Camurus Capital Markets and R&D Day 2016Camurus Capital Markets and R&D Day 2016 Camurus Advancing...

Camurus Capital Markets and R&D Day 2016

Camurus

Advancing late stage pipeline

with high market potential

Presentation, 14 December, 2016

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

2Camurus Capital Markets and R&D Day, December 14, 2016

Camurus’ Capital Markets and R&D Day agenda

Time Topic Presenter

13:00 – 13:30 Registration and coffee

13:30 – 14:45 Welcome and introduction Fredrik Tiberg, CEO and Head R&D

Rein Piir, VP IR

The FluidCrystal® technology Markus Johnsson, VP Pharm. Dev.

Weekly and monthly buprenorphine depots

(CAM2038): Overview and clinical development

update

Peter Hjelmström, Senior Director Medical Affairs

Fredrik Tiberg, CEO and Head R&D

Clinician’s view on long-acting depots for opiod use

disorder – a potential new treatment paradigm

Edward Nunes, MD, Professor of Psychiatry

Columbia University Medical Center

14:45 – 15:00 Q&A Lars Frick, Moderator

15:00 – 15:20 Refreshments

15:20 – 16:45 CAM2038: US market perspectives Behshad Sheldon, CEO Braeburn Pharmaceuticals

CAM2038: EU market perspectives and

commercialisation

Richard Jameson, CCO

Advancing the pipeline: Late and early stage projects

update

Fredrik Tiberg, CEO and Head R&D

Markus Johnsson, VP Pharm. Dev.

16:45 – 17:00 Conclusions and Q&A Lars Frick, Moderator


Camurus in brief

• Innovation that delivers

− Award-winning FluidCrystal® technology

− Late-stage, diversified pipeline

− Strong, strategic partners

• Patient centric product development

− Long-acting medications for better treatment

outcomes and quality of life for patients

− Focus on attractive, underserved specialty

markets

• Entrepreneurial company culture

− Strong, experienced management team

− 63 employees with 45 in R&D

− Agile, passionate, collaborative and

result focused

4

LISTED ON

NASDAQ

STOCKHOLM3rd DEC, 2015

MARKET CAP

~450million USD

CASH POSITION

60million USD

END Q3 2016

Camurus Capital Markets and R&D Day, December 14, 2016

Building value throughout the medical product life-cycle

5

Time and cost-effective development of innovative and differentiated medications

− combining clinically documented APIs with leading and proven technologies

Value

created

Value

Spent

Time

Decreased time to market505(b)(2), hybrid regulatory pathway

0

Value

created

Value

Spent

Time

Deeper market penetrationBest-in-class treatment potential

0

Value

create

d

Value

Spent

Time

Expanding end of cycle salesLong-acting barriers to generics

0


6

Late-stage, diversified pipeline with block-buster potential

PARTNERS PRODUCT PRECLINICAL PHASE 1/2 PHASE 3 REGISTRATION

CAM2038 Weekly Opioid dependence

CAM2038 Monthly Opioid dependence

CAM2038 Weekly Chronic pain

CAM2038 Monhly Chronic pain

CAM2029 Neuroendocrine tumours

CAM2029 Acromegaly

CAM2032 Prostate cancer

CAM4071 Not disclosed

CAM2047 CINV*

CAM2048 Pain

CAM2058 Pain, nausea and vomiting


*CINV Chemotherapy nausea and vomiting

7

Pipeline expansion with new attractive preclinical candidates

PARTNERS PRODUCT PRECLIN PH 1/2 PH 3 REG

CAM4072 Genetic obesity

CAM2043 PAH*

CAM2046 Diabetes

STATUS

Rhythm preparing to enter clinical

development in 2017

GLP tox ongoing. Initiation of

clinical development H1 2017

Formulation development

Several early stage collaborations

with pharma partnersFormulation development


*PAH: Pulmonary arterial hypertension

PRODUCT EVENT TIME

CAM2038 Opioid dependence • Positive top-line pivotal Phase 3 efficacy trial

• Completed enrollment in Phase 3 long-term safety trial

• Positive results from Phase 2 opioid challenge trial

November

April

May

CAM2038 Chronic pain • First patient enrolled in Phase 3 efficacy trial

• Completed enrollment in pivotal Phase 2 chronic pain trial

September

April

CAM2029 Acromegaly & NET* • Positive results from Phase 2 trial in acromegaly and NET July

CAM2032 Prostate cancer • Positive results from Phase 2 trial in prostate cancer June

CAM4071 Not disclosed indication • Phase 1 clinical trial completed June

CAM2047 CINV**

CAM2048 Pain

CAM2058 Pain & nausea and vomiting

• Initiation of clinical Phase I trial October

8

Clinical pipeline highlights in 2016

*NET: Neuroendocrine tumours

**CINV: Chemotherapy induced nausea and vomiting


9

Year highlight. Positive topline Phase 3 results



FluidCrystal® technology

10

Markus Johnsson, PhD, VP Pharm. Dev.

FluidCrystal® technology

The FluidCrystal® technology is based on

functional liquid crystal nanostructures

FluidCrystal® injection depot

FluidCrystal® topical bioadhesive

FluidCrystal® nanoparticles

water PC

GDO

H2

La

I2

L2


12

FluidCrystal® injection depot: How it works

In situ gelling principles


FluidCrystal® injection depot: How it works


FluidCrystal® injection depot: Tuning of release rates

14

In vitro release (37°C) of model drug substance


Convenience

Treatment

adherence

Efficacy

FluidCrystal® injection depot: Focus on the patient

0

1

10

100

0 7 14 21 28

Pla

sm

a B

PN

concentr

ation (

ng/m

L)

Time (days)

Conc (q1w 16 mg obs) Conc (q1w 16 mg pred) Conc (q4w 64 mg obs) Conc (q4w 64 mg obs SD)

Conc (q4w 64 mg pred SS) Conc (SL BPN 8 mg obs) Conc (SL BPN 8 mg pred)

Note: obs = observed, pred = predicted, SD = single dose, SS = steady state, SL = sublingual



• Scope

‒ Broadly applicable across molecular classes; small

molecules, peptides and proteins

16

Buprenorphine MW 468 g/mol

Octreotide MW 1019 g/mol

Glucagon-like Peptide 1 MW 3356 g/mol

Broadlyapplicable



17

• Safety

‒ Natural (endogenous) lipid components

‒ Biocompatible solvents

‒ Biodegradable liquid crystal matrix

‒ ~1500 subjects have received >10,000 injections in

clinical trials

Phosphatidylcholine (abundant cell membrane lipid)

Glycerol dioleate (first metabolite of standard triglyceride such as olive oil)

Safe



• Function

‒ Efficient encapsulation of drugs in liquid crystal

structure

‒ Immediate onset of release

‒ Long-acting treatment, from weeks to months

‒ Tunable release rates by simple means

18

0,01

0,1

1

10

100

1000

0 5 10 15 20 25 30

Pla

sm

a c

oncentr

ation (

ng/m

L)

Time (days)

FC pasireotide

FC octreotide

FC somatostatin 1-14

Single dose injection at t=0; n=6 (SC); rodent; mean values

Effective



• Scale

‒ Commercially available high quality sources of key

components

‒ Manufacturing using conventional pharmaceutical

processing steps

‒ Straightforward up-scaling

Compounding Filtration Filling

Scalable

Camurus Capital Markets and R&D Day, December 14, 2016 19


• Convenience

‒ Compatible with pre-filled syringes

‒ Compatible with injection aid devices such as

autoinjectors

‒ Enabling patient self-administration

Convenient


Active intellectual property strategy supporting FluidCrystal®

• Intellectual property status

‒ 35 patent families

‒ More than 400 approved and/or pending patents

‒ Solid IP position for the FluidCrystal® technology with

patent coverage at least until 2025 and up to 2032

‒ Product-specific patents covering internal and

partnered products

‒ IP portfolio covering all major markets (US, EU-5,

Japan)

21

FluidCrystal® injection depot for longer lasting treatment effects

Long-acting release with weekly and monthly dosing

Good safety and local tolerability

Easy and convenient dosing

Applicable across substance classes

Standard manufacturing processes

~1500SUBJECTS HAVE

RECEIVED >10,000

INJECTIONS IN

CLINICAL TRIALS



CAM2038

Opioid dependence overview

23

Peter Hjelmström, MD, PhD, Sen. Dir., Medical Affairs

6,0 6,27,3

9,510,6

11,712,9

15,816,8

17,818,9

19,7

21,3 21,9

24,5

28,630,1

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

20

07

20

08

20

09

20

10

20

11

20

12

20

13

20

14

20

15

Opioid dependence is a growing global health problem

• 33 million people misuse opioids globally

‒ Largest society burden of all drugs1

‒ About 4 million diagnosed patients in Europe and the US

‒ About 2 million in treatment (Europe and US2,3)

• Escalating opioid crisis

‒ 207,400 drug related deaths worldwide

• 30,000 US opioid overdose deaths in 2015,

12,990 from heroin (+23%).

