ATACs fighting Cancer - July 2018 - Heidelberg Pharma

 
ATACs fighting Cancer - July 2018 - Heidelberg Pharma
ATACs fighting Cancer
July 2018
ATACs fighting Cancer - July 2018 - Heidelberg Pharma
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absence of sales and marketing experience and limited
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technologically skilled employees, dependence on licenses,
patents and proprietary technology, dependence upon
collaborators, future capital needs and the uncertainty of

© Heidelberg Pharma AG                                                                                                         2
ATACs fighting Cancer - July 2018 - Heidelberg Pharma
Corporate                ATAC       ATAC       Proprietary   Financials &
   Overview              Technology   Business   ATAC Project     Outlook
                          Platform     Model       HDP-101

© Heidelberg Pharma AG                                                         3
ATACs fighting Cancer - July 2018 - Heidelberg Pharma
Heidelberg Pharma at a Glance

                Developing new options to address major challenges in cancer therapy

          Our Company                         Our Mission                    Our Approach

 WILEX AG becomes Heidelberg         Improving efficacy              New mode of action in cancer
 Pharma AG                                                           therapy - Antibody Targeted
                                     Overcoming resistance           Amanitin Conjugates (ATACs)
 Frankfurt Stock Exchange: WL6       mechanisms
                                                                     • Induction of apoptosis by
 Shares outstanding: 28.10 million   Killing dormant tumor cells       inhibition of RNA Polymerase II
 Market cap: ~€76 million            New options in cancer therapy   • Application of innovative
 Headquarters: Ladenburg,                                              payload harnessing ADC
 Germany                                                               technology

 65 employees (June 2018)

© Heidelberg Pharma AG                                                                                   4
ATACs fighting Cancer - July 2018 - Heidelberg Pharma
Strategic Cornerstones

                                                           Additional upside potential
    Build proprietary ATAC    Sign technology licensing
                                                            with partnered non-ATAC
           pipeline                 collaborations
                                                              legacy clinical assets

Proprietary lead candidate                                    ATAC technology partnering
HDP-101                                                         with pharma and biotech
                                                 ATAC
                               Lead ATAC
                                              technology
                                HDP-101
                                                partner

ATAC third-party                   ATAC                       MESUPRON® (RedHill, Link Health)
collaborations + other                          Clinical      REDECTANE® (Telix)
                              collaboration
                                                assets
proprietary ATAC candidates    & pipeline                     RENCAREX®

© Heidelberg Pharma AG                                                                      5
ATACs fighting Cancer - July 2018 - Heidelberg Pharma
Management Team with Strong Pharma
and R&D Experience

                          Dr. Jan                                               Prof. Dr.
                         Schmidt-                                               Andreas
                          Brand                                                   Pahl

  CEO / CFO                                            CSO
  @ Heidelberg Pharma since 2001                       @ Heidelberg Pharma since 2012
  20 years’ experience in commercial and financial     20 years’ experience in research and higher education
  leadership positions in pharma and chemical
  companies, including BASF                            Head of Late Pharmacology at Nycomed and Takeda
                                                       Pharmaceuticals from 2008 to 2012
  Managing Director of an Austrian BASF Pharma
  subsidiary (EBEWE Arzneimittel GmbH) from 1997       Professor of Pharmacology and Toxicology at the
  to 2001, prior several positions at the BASF Group   University of Erlangen-Nuremberg (FAU)

  Member of the board of directors of                  PhD in chemistry from the University of Berlin
  BIO Deutschland e.V.
  LLD from the University of Mannheim

© Heidelberg Pharma AG                                                                                         6
ATACs fighting Cancer - July 2018 - Heidelberg Pharma
Corporate                ATAC       ATAC       Proprietary   Financials &
   Overview              Technology   Business   ATAC Project     Outlook
                          Platform     Model       HDP-101

© Heidelberg Pharma AG                                                         7
ATACs fighting Cancer - July 2018 - Heidelberg Pharma
Innovative Potential First-in-humans Mode of Action
with Compelling Clinical Potential

 Unique mode of action of Amanitin as toxic payload…

• Amanitin kills dividing AND quiescent tumor cells by binding and
  inhibiting RNA polymerase II
                                                                                 Death cap mushroom

