SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): November 18, 2018
AIMMUNE THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
(State or other jurisdiction
8000 Marina Blvd, Suite 300
Brisbane, CA 94005
(Address of principal executive offices, including Zip Code)
Registrants telephone number, including area code: (650) 614-5220
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instructions A.2. below):
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
|Item 7.01|| |
Regulation FD Disclosure.
On November 18, 2018, Aimmune Therapeutics, Inc. (Aimmune or the Company) issued a press release announcing the publication of its Phase 3 PALISADE trial of AR101 in the New England Journal of Medicine (the Press Release). A copy of the Press Release is furnished as Exhibit 99.1 to this Current Report and is incorporated herein by reference.
The Company is also hosting an investor conference call at 5:00 AM PT (8:00 AM ET) on Monday, November 19, 2018 to discuss the New England Journal of Medicine publication and present the information in the presentation slides, including topline results from the Companys RAMSES study of AR101, attached hereto as Exhibit 99.2 (the Company Presentation). Conference call information is as follows:
Conference Call Numbers 1-877-497-1438 (domestic) or 1-262-558-6296 (international); Conference ID# 6672628
The information in this Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1, shall not be deemed filed for purposes of Section 18 of the Securities Act of 1934, as amended (the Exchange Act), or otherwise subject to the liabilities of that Section, or incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such filing.
|Item 8.01|| |
On November 19, 2018, the Company presented the information in the Company Presentation, including topline results from the Companys RAMSES study of AR101, during an investor conference call. The full Company Presentation is filed as Exhibit 99.2 and is incorporated herein by reference.
|Item 9.01|| |
Financial Statements and Exhibits.
|99.1||Press release titled, Landmark PALISADE Trial of AR101 Published in New England Journal of Medicine dated November 18, 2018.|
|99.2||Company slide presentation dated November 19, 2018.|
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
|AIMMUNE THERAPEUTICS, INC.|
|Date: November 19, 2018||By:|
|Douglas T. Sheehy|
|General Counsel and Secretary|
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Landmark PALISADE Trial of AR101 Published in
New England Journal of Medicine
Treatment with AR101 significantly increased the amount of peanut protein tolerated and reduced the number and severity of reactions to peanut protein
Aimmune conference call Monday, November 19 at 8:00 a.m. Eastern
BRISBANE, California, November 18, 2018 Aimmune Therapeutics, Inc. (Nasdaq:AIMT), a biopharmaceutical company developing treatments for potentially life-threatening food allergies, today announced that the New England Journal of Medicine (NEJM) has published the full results of the landmark phase 3 PALISADE clinical trial of AR101, Aimmunes investigational biologic oral immunotherapy for desensitization of patients with peanut allergy. PALISADE is the largest and first successful phase 3 peanut allergy immunotherapy trial to date.
This publication in the New England Journal of Medicine recognizes the rigor, scale and importance of the PALISADE trial, which will inform ongoing research in food allergy and could change practice for peanut allergy, said A. Wesley Burks, M.D., Executive Dean and Curnen Distinguished Professor of Pediatrics, University of North Carolina School of Medicine, member of the Aimmune Scientific Advisory Board, and senior author of the NEJM publication. Peanut allergy demands lifelong vigilance to avoid accidental exposures, and the unpredictable severity of reactions that do occur can take a toll on children and families. By significantly reducing the frequency and severity of allergic reactions to peanut, AR101 could provide reassurance and make a meaningful, beneficial impact on peoples daily lives.
As reported in the NEJM article, AR101 Oral Immunotherapy for Peanut Allergy,1 PALISADE met its primary endpoint and key secondary endpoints. In the trials primary analysis of peanut-allergic children and adolescents ages 417, AR101 treatment resulted in a significant increase in the amount of peanut protein tolerated, compared to placebo. The increase, which was measured through a series of doses in an exit food challenge, suggests that AR101-treated patients could expect to have protection against reactions to accidental peanut exposures.
In a real-world translation of the amounts of peanut protein tolerated (where one whole peanut kernel contains approximately 250300 mg of peanut protein), 67% of AR101 patients tolerated a single dose of at least 2 peanuts; among AR101 patients who completed the trial, 85% percent tolerated this level, which is equivalent to 34 peanuts of total exposure. Also, 50% of AR101 patients tolerated the highest challenge level, a single dose equivalent to 34 peanuts (78 peanuts total exposure).
