RYTM: ENDO Update and Expert Insights Validate Setmel/MC4R Differentiation in PWS and Support Our Blockbuster View; Reiterate BUY and $143 PT

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RYTM: ENDO Update and Expert Insights Validate Setmel/MC4R Differentiation in PWS and Support Our Blockbuster View; Reiterate BUY and $143 PT

June 14, 2026

Seamus Fernandez seamus.fernandez@guggenheimpartners.com RYTM: ENDO Update and Expert Insights Validate

617 859 4637 Setmel/MC4R Differentiation in PWS and Support Our

Evan Wang

evan.wang@guggenheimpartners.com Blockbuster View; Reiterate BUY and $143 PT

212 651 9756

Zach Dunn, Ph.D. Key Message: At the ENDO 2026 conference, RYTM shared what we and experts zach.dunn@guggenheimpartners.com here at the meeting viewed to be a clearly positive update for setmelanotide in 617 859 4603

Prader-Willi syndrome (PWS). We are increasingly convinced that PWS offers a

Alana Lelo, Ph.D. blockbuster opportunity that should be added to models broadly for RYTM driven

alana.lelo@guggenheimpartners.com by (a) differentiated weight-loss benefits through 6 months across most patients, (b)

212 518 9955 encouraging commentary on RYTM’s Saturday morning call that responders continue

Colleen Garvey, Ph.D. losing weight through 12 months, and (c) evidence supporting substantive behavioral

colleen.garvey@guggenheimpartners.com improvements. We caught up with Drs. Miller and Shoemaker at the conference who

617 859 4664 indicated that they would use setmelanotide in most of their PWS patients based on

both BMI reduction and confidence around clinically meaningful behavioral benefits

(more details below). While the timelines and path forward for setmel vs. next-gen oral

bivamelagon or once-weekly injectable RM-718 is not fully clear, net-net data add to our

conviction that the FDA's WL or BMI Z-score threshold for a weight loss indication areRYTM BUY achievable and support our 65% POS for PWS and our risk-adjusted $1.3B+ estimate.