View
0
Download
0
Category
Preview:
Citation preview
Company Update
February 2017
© WILEX AG February 2017
Safe Harbor
2
Forward looking statements
This communication contains certain forward-looking statements, relating to the Company’s business, which can be identified by the
use of forward-looking terminology such as “estimates”, “believes”, “expects”, “may”, “will” “should” “future”, “potential” or similar
expressions or by general discussion of strategy, plans or intentions of the Company. Such forward-looking statements involve known
and unknown risks, uncertainties and other factors, which may cause our actual results of operations, financial condition, performance,
or achievements, or industry results, to be materially different from any future results, performance or achievements expressed or
implied by such forward-looking statements.
Such factors include, among others, the following: uncertainties related to results of our clinical trials, the uncertainty of regulatory
approval and commercial uncertainty, reimbursement and drug price uncertainty, the absence of sales and marketing experience and
limited manufacturing capabilities, attraction and retention of technologically skilled employees, dependence on licenses, patents and
proprietary technology, dependence upon collaborators, future capital needs and the uncertainty of additional funding, risks of product
liability and limitations of insurance, limitations of supplies, competition from other biopharmaceutical, chemical and pharmaceutical
companies, environmental, health and safety matters, availability of licensing arrangements, currency fluctuations, adverse changes in
governmental rules and fiscal policies, civil unrest, acts of God, acts of war, and other factors referenced in this communication.
Given these uncertainties, prospective investors and partners are cautioned not to place undue reliance on such forward-looking
statements. We disclaim any obligation to update any such forward-looking statements to reflect future events or developments.
This material is not intended as an offer or solicitation for the purchase or sale of shares of WILEX AG. This material may not be
distributed within countries where it may violate applicable law.
© WILEX AG February 2017 3
Company Overview
Development of the ATAC
Technology Platform
Financials and Outlook
© WILEX AG February 2017
WILEX at a Glance
4
Frankfurt Stock Exchange:WL6, 4 FTEs
Partnering (WILEX legacy portfolio)
Holding activities (Heidelberg Pharma shares)
(100% subsidiary since 2011, 48 FTEs)
Developing unique, proprietary and innovative cancer therapies
Antibody-Targeted Amanitin Conjugates (ATACs)
Biopharma partnering & proprietary pipeline of ATACs
Preclinical service business
Heidelberg Pharma GmbH
WILEX AG
© WILEX AG February 2017
Management Team with Strong Pharma and R&D
Experience
5
Dr. Jan Schmidt-Brand Prof. Dr. Andreas Pahl
Spokesman of the Executive Management Board since 2014 and CFO since 2012 @WILEX
Managing Director @Heidelberg Pharma since 2001
20 years’ experience in leading positions in the commercial and the fiscal sector of pharma companies
Managing Director of EBEWE Arzneimittel GmbH, an Austrian BASF Pharma subsidiary from 1997 to 2001, prior several positions at the BASF Group
Member of the board of directors of BIO Deutschland e.V. and head of the Finance and Tax working group since 2007
LLD from the University of Mannheim
Head of R&D and Member of the Executive Management Board @WILEX since 2016
Chief Scientific Officer and member of the executive management @Heidelberg Pharma since 2012
20 years’ experience in research and higher education
Head of Late Pharmacology at Nycomed and Takeda Pharmaceuticals from 2008 to 2012
Professor of Pharmacology and Toxicology at the University of Erlangen-Nuremberg (FAU)
PhD in chemistry from the University of Berlin
© WILEX AG February 2017
WILEX Group Fields of Business
6
REDECTANE® RENCAREX®
MESUPRON®
Follow-up proprietary ATAC candidates & technology
ATAC partnering programs with pharma and biotech
Proprietary lead candidate HDP-101
ATAC lead candidate
ATAC partnering
Clinical assets
ATAC technology & pipeline
© WILEX AG February 2017 7
Company Overview
Development of the ATAC
Technology Platform
Financials and Outlook
© WILEX AG February 2017
Amanitin – Innovative Tumor-Killing Payload
8
Anti-cancer agent with major potential and a new mode of action
Unique mode of action of Amanitin as toxic payload…
Amanitin kills dividing AND quiescent tumor cells
Most effective and specific inhibitor of eukaryotic