…results in potential clinical benefits by
                                                                     Chemical
                                                                     synthesis
Antibody Targeted Amanitin Conjugates (ATACs) as targeted therapy

• Strong efficacy in vivo and in vitro models

• Ability to overcome resistance

• Kill dormant tumor cells causing metastasis & tumor relapse,
  independent of cell proliferation

• ATAC technology applicable to every tumor entity
                                                                                          ATAC

© Heidelberg Pharma AG                                                                                8
ATACs fighting Cancer - July 2018 - Heidelberg Pharma
Antibody Drug Conjugate Technology – Proven &
Established Technology

ADC: Combining the best of two therapeutic modalities

 Antibody specificity + toxin efficacy → improved therapeutic window and fewer side effects

© Heidelberg Pharma AG                                                                        9
ATACs fighting Cancer - July 2018 - Heidelberg Pharma
Amanitin Compared Favorably to Approved ADC
Toxins

                            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
                                low             low           low             high
non-dividing cells

Activity on multi-drug
                                low             low           low             high
resistant cells

Aggregation of conjugates       high           high           high            low

Conjugation chemistry          organic        organic        organic        aqueous

Payload determination
                                 no             no             no             yes
by UV

Clinical data                   yes             yes            yes             no

© Heidelberg Pharma AG                                                                    10
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

                                                 Kadcyla could not achieve remission

                                                 Comparison with auristatin-ADC confirmed
                                                 superiority of Amanitin payload

© Heidelberg Pharma AG                                                                      11
ATACs – Novel Approach to Cancer Therapy

Heidelberg Pharma is the first company using Amanitin for cancer treatment

 IP protection for ATACs
                                                      World-class collaboration network includes
 (est. 2029 up to 2038)
• Chemical synthesis of toxin                        • German Cancer Research Center (DKFZ)

• Optimal linker attachment sites                    • Heidelberg University
• Portfolio of different linkers to select optimal   • MD Anderson (Texas)
  linker for each antibody, target & tumor
                                                     • Indiana University’s Simon Cancer Center
• Site-specific conjugation technology
  adapted for Amanitin

• Specific biomarker 17p deletion

                                               A
                                                          A

© Heidelberg Pharma AG                                                                            12
Corporate                ATAC       ATAC       Proprietary   Financials &
   Overview              Technology   Business   ATAC Project     Outlook
                          Platform     Model       HDP-101

© Heidelberg Pharma AG                                                         13
Early Validation and Cash Through Pharma Collaborations
+ Future High Value Potential with Proprietary Portfolio

                                       Partnering target by target

    Antibodies from partners, license to the
    partner, development by the partner                               A       A
                                                         A       A

                                                                     Defined payload
    ATAC toolbox:
                                                                     Linker variations
    customized and target-optimized
    toxins and linkers                                               Amanitin derivates

    In-licensed antibodies, internal
    development activities                           A       A            A       A

                                               Proprietary

© Heidelberg Pharma AG                                                                    14
Multi-Target Research and Option Agreements with
Takeda and Magenta

 Research & Option Agreements                                Financials
 • Synthesis of ATACs using antibodies from the              • Upfront technology access fees and R&D support
   Takeda/Magenta portfolio
                                                             • Option fee for each option exercised
 • Both companies have exclusive target licensing            • Clinical development, regulatory and sales-related
   option for global development and marketing rights          milestone payments:
   for development candidates
                                                                  • Takeda of up to USD 113 million for each
 • Option for several exclusive targets
                                                                    product candidate; up to three targets
 • If option exercised, partner is responsible for further
                                                                  • Magenta: totaling up to more than USD 330
   preclinical and clinical development as well as
                                                                    million for up to four potential targets
   commercialization
                                                             • Royalties on sales

        One of the top 15 pharmaceutical                     New and fast growing player in the field of
             companies worldwide                                        stem cell research
© Heidelberg Pharma AG                                                                                              15
Magenta – Integrated Company Addressing
all Aspects of Bone Marrow Transplant

 Transplant conditioning: Precision approach to transplant via antibody drug conjugates