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AR101 treatment also resulted in a reduction in the number and severity of reactions in the exit food challenge, compared to placebo. In the exit challenge,10% of AR101 patients received epinephrine, and the median dose at which it was given was 1,000 mg of peanut protein (or 2,043 mg of total exposure), compared to 53% of placebo patients at a median dose of 100 mg. This corresponds to an overall 81% reduction in epinephrine use in AR101 patients across all levels of the exit challenge, with a 99% reduction at the 300-mg level and a 94% reduction at the 600-mg level.
AR101 demonstrated a favorable safety profile in the highly atopic patient population enrolled in PALISADE. Treatment-emergent adverse events occurred in more than 95% of patients in both trial groups, and nearly all were mild or moderate in severity. In AR101 patients who experienced treatment-related adverse events, 2.4% experienced severe adverse events and 1.1% experienced serious adverse events. Epinephrine was used for severe adverse events in two patients, one of which was the single case of anaphylaxis in the trial.
PALISADE is the largest and most rigorously conducted oral immunotherapy trial for peanut allergy ever reported, as well as the first to use an independent, blinded assessor, and the first to accept participants with a past medical history of severe or life-threatening anaphylaxis, said Daniel C. Adelman, M.D., Chief Medical Officer of Aimmune. Were pleased and grateful to share the success of this groundbreaking trial and its recognition by the New England Journal of Medicine with all of the patients and their families who made it possible, along with the allergists, clinical and research teams, and advocates who put years of collaborative effort toward having an effective, approved treatment for food allergy.
This publication in the New England Journal of Medicine signifies our progress and momentum towards making an approved therapy available to the millions of families who want a robust, reliable peanut allergy treatment that can provide protection in cases of accidental exposures. We are excited to be submitting our applications for marketing approval in the United States next month and in Europe in the middle of next year, said Jayson Dallas, M.D., President and CEO of Aimmune. At the same time, the publication exemplifies our commitment to the entire food allergy community to not only be transparent, but also to contribute to our collective understanding and advance the field of food allergy.
Conference Call and Webcast Information
Aimmune will host a conference call and live audio webcast Monday, November 19, 2018, at 8:00 a.m. EST / 5:00 a.m. PST to discuss the New England Journal of Medicine publication of the PALISADE results. The conference call and associated slide
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deck will be accessible via the companys website at www.aimmune.com on the Events page under Investor Relations. Please connect to the companys website at least 15 minutes prior to the start of the conference call to ensure adequate time for any software download that may be required to listen to the webcast. Alternatively, participants may dial 1-877-497-1438 (domestic) or 1-262-558-6296 (international) and refer to conference ID 6672628. An archived copy of the webcast will be available on the companys website for at least 30 days after the conference call.
PALISADE (Peanut Allergy oral Immunotherapy Study of AR101 for Desensitization, clinicaltrials.gov number NCT02635776) was an international, randomized (3:1), double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy and safety of AR101 in patients with peanut allergy. PALISADE was conducted at 66 sites in 10 countries in North American and Europe, where 496 patients ages 417 received either AR101 or placebo (372 AR101, 124 placebo), along with 55 adults ages 1849, who were not part of the primary analysis. To meet PALISADEs inclusion criteria, patients could tolerate no more than the 30-mg dose of peanut protein in an entry double-blind, placebo-controlled food challenge (DBPCFC), which consisted of consecutive doses of 1, 3, 10, 30 and 100 mg of peanut protein, given 20 to 30 minutes apart, as tolerated with no more than mild symptoms. Patients enrolled in PALISADE underwent a dose escalation period of approximately 22 weeks to reach a maintenance dose of 300 mg per day of AR101 or placebo, then continued with daily maintenance at 300 mg per day of AR101 or placebo for approximately six months. At that point, patients underwent an exit DBPCFC, which tested consecutive doses of 3, 10, 30, 100, 300, 600 and 1,000 mg of peanut protein, given 20 to 30 minutes apart, as tolerated with no more than mild symptoms. Both the entry and exit DBPCFCs used an independent, blinded assessor. Following the completion of the exit DBPCFC, patients were unblinded and eligible to rollover or crossover into the follow-on ARC004 clinical trial, as appropriate.
