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COMPANY
PRESENTATION
APRIL 2019
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MOLOGEN SNAPSHOT
• Based in Berlin, Germany; founded 1998
• Frankfurt Stock Exchange Prime Standard
• Approx. 50 employees
• One of the pioneers in immunotherapies in
cancer and HIV
• Core expertise: TLR9 agonists
• Lead compound: lefitolimod (phase III for
colorectal cancer, phase II for small-cell lung
cancer, phase I for HIV)
• EnanDIM® technology platform for the
development of additional compounds
Structure of lefitolimod
Structure of EnanDIM®
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TLR9 AGONISTS ACTIVATE BOTH INNATE AND ADAPTIVE
IMMUNE PATHWAYS AGAINST CANCER
• MOLOGEN’s TLR 9 agonists offer:
• Clearly proven mode-of-action in immune stimulation
• Systemic (sub-cutaneous) as well as local (intra-tumoral) administration
• Long-term treatment opportunity due to favorable safety profile
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TLR9 AGONISTS: RATIONALE FOR USE IN ONCOLOGY
• Lefitolimod monotherapy: maintenance therapy after first-line chemotherapy
• Initial chemotherapy leads to decrease in tumor burden and release of tumor-
associated antigens
• Lefitolimod reactivates the immune system to recognize said antigens and initiate
broad systemic anti-tumor response
• Lefitolimod combination therapy with checkpoint inhibitors:
• Checkpoint inhibitors decrease tumor-induced immune suppression but are
efficacious only in presence of sufficient general immune activity
• Lefitolimod causes a broad immune activation upstream of the checkpoint inhibitor
cascade and leads to an inflow of immune cells into tumor tissue (turning “cold”
tumors “hot”)
• Thus, lefitolimod increases therapeutic potential of checkpoint inhibitors
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PRODUCT PIPELINE: FOCUS ON CANCER IMMUNOTHERAPIES
WITH WIDE RANGE OF POTENTIAL INDICATIONS
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LEFITOLIMOD:
MODE-OF-ACTION IN ONCOLOGY
• The patient’s immune system generally polices the development of cancer cells;
Occasionally, cells evade that system, developing into cancer
• Lefitolimod reactivates the patient’s own immune system for anti-cancer surveillance
• Lefitolimod can work safely alongside other treatments leveraging the body’s own immune
surveillance system
Notes: mDC myeloid dendritic cell I NK cell natural killer cell I NKT cell natural killer T cell I pDC plasmacytoid dendritic cell
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Unique Molecular Structure
LEFITOLIMOD:
BEST-IN-CLASS TLR9-AGONIST
Superior Characteristics
Dumbbell-shaped DNA molecule
• No unnatural components due to covalently-
closed structure (116 nucleotides)
• 3 effective non-methylated CG motifs in each loop
• Stability against enzymatic degradation w/o chemical modification
• Unique immunomodulation profile
• Combination of efficacy & safety by design
• Large potential for clinical benefit
Broad immunologic activation combined
with favorable safety profile given lefitolimod’s
specific molecular composition
• Pure natural DNA
• Strong induction of Type I IFN response without triggering generalized inflammatory reaction
• Absence of toxicity seen with other chemically-modified TLR9 agonists
• Broad therapeutic window
• Systemic (s.c.) & intratumoraladministration
• High dosing schedules over prolonged periods of time
• Safety established with more than 20,000
administrations in over 460 subjects to date
Notes: Light blue area Motifs recognized by TLR9 receptor
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LEFITOLIMOD: PHASE II RESULTS IN mCRC SHOW CLEAR
EFFECT ON PFS AND GUIDE PHASE III DESIGN
