ATACs fighting Cancer - July 2018 - Heidelberg Pharma
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
ATACs fighting Cancer July 2018
Safe Harbor
Forward looking statements
This communication contains certain forward-looking additional funding, risks of product liability and limitations of
statements, relating to the Company’s business, which can be insurance, limitations of supplies, competition from other
identified by the use of forward-looking terminology such as biopharmaceutical, chemical and pharmaceutical companies,
“estimates”, “believes”, “expects”, “may”, “will” “should” environmental, health and safety matters, availability of
“future”, “potential” or similar expressions or by general licensing arrangements, currency fluctuations, adverse
discussion of strategy, plans or intentions of the Company. changes in governmental rules and fiscal policies, civil unrest,
Such forward-looking statements involve known and acts of God, acts of war, and other factors referenced in this
unknown risks, uncertainties and other factors, which may communication.
cause our actual results of operations, financial condition,
Given these uncertainties, prospective investors and partners
performance, or achievements, or industry results, to be
are cautioned not to place undue reliance on such forward-
materially different from any future results, performance or
looking statements. We disclaim any obligation to update any
achievements expressed or implied by such forward-looking
such forward-looking statements to reflect future events or
statements.
developments.
Such factors include, among others, the following:
This material is not intended as an offer or solicitation for the
uncertainties related to results of our clinical trials, the
purchase or sale of shares of Heidelberg Pharma AG. This
uncertainty of regulatory approval and commercial
material may not be distributed within countries where it
uncertainty, reimbursement and drug price uncertainty, the
may violate applicable law.
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
© Heidelberg Pharma AG 2
Corporate ATAC ATAC Proprietary Financials &
Overview Technology Business ATAC Project Outlook
Platform Model HDP-101
© Heidelberg Pharma AG 3
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
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
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
Corporate ATAC ATAC Proprietary Financials &
Overview Technology Business ATAC Project Outlook
Platform Model HDP-101
© Heidelberg Pharma AG 7
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
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
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 10ATACs – 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 11ATACs – 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 12Corporate ATAC ATAC Proprietary Financials &
Overview Technology Business ATAC Project Outlook
Platform Model HDP-101
© Heidelberg Pharma AG 13Early 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 14Multi-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 15Magenta – 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 16ATACs – 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 17Corporate ATAC ATAC Proprietary Financials &
Overview Technology Business ATAC Project Outlook
Platform Model HDP-101
© Heidelberg Pharma AG 18Lead 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 19BCMA 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 20Multiple 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 22HDP-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 23HDP-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
24BCMA 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 25Corporate ATAC ATAC Proprietary Financials &
Overview Technology Business ATAC Project Outlook
Platform Model HDP-101
© Heidelberg Pharma AG 26Financials
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
27Heidelberg 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 28Next 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 29Investment 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 30Contact 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
31You can also read