• Growing concerns in Europe with at least 6,800

overdose deaths in 20144

• A chronic relapsing disease

‒ Opioid-use trajectories show that the disease is chronic

with less than 30% abstinence achieved over time

‒ Opioid dependence mortality continues to increase over

time6

US overdose epidemic4

Thousands

Source: 1. UNODC, World Drug Report 2015; 2. SAHMSA, National Survey on Drug Use and Health (NSDUH) – 2014; 3. EMCDD, European Drug Report Trends

and Developments 2015; 4. Center for Disease Control & Prevention 2016; 5. Toxreg 2016; 6. Hser et al. Harvard Review Psychiatry 2015; 23: 76-89

24

0

100

200

300

400

500

600

700

800

900

1000

Heroin Non-heroin opioids Other drugs

Opioid deaths in Sweden5

Annual deaths with illicit drugs or opioid pharmaceutics

present during forensic examination


Issues with current daily treatments of opioid dependence

• Buprenorphine and methadone has demonstrated efficacy in the treatment of opioid use disorders

‒ Suppress opioid withdrawal symptoms

‒ Reduce craving for opioids

‒ Produce blockade of opioids

• These all lead to reduced illicit drug use

‒ Creates a sustained opportunity to address other psychosocial issues

• Large scientific evidence base of efficacy

• On the World Health Organization’s Essential Medicines List


• Limited treatment adherence with continued illicit opioid use and treatment discontinuations

• Extensive misuse and diversion of medications

• Accidental pediatric exposure

• Safety concerns incl. respiratory depression and overdoses and cardiac events (e.g. methadone)

• Need for daily and often supervised dosing, resulting in inconvenience, stigma and reduced quality of life for patients as well as burdens to the healthcare and criminal justice systems

Medication assisted treatment (MAT) Limitations of medication assisted treatment

Source; 1. Benyamina and Stöver, Heroin Addict Relat Clin Probl 2012; 14(4): 65-80

Potential benefits of a sustained release buprenorphine formulation

• Reduces need for daily dosing and decisions

‒ Convenient for the patient

‒ Less staffing for supervision

• Reduces need for substantial drug supply at home

‒ Reduces risk of overdose, accidental ingestion

‒ Minimizes risk of misuse, abuse, diversion and theft

• Providing more stable blood levels over time

• Physician can be confident that patient has appropriate dose

exposure (adherence)



CAM2038

Clinical development update,

Phase 3 results, and pathway

to market registrations

27

Fredrik Tiberg, PhD, CEO and Head R&D

Flexible and individualized opioid dependence treatment– across treatment phases

Treatment initiation

- induction

Weekly CAM2038

Stabilization Weekly

CAM2038Maintenance

treatment

Monthly or Weekly CAM2038


Weekly and monthly CAM2038 are administered as small dose volumesubcutaneous (SC) injections by a prefilled syringe with a thin 23G needle

Development strategy for CAM2038 for opioid dependence

• Demonstrate efficacy and safety for weekly and monthly CAM2038 for opioid dependence treatment

‒ Versus sublingual (SL) buprenorphine/naloxone “Standard of Care”

‒ Across treatment phases – from initiation and early stabilization to longer-term maintenance treatment

‒ Flexible and individualized treatment regimen

• Development program aligned with FDA and EMA/CHMP advices and includes SL buprenorphine and buprenorphine/naloxone as active comparators

‒ Phase 1 pharmacokinetic studies of weekly & monthly CAM2038 versus SL and IV buprenorphine (EU)

‒ Phase 2 opioid challenge study of opioid blocking and withdrawal suppression by weekly CAM2038 (US)

‒ Phase 3 double-dummy, double-blind efficacy study of weekly & monthly CAM2038 versus SL buprenorphine/naloxone (US)

‒ Phase 3 long-term, open-label, safety study of weekly & monthly CAM2038 (EU, AUS, and US)

• Additional studies

‒ Phase 2 pharmacokinetic and pharmacodynamic study of weekly CAM2038 (EU)

‒ Phase 2 pharmacokinetic study of weekly and monthly CAM2038, including different SC injection sites (US)

• Supportive of global market registration approvals


Clinical program for CAM2038 in opioid dependence

HS-11-426 Phase 1 60 healthy volunteers

under naltrexone block

HS-13-487 Phase 1 87 healthy volunteers

under naltrexone block

HS-07-307 Phase 2 41 patients

Trial no. Subjects Key results / Study design Status

Dose proportional extended release further

supported by pharmacodynamics results for

withdrawal symptoms over time and time to

rescue medication.

Extended release suited for weekly respective

monthly dosing. 6-8 times higher bioavailability.

Acceptability of CAM2038 dosing higher than

SL tablets.

Extended release of BPN suited for once

weekly dosing. Dose proportional exposure. 6-8

times higher bioavailability versus SL BPN

tablets.

HS-14-478 Phase 2

HS-14-549 Phase 2

Opioid challenge study of CAM2038 in opioid dependent patients (US)

Repeat dose pharmacokinetic study of CAM2038 in opioid dependent pain patients (US),

including injections in different subcutaneous injection sites

Positive results

Under completion

HS-11-421 Phase 3

HS-14-499 Phase 3

Double blind, double dummy Phase 3 efficacy trial of CAM2038 versus sublingual

buprenorphine (US)

Open label Phase 3 long-term safety trial in patients with opioid dependence (EU, US,

AUS)

Positive results

Under completion

Good safety

and local

tolerability for

CAM2038,

weekly and

monthly

formulations

7COMPLETED

OR ONGOING

CLINICAL TRIALS

+900STUDY

PARTICIPANTS

DOSED WITH

CAM2038 OR

PLACEBO


Pivotal Phase 2 opioid challenge study with weekly CAM2038

• Randomized, multiple-dose opioid challenge

study to assess blockade of subjective opioid

effects by weekly CAM2038 in adults with opioid

use disorder

• N=47

• Treatment with two weekly CAM2038

subcutaneous (SC) injections

• Opioid challenges with randomized

hydromorphone intramuscular (IM) injections

before CAM2038 dosing and on Days 1-3, 4-6,

8-10, and 11-13 of treatment

31

• Visual Analog Scores

‒ Primary: Drug Liking [bipolar scale]

‒ Secondary: Good Effects, High, Bad Effects, Any

Drug Effect, Desire to Use [unipolar scale],

Alertness/Drowsiness [bipolar scale]

• Opioid Withdrawal

‒ Clinical opioid withdrawal scale (COWS)

‒ Objective opioid withdrawal scale (OOWS)

• Pharmacokinetic Outcomes

• Safety Outcomes

Study design Key Primary and Secondary Outcomes


CAM2038 shows rapid and sustained opioid blockade

“At this moment, my liking for this drug is”

32

Presentation, S27, ISAM & CSAM-SMCA 2016 Montreal, Canada Oct 20-22, 2016, Sharon L Walsh, Sandra Comer, Michelle Lofwall, Bradley Vince, Debra Kersh, Marion A Coe,

Jermaine D Jones, Fredrik Tiberg, Behshad Sheldon, Sonnie Kim. http://www.csam-smca.org/resources-and-documents/past-annual-meeting-presentations/2016-abstracts/

CAM2038 q1w 24 mg

CAM2038 q1w 32 mg

0

40

50

70

80

100

Pe

ak S

co

re (

mm

)

0 6 18

Hydromorphone (mg, IM)

0 6 18 0 6 18 0 6 18 0 6 18

Qualification (Days 1-3) (Days 4-6) (Days 1-3) (Days 4-6)

Weekly CAM2038

Injection 1

60

90

11 pt. difference

Prespecified complete blocking

criteria Neutral

Strong Disliking

Strong Liking

Weekly CAM2038

Injection 2


CAM2038 show effective suppression of withdrawal

Effective suppression of clinical opiate withdrawal scale (COWS) scores from treatment initiation

33

0

3

6

9

12

48

To

tal C

OW

S S

co

re

BL 1 2

Treatment Days

3 4 5 6 7 8 9 10 11 12 13 14

CAM2038 24 mg

CAM2038 32 mg

Weekly CAM2038

Injection 2

Weekly CAM2038

Injection 1


WithdrawalCOWS

Score

– <5

Mild 5-12

Moderate 13-24

Moderate to

Severe

25-36

Severe >36

Phase 3 efficacy study of weekly and monthly CAM2038

• 24-week, double-blind, double-dummy,

randomized, active-controlled Phase 3 study

‒ Treatment-seeking patients with moderate to severe

opioid use disorder, not currently on medication

assisted treatment (MAT)

‒ Assessed from treatment initiation to maintenance

‒ Non-inferiority and superiority objectives

‒ CAM2038 vs. sublingual buprenorphine/naloxone

BPN/NX – “Standard of Care”

34

• Primary Endpoint

‒ EMA: Negative Urines with NI margin of -11%

‒ FDA: Response Rate* with NI margin of -10%

• Key Secondary Endpoint:

‒ EMA: Cumulative Distribution Function (CDF)

of urines negative for illicit opioids from Week 5 to 25.

