ASARINA PHARMA Remain in control of your life - Presentation to Aktiespararna Kvinnokväll 8 April 2019 - Skrivskyddad
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ASARINA PHARMA Remain in control of your life Presentation to Aktiespararna Kvinnokväll 8 April 2019 Karin Ekberg Otto Skolling 1
Asarina Pharma Overview • Efficacy in humans established for Sepranolone in premenstrual Clinical midstage company with pipeline in dysphoric disorder (PMDD) women’s health • Additional indications with high unmet medical need • Novel therapy with unique Mode of Action First-in-class therapy for PMDD – • Substantial unmet medical need: a highly underserved indication Disabling condition affecting 4-5 % of women in fertile age • Significant medical costs for society create large market potential Phase IIb patient recruitment initiated in • Phase IIb study in UK, Poland, Germany and Sweden April 2018. Topline results early 2020 with 225 patients Additional indication with short term • Phase IIa Proof of Concept study in 80-90 women with Menstrual significant value inflection point Migraine with study initiation June 2019 and read-out H2 2020 • Building a Scandinavian franchise in women’s health Significant commercial potential – • Potential PMDD annual peak sales: USD 600 million worldwide total peak sales > USD 1.4 billion • Potential for attractive license deals to fund further growth 2
Advancing a robust product portfolio 2018 2019 2020 2021 2022 1st generation Sepranolone PMDD Phase IIb PMDD Phase III (with autoinjector) Menstrual Migraine Menstrual Migraine Phase IIa Phase IIb Gel/vaginal ring/sustained 2nd generation 2nd generation development process Sepranolone release/tablet selection process CMC & Upscaling API & DP scale up 3
Management Jakob Dynnes Karin Ekberg Peter Nordkild* Hansen* COO CEO CFO PhD, clinical MD MSc, MBA Novo Nordisk physiology Novo Nordisk Zealand Pharma Creative Peptides Ferring, Egalet, Umecrine Cognition Pharmexa Evolva, Nordea Märta Segerdahl Otto Skolling* Sven Göthe* CMO CBO Production/CMC PhD, Med. Sci. MSc, PhD, Astra Zeneca Pharmacia & Upjohn Pharmacia & Upjohn Lundbeck Siemens Medical Kabi Fresenuis Novozymes Karolinska Development 4 * Management and/or Board experience in listed companies
Our science Remain in control of your life 5
Allopregnanolone – ”the good and the bad” • Allopregnanolone (ALLO) is an endogenous, very potent positive allosteric modulator (PAM*) of the GABAA receptor - Moderately elevated concentrations of ALLO can cause aggression 1, irritability, depression, movement disorders 2, and at withdrawal migraine 3 and epilepsy 4 in some individuals • Asarina is designing, testing and developing drugs, that inhibit the deleterious actions of ALLO in the brain • The lead compound, Sepranolone inhibits the effect of ALLO on the GABAA receptor in a non-competitive, dose dependent manner • Sepranolone is based on 40 years of world class GABAA receptor research 5 by Prof Torbjörn Bäckström and his team at University of Umeå 1. Bäckström et al. Curr Psychiatry Rep 2015 2. Bortolato et al. Neuroendocrinol 2013 3. MacGregor et al. Neurology 2006 4. Joshi and Kapur. Brain Research 2018 (in press) 5. Bäckström Acta Neurol Scand 1976 *other PAM are e.g. benzodiazepines and alcohol 6
Sepranolone normalises GABAA-receptor activity, targeting underlying cause of PMDD Extrasynaptic receptors PMDD patients have increased sensitivity to contain a subunit GABAA steroid allopregnanolone (ALLO), a Cl- GABA PAM b which is elevated during the premenstrual (luteal) phase of the menstrual cycle Extrasynaptic GABAA receptors Novel PAM Sepranolone inhibits the Positive Allosteric binding site Modulation (PAM) effect of ALLO on the Increased tonic GABAergic current Postsynaptic terminal GABAA receptor through • Fine tuned receptor activity without overstimulation • High selectivity • Minimal off-target effects 7
