Remain in control of your life...• This presentation may contain specific forward-looking...
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ASARINA PHARMARemain in control of your life
Corporate presentationJPM 2020
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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 ”believe”, ”assume”, ”expert” or similar expressions. Such forward-looking statements are subject to known and unknown risks, uncertainties and other factors which may result in a substantial divergence between the actual results, financial situation, development or performance of Asarina and those explicitly or implicitly presumed in these statements
• Against the background of these uncertainties readers should not rely on forward-looking statements
• Asarina assumes no responsibility to update forward-looking statements or to adapt them to future events or developments
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• Phase IIa Proof of concept study in 80-90 women with Menstrual Migraine in 7 centers in Sweden and Finland> 50 % of subjects enrolled after 4 months recruitment
Asarina Pharma Overview
• Potential PMDD/MM annual peak sales: > USD 2.000 mio worldwide• Potential Orphan Tourette annual peak sales: > USD 1.000 mio worldwide• Building a Scandinavian franchise in women’s health/neurology
Menstrual Migraine: mid-term significant value inflection point
• Novel therapy with unique Mode of Action• Substantial unmet medical need:
Disabling condition affecting 4-5 % of women in fertile age
First-in-class therapy for PMDD –a highly underserved indication
• Phase IIb study with 14 centers in UK, Poland, Germany and Sweden recruiting 206 patients completed randomization December 2019
Phase IIb randomiza?on finalized dec 2019. Topline results April 2020
• Phase IIb Premenstrual Dysphoric Disorder – topline results April 2020 • Phase IIa study in Menstrual Migraine with topline results Q4 2020 • Phase IIa study in Tourette to start Q3 2020
Clinical mid-stage company with pipeline in women’s health and neurology
Significant commercial potential –total peak sales > USD 3 billion
• Strong Pre-clinical efficacy data on par with antipsychotics but without side effects published in Journal of Neuroendocrinology May 2019Phase IIa study with 20 subjects to start at Danish Tourette center Q3 2020
Tourette syndromeAn Orphan opportunity
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The Asarina team
Peter NordkildCEO
MDNovo Nordisk Ferring, Egalet, Pharmexa
Jakob DynnesHansen
CFOMSc, MBANovo Nordisk Zealand PharmaEvolva, Nordea
Otto Skolling CBO
MScPharmacia & UpjohnSiemens MedicalNovozymesKarolinska Development
Karin EkbergCOO
PhD, clinical physiologyCreafve Pepfdes Umecrine Cognifon
Märta SegerdahlCMO
MD, PhDAstra ZenecaLundbeck
Sven GötheCMC
PhDPharmacia & UpjohnKabi Fresenuis
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Major shareholders+85% are institutional investors
Kurma Biofund (France)
Östersjöstiftelsen (Sweden)
Idinvest Patrimonie (France)
Swedbank Robur Fonder (Sweden)
Fourth Swedish National pension fund
Rosetta Capital (UK)
Sectoral Asset Management (Canada)
Catella Fonder (Sweden)
Länsförsäkringar (Sweden)
Handelsbanken Fonder (Sweden)
PEG Capital (Sweden)
CEO & Founder
Others (incl. 660 private shareholders)
Total
17.1%
14.5%
8.9%
7.3%
6.2%
5.8%
5.4%
5.1%
4.9%
3.3%
2.6%
3.1%
16,8%
100.0%
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Pipeline Asarina Pharma2020 2021 2022 2023 2024
PMDD Phase IIb
PMDD Phase III US & EU
PMDDRegulatory
Menstrual Migraine Phase IIa
Mentrual MigrainePhase IIb
MMPhase III
Tourette Preclinical
Tourette Syndrome Phase IIa
Oral Lead UC2016Preclinical
Oral Lead UC2016 Phase I
Feasibility SepranoloneNew administration form
Preclinical SepranoloneNew administration form Phase I Bio Eq. Sepranolone
New adm. form
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Sepranolone normalises GABAA-receptoractivity, targeting underlying cause of PMDD
PMDD patients have increased sensitivity to GABAA steroid allopregnanolone (ALLO), which is elevated during the premenstrual (luteal) phase of the menstrual cycle
Sepranolone inhibits the Positive Allosteric Modulation (PAM) effect of ALLO on the GABAA receptor through • Fine tuned receptor activity
without overstimulation• High selectivity• Minimal off-target effects
PAM
Increased tonic GABAergic current
Novel PAMbinding site
Postsynaptic terminal
GABACl-
Extrasynaptic receptorscontain a 𝛿 subunit
ba
Extrasynaptic GABAA
receptors
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Sepranolone in Premenstrual Dysphoric Disorder
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• 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- 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
• 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
PMDD affects > 3.5 mio women in the US
Irritability
Bloa?ng
Anxiety/Depression
* Diagnostic and statistical manual of Mental Disorders
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SSRI Antidepressant Hormonal Therapy
Agent Fluoxetine YAZ oral contraceptive GnRH agonists
Efficacy Moderate (50-60%) Moderate High
Side Effects
Often persistent in PMDD patients
46% discontinued in 6 months due to side
effects
Black Box Warning
Suppress hormonal cycles
Require hormonal add-back
Approved U.S. U.S. U.S.
