DBV Technologies S.A 6-K, filed Jan 13, 2020
DBV Technologies S.A. (DBVT)
About this 6-K
DBV Technologies S.A filed this 6-K on January 13, 2020.
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 6-K
REPORT OF FOREIGN PRIVATE ISSUER
PURSUANT TO RULE 13a-16 OR 15d-16
UNDER THE SECURITIES EXCHANGE ACT OF 1934
For the Month of January 2020
Commission File Number: 001-36697
DBV TECHNOLOGIES S.A.
(Translation of registrant’s name into English)
177-181 avenue Pierre Brossolette
92120 Montrouge France
(Address of principal executive office)
Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F:
☒ Form 20-F ☐ Form 40-F
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1): ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ☐
EXPLANATORY NOTE
On January 13, 2020, DBV Technologies S.A. updated its corporate presentation that it intends to use in conferences and meetings with investors. A copy of the presentation is furnished with this Report of Foreign Private Issuer on Form 6-K as Exhibit 99.1 and is incorporated herein by reference.
EXHIBIT LIST
| Exhibit |
Description | |
| 99.1 | Corporate Presentation of DBV Technologies S.A. dated January 2020. | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| DBV TECHNOLOGIES S.A. | ||||||
| Date: January 13, 2020 | By: | /s/ Ramzi Benamar | ||||
| Name: | Ramzi Benamar | |||||
| Title: | Chief Financial Officer | |||||
Exhibit 99.1 Unlocking the Powerful Immune Properties of the Skin to Offer Innovative Treatments to Patients January 2020Exhibit 99.1 Unlocking the Powerful Immune Properties of the Skin to Offer Innovative Treatments to Patients January 2020
Safe Harbor This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of DBV’s clinical trials; its ability to successfully gain regulatory approvals and commercialize products; its ability to successfully advance its pipeline of product candidates; the rate and degree of market acceptance of its products; and its ability to develop sales and marketing capabilities. Forward looking statements are subject to a number of risks, uncertainties and assumptions. Moreover, DBV operates in a very competitive and rapidly changing environment. New risks emerge from time to time. It is not possible for DBV’s management to predict all risks, nor can DBV assess the impact of all factors on its business or the extent to which any factor, or combination of factors, may cause actual results to differ materially fromthose containedinany forwardlookingstatementsit may make. In light of these risks, uncertainties and assumptions, the forward looking events and circumstances discussed in this presentation may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward looking statements. You should not rely upon forward looking statements as predictions of future events. Although DBV believes that the expectations reflected in the forward looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward looking statements will be achieved or occur. Moreover, except as required by law, neither DBV nor any other person assumes responsibility for the accuracy and completeness of the forward looking statements. Forward looking statements in this presentation represent DBV’s views only as of the date of this presentation. DBV undertakes no obligation to update or review any forward looking statement, whether as a result of new information, future developments or otherwise, except as required by law. Epicutaneous immunotherapy and Viaskin® Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 2Safe Harbor This presentation contains forward looking statements including, but not limited to, statements concerning the outcome or success of DBV’s clinical trials; its ability to successfully gain regulatory approvals and commercialize products; its ability to successfully advance its pipeline of product candidates; the rate and degree of market acceptance of its products; and its ability to develop sales and marketing capabilities. Forward looking statements are subject to a number of risks, uncertainties and assumptions. Moreover, DBV operates in a very competitive and rapidly changing environment. New risks emerge from time to time. It is not possible for DBV’s management to predict all risks, nor can DBV assess the impact of all factors on its business or the extent to which any factor, or combination of factors, may cause actual results to differ materially fromthose containedinany forwardlookingstatementsit may make. In light of these risks, uncertainties and assumptions, the forward looking events and circumstances discussed in this presentation may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward looking statements. You should not rely upon forward looking statements as predictions of future events. Although DBV believes that the expectations reflected in the forward looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward looking statements will be achieved or occur. Moreover, except as required by law, neither DBV nor any other person assumes responsibility for the accuracy and completeness of the forward looking statements. Forward looking statements in this presentation represent DBV’s views only as of the date of this presentation. DBV undertakes no obligation to update or review any forward looking statement, whether as a result of new information, future developments or otherwise, except as required by law. Epicutaneous immunotherapy and Viaskin® Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 2
Pioneering a New Class of Immunotherapy We are focused on discovering, developing and commercializing our novel skin immunotherapy product candidates using our proprietary Viaskin® Technology Platform TM • Epicutaneous immunotherapy (EPIT ) targets the immune system via intact skin with the Viaskin patch • Antigen does not enter the bloodstream, as observed in animal models • EPIT has the potential to modify the immune response in a durable way to provide clinically meaningful desensitization over time for treating food allergies • Proprietary manufacturing equipment and process designed, engineered and developed by DBV 3 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.Pioneering a New Class of Immunotherapy We are focused on discovering, developing and commercializing our novel skin immunotherapy product candidates using our proprietary Viaskin® Technology Platform TM • Epicutaneous immunotherapy (EPIT ) targets the immune system via intact skin with the Viaskin patch • Antigen does not enter the bloodstream, as observed in animal models • EPIT has the potential to modify the immune response in a durable way to provide clinically meaningful desensitization over time for treating food allergies • Proprietary manufacturing equipment and process designed, engineered and developed by DBV 3 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.
Merging Science and Technology to Develop Novel Viaskin Technology Platform Patented electrostatic EPIT Activates the Immune System patch with Through Intact Skin condensation chamber allows the antigen to penetrate upper layer Electrospray: patented of epidermis patch manufacturing technology that allows for precise antigen deposits without adjuvants Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 4 Dioszeghy V, et al. J Immunol. 2011;186:5629-5637. Mondoulet L, et al. Immunotherapy. 2015;7:1293-1305.Merging Science and Technology to Develop Novel Viaskin Technology Platform Patented electrostatic EPIT Activates the Immune System patch with Through Intact Skin condensation chamber allows the antigen to penetrate upper layer Electrospray: patented of epidermis patch manufacturing technology that allows for precise antigen deposits without adjuvants Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 4 Dioszeghy V, et al. J Immunol. 2011;186:5629-5637. Mondoulet L, et al. Immunotherapy. 2015;7:1293-1305.
Significant Achievements in 2019 Provide Path to Potential U.S. Approval of Viaskin Peanut in 2H 2020 2019 1H 2020 2H 2020 ü Viaskin Peanut BLA accepted for review by US FDA on ü PEOPLE 3-year results showed • Viaskin Peanut Target Action Oct. 4, 2019 durable, long-term clinical benefit Date of August 5, 2020 with an additional two years of ü Expansion of leadership team to meet needs of treatment • Potential US launch of Viaskin evolving organization Peanut, if approved • EPITOPE Part A results and ü Ramzi Benamar joined as CFO on Jan. 6, 2020, bringing expectations for enrollment • Potential EMA filing for deep biotechnology financial operations experience ü Dr. Pharis Mohideen joined as CMO, bringing extensive completion of Part B Viaskin Peanut clinical drug development experience ü Adam Slatter joined as Head of Quality, PAI readiness • Anticipated Viaskin Peanut FDA preparation underway Advisory Committee ü Increased cash position to support Viaskin Peanut pre-commercialization ü Cash position of €195.8M as of 3Q 2019* • Organizational structure in place to support evolution into a potential commercial-stage company • U.S. launch preparation ongoing with experienced commercial team in place in Summit, NJ 5 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *3Q 2019 cash position of €73.0 million + approximately €122.8 million in net proceeds from October 2019 financingSignificant Achievements in 2019 Provide Path to Potential U.S. Approval of Viaskin Peanut in 2H 2020 2019 1H 2020 2H 2020 ü Viaskin Peanut BLA accepted for review by US FDA on ü PEOPLE 3-year results showed • Viaskin Peanut Target Action Oct. 4, 2019 durable, long-term clinical benefit Date of August 5, 2020 with an additional two years of ü Expansion of leadership team to meet needs of treatment • Potential US launch of Viaskin evolving organization Peanut, if approved • EPITOPE Part A results and ü Ramzi Benamar joined as CFO on Jan. 6, 2020, bringing expectations for enrollment • Potential EMA filing for deep biotechnology financial operations experience ü Dr. Pharis Mohideen joined as CMO, bringing extensive completion of Part B Viaskin Peanut clinical drug development experience ü Adam Slatter joined as Head of Quality, PAI readiness • Anticipated Viaskin Peanut FDA preparation underway Advisory Committee ü Increased cash position to support Viaskin Peanut pre-commercialization ü Cash position of €195.8M as of 3Q 2019* • Organizational structure in place to support evolution into a potential commercial-stage company • U.S. launch preparation ongoing with experienced commercial team in place in Summit, NJ 5 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *3Q 2019 cash position of €73.0 million + approximately €122.8 million in net proceeds from October 2019 financing
Peanut Allergy Places Major Burden on Patients, Families and Society 1 • 859,000 children ages 4-11 are diagnosed with peanut allergy in the United States 2 Significant Prevalence • Most peanut allergy patients are diagnosed by 5 years of age and 80% will not outgrow their allergy Especially in Children • All peanut-allergic children are at risk of having a severe life-threatening reaction, even if they’ve had only 3 mild reactions in the past 4 • 23% of patients with peanut allergy visit the ER annually for food allergy events and every three minutes a 5 Direct & Indirect Costs Are child goes to the emergency room for an allergic reaction to food 6 Major Burden to Health Care • $4.3B in direct medical costs each year for food allergy in the United States 7 • The estimated indirect economic cost of any food allergy in US children at more than $20 billion annually • Fear of life-threatening reactions triggered by everyday activities leads to increased anxiety and decreased 8, 9, 10 quality of life for patients and their families Peanut Allergy Quality of Life • More than 50% of parents have missed important school functions, altered vacation plans and left a 11 is Impacted restaurant because of their child’s food allergy • When asked how often parents think about their child’s food allergy, 82% say it’s always in the back of their 11 minds Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 1. Data on file. DBV analytics. 2. FARE Peanut Allergy; Neuman-Sunshine 2012; Skolnick 2001. 3. Boyce (NIAID Guidelines) 2010, 4. 2019 Gupta et al Caregiver Survey (0-18YO) 5. Clark S, Espinola J, Rudders SA, Banerji, A, Camargo CA. Frequency of US emergency department visits for food-related acute allergic reactions. J Allergy Clin Immunol. 2011; 127(3):682-683 6. Gupta JAMA Pediatrics 2013. 7. Cannon, H. Eric, PharmD, FAMCP. The Economic Impact of Peanut Allergies. AJMC, 2012. 8. Greenhawt M, et al. Ann Allergy 6 Asthma Immunol. 2018; 121: 575-579. 9. Stallings VA, Oria MP. National Academies Press (US). 2017. 10. Birdi G, et al. J Allergy (Cairo). 2016; 2016:1497375. 11. Asthma and Allergy Foundation of America. (2019). My Life With Food Allergy: Parent Survey Report. Retrieved from aafa.org/foodallergylifePeanut Allergy Places Major Burden on Patients, Families and Society 1 • 859,000 children ages 4-11 are diagnosed with peanut allergy in the United States 2 Significant Prevalence • Most peanut allergy patients are diagnosed by 5 years of age and 80% will not outgrow their allergy Especially in Children • All peanut-allergic children are at risk of having a severe life-threatening reaction, even if they’ve had only 3 mild reactions in the past 4 • 23% of patients with peanut allergy visit the ER annually for food allergy events and every three minutes a 5 Direct & Indirect Costs Are child goes to the emergency room for an allergic reaction to food 6 Major Burden to Health Care • $4.3B in direct medical costs each year for food allergy in the United States 7 • The estimated indirect economic cost of any food allergy in US children at more than $20 billion annually • Fear of life-threatening reactions triggered by everyday activities leads to increased anxiety and decreased 8, 9, 10 quality of life for patients and their families Peanut Allergy Quality of Life • More than 50% of parents have missed important school functions, altered vacation plans and left a 11 is Impacted restaurant because of their child’s food allergy • When asked how often parents think about their child’s food allergy, 82% say it’s always in the back of their 11 minds Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 1. Data on file. DBV analytics. 2. FARE Peanut Allergy; Neuman-Sunshine 2012; Skolnick 2001. 3. Boyce (NIAID Guidelines) 2010, 4. 2019 Gupta et al Caregiver Survey (0-18YO) 5. Clark S, Espinola J, Rudders SA, Banerji, A, Camargo CA. Frequency of US emergency department visits for food-related acute allergic reactions. J Allergy Clin Immunol. 2011; 127(3):682-683 6. Gupta JAMA Pediatrics 2013. 7. Cannon, H. Eric, PharmD, FAMCP. The Economic Impact of Peanut Allergies. AJMC, 2012. 8. Greenhawt M, et al. Ann Allergy 6 Asthma Immunol. 2018; 121: 575-579. 9. Stallings VA, Oria MP. National Academies Press (US). 2017. 10. Birdi G, et al. J Allergy (Cairo). 2016; 2016:1497375. 11. Asthma and Allergy Foundation of America. (2019). My Life With Food Allergy: Parent Survey Report. Retrieved from aafa.org/foodallergylife
Avoidance Isn’t Enough for Patients: Goal Is to Offer Additional Protection to Address This Unmet Need 1,2 Top Priority Treatment Goals for Caregivers and Physicians are the Same--They Are Seeking a Treatment That: 1. Reduces the likelihood of an allergic reaction in case of accidental exposure 2. Low risk of a serious reaction caused by the treatment and low side effects 3. Treatment is accepted by the caregiver and child Quantitative modeling suggests desensitization therapies could offer significant reduction of the risks associated with 3, 4, 5 accidental exposures by increasing the dose of peanut protein at which patients react (the eliciting dose) 1 mg 3 mg 10 mg 30 mg 100 mg 300 mg 1000 mg 1 peanut is ~250-300 mg >95% Risk Reduction* Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 1. Greenhawt M, et al. Ann Allergy Asthma Immunol. https://doi.org/10.1016/j.anai.2018.06.018 2. Based on primary market research among 100 allergists in the United States. Survey question: If a new peanut allergy desensitization treatment for children 4 to 11 years of age became FDA approved and available for use, what would be the importance of each of the following attributes to you? Please use a 0- to 7-point scale where 0 means “not at all important to me” and 7 means “very important to me.” 3. Remington, B, et al. Ann Allergy Asthma Immunol. doi: http://dx.doi.org/10.1016/j.anai.2017.08.224, Baumert JL, et al. J Allergy Clin Immunol Pract. 2017. doi:10.1016/j.jaip.2017.05.006. 4. Shreffler W, et al. Ann Allergy Asthma Immunol 2017; 1081-1206. 5. Remington, B et al. ACAAI 2018 #A302. 7 *The QRA model inputs variables including the clinical threshold for peanut-allergic individuals and the exposure dose of peanut residue to predict the allergenic risk associated with the exposure to residual peanut protein. This model is based on a previous model and was modified to incorporate a Bayesian framework to better estimate the risk of allergic reaction.Avoidance Isn’t Enough for Patients: Goal Is to Offer Additional Protection to Address This Unmet Need 1,2 Top Priority Treatment Goals for Caregivers and Physicians are the Same--They Are Seeking a Treatment That: 1. Reduces the likelihood of an allergic reaction in case of accidental exposure 2. Low risk of a serious reaction caused by the treatment and low side effects 3. Treatment is accepted by the caregiver and child Quantitative modeling suggests desensitization therapies could offer significant reduction of the risks associated with 3, 4, 5 accidental exposures by increasing the dose of peanut protein at which patients react (the eliciting dose) 1 mg 3 mg 10 mg 30 mg 100 mg 300 mg 1000 mg 1 peanut is ~250-300 mg >95% Risk Reduction* Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 1. Greenhawt M, et al. Ann Allergy Asthma Immunol. https://doi.org/10.1016/j.anai.2018.06.018 2. Based on primary market research among 100 allergists in the United States. Survey question: If a new peanut allergy desensitization treatment for children 4 to 11 years of age became FDA approved and available for use, what would be the importance of each of the following attributes to you? Please use a 0- to 7-point scale where 0 means “not at all important to me” and 7 means “very important to me.” 3. Remington, B, et al. Ann Allergy Asthma Immunol. doi: http://dx.doi.org/10.1016/j.anai.2017.08.224, Baumert JL, et al. J Allergy Clin Immunol Pract. 2017. doi:10.1016/j.jaip.2017.05.006. 4. Shreffler W, et al. Ann Allergy Asthma Immunol 2017; 1081-1206. 5. Remington, B et al. ACAAI 2018 #A302. 7 *The QRA model inputs variables including the clinical threshold for peanut-allergic individuals and the exposure dose of peanut residue to predict the allergenic risk associated with the exposure to residual peanut protein. This model is based on a previous model and was modified to incorporate a Bayesian framework to better estimate the risk of allergic reaction.
