CLCD Colucid Pharmaceuticals, Inc.

CoLucid Pharmaceuticals, Inc. (Nasdaq:CLCD), a biopharmaceutical company that is developing lasmiditan oral tablets for the acute treatment of migraine in adults, with or without aura, provided additional data regarding onset of action demonstrated as soon as 30 minutes after dosing for 100 mg and 200 mg of lasmiditan from its Phase 3 pivotal trial evaluating lasmiditan, the SAMURAI study. In addition, CoLucid had presented non-clinical data at the 5th European Headache and Migraine Trust International Congress (EHMTIC) in Glasgow, Scotland, U.K., supporting the mechanism of action of lasmiditan through central nervous system (CNS) penetration, distribution into areas of the brain relevant to migraine pathophysiology, expression of the 5-HTIF receptor mRNA in relevant regions of the brain, inhibition of trigeminal nociceptive responses, and lack of any vasoconstrictive activity in non-clinical models.

Data from the SAMURAI study were collected using electronic diaries during the treated attack. Beginning pre-dose, patients indicated their degree of headache pain on a 4-point scale: 0, no pain; 1, mild pain; 2, moderate pain; or 3, severe pain. Migraine headache relief was defined as moderate or severe headache pain at baseline reduced to mild or no headache pain at the time point assessment. Lasmiditan was effective at both the 100 mg dose and the 200 mg dose in relieving migraine headache pain as soon as 30 minutes (p ≤ 0.004) as compared to placebo.  The following table sets forth the number and percentage of patients in the intent to treat (ITT) population who experienced headache pain relief during the two hours following dosing and a comparison of each to dose to placebo.

HEADACHE PAIN RELIEF (ITT)	Lasmiditan 100mg(N=562)	Lasmiditan 200mg(N=555)	Placebo(N=554)
Number (%) of patients migraine headache pain relief at 30 minutes	106 (18.9%)	106 (19.1%)	70 (12.6%)
Odds Ratio (95% confidence interval)	1.6 (1.2, 2.3)	1.7 (1.2, 2.4)
p-value	p = 0.004	p = 0.002
Number (%) of patients migraine headache pain relief at 1 hour	232 (41.3%)	241 (43.4%)	164 (29.6%)
Odds Ratio (95% confidence interval)	1.8 (1.3, 2.3)	2.1 (1.6, 2.7)
p-value	p < 0.001	p < 0.001
Number (%) of patients migraine headache pain relief at 1 ½ hours	303 (53.9%)	296 (53.3%)	216 (39.0%)
Odds Ratio (95% confidence interval)	2.0 (1.6, 2.6)	2.1 (1.6, 2.8)
p-value	p < 0.001	p < 0.001
Number (%) of patients migraine headache pain relief at 2 hours	334 (59.4%)	330 (59.5%)	234 (42.2%)
Odds Ratio (95% confidence interval)	2.4 (1.8, 3.1)	2.5 (1.9, 3.3)
p-value	p < 0.001	p < 0.001

Patients also indicated the presence or absence of nausea, phonophobia or photophobia, and at the pre-dose time point identified the associated symptom present that was “most bothersome.” At each time point assessment, patients were asked to indicate the degree of headache pain and the presence or absence of each associated symptom. The MBS endpoint was patient-centric and measured treatment effect of study drug on associated symptoms. Lasmiditan treated patients were more likely to achieve MBS freedom as soon as 30 minutes after dosing (p ≤ 0.015) as compared to patients treated with placebo.  The following table sets forth the number of patients in the modified ITT (mITT) population who recorded a MBS at the time of dosing and the number and percentage of those patients who experienced MBS freedom during the two hours following dosing, as well as a comparison of each dose to placebo. 

MBS FREE (mITT)	Lasmiditan 100mgN=503	Lasmiditan 200mgN=518	PlaceboN=524
MBS recorded at time of dosing	469	481	488
Number (%) of patients MBS free at 30 minutes	59 (12.6%)	61 (12.7%)	38 (7.8%)
Odds Ratio (95% confidence interval)	1.7 (1.1, 2.6)	1.7 (1.1, 2.6)
p-value	p = 0.015	p = 0.013
Number (%) of patients MBS free at 1 hour	129 (27.5%)	130 (27.0%)	84 (17.2%)
Odds Ratio (95% confidence interval)	1.8 (1.3, 2.5)	1.8 (1.3, 2.4)
p-value	p < 0.001	p < 0.001
Number (%) of patients MBS free at 1 ½ hours	162 (34.5%)	161 (33.5%)	117 (24.0%)
Odds Ratio (95% confidence interval)	1.7 (1.3, 2.2)	1.6 (1.2, 2.1)
p-value	p < 0.001	p = 0.001
Number (%) of patients MBS free at 2 hours	192 (40.9%)	196 (40.7%)	144 (29.5%)
Odds Ratio (95% confidence interval)	1.7 (1.3, 2.2)	1.6 (1.3, 2.1)
p-value	p < 0.001	p < 0.001

