Tonix Pharmaceuticals Presents Non-clinical Data on TNX-201 at the 57th Annual Scientific Meeting of the American Headache Society

Tonix Pharmaceuticals HoldingCorp. (Nasdaq: TNXP) ("Tonix"), a clinical-stage company developingnext-generation medicines for fibromyalgia, post-traumatic stress disorder,and episodic tension-type headache, announced that it presented non-clinicaldata from its TNX-201 (dexisometheptene mucate) program in two posters atthe 57(th) Annual Scientific Meeting of the American Headache Society inWashington, DC. Tonix is currently evaluating TNX-201 in a Phase 2proof-of-concept (POC) study in episodic tension-type headache. To learnmore, please visit www.clinicaltrials.gov (NCT02423408). The active ingredient in TNX-201, dexisometheptene mucate, contains(R)-isometheptene, or (R)-IMH, a single optical isomer of isometheptene.Racemic IMH, a mixture of both the (R) and (S) isomers, had been widely usedas a single-agent prescription medicine and as a component of combinationdrug products (e.g., Midrin(R) ) for many decades in the U.S. for variousindications including tension-type headache. IMH was introduced as apharmaceutical prior to 1962, and no products containing IMH are currentlyapproved by the U.S. Food and Drug Administration (FDA) for any indication.TNX-201 is being developed as a new chemical entity for the treatment ofepisodic tension-type headache, based on current FDA drug registrationrequirements. The two posters are summarized below, and are available on Tonix's websiteat www.tonixpharma.com. Abstract PS29. "(R)-Isometheptene (IMH) Binds to the Imidazoline-1 Receptorand (S)-IMH Increases Blood Pressure: Potentially Superior Benefit-to-RiskRatio for (R)-IMH as an Analgesic for Headache"(1) Key points: -- Data from receptor binding studies, taken together with the recent description of a decreased pain threshold in imidazoline-1 receptor(I1R) knock-out mice(2), suggest that I1R may be the primary site of actionfor racemic IMH's analgesic effects. Since (R)-IMH, the active ingredient in TNX-201, binds I1R with approximately 60-fold greater affinity than (S)-IMH, TNX-201 may be responsible for the therapeutic effect ofracemic IMH. -- In anesthetized rats, treatment with (S)-IMH resulted in dose-dependent and statistically-significant blood pressure increases that were higher relative to those produced by the (R)-isomer. Abstract PS58. "The (R)-isomer of isometheptene, decreases trigeminalsensitivity in the Inflammatory Soup and Spontaneous Trigeminal Allodyniarat models"(3) Key points: -- The effects of (R)-IMH and (S)-IMH were evaluated in two rat models of trigeminal pain which feature aspects of chronic migraine: the Inflammatory Soup (IS) model and the Spontaneous Trigeminal Allodynia (STA) model.(4,5) These models had been developed to allow for the testing of therapeutic compounds for migraine. Both of these models experience similar symptoms to human migraine patients such as episodic or chronic trigeminal hypersensitivity, phonophobia, responsiveness to abortive and prophylactic headache treatments, and sensitivity to migraine triggers. -- In the IS model, treatment with 30 mg/kg of (R)-IMH mucate significantly increased trigeminal thresholds at each of the 0.5 hour (hr) (2.3-fold, p<0.01), 1.5 hr (3.0-fold, p<0.01), 2.5 hr (2.9-fold, p<0.001), and 3.5 hr (1.7-fold, p<0.05) time points. -- In the STA model, treatment with 30 mg/kg of (R)-IMH mucatesignificantly increased trigeminal thresholds at the 0.5 hr (7.8-fold, p<0.01), 1.5 hr (4.3-fold, p<0.05), 2.5 hr (4.5-fold, p<0.01), 3.5 hr (8.5-fold,p<0.01), and 24 hr (8.2-fold, p<0.01) time points. -- Treatment with 30 mg/kg of (S)-IMH mucate had no effect on trigeminal sensitivity in either the IS or STA models. "Our findings that TNX-201 selectively modulates a receptor in the centralnervous system that appears to regulate pain perception and responses,together with positive data in two rodent models representative of migraine,support the development of TNX-201 as a therapeutic for headache andpotentially other pain indications and one that may be differentiated fromcurrently-approved products," said Bruce Daugherty, Ph.D., Tonix's chiefscientific officer. "We look forward to reporting the results of our Phase 2POC study in episodic tension-type headache in the fourth quarter of thisyear." References (1) Daugherty BL, Gershell L, and Lederman S. (R)-isometheptene (IMH) bindsto the imidazoline-1 receptor and (S)-isometheptene increases bloodpressure: potentially superior benefit to risk ratio for (R)-IMH as ananalgesic for headache. Headache 2015;June 55(53):Abstract PS29. 172. (2) Zhang L et al. CNS Neurosci Ther 2013;19:978-81. (3) Fried NT, Oshinsky MI, Daugherty BL, Lederman S and Elliott MB. The (R)isomer of isometheptene decreases trigeminal sensitivity in a rat model ofprimary headache. Headache 2015;June 55(53):Abstract PS58. 184. (4) Oshinsky ML and Gomonchareonsiri S. Headache 2007;47:1026-36. (5) Oshinsky ML et al. Headache 2012;52:1336-1349. About Episodic Tension-Type Headache Episodic tension-type headache is the most common type of headache. It isestimated that approximately 30% of U.S. adults experience frequent episodictension-type headaches (one to 15 headaches per month over a three-monthperiod). Tension-type headache pain is often described as a constantpressure on both sides of the head, and typically lasts for several hours.All of the FDA-approved prescription options for tension-type headachecontain barbiturates.