Investor Symposium on Peanut Allergy Treatment - December 1, 2017 - Aimmune Therapeutics

 
Investor Symposium on Peanut Allergy Treatment - December 1, 2017 - Aimmune Therapeutics
Investor Symposium on      December 1, 2017
Peanut Allergy Treatment
Investor Symposium on Peanut Allergy Treatment - December 1, 2017 - Aimmune Therapeutics
Welcome

Laura Hansen, PhD
VP, Investor Relations, Aimmune
Investor Symposium on Peanut Allergy Treatment - December 1, 2017 - Aimmune Therapeutics
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           Daniel Adelman, MD
                for the Treatment of Peanut Allergy                    Chief Medical Officer, Aimmune

    8:45 a.m.   The Community Allergist and the                        Stephen Tilles, MD
                Role of Professional Organizations                     University of Washington
                                                                       Northwest Asthma and Allergy Center
    9:00 a.m.   Treating Peanut Allergy: Perspectives from a Current   Ellen Sher, MD
                Principal Investigator of Oral Immunotherapy           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

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Investor Symposium on Peanut Allergy Treatment - December 1, 2017 - Aimmune Therapeutics
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, 2017. Copies of this filing are available online at www.sec.gov or www.aimmune.com. Any forward-
    looking 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
Investor Symposium on Peanut Allergy Treatment - December 1, 2017 - Aimmune Therapeutics
Aimmune Overview

Stephen Dilly, MBBS, PhD
Chief Executive Officer, Aimmune
Investor Symposium on Peanut Allergy Treatment - December 1, 2017 - Aimmune Therapeutics
Allergy & Immunology Experts Speaking Today

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

6
Investor Symposium on Peanut Allergy Treatment - December 1, 2017 - Aimmune Therapeutics
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-to-
                                                                                  treat 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

    *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.
7   Source: Bird JA et al. The Journal of Allergy and Clinical Immunology: In Practice. Published online: October 30, 2017
Investor Symposium on Peanut Allergy Treatment - December 1, 2017 - Aimmune Therapeutics
AR101 Phase 2 Data Supported Advancement into Phase 3 Trials

                                                                                                            This is the first randomized, placebo-
                                                                                                          controlled phase 2 peanut OIT study with
                                                                                                             entry and exit double-blind, placebo-
                                                                                                              controlled 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
Investor Symposium on Peanut Allergy Treatment - December 1, 2017 - Aimmune Therapeutics
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)*                                                                          Completers
                     n=29 active, n=26 placebo                                                                       n=23 active, n=26 placebo
                                                                                                                                          p < 0.0001
                       100                                                                                             100

                                          p
Investor Symposium on Peanut Allergy Treatment - December 1, 2017 - Aimmune Therapeutics
Three Key Parameters in Drug Development

                                                 Patient
                Product         Protocol
                                                Selection

10
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
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

                                     Each Up-Dose is                          300 mg
                                     Conducted at the                240 mg
                                     Allergist’s Office         200 mg                      300 mg Sachets for At-Home
                                                            160 mg                           Daily Maintenance Dosing
                                                       120 mg
                                                    80 mg
                                                40 mg
                     Initial                20 mg
                   Escalation           12 mg
                           6 mg      6 mg
                                  3 mg                      Calendar Pack for
                  0.5 mg
                                                            At-Home 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
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                       96%*                100%                       94%       Flexibility during
           ~6 months of up-dosing                                                          61%
                                                                                                                       up-dosing,
                                                            ITT             Completers     ITT         Completers   e.g., drug hiatus,
                                                                                                                      staying at the
                                        Low / Moderate / High (100 kU/L)
                                                                                                                     same dose, or
                                                                      n = 27                     n = 28               down-dosing,
          Treatment-related Withdrawal                                  0                         10
                                                                                                                       may benefit
                                                                                                                     these patients
          Failed Exit Challenge                                         0                          1

          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%

     Source: ARC001 and ARC002 Phase 2 data
13   *One non-treatment related withdrawal in the
Drug Development Lessons Learned

14
Benefit and Risk Assessment

     Approval Lies in Demonstrating a Positive Relationship of Benefit and Risk Uncertainty

           Risk Uncertainty                                       Benefit
           1. Observed safety signals                             1. Relevance of the
           2. What might have been                                   endpoint to the disease
              missed (uncertainty)                                2. Reliability of data
           3. Unintended                                          3. Magnitude of
              consequences                                           observed effect
              of treatment                                        4. Consistency of effect
                                                                  5. Speed of onset

                      Does Treatment Make the Situation Better or Worse?