About Peanut Allergy
Peanut allergy is increasingly prevalent among children in the United States and other industrialized countries; in the United States from 1997 to 2008, peanut allergy tripled (from 1-in-250 children to 1-in-70 children).2-5 Peanut allergy usually persists into adulthood,6-9 can be life-threatening, and accounts for the majority of deaths related to food allergy.10 There are no approved treatment options for peanut allergy11 the standard of care has been a strict elimination diet and the timely administration of rescue medications in case of an allergic reaction from accidental exposure.12-14 Despite vigilance, accidental exposures may occur15,16 and cause reactions of unpredictable severity,17 leading to a lifelong risk of severe reactions.
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AR101 is a new, peanut-derived investigational oral biologic drug for use in oral immunotherapy in patients with peanut allergy. The drug, which is manufactured in accordance with current Good Manufacturing Practices (cGMP), delivers a daily dose of peanut protein with a characterized protein profile, analyzed to ensure consistent major allergen content. The amount of active ingredient in each AR101 capsule is controlled to ensure minimal variability of allergen content across doses of a given strength. AR101 is administered as an oral powder in graduated doses in pull-apart capsules or foil-laminate sachets. The contents are mixed thoroughly with a few spoonfuls of age-appropriate, unheated food of the patients choice.
About Aimmune Therapeutics
Aimmune Therapeutics, Inc., is a biopharmaceutical company developing treatments for life-threatening food allergies. The companys Characterized Oral Desensitization ImmunoTherapy (CODIT) approach is intended to provide meaningful levels of protection against allergic reactions resulting from accidental exposure to food allergens by desensitizing patients with defined, precise amounts of key allergens. Aimmunes first investigational biologic product using CODIT, AR101 for the treatment of peanut allergy, has received the FDAs Breakthrough Therapy Designation for the desensitization of peanut-allergic patients 417 years of age. Aimmune plans to submit regulatory filings for marketing approval of AR101 in the United States and Europe based on data from the pivotal Phase 3 PALISADE clinical trial of AR101, which in 417-year-old subjects met its primary and key secondary endpoints, and additional ongoing and completed AR101 clinical trials. For more information, please see www.aimmune.com.
Statements contained in this press release regarding matters that are not historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: Aimmunes expectations regarding the potential benefits of AR101; Aimmunes expectations regarding the anticipated timing of any future clinical trials; Aimmunes expectations on regulatory submissions for marketing approval of AR101 for peanut allergy in the United States and Europe, including the timing of these submissions; Aimmunes expectations regarding the potential commercial launch of AR101, including the timing of a potential approval of AR101; and Aimmunes expectations regarding potential applications of the CODIT approach to treating life-threatening food allergies. Risks and uncertainties that contribute to the uncertain nature of the forward-looking statements include: the expectation that Aimmune will need additional funds to finance its operations; Aimmunes or any of its collaborative
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partners ability to initiate and/or complete clinical trials; the unpredictability of the regulatory process; the possibility that Aimmunes or any of its collaborative partners clinical trials will not be successful; Aimmunes dependence on the success of AR101; Aimmunes reliance on third parties for the manufacture of Aimmunes product candidates; possible regulatory developments in the United States and foreign countries; and Aimmunes ability to attract and retain senior management personnel. These and other risks and uncertainties are described more fully in Aimmunes most recent filings with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended September 30, 2018. All forward-looking statements contained in this press release speak only as of the date on which they were made. Aimmune undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
This press release concerns a product that is under clinical investigation and that has not yet been approved for marketing by the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA). It is currently limited to investigational use, and no representation is made as to its safety or effectiveness for the purposes for which it is being investigated.
Vickery BP, Vereda A, Casale TB, et al. AR101 oral immunotherapy for peanut allergy. New Engl J Med 2018; DOI: 10.1056/NEJMoa1812856.
Gupta RS, Springston EE, Warrier MR, et al. The prevalence, severity and distribution of childhood food allergy in the United States. Pediatrics 2011;128(1):e9-e17.
Sicherer SH, Muñoz-Furlong A, Burks AW, Sampson HA. Prevalence of peanut and tree nut allergy in the US determined by a random digit dial telephone survey. J Allergy Clin Immunol 1999;103:559-62.
Sicherer SH, Muñoz-Furlong A, Godbold JH, Sampson HA. US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up. J Allergy Clin Immunol 2010;125:1322-6.
Grimshaw KE, Bryant T, Oliver EM, et al. Incidence and risk factors for food hypersensitivity in UK infants: results from a birth cohort study. Clin Transl Allergy 2016;6:1.