(Sampling Weeks)

‒ FDA: CDF of negative urines plus self-reports

negative for illicit opioids from Week 5 to 25

(Sampling Weeks).

‒ Multiple additional secondary and explorative

endpoints: retention; craving, morning cravings,

withdrawal (SOWS and COWS)

Study design Key Primary and Secondary Outcomes


* Responder defined as displaying negative urine samples, including self-reports, for;

treatment week 12 and month 6, at least 2 of treatment weeks 9, 10 and 11 and 12,

and at least 5 of the 6 samples obtained during treatment weeks 12 through 24.

Comparison between pivotal Phase 3 studies of CAM2038 versus RBP-6000

CAM2038 Phase 3 study (HS-11-421) RBP-6000 Phase 3 study (RB-US-13-0001)

Active controlled study (non-inferiority & superiority

analysis)

Placebo controlled study (superiority analysis)

Primary and key secondary study endpoints were

aligned with EMA/CHMP and FDA advices

The primary endpoint was “the regulatory-agreed

primary endpoint of the study”

Study included treatment initiation (induction) and

early stabilization (double-blind, double-dummy)

Study excluded up to 2 weeks of open-label

treatment initiation (induction) and early stabilization

Primary endpoints included entire treatment period Primary endpoint excluded a 4-week ”Grace Period”

- effectively 6 weeks, including the open label phase

Excluded patients with moderate-to-severe non-opioid

substance use disorders, but allowed positive UDS for

e.g. benzodiazepines, cocaine, methamphetamine,

marijuana.

Excluded patients with substance use disorders (other

than: mild cocaine and cannabis if UDS negative at

screening; mild alcohol or nicotine use disorders).


Abbreviation: UDS, urine drug screen

Pivotal phase 3 study design. Randomized, double-blind, double-dummy study of CAM2038 vs. SL buprenorphine/naloxone (N=428)


Screening Phase 1: Weekly Visits Phase 2: Monthly Visits Follow-Up

3 Weeks 12 Weeks 12 Weeks 1 Month

Opioid dependentpatients seeking

treatment

SL BPN/NX8-24 mg/day

CAM2038 q1w Placebo

SL BPN/NX8-32 mg/day

CAM2038 q4w Placebo

SL PlaceboCAM2038 q1w8-32 mg/week

SL PlaceboCAM2038 q4w

64-160 mg/month

R

Subject demographics in Phase 3 trial, HS-11-421


SL BPN/NX

N=215

CAM2038

N=213

TOTAL

N=428

Mean age 38 39 38

Male / Female 66% / 36% 57% / 43% 61% / 39%

Race

White 76% 75% 76%

Black or African American 22% 22% 22%

Others 1% 3% 2%

Mean height 173 cm 172 cm 172 cm

Mean BMI 26 kg/m2 26 kg/m2 26 kg/m2

Baseline clinical characteristics show representative patient population with significant non-opioid drug use at screening


Participant demographics SL BPN/NX

N=215

CAM2038

N=213

TOTAL

(N=428)

Drug use history

Heroin 70% 71% 71%

Prescription opioid pain relievers 28% 26% 27%

Substance use at screening, e.g.: 55% 60% 58%

Benzodiazepine 16% 14% 15%

Cocaine 25% 25% 25%

Amphetamine 15% 18% 16%

Marijuana 30% 27% 28%

Psychatric disorder history

Anxiety 19% 14% 16%

Attention deficit/hyperactivity disorder 5% 5% 5%

Depression 13% 12% 12%

CAM2038 vs SL BPN/NX 95%CI Non-inferiority (NI)Non-Inferiority

p-value

EMA:Primary Efficacy Endpoint - Mean % Urine SamplesNegative for Illicit Opioids

(-0.1%, 13.3%) <0.001

FDA:Primary Efficacy Endpoint - Response Rate

(-3.5%, 10.4%) <0.001

CAM2038 met both FDA and EMA primary endpoints of non-inferiority versus SL BPN/NX – “Standard of Care”(ITT)

-0,2 -0,1 0 0,1 0,2

Difference (95% CI)

Favors CAM2038Favors SL BPN/NX

11%

10%5%

5%


NI margin

NI margin

CAM2038 vs SL BPN/NX 95%CI Non-inferiority (NI)Superiority

p-value

Study phase 1:Mean % Urine SamplesNegative for Illicit Opioids

(-1.3, 13.1) 0.110

Study phase 2:Mean % Urine SamplesNegative for Illicit Opioids

(1.2, 15.7) 0.023

Non-inferiority shown in phase 1 and superiority in phase 2 versus SL BPN/NX (ITT)

Difference (95% CI)

Favors CAM2038Favors SL BPN/NX


-0,2 -0,1 0 0,1 0,2

5%10%

NI margin

CAM2038 met statistical superiority versus SL/BPN/NX for secondary endpoint of CDF for negative urines +/- self-reports throughout the study (ITT)


Grace Period

Weeks

Treatment

Weeks

Sampling

Weeks

Superiority

p-value (FDA)

Superiority

p-value (EMA)

0 1-24 2-25 0.006 0.011

1 2-24 3-25 0.005 0.010

3a 4-24 5-25 0.004 0.008

4b 5-24 6-25 0.001 0.003

6c 7-24 8-25 0.001 0.002

a Secondary endpoint for FDA and EMA; b Primary endpoint in RB-US-13-0001; c Including 2-week open label phase in RB-US-13-0001).

CDF – cumulative distribution function

CAM2038 was well tolerated with no unexpected safety findings


Treatment emergent adverse events,

TEAEs

SL BPN/NX

N=215

CAM2038

N=213

TOTAL

N=428

Any TEAE 55% 60% 58%

Serious TEAEs 6% 2% 4%

Severe TEAEs 7% 3% 5%

AEs leading to treatment discontinuation 1% 3% 2%

Suspected drug-related TEAEs 30% 33% 31%

TEAEs that resulted in death* 0% 0.5% 0.2%

Drug overdoses 2% 0% 1%

*Not-related, traffic accident

CAM2038 was well tolerated with low frequency of injection site reactions

0

20

40

60

80

100

Mild Moderate Severe

Inje

ction

site

rea

ction

s(%

)

Severity

SL BPN/NX (placebo) CAM2038


Only mild and moderate reactions

% patients with at least one injection site reaction (total injections >5000)

CAM2038 demonstrate non-inferior and superior efficacyacross treatment phases versus daily SL BPN/NX

• Met both FDA and EMA primary endpoints

• Statistical superiority met for the key secondary endpoint of CDF for negative urines, with and without self reports

• Efficacy demonstrated throughout treatment phases

‒ From initiation to maintenance

• CAM2038 safety profile comparable to daily sublingual buprenorphine/naloxone

‒ Fewer SAEs (3.2% vs. 6%)

‒ No opioid overdoses vs four overdoses

• Clinical data support MAA and NDA submissions in mid-2017

44

CAM2038 show robust treatment efficacy

in Phase 3 trial versus Standard of Care Urgent need for new treatments!

Deaths from the drugs are rising sharply in

the U.S.