15
Benefit and Risk Assessment

     Approval Lies in Demonstrating a Positive Relationship of Benefit and Risk Uncertainty

           Risk Uncertainty                                       Benefit
           1. Observed safety events                              1. Relevance of the
           2. What might have been                                   endpoint to the disease
              missed (uncertainty)                                2. Reliability of data
           3. Unintended                                          3. Magnitude of
              consequences                                           observed effect
              of treatment                                        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
Benefit and Risk Assessment

     Approval Lies in Demonstrating a Positive Relationship of Benefit and Risk Uncertainty

           Risk Uncertainty                                       Benefit
           1. Observed safety signals                             1. Relevance of the
           2. What might have been                                   endpoint to the disease
              missed (uncertainty)                                2. Reliability of data
           3. Unintended                                          3. Magnitude of
              consequences                                           observed effect
              of treatment                                        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
Understanding the Clinical Trial Endpoint: Tolerated Dose

      Double-Blind, Placebo-Controlled Food Challenge Is a Surrogate for Accidental Exposure

                                                                                                                             • DBPCFC is done at trial
             Patients Receive Increasing Doses of Peanut Protein Every 20-30 Minutes
                                                                                                                               entry and exit

            ENTRY                                                                                                            • Subjectivity of symptom
                                  3             10              30             100
            React                                                                                                              based endpoint requires
                              React            React          React           React                                            strict blinding of
                               Milligrams of Peanut Protein                                                                    assessing physician to
            EXIT                                                                                                               treatment group.
                                  3             10              30             100           300        600       1,000
            Tolerate
                                                                                                                             • Given dose level is
                             Tolerate       Tolerate        Tolerate        Tolerate        Tolerate   Tolerate   Tolerate
                                                                                                                               tolerated if patient
                      Dose is ‘Tolerated’ if Ingested with No Dose Limiting Symptoms                                           successfully ingests it
                                                                                                                               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)

18
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)

     Source: Deschildre A, et al. Peanut-allergic patients in the MIRABEL survey: characteristics, allergists' dietary advice and lessons from real life. Clin Exp Allergy.
19   2016 Apr;46(4):610-20
Understanding the Clinical Trial Endpoint: Tolerated Dose

      Double-Blind, Placebo-Controlled Food Challenge Is a Surrogate for Accidental Exposure

                                                                                                                                                             • Rigorous ‘masking plan’
                  Average Accidental Exposure Level Triggering an Allergic Reaction*
                                                                                                                                                               agreed with FDA prior to
            ENTRY                                                                                                                                              study start. Includes
            React
                                  3              10              30             100                                                                            blinded ‘assessor’ at
                               React           React           React           React                                                                           each site
                               Milligrams of Peanut Protein
                                                                                                                                                             • Endpoint set to give
            EXIT
                                  3              10              30             100             300             600            1,000                           ‘safety margin’ above
            Tolerate
                                                                                                                                                               likely accidental
                             Tolerate        Tolerate        Tolerate        Tolerate         Tolerate
                                                                                                                                                               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)

      *Deschildre A, et al. Peanut-allergic patients in the MIRABEL survey: characteristics, allergists' dietary advice and lessons from real life. Clin Exp Allergy. 2016
20     Apr;46(4):610-20
Building the Right Team with the Right Mix

       Experienced
       Team of Drug
                                                  Deep Domain
        Developers
         with 30+                                 Experience in
       NDAs, BLAs                                 Food Allergy
        and MAAs

21
Collaborations Focused on Advancing the Field of Food Allergy

                 • $145M Strategic Equity Investment                                                        • Clinical Collaboration (Oct 2017)
                   (Nov 2016)                                                                                 with Aimmune–Regeneron/Sanofi
                                                                                                              Joint Development Committee
                 • Two-year Working Collaboration
                                                                                                            • Phase 2 of AR101 with adjunctive
                 • Aimmune Retains Full Global Rights
                                                                                                              dupilumab expected to start in 2018*
                   to All CODIT™ Pipeline Assets,
                   Including AR101                                                                          • Plan to explore sustained
                                                                                                              unresponsiveness in peanut allergy

