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Capital Markets and R&D Day The Royal Society for Engineering Science (IVA) Stockholm, Sweden December 11, 2018
Capital Markets and R&D Day
The Royal Society for Engineering Science (IVA) Stockholm, SwedenDecember 11, 2018
2
Today’s presenters
Fredrik Tiberg, PhDPresident & CEO Head R&D, Head R&D Camurus
Richard JamesonCCO, Camurus
Mike DerkaczPresident & CEO, Braeburn, USA
Diego Ferone, MD, PhDProf. University of Genova, Italy
James Seibold, MDScleroderma Consultants, USA
Charlotte Stjerngren, Moderator Cord Communications
Forward-looking statements
This presentation contains forward-looking statements that provide our expectations or forecasts of future events such as new product developments and regulatory approvals and financial performance. Camurus is providing the following cautionary statement. Such forward-looking statements are subject to risks, uncertainties and inaccurate assumptions. This may cause actual results to differ materially from expectations and it may cause any or all of our forward-looking statements here or in other publications to be wrong. Factors that may affect future results include currency exchange rate fluctuations, delay or failure of development projects, loss or expiry of patents, production problems, unexpected contract, patent, breaches or terminations, government-mandated or market-driven price decreases, introduction of competing products, Camurus‘ ability to successfully market products, exposure to product liability claims and other lawsuits, changes in reimbursement rules and governmental laws and interpretation thereof, and unexpected cost increases. Camurus undertakes no obligation to update forward-looking statements
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2018Transformative Year
for Camurus
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5
Investment highlights
Listed on Nasdaq STO (ticker CAMX)Market Cap: SEK ~4 billionCash position: SEK ~216 million (Q3 2018)Employees: 94HQ: Lund, SwedenRegional offices: Cambridge, Mannheim, Paris, Sydney
Unique FluidCrystal®delivery technology
Broad, late-stage R&D pipeline
Own commercial organization
Value adding partnerships
Experienced management and dedicated teams
• Developed in-house with strong IP protection• Proven in 20+ clinical trials• Validated by regulatory approvals
• 10+ clinical programs in opioid addiction, pain, cancer, obesity, endocrine and CV disease
• 2018 EMA/TGA approvals and FDA decision
• Fully operational for 2019 Buvidal® launches in Europe and Australia
• Braeburn, Rhythm, Medison, Solasia Pharma…• Significant near-term milestone payments
6
Broad and diversified product pipeline
6
1. Braeburn holds the rights to North America; 2. Postoperative nausea and vomiting; 3. Developed by Rhythm Pharmaceuticals under a worldwide license to FluidCrystal®
PRODUCT PRECLINICAL PHASE 1-2 PHASE 3 REGISTRATION MARKETBuvidal® (CAM2038) q1w OPIOID DEPENDENCE1 APPROVED
Buvidal® (CAM2038) q4w OPIOID DEPENDENCE1 APPROVED
CAM2038 q1w CHRONIC PAIN1 PHASE 3
CAM2038 q4w CHRONIC PAIN1 PHASE 3
CAM2029 ACROMEGALY PHASE 1-2
CAM2029 NEUROENDOCRINE TUMORS PHASE 1-2
CAM2032 PROSTATE CANCER PHASE 1-2
CAM2047 CHEMOTHERAPY INDUCED NAUSEA & VOMITING PHASE 1-2
CAM2048/58 POSTOPERATIVE PAIN & PONV1,2 PHASE 1-2
CAM4072 GENETIC OBESITY DISORDERS3 PHASE 1-2
CAM2043 PULMONARY ARTERIAL HYPERTENSION PHASE 1-2
Strong 2018 news flow
7
PRODUCT EVENT TIMECAM2038 Opioid dependence CRL issued by FDA
NDA resubmitted to the FDA √Publication of pivotal Phase 3 results in JAMA Int. Med. √FDA issued PDUFA goal date of 26 December 2018 √Positive CHMP opinion recommending EU approval √EU approval √Australian approval √US approval decisions
January 2018
May 2018
May 2018
July 2018
Sept 2018
Nov 2018
Nov 2018
Dec 2018
CAM2038 Chronic pain Positive Phase 3 efficacy results √ Sept 2018
CAM2029 Acromegaly / NET Exclusive rights to CAM2029 regained from Novartis √ July 2018
CAM2043 PAH / 2nd indication Positive Phase 1 SAD and MAD results√ May 2018
CAM4072 Genetic obesity First clinical milestone achieved √ Feb 2018
7
Long-acting medications address key healthcare challenges
8
9
Unique FluidCrystal® nanotechnology platform
LIQUID DRUG PRODUCTFORMULATION BEFORE INJECTION:
SPC+GDO+SOLVENT+DRUG
WATER ABSORPTION
SOLVENT RELEASE
DRUG RELEASE
LIQUID CRYSTAL (LC)
INJECTION
DEPOT BIODEGRADATION TO COMPLETE RESOLUTION
WEEKS / MONTHSHOURS SECONDS
400+ PATENTS &
APPLICATIONS
>2000 SUBJECTS HAVE RECEIVED
~20,000 INJECTIONS IN20 CLINICAL TRIALS
Easy to administer Rapid onset & long-acting release Applicable across substance classes
Good safety and tolerability profile Unique mixtures of endogenous lipids Validated by regulatory approvals
Tiberg F, Johnsson M, Jankunec M et al., Chemistry Letters 2012; 41(10): 1090-1092; Tiberg F, Johnsson M., J. Drug Delivery Science Techn. 2011; 21 (1): 101-109.
0,1
1
10
0 7 14 21 28
Pasi
reot
ide
plas
ma
conc
entra
tion
(ng/
mL)
Time (days)
Pasireotide IR 600 ug(SC thigh, n = 94)
Long-acting pasireotide (CAM4071)Immediate-release pasireotide (Signifor®)
Long-acting pasireotide, formulated with FluidCrystal®
Single dose injection at t=0; clinical Phase 1 data, mean values. Tiberg F et al, Poster presentation at ECE, Barcelona, May 2018. 10
0,1
1
10
0 7 14 21 28
Pasi
reot
ide
plas
ma
conc
entra
tion
(ng/
mL)
Time (days)
Pasireotide FluidCrystal20 mg (SC thigh, n = 12)
ADVANCING PIPELINE
Highlights 2018
11
Approval of Buvidal® (CAM2038) in EU and AustraliaThe first long-acting treatment for opioid dependence
• First clinically differentiated treatment for opioid dependence (ODT) in ~20 years
• Strong Buvidal® labels ‒ Broad indication statements‒ Superiority claim versus daily sublingual
buprenorphine/naloxone
• Robust clinical evidence base• US FDA decision expected by 26 December 2018!1
• Commercial organizations launch ready for Europe, Australia and the US
121PDUFA goal date issued by the US Food and Drug Administration (FDA)
$264 m
GlobalData estimates of opioid dependence market (US, CA, DE, AUS)1
13
Significant market potential expectedfor Buvidal® (CAM2038)
Source: 1. Opioid Use Disorder (OUD): Opportunity Analysis and Forecasts to 2027, GlobalData, Nov. 2018
• Escalating opioid crisis• High unmet medical need• Increasing disease awareness• Significant interest from patients,
prescribers and payers • Opioid dependence market predicted
to grow by 10.2% CAGR1
– Long-acting injectables are likely to become the new gold standard of treatment
– Over 100,000 US patients estimated to be treated with CAM2038 in 2027
– CAM2038 (Buvidal®) market forecastof US$ 1.4 billion in 20271
2017 2027
Long-acting injectablesDaily medication
US$ 1.8 billion
US$ 4.8 billion
$1.5 billion$3.4 billion
$1.4 billion
14
Positive Phase 3 results for CAM2038 in second indication of chronic pain
Enriched enrollment randomized withdrawal study design• Primary endpoint change from Week 12 to baseline
‒ 1.03 (95% CI, 0.49 to 1.57; p<0.001) difference to placebo (+rescue)
• Key secondary endpoint of worst pain intensity, ‒ 1.11 (95% CI, 0.49 to 1.57; p<0.001) difference to placebo (+rescue)
• Statistical treatment difference for additional endpoints:‒ Time to loss of efficacy, p=0.002; patient global impression of change
improvement, p<0.001; work productivity and activity impairment subscale, p=0.005
• Favorable safety profile consistent with buprenorphine‒ Mild to moderate injection site reactions in a minority of subjects
API average pain intensity Research N Reports 2018, Chronic Low Back Pain Market - Global Insights, Growth, Size, Comparative Analysis, Trends and Forecast, 2017-2025. 2. Journal of Pain 2012, 13:715-724.
0
1
2
3
4
5
6
7
8
Baseline End OLT withCAM2038
Aver
ga p
ain
inte
nsity
sco
re
Average pain intensity (API) score decreased 64% from 7 to 2.5 during CAM2038 open-label titration
64% decrease in pain score
15
Registration program for CAM2038 in chronic pain targets opioid experienced patients
1 IN 5 INDIVIDUALS SUFFERFROM CHRONIC PAIN1
CHRONIC PAIN ESTIMATED
~US$560-635bn
ANNUAL COST TO SOCIETY2
Completion of long-term safety extension study
Scientific advice/pre-MAA meetings with health authorities
MAA submissions to EMA and TGA expected first half of 2020
Focus on high risk, high need opioid experienced patients
SOMATOSTATIN ANALOG SALES1
16
CAM2029: A next generation long-acting octreotide entering Phase 3
Source: 1. GlobalData 2017; 2. US weighted average cost for mid-range doses, 2018.
02505007501000125015001750200022502500Somatuline® (Ipsen)
Sandostatin® LAR® (Novartis)
mUS$• Octreotide subcutaneous depot (CAM2029) for acromegaly and neuroendocrine tumors (NET)‒ FluidCrystal® formulated for patient convenience and
controlled release‒ Potential for improved efficacy – Phase 2 data‒ Phase 3 program planned to start Q2 2019
• Additional innovative SSA products under development targeting rare endocrine diseases‒ Preclinical data suggest effective hormonal secretion
and tumor growth inhibition and good tolerability – 20 years of strong market growth– Concentrated prescriber base – Long-acting SSA US price-range
US$51,000 to US$146,000 WAC/year2
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CAM2043 treprostinil SC depot for pulmonary arterial hypertension (PAH)
• Subcutaneous depot alternative to IV/SC infusion products ‒ Associated with significant limitations and risks for
patients
• Positive results from Phase 1 SAD and MAD study with CAM2043‒ Dose proportional pharmacokinetics with duration
of at least 7 days
• Phase 2 study in PAH patients planned to start 2019 ‒ Pilot study in scleroderma patients with
Raynaud’s phenomenon also under way
Source: 1. Opportunity Analyzer: Pulmonary Arterial Hypertension, GlobalData 2017. 2. Pulmonary Hypertension Association, 2017; 3. Remodulin® US label; 4. Simoneau et al., Am J Respir Crit Care Med. 2002 Mar 165(6):800-4.
