Investor Symposium on Peanut Allergy Treatment. December 1, 2017

Transcription

1 Investor Symposium on Peanut Allergy Treatment December 1, 2017

2 Welcome Laura Hansen, PhD VP, Investor Relations, Aimmune

3 Today s Agenda Time Topic Presenter 8:00 a.m. Welcome Laura Hansen, PhD VP, Investor Relations, Aimmune 8:05 a.m. Aimmune Overview Stephen Dilly, MBBS, PhD Chief Executive Officer, Aimmune 8:25 a.m. Aimmune s AR101 Clinical Development Program for the Treatment of Peanut Allergy 8:45 a.m. The Community Allergist and the Role of Professional Organizations 9:00 a.m. Treating Peanut Allergy: Perspectives from a Current Principal Investigator of Oral Immunotherapy Daniel Adelman, MD Chief Medical Officer, Aimmune Stephen Tilles, MD University of Washington Northwest Asthma and Allergy Center Ellen Sher, MD Allergy Partners of New Jersey Drexel University College of Medicine 9:15 a.m. Preparing for Potential Commercialization of AR101 Jeff Knapp Chief Operating Officer, Aimmune 9:50 a.m. Looking Ahead: Anticipated Milestones Jeff Knapp Chief Operating Officer, Aimmune 9:55 a.m. Q&A with Speaker Panel Mary Rozenman, PhD (Moderator) SVP, Corporate Development and Strategy, Aimmune 3

4 Forward-Looking Statements This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, clinical development plans, anticipated milestones, product candidate benefits, potential market size, product adoption, market positioning, competitive strengths, product development, and other clinical, business and financial matters. Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially. Risks and uncertainties include, but are not limited to, our limited operating history, our need for additional financing to achieve our goals, our dependence on our lead product AR101, the need for additional clinical testing of AR101, uncertainties relating to the regulatory process, uncertainties relating to the timing and operation of clinical trials, potential safety issues, possible lack of market acceptance of our product candidates, the intense competition in the biopharmaceutical industry, our dependence on exclusive third-party suppliers and manufacturers, and limitations on intellectual property protection. A further list and description of these risks, uncertainties and other factors can be found in our report on Form 10-Q filed on November 07, Copies of this filing are available online at or Any forwardlooking statements made in this presentation speak only as of the date of the presentation. We do not undertake to update any forward-looking statements as a result of new information or future events or developments. 4

5 Aimmune Overview Stephen Dilly, MBBS, PhD Chief Executive Officer, Aimmune

6 Allergy & Immunology Experts Speaking Today Daniel Adelman, MD UCSF Aimmune Therapeutics Disclosures: Aimmune Therapeutics Employee Stephen Tilles, MD University of Washington Northwest Asthma and Allergy Center Disclosures: Consultant: Aimmune, DBV Technologies, Sanofi, Before Brands, DOTS Technology Clinical Research Principal Investigator: Aimmune, DBV Technologies, AnaptysBio, Astellas, Sanofi Ellen Sher, MD Allergy Partners of New Jersey Disclosures: Clinical Research Principal Investigator: Aimmune 6

7 AR101: Investigational Treatment for Peanut Allergy Oral biologic immunotherapy; first CODIT application Breakthrough Therapy Designation for peanut-allergic patients 4-17 years old Approximately 60% efficacy in Phase 2 on an intent-totreat basis for the Phase 3 endpoint of tolerating at least 600 mg of peanut protein (~ 2 peanuts) in the exit food challenge * In Phase 2, greater than 96% of treatment-related adverse events were mild, consistent with exposure to low levels of food allergen (itchy mouth, hives, GI intolerance); remaining 4% were moderate 7 *The primary endpoint of the PALISADE Phase 3 trial is the proportion of subjects who tolerate at least 600 mg of peanut protein in the U.S. and the proportion of subjects who tolerate at least 1,000 mg of peanut protein in the EU. Source: Bird JA et al. The Journal of Allergy and Clinical Immunology: In Practice. Published online: October 30, 2017

8 AR101 Phase 2 Data Supported Advancement into Phase 3 Trials This is the first randomized, placebocontrolled phase 2 peanut OIT study with entry and exit double-blind, placebocontrolled food challenges using a current good manufacturing practice (cgmp) manufactured characterized biologic drug product demonstrating clinical and immunomodulatory changes indicating desensitization. 8 Source: Bird JA et al. The Journal of Allergy and Clinical Immunology: In Practice. Published online: October 30, 2017

9 ARC001 Phase 2 Met Its Primary Efficacy Endpoint Percentage of Subjects Who Tolerated Specific Test Dose Levels Without Dose-Limiting Symptoms at 6-Month Exit Food Challenge 300 mg is ~ 1 peanut Intent-to-Treat (ITT) * n=29 active, n=26 placebo Completers n=23 active, n=26 placebo p < Single Highest Tolerated Dose: 19% p< % 0% 62% % 100% Placebo AR101 Placebo AR101 Placebo AR101 Placebo AR mg 600 mg p< Single Highest Tolerated Dose: 0% p < % 300 mg 600 mg 9 Defined as the proportion of subjects who were able to successfully consume a single dose of 300 mg of peanut protein with no dose-limiting symptoms at exit DBPCFC The six AR101 subjects who discontinued treatment before the exit Double-Blind Placebo-Controlled Food Challenge were considered nonresponders. Source: Bird JA et al. The Journal of Allergy and Clinical Immunology: In Practice. Published online: October 30, 2017

10 Three Key Parameters in Drug Development Product Protocol Patient Selection 10

11 The AR101 Production Process Our Florida plant can produce AR101 for peanut allergy for the global market Contains 20,000+ square feet of space and will handle full-scale cgmp (current Good Manufacturing Practices) commercial production of AR101 in anticipation of potential regulatory approvals In early 2018, the plant will have capacity to manufacture approximately 450 million capsules of AR101 per year (sufficient to treat ~0.5M patients p.a.) CMC is an Important, Often Neglected Aspect of Drug Development 11

