<h3>Objective:</h3> Obtain evidence for a digital working alliance (DWA) between participants with migraine and an investigational precursor of a prescription digital therapeutic (PDT). <h3>Background:</h3> Recommended migraine treatments including cognitive behavioral therapy, biofeedback, and muscle relaxation are underutilized. PDTs can standardize such approaches to migraine treatment and overcome utilization barriers including provider availability and cost. A therapeutic alliance, which identifies patient goals, builds rapport, and establishes patient commitment to treatment, is a critical factor in successful face-to-face treatments. A digital working alliance (DWA), akin to the therapeutic alliance, is likely to be necessary in an effective PDT. Development of an effective DWA has not been assessed in participants with migraine. <h3>Design/Methods:</h3> Single-center, exploratory, single-arm, 2-week study of a precursor version of a PDT in individuals (18–64yrs) with physician-diagnosed migraine (N=60). Participants were asked to complete a lesson each day. DWA was interpreted on a 7-item Likert scale (Mobile Agnew Relationship Measure [mARM]) at end of treatment. <h3>Results:</h3> Correlating with real-world prevalence, Participants were majority female (90%) with a median age (IQR) of 38 years (34, 49). Most (73.3%) had episodic migraine and reported a median (IQR) Migraine Disability Assessment Scale score of 32.5 (18, 45.3). Participants completed a median (IQR) of 14 (13, 14) lessons and a total of 204 therapeutic skill modules. The median (IQR) overall mARM score was 5.9 (5.4, 6.2). <h3>Conclusions:</h3> This is the first study to report that participants with severe migraine related disability form a positive DWA with a PDT. Consistent with this, most participants completed a majority of daily lessons and therapeutic skill modules available to them. This evidence supports further development of PDTs for migraine and is a first step towards refinement and assessment in randomized controlled trials to evaluate clinical efficacy and safety in migraine. <b>Disclosure:</b> Dr. Snipes has received personal compensation for serving as an employee of Click Therapeutics. Dr. Snipes has received publishing royalties from a publication relating to health care. Dr. Kuka has received personal compensation for serving as an employee of Click Therapeutics. Miss Besedina has received personal compensation for serving as an employee of Click Therapeutics Inc.. Laura Taraboanta has received personal compensation for serving as an employee of Click Therapeutics. Laura Taraboanta has stock in Click Therapeutics. Mr. Hare has received personal compensation for serving as an employee of Click Therapeutics, Inc.. Dr. Gupta has received personal compensation for serving as an employee of Click Therapeutics. Dr. Lakhan has received personal compensation for serving as an employee of Zogenix, Fern Health, Thriveworks, The Learning Corp, Click Therapeutics. Dr. Lakhan has received personal compensation in the range of $500,000-$999,999 for serving as a Consultant for Shaheen Lakhan, MD. Dr. Lakhan has received personal compensation in the range of $100,000-$499,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurocrine, Fern Health, Lin Health. Dr. Lakhan has received personal compensation in the range of $500,000-$999,999 for serving as an officer or member of the Board of Directors for Click Therapeutics, SpineThera. Dr. Lakhan has stock in Zogenix, NeuroSport, Click Therapeutics, SpineThera.