Epicutaneous Immunotherapy Is an Innovative Approach to Potentially Offer Long-Term Benefit Protection from Long-Term Sustained Accidental Exposure Maintenance of Effect Unresponsiveness EPIT Utilizes the Immune Tolerizing Large Dataset of 141 Children Treated OLFUS and PEOPLE Show Potential for Properties of the Skin for Three Years in PEOPLE Sustained Protection ü Differentiated proposed mechanism, ü Patients demonstrated durable, long-ü Month-38 DBPCFC to explore including potentially promoting term clinical benefit with an “sustained unresponsiveness” sustained effect additional two years of treatmentü In PEOPLE, 77.8% (14/18) of the ü Takes time for immune system to ü Low discontinuations due to adverse children who completed the oral induce protective response events observed food challenge at Month 38, after ü EPIT-induced Tregs observed to have ü Largest long-term peanut allergy two months off treatment with pronounced immunosuppressive immunotherapy trial to date, with peanut-free diet,* maintained functionality high compliance enabling extended desensitization with an ED ≥1,000 mg study participation Ultimate goal of any food allergen immunotherapy is long-term tolerance 8 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *All participants who reached an ED ≥ 1,000 mg at Month 36 were eligible to continue the study for two additional months without treatment and required to maintain a peanut-free diet. An oral food challenge was administered at the end of this period (Month 38). Epicutaneous Immunotherapy Is an Innovative Approach to Potentially Offer Long-Term Benefit Protection from Long-Term Sustained Accidental Exposure Maintenance of Effect Unresponsiveness EPIT Utilizes the Immune Tolerizing Large Dataset of 141 Children Treated OLFUS and PEOPLE Show Potential for Properties of the Skin for Three Years in PEOPLE Sustained Protection ü Differentiated proposed mechanism, ü Patients demonstrated durable, long-ü Month-38 DBPCFC to explore including potentially promoting term clinical benefit with an “sustained unresponsiveness” sustained effect additional two years of treatmentü In PEOPLE, 77.8% (14/18) of the ü Takes time for immune system to ü Low discontinuations due to adverse children who completed the oral induce protective response events observed food challenge at Month 38, after ü EPIT-induced Tregs observed to have ü Largest long-term peanut allergy two months off treatment with pronounced immunosuppressive immunotherapy trial to date, with peanut-free diet,* maintained functionality high compliance enabling extended desensitization with an ED ≥1,000 mg study participation Ultimate goal of any food allergen immunotherapy is long-term tolerance 8 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *All participants who reached an ED ≥ 1,000 mg at Month 36 were eligible to continue the study for two additional months without treatment and required to maintain a peanut-free diet. An oral food challenge was administered at the end of this period (Month 38).
Viaskin Peanut May Offer A Convenient, Easy-to-Use Treatment for Patients and Their Families • Small patch, ~1” square • Single, daily 250 µg patch applied to the back of peanut- allergic children offering constant dosing • 2-week treatment initiation leading to 24-hour wear time • Applied once daily at home on a schedule that fits the household • No restrictions to daily activities required • No consumption/ingestion of peanut required In study of 200 peanut-allergic children, children expressed a preference for a patch treatment option over an oral 1 treatment option, mainly due to perceived difficulty of therapy administration and fear of ingesting peanuts 9 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 1. Greenhawt M, et al. Presented at: Annual Meeting of the American College of Allergy, Asthma & Immunology. November 7-11, 2019; Houston, TX. Abstract #D302.Viaskin Peanut May Offer A Convenient, Easy-to-Use Treatment for Patients and Their Families • Small patch, ~1” square • Single, daily 250 µg patch applied to the back of peanut- allergic children offering constant dosing • 2-week treatment initiation leading to 24-hour wear time • Applied once daily at home on a schedule that fits the household • No restrictions to daily activities required • No consumption/ingestion of peanut required In study of 200 peanut-allergic children, children expressed a preference for a patch treatment option over an oral 1 treatment option, mainly due to perceived difficulty of therapy administration and fear of ingesting peanuts 9 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 1. Greenhawt M, et al. Presented at: Annual Meeting of the American College of Allergy, Asthma & Immunology. November 7-11, 2019; Houston, TX. Abstract #D302.
Viaskin Peanut Leads Our Food Allergy Pipeline with a Long-Term, Focused Clinical Program 1575 patient-years to date in Phase III program Consistent treatment benefit observed in multiple trials Year 1 Year 2 Year 3 Year 4 Year 5 VIPES OLFUS-VIPES DBPC Open Label Extension 6-55 y.o N=221 6-55 y.o. N=171 ARACHILD DBPC Phase Open Label Phase Phase 2 5-17 y.o. N=54 5-17 y.o. N=30 CoFAR6 DBPC Phase Open Label Phase 4-25 y.o. N=74 4-25 y.o. N=66 PEPITES PEOPLE DBPC Open Label Extension 4-11 y.o. N=356 4-11 y.o. N=298 REALISE DBPC Phase Open-Label Phase Phase 3 4-11 y.o., N=393 4-11 y.o. N=383 EPITOPE EPOPEX DBPC Open Label Extension 1-3 y.o. N=400 1-3 y.o. Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 1 Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113, #L32. 2 Sampson et al. JAMA. 2017;318(18):1798-1809. doi:10.1001/jama.2017.16591; Shreffler et al. AAAAI 2017, #L7 3 Remington B, et al. Quantitative Risk Reduction Through Epicutaneous 10 Immunotherapy: Results From The PEPITES Phase III Trial. Annals of Allergy, Asthma & Immunology, Vol. 121, Issue 5; Nov 2018, Page S11 4 Dunn Galvin A, et al. Improvements in Quality of Life Following Peanut Epicutaneous Immunotherapy: PEPITES and PEOPLE Studies; Nov 2019.Viaskin Peanut Leads Our Food Allergy Pipeline with a Long-Term, Focused Clinical Program 1575 patient-years to date in Phase III program Consistent treatment benefit observed in multiple trials Year 1 Year 2 Year 3 Year 4 Year 5 VIPES OLFUS-VIPES DBPC Open Label Extension 6-55 y.o N=221 6-55 y.o. N=171 ARACHILD DBPC Phase Open Label Phase Phase 2 5-17 y.o. N=54 5-17 y.o. N=30 CoFAR6 DBPC Phase Open Label Phase 4-25 y.o. N=74 4-25 y.o. N=66 PEPITES PEOPLE DBPC Open Label Extension 4-11 y.o. N=356 4-11 y.o. N=298 REALISE DBPC Phase Open-Label Phase Phase 3 4-11 y.o., N=393 4-11 y.o. N=383 EPITOPE EPOPEX DBPC Open Label Extension 1-3 y.o. N=400 1-3 y.o. Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 1 Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113, #L32. 2 Sampson et al. JAMA. 2017;318(18):1798-1809. doi:10.1001/jama.2017.16591; Shreffler et al. AAAAI 2017, #L7 3 Remington B, et al. Quantitative Risk Reduction Through Epicutaneous 10 Immunotherapy: Results From The PEPITES Phase III Trial. Annals of Allergy, Asthma & Immunology, Vol. 121, Issue 5; Nov 2018, Page S11 4 Dunn Galvin A, et al. Improvements in Quality of Life Following Peanut Epicutaneous Immunotherapy: PEPITES and PEOPLE Studies; Nov 2019.
PEPITES Pivotal Phase III Trial Results (Fleischer, JAMA 2019) Placebo Pivotal Global Randomized DBPC Phase 3 Trial Screening • 356 children aged 4 to 11 years 250 µg • 31 study locations (United States, Canada, Australia, Germany, and Ireland) M12 M0 NCT02636699 DBPCFC Randomization* † Primary Endpoint Food Challenge Symptom Scoring • Food challenges were discontinued when objective signs/symptoms Treatment responder definition (assessed using DBPCFC) emerged meeting prespecified stopping criteria requiring treatment • For patients with a M0 ED ≤10 mg: responder if ED ≥300 mg at M12 • Subjective symptoms (eg, abdominal pain or oropharyngeal itching) • For patients with a M0 ED > 10 mg and ≤300 mg: responder if ED were assessed and recorded, but alone were insufficient to stop the ≥1000 mg at M12 challenge Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. † *Subjects were randomized 2:1, stratified by ED, to receive either Viaskin Peanut 250 µg or placebo patch. A threshold of 15% or more on the lower bound of a 95% CI around responder rate difference was prespecified to determine a positive trial result. The 1 prespecified 15% lower bound of the 95% CI of the difference between treatment groups was not met (95% CI:12.4, 29.8) in the PEPITES trial. The authors of the JAMA publication concluded that the clinical relevance of this is not known. 11 DBPC= double-blind, placebo-controlled; DBPCFC=DBPC food challenge; ED=eliciting dose; M=month. 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113.PEPITES Pivotal Phase III Trial Results (Fleischer, JAMA 2019) Placebo Pivotal Global Randomized DBPC Phase 3 Trial Screening • 356 children aged 4 to 11 years 250 µg • 31 study locations (United States, Canada, Australia, Germany, and Ireland) M12 M0 NCT02636699 DBPCFC Randomization* † Primary Endpoint Food Challenge Symptom Scoring • Food challenges were discontinued when objective signs/symptoms Treatment responder definition (assessed using DBPCFC) emerged meeting prespecified stopping criteria requiring treatment • For patients with a M0 ED ≤10 mg: responder if ED ≥300 mg at M12 • Subjective symptoms (eg, abdominal pain or oropharyngeal itching) • For patients with a M0 ED > 10 mg and ≤300 mg: responder if ED were assessed and recorded, but alone were insufficient to stop the ≥1000 mg at M12 challenge Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. † *Subjects were randomized 2:1, stratified by ED, to receive either Viaskin Peanut 250 µg or placebo patch. A threshold of 15% or more on the lower bound of a 95% CI around responder rate difference was prespecified to determine a positive trial result. The 1 prespecified 15% lower bound of the 95% CI of the difference between treatment groups was not met (95% CI:12.4, 29.8) in the PEPITES trial. The authors of the JAMA publication concluded that the clinical relevance of this is not known. 11 DBPC= double-blind, placebo-controlled; DBPCFC=DBPC food challenge; ED=eliciting dose; M=month. 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113.
Data from Phase II and III Studies Showed Statistically Significant Treatment Effect • After 12 months, a significantly larger percentage 1 of participants responded to Viaskin Peanut Response Rate (ITT) treatment vs placebo patch 35.3% vs 13.6% 40 1 P<0.001 (P<0.001) 35 − The prespecified 15% lower bound of the 95% CI of the difference between treatment groups was not 35.3% 30 met (95% CI: 12.4, 29.8) Δ= 21.7% 25 − Per JAMA publication, the clinical relevance in food (95% CI: 12.4, 29.8) allergy is unknown 20 • Favorable tolerability observed in clinical trials of 15 Viaskin Peanut to date 10 13.6% • Over 95% compliance observed for up to three years of treatment 5 • Treatment as measured by changes in ED at 0 Month 12 DBPCFC resulted in significant Placebo Viaskin Peanut 250 μg 2 improvement in HRQL n=118 n=238 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 12 CI=confidence interval; ITT=intention-to-treat; HQRL=health-related quality of life. 1 Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2. Dunn Galvin A, et al. Presented at: Annual Meeting of the American College of Allergy, Asthma & Immunology. November 7-11, 2019; Houston, TX. Abstract #D303Data from Phase II and III Studies Showed Statistically Significant Treatment Effect • After 12 months, a significantly larger percentage 1 of participants responded to Viaskin Peanut Response Rate (ITT) treatment vs placebo patch 35.3% vs 13.6% 40 1 P<0.001 (P<0.001) 35 − The prespecified 15% lower bound of the 95% CI of the difference between treatment groups was not 35.3% 30 met (95% CI: 12.4, 29.8) Δ= 21.7% 25 − Per JAMA publication, the clinical relevance in food (95% CI: 12.4, 29.8) allergy is unknown 20 • Favorable tolerability observed in clinical trials of 15 Viaskin Peanut to date 10 13.6% • Over 95% compliance observed for up to three years of treatment 5 • Treatment as measured by changes in ED at 0 Month 12 DBPCFC resulted in significant Placebo Viaskin Peanut 250 μg 2 improvement in HRQL n=118 n=238 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 12 CI=confidence interval; ITT=intention-to-treat; HQRL=health-related quality of life. 1 Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2. Dunn Galvin A, et al. Presented at: Annual Meeting of the American College of Allergy, Asthma & Immunology. November 7-11, 2019; Houston, TX. Abstract #D303
Quantitative Risk Assessment Modeling Suggests Reduced Risk of Accidental Ingestion Reactions Change in ED in Children 4 to 11 years of 1,3† age after 12 months 100% ED Increase • In a post-hoc analysis, 53.1% of >4x more likely in subjects on Viaskin Peanut 250 µg ED Stable Viaskin Peanut 28.0% 250 µg group increased their baseline ED from ED Decrease 80% (OR=4.3) ≤100 mg to ≥300 mg, vs only 19% on 1 placebo patch 62.6% − Based on risk assessment modeling, 60% raising ED from ≤100 mg to ≥300 mg is 38.1% predicted to reduce the risk of reactions due to accidental 2, exposure by >95% * 40% − An increase in ED was 4 times more likely to occur in the Viaskin Peanut 3 30.7% group compared to placebo (OR=4.3) 20% >7x more 33.9% likely in − Odds of a decrease in ED were 7-times placebo group more likely in the placebo group (OR=7.1) 6.7% compared to the active group 0% 3 Placebo (n=118) VP250 µg (n=238) (OR=7.1) Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 2 *Based on quantitative risk assessment modeling using national database of consumption data and levels of peanut protein contamination for selected pre-packaged foods. † 3 Based on ITT population; missing data calculated using mBOCF. ITT=intention-to-treat; mBOCF=modified baseline carried forward; OR=odds ratio; VP=Viaskin Peanut. 13 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2. Baumert JL, et al. J Allergy Clin Immunol Pract. 2018;6:457-465. 3. Davis, Carla, et al. Presented at: Annual Meeting of the American College of Allergy, Asthma & Immunology, Seattle, Washington, November 15-19, 2018. Abstract #A303 Percent of Subjects Percent of Responders (%)Quantitative Risk Assessment Modeling Suggests Reduced Risk of Accidental Ingestion Reactions Change in ED in Children 4 to 11 years of 1,3† age after 12 months 100% ED Increase • In a post-hoc analysis, 53.1% of >4x more likely in subjects on Viaskin Peanut 250 µg ED Stable Viaskin Peanut 28.0% 250 µg group increased their baseline ED from ED Decrease 80% (OR=4.3) ≤100 mg to ≥300 mg, vs only 19% on 1 placebo patch 62.6% − Based on risk assessment modeling, 60% raising ED from ≤100 mg to ≥300 mg is 38.1% predicted to reduce the risk of reactions due to accidental 2, exposure by >95% * 40% − An increase in ED was 4 times more likely to occur in the Viaskin Peanut 3 30.7% group compared to placebo (OR=4.3) 20% >7x more 33.9% likely in − Odds of a decrease in ED were 7-times placebo group more likely in the placebo group (OR=7.1) 6.7% compared to the active group 0% 3 Placebo (n=118) VP250 µg (n=238) (OR=7.1) Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 2 *Based on quantitative risk assessment modeling using national database of consumption data and levels of peanut protein contamination for selected pre-packaged foods. † 3 Based on ITT population; missing data calculated using mBOCF. ITT=intention-to-treat; mBOCF=modified baseline carried forward; OR=odds ratio; VP=Viaskin Peanut. 13 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2. Baumert JL, et al. J Allergy Clin Immunol Pract. 2018;6:457-465. 3. Davis, Carla, et al. Presented at: Annual Meeting of the American College of Allergy, Asthma & Immunology, Seattle, Washington, November 15-19, 2018. Abstract #A303 Percent of Subjects Percent of Responders (%)
Treatment Adherence Is High While Discontinuation Due to AEs is Low • 89.9% of all subjects completed the study, with similar discontinuation rates observed between treatment groups (10.5% in Viaskin Peanut group, 9.3% in placebo group) EPIT has a very • Treatment adherence* was high (98.5%) across the total population, and comparable between low rate of side groups effects and may • 4/238 (1.7%) subjects treated with Viaskin Peanut discontinued due to TEAEs; there were no require fewer severe cases of anaphylaxis − 2 due to moderate anaphylaxis; 2 due to skin reactions ≤ grade 3 clinical 3 • Viaskin Peanut 250 µg: 12 SAEs** in 10 participants (4.2%); Placebo: 6 SAEs in 6 participants resources (5.1%) − 4 SAEs in 3 Viaskin Peanut participants considered related to treatment (1 probably related, 3 possibly related) − All were moderate anaphylaxis without evidence of cardiovascular, neurologic, or respiratory compromise − All resolved with standard treatment, including 1 dose of epinephrine per participant Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *Defined as the total number of patches applied in the treatment period divided by the number of days in that period **Serious AE defined according to the International Conference on Harmonization-Good Clinical Practice as any untoward medical occurrence that at any dose results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; is an important medical event that may not be immediately life-threatening or result in death or hospitalization but that may jeopardize the participant or require 14 intervention to prevent one of the above outcomes. 1 Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2 DBV Technologies. Data on file, 2019. 3 Pamela A. Guerrerio, MD, PhD, National Institutes of Health, Sept 13, 2019. Treatment Adherence Is High While Discontinuation Due to AEs is Low • 89.9% of all subjects completed the study, with similar discontinuation rates observed between treatment groups (10.5% in Viaskin Peanut group, 9.3% in placebo group) EPIT has a very • Treatment adherence* was high (98.5%) across the total population, and comparable between low rate of side groups effects and may • 4/238 (1.7%) subjects treated with Viaskin Peanut discontinued due to TEAEs; there were no require fewer severe cases of anaphylaxis − 2 due to moderate anaphylaxis; 2 due to skin reactions ≤ grade 3 clinical 3 • Viaskin Peanut 250 µg: 12 SAEs** in 10 participants (4.2%); Placebo: 6 SAEs in 6 participants resources (5.1%) − 4 SAEs in 3 Viaskin Peanut participants considered related to treatment (1 probably related, 3 possibly related) − All were moderate anaphylaxis without evidence of cardiovascular, neurologic, or respiratory compromise − All resolved with standard treatment, including 1 dose of epinephrine per participant Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *Defined as the total number of patches applied in the treatment period divided by the number of days in that period **Serious AE defined according to the International Conference on Harmonization-Good Clinical Practice as any untoward medical occurrence that at any dose results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; is an important medical event that may not be immediately life-threatening or result in death or hospitalization but that may jeopardize the participant or require 14 intervention to prevent one of the above outcomes. 1 Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2 DBV Technologies. Data on file, 2019. 3 Pamela A. Guerrerio, MD, PhD, National Institutes of Health, Sept 13, 2019.