12 AR101 Investigational Dosing Schedule: Based on Standardized Steps with the Flexibility to Personalize the Rate of Up-Dosing AR101 Investigational Treatment Protocol Up-Dosing Phase ~6 Months Ongoing Maintenance Initial Escalation 0.5 mg 6 mg 6 mg 3 mg Each Up-Dose is Conducted at the Allergist s Office 20 mg 12 mg 40 mg 80 mg 160 mg 120 mg 200 mg 240 mg 300 mg Calendar Pack for At-Home Dosing 300 mg Sachets for At-Home Daily Maintenance Dosing Begin with low dose (0.5 mg), first home dose is 3 mg (~1% of a peanut) Time between up-dosing is two weeks, or longer based on patient needs In-office up-dosing flexibility to accommodate patient medical needs and family schedules 12

13 Patient Selection: Exploring the Potential to Predict Patient Experience to Peanut Allergy Treatment with AR101 ARC001/ARC002 Retrospective Cohort Analysis Based on psige Proportion of subjects who tolerated 300 mg post ~6 months of up-dosing 96%* ITT 100% Completers Low / Moderate / High (<100 ku/l) 61% ITT 94% Completers Very High (>100 ku/l) n = 27 n = 28 Treatment-related Withdrawal 0 10 Failed Exit Challenge 0 1 Flexibility during up-dosing, e.g., drug hiatus, staying at the same dose, or down-dosing, may benefit these patients Mean Skin Prick Test at Entry 15 mm 13 mm Mean Tolerated Dose at Entry 20 mg 19 mg % of Peanut Allergic Patients across published data ~80% ~20% 13 Source: ARC001 and ARC002 Phase 2 data *One non-treatment related withdrawal in the <100 psige cohort

14 14 Drug Development Lessons Learned

15 Benefit and Risk Assessment Approval Lies in Demonstrating a Positive Relationship of Benefit and Risk Uncertainty Risk Uncertainty 1. Observed safety signals 2. What might have been missed (uncertainty) 3. Unintended consequences of treatment Benefit 1. Relevance of the endpoint to the disease 2. Reliability of data 3. Magnitude of observed effect 4. Consistency of effect 5. Speed of onset Does Treatment Make the Situation Better or Worse? 15

16 Benefit and Risk Assessment Approval Lies in Demonstrating a Positive Relationship of Benefit and Risk Uncertainty Risk Uncertainty 1. Observed safety events 2. What might have been missed (uncertainty) 3. Unintended consequences of treatment Benefit 1. Relevance of the endpoint to the disease 2. Reliability of data 3. Magnitude of observed effect 4. Consistency of effect 5. Speed of onset A Key Consideration in Peanut Allergy is the Potential Risk of False Sense of Security as Patients Who Believe They are Protected May be Less Vigilant 16

17 Benefit and Risk Assessment Approval Lies in Demonstrating a Positive Relationship of Benefit and Risk Uncertainty Risk Uncertainty 1. Observed safety signals 2. What might have been missed (uncertainty) 3. Unintended consequences of treatment Benefit 1. Relevance of the endpoint to the disease 2. Reliability of data 3. Magnitude of observed effect 4. Consistency of effect 5. Speed of onset A Robust and Reliable Treatment Effect is Important to the Assessment of an Acceptable Tolerability and Safety Profile 17

18 Understanding the Clinical Trial Endpoint: Tolerated Dose Double-Blind, Placebo-Controlled Food Challenge Is a Surrogate for Accidental Exposure Patients Receive Increasing Doses of Peanut Protein Every Minutes ENTRY React EXIT Tolerate React React React Milligrams of Peanut Protein React ,000 Tolerate Tolerate Tolerate Tolerate Tolerate Tolerate Tolerate Dose is Tolerated if Ingested with No Dose Limiting Symptoms 300 mg is ~ 1 peanut 600 mg is ~ 2 peanuts (e.g., approximately a child s bite of peanut butter sandwich) DBPCFC is done at trial entry and exit Subjectivity of symptom based endpoint requires strict blinding of assessing physician to treatment group. Given dose level is tolerated if patient successfully ingests it with no dose-limiting symptoms 18

19 Amount of Peanut Protein Triggering an Allergic Reaction in Real Life: Lessons from the MIRABEL Survey on Peanut Allergy Observational study conducted in France, Belgium and Luxemburg 70 allergists participated 785 patients of whom 85% were initially allergic 30% of patients reported severe or potentially severe allergic reactions For 238 allergic patients (36%), the allergist could estimate the amount of food triggering the allergic reaction The Eliciting Dose was 100 mg in ~57% of Patients (median eliciting dose 125 mg) 19 Source: Deschildre A, et al. Peanut-allergic patients in the MIRABEL survey: characteristics, allergists' dietary advice and lessons from real life. Clin Exp Allergy Apr;46(4):610-20

20 Understanding the Clinical Trial Endpoint: Tolerated Dose Double-Blind, Placebo-Controlled Food Challenge Is a Surrogate for Accidental Exposure ENTRY React EXIT Tolerate Average Accidental Exposure Level Triggering an Allergic Reaction * React React React Milligrams of Peanut Protein React Tolerate Tolerate Tolerate Tolerate Tolerate 1,000 Rigorous masking plan agreed with FDA prior to study start. Includes blinded assessor at each site Endpoint set to give safety margin above likely accidental exposure levels Primary Phase 3 Endpoint for U.S. is Tolerating 600 mg and for EU is 1,000 mg in the Exit Food Challenge, as Agreed with FDA and EMA 300 mg is ~ 1 peanut 600 mg is ~ 2 peanuts (e.g., approximately a child s bite of peanut butter sandwich) 20 *Deschildre A, et al. Peanut-allergic patients in the MIRABEL survey: characteristics, allergists' dietary advice and lessons from real life. Clin Exp Allergy Apr;46(4):610-20

21 Building the Right Team with the Right Mix Experienced Team of Drug Developers with 30+ NDAs, BLAs and MAAs Deep Domain Experience in Food Allergy 21