Crespo JF, James JM, Fernandez-Rodriguez C, Rodriguez J. Food allergy: nuts and tree nuts. Br J Nutr 2006; 96:Suppl 2:S95-S102.
Moreno MA. Guidelines for children with peanut allergy. JAMA Pediatr 2017;171:100.
Skolnick HS, Conover-Walker MK, Koerner CB, Sampson HA, Burks W, Wood RA. The natural history of peanut allergy. J Allergy Clin Immunol 2001;107:367-74.
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Fleischer DM, Conover-Walker MK, Christie L, Burks AW, Wood RA. The natural progression of peanut allergy: resolution and the possibility of recurrence. J Allergy Clin Immunol 2003;112:183-9.
Bock SA, Muñoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol 2001;107:191-3.
Yu W, Freeland DMH, Nadeau KC. Food allergy: immune mechanisms, diagnosis and immunotherapy. Nat Rev Immunol 2016;16:751-65.
Boyce JA, Assaad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol 2010;126:Suppl:S1-S58.
Sampson HA, Aceves S, Bock SA, et al. Food allergy: a practice parameter update 2014. J Allergy Clin Immunol 2014;134(5):1016-25.e43.
Muraro A, Werfel T, Hoffmann-Sommergruber K, et al. EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy. Allergy 2014;69:1008-25.
Rimbaud L, Heraud F, La Vieille S, Leblanc J-C, Crépet A. Quantitative risk assessment relating to the inadvertent presence of peanut allergens in various food product. Int Food Risk Anal J 2013;3:1-11.
Vander Leek TK, Liu AH, Stefanski K, Blacker B, Bock SA. The natural history of peanut allergy in young children and its association with serum peanut-specific IgE. J Pediatr 2000;137:749-55.
Allen KJ, Remington BC, Baumert JL, et al. Allergen reference doses for precautionary labeling (VITAL 2.0): clinical implications. J Allergy Clin Immunol 2014;133:156-64.
# # #
Laura Hansen, Ph.D.
Nov 19, 2018 Conference Call for Investment Community Exhibit 99.2
Agenda for Today’s Call Topic Speaker Safe Harbor Statement Laura Hansen, PhD, VP, Investor Relations Opening Remarks Jayson Dallas, MD, President & Chief Executive Officer AR101 for Peanut Allergy NEJM publication of PALISADE RAMSES Topline Results Daniel Adelman, MD, Chief Medical Officer Q&A Jayson Dallas, MD, President & Chief Executive Officer Daniel Adelman, MD, Chief Medical Officer Eric Bjerkholt, Chief Financial Officer Stephen Tilles, MD, Clinical Professor at the Univ. of Washington; Consultant to Aimmune Therapeutics Closing Remarks Jayson Dallas, MD, President & Chief Executive Officer
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 8, 2018. 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.
Aimmune’s food allergy treatments are investigational and are not FDA-approved
PALISADE Phase 3 Results Published in NEJM (Nov 18, 2018) “…treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo.” Vickery et al., NEJM, November 18, 2018 (online publication)
Executive Summary Aimmune Therapeutics is leading the field in developing novel treatments for food allergies New England Journal of Medicine publication highlights phase 3 PALISADE trial of AR101 Recently completed RAMSES phase 3 safety showed favorable safety profile; consistent with PALISADE In PALISADE, AR101 reduced the frequency and severity of reactions during the exit food challenge, which mimics accidental exposure We are on track to submit a Biologics License Application for AR101 in December We are preparing for a successful U.S. launch of AR101 in 2019, assuming approval
Peanut Allergy is One of the Most Common Food Allergies 4 out of 10 children with peanut allergy experienced a severe reaction over a 3-year period 8 out of 10 children with peanut allergy never outgrow it Over 1.6 million kids and teens affected in United States
Our Precision Medicine Approach Will Leverage the Oral Route Characterized allergen profile and FDA-regulated biologic products Convenient, once-daily oral dose taken with spoonfuls of food Research shows high levels of desensitization can be achieved with oral immunotherapy that may not be possible with other routes Goal of oral immunotherapy is to minimize the body’s reaction to trigger foods