• Phase II IMPACT trial allowed for optimized design of pivotal phase III
n=43 MGN1703
(n=29)
Placebo
(n=14)
HR=0.40 [95% CI: 0.19-0.84]
Log-rank test p=0.009
Phase 1/2 Solid Tumors
Safety
Pharmacokinetics
Pharmacodynamics
Dosing regimen
Phase 2 IMPACT mCRC
Safety
Pharmacodynamics
PFS signal
Responder characteristics
Phase 3 IMPALA mCRC
Aim: Significant OS benefit
vs standard-of-care
Ongoing, data expected
H2-2019
• Progression-free survival (PFS) in mCRC
patients who responded to first-line
chemotherapy
• Selected as inclusion criteria for Phase III
• Additional potential biomarkers chosen as
stratification factors in Phase III
IRR
, In
dependent
Radio
logic
al R
evie
w
Source: Schmoll et.al. Cancer Res Clin Oncol 2014, 140(9); 1615-1624
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LEFITOLIMOD: PIVOTAL PHASE III IN mCRC
ONGOING TO CONFIRM MEANINGFUL CLINICAL BENEFIT
• Primary endpoint: Overall survival (OS)
• Structure: Open, randomized, controlled, two-arm, multinational
• Size: 540 patients, 122 sites, 8 EU countries
• Readout: After 365 events
• Design: Maintenance therapy in patients with partial or complete response to 1st
line chemotherapy vs. local standard of care
• Timeline: Recruiting completed, readout predicted for H2-2019
PD
Lefitolimod
Trial Treatment Period
Re-Induction
Induction
chemo
12–30 weeks
(Standard
1st line chemo)
PR / CR Screening/
Randomization
Control
groupPD
Lefitolimod
with
induction
chemo
Induction
chemo
PD
Start of
2nd line
PD
Maintenance
Notes: Chemo chemotherapy | PR partial response | CR complete response | PD progressive disease
• IMPALA was designed for achieving regulatory approval on significant OS benefit
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LEFITOLIMOD: SMALL-CELL LUNG CANCER PHASE II SHOWED
POSITIVE RESULTS IN TWO SUBGROUPS OF PATIENTS
• Results provide significant guidance for defining pathway to approval
IMPULSE: Exploratory phase II trial with 103 patients with extensive disease small-cell lung cancer
(SCLC); control group: local standard of care
• Primary endpoint “overall survival” not met in the overall study population
• Positive results in two pre-defined and clinically relevant subgroups of patients with clear overall
survival benefit in comparison to the control arm:
1. Patients with a low count of activated B cells. Hazard ratio: 0.53
2. Patients with reported Chronic Obstructive Pulmonary Disease (COPD),
a frequent comorbidity. Hazard ratio: 0.48
• Final results presented at ESMO 2018 (EUROPEAN SOCIETY FOR MEDICAL ONCOLOGY) and
published in “Annals of Oncology“1
1 Thomas et.al., Ann Oncol 2018, 29(10): 2076-2084
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LEFITOLIMOD: SMALL-CELL LUNG CANCER PHASE II SHOWED
SUBSTANTIAL OS BENEFIT IN CLEARLY DEFINED SUBGROUPS
Overall survival (OS) in a pre-defined patient subgroup – low number of activated B cells
Subgroup characteristics in line with TLR9 mode-of-action
OS is the time after randomization to death. Patients without event are censored at the date of last information available from the patient
23 23 18 13 9 7 4 4 2 0
15 14 10 4 2 1 1 1 0
Patients at riskLEFITOLIMOD (MGN1703)
CONTROL
0 90 183 270 365 455 548 638 730 793 820
Time to Event [days]
0.0
0.2
0.4
0.6
0.8
1.0
Ove
rall S
urv
ival
Censored
CONTROLLEFITOLIMOD (MGN1703)
1.0
0.8
0.6
0.4
0.2
0.0
0 90 183 270 365 455 548 638 730 820
Time to event (days)
Overa
ll surv
ival
LefitolimodControl
23 23 18 13 9 7 4 4 2
15 14 10 4 2 1 1 1 0
Lefitolimod
Control
Patients
at risk
0
793
n=38
Lefitolimod
(n=23)
Control
(n=15)
Median OS
[95% CI]
300.0 days
[189.0; 526.0]
231.5 days
[171.0; 272.0]
HR [95% CI] 0.53 [0.26; 1.08]
• Strong OS benefit in pre-defined subgroup forms basis for future development