22 Collaborations Focused on Advancing the Field of Food Allergy $145M Strategic Equity Investment (Nov 2016) Two-year Working Collaboration Aimmune Retains Full Global Rights to All CODIT Pipeline Assets, Including AR101 Clinical Collaboration (Oct 2017) with Aimmune Regeneron/Sanofi Joint Development Committee Phase 2 of AR101 with adjunctive dupilumab expected to start in 2018 * Plan to explore sustained unresponsiveness in peanut allergy Building AR101 Value Pipeline Expansion Scientific Discovery and Innovation 22 *Regeneron will sponsor the trial, with Aimmune to provide clinical supply of AR101 and food challenge materials

23 Objectives for Today s Symposium 1. Articulate Aimmune s vision and strategy 2. Review AR101 Clinical Development Program 3. Gain insights on allergy practice in the community setting 4. Share market insights and commercial strategy in peanut allergy 5. Review anticipated milestones 23

24 Aimmune s AR101 Clinical Development Program Daniel Adelman, MD Chief Medical Officer, Aimmune

25 Topics for Today 1. PALISADE: AR101 Core Phase 3 efficacy trial 2. AR101 Phase 3 Program: Supporting trials; building safety database 3. AR101 Future Directions: Expand label to potentially include infants, toddlers and adults and explore sustained unresponsiveness 25

26 PALISADE Phase 3 Design Considerations (U.S.) 1. FDA requirement to show clinically meaningful difference Must demonstrate at least a 15 percent lower bound of the two-sided 95 percent confidence interval of the difference between AR101 and placebo The lower bound of the 95 percent confidence interval on the ARC001 Phase 2 Intent-to- Treat analysis of the 600 mg endpoint was 37 percent 2. Primary endpoint is the proportion of subjects who tolerate 600 mg without doselimiting symptoms after 6 months of maintenance at 300 mg/day Exceeds the average level of accidental exposure in real life None of the placebo patients in Phase 2 tolerated the 600 mg step Expect that a few placebo patients in Phase 3 may tolerate the 600 mg step 3. Blinding and masking plans to maintain trial integrity Including independent assessor at each study site to conduct the exit food challenge 26

27 1. FDA Requirement to Show Clinically Meaningful Difference Must demonstrate at least a 15 percent lower bound of the two-sided 95 percent confidence interval of the difference between AR101 and placebo 27

28 Demonstrating a Clinically Meaning Treatment Effect There is a clinically meaningful difference between the new treatment and the comparator based on the pre-specified delta 28 Source: Massie T. Statistical Criteria for Establishing Safety and Efficacy of Allergenic Products, Allergenic Products Advisory Committee May 2011

29 Understanding the Clinical Trial Endpoint: Tolerated Dose Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) ENTRY React EXIT Tolerate Average Accidental Exposure Level Triggering an Allergic Reaction * React React React Milligrams of Peanut Protein React Tolerate Tolerate Tolerate Tolerate 300 mg is ~ 1 peanut 600 mg is ~ 2 peanuts (e.g., approximately a child s bite of peanut butter sandwich) 1,000 Primary Phase 3 Endpoint for U.S. is Tolerating 600 mg and for EU is 1,000 mg in the Exit Food Challenge, as Agreed with FDA and EMA DBPCFC is done at trial entry and exit; independent assessor at each site DBPCFC patients are given increasing doses of peanut protein every minutes to measure their tolerated and reactive levels Given dose level is tolerated if patient successfully ingests it with no dose-limiting symptoms; allergist must be willing to give the patient the next higher challenge dose 29 *Deschildre A, et al. Peanut-allergic patients in the MIRABEL survey: characteristics, allergists' dietary advice and lessons from real life. Clin Exp Allergy Apr;46(4):610-20

30 ARC001 Phase 2 Met Its Primary Efficacy Endpoint Percentage of Subjects Who Tolerated Specific Test Dose Levels Without Dose-Limiting Symptoms at 6-Month Exit Food Challenge Single Highest Tolerated Dose: Intent-to-Treat (ITT) * n=29 active, n=26 placebo Difference between groups = 60% p< % CI: 34%, 87% 19% 79% Difference between groups = 62% p< % CI: 37%, 87% 0% 62% % p < % Placebo AR101 Placebo AR101 Placebo AR101 Placebo AR mg 600 mg Single Highest Tolerated Dose: Completers n=23 active, n=26 placebo 0% p < % 300 mg 600 mg 30 Defined as the proportion of subjects who were able to successfully consume a single dose of 300 mg of peanut protein with no dose-limiting symptoms at exit DBPCFC The six AR101 subjects who discontinued treatment before the exit DBPCFC were considered nonresponders. Source: Bird JA et al. The Journal of Allergy and Clinical Immunology: In Practice. Published online: October 30, 2017

31 1. FDA Requirement to Show Clinically Meaningful Difference Must demonstrate at least a 15 percent lower bound of the two-sided 95 percent confidence interval of the difference between AR101 and placebo The lower bound of the 95 percent confidence interval on the ARC001 Phase 2 Intent-to-Treat analysis of the 600 mg endpoint was 37 percent 31

32 2. Phase 3 Primary Endpoint The proportion of Subjects Who Tolerate 600 mg Without Dose-Limiting Symptoms After 6 Months of Maintenance at 300 mg/day Exceeds the average level of accidental exposure in real life None of the placebo patients in Phase 2 tolerated the 600 mg step Expect that a few placebo patients in Phase 3 may tolerate the 600 mg step 32

33 ARC001/002 Phase 2 Data After 6 Months of AR101 Therapy 6-Month Exit Food Challenge Conducted After Up-Dosing * Placebo 100% n=26 n=25 n=23 n=17 n=12 n=6 AR101 50% 0% Single Dose: 3 mg 10 mg 30 mg 100 mg 300 mg 600 mg Real World: 100% 50% n=44 n=44 n=44 n=44 n=44 n=42 Maximal Severity of Reported Symptoms Severe Moderate Mild None 300 mg is ~ 1 peanut 600 mg is ~ 2 peanuts (e.g., approximately a child s bite of peanut butter sandwich) 0% Single Dose: 3 mg 10 mg 30 mg 100 mg 300 mg 600 mg 33 *Includes placebo patients who crossed over to AR101 Burks W, et al. EAACI 2015; Bird A, et al. AAAAI 2016