The number of deaths from heroin overdoses

surged by 23% to 12,990 in 2015, while fatal

overdoses from powerful synthetic opioids such

as fentanyl rose by more than 73% to 9,580,

Centers for Disease Control and Prevention

12,990fatal heroin

overdoses

2015

9,580fatal synthetic

opioid

overdoses

2015MAA – Market Authorisation Application

45

Phase 3 long-term safety trial under completion in Europe, Australia and the United States (N=228, enrolled)

Screening Period Treatment Period Follow-Up

Weeks -3 to -1 4 Weeks

Patients who are new treatment seekers or on

weekly SL BNP prescriptions

Patients who are on monthly SL BNP

prescriptions

Week -3 Week 0

Week 4

Week 48

Up to 48 Weeks

CAM2038 q1w

CAM2038 q4w


Proceeding towards market approval authorizationsubmissions in Europe and the US

• Regulatory

‒ Fast Track designation for both Weekly and Monthly CAM2038 by US FDA, August 2015

‒ Positive decision for eligibility for centralized procedure for CAM2038 by EMA, October 2016

‒ Pre-MAA meeting with EMA in January 2017

‒ NDA submission to FDA in mid-2017

‒ MAA submission to EMA mid-2017

• Clinical development

‒ Completion of Phase 3 long-term safety and repeat dose PK study

• Presentations and publications

‒ Planned participation and presentations at key conferences and meetings during 2017, including:

‒ Peer reviewed publications


ASAM

6-9 Apr

New Orleans, USA

INRC

9-14 July

Chicago, USA

ISAM

26-29 Oct

Abu Dhabi, UAE

CPDD

17-22 June

Montréal, Canada

AMCP1

27-30 Mar

Colorado, USA

ECNP

2-5 Sep

Paris, France

CAM2038 has potential to improve and transform the treatment of opioid dependence

Weekly & monthly coverage for individualized treatment

Effective suppression of withdrawal and cravings

Rapid and sustained opioid blockade (“complete blockade”)

Documented efficacy across treatment phases; non-inferior/superior to daily SL BPN/NX – “Standard of Care”

Safe and locally tolerable

47

No daily

dosing or

supervision

No accidental

pediatric

exposure

Minimal risk

of misuse and

diversion


48

Two companies – One team


• Behshad Sheldon, President & CEO

• Fredrik Tiberg, President & CEO, Head of R&D

• Sonnie Kim, Senior VP Clinical & Medical Affairs

• Margareta Linden, VP Program Management

• Frank Young, EVP Medical and Regulatory

• Agneta Svedberg, VP Clinical and Regulatory

• Craig Brown, SVP, Commercial & Project Man

• Markus Johnsson, VP Pharmaceutical Development

• Sonia Oosman, Director, Clinical Operations

• Torsten Malmström, VP Technical Operations

• Sheila Mathews, Director Regulatory

• Anna-Karin Lindqvist, Senior Dir. Preclinical Research

• Ryan Dannerman, Sen. Dir. Medical Affairs

• Kerstin Strandgården, Sen. Pharmacokineticist

• John Diaz, Ass. Dir. Clinical Ops.

• Hanna Liedman, Medical Writer

• Mathews Adera, Exec. Director Clinical Development

• Peter Hjelmström, Sen. Dir. Medical Affairs

• CMC and Non-Clin Teams

• Michael Chen and Stefan Peterson, Biostatistics,

Consultants

• Investigators, staff and study participants


Clinician’s view

Long-acting depots – a potential

new treatment paradigm for OUD

Prof. Edward Nunes, MD, PhD, Columbia Medical School

Prof Edward Nunes, MD PhD

• Prof. Nunes is Professor of Psychiatry at Columbia University Medical School

• Principal Investigator of the Greater New York Node of the National Institute on Drug Abuse (NIDA) Clinical

Trials Network on behavioral and medication treatments for substance dependence and related psychiatric

disorders

• Interests and ongoing studies include treatments for cocaine dependence in general, heroin and other opioid

dependence, for nicotine dependence in general, and for addicted patients with co-occurring psychiatric

disorders including depression, and post-traumatic stress disorder.

• Types of treatment under study include medication treatments (buprenorphine, naltrexone, mirtazapine) as well

as behavioral and psychotherapeutic approaches and computer-delivered treatments.

• Dr. Nunes also studies the challenges involved in implementing evidence-based treatments for substance use

disorders in real-world community-based treatments settings.

• Dr. Nunes also serves on the American Board of Addiction Medicine, Co-Chair of the Columbia/ New York

State Psychiatric Institute’s Institutional Review Board, and has been appointed to the National Advisory

Council on Drug Abuse.

• Clinical investigator on CAM2038 Phase 3 trials HS-11-421 and HS-14-499.

50


CAM2038

US market perspectives

Behshad Sheldon, President & CEO

Braeburn Pharmaceuticals

Camurus Capital Markets and R&D DayDecember 14, 2016

Behshad Sheldon President and CEO

Braeburn Overview and Vision

• Chronic specialty CNS diseases affect all walks of life

• Novel long-acting injectables and implantables help solve public health crises

• Personalized care with steady blood levels and increased compliance essential for improving patient

clinical outcomes

• Reduced relapse, diversion and abuse meaningfully improve social outcomes

53

Founded in December 2012

Based in Princeton, New Jersey

Apple Tree Partners Company

First FDA Approval in May 2016

Vision:

Experienced Management Team

54

Craig Brown

SVP, Commercial, Project

Management & Manufacturing

David Byram

VP, Market Access &

Governmental Affairs

Frank Young, MD, PhD

EVP, Medical and Regulatory

Behshad Sheldon

President & CEO

David J. McIntyre

CFO

Otsuka Pharmaceuticals, SVP Global Commercial Lead and Board

Member of Otsuka R&D

• Launched and led development and commercialization efforts for Abilify® for 12 years

• Otsuka / Lundbeck landmark $10B CNS co-commercialization deal

Bristol-Myers Squibb / Smithkline Beecham

• Plavix®, Glucophage®, Abilify®, Bactroban

Partner at Apple Tree Partners

HeartWare International: Executive VP, CFO 2005 - 2011; COO global

commercialization phase 2008 - 2011

Baker & McKenzie and KPMG, senior attorney in private practice

specializing in corporate, M&A and ECM

Various senior financial roles in multi-national companies including Coal

& Allied Limited, a publicly traded subsidiary of the Rio Tinto Group

Sonnie Kim, PharmD

SVP, Clinical and Medical Affairs

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwit9v35x_PPAhUDHD4KHZzQAqsQjRwIBw&url=http://businesscasestudies.co.uk/smithkline-beecham/&psig=AFQjCNHnuQQ1uGgYh4cZ9YRsQpsxHoeVNg&ust=1477402624016828

Large and Growing Markets with High Unmet Needs

Opioid Use Disorder Population Pain Population

• ~13.2mm people in U.S. misuse opioid painkillers and heroin

• ~30,000 opioid overdose deaths per year

• ~100mm people suffer from chronic pain in the U.S.

• ~23mm adults report a lot of daily pain

• Up to ~12 saved for every $1 spent on treatment

• ~$2.0bn sales of buprenorphine

• ~$80 billion annual economic impact

• CDC directive that full agonists are overprescribed for chronic pain –

alternatives needed

• $635bn annual economic impact

Our long acting medications will address markets with ~$870bn annual impact

55

~228mm TRxopioids

analgesics

~6.7mm TRx

buprenorphine

~3mm TRxmethadone

~13.2mm people.

misuse opioid pain

killers and heroin in U.S

~2.6mm diagnosed with

opioid use disorder

~1.1mm treated

~0.7mm patientson buprenorphine

therapy

Our Product Portfolio

56

Product BRBN Rights

Ad

dic

tio

nP

ain

Ph 1 Ph 2 Ph 3 ApvlIndication Form

1 Exclusively sub-licensed to Knight Therapeutics, Inc. in Canada2 Option rights for Japan, China, South Korea, and Taiwan

Compound(s)

Probuphine (6-month) Opioid Addiction Implant US, Canada1Buprenorphine

CAM2038 Weekly Opioid Addiction Injectable North America2Buprenorphine

CAM2038 Monthly Opioid Addiction Injectable North America2Buprenorphine

CAM2038 Weekly Chronic Pain Injectable North America2Buprenorphine

CAM2038 Monthly Chronic Pain Injectable North America2Buprenorphine

Probuphine (6-month) Chronic Pain Implant US, Canada1Buprenorphine

Sch

izo

ph

ren

ia

BB0817 (6-month) Schizophrenia Implant WorldwideRisperidone

BB1216 (6-month)Clinic

readySpasticity Implant WorldwideTizanidine

BB0417 (3-5-day) Post op /Acute Pain Injectable North America2Buprenorphine

+ Granisetron

Sp

asti

cit

y

May 2016

Expected NDA

submission

1H17

Opioid Addiction: A Public Health Epidemic

• US: ~5% of global population,

>80% of opioid prescriptions

• ~4x increase in opioid

prescriptions and opioid

overdoses since 1999

• ~3,900 people daily begin abusing

opioids

• ~30,000 deaths per year from

opioid overdose

• 1 death every ~18 minutes

57

“Deaths from drug overdoses have jumped in nearly every county across the United States, driven largely by an

explosion in addiction to prescription painkillers and heroin”

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiF9-_L2OrPAhXIPT4KHXnjC7oQjRwIBw&url=http://www.cweb.com/entertainment/296992-prince-musician-died-due-to-accidental-overdose-of-opioid-fentanyl-medical-examiner-says-watch-never-seen-prince-video-france-cweb.html&psig=AFQjCNEuq8C24Pn3XWE_uNre536MOeF1QQ&ust=1477097805399511