No current drugs directly target the underlying mechanism of PMDD1,2,3
SepranoloneInitial formulary placement: 2nd 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-y2. Yonkers K.et.al. Ob&Gyn 2005;106(3):492.3. Yaz Full Prescribing Information
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Statistically significant reduction in total premenstrual symptom score (p=0.041) compared to placebo
Sepranolone meets primary (FDA*) endpoint in phase IIa study
Placebo n=36
Active n=70
• 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
*Total symptom score of 11 symptoms
n=26 n=34Placebo Sepranolone
Highly stafsfcally significant reducfon in pre-menstrual symptom score in “treated as intended” populafon (p = 0.006)
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Fully randomized phase IIb study with topline results in April 2020
Design• RCT, double-blinded, placebo-
controlled, with two cycles of diagnosis, three treatment cycles and 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 treatment cycles
Secondary Endpoints• Safety• Responder analysis
e-PRO• DRSP according to DSM-5 as
diagnostic screener for PMDD
Baseline/DiagnosisTwo cycles
1 month follow-up3 treatment cycles
ScreenMulticenterD, UK, PL, S
Sepranolonedose 10 mg
Placebo
RandomizeN= ~206
(Double-blind)
PMDD (DSM-5) verified in at least two
menstrual cycles
Sepranolonedose 16 mg
Overwhelming interest/very low drop out rate of < 15%
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Overwhelming patient interest
“News” re PMDD& advertisements
Google Ads
Web screener
Telephonescreen
Clinicvisit 1
DRSPePRO
PMDDdiagnosis
Patient IC Randomisation
1,191,322 visits on study landing page
248,315 completed web-screener on the page
7,514 women chose to register on ClinLife study page
~10% final contact with site for telephone screen
• All patients recruited via a media campaign through geotargeted advertisement
~470 has signed informed consent
206 randomised patients
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PMDD
• Posifve data from Phase IIa study in 2015
• Phase IIb study reading out in April 2020- All pafents now randomized
- High treatment compliance
- Low number of withdrawals
• No safety signals, preclinically or clinically
• Long-term tox starfng April 2020
• Preparafons including upscaling of producfon and autoinjector for Phase III are ongoing. Esfmated start H2 2021, approximately 2 years study durafon.