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LEFITOLIMOD:
SMALL-CELL LUNG CANCER: OUTLOOK
Next steps
Detailed expert discussions of results and further development options
Design of future development program toward approval in EU & US
• Single-agent maintenance treatment in clearly defined subgroup of SCLC patients
• Combination with checkpoint inhibitors
Scientific advice in EU & US to de-risk / educate development approach
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LEFITOLIMOD: BREAK-THROUGH POTENTIAL FOR
COMBINATIONS WITH CHECKPOINT INHIBITORS
• Lefitolimod is ideally suited to overcome the limitations of checkpoint inhibitor therapy
• In mouse tumor models, combination with lefitolimod clearly improved the anti-tumor
effect of checkpoint inhibitors:
• Increased immune cell activation
• Reduced tumor growth further compared to either compound as monotherapy
• Clearly prolonged survival
• Promising potential for the combination of lefitolimod with checkpoint inhibitors
• First preclinical confirmation of combination of lefitolimod with checkpoint inhibitors in
treatment of cancer
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LEFITOLIMOD AND CHECKPOINT INHIBITORS:
ONGOING AND FUTURE CLINICAL STUDIES
Combination study lefitolimod with ipilimumab (Yervoy®) in solid tumors
• Collaboration with MD Anderson Cancer Center, Texas, US
• First combination trial of lefitolimod with ipilimumab (Yervoy®, Bristol-Myers Squibb)
• Phase I study in patients with advanced solid tumors
• Evaluation of safety and tolerability of combination
• Exploration of efficacy signals and effects on tumor micro-environment
Further combination studies lefitolimod / checkpoint inhibitors in solid tumors
• In advanced planning in cooperation with leading clinical centers
• First results show beneficial effect on tumor micro-environment
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Lefitolimod substantially enhances effect of checkpoint inhibitors in different mouse models
Notes: Experimental details: CT 26 colon carcinoma model, 11 intra-tumoral injections of
lefitolimod, 4 intra-peritoneal injections of mouse-specific aPD-1 antibody
0 10 20 30 40 50 60 70
0
500
1000
1500
2000
2500
3000
Days
Mean
tu
mo
r vo
lum
en
[m
m3]
Lefitolimod + aPD-1
Lefitolimod
ControlaPD-1
0 10 20 30 40 50 60 700
20
40
60
80
100
Days
Su
rviv
al
[%]
Control
aPD-1
Lefitolimod
Lefitolimod + aPD-1
Vehicle
Vehicle
• PRE-CLINICAL SETTING • FIRST CLINICAL RESULTS
LEFITOLIMOD AND CHECKPOINT INHIBITORS:
RESULTS
First results from Phase I trial in combination with
ipilimumab show:
• Increased T cell infiltration into tumor
• No dose-limiting toxicities at maximum dose
• two patients with stable disease
Source: SITC 2018 poster. Reilly et. al. Data from Phase I trial at MD Anderson Cancer
Center
CD8+ T cell infiltration into tumor in 5 patients
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DEVELOPMENT OF LEFITOLIMOD IN HIV
TEACH – Phase I trial with first application of lefitolimod in HIV
• Phase I trial at University Hospital Aarhus, DK (readout summer 2017)
• Activation of relevant immune cell population makes lefitolimod intriguing treatment option
for reduction of viral reservoir in HIV
• Results:
• Remarkable immunostimulatory potency
confirmed
• Lefitolimod enhanced type-I IFN response
in the sigmoid colon, direct proof of systemic
effect without inflammation
• Eradication of HIV viral reservoir in single-agent
setting not achieved
• First clinical trials exploring TLR9 agonists’ potential in fighting HIV
Upregulation of type-I-interferon
induced gene MX1
Lefitolimod induces strong immune
response in colon tissue of HIV
patients
Source: Krarup et.al. Mucosal Immunol. 2017;11(2):449-61.