PEOPLE: Largest Long-Term Peanut Allergy Immunotherapy Trial to Date M36 M38 M48 M60 PEPITES PEOPLE M24 N=356 213 198 184 148 250 µg (n=238) SU 4-11 years Placebo (n=118) SU 107 100 91 83 Roll-over M0 to 250 μg M12 M12 M24 M36 M38 M48 M60 93% of patients that completed PEPITES enrolled in PEOPLE Double-blind, placebo-controlled food challenge. Viaskin Peanut 250 µg (PEPITES) à Viaskin Peanut 250 µg (PEOPLE) Populations Placebo (PEPITES) à Viaskin Peanut 250 µg (PEOPLE) • Completers*=148 PEOPLE key efficacy measurement • Per Protocol (PP)=141 • Percentage of patients reaching an ED ≥1000 mg after • Full Analysis Set for Safety=198 24 months of additional treatment with 250 μg Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. ED=eliciting dose; SU=sustained unresponsiveness. 15 *The population for the key efficacy measurement per the Statistical Analysis Plan submitted to FDA. 1. Fleischer DM, et al. JAMA. 2019;321:946-955.PEOPLE: Largest Long-Term Peanut Allergy Immunotherapy Trial to Date M36 M38 M48 M60 PEPITES PEOPLE M24 N=356 213 198 184 148 250 µg (n=238) SU 4-11 years Placebo (n=118) SU 107 100 91 83 Roll-over M0 to 250 μg M12 M12 M24 M36 M38 M48 M60 93% of patients that completed PEPITES enrolled in PEOPLE Double-blind, placebo-controlled food challenge. Viaskin Peanut 250 µg (PEPITES) à Viaskin Peanut 250 µg (PEOPLE) Populations Placebo (PEPITES) à Viaskin Peanut 250 µg (PEOPLE) • Completers*=148 PEOPLE key efficacy measurement • Per Protocol (PP)=141 • Percentage of patients reaching an ED ≥1000 mg after • Full Analysis Set for Safety=198 24 months of additional treatment with 250 μg Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. ED=eliciting dose; SU=sustained unresponsiveness. 15 *The population for the key efficacy measurement per the Statistical Analysis Plan submitted to FDA. 1. Fleischer DM, et al. JAMA. 2019;321:946-955.
Clinically Meaningful Changes in Eliciting Dose Maintained or Improved Over 3 Years PEOPLE PP (N=141) % of Patients M0 M12 M36 • 75.9% (107/141) demonstrated an increase in ED from baseline (M0) to Month 36 4 18 >2000* 14 6 2000 • 51.8% (73/141) reached an ED of ≥1,000 mg at 22 27 1000 Month 36 35 32 25 300 − 40.4% (57/141) reached an ED of ≥1,000 mg at 40 23 16 100 † Month 12 30 12 5 4 • 67.4% (62/92) of patients who had a Month 0 ED of 10 10 2 ≤100 mg reached an ED of at least 300 mg 3 3 1 1 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *ED >2000 mg included subjects: passing the 2000 mg dose at M12 without stopping criteria, passing the 2000 mg dose at M36 without stopping criteria, OR starting the second dose of 2000 mg at M36. † PEOPLE criterion: ∆ (M36-M12)=11.3% [2.8%; 19.6%]. Per the Statistical Analysis Plan submitted to FDA, the If the last dose given is only partially ingested by the patient prior to the DBPCFC stop, then the dose to be considered for ED value is: 16 1) the previous dose given if the quantity of the last dose given actually ingested by the subject is ≤ to the previous dose ingested; or 2) the last dose given if the quantity of the last dose given actually ingested by the subject is > than the previous dose ingested.Clinically Meaningful Changes in Eliciting Dose Maintained or Improved Over 3 Years PEOPLE PP (N=141) % of Patients M0 M12 M36 • 75.9% (107/141) demonstrated an increase in ED from baseline (M0) to Month 36 4 18 >2000* 14 6 2000 • 51.8% (73/141) reached an ED of ≥1,000 mg at 22 27 1000 Month 36 35 32 25 300 − 40.4% (57/141) reached an ED of ≥1,000 mg at 40 23 16 100 † Month 12 30 12 5 4 • 67.4% (62/92) of patients who had a Month 0 ED of 10 10 2 ≤100 mg reached an ED of at least 300 mg 3 3 1 1 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *ED >2000 mg included subjects: passing the 2000 mg dose at M12 without stopping criteria, passing the 2000 mg dose at M36 without stopping criteria, OR starting the second dose of 2000 mg at M36. † PEOPLE criterion: ∆ (M36-M12)=11.3% [2.8%; 19.6%]. Per the Statistical Analysis Plan submitted to FDA, the If the last dose given is only partially ingested by the patient prior to the DBPCFC stop, then the dose to be considered for ED value is: 16 1) the previous dose given if the quantity of the last dose given actually ingested by the subject is ≤ to the previous dose ingested; or 2) the last dose given if the quantity of the last dose given actually ingested by the subject is > than the previous dose ingested.
Marked Improvements in Cumulative Reactive Dose (CRD) with Long-Term EPIT Treatment 3,000 • In PEOPLE, 13.5% (19/141) of patients tolerated* - median value the full DBPCFC at 36 months (cumulative dose of 2,500 5,444 mg) 2,000 • Mean CRD of 1,768.8 mg, equivalent to roughly 1768.8 6 peanuts, at Month 36 1,500 – 24.1% (34/141) reached a CRD of 3,444 mg at 1120.4 month 36 compared to 15.6% (22/141) at 1,000 944 † month 12 – 17.7% (25/141) reached a CRD of 5,444 mg at 500 444 223.8 † month 36 144 0 Baseline Month 12 Month 36 Baseline Month 36 Month 12 PEOPLE Per Protocol † DBPCFC 1 mg 3 mg 10 mg 30 mg 100 mg 300 mg 1,000 mg 2,000 mg 2,000 mg Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. DBPCFC=double-blind, placebo-controlled food challenge. *Tolerated=passed the DBPCFC without meeting PRACTALL stopping criteria. † At month 12, the starting dose of the DBPCFC is 1 mg of peanut protein and escalates up to the highest dose of 2,000 mg to reach a maximum total cumulative dose of 3,444 mg of peanut protein. At month 36, the starting dose of the DBPCFC is 1 mg of peanut protein and escalates up to the highest dose of 2,000 mg peanut protein, possibly repeated once to reach a maximum total cumulative dose of 5,444 mg of peanut protein. For month 48 and 60, the starting dose will be 10 mg of peanut protein and the maximum 17 dose will be 3,000 mg of peanut protein, giving a maximum cumulative dose of 6,440 mg. Cumulative reactive dose (mg) Mean, Median (IQ) Marked Improvements in Cumulative Reactive Dose (CRD) with Long-Term EPIT Treatment 3,000 • In PEOPLE, 13.5% (19/141) of patients tolerated* - median value the full DBPCFC at 36 months (cumulative dose of 2,500 5,444 mg) 2,000 • Mean CRD of 1,768.8 mg, equivalent to roughly 1768.8 6 peanuts, at Month 36 1,500 – 24.1% (34/141) reached a CRD of 3,444 mg at 1120.4 month 36 compared to 15.6% (22/141) at 1,000 944 † month 12 – 17.7% (25/141) reached a CRD of 5,444 mg at 500 444 223.8 † month 36 144 0 Baseline Month 12 Month 36 Baseline Month 36 Month 12 PEOPLE Per Protocol † DBPCFC 1 mg 3 mg 10 mg 30 mg 100 mg 300 mg 1,000 mg 2,000 mg 2,000 mg Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. DBPCFC=double-blind, placebo-controlled food challenge. *Tolerated=passed the DBPCFC without meeting PRACTALL stopping criteria. † At month 12, the starting dose of the DBPCFC is 1 mg of peanut protein and escalates up to the highest dose of 2,000 mg to reach a maximum total cumulative dose of 3,444 mg of peanut protein. At month 36, the starting dose of the DBPCFC is 1 mg of peanut protein and escalates up to the highest dose of 2,000 mg peanut protein, possibly repeated once to reach a maximum total cumulative dose of 5,444 mg of peanut protein. For month 48 and 60, the starting dose will be 10 mg of peanut protein and the maximum 17 dose will be 3,000 mg of peanut protein, giving a maximum cumulative dose of 6,440 mg. Cumulative reactive dose (mg) Mean, Median (IQ)
Consistent Treatment Effect Across Studies Using Different Endpoint Criteria PEOPLE results when analyzed per: PEOPLE PEPITES OLFUS • Phase III PEOPLE key efficacy measurement: 51.8% reached an ED of Criterion Criterion Criterion 100% ≥1000 mg at Month 36 PEOPLE Per Protocol (PP) − Phase III PEPITES response criteria: 55.3% (78/141) reached 80% 66.0% an ED of ≥300 mg (for patients with a baseline ED ≤10 mg) or ≥1000 mg (for patients with a baseline ED >10 mg and ≤300 55.3% 53.9% mg) at Month 36 51.8% 60% 44.7% 40.4% − Phase II OLFUS response criteria: 66.0% (93/141) reached an ED of ≥1,000 mg or ≥10-fold the baseline ED at Month 36 40% − As a reminder, in the OLFUS study, 83% (15/18) of patients 1,* responded at Month 36 20% † Sustained unresponsiveness (SU) : • Results suggest that desensitization is maintained after discontinuing 0% treatment for 2 months (Month 37 & 38) M12 M36 − 77.8% (14/18) met the SU criteria in PEOPLE 2,‡ − 73.7% (14/19) met the SU criteria in OLFUS Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. † *Results for 250 µg cohort, ages 6-11; SU defined in PEOPLE as maintaining ED ≥1,000 mg; all participants who reached an ED ≥1,000 mg at Month 36 were eligible to continue the study for 2 additional months without treatment and required to maintain a peanut- free diet. A DBPCFC was administered at Month 38. SU defined in OLFUS as patients who did not react to a CRD >1,440 mg; patients needed to be unresponsive to a CRD of ≥1,440 mg peanut protein at the Month 24 DBPCFC to continue the study for two additional 18 months without treatment and required to maintain a peanut-free diet. ‡Results for 250 µg cohort during OLFUS, ages 6-11 1. Sampson HA, et al. JAMA. 2017;318:1798-1809. 2. Brown-Whitehorn T, et al. Presented at: Annual Meeting of the European Academy of Allergy and Clinical Immunology; May 26-30, 2018; Munich, Germany. Percentage of Subjects (%)Consistent Treatment Effect Across Studies Using Different Endpoint Criteria PEOPLE results when analyzed per: PEOPLE PEPITES OLFUS • Phase III PEOPLE key efficacy measurement: 51.8% reached an ED of Criterion Criterion Criterion 100% ≥1000 mg at Month 36 PEOPLE Per Protocol (PP) − Phase III PEPITES response criteria: 55.3% (78/141) reached 80% 66.0% an ED of ≥300 mg (for patients with a baseline ED ≤10 mg) or ≥1000 mg (for patients with a baseline ED >10 mg and ≤300 55.3% 53.9% mg) at Month 36 51.8% 60% 44.7% 40.4% − Phase II OLFUS response criteria: 66.0% (93/141) reached an ED of ≥1,000 mg or ≥10-fold the baseline ED at Month 36 40% − As a reminder, in the OLFUS study, 83% (15/18) of patients 1,* responded at Month 36 20% † Sustained unresponsiveness (SU) : • Results suggest that desensitization is maintained after discontinuing 0% treatment for 2 months (Month 37 & 38) M12 M36 − 77.8% (14/18) met the SU criteria in PEOPLE 2,‡ − 73.7% (14/19) met the SU criteria in OLFUS Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. † *Results for 250 µg cohort, ages 6-11; SU defined in PEOPLE as maintaining ED ≥1,000 mg; all participants who reached an ED ≥1,000 mg at Month 36 were eligible to continue the study for 2 additional months without treatment and required to maintain a peanut- free diet. A DBPCFC was administered at Month 38. SU defined in OLFUS as patients who did not react to a CRD >1,440 mg; patients needed to be unresponsive to a CRD of ≥1,440 mg peanut protein at the Month 24 DBPCFC to continue the study for two additional 18 months without treatment and required to maintain a peanut-free diet. ‡Results for 250 µg cohort during OLFUS, ages 6-11 1. Sampson HA, et al. JAMA. 2017;318:1798-1809. 2. Brown-Whitehorn T, et al. Presented at: Annual Meeting of the European Academy of Allergy and Clinical Immunology; May 26-30, 2018; Munich, Germany. Percentage of Subjects (%)
Continued Immune Modulation Beyond 12 Months • Exploratory analyses across both PEPITES and PEOPLE showed that changes in peanut-specific biomarkers, including immunoglobulin G4 (IgG4) and immunoglobulin E (IgE), support the immunomodulatory effect with Viaskin Peanut • Peanut IgG4 levels progressively increased throughout the first 18 months of treatment and remained at peak levels for the remainder of the treatment to 36 months • IgE levels increased initially at the start of the study and then returned to baseline, remaining around baseline through 36 months 2,000 200 1,800 160 1,600 1,400 120 1,200 80 1,000 40 800 600 0 400 -40 200 0 -80 0 6 12 18 24 30 36 42 0 6 12 18 24 30 36 42 Months Months 19 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Relative change from baseline of peanut-specific IgG4 (%) Median (IQ) Relative change from baseline of peanut-specific IgE (%) Median (IQ) Continued Immune Modulation Beyond 12 Months • Exploratory analyses across both PEPITES and PEOPLE showed that changes in peanut-specific biomarkers, including immunoglobulin G4 (IgG4) and immunoglobulin E (IgE), support the immunomodulatory effect with Viaskin Peanut • Peanut IgG4 levels progressively increased throughout the first 18 months of treatment and remained at peak levels for the remainder of the treatment to 36 months • IgE levels increased initially at the start of the study and then returned to baseline, remaining around baseline through 36 months 2,000 200 1,800 160 1,600 1,400 120 1,200 80 1,000 40 800 600 0 400 -40 200 0 -80 0 6 12 18 24 30 36 42 0 6 12 18 24 30 36 42 Months Months 19 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Relative change from baseline of peanut-specific IgG4 (%) Median (IQ) Relative change from baseline of peanut-specific IgE (%) Median (IQ)
Safety Profile Consistent with that Observed in the Clinical Program to Date • No treatment-related serious adverse events (SAEs) were reported • Most commonly reported treatment-related AEs were mild to moderate skin reactions – Local administration site reactions observed in 92.9% (184/198) of patients over 36 months – In year 3 of treatment, local skin reactions observed in 29.9% (55/198) of patients • 4 children discontinued due to treatment-emergent AEs (TEAEs) between the start of PEOPLE and Month 36 – 2 of the 4 children discontinued due to treatment-related TEAEs • No epinephrine intake related to treatment observed in the PEOPLE study • 1 patient experienced 1 possibly-related mild anaphylaxis* that resolved without treatment • Treatment compliance remained high throughout the study – Mean compliance of 98% observed over 3 years of treatment • High adherence and low dropout rate † – 50 patients discontinued between the start of PEOPLE and Month 36 • 27 patients discontinued between Month 30-36, with 21 of the 27 identifying food challenge fright/distaste as the reason for consent withdrawal Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 20 *Anaphylaxis was defined according to NIAID, which has been shown to be highly sensitive but moderately specific, in an attempt to capture as many reactions as possible. Severe anaphylaxis was defined by presence of cyanosis, hypoxia, hypotension, † confusion, loss of consciousness, or incontinence. Includes those who discontinued prior to or during the Month 36 DBPCFC.Safety Profile Consistent with that Observed in the Clinical Program to Date • No treatment-related serious adverse events (SAEs) were reported • Most commonly reported treatment-related AEs were mild to moderate skin reactions – Local administration site reactions observed in 92.9% (184/198) of patients over 36 months – In year 3 of treatment, local skin reactions observed in 29.9% (55/198) of patients • 4 children discontinued due to treatment-emergent AEs (TEAEs) between the start of PEOPLE and Month 36 – 2 of the 4 children discontinued due to treatment-related TEAEs • No epinephrine intake related to treatment observed in the PEOPLE study • 1 patient experienced 1 possibly-related mild anaphylaxis* that resolved without treatment • Treatment compliance remained high throughout the study – Mean compliance of 98% observed over 3 years of treatment • High adherence and low dropout rate † – 50 patients discontinued between the start of PEOPLE and Month 36 • 27 patients discontinued between Month 30-36, with 21 of the 27 identifying food challenge fright/distaste as the reason for consent withdrawal Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 20 *Anaphylaxis was defined according to NIAID, which has been shown to be highly sensitive but moderately specific, in an attempt to capture as many reactions as possible. Severe anaphylaxis was defined by presence of cyanosis, hypoxia, hypotension, † confusion, loss of consciousness, or incontinence. Includes those who discontinued prior to or during the Month 36 DBPCFC.
