Company Presentation February 2016 - MOLOGEN AG · Market lefitolimod (MGN1703) – Cancer...

MOLOGEN AG

Company Presentation

February 2016

© 2016 1

MOLOGEN AG

Agenda

Business Overview

Market

Lefitolimod (MGN1703) – Cancer Immunotherapy

MGN1601 – Therapeutic Vaccination against Cancer

EnanDIM – New Generation of Immunomodulators

Key Financials and Outlook 2015

Appendix

© 2016 2

MOLOGEN AG

MOLOGEN Snapshot

• Based in Berlin, Germany; founded 1998

• ~ 60 employees

Management Board

Extensive expertise and experience in the biotechnological and

pharmaceutical industry

Co-founder of biopharmaceutical company PAION AG, Germany

Long-standing and extensive expertise in the pharmaceutical industry

(e.g. Roche)

Worked as Medical Advisor at the European Organization for Research

and Treatment of Cancer (EORTC) in Brussels, Belgium

Dr. Mariola Soehngen, CEO (since Nov 2015)

Dr. Alfredo Zurlo, CMO (since Apr 2013)

© 2016 3

MOLOGEN AG

MOLOGEN Shares

24%

6%

6%

5%

5%

54%

Global Derivative Trading GmbH

Baloise Holding

Deutscher Ring Krankenversicherungsverein a.G.

Salvator Vermoegensverwaltungs GmbH

Deutsche Balaton Aktiengesellschaft

Freefloat

• ISIN DE0006637200

• Shares issued: 22,631,501

• Market capitalization ~ €106m (30 Dec 2015)

• Frankfurt Stock Exchange (Prime Standard): MGN | Reuters: MGNG.DE

© 2016 4

MOLOGEN AG

Close network with scientific

institutions & experts

Biotechnology company with

focus on immunotherapies

• One of the pioneers in

immunotherapies

Highly qualified &

dedicated team

• Long-term experience, in

particular in R&D of DNA- and

cell-based products

Advanced products /

promising pipeline

• Lead product lefitolimod

(MGN1703) in registration study

• Three proprietary immunotherapy

platforms

Highly attractive markets

• Immunotherapies: A new

megatrend

• Cancer treatments: A multi-billion

US-$ market

MOLOGEN AG

Company Overview

© 2016 5

MOLOGEN AG

MOLOGEN’s Proprietary Immunotherapy Platforms

Lefitolimod (MGN1703)

• TLR9 agonist

• In registration study

• Applicable in various

indications:

• Suitable for mono-

and combination-

therapies

• DNA-based, non-viral

vector system: gene

ferries

• Three products in

development:

• MGN1404

(malignant

melanoma)

• MGN1331

(leishmaniasis)

• MGN1333

(hepatitis B)

• Genetically modified

human renal cancer

cell line - using

MIDGE® platform –

combined with low-

dose lefitolimod as

adjuvant

• Phase I/II data

available

• Orphan drug status

Cell-based therapeutic

vaccination (MGN1601)

MIDGE® Vector System

SCLC small cell lung cancer

© 2016 6

MOLOGEN AG

Advanced Product Pipeline with

Strong Focus on Cancer Immunotherapies

Lefitolimod

(MGN1703)1,6

HIV

EnanDIM1

Oncology &

Anti-infectives

Preclinical Phase II Phase III

Lefitolimod

(MGN1703)1

SCLC

Lefitolimod

(MGN1703)1

Colorectal cancer

Phase I

1 TLR9 agonist

2 MIDGE® vector system

3 Cell line modified using MIDGE technology with adjuvant low-dose

Lefitolimod

4 Collaboration with Max-Delbrueck-Center for Molecular Medicine and

Charité Universitaetsmedizin, Berlin

5 Various diseases caused by parasites; mainly present in subtropical and

tropical regions (major neglected disease)

