Asarina Pharma AB (publ) — Investor Day (March 2020)
49 slides from Asarina Pharma AB (publ)'s investor day presentation, Mar 26, 2020
Slide 1: On Track to Phase III and Commercialisation
ASARINA PHARMA REMAIN IN CONTROL OF YOUR LIFE On Track to Phase III and Commercialisation R&D Day Presentation 26th March 2020 1
Slide 2: Disclaimer
Disclaimer • The shares of Asarina Pharma (”Asarina”) are traded on NASDAQ First North in Stockholm (ticker: ”ASAP”) • This presentation may contain specific forward-looking statements, relating to Asarina´s future business, development and economic performance e.g. statements including terms like ”
Slide 3: R&D Day Agenda
R&D Day Agenda • 14.00 – Introduction – Dr Peter Nordkild, CEO • 14.10 – Patient perspective – Olivia Hahne • 14.20 – The PMDD study: 4 key metrics for results - Karin Ekberg, COO • 14.40 – The clinical need – Prof Torbjörn Bäckström, CSO • 14.55 – Experiences from the field – Dr Paula Briggs, Lead
Slide 4: Introduction: Peter Nordkild, CEO
Introduction: Peter Nordkild, CEO • Physician by training • 13 years in senior management at Novo Nordisk • 6 years in corporate management at Ferring • Danish serial biotech entrepreneur as founder or co-founder of 4 Danish biotech companies 4
Slide 5: Portfolio Approach to Women's Health & Neurology
Portfolio Approach to Women’s Health & Neurology Sepranolone – Remain in Control of Your Life PMDD Menstrual Tourette’s Migraine Innovative customer centric products Chronic conditions Large markets 5
Slide 6: Asarina Pharma – Highlights
Asarina Pharma – Highlights • On track to complete clinical development of a first therapeutic solely focused on premenstrual dysphoric disorder (PMDD) - Annual ww peak sales of Sepranolone > USD 1.0 bill in PMDD • Ongoing phase IIa studies in two other indications with clear unmet medical need - Me
Slide 7: The Asarina Team
The Asarina Team Peter Nordkild, CEO Jakob Dynnes Hansen, CFO Karin Ekberg, COO MD MSc, MBA PhD Novo Nordisk Ferring, Egalet, Pharmexa Novo Nordisk Zealand Pharma Clinical physiology Evolva, Nordea Creative Peptides Umecrine Cognition Märta Segerdahl, CMO Otto Skolling, CBO Sven Göthe, CMC MD, PhD M
Slide 8: The Asarina Scientific Advisory Board
The Asarina Scientific Advisory Board World Leading KOLs Torbjörn Bäckström Neill Epperson Marie Bixo Chairman Premenstrual dysphoric disorder Premenstrual Dysphoric Disorder Senior Professor, Department of Clinical Science, Professor of Psychiatry, School of Professor in Obstetrics and Obstetrics a
Slide 9: Major Shareholders
Major Shareholders +80% are institutional investors Kurma Biofund (France) 16.8% Östersjöstiftelsen (Sweden) 14.2% Fourth Swedish National pension fund 9.0% Idinvest Patrimonie (France) 8.7% Swedbank Robur Fonder (Sweden) 8.0% Sectoral Asset Management (Canada) 5.3% Länsförsäkringar (Sweden) 4.8% Ca
Slide 10: Ongoing Phase II Programs Addressing $2bn+ Market Opportunity in Women's Health
Ongoing Phase II Programs Addressing $2bn+ Market Opportunity in Women’s Health • IPO in Sep 2018 on Nasdaq First North Stockholm • Market Cap: approx. EUR 40 M • Cash position end-2019: EUR 13 M 10 • Annual burn rate: EUR 8 M
Slide 11: PMDD: Epidemiology
PMDD: Epidemiology All women with As many as 50-80% 3-8% have premenstrual 22-26% menstrual cycles symptoms1 PMS2 PMDD3 1. de la Gandara Martin and de Diego Herrero, 1996; Hylan et al., 1999; Ramcharan et al., 1992; Wittchen et al., 2002; Woods et al., 1982 2. Angst et al., 2001; Wittchen et al., 20
Slide 12: PMDD – Prevalence & Market Need