44,7%41,2%
10,0%4,0% Endothelin Receptor
AntagonistsProstacyclin & Prostacyclin AnaloguesPDE5 Inhibitors
sGC Stimulators
PAH market by drug class1
0
500
1000
1500
Mill
ion
US$
TREPROSTINIL PRODUCT SALES1
Remodulin Tyvaso Orenitram
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Continued value creation through partnerships
Outlicensing and co-development of internal programs
Technology product partnerships
‒ Expected CAM2038 OUD launch in the US
‒ Continued development of CAM2038 for chronic pain
‒ Submission of CAM2038 MAA targeted for Q1 2019
‒ Expected launch in Q1 2020
‒ episil® launched in Japan in May 2018 by partner Meiji Seika
‒ Positive Phase 3 data supporting registration in China1
‒ Clinical proof-of-concept achieved for once-weekly setmelanotide (CAM4072)
‒ Preparing for clinical registration studies
NEW PARTNERSHIPS
NEW PARTNERSHIPS
Source: 1. Chen Y, et al, OncoTargets and Therapy 2018, Vol 11, p. 8555-8564, OUD opioid use disorder, ODT opioid dependence treatment
Validated FluidCrystal® technology
Innovative treatment approved
Rich and diversified pipeline
Great team ready to deliver value
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Experienced and committed leadership
Fredrik Tiberg, PhDPresident & CEO, Head R&D
In Company since: 2002Holdings: 1,512,551 shares & 205,000 warrants
Eva Pinotti-Lindqvist Chief Financial Officer
In Company since: 2014Holdings: 36,391 shares & 33,882 warrants
Richard JamesonChief Commercial Officer
In Company since: 2016Holdings: 16,395 shares & 120,000 warrants
Fredrik Joabsson, PhD Vice President, Business Development
In Company since: 2001Holdings: 36,391 shares & 40,000 warrants
Torsten Malmström, PhD Vice President, Technical OperationsIn Company since: 2013Holdings: 36,391 shares & 28,000 subscription warrants
Agneta SvedbergVice President, Clinical & Regulatory Development
In Company since: 2015Holdings: 9,073 shares & 70,000 subscription warrants
Urban PaulssonVice President Corporate Dev.& General Counsel
In Company since: 2017Holdings: 6,500 shares & 115,000 warrants
Cecilia CallmerVice President, Human Resources
In Company since: 2017Holdings: 26,000 warrants
Weekly and monthlybuprenorphine depots– A game changer in opioid dependence treatment
Buvidal®
Opioid dependence: an escalating global health crisis
• Largest societal burden of all drugs1
• Public health epidemic in the US• Patients need better access to care and
new treatment choices• Investment in treatment brings
significant value
Source: 1. UNODC, World Drug Report 2017; 2. Center for Disease Control & Prevention 2018; 3. The Council of Economic Advisers, November 2017; 4. Frazier at al, 2017, Journal of the American Medical Association; 5. Crow D. Financial Times.com, accessed on March 13, 2018, https://www.ft.com/content/d22e742c-e65c-11e7-97e2-916d4fbac0da
WHITE HOUSE ESTIMATES
US$ 504 billion PRICE TAG FOR US OPIOID CRISIS3
22
Mounting US opioid overdose deaths2
(thousands)
5
10
15
20
25
30
35
40
45
50
* Provisional data
− #1 cause of death for people below 50 in the US− 30:1 non-fatal to fatal overdoses4
− Recent US life expectancy decline largely due to opioids5
• Flexible dosing to match patient needsEnhanced continuum of care with direct initiation and switching from daily treatments (‘dose matching’)
• Removes burden and stigma of daily medication and increases adherence
• HCP administration safeguards against diversion, misuse and pediatric exposure
• Potential game changer in opioid dependence treatment
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Buvidal® has a unique and differentiated product profile
SMALL NEEDLE
LOW VOLUMES
ROOM TEMP STORAGE
CLINICAL DATA VS ACTIVE CONTROL
23 gauge 0.16 – 0.64 mL
WEEKLY DOSING
MONTHLY DOSING
MULTIPLE DOSES
CHOICE OF INJECTION
SITES
• Non-inferior and superior efficacy shown in pivotal Phase 3 study versus standard daily SL BPN/NX1
• Effective suppression of withdrawal and cravings1,2,3
• Blockade of opioid effects from the first dose2
• Pharmacokinetic profiles for weekly and monthly dosing4
• Safety profile comparable to SL BPN/NX except for mild and moderate injection site reactions1
• No opioid overdoses across clinical studies for participants treated with Buvidal® 1,2,3,5
• High patient satisfaction including versus SL BPN6
Compelling clinical data for Buvidal®versus daily standard treatment
241Lofwall et al, JAMA Int. Med. 2018;178(6); 764-773; 2Walsh et al, JAMA Psychiatry 2017;74(9):894-902; 3Haasen C et al, J Subst Abuse Treat. 2017;78:22-29; 4Albayaty M et al, Adv Ther. 2017 34(2):560-575; 5Lintzeris et al, Drug and alcohol review. 2017;36(S1):47-48, 6Study HS-14-499, data on file. SL BPN: sublingual buprenorphine/naloxone.
Screening
Opioid dependent
patients seeking BPN
treatment(N=600)
Phase 1: weekly visits
• 8–24 mg/day• Placebo injection
• 16–32 mg/week• SL placebo
1 weekinitiation
11 weeksstabilization
Phase 2: monthly visits
• 64–160 mg/month • SL placebo
• 8–32 mg/day• Placebo injection
12 weeksmaintenance
1 monthfollow-up
CAM2038N=213
SL BPN/NXN=215
RN=428
BPN:buprenorphine; SL:sublingual; BPN/NX:buprenorphine/naloxone25
CAM2038 Phase 3 design – pivotal study with active control and treatment initiation on Day 1
Lofwall M et al, JAMA Internal Medicine. 2018;178(6); 764-773.
26
Representative demographics and baseline characteristics
CharacteristicSL BPN/NX
(n=215)CAM2038
(n=213)
Age, y, mean (SD) 38.0 (10.9) 38.7 (11.2)
Male, number (%) 142 (66.0) 121 (56.8)
White, number. (%) 164 (76.3) 159 (74.6)
BMI, mean (SD) 26.0 (5.6) 26.0 (5.0)
Employed, number (%) 72 (33.5) 76 (35.7)
History of any arrest, number (%) 144 (67.0) 130 (61.0)
Primary opioid of use, number (%)Heroin 151 (70.2) 152 (71.4)
Prescription opioids 64 (29.8) 61 (28.6)
Injection use history, number (%) 110 (51.2) 114 (53.5)
Hep C antibody pos, number (%) 81 (37.7) 81 (38.0)
CharacteristicSL BPN/NX
(n=215)CAM2038 (n=213)
Non-opioid drug use screening, number (%) 149 (69.3) 155 (72.8)
Amphetamine 32 (14.9) 38 (18.0)
Benzodiazepine 35 (16.3) 30 (14.2)
Cocaine 53 (24.7) 53 (25.1)
Marijuana 64 (29.8) 57 (27.0)
Baseline opioid craving and withdrawal scores, mean (SD)
Craving: need to use VAS (0–100) 76 (24.9) 77 (25.4)
Craving: desire to use VAS (0–100) 77 (25.4) 77 (26.2)
COWS score (0-48) 12 (6.0) 12 (5.4)
SOWS score (0-64) 31 (16.1) 32 (15.4)
Lofwall M et al, JAMA Internal Medicine. 2018;178(6); 764-773.
27
Primary and key secondary Phase 3 study endpoints met1
Non-inferiority for mean % urines negative for illicit opioids, p<0.001
Superiority CDF % negative urines weeks 4-24; median 26.7% versus 6.7%, p=0.0082
-20% -15% -10% -5% 0% 5% 10% 15% 20%
Treatment difference mean (95% CI)
Favors CAM2038Favors SL BPN/NX
-11%
NI margin-11%
NI margin
-0.1% 6.7% 13.6%
0.9% 8.7% 16.4%
EMA primary endpoint:Missing samples imputed as positive
Sensitivity analysisMissing samples not imputed
1Lofwall et al., JAMA Int. Med. 2018,178(6); 764-773. 2Missing samples imputed as positive; CDF : cumulative distribution function .Pa
rtici
pant
s (%
)
% opioid-negative urine samples: week 4-24
(n=213) (n=215)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70 80 90 100
CAM2038 SL BPN/NX
EMA key secondary endpoint;
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Patients treated with CAM2038 had more negative urine tests than patients treated with SL BPN/NX
0
10
20
30
40
50
60
70
80
90
100
0 2 4 6 8 10 12 14 16 18 20 22 24
CAM2038 SL BN/NX
Treatment week% p
atie
nts
with
opi
oid-
nega
tive
urin
e sa
mpl
es a
nd s
elf-r
epor
ts
* * * * * * * 0
10
20
30
40
50
60
70
80
90
100
0 2 4 6 8 1 0 1 2 1 6 2 0 2 4
CAM2038 SL BPN/NX
Treatment week% p
atie
nts
with
opi
oid-
nega
tive
urin
e sa
mpl
es a
nd s
elf-r
epor
ts
Missing urine samples imputed as positive. *P<0.05 Missing urine samples not imputed. *P<0.05
Random urine samples collected during the month
* * * * * * * * * *
Source: Lofwall et al, JAMA Int. Med. 2018,178(6); 764-773.
