July 22, 2026
BIOINVEST NEWS: Celldex (CLDX)
After the close, CLDX announced that treatment with barvolvolimab (“barzo”) did not work in the Phase IIb trial in prurigo nodularis (PN). While barzo significantly and safely depleted mast cells, PN is complex immune-mediated neurological condition that is not obviously driven by primarily mast cells – which urticaria is. The Phase III CSU data – the key clinical trials for CLDX – is expected now in September/October (prior guidance was Q4:26). BUY
PN Miss
The Phase IIb results showed barzo did not improve vs. placebo on the primary endpoint of itch response (% of patients with >4-point improvement on the Worst Itch Numeric Rating Scale (WI-NRS)), or key secondary endpoints of disease severity (including IGA-CNPG-S) at Week 12 at both doses tested. Despite showing encouraging Phase Ib data in a small earlier trial (n=23) with clinically meaningful WI-NRS and IGA responses at 8 weeks (after single IV infusion of barzo at the highest dose tested), this study further suggests PN is a complex neuroimmune inflammatory disease that stimulates various immune cells and not a classical mast cell-driven disease like CSU or CIndU.
Bolus Dose Showed Safety & Early Mast Cell Depletion
Although the PN stud was unsuccessful for efficacy, barzo’s safety was rather benign and similar to previous studies (e.g., reversible hair color change and hypopigmentation) and little to no neutropenia. This is important as the study was the first to report the use the 450mg barzo loading dose – which is also included in the upcoming CSU registration trials. Moreover, the loading dose significantly depressed mast cells via tryptase response that kept levels low for the entire 24 weeks. Hence, this observation represents further support that the urticaria studies will prove successful.
CSU Studies Now Due September/October
The major clinical trials – EMBARQ-1 and EMBARQ-2 with barzo are now due by September/October – vs. a prior guidance of Q4:26. Hence, we are only about 2+ months away from the first Phase III data – which for so many reasons (previously large unprecedented Phase IIb data and highly mast cell driven biology and pathophysiology of CSU + safety) we expect positive results. The bolus 450mg loading dose including in today’s release adds further confident to the efficacy and safety hypothesis of barzo in CSU.
Conclusion. BUY CLDX
From what we understand, certain investors were awaiting the more uncertain outcome of the PN trial before stepping into CLDX stock ahead of the much likely CSU results. Hence, while disappointing, PN is now behind us and CSU is closer than we previously thought. At the current valuation ($2.6 b), as the next leader in multi-billion urticaria market, we. Believe Celldex is very undervalued. Phase III Sep/Oct/NDA filing 2027/FDA approval end 2027/2028. Co. already in beginning discussion with payors for the urticaria indications. There are over 50 mast cell driven conditions and we believe barzo will work in several of them.