annual report 2020 - seeking alpha
TRANSCRIPT
1
Annual Report 2020
Press & Analyst Conference Call
Martinsried, 25 March 2021
2
Forward looking statements disclaimer
All of the information herein has been prepared by the Company solely for use in this presentation. The information contained in this presentation has
not been independently verified. No representation, warranty or undertaking, express or implied, is made as to, and no reliance should be placed on,
the fairness, accuracy, completeness or correctness of the information or the opinions contained herein. The information contained in this
presentation should be considered in the context of the circumstances prevailing at that time and has not been, and will not be, updated to reflect
material developments which may occur after the date of the presentation. The Company may alter, modify or otherwise change in any manner the
content of this presentation, without obligation to notify any person of such revision or changes.
This presentation may contain certain forward-looking statements and forecasts which relate to events and depend on circumstances that will occur
in the future and which, by their nature, will have an impact on the Company’s business, financial condition and results of operations. The terms
“anticipates”, “assumes”, “believes”, “can”, “could”, “estimates”, “expects”, “forecasts”, “intends”, “may”, “might”, “plans”, “should”, “projects”, “will”,
“would” or, in each case, their negative, or other variations or comparable terminology are used to identify forward-looking statements. There are a
number of factors that could cause actual results and developments to differ materially from those expressed or implied in a forward-looking
statement or affect the extent to which a particular projection is realised. Factors that could cause these differences include, but are not limited to,
implementation of the Company’s strategy and its ability to further grow, risks associated with the development and/or approval of the Company’s
products candidates, ongoing clinical trials and expected trial results, technology changes and new products in the Company’s potential market and
industry, the ability to develop new products and enhance existing products, the impact of competition, changes in general economy and industry
conditions and legislative, regulatory and political factors. While we always intend to express our best judgment when we make statements about
what we believe will occur in the future, and although we base these statements on assumptions that we believe to be reasonable when made, these
forward-looking statements are not a guarantee of our performance, and you should not place undue reliance on such statements. Forward-looking
statements are subject to many risks, uncertainties and other variable circumstances. Such risks and uncertainties may cause the statements to be
inaccurate and readers are cautioned not to place undue reliance on such statements. Many of these risks are outside of our control and could cause
our actual results to differ materially from those we thought would occur. The forward-looking statements included in this presentation are made only
as of the date hereof. We do not undertake, and specifically decline, any obligation to update any such statements or to publicly announce the results
of any revisions to any of such statements to reflect future events or developments.
3
Medigene – Key messages
Prof. Dolores J. Schendel
CEO & CSO
Focus on innovative T cell-based immunotherapies
Excellence in TCR discovery
Healthy TCR repertoires screened: scale & speed
Optimal TCR properties: avidity & specificity
Antigen targets of choice
Excellence in functional enhancements of therapeutic T cells
Resistance to inhibitory tumor microenvironment
Augmented metabolic fitness
New product developmental focus shifted to solid cancers
TCR: T cell receptor
4
Key information
COVID-19 Situation Update
Personnel
Work from home and on-site
Partner Programs
Continued R&D activities at Medigene support partners
Clinical Development
Largely unaffected
Company
Martinsried, near Munich, Germany
~80 employees*
~€30 m cash**
Listing
Frankfurt Stock Exchange (MDG1)
~24.6 m shares outstanding
~€95 m market cap***
Outlook
MDG1011 Phase I trial dose escalation top-line data
expected in 2021
TCR discovery against novel antigens progressing
(UdeM/IRICoR)
Publication of clinical and preclinical data at conferences
Supporting partnered programs progressing towards first
clinical trials
*As of 1 Apr 2021; **As of 31 Dec 2020; ***As of 24 Mar 2021; UdeM: Université de Montréal; IRICoR: Pan-Canadian drug discovery research commercialization center
5
6
Growing immunotherapy pipeline
Project Target Preclinical Phase I Phase II Partner
MDG1011AML, MDS
(PRAME)
MDG10XXSolid tumors
(undisclosed)
bluebird bioUndisclosed
(MAGE-A4)
Cytovant
(CVT-TCR-01)