 Collaboration enables and accelerates Magenta’s research and development efforts across
      several targeted conditioning programs for bone marrow transplant with ATACs       16
ATACs – Growing Pipeline of Proprietary and
Partnered Programs

Additional proprietary ATACs in research and preclinical development
• Targets: PSMA, CD19, others
• Excellent preclinical efficacy in mice and very good tolerability in cynomolgus monkeys

Product             Target   Indication                     Research Preclinic       Clinic         Partner

Proprietary                                                                      I     II     III

HDP-101             BCMA     Multiple myeloma (DLBCL/CLL)                                           Proprietary

PSMA-ATAC           PSMA     Prostate cancer                                                        Proprietary

CD19-ATAC           CD19     Hematological tumors                                                   Proprietary

NN-ATACs            n/a      Leukemias                                                              Nordic Nanovector

ATAC technology partner

                                                                                                    Takeda/
TAK-XX-ATACs       n/a       n/a
                                                                                                    Millennium

                             Conditioning programs for
MGTA-XX-ATACs      n/a                                                                              Magenta
                             bone marrow transplant

© Heidelberg Pharma AG                                                                                              17
Corporate                ATAC       ATAC      Proprietary    Financials &
   Overview              Technology   Business   ATAC Project     Outlook
                          Platform     Model       HDP-101

© Heidelberg Pharma AG                                                         18
Lead Proprietary ATAC Candidate HDP-101 –
Strong Case for Multiple Myeloma

• BCMA antibody selected under collaboration with Max Delbrück Center for Molecular Medicine in the
  Helmholtz Association
• Amatoxin + Linker + BCMA antibody = HDP-101
• Ideal for multiple myeloma (MM) treatment
  • BCMA expression highly restricted in MM, a mature B-cell neoplasm and malignant CLL/DLBCL
  • Hematological tumor type = good accessibility to tumor cells

• Additional indications: Diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL)

• Favorable market: est. peak sales 1.8 billion EUR for HDP-101

                 BCMA ideal target for an ATAC approach, validated through CAR-Ts

© Heidelberg Pharma AG                                                                                   19
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.

© Heidelberg Pharma AG                                                                   20
Multiple Myeloma – Major Unmet Medical Need

• Second most prevalent hematopoietic
  malignancy*
• MM represents about 0.8-1% of all cancers
  worldwide, with 70,000 deaths annually; 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)
*https://www.krebsgesellschaft.de/onko-internetportal/basis-informationen-krebs/krebsarten/multiples-
myelom-plasmozytom-morbus-kahler/definition-und-haeufigkeit.html

© Heidelberg Pharma AG                                                                                  21
HDP-101: High Efficacy in Multiple Myeloma Xenograft;
Long-lasting Remission after Single Treatment

Day 40 : Control Group                                                                                                                                                                                                   Groups treated with ascending doses of HDP-101

                                                                                                                                                                                                                                                                          0.1 mg/kg

                                                                                                                                                                                                                                                                          0.3 mg/kg
Disease progression monitored with bioimaging
                                11
                           10
                                                                                                                                                          P B S [ 1 0 m l/k g ]

                                                                                                                                                          J 2 2 .9 - IS Y - D 2 6 5 C - 3 0 .2 1 1 5 [ 0 .1 m g /k g ]

                                10                                                                                                                        J 2 2 .9 - IS Y - D 2 6 5 C - 3 0 .2 1 1 5 [ 0 .3 m g /k g ]
                           10

                                                                                                                                                                                                                                                                          1 mg/kg
                                                                                                                                                          J 2 2 .9 -IS Y -D 2 6 5 C -3 0 .2 1 1 5 [1 m g /k g ]

                                                                                                                                                          J 2 2 .9 -IS Y -D 2 6 5 C -3 0 .2 1 1 5 [2 m g /k g ]

                           10    9                                                                                                                        B a c k g ro u n d L e v e l
T o ta l F lu x [p /s ]

                                 8
                           10

                                                                                                                                          *
                                 7
                           10

                                                                                                                                         *
                                 6
                           10

                           10    5
                                         T re a t m e n t ( s in g le d o s e iv )
                                                                                                                                                                                                                                                                           2 mg/kg
                                     0     7      14     21      28      35     42   49    56    63     70        77       84       91        98
                                                              D a y s P o s t T u m o r C e ll In o c u la tio n