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwim1deq2erPAhVDVz4KHfS6DSIQjRwIBw&url=http://www.anesecavanaugh.com/about/articles-interviews/&bvm=bv.136499718,d.cWw&psig=AFQjCNFJqBCghVoG4hNcWBVczefmgNqUzg&ust=1477098030853112

Lost productivity accounts for an estimated $42 billion annually while

criminal justice accounts for $8.2 billion3*

Opioid abusers are 4× more likely to visit the ER, 11× more likely to visit

a mental health clinic and 12× more likely to be admitted as an inpatient2

Misuse treatment accounts for $2.2 billion annually3*

$944 million has been estimated to be spent on management of medical

complications, with the vast majority relating to the management of HIV

and Hep-C infections3*

The estimated total cost of nonmedical use of prescription opioids in the

US has been estimated at $53.4 billion annually3*

Drug diversion costs payers up to $72.5 billion annually in direct costs and

indirect costs associated with medical complications arising from abuse1

Nonmedical use

and Diversion

Intensive and costly

clinical management

Impact on Productivity

* Based on a 2006 estimate1. Coalition Against Insurance Fraud. Prescription for peril: how insurance fraud finances theft and abuse of addictive prescription drugs.

http://www.insurancefraud.org/downloads/drugDiversion.pdf. Accessed on May 31, 2016

2. Meyer et al., Popul Health Manag 2014;17(6): 2014

3. Hansen R et al., Clin J Pain 2011;27(3): 194-202

Financial Impact of Opioid Use Disorder

Opioid Use Disorder Financial Impact on US Health Plans

1. Ghate SR et al., J Pain palliative care 2010;24: 251-258

The annual direct health care costs for privately insured opioid abusers based on 6 months

prior and post diagnosis is estimated to be 8 times higher than non-abusers

Cost (U

SD

)

Patient numbers n=740 n=2220 n=50,162 n=150,486

Total cost $15,884 $1,830 $13,658 $7,008

$657

$2,034

$5,398

$7,795

$185

$386

$928

$331

$4,159

$8,265

$1,234

$2,473

$4,275

$260

Administrative claims database analysis. Cases were included based on a opioid abuse related ICD-9 code (304.0X, 304.7x, 305.5X, 965.0X) with each patient

matched to 3 controls based on age, gender, geographical region, and employment status. Analysis was conducted over one year

US Buprenorphine Oral Market Continues to Grow

60

• $2 Billion in sales in 2015

• The market continues to grow despite

4 generic competitors

• 11.6 million TRx in 2015

• TRx robust growth continued

• Market grew 1.9x in the past 5 years

• Very concentrated market, with >90+%

of Rx’s from ~6,000 prescribers

+58%+19%

+16%+13%

+12%

Source: TRx IMS NPA; Sales IMS NSP

+8%

Expanding Access to Buprenorphine in the USPolicy update

61

US Surgeon General’s Report

• Substance use disorder (SUD) is a chronic, relapsing disease of the brain and not a moral

weakness

• Treatment gap for individuals with SUD due to lack of screening, stigma, inadequate access

to treatment, and cost of care

• Medication reduces illicit opioid use and improves outcomes, including employment,

criminal justice involvement, and HIV risk

• Explicitly references buprenorphine implant for treatment in stable patients

Expanding Access to Buprenorphine treatment

US Congress: Comprehensive Addiction and Recovery Act (CARA)

• Expanded prescribing privileges to nurse practitioners and physicians assistants (NPs/PAs)

• Authorized HHS to set patient limit

• NPs/PAs can currently treat up to 30 patients for one year

• HHS will write a new rule raising the limit to 100 after NPs/PAs have one year of experience

US Administration: HHS Regulation

• Increased physicians’ patient limit to 275, with qualifications:

• Physicians must have a waiver to treat 100 patients for at least one year and either

• Hold board certification by an accredited entity, or

• Practice in a qualified practice setting (i.e. uses electronic medical records, utilizes the

state PDMPs, and accepts insurance)

• >2200 physicians have filed for increase to 275, ~400K increase in capacity

21st Century Cures Act: SUD Treatment

Bipartisan Congressional bill

• Passed overwhelmingly (House vote: 392-26; Senate vote: 94-5)

• Reflects an enthusiastic congressional climate for biomedical research and innovation

Grant Programs (requiring separate appropriations)

• Authorizes $1 billion ($500 million this year and $500 million next year) for state grants to address

the opioid overdose crisis; first $500 million likely to be appropriated on December 12

• May be used for:

− Training for HCPs on opioid prescribing, pain management, recognizing a substance use

disorder (SUD), and referrals to treatment

− Supporting access to health care services, and other activities

• Provides five-year grants for medical residents and fellows who practice psychiatry and addiction

medicine

• Reauthorizes the Substance Abuse Prevention and Treatment Block Grant at $1.858 billion for

fiscal years 2018-2022

Parity Enforcement

• Requires HHS to convene a public meeting within six months of enactment to produce an action

plan for improved federal and state parity enforcement

Opioid Addiction: Evolution of Continuum of Care

65

Limitations of Current Therapies

CAM2038 Weekly

Oral daily buprenorphine

CAM2038 Weekly


CAM2038 Monthly


CAM2038 Monthly/

Probuphine 6-mo


Daily/Weekly Weekly Monthly Less frequent

Treatment

Options

MD Visits

InitiationInitial

stabilization

Medium-term

stabilization

Long-term

maintenanceTreatment

Stage

• Patients forget or choose not to take daily medications

• Increased risk of relapse / overdose

• Stigma of daily medication

• Daily reminders of disease and addiction

• Fear of accidental pediatric exposure

• Street value leads to creation of "pill mills"

• Opportunities for diversion, misuse and abuse

• High hospitalization costs

Suboptimal medication

compliance impeding outcomes

Suboptimal quality

of lifePublic health impact

Braeburn’s comprehensive suite of products seeks to provide solutions for patients from

initiation of treatment through long-term maintenance

Opioid Addiction: CAM2038 Phase 3 Update

66

Key Phase 3 results Announced Nov. 2016

• Multicenter, randomized double blind, double dummy, active controlled study with 428 patients

• First and only long-acting buprenorphine study vs. current standard of care

• Met both FDA and EMA primary endpoints of non-inferiority vs. SOC (p < 0.001)

• Superiority for secondary endpoint of Cumulative Distribution Function (CDF) of negative urine samples (p = 0.004)

• Few serious adverse events and similar in CAM2038 vs SL BPN / NX (3.2% vs. 6%)

• 4 non-fatal overdoses in SL BPN/NX arm vs 0 in CAM2038 arm

(-0.2%, 13.7%)

Difference (95% CI)

Favors CAM2038Favors SL BPN

Non-inferiority

10%

Non-inferiority

11% 5%

5%

Responder Rate

% Urine Samples Negative

for Illicit Opioids

(-3.5%, 10.4%)

p-valueNon-Inferiority

<0.001

<0.001

Primary Endpoints (FDA and EMA)

CAM2038 met both FDA and EMA primary endpoints of non-inferiority versus the standard of

care in its Phase 3 trials

Probuphine: Model of Execution

Braeburn successfully executed on an aggressive trial schedule and NDA submission

67

1 IMS National Sales Perspective. Dollars MAT March 20152 IMS National Sales Perspective. Dollars Calendar 2014

May 26, 2016:• Approved

June 2016:• Shipped Product

Enrollment of 177 patients

in 4 months far outpaced

typical enrollment schedule

of 6-9 months

Filed NDA within

3 months from

database lock

May 15 2014:• Final FDA advice on

proposed protocol

July 17 2014:• First patient enrolled

June 2015: • Positive topline data

released

FDA Approval Media Coverage

Trade Media Coverage

Buprenorphine implant helps opioid-

dependent patients stay abstinent longer

New Rule Expands Access to

Buprenorphine

First Patients Implanted June 2016

Social Media: Amplifying the Probuphine Story

71

2,507+ mentions

12.6 million+ impressions

Opioid Addiction: Probuphine Sales Evolution Plan

Probuphine

FDA Approval

(May 26, 2016)

Q2 2016 Q3 2016 Q4 2016 Q1 2017

Hiring and training

of clinical educator

field force

6,000 physicians

represent ~90% of

buprenorphine

Rx’s

Top 100 payers

represent ~85% of

buprenorphine

Rx’s

Increase physician

adoption

Support full scale

launch

Build Clinical Educators Team to

Support Medical Affairs Launch

Train & Certify Physicians

Expand Payer Coverage and

Reimbursement

Broaden Distribution Channels

Build Sales Force

46

114

Key Metric/Goal

27 27 25

2,4002,800

73

CMS grants J-code

(J0570)

‘Buy-and-bill’ systemSpecialty pharmacy in

addition to ‘Buy-and-bill’

1

2

3

5

4

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiPpZ7p_urPAhVTID4KHbNhAswQjRwIBw&url=https://www.aetna.com/&bvm=bv.136499718,d.cWw&psig=AFQjCNGYmCCSzKI3K7a3u69ho_nVDAC9Tg&ust=1477108129156496

https://tranquilshores.org/cigna-logo/

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiNzayk_-rPAhUCID4KHSeuB1IQjRwIBw&url=http://dekalbcountyonline.com/2015/11/2016-changes-to-blue-cross-blue-shield-of-illinois-blue-choice-ppo-plan/&bvm=bv.136499718,d.cWw&psig=AFQjCNGu8JSGEwIbmooOSuZVtjHo8G3uJQ&ust=1477108271524686

Pain: Market Overview

73

Belbuca

Butrans

~228mm TRx Opioids

Analgesics

~6.7mmTRx

Buprenorphine

~3mm TRx Methadone

• 100mm people suffer from chronic pain in the

U.S.