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Comparable AE profiles for CAM2038 and SL BPN
Study group, number (%) of participants
Adverse event characteristic SL-BPN/NX (n=215) CAM2038 (n=213) All (n=428)
≥1 Any 119 (55.3) 128 (60.1) 247 (57.7)≥1 Drug-related 64 (29.8) 70 (32.9) 134 (31.3)≥1 Severe 15 (7.0) 6 (2.8) 21 (4.9)Nonfatal serious 13 (6.0) 5 (2.3) 18 (4.2)Deaths* 0 1 (0.5) 1 (0.2)Hospitalizations 12 (5.6) 3 (1.4) 15 (3.5)Drug overdoses 5 (2.3) 0 5 (1.2)Led to discontinuation of treatment 3 (1.4) 7 (3.3) 10 (2.3)Occurred in ≥5% of participants
Injection-site pain 17 (7.9) 19 (8.9) 36 (8.4)Headache 17 (7.9) 16 (7.5) 33 (7.7)Constipation 16 (7.4) 16 (7.5) 32 (7.5)Nausea 17 (7.9) 15 (7.0) 32 (7.5)Injection-site pruritus 13 (6.0) 13 (6.1) 26 (6.1)Injection-site erythema 12 (5.6) 12 (5.6) 24 (5.6)Urinary tract infection 10 (4.7) 11 (5.2) 21 (4.9)Insomnia 6 (2.8) 12 (5.6) 18 (4.2)
*1 patient, pedestrian hit by car.
Source: Lofwall MR et al, JAMA Intern Med. 2018.
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Phase 3 long-term (48-week), open-label, safety study with flexible dosing regimen
Screening period
Week -3
New to treatmentor
Transferred from SL BPN
Transferred from SL BPN
Treatment period(up to 48 weeks)
Week 1 Flexible titration (increase or decrease doses)
Flexible dosing intervals(switch from weekly to monthly or vice versa)
CAM2038 weekly treatment
CAM2038 monthly treatment
Follow-up period:
4 additional weeks
Week 48
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Impressive 48-week treatment retention for transfer and new to treatment patients
0%
20%
40%
60%
80%
100%
0 4 8 12 16 20 24 28 32 36 40 44 48
Ret
entio
n in
trea
tmen
t(%
)
Treatment Week
All patients
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Clinical opiate withdrawal scale (COWS) score and opioid craving score, need to use VAS
CO
WS
(Tot
al s
core
)
Treatment day
48
0
2
4
6
8
10
12
0 50 100 150 200 250 300 350
Transferred from SL BPN (n=190)
New to treatment (n=37)
0
10
20
30
40
50
60
70
80
90
100
0 50 100 150 200 250 300 350
Transferred from SL BPN (n=190)
New to treatment (n=37)
Treatment day
Nee
d to
use
VAS
(mm
)
Withdrawal symptoms Need to use
33
Favorable safety profile confirmed in 48-week long term safety study
Overall Safety Population
CategoryTransferred fromSL BPN (n, (%))
N=190
New to BPNtreatment (n, (%))
N=37
Overall (n, (%))N=227
A least 1 AE 131 (68.9) 12 (32.4) 143 (63.0)
At least 1 drug-related AE 58 (30.5) 2 (5.4) 60 (26.4)
Injection site AE 43 (22.6) 2 (5.4) 45 (19.8)
Non-injection site AE 23 (12.1) 1 (2.7) 24 (10.6)
AEs leading to study drug discontinuation 3 (1.6) 0 (0) 3 (1.3)
At least 1 SAE 10 (5.3) 2 (5.4) 12 (5.3)
Hospitalizations 9 (4.7) 1 (2.7) 10 (4.4)
At least 1 drug-related SAE 0 (0) 0 (0) 0 (0)
Deaths 0 (0) 0 (0) 0 (0)
BPN, buprenorphine; SL BPN, sublingual buprenorphine; SAE, serious adverse event.
H
“CAM2038 compared to my previously prescribed sublingual buprenorphine treatment”
Much worse
Slightly worse
About the same
Slightly better
Much better
83% POSITIVEN=133
High satisfaction amongst patients
Source: Poster presentation ASAM 2018. Phase 3 Long-Term Safety Study HS-14-499, data on file. 34
35
Patient and physician voices
Source: FDA Advisory Committee November 1, 2017.
”
“ For the first time in years I was not reminded every day of the shame and failure one feels as an opiate addict. The Suboxone tablets were a daily reminder that I hated myself and what I had become. The injection removed that obstacle and slowly my self-confidence returned.
“ The biggest thing with the CAM injection is how simple life has become and how the obsession to use was gone. ”
As a clinician, I see a number of advantages to CAM2038. It offers us the ability to offer a medication-assisted treatment to our patients with a minimal risk of poor adherence and diversion, there is no daily decision to take a sublingual tablet and no tablet or film to be diverted.
“
”
The weekly and monthly buprenorphine injections will provide practitioners with flexible dosing options. Practitioners may individualize treatment based on the specific needs of the patient.
“
”
”
36
Long-acting injectables for ODT on key global markets
Approved Nov 2017
Approved 2010
Source: 1. Indivior, Q2 Financial Results, May 2, 2018; 2. GlobalData 2018.
Long-acting buprenorphine injectables
Long-acting naltrexone injectables
Camurus/Braeburn
Indivior
Alkermes
PRECLINICAL PHASE I PHASE II PHASE III REGISTRATION APPROVAL
US
US
Vivitrol® 2017 sales $269M2 US
Europe
Europe
Australia
AustraliaN/A
Estimated Q3 2019
CAM2038 Weekly & Monthly
Sublocade™ Monthly
PDUFA 26 Dec 2018
Approved Nov 2018
Approved Nov 2018
Broad and competitive product labels received for Buvidal® in the EU and Australia
• Indication statement in EU: For treatment of opioid dependence within a framework of medical, social and psychological treatment in adults and adolescents from 16 years
• Label covers all treatment phases: Treatment initiation, switching from daily medications and long-term maintenance treatment
• Superiority versus daily standard treatment with sublingual buprenorphine/naloxone for CDF % urine tests negative for illicit opioids included in clinical outcomes
37
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Expanding the evidence base and utility of Buvidal®
Recently started studies • DEBUT study
‒ Objective: to compare treatment outcomes, including patient satisfaction, with CAM2038 to BPN standard of care in adult outpatients with opioid dependence
‒ Status: ongoing with ~30% patients enrolled‒ Sponsored by Camurus
UNLOC-T study‒ Objective: assess safety and feasibility of
depot buprenorphine injection (CAM2038) for the treatment of adult custodial population with opioid use disorder
‒ Status: first patients enrolled‒ Sponsored by NSW Ministry of Health with
product supply from Camurus
DEBUT
Day -28 to -1 Day 1 Week 24
Screening
SC CAM2038 q1w or q4w at flexible doses
Follow-upperiod
Week 26
UNLOC-T
Screening
Day 0 Day 1 Week 16 Week 48Week 4
Extended safety monitoring
Active follow-up
BPN standard of careat flexible doses
E
Methadone
CAM2038 q1w
CAM2038 q4w
CAM2038 q4w
n=1201
1Target sample size. Australian New Zealand Clinical Trials Registry .
R
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2019: Buvidal® (CAM2028) launches in key global markets
Source. 1. World drug report 2018.
ESTIMATED
34 millionWORLDWIDE
OPIOID USERS 20161
Braeburn Braeburn option rightCamurus 1st entry markets Medison (Israel)Camurus
127,000OPIOID OVERDOSE
DEATHS1
11.2 millionINJECTION
USERS1
5.5 millionWITH HEPATATIS C1
1.2 millionWITH HIV1
Ready for launch inEurope and AustraliaRichard JamesonChief Commercial Officer, Camurus
Buvidal®
Mannheim,Germany
Paris,France
Cambridge,UK
HQLund,Sweden
Track record of successful commercialization in the opioid dependence market‒ EU/AUS team of 45 professionals, expanding to 75 in 2019 ‒ Extensive experience from the opioid dependence and related
specialty areas‒ Market access, pricing and reimbursement expertise‒ Strong relationships with KOLs through collaborations ‒ Infrastructure and effective pathways for
patient access under development‒ 85% of patients in treatment are
in EU5, Nordics and Australia
41
Leading commercialization platform established in EU and Australia
SydneyAustralia
Northern Europe
Southern EuropeCentral Europe
Australia
Regions
Focus on accelerating growth trajectory of Buvidal®
Opioid dependence treatment (ODT) situation in Europe and Australia
~1.3 million high-risk opioid users in Europe and ~150,000 in Australia1,2
‒ Less than 50% in treatment1
1. EMCDDA. European Drug Report 2018 2. Degenhardt L, Charlson F, Mathers B, et al.. Addiction. 2014;109(8):1320–1333.
0
50 000
100 000
150 000
200 000
250 000
300 000
350 000
400 000
Germany UK Italy Spain France Australia
42
High-risk opioid users
In treatment
• Improves public health• Improves social functioning/QoL• Reduces crime• Provides value for money
43
Opioid dependence treatment is effective
• Reduces illicit opioid use• Decreases mortality• Limits spread of blood-borne
viruses• Improves quality of life
Sources: Bell J: Medications in Recovery: Re-Orientating Drug Dependence Treatment. Appendix C - Opioid Substitution Treatment and Its Effectiveness: Review of the Evidence, 2012; Black 2016, An independent review of the impact on employment outcomes of drug or alcohol addiction.