PMDD – Prevalence & Market Need • 75% of all women in fertile age experience Moderate to Severe PMS Severe PMS some degree of premenstrual symptoms 30% • May have a genetic disposition PMDD 3-8%1 - daughters of mothers with PMDD Mild PMS 40% - 93% of identical twins - 44% of fraternal twins • Unmet
Slide 13: PMDD Affects ~3.5 Million Women in the US
PMDD Affects ~3.5 Million Women in the US • Defined by WHO in ICD-11 as a Gynecological disease • Diagnostic criteria established in DSM-5 * - Affective: Emotional lability, depressed mood, irritability, anxiety - Somatic: Lethargy, bloating, joint pain, hypersomnia Irritability/Anger - Cognitive: D
Slide 14: Near Term Value Inflection Points
Near Term Value Inflection Points 2020 2021 Top line APH205 study Initiation Phase III results initiation in trial PMDD PMDD Tourette’s IND approval Menstrual Top line Tourette’s Top Sepranolone Migraine results Line data PMDD last patient Menstrual last dose Migraine April 2020 Q1- 2021 Q4 - 2021 A
Slide 15: Join Us May 4 for Our Next Investors' Meeting
JOIN US MAY 4 FOR OUR NEXT INVESTORS’ MEETING 15
Slide 16: Patient Perspective: Olivia Hahne
Patient Perspective: Olivia Hahne PMDD Patient / Communications at Asarina Pharma • International communications & media sales consultant • Consulting to Asarina Pharma • Has PMDD • Patient on Phase IIA trial (2013) 16
Slide 17: The PMDD Clinical Phase IIb Study: 4 key metrics for results
The PMDD Clinical Phase IIb Study 4 key metrics for results Karin Ekberg, COO PhD, experience from clinical and pre- clinical project management within biotech companies active within diabetes and cognitive impairment. 20+ years of experience in human experimental and clinical scientific work at Kar
Slide 18: Phase IIb Clinical Study Design
Phase IIb Clinical Study Design A randomised, double-blind, placebo-controlled, parallel-group, multicentre study investigating the efficacy and safety of Sepranolone (UC1010) in patients with PMDD 2 cycles 3 cycles 1 cycle baseline / diagnosis treatment follow-up Sepranolone dose 10 mg Advertisemen
Slide 19: The PMDD Diagnosis
The PMDD Diagnosis Example from a patient’s diary, showing daily ratings of the The PMDD diagnosis is included in depressive symptoms during two cycles of diagnostic screening • the American diagnostic manual for mental disorders called DSM-51 • the WHO criteria ICD-11, since May 2019, as a gynecolo
Slide 20: Phase IIb Clinical Study Patient Population
Phase IIb Clinical Study Patient Population • 476 women enrolled at first site visit 270 screen failures, i.e. women not matching the criteria for PMDD or other eligibility criteria • 206 patients randomised after completed screening - Average 33 years of age UK DE - Drop-out rates <20%, which is mo
Slide 21: Phase IIb Clinical Study Injections and Dose
Phase IIb Clinical Study Injections and Dose Sepranolone Injections 0.4 mL prefilled in a single use syringe for patients self administration Two strengths (10 and 16 mg per dose) - treatment start 14 days prior to next estimated menstruation start - every second day during luteal phase until menstr
Slide 22: Phase IIb Clinical Study Treatment safety
Phase IIb Clinical Study Treatment safety • 3,042 doses (Sepranolone and placebo) have been injected by the patients 85% of cycles with 6 or 7 injections taken and in appropriate time in relation to patient’s premenstrual symptom peak. 7% of all injections with a reported AE, occurred in 16% of pati
Slide 23: Phase IIb Study Measuring the Efficacy of Sepranolone