34 ARC001/002 Phase 2: Safety and Tolerability Profile Promising 80% (44/55) of patients completed AR101 up-dosing 18% (10/55) withdrew during up-dosing due to gastrointestinal (GI) adverse events (AEs) Biopsy-confirmed EoE was seen in 1 subject (1.8%) All had peanut-specific IgE > 100 ku/l at baseline 95% at-home up-dosing adherence * >90% of treatment-related AEs were mild, consistent with exposure to low levels of food allergen (itchy mouth, hives, GI intolerance); rest were moderate Treatment-related AE rate decreased with time on therapy 1 AE per patient 30 days during up-dosing ** 1 AE per patient 574 days during maintenance 34 *Jones S, et al AAAAI 2017: ARC001 actives (N=29) and placebo (N=26); ** Bird A, et al AAAAI 2016: ARC002 placebo crossovers (N=26); Rachid R, et al EAACI 2016: ARC002 Part 2 low-dose extended maintenance (N=11)

35 3. Blinding and Masking Plans to Maintain Trial Integrity Double-blind, placebo-controlled food challenge (DBPCFC) Food challenge material taste masked Independent assessor at each study site to conduct the exit food challenge 35

36 Double-Blind, Placebo-Controlled Food Challenge and Reporting the Single Highest Tolerated Dose Diagnostic Eliciting Dose Reactive Dose Cumulative Reactive Dose Treatment Outcome Single Highest Tolerated Dose * DBPCFC steps (mg): * 1,000 ** Tolerated Doses Single Highest Tolerated Dose Reactive Dose This is not a tolerated dose 36 *Primary endpoint for PALISADE agreed with FDA **Primary endpoint for PALISADE agreed with EU regulatory authorities

37 PALISADE: Core Phase 3 Efficacy and Safety Trial of AR patients ages 4-49 enrolled (U.S., CAN, EU); Up-dosing complete, final study visits expected around year-end 2017 Up-Dosing ~6 Months Maintenance ~6 Months Primary efficacy analysis in 4-17 age group (90% of enrolled patients); adults analyzed separately Primary efficacy endpoint is the proportion of subjects who tolerate a single highest dose of at least 600 mg (U.S.) and 1,000 mg (EU) Entry DBPCFC Tolerate 30 mg AR101 3:1 Placebo 3 mg Daily dose at home Dose escalations in allergist office every 2 weeks 300 mg Daily 300 mg dose at home Exit DBPCFC Tolerate 600 mg Using an independent and blinded assessor for the entry and exit oral food challenges to maintain integrity of the blind Total treatment duration ~12 Months 37 PALISADE = Peanut ALlergy Oral Immunotherapy Study of AR101 for DEsensitization in Children and Adults DBPCFC = Double-Blind, Placebo-Controlled Food Challenge Tolerate = dose is successfully ingested with no dose-limiting symptoms

38 AR101 Phase 3 PALISADE Summary Largest and rigorously controlled clinical study of oral immunotherapy in medical history Greater than 90 percent powered to detect at least a 15 percent lower bound of the two-sided 95 percent confidence interval of the difference between AR101 and placebo Over-enrolled Demonstrated scalability, moving from eight KOL centers in Phase 2 to more than 70 international centers in Phase 3 with majority being community-based centers Independent Data Monitoring Committee reviewed unblinded safety data regularly throughout PALISADE and has consistently recommended continuing without protocol modifications Data readout expected in 1Q

39 Phase 3 Program Designed to Support Regulatory Submissions and to Position AR101 for Commercial Success Needed for BLA Submission RAMSES (ARC007) Phase 2 studies (ARC001 and ARC002) PALISADE (ARC003) Data cuts from: ARC004 and ARC008 ARTEMIS (ARC010) ARC005 (FPI fulfills PIP requirement) Needed for MAA Submission RAMSES * ARTEMIS 39 * Available safety data from RAMSES will be included in MAA

40 Exploring AR101 in Infants and Toddlers: ARC005 Trial in Peanut-Allergic Children Ages 6 to 48 Months International double-blind, placebo-controlled trial Entry food challenge is likely: reactive at or before 300 mg dose Two arms (placebo, AR101) Up-dosing to 300 mg and maintenance of at least one year blinded treatment before exit DBPCFC Opportunity to explore sustained unresponsiveness Expected to begin in

41 Exploring the Potential to Deplete Peanut-Specific T H 2A Cells T H 2A cells appear to be important components in the allergic response In a small pilot experiment, AR101 treatment was associated with a significant reduction of T H 2A cells in blood samples from a subset of peanut-allergic patients from ARC001 We are interested in exploring the potential to augment this observed AR101 activity with adjunctive use of other biologic immunomodulating agents Placebo Group n=3 AR101 Group n=4 41 Source: Wambre E, et al. Sci Transl Med Aug 2;9(401).

42 The Community Allergist and the Role of Professional Organizations Stephen Tilles, MD University of Washington Northwest Asthma and Allergy Center

43 Introduction and Practice Background Years in practice: 22 Location: Seattle, Washington Specialty: Single specialty Allergy/Immunology group practice 15 Board Certified allergists 1 NP 8 offices in Washington State Patients: Pediatric and adult Most food allergy patients are children Experience with OIT: Only in the context of the ongoing clinical research trials, no off label OIT Other Activities Executive Director of ASTHMA Inc. Clinical Research Center Immediate Past-President of the American College of Allergy, Asthma, and Immunology (ACAAI) FARE Clinical Advisory Board Executive Committee 43

44 Disclosure I am NOT speaking on behalf of either the ACAAI or FARE today, and examples I will use should not be assumed to be the position of the ACAAI or FARE 44

45 Topics for Today 1. History of and current practice of allergy in the community setting (U.S.) 2. Considerations for development of oral immunotherapy for treating food allergies 3. Role of professional societies 4. Future practice of allergy in the community setting (U.S.) 45

