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).
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We have subsequently completed 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%) achieving EASI-50, of which three patients (25%) also achieved EASI score improvement of 75% relative to baseline (EASI-75). Day 29 results exceeded the primary efficacy objective of the trial with 10 of 12 patients (83%) achieving EASI-50, of which four patients (33%) also achieved EASI-75. Efficacy was sustained through day 140 following single dose administration of ANB020 with five of 12 patients (42%) 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.
We also observed that clinical efficacy was consistent with certain biomarkers tested in this Phase 2a trial. Circulating blood eosinophil levels were reduced by a maximum of 40% at Day 29 post-ANB020 administration relative to baseline, which is aligned with genotypic studies that associate lower eosinophil counts with human IL-33 loss-of-function mutations (link to publication to be added in publications page). In addition, clinical efficacy in this Phase 2a trial was consistent with an ex vivo pharmacodynamic assay measuring IL-33 mediated interferon-gamma release, where 98% inhibition was observed within 72 hours following ANB020 administration and 86% inhibition was sustained at day 57 post-ANB020 administration, which is consistent with the pharmacodynamic activity observed using the same assay in our prior Phase 1 trial of ANB020 in healthy volunteers.
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 and the European Academy of Allergy and Clinical Immunology Congress on May 29th 2018, (click here to download).
As further development in atopic dermatitis, we have initiated, during the first half of 2018, a Phase 2b randomized, double-blinded, placebo-controlled study in 300 adults patients with moderate-to-severe atopic dermatitis to evaluate multi-dose subcutaneous administration of ANB020. We anticipate data from this Phase 2b trial in 2019.
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.
We are conducting a blinded, placebo-controlled Phase 2a trial of ANB020 with 20 adult peanut allergy patients with a clinical history of anaphylaxis. Baseline peanut tolerance in each patient was evaluated upon enrollment using a blinded, placebo-controlled oral food challenge (OFC) according to PRACTALL guidelines, where each patient experienced dose limiting symptoms at or before a cumulative 500mg dose of peanut. Patients were subsequently randomized on a 3:1 basis to receive a single intravenous 300mg dose of ANB020 or placebo at 14 days following the baseline OFC, and then administered a second OFC at 14 days after dosing. Each OFC was limited to a maximum of 500mg cumulative peanut dose. Symptom severity was adjudicated by an independent, blinded assessor that was not involved in performing the baseline or day 14 OFC. An interim analysis of this trial was focused on patients with moderate-to-severe baseline symptoms, which is the patient population that AnaptysBio plans to target for future development of ANB020 in adult peanut allergy.
Thirteen ANB020 dosed and three placebo dosed patients exhibiting moderate-to-severe symptoms during the baseline OFC were included in the analysis, while two ANB020 dosed and two placebo dosed patients with mild baseline symptoms were excluded. The average age and baseline peanut tolerability of moderate-to-severe baseline patients was 31 and 239mg, respectively, which were consistent with the age and baseline peanut tolerance of all 20 enrolled patients. In patients with moderate-to-severe symptoms at baseline, six of 13 (46%) patients administered a single dose of ANB020 improved peanut tolerance at the day 14 OFC to the maximum tested cumulative 500mg dose, compared to none of the placebo dosed patients. Amongst the patients excluded due to mild baseline symptoms, one ANB020 dosed patient and two placebo dosed patients improved peanut tolerance to the 500mg cumulative dose at the day 14 OFC. Concomitant allergy symptoms, typically overlapping with peanut allergy, including urticaria, pruritus, rhinitis, asthma flares and other nut allergies, occurred in four of five (80%) patients following placebo administration but only occurred in one of fifteen (7%) patients after ANB020 dosing. ANB020 was generally well-tolerated during the study and all 20 patients remain enrolled with no dropouts. No serious adverse events have been reported and the most frequent treatment-emergent adverse event reported in ANB020 dosed patients was headache in four of fifteen patients, of which three were mild cases and one was moderate severity, while the most frequently reported adverse events in placebo dosed patients were mild and moderate severity allergy-related events in four of five patients.
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).
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 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 third quarter of 2018.
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.