transcription (binds and inhibits RNA polymerase II)
Low toxicity of free toxin due to low membrane permeability
…results in potential clinical benefits by antibody-targeted Amanitin conjugates (ATACs)
Strong efficacy in vivo and in vitro models
Ability to overcome resistance
Kill dormant tumor cells causing metastasis & tumor relapse, independent of cell proliferation
© WILEX AG February 2017
Antibody Drug Conjugate Technology
9
ADC: combining the best of two therapeutic modalities
Combining antibody specificity with toxin efficacy leads to improved therapeutic window
and fewer side effects
© WILEX AG February 2017
Amanitin Compared with Other Toxins for ADC
10
Calicheamicin Auristatin Maytansinoids Amanitin
Target DNA Tubulin Tubulin RNA Pol II
Target concentration ? 10-5 M 10-5 M 10-8 - 10-9 M
Structure hydrophobic hydrophobic hydrophobic hydrophilic
Activity on non-dividing
cells low low low high
Activity on multi-drug
resistant cells low low low high
Aggregation of
conjugates high high high low
Conjugation chemistry organic organic organic aqueous
Payload determination
by UV no no no yes
Clinical data yes yes yes no
© WILEX AG February 2017
ATACs: Highly Potent Payload, Superior to Existing
Payloads
11
Complete remissions in JIMT-1 xenograft models after single dose application of 2.9mg/kg Her2-ATAC
Clinical dose of T-DM1 ineffective (FDA approved Kadcyla®)
Equivalent dose of Her2-ATAC shows complete remission
0 1 0 2 0 3 0 4 0 5 0
0
5 0 0
1 0 0 0
1 5 0 0
D a y s a fte r f irs t in je c t io n
Me
an
tu
mo
r v
olu
me
[m
m3
]
T -D M 1 3 x 3 0 m g /k g Ig G
T -D M 1 2 .9 m g /k g Ig G
H e r-3 0 .0 6 4 3 2 .9 m g /k g Ig G
H e r-3 0 .0 6 4 3 0 .7 m g /k g Ig G
V e h ic le
( ( ) ) Kadcyla could not achieve remission
Comparison with auristatin-ADC confirmed
superiority of Amanitin payload
© WILEX AG February 2017
Antibody-Targeted Amanitin Conjugates (ATACs) -
Novel Approach to Cancer Therapy
12
Heidelberg Pharma is the first company using Amanitin for cancer treatment
Significant IP protection for ATACs (est. 2029 to 2040)
Chemical synthesis of toxin established
Optimal linker attachment sites identified
Portfolio of different linkers to select optimal linker for each antibody, target & tumor
Site-specific conjugation technology adapted for Amanitin
© WILEX AG February 2017
HDP-101: Strong Case for Multiple Myeloma
13
HDP-101
Amatoxin + Linker + BCMA antibody = HDP-101
Ideal for multiple myeloma (MM) treatment
o BCMA expression highly restricted in MM, a mature B-cell
neoplasm, and malignant CLL / DLBCL
o Hematological tumor type = good accessibility to tumor cells
High unmet medical need
Favorable market: peak sales 1.8 billion EUR
Additional indications: Diffuse large B-cell lymphoma (DLBCL)
and chronic lymphocytic leukemia (CLL)
BCMA ideal target for an ATAC approach
13
„Celgene acquired Engmab for $600
million. B-cell maturation antigen (BCMA) is
highly and selectively expressed on the
surface of malignant plasma cells in MM”
Oct 3, 2016
© WILEX AG February 2017
BCMA-Marker for (Malignant) Plasma Cells
14
BCMA is expressed on mature but not on healthy earlier stage plasma cells
BCMA is specifically expressed in multiple myeloma (MM), a mature B-cell neoplasm
BCMA
Upside: approximately 50% of CLL and
DLBCL patients express BCMA on B-
cells and may also profit from BCMA-
ATAC therapy BCMA
© WILEX AG February 2017
Multiple Myeloma – Major Unmet Medical Need
15
Strong case for multiple myeloma
Third most prevalent hematopoietic malignancy
MM represents about 0.8-1% of all cancers worldwide, global mortality 70.000
cases yearly, median age at diagnosis is 65-70 years
Malignancy characterized by the proliferation of single clone of plasma cells
derived from B-cells which produce abnormal antibody proteins
MM is initially confined to bone marrow, natural progression of disease can
result in end organ damage
MM is still considered incurable, median survival of ~30-60 months
Current treatment options: chemotherapy, immunomodulatory drugs,
proteasome inhibitors and autologous stem cell transplantation (ASCT)
© WILEX AG February 2017
HDP-101: Strong Efficacy in Multiple Myeloma
Xenograft Model
16
Intravenous multiple myeloma xenograft model (MM1.S-Luc)
Disease progression monitored with bioimaging
Highly efficient treatment with HDP-101
Day 40 : Control Group Groups treated with ascending doses of HDP-101
© WILEX AG February 2017
HDP-101: Strong Efficacy in Other Multiple Myeloma
Xenograft Models
17
Complete tumor remission in a subcutaneous multiple myeloma mouse model
At 4 mg/kg a complete remission was achieved for 3 months.