                                                                                                                               Scientific Discovery
              Building AR101 Value                                               Pipeline Expansion
                                                                                                                                 and Innovation

22   *Regeneron will sponsor the trial, with Aimmune to provide clinical supply of AR101 and food challenge materials
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
Aimmune’s AR101 Clinical Development Program

Daniel Adelman, MD
Chief Medical Officer, Aimmune
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
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 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
     3. Blinding and masking plans to maintain trial integrity
       – Including independent assessor at each study site to conduct the exit food challenge
26
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
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
Understanding the Clinical Trial Endpoint: Tolerated Dose

      Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)

                                                                                                                                                              • DBPCFC is done at trial
                  Average Accidental Exposure Level Triggering an Allergic Reaction*                                                                            entry and exit; independent
                                                                                                                                                                assessor at each site
           ENTRY
                                  3              10              30              100                                                                          • DBPCFC patients are given
           React
                               React           React           React            React                                                                           increasing doses of peanut
                                Milligrams of Peanut Protein                                                                                                    protein every 20-30 minutes
                                                                                                                                                                to measure their tolerated
           EXIT                                                                                                                                                 and reactive levels
                                  3              10              30             100             300              600            1,000
           Tolerate
                             Tolerate        Tolerate         Tolerate       Tolerate
                                                                                                                                                              • Given dose level is
                                                                                                                                                                tolerated if patient
                                                         Primary Phase 3 Endpoint for U.S. is Tolerating                                                        successfully ingests it with
                                                         600 mg and for EU is 1,000 mg in the Exit Food                                                         no dose-limiting symptoms;
                                                            Challenge, as Agreed with FDA and EMA                                                               allergist must be willing to
                                                                                                                                                                give the patient the next
     300 mg is ~ 1 peanut                                                                                                                                       higher challenge dose
     600 mg is ~ 2 peanuts (e.g., approximately a child’s bite of peanut butter sandwich)

      *Deschildre A, et al. Peanut-allergic patients in the MIRABEL survey: characteristics, allergists' dietary advice and lessons from real life. Clin Exp Allergy.
29    2016 Apr;46(4):610-20
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

                      Intent-to-Treat (ITT)*                                                                           Completers
                      n=29 active, n=26 placebo                                                                        n=23 active, n=26 placebo
                                 Difference
                                 between groups =
                                 60%                                                                                                         p < 0.0001
                        100                                  Difference between                                           100
                                 p
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
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
ARC001/002 Phase 2 Data After 6 Months of AR101 Therapy
     6-Month Exit Food Challenge Conducted After Up-Dosing*

                                                             n=26   n=25    n=23     n=17     n=12     n=6
                           Placebo
                                                  100%

                                                    50%                                                           Maximal Severity
                                                                                                                    of Reported
                                                     0%                                                             Symptoms
                                       Single Dose:          3 mg   10 mg   30 mg   100 mg   300 mg   600 mg            Severe
                                                                                                                        Moderate

                                         Real World:                                                                    Mild
                                                                                                                        None
                                                             n=44   n=44    n=44     n=44     n=44     n=42
                           AR101                  100%
                                                                                                               300 mg is ~ 1 peanut
                                                                                                               600 mg is ~ 2 peanuts (e.g.,
                                                                                                               approximately a child’s bite of
                                                   50%                                                         peanut butter sandwich)

                                                    0%
                                        Single Dose:         3 mg   10 mg   30 mg   100 mg   300 mg   600 mg

     *Includes placebo patients who crossed over to AR101
33   Burks W, et al. EAACI 2015; Bird A, et al. AAAAI 2016
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†

     *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);
34   †Rachid R, et al EAACI 2016: ARC002 Part 2 low-dose extended maintenance (N=11)
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
Double-Blind, Placebo-Controlled Food Challenge and
     Reporting the Single Highest Tolerated Dose

                                                        Diagnostic                                              Treatment
                                                      Eliciting Dose                                            Outcome
                                                     Reactive Dose                                               Single Highest
                                                 Cumulative Reactive Dose                                       Tolerated Dose*