LIMITATIONS ADDRESSED BY DEPOT
44
Current daily ODT has significant limitations that can be addressed by long-acting injections
Limited treatment adherence1
– Increased risk of relapse/overdose
Significant burdens and stigma for patients2
– Strict controls and supervised administration– Limited access and stringent entry criteria
Public health impact – Medication misuse, abuse and diversion– Huge healthcare and societal costs3
High relapse rates and repeated treatment journeys4
– 40−50% of patients terminate treatment with buprenorphine in the first 6 months1
1. Kaur AK, et al. 2008, Journal of Managed Care Pharmacy; 2. Benyamina et al 2013 Heroin Addiction and Related Clinical Problems 14 (4): 65-80; 3. Public Health England https://www.gov.uk/government/publications/alcohol-and-drug-prevention-treatment-and-recovery-why-invest/alcohol-and-drug-prevention-treatment-and-recovery-why-invest; 4. Fischer G et al Heroin Addict Relat Clin Probl 2012; 14(4): 39-50
Buvidal®
Perceptions of patients, prescribers and payers
46
Patients recognize the advantages of Buvidal ®
and are willing to try
26%
22%24%
11%
17%
Yes definitely
Yes probably
Yes maybe but not now
No unlikely
Definitely not
Would you be willing to change your current treatment to this new treatment?1
1. Camurus data: Patient research program project 2017; 2. Camurus data of file : Patient qualitative research 2018
Weekly dosing seen as animportant stepping point2
47
Patients & users perceive quality of life benefits with Buvidal ®
• Makes life easier
• No need for daily medication pick up
• Reduce problem of stigma or privacyrelated to taking medication
• Right dose consistently
1. Gilman et al Patient Preference and Adherence, Vol. 12, 2018, p. 2123-2129
Potential benefits of a depot medication for patients & users not in treatment1:
11 6 3 20 11 17 31
3 6 6 9 6 31 40
11 11 6 20 20 31
6 3 11 9 14 57
NeutralDisagree strongly
Agree strongly
1 2 3 4 5 6 7
48
HCPs and payers understand the value of Buvidal®
HCP value drivers1,2
Improved outcomes of Buvidal® vs SoC• Improves treatment compliance• Reduces misuse and diversion• Reduces risk of paediatric exposure• Reduces social stigma & burden• Reduced burden on healthcare system
Payer value
drivers2
Clear differentiation of Buvidal® vs SoC• Clinical and societal drivers resonateValue drivers• Outcomes/reduced burden, M&D & overdose Price aligned with other CNS depots
“Even greater benefit (for Buvidal) can be implied in practice, given that many patients today receive suboptimal dosing of SoC”
− Payer, UK2
“HCPs highly value the quality of evidence and ability to prevent misuse/diversion when prescribing treatments”
- HCP research 20182
1. Market access dynamics in opioid addiction, Decision Resources 2015 2. Camurus data: Simon Kucher and Partners pricing research 2018 Buvidal TPP.
96%
n=52
49
High HCPs’ willingness to prescribe Buvidal® (EU5)1
Source: 1. Market access dynamics in opioid addiction, Decision Resources 2015.
HCPs’ willingness to prescribe CAM2038 Anticipated share of patients on CAM2038 q4w if available Anticipated share of patients on CAM2038 q1w if available
96%
n=50
39%q4w
22%q1w
94%
n=50
36%q4w
25%q1w
86%
n=50
43%q4w
27%q1w
France169,700patients
86%
n=51
31%q4w
30%q1w
Germany78,800 patients
UK138,400 patients
Italy62,800 patients
Spain59,200 patients
37%q4w
22%q1w
50
HCPs ascribe high % patient share to Buvidal® at peak
PEAK SHARE RELAPSING PATIENTS1 PEAK SHARE STABLE PATIENTS1
52%
40% 60%
37%UK
GERMANY
Source: 1. Camurus data on file: Simon Kucher and Partners pricing research 2018, n=60
Buvidal® Daily medication
Buvidal®
The addressable market
52
Estimated addressable market of ~740,000 patients in EU and Australia
1. EMCDDA 2018 Drug report 2. Camurus estimate 3. Benyamina et al 2013 Heroin Addiction and Related Clinical Problems 14 (4): 65-80. 4. Camurus data on file 2018 Patient qualitative study .
Patients on Bup1 Patients on low dose Methadone ≤30mg2
Patients recycling within a year1
Users out of treatment
due to rules & burden1,3,4
Total addressable
market
53
Market potential of long-acting injectables in opioid dependence in EU and Australia
740,0001
patients in addressable market in EU and Australia
20 – 30% suitable for depot
medication2,3,
Average length of treatment ~180 days
Price point comparable
to depot antipsychotic medications
Estimated market size
€200 - €300m for LAIs at peak
1.See previous slide; 2.Market access dynamics in opioid addiction, Decision Resources 2015; 3. Camurus data Simon Kucher and Partners pricing research 2018;
Buvidal®
Launch readiness in EU and Australia
55
Buvidal® – launch sequence EU/Australia/RoW
WAVE 1 WAVE 2 WAVE 3 WAVE 4
GermanyUK
AustraliaFinlandSwedenDenmarkNorway
ItalySpain
FranceIsrael
BeneluxPortugalGreeceCroatiaIrelandCzechAustriaPoland
RoW
310,000 patients:45% of totalEU/Aus
+299,000 patients89% of totalEU/Aus
+86,000 patients98% of totalEU/Aus
Market shaping
Wave 1 markets‒ Team recruited and accelerated onboarding
• 55 heads, 83% customer facing‒ Finalizing reimbursement‒ Launch activities‒ Supporting patients networks‒ Manage supplier network
Wave 2 markets‒ Key functions onboarded (10 heads)‒ Focus on pricing & reimbursement‒ Medical education ‒ Engagement of patient foundations
56
Launch readiness for Buvidal® in wave 1 markets, preparing wave 2
Wave 1 markets
Wave 3 market growthWave 2 markets
Wave 4 market expansion
Launch sequence
Country # patients in treatment1
Treatment model # target prescribers
Reimbursement Estimated launch
~100,0002 Specialized centers and primary healthcare system ~ 2000 No HTA
Clinical decision Q1 2019
138,000 Community health clinics and NHS providers ~ 3000 No HTA England
Local formulary approval Q1 2019
22,000 Specialized centers and primary healthcare system ~ 2000 Municipalities fund
HTA Norway Q2 Q1-Q2 2019
49,000 Specialized centers and primary healthcare system ~ 500 HTA decision Q2 Q2 2019
57
Wave 1 markets: patients concentrated to limited prescriber base & fast HTA/reimbursement approval
1. ECMDDA 2018 drug report 2. Internal data based on ECMDDA & adjusted to account for reporting methodology.
Country # patients in treatment1
Treatment model # target prescribers
Reimbursement Estimated launch
62,6862Servizi Tossicodipendenze
(Ser.T.) and private and non-profit organizations
~ 2000 9-12 months Q3-Q4 2019
59,264 Specialized centers ~ 2000 9-12 months Q3-Q4 2019
169,750 Specialized centers and GP practices ~ 4000 9-12 months Q1 2020
58
Wave 2 markets: Slower HTA/reimbursement approval process
1. ECMDDA 2018 drug report; 2 likely under reported as not all regions provide data 2. EFPIA Market Access delays Analysis 2018 www.efpia.eu
59
Launch readiness – wave 1 distribution chain
Import/export
licences
Delivery to wholesaler
Delivery to
Clinic/HCP
Manufacture
Delivery to hospital
or retail pharmacy
Clinic ability to
store schedule
drug
Clinic depot administration
capability
4 weeks 3–5 weeks ~24 hours
• Wave 1 countries launch ready‒ Subsidiaries established‒ Reimbursement in final stages‒ Recruitment of experience teams completed‒ Wide stakeholder engagement
• Manufacturing completed
• Infrastructure and pathways to ensure patient access well advanced
• 740,000 addressable patients
• Buvidal clearly addresses many of the limitations of daily treatments
• Patients, physician willing to try and prescribe
• Payers differentiate Buvidal from SoC
• Payers attribute value in line with other CNS depot products
Opportunity Readiness
60
Buvidal in EU and Australia: launch ready
Focus on accelerating growth trajectory of Buvidal®
© 2018 Braeburn. All rights reserved
U.S. – CAM2038Camurus Capital Markets and R&D DayDecember 11, 2018
Mike DerkaczPresident and CEO
62
Some of the statements in this presentation constitute forward-looking statements. Forward-looking statements relate to expectations, beliefs, projections, future plans and strategies, anticipated events or trends and similar expressions concerning matters that are not historical facts. The forward-looking statements contained in this presentation involve risks and uncertainties as well as statements as to:
• the accuracy of our estimates regarding expenses, future revenues, cash forecasts and capital requirements;• the expected timing of progress and reporting results from our clinical trials and expected timing of regulatory filings and approvals, including the timing for
submitting an NDA to the FDA for such product candidates;• our ability to successfully commercialize weekly and monthly CAM2038, if approved, for the treatment of opioid addiction, based on our sales and marketing plan;• our commercialization, marketing and manufacturing capabilities and strategy;• the willingness of healthcare providers to prescribe and patients to use our injectable medications;• the performance of our third-party contract manufacturers and contract research organizations;• the rate and degree of market acceptance of our products for any indication once approved• our intellectual property position; and• regulatory and political developments in the United States and foreign countries.