• ~23mm adults report a lot of daily pain

• New guidelines from CDC on opioid painkillers

• Two approved buprenorphine pain drugs

− Butrans (patch)

− Belbuca (film)…

• …only available in low doses

• …risk of abuse and pediatric exposure

No higher-dose oral buprenorphine products used for opioid addiction approved for chronic pain

Buprenorphine: Mechanistic Advantages Over Other Pain Medications

74

Reduced hyperalgesia

Ceiling effect makes overdose unlikely on buprenorphine alone

Potential for fewer side effects

Lower risk of respiratory depression vs. full mu agonists

Possible anti-depressant effect due to kappa antagonist activity

Mu

(analgesia,

euphoria,

respiratory

depression)

Kappa

(dysphoria,

hyperalgesia,

antinorciceptive)

Delta

(minor

analgesia)

ORL1

(spinal

analgesia)

Partial agonist

Strong affinity

Antagonist

Strong affinity

Antagonist

Moderate

affinity

Agonist

Full agonist

Moderate

affinity

Weak agonist

Very Low affinity

Weak agonist

Very low affinity N/A

Mo

rph

ine, o

xyco

do

ne,

fen

tan

yl,

hyd

rom

orp

ho

ne

Bu

pre

no

rph

ine

Key buprenorphine attributes

Pain: Our Portfolio

75

Opioid-naïve

patients

Low, fixed opioid

doses

Flexible medium to

high opioid dosesPost op / acute

Our comprehensive pain management approach

Low-dose CAM2038

Weekly and Monthly Probuphine Implant

Higher dose

CAM2038 Weekly

and Monthly

Low-dose combination

of Buprenorphine and

Granisetron

Our long-acting medications, if approved, will provide steady, around-the-clock therapy, resulting in

improved pain management

• Probuphine 6-month Implant

− First implantable buprenorphine

− Short in-office procedure

• CAM2038 Weekly and Monthly

− Subcutaneous injection

− Fast in-office shot

• Buprenophrine + Granisetron

− Subcutaneous injection

− Fast in-office or in-hospital shot

Physicians View Long-Acting Buprenorphine as a Long-Term Solution to

the Problems Created by Use of Opioids for Pain

76

~82% of all MDs and 94% of MDs with a

high volume of patients would “possibly,”“probably,” or “definitely” prescribe

buprenorphine injection if approved

Key reasons for adoption:

Less abuse

Less diversion

Steadier dose

Limits opioid dependency

Convenience

MDs predict they will prescribe the buprenorphine

injection to 9% of their patients

Buprenorphine Injection Market Share Capture from

Other Prescribed Chronic Pain Treatments

4%

9%2%

3%

Full Opioid Agonists

Anticonvulsants / Antiepileptics

Other Buprenorphine Injections

228mm prescriptions annually

Large market opportunity for Braeburn

2014 Current Target potential

1 Clinic 1 Approved

2 Clinic

3 Approved

4 Clinic 4 Approved

1 Clinic 1 Approved

1 Clinic-Ready 1 Clinic

Approved: 0

Clinic or Clinic-Ready: 1

Approved: 1


Approved: 8


In-licensed and acquired long-

acting technologies from Titan,

Camurus and Endo

ProNeura Implantable Platform

FluidCrystal Injectable Platform

MedLaunch Implant Platform

Licensing & acquiring new

delivery technologies to drive

future growth

77

Company

Employees

Technologies

Schizophrenia

Pain

Opioid Addiction

Spasticity

Total

Field PersonnelTotal Employees

76

38

2016

7

2014

~200

~150

2017E+

Th

era

pe

uti

c A

rea

sOur Growth Trajectory


CAM2038

EU market perspectives

and commercialisation

Richard Jameson, CCO

Opioid dependence in the EU is a significant burden on society

• Estimated 1.3m problem drug users in EU

‒ Largest burden to society of all drugs1

‒ It is estimated that over 70 000 lives were lost to drug overdoses in

Europe in the first decade of the twenty-first century4

‒ Every year drug addiction costs society $18.4bn in UK2

‒ Any drug dependent user not in treatment costs society €31k a year

through crime costs in UK2

• Growing concern with prescription drug dependence in EU

with an estimated 400 000 patients affected5

79

Source: 1. UNODC, World Drug Report 2015; 2. Why treat NTA 2014; 3. EMCDD, European Drug Report Trends and Developments 2015; 4. http://www.emcdda.europa.eu/publications/pods/preventing-overdose-

deaths; 5. Alho, H. and Strydom, M. (2013). “Prevalence of prescription opioid-dependency in Europe and risk factors for abuse.” Presented at the International Society of Addiction Medicine Annual Meeting 2013.

Kuala Lumpur, Malaysia. 21–23 Nov 2013


http://www.emcdda.europa.eu/publications/pods/preventing-overdose-deaths

Overview of Medication Assisted Treatment in Europe – a heterogenous treatment system

Medication Assisted Treatment (MAT) Overview

• Approximately 700,000 patients in treatment

‒ 80% patients in EU5 + Nordics

• Methadone now the most common treatment in

EU

• Buprenorphine is accepted as treatment of

choice with a growing patient share

‒ About 250,000 patients on buprenorphine

‒ Largest market shares in France and the Nordics

• Average treatment time in Europe is 3.7 years

but ranges from 2.2 – 5.9 years

‒ Frequently drop out and re-entering in treatment

‒ Majority users and patients have previous treatment

episodes (1 to 4+)

80

MAT at national level (2014)

Methadone67%

Buprenorphine20%

Methadone = Buprenorphine

13%


Source: European Drug Report 2014 and 2016; Equator Dec 2012. Note: 1) According to percentage of Buprenorphine

patients according to the European Drug Report Statistical Bulletin 2014, applied on number of patients in OMT

Methadone >50% share

Buprenorphine >50% share

Buprenorphine = Methadone

Camurus Capital Markets and R&D Day 2016 81

Treatment systems in place are concentrated to specialists

77,500

148,686

161,388

75,964

~21%

~66%

~25%

Specialised centers and primary

health care system

Community health clinics and NHS

providers

Specialised centers and GP

practices

Servizi Tossicodipendenze (Ser.T.),

private and non-profit organisations

CountryNumber patients in

treatment 1Treatment model

% patients receiving

buprenorphine3

Specialised Centres

Specialised centers and primary

healthcare system

61,954

16,535

~25%

~6%

~50%

~ 3000

~ 6000

~ 2000

~ 3000

~ 2000

~ 2000

1. ECMDDA 2016 drug report; 2. Internal data; 3. IMS 2014.

Estimated key Rxers 2

Limitations of current treatment

Camurus Capital Markets and R&D Day 2016 82

1. Bell J: Medications in Recovery: Re-Orientating Drug Dependence Treatment. Appendix C - Opioid Substitution Treatment and Its Effectiveness: Review of the Evidence, 2012; 2. Black

2016, An independent review of the impact on employment outcomes of drug or alcohol addiction

Medically assisted treatment (MAT) has

demonstrated effectiveness1,2

However associated with significant

limitations

• Improves public health

• Reduces heroin use

• Improves social functioning

• Redues overdose deaths

• Reduces crime

• Limits spread of blood borne viruses

• Provides value for money for the taxpayer

• Frequent relapses

• Limited adherence − Continued “use on top”