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PMDD Phase III Clinical Program
• Asarina Pharma plans for two pivotal studies, randomized, double-blind parallel groups, one dose level vs. placeboOne in North America and one in EU/ ROW. The studies will each include ~500 patients
• Population: Women age 18-45, fulfilling diagnostic criteria for PMDD according to DSM-5 – the Daily Record of Severity of Problems (DRSP) score – the same as in Phase IIb
• The study will consist of a baseline/ diagnostic phase of 2 menstrual cycles, followed by a double-blind treatment of 3 menstrual cycles, then followed by an open label extension phase of 3 menstrual cycles, and a safety follow-up cycle. Treatment will consist of self-administered s.c. injections of Sepranolone every 48 hours during the woman’s luteal phase, starting on Day -14, totalling up to 7 injections
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PMDD Phase III Clinical Program
• The women will rate their PMDD symptoms daily on the DRSP scale using a web based eDiary. Primary endpoint is reduction in the DRSP score during the treatment cycles, compared to baseline
• Start of dosing in each cycle will be led by tracking of menstrual flow using the eDiary
• In parallel, a clinical pharmacology program for special populations, abuse potential, etc. will be conducted. Deferral will be requested for pediatric studies
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Market opportunity PMDD
• Assumptions:> 4% of women suffer from PMDD (~10.600.000)> 25% or 2,5 mio in EU/US/Japan seek treatment> 50% are refractory to present treatment
- Sepranolone market introduction end 2024- Sepranolone market penetration of 20% at peak sales- 250.000 patients being treated with Sepranolone
- Annual Sepranolone pricing e.g. USD 6.000 (Aimovig for Migraine: USD 6.900 annually)(Elagolix for Endometriosis: USD 10.000 annually)(Relugolix for Uterine fibrosis: USD 7.200 annully)
- Annual ww peak sales of Sepranolone > USD 1.0 bill
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Sepranolone in menstrual migraine
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Menstrual migraine –Prophylaxis is the best cure
• MM occurs from 2 days before to 3 days into menstruafon• MM is predictable but harder to treat and avacks are longer• MM pain does not respond well to state of the art migraine treatment
with triptanes and NSAID´s • MM pafents seems to have livle or no response to prophylacfc treatment
with CGRP anfbodies• 1 out of 5 women migraineurs suffers from menstrual migraine.
Only symptomafc treatments (triptans, NSAID) are available Sepranolone aims to prevent the inifafon of the migraine avack, by avenuafng the hyperexcitability of hypothalamic GABAA neurons
Prof Nissilä: “My experience was that MM a:acks were the only kind to keep persis=ng throughout CGRP medica=on. Neither triptans nor CGRP an=bodies are fully effec=ve against MM”
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Migraine attacks during 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
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Changes in circulating neurosteroid levels areassociated with migraine
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> 50 % of patients enrolled in phase IIaProof of Concept study
• The ongoing Phase IIa study is a randomized, double blind, parallel group study in women age 18-45 comparing two doses of Sepranolone and placebo. Esfmated top line results in Q4 2020
• The study consists of a diagnosfc/ baseline phase of three menstrual cycles, followed by three cycles of Sepranolone treatment. Women self-administer Sepranolone every 48 hours during the luteal phase of their menstrual cycle
• Primary endpoint is reducfon from baseline in number of migraine days
• Enrollment is on track, with half of pafents enrolled at year end 2019
• Phase IIb will include different dosing regimens, trying to reduce the number of injecfons
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Market opportunity Menstrual Migraine
• Assumptions:> 6% of women suffer from Menstrual Migraine (~14.000.000)> 50% or 7 mio in EU/US/Japan seek treatment> 30% are refractory to present treatment
- Sepranolone market introduction 2026- Sepranolone market penetration of 10% at peak sales- 200.000 patients being treated with Sepranolone
- Annual Sepranolone pricing e.g. USD 6.000 (Aimovig, Avojy, Emgality for Migraine: USD 6.900 annually)
- Annual ww peak sales of Sepranolone > USD 1.0 bill
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Sepranolone in Tourette Syndrome- a new opportunity
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2018 Impact Survey by US Tourette Association in 1.000 patients
Children:
- 63% felt discriminated against- 32% have considered suicide/self harming behavior- 40% were forced to miss school
- 59% take prescription medications to manage TS- 29% have tried 5 or more different medications- 44% of parents feel that their childs symptoms are
