Immunicum Establishing a unique immuno-oncology approach by developing allogeneic, off-the-shelf, cell-based therapies
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Immunicum Establishing a unique immuno-oncology approach by developing allogeneic, off-the-shelf, cell-based therapies Investor presentation May 2019
Disclaimer
This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical
facts, contained in this presentation, including statements regarding Immunicum’s view on strategy, future operations, future clinical development plans and
objectives, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. The
words “anticipate”, “believe”, “estimate”, “expect”, “intend”, “may”, “plan”, “predict”, “project”, “target”, “potential”, “will”, “would” “can”, “could”, “shall”,
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undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in
the forward-looking statements we make. The forward-looking statements contained in this presentation reflect Immunicum’s current views with respect to
future events, and Immunicum assumes no obligation to update any forward-looking statements except as required by applicable law. Our actual results
and/or actual events could differ materially from those anticipated in forward-looking statements for many reasons, including, without limitation, risks
associated with our clinical development activities, chemistry, manufacturing and controls, regulatory oversight, product commercialization, upholding of
intellectual property rights or intellectual property claims, general market developments and other risks, uncertainties and factors within and outside of our
control. Given these risks, uncertainties and other factors, you should not place undue reliance on forward-looking statements, and we assume no
obligation to update forward-looking statements, even if new information becomes available in the future, or to provide information regarding the reasons
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should instead make or, if you are not qualified to do so, seek the assistance of qualified and professional counsel in making, an independent and
adequately substantiated assessment of us, our operations, current and future activities and commercial potential based on all available information about
us, as presented in financial reports, press releases and in other contexts, and about the business fields and markets in which we are active, as presented
in, inter alia, scientific and other publications (although we do not assume any responsibility for information about us obtained from third parties).
2
Immunicum Corporate Overview
Uniquely Positioned Backbone Immune Primer
• Off-the-shelf allogeneic cell therapy as intratumoral immune primer against neoantigens
Advanced Stage
• Phase II study in RCC fully enrolled; top-line results Q3 2019
• Excellent safety profile in over 90 patients in various solid tumors
• Robust GMP manufacturing in place and commercial scale activities initiated
Validated Approach
• Global regulatory interactions with US IND in place, EU CTAs & ATMP Certification
• collaboration/supply agreement for Phase II part of new study
Growth Opportunity
• Recent capital raise of $39 M at Nasdaq Stockholm with strong institutional investors
• Well-positioned to achieve data-driven value-inflection points in next 12 months
Experienced Team
• Extensive experience in pharma, business development, CMC and Regulatory
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Immunicum: advanced pipeline in solid tumor indications
Product & Indication Combination Preclinical Phase I Phase II Phase III
Ilixadencel: an off-the-shelf cancer immune primer
Immunicum’s lead product consists of allogeneic pro-inflammatory dendritic cells injected in the patient’s tumor to prime and activate the
patient’s own immune system to recognize and attack the tumor.
Kidney cancer Kinase inhibitors top-line results Q3 2019
Liver cancer Kinase inhibitors
Gastrointestinal stromal tumors Kinase inhibitors
Head and neck cancer Checkpoint inhibitors
Non-small cell lung cancer Checkpoint inhibitors
Gastric cancer Checkpoint inhibitors
IMM-2: allogeneic dendritic cells with adenovirus coding for tumor antigens
Immunicum’s proprietary adenovector can be used to deliver genes, coding for oncoviral antigens or neoantigens and immune-boosting
factors, into allogeneic dendritic cells, to create a cancer vaccine with optimal immune priming capacity.
IMM-3: optimized CAR-T expansion protocol for improved anti-cancer activity
Immunicum’s CD70 platform uses our core expertise in dendritic cell biology to provide superior expansion of CAR-T cells with improved
anti-tumor activity as well as higher resistance to oxidative stress and immunosuppressive factors in the solid tumor environment.
4
Ilixadencel: a unique off-the-shelf immune primer
Cell based, off-the-shelf immunotherapy product
• Allogeneic cells from healthy donor leukapheresis
• GMP-production at German CMO
• Proprietary method with cocktail to create pro-inflammatory dendritic cells
not a vaccine!
Intratumoral administration
• Applicable to all injectable solid tumors
• Using the tumor as the source of neoantigens as in situ vaccination
• Off-the-shelf approach inducing an individualized response
ILIXADENCEL PRODUCTION
Healthy
1x donor
sample
100x ilixadencel
doses 50x Patients
treated
3 YEAR SHELF-LIFE
5
Ilixadencel: mechanism of action in the tumor
Recruits and activates the patient’s own immune cells to prime a cytotoxic Th1 response against the released neoantigens
6
The immune primer positioning: starting the immune response
immune primers immune enhancers checkpoint inhibitors
TLR/STING, oncolytic viruses, vaccines IL-2, 4-1BB PD-(L)1, TIM-3, LAG-3
ilixadencel
prime T cell population expand T cell population block tumor’s defenses
“start the engine” “push the gas” “release the brake”
7The immune primer landscape: from traditional vaccines to
neoantigen-based approaches
Immune primer/vaccine approach
Tumor-associated antigens
Neoantigens
(tumor-specific antigens)
Neoantigens using tumor as source
Traditional vaccines
(e.g. Dendreon, Bavarian, Inovio)
Ex vivo / autologous vaccines
(e.g. Neon Tx, Gritstone, BioNTech) TLR ligands (e.g. Idera)
Challenges! STING ligands (e.g. Aduro)
Oncolytic viruses (e.g. Viralytics) ilixadencel
• Not tumor-specific Challenges!