• Misuse, abuse and diversion

• Accidental pediatric exposure

• Stringent treatment rules− Patients drop out of treatment

− Users do not enter treatment

In EU no new interventions in medication assisted treatment for >10 years

A paradigm shift in opioid dependence treatment

• Weekly and monthly buprenorphine injections for

initiation, stabilization and maintenance treatment

• Flexible dosing for individualized treatment

• Ready to use and easy to administer

• Room temperature storage

• Well tolerated, locally and systemically

• Best-in-class treatment potential

Continuous treatment effectReduced number of doses and decisions

from 365 to 52 or 12 times per yearSafeguards against misuse, abuse, diversion

and pediatric exposureNo daily supervised dosing and related

stigma

Improved treatment adherence

– dose given is dose taken

Rapid and sustained opioid blockade

reduces use on top

Key attributesCAM2038 overview

83Camurus Capital Markets and R&D Day 2016

CAM2038 has potential to bring significant values to patients, physicians, payors and society

84

• Less supervision of patients

• Improved patient treatment outcomes

• Reduced burden of diversion, misuse and abuse

• Encouraging users into treatment – reducing

societal costs

• Reduced healthcare utilisation

• Improved outcomes potential for less social

welfare and CJ costs

Clear differentiation with several benefits

Current treatment

Value of

CAM2038CAM 2038

Value

Benefits to health care systems, society and patients suggests that the value CAM2038 can

bring can be realised through robust HEOR and wider value demonstrating programmes

Country Physicians willingness to prescribe CAM20381 % patients*: q4w q1w

85

Majority of clinicians identify patients suitable for CAM2038

Large markets with high willingness to prescribe weekly and monthly depots

86%

94%

86%

96%N=50

Source. 1. Market access dynamics in opioid addiction, Decision Resources 2015 * % patients prescribers thought would be prescribed CAM2038 of those currently prescribed medication

N= 47

31%

30%

36%

25%

N= 4843%

27%

39%

22%

N=51

N=50

N=50


CAM2038 addressing unmet need for patients and users

86

Problem

Opioid

Users

Patients

currently

in treatment

Users out of

treatmentUsers starting

new

treatment

journey

Users willing

to enter with

new treatment

option

Users not

Accessing

treatment

Users not entering treatment due to impact on daily life

“Recycling” users entering new patient journey or naïve patients

• Motivated patients ready for change

• Patients in treatment wanting reduced burden of treatment

• Patients struggling with compliance/adherence

Illustrative

Users not

recycling

Rationale for own commercialization of CAM2038 in Europe

87

Positive market drivers support pricing strategy and reimbursement on European markets

Specialist market

~700 000 patients in treatment

CAM2038 addresses unmet need

Sizeable socio-economic benefits

On-going paradigm shift

Accessible and concentrated

market

Cost efficient roll-out and

creation of significant value

Rationale Overview of market rights and Camurus’ primary markets

Braeburn exclusive markets Braeburn option right Camurus markets


Building the commercial organization – stage 1 completed

• Strong and internationally experienced leadership

team

‒ Specialist pharma leadership

‒ Market access

‒ Medical affairs

‒ Global strategy

‒ Opioid use disorder & pain

• Stepwise build – right time, right place principles

88

2016

• EU leadership team

• GMs in early reimbursed markets

• Pricing, market access, medical affairs

2017

• Regional leadership teams early reimbursed markets

• GMs 2nd wave markets

2018

• Regional leadership teams 2nd

wave markets

• Full key account teams for CAM2038 launch

Strategic pre-commercialisation focus 2017

Country operating models

Establish subsidiaries Establish specialist teams Patient access

Strategic marketing & building the brand

Understand the market Awareness Differentiation Communication

Medical affairs

KOL development programs Medical education Building the evidence base

HEOR, pricing and market access

Policy Pricing Market Access HEOR/SEOR

CAM2038 – first step in Camurus commercialisation strategy to create value

• CAM2038 commercial organisation is the

basis for the future expansion of the

portfolio of marketed products

• Retain commercial rights for product

assets within Camurus focus

areas/commercial model

‒ Areas of unmet need and high value

‒ Concentrated treatment systems

‒ Cost efficient roll-out

‒ Potential synergies to leverage existing

infrastructure

• Seek product partnerships

‒ Adjacencies to portfolio

‒ Meets commercial model

90

Product partnerships In-house products

Commercialisation strategy will create value

through in house products and partnerships

Secure

com

merc

ial rights

Re

tain

co

mm

erc

ial rig

hts

Leverage Camurus commercialisation organisation for roll-out of new product candidates


Our vision Provide all patients suffering

from opioid dependence

access to the most effective

treatments for improving

outcomes and quality of life

Advancing the pipeline

Late & early stage projects update

92

Fredrik Tiberg, PhD, CEO and Head R&D

93

Late-stage, diversified pipeline with block-buster potential

PARTNERS PRODUCT PRECLINICAL PHASE 1/2 PHASE 3 REGISTRATION

CAM2038 Weekly Opioid dependence

CAM2038 Monthly Opioid dependence

CAM2038 Weekly Chronic pain

CAM2038 Monhly Chronic pain

CAM2029 Neuroendocrine tumours

CAM2029 Acromegaly

CAM2032 Prostate cancer

CAM4071 Not disclosed

CAM2047 CINV

CAM2048 Pain

CAM2058 Pain & nausea and vomiting


Chronic pain is a common condition with large impact on qualityof life

• Chronic pain is defined as pain lasting longer

than 3 months

• About 20% of the population suffer from chronic

non-cancer pain1

• Major chronic pain segments in 20142:

‒ More than 70 million people in the US and Europe an

suffer from chronic low back pain

‒ 63 million people suffer from arthritis pain

• Chronic pain has a detrimental impact on QoL3

‒ For 2/3 the pain inflicting on sleep

‒ 50% report difficulties with household tasks

• Global opioid analgesics market worth

$22 billion in 2014, anticipated to reach 28 billion

in 20212

Sources. 1. Pain Practice 2014, 14, 79–94 2. Disease Landscape and Forecast Chronic Pain, Decision Resources 2015 3. Persistence Market Research 2016

Fibromyalgia Chronic daily headache

Cancer pain

Postherpetic neralgia

Chronic low back pain

Chronic Migraine

Rheumatoid Arthritic Pain

Osteoarthritic pain

Painful diabetic neuropathy

Buprenorphine is an effective analgesic with an unique pharmacological profile

• Treating broad spectrum of pain with various etiologies

• Demonstrated analgesic potency at least 30 times higher than that of morphine

• Associated with lower analgesic tolerance – dose escalation and hyper-algesia

• Less constipation than other potent µ-agonists, and does not adversely affect the sphincter of Oddi

• Improved safety versus full µ-agonists with ceiling effect at higher doses minimizes risk of respiratory depression

• Reduced risk of dependence, misuse and diversion corroborated long-acting

95

Buprenorphine offers effective pain treatment with established safety profile and reduced abuse liability

OpioidGI safety –

constipationCNS – Sedation

Respiratory

distress

Immune

suppressionTolerance Addiction Hyperalgesia

Morphine Yes Yes

Oxycodone Yes

Hydromorphone Yes

Fentanyl TD Yes

Methadone

Buprenorphine

TD/SL Limited

Anti-

hyperalgesia

Source: Journal of Pain Research 2015:8 859–87

Ongoing phase 3 study in chronic low back pain patients. Randomized, double-blind, placebo-controlled, enriched-enrollment withdrawal design (Nest.=340)


Screening Transition Double-Blind treatment Follow-Up

2 Weeks Upto 10 Weeks 12 Weeks 4 weeks

Moderate tosevere lowerback pain on

high daily dose of opioids(incl SL BPN)

CAM2038 q1w8-32 mg/week

Titrated to effecton a stable dose of

CAM2038

CAM2038 Placebo

CAM2038 q1w 8 -12 mg/day orCAM2038 q4w 64-128 mg/day

R

Open-label titration

2 Weeks

Down-titrationof opioid dose and

transitionedto IR morphine

(only if noton SL BPN)

Primary and key secondary endpoints:

Worst and average pain intensity as measured by 11-point

numerical rating scale

Significant potential in converting Sandostatin® LAR ® patients to CAM2029

CAM2029 for treatment of acromegaly and neuroendocrine tumors

• Acromegaly is a rare, chronic and insidious

hormonal disorder

‒ Occurs when the pituitary gland produces excess growth

hormone (GH) and insulin-like growth factor-1 (IGF-1)

‒ Current gold-standard medical treatment include

somatostatin analogues

• Neuroendocrine tumors (NETs) are malignant

neoplasms

‒ Somatostatin analogues constitute the current standard of

safe and effective medical therapy for symptom control

‒ Somatostatin analogues also show anti-tumor effects

Overview of acromegaly and NET Strong market growth over 15 years1

Source1. Medtrack

97

2015

1 802

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Sandostatin® (Novartis) Somatuline® (Ipsen)

Sandostatin® : 7%

Somatuline® : 16%

(USDm)

CAGR 2004-2014:

