Significant Events and Transactions | Note 2: Significant Events and Transactions Clinical programs United States Regulatory History and Current Status In January 2021, the Company received written responses from the FDA to questions provided in the Type A meeting request the Company submitted in October 2020 following receipt of the Complete Response Letter. The FDA agreed with its position that a modified Viaskin Peanut patch should not be considered as a new product entity provided the occlusion chamber of the current Viaskin Peanut patch and the peanut protein dose of 250 µg (approximately 1/1000 of one peanut) remains unchanged and performs in the same way it has performed previously. In order to confirm the consistency of efficacy data between the existing and a modified patch, FDA requested an assessment comparing the uptake of allergen (peanut protein) between the patches in peanut allergic children ages 4-11. 6-month, Based on the January 2021 FDA feedback, the Company defined three parallel workstreams: 1. Identify a modified Viaskin patch (which the Company calls “mVP”). 2. Generate the 6-month 3. Demonstrate the equivalence in allergen uptake between the current and modified patches in the intended patient population via EQUAL. The complexity of EQUAL hinged on the lack of established clinical and regulatory criteria to characterize allergen uptake via an epicutaneous patch. To support those exchanges, the Company outlined its proposed approach to demonstrate allergen uptake equivalence between the two patches, and allotted time to generate informative data through two additional Phase 1 clinical trials in healthy adult volunteers: a. PREQUAL, a Phase 1 study with adult healthy volunteers to optimize the allergen sample collection methodologies and validate the assays we intend to use in EQUAL . b. ‘EQUAL in adults’—a second Phase I study with adult healthy volunteers to compare the allergen uptake of cVP and mVP; In March 2021, the Company commenced CHAMP (Comparison of adHesion Among Modified Patches), a Phase 1 trial in healthy adult volunteers to evaluate the adhesion of five modified Viaskin Peanut patches. The Company completed CHAMP in the second quarter of 2021. All modified Viaskin Peanut patches demonstrated better adhesion performance as compared to the then-current Viaskin Peanut patch, and the Company then selected two modified patches that performed best out of the five modified patches studied for further development. The Company then selected the circular patch for further development, which is larger in size relative to the current patch and circular in shape. In May 2021, the Company submitted its proposed STAMP protocol to the FDA, and on October 14, 2021, the Company received an Advice/Information Request letter from the FDA. In this letter, the FDA requested a stepwise approach to the modified Viaskin patch development program and provided partial feedback on the STAMP protocol. Specifically, the FDA requested that the Company conduct allergen uptake comparison studies (i.e., ‘EQUAL in Adults’, EQUAL), and submit the allergen uptake comparison data for FDA review and feedback prior to starting the STAMP study. The FDA’s explanation was that the results from the allergen uptake studies might affect the design of the STAMP study. After careful review of the FDA’s information requests, in December 2021, the Company decided not to pursue the sequential approach to the development plans for Viaskin Peanut as requested by the FDA in the October 2021 feedback. The Company estimated that the FDA’s newly proposed sequential approach would require at least five rounds of exchanges that necessitate FDA alignment prior to initiating STAMP, the 6-month exchanges. In 2022, the Company announced the new Phase 3 pivotal study for modified Viaskin Peanut (mVP) patch would be in younger (4-7 On September 7, 2022, the Company announced the initiation of VITESSE, a new Phase 3 pivotal study of the modified Viaskin Peanut (mVP) patch in children ages 4-7 al On September 21, 2022, the Company announced it received feedback from the U.S. FDA in the form of a partial clinical hold on VITESSE. In the partial clinical hold letter, the FDA specified changes to elements of the VITESSE protocol, acknowledging the intent for the trial to support a future BLA submission. In the following months, we engaged with the FDA to address the feedback provided in the partial clinical hold letter and to finalize the VITESSE protocol. In addition, we continued internal preparations for VITESSE and conducted certain site assessment and start-up On December 23, 2022, the Company announced the FDA lifted the partial clinical hold and confirmed we satisfactorily addressed all clinical hold issues. The FDA stated that VITESSE may proceed with the revised trial protocol. On March 2, 2023, the Company announced the completion of EVOLVE, a 12-week 4–11-years On March 7, 2023, the Company announced that the first patient was screened in the VITESSE study. Screening of the last patient is anticipated in the first half in 2024 and topline results in the first half in 2025. On April 19, 2023, the Company outlined the 1-3 pre-specified Viaskin Peanut for children ages 4-11—European On August 2, 2021, the Company announced it received from the European Medicines Agency (“EMA”) of the Day 180 list of outstanding issues, which is an established part of the prescribed EMA review process. It is a letter that is meant to include any remaining questions or objections at that stage in the process. The EMA indicated many of their objections and major objections from the Day 120 list of questions had been answered. One major objection remained at Day 180. The Major Objection questioned the limitations of the data, for example, the clinical relevance and effect size supported by a single pivotal study. On December 20, 2021, the Company announced it had withdrawn the Marketing Authorization Application (“MAA”) for Viaskin Peanut and formally notified the EMA of our decision. The initial filing was supported by data from a single, placebo-controlled Phase 3 pivotal trial known as PEPITES (V712-301). Viaskin Peanut for children ages 1-3 In June 2020, the Company announced that in Part A, patients in both treatment arms showed consistent treatment effects after 12 months of therapy, as assessed by a double-blind placebo-controlled food challenge and biomarker results. Part A subjects were not included in Part B and the efficacy analyses from Part A were not statistically powered to demonstrate superiority of either dose versus placebo. These results validate the ongoing investigation of the 250 µg dose in this age group, which is the dose being studied in Part B of the study. Enrollment for Part B of EPITOPE was completed in the first quarter of 2021. In June 2022, the Company announced positive topline results from Part B of EPITOPE, which enrolled 362 subjects ages 1 to 3 years, of which 244 and 118 were in the active and placebo arms respectively. Enrollment was balance for age and baseline disease characteristics between the active and placebo treatment arms. On April 19, 2023, the Company announced it will begin a new safety study after it received confirmation from the FDA that the EPITOPE study meets the pre-specified On May 10, 2023, the New England Journal of Medicine (NEJM) published results that demonstrated epicutaneous immunotherapy (EPIT) with VP was statistically superior to placebo in desensitizing children to peanut exposure 1-3 Viaskin Peanut for Children ages 4-7 On September 7, 2022, the Company announced the initiation of VITESSE, a new Phase 3 pivotal study of the modified Viaskin Peanut (mVP) patch in children ages 4-7 On September 21, 2022, the Company announced we had received feedback from the FDA in the form of a partial clinical hold on VITESSE. In the partial clinical hold letter, the FDA specified changes to elements of the VITESSE protocol, acknowledging the intent for the trial to support a future BLA submission. In the following months, we engaged with the FDA to address the feedback provided in the partial clinical hold letter and to finalize the VITESSE protocol. In addition, we continued internal preparations for VITESSE and conducted certain site assessment and start-up On December 23, 2022, the Company announced the FDA lifted the partial clinical hold and confirmed we satisfactorily addressed all clinical hold issues. The FDA stated that VITESSE may proceed with the revised trial protocol. On March 7, 2023, the Company announced that the first patient was screened in the VITESSE trial. Screening of the last patient is anticipated in the first half in 2024 and topline results in the first half in 2025. Financing In June 2023, the Company issued and completed sales of new ordinary shares (the “Ordinary Shares”) in the At-The-Market the one-half Legal Proceedings From time to time, the Company may become subject to various legal proceedings and claims that arise in the ordinary course of our business activities. The Company is not currently subject to any material legal proceedings. |