Company Update. February 2017

Transcription

1 Company Update February 2017

2 Safe Harbor 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. 2

3 Company Overview Development of the ATAC Technology Platform Financials and Outlook 3

4 WILEX at a Glance WILEX AG Frankfurt Stock Exchange:WL6, 4 FTEs Partnering (WILEX legacy portfolio) Holding activities (Heidelberg Pharma shares) Heidelberg Pharma GmbH (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 4

5 Management Team with Strong Pharma and R&D Experience Dr. Jan Schmidt-Brand Spokesman of the Executive Management Board since 2014 and CFO since Managing Pharma since 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 Prof. Dr. Andreas Pahl Head of R&D and Member of the Executive Management since 2016 Chief Scientific Officer and member of the executive Pharma since 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 5

6 WILEX Group Fields of Business Proprietary lead candidate HDP-101 ATAC partnering programs with pharma and biotech ATAC lead candidate ATAC partnering ATAC technology & pipeline Clinical assets Follow-up proprietary ATAC candidates & technology REDECTANE RENCAREX MESUPRON 6

7 Company Overview Development of the ATAC Technology Platform Financials and Outlook 7

8 Amanitin Innovative Tumor-Killing Payload 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 8

9 Antibody Drug Conjugate Technology ADC: combining the best of two therapeutic modalities Combining antibody specificity with toxin efficacy leads to improved therapeutic window and fewer side effects 9

10 Amanitin Compared with Other Toxins for ADC Calicheamicin Auristatin Maytansinoids Amanitin Target DNA Tubulin Tubulin RNA Pol II Target concentration? 10-5 M 10-5 M M Structure hydrophobic hydrophobic hydrophobic hydrophilic Activity on non-dividing cells Activity on multi-drug resistant cells Aggregation of conjugates low low low high low low low high high high high low Conjugation chemistry organic organic organic aqueous Payload determination by UV no no no yes Clinical data yes yes yes no 10

11 M e a n t u m o r v o lu m e [ m m 3 ] ATACs: Highly Potent Payload, Superior to Existing Payloads 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 ( ) ( ) D a y s a fte r firs t in je c tio n Kadcyla could not achieve remission V e h ic le T -D M m g /k g Ig G T -D M 1 3 x 3 0 m g /k g Ig G H e r m g /k g Ig G H e r m g /k g Ig G Comparison with auristatin-adc confirmed superiority of Amanitin payload 11

12 Antibody-Targeted Amanitin Conjugates (ATACs) - Novel Approach to Cancer Therapy Heidelberg Pharma is the first company using Amanitin for cancer treatment Significant IP protection for ATACs (est 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 12

13 HDP-101: Strong Case for Multiple Myeloma HDP-101 Amatoxin + Linker + BCMA antibody = HDP-101 Ideal for multiple myeloma (MM) treatment o o BCMA expression highly restricted in MM, a mature B-cell neoplasm, and malignant CLL / DLBCL 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 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,

14 BCMA-Marker for (Malignant) Plasma Cells 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 Upside: approximately 50% of CLL and DLBCL patients express BCMA on B- cells and may also profit from BCMA- ATAC therapy BCMA BCMA 14

15 Multiple Myeloma Major Unmet Medical Need Strong case for multiple myeloma Third most prevalent hematopoietic malignancy MM represents about 0.8-1% of all cancers worldwide, global mortality cases yearly, median age at diagnosis is 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) 15

16 HDP-101: Strong Efficacy in Multiple Myeloma Xenograft Model Intravenous multiple myeloma xenograft model (MM1.S-Luc) Disease progression monitored with bioimaging Day 40 : Control Group Groups treated with ascending doses of HDP-101 Highly efficient treatment with HDP

17 HDP-101: Strong Efficacy in Other Multiple Myeloma Xenograft Models Complete tumor remission in a subcutaneous multiple myeloma mouse model Subcutaneous NCI-H929 murine xenograft model for multiple myeloma Animals were treated with a placebo (PBS) or a single dose of HDP-101 BCMA-ATAC (2mg/kg) Very good safety & tolerability profile after multiple dosing in various species o No liver toxicity seen BCMA-ATAC (4mg/kg) At 4 mg/kg a complete remission was achieved for 3 months. 17

18 HDP-101 Development Process and Milestones Major milestones in preclinical development of HDP-101 achieved preparation for the clinic Humanisation of therapeutic BCMA antibody Very good tolerability in non-human primate Optimization of linker payload combination with best studies (cynomolgus monkeys) efficacy and toxicity profile GMP antibody manufacturing started Conjugation with Amanitin to generate HDP-101 GMP Amatoxin manufacturing started Preclinical studies in mice showed excellent efficacy Regulatory process initiated (subcutaneous and i.v. MM mouse model) Preclinical development GLP / GMP / IND enabling Start clinical development Candidate nomination Scientific Advice PEI / FDA GLP tox GMP ATAC IND approval 18

19 ATACs: Pipeline of Proprietary and Partnered Programs 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 HDP-101 BCMA Multiple Myeloma (DLBCL/CLL) I II III 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 19

20 Hybrid Business Model: Exploiting the Payload Potential Partnering Antibodies from partners, license to the partner, development at the partner A A A A HDP toolbox: customized and target-optimized toxins and linkers Defined payload Linker variations Amanitin derivates In-licensed antibodies, internal development activities A A A A Proprietary 20

21 ATAC Partnering Activities: Generating Revenue to Support the Pipeline 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 MTA Tech Evaluation 1st Management Approval Science Workplan Due Diligence License Deal L-Pharma (>15b ) MS-Pharma (>5b ) S-Pharma (1b ) Several Research Collaborations 21

22 Company Overview Development of the ATAC Technology Platform Financials and Outlook 22

23 Financials in m 2015 Guidance 2016 Shareholders Sales revenue and other income Operating expenses Operating result (EBIT) (6.5) ( ) Freefloat 23% Corporate bodies 1% Gilbert Gerber 3% Funds required Funds required per month UCB 9% dievini and affiliated companies* 64% Sales mainly driven by service and ATAC technology business Other income mainly includes government grants Sufficient funding secured to finance operations into Q (incl. full commitment of majority shareholder) * Including dievini Hopp BioTech, DH-Holding Verwaltungs GmbH 23

24 Solid R&D Progress in 2016 ATAC technology 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 pipeline MESUPRON partner Link Health submitted IND application for clinical Phase I trial in China, 0.5 m milestone payments received 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 24

25 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 Clinical assets 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 25

26 ADC Development - Hot Topic in 2016 NBE Therapeutics AG (Switzerland) raises CHF20 m ($20.2 m) in a series B financing Status: preclinical development, targets not disclosed 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 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 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). 26

27 Investment Summary Reasons to invest 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 27

28 Contact Us WILEX AG Grillparzerstr Munich, Germany Tel.: +49 (0) Fax: +49 (0) Website: IR/PR support MC Services AG Katja Arnold (CIRO) katja.arnold[at]mc-services.eu Tel.: +49 (0) Ticker data ISIN: DE000A11QVV0 Symbol: WL6 Reuters: WL6G.DE Bloomberg: WL6.GR 28