July 12, 2021
BIOINVEST NEWS: Celldex (CLDX)
Celldex (CLDX) Delivers Outstanding Phase 1b Data, 19 of 20 Urticarial Patients Demonstrate Complete Response After Single Dose of CDX-0159, Raising BUY to 47 (from 30) and TARGET to 70 (from 40), Best in Class and a Pipeline in a Pill?
– 95% complete response rate after single dose of CDX-0159
– Rapid, profound and durable responses offer patients opportunity for quick, lasting, meaningful relief
– Median duration of response 77+ days in Cold Urticaria and 57+ days in Symptomatic Dermographism
– Serum tryptase and skin mast cell depletion mirror clinical activity
– Favorable safety profile
CLDX announced outstanding updated data from the Company’s ongoing, open label Phase Ib trial of CDX-0159 in patients with antihistamine refractory cold urticaria and symptomatic dermographism, the two most common forms of chronic inducible urticarial (hives). These diseases, which are often severe and debilitating, can significantly impact patients’ lives. CDX-0159 is a humanized monoclonal antibody that specifically binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity. These data were presented by Dr. Marcus Maurer, Professor of Dermatology and Allergy at Charité in Berlin during a late-breaking poster discussion session (#1046) as part of the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress 2021. In our view, ‘0159 is continuing its metamorphosis into both a potential best in class molecule and also a pipeline in a pill. Given our increased confidence in ‘0159 and the emerging cancer pipeline we are raising our BUY to 47 (from 30) and our TARGET PRICE to 70 (from 40).
All 19/19 (100%) patients who received a single full dose of CDX-0159 experienced a clinical response to provocation testing. 18/19 (95%) experienced a complete response and 1/19 (5%) experienced a marked partial response. Responses were rapid, profound, and durable and correlated with a depletion of skin mast cells. The ‘0159 data compares extremely well with current treatment Xolair which showed a 53% (10/19) complete response rate at week 10 in symptomatic dermographism urticaria, and a 44% (4/9) complete response rate in cold urticaria. The achievement of a 95% complete response rate, rapid onset and sustained durability after a single dose is unprecedented in this patient population and clearly demonstrates that CDX-0159 has the potential to become the best in class mast cell inhibitor.
CDX-0159 was generally well tolerated. The most common adverse events were hair color changes, mild infusion reactions, and transient changes in taste perception. Hair color changes (generally small areas of hair color lightening) and taste disorders (generally partial changes of ability to taste salt) are consistent with inhibiting KIT signaling in other cell types and are expected to be fully reversible. As previously reported, a single severe infusion reaction of brief loss of consciousness was observed in a patient with a history of fainting. The patient rapidly recovered. Importantly, no evidence of mast cell activation as measured by serum tryptase monitoring was observed.
Next Step
The sub-q formulation of ‘0159 will enter the clinic in the third quarter of 2021. The Company plans to initiate a study in prurigo nodularis in the fourth quarter of 2021. CLDX remains on track to initiate the Phase II trials in both spontaneous and inducible urticaria in the first half of 2022. Initial results from the cholinergic cohort are planned for presentation at a scientific congress in the first quarter of 2022. Treatment results from the Phase 1b study in chronic spontaneous urticaria are planned for presentation at a scientific congress in early summer of 2022. The Company plans to expand development into a fourth indication by year end 2022. Remember there are huge opportunities in other inflammatory diseases where over active mast cells are implicated including asthma.
In our view, the strong ‘0159 data validates that urticarias are mast cell driven and has a positive read through for other mast cell driven conditions. Importantly it also de-risks the antibody and increases our confidence in ultimate success. The fact that one patient with symptomatic dermographism enrolled in the study also had a diagnosis of prurigo nodularis and experienced both a complete response of symptomatic dermographism and a notable improvement of the prurigo nodularis also bodes well for clinical success in other mast cell indications. In our view, ‘0159 is continuing its metamorphosis into both a potential best in class molecule and also a pipeline in a pill. Given our increased confidence in ‘0159 and the emerging cancer pipeline we are raising our BUY to 47 (from 30) and our TARGET PRICE to 70 (from 40).