6 Collaboration with University Hospital Aarhus, Denmark

7 Collaboration with MD Anderson Cancer Center, Texas, US; study is

expected to start in H1 2016

Lefitolimod

(MGN1703)1

Other solid tumors

Lefitolimod (MGN1703)1

+ ipilimumab (Yervoy®)7

Advanced solid malignancies

MGN16013

Renal cancer

MGN13312

Leishmaniasis5

MGN13332

Hepatitis B

SCLC small cell lung cancer

MGN14042,4

Malignant melanoma

Oncology

Infectious diseases

Oncology & Infectious diseases

Oncology combination trials

© 2016 7

MOLOGEN AG

Strategic Focus: Outlicensing of Products to Generate

High Returns

High returns in the mid- and long-term

Partnering agreement for

lefitolimod (MGN1703)

Continue clinical development

of MGN1601 Unique proprietary technology

High market potential Ensure funding of lefitolimod

(MGN1703) until filing/approval

Initiate new projects Initiate combi trials; extend and advance

product pipeline: ensure long-term growth

Develop vaccine candidates Support to treat diseases with high unmet

medical need: Leishmaniasis & hepatitis B

© 2016 8

MOLOGEN AG

Agenda

Business Overview

Market





Appendix

© 2016 9

MOLOGEN AG

Oncology Market: Leading Therapy Category

Business Overview

Market

lefitolimod (MGN1703) – Cancer Immunotherapy




Appendix

Worldwide Prescription Drugs in US$ billion Worldwide Oncology Drugs in US$ billion

• Pharmaceutical Industry struggled with

weak economic growth in recent years

• “Patent cliff” overcome

• Major therapy category

• Highest growth rate & strongest sales

increase worldwide in the long-term

• Immunotherapies represent emerging

field => new mega-trend with

US$ 35 billion market potential

717

1,017

2013 2020

CAGR

+5.1%

73

153

2013 2020

CAGR

+11.2%

Source: EvaluatePharma 2014 | CAGR Compound Annual Growth Rate

© 2016 10

MOLOGEN AG

Colorectal and Lung Cancer: High Growth Expected

Colorectal Cancer Sales in US$ billion1 Lung Cancer Sales in $US billion2

• Launch of premium-priced adjuvant /

maintenance therapies will extend first-

line treatment

• Most common cancer worldwide in terms

of incidence and death

• High income countries have more than

double the lung cancer incidence of low

income countries

5

8

2013 2023

CAGR

+4.9%

4

13

2010 2020

CAGR

+12.5%

1 5EU, US, Japan & China; Source: GlobalData Nov 2014 | 2 G7 Countries; Source: MarketsandMarkets Nov 2011 |

CAGR Compound Annual Growth Rate

© 2016 11

MOLOGEN AG

Incidences Oncology1 Incidences by Oncology indication 20122

• Aging populations will increase incident

case rates in all markets covered

• Cancer rates for all cancers combined

rise with increasing levels of country

income

• Total number of estimated cancer

cases: 14.1 million

Oncology Market: Sharp Increase of Incidences

14m

20m

2012 2025

+40% 1.8m

1.7m

1.4m 9.2m

Lung

Breast

Colorectum

Other

1 World, Source: IARC “World Cancer Report 2014“ | 2 World, Source: WHO GLOBOCAN 2012 (IARC)

© 2016 12

MOLOGEN AG

Cancer Immunotherapies: New Megatrend

Science Magazine:

“Breakthrough of the Year 2013“

US$ 35,000,000,000

market potential*

*Source: Citi-Bank 2013 – estimated peak sales

© 2016 13

MOLOGEN AG

Immunotherapy: Superior Treatment Immunotherapy: Superior Treatment

Chemotherapy

• Fast effect in many patients

• Effect not lasting

Immunotherapy

• Needs time to be effective

• Long-lasting effect in a minority

of patients

Control

group

Chemotherapy

time

Patients

alive in %

Immunotherapy

Control

group time

Patients

alive in %

Source: "Immuno-oncology: The new weapon in the war against cancer”, Alistair Campbell; Berenberg Equity Highlights, February 2014

