Alligator Bioscience AB - Redeye

Alligator Bioscience AB
Cancer Immunotherapy
Sibylle Lenz, CEO
T-lymphocytes and cancer cell, SEM
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CONFIDENTIAL

Alligator Bioscience - 2013
Ø Focus on Cancer Immunotherapy
Ø Growing pipeline of proprietary drug candidates
Ø Novel concept for development of next generation IMmunotherapy
of CANcer (IMCAN) - local administration
Ø New human Antibody library, SCALA-11
Ø Superior protein optimization technology, FIND ® (Fragment
INduced Diversity) for novel and second generation biologics
Ø Strong IP protection on FIND ® and drug candidates
Background: Founded in 2001, Privately owned, 25+ employees
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Technology & Product Growth
FIND ®
Validation
Pipeline
Development
2007
Oncology &
Immunology
2008
2010
Oncology
Immunotherapy
2011 2012
2013
R&D
Company
2001
New CEO &
Mgt Team
Alligator
Foundation
Pipeline
Focus
IMCAN
Initiation
Antibody
Library
Bispecific
Compounds
Antibody
Formats
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Pipeline Projects
PROJECT MOLECULE INDICATION RESEARCH PRECLINICAL CLINICAL
ADC-1013 Antibody Immunotherapy - Local
2014
ADC-1015 Bispecific Ab Immunotherapy - Local
ADC-1016 Bispecific Ab Immunotherapy - Syst.
2015
2014
External Undisclosed Various
Pipeline Management
Ø One ADC-project in production at all times
Ø Discovery pool of research projects as backup compounds/projects
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CONFIDENTIAL

Immunotherapy
of Cancer
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Immunotherapy of Cancer
Objective: To develop immunotherapies to boost the immune system
to eradicate tumors and metastases with minimal systemic toxicity.
Clinical Validation of Immunotherapy
Ø Yervoy® (BMS) approved by FDA for metastatic melanoma
Ø Clinical effect at the cost of severe immune-mediated adverse effects
Drawback of Immunotherapy Addressed by Intratumoral Administration*
Ø Concept of local immunotherapy pioneered by Prof. Tötterman
Ø Alligator has collaborated with Prof. Tötterman since 2008 in order to develop
the first therapeutic antibodies for local immunotherapy of cancer
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*) Malmström et al., Clinical Cancer Research 2010:16 : 3279-87
Pesonen et al., Cancer Research 2012: 72: 1621-31
Castro et al., Cancer Research 2012: 72: 2937-48
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Local Immunotherapy: Competitive Edge
Local immunotherapy of cancer gives superior systemic anticancer
effect with minimal systemic toxicity.
Metastases
Tumor
= immune activation
Systemic immunotherapy:
Unselective immune activation with
limited efficacy and severe toxicity
Local immunotherapy: Tumorselective
immune activation:
improved efficacy, less toxicity*
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*) von Euler et al., Journal of Immunotherapy 2008: 31: 377-84
Fransen et al., Clinical Cancer Research 2011: 17: 2270-80
CONFIDENTIAL

ADC-1013
CD40 agonistic antibody
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Designing ADC-1013 for Local Immunotherapy
ADC-1013 is FIND®-optimized for superior properties in the tumor
micro-environment, including modifications for both efficacy and safety.
Optimized for local immunotherapy
Ø Full functionality in tumor
microenvironment
Ø High affinity and potency
Ø Strong tumor retention
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In Vivo Data Requirements
Alligator has defined specifications for success including essential
criteria for efficacy as well as safety.
Success-criteria local administration
1. Systemic anti-tumor effect
2. Long term tumor immunity
3. Effective at lower dose compared to systemic administration
4. Superior safety profile compared to systemic administration
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1. Systemic Anti-Tumor Effect
Twin tumor model: Two tumors are implanted under the skin, one
tumor receives immunotherapy treatment.
Success criteria: Response to treatment of both tumors à cure
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1. Systemic Anti-Tumor Effect
Local immunotherapy treatment of one tumor (blue) prevents growth
also of the untreated tumor (green).
Rapid tumor growth is seen of the two tumors in control mice (red).
N = 8 in
each group
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2. Long Term Immunity
Cured mice re-challenged with new tumor and without treatment.
Mice are immune to the tumor (cured).
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2. Long Term Immunity
Re-challenge of cured mice (after 2 months) are resistant to tumor
growth (green). Mice without prior treatment are unprotected (red).
†
N = 8 in
each group
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Transgenic Mice
Transgenic mice - generated by insertion of the gene for a human
target in the mouse DNA. The mouse express the human target on
its immune cells. ADC-1013 is tested in this humanized mouse
model.
Wild type mouse
Transgenic mouse
Generation
0
Generation
1
Generation
XX
Breeding
Test of mouse Ab
Test of human Ab
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CONFIDENTIAL