Sepranolone in Premenstrual Dysphoric Disorder Remain in control of your life 8
PMDD affects > 3.5 mio women in the US • Diagnostic criteria established in DSM-5 * - Affective: Emotional lability, depressed mood, irritability, anxiety - Somatic: Lethargy, bloating, joint pain, hypersomnia Irritability - Cognitive: Difficulty concentrating • Occurs only during the late luteal phase of the menstrual cycle • Symptoms are present one to two weeks before menses and disappear within a few days after onset of menstruation Anxiety/Depression • More than a third of PMDD women have suicidal thoughts and are 4 times more likely to attempt suicide • Interferes with work, social activities and relationships • Refractory patients undergo treatment with GnRH agonists or hysterectomy and oophorectomy to eliminate PMDD symptoms Bloating * Diagnostic and statistical manual of Mental Disorders 9
No current drugs directly target the underlying mechanism of PMDD1,2,3 SSRI Antidepressant Hormonal Therapy YAZ oral Agent Fluoxetine GnRH agonists contraceptive Efficacy Moderate (50-60%) Moderate High Often persistent in PMDD Suppress patients hormonal cycles Side Effects 46% discontinued in 6 Black Box Warning Require hormonal months due to side add-back effects Approved U.S. U.S. U.S. Sepranolone Initial formulary placement: 2nd or 3rd line therapy Current 1st line therapies only moderately effective 1. Nevatte T., et al. Arch Women Ment Health. 2003: online at DOI 10.1007/s00737-013-0346-y 2. Yonkers K.et.al. Ob&Gyn 2005;106(3):492. 3. Yaz Full Prescribing Information 10
Sepranolone meets primary (FDA*) endpoint in phase IIa study • Double-blind, placebo controlled trial in 120 randomized patients • Patients received five doses over 10 days from ovulation • Two doses, 10mg and 16mg tested; pooled data below Highly statistically significant reduction in pre- menstrual symptom score in “treated as Sepranolone twice as effective as intended” population (p = 0.006) YAZ by indirect comparison Sepranolone has a standardized effect size of 0.61 in total symptom reduction as compared to placebo, vs. YAZ standardized treatment effect size of 0.31* *KA Yonkers, et.al .Efficacy of a New Low-Dose Oral n=26 n=34 Contraceptive With Drospirenone in Placebo Sepranolone Premenstrual Dysphoric Disorder. Ob&Gyn.2005.106(3);492. *Total symptom score of 11 symptoms 11
Sepranolone effect on PMDD symptoms Improvments+during+treatment++ Improvements During Treatment 7" 6" ** ** 5" * 4" ** ** Sepranolone 3" * ** ** 2" 1" UC1010" 0" Placebo" f "c " nx " c> it" on es" pp e" 9. te" 22 l" " ng y" en ."Ph tr" 3. ety" "F a " 2. ress p 4) 7. ntr su sica 4. bilit 8. >gu ut ee r irm 11 on M2 e> 6. vi> 5. /Ir ce i ."O "Sl ep y La "A m "D "o "A "A "A "C 1. t"( 10 pa m .I 12 The effects are calculated as the difference between luteal and follicular phase scores at baseline minus the corresponding difference during treatment. ** p
Phase IIB: recruitment initiated April 2018 Expected readout Q1 2020 Design • RCT, double-blinded, placebo- controlled, with two cycles of Baseline/Diagnosis 3 treatment cycles 1 month follow-up diagnosis, three treatment cycles and Two cycles a follow-up cycle. Treatment cycle will be for 14 days (7 injections every other day) Primary Endpoint • Change in premenstrual symptom severity questionnaire (DRSP) range before and during three Sepranolone treatment cycles dose 10 mg Secondary Endpoints • Safety PMDD Screen (DSM-5) verified Randomize Sepranolone • Responder analysis Multicenter N= ~225-250 D, UK, PL, S in at least two (Double-blind) dose 16 mg menstrual cycles e-PRO • DRSP according to DSM-5 as diagnostic screener for PMDD Placebo 13
PMDD – the commercial potential Remain in control of your life 14