• One product per patient: time
consuming and expensive Challenges!
• Limited recruitment / activation Recruits immune cells
Induces tumor cell death
Activates immune response
8The immune primer landscape: moving to more complete MoA
Comparative approaches starting to add cytokines and chemokines to their MoA based on initial clinical findings
First generation Second generation Third generation
TLR STING / RIG-I TLR + Flt3L
TLR, STING, RIG-I
Phase III Phase I Preclinical
OV GM-CSF OV + TNF⍺ IL-2 OV + IL-12 Flt3L CCL4
Oncolytic viruses
Phase III Preclinical Preclinical
IL-12 plasmid IL-12 / cytokine cocktail IL-12 + CXCL-9 ⍺CD3
IL-12
Phase II Preclinical Preclinical
Cytokines (e.g. IL-12)
ilixadencel Chemokines (e.g. XCL-1, CXCL-9) Phase II
Alloreactive T cells
9Ilixadencel – RCC Phase I/II Study Completed
Phase I/II RCC: intratumoral injection in kidney of metastatic
patients results in tumor-specific CD8+ T cell in blood and tumor
RENAL CELL CARCINOMA (RCC)
S
KIDNEY
TUMOR
Normal kidney tissue surrounding
Untreated tumor area (reference) Treated tumor area Metastasis
treated tumor area
A reference slide demonstrating the A massive infiltration of cancer specific A clear absence of T cells outside of A clear increased presence of CD8+ T
amount of T cells (black dots) in a CD8+ T cells in the tumor after the tumor site (similar to a healthy cells at a distant metastasis
non-treated tumor. injection of ilixadencel. tissue) supporting that the massive demonstrates that the immune system
infiltration is tumor-specific. is also able to identify and target
cancer cells in other parts of the body.
Laurell et al., Journal for ImmunoTherapy of Cancer 2017
11Phase I/II RCC: overall survival in mRCC patients more than
tripled vs historical data
Historical median OS of 14-16 months with sunitinib in newly Median OS of 48 months with ilixadencel
diagnosed mRCC patients (Heng 2009; Ko 2014; Mejean 2018) (Laurell et al., J Immunother Cancer 2017)
Still alive
Start of TKI
0 10 20 30 40 50 60 70
Time (in months) from start of ilixadencel treatment (as of January 2018)
12Phase I/II case report: ilixadencel followed by sunitinib results
in complete remission of brain and liver metastases
• Poor prognosis patient with multiple brain, lung and liver metastases PRIOR TO TREATMENT 6 MONTHS POST TREATMENT
• Received sunitinib due to progression after ilixadencel and surgery
• Complete response of all brain and liver metastases
• 66 months after ilixadencel treatment patient is still alive (October 2018*)
• Literature on RCC patients with brain metastases1:
Complete response of the brain
• 0% response in brain metastases to sunitinib (0/16 patients) Patient with brain metastases before
sunitinib treatment
metastases 6 months after start of
sunitinib
• 6.3 months overall survival in these 16 patients
• Potential combination synergy as sunitinib may block tumor’s defense against activated immune response
• Phase II study includes sunitinib for all patients after ilixadencel injections, versus sunitinib alone
* Later follow-up than included in survival graph
1) Chevreau et al., Clin Genitourin Cancer 2014
13Ilixadencel Backbone Immunotherapy for Solid Tumors in Major Indications
Ilixadencel in combination: kinase and checkpoint inhibitors
TYROSINE KINASE INHIBITORS (TKIs) CHECKPOINT INHIBITORS (CPIs)
Kidney Liver Gastrointestinal Head and Neck Lung Gastric
(RCC) (HCC) (GIST) (HNSCC) (NSCLC) (GA/GEJ)
Phase II study in RCC (MERECA) fully enrolled Phase Ib/II multi-indication study (ILIAD) now initiating
• Randomized controlled study in 88 patients in EU and US • Recent FDA approval to allow initiation of study in US
• Ilixadencel followed by sunitinib vs. sunitinib alone • Phase Ib study (n=21) with PD1 inhibitor pembrolizumab
• Q3 2019: top-line results on overall survival, tumor • Subsequent Phase II controlled studies per indication
response, tumor infiltration, etc.
• Nov' 2018: collaboration for Phase II
• 2019: initial safety and dosing results expected
Phase I/II study in HCC completed; GIST ongoing
Preclinical studies with CPIs and immune enhancers
• Jan’ 2019: publication of HCC results
• Oct’ 2018: poster with results at ESMO conference
• 2019: top-line results in GIST expected
• 2019: additional preclinical studies planned
15Ilixadencel: delivering program to pivotal stage of development
Preclinical: efficacy with checkpoint inhibitors
Clinical: controlled efficacy with standard-of-care
ongoing: MERECA Phase II, read-out Q3 2019
Clinical: CD8+ T cells in tumor and blood
Clinical: efficacy with checkpoint inhibitors
ongoing: ILIAD Phase Ib/II, read-outs 2019-2020
Clinical: infiltration and effects in metastases
Manufacturing: commercial scale at global CMO
Clinical: safety in over 90 patients ongoing: process development with Hitachi
Regulatory: studies in US and EU
Manufacturing: clinical scale at CMO
16Financial snapshot: recent capital raise of $39 M (SEK 351 M)
• December 2018: Directed & Rights Issue with a total of $39 M (SEK 351 M) with strong institutional investors
• $41 M cash (SEK 393 M; Q1 2019) provides financing towards end 2021 across value-inflection points
• Proceeds used for clinical studies, manufacturing commercial scale activities and preclinical studies