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DEVELOPMENT OF LEFITOLIMOD IN HIV: FUTURE TRIAL
TITAN - lefitolimod in combination with virus-neutralizing antibodies in HIV
• Collaboration with University Hospital Aarhus and Rockefeller Institute
• Funded by a grant from Gilead Sciences to University Hospital Aarhus
• Planned start: spring 2019
• Aiming to study the combined effect of lefitolimod and broadly neutralizing antibodies
on the viral reservoir in HIV patients
• Potential to make meaningful impact on patients’ lives
• Combining TLR9 agonists and broadly neutralizing antibodies in fighting HIV
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3rd party TLR9 agonists
FOLLOW-UP MOLECULES ENANDIM®:
NEXT-GENERATION TLR9 AGONISTS
• Linear molecules
• Simple, cost-effective
production
• Stability through chemically
modified structure
• Usually unfavorable
risk / benefit ratio
Lefitolimod
• Stability through closed,
dumbbell-shaped structure
• Complex production
• Only natural DNA
components
• Good safety and
tolerability profile
EnanDIM®
• Linear molecules; stability
through specific feature
• Simple, cost-effective
production
• No chemical modifications,
only natural DNA components:
• Good safety and
tolerability profile
expected
Notes: EnanDIM® Enantiomeric DNA-based ImmunoModulator | DNA sequence essential for function (so-called “CG motifs”) |
new structural feature in EnanDIM® providing protection against degradation | phosphorothioate backbone (chemical modification)
• Two lead candidates from EnanDIM® platform technology: one for oncology, one for HIV
• Highly convincing anti-tumor effects in various tumor models as monotherapy and in combination with checkpoint inhibitors
• Start of clinical development planned for 2019
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ENANDIM®: SUMMARY HIGHLIGHTS
EnanDIM® family
• TLR9 agonist platform technology with promising safety profile
• Two distinct lead candidates for separate development in oncology and HIV
• Anti-tumor effect in multiple murine tumor models as single-agent
• Anti-tumor effect of anti-PD-1 enhanced by EnanDIM® in pre-clinical models
• Proven modulation of tumor micro-environment
• Optimal combination partner for checkpoint inhibitors (CPI)
• Enhancement of CPI efficacy → reduction of CPI dose → reduction of toxicity
• Potential to break resistance to CPI → re-sensitization towards CPI
• Status: IND-ready in 2019
• EnanDIM® platform promises broad potential in immunotherapy strategies
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ENANDIM®: PRE-CLINICAL HIGHLIGHTS (I)
EnanDIM® candidates show
• strong enhancement of checkpoint inhibitor effect in different tumor models
EnanDIM® candidates show
• beneficial modulation of tumor micro-environment
Murine model of colon carcinoma (CT26):
Combination of EnanDIM® and aPD-1
improves survival in comparison to aPD-1
monotherapy
EnanDIM® leads to strong infiltration of
T cells into the tumor in comparison to
vehicle control
• EnanDIM® platform offers huge potential in single-agent and combination setting
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• EnanDIM® platform offers huge potential in single-agent and combination setting
ENANDIM®: PRE-CLINICAL HIGHLIGHTS (II)
Induction of persistent anti-tumor immune memory
• EnanDIM® platform offers huge potential in single-agent and combination setting
• EnanDIM® candidates show dramatic anti-tumor effect and induction of sustained
immune memory against tumors in single-agent setting
• Immune memory protection extends beyond the initial challenge tumor cell line!
10 animals were initially inoculated with EMT-6
breast cancer cells. All 8 surviving animals were
protected against re-challenge with EMT-6 breast
cancer cells, and also against a subsequent
challenge with CT26 colon carcinoma cells.
