ASARINA PHARMA Remain in control of your life Corporate - - PowerPoint PPT Presentation

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ASARINA PHARMA

Remain in control of your life

Corporate presentation DnB December 12th 2019

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Disclaimer

• The shares of Asarina Pharma (”Asarina”) are traded on NASDAQ First North in

Stockholm (Dcker: ”ASAP”)

• This presentaDon may contain specific forward-looking statements, relaDng 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, uncertainDes and other factors which may result in a substanDal divergence between the actual results, financial situaDon, development or performance of Asarina and those explicitly or implicitly presumed in these statements

• Against the background of these uncertainDes 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. > 40 % of subjects enrolled after 3 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

recruiDng 205 paDents completed enrolment August 2019 Phase IIb enrollment closed August 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 2019 Phase IIa study with 40 subjects to start at Danish Tourette center Q3 2020 Tourette syndrome An Orphan opportunity

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The Asarina team

Peter Nordkild CEO MD

Novo Nordisk Ferring, Egalet, Pharmexa

Jakob Dynnes Hansen CFO MSc, MBA

Novo Nordisk Zealand Pharma Evolva, Nordea

Otto Skolling CBO MSc

Pharmacia & Upjohn Siemens Medical Novozymes Karolinska Development

Karin Ekberg COO PhD, clinical physiology

Creative Peptides Umecrine Cognition

Märta Segerdahl CMO MD, PhD

Astra Zeneca Lundbeck

Sven Göthe CMC PhD

Pharmacia & Upjohn Kabi 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 Pharma

2020 2021 2022 2023 2024 PMDD Phase IIb PMDD Phase III US & EU PMDD Regulatory Menstrual Migraine Phase IIa Mentrual Migraine Phase IIb MM Phase III Tourette Preclinical Tourette Syndrome Phase IIa Oral Lead UC2016 Preclinical Oral Lead UC2016 Phase I Feasibility Sepranolone New administration form Preclinical Sepranolone New administration form Phase I Bio Eq. Sepranolone New adm. form

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Sepranolone normalises GABAA-receptor activity, 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 PAM binding site

Postsynapticterminal GABA Cl-

Extrasynaptic receptors contain a 𝜀subunit b a

Extrasynaptic GABAA receptors

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Sepranolone in Premenstrual Dysphoric Disorder

Remain in control of your life

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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 Bloating 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

Sepranolone

Initial 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-y 2. 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=34

Placebo Sepranolone

Highly statistically significant reduction in pre-menstrual symptom score in “treated as intended” population (p = 0.006)

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Fully enrolled 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

• ther 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/Diagnosis Two cycles 1 month follow-up 3 treatment cycles

Screen

Multicenter D, UK, PL, S

Sepranolone dose 10 mg Placebo

Randomize

N= ~225 (Double-blind)

PMDD

(DSM-5) verified in at least two menstrual cycles

Sepranolone dose 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 Telephone screen Clinic visit 1 DRSP ePRO PMDD diagnosis 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 ~210-230 randomised patients

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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 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 menstruaDon
• 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 paDents seems to have livle or no response to

prophylacDc treatment with CGRP anDbodies

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 are associated with migraine

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> 40 % of patients enrolled in phase IIa Proof of Concept study

TRIAL DESIGN

RCT, double-blinded, placebo-controlled with 80-90 paDents in parallel dose groups Three treatment cycles with intermivent 14 days exposure (7 injecDons every other day with start 12 days prior to next menstruaDon) Primary endpoint: Change in number of migraine days per cycle measured before and during 3 treatment cycles Secondary endpoints: DuraDon and severity of migraine avacks Screen

7 centers in Denmark, Sweden and Finland

Sepranolone dose 10 mg

Placebo Randomize

N=80-90 (Double-blind)

Menstrual migraine

Diagnosis verified in 3 baseline cycles

Sepranolone dose 16 mg

baseline / diagnosis 3 cycles treatment follow-up

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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 prescripDon medicaDons to manage TS
• 29% have tried 5 or more different medicaDons
• 44% of parents feel that their childs symptoms are

not adequately controlled by exisDng medicaDons

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Source of Variation Interaction Row Factor Column Factor ANOVA table Interaction Row Factor Column Factor % of total variation 7.461 14.12 42.96 SS 0.2326 0.4402 1.339 P value 0.0385 0.0008 < 0.0001 DF 2 1 2 P value summary * *** **** MS 0.1163 0.4402 0.6696 Significant? Yes Yes Yes F (DFn, DFd) F (2, 30) = 3.637 F (1, 30) = 13.77 F (2, 30) = 20.94 P value P = 0.0385 P = 0.0008 P < 0.0001

Spatial confinement

WT D1CT-7 0.00 0.25 0.50 0.75 1.00 1.25 1.50 Vehicle (SC) Sepranolone (5 mg/kg, SC) Sepranolone (10 mg/kg, SC)

# Tics/min

P<0.0001 P<0.00001 P<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-7 0.00 0.25 0.50 0.75 1.00 1.25 1.50 Vehicle (SC) Sepranolone (10 mg/kg, SC) Haloperidol (0.3 mg/kg, IP)

# Tics/min

P<0.00001 P<0.00001 P<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 Variation Interaction Row Factor Column Factor ANOVA table Interaction Row Factor Column Factor % of total variation 16.23 23.85 33.18 SS (Type III) 0.4598 0.6754 0.9398 P value <0.0001 <0.0001 <0.0001 DF 3 1 3 P value summary **** **** **** MS 0.1533 0.6754 0.3133 Significant? Yes Yes Yes F (DFn, DFd) F (3, 48) = 9.716 F (1, 48) = 42.82 F (3, 48) = 19.86 P value P<0.0001 P<0.0001 P<0.0001

NS Finasteride (25 mg/kg, IP) P<0.00001

Efficacy on par with Haldol and Finasteride

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Market opportunity

• 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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Autoinjector Convenient 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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Value generation

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Value inflection points – external communication 2019-2020

July 2019

Menstrual Migraine study 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

Menstrual Migraine 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 2019 ü IND approval for Sepranolone in Menstrual Migraine July 2019

IND approval Sepranolone PMDD

Q3-4 - 2020

APH205 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 205 subjects/14 centers from Phase IIb PMDD study ü 40 % of 80-90 subjects in 7 centers for Phase IIa study in Menstrual Migraine enrolled by December 1st 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