Certain information contained in this presentation should be considered "forward-looking statements" as defined by Section 21E of the Private Securities Litigation Reform Act of 1995. All statements in this presentation other than historical information may be deemed forward-looking statements. These statements present (without limitation) the expectations, beliefs, plans and objectives of management and future financial performance and assumptions underlying, or judgments concerning, the matters discussed in the statements. The words "believe," "estimate," "anticipate," "project" and "expect," and similar expressions, are intended to identify forward-looking statements. Forward-looking statements represent our management’s beliefs and assumptions only as of the date hereof and should not be relied upon as representing management’s views as of any subsequent date. Our actual future results may be materially different from what we expect. We explicitly disclaim any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
Forward-looking statements
63
Drug overdose: #1 cause of death for people under 50 years old1
National drug overdose deaths by opioid category(US 2002 to 2017)2
*Significant increasing trend from 1999 to 2016 with different rates of increase over time, p<0.05; **Significant increasing trend from 1999 to 2006, then decreasing from 2006 to 2016, p<0.05. ^Provisional counts for 2017 are based on data available through 12/17 but are not yet finalized. 1. Centers for Disease Control and Prevention. CDC Wonder, Accessed on February 19, 2018, https://wonder.cdc.gov/controller/datarequest/D76 2. National Center on Health Statistics, CDC WONDER, Accessed on December 8, 2018; https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates. 6. Frazier at al, 2017, Journal of the American Medical Association
Study of PA Medicaid enrollees indicate that there are 30 nonfatal overdoses for every 1 fatal overdose630:1
2015 & 2016 declines largely due to overdoses, and follow more than a decade of increases3U
S Li
feEx
pect
ancy
Any Opioid
Heroin
Synthetic Opioid, i.e. fentanyl, tramadol (non-Methadone)
Subutex Launch Suboxone Film Launch
0
5 000
10 000
15 000
20 000
25 000
30 000
35 000
40 000
45 000
50 000
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
U.S
. Ove
rdos
e D
eath
s
Natural & Semisynthetic Opioids, i.e. oxycodone, hydrocodone
Methadone
64
Opioid use disorder – addressable market
1. SAMHSA, Results from the 2017 National Survey on Drug Use and Health, Sep. 2018. 2. The Council of Economic Advisors, November 2017. The Underestimated Cost of the Opioid Crisis. Accessed on January 18, 2018, https://www.whitehouse.gov/sites/whitehouse.gov/files/images/The%20Underestimated%20Cost%20of%20the%20Opioid%20Crisis.pdf . 3. Derived from Symphony Health Solution Patient Tracker, 2016 4. Symphony Health Solutions, Integrated Audit, February 2018
$504 billion in annual economic
burden2
600,000 Rxs will be written today
in the US
11.4 M people misuse opioids1
SAMHSA 2018
2.4 M patientswith OUD1
1.5 MMAT patients4
1.1 M patientstreated with
Buprenorphine4
65
Buprenorphine: An essential treatment for opioid addiction
Total annual TRx volume1
1. SAMHSA, Results from the 2016 National Survey on Drug Use and Health, Sep. 2017.Source: Symphony Health, PHAST Prescription and Integrated WAC Dollars
3 434 4 881
6 143 7 288
8 739 9 849
10 790 11 612
12 445 13 741
0
5 000
10 000
15 000
2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
TRx
Volu
me
(000
s)
Vivitrol
GenericBuprenorphine
Buprenorphine /Naloxone
+10% 5-year CAGR
66
Oral OUD treatments are associated with non-adherence1
*The study examined commercial claims only, and did not evaluate the specific causes for discontinuation. 1. Shuckit, M, 2016, New England Journal of Medicine 2. Morgan et al, 2017, Journal of Substance Abuse and Treatment 3. Kaur AK, et al. 2008, Journal of Managed Care Pharmacy. 4. Coleman, C, 2012, NCBI-Journal of Managed Care Pharmacy 5. SAMSHA TIP 40. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Accessed on March 22, 2018, https://www.naabt.org/documents/TIP40.pdf
0%
20%
40%
60%
80%
100%
0 30 60 90 120 150 180
Percent remaining on MAT therapy
In 30 days or less,* 58% of patients have discontinued
sublingual buprenorphine2
Within 180 days, Approximately 72% of patients have
discontinued sublingual buprenorphine3
• Increased dosing frequency has been proven to negatively impact adherence4
Patients may need to take oral buprenorphine 1‒4x/day
• Physicians are spending a significant amount of time policing compliance by their patients rather than focusing on treating the disease and counseling during the patient visit
Inefficient clinical practice5
67
Oral buprenorphine – unintended consequences
1. SAMHSA TIP 63, Medications for Opioid Use Disorder. Accessed on February 22, 2018, https://store.samhsa.gov/shin/content//SMA18-5063FULLDOC/SMA18-5063FULLDOC.pdf 2. Smyth et al, 2010, Irish Medical Journal. 3. Tkacz et al, 2012, The American Journal of Addictions 4. Press Announcements - Statement from FDA Commissioner Scott Gottlieb, M.D., U S Food and Drug Administration Home Page. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm587315.htm. Accessed April 2, 2018
Diversion Abuse & misuse Safety issues
Street valueLow adherence
self-directed administration
Life-threatening pediatric
exposure1
Out of HCP control Potential for relapse2,3
Overdoseneeding emergency
treatment
The FDA is interested in new treatment options
The FDA is taking steps to facilitate the development of new medications for the treatment of opioid use disorder. As part of our effort to support the development of new formulations of existing MAT, the FDA intends to issue two guidance documents.4
— Scott Gottlieb, M.D.,FDA Commissioner
February 6, 2018
68
Healthcare payer strategies are evolving to address the opioid crisis
*List of participating payers in appendix1. White Paper, 2017, Health Fraud Prevention Partnership and the University of Chicago 2. Lee B, Forbes, Accessed on January 18, 2018, https://www.ahip.org/health-plans-launch-new-stop-initiative-to-help-battle-opioid-crisis-in-america/
16 major health insurance companies adoptthe National Principles of Care1 8 Principles of Care2
Universal screening for SUD across medical care settings
Access to FDA-approved Medications
Rapid access to appropriate SUD care
Engagement in continuing long-term outpatient care, with monitoring and adjustments to treatment
Concurrent, coordinated care for physical and mental illness
Access to accredited behavioral health professionals
Personalized diagnosis, assessment, & treatment planning
Access to non-medical recovery support services
1
2
3
4
5
6
7
8
CAM2038 weekly and monthlyIndividualized therapy from day 1 of recovery
...focused on becoming the leader in the treatment of opioid addiction.
70
CAM2038 – Flexible dosing to match treatment paradigm
Sources: Symphony Health Solutions, Patient Tracker, 2017, MAT Social Listening conducted by Fingerpaint 1Q2018, HCP Competitive Launch Pulse December 2017,Creative Concept Research Jan 2018
~40% of Oral Buprenorphine Rxsare 7 days or less
40%
26%
34% 7 day Rxmost common
8–27 day Rx
28 days+Rx
Initiation Stabilization Maintenance
CAM Weekly
CAM Monthly
Weekly CAM2038 Monthly CAM20388 mg –16 mg 64 mg24 mg 96 mg32 mg 128 mg
Key to a successful CAM2038 launch:Fast product access with a purpose-built specialty channel infrastructure
...focused on becoming the leader in the treatment of opioid addiction.
72
2018: Preparing for successful CAM2038 launch in U.S.
2 May 201820 April 201819 Jan 2018 July 2018 Q3 2018 26 Dec 2018 Q1 2019
Raised $110M
Led by Wellington,with Avista,
Deerfield, New Leaf, RA Capital & Rock Springs
Launched BRAVE Action
Presented data demonstrating
Conversion from SL to CAM2038
Pivotal Study Published in
JAMA
FDA acceptance of NDA for
CAM2038 with Priority Review
Refining Specialty Pharmacy
Network – Payer Discussions
CAM2038 PDUFA:
Dec. 26, 2018Expected Launch
73
Market Demand for Long-Acting Injectable in OUD
Market demand is confirmed and Braeburn is fast follower to Indivior
10,000 +Treatment Initiations
~2,000Physicians Prescribing
74
Speed to product
5 critical pillars for a successful OUD specialty launch
Team expertise
Product profile
Product access
Intelligent SP network
Streamlined payer
access
75
Rapid delivery – integrated & seamless – technology enabled
Broad, connected specialty
pharmacy network
Specialty distributor Providers Patients
Providers Patients
Minimize time
Buy-and-bill distribution: estimated 20%–30%
Specialty pharmacy distribution: estimated 70%–80%
Optionalhub
Easycustomer
experience
SimplifiedDigital
ConnectedTransparent
76
Geo-targeting: Hyper-focused on high OUD volume injection offices
*In late 2017, the White House Council of Economic Advisors quantified the estimated cost using the Value of a Statistical Life (VSL) formula. Includes $432 billion in fatality costs and $72 billion in non-fatality costs.31. Centers for Disease Control and Prevention: Drug Overdose Death Data, Accessed on February 14, 2018, https://www.cdc.gov/drugoverdose/data/statedeaths.html 2. Rudd RA. Centers for Disease Control and Prevention MMWR, December 30,2016. Accessed on April 2 13, 2018,3. The Council of Economic Advisors, November 2017. The Underestimated Cost of the Opioid Crisis. Accessed on January 18, 2018, https://www.whitehouse.gov/sites/whitehouse.gov/files/images/The%20Underestimated%20Cost%20of%20the%20Opioid%20Crisis.pdf
TX
OK
OR MN
IA
NY
PA
IN
CA
HI
CT
NJ
DE
AK
ME
VTNHMA
RI
MD
WVVA
NC
SC
TN
KY
OH
MI
WI
IL
MO
AR
LA
MS AL GA
FL
WA
ND
SD
NE
KS
NM
CO
WY
MT
ID
NVUT
AZ
13.6 to 16.011.1 to 13.56.9 to 11.0
16.1 to 18.518.6 to 21.021.1 to 52.0
(Deaths per 100,000)Office-based Opioid Treatment Centers
75%
Strategic Accounts25%
77
Braeburn management team: 50+ specialty launches
Mike DerkaczPresident & CEO
David McIntyreChief Financial Officer & EVP
Richard Malamut, M.D. Chief Medical Officer
Paul JohnsonChief Commercial Officer
Ted BuckleyHead of Government Affairs & Advocacy
Susan FranksSVP & Head of Regulatory Affairs
Apple Tree Partners: $1.5 billion dedicated to building life sciences companies
78
CAM2038 represents fundamentally different product offering – Flexible Weekly + Monthly dosing– PDUFA date of December 26, 2018
Payers under pressure due to extreme economic burden - $504 Billion– Significant interest and traction in pre-launch Market Access discussions
Strong govt / political pressure on payers to increase access to MAT– Aligned interests create favorable tailwinds
Rapidly worsening opioid addiction crisis– Oral non-compliance, abuse, and diversion drive costs and overdose
1 million+ patients; market growing at 10% CAGR – Market drivers focused on conversion from orals to injectables
Braeburn opportunity Urgent need for alternatives to address opioid addiction crisis
...focused on becoming the leader in the treatment of opioid addiction.
CAM2038 offers significant value to:
PATIENT
PAYER
PHYSICIAN
Thank you
Q&AFredrik Tiberg, President & CEO, Camurus
Richard Jameson, CCO, CamurusMike Derkacz, President and CEO, Braeburn
80
Long-acting SSAs for neuroendocrine tumors (NET) and acromegalyProf Diego Ferone MD, PhD
82
The multiple functions of somatostatin - inhibition of secretion, cell growth and proliferation
Digestive tract actions
EndocrineSecretions
Neuronal actionsImmuneactions
-GH-PRL-TSH
-Insulin-Glucagon
ThyroidOvaryAdrenal
Pituitary
Pancreas
GI secretionsBowel motilityGastric emptyingIntestinal absorption
NeurotransmitterNeuropeptideNeuromodulator
T-cellsB-cells
Monocytes-macrophages
SST, somatostatin; GI, gastrointestinal; GH, growth hormone; PRL, prolactin; TSH, thyreotropin secreting hormone
83
Somatostatin receptor subtypes:Functional characteristics
SSTR1 SSTR2 SSTR3 SSTR3 SSTR5
Source: Weckbecker et al. Nature Rev 2003
84
Somatostatin analogs
Ala Gly Cys Lys Asn Phe Phe
Cys Ser Thr Phe Thr
Trp
Lys
S
S
Cys
Cys
Phe
Thr
Phe
Thr
Trp
LysSS
Cys
Cys
Dβnal
Thr
Tyr
Val
DTrp
LysSS
sst2
sst5
octreotide
lanreotide
somatostatin
Tissue expression and binding affinities of SSAs to somatostatin receptors
85Bruns et al. Eur J Endocrinology. 2001;14(5);707-716SSA, somatostatin analogs; SSTR, somatostatin receptor subtypes; min, minutes
SSTR1 SSTR2 SSTR3 SSTR4 SSTR5 t1/2
Tissue expression
BrainLungStomach Jejunum KidneysLiverPancreas
BrainJejunumColonPancreas Liver and adrenals
BrainThyroidPancreas
BrainLungs
BrainHeartAdrenal glandThyroid glandPlacentaPituitarySmall intestinePancreas
Plasma half-life
somatostatin-14 0.9 0.2 0.6 1.5 0.3 2-3 min
octreotide 280 0.4 7.1 >1000 6.3 90 min
lanreotide 180 0.5 14 230 17 70 min
pasireotide 9.3 1.0 1.5 >100 0.2 12 hours
Binding affinity and IC50 : half maximal inhibitory concentration in nM (50% inhibition in vitro).
