Study to Determine Safety and Efficacy of B244 in Subjects With Episodic Migraine

This is a Prospective, Randomized, Vehicle‐controlled, Double‐blind, Multi-center, 3-arm
study assessing the safety, tolerability, and efficacy of B244 delivered as an intranasal
spray for preventive treatment in subjects with episodic migraine.

At Screening and Baseline, all subjects must experiences 4-14 migraine days per month and
3-14 migraine attacks per month and no more than 14 headache days per month in the 3 months
prior to screening.

The total duration of the study will be approximately 16 weeks. Participants will report for
a Screening visit and if all inclusion criteria are met, subjects will go through a one month
baseline period prior to randomization. Subjects will come in for visits at Day 28 (Week 4),
Day 56 (Week8), Day 84 (Week12), and Day 112 (Week 16).

Efficacy will be assessed by change in migraine attacks, days, and hours. Blood and urine
samples will be collected for standard safety laboratory testing and the effect of the drug
on inflammatory biomarkers. Safety will be monitored throughout the study.

Investigators plan to enroll 303 total subjects. Subjects will be randomized 1:1:1 so that an
equal number of subjects will be treated in each arm of the study.

Inclusion Criteria:

- Males and Females, 18 to 65 years of age.

- In good general health as determined by a thorough medical history and physical
examination, and vital signs.

- At least a 1-year history of migraine with or without aura that began before the age
of 50 years old and consistent with a diagnosis of migraine with or without aura
according to the International Classification of Headache Disorders, 3rd edition, beta
version.

- Experiences 4-14 migraine days per month and 3-14 migraine attacks per month and no
more than 14 headache days per month (including migraine and non-migraine headache
days) in the 3 months prior to screening.

- Experiences 4-14 migraine headache days per month during the baseline period.

- Ability and willingness to abstain from taking medications not allowed by the protocol
or administering any foreign substance intranasally.

- Ability and willingness to complete a migraine-history diary from screening to
treatment with study drug and a migraine-treatment diary from prevention treatment
through the remainder of the follow-up period.

Exclusion Criteria:

- Headache on greater than 14 days/month in any of the three months (90 days) preceding
entry into the study.

- Use of acute migraine-specific medications (e.g., ergotamine, triptan) on more than 10
days per month in the previous 3 months and during study.

- Use of intranasal migraine medications during study.

- Use of any intranasally administered over-the-counter product or nasal irrigation
(e.g., neti pot) during study.

- Opioids/barbiturates used on more than 4 days per month in the previous 3 months and
throughout the duration of the study.

- Use of analgesics (including acetaminophen, nonsteroidal anti-inflammatory drugs
[NSAIDs], acetylsalicylic acid, or combination analgesics) for migraine and
non-migraine headaches on more than 14 days per month in the - Use of migraine
prevention medication within two months prior to study and throughout the duration of
the study.

- Botulinum toxin injection within 3 months prior to screening or during study.

- Anti-CGRP monoclonal antibody (e.g., erenumab, fremanezumab, galcanezumab, and
eptinezumab) injection or infusion within 4 months prior to screening or during study.

- Small molecule anti-CGRP medications in the 30 days prior to the screening visit.

- Use of systemic antibiotics during study.

- Pregnancy or breast-feeding.

- Female of childbearing potential not using adequate contraceptive measures.

- Inability to give informed consent.

- History of neurological, psychiatric, or any other medical condition that in the
opinion of the investigator may compromise the subject's ability to safely participate
in the study.

- Subjects with any significant clinical abnormalities which may interfere with study
participation.

- Prior use of AO+ Mist.

- Subjects with immunodeficiencies, nasal lesions, nasal polyps, or sinus infections.

- Subjects who have participated in an investigational drug trial in the 30 days prior
to the screening visit.

- Inability to maintain at least 80% diary compliance during the study from baseline to
follow-up.