The onset of action of lasmiditan as soon as 30 minutes after dosing in SAMURAI is consistent with findings presented at EHMTIC on September 15-18, 2016. In a poster presentation by Joseph Kovalchin, Ph.D. (CoLucid), in vivo non-clinical models demonstrated that lasmiditan was able to cross the blood brain barrier as early as 30 minutes after oral or IV dosing.  Lasmiditan was also shown to distribute to areas of the brain relevant to migraine.

In a poster presented by Marta Vila-Pueyo from Dr. Philip Holland’s laboratory at King’s College London, U.K., IV lasmiditan significantly inhibited trigeminal nociceptive responses in rats as early as 30 minutes after dosing, which is indicative of acute anti-migraine therapeutic efficacy.  Moreover, 5-HT1F receptor mRNA was found widely expressed in cortical, diencephalic and brainstem regions of the human brain known to be of importance to migraine pathophysiology.  Together, the data suggests that, unlike triptan therapies, lasmiditan likely acts directly in brain regions involved in the pathophysiology of migraine that express 5-HT1F receptor mRNA.

• A copy of the Kovalchin poster is available on CoLucid’s website at: http://www.colucid.com/wp-content/uploads/2016/10/CoLucid-Kovalchin-Poster-90x120-13-Sep-16.pdf
• A copy of the Vila-Pueyo poster is available at: http://www.colucid.com/wp-content/uploads/2016/10/Vila-Pueyo-poster.pdf

Lasmiditan was also shown to be devoid of vasoconstrictive activity in the coronary and carotid arteries in non-clinical models. In a poster presented by Elíosa Rubio-Beltran from Dr. Antoinette Maassen van den Brink’s laboratory at Erasmus University Medical Center, Rotterdam, The Netherlands, lasmiditan was evaluated for vasoconstrictive activity using in vitro assays with either human internal mammary or human coronary arteries.  Under normal and/or pre-contractile conditions, the latter achieved by using threshold concentrations of the thromboxane A2 analogue U46619, lasmiditan had no vasoconstrictive activity even at supratherapeutic concentrations.  Sumatriptan, the most widely prescribed triptan in 2015, according to IMS Analytics, was shown to induce vasoconstriction of human coronary arteries, already at clinically relevant concentrations. The distal coronary arteries were shown to have had greater vasoconstriction in response to sumatriptan than the proximal coronary arteries. In an in vivo model conducted by CorDynamics (Chicago, IL), lasmiditan showed no vasoconstrictive activity in the coronary and carotid arteries, even at supratherapeutic doses. Sumatriptan, used as positive control, induced significant vasoconstriction of both the coronary and carotid arteries, at doses calculated to be clinically relevant. A copy of the Rubio-Beltran poster is available on CoLucid’s website at: http://www.colucid.com/wp-content/uploads/2016/10/Rubio-Beltran-poster.pdf

“One of the greatest unmet needs in the acute treatment of migraine is speed of relief for patients suffering from an attack,” said Thomas P. Mathers, President and CEO of CoLucid. “The SAMURAI trial provides important data regarding onset of action of lasmiditan in treating migraine headache pain as well as the most bothersome associated symptom to the patient. We know that rapid relief is clinically meaningful to the patients during a migraine attack - patients want to feel better, and fast. We will continue to analyze the data and study lasmiditan, with the hope that it can provide relief utilizing a novel mechanism of action that does not have the vasoconstrictive effects of other acute treatments such as triptans.”

About LasmiditanLasmiditan has been designed for the acute treatment of migraine headaches in adults without the vasoconstrictor activity associated with previous generations of migraine therapies.  It selectively targets 5-HT1F receptors expressed in the trigeminal pathway.  Lasmiditan has been given the generic stem name “ditan,” which distinguishes it from other drug classes, including triptans, the current standard of care for migraine.