Somatostatin and its peptide analogues (SSAs) – the cornerstone of neuroendocrine disease treatment
• Universal endocrine ‘off-switch’ inhibiting growth and GI hormones and neuroendocrine cell proliferation‒ Can induce cell cycle arrests and induce apoptosis in NET cells
• Mediated by five somatostatin receptor proteins, SSTR1-SSTR5 ‒ Each with specific receptor functions and tissue expression
• SSTR2 over-expressed in neuroendocrine and pituitary tumors‒ Target for inhibition of GH and IGF-1 secretion by octreotide and
lanreotide
• Down-regulation of GPCR and mRNA synthesis can lead to SSA treatment resistance
Cell cycle inhibition
Pro-apoptotic effects
Angio-genesis inhibition
Mod. of immune system
Growth factor inhibition effects
Release inhibition of growth factors & tropic
hormones
SSAs
Bind to SSTRs of tumor cells
Inhibit of growth factors GH & IGF-1
Indirect anti-tumor effects
86
somatostatin-14octreotidelanreotidepasireotide
GI, gastrointestinal; NET, neuroendocrine tumors; SSTR, somatostatin receptor subtypes; GH, growth hormone; IGF-1, insulin-like growth factor 1;GPCR, G protein coupled receptors; SSA, somatostatin analogs; SoC, standard of care
Prevalence (7MM)1
‒ 60,610 cases in 2016‒ Expected to reach 65,337 in 2027‒ Orphan disease
Treatment options‒ Trans-sphenoidal surgery of micro- and
macro-adenomas‒ Medical therapy for over 50% of the patients
• SSA, octreotide and lanreotide, first-line SoC treatment for about 20 years
• Dopamine agonists• GH-receptor antagonists• Pasireotide
87
Acromegaly: symptoms and treatment
GH, growth hormone; IGF-1, insulin-like growth factor 1; SSA, somatostatin analogs; SoC, standard of care
Benign pituitary tumor causing excess GH secretion andconsequent IGF-1 increase
Pulmonary: • Sleep apnoea• Narcolepsy• Obstruction of upper airways
Endocrine and metabolic:• Diabetes mellitus• Impaired glucose tolerance,
lipids, minerals, electrolytes • Thyroid disorder• Hyperprolactinaemia• Hypopituitarism
Cardiovascular:• Hypertension• Left ventricular hypertrophy• Cardiomyopathy• Congestive heart failure• Dysrhythmias• Coronary atherosclerosis
Bone overgrowth and organ enlargement
Reproductive: • Decreased libido• Erectile dysfunction
“Osteoporosis”, joint pain
• Treatment objectives ‒ Normalize GH and IGF-1 levels‒ Control or reduce tumor size‒ Improve comorbidities
• Alternative to surgery in patients with controlled GH and IGF-I1
• Long-acting octreotide and lanreotideconstitutes gold standard treatment
• Potential for improved response rate by optimizing plasma exposure
SSA treatment in acromegaly Pituitary tumor volume and serum GH levels1
88
Tumor volume shrinkage and growth hormone reduction in acromegaly
0
20
40
60
80
100
0 12 24 36 48 60
Perc
enta
ge o
f ini
tial v
alue
s
Time (days)
Total pituitary volumeSerum GH levels
The effects of octreotide total pituitary volume and serum GH levels during treatment of 18 patients with acromegaly, expressed aspercentages of the pre-treatment values (mean 6 SEM). Redrawn from 1Lundin P et al, AJNR Am J Neuroradiol 1997:18:765–772
GH, growth hormone; IGF-1, insulin-like growth factor 1; SSA, somatostatin analogs
At Week 24, median IGF-1 and GH levels were improved in patients treated with high-dose and high-frequency octreotide LAR:• Significant reduction in IGF-1 and GH-levels
with increased dose to octreotide LAR 60 mg/month
• Trend of improved efficacy with increased frequency
• Effects related to increased octreotideplasma exposure
89
High-dose octreotide LAR significantly reduced GH and IGF-1 levels
*P<0.05 vs baseline
High dose (60 mg q4w)High frequency (30 mg q3w)
* *
Baseline Week 12 Week 24
200
250
300
350
400
450
500
Med
ian
IGF-
1 (μ
g/L)
2
3
4
5
6
7
Med
ian
GH
(μg/
L)
IGF-1 GH
LAR, long-acting release; GH, growth hormone; IGF-1, insulin-like growth factor 1; SSA, somatostatin analogs
Prevalence (7MM)1
‒ The total prevalent population of NETs was found to be 442,100 in the year 2016.
‒ Incidence growth due to improved awareness and diagnosis
Treatment options‒ Depends on patient segmentation‒ SSAs are the preferred 1st line therapy for well-
differentiated patients (G1 and G2) and for both symptom management and tumor size control
‒ SSAs can be used in combination with targeted treatment
90
Neuroendocrine tumors: symptoms and treatment
Anatomical distribution of NETs1
Foregut
Midgut
Hindgut
Lung (20-25%)
Pancreas (17-20%)
Small intestine (55%)Rectum/colon (<5%)
= Primary (% occurrence)
Source: 1. M. Sue O’Dorisio, MD, PhD; SPORE in Neuroendocrine Tumors, University of Iowa; 2. Neuroendocrine Tumors (NETs) - Market Insights, Epidemiology and Market Forecast, Research and Markets, Nov 2018.NETs, neuroendocrine tumors; SSAs, somatostatin analogs
Placebo: 32 patients/28 eventsMedian TTP, 6.14 months
Long-acting octreotide: 32 patients/14 eventsMedian TTP, 28.78 months
Prop
ortio
n W
ithou
t Pro
gres
sion
1.00
0.75
0.50
0.25
0908478726660544842363024181260
Time (months)
HR: 0.21 (95% CI: 0.10-0.44) P<0.0001
PROMID1
Patient characteristicsDisease status Treatment-naïve
Ki-67 (or grade) Ki-67 ≤2%: 95%
Primary endpoint results
TTPoctreotide 14.3
placebo 6.0
HR for TTP 0.32 (95% CI, 0.19-0.55)P = 0.000015
Octreotide LAR vs placebo Patients with hepatic tumor load ≤10%2
91
Octreotide controls tumor growth in patients with metastatic NETs
Source: 1. Rinke A, et al. J Clin Oncol. 2009;27:4656-4663. 2. Arnold R et al. Presented at: ASCO 2009 Annual Meeting; May 29-June 2, 2009; Orlando, FL. Abstract 4508.NETs, neuroendocrine tumors; LAR, long-acting release; TTP, time to progression; HR; Hazard ratio; CI, coefficient interval
No QoL reduction seen with SSAs vs placebo in PROMID1
CLARINETPatient characteristicsDisease status SD in 96% at baseline
Ki-67 (or grade) Ki-67 ≤2%: 69%Ki-67 3-10%: 30%
Primary endpoint results
TTPlanreotide Not reached
placebo 18.0
HR for TTP 0.47 (95% CI, 0.30-0.73)P = 0.001
Lanreotide vs placebo Patients with hepatic tumor volume ≤25%
92
Are there any patients for whom you would choose a ‘watch and wait’ approach?
Time (months)0 3 6 9 12 18 24 27
010
2030
40
5060
70
80
90100
Patie
nts
aliv
e an
d w
ithou
t pr
ogre
ssio
n, (%
)No QoL reduction seen with SSAs vs placebo in CLARINET
Lanreotide: 14 events/62 patientsMedian PFS, not reached
Placebo: 41 events/75 patientsMedian PFS, 21.1 months (95% CI, 17.6-24.4)
Source: Caplin M. et New Engl J Med.2014; 371:224-233.NETs, neuroendocrine tumors; LAR, long-acting release; TTP, time to progression; HR; Hazard ratio; CI, coefficient interval; PFS, progression free survival
HR, 0.34 (95% CI, 0.18-0.62)
• Standard 30 mg dose and increased dosing frequency, every third week vs every fourth week• Phase 2 results in patients with progressive disease
Phase 2 data suggests that high octreotide exposure can give improved efficacy
Can tumor control in NET be optimized by enhanced exposure?
93
Time to tumor progressionP < 0.0001
Source: 1. Open-label, single-treatment arm (q21d); prospective study that compared patient response to their retrospective response to q28d octreotide. Ferolla P et al. JEI 2012NET, neuroendocrine tumors; SSA, somatostatin analog; PD, progressive disease; q21/28d, every 21/28 days.
Long-acting octreotide 30 mg q21d
Long-acting octreotide 30 mg q28d
Time (months)
1.0
0 10 20 30 40 50
Prop
ortio
n of
pat
ient
s
0.2
0.0
0.8
0.4
0.6
Median 30 months
Median 9 months
94
There is a high need for improved SSA therapies
??
Source: 1. Colao AM et al, Pituitary 2016; 19: 235–247. 2. Ferolla P et al. J. Endocrine Inv. 2012, 3. Riechelmann RP et al, Ther Adv Med Oncol. 2017 Feb; 9(2): 127–137SSAs, somatostatin analogs; CS, carcinoid syndrome; PFS: progression-free survival.
