Company Update - Heidelberg Pharma GmbHheidelberg-pharma.com/wp-content/uploads/2015/01/... · 2019-06-26 · This communication contains certain forward-looking statements, relating

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 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


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 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


Company Overview


Technology Platform



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


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


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


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


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


HDP-101: Strong Case for Multiple Myeloma

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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


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


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)


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


HDP-101: Strong Efficacy in Other Multiple Myeloma

Xenograft Models

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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


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


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


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


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


Company Overview


Technology Platform



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


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


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


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


Investment Summary

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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 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

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Company Update - Heidelberg Pharma GmbHheidelberg-pharma.com/wp-content/uploads/2015/01/... · 2019-06-26 · This communication contains certain forward-looking statements, relating