46 Allergies in the United States 2014 National Health Interview Survey - CDC Children under age % hay fever 10% respiratory allergies (asthma) 5.4% food allergies 11.6% skin allergies. 46

47 Current Practice of Allergy in the Community Setting (U.S.) ~5,500 allergists in the U.S. Dominated by single-specialty and multi-specialty group practices Therapeutic focus areas: Allergy and Asthma Subcutaneous immunotherapy (allergy shots) for environmental allergies Asthma therapy Food allergies Atopic dermatitis (eczema) Other (e.g. drug allergies, stinging insect allergies) Main business drivers today Subcutaneous immunotherapy compounded in labs within allergy practices Allergy skin testing 47

48 Focus of Allergy Specialists in U.S. Evolution of Unmet Needs and Availability of Innovative Treatments Environmental Allergies Asthma Food Allergies 1960 s 1980 s Limited safe and effective medications Immunotherapy (allergy shots) prescribed for majority Care centered around theophylline/bronchodilators Preventative medications had problematic side effects Uncommon 48

49 Focus of Allergy Specialists in U.S. Evolution of Unmet Needs and Availability of Innovative Treatments Environmental Allergies Asthma Food Allergies 1960 s 1980 s Limited safe and effective medications Immunotherapy (allergy shots) prescribed for majority 1990 s Non-sedating antihistamines (Seldane, Claritin, Zyrtec) Nasal steroids (Flonase, Beconase) Allergy shots still going strong Care centered around theophylline/bronchodilators Preventative medications had problematic side effects Need to control underlying inflammation better understood High potency inhaled steroids (Flovent, Pulmicort); long-acting beta agonists (Serevent) Uncommon Increasing incidence, but still considered not common 49

50 Focus of Allergy Specialists in U.S. Evolution of Unmet Needs and Availability of Innovative Treatments Environmental Allergies Asthma Food Allergies 1960 s 1980 s Limited safe and effective medications Immunotherapy (allergy shots) prescribed for majority 1990 s Non-sedating antihistamines (Seldane, Claritin, Zyrtec) Nasal steroids (Flonase, Beconase) Allergy shots still going strong 2000 s Fewer patients opting for allergy shots (safe and effective medications appropriately used) Care centered around theophylline/bronchodilators Preventative medications had problematic side effects Need to control underlying inflammation better understood High potency inhaled steroids (Flovent, Pulmicort); long-acting beta agonists (Serevent) Unmet need being better addressed (Advair, Symbicort) Uncontrolled asthma smaller niche but target of intense drug development First biologic for asthma (omalizumab) not initially targeted to allergists Uncommon Increasing incidence, but still considered not common Incidence and prevalence rising rapidly Therapeutics development not keeping up with unmet needs 50

51 Focus of Allergy Specialists in U.S. Evolution of Unmet Needs and Availability of Innovative Treatments: 2010 s Environmental Allergies First wave of innovative medications now generic; often prescribed by primary care providers Allergy shots continuing to shrink; remains an important option for severe allergies Orally dissolvable tablets will be increasingly prescribed, shifting management of allergic rhinitis towards primary care providers 51

52 Focus of Allergy Specialists in U.S. Evolution of Unmet Needs and Availability of Innovative Treatments: 2010 s Environmental Allergies First wave of innovative medications now generic; often prescribed by primary care providers Allergy shots continuing to shrink; remains an important option for severe allergies Orally dissolvable tablets will be increasingly prescribed, shifting management of allergic rhinitis towards primary care providers Asthma Effective medications widely available Multiple protein biologics, many of which are now being developed for other allergic disease indications (e.g., IL-5, IL-4/IL-13 inhibitors) 52

53 Focus of Allergy Specialists in U.S. Evolution of Unmet Needs and Availability of Innovative Treatments: 2010 s Environmental Allergies Asthma Food Allergies First wave of innovative medications now generic; often prescribed by primary care providers Allergy shots continuing to shrink; remains an important option for severe allergies Orally dissolvable tablets will be increasingly prescribed, shifting management of allergic rhinitis towards primary care providers Effective medications widely available Multiple protein biologics, many of which are now being developed for other allergic disease indications (e.g., IL-5, IL-4/IL-13 inhibitors) Unmet medical need growing Still no FDA approved therapies Children disproportionately affected 53

54 Focus of Allergy Specialists in U.S. Evolution of Unmet Needs and Availability of Innovative Treatments: 2010 s Environmental Allergies Asthma Food Allergies First wave of innovative medications now generic; often prescribed by primary care providers Managed Care Maturing High deductibles, high co-pay Allergy shots continuing to shrink; remains an important option for severe allergies Orally dissolvable tablets will be increasingly prescribed, shifting management of allergic rhinitis towards primary care providers Effective medications widely available Multiple protein biologics, many of which are now being developed for other allergic disease indications (e.g., IL-5, IL-4/IL-13 inhibitors) Unmet medical need growing Still no FDA approved therapies Children disproportionately affected Medication prices now felt by individual patients; subject of regular discussion with providers 54

55 Overview of Allergen Immunotherapy Respiratory Allergies SCIT (subcutaneous - shots) pollens, cat, dog, dust mite, etc. SLIT (sublingual) FDA approved only for grass pollen, ragweed, and dust mite Food Allergies OIT (oral immunotherapy) peanut in FDA Phase 3 EPIT (epicutaneous - patch) peanut in FDA Phase 3 SCIT (subcutaneous - shots) peanut FDA Phase 1 55

56 Oral Immunotherapy Works in a Variety of Food Allergies Study / Literature Source Allergen Jones (2009) 100% of completers achieved clinical desensitization Meglio (2004) 71% of patients fully desensitized after 6 months Burks (2012) 75% of children desensitized after 6 months Scurlock (2016) 5g increase in tolerated amount of walnut after 38 weeks 56

57 Oral Immunotherapy Has Most Extensively Been Studied in Peanut Allergy 30+ clinical trials, mostly Phase 1 and Phase 2 57 Source: Wood, RA J. Investig Allergol Clin Immunol 2017; Vol. 27(3):