Phase IIb Study Measuring the Efficacy of Sepranolone Result to reflect reality • For regulators • For clinicians • For patients • For society (families, children, employers) Real results, real efficacy • Regulatory endpoint met • Effect by Sepranolone over placebo measured and compared with standar
Slide 24: 4 key metrics to measure efficacy of Sepranolone
Phase IIb Clincial Study 4 key metrics to measure efficacy of Sepranolone 4 key boxes to tick Variables ü Total symptom score primary end-point ü Cardinal symptom score secondary end-point ü Impairment score secondary end-point ü Safety AE, doctors’ examination, blood tests, etc. 24
Slide 25: Daily Record of Severity of Problems (DRSP)
Daily Record of Severity of Problems (DRSP) 24 DRSP questions, representing 11 symptoms and 3 impairment aspects, all rated from 1 “not at all” to 6 “extreme” Q1 1a Felt depressed, sad, “down”, or “blue” Q2 1b Felt hopeless Cardinal symptoms Q3 1c Felt worthless or guilty Q4 2 Felt anxious, tense, ”
Slide 26: Total Symptom Score – Primary Variable
Total Symptom Score – Primary Variable Total symptom score (Lmax Sum21) is is the sum of symptom severity for all 11 symptoms. The score is calculated as the average of Sum21 for the 5 consecutive days with the highest score during Day -6 to Day 1 (the “green days”). Lmax Sum21 extreme severe modera
Slide 27: 4 key metrics to measure efficacy of Sepranolone
Phase IIb Clincial Study 4 key metrics to measure efficacy of Sepranolone 4 key boxes to tick ü Total symptom score Statistical difference Lmax Sum21 and sufficiently large effect driven by effect on the most relevant symptoms, i.e. the … ü Cardinal symptom score Sum of Q1-Q8 – depression, anxiety,
Slide 28: 4 Key Metrics: Efficacy compared with today's treatments
4 Key Metrics Efficacy compared with today’s treatments Comparison with other RCT in PMDD studies using DRSP Total symptom scores (Sum 21) Improvements by existing therapies Fluoxetine Fluoxetine Sertraline Yaz Standard 20 mg Cohen, 2002 20mg Miner, 2002 Halbreich 2002 Yonkers 2005 of Care N=174 N=1
Slide 29: Phase IIb Clinical Study In Conclusion
Phase IIb Clinical Study In Conclusion • The preliminary baseline data show that the intended patient population is recruited - strict criteria for inclusion has given a well defined patient population • Study medication treatment well tolerated and compliance has been very good • Quality of the dat
Slide 30: The Clinical Need in PMDD: Torbjörn Bäckström
The Clinical Need in PMDD Torbjörn Bäckström, MD, PhD Founder of Asarina Pharma AB, Professor at Department of Clinical Sciences, Obstetrics and Gynecology, Norrlands University Hospital, Umeå, Sweden Support: EU structural fund, objective 1, Swedish research council, Medicine, Västerbottens county,
Slide 31: Mood Changes in Women of Fertile Age Coincide with Increased Levels of Allopregnanolone
Mood Changes in Women of Fertile Age Coincide with Increased Levels of Allopregnanolone 6 maximal symptoms 4 2 0 no symptoms Allopregnanolone 6 100 LH (U/L) (nmol/L) 4 50 2 0 0 Progesterone 60 0.6 Estradiol (nmol/L) (nmol/L) 40 0.3 20 0 0 Follicular Luteal phase Ovulation Wang et al. J. Clin. Endocr
Slide 32: No Ovulation – No Symptoms
No Ovulation – No Symptoms Ratings of depression during two menstrual cycles in the same PMDD patients, in one ovulatory and one spontaneous anovulatory cycle, respectively, per patient. That are no symptoms when the provoking steroids are not produced. Depression rating ovulatory cycle Post mens. M
Slide 33: Negative Mood Symptoms Re-occur when Progesterone Is Replaced