     DBPCFC                    1                   3                   10       30           100          300       600*          1,000**
     steps (mg):

                                                       Tolerated              Single      Reactive
                                                        Doses                 Highest      Dose
                                                                             Tolerated    This is not a
                                                                               Dose      tolerated dose

     *Primary endpoint for PALISADE agreed with FDA
36   **Primary endpoint for PALISADE agreed with EU regulatory authorities
PALISADE: Core Phase 3 Efficacy and Safety Trial of AR101

     • 554 patients ages 4-49 enrolled (U.S.,
       CAN, EU); Up-dosing complete, final
       study visits expected around year-end                                                                           Up-Dosing                   Maintenance
                                                                                                                       ~6 Months                    ~6 Months
       2017

     • Primary efficacy analysis in 4-17 age                                                 AR101            3                            300
       group (90% of enrolled patients); adults                                                               mg                           mg
       analyzed separately                                                                                         • Daily dose                  • Daily 300 mg
                                                                                                                     at home                       dose at home
                                                                               Entry        3:1                                                                     Exit
     • Primary efficacy endpoint is the                                                                            • Dose escalations
                                                                              DBPCFC                                 in allergist office                          DBPCFC
       proportion of subjects who tolerate a                                  Tolerate                               every 2 weeks                                   Tolerate
       single highest dose of at least 600 mg                                 ≤ 30 mg                                                                                ≥ 600 mg
       (U.S.) and 1,000 mg (EU)                                                             Placebo

     • Using an independent and blinded
                                                                                                                             Total treatment duration
       assessor for the entry and exit oral                                                                                         ~12 Months
       food challenges to maintain integrity of
       the blind

     PALISADE = Peanut ALlergy Oral Immunotherapy Study of AR101 for DEsensitization in Children and Adults
     DBPCFC = Double-Blind, Placebo-Controlled Food Challenge
37   Tolerate = dose is successfully ingested with no dose-limiting symptoms
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 2018

38
Phase 3 Program Designed to Support Regulatory Submissions
     and to Position AR101 for Commercial Success

                                                                   • Phase 2 studies
                                                                     (ARC001 and
                                                                     ARC002)
                                                                                       • ARTEMIS
                                                                   • PALISADE            (ARC010)
     Needed for BLA                         • RAMSES                                                         Needed for MAA
                                                                     (ARC003)
      Submission                              (ARC007)                                 • ARC005                Submission
                                                                   • Data cuts from:     (FPI fulfills PIP
                                                                     – ARC004 and        requirement)
                                                                       ARC008
                                                                     – RAMSES*
                                                                     – ARTEMIS

39   * Available safety data from RAMSES will be included in MAA
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 2018

40
Exploring the Potential to Deplete Peanut-Specific TH2A Cells

     • TH2A cells appear to be important
       components in the allergic response                         Placebo Group   AR101 Group
                                                                        n=3            n=4
     • In a small pilot experiment, AR101
       treatment was associated with a
       significant reduction of TH2A 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

41   Source: Wambre E, et al. Sci Transl Med. 2017 Aug 2;9(401).
The Community Allergist and the
Role of Professional Organizations

Stephen Tilles, MD
University of Washington
Northwest Asthma and Allergy Center
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
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
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
Allergies in the United States

     2014 National Health Interview Survey - CDC

     • Children under age 18
       – 8.4% hay fever
       – 10% respiratory allergies (asthma)
       – 5.4% food allergies
       – 11.6% skin allergies.

46
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
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      • Care centered around           • Uncommon
                         medications                       theophylline/bronchodilators
                       • Immunotherapy (allergy shots)   • Preventative medications had
                         prescribed for majority           problematic side effects

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         • Care centered around                     • Uncommon
                         medications                          theophylline/bronchodilators
                       • Immunotherapy (allergy shots)      • Preventative medications had
                         prescribed for majority              problematic side effects
     1990’s            • Non-sedating antihistamines        • Need to control underlying               • Increasing incidence,
                         (Seldane, Claritin, Zyrtec)          inflammation better understood             but still considered not
                       • Nasal steroids (Flonase,           • High potency inhaled steroids              common
                         Beconase)                            (Flovent, Pulmicort); long-acting beta
                       • Allergy shots still going strong     agonists (Serevent)