10%

© 2016 14

MOLOGEN AG

Agenda

Business Overview

Market





Appendix

© 2016 15

MOLOGEN AG

Lefitolimod (MGN1703): ‘Best in Class’ TLR9 Agonist

• Activation profile and chemical structure supports application in

cancer therapy

• High dosing over long periods of time without major toxic effects

• Clinical strategy optimized for lefitolimod (MGN1703) TLR9

activation pattern

Light blue area: recognized by TLR9 receptor

Maximized probability of success compared to other TLR9 agonists

© 2016 16

MOLOGEN AG

Activating the Immune System to Fight Cancer

mDC myeloid dendritic cell | NK cell natural killer cell | NKT cell natural killer T cell | pDC plasmacytoid dendritic cell

Cancer

patient

© 2016 17

MOLOGEN AG

IMPACT – Phase II Study in Colorectal Cancer

Generated Sustained Long-Term Responses

• Primary endpoint met: Progression free survival

• Secondary endpoint “Overall Survival”: Median OS 22.6 (lefitolimod (MGN1703))

vs. 15.1 months (p=ns)

• Predictive biomarkers identified: Tumor reduction by induction therapy, CEA level,

presence of activated NKTs

• Follow-up of four patients who continued MGN1703 treatment in compassionate use

programs since no relapse at end of study:

Three patients progression-free in excess of 47-55 months as of August 2015

Excellent safety and tolerability, also when treated long-term

Findings from subgroup analyses were used to optimize the phase III study design

CEA carcinoembryonic antigen - a tumor marker for colorectal cancer | NKT Natural Killer T cells | ns not significant

© 2016 18

MOLOGEN AG

IMPACT – Sustained Efficacy

April 2010: Patient 049 – Initial diagnosis

• Colon carcinoma with multiple liver metastases

December 2010: After induction chemotherapy

• 06/2010 - 11/2010: 9 courses of CT (FOLFIRI) +

bevacizumab (biologic)

• 12/2010: Response to induction CT: PR*

March 2015: Under maintenance therapy

• Since 12/2010: Lefitolimod (MGN1703) maintenance

therapy

• New PR* after 9 months

• Still ongoing PR (46 months as of August 2015)

• Good medical condition, mild local skin reactions, no

further toxicities

CT chemotherapy | PR partial response | *confirmed by two independent radiologists

© 2016 19

MOLOGEN AG

Lefitolimod (MGN1703) – Ongoing Clinical Trials

IMPALA IMPULSE TEACH

• Pivotal trial

(phase III)

• 540 patients

• 8 European

countries:

Austria, Belgium,

Estonia, France,

Germany, Italy,

Spain, UK

• Currently

Recruiting

• Randomized

study

• 100 patients

• 4 European

countries:

Austria, Belgium,

Germany, Spain

• Recruitment

completed (Oct

2015)

• Early Stage

Study (phase I)

• 16 patients

• Denmark

• Recruitment

completed (Sep

2015)

Metastatic Colorectal

Cancer (mCRC)

Small Cell Lung

Cancer (SCLC) HIV

(Infectious Disease)

Combination trial

• Lefitolimod

(MGN1703)

+ ipilimumab

(Yervoy®)

• Early Stage

Study (phase I)

• 50-60 patients

• Texas, US

• Study expected

to start in H1

2016

Advanced solid

malignancies

© 2016 20

MOLOGEN AG

IMPALA – mCRC Pivotal Phase III Study Started

in Sep 2014

PD

Lefitolimod

(MGN1703)

Maintenance Re-Induction

Trial Treatment Period

Induction CT

12–30 weeks

Standard first-line

CT for mCRC

PR/CR

Responder

Screening/

Randomization

1:1 Control

group PD

Lefitolimod

(MGN1703)

with

induction CT

Induction

CT

PD

Start of

2nd line

• Primary endpoint: Overall survival

• Open-label, randomized, controlled, two-arm, multinational phase III trial

• 540 patients in around 120 sites in eight European countries, including Top 5 European

pharma markets

• Biomarkers used as stratification factors: CEA level and NKT activation

CT chemotherapy | CR complete response | PR partial response | PD progressive disease | mCRC metastatic colorectal cancer |

CEA carcinoembryonic antigen - a tumor marker for colorectal cancer | NKT Natural Killer T cells