                                                                                                             *   9 / 1 0 a n im a l s : b a c k g r o u n d l e v e l

Single treatment with HDP-101 at low doses of
0.1 mg/kg leads to long lasting complete remission

                          © Heidelberg Pharma AG                                                                                                                                                                                                                          22
HDP-101 – Good Tolerability in Monkeys

No signs of liver toxicity in dose escalation and repeat dosing in cynomolgus monkeys

                                                                             3 animals per group
                                                                                3 week schedule
                                                                            * Scheduled sacrifice

                                                                            ---- min/mean/max/
                                                                             values of untreated
                                                                                         animals

• No clinical side effects, LDH most sensitive parameter from clinical chemistry
• Accompanied by transient increase of neutrophils & decrease of monocytes and lymphocytes
• TI: HNSTD (3mg/kg repeated in NHP) / MED (0.1 mg/kg single in murine disseminating xenograft)
• Therapeutic index based on Body Surface Area: 120, based on AUC: 60

© Heidelberg Pharma AG                                                                              23
HDP-101 – Results from Research Collaboration with
Heidelberg University and the DKFZ Presented at ASH

Comparison with MMAF (BCMA-Antibody Auristatin Conjugate as used by GSK) on MM Patient Cells
    • Green lines: Non-dividing (quiescent) cells isolated from multiple myeloma patient bone marrow biopsies
    • Black lines: Dividing tumor cells from lab cell lines

      anti-BCMA-Ab coupled with GSK payload MMAF                        HDP-101 (anti-BCMA-Ab coupled with payload Amanitin)

• Strong cytotoxic effect at very low doses, even in cancer cells with a low concentration of BCMA antigens
• No toxicity on non-BCMA expressing control cells
• First time that the efficacy of Amanitin on cancer cells taken from human patients was demonstrated

      Only HDP-101 is efficacious on non-dividing primary tumor cells isolated from multiple myeloma patients

                                                                                                                               24
BCMA Validated Target – Therapy Overview

    ADCs targeting BCMA – small competitive environment
    −   GSK: BCMA-MMAE ADC, Phase II data presented @ASH 12/2017: Overall response rate of 60%
    −   HDP-101: IND in preparation, 1st patient-in H1/2019
    −   Celgene / Sutro collaboration: IND in preparation, undisclosed payload
    −   Medimmune: Preclinical stage

 Bispecific BCMA mAbs                                         CAR-T Cell BCMA therapies
-   Celgene/Engmab: Start Phase I Q1 2018                     - Bluebird (Celgene): Start Phase I Q1 2016 (ASH 12/2017);
-   Boehringer Ingelheim/Amgen: Start Phase I Q4 2017           Start Phase II Q4 2017
-   Pfizer: Start Phase I Q4 2017                             - Kite (Gilead): Start Phase I Q4 2017
-   J&J: Start Phase I Q2 2017                                - Nanjing Legend Biotech: Phase I (ASCO 06/2017)
-   TeneoBio: Start Phase I Q4 2018                           - Poseida Therapeutics: Start Phase I Q3 2017
-   Affimed: preclinical                                      - Autolus Limited: Start Phase I Q4 2017
                                                              - The Pregene Biotech Comp: Start Phase I Q4 2017
                                                              - University Pennsylvania: Phase I (ASH 12/2017); inactive
                                                              - Carsgen Therapeutics Start Phase I Q1 2018
                                                              - Cartesian Therapeutics: Start Phase I Q1 2018
                                                              - Juno (Celgene): Start Phase I Q1 2018
© Heidelberg Pharma AG                                                                                               25
Corporate                ATAC       ATAC       Proprietary   Financials &
   Overview              Technology   Business   ATAC Project     Outlook
                          Platform     Model       HDP-101

© Heidelberg Pharma AG                                                     26
Financials

in € m                                            FY 2017             H1 2018         Guidance 2018
Sales revenue and other income                         2.5                  2.2             3.0 to 5.0
Operating expenses                                    13.2                  6.9           16.0 to 20.0
Operating result (EBIT)                              -10.8                 -4.7         -12.0 to -16.0
Funds required                                        8.6*                4.9*            13.0 to 17.0
Funds required per month                              0.7*                0.8*              1.1 to 1.4
* Excluding capital increases and loan