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          • Care centered around                     • Uncommon
                         medications                           theophylline/bronchodilators
                       • Immunotherapy (allergy shots)       • Preventative medications had
                         prescribed for majority               problematic side effects
     1990’s            • Non-sedating antihistamines         • Need to control underlying               • Increasing incidence,
                         (Seldane, Claritin, Zyrtec)           inflammation better understood             but still considered not
                       • Nasal steroids (Flonase,            • High potency inhaled steroids              common
                         Beconase)                             (Flovent, Pulmicort); long-acting beta
                       • Allergy shots still going strong      agonists (Serevent)

     2000’s            • Fewer patients opting for allergy   • Unmet need being better addressed        • Incidence and
                         shots (safe and effective             (Advair, Symbicort)                        prevalence rising rapidly
                         medications appropriately used)     • Uncontrolled asthma – smaller niche      • Therapeutics
                                                               but target of intense drug development     development not
                                                             • First biologic for asthma (omalizumab)     keeping up with unmet
                                                               – not initially targeted to allergists     needs

50
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
Focus of Allergy Specialists in U.S. – Evolution of Unmet Needs
     and Availability of Innovative Treatments: 2010’s

     Environmental Allergies                 Asthma

     • First wave of innovative              • Effective medications
       medications now generic;                widely available
       often prescribed by primary
                                             • Multiple protein biologics, many of
       care providers
                                               which are now being developed for
     • Allergy shots continuing to shrink;     other allergic disease indications
       remains an important option for         (e.g., IL-5, IL-4/IL-13 inhibitors)
       severe allergies
     • Orally dissolvable tablets will be
       increasingly prescribed, shifting
       management of allergic rhinitis
       towards primary care providers

52
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              • Effective medications                 • Unmet medical need growing
       medications now generic;                widely available
                                                                                     • Still no FDA approved therapies
       often prescribed by primary
                                             • Multiple protein biologics, many of
       care providers                                                                • Children disproportionately affected
                                               which are now being developed for
     • Allergy shots continuing to shrink;     other allergic disease indications
       remains an important option for         (e.g., IL-5, IL-4/IL-13 inhibitors)
       severe allergies
     • Orally dissolvable tablets will be
       increasingly prescribed, shifting
       management of allergic rhinitis
       towards primary care providers

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              • Effective medications                    • Unmet medical need growing
       medications now generic;                widely available
                                                                                        • Still no FDA approved therapies
       often prescribed by primary
       Managed       Care Maturing            • Multiple protein biologics, many of
       care  providers                                                                  • Children disproportionately affected
                                                which are now being developed for
       • Highshots
     • Allergy        continuing to
                 deductibles,       shrink;
                                  high   co-pay other allergic disease indications
       remains an important option for          (e.g., IL-5, IL-4/IL-13 inhibitors)
       • Medication
       severe  allergies prices now felt by individual patients; subject of           regular discussion
          withdissolvable
     • Orally   providers tablets will be
       increasingly prescribed, shifting
       management of allergic rhinitis
       towards primary care providers

54
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
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
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): 151-159
The Evolution of Oral Immunotherapy (OIT)

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

58   Sources: *Schneider (2013), Yee (2016)
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
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
American College of Allergy, Asthma, and Immunology (ACAAI)
     Helps Its Members with Practice Management

61   Source: http://college.acaai.org/practice-management-center
American College of Allergy, Asthma, and Immunology (ACAAI)
     Provides Toolkits Related to Practice Management

62   Source: http://college.acaai.org/practice-management-center
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
64
65
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         • Capacity to introduce novel biologics
         and Capacity for New          – Omalizumab, dupilumab, mepolizumab, reslizumab,
       Therapeutic Offerings Will        benralizumab, etc.
       Drive the Future of Allergy
                                       – AR101 alone and with adjunctive investigational agents
           Practice in the U.S.
                                         if approved by FDA