BCMA-ATAC (2mg/kg)
BCMA-ATAC (4mg/kg)
Subcutaneous NCI-H929 murine
xenograft model for multiple myeloma
Animals were treated with a placebo
(PBS) or a single dose of HDP-101
Very good safety & tolerability profile
after multiple dosing in various
species
o No liver toxicity seen
© WILEX AG February 2017
HDP-101 – Development Process and Milestones
Major milestones in preclinical development of HDP-101 achieved – preparation for the clinic
Humanisation of therapeutic BCMA antibody
Optimization of linker payload combination with best
efficacy and toxicity profile
Conjugation with Amanitin to generate HDP-101
Preclinical studies in mice showed excellent efficacy
(subcutaneous and i.v. MM mouse model)
Very good tolerability in non-human primate
studies (cynomolgus monkeys)
GMP antibody manufacturing started
GMP Amatoxin manufacturing started
Regulatory process initiated
Preclinical
development GLP / GMP / IND enabling Start clinical development
GMP ATAC IND approval Scientific Advice
PEI / FDA
2016 2017 2018
Candidate nomination GLP tox
2019 ….
18
© WILEX AG February 2017
ATACs: Pipeline of Proprietary and Partnered
Programs
19
Additional proprietary ATACs in research and preclinical development
Targets: PSMA, CD19, others
Excellent preclinical efficacy data in mice
Very good tolerability in cynomolgus monkeys
Product Target Indication Research Preclinic Clinic Partner
I II III
HDP-101 BCMA Multiple Myeloma
(DLBCL/CLL) Proprietary
PSMA-ATAC PSMA Prostate cancer Proprietary
CD19-ATAC CD19 Hematological tumours Proprietary
HuMAB 5B1-ATAC n.a Metastatic pancreatic
cancer MabVax
NN-ATACs n.a. Leukemias Nordic Nanovector
© WILEX AG February 2017
Hybrid Business Model: Exploiting the Payload
Potential
20
Partnering
Proprietary
HDP toolbox:
customized and target-optimized
toxins and linkers
Antibodies from partners, license to the
partner, development at the partner
In-licensed antibodies, internal
development activities
A A
A A
A A
A A
Defined payload
Linker variations
Amanitin derivates
© WILEX AG February 2017
Company MTA Tech
Evaluation
1st Management
Approval
Science
Workplan Due Diligence License Deal
L-Pharma (>15b€)
MS-Pharma (>5b€)
S-Pharma (1b€)
Several Research Collaborations
ATAC Partnering Activities: Generating Revenue to
Support the Pipeline
21
Status of partnering activities
Target Structure of Technology Partnering
Partner applies ATAC technology to its own antibody – Technology License
Partner licenses ATAC project from HDP – Product License
Signing Fee – Support Fee – Milestone Payments – Royalties
© WILEX AG February 2017 22
Company Overview
Development of the ATAC
Technology Platform
Financials and Outlook
© WILEX AG February 2017
dievini and affiliated
companies* 64%
UCB 9%
Freefloat 23%
Corporate bodies
1%
Gilbert Gerber
3%
Financials
23
• Sales mainly driven by service and ATAC technology
business
• Other income mainly includes government grants
• Sufficient funding secured to finance operations into Q2 2017
(incl. full commitment of majority shareholder)
in € m 2015 Guidance 2016
Sales revenue and other income 3.9 2.0 – 3.0
Operating expenses 10.4 7.0 – 10.0
Operating result (EBIT) (6.5) (4.0 – 8.0)
Funds required 5.0 4.0 – 8.0
Funds required per month 0.4 0.4 – 0.6
Shareholders
* Including dievini Hopp BioTech, DH-Holding Verwaltungs GmbH
© WILEX AG February 2017
ATAC technology
Clinical pipeline
Solid R&D Progress in 2016
