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It's a smart bet I have a slightly different perspective on it: Dupi's 2031 LOE will be unique in a way where they will still be a Best in Disease gold standard product. When dupi biosimilars come into the market they will be widely used bc of this gold standard efficacy and safety combined with the discounted price (40-70% discount) This creates a dynamic where payers will need to evaluate whether the premium they're paying for your drug is more value than a dupi biosimilar. This also increases the amount of dupi failures and dupi experienced AD in the market So the question every drug program should be asking is: 1. How much do they differentiate (efficacy, safety, administration route, dosing frequency, durability) to a dupi? And is that enough to justify the pricing premium of your drug? 2. If I can't beat dupi on a price adjusted basis, can I work on dupi experienced and/or failure AD pts? (There's also the ability capture that AD pt population that has a Asthma comorbidity but you still need to beat dupi here.) Any drug program creating me-too drugs or dodging dupi-experienced and dupi failures pts in their phase 2 and 3 trials are essentially shooting themselves in the foot. This is my view on these names: $KYMR's KT-621: MOA-wise they won't be beating dupi since they only target one source of that Th2 inflammation whereas dupi could hit the others. They will struggle on mixed Th2/Th17 diseases so if they have any asian sites or more African American patients, I'd be scared of being positioned in those readouts. It is an oral so I think they can capture pts that have needle phobia at 1L. After that, I'm not sure where they would fit especially if efficacy and safety doesn't hold up. Also $SNY dropped $KYMR's IRAK4 program so that partnership is not safe if efficacy doesn't hold up. $NKTR should be able to work on dupi experienced and failures hence, why I'm confused why they had to filter for a biologic naive pt pop in their phase 2bs so now they have nothing to guide their phase 3 design. Their durability is real though. It looks like you have to dose for a longer period to balance the Treg/teff ratio to get more efficscy that's why phase 3 has a 24wk induction period. IL-13s have some data on being able to work on dupi experienced and failures so they will have a place in this market and I believe $APGE (APG-777) dosing frequency can set itself apart Ox-40s are essentially dead but if amli still sells, I'd say that's a good sign that the market is still looking for options JAK inhibitors will still have a place in severe-very severe patients. I can actually envision a treatment landscape where JAK inhibitors are used in short course to quickly control disease and then Treg inducers $NKTR, $CRVS to maintain the response. Need to look at $EVMN's programs but new MOAs and orals will carve a market share Bispecifics will be interesting but it's all about whether they can best dupi and can work on dupi failures (especially IL17A/F x IL13, not sure about IL13xTSLP) $CRVS program to me is the best suited to survive in this post-dupi LOE world. It's an oral and a new MOA. Works on dupi and JAK failures. Can work on th2/th17 diseases and CTCL pts that present themselves like AD (which allows it to be used 1L for some patients). It can work on Asthma comorbidity with it's effects on ILC2s and reduction of IL-5 and it can even work on the neutrophilic asthma pts where dupi is ineffective. Durability is similar to $NKTR's durability and good to know that longer dosing (more tregs) can lead to extended effects (increased EASI-100s). There's an unknown on safety though Ritlecitinib (hits ITK and JAK3 can provide some read-through as it is viewed as the safest JAK. It's early tho but mgt clinical development design, planning, and execution are top notch. It's hard not to be bullish when looking at it this way.