Aimmune Therapeutics: Leading the Field in Developing Food Allergy Treatments Backed by rigorous science, our approach aims to transform food allergy treatment First-of-its-kind therapy to reduce the frequency and severity of peanut allergy reactions Food allergies are a growing, often life-threatening condition with no approved treatments Focused on reliable protection for patients and enabling allergists to be leaders in peanut allergy care
Largest and most rigorously conducted oral immunotherapy trial for peanut allergy ever reported First to use an independent blinded assessor DBPCFC at both baseline and exit First and only peanut OIT study to exceed the pre-specified, FDA-mandated superiority margin for efficacy First to accept participants with past medical history of severe or life-threatening anaphylaxis 12-month intervention period (6 months up-dosing, 6 months maintenance at 300 mg per day) PALISADE Was the Largest, Most Rigorous Phase 3 Trial of Immunotherapy for Peanut Allergy
Participant Disposition Safety Population (N=496*) Completer Population (N=412†) *3 were randomized in error; 496 exposed to ≥ 1 dose of study product †2 AR101 and 1 placebo subjects had an evaluable exit DBPCFC but did not complete the study per protocol. Vickery et al., NEJM, November 18, 2018 (online publication) Screened (n=750) Failed Screening (n=251) AR101 (n=374) Received AR101 (n=372) Did not receive AR101 (n=2) Placebo (n=125) Received AR101 (n=124) Did not receive AR101 (n=1) Withdrawn (n=80) Not due to AE (n=37) Due to AE (n=43) Completed study (n=294) Withdrawn (n=10) Not due to AE (n=7) Due to AE (n=3, 2.4%) Completed study (n=115)
PALISADE Hit Primary and Secondary Efficacy Endpoints Patients Ages 4-17 Who Tolerated Each Dose Level at Exit DBPCFC *p<0.00001 for Treatment Difference >15% DBPCFC: Double-Blind, Placebo-Controlled Food Challenge Intent-to-Treat Analysis1 Primary Endpoint Key Secondary Endpoints *p<0.00001 Peanut Protein Tolerated (mg) Peanut Protein Tolerated (mg) Single Dose 300 600 1000 Cumulative Dose 443 1043 2043 Vickery et al., NEJM, November 18, 2018 (online publication) Jones S, et al. AAAAI 2018 Single Dose 300 600 1000 Cumulative Dose 443 1043 2043 Completer Analysis2 Primary endpoint: Difference between groups = 63% (95% CI: 53,73) p<0.00001
Response was Consistent Across All Age Groups Studied Percentage of Patients Who Completed the Trial and Tolerated 600 mg of Peanut Protein at Exit DBPCFC (n=33) (n=131) (n=281) Responders % (n=84) (n=197) (n=99) (n=20) (n=32) (n=13) ITT analysis of adults AR101 41.5% vs Placebo 14.3% (p=0.07) DBPCFC: Double-Blind, Placebo-Controlled Food Challenge ITT: Intent-to-Treat
PALISADE Participants Were Highly Atopic Percentage of Participants with Past Medical History Vickery et al., NEJM, November 18, 2018 (online publication)
In an Atopic Population, Adverse Events are Expected *Treatment-Emergent Adverse Events (TEAEs) regardless of relatedness to treatment 99% and 95% of AR101 and Placebo participants, respectively, experienced at least 1 TEAE* Vickery et al., NEJM, November 18, 2018 (online publication)
0.004 0.005 Number of AR101-Related TEAEs Per Month of Exposure Adverse Events were Mostly Mild or Moderate Vickery et al., NEJM, November 18, 2018 (online publication)
Trigger Foods Cause Allergic Reactions of Different Severities MILD (Grade 1) Transient skin hive Tingling around the mouth Gastrointestinal discomfort MODERATE (Grade 2) Persistent hives Wheezing Abdominal discomfort Vomiting SEVERE (Grade 3) Labored breathing Transient hypotension Medical intervention/ therapy is required Hospitalization is possible Examples of Classification Categories CoFAR = Consortium of Food Allergy Research. Burks AW, et al. N Engl J Med. 2012;367:233-43. DOI: 10.1056/NEJMoa1200435.