58 The Evolution of Oral Immunotherapy (OIT) Historical Observations High variability in OIT dosing regimens and protocols For peanut-allergic patients, the taste of peanut can cause aversion, reducing compliance * Acceptable safety profile, but side effects (mostly GI) contribute to a ~20% dropout rate Suggestions that long-term benefit can be achieved Current Questions What is the right protocol? How can we maximize tolerability and patient compliance? Can biomarkers predict treatment experience? Can OIT induce tolerance? 58 Sources: *Schneider (2013), Yee (2016)

59 Considerations for the Development of Oral Immunotherapy (OIT) 2015 AAAAI survey * showed that nearly 90% of allergists did not participate in using OIT, but 75% would if there were an FDA-approved therapy Considerations for broad adoption of OIT An FDA-approved drug supported by large, well designed and adequately controlled Phase 3 trials (i.e., demonstrated to be safe and effective) If OIT logistically complex, must lend itself to systematic approach Drug readily available and easy to use by the office staff and by patients Flexibility to tailor dosing regimen based on individual needs (updosing, downdosing, etc.) Reimbursement for supporting medical services (physician) Reimbursement for drug (patient) Practice management support 59 *Greenhawt, MH and Vickery, BP (2015) J Allergy Clin Immunol Pract

60 Role of Professional Societies AAAAI and ACAAI in the U.S. / EAACI in Europe Supporting allergists and allied health professionals Practice management Advocacy Updating practice parameters Supporting patients Supporting newly approved therapies Educating physicians (e.g. ACAAI toolkits ; CME programs) Coding Working with payers 60

61 American College of Allergy, Asthma, and Immunology (ACAAI) Helps Its Members with Practice Management 61 Source:

62 American College of Allergy, Asthma, and Immunology (ACAAI) Provides Toolkits Related to Practice Management 62 Source:

63 Case Study: Immunotherapy Shared Decision-making Toolkit In response to FDA approval of sublingual immunotherapy products Includes a primer on the overall treatment of respiratory allergies Allergen avoidance Medications Immunotherapy SCIT SLIT Online decision-making tool to help patients decide which therapy is best 63

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66 Future Practice of Allergy in the Community Setting (U.S.) Practice of allergy is under stress Reimbursement for routine care declining Sublingual immunotherapy competition with subcutaneous immunotherapy Management of AR shifting increasingly to primary care setting Creates need for new business models New Business Models and Capacity for New Therapeutic Offerings Will Drive the Future of Allergy Practice in the U.S. Capacity to introduce novel biologics Omalizumab, dupilumab, mepolizumab, reslizumab, benralizumab, etc. AR101 alone and with adjunctive investigational agents if approved by FDA 66

67 Treating Peanut Allergy: Perspectives from a Current Principal Investigator of Oral Immunotherapy Ellen Sher, MD Allergy Partners of New Jersey Drexel University College of Medicine

68 Introduction and Practice Background Years in practice: 23 Location: New Jersey Specialty: Single specialty group practice; 135 allergists, 75 offices, 23 states All aspects of allergic and immunologic diseases: asthma, rhinitis, food allergy, immune deficiency, sinus disease, urticaria, atopic dermatitis, contact dermatitis, insect and drug allergies Patients: Pediatric and adult Most food allergy patients are children Experience with OIT: only in the context of the ongoing AR101 trials, no off label OIT Other Activities: Assistant Clinical Professor at Drexel University College of Medicine Past president of NJ Allergy & Immunology Society Member of multiple AAAAI and ACAAI Committees 68

69 Topics for Today 1. Peanut allergy: the burden and risk of avoidance 2. What do patients and physicians want from a treatment for peanut allergy? 3. Planning for future potential FDA-approved oral immunotherapy 69

70 Up to 15 million Americans have Food Allergies 5.9 M children < 18 years of age One out of every 13 children Two children in every classroom Prevalence has increased by 50% between Every 3 minutes, a food allergy reaction sends someone to the ER 200,000 people per year visit ER About 30% of children with food allergies have multiple food allergies Caring for children with food allergies costs nearly $25 billion annually 70 Sources: National Institute of Allergy and Infectious Diseases, National Institutes of Health. Report of the NIH Expert Panel on Food Allergy Research Retrieved from United States Census Bureau Quick Facts (2015 estimates); Gupta RS, et al. Pediatrics 2011; 128(1):e9-17; Gupta R, et al. JAMA Pediatr Nov; 167(11): Clark S, et al. J Allergy Clin Immunol. 2011; 127(3):

71 Approximately 3 Million Americans Have Peanut Allergy The prevalence of childhood peanut or tree nut allergy appears to have more than tripled between 1997 and 2008 Peanut allergy develops early in life and is rarely outgrown 71 Source: Sicherer SH, et al. J Allergy Clin Immunol 2010;125:1322-6;

72 Peanuts Have Been a Popular Source of Nutrition and Flavor Readily available Palatable High protein Cheap 72

73 73 Now People Are Afraid of Peanuts

74 Avoiding Peanuts Is Not as Easy as It Seems Peanut Protein Can Appear in Unexpected Places One Accident Can be Fatal 74

75 Tolerated Peanut Protein Dose Level of Sensitivity to Peanut Protein Varies Baseline Sensitivity Desensitization Period Maintenance Therapy ~ Safety Buffer ~0.3 Time Patients Need a Reliable Margin of Protection from Allergic Reactions Because Some Days the Amount of Tolerated Peanut Protein Is Lower Than Others 75

76 Managing Peanut Allergy Affects All Aspects of Daily Life In Real Life, the Amount of Peanut Protein Triggering an Allergic Reaction May be 100 mg (~1/3 a peanut) in More than Half the Cases * 76 *Deschildre A, et al. Peanut-allergic patients in the MIRABEL survey: characteristics, allergists' dietary advice and lessons from real life. Clin Exp Allergy Apr;46(4):610-20

77 Impact of Peanut Allergy on Quality of Life MyFoodAllergyTeam (a free social network) conducted a 15-minute online survey sent to caregivers of peanut allergy patients aged 1-17 N=67 Social Media User from MyFoodAllergy Team members + Facebook + No Nuts Moms The survey was live from September 8 to September 22,

78 Peanut Allergy Has a Negative Impact on Quality of Life (N=67) 6% 5% 3% 10% 8% 21% Strongly Disagree 34% 13% 19% 46% 49% 29% 24% 49% 27% 13% 22% 13% 5% 3% Strongly Agree Hard to attend social events Interferes w/ quality of life overall Disrupts education Unable to have open conversations w/ doctor 78 Survey Question: For each of the following statements, please indicate how much you agree or disagree that peanut allergies (impact attending social events, education/school, quality of life overall or unable to have open and meaningful conversations with treating doctor).