Preparation Underway for Potential Viaskin Peanut Launch in the U.S. in 2H 2020 Patients and Families Market Access Healthcare Professionals Allergists • Education and marketing initiatives • Predominately commercial market 2 • Approximately 4,500 allergists in the U.S. focused on caregivers of peanut-allergic • Top 8 commercial payers represent children ages 4-11 • Allergists are familiar with long-term 4 approx. 80% of children ages 4-11 immunotherapy • Most caregivers are ages 25-44 with • Payer market research indicates high 1 • All allergists potentially able to offer Viaskin strong social media participation awareness of peanut allergy and Peanut, if approved • Many seek expert advice from other 5 understanding of the need for treatment Pediatricians caregivers • Payers are intrigued by product profile • Most caregivers of peanut-allergic children rely on and potential MOA and effectiveness of allergists to manage their allergy 5 Viaskin Peanut • Pediatricians indicate they will refer more patients 3 once there are FDA-approved treatments • Payer engagement ongoing Sales leadership team hired and onboarded; customer-facing team of ~70 individuals to be onboarded throughout 2020; 8 MSLs in the field in 2019, recruitment of ~8-12 additional MSLs in 2020 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 21 1. DBV market research 4Q 2018: survey with ~400 caregivers 2. DBV internal medical claims data analysis 3. DBV market research 4Q 2019: survey with 100 pediatricians 4. DRG Finger Tip Formulary, December 2017, 5. DBV market research 2Q 2018: survey with 40 medical and pharmacy directors of US managed care organizationsPreparation Underway for Potential Viaskin Peanut Launch in the U.S. in 2H 2020 Patients and Families Market Access Healthcare Professionals Allergists • Education and marketing initiatives • Predominately commercial market 2 • Approximately 4,500 allergists in the U.S. focused on caregivers of peanut-allergic • Top 8 commercial payers represent children ages 4-11 • Allergists are familiar with long-term 4 approx. 80% of children ages 4-11 immunotherapy • Most caregivers are ages 25-44 with • Payer market research indicates high 1 • All allergists potentially able to offer Viaskin strong social media participation awareness of peanut allergy and Peanut, if approved • Many seek expert advice from other 5 understanding of the need for treatment Pediatricians caregivers • Payers are intrigued by product profile • Most caregivers of peanut-allergic children rely on and potential MOA and effectiveness of allergists to manage their allergy 5 Viaskin Peanut • Pediatricians indicate they will refer more patients 3 once there are FDA-approved treatments • Payer engagement ongoing Sales leadership team hired and onboarded; customer-facing team of ~70 individuals to be onboarded throughout 2020; 8 MSLs in the field in 2019, recruitment of ~8-12 additional MSLs in 2020 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 21 1. DBV market research 4Q 2018: survey with ~400 caregivers 2. DBV internal medical claims data analysis 3. DBV market research 4Q 2019: survey with 100 pediatricians 4. DRG Finger Tip Formulary, December 2017, 5. DBV market research 2Q 2018: survey with 40 medical and pharmacy directors of US managed care organizations
Looking Ahead to Viaskin Peanut for Toddlers: Ongoing Phase III Trial in Children Ages 1-3 Positive DSMB from Part A: No safety concerns identified Part B: ~350 additional patients Highest safe dose (250 µg) Part A: 51 patients randomized n = ~233 Placebo (n = ~10) EPOPEX 100 µg (n = ~20) Open Label Placebo 250 µg (n = ~20) Extension n = ~117 100 µg dose n = ~20 M3 M0 M0 M12 Clinical Trial Patient Population Efficacy Endpoints Children ages 1-3 with peanut allergy Primary endpoint at M12* • > 0.7 kUI/ L peanut-specific IgE and ≥ 6 mm Treatment responders (%) in active group compared to placebo at DBPCFC: SPT* wheal • For patients with a M0 ED ≤ 10mg: responder if ED ≥ 300 mg at M12 • Reactive dose at M0 ≤ 300 mg peanut protein • For patients with a M0 ED > 10mg: responder if ED ≥ 1,000 mg at M12 Main secondary endpoints: CRD, changes in peanut sIgE and sIgG4 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. SPT: skin prick test, ED: eliciting dose; CRD: cumulative reactive dose at food challenge. *The primary analysis evaluating the difference between Viaskin Peanut 250 μg and placebo is defined by reaching a lower bound of the two-sided 95% confidence interval (CI) of ≥15% 22 Denotes a completed food challenge; Denotes a pending food challenge Looking Ahead to Viaskin Peanut for Toddlers: Ongoing Phase III Trial in Children Ages 1-3 Positive DSMB from Part A: No safety concerns identified Part B: ~350 additional patients Highest safe dose (250 µg) Part A: 51 patients randomized n = ~233 Placebo (n = ~10) EPOPEX 100 µg (n = ~20) Open Label Placebo 250 µg (n = ~20) Extension n = ~117 100 µg dose n = ~20 M3 M0 M0 M12 Clinical Trial Patient Population Efficacy Endpoints Children ages 1-3 with peanut allergy Primary endpoint at M12* • > 0.7 kUI/ L peanut-specific IgE and ≥ 6 mm Treatment responders (%) in active group compared to placebo at DBPCFC: SPT* wheal • For patients with a M0 ED ≤ 10mg: responder if ED ≥ 300 mg at M12 • Reactive dose at M0 ≤ 300 mg peanut protein • For patients with a M0 ED > 10mg: responder if ED ≥ 1,000 mg at M12 Main secondary endpoints: CRD, changes in peanut sIgE and sIgG4 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. SPT: skin prick test, ED: eliciting dose; CRD: cumulative reactive dose at food challenge. *The primary analysis evaluating the difference between Viaskin Peanut 250 μg and placebo is defined by reaching a lower bound of the two-sided 95% confidence interval (CI) of ≥15% 22 Denotes a completed food challenge; Denotes a pending food challenge
Applying This Novel, Innovative Platform to Other Food Allergies Where Unmet Needs Exist Following Potential Commercialization of Viaskin Peanut, If Approved, Comprehensive Pipeline Review Planned DEVELOPMENT STAGE PROGRAM INDICATION DISCOVERY PRE-CLINICAL PHASE I PHASE II PHASE III FDA Review Ages 4-11 (Breakthrough Therapy and Fast Track Designation*) Viaskin Peanut Peanut Allergy Ages 1-3 Adolescents & Adults Cow’s Milk Protein Viaskin Milk Ages 2-17 (Fast Track Designation**) Allergy Viaskin Egg Hen’s Egg Allergy Proof of Concept Eosinophilic Esophagitis Ages 4-17 5 Programs Undisclosed Diagnostics with Cow’s Milk Protein Infants Nestlé Health Science Allergy * US FDA Breakthrough Therapy and Fast Track designation in children ** US FDA Fast Track designation in pediatric patients two and older 23 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.Applying This Novel, Innovative Platform to Other Food Allergies Where Unmet Needs Exist Following Potential Commercialization of Viaskin Peanut, If Approved, Comprehensive Pipeline Review Planned DEVELOPMENT STAGE PROGRAM INDICATION DISCOVERY PRE-CLINICAL PHASE I PHASE II PHASE III FDA Review Ages 4-11 (Breakthrough Therapy and Fast Track Designation*) Viaskin Peanut Peanut Allergy Ages 1-3 Adolescents & Adults Cow’s Milk Protein Viaskin Milk Ages 2-17 (Fast Track Designation**) Allergy Viaskin Egg Hen’s Egg Allergy Proof of Concept Eosinophilic Esophagitis Ages 4-17 5 Programs Undisclosed Diagnostics with Cow’s Milk Protein Infants Nestlé Health Science Allergy * US FDA Breakthrough Therapy and Fast Track designation in children ** US FDA Fast Track designation in pediatric patients two and older 23 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.
DBV Is Positioned to Deliver the First Epicutaneous Immunotherapy to Peanut-Allergic Children in 2H 2020 2H 2020 1H 2020 Potential FDA approval of PEOPLE 3-year topline results Viaskin Peanut EPITOPE Part A results and Potential US launch of Viaskin Peanut, if approved enrollment update for Part B Anticipated Viaskin Peanut Potential EMA filing of Viaskin FDA Advisory Committee Peanut We are laser-focused on bringing a treatment option to peanut-allergic children in the second half of 2020, if approved 24 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.DBV Is Positioned to Deliver the First Epicutaneous Immunotherapy to Peanut-Allergic Children in 2H 2020 2H 2020 1H 2020 Potential FDA approval of PEOPLE 3-year topline results Viaskin Peanut EPITOPE Part A results and Potential US launch of Viaskin Peanut, if approved enrollment update for Part B Anticipated Viaskin Peanut Potential EMA filing of Viaskin FDA Advisory Committee Peanut We are laser-focused on bringing a treatment option to peanut-allergic children in the second half of 2020, if approved 24 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.
APPENDIXAPPENDIX
Viaskin PlatformViaskin Platform
EPIT: Unlocking the Immune Properties of the Skin with the Viaskin Patch EPIT targets the immune system on intact skin • Condensation chamber formed by Viaskin patch allows natural epidermal water loss to solubilize dry antigens • Langerhans cells capture solubilized antigen in the epidermis • Keratinocytes help distinguish pathogens from harmless agents, influencing Langerhans cells to generate an appropriate immune response • Langerhans cells can process antigens and migrate to regional lymph nodes Transmission of immunogenic information, with no allergen passage to the bloodstream Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 28 Image: ©Genoskin Dioszeghy V, et al. J Immunol. 2011;186:5629-5637. EPIT: Unlocking the Immune Properties of the Skin with the Viaskin Patch EPIT targets the immune system on intact skin • Condensation chamber formed by Viaskin patch allows natural epidermal water loss to solubilize dry antigens • Langerhans cells capture solubilized antigen in the epidermis • Keratinocytes help distinguish pathogens from harmless agents, influencing Langerhans cells to generate an appropriate immune response • Langerhans cells can process antigens and migrate to regional lymph nodes Transmission of immunogenic information, with no allergen passage to the bloodstream Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 28 Image: ©Genoskin Dioszeghy V, et al. J Immunol. 2011;186:5629-5637.
The Skin Has Important Immune Properties • Immune functions of the skin include – Responding to trauma, toxins, and infectious agents – Maintaining self-tolerance, preventing allergy, Keratinocyte and inhibiting autoimmunity Epidermis • Keratinocytes Langerhans cell – Distinguish pathogens from harmless agents – Influence nearby Langerhans cells to generate an appropriate immune response • Langerhans cells – Antigen-presenting cells that can process antigens and migrate to regional lymph nodes Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Di Meglio P, et al. Immunity. 2011;35:857-869. Nestle FO, et al. Nat Rev Immunol. 2009;9:679-691. Senti G, et al. Allergy. 2011;66:798-809. Metz M, et al. Curr Opin Immunol. 29 2009;21:687-693.The Skin Has Important Immune Properties • Immune functions of the skin include – Responding to trauma, toxins, and infectious agents – Maintaining self-tolerance, preventing allergy, Keratinocyte and inhibiting autoimmunity Epidermis • Keratinocytes Langerhans cell – Distinguish pathogens from harmless agents – Influence nearby Langerhans cells to generate an appropriate immune response • Langerhans cells – Antigen-presenting cells that can process antigens and migrate to regional lymph nodes Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Di Meglio P, et al. Immunity. 2011;35:857-869. Nestle FO, et al. Nat Rev Immunol. 2009;9:679-691. Senti G, et al. Allergy. 2011;66:798-809. Metz M, et al. Curr Opin Immunol. 29 2009;21:687-693.
Core Innovation: Differentiated Electrospray Technology Regulated flow of dissolved antigen • Dose flexibility – Biological API deposit between 20 and 500 µg/cm2 • API stability Capillary – Solid & soluble protein layer, no glue nozzle High voltage • Homogeneous repartition of API (up to 20,000 V) – Uniform delivery into skin Fine spray of • Replicability electrically – High dosage control in each patch charged droplets • Bioavailability Electrical ground – High solubility from electrostatic forces Dry layer of antigen instead of glue 30 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.Core Innovation: Differentiated Electrospray Technology Regulated flow of dissolved antigen • Dose flexibility – Biological API deposit between 20 and 500 µg/cm2 • API stability Capillary – Solid & soluble protein layer, no glue nozzle High voltage • Homogeneous repartition of API (up to 20,000 V) – Uniform delivery into skin Fine spray of • Replicability electrically – High dosage control in each patch charged droplets • Bioavailability Electrical ground – High solubility from electrostatic forces Dry layer of antigen instead of glue 30 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.