Low Instance of Anaphylaxis* 87% Gastrointestinal Skin Respiratory Immune System 14.2% ALLERGIC REACTIONS SYSTEMIC ALLERGIC REACTIONS More than 1 Body System ANAPHYLAXIS Grade ≥3 0.3% (n=1, Grade 3) 98% mild or moderate *single case (0.3% of subjects) Vickery et al., NEJM, November 18, 2018 (online publication) Percent of AR101 Subjects Experiencing an Allergic Reaction (regardless of relatedness to treatment)
Epinephrine Use Was Infrequent and Not a Surrogate Measure of Anaphylaxis or Systemic Allergic Reaction Severity Percent of Subjects Using Epinephrine Severity of Events Associated with Epinephrine 7.5% ∆ * Includes the single case of severe anaphylaxis Vickery et al., NEJM, November 18, 2018 (online publication) 0% *
RAMSES Phase 3 Safety Trial Was Consistent with PALISADE
Simulated real-world clinical practice and did not require a food challenge Replicated the PALISADE up-dosing period Like PALISADE, prophylactic anti-histamines, to mitigate allergic reactions, were not allowed ~80% of participants completed up-dosing and moved on to maintenance dose in both studies AR101 safety profile in RAMSES was consistent with that observed in PALISADE RAMSES Phase 3 Safety Trial of AR101 in Peanut-Allergic Children and Adolescents
RAMSES Population Compared to PALISADE Baseline Characteristics (Ages 4-17) PALISADE RAMSES Characteristic, n (%) AR101 (n=372) Placebo (n=124) AR101 ( n=337 ) Placebo ( n=168 ) Sex Male 208 (56%) 76 (61%) 218 (64.7%) 102 (60.7%) Age 4-11 years 12-17 years 238 (64%) 134 (36%) 89 (72%) 35 (28%) 226( 67.1%) 111 (32.9%) 114 ( 67.9%) 54 (32.1%) Race Non-Hispanic Caucasian Other 292 (78%) 80 (22%) 97 (78%) 27 (22%) 277 (82.2%) 60 (17.8% ) 123 (73.2%) 45 (26.8%) Baseline peanut sensitivity Median (IQR) SPT average wheal (mm) Median (IQR) Peanut-specific IgE (kUA/L) Median (IQR) maximum tolerated dose (mg) 11 (9, 14.5) 69 (19, 194) 10 (3,30) 12 (9, 15.3) 75 (29, 251) 10 (3,30) 13.5 (10.5, 19) 97 (49, 216) NA 13.5 ( 11.00. 18.50) 82 ( 38, 174) NA History of pre-study peanut anaphylaxis 269 (72%) 89 (72%) 204 (60.5%) 107 (63.7%) Previous or present asthma 198 (53%) 65 (52%) 176 ( 52.2%) 77 (45.8%) Multiple food allergies 245 (66%) 80 (65%) 219 (65%) 90 (53.6%) NA = Not available or Not done Preliminary data
AR101 Had a Consistent Safety Profile in Both Phase 3 Trials RAMSES IDE + Up-dosing PALISADE IDE + Up-dosing AR101 (n= 337) Placebo (n=168) AR101 (n=372) Placebo (n=124) Treatment-emergent adverse events 99.1% 94.6% 96.8% 88.7% Epinephrine Use 11.0% 5.4% 10.8% 4.0% Serious adverse events 0.6%* 1.2%* 1.1% 0% Systemic Allergic Reactions (Investigator Reported) 10.7% 5.4% 8.6% 1.6% Anaphylaxis 1.2%† 0% 0%† 0% Eosinophilic Esophagitis (EoE) 0.6% 0% 0.3% 0% Deaths or SUSARs 0% 0.6%‡ 0% 0% *Neither of the two serious adverse events (SAEs) in the AR101 group were related to AR101 (one SAE of acute lymphocytic leukemia and one SAE of mycoplasma pneumonia); neither of the two SAEs in the placebo group were treatment-related (one SAE of acute appendicitis and one SAE of traumatic brain injury) † In RAMSES, there were 4 cases of non-serious anaphylaxis (2 withdrew, 2 completed); in PALISADE, there was one case of anaphylaxis that occurred in maintenance ‡ Death due to traumatic brain injury resulting from motor-vehicle accident in which the participant was a passenger SUSAR: suspected unexpected serious adverse reaction
PALISADE Demonstrated that AR101 Reduces the Frequency and Severity of Allergic Reactions to Peanut* *During the DBPCFC at study exit
