Rimegepant is Effective for the Acute Treatment of in Patients with a History of Treatment Failure: Pooled Analyses from 3 Phase 3 Clinical Trials Richard B. Lipton, MD1; Andrew Blumenfeld, MD2; Robert Croop, MD3; Christopher M. Jensen, PharmD3; Alexandra Thiry, PhD3; Elyse G. Stock, MD3; Charles M. Conway, PhD3; Beth A. Morris, BA3, Vladimir Coric, MD3; Peter J. Goadsby, MD4 1Albert Einstein College of Medicine, Bronx, NY; 2Headache Center of Southern California, Carlsbad, CA; 3Biohaven Pharmaceuticals, New Haven, CT; 4NIHR-Wellcome Trust King’s Clinical Research Facility, King’s College Hospital/SLaM Biomedical Research Centre, King’s College London, UK and University of California, San Francisco, San Francisco, CA

Introduction Results Results cont. Results cont.

• For the acute treatment of migraine, the use of and other 5‐HT1B/1D receptor agonists () lead to an inadequate response in one third of patients Subjects Efficacy Efficacy and recurrence of symptoms in up to 40% of patients. Their clinical utility may also • Of the 3507 subjects participating across the 3 trials (rimegepant n=1749, placebo • Among subjects with triptan treatment failure by history and among those using Figure 4. Sustained Pain Relief Through 48 Hours be limited by adverse events (AEs), some of which lead to discontinuation, and n=1758), 1235 (35.2%) subjects had a history of triptan treatment failure triptans prior to enrollment, a single dose of rimegepant 75 mg was more effective 1 cardiovascular contraindications (rimegepant n=598 [34.2%], placebo n=637 [(36.2%)]), and 1069 (30.5%) were than placebo on multiple secondary efficacy endpoints (Table 1), including: • Rimegepant is an FDA-approved orally administered small molecule gene-related that has demonstrated efficacy and using triptans prior to enrollment (rimegepant n=510 [29.2%], placebo n=559 – Freedom from migraine associated symptoms safety in the acute treatment of migraine in 3 separate Phase 3 clinical trials2-4 [31.8%]) – Sustained efficacy endpoints from 2 through 48 hours postdose • Rimegepant orally disintegrating tablet (ODT) demonstrated statistically significant • There were 474 (13.5%) subjects (rimegepant n=225 [12.9%], placebo n=249 – Rescue medication use within 24 hours postdose (Figure 4) pain relief and return to normal function at 60 minutes sustained through 48 hours [14.2%]) who had a history of triptan treatment failure and who were using a triptan postdose prior to enrollment; they were included in both subgroups for efficacy analyses Table 1. Secondary Efficacy Endpoints • Response to rimegepant among past and current triptan users has not been • Most subjects (86%) were female; their mean age was approximately 40 years previously reported • The mean history of moderate to severe attacks per month was 4.6, and the mean duration of untreated attacks was approximately 30 hours Rimegepant Placebo Objective • Among subjects using triptans just prior to enrollment, oral sumatriptan (n=637 Subgroup 75 mg N=1196 P valuea • Compare the efficacy of rimegepant with placebo in the acute treatment of [59.6%]) and oral (n=262 [24.5%]) were the agents most commonly used Endpoint N=1108 n (%) migraine among subjects 1) with a history of triptan treatment failure due to • Among subjects with a history of treatment failure with ≥1 triptan, 862 (69.8%) had n (%) inadequate efficacy or poor tolerability and 2) among subjects who were using discontinued oral sumatriptan and 330 (26.7%) had discontinued oral rizatriptan triptans as part of their standard migraine therapy prior to enrollment Methods Efficacy HISTORY OF TRIPTAN TREATMENT FAILURE N=598 N=637 • In subjects with triptan treatment failure by history (n=1235) and those using triptans Pain relief, 2 h 366 (61.2) 262 (41.1) <.0001 • Three double-blind, randomized, placebo-controlled, multicenter trials of identical prior to enrollment (n=1069), rimegepant was more effective than placebo for: Safety design (Figure 1) were conducted utilizing an oral tablet (Study 301, Ability to function normally, 2 h 207 (34.6) 132 (20.7) <.0001 NCT03235479; Study 302, NCT03237845) and an ODT (Study 303, − The coprimary efficacy endpoints of freedom from pain (P<.0001) and freedom • Rimegepant was well tolerated, as shown in Table 3 from the MBS (P<.0001) at 2 hours postdose (Figure 2) NCT03461757) Sustained pain relief, 2–24 h 274 (45.8) 151 (23.7) <.0001 • The most common AEs were nausea and urinary tract infection (≤1.5%) − Secondary endpoints demonstrating a broad, clinically meaningful response, • No serious treatment-related AEs were reported Figure 1. Study Design including pain