Robust IP Portfolio: Core Technology, MoA & Specific Indications ALLERGY 0110 – EPIT Peanut 0109 – EPIT Method MANUFACTURING 0111 - Eczema treatment Broad geographic applications • USA, Europe, Australia, 0117 - Encapsulated food allergen 0121 – ElectroFlow Canada 0112 – Eosinophilic esophagitis 0107 - Electrospray Long patent protection CORE TECHNOLOGY 0114 – Allergic March • Initial core patents through 0101 - 2022 Viaskin I 0104 - • Other key patents through 0108 - Vaccination Viaskin II 0102 - Applicator 2029-35 0105 – Skin Stripping 0113 - Vaccine boost Innovation-driven patent lifecycle 0106 – Bracelet Patch 0119 – B.pertussis vaccination management 0103 - Microcontour VACCINATION PLATFORM 31 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.Robust IP Portfolio: Core Technology, MoA & Specific Indications ALLERGY 0110 – EPIT Peanut 0109 – EPIT Method MANUFACTURING 0111 - Eczema treatment Broad geographic applications • USA, Europe, Australia, 0117 - Encapsulated food allergen 0121 – ElectroFlow Canada 0112 – Eosinophilic esophagitis 0107 - Electrospray Long patent protection CORE TECHNOLOGY 0114 – Allergic March • Initial core patents through 0101 - 2022 Viaskin I 0104 - • Other key patents through 0108 - Vaccination Viaskin II 0102 - Applicator 2029-35 0105 – Skin Stripping 0113 - Vaccine boost Innovation-driven patent lifecycle 0106 – Bracelet Patch 0119 – B.pertussis vaccination management 0103 - Microcontour VACCINATION PLATFORM 31 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.
Operational Readiness: Fully-Integrated End-to-End Process In-Place Active Pharmaceutical Ingredient Primary Packaging (API) Raw Source Bulk Final Material Material formulation Product (SM) API process at Sanofi Source Material process Final Product process at Fareva API dry powder: highly purified allergen extract Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 32Operational Readiness: Fully-Integrated End-to-End Process In-Place Active Pharmaceutical Ingredient Primary Packaging (API) Raw Source Bulk Final Material Material formulation Product (SM) API process at Sanofi Source Material process Final Product process at Fareva API dry powder: highly purified allergen extract Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 32
Established Proprietary & Patented Manufacturing Capabilities Developed by DBV • Sufficient supply for anticipated launch of Viaskin Peanut in 2H 2020, if approved • Modular components à technology versatility – Highly scalable – Broadly applicable platform • Manufacturing capabilities – In-house development and engineering [ES GEN4.0 machine] of electrospray machines – Development and engineering expertise at DBV Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 33Established Proprietary & Patented Manufacturing Capabilities Developed by DBV • Sufficient supply for anticipated launch of Viaskin Peanut in 2H 2020, if approved • Modular components à technology versatility – Highly scalable – Broadly applicable platform • Manufacturing capabilities – In-house development and engineering [ES GEN4.0 machine] of electrospray machines – Development and engineering expertise at DBV Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 33
Viaskin Peanut Phase III Program: PEPITES & REALISEViaskin Peanut Phase III Program: PEPITES & REALISE
Measuring Efficacy: Double-Blind Placebo-Controlled Food Challenge Baseline 1 mg 3 mg 10 mg 30 mg 100 mg 300 mg Month 12* 1 mg 3 mg 10 mg 30 mg 100 mg 300 mg 1,000 mg 2,000 mg DBPCFC: Efficacy Outcome Scoring with Standardized Challenge Matrix • Standardized GMP challenge CATEGORIES OBJECTIVE SYMPTOMS GRADE SUBJECTIVE SYMPTOMS 1 A. Erythematous rash: % area involved matrix B. Pruritus 01 23 I. SKIN C. Urticaria/Angioedema 01 23 • Standardized semi-logarithmic D. Rash 01 23 increase of peanut protein A. Sneezing/Itching 01 23 2 B. Nasal congestion 01 23 doses (DBPCFC as per II. UPPER RESPIRATORY C. Rhinorrhea 01 23 3 PRACTALL ) D. Laryngeal 01 23 III LOWER RESPIRATORY A. Wheezing 0 12 3 A. Subjective Complaints • Allergic symptoms are graded 01 23 Itchy mouth from a standardized published 01 23 Itchy throat 4 01 23 Nausea protocol IV. GASTROINTESTINAL 01 23 Abdominal pain B. Objective Complaints • Challenge stopped by clear Diarrhea 0 12 3 objective symptoms Vomiting 0 12 3 V. CARDIOVASCULAR Normal heart rate to bradycardia 0 12 3 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. * DBPCFC in PEPITES and VIPES at month 12, in OLFUS-VIPES DBPCFC included an additional 1,600mg step after the 1,000mg step at month 24 & 36 1. Cochrane et al, Allergy 2012 2. Double-Blind, Placebo-Controlled Food Challenge 35 3. Sampson et al, JACI 2012 4. Nowak-Wegrzyn et al, JACI 2009Measuring Efficacy: Double-Blind Placebo-Controlled Food Challenge Baseline 1 mg 3 mg 10 mg 30 mg 100 mg 300 mg Month 12* 1 mg 3 mg 10 mg 30 mg 100 mg 300 mg 1,000 mg 2,000 mg DBPCFC: Efficacy Outcome Scoring with Standardized Challenge Matrix • Standardized GMP challenge CATEGORIES OBJECTIVE SYMPTOMS GRADE SUBJECTIVE SYMPTOMS 1 A. Erythematous rash: % area involved matrix B. Pruritus 01 23 I. SKIN C. Urticaria/Angioedema 01 23 • Standardized semi-logarithmic D. Rash 01 23 increase of peanut protein A. Sneezing/Itching 01 23 2 B. Nasal congestion 01 23 doses (DBPCFC as per II. UPPER RESPIRATORY C. Rhinorrhea 01 23 3 PRACTALL ) D. Laryngeal 01 23 III LOWER RESPIRATORY A. Wheezing 0 12 3 A. Subjective Complaints • Allergic symptoms are graded 01 23 Itchy mouth from a standardized published 01 23 Itchy throat 4 01 23 Nausea protocol IV. GASTROINTESTINAL 01 23 Abdominal pain B. Objective Complaints • Challenge stopped by clear Diarrhea 0 12 3 objective symptoms Vomiting 0 12 3 V. CARDIOVASCULAR Normal heart rate to bradycardia 0 12 3 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. * DBPCFC in PEPITES and VIPES at month 12, in OLFUS-VIPES DBPCFC included an additional 1,600mg step after the 1,000mg step at month 24 & 36 1. Cochrane et al, Allergy 2012 2. Double-Blind, Placebo-Controlled Food Challenge 35 3. Sampson et al, JACI 2012 4. Nowak-Wegrzyn et al, JACI 2009
PEPITES Pivotal Phase III Trial Results (Fleischer, JAMA 2019) Placebo Pivotal Global Randomized DBPC Phase 3 Trial Screening • 356 children aged 4 to 11 years 250 µg • 31 study locations (United States, Canada, Australia, Germany, and Ireland) M12 M0 NCT02636699 DBPCFC Randomization* Primary Endpoint Food Challenge Symptom Scoring • Food challenges were discontinued when objective signs/symptoms Treatment responder definition (assessed using DBPCFC) emerged meeting prespecified stopping criteria requiring treatment • For patients with a M0 ED ≤ 10 mg: responder if ED ≥300 mg at M12 • Subjective symptoms (eg, abdominal pain or oropharyngeal itching) • For patients with a M0 ED > 10 mg and ≤ 300 mg: responder if ED were assessed and recorded, but alone were insufficient to stop the ≥1000 mg at M12 challenge Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *Subjects were randomized 2:1, stratified by ED, to receive either Viaskin Peanut 250 µg or placebo patch. DBPC= double-blind, placebo-controlled; DBPCFC=DBPC food challenge; ED=eliciting dose; M=month. 36 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113.PEPITES Pivotal Phase III Trial Results (Fleischer, JAMA 2019) Placebo Pivotal Global Randomized DBPC Phase 3 Trial Screening • 356 children aged 4 to 11 years 250 µg • 31 study locations (United States, Canada, Australia, Germany, and Ireland) M12 M0 NCT02636699 DBPCFC Randomization* Primary Endpoint Food Challenge Symptom Scoring • Food challenges were discontinued when objective signs/symptoms Treatment responder definition (assessed using DBPCFC) emerged meeting prespecified stopping criteria requiring treatment • For patients with a M0 ED ≤ 10 mg: responder if ED ≥300 mg at M12 • Subjective symptoms (eg, abdominal pain or oropharyngeal itching) • For patients with a M0 ED > 10 mg and ≤ 300 mg: responder if ED were assessed and recorded, but alone were insufficient to stop the ≥1000 mg at M12 challenge Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *Subjects were randomized 2:1, stratified by ED, to receive either Viaskin Peanut 250 µg or placebo patch. DBPC= double-blind, placebo-controlled; DBPCFC=DBPC food challenge; ED=eliciting dose; M=month. 36 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113.
Trial Population Included Patients with Multiple Allergic Conditions (Fleischer, JAMA 2019) • Patient population included a high percentage of subjects with additional allergic conditions 356 Patients Randomized, n (%) Medical History of Patients* 100% • Active (VP250 μg): 238 (67%) 85.7% • Placebo: 118 (33%) 80% Peanut Eliciting Dose (mg) 61.2% 60% 55.9% • Median: 100 47.5% • Mean: 140 40% Age, years, median (Q1, Q3) • Active: 7 (6,9) 20% • Placebo: 7 (5,9) 0% Gender, n (%) Polyallergic Eczema/Atopic Allergic Asthma • Male: 218 (61.2%) Dermatitis Rhinitis • Female: 138 (38.8%) Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *Medical History displayed as summary of the trial population. VP250 μg patients: polyallergic n=205 (86.1%), eczema/atopic dermatitis n=139 (58.4%), allergic rhinitis n=132 (55.5%), asthma n=117 (49.2%); placebo patients: polyallergic n=100 (84.7%), eczema/atopic dermatitis n=79 (66.9%), allergic rhinitis n=67 (56.8%), asthma n=52 (44.1%). 37 Q=quartile; VP250=Viaskin Peanut 250 μg. 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. Percent of patientsTrial Population Included Patients with Multiple Allergic Conditions (Fleischer, JAMA 2019) • Patient population included a high percentage of subjects with additional allergic conditions 356 Patients Randomized, n (%) Medical History of Patients* 100% • Active (VP250 μg): 238 (67%) 85.7% • Placebo: 118 (33%) 80% Peanut Eliciting Dose (mg) 61.2% 60% 55.9% • Median: 100 47.5% • Mean: 140 40% Age, years, median (Q1, Q3) • Active: 7 (6,9) 20% • Placebo: 7 (5,9) 0% Gender, n (%) Polyallergic Eczema/Atopic Allergic Asthma • Male: 218 (61.2%) Dermatitis Rhinitis • Female: 138 (38.8%) Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *Medical History displayed as summary of the trial population. VP250 μg patients: polyallergic n=205 (86.1%), eczema/atopic dermatitis n=139 (58.4%), allergic rhinitis n=132 (55.5%), asthma n=117 (49.2%); placebo patients: polyallergic n=100 (84.7%), eczema/atopic dermatitis n=79 (66.9%), allergic rhinitis n=67 (56.8%), asthma n=52 (44.1%). 37 Q=quartile; VP250=Viaskin Peanut 250 μg. 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. Percent of patients
Primary Efficacy Outcome Showed Statistically Significant Treatment Effect (Fleischer, JAMA 2019) Response Rate (ITT) • After 12 months, a significantly larger 40 percentage of participants responded to P<0.001 Viaskin Peanut treatment vs placebo patch 35 35.3% vs 13.6% (P<0.001) 35.3% 30 Δ= 21.7% 25 (95% CI: 12.4, 29.8) 20 • The prespecified 15% lower bound of the 95% CI of the difference between 15 treatment groups was not met (95% CI: 10 13.6% 12.4, 29.8) 5 – The authors of the publication concluded 0 that the clinical relevance of this is not Placebo Viaskin Peanut 250 μg known n=118 n=238 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. CI=confidence interval; ITT=intention-to-treat. 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 38 Percent of Responders (%)Primary Efficacy Outcome Showed Statistically Significant Treatment Effect (Fleischer, JAMA 2019) Response Rate (ITT) • After 12 months, a significantly larger 40 percentage of participants responded to P<0.001 Viaskin Peanut treatment vs placebo patch 35 35.3% vs 13.6% (P<0.001) 35.3% 30 Δ= 21.7% 25 (95% CI: 12.4, 29.8) 20 • The prespecified 15% lower bound of the 95% CI of the difference between 15 treatment groups was not met (95% CI: 10 13.6% 12.4, 29.8) 5 – The authors of the publication concluded 0 that the clinical relevance of this is not Placebo Viaskin Peanut 250 μg known n=118 n=238 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. CI=confidence interval; ITT=intention-to-treat. 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 38 Percent of Responders (%)
Cumulative Reactive Dose (CRD) Increased Over 12 Months of Treatment (Fleischer, JAMA 2019) CRD After 12 Months • A difference in CRD was observed 1200 P<0.001* between the active and placebo Median groups (P<0.001*) 1000 905.7 800 • The median CRD in participants in the 600 Viaskin® Peanut 250 µg group 444 increased from 144 mg at baseline to 361 400 444 mg at Month 12 212.5 211.7 200 144 144 144 0 Placebo Placebo VP250µg VP250µg Placebo baseline Viaskin baseline Placebo M12 Viaskin M12 n=118 n=118 n=238 n=238 12 Months Baseline *Nominal P value. Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. CI=confidence interval; VP=Viaskin Peanut. 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2. DBV Technologies, Data on File. February 2019. 39 Mean (95% CI) (mg)Cumulative Reactive Dose (CRD) Increased Over 12 Months of Treatment (Fleischer, JAMA 2019) CRD After 12 Months • A difference in CRD was observed 1200 P<0.001* between the active and placebo Median groups (P<0.001*) 1000 905.7 800 • The median CRD in participants in the 600 Viaskin® Peanut 250 µg group 444 increased from 144 mg at baseline to 361 400 444 mg at Month 12 212.5 211.7 200 144 144 144 0 Placebo Placebo VP250µg VP250µg Placebo baseline Viaskin baseline Placebo M12 Viaskin M12 n=118 n=118 n=238 n=238 12 Months Baseline *Nominal P value. Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. CI=confidence interval; VP=Viaskin Peanut. 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2. DBV Technologies, Data on File. February 2019. 39 Mean (95% CI) (mg)
Increased ED in Majority of Participants Treated with Viaskin Peanut (Fleischer, JAMA 2019) 1,3† Change in ED in Children 4 to 11 years of age • In a post-hoc analysis, 53.1% of 100% ED Increase subjects on Viaskin Peanut 250 µg >4x more likely in Viaskin Peanut ED Stable increased their baseline ED from 28.0% 250 µg group ED Decrease ≤100 mg to ≥300 mg, vs only 19% 80% (OR=4.3) 1 on placebo patch 62.6% – Based on risk assessment modeling, 60% raising ED from ≤100 mg to ≥300 38.1% mg is predicted to reduce the risk of reactions due to accidental 40% 2* exposure by >95% • An increase in ED was 4 times more 30.7% 20% >7x more 33.9% likely to occur in the Viaskin Peanut likely in placebo group group compared to placebo (OR=7.1) 6.7% 3 0% (OR=4.3) VP250 µg (n=238) Placebo (n=118) Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 2 *Based on quantitative risk assessment modeling using national database of consumption data and levels of peanut protein contamination for selected pre-packaged foods. † 3 Based on ITT population; missing data calculated using mBOCF. ITT=intention-to-treat; mBOCF=modified baseline carried forward; OR=odds ratio; VP=Viaskin Peanut. 40 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2. Baumert JL, et al. J Allergy Clin Immunol Pract. 2018;6:457-465. 3. DBV Technologies, Data on File, February 2019. Percent of SubjectsIncreased ED in Majority of Participants Treated with Viaskin Peanut (Fleischer, JAMA 2019) 1,3† Change in ED in Children 4 to 11 years of age • In a post-hoc analysis, 53.1% of 100% ED Increase subjects on Viaskin Peanut 250 µg >4x more likely in Viaskin Peanut ED Stable increased their baseline ED from 28.0% 250 µg group ED Decrease ≤100 mg to ≥300 mg, vs only 19% 80% (OR=4.3) 1 on placebo patch 62.6% – Based on risk assessment modeling, 60% raising ED from ≤100 mg to ≥300 38.1% mg is predicted to reduce the risk of reactions due to accidental 40% 2* exposure by >95% • An increase in ED was 4 times more 30.7% 20% >7x more 33.9% likely to occur in the Viaskin Peanut likely in placebo group group compared to placebo (OR=7.1) 6.7% 3 0% (OR=4.3) VP250 µg (n=238) Placebo (n=118) Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 2 *Based on quantitative risk assessment modeling using national database of consumption data and levels of peanut protein contamination for selected pre-packaged foods. † 3 Based on ITT population; missing data calculated using mBOCF. ITT=intention-to-treat; mBOCF=modified baseline carried forward; OR=odds ratio; VP=Viaskin Peanut. 40 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2. Baumert JL, et al. J Allergy Clin Immunol Pract. 2018;6:457-465. 3. DBV Technologies, Data on File, February 2019. Percent of Subjects
