Attached files
| file | filename |
|---|---|
| 8-K - 8-K - Salarius Pharmaceuticals, Inc. | a201604198-k.htm |
| EX-99.1 - EXHIBIT 99.1 - Salarius Pharmaceuticals, Inc. | aan2016poster.htm |
Orally-administered TRPV1 and TRPA1 Activators Reduce Night Leg Cramps in a Randomized, Blinded, Placebo- Controlled, Crossover Human trial AAN Meeting, Vancouver, BC April 19, 2016 Jennifer Cermak, Laura B. Rosen, Brooke Hegarty, Bruce Bean, Rod MacKinnon, Christoph Westphal, and Thomas Wessel
Therapeutic Mechanism: Chemical Neuro Stimulation 0 25 50 75 100 125 0 50 100 150 200 Time (sec) EM G S ig na l ( uV ) Electrical stimulation to cause cramp Cramp, with Area Under the Curve (AUC) EM G S ig na l ( uV ) Subject no longer In cramp EM G ( be fo re s tim ul at io n) 0 25 50 75 100 125 0 50 100 150 200 Time (sec) EM G S ig na l ( uV ) Electrical stimulation to cause cramp EM G S ig na l ( uV ) Electrically Induced Cramp (EIC) Model
Flex-100 Nocturnal Leg Cramps Study Baseline Period 1 TRP Stim Beverage 14 days Period 2 TRP Stim Beverage 14 days Period 1 Placebo Beverage 14 days Period 2 Placebo Beverage 14 days ★ ★ ★ ★ Study Visits Completers N=50 ★ Recruitment and Screening (cramps for ≥ 3-4 nights per week for 4 consecutive weeks prior to Screening) Entered Run-In Period N=64 Exclude Placebo Responders Randomized N=51 Run-In Period (Placebo Capsule) 14 days Nocturnal leg cramps (NLC) • 50% >age 50 have NLC and >4 million in the US >65 years suffer daily • Quinine (Rx for NLC in UK) is associated with thrombocytopenia, hypersensitivity reactions and QT prolongation and was banned by FDA for NLC in 1994 Flex multicenter US Trial in NLC: Randomized, double-blind, placebo-controlled, 2-period cross-over study to evaluate the effects of TRP stim on the frequency of NLC when taken ~ 45 minutes before going to bed
Flex-100 Results • Treatment with TRP activators resulted in concordant clinically meaningful effects: Cramp frequency (p<0.05) Cramp-free days (p<0.01) Physician-rated Clinical Global Impression of Change (p<0.01) “Difficulty staying asleep” question on ISI (p<0.05) VAS pain intensity over the last 3 days of each treatment period (p<0.05) • Large proportion of patients had a positive and consistent beneficial response • 40% vs 24% “Very much improved” and “Much improved” on CGI-C • No serious adverse events; generally well tolerated • Magnitude of cramp reduction appears to be similar to published “Class 1 level” quinine efficacy studies (AAN evidence-based review, Katzberg et al, 2010) • Chemical Neuro Stimulation of TRPV1 and TRPA1 channels in the oral mucosa may be a general method to treat disorders stemming from α-motor neuron hyperexcitability • Clinical studies are being initiated using a potent single-molecule TRP activator for NLC and neurological indications ALS and MS