PD

© 2016 21

MOLOGEN AG

IMPULSE - SCLC Randomized Study

• Primary endpoint: Overall survival

• Randomized, controlled, two-arm, multinational trial with 100 patients in Belgium, Austria,

Germany and Spain

• Biomarkers used as stratification factors: NSE level and NKT activation

• Patient enrollment completed: end of October 2015

CR complete response | CT chemotherapy | NKT Natural Killer T cells | NSE neuron specific enolase - a tumor marker for lung cancer |

PD progressive disease | PR partial response | SCLC small cell lung cancer

Maintenance


Induction CT

4 cycles of

platinum-based

therapy

Standard first-line

CT for extensive

disease SCLC

PR/CR

Responder

Screening/

Randomization

3:2

Experimental Group:

5th cycle of platinum based

CT followed by lefitolimod

(MGN1703) maintenance

Control Group:

5th cycle of platinum

based CT followed by

local practice

PD

PD

Start of

2nd line

© 2016 22

MOLOGEN AG

TEACH – Early Stage Study in HIV Completed

Recruitment in September 2015

• Collaboration agreement with Aarhus University Hospital, DK

• Aarhus University Hospital conducts the study – funding

received from the American Foundation for AIDS research (amfAR)

• MOLOGEN provides lefitolimod (MGN1703)

• First time to evaluate lefitolimod (MGN1703) in other disease

than cancer

• Top-line results expected Q2 2016

Potential expansion of applications

© 2016 23

MOLOGEN AG

Combination Trial with Lefitolimod (MGN1703) and

Ipilimumab (Yervoy®)

• Collaboration with MD Anderson Cancer Center, US, Texas

• First combination study of lefitolimod (MGN1703) with checkpoint

inhibitor, commercially available ipilimumab (Yervoy®),

manufactured by Bristol-Myers Squibb Co.

• MD Anderson Cancer Center conducts the trial; MOLOGEN

provides lefitolimod (MGN1703) and funding for the trial

• Phase I trial in patients with advanced solid malignancies

Potential expansion of applications

© 2016 24

MOLOGEN AG

Lefitolimod (MGN1703) – Milestones Clinical Trials

IMPALA (mCRC) –

Pivotal study

IMPULSE (SCLC) –

Randomized study

TEACH (HIV) –

Phase I

First patient in (FPI)

Recruitment

completed

Start of primary

analyses

Results

Recruitment started

and completed

Start of primary

analyses; results (H1)

2014

2015

2016

2017

2018

2019

First patient in (FPI)

Recruitment completed

Primary endpoint

analysis (OS)

mCRC metastatic colorectal cancer | SCLC small cell lung cancer I * Study expected to start in H1 2016

End of recruitment

Combination trial –

Phase I

First patient in (FPI) *

© 2016 25

MOLOGEN AG

Conclusion: Late-Stage Product Lefitolimod (MGN1703)

with Unique Profile and Huge Market Potential

Best in class and most advanced in mCRC (pivotal

trial)

Long-term treatment

Usable for various indications (mCRC, SCLC,…)

Superior safety and tolerability

Suitable for mono- and combination therapy

Patient selection via biomarker

Blockbuster

potential

mCRC metastatic colorectal cancer | SCLC small cell lung cancer

Best in class TLR9 agonist and most advanced in

mCRC (pivotal trial)

Long-term treatment

Usable for various indications (mCRC, SCLC,…)

Superior safety and tolerability

© 2016 26

MOLOGEN AG

Agenda

Business Overview

Market





Appendix

© 2016 27

MOLOGEN AG

MGN1601 – Unique Therapeutic Cancer Vaccination

© 2016 28

MOLOGEN AG

ASET Trial with MGN1601: Promising Data

Phase I/II study (12/2010 – 08/2013):