Changes in Biomarkers Support Immunomodulatory Effect of Viaskin Peanut (Fleischer, JAMA 2019) • Levels of IgE increased initially then returned to baseline • Treatment groups were distinguishable based on levels of peanut-specific IgG4 as early as month 3 – Levels of IgG4 steadily increased in Viaskin Peanut subjects and were greater than placebo at all time points PS-IgE Changes Over Time PS-IgG4 Changes Over Time VP250 µg Placebo VP250 µg Placebo N=108–117 N=224–238 N=109–117 N=224–238 1200 200 1000 150 800 100 600 400 50 200 0 0 -50 -200 03 12 6 03 6 12 Month Month Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. IQR=interquartile range; PS=peanut-specific; VP=Viaskin Peanut. 41 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2. DBV Technologies, Data on File. February 2019. Median (IQR) Relative Change in IgE (%) Median (IQR) Relative Change in IgG4 (%)Changes in Biomarkers Support Immunomodulatory Effect of Viaskin Peanut (Fleischer, JAMA 2019) • Levels of IgE increased initially then returned to baseline • Treatment groups were distinguishable based on levels of peanut-specific IgG4 as early as month 3 – Levels of IgG4 steadily increased in Viaskin Peanut subjects and were greater than placebo at all time points PS-IgE Changes Over Time PS-IgG4 Changes Over Time VP250 µg Placebo VP250 µg Placebo N=108–117 N=224–238 N=109–117 N=224–238 1200 200 1000 150 800 100 600 400 50 200 0 0 -50 -200 03 12 6 03 6 12 Month Month Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. IQR=interquartile range; PS=peanut-specific; VP=Viaskin Peanut. 41 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2. DBV Technologies, Data on File. February 2019. Median (IQR) Relative Change in IgE (%) Median (IQR) Relative Change in IgG4 (%)
High Adherence and Low Discontinuation Due to TEAEs (Fleischer, JAMA 2019) • 89.9% of all subjects completed the study, with similar discontinuation rates observed between treatment groups (10.5% in Viaskin® Peanut group, 9.3% in placebo group) • Treatment adherence* was high (98.5%) across the total population, and comparable between groups • 4/238 (1.7%) subjects treated with Viaskin Peanut discontinued due to TEAEs – 2 due to moderate anaphylaxis; 2 due to skin reactions ≤ grade 3 Viaskin Peanut Placebo Total n (%) n (%) n (%) Enrolled 238 118 356 Completed 213 (89.5%) 107 (90.7%) 320 (89.9%) † Discontinued 25 (10.5%) 11 (9.3%) 36 (10.1%) ‡ Due to consent withdrawal 13 (5.5%) 6 (5.1%) 19 (5.3%) Due to TEAE 4 (1.7%) 0 (0%) 4 (1.1%) Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 1 *Defined as the total number of patches applied in the treatment period divided by the number of days in that period. † 1 Additional reasons for discontinuation from the Viaskin Peanut group included lost to follow-up (n=3), noncompliance (n=2), and other (n=3). ‡ 1 Includes one patient who experienced mild anaphylaxis but did not discontinue until 4 days after the event, due to parental consent withdrawal. TEAE=treatment-emergent adverse events. 42 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2. DBV Technologies. Data on file, 2019.High Adherence and Low Discontinuation Due to TEAEs (Fleischer, JAMA 2019) • 89.9% of all subjects completed the study, with similar discontinuation rates observed between treatment groups (10.5% in Viaskin® Peanut group, 9.3% in placebo group) • Treatment adherence* was high (98.5%) across the total population, and comparable between groups • 4/238 (1.7%) subjects treated with Viaskin Peanut discontinued due to TEAEs – 2 due to moderate anaphylaxis; 2 due to skin reactions ≤ grade 3 Viaskin Peanut Placebo Total n (%) n (%) n (%) Enrolled 238 118 356 Completed 213 (89.5%) 107 (90.7%) 320 (89.9%) † Discontinued 25 (10.5%) 11 (9.3%) 36 (10.1%) ‡ Due to consent withdrawal 13 (5.5%) 6 (5.1%) 19 (5.3%) Due to TEAE 4 (1.7%) 0 (0%) 4 (1.1%) Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 1 *Defined as the total number of patches applied in the treatment period divided by the number of days in that period. † 1 Additional reasons for discontinuation from the Viaskin Peanut group included lost to follow-up (n=3), noncompliance (n=2), and other (n=3). ‡ 1 Includes one patient who experienced mild anaphylaxis but did not discontinue until 4 days after the event, due to parental consent withdrawal. TEAE=treatment-emergent adverse events. 42 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2. DBV Technologies. Data on file, 2019.
Low Rates of Treatment-Related Serious AEs (Fleischer, JAMA 2019) • Viaskin Peanut 250 µg: 12 SAEs* in 10 Serious AEs* participants (4.2%); Placebo: 6 SAEs in 6 10% Placebo, n=118 participants (5.1%) Viaskin Peanut 250 µg, n=238 8% – 4 SAEs in 3 Viaskin Peanut participants considered related to treatment (1 probably 6% related, 3 possibly related) 5.1% 4.2% • All were moderate anaphylaxis without 4% evidence of cardiovascular, neurologic, or respiratory compromise 2% 1.3% • All resolved with standard treatment, 0.0% including 1 dose of epinephrine per 0% n=6 n=10 n=0 n=3 participant Any Treatment-related Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *Serious AE defined according to the International Conference on Harmonization-Good Clinical Practice as any untoward medical occurrence that at any dose results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; is an important medical event that may not be immediately life-threatening or result in death or hospitalization but that may jeopardize the participant or require intervention to prevent one of the above outcomes. AE=adverse event; SAE=serious adverse event. 43 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2. DBV Technologies. Data on file, 2019. % SubjectsLow Rates of Treatment-Related Serious AEs (Fleischer, JAMA 2019) • Viaskin Peanut 250 µg: 12 SAEs* in 10 Serious AEs* participants (4.2%); Placebo: 6 SAEs in 6 10% Placebo, n=118 participants (5.1%) Viaskin Peanut 250 µg, n=238 8% – 4 SAEs in 3 Viaskin Peanut participants considered related to treatment (1 probably 6% related, 3 possibly related) 5.1% 4.2% • All were moderate anaphylaxis without 4% evidence of cardiovascular, neurologic, or respiratory compromise 2% 1.3% • All resolved with standard treatment, 0.0% including 1 dose of epinephrine per 0% n=6 n=10 n=0 n=3 participant Any Treatment-related Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *Serious AE defined according to the International Conference on Harmonization-Good Clinical Practice as any untoward medical occurrence that at any dose results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; is an important medical event that may not be immediately life-threatening or result in death or hospitalization but that may jeopardize the participant or require intervention to prevent one of the above outcomes. AE=adverse event; SAE=serious adverse event. 43 1. Fleischer DM, et al. JAMA. 2019. doi:10.1001/jama.2019.1113. 2. DBV Technologies. Data on file, 2019. % Subjects
PEPITES Post-Hoc Analysis Using VIPES Responder Definition Suggests Consistent Treatment Effect Observed from Phase II to Phase III Actual Reported Response PEPITES Response Rate Using Rate in PEPITES (%) the VIPES Response Criteria 50 50 45.8% LCL 12.4 LCL 18.9 UCL 29.8 UCL 37.4 40 40 35.3% Δ = 28.8% 30 30 p < 0.0001 Δ = 21.7% p < 0.00001 20 20 16.9% 13.6% 10 10 0 0 Placebo VP 250 Placebo VP 250 n = 118 n = 238 n = 118 n = 238 44 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. % of Responders % of RespondersPEPITES Post-Hoc Analysis Using VIPES Responder Definition Suggests Consistent Treatment Effect Observed from Phase II to Phase III Actual Reported Response PEPITES Response Rate Using Rate in PEPITES (%) the VIPES Response Criteria 50 50 45.8% LCL 12.4 LCL 18.9 UCL 29.8 UCL 37.4 40 40 35.3% Δ = 28.8% 30 30 p < 0.0001 Δ = 21.7% p < 0.00001 20 20 16.9% 13.6% 10 10 0 0 Placebo VP 250 Placebo VP 250 n = 118 n = 238 n = 118 n = 238 44 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. % of Responders % of Responders
Positive Phase III REALISE Results Support Regulatory Filings for Viaskin Peanut Positive 6-month safety results confirmed the safety and tolerability profile observed in PEPITES, VIPES and CoFAR6 Placebo 250 µg 393 peanut allergic children 32 centers in North America 250 µg Safety Safety Safety Safety Endpoint Checkpoint Checkpoint Checkpoint M0 M6 M12 M24 M36 Open Label Clinical Trial Patient Population Safety & Exploratory Endpoints Patients 4 to 11 with history of IgE-mediated Primary endpoint to assess safety at M6 reactions to peanut • Treatment Emergent Adverse Events • Including patients with severe anaphylaxis No oral food challenges are required at baseline ≥ 14 kU/L peanut-specific IgE and ≥ 8 mm SPT* Exploratory endpoints wheal • Quality of Life Questionnaires (FAQLQ & FAIM) • Evolution of peanut-specific serological markers over time (IgE, IgG4, SPT wheal) * SPT: Skin Prick Test 45 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.Positive Phase III REALISE Results Support Regulatory Filings for Viaskin Peanut Positive 6-month safety results confirmed the safety and tolerability profile observed in PEPITES, VIPES and CoFAR6 Placebo 250 µg 393 peanut allergic children 32 centers in North America 250 µg Safety Safety Safety Safety Endpoint Checkpoint Checkpoint Checkpoint M0 M6 M12 M24 M36 Open Label Clinical Trial Patient Population Safety & Exploratory Endpoints Patients 4 to 11 with history of IgE-mediated Primary endpoint to assess safety at M6 reactions to peanut • Treatment Emergent Adverse Events • Including patients with severe anaphylaxis No oral food challenges are required at baseline ≥ 14 kU/L peanut-specific IgE and ≥ 8 mm SPT* Exploratory endpoints wheal • Quality of Life Questionnaires (FAQLQ & FAIM) • Evolution of peanut-specific serological markers over time (IgE, IgG4, SPT wheal) * SPT: Skin Prick Test 45 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.
Viaskin Peanut Phase II Program: VIPES, OLFUS-VIPES & COFAR6Viaskin Peanut Phase II Program: VIPES, OLFUS-VIPES & COFAR6
VIPES: Dose-Finding Phase IIb Efficacy and Safety Trial (Sampson, JAMA 2017) Placebo 50 µg 221 stratified patients, 22 250 µg centers in US, Canada, France, 100 µg Poland, and Netherlands 250 µg M0 M12 M0 M12 M24 M26 OLFUS-VIPES VIPES Open Label Follow-Up Study Dose-finding Clinical Trial Patient Population VIPES & OLFUS-VIPES Efficacy Highly allergic patients Primary endpoint at M12, M24 and M36 • > 0.7 kU/L peanut-specific IgE and ≥ 8 mm • ≥ 1000 mg reactive dose OR SPT* wheal • ≥ 10-fold of the initial reactive dose • Reactive dose at M0 ≤ 300 mg peanut protein Main secondary endpoints: (ie. approx 1 peanut) • CRD**, changes in peanut sIgE and sIgG4 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *SPT: Skin Prick Test **CRD: Cumulative Reactive Dose at Food Challenge 47 Denotes a completed food challenge VIPES: Dose-Finding Phase IIb Efficacy and Safety Trial (Sampson, JAMA 2017) Placebo 50 µg 221 stratified patients, 22 250 µg centers in US, Canada, France, 100 µg Poland, and Netherlands 250 µg M0 M12 M0 M12 M24 M26 OLFUS-VIPES VIPES Open Label Follow-Up Study Dose-finding Clinical Trial Patient Population VIPES & OLFUS-VIPES Efficacy Highly allergic patients Primary endpoint at M12, M24 and M36 • > 0.7 kU/L peanut-specific IgE and ≥ 8 mm • ≥ 1000 mg reactive dose OR SPT* wheal • ≥ 10-fold of the initial reactive dose • Reactive dose at M0 ≤ 300 mg peanut protein Main secondary endpoints: (ie. approx 1 peanut) • CRD**, changes in peanut sIgE and sIgG4 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *SPT: Skin Prick Test **CRD: Cumulative Reactive Dose at Food Challenge 47 Denotes a completed food challenge
VIPES: Patient Population Snapshot at Baseline 221 patients randomized 40 39 38 • 113 Children (6-11) • 73 Adolescents (12-17) & 35 Adults (18+) Highly allergic patients (median) 23 • Children = 30 mg 18 • Adolescents & Adults = 100 mg 17 13 13 Very high IgE levels: > 100 kU/L 11 • 47% of Children 6 • 38% of All Patients 2 1 Medical History of Patients 1 3 10 30 100 300 n% • Asthma 130 58.8 Peanut Protein Eliciting Dose (mg) • Eczema/Atopic Dermatitis 114 51.6 Children Adolescents/Adults • Allergic Rhinitis 96 43.4 • Polyallergic 183 82.8 48 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Randomized Patients (n) VIPES: Patient Population Snapshot at Baseline 221 patients randomized 40 39 38 • 113 Children (6-11) • 73 Adolescents (12-17) & 35 Adults (18+) Highly allergic patients (median) 23 • Children = 30 mg 18 • Adolescents & Adults = 100 mg 17 13 13 Very high IgE levels: > 100 kU/L 11 • 47% of Children 6 • 38% of All Patients 2 1 Medical History of Patients 1 3 10 30 100 300 n% • Asthma 130 58.8 Peanut Protein Eliciting Dose (mg) • Eczema/Atopic Dermatitis 114 51.6 Children Adolescents/Adults • Allergic Rhinitis 96 43.4 • Polyallergic 183 82.8 48 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Randomized Patients (n)
VIPES: Phase IIb Results Key Conclusions • Primary endpoint met with Viaskin Peanut 250 µg – Greatest response in children ages 6-11 (53.6% vs. 19.4%, p = 0.008) • Increase in threshold reactivity of peanut protein showed a clear dose response with greatest benefit in the 250 µg arm – In the children subgroup, mean CRD* at month 12 was 1211.9 mg (median 444 mg) in active vs. 239.1 mg (median 144 mg) in placebo (p < 0.001) • Immunological data supports treatment effect • Favorable safety and tolerability profile – 6.3% discontinuation rate (0.9% related to treatment) – Most frequent related AEs: local cutaneous reaction > 90% of patients mainly mild and moderate (50% with a duration < 2 months) – Median treatment compliance of 97.6% Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *CRD: Cumulative Reactive Dose at Food Challenge 49 JAMA. 2017;318(18):1798-1809. doi:10.1001/jama.2017.16591VIPES: Phase IIb Results Key Conclusions • Primary endpoint met with Viaskin Peanut 250 µg – Greatest response in children ages 6-11 (53.6% vs. 19.4%, p = 0.008) • Increase in threshold reactivity of peanut protein showed a clear dose response with greatest benefit in the 250 µg arm – In the children subgroup, mean CRD* at month 12 was 1211.9 mg (median 444 mg) in active vs. 239.1 mg (median 144 mg) in placebo (p < 0.001) • Immunological data supports treatment effect • Favorable safety and tolerability profile – 6.3% discontinuation rate (0.9% related to treatment) – Most frequent related AEs: local cutaneous reaction > 90% of patients mainly mild and moderate (50% with a duration < 2 months) – Median treatment compliance of 97.6% Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *CRD: Cumulative Reactive Dose at Food Challenge 49 JAMA. 2017;318(18):1798-1809. doi:10.1001/jama.2017.16591
VIPES: Primary Endpoint Met; Focus On Children (Ages 6-11) Response rate in children across doses after 12 months p = 0.008 80% 70% 60% 50% 40% 30% 57.1% 53.6% 46.2% 20% 10% 19.4% 0% Placebo 50 µg 100 µg 250 µg n = 31 n = 28 n = 26 n = 28 50 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. % of Responders (95% CI)VIPES: Primary Endpoint Met; Focus On Children (Ages 6-11) Response rate in children across doses after 12 months p = 0.008 80% 70% 60% 50% 40% 30% 57.1% 53.6% 46.2% 20% 10% 19.4% 0% Placebo 50 µg 100 µg 250 µg n = 31 n = 28 n = 26 n = 28 50 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. % of Responders (95% CI)
VIPES: Peanut Consumption In Children (Ages 6-11) Clear Dose Response, Clear Magnitude Of Effect Increase in CRD in children after 12 months (Mean and Median)* p < 0.001 2,000 mg 4-5 peanuts 1,500 mg 1,121.0 mg 1,000 mg 570.0 mg 471.2 mg Median = 400.0 500 mg Median = 114.5 60.8 mg Median = 135.0 Median = 0.0 Placebo 50 µg 100 µg 250 µg 0 mg n = 31 n = 28 n = 26 n = 28 * Excluding missing data 51 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Mean CRD Increase (95% CI)VIPES: Peanut Consumption In Children (Ages 6-11) Clear Dose Response, Clear Magnitude Of Effect Increase in CRD in children after 12 months (Mean and Median)* p < 0.001 2,000 mg 4-5 peanuts 1,500 mg 1,121.0 mg 1,000 mg 570.0 mg 471.2 mg Median = 400.0 500 mg Median = 114.5 60.8 mg Median = 135.0 Median = 0.0 Placebo 50 µg 100 µg 250 µg 0 mg n = 31 n = 28 n = 26 n = 28 * Excluding missing data 51 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Mean CRD Increase (95% CI)
VIPES: Immunological Changes In Children (Ages 6- 11) Supports Treatment Effect Peanut-specific IgE (kU/L) Peanut-specific IgG4 (mg/L) 52 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.VIPES: Immunological Changes In Children (Ages 6- 11) Supports Treatment Effect Peanut-specific IgE (kU/L) Peanut-specific IgG4 (mg/L) 52 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.