CoLucid has completed its first pivotal Phase 3 clinical trial of lasmiditan oral tablets, SAMURAI, which was a randomized, double-blind, placebo-controlled parallel group study designed to evaluate the efficacy and safety of lasmiditan (100 mg and 200 mg) in comparison to placebo. Both the 100 mg and 200 mg doses of lasmiditan were efficacious on headache pain freedom, the primary endpoint, and most bothersome symptom freedom, the key secondary endpoint, at the two-hour time point (p < 0.001). Both the primary and key secondary endpoints of SAMURAI conform to the FDA’s draft Guidance for Industry, Migraine: Developing Drugs for Acute Treatment, issued in October 2014.  Both the 100 mg and 200 mg doses of lasmiditan demonstrated onset of action as soon as 30 minutes on headache pain relief (p ≤ 0.004) and the most bothersome symptom (p ≤ 0.015). Both the 100 mg and 200 mg doses of lasmiditan were also efficacious on headache pain relief at the two-hour time point (p < 0.001), efficacious as a rescue medication on headache pain freedom at the two-hour time point (p < 0.001 and p < 0.012), and effective in reducing migraine related disability at the two-hour time point (p < 0.001) and improving Patient Global Impression of Change (p < 0.001). Lasmiditan was well tolerated with no significant difference in cardiovascular adverse events in patients dosed with lasmiditan versus placebo. SAMURAI is the first of two Phase 3 pivotal trials of lasmiditan, each being conducted under a Special Protocol Assessment agreement (“SPA”) with the U.S. Food and Drug Administration (“FDA”).

CoLucid is currently enrolling patients in a second pivotal Phase 3 clinical trial of lasmiditan oral tablets, SPARTAN. The objective of SPARTAN is to evaluate the safety and efficacy of lasmiditan (50 mg, 100 mg and 200 mg) in comparison to placebo two hours after dosing on freedom from migraine headache pain, which is the primary endpoint, and on freedom from the most bothersome associated symptom of migraine (nausea, phonophobia or photophobia), which is the key secondary endpoint. SPARTAN is a randomized, double-blind, placebo-controlled parallel group study.  The study is expected to treat a single migraine in up to 2,226 migraine patients with lasmiditan at approximately 140 sites in the United States, United Kingdom and Germany.  CoLucid expects that migraine patients enrolled in SPARTAN will include those who also have one or more cardiovascular risk factors, stable cardiovascular disease or known coronary artery disease (“CAD”). CoLucid has obtained an SPA agreement from the FDA for SPARTAN. Top-line results from SPARTAN are expected in the second half of 2017.

CoLucid is also currently enrolling patients in GLADIATOR, a Phase 3 long-term, open-label trial of lasmiditan. GLADIATOR’s objective is to evaluate the safety and efficacy of lasmiditan, (both the 100 mg and 200 mg dose) as well as resource utilization, functional outcomes and disability. Based on the results of GLADIATOR, CoLucid intends to build an appropriate safety database to support a New Drug Application (“NDA”) for lasmiditan. At the time of the NDA submission, it is anticipated that there will be more than 15,000 patient exposures to lasmiditan in the entire clinical program.

About MigraineMigraine is the leading cause of disability among neurological disorders in the United States according to the American Migraine Foundation.  An estimated 36 million Americans suffer from migraine.  Migraine can be extremely disabling and costly, accounting for more than an estimated $20 billion in direct (e.g., doctor visits, medications) and indirect (e.g., missed work, lost productivity) expenses each year in the United States.

About CoLucid Pharmaceuticals, Inc.CoLucid was founded in 2005 and is developing lasmiditan oral tablets for the acute treatment of migraine headaches in adults and intravenous lasmiditan for the acute treatment of headache pain associated with migraine in adults in emergency room and other urgent care settings.

Forward-Looking Statements

Certain of the statements made in this press release are forward looking, such as those, among others, relating to CoLucid’s expectations for lasmiditan’s efficacy, anticipated marked demand, anticipated physician prescribing patterns, clinical trial enrollment goals and the timing of future clinical trials. Actual enrollment results, market demand, use of cash and other developments may occur that differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include risks that enrollment goals will not be met, trials may not be commenced or successful or may take longer to complete than anticipated, regulatory approval may not be obtained, physicians may not prescribe lasmiditan, and projected cash needs and expected financial results may be different. More information about the risks and uncertainties faced by CoLucid are contained in its periodic reports filed with the Securities and Exchange Commission. CoLucid disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

CONTACT

Thomas Mathers
Chief Executive Officer
CoLucid Pharmaceuticals, Inc.
(857) 285-6494                              

Hans Vitzthum
Managing Director
LifeSci Advisors, LLC.
(212) 915-2568