Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP
Tonix Pharmaceuticals — World Orphan Drug Congress 2022
19 slides from Tonix Pharmaceuticals's conference presentation, Jul 11, 2022
Slide 1: TNX-2900 in Development for Hyperphagia in Prader-Willi Syndrome
TNX-2900* (Intranasal Oxytocin + Magnesium) in Development for the Treatment of Hyperphagia in Adolescents and Young Adults with Prader-Willi Syndrome *TNX-2900 is an investigational drug in the pre-IND stage of development and has not been approved for any indication Version P0362 July 11, 2022 (Do
Slide 2: Cautionary Note on Forward-Looking Statements
Cautionary Note on Forward-Looking Statements RARE DISEASE PORTFOLIO Certain statements in this presentation regarding strategic plans, expectations and objectives for future operations or results are “forward-looking statements” as defined by the Private Securities Litigation Reform Act of 1995. Th
Slide 3: TNX-2900: Prader-Willi Syndrome
TNX-2900*: Prader-Willi Syndrome Intranasal Potentiated Oxytocin (OT) with Magnesium RARE DISEASE PORTFOLIO PROFILE DEVELOPMENT PROGRAM Prader-Willi Syndrome is the most common Market Entry: Treatment of hyperphagia genetic cause of life-threatening childhood in adolescents and young adults with obe
Slide 4: Prader-Willi Syndrome (PWS)
Prader-Willi Syndrome (PWS) RARE DISEASE PORTFOLIO ~65% of cases are due to a new deletion on Cause paternal chromosome 15; first genetic imprinting disorder recognized in humans 1 in 10,000 to 1 in 30,0001,2; Prevalence most common syndromic cause of obesity In infants, severe hypotonia and difficu
Slide 5: Progression of Prader-Willi Syndrome
Progression of Prader-Willi Syndrome1 RARE DISEASE PORTFOLIO Average age at death: 0 to 9 Phase 2a 0 yrs Weight increase without 29.5 years2 months appetite increase 9 to 25 months Phase 2b Weight and appetite increase; obesity Phase 0 2 to 4.5 occurs if allowed to eat what they want Low birth weigh
Slide 6: Dangers of PWS Hyperphagia
Dangers of PWS Hyperphagia RARE DISEASE PORTFOLIO Behaviors around food1-4: Consequences1-5: Caretaker Burden1-4: • Foraging or hoarding • Life-threatening obesity • 24/7 supervision • Temper tantrums and meltdowns • Risk of choking or • Restricted food intake • Binge eating gastrointestinal perfora
Slide 7: Abnormalities of the Oxytocin System in Patients with PWS
Abnormalities of the Oxytocin System in Patients with PWS RARE DISEASE PORTFOLIO PWS patients have Increased oxytocin in blood plasma1,2 Decreased oxytocin mRNA1 Low levels of oxytocin receptor expression2 Decreased or abnormal oxytocin neurons (especially in the PVN)1 7 PVN=paraventricular nucleus.
Slide 8: History of Oxytocin Use
History of Oxytocin Use RARE DISEASE PORTFOLIO Synthetic oxytocin has been used to induce labor for over 65 years1 Due to the role of endogenous oxytocin in pain regulation and social behavior, the administration of exogenous oxytocin has been studied in a wide variety of therapeutic areas2 Intraven
Slide 9: Functions of Natural and Therapeutic Oxytocin
Functions of Natural and Therapeutic Oxytocin RARE DISEASE PORTFOLIO Childbirth1-3: Breastfeeding1,4,5: Behavioral regulation1,6: Natural Natural Natural • Stimulates uterine • Oxytocin is responsible for the • Oxytocin plays a role in contractions during let-down reflex prosocial behaviors and chil
Slide 10: Oxytocin Plays Major Role in Satiety
Oxytocin Plays Major Role in Satiety1-3 RARE DISEASE PORTFOLIO Induces leptin and Induces satiety Oxytocin insulin secretion Leptin Satiety signal Increases Decreases dopamine reward food intake 10 1. Correa-da-Silva F, et al. J Neuroendocrinol. 2021;33(7):e12994. 2. McCormack SE, et al. Endocr Rev.
Slide 11: Intranasal Use of Oxytocin
Intranasal Use of Oxytocin RARE DISEASE PORTFOLIO • Intranasal oxytocin was introduced as a lactation aid in the early 1960s1 • Numerous studies have investigated chronic and acute intranasal oxytocin for the treatment of neuropsychiatric disorders and pain2 o Intranasal oxytocin has been studied in
Slide 12: Intranasal (IN) Oxytocin As PWS Treatment
Intranasal (IN) Oxytocin As PWS Treatment RARE DISEASE PORTFOLIO 2014 2017 Hyperphagia and IN oxytocin safety behavior improve assessed in PWS with IN oxytocin1,3 patients1,5 The only significant There is no significant improvement occurs in difference in the safety PWS patients younger profile of I
Slide 13: Challenges in Intranasal Oxytocin Studies in PWS
Challenges in Intranasal Oxytocin Studies in PWS RARE DISEASE PORTFOLIO • No significant difference • Central oxytocin levels are • Recent reports show that with IN oxytocin treatment difficult to measure1 magnesium is needed for but significantly increased full oxytocin receptor tantrums at higher
Slide 14: Oxytocin Receptor (OXTR)
Oxytocin Receptor (OXTR) RARE DISEASE PORTFOLIO OXTR Signaling Cascade OXTR Binding to Agonists1 80 58.4 Oxytocin 70 60 Ki values, nM (SD) OXTR 50 40 30 Gq/11 Unknown 20 11 10 6.62 7 0.79 0 Phospho- Receptor agonists EGFR lipase C Oxytocin TGOT = highly selective agonist Atosiban = functionally sele
Slide 15: Oxytocin+Mg2+ Activates OXTR Secondary Messengers
Oxytocin+Mg2+ Activates OXTR Secondary Messengers RARE DISEASE PORTFOLIO 100000 3200 10000 Concentration needed for 50% response (EC50, nM) 1000 Magnesium is needed not only for oxytocin binding to OXTR but also for OXTR activation 100 5.1 10 1 Oxytocin+ Oxytocin+ Mg2+ EDTA BRET assay in HEK-293 cel
Slide 16: Oxytocin Requires Magnesium for Receptor Binding
Oxytocin Requires Magnesium for Receptor Binding RARE DISEASE PORTFOLIO • OXTR exists in 2 conformational states1: • Low affinity R34 • High affinity • Magnesium ions are necessary for the Pro7 E42 high-affinity state1,2 • Without magnesium ions present, oxytocin cannot achieve full binding to OXTR2
Slide 17: Addition of Mg2+ Expands the in vivo Useful Dose Range of Intranasal Oxytocin
Addition of Mg2+ Expands the in vivo Useful Dose Range of Intranasal Oxytocin in Animals RARE DISEASE PORTFOLIO 20 Oxytocin only • A nonlinear dose response has been Hyperpolarization (mV) Oxytocin with 1.75 nM Mg2+ demonstrated in the use of intranasal * 15 oxytocin * * * • This decreases efficacy
Slide 18: Highlights
Highlights RARE DISEASE PORTFOLIO • Hyperphagia in Prader-Willi syndrome (PWS) is severe and life-threatening • There is currently no treatment for hyperphagia in adolescents and young adults with PWS • Oxytocin is one of the hormones responsible for signaling satiety • The oxytocin receptor require
Slide 19: Thank You
THANK YOU © 2022 Tonix Pharmaceuticals Holding Corp.
Tonix Pharmaceuticals Holding — World Orphan Drug Congress 2022 on 6ix