Synovial sarcoma,
MM, solid tumors
(NY-ESO-1)
DC vaccineAML
(WT-1 / PRAME)
Cytovant
(CVT-DC-01)
AML
(WT-1 / PRAME)
TC
R-T
DC
In preparationCompleted; Ongoing;
AML: Acute myeliod lymphoma; MDS: Myelodysplastic syndrome; PRAME, MAGE-A4, NY-ESO-1, WT1: Tumor antigens; DC: Dendritic cell;
7
MDG1011 – TCR-Ts fighting blood cancer
Target antigen:
PRAME (Preferentially Expressed Antigen in Melanoma)
PRAME is a well-characterized tumor antigen, which is
expressed in many hematological and solid tumor indications
The study:
Combined Phase I/II Study evaluating safety, feasibility and
early signs of efficacy
Indications for the Phase I part:
Acute myeloid leukemia (AML)
Myelodysplastic Syndrome (MDS)
Conditional on Phase I results, progress into Phase II part only
with a partner
ASH poster, 7 December 2020
Other
Phase I
Single defined dose of TCR-T cells/kg
≥1 AML/MDS
(+3)
1x105
(+3)
1x106
(+3)
5x106
(+3)
Up to 1x107
HLA: Human leukocyte antigen, molecule on the cell surface that presents antigens to immune cells
8
9
Medigene’s antigen and epitope selection platform
Addressing diversity
HLA types
Antigen Targets
Expression levels
Cells
Tumors
Healthy tissues
Epitopes
Processing and presentation
Activation of T cells
Immune response optimization
Broadened T cell responses
Clinically relevant epitopes
Multiple epitopes for one HLA-type
Multiple HLAs per antigen
Class I and II HLA presentation
→ Maximized commercial opportunity with simple combinations
Immunogenicity
screening
Target specific activation of T cells
Mass spectrometry
HLA-A*XX HLA-B*XX HLA-C*XX
Engineered reporter cell lines / ‘dark’ TSAs
TSA: Tumor-specific antigen
10
Collaboration to identify ‘dark matter’ antigens
Exclusive collaboration with University of Montréal / IRICoR
In normal cells, non-exomic regions (‘dark matter’) of the genome are not transcribed into proteins. In cancer
cells, some dark sequences are transcribed into peptides which may be recognized by TCRs
These peptides, presented by cancer cells but not healthy cells, are potential tumor-specific antigens (TSAs)
HLA-peptide complexes have been identified by mass spectrometry of freshly resected tumors and
characterized as potential TSAs
Includes peptides from ovarian, breast and lung cancers which were functionally immunogenic but not detected in
healthy tissues
Potential peptide-
HLA ‘dark matter’
antigen candidates
identified by mass
spectrometry of
freshly resected
tumors
Minigene constructs
(incorporating gene
sequences which
encode all peptides per
respective HLA)
DC priming against
TSAs with CD8+ T cells
0.19%
CD137
FS
C
Screening and
identification of
peptide-specificity and
HLA-restriction giving a
list of immunogenic
TSAs and sequencing
of TSA-specific TCRs
Enrichment and single
cell sorting of TSA-
positive target cells
minigene RNA
11
TCR leads from responding T cells of healthy donors
Healthy donors
Prime T cells with
TSA-loaded DCs
Isolate antigen-
specific T cells
Medigene’s Approach
Patient TIL or PBL
Search for TSA-specific
T cells
Standard Approach
Identify TSAs
for vaccine use or isolate
T cells for TCR-based
therapies
Dependent on pre-existing T
cell responses in patients
Patient-independent by use of
T cells of healthy donors
Identify TSAs
for vaccine and TCR-based
immunotherapies
No need
for patient
T cells
(TIL or PBL)
tumor & normal tissue
Identify mutations
by NGS
Define potential TSAs
(Binding of epitopes to
selected HLAs)
Neoantigen Identification
normal
tissue
TIL: Tumor-infiltrating lymphocyte; PBL: Peripheral blood lymphocyte; NGS: Next-generation sequencing
12
Efficient TCR discovery – At scale and at speed
TCR leads
Functional
selection
Expansion of single
T cell clones
Multiple healthy donors
used for primings with
DC-T cell co-cultures
Antigen selection
High throughput automation
Highest level of standardization and
reproducibility:
Automatic well screening
Tens of thousands of screened
clones
Thousands of specific T cell
clones characterized
Fast isolation of high avidity TCRs
Natural TCRs without mutations for
higher safety
TCRs for all HLA-A, -B and -C alleles
Tens of thousands
of clones screened
Thousands of clones
characterized
Tens of clones fully
characterized and
sequenced
13
Overcoming inhibitory signals
in the tumor milieu through
additional co-stimulation
and reduced inhibition
Overcoming inhibitory signals
in the tumor milieu through
additional co-stimulation
and reduced inhibition
Advancing towards solid tumors –
Co-stimulatory switch receptor PD1-41BB
Inhibition
Exhaustion
Apoptosis
Effector functions
Survival
Longevity
Impact on T cell
Impact on T cell
Apoptotic tumor cell
Hypo-active T cell
T
T
T T
Tumor
cell
Tumor
cell
Tumor
cell
Inhibition
Activation
A
TC
A
TC
14
Expression of PD1-41BB in TCR-Ts leads to improved
repetitive killing capacity
• TCR-T cells expressing PD1-41BB – improved killing of PD-L1-positive tumor cells.
