ANB020 is an antibody that inhibits the activity of IL-33, a pro-inflammatory cytokine that multiple studies have indicated is a central mediator of atopic diseases, including atopic dermatitis, food allergies and asthma. IL-33 directly mediates release of disease-associated downstream cytokines, which recruit pro-inflammatory cells that mediate atopic disease. Because ANB020 inhibits IL-33 function, and acts upstream broadly across the key cell types and cytokines involved in atopy, we believe that its mechanism has advantages in the treatment of atopic diseases over competing agents that block only a subset of the downstream cytokines responsible for atopic diseases. The role of IL-33 signaling in asthma has been recently genetically validated through human studies published in the medical literature.
A single and multiple ascending dose Phase 1 trial of ANB020 in healthy volunteers. reported a favorable safety profile and pharmacodynamic properties of ANB020, where a single dose was sufficient to suppress IL-33 function for 85 days post-dosing as measured by an ex vivo pharmacodynamic assay. We presented these results at the 2017 American Academy of Dermatology Annual Meeting and the American Academy of Allergy, Asthma and Immunology 2017 Annual Meeting in March 2017, (click here to download).
We have subsequently completed of a Phase 2a trial where a single dose of ANB020 was administered to 12 moderate-to-severe adult atopic dermatitis patients that were inadequately controlled with topical corticosteroids. Each patient was dosed with placebo 14 days following enrollment, and subsequently administered a single 300mg intravenous dose of ANB020 one week after placebo.
ANB020 was efficacious in all 12 patients enrolled in this Phase 2a trial with each patient achieving 50% or better improvement in their Eczema Area Severity Index (EASI) relative to enrollment baseline (EASI-50) on or before day 57 post-ANB020 administration. Rapid clinical response was observed by day 15 post-ANB020 administration with nine of 12 patients (75 percent) achieving EASI-50, of which three patients (25 percent) also achieved EASI score improvement of 75 percent relative to baseline (EASI-75). Day 29 results exceeded the primary efficacy objective of the trial with 10 of 12 patients (83 percent) achieving EASI-50, of which four patients (33 percent) also achieved EASI-75. Efficacy was sustained through day 140 following single dose administration of ANB020 with five of 12 patients (42 percent) achieving EASI-50, of which three patients (25%) also achieved EASI-75. ANB020 efficacy was not limited by disease severity as ANB020 was similarly efficacious in the seven of 12 enrolled patients treated with systemic immuno-modulators pre-study, which exhibited an average EASI baseline score of 36 upon enrollment, relative to the remaining five of 12 enrolled patients that did not require systemic immuno-modulators pre-study and exhibited an average EASI baseline score of 27. The average baseline EASI score upon enrollment across all 12 patients was 32. Investigator’s Global Assessment (IGA) scores of zero or 1 (clear/almost clear skin) were observed in three of 12 patients (25%). Other atopic dermatitis efficacy endpoints, including the SCORing Atopic Dermatitis (SCORAD) scale, Dermatology Life Quality Index (DLQI) and the 5-dimensional pruritus scale, demonstrated rapid and sustained single dose ANB020 efficacy results in a similar manner to the aforementioned EASI results. ANB020 was generally well-tolerated by all patients and no drug-related safety signals were observed. The most frequent adverse events reported were dizziness in 17% of patients post-placebo and headache in 25% of patients post-ANB020 administration. A single serious adverse event of depression was reported on Day 140 post-ANB020 administration, which was consistent with the patient’s pre-trial history of depression and was deemed not drug-related. We presented these results at the 2018 American Academy of Dermatology Annual Meeting on February 17th 2018, (click here to download).
As further development in atopic dermatitis, we plan to initiate, during the first half of 2018, a Phase 2b randomized, double-blinded, placebo-controlled study in 200-300 adults patients with moderate-to-severe atopic dermatitis to evaluate multi-dose subcutaneous administration of ANB020.
We are conducting a Phase 2a trial of ANB020 in the United States with 20 severe adult peanut allergy patients, where efficacy will be assessed by measuring the cumulative dose of peanut tolerated in an oral food challenge before and after a single dose of ANB020 or placebo, where we anticipate top-line data will be available during the first quarter of 2018. We are also conducting a Phase 2a trial of ANB020 with 24 severe adult eosinophilic asthma patients, where efficacy will be assessed using improvement in Forced Expiratory Volume in One Second after administration of a single dose of ANB020 or placebo, where we anticipate top-line data during the second quarter of 2018.
Based on our analysis of publicly available data sources and interviews with physicians and key opinion leaders in the field of atopic dermatitis, we estimate approximately 1.4 million adults in the United States are affected by atopic dermatitis, of which approximately 280,000 are diagnosed with a moderate-to-severe form of this disease. Peanut allergy is the most common cause of food-induced allergy in the United States. Based on our analysis of publicly available data sources and interviews with physicians and key opinion leaders in the food allergy field, we estimate approximately 1.7 million adults are affected by peanut allergy, of which approximately 600,000 are treated by allergists and approximately 400,000 are at risk for severe reactions and therefore we believe are suitable for treatment with systemic biological therapies in the United States. We estimate, based on our analysis of publicly available data sources and interviews with physicians and key opinion leaders focused on asthma, that asthma affects approximately 19.0 million individuals, of which approximately 1.1 million have severe disease that cannot be controlled by standard-of-care therapy.
A translational research study, conducted by the laboratory of Dr. Erik Wambre at the Benaroya Research Institute in collaboration with AnaptysBio, assessed the biology of a distinct subset of T cells, called TH2A cells, which are found in elevated frequency in peanut allergic patients when compared to non-allergic individuals. TH2A cells isolated from peanut allergy patients demonstrated increased sensitivity to IL-33 signaling as a result of elevated expression of the IL-33 receptor. Data showed that, upon stimulus with IL-33, TH2A cells express significantly greater levels of effector cytokines IL-4, IL-5, and IL-13, which are believed to be associated with severe peanut allergy. The research concluded that IL-33 is a key checkpoint of allergic responses, and blocking IL-33 has the potential to reduce expression of the effector cytokines involved in severe peanut allergy. Data from this translational research study was presented at the American Academy of Allergy, Asthma and Immunology (AAAAI) 2017 Annual Meeting
, (click here to download).
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