Understanding PALISADE Efficacy Endpoint: Tolerated Dose Subjects needed to react (stop food challenge) at 100 mg peanut protein, or less, at entry Single Tolerated Dose 3 10 30 100 300 600 1000 DBPCFC was done at trial entry and exit; independent assessor at each site Increasing doses of peanut protein were given every 20-30 minutes Dose level is tolerated if subject successfully ingests it with no dose-limiting symptoms Primary endpoint of 600 mg was set to provide safety buffer over typical real-world accidental exposure (median=125mg)* Tolerate Tolerate Tolerate Tolerate Tolerate Primary Secondary Tolerate Tolerate *The median estimated eliciting dose in real life was 125 mg (N=238 peanut-allergic patients) as reported by Deschildre A, et al. Clinical & Experimental Allergy; 46:610-620 3 13 43 143 443 1043 2043 Cumulative Tolerated Dose Tolerate Tolerate Tolerate Tolerate Tolerate Tolerate Tolerate Secondary Efficacy Endpoints Milligrams of Peanut Protein Exit Double-Blind, Placebo-Controlled Food Challenge
AR101 Significantly Reduced Both Frequency and Severity of Allergic Reactions to Peanut AR101 Placebo Key Findings Compared to placebo, the AR101 group: Developed fewer moderate and severe symptoms Tolerated more peanut exposure before the onset of symptoms Was more likely to complete the challenge DBPCFC: Double-Blind, Placebo-Controlled Food Challenge Single Dose: 3 mg 10 mg 600 mg 30 mg 100 mg 300 mg 1000 mg Cumulative Dose: 3 mg 13 mg 1043 mg 43 mg 143 mg 443 mg 2043 mg 3 mg 10 mg 600 mg 30 mg 100 mg 300 mg 1000 mg 3 mg 13 mg 1043 mg 43 mg 143 mg 443 mg 2043 mg Single Dose: Cumulative Dose: Subjects Attempting Dose Subjects Attempting Dose Vickery et al., NEJM, November 18, 2018 (online publication) Symptom Severity at 12-Month Exit DBPCFC, Ages 4-17
AR101 Significantly Reduced Epinephrine Use Due to Peanut Exposure1 125 mg (~1/2 peanut) is the median eliciting dose in the real world2 1 During the Double-Blind, Placebo-Controlled Food Challenge at study exit 2 The median estimated eliciting dose in real life was 125 mg (N=238 peanut-allergic patients) as reported by Deschildre A, et al. Clinical & Experimental Allergy; 46:610-620 0% 0.9% 0% 6.4% 0% 16% 0.3% 23.4% 0.3% 51.5% 2.5% 41.7% 7.6% 40.0% 99% ↓ 99% ↓ 94% ↓ 81% ↓
Clinical Data Show Robust Efficacy and Safety of AR101 in Highly Sensitive Peanut-Allergic Children and Adolescents AR101 Efficacy at 12-Month DBPCFC in PALISADE1 AR101 Safety Profile in PALISADE1 and RAMSES Robust: Median tolerated dose increased 100-fold, up to ~3-4 peanuts (~6-8 peanuts, cumulatively) Reliable: 80% of AR101 participants completed the study, and nearly all tolerated the equivalent of ~ 1 peanut; 63% tolerated 1,000 mg (cumulative 2,043 mg) After desensitization, the exit food challenge results showed that AR101 reduced frequency and severity of allergic reactions to amounts of peanut protein typical of real-world accidental exposures Treatment-emergent adverse events (TEAEs) were common in both AR101 and placebo groups Vast majority of participants experienced mild/moderate symptoms in both trials TEAEs were lower in maintenance in PALISADE (no maintenance in RAMSES) Epinephrine use was infrequent and not a surrogate of anaphylaxis or symptom severity Low instances of anaphylaxis and EoE 1 Vickery et al., NEJM, November 18, 2018 (online publication)
PALISADE Phase 3 Results Published in NEJM (Nov 18, 2018) “…treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo.” Vickery et al., NEJM, November 18, 2018 (online publication)
Aiming to Deliver on Our Promise to the Food Allergy Community Next year, AR101 could be the first approved treatment for peanut allergy Biologics License Application (BLA) for AR101 is on track for submission to the U.S. Food and Drug Administration (FDA) in December 2018 as planned; Marketing Authorisation Application (MAA) for Europe in mid-2019 also on track The recently announced investment of $98 million from Nestlé Health Science*, combined with our $255 million of cash as of the end of 3Q 2018, puts us in a great position to: Deliver AR101 to patients in the United States Continue to advance AR101 in Europe Develop our pipeline of treatments for other food allergies *Transaction expected to close in 2018