not adequately controlled by existing medications
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Phase IIa study in Tourette Syndrome
• In a mouse model of TS, Sepranolone reduces tic behavior similarly to Haloperidol and Finesteride
• Asarina Pharma will in September 2020 initiate a randomized parallel groupPhase IIa study in adolescent and adult patients with TS
• The study will include 20 male and female TS patients, ages 14-45, randomizedto sepranolone or no treatment
• After a 1-month baseline period, patients will receive sepranolone every otherday during 3 months*. Endpoint is reduction of tics on the YGTSS** scale
* Due to natural waxing and waning of tics, too short observation periods tend to overestimate effects **Yale Global Tic Severity Scale (YGTSS) (McGuire et al 2018)
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Source of VariationInteractionRow FactorColumn Factor
ANOVA tableInteractionRow FactorColumn Factor
% of total variation7.46114.1242.96
SS0.23260.44021.339
P value0.03850.0008< 0.0001
DF212
P value summary********
MS0.11630.44020.6696
Significant?YesYesYes
F (DFn, DFd)F (2, 30) = 3.637F (1, 30) = 13.77F (2, 30) = 20.94
P valueP = 0.0385P = 0.0008P < 0.0001
Spatial confinement
WT D1CT-70.00
0.25
0.50
0.75
1.00
1.25
1.50Vehicle (SC)Sepranolone (5 mg/kg, SC)Sepranolone (10 mg/kg, SC)
# Ti
cs/m
in
P<0.0001P<0.00001P<0.0001
NS
NS
All movements were scored by personnel blinded to treatment and genotype; n=5-7/group
Analysis: 2-way ANOVA followed by Tukey’s post-hoc tests
Dose dependent tic reduction with Sepranolone
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Spatial confinement
WT D1CT-70.00
0.25
0.50
0.75
1.00
1.25
1.50Vehicle (SC)Sepranolone (10 mg/kg, SC)Haloperidol (0.3 mg/kg, IP)
# Ti
cs/m
in
P<0.00001P<0.00001P<0.0001
NS
NS
All movements were scored by personnel blinded to treatment and genotype; n=7/group
Analysis: 2-way ANOVA followed by Tukey’s post-hoc tests
Source of VariationInteractionRow FactorColumn Factor
ANOVA tableInteractionRow FactorColumn Factor
% of total variation16.2323.8533.18
SS (Type III)0.45980.67540.9398
P value<0.0001<0.0001<0.0001
DF313
P value summary************
MS0.15330.67540.3133
Significant?YesYesYes
F (DFn, DFd)F (3, 48) = 9.716F (1, 48) = 42.82F (3, 48) = 19.86
P valueP<0.0001P<0.0001P<0.0001
NS
Finasteride (25 mg/kg, IP)P<0.00001
Efficacy on par with Haldol and Finasteride
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Market opportunity Tourette Syndrome
• Assumptions:- 600.000 TS patients in US/EU/Japan> 300.000 patients in US/EU/Japan treated with drugs
- Sepranolone market introduction 2025- Sepranolone market penetration of 10% at peak sales- 10% or 30.000 patients being treated with Sepranolone
- Annual Sepranolone pricing e.g. USD 50.000 (Ingrezza for TD: USD 64.400 annually)
- Annual ww peak sales of Sepranolone > USD 1.0 bill
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AutoinjectorConvenient and easy administration
Ypsomed (Ypsomate™) selected as Autoinjector• Compatible with Sepranolone syringe
• Single, fixed dose
• Automatic injection
• Disposable
• Provide needle shielding system
• Secondary packaging
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AUTO-INJECTORS ASSEMBLY EXPERTISE
Secondary Packaging of AIs: • Good space-saving packaging
• Several options:
Leaflet on the top
Top opening
Size: 147mm X 112mm X 31mm Carton thickness: 305g/m² + double lid and double walls
Insert on the side
1 unit per carton box
Different closure types
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Value generation
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Value inflection points – external communication 2019-2020
July 2019
Menstrual Migrainestudy initiation
August 2019
Last patient first visit UM203 PMDD
April - 2020
Top line results PMDD
Q1 - 2020
Oral proof of concept in animals
Q3 - 2020
MenstrualMigraine last patient first dose
Q3 - 2020
Top line results Menstrual Migraine
2019 2020
ü
ü
ü PMDD got its own code in ICD-11 May 2019ü IND approval for Sepranolone in Menstrual Migraine July 2019
IND approval SepranolonePMDD
Q3-4 - 2020APH205 study initiation Tourette’s
Q4 - 2020
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Asarina Pharma - summary
ü First treatment to target Premenstrual Dysphoric Disorder and Menstrual Migraine
with potential disease modifying effect targeting the origin of these diseases
ü Significant unmet medical need in both indications with US market opportunity
alone of > USD 1 billion and a similar size market opportunity in Europe and ROW
ü Topline results in April 2020 in 206 subjects/14 centers from
Phase IIb PMDD study
ü > 50 % of 80-90 subjects in 7 centers for Phase IIa study in Menstrual Migraine
enrolled by December 31st
ü Tourette Phase IIa study to be initiated Q3 2020 with read out Q3 2021
ü Strong cash position to finalize all three studies and production scale up for Phase III