relief (P<.0001) and the ability to function normally at 2 hours Rescue medication use within 24 h 118 (19.7) 236 (37.1) <.0001 postdose (P<.0001, Figure 3) • No liver safety concerns were identified Sustained pain relief, 2–48 h 236 (39.5) 126 (19.8) <.0001 Table 2. Pooled On-Study Adverse Events Figure 2. Pain Freedom and MBS Freedom at 2 Hours Freedom from photophobia, 2 h 187/533 (35.1) 122/574 (21.3) <.0001 Rimegepant 75 mg Placebo Sustained pain freedom, 2–24 h 92 (15.4) 41 (6.4) <.0001 N=1771 N=1782 n (%) n (%) Freedom from phonophobia, 2 h 165/393 (42.0) 129/434 (29.7) .0002 Sustained pain freedom, 2–48 h 75 (12.5) 38 (6.0) <.0001 ≥1 AE 252 (14.2) 209 (11.7) Nausea 26 (1.5) 15 (0.8) • Subjects used an eDiary to record data from predose through 48 hours postdose Freedom from nausea, 2 h 187/378 (49.5) 187/429 (43.6) .0882 Urinary tract infection 20 (1.1) 10 (0.6) Subjects Pain relapse, 2–48 h 48/123 (39.0) 37/75 (49.2) .1621 ≥1 treatment-related AE 113 (6.4) 85 (4.8) a • Aged ≥18 years, with ≥1-year history of migraine with or without aura USING TRIPTANS PRIOR TO ENROLLMENT N=510 N=559 Serious AEs 3 (0.2) 3 (0.2) • Two to 8 monthly migraine attacks with moderate or severe pain; <15 monthly AE, adverse event headache days (migraine or nonmigraine) over the last 3 months Pain relief, 2 h 319 (62.6) 236 (42.1) <.0001 aTwo subjects with an SAE in the rimegepant group had not been dosed before onset of the SAE; the other • Preventive migraine medication dose stable for ≥3 months (if using) subject with an SAE had low back pain determined by the investigator to be unrelated to treatment. Ability to function normally, 2 h 189 (37.1) 92 (16.4) <.0001 Assessments Sustained pain relief, 2–24 h 244 (47.9) 121 (21.5) <.0001 • Co-primary efficacy endpoints: pain freedom at 2 hours postdose and freedom from the most bothersome symptom (MBS) at 2 hours postdose Figure 3. Pain Relief and Ability to Function Normally at 2 Hours Rescue medication use within 24 h 112 (22.0) 236 (42.2) <.0001 Conclusions • Safety assessments: AEs, ECGs, vital signs, physical measurements, routine laboratory tests, including liver function tests Sustained pain relief, 2–48 h 213 (41.8) 101 (17.9) <.0001 • A single oral dose of rimegepant 75 mg was effective for the acute treatment of migraine in subjects with a history of triptan treatment Freedom from photophobia, 2 h 161/440 (36.7) 98/500 (19.5) <.0001 Statistical Analysis failure • Efficacy analyses were performed on the modified intent-to-treat population: Sustained pain freedom, 2–24 h 78 (15.2) 22 (3.9) <.0001 randomized subjects who had a qualifying migraine attack, took study medication, • The efficacy of rimegepant in triptan-experienced subjects was and provided ≥1 evaluable postbaseline efficacy data point Freedom from phonophobia, 2 h 131/336 (39.0) 99/372 (26.5) .0004 consistent with the overall trial results • Efficacy endpoints were evaluated using Cochran-Mantel Haenszel tests and stratified by the use of preventive medication at randomization. Subjects who (1) Sustained pain freedom, 2–48 h 66 (12.9) 21 (3.8) <.0001 • The tolerability and safety of rimegepant were comparable to placebo were missing data at the time point or (2) took rescue medication at or before the time point were classified as failures Freedom from nausea, 2 h 164/302 (54.3) 135/348 (38.8) <.0001 • Rimegepant may serve as a novel treatment option for patients who do • The subpopulations assessed for efficacy included subjects who 1) had a history not respond to, cannot tolerate, or have contraindications to triptans of triptan treatment failure due to inadequate efficacy or poor tolerability and 2) Pain relapse, 2–48 h 42/108 (39.1) 27/48 (56.2) .0467 subjects who were using triptans just prior to enrollment MBS, most bothersome symptom • Safety analyses were conducted on enrolled subjects who took any dose of study aP-values not adjusted for multiplicity medication (rimegepant or placebo) This material is being made available for informational purposes only References: 1. Derry CJ et al. Cochrane Database Syst Rev. 2012;(2):CD008615; 2. Lipton R et al. Headache. 2018;58:1336–37 (Poster #PS123LB); 3. Lipton RB et al. N Engl J Med. 2019;381:142-49; 4. Croop R et al. Lancet. 2019;394(10200):737-745. Disclosures This study was sponsored by Biohaven Pharmaceuticals. RC, CMJ, AT, EGS, CMC, BAM, and VC are employed by and own through Biohaven Medical Affairs. stock/stock options in Biohaven Pharmaceuticals. RBL and AB have received honoraria and research support from Biohaven Pharmaceuticals; RBL is also a stockholder. 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