Dosing Acromegaly NET NET, Carcinoid Syndrome Activity
Biochemical control with
modest response~20-60%1
Symptom control in 50% pts. – CS often refractory3
SSAs are safe and effective, but dose and exposure may
be suboptimal
IM or deep SC dosing with large
bore needlesNo options for
self-administration
Tumor control and PFS – potential for
improved response2
Significant potential for improvement of first generation long-acting octreotide and lanreotide treatments
• Sandostatin® LAR® has very low bioavailability
• Increased evidence that higher plasma somatostatin analog levels can improve efficacy ‒ Only about half of acromegaly patients are
controlled (IGF-1 and GH) • 57% and 67% for octreotide LAR • 47% and 48% for lanreotide depot
‒ Significant room for improvement of symptom and tumor control in patients with GI- NET
• A majority of patients on pasireotide experience increased glucose levels within the first 2-3 weeks of treatment
• Complex reconstitution – prone to handling errors and needle clogging (octreotide and pasireotide)
• Intramuscular or deep subcutaneous injections with large needles (octreotide, lanreotide, pasireotide)
• Inconvenient dosing with need for frequent physician office visits
• No self-administration option for patients
Current drug administration Current clinical efficacy and safety
95
CAM2029 aims to address unmet needs of current long-acting SSA treatments
GI, gastrointestinal; NET, neuroendocrine tumors; GH, growth hormone; IGF-1, insulin-like growth factor 1; LAR, long-acting release
96
CAM2029 combines superior ease of administration with potential for improved efficacy
Note: 1) Illustrative. Final product configuration may be different.
NO RECONSTITUTIONCAM20291
10, 20 mg/0.5-1.0 mLready-to-use
FluidCrystal® technology SMALL VOLUME
THIN NEEDLE
≥22G
20G
18G/19G
Subcutaneous(12.5mm)
Intramuscular(40mm)
Deep subcutaneous(20mm)
Sandostatin® LAR® Octreotide10, 20, 30 mg/2.5 mL
reconstitution/30-60 min reconditioningPLGA microsphere system
Somatuline® Autogel® Lanreotide60, 90, 120 mg/0.2-0.5 mLready-to-use/refrigerated≥ 30 min reconditioning
Self-associated gel
Octreotide plasma concentrations IGF-1 concentrations
97
CAM2029 provides enhanced octreotide exposure and a rapid and sustained IGF-1 suppression in healthy subjects
Source: Tiberg F, Br J Clin Pharmacol. 2015 Sep;80(3):460-72. OCT, octreotide; IGF-1, insulin-like growth factor 1
0,01
0,1
1
10
100
0 14 28 42 56 70 84 98
Plas
ma
OCT
con
c (n
g/m
L)
Time (days)
CAM2029 30mg q4wOCT LAR 30mg q4w
0
100
200
300
0 14 28 42 56 70 84 98
IGF-
1 co
nc (n
g/m
L)
Time (days)
CAM2029-BR 30mg q4wOCT LAR 30mg q4w
0
50
100
150
200
250
Day -28 - Day 0 Day 0 - Day 28 Day 28 - Day 56 Day 56 - Day 84
Tim
e w
eigh
ted
aver
age
(% o
f ULN
)
Patient 1 Patient 2 Patient 3Patient 4 Patient 5
IGF-1 & GH: acromegaly patients, n=5 Flushing and diarrhea: NET patient, n=5
98
Pilot study indicates improved biochemical and symptom control when switching from octreotide LAR to CAM2029
Analysis of data from Pavel M et al, Cancer Chemotherapy and Pharmacology, 2018 in press.GH, growth hormone; IGF-1, insulin-like growth factor 1; LAR, long-acting release; NET, neuorendocrine tumors
0
0,5
1
1,5
2
Day -28 - Day 0 Day 0- Day 28 Day 28 - Day 56 Day 56 - Day 84
Mon
thly
mea
nnu
mbe
rsym
ptom
s/da
y
Bowel movementsFlushings
Oct-LAR CAM2029 Oct-LAR CAM2029
• Dose proportional long-acting octreotide release suitable for once monthly dosing1
• Rapid and sustained suppression of insulin growth factor-1 (IGF-1) in healthy volunteers1
• Well maintained or improved biochemical control indicated in patients with acromegaly2
• Well maintained or improved symptom control indicated in NET patients2
• Good safety profile and local tolerability1-2
99
CAM2029 is supported by data from four clinical studies
Completed clinical trials Three Phase 1 studies assessing pharmacokinetics (PK), pharmacodynamics (PD)
and safety in healthy volunteers (N=249) One Phase 2 study evaluating PK, disease biomarkers and symptoms in acromegaly
and NET patients (N=12)
Source: 1. Tiberg F, Br J Clin Pharmacol. 2015 Sep;80(3):460-72; 2. Ferone D. Poster Presentation ENDO 2017, Pavel.
100
Plans for continued development of CAM2029
Four clinical trials completed in healthy subjects and patients characterizing PK, PD and safety profile (N=249)
Phase 1, SAD
Phase 1, MAD
Phase 1, MAD
Phase 2, MAD Placebo controlled (PC) Phase 3
study in SSA responders (N~80). Open label, long-term safety
extension in full/partial responders
ACRO Phase 3 LTSE
ACRO Phase 3 PC
H2 2019 2021
Active controlled (AC) Phase 3 study in patients with metastatic, well or moderately differentiated NET.
NET Phase 3 AC + LTSE
CAM2043 (treprostinilFluidCrystal® injection depot)
Strategy for Development in Pulmonary Arterial Hypertension and Raynaud Phenomenon
James Seibold, MDPrincipal, Scleroderma Research Consultants LLC
101
Treprostinil
• Chemically stable tricyclic analog of prostacyclin• Potent direct vasodilator• Inhibits platelet activation• Inhibits neutrophil adherence• Antiproliferative including synergistic actions with PPAR-γ• Licensed for WHO Group 1 PAH as:
‒ Remodulin® (parenteral (IV, SQ))‒ Tyvaso® (inhaled)‒ Orenitram® (oral)
102
Pulmonary arterial hypertension is a rare and severe condition characterized by vascular proliferation and remodeling of the small pulmonary arteries
103
PAH: a progressive and life-threatening disease
Source: 1. World Symposium on Pulmonary Hypertension; 2. Adapted from: Hill NS. Pulmonary Hypertension Therapy. Summit Communications, LLC; 2006:9.
Right ventricle Left ventricle
Pulmonary arteries
Enlarged right ventricle
Constricted pulmonary arteries
5th WSPH1 consensus definitions
Pulmonary hypertension
Mean pulmonary artery pressure (mPAP) ≥25 mm Hg
Pulmonary arterial hypertension
Mean pulmonary artery pressure (mPAP) ≥25 mm Hg
Mean pulmonary artery occlusion pressure (PAOP) ≤15 mm Hg
Pulmonary vascular resistance (PVR) >3 Wood units
Normal heart
PAH heart
104
5th WSPH Classification Scheme
Source: Adapted from: Condliffe R, et al. F1000Prime Rep. 2015;7:06 .
3. PH-lung disease/hypoxia– COPD– Interstitial lung disease– Sleep disorder– Alveolar hypoventilation
2. PH-left heart– Systolic dysfunction– Diastolic dysfunction– Valvular disease
1. Pulmonary arterial hypertension– Idiopathic/heritable– Drugs/toxins– Connective tissue disease– HIV– Portal hypertension– Congenital heart disease– Schistosomiasis
1’– Pulmonary veno-occlusive disease– Pulmonary capillary
haemagiomatosis
4. Chronic thromboembolic pulmonary hypertension
– Operable– Inoperable
105
Schematic progression of PAH
Source: Adapted from: Hill NS. Pulmonary Hypertension Therapy. Summit Communications, LLC; 2006:9.
PRESYMPTOMATIC/ COMPENSATED
Cardiac output
SYMPTOMATIC/ DECOMPENSATING
DECLINING/ DECOMPENSATED
Usual time of diagnosis
Right heart dysfunction time
106
Five classes of PAH drugs – targeting the involvement of the endothelin, nitric oxide and prostacyclin (PGI2) pathways1
Drug Class Drug Name Brand Name Company Launch US Launch EU
Endothelinreceptor antagonists
bosentan Tracleer J&J (Actelion) 2001 2002
ambrisentan Volibris GSK/Gilead 2007 2008
macitentan Opsumit United Therapeutics 2013 2013
PDE5 inhibitors sildenafil Revatio Pfizer 2005 2005
tadalafil Adcirca Eli Lilly 2008 2009
GuanylateCyclaseStimulators
riociguat Adempas Bayer 2013 2014
Prostacyclinderivatives
epoprostenol Flolan GSK 1995 1980
epoprostenol Veletri J&J (Actelion) 2008 2013
iloprost Ventavis J&J (Actelion) 2004 2003
treprostinil Remodulin United Therapeutics 2002 2004
Tyvaso United Therapeutics 2009 N/A
Orenitram United Therapeutics 2013 N/A
Prostacyclin IP Receptor Agonists
selexipag Uptravi J&J (Actelion) 2016 2016
1. Irene M. Lang and Sean P Gaine, Eur Respir Rev 2015;24:630-641.
107
Evolution of recommendations for initial treatment of PAH
1. Galie N, et al. J Am Coll Cardiol. 2013;62:D60-72. 2. Taichman DB, et al. Chest. 2014;146:449-475. 3. Galie N, et al. Eur Respir J. 2015;46:903-975.
Year, Source WHO FC II WHO FC III WHO FC IV
2013: 5th WSPH1 Oral therapy Any approved PAH drug
Epoprostenol is recommended. Initial combination therapy may be considered in case of nonavailability of IV prostanoids.
2014: CHEST2 Oral monotherapy
Oral monotherapy in patients without markers of poor prognosis.Parenteral prostacyclin
or Inhaled prostacyclin with ERA in patients with markers of poor prognosis.
Parenteral prostacyclin or
Inhaled prostacyclin with ERA
2015: ESC/ERS3 Oral monotherapy or combination therapy Combination including IV prostacyclin
Limitations with current treatments
108
IV and SC infusion pumps• Complex programming and error prone filling • Infusion system complications (in 28% of
patients in controlled clinical studies1) • Infusion site pain in 85% of patients, 32%
needing opioid painkillers2
• Non-aseptic technique can cause blood stream infection and sepsis which may lead to death
• Patient inconvenience:‒ Not water resistant ‒ Back-up pump needed 24 hours a day
Inhaled and oral • Not recommended for patients
with severe PAH (WHO FC IV)• Complex dosing schedules with
inhalation 4 x 3 minutes a day• Sub-efficacious plasma drug
levels during night• Patient inconvenience: daily
cleaning of nebulizer
Prostacyclin drugs are potent but have several limitations
Source: Adapted from ”Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension” Eur Respir Rev 2015; 24: 630–641.