66
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
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
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
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
       1997-2011
     • 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
     Sources: National Institute of Allergy and Infectious Diseases, National Institutes of Health. Report of the NIH Expert Panel on Food Allergy Research. 2006. Retrieved
     from www.niaid.nih.gov/topics/foodallergy/research/pages/reportfoodallergy.aspx; United States Census Bureau Quick Facts (2015 estimates); Gupta RS, et al.
70   Pediatrics 2011; 128(1):e9-17; Gupta R, et al. JAMA Pediatr. 2013 Nov; 167(11):1026-31. Clark S, et al. J Allergy Clin Immunol. 2011; 127(3):682-683
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;
Peanuts Have Been a Popular Source of Nutrition and Flavor

       Readily available

       Palatable

       High protein

       Cheap

72
Now People Are Afraid of Peanuts

73
Avoiding Peanuts Is Not as Easy as It Seems

     Peanut Protein
     Can Appear in
     Unexpected
     Places

     One Accident
     Can be Fatal

74
Level of Sensitivity to Peanut Protein Varies

                                               Baseline Sensitivity      Desensitization Period   Maintenance Therapy

                                                                                                                         ~3-4
               Tolerated Peanut Protein Dose

                                                                                                         Safety Buffer
                                                                                           1-2

                                                                  ~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
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*

     *Deschildre A, et al. Peanut-allergic patients in the MIRABEL survey: characteristics, allergists' dietary advice and lessons from real life. Clin Exp Allergy.
76   2016 Apr;46(4):610-20
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, 2017

77
Peanut Allergy Has a Negative Impact on Quality of Life (N=67)
                                6%                            5%                                                                                       Strongly Disagree
                                3%                                                         21%
                                                             10%
                                8%

                                                             13%                                                        46%
                                                                                           19%
                               34%

                                                             49%                           29%
                                                                                                                        24%

                               49%                                                                                      13%
                                                                                           27%
                                                             22%                                                        13%
                                                                                            5%                           3%                            Strongly Agree
                      Hard to attend social        Interferes w/ quality of        Disrupts education         Unable to have open
                             events                       life overall                                       conversations w/ doctor

     Survey Question: For each of the following statements, please indicate how much you agree or disagree that peanut allergies (impact attending social events,
78   education/school, quality of life overall or unable to have open and meaningful conversations with treating doctor).
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
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
AR101 Practice Flow Is Similar to Widely-Used Allergy Shots

         Practice Flow                                    Allergy Shots                    AR101
         Check-in / Check-out                                              10 mins

         Dosing                                                            10 mins

         Monitoring                                          30 mins                   60-90 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
AR101 Practice Flow:
     Six Patients Up-Dosed per 3-Hour Session

                      Check-in         Dosing            Monitoring            Check-out

              #1
                       5 mins          10 mins           60-90 mins             5 mins
                     per patient      per patient        per patient          per patient

                        1:1              1:1                                      1:1

                                                    Common waiting area
                                                                                                       #6

                   6 patients                  1 doctor                    1-2 nurses
              Each spends < 2 hours      1 hour for all 6 patients     ~2.5 hours for all 6 patients
82
Potentially a Third Wave of Therapies for Allergists to “Own”

                  1                   2                  3

                                 Potent Inhaled          Oral
             Immunotherapy
                                  Steroids and      Immunotherapy
                Shots for
                                  Biologics for       with FDA-
              Aeroallergens
                                    Asthma          Approved Drugs

83
Preparing for Potential Commercialization of AR101

Jeff Knapp
Chief Operating Officer, Aimmune
Currently, There Are ~1M Peanut Allergic Patients (4-17)
     Diagnosed in the U.S.
                                              2017 PA Patient Snapshot

            1.6M                                                                                      1M / 1.6M equates to
                                                                  Unknown patients;
                                               +600K                                                ~60% of peanut allergic
         Prevalent                                                not actively being
                                                                  managed by a HCP                patients already diagnosed,
        Population
                                                                                                    despite the absence of
                                                                                                    standardized therapies
                                                                  Diagnosed and wholly
                                               +300K              managed by Pediatricians

          1M                                   +300K
                                                                  Diagnosed by Pediatrician;
                                                                  Managed by Allergist
                                                                                               Majority (70%) of the
      Total PA                                                                                 diagnosed peanut allergic
      Patients                                                                                 patients are seen by an
                                                                  Diagnosed AND                Allergist – Aimmune’s
                                                400K              managed by Allergist
                                                                                               target audience

85   Source: Symphony Health Patient Claims (Jan 2011-Jun 2017)
Of the 1M U.S. Peanut Allergic Patients Diagnosed, AR101 Has
     the Potential to Capture Meaningful Market Share

                                               1.6 Million Potential Patients age 4-17
                                                  ~1 million clinically managed today
           30%
      Diagnosed and
                                                            Potential Future
       Managed by
                                                          Referrals to Allergists
      Pediatricians                                                                                Expected Drivers of
         (top 4% manage
         40% of patients)                                                                          Patient Motivation to
                                                         AR101                                     Seek AR101 Therapy
                                                                                    AR101 is the
           70%                                                                      Only Phase 3
     Diagnosed and/or                                                                Therapy in     • Reaction History
       Managed by                                                                   Development
        Allergists                                                                    for Ages
                                                                                                    • Anxiety
                                                 AR101 Would Fit Well Into              12-17       • Family Support
                                                  Current Allergy Practice
                                                                                                    • Access to an
                                                                                                      Allergist
                                                          70%                           30%
                                                        Ages 4-11                    Ages 12-17
86   Source: Symphony claims data, 2011-2017
High Unmet Need for Desensitization to Peanuts
     Based on U.S. Patient Claims Data

                       1M                                                 First Experience
          Total Diagnosed                                                                                                                       Accidental
                                                                          With PA Can Be
     Peanut Allergy (PA) Patients                                                                                                          Exposure Resulting
                                                                           Very Traumatic
            (Age 4 to 17)                                                                                                                   In ER or HCP Visit
                                                                         Almost one in five*
                                                                                                                                            About one-third* of
                                                                          diagnosed PA pts
                                                                                                                                              pts experienced
                                                                         learned about their
                                                                                                                                             anaphylaxis after
                                                                           condition via an
                                                                                                                                             they had already
                                                                         anaphylactic event
                                                                                                                                           been made aware of
                                                                        that resulted in a trip
                                                                                                                                               their condition
                                                                              to the ER
                         1M
                                                                                                                                                       30%
                                                                                   17.5%
                                                                                   175K                                                               300K

     *Average 3-year observation period
     Source: Symphony Health Patient Claims (Jan 2011-Jun 2017); anaphylaxis codes: 995.61, 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
87
AR101 Has the Potential to Address Key Unmet Needs and to
     Change the Treatment Paradigm for Peanut Allergy

                                             • Lack of treatment options
             Unmet Need                      • High risk of potentially life-threatening reaction
                                             • High impact on parent / patient quality of life

                                             • Likelihood to prescribe AR101 was 6.1 on a scale of 1 to 7 (n=30)
              Likelihood                     • Value proposition based on Phase 2 data compelling, primarily as a
             to Prescribe                      safety net against severe reactions due to accidental exposure

                                             • Allergists offering “homebrew” OIT today believe, if approved, AR101
           “Homebrew”                          will address most of their pain points
          OIT 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
Allergists are the Ideal Specialty to “Own” AR101

        1. Allergists have resources and training
           to optimally treat food allergic patients                        “Patients will call us once the word is
                                                                           out. We won’t have to call the patients.”

        2. Patients with food allergies are
           generally followed by an allergist                                                         “If I’m not offering it, I’m at
                                                                                                       a disadvantage as other
        3. Allergists have a strong desire                                                                   Allergists will.”
           to treat their patients with food allergies

        4. Allergists are losing some patient                               “These patients only come in once a
           populations to other specialties such                            year now. They will have more office
           as pediatricians                                                  visits with this program. Also, I may
                                                                              attract new patients if I offer this.”

89   Source: Aimmune Physician and Practice Manager Market Research 2017
If Approved, AR101 Can Be Integrated into Allergy Offices with
     Existing Available Capacity and Will Be Further Optimized Over Time

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

90   Sources: Aimmune Market Research 2017
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

                                     Each Up-Dose is                          300 mg
                                     Conducted at the                240 mg
                                     Allergist’s Office         200 mg                      300 mg Sachets for At-Home
                                                            160 mg                           Daily Maintenance Dosing
                                                       120 mg
                                                    80 mg
                                                40 mg
                     Initial                20 mg
                   Escalation           12 mg
                           6 mg      6 mg
                                  3 mg                      Calendar Pack for
                  0.5 mg
                                                            At-Home 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
Access to AR101 Throughout Treatment is Intended to be
     Seamless to Support a Positive Patient Experience
         Peanut Allergy        Initial Day                                                       Maintenance
          Diagnoses &          Escalation       Day 1       Days 2-14                           30 Day Supply
       Treatment Decision       (in office)    Level 1       Level 1                               (at home)
                                              (in office)   (at home)

                                                                                      Repeat
                                                                                     through
                                                                                     Level 11

                                          AR101 Patient Support Services – Many industry standard

                            Initiation Support              Ongoing Support
                            • Benefits investigation        • Logistics coordination with patient and office
                            • PA processed                  • Refill reminders and messaging
                            • Financial counseling          • Adherence and compliance support
                            • Starter program               • Out-of-pocket support

92
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

                                       Initial Diagnosis                      Up-dosing involves a combination of
                                                                              one or more allergy immunotherapy
     “Home-brew”                       • Standard office visit code (992xx)   codes:
         OIT                                                                  • 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

                                       Initial Diagnosis                      Up-dosing could be reduced to one time
                                       • Standard office visit code (992xx)   bound code
            AR101
                                                                              • Requires support from societies
                                                                                (ACAAI & AAAAI)

93   Source: Aimmune Physician and Practice Manager Market Research 2017
U.S. Payer Reimbursement Outlook for AR101 Appears Favorable

                                                                   • Not surprisingly, ~90% of payers surveyed exert low or no
               Payer Management
                                                                     effort in managing food and peanut allergy today
                of Peanut Allergy
               Expected to be Low                                  • Management not expected to increase significantly in near
                                                                     term given low spend vs. other therapeutic areas

                Payers Likely to                                   • In recent ad board, 10/10 payers indicated they expect to
                                                                     add AR101, if approved, to formulary (tier variable) based on:
              Cover AR101 Given
                                                                           • promising clinical value
              Promising Value and
                                                                           • pediatric indication
               High Unmet Need                                             • lack of alternatives

                                                                   • In blinded research, 90% of payers expect to require a
              Payers Expected to
                                                                     standard annual Prior Authorization (PA) for AR101
              Require a Standard
             Prior Auth. 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
Preparing for AR101’s Potential Launch (est. 2019)

        Partner with Allergy Community                Launch Preparation
      • Engage stakeholders                  • AR101 positioning underway
        − Allergists (KOLs, Community)       • Publication strategy and execution
        − Allied Health Care Professionals   • Commercial packaging finalized
        − Pediatricians (for referrals)      • Build optimal field teams at the right time
                                               − Medical Science Liaisons
      • Create successful collaborations
                                               − Nurse educators
        − Support professional societies
                                               − Account Mgmt (e.g. payers)
          (ACAAI, AAAAI, EAACI, etc.)
                                               − Sales force of
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
Looking Ahead: Anticipated Milestones

        Ongoing Phase 3 Trials with AR101                        Upcoming Trials and Programs
      • Core PALISADE Phase 3 trial                          • ARC005 trial of AR101 in infants and toddlers
        – Final study visits expected around year-end 2017     – Initiate in 2018
        – Topline data expected 1Q 2018
        – BLA submission planned for late 2018, followed     • AR101 and Adjunctive Dupilumab
          by MAA submission                                    – Initiate Phase 2 trial in 2018 (Regeneron/Sanofi)

      • ARC004 trial (PALISADE roll-over)                    • Egg allergy program
        – Data-cut in 3Q 2018 to support BLA/MAA               – Investigational New Drug application in 2018
                                                             • Walnut allergy program
      • RAMSES real-world trial (U.S.)
                                                               – Investigational New Drug application in 2019
        – Enrollment to complete around year-end 2017
        – Data available in 2H 2018

      • ARTEMIS (EU)
        – Enrollment complete late 2017/early 2018
        – Data available in 2H 2018

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Q&A with Speaker Panel

Moderator: Mary Rozenman, PhD
SVP, Corporate Development & Strategy, Aimmune
Thank you.
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