• Open-label, proof-of-principle, multi-center phase I/II trial

• 19 patients with advanced renal cell carcinoma who failed prior

systemic therapies

• Primary endpoint met: Favorable safety and tolerability profile

• Promising overall survival data in subgroup of patients

• Identification of potential biomarkers

© 2016 29

MOLOGEN AG

Agenda

Business Overview

Market





Appendix

© 2016 30

MOLOGEN AG

EnanDIM® – New Generation of Immunomodulators…

• New class of linear TLR9 agonists

Combines advantages of molecules containing only natural DNA

components with benefits from linear molecules

Specific structure protects against degradation - no chemical

modifications needed

• Broad immune activation shown in pre-clinical models

• Potential application in the fields of cancer and anti-infective therapies

© 2016 31

MOLOGEN AG

…Combining Advantages of Two Types of Agonists:

Linear and Not Chemically Modified Structure

• Linear molecules

• Easy and cost-effective production

• Chemically modified structure ( )

Linear

DNA-structure

• Closed, dumbbell-shaped structure

• Only natural DNA components

• Good safety and tolerability profile

• One additional production step

lefitolimod

(MGN1703)

EnanDIM® = Enantiomeric DNA-based ImmunoModulator

New structural feature

Protection against

degradation

• Linear molecules

• No chemical modifications

• Good safety and tolerability profile expected

• Easy and cost-effective production

DNA sequence essential

for function

(so-called “CG motifs”)

© 2016 33

MOLOGEN AG

Key Financials 9M 2015

In € million 9M 2015 9M 2014 ∆

R&D expenses 10.4 10.5 -1%

EBIT -13.3 -13.3 0%

Cash flows from operating

activities -9.0 -11.5 -22%

Cash flows from financing

activities 26.1 14.7 81%

Monthly cash burn 1.3 1.4 7%

• R&D costs almost unchanged

• Monthly cash burn accordingly

• Capital increase reflected in

financing cash flows

• Main items impacted by

capital increase of €28.3 m

gross

In € million 30 Sep 2015 31 Dec 2014 ∆

Total assets 32.7 15.1 117%

Cash & cash equivalents 30.5 13.6 124%

Equity ratio 81% 88% -8%

© 2016 34

MOLOGEN AG

FY 2015: Outlook Confirmed

• Development of product pipeline well on track

Intensify clinical development of lefitolimod (MGN1703):

• Registration study IMPALA: Continue patient recruitment

• Randomized study IMPULSE: Finalize patient recruitment

MGN1601: Plan and prepare continuative study in renal cancer

• Continue partnering discussions

• Increase of R&D expenses due to studies with lefitolimod (MGN1703),

mainly IMPALA

© 2016 35

MOLOGEN AG

• 22 March 2016

Annual Financial Statements and

Annual Report 2015

• 12 May 2016

Quarterly Report as of 31 March 2016

• 31 May 2016

Annual General Meeting

• 11 August 2016

Half-Year Report as of 30 June 2016

• 07 November 2016

Quarterly Report as of 30 September 2016

Claudia Nickolaus

Head of Investor Relations &

Corporate Communications

Phone: +49-30-841788-38

Fax: +49-30-841788-50

[email protected]

www.mologen.com

MOLOGEN®, MIDGE®, dSLIM®, and EnanDIM® are registered trademarks of the MOLOGEN AG

Financial Calendar and Contact Details

© 2016 37

MOLOGEN AG

IMPACT – Phase II Study Design and Results

• Primary endpoint: Progression-free survival

• Double-blind, randomized, placebo-controlled, two-arm, multinational phase II trial with 59 mCRC patients

• Predictive biomarkers identified: Tumor reduction by induction therapy, CEA level, NKT activation

• Start: June 2010 – primary completion date: February 2013

CEA carcinoembryonic antigen - a tumor marker for colorectal cancer | CT chemotherapy | mCRC metastatic colorectal cancer | NKT Natural

Killer T cells | PD progressive disease | s.c. subcutaneous injection | SD stable disease

*at investigators discretion

Maintenance


Induction CT

4.5-6 months

mCRC patients

treated first-line

with FOLFOX /

XELOX or

FOLFIRI +/-

bevacizumab*

At least

SD

Experimental Group:

60mg lefitolimod

(MGN1703)

twice weekly s.c.

No maintenance

Placebo

Twice weekly s.c.