109
CAM2043 designed as convenient once-weekly subcutaneous treprostinil treatment
Key features• Predictable long-acting delivery of treprostinil over at least 7 days
• FluidCrystal® injection depot technology
• Ready-to-use formulation in prefilled syringe
• Once-weekly subcutaneous dosing
• No need for complex extracorporal pump systems
• No risk of infusion site related infections and sepsis
Key results from completed clinical Phase 1 study Dose proportional, long-acting release of treprostinil Steady state accumulation factor ~2 Acceptable safety profile with no unexpected or serious adverse events
Single dose pharmacokinetic profiles1 Repeat dose pharmacokinetic profiles1
110
CAM2043: dose dependent and long-acting pharmacokinetics – Phase 1 SAD/MAD study
0,01
0,1
1
10
0 1 2 3 4 5 6 7
Trep
rost
inil
plas
ma
conc
entra
tion
(ng/
mL)
Time (days)
1 mg2.5 mg5 mg10 mg
0,0100
0,1000
1,0000
10,0000
0 1 2 3 4 5 6 7
Trep
rost
inil
plas
ma
conc
entra
tion
(ng/
mL)
Time (days)
First dose
Third dose
Source: 1. Camurus data on file 2018. Maximum dose exposure limited by healthy volunteer study population. Plasma concentration accumulation to steady state =2.
111
Safety observations in Phase 1 study
• 57 out of 60 enrolled subjects completed the study • Acceptable safety profile with no serious or unexpected adverse
events reported• All adverse events were resolved during the study, including
injection site reactions (eg pain, swelling and erythema) • No severe injection site reactions reported• No clinically relevant changes in vital signs, ECG or pulse oximetry
or labs observed
112
CAM2043: target PAH population
Oral therapy Oral or inhaled therapy
Parenteral therapy
WHO FC II WHO FC III WHO FC IV
CAM2043
Disease severity
• PAH patients (class II-III) switched from oral or inhaled prostacyclin agonist therapy
• Assessing efficacy, pharmacokinetics, safety and tolerability
• Endpoints include exercise capacity, treatment satisfaction and PAH symptoms
• Study to be performed under US IND
A 12-week, open label, flexible dose Phase 2 study of weekly CAM2043 in patients with PAH
113
Planned Phase 2 study of CAM2043 in PAH
Potential benefits of CAM2043 in PAH
1. CAM2043 may be introduced earlier in treatment with the potential for improved outcomes1
2. More steady plasma profiles may improve efficacy versus oral and inhaled prostacyclin products
3. Improved convenience for patients with no need for infusion pumps, thus eliminating risks of catheter-related complications and pump user errors
4. No risk of infusion related blood stream infections
5. Enhanced quality of life by not having to worry about pumps and catheters during every day activities like exercising, taking a bath or sleeping
6. Eliminating burdens of pump system management
Source: 1. Bartolome S et al, American Journal of Respiratory and Critical Care Medicine 2018;197:A7587.
IMPROVED
SURVIVAL RATES FOR PATIENTS
INITIATING PROSTACYCLIN SC OR IV THERAPY EARLY
< 1 YEAR VS > 1 YEAR
HR 2.35, P>0.011
CAM2043Potential additional indication in systemic sclerosis (scleroderma)
A generalized disorder of connective tissue characterized by:‒ Fibrosis of skin and internal organs‒ Characteristic immunologic features‒ Arteriolar fibrosis
There is significant overlap between PAH and scleroderma‒ 15% percent of scleroderma patients develop pulmonary arterial
hypertension (PAH) which is fatal1, 2
‒ 96% of scleroderma patients develop Raynaud’s phenomenon and 30% go on to develop digital ulcers
‒ Incidence 24 per million per year (NA, EU)‒ Prevalence 300 per million‒ Approximately 100,000 cases in the EU and NA2
116
Systemic sclerosis (scleroderma)
Source: 1. Muangchang et al 2013, 2. Global Data 2014, 2017.
4211
4948
5756
7836
8478
1160
2
8829
8
4871
5164
6191
8028
9129
1212
4
9599
2
0
50 000
100 000
150 00020142024
Diagnosed prevalent cases of scleroderma2
117
Digital vascular injury in scleroderma
0
250
500
750
1000
1250
1500
1750
2000
2250
0 1 2 3 4 5 6 7 8 9 10 11 12
Plas
ma
trepr
ostin
il co
nc. (
pg/m
L)
Time (h)
2 mg BID
4 mg BID
Mean concentration vs time profiles (2 mg and 4 mg) Perfusion before and 12 hrs after dosing - 4 mg
118
DISTOL-1:Trial of oral treprostinil in scleroderma patients
Remodulin 10 ng/kg/min
• Preliminary data show an increased perfusion after treprostinil dosing
Source: 1. Shah et al. Arthritis Research & Therapy 2013, 16:R54
Primary Endpoint: Net ulcer burden mean change
119
-1
-0,5
0
0,5
1
We ek 5 We ek 1 0 We ek 1 5 We ek 2 0
Mea
n ch
ange
from
ba
selin
e in
net
ulc
er b
urde
n Active (n=71) Placebo (n=76)
DISTOL-1:Treprostinil reduced net ulcer burdens
Week 5 Week 10 Week 15 Week 20
Secondary endpointsN= active 71/
placebo 76Change from baseline at week 20
P value
(N= Active 71/ placebo 76)
Patient Global Digital Ulcer VAS 0.12
Patient Digital Ulcer Pain VAS 0.31
Physician Global Digital Ulcer VAS
0.04
Patient Impression of ChangeDigital UlcersRaynaud’s PhenomenonOverall
0.210.000040.019
Cochin Hand Function Scale 0.47
Source: 1. Seibold et al. J Scleroderma Rel Dis 2017; 2: 42-49
p=0.63 p=0.43 p=0.05 p=0.20
120
Conceptual map of scleroderma-Raynaud's phenomenon
Source: 1. Pauling et al. Arthritis Care & Research 2018 Sep;70(9):1373-1384
TRIGGERS & EXACERBATING FACTORSIMPA
CT
ON
DAI
LY L
IFE
ADAP
TATI
ON
OVE
R T
IME
Raynaud’s attacks
Pain
Numbness
Hypersensitivity
Difficulty using hands
Digital colour changes
Feeling cold
DurationFrequency
PHYSICAL SYMPTOMS
EMOTIONAL IMPACT
• Explore dose-response (PK/PD) in small number of patients with Reynaud’s phenomenon
• Goal – affirm efficacy by thermography
• No drugs approved for the treatment of secondary Raynaud’s
• Bosentan has an approval in the EU for the prevention of digital ulcers
• An oral formulation of treprostinil was studied in a large randomized trial – with the intent to show effect on digital ulcers…DISTOL-1
Large unmet medical need Study of CAM2043 under way
121
CAM2043 is a promising candidate for the treatment of Raynaud’s phenomenon (RP) secondary to scleroderma
Conclusions
• Treprostinil is established mechanistically and well-suited to disorders associated with endothelial injury and structural vasculopathy
• Treprostinil has proven efficacy in PAH and scleroderma-Raynaud's phenomenon
• PAH and scleroderma-Raynaud's phenomenon are classified as orphan diseases and eligible for 505(b)(2) development pathway
• Usefulness is limited by cumbersome and expensive delivery systems and by adverse effects, which in turn are related to suboptimal pharmacokinetics
• CAM2043 offers both convenience and a favorable pharmacokinetic profile
122
Next steps and concluding remarks
Fredrik Tiberg, President & CEO, Head R&D
123
124
Selection of expected milestone events to 2021
2019 2020
Com
mer
cial
R&D
H1 H2 H1 H2
Start CAM2029 Phase 3 ACRO studyStart CAM2043 Phase 2
Start CAM2029 Phase 3 NET studyStart CAM2043 Phase 2 in PAH
MAA submissions for CAM2038 chronic painUNLOC-T study completed
MAA approval decision for CAM2038 in EU
H1 H2 H1 H2
2021
Buvidal launches in EU and AustraliaUS launch of CAM2038
Buvidal 2nd wave launches in EU
Buvidal 3rd wave launches in EU and Israel
Buvidal geographic expansion
CAM2038 launch in chronic pain
Continued strong pipeline progressNew technology licensesCommercial infrastructure built out in EU and Australia
Out-licensing of own clinical product candidateIn licensing of complementing commercial asset
Sustained profitabilityThree commercial stage assets
Cor
pora
te
MAA approval for CAM2038 in EU/AUSPhase 3 results CAM2029 ACRO
125
Commitmentto developing best-in-class
therapeutics for severe and chronic diseases
Advance our pipeline
using our leading development expertise and FluidCrystal® technologies
Partnerships and own commercialization to
maximize the value
of our products & technologies
Continue
building our entrepreneurial, scientific and inclusive
cultureto improve patients’ lives
Camurus positioned for continued value creation
126
• Leading FluidCrystal® technology platform used in in-house and in partnership programs and registered products
• Broad and de-risked clinical pipeline targeting unmet needs in multibillion dollar specialty markets
• Multiple levers for value creation including product approvals, partnerships and own commercialization
• Buvidal®/CAM2038 launches in Europe and Australia, and the US (Braeburn)• Potential for significant near-term milestones, royalty and sales revenues• 10 year track record of successful product, business and corporate development
Q&AFredrik Tiberg President & CEO, Camurus
Prof. Diego Ferone MD, University of GenuaJames Seibold MD, Scleroderma Consultants
127
128
Key financialsSandberg
Development AB
53,2%
Gladiator4,8%
Fredrik Tiberg3,9%
Swedbank Robur Fonder3,0%
Catella Fondforvaltning
2,6%
Fjärde AP-fonden2,3%
Others30,1%
Key Shareholders (30 November 2018)
Listed on Nasdaq STO (ticker CAMX)Market Cap: SEK ~4 billionCash position: SEK 216 million (Q3 2018)Employees: 94HQ: Lund, SwedenRegional offices: Cambridge, Mannheim, Paris, Sydney
MSEK Q3 2018
Q3 2017
Q1-Q3 2018
Q1-Q3 2017 FY 2017
Net Sales 19.6 12.5 41.5 48.8 54.3
Operating result -56.4 -67.1 -184.0 -177.4 -243.5
Result after tax -43.8 -52.3 -147.5 -138.4 -190.6
Earnings per share SEK before and after dilution
-1.14 -1.40 -3.92 -3.71 -5.11
Cash position 216.3 369.7 216.3 369.7 314.5
