,the lungs of the patients with COPD are destroyed over time, which means it becomes more challenging to show symptomimprovement.EUROPEAN BIOPHARMACEUTICALS (*) placebo adjustedSource: SanofiEXHIBIT 4:Itepekimab tolerance profile (AERIFY-2)64%71%0%10%20%30%40%50%60%70%80%AEsItepekimab every 2wAEs: adverse eventsSource: Sanofi 2 Source: ERS (European Respiratory Society 2024 congress)Lunsekimig (