79 Which Patients Would I Treat with an Approved OIT? Key Learnings from AR101 Clinical Trial Experience Our clinical research site is participating in PALISADE, ARC004 and RAMSES Major factors driving patient and parent interest Fear Desire for normalcy Quality of Life Key learnings from patient experience on the trial Requires a significant investment of time and commitment Similar to allergy shots Worth the effort if successful 79

80 Planning for an Approved Oral Immunotherapy (OIT) At Allergy Partners of NJ, allergy shots are the main business driver today Major focus on preparing the practice for an approved OIT Experience with managing patients through allergy shots is highly applicable Practice modifications to implement OIT include adding a Nurse Practitioner, rooms and billing/front desk support 80

81 AR101 Practice Flow Is Similar to Widely-Used Allergy Shots Practice Flow Allergy Shots AR101 Check-in / Check-out Dosing 10 mins 10 mins Monitoring 30 mins mins HCP time per visit 10 mins / patient Visit frequency during up-dosing Once every 1-2 weeks Once every 2 weeks Total up-dosing duration 3-6 months 6 months Visit frequency during chronic maintenance Once every ~4 weeks TBD 81 Source: AAAAI, current AR101 treatment protocol

82 AR101 Practice Flow: Six Patients Up-Dosed per 3-Hour Session Check-in Dosing Monitoring Check-out #1 5 mins per patient 10 mins per patient mins per patient 5 mins per patient 1 : 1 1 : 1 1 : 1 Common waiting area #6 6 patients Each spends < 2 hours 1 doctor 1 hour for all 6 patients 1-2 nurses ~2.5 hours for all 6 patients 82

83 Potentially a Third Wave of Therapies for Allergists to Own Immunotherapy Shots for Aeroallergens Potent Inhaled Steroids and Biologics for Asthma Oral Immunotherapy with FDA- Approved Drugs 83

84 Preparing for Potential Commercialization of AR101 Jeff Knapp Chief Operating Officer, Aimmune

85 Currently, There Are ~1M Peanut Allergic Patients (4-17) Diagnosed in the U.S PA Patient Snapshot 1.6M Prevalent Population +600K Unknown patients; not actively being managed by a HCP 1M / 1.6M equates to ~60% of peanut allergic patients already diagnosed, despite the absence of standardized therapies +300K Diagnosed and wholly managed by Pediatricians 1M Total PA Patients +300K 400K Diagnosed by Pediatrician; Managed by Allergist Diagnosed AND managed by Allergist Majority (70%) of the diagnosed peanut allergic patients are seen by an Allergist Aimmune s target audience 85 Source: Symphony Health Patient Claims (Jan 2011-Jun 2017)

86 Of the 1M U.S. Peanut Allergic Patients Diagnosed, AR101 Has the Potential to Capture Meaningful Market Share 30% Diagnosed and Managed by Pediatricians (top 4% manage 40% of patients) 70% Diagnosed and/or Managed by Allergists 1.6 Million Potential Patients age 4-17 ~1 million clinically managed today Potential Future Referrals to Allergists AR101 AR101 Would Fit Well Into Current Allergy Practice AR101 is the Only Phase 3 Therapy in Development for Ages % 30% Ages 4-11 Ages Expected Drivers of Patient Motivation to Seek AR101 Therapy Reaction History Anxiety Family Support Access to an Allergist 86 Source: Symphony claims data,

87 High Unmet Need for Desensitization to Peanuts Based on U.S. Patient Claims Data 1M Total Diagnosed Peanut Allergy (PA) Patients (Age 4 to 17) 1M First Experience With PA Can Be Very Traumatic Almost one in five* diagnosed PA pts learned about their condition via an anaphylactic event that resulted in a trip to the ER 17.5% 175K Accidental Exposure Resulting In ER or HCP Visit About one-third* of pts experienced anaphylaxis after they had already been made aware of their condition 30% 300K 87 *Average 3-year observation period Source: Symphony Health Patient Claims (Jan 2011-Jun 2017); anaphylaxis codes: , T78.01XX, L50, L50.1, L50.3 L50.8, L50.9, T78.3, 708.0, 708.1, 708.3, 708.8, 708.9, 995.1

88 AR101 Has the Potential to Address Key Unmet Needs and to Change the Treatment Paradigm for Peanut Allergy Unmet Need Lack of treatment options High risk of potentially life-threatening reaction High impact on parent / patient quality of life Likelihood to Prescribe Likelihood to prescribe AR101 was 6.1 on a scale of 1 to 7 (n=30) Value proposition based on Phase 2 data compelling, primarily as a safety net against severe reactions due to accidental exposure Homebrew OIT Pain Points Allergists offering homebrew OIT today believe, if approved, AR101 will address most of their pain points The need for an FDA approved product The need for a standardized product and a well tested, consistent protocol Limited and unpredictable reimbursement 88 Sources: Aimmune Market Research 2017

89 Allergists are the Ideal Specialty to Own AR Allergists have resources and training to optimally treat food allergic patients 2. Patients with food allergies are generally followed by an allergist 3. Allergists have a strong desire to treat their patients with food allergies 4. Allergists are losing some patient populations to other specialties such as pediatricians Patients will call us once the word is out. We won t have to call the patients. These patients only come in once a year now. They will have more office visits with this program. Also, I may attract new patients if I offer this. If I m not offering it, I m at a disadvantage as other Allergists will. 89 Source: Aimmune Physician and Practice Manager Market Research 2017