Negative Mood Symptoms Re-occur when Progesterone / Allopregnanolone is Replaced in Post-menopausal Women During HRT Negative mood score 8 7 6 5 4 3 2 Estradiol 2 mg/day 1 400 mg/day Progesterone / placebo 0 0 10 20 30 Day of treatment cycle 33 Andreén et al, Psyconeuroendocrinol 2005
Slide 34: Severe Impairment in Consecutive Unselected Patients
Severe Impairment in 55 Consecutive Unselected Patients Consulting for PMS/PMDD at a Gynecologic Outpatient Department Percent patients impaired per day Self Family Social life Work capacity Day of menstrual cycle Bäckström et al Gynecology forum 2009 34
Slide 35: In PMDD Patients 100% Feel Self-impaired
In PMDD Patients 100% Feel Self-impaired in up to 10 Days and 25 - 50% Work-impaired in up to 12 Key Days Impairment per menstrual cycle day (% of patients with PMDD) in consecutive patients seeking help for PMS/PMDD Percent patients impaired per day Self Family Work Day of menstrual cycle 35 Ekholm
Slide 36: Sepranolone's Target: the GABAA Receptor
Sepranolone’s Target: the GABAA Receptor • The GABA system is the generally moderating receptor system in CNS. • The GABAA receptor (a chloride channel) is target for - GABA - neurosteroids – GABA steroids - barbiturates and benzodiazepines - alcohol The GABAA receptor emotional center α2 α4 amygdal
Slide 37: Sepranolone Normalizes Spontaneous GABAA Receptor Activity
Sepranolone Normalizes Spontaneous GABAA Receptor Activity Induced by Allopregnanolone Electrical current (patch clamp experiment) GABA$+$ALLO Sepranolone UC1010% GABA$+$ALLO GABA$+$ALLO$ Sepranolone +%UC1010% GABA$ GABA$ GABA$ GABA$ GABA$ Sepranolone attenuates allopregnanolone (ALLO) – enhanced GA
Slide 38: No Dedicated Treatment Exists Yet
No Dedicated Treatment Exists Yet Huge partly undiagnosed and untreated patient population No drug specifically developed to target the underlying mechanism of PMDD Selective Serotonin Reuptake Hormone Therapy Inhibitors (SSRIs) Fluoxetine, Sertraline Oral contraceptive Yaz (SSRI antidepressants) •
Slide 39: No Current Drugs Directly Target the Underlying Mechanism of PMDD
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 Bla
Slide 40: The Clinical Need in PMDD: Dr. Paula Briggs
The Clinical Need in PMDD Dr. Paula Briggs Consultant in Sexual and Reproductive Health Liverpool Women’s Hospital, Liverpool, United Kingdom 40
Slide 41: UK Study Site: Liverpool Women's Hospital
UK Study Site: Liverpool Women’s Hospital 41
Slide 42: Dr. Paula Briggs
Dr. Paula Briggs • How many patients I see with PMDD • Which PMDD symptoms patients most need help with 42
Slide 43: Daily Record of Severity of Problems (DRSP)
Daily Record of Severity of Problems (DRSP) 24 DRSP questions, representing 11 symptoms and 3 impairment aspects, all rated from 1 “not at all” to 6 “extreme” Q1 1a Felt depressed, sad, “down”, or “blue” Q2 1b Felt hopeless Cardinal symptoms Q3 1c Felt worthless or guilty Q4 2 Felt anxious, tense, ”
Slide 44: Dr. Paula Briggs
Dr. Paula Briggs • Level of impairment: - efficacy of current treatments • Sepranolone: - Safety profile - Side effect profile 44
Slide 45: Dr. Paula Briggs
Dr. Paula Briggs • PMDD awareness in the UK: - Impact of the study - Global influence 45
Slide 46: Dr. Paula Briggs
Dr. Paula Briggs • Sepranolone: - Safety profile - Side effect profile • Patient feedback - In relation to the Sepranolone study 46
Slide 47: Liverpool
YY Liverpool Women’s ¢ Liverpool
Slide 48: Join Us May 4 for Our Next Investors' Meeting
JOIN US MAY 4 FOR OUR NEXT INVESTORS’ MEETING 48
Slide 49: Thank you for attending!
» ASARINA PHARMA Thank you for attending!