• Higher Operating Expenses in 2018 due to preparation of clinical development for HDP-101 (GMP, Tox) in multiple
  myeloma
• H1 figures in lines with guidance, cash at the end of H1: €25.5 m

Financing
 Rights issue in May 2017 - €5 m gross proceeds
 Mixed non-cash and cash capital increase in November 2017 - €34.4 m total transaction volume
 Cash reach is secured until 2020 based on current budget planning

                                                                                                                    27
Heidelberg Pharma Shares

 Share performance 2018                                 Share ownership as of 30 June 2018

 • High: €3.980 (15 January 2018)                                                         Corporate
                                                                                           bodies *
 • Low: €2.580 (8 June 2018)                                                                 1%

 • Daily trading volume: 34,118 shares (2017: 14,049)              Freefloat
                                                                     20%

 • Shares outstanding: 28,129,782 (as of 30 May 2018)
 • Current market cap: ~€76 m (June 2018)                         UCB
                                                                  4%

Analyst coverage                                                                                          Dietmar Hopp
                                                                                                          and affiliated
                                                                                                          companies**
                                                                                                              75%
• Baader Helvea 04/18: target €4.40
                                                         * held directly
• Equinet 04/18: target €3.50                           ** dievini Hopp BioTech holding GmbH & Co. KG +
                                                           DH Holding Verwaltungs GmbH

• EQUI.TS 03/18: target €5.02

© Heidelberg Pharma AG                                                                                                     28
Next Steps and Potential Milestones:
First Program Expected to Enter Clinic by End of 2018

 ATAC technology and proprietary pipeline                     Partnered legacy clinical programs

• HDP-101                                                     MESUPRON®

      • Biomarker development program matured to RUO status   • Link Health: IND approval and start
                                                                clinical development in China
      • Preparation of Clinical Trial Application             • RedHill to start Phase I/II in pancreatic
                                                                cancer in Germany
      • Complete GMP manufacturing of HDP-101
                                                              REDECTANE®
      • Start GLP toxicity study for HDP-101                  •   Telix to prepare Phase III program

• Sign additional license and collaboration agreements with
   biopharma partners

• Reach next milestones with our partners

© Heidelberg Pharma AG                                                                                      29
Investment Summary

Developing new options to address major challenges in cancer therapy

• Heidelberg Pharma is developing new treatment options with Amanitin for different cancer
  indications, also validated by high quality collaborations
• The innovative first in humans mode of action provides high efficacy and potential for unique clinical
  advantages including treatment of dormant tumor cells
• Value step-up ahead due to transition to clinical stage of lead product HDP-101 in Multiple Myeloma
• Dual business model – early validation and cash through pharma collaborations + future high value
  potential with proprietary portfolio

                                                                                   A                A

© Heidelberg Pharma AG                                                                                     30
Contact us

Upcoming conferences & events H2 2018                                 Venue                 Date
Herbstkonferenz                                                       Frankfurt             3 – 4 September 2018
Baader Investment Conference                                          Munich                    24 – 27 September 2018
Interim management statement on the first nine months of 2018         Heidelberg            11 October 2018
BIO Investor Forum                                                    San Francisco         17 – 18 October 2018
BIO-Europe                                                            Copenhagen            05 – 07 November 2018
Germany Equity Forum                                                  Frankfurt             26 – 28 November 2018
60th ASH Annual Meeting & Exposition                                  San Diego             01 – 04 December 2018

Heidelberg Pharma AG                   IR/PR support                               Ticker data

Schriesheimer Strasse 101              MC Services AG                              ISIN:         DE000A11QVV0
68526 Ladenburg, Germany               Katja Arnold (CIRO)                         Symbol:       WL6
Tel.: +49 6203 1009-0                  Tel.: +49 89 210 288-40                     Reuters:      WL6G.DE
Fax: +49 6203 1009-19                  Email: katja.arnold[at]mc-services.eu       Bloomberg:    WL6.GR
Website: www.heidelberg-pharma.com
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