VIPES: Primary Efficacy Endpoint Met Identified Viaskin 250 µg As Phase III Dose Response rate across doses after 12 months p = 0.01 70% 60% 50% 40% 30% 50.0% 45.3% 20% 41.1% 10% 25.0% 0% Placebo 50 µg 100 µg 250 µg n = 56 n = 53 n = 56 n = 56 53 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. % of Responders (95% CI)VIPES: Primary Efficacy Endpoint Met Identified Viaskin 250 µg As Phase III Dose Response rate across doses after 12 months p = 0.01 70% 60% 50% 40% 30% 50.0% 45.3% 20% 41.1% 10% 25.0% 0% Placebo 50 µg 100 µg 250 µg n = 56 n = 53 n = 56 n = 56 53 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. % of Responders (95% CI)
VIPES: Adolescents & Adults High Placebo Response Rate Distorts Analysis Patients aged 12-55 response rate across doses p = 0.40 70% 60% 50% 40% 30% 46.4% 20% 36.7% 10% 32.0% 32.0% 0% Placebo 50 µg 100 µg 250 µg n = 25 n = 25 n = 30 n = 28 54 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. % of Responders (95% CI)VIPES: Adolescents & Adults High Placebo Response Rate Distorts Analysis Patients aged 12-55 response rate across doses p = 0.40 70% 60% 50% 40% 30% 46.4% 20% 36.7% 10% 32.0% 32.0% 0% Placebo 50 µg 100 µg 250 µg n = 25 n = 25 n = 30 n = 28 54 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. % of Responders (95% CI)
VIPES: Adolescents & Adults Changes From Baseline CRD Indicate Dose Response Trend Patients aged 12-55 increase in baseline CRD at 12 months across doses 1,500.0 mg 1,000.0 mg 842.3 mg 837.4 mg 619.2 mg 528.4 mg 500.0 mg Median = 335.0 Median = 30.0 Median = 0.0 Median = 10.0 0.0 mg Placebo 50 μg 100 µg 250 μg n = 25 n = 28 n = 30 n = 28 55 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Mean CRD Increase (95% CI)VIPES: Adolescents & Adults Changes From Baseline CRD Indicate Dose Response Trend Patients aged 12-55 increase in baseline CRD at 12 months across doses 1,500.0 mg 1,000.0 mg 842.3 mg 837.4 mg 619.2 mg 528.4 mg 500.0 mg Median = 335.0 Median = 30.0 Median = 0.0 Median = 10.0 0.0 mg Placebo 50 μg 100 µg 250 μg n = 25 n = 28 n = 30 n = 28 55 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Mean CRD Increase (95% CI)
VIPES: Adolescents & Adults Immunological Changes Support Dose Response Trend Peanut-specific IgE (kU/L) Peanut-specific IgG4 (mg/L) 56 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.VIPES: Adolescents & Adults Immunological Changes Support Dose Response Trend Peanut-specific IgE (kU/L) Peanut-specific IgG4 (mg/L) 56 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.
VIPES: Post Hoc Analysis Using PEPITES Responder Definition VIPES Children (6-11 years) - Viaskin 250 μg at M12 Reported Response Rate VIPES Response Rate Using the PEPITES Response Criteria 80% 80% p = 0.0007 p = 0.008 70% 70% 60% 60% 50% 50% 40% 40% 30% 30% 53.6% 46.4% 20% 20% 10% 10% 6.5% 19.4% 0% 0% Placebo 250 µg Placebo 250 µg n = 31 n = 28 n = 31 n = 28 57 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. % of Responders % of RespondersVIPES: Post Hoc Analysis Using PEPITES Responder Definition VIPES Children (6-11 years) - Viaskin 250 μg at M12 Reported Response Rate VIPES Response Rate Using the PEPITES Response Criteria 80% 80% p = 0.0007 p = 0.008 70% 70% 60% 60% 50% 50% 40% 40% 30% 30% 53.6% 46.4% 20% 20% 10% 10% 6.5% 19.4% 0% 0% Placebo 250 µg Placebo 250 µg n = 31 n = 28 n = 31 n = 28 57 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. % of Responders % of Responders
OLFUS-VIPES: Open-label Follow-up Trial To VIPES Extension Trial To Support Use Of Viaskin Peanut Placebo 221 stratified patients, 22 50 µg 250 µg centers in US, Canada, 100 µg France, Poland, and Netherlands 250 µg M0 M12 M0 M12 M24 M26 OLFUS-VIPES VIPES Open Label Follow-Up Study Dose-finding 171 patients opted to enroll in OLFUS (overall 83% roll-over rate from VIPES) • 97 children and 74 adolescents & adults Assessed long-term safety and efficacy Double-Blind Placebo-Controlled Food Challenge (DBPCFC) administered at month-12 and month-24 Month-26 DBPCFC to explore “sustained unresponsiveness” • Patients unresponsive to CRD* > 1,440 mg at month-24 DBPCFC were eligible to continue study • Two-month period without treatment or consumption of peanut to assess durability of response *CRD: Cumulative Reactive Dose at Food Challenge Denotes a completed food challenge 58 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.OLFUS-VIPES: Open-label Follow-up Trial To VIPES Extension Trial To Support Use Of Viaskin Peanut Placebo 221 stratified patients, 22 50 µg 250 µg centers in US, Canada, 100 µg France, Poland, and Netherlands 250 µg M0 M12 M0 M12 M24 M26 OLFUS-VIPES VIPES Open Label Follow-Up Study Dose-finding 171 patients opted to enroll in OLFUS (overall 83% roll-over rate from VIPES) • 97 children and 74 adolescents & adults Assessed long-term safety and efficacy Double-Blind Placebo-Controlled Food Challenge (DBPCFC) administered at month-12 and month-24 Month-26 DBPCFC to explore “sustained unresponsiveness” • Patients unresponsive to CRD* > 1,440 mg at month-24 DBPCFC were eligible to continue study • Two-month period without treatment or consumption of peanut to assess durability of response *CRD: Cumulative Reactive Dose at Food Challenge Denotes a completed food challenge 58 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority.
OLFUS-VIPES: Long-term Extension Data Shows Benefit Increases Over Time in Phase IIb Study Response Rate at OLFUS: Cumulative Reactive Dose in OLFUS Baseline, Year-1 and Year-2 Mean ± 95% CI Observed values, ITT 100% 5,000 mg 2,453.9 mg 3,000 mg 80% 1,883.5 mg 2,000 mg 60% Median = Median = 1,067.8 mg 1,440 mg 1,440 mg 40% 80.0% 83.3% 1,000 mg (16/20) (15/18) 20% 57.1% Median = 444 mg (12/21) 84.5 mg Median = 44 mg 0 mg 0% OLFUS baseline OLFUS year 1 OLFUS year 2 VIPES baseline OLFUS baseline OLFUS year 1 OLFUS year 2 n = 21 n = 20* n = 18** n = 21 n = 21 n = 20 n = 18 Excluding missing data Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Results shown for Viaskin Peanut 250 µg * 1 child discontinued (not related to Viaskin Peanut) 59 ** 2 children discontinued (none related to Viaskin Peanut) Sampson et al. JAMA. 2017;318(18):1798-1809. doi:10.1001/jama.2017.16591,. Shreffler et al. AAAAI 2017, #L7OLFUS-VIPES: Long-term Extension Data Shows Benefit Increases Over Time in Phase IIb Study Response Rate at OLFUS: Cumulative Reactive Dose in OLFUS Baseline, Year-1 and Year-2 Mean ± 95% CI Observed values, ITT 100% 5,000 mg 2,453.9 mg 3,000 mg 80% 1,883.5 mg 2,000 mg 60% Median = Median = 1,067.8 mg 1,440 mg 1,440 mg 40% 80.0% 83.3% 1,000 mg (16/20) (15/18) 20% 57.1% Median = 444 mg (12/21) 84.5 mg Median = 44 mg 0 mg 0% OLFUS baseline OLFUS year 1 OLFUS year 2 VIPES baseline OLFUS baseline OLFUS year 1 OLFUS year 2 n = 21 n = 20* n = 18** n = 21 n = 21 n = 20 n = 18 Excluding missing data Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Results shown for Viaskin Peanut 250 µg * 1 child discontinued (not related to Viaskin Peanut) 59 ** 2 children discontinued (none related to Viaskin Peanut) Sampson et al. JAMA. 2017;318(18):1798-1809. doi:10.1001/jama.2017.16591,. Shreffler et al. AAAAI 2017, #L7
OLFUS-VIPES: Immunological Changes, Ages 6-11 Relative Change IgE Relative Change IgG4 Median ± IQ Median ± IQ 4,000 100 3,000 2,000 50 1,000 0 500 -50 0 3 6 12 18 24 30 36 Months 0 3 6 12 18 24 30 36 Months Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Median relative change = 100 x (Month xx – Baseline)/Baseline 60 Viaskin Peanut 250 µg, n = 18OLFUS-VIPES: Immunological Changes, Ages 6-11 Relative Change IgE Relative Change IgG4 Median ± IQ Median ± IQ 4,000 100 3,000 2,000 50 1,000 0 500 -50 0 3 6 12 18 24 30 36 Months 0 3 6 12 18 24 30 36 Months Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Median relative change = 100 x (Month xx – Baseline)/Baseline 60 Viaskin Peanut 250 µg, n = 18
OLFUS-VIPES: Long-term Follow-up Data Key Conclusions Late Breaking Oral Presentation at AAAAI 2017 • In children treated for three years with a 250 µg dose there was a trend of progressive response to treatment as measured by increased response rate, higher CRD* and serological changes – Treatment benefit was observed to be long-lasting for three years – 83.3% response rate after three years, an increase from 57.1% at OLFUS baseline – Mean CRD reached 2,453.9 mg at the end of OLFUS, from 1,067.8 mg at OLFUS baseline • No decreased compliance or increased frequency of AEs in VIPES patients treated for 24 additional months – 95.5 % overall compliance rate was observed throughout the study – No SAEs or epinephrine use due to treatment was reported in 36 months – Most adverse events were related to application site and were mild to moderate, with decreasing severity and frequency over time Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Shreffler et al. AAAAI 2017, #L7 61 *CRD: Cumulative Reactive Dose at Food ChallengeOLFUS-VIPES: Long-term Follow-up Data Key Conclusions Late Breaking Oral Presentation at AAAAI 2017 • In children treated for three years with a 250 µg dose there was a trend of progressive response to treatment as measured by increased response rate, higher CRD* and serological changes – Treatment benefit was observed to be long-lasting for three years – 83.3% response rate after three years, an increase from 57.1% at OLFUS baseline – Mean CRD reached 2,453.9 mg at the end of OLFUS, from 1,067.8 mg at OLFUS baseline • No decreased compliance or increased frequency of AEs in VIPES patients treated for 24 additional months – 95.5 % overall compliance rate was observed throughout the study – No SAEs or epinephrine use due to treatment was reported in 36 months – Most adverse events were related to application site and were mild to moderate, with decreasing severity and frequency over time Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Shreffler et al. AAAAI 2017, #L7 61 *CRD: Cumulative Reactive Dose at Food Challenge
CoFAR6: Efficacy And Safety – NIAID Sponsored Phase II 250 mg Viaskin Peanut Enrollment 221 stratified patients, 22 100 mg Viaskin Peanut n = 75 250 mg Viaskin Peanut centers in US, Canada, France, Poland, and Entry OFC positive Netherlands Placebo to cumulative dose of < 1044 mg Week 130 peanut protein 5044 mg OFC Randomization Week 52 [End of study] 1:1:1 5044 mg OFC Defined Endpoints Primary endpoint: Proportion with a treatment success following Secondary endpoints: 52 weeks of blinded treatment • Comparison of Viaskin Peanut 100 µg vs Viaskin Peanut 250 µg doses at week 52 • Passing a 5044 mg OFC* to peanut protein at week 52 OR ≥ 10-fold increase in the successfully consumed dose (SCD) of peanut protein • Desensitization and sustained unresponsiveness at week 130 at week 52 compared to baseline OFC • Incidence of all adverse events • Changes in immune markers Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Jones SM, et al. J Allergy Clin Immunol. 2017;139:1242-1252 *OFC: Oral Food Challenge 62 Denotes a completed food challenge; Denotes a pending food challengeCoFAR6: Efficacy And Safety – NIAID Sponsored Phase II 250 mg Viaskin Peanut Enrollment 221 stratified patients, 22 100 mg Viaskin Peanut n = 75 250 mg Viaskin Peanut centers in US, Canada, France, Poland, and Entry OFC positive Netherlands Placebo to cumulative dose of < 1044 mg Week 130 peanut protein 5044 mg OFC Randomization Week 52 [End of study] 1:1:1 5044 mg OFC Defined Endpoints Primary endpoint: Proportion with a treatment success following Secondary endpoints: 52 weeks of blinded treatment • Comparison of Viaskin Peanut 100 µg vs Viaskin Peanut 250 µg doses at week 52 • Passing a 5044 mg OFC* to peanut protein at week 52 OR ≥ 10-fold increase in the successfully consumed dose (SCD) of peanut protein • Desensitization and sustained unresponsiveness at week 130 at week 52 compared to baseline OFC • Incidence of all adverse events • Changes in immune markers Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. Jones SM, et al. J Allergy Clin Immunol. 2017;139:1242-1252 *OFC: Oral Food Challenge 62 Denotes a completed food challenge; Denotes a pending food challenge
CoFAR6: Primary Endpoint Was Met All Patients 4 – 11 Years Primary Endpoint Pre-specified Analysis • No SAEs or Epinephrine p = <0.001 p = 0.003 due to drug p = <0.001 p = 0.005 100 100 • 96% compliance 61.1% 58.8% • Primary endpoint met (p 48.0% = 0.003) 50 50 45.8% • Significant age by treatment interaction – ~1/3 of children treated 12.0% with 250 µg were able 5.6% to tolerate > 1,000 mg 0 0 protein (~4 peanuts) Placebo 100 µg 250 µg Placebo 100 µg 250 µg – Significant increase in n = 25 n = 24 n = 25 n = 18 n = 17 n = 18 IgG4 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 63 Jones SM, et al. J Allergy Clin Immunol. 2017;139:1242-1252 Treatment Success (%) Treatment Success (%)CoFAR6: Primary Endpoint Was Met All Patients 4 – 11 Years Primary Endpoint Pre-specified Analysis • No SAEs or Epinephrine p = <0.001 p = 0.003 due to drug p = <0.001 p = 0.005 100 100 • 96% compliance 61.1% 58.8% • Primary endpoint met (p 48.0% = 0.003) 50 50 45.8% • Significant age by treatment interaction – ~1/3 of children treated 12.0% with 250 µg were able 5.6% to tolerate > 1,000 mg 0 0 protein (~4 peanuts) Placebo 100 µg 250 µg Placebo 100 µg 250 µg – Significant increase in n = 25 n = 24 n = 25 n = 18 n = 17 n = 18 IgG4 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 63 Jones SM, et al. J Allergy Clin Immunol. 2017;139:1242-1252 Treatment Success (%) Treatment Success (%)