90 If Approved, AR101 Can Be Integrated into Allergy Offices with Existing Available Capacity and Will Be Further Optimized Over Time Seamless Integration High Patient Capacity Logistics: If approved, practice management with AR101 should be similar to allergy shots, which represents ~30% of their business Additive: Allergists surveyed believe their practices today have the capacity to meet the future unmet need of peanut allergic patients seeking AR101 At peak 3,000 unique Allergy offices each able to up-dose ~50 patients per year = 150,000 patients At launch, Aimmune will initially target larger group Allergy practices, representing ~70% of offices New Patient Starts per 6-Month Period 3 patients per day 4 days per week for 2 weeks 24 patients total Repeat 6 months later ~50 patients per year 90 Sources: Aimmune Market Research 2017

91 AR101 Investigational Dosing Schedule: Based on Standardized Steps with the Flexibility to Personalize the Rate of Up-Dosing AR101 Investigational Treatment Protocol Up-Dosing Phase ~6 Months Ongoing Maintenance Initial Escalation 0.5 mg 6 mg 6 mg 3 mg Each Up-Dose is Conducted at the Allergist s Office 20 mg 12 mg 40 mg 80 mg 160 mg 120 mg 200 mg 240 mg 300 mg Calendar Pack for At-Home Dosing 300 mg Sachets for At-Home Daily Maintenance Dosing Begin with low dose (0.5 mg), first home dose is 3 mg (~1% of a peanut) Time between up-dosing is two weeks, or longer based on patient needs In-office up-dosing flexibility to accommodate patient medical needs and family schedules 91

92 Access to AR101 Throughout Treatment is Intended to be Seamless to Support a Positive Patient Experience Peanut Allergy Diagnoses & Treatment Decision Initial Day Escalation (in office) Day 1 Level 1 (in office) Days 2-14 Level 1 (at home) Maintenance 30 Day Supply (at home) Repeat through Level 11 AR101 Patient Support Services Many industry standard Initiation Support Benefits investigation PA processed Financial counseling Starter program Ongoing Support Logistics coordination with patient and office Refill reminders and messaging Adherence and compliance support Out-of-pocket support 92

93 Some Existing Reimbursement Codes Used Today but New Code(s) May Simplify AR101 Learning Curve For HCPs and Payers Today: Existing codes provide adequate reimbursement according to some home-brew OIT offices Home-brew OIT Initial Diagnosis Standard office visit code (992xx) Up-dosing involves a combination of one or more allergy immunotherapy codes: Rapid desensitization code (95180) Oral food challenge codes (95076) Standard office visit code (992xx) Potential Future: Oral immunotherapy code specification for up-dosing could simplify reimbursement AR101 Initial Diagnosis Standard office visit code (992xx) Up-dosing could be reduced to one time bound code Requires support from societies (ACAAI & AAAAI) 93 Source: Aimmune Physician and Practice Manager Market Research 2017

94 U.S. Payer Reimbursement Outlook for AR101 Appears Favorable Payer Management of Peanut Allergy Expected to be Low Payers Likely to Cover AR101 Given Promising Value and High Unmet Need Payers Expected to Require a Standard Prior Auth. for AR101 Not surprisingly, ~90% of payers surveyed exert low or no effort in managing food and peanut allergy today Management not expected to increase significantly in near term given low spend vs. other therapeutic areas In recent ad board, 10/10 payers indicated they expect to add AR101, if approved, to formulary (tier variable) based on: promising clinical value pediatric indication lack of alternatives In blinded research, 90% of payers expect to require a standard annual Prior Authorization (PA) for AR101 PA criteria may include prescription by an allergist and confirmed documented diagnosis of peanut allergy 94 Sources: Payer Online Market Research (n=30), Aug 2017; Payer Advisory Board (n=10), Oct 2017

95 Preparing for AR101 s Potential Launch (est. 2019) Partner with Allergy Community Engage stakeholders Allergists (KOLs, Community) Allied Health Care Professionals Pediatricians (for referrals) Create successful collaborations Support professional societies (ACAAI, AAAAI, EAACI, etc.) Understand patient and caregiver needs & perspectives Advocacy organizations Patient & caregiver groups Launch Preparation AR101 positioning underway Publication strategy and execution Commercial packaging finalized Build optimal field teams at the right time Medical Science Liaisons Nurse educators Account Mgmt (e.g. payers) Sales force of <100 Understand payer perspectives and define pricing/reimbursement strategy Advisory boards and market research Develop resources to optimize treatment capacity within allergy offices 95

96 Summary - Commercial Outlook for AR101 Very large peanut allergic population with no existing treatment options Majority of existing peanut allergic patients are seen by Allergists Allergists are well equipped to treat peanut allergic patients with AR101 High likelihood to prescribe AR101 based on existing data/profile Allergists are eager to own something other specialties are not equipped to utilize Allergists have capacity to incorporate AR101 patients. This will be an additive source of patient volume Administration of allergy shots is similar to the OIT process & the adoption of AR101 is a natural progression Aimmune will be ready to execute a successful launch! 96

97 Looking Ahead: Anticipated Milestones Ongoing Phase 3 Trials with AR101 Core PALISADE Phase 3 trial Final study visits expected around year-end 2017 Topline data expected 1Q 2018 BLA submission planned for late 2018, followed by MAA submission ARC004 trial (PALISADE roll-over) Data-cut in 3Q 2018 to support BLA/MAA RAMSES real-world trial (U.S.) Enrollment to complete around year-end 2017 Data available in 2H 2018 Upcoming Trials and Programs ARC005 trial of AR101 in infants and toddlers Initiate in 2018 AR101 and Adjunctive Dupilumab Initiate Phase 2 trial in 2018 (Regeneron/Sanofi) Egg allergy program Investigational New Drug application in 2018 Walnut allergy program Investigational New Drug application in 2019 ARTEMIS (EU) Enrollment complete late 2017/early 2018 Data available in 2H

98 Q&A with Speaker Panel Moderator: Mary Rozenman, PhD SVP, Corporate Development & Strategy, Aimmune

99 Thank you.