Transgenic Mice: Bladder Cancer Model
Bladder cancer model in transgenic mice: ADC-1013 is locally
injected: 7 out of 8 mice are cured by ADC-1013 (black), compared to
1 out of 8 mice in the control group (gray)
CR=7 (8)
CR=1 (8)
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CR= Complete Responders
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ADC-1013 Status and Development Plan
ADC-1013 is currently being manufactured for toxicology and clinical
studies. Clinical trial in cancer patients in H1 2014.
Toxicology
C
T
A
Clinical
Phase I
Clinical
Phase Ib
C
T
A
Clinical
Phase II
2013 2014 2015
2016
Q1/2 Q3/4 Q1/2 Q3/4 Q1/2 Q3/4
Q1/2 Q3/4
2017
Q1/2 Q3/4
Manufacturing
BD – Partnering activities
CTA = Clinical Trial Application
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CONFIDENTIAL

ADC-1015
Bispecific antibody
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ADC-1015: A Bispecific Immune Activator
Alligator is developing a bispecific immune activating antibody for local
treatment of metastasizing cancer - ADC-1015.
Ø Superior to combination of two monospecific compounds
Ø Novelty – strong IP can be obtained
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CONFIDENTIAL

ADC-1015: A Bispecific Immune Activator
Alligator is developing a bispecific immune activating antibody for local
treatment of metastasizing cancer - ADC-1015.
Ø Superior to combination of two monospecific compounds
Ø Novelty – strong IP can be obtained
ADC-1014 ADC-1015 Undisclosed
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CONFIDENTIAL

World Class Key Opinion Leaders
Alligator is building a network of international opinion leaders within
key areas for immunotherapy of cancer.
Professor Thomas Tötterman et al.,
Clinical Immunology, Uppsala University
Professor Carl Borrebaeck et al.,
Immunotechnology, Lund University
Professor Jeffrey Weber
Immunotherapy of Cancer, Moffitt Cancer Center, US
Professor Ronald Levy et al.,
Immunotherapy of Cancer, Stanford University, US
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Alligator Bioscience AB
Cancer Immunotherapy
Sibylle Lenz, CEO
T-lymphocytes and cancer cell, SEM
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CONFIDENTIAL

Financing Needs Rest of 2013
Ø Ongoing emission: 46 MSEK
Ø To be issued: 6 613 595 Units
Ø 1 Unit = 1 share + 1 option
Ø Share price = 7 SEK per share
Ø Purchase of one share grants one option to be purchased
later for 3 SEK
Ø The option must be exercised before 15 th July 2014
More information can be found on Alligator web-site:
http://www.alligatorbioscience.se/en/
c-195-12Mars2013,AlligatorBioscienceABgenomförriktadnyemission.aspx
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Financing – Earlier in 2013
Directed emission – according to AGM 2012 resolution:
Ø 12,1 MSEK raised in a directed share issue
Ø Registered in January 2013
Ø New total number of shares: 24 732 949
Ø Total Share Capital: SEK 9 893 180
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Share Capital – February 18, 2013
Shareholder
Total Shares % Ownership
SUNSTONE CAPITAL 4 880 860 19,73%
STENA AKTIEBOLAG 2 888 088 11,68%
BANQUE INTERNATIONALE À LUXEMBOURG SA 2 522 154 10,20%
STAFFAN RASJÖ 2 098 864 8,49%
LARS SPÅNBERG Incl. Co. 1 921 429 7,77%
SYDSVENSK ENTREPRENÖRFOND AB 1 041 666 4,21%
MIKAEL LÖNN 750 000 3,03%
JOHAN RAPP 694 403 2,81%
MAGNUS CLAESSON Incl. Co. 681 949 2,76%
UNIONEN (SIF) 643 833 2,60%
JOHAN CLAESSON, Incl. Co. 576 034 2,33%
PER-­‐OLOF MÅRTENSSON Incl. Co. 425 666 1,72%
KENTH PETERSSON 408 000 1,65%
Others 5 200 003 21,02%
Total Number of Shares 24 732 949 100,00%
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