Viaskin Milk Phase II Program: MILESViaskin Milk Phase II Program: MILES
Viaskin Milk: Milk Allergy (CMPA) Phase II Study Identified Safe/Effective Dose for Children Open Label Phase I (Part A) Phase II (Part B) Cohort at 500µg dose Placebo DSMB FDA & 150 µg 300 µg*** Pediatric Phase I/II DSMB 300 µg USA & Canada Cohort at 300µg dose Part A: 18 patients 500 µg DSMB Part B: 180 patients M0 M12 M24 M36 Cohort at Food challenges optional following 12 and 24 150µg dose months of receiving 300 µg Clinical Trial Patient Population Efficacy Endpoints • Children (2-11) and adolescents (12-17) Treatment responder definition at M12: • Highly sensitive to milk (≥ 10 kU/L milk- • ≥ 10-fold increase in CRD** and at least 144 mg of CMP specific IgE and ≥ 6 mm SPT* wheal) • OR CRD ≥ 1,444 mg • Reactive dose at baseline (M0) ≤300 mg cow’s Key secondary endpoints: milk protein (CMP) (~ ≤ 9.4 mL of cow’s milk) • Change from baseline in IgE, IgG4 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. * SPT: Skin Prick Test ** CRD: Cumulative Reactive Dose at Food Challenge 65 ***Protocol change implemented in August 2018 to switch all patients to 300 µg (from 500 µg) for treatment up to 24 months Denotes a completed food challenge; Denotes a pending, optional food challenge Viaskin Milk: Milk Allergy (CMPA) Phase II Study Identified Safe/Effective Dose for Children Open Label Phase I (Part A) Phase II (Part B) Cohort at 500µg dose Placebo DSMB FDA & 150 µg 300 µg*** Pediatric Phase I/II DSMB 300 µg USA & Canada Cohort at 300µg dose Part A: 18 patients 500 µg DSMB Part B: 180 patients M0 M12 M24 M36 Cohort at Food challenges optional following 12 and 24 150µg dose months of receiving 300 µg Clinical Trial Patient Population Efficacy Endpoints • Children (2-11) and adolescents (12-17) Treatment responder definition at M12: • Highly sensitive to milk (≥ 10 kU/L milk- • ≥ 10-fold increase in CRD** and at least 144 mg of CMP specific IgE and ≥ 6 mm SPT* wheal) • OR CRD ≥ 1,444 mg • Reactive dose at baseline (M0) ≤300 mg cow’s Key secondary endpoints: milk protein (CMP) (~ ≤ 9.4 mL of cow’s milk) • Change from baseline in IgE, IgG4 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. * SPT: Skin Prick Test ** CRD: Cumulative Reactive Dose at Food Challenge 65 ***Protocol change implemented in August 2018 to switch all patients to 300 µg (from 500 µg) for treatment up to 24 months Denotes a completed food challenge; Denotes a pending, optional food challenge
MILES Patient Population at Baseline Medical history of patients 198 patients randomized n% • 152 Children (2-11) Asthma 139 70.2 • 46 Adolescents (12-17) Atopic Dermatitis 139 70.2 CRD of Cow’s Milk Allergic Rhinitis 144 72.7 Polyallergic 178 89.9 Mean • Children: 216.3 mg Mean Cow’s Milk sIgE • Adolescents: 222.0 mg • Children: 135.2 kU/L Median • Adolescents: 127.9 kU/L • Children: 144 mg • Adolescents: 144 mg Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 66MILES Patient Population at Baseline Medical history of patients 198 patients randomized n% • 152 Children (2-11) Asthma 139 70.2 • 46 Adolescents (12-17) Atopic Dermatitis 139 70.2 CRD of Cow’s Milk Allergic Rhinitis 144 72.7 Polyallergic 178 89.9 Mean • Children: 216.3 mg Mean Cow’s Milk sIgE • Adolescents: 222.0 mg • Children: 135.2 kU/L Median • Adolescents: 127.9 kU/L • Children: 144 mg • Adolescents: 144 mg Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 66
MILES Results: Support Viaskin Milk 300µg as the Potential First Treatment for CMPA in Children 2-11 Response Rate (ITT*) Favorable safety, tolerability and compliance p = 0.733 • Overall discontinuation rate of 4.5% p = 0.042 p > 0.999 – 1.5% dropout due to AEs • Most AEs related to application site (mild to moderate) • No severe anaphylaxis 57.9% • No SAEs or epinephrine related to 38.9% 34.2% 32.5% treatment • Treatment adherence was high Placebo 150 µg 300 µg 500 µg – Mean patient compliance > 95% n = 40 n = 38 n = 38 n = 36 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. * Missing data: failure imputation (considered as non-responders) in ITT population 67 P-values obtained using exact logistic regression ITT, Intent-to-Treat % of Responders (90% CI)MILES Results: Support Viaskin Milk 300µg as the Potential First Treatment for CMPA in Children 2-11 Response Rate (ITT*) Favorable safety, tolerability and compliance p = 0.733 • Overall discontinuation rate of 4.5% p = 0.042 p > 0.999 – 1.5% dropout due to AEs • Most AEs related to application site (mild to moderate) • No severe anaphylaxis 57.9% • No SAEs or epinephrine related to 38.9% 34.2% 32.5% treatment • Treatment adherence was high Placebo 150 µg 300 µg 500 µg – Mean patient compliance > 95% n = 40 n = 38 n = 38 n = 36 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. * Missing data: failure imputation (considered as non-responders) in ITT population 67 P-values obtained using exact logistic regression ITT, Intent-to-Treat % of Responders (90% CI)
MILES Results: Significant Improvement in Threshold Reactivity with Viaskin Milk 300µg in Children 2-11 Change of CRD (PP*) Change of CRD (ITT*†) p = 0.822 p = 0.985 1800 1800 p = 0.043 p = 0.045 1600 1600 p = 0.809 p = 0.617 1340.3 1400 1400 1322.4 1200 1200 1000 1000 1000 848.0 1000 839.8 800 800 624.6 569.6 600 565.6 600 510.8 400 400 300 200 200 120 106 100 62 25 0 0 Placebo VM150 µg VM300 µg VM500 µg Placebo VM150 µg VM300 µg VM500 µg n = 39 n = 37 n = 36 n = 34 n = 35 n = 28 n = 32 n = 32 – Median Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *Among patients with evaluable CRD assessment at Month 12. † Note, not all subjects underwent a Month-12 OFC: 1 subject in PBO, 1 subject in VM150 µg, 2 in VM300 µg, and 2 in VM500 µg did not report Month-12 CRD. 68 P-values obtained from ANCOVA model including on CRD at M0 and treatment group as fixed effect, using log-transformed data. Mean (SE) Change of CRD at M12 vs Baseline, mg* Mean (SE) Change of CRD at M12 vs Baseline, mg*MILES Results: Significant Improvement in Threshold Reactivity with Viaskin Milk 300µg in Children 2-11 Change of CRD (PP*) Change of CRD (ITT*†) p = 0.822 p = 0.985 1800 1800 p = 0.043 p = 0.045 1600 1600 p = 0.809 p = 0.617 1340.3 1400 1400 1322.4 1200 1200 1000 1000 1000 848.0 1000 839.8 800 800 624.6 569.6 600 565.6 600 510.8 400 400 300 200 200 120 106 100 62 25 0 0 Placebo VM150 µg VM300 µg VM500 µg Placebo VM150 µg VM300 µg VM500 µg n = 39 n = 37 n = 36 n = 34 n = 35 n = 28 n = 32 n = 32 – Median Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *Among patients with evaluable CRD assessment at Month 12. † Note, not all subjects underwent a Month-12 OFC: 1 subject in PBO, 1 subject in VM150 µg, 2 in VM300 µg, and 2 in VM500 µg did not report Month-12 CRD. 68 P-values obtained from ANCOVA model including on CRD at M0 and treatment group as fixed effect, using log-transformed data. Mean (SE) Change of CRD at M12 vs Baseline, mg* Mean (SE) Change of CRD at M12 vs Baseline, mg*
MILES Results: All Dose Cohorts At Month-12 Response Rate, Overall Population (ITT*) Response Rate (ITT*) Response Rate (PP) p = 0.522 p = 0.682 p = 0.027 70 70 p = 0.649 p = 0.085 p = 0.641 60 60 50 50 40 40 30 30 55.0% 49.0% 20 20 36.7% 37.2% 36.2% 36.1% 30.2% 28.9% 10 10 0 0 Placebo VM150 µg VM300 µg VM500 µg Placebo VM150 µg VM300 µg VM500 µg n = 53 n = 49 n = 49 n =47 n = 45 n = 36 n = 40 n = 43 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *Missing data: failure imputation (considered as non-responders) in ITT population 69 P-values obtained using exact logistic regression ITT=Intent-to-Treat; PP=Per Protocol % of Responders (95% CI) % of Responders (95% CI)MILES Results: All Dose Cohorts At Month-12 Response Rate, Overall Population (ITT*) Response Rate (ITT*) Response Rate (PP) p = 0.522 p = 0.682 p = 0.027 70 70 p = 0.649 p = 0.085 p = 0.641 60 60 50 50 40 40 30 30 55.0% 49.0% 20 20 36.7% 37.2% 36.2% 36.1% 30.2% 28.9% 10 10 0 0 Placebo VM150 µg VM300 µg VM500 µg Placebo VM150 µg VM300 µg VM500 µg n = 53 n = 49 n = 49 n =47 n = 45 n = 36 n = 40 n = 43 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *Missing data: failure imputation (considered as non-responders) in ITT population 69 P-values obtained using exact logistic regression ITT=Intent-to-Treat; PP=Per Protocol % of Responders (95% CI) % of Responders (95% CI)
MILES Results: All Dose Cohorts At Month-12 CRD, Overall Population (ITT) Mean Increase in CRD p = 0.736 p = 0.008 p = 0.189 1,201.0 745.1 723.5 555.5 Median Median 400 mg 300 mg Median Median 100 mg 93 mg Placebo 150 µg 300 µg 500 µg n = 39 n = 37 n = 36 n = 34 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *Among patients with evaluable CRD assessment at Month 12 † Note, not all subjects underwent a Month-12 OFC: 1 subject in PBO, 1 subject in VM150 µg, 4 in VM300 µg, and 2 in VM500 µg did not report Month-12 CRD P-values obtained from ANCOVA model including on CRD at M0 and treatment group as fixed effect, using log-transformed data 70 ITT=Intent-to-Treat; PP=Per Protocol; SE=Standard Error Mean CRD Increase at M12 vs Baseline, mg*MILES Results: All Dose Cohorts At Month-12 CRD, Overall Population (ITT) Mean Increase in CRD p = 0.736 p = 0.008 p = 0.189 1,201.0 745.1 723.5 555.5 Median Median 400 mg 300 mg Median Median 100 mg 93 mg Placebo 150 µg 300 µg 500 µg n = 39 n = 37 n = 36 n = 34 Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. *Among patients with evaluable CRD assessment at Month 12 † Note, not all subjects underwent a Month-12 OFC: 1 subject in PBO, 1 subject in VM150 µg, 4 in VM300 µg, and 2 in VM500 µg did not report Month-12 CRD P-values obtained from ANCOVA model including on CRD at M0 and treatment group as fixed effect, using log-transformed data 70 ITT=Intent-to-Treat; PP=Per Protocol; SE=Standard Error Mean CRD Increase at M12 vs Baseline, mg*
MILES Immunologic Data in Children 2-11 (ITT): Significant Immunomodulation with Viaskin Milk sIgG4 casein, mg/L sIgG4 α-lactalbumin, mg/L sIgG4 β-lactoglobulin, mg/L p ˂ 0.001 p ˂ 0.001 p ˂ 0.001 p ˂ 0.001 p ˂ 0.001 p ˂ 0.001 p ˂ 0.001 p ˂ 0.001 p ˂ 0.001 • For sIgE levels in children, there is a trend towards reduction with VM doses • No changes observed in SPT responses Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. P-values obtained from repeated-measures ANCOVA model including treatment group, timepoint, treatment-by-timepoint interaction and M0 value as fixed effect, using log-transformed data; ITT=Intent-to-Treat 71 Geometric Mean (90% CI) Geometric Mean (90% CI) Geometric Mean (90% CI) MILES Immunologic Data in Children 2-11 (ITT): Significant Immunomodulation with Viaskin Milk sIgG4 casein, mg/L sIgG4 α-lactalbumin, mg/L sIgG4 β-lactoglobulin, mg/L p ˂ 0.001 p ˂ 0.001 p ˂ 0.001 p ˂ 0.001 p ˂ 0.001 p ˂ 0.001 p ˂ 0.001 p ˂ 0.001 p ˂ 0.001 • For sIgE levels in children, there is a trend towards reduction with VM doses • No changes observed in SPT responses Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. P-values obtained from repeated-measures ANCOVA model including treatment group, timepoint, treatment-by-timepoint interaction and M0 value as fixed effect, using log-transformed data; ITT=Intent-to-Treat 71 Geometric Mean (90% CI) Geometric Mean (90% CI) Geometric Mean (90% CI)
MILES Immunologic Data in Children 2-11 (ITT): Significant Immunomodulation with Viaskin Milk sIgE casein, kUA/L sIgE α-lactalbumin, kUA/L sIgE β-lactoglobulin, kUA/L p = 0.018 p = 0.003 p = 0.008 p = 0.166 p = 0.336 p = 0.201 p = 0.307 p = 0.090 p = 0.172 • There is a trend towards reduction of sIgE levels in VM doses Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 72 P-values obtained from repeated-measures ANCOVA model including treatment group, timepoint, treatment-by-timepoint interaction and M0 value as fixed effect, using log-transformed data; ITT=Intent-to-Treat Geometric Mean (90% CI) Geometric Mean (90% CI) Geometric Mean (90% CI) MILES Immunologic Data in Children 2-11 (ITT): Significant Immunomodulation with Viaskin Milk sIgE casein, kUA/L sIgE α-lactalbumin, kUA/L sIgE β-lactoglobulin, kUA/L p = 0.018 p = 0.003 p = 0.008 p = 0.166 p = 0.336 p = 0.201 p = 0.307 p = 0.090 p = 0.172 • There is a trend towards reduction of sIgE levels in VM doses Epicutaneous immunotherapy and Viaskin™ Peanut are under clinical investigation and have not been approved for marketing by any health or regulatory authority. 72 P-values obtained from repeated-measures ANCOVA model including treatment group, timepoint, treatment-by-timepoint interaction and M0 value as fixed effect, using log-transformed data; ITT=Intent-to-Treat Geometric Mean (90% CI) Geometric Mean (90% CI) Geometric Mean (90% CI)