• PD1-41BB overcomes the inhibitory signal delivered via the PD-1/PD-L1 checkpoint pathway.
• TCR-T cells expressing PD1-41BB – improved killing of PD-L1-positive tumor cells.
• PD1-41BB overcomes the inhibitory signal delivered via the PD-1/PD-L1 checkpoint pathway.
Images of TCR-T cells expressing PD1-41BB_TCR I or TCR I only in co-culture with PRAME-positive and PD-L1-positive tumor cells (red-labelled) recorded at the indicated time points. Tumor cell killing
mediated by TCR-T cells is evident by the reduction of red-labelled cells. The arrows indicate addition of a new tumor cell spheroid simulating repeated exposure of TCR-T cells to tumor cells.
15
Summary: Enhanced TCR-Ts for solid tumors
Excellence in TCR selection
Exclusive access to selected target antigens in new class (UdeM/IRICoR)
TCR repertoires from healthy donors as source of TCRs
Assay tree to select optimal target-specific TCRs
Potency – high avidity – low density peptide-HLA per target cell
Safety/specificity – exhaustive assessment to minimize potential cross-reactivity
Functional enhancement of TCR-Ts through PD1-41BB
Checkpoint pathway – inhibition turned into activation
Antigen specific activity
Metabolic fitness
TCR-Ts able to function in hostile tumor microenvironment
Duration of activity
TCR-Ts able to kill repeatedly over many cycles
Longevity of TCR-Ts to favor sustained clinical responses
16
17
Partnerships validate Medigene’s technologies
bluebird bio
TCR discovery projects for multiple antigen/HLA
combinations
Worldwide development and commercial rights and
exclusive license for IP
First TCR lead for MAGE-A4/HLA-A2 in preclinical
development
MDG eligible for R&D funding, development,
regulatory and sales milestones and tiered, up to
double digit % royalties
Roivant / Cytovant
Research-stage TCR specific for the target
NY-ESO-1; clinical indications chosen
DC vaccine program for AML
Discovery projects for 2 further TCRs tailored for
Asian population
Regional license rights for Greater China, South
Korea and Japan
MDG eligible for R&D funding, development,
regulatory and sales milestones and tiered, up to
double digit % royalties
18
Financial outlook
Cash and cash equivalents as of 3 ec 2020 amounted to ~€30 m
No milestone payments or cash inflows are included from existing or future partnerships or
transactions
Medigene has sufficient financial resources to fund business operations into Q3 2022
Guidance 2020 FY 2020 Guidance 2021
Total revenues €7-9 m €8.8 m €7-9 m
R&D expenses €22-26 m €22.3 m € -20 m
EBITDA loss € 7-24 m €22.2 m € 0-17 m
19
Key messages
Medigene to build value through tightly focused operations and focus on solid cancers
Proprietary programs
Complete MDG1011 Phase I dose escalation trial
Focused on next-generation TCR-T therapies with T cell enhancement
TC s against novel class of shared cancer antigens (‘dark matter’)
Partners
Supporting partnered programs progressing towards first clinical trials
Business development
Continue to support collaborations with bluebird bio and Roivant/Cytovant
Global outreach for additional partnerships
Financials
Cash runway into Q3 2022
20
21
Medigene AG
Lochhamer Str. 11
82152 Planegg / Martinsried
Germany
T +49 89 2000 33 0
F +49 89 2000 33 2920
www.medigene.com
© Medigene AG
Contact
Dr. Gary Waanders
VP Investor Relations
+49 89 2000 3333 01
Dr. Anna Niedl
Director Investor Relations
+49 89 2000 3333 01