339 412

488

607 695

917 998 1 031

1 169

1 300 1 350

1 516

1 705

1 917

2 032 2 069


CAM2029 is a convenient, safe and effective treatment option


Easy subcutaneous administration

using prefilled syringe

Self-administration option with significant

convenience benefits and cost savings

Increased bioavailability (500%) with potential for

enhanced treatment efficacy1

Thin needle and small injection volumes

Room temperature stability avoiding cold chain

distribution and conditioning before use

Key attributesCAM2029 overview

1. Novartis Q2 and H1 Condensed Interim Financial Report

2. Tiberg F, Roberts J, Cervin C, et al. Br J Clin Pharmacol. 2015;80:460-472.

• Ready-to-use, long-acting octreotide for

treatment of acromegaly and neuroendocrine

tumors (NETs)

• Exclusive partnership with Novartis

‒ "Novartis Oncology continues its commitment to

developing a new formulation of octreotide through a

collaboration with Camurus”

• Positive Phase 2 results

‒ Control of symptoms and disease markers

• Planned start of Phase 3 in 2017

CAM2029 supported by comprehensive clinical program

HS-05-194

Phase 132 volunteers

HS-07-291


HS-11-411


Trial no. Subjects Key results / Study design Status

Rapid and long-acting release of octreotide

and suppression of IGF-1. Dose proportional

octreotide exposure with 5 times higher bio-

availability compared with Sandostatin LAR 30 mg.

Dose proportional octreotide exposure during

repeated dosing of CAM2029 mg.

Rapid and long-acting release of octreotide.

Rapid and long-acting release of octreotide One

month suppression of the growth factor IGF-1.

HS-12-455

Phase 2

12 patients in two

groups with

acromegaly and NETs

Positive results

Phase 3Two Phase 3 trials of CAM2029 versus active control, Sandostatin® LAR®, in patients with

neuroendocrine tumours (NETs) and acromegaly, respectively (Global)

3 trials in preparation,

start in 2017

Good safety

and local

tolerability

demonstrated

in all trials

Randomised multi-centre study of the pharmacokinetics,

pharmacodynamics, efficacy and safety of CAM2029 in two

patients groups with acromegaly and neuroendocrine tumours

(NET) previously treated with Sandostatin® LAR®


Positive topline Phase 2 results announced in 2016

• Multicenter, randomized study of CAM2029 in

patients with functioning NETs and

acromegaly previously treated with

Sandostatin LAR

• Characterize the PK profile and to assess the

efficacy, safety and tolerability of CAM2029

verus Sandostatin® LAR®

• 16 week study including switch from

Sandostatin® LAR® to CAM2029 after Week 4


• CAM2029 provided high sustained plasma

octreotide exposure in both patient

populations over 4-week dosing interval

• The control of disease biomarkers and

symptoms were maintained or improved

when switching from Sandostatin® LAR®

• Both treatments were well tolerated

• Detailed results to be presented at

international conferences and in a peer

reviewed publication during 2017

Phase 2 study design Topline Phase 2 results for CAM2029

No reconstitutionCAM2029 10, 20 mg

0.5 -1.0 mL/ready-to-use/

no reconditioning/room temperature

Based on FluidCrystal® system

Sandostatin® LAR® 10, 20, 30 mg

2.0 mL/reconstitution/

refrigerated/30-60 min reconditioning

Based on PLGA microsphere system

Somatuline® Autogel® 60, 90, 120 mg

0.2-0.5 mL/ready-to-use/refrigerated

≥ 30 min reconditioning

Self-associated gel

Small volume

Thin needle

≥22G

20G

18G/19G

Subcutaneous

(12.5mm)

Intramuscular

(40mm)

Deep subcutaneous

(20mm)

Note: 1) Illustrative. Final product configuration may be different.

Ready-to-use in prefilled syringe with small needle


Early stage pipeline

102

Markus Johnsson, PhD, VP Pharm. Dev.


Selection criteria for growing our pipeline

Unmet medical need

• Patients and prescribers in focus

• Better treatment outcomes; convenience, compliance,health care cost savings

Technology match

• Value creation by use of FluidCrystal®

technology platforms

• Technology fit (solubility, stability, and in vitro and in vivo release)

Expeditious clinical development and market registration

• 505(b)(2) registration pathway

• Accelerated approvals

Patent protection

• Existing platform patents

• Product patent opportunities

Attractive market

• Potential for pricing and reimbursement

• Concentrated customer base, prescribers

• Large market potential

• Commercial synergies


Camurus’ development engine supporting different strategicdirections

Compounds Preclinical assessment Clinical development and commercial strategy

In-house

innovation

Established

APIs

Partner

initiated

Partner

NCEs

Own development & commercialisation

and licensing partnerships

Partner development and commercialisation

supported by Camurus R&D

Camurus development

Early stage projects


Project Product Indication Development

status

Near-term

development

milestone

CAM2047 granisetron FluidCrystal®

injection depot

Prevention of

chemotherapy-induced

nausea and vomiting

(CINV)

Phase 1 ongoing Results Q2 2017

CAM2048 buprenorphine

FluidCrystal® injection

depot

Pain Phase 1 ongoing Results Q2 2017

CAM2058 granisetron /

buprenorphine

FluidCrystal® injection

depot

Pain, nausea and vomiting Phase 1 ongoing Results Q2 2017

CAM2043 treprostinil FluidCrystal®

injection depot

Pulmonary Arterial

Hypertension (PAH)

Pre-clinical Bridging toxicology

program finalized

Q1 2017

CAM2043 is a novel sustained release trepostinil under development for treatment of pulmonary arterial hypertension

• Pulmonary arterial hypertension (PAH) is a

progressive, life-threatening disease

• Orphan indication of 15-50 cases per million

‒ Fewer than 200 treatment centers in the US

• PAH market exceeded 4 billion USD with

aggregated trepostinil product sales of about

1.1 billion in 2015

‒ Remodulin (United Therapeutics) sales of ~$572

million in 2015, ~12% CAGR1


• Limitations of current parenteral treatments

‒ Infusion site pain in 85% of patients

• Treatment limiting in 8% of patients

‒ Infections and sepsis relating to administration by

continuous infusion

‒ Need for extra-corporal pump device limiting

convenience and quality of life

• Requiring programming, drug dilution and filling

with associated complications in 28% of patients

• Pump not water resistant

• Includes meta-cresol preservative

Source: 1. PharmaCircle

CAM2043 has multiple potential treatment benefits versusparenteral infusion for PAH patients

• CAM2043 is a convenient subcutaneous depot

‒ E.g. weekly SC dosing

‒ Individualized treatment

• Steady exposure levels adjustable by dose

‒ In dose range of current products

‒ Maintain efficacy of parenteral products

• Potential for improved local tolerability

‒ Injection site pain and local reactions

‒ Risks of infections and sepsis

‒ No need for meta-cresol preservative


• CAM2043 pharmacokinetic profile

Time (hours)

24 48 72 96 120 144 168

Pla

sm

a T

PN

con

c (

ng

/mL)

0,1

1

10

100

treprostinil SC 22.5mg

treprostinil SC 30 mg

Source: Company data (dog PK)


Conclusion

PARTNERS PRODUCT EVENT TIME

CAM2038 Opioid dependence Phase 3 study results, long-term safety trial

NDA & MAA submissions

Q1, 2017

Mid-2017

CAM2038 Chronic pain Phase 2 results

Phase 3 efficacy results

Q1, 2017

H2, 2017

CAM2029 Acromegaly & NET Phase 3 trial initiations, NET & acromegaly 2017

CAM2047 CINV Phase 1 study results Q2, 2017

CAM2048 Pain

CAM2058 Pain, nausea and vomiting

Phase 1 study results

Phase 2 study initiations

Q2, 2017

Q2, 2017

Early partnerships Start of Phase 1 trial for weekly setmelanotide 2017

New program CTA approval 2017

109

Significant news flow expected during 2016-17


Conclusions

• De-risked, late-stage, differentiated pipeline

‒ Opioid addiction, pain, cancer and acromegaly

‒ Successful Phase 3 study results in addiction

‒ Attractive multi-billion dollar specialty pharmaceutical markets

‒ Concentrated prescriber audiences and active patient advocacy groups

• Strong collaborations with dedicated partners

‒ Novartis, Braeburn Pharmaceuticals, Rhythm, Solasia, R-Pharm US

• Several levers for pipeline and business expansion

‒ New product candidates entering clinical development

‒ Growth opportunities via proven technology platforms and business development

• European commercial organisation

‒ Leadership team established

‒ Pre-launch activities for CAM2038 ongoing

• Solid financial position


Camurus AB, Ideon Science Park, SE-223 70 Lund, Sweden

[email protected] www.camurus.com

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