• MESUPRON® partner Link Health submitted IND application for clinical Phase I
trial in China, € 0.5 m milestone payments received
24
Corporate events
• €10 m secured in 2016 via rights issues and shareholder loan
• Prof Dr Andreas Pahl appointed Head of Research and Development at WILEX AG
• Contract with CDMO Celonic for antibody development and production
• Start of cooperation with Advanced Proteome Therapeutics to combine proprietary
site-specific protein modification technology with ATAC technology
• Collaboration with Nordic Nanovector to develop novel ATACs
• BCMA-ATAC HDP-101 chosen as first proprietary project and lead candidate
• Option agreement with Max Delbrück Center for BCMA antibody signed
• Data from animal models presented at key scientific conferences, inc. AACR
• EU patent granted for chemical building block for Amatoxin
• US patent granted for ATACs for tumor therapy
© WILEX AG February 2017
Clinical assets
Potential Newsflow 2017
ATAC business
License and collaboration agreements with pharma partners
GMP manufacturing of first proprietary ATAC candidate to be completed
Preclinical development of partnered projects (e.g., Nordic Nanovector) and research projects under MTA
Preclinical validation of new biomarker (based on Nature publication with MD Anderson )
New ATAC pipeline candidates
25
REDECTANE® – diagnostic agent for molecular imaging with PET/CT
Licensing agreement with Telix Pharmaceuticals - up-front and milestone payments totaling USD 3.7 m, significant royalties on global net sales
MESUPRON® – uPA inhibitor
Start clinical development in China at partner Link Health and preparation for further clinical development at partner RedHill Biopharma
RENCAREX® – therapeutic antibody
Licensing agreement - New partners for development and commercialization
© WILEX AG February 2017
Launch of Fortis Therapeutics Inc. (USA) with $18 m
in a series A financing
Status: preclinical ADC, undisclosed target in several
cancer types, e.g., MM and prostate cancer
Immunomedics Inc. (USA) raises $30 m in follow-on
Status: ADC in clinical Phase II trial to treat solid
tumors, target epithelial glycoprotein-1 (EGP-1).
ADC Therapeutics SA (Switzerland) raises $105 m
Status: Various clinical ADC candidates in multiple trials
to treat lymphoma and leukemia subtypes, other ADCs
in preclinical development
ADC Development - Hot Topic in 2016
26
NBE Therapeutics AG (Switzerland) raises CHF20 m
($20.2 m) in a series B financing
Status: preclinical development, targets not disclosed
© WILEX AG February 2017
Investment Summary
27
Innovative potential “first in man” mode of action with compelling clinical potential
Multiple tumor targets/antibodies can be used to treat different tumor indications
Business model combining early validation and cash through industry collaboration with future high value potential based on portfolio
Working in important area of drug development – Recent attractive deal flows and financings for ADC technologies
A A
Reasons to invest
© WILEX AG February 2017 28
WILEX AG Grillparzerstr. 18
81675 Munich, Germany
Tel.: +49 (0)89-41 31 38-0
Fax: +49 (0)89-41 31 38-99
Website: www.wilex.com
IR/PR support MC Services AG
Katja Arnold (CIRO)
Email: katja.arnold[at]mc-services.eu
Tel.: +49 (0)89-210 288 40
Ticker data ISIN: DE000A11QVV0
Symbol: WL6
Reuters: WL6G.DE
Bloomberg: WL6.GR
Contact Us
Recommended