Screening /

Randomization

2:1

PD**

PD**

** Treatment

after PD at

investigators

discretion

© 2016 39

MOLOGEN AG

MGN1601 – ASET Study Design

• Primary endpoints met: safety and tolerability

• Open-label, proof-of-principle, multi-center phase I/II trial

• 19 patients with advanced renal cell carcinoma who failed prior systemic therapies

• Orphan drug designation from EMA

• Start: December 2010 – primary completion date: August 2013

DC Disease Control | EMA European Medicines Agency | i.d. intradermal injection | PD progressive disease | TPP Treatment per protocol

TPP Extension phase

Patients

with

advanced

renal cell

cancer

No

standard

therapy

available

Trial

inclusion

8 applications

of MGN1601

in 12

weeks i.d.

DC

Max. 5

applications in

week 24, 36, 48,

72 and 120


DC PD**

PD**

** Treatment

after PD at

investigators

discretion 8 applications

of MGN1601

in 12

weeks i.d.

© 2016 40

MOLOGEN AG

MGN1601 – ASET Study Results

Trial

inclusion

DC DC PD**

PD**

• Median OS: 24.8 weeks (ITT group): 115.3 weeks (PP group)

• Potential biomarker identified

MSKCC Score & NLR may have predictive value for longer OS

First evidence of cytotoxic antitumor immune response after

MGN1601 vaccination (in patient subgroup)

Significant improvement of cellular immune function during treatment

(in patient subgroup)

MSKCC Memorial Sloan–Kettering Cancer Center | NLR Neutrophil-Lymphocyte Ratios

© 2016 41

MOLOGEN AG

Quarterly Key Financials

[in € million] Q3

2015

Q2

2015

Q1

2015

Q4

2014

Q3

2014

Q2

2014

Q1

2014

Q4

2013

Q3

2013

Q2

2013

Q1

2013 2014 2013

R&D expenses 5.2 2.8 2.4 2.8 4.6 3.0 2.9 3.4 1.7 1.4 1.4 13.3 7.9

EBIT -6.4 -3.7 -3.2 -3.8 -5.4 -3.8 -4.1 -4.2 -2.5 -2.0 -2.2 - 17.1 -10.9

Cash flow from

operating activities -4.3 -2.5 -2.2 -4.1 -5.0 -3.3 -3.2 -2.8 -2.3 -1.8 -2.0 -15.6 -8.9

Cash flow from

financing activities 0 26.8 -0.7 -0.2 - -0.1 14.8 - - - - 14.5 -

Monthly cash burn 1.5 1.4 1.0 1.4 1.7 1.1 1.4 0.9 0.8 0.6 0.7 1.4 0.8

© 2016 42

MOLOGEN AG

Q3

Quirin Champ. Frankfurt

HSBC HCC Frankfurt

ASCO Chicago, US

WCLC Vienna

EKF FFM

SITC US New

Harbour

EACR UK

Keystone CA, US

DE Krebs- kongress

Berlin

Scientific Conferences Financial Reporting Investor Conferences Clinical Trials

ODDO Frankfurt

AACR New Orleans, US

ODDO Lyon

Q1

Q2

TEACH Topline results

AGM

IMPULSE Start Primary analyses (OS)

FY 2014

JPM HCC SanFran,

US CROI Conf Boston, US

ASGCT Washington, US

BioEquity, DK

CIMT Mainz ESMO WCGIC

Barcelona Berenberg GS Conf.

MUC

ESMO IO Copenhagen

IMPALA Recruitment completed

Q4

2016

Main Events 2016

Q1 Q2 Q3

CROI Conference on Retroviruses and Opportunistic Infections | ASGCT American Society of Gene Cell Therapy | CIMT Cancer Immunotherapy | EACR European Association of Cancer Research | WCLC World Conference on Lung Cancer | SITC Society for Immunotherapy of Cancer

ASCO GI, SanFran

MOLOGEN AG

Company Presentation

February 2016

Company Presentation February 2016 - MOLOGEN AG · Market lefitolimod (MGN1703) – Cancer...

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