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MGN1601: ALLOGENEIC CELL-BASED CANCER VACCINE
• Allogeneic therapeutic cancer vaccine
• Used off the shelf – no patient-specific CMC needed
• Consisting of
• a proprietary human cancer cell line
• … which is genetically modified fourfold by MOLOGEN’s vector technology MIDGE®
• … and given in combination with MOLOGEN’s TLR9 agonists
• Has shown promising signals in a Phase I/II trial in renal cell carcinoma patients
• Off-the-shelf therapeutic cancer vaccine as novel immunotherapeutic approach
ASET trial: single-arm phase I/II in 19 renal cell
carcinoma patients
• Median OS:
115.3 weeks (per protocol group) vs 24.8
weeks (intent to treat group)
• Two patients had no progression after 12
weeks and continued treatment for more than
48 weeks without progression
• Favorable safety and tolerability profile
Notes: CMC chemistry, manufacturing, and control
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LEFITOLIMOD: LICENSE AGREEMENT WITH ONCOLOGIE
INC. FOR ASIAN TERRITORIES
• Feb 2018: MOLOGEN signed a license and initial co-development agreement with
ONCOLOGIE for lead compound lefitolimod:
• License for China, Hong Kong, Macao, Taiwan, and Singapore
• Co-development: Leveraging innovative biomarker technologies from ONCOLOGIE
• ONCOLOGIE INC. (www.oncologie.international):
• Objective to develop personalized medicine in immuno-oncology
• Dedicated to biomarker-driven development of large and small molecules
• Strong leadership of industry veterans
• Headquartered in Boston, U:S., with operations in Boston and Shanghai
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20%
7%
3%
3%
67%
Global Derivative Trading GmbH, DE
Deutsche Balaton Aktiengesellschaft, DE
SIGNAL IDUNA Krankenversicherung a.G., DE
Axxion S.A., LUX
Freefloat
EXECUTIVE BOARD
AND CURRENT SHAREHOLDER STRUCTURE
Dr Matthias Baumann
CMO
• About 30 years industry expertise
• R&D and corporate leadership positions in
pharma, CRO and biotech
• Boehringer Mannheim, Roche, FOCUS,
NOXXON
Shareholder Structure
as of February 2019 (estimates)
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DISCLAIMER
This presentation does not constitute an offer to buy shares or other securities of MOLOGEN AG and doesnot replace the prospectus. This announcement does not contain or constitute an offer of, or the solicitationof an offer to buy or subscribe for, securities to any person in the United States of America (the “UnitedStates”), Australia, Canada or Japan or in any jurisdiction. The securities referred to in this announcementwill not be and have not been registered under the U.S. Securities Act of 1933, as amended (the “U.S.Securities Act”) and may not be offered or sold in the United States absent registration or an applicableexemption from registration requirements under the U.S. Securities Act. There will be no public offer of thesecurities in the United States. Subject to certain exceptions, the securities referred to in this announcementmay not be offered or sold in Australia, Canada or Japan, or to, or for the account or benefit of, any national,resident or citizen of Australia, Canada or Japan. The offer and sale of the securities referred to in thisannouncement has not been and will not be registered under the U.S. Securities Act or under the applicablesecurities laws of Australia, Canada or Japan. There will be no public offer of the securities in the UnitedStates.
Note about risk for future predictionsCertain statements in this presentation contain formulations or terms referring to the future or futuredevelopments, as well as negations of such formulations or terms, or similar terminology. These aredescribed as forward-looking statements. In addition, all information in this presentation regarding plannedor future results of business segments, financial classification numbers, developments of the financialsituation, or other financial or statistical data contains such forward-looking statements. The companycautions prospective investors not to rely on such forward-looking statements as certain prognoses ofactual future events and developments. The company is neither responsible nor liable for these forward-looking statements. It is not responsible for updating such information, which only represents the state ofaffairs on the day of publication.
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CONTACT
Investor Relations
Phone: +49-30-841788-37
Fax: +49-30-841788-50
www.mologen.com
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COMPANY
PRESENTATION
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