US: > 200k women non-responsive to current treatment Breakdown of women with PMDD in the U.S. Percent of women ~164m ~85m ~3.5m ~1.7m ~869k ~614k ~218k 100 Pre- PMDD: menstruation pursue 90 ~15% PMDD: non- do not pharma- 80 No PMDD cologic seek Post- diagnosis ~25-30% treatment PMDD: 70 menopausal ~50-70% No PMS ~50% Responsive ~35% /PMDD ~65-70% 60 ~71% PMDD: Non- 50 responsive PMDD: 100% 40 pursue PMDD: pharma- 30 Childbearing cologic seek PMDD age ~70-75% treatment diagnosis PMDD: ~50% 20 ~50% ~30-50% Non- PMS responsive ~25% ~25-30% 10 PMDD 0 ~4% Reproductive Condition Seek treatment Diagnosed Pursue treatment Response to Not responsive to stage of females for PMDD with PMDD pharmacologic current treatments in the U.S. Source: L.E.K. analysis of physician interviews; secondary sources 15
Sepranolone in menstrual migraine Remain in control of your life 16
Migraine related to the menstrual cycle Menstrual exacerbation of migraine occurs in ~ 50% of women with migraine MacGregor et al., NEUROLOGY 2006;67:2154–2158 Incidence of migraine, urinary estrone-3-glucuronide (E1G) and pregnanediol-3-glucuronide (PdG) levels on each day of the menstrual cycle in 120 cycles from 38 women 17
Potential US sales up to USD 500 mio Potential gross revenues for Sepranolone aspirational profile in Menstrual Migraine U.S. Estimated Millions $ Source assumptions population ~$150-500M 500 Female population, ages 12- ~91M l U.S. census 51 (#) 400 l International Estimated prevalence of ~6% ~5.4M Headache Reflects opportunity menstrual migraine Society within existing, 300 non-refractory Menstrual migraine patients menstrual migraine who seek treatment from a l Physician 50% ~2.7M patients interviews physician (%) 200 Physician adoption of Product l Physician Y for existing menstrual ~20% survey migraine patients, non- Reflects refractory (%) 100 opportunity within refractory Physician adoption of Product l Physician menstrual Y for refractory menstrual ~20%-25% survey migraine patients migraine patients (%) 0 Source: L.E.K. analysis of U.S. Census, American Journal of Psychiatry American Headache Society, International Headache Society, L.E.K. interviews, L.E.K. survey 18
Phase IIa clinical POC trial in menstrual migraine baseline / diagnosis 3 cycles treatment follow-up TRIAL DESIGN RCT, double-blinded, placebo-controlled with 80 – 90 patients in parallel dose groups Three treatment cycles with intermittent 16 days exposure (8 injections every other day with start 14 days prior to next menstruation) Primary endpoint: Change in number of migraine days per cycle measured before and during 3 treatment cycles Sepranolone Secondary endpoints: Duration and severity of migraine attacks dose 10 mg Menstrual Screen Randomize Sepranolone 2 centers in migraine N=150 the UK and Sweden Diagnosis verified in 2 (Double-blind) dose 16 mg baseline cycles Placebo 19
Financials Remain in control of your life 20
Financials 2018 (un-audited) 2018 2017 Net sales - 1,7 Research and dev. 39,0 23,0 Other external costs 6,2 3,5 Staff costs 6,4 3,9 Depreciation - 3,9 Highlights • Impact from phase IIB Financial items (net) 0,0 0,2 study in PMDD Tax (income) 7,6 4,0 • Danish tax credit Net result - 44,0 - 28,3 Cash position 140 12 21
Major shareholders > 50% are non-Swedish investors Kurma Biofund (France) 19.6% Östersjöstiftelsen (Sweden) 14.7% Rosetta Capital (UK) 12.8% Idinvest Patrimonie (France) 10.2% Swedbank Robur Fonder (Sweden) 7.4% Sectoral Asset Management (Canada) 7.4% Catella Fonder (Sweden) 5.2% Ergomed plc (UK) 2.4% Handelsbanken Fonder (Sweden) 2.4% Nordnet Pensionsförsäkring (Sweden) 1.7% Others (incl. 740 private shareholders) 16.1% Total 100.0% 22
Summary • Womens’ health company with experienced management team • Innovative approach to diseases with serious un-met medical need • Ongoing phase IIB study in Premenstrual Dysphoric Disorder (PMDD) • Phase IIA in menstrual migraine to commence in June/2019 • Solid share performance since IPO in September 2018 23
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