Investor Symposium on Peanut Allergy Treatment - December 1, 2017 - Aimmune Therapeutics
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Investor Symposium on December 1, 2017 Peanut Allergy Treatment
Welcome Laura Hansen, PhD VP, Investor Relations, Aimmune
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
3
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
Aimmune Overview Stephen Dilly, MBBS, PhD Chief Executive Officer, Aimmune
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
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
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
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
Three Key Parameters in Drug Development
Patient
Product Protocol
Selection
10The 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
11AR101 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
12Patient 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 theDrug 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?
15Benefit 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
16Benefit 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
17Understanding 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)
18Amount 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):610-20Understanding 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):610-20Building the Right Team with the Right Mix
Experienced
Team of Drug
Deep Domain
Developers
with 30+ Experience in
NDAs, BLAs Food Allergy
and MAAs
21Collaborations 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 materialsObjectives 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
23Aimmune’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
25PALISADE 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
261. 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
27Demonstrating 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 2011Understanding 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):610-20ARC001 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
p1. 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
312. 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
32ARC001/002 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 2016ARC001/002 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
35Double-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 authoritiesPALISADE: 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 symptomsAR101 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
38Phase 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 MAAExploring 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
40Exploring 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
43Disclosure
• 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
44Topics 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.)
45Allergies 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.
46Current 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
47Focus 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
48Focus 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)
49Focus 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
50Focus 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
51Focus 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
52Focus 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
53Focus 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
54Overview 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
55Oral 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
56Oral 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): 151-159The 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 PractRole 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
60American College of Allergy, Asthma, and Immunology (ACAAI)
Helps Its Members with Practice Management
61 Source: http://college.acaai.org/practice-management-centerAmerican College of Allergy, Asthma, and Immunology (ACAAI)
Provides Toolkits Related to Practice Management
62 Source: http://college.acaai.org/practice-management-centerCase 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
6364
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
66Treating 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
68Topics 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
69Up 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):682-683Approximately 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
72Now 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
74Level 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
75Managing 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):610-20Impact 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
77Peanut 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
79Planning 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
80AR101 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 protocolAR101 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
82Potentially 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
83Preparing 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, 2011-2017High 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
87AR101 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 2017Allergists 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 2017If 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 2017AR101 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
91Access 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
92Some 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 2017U.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 2017Preparing 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 ofSummary - 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!
96Looking 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
97Q&A with Speaker Panel Moderator: Mary Rozenman, PhD SVP, Corporate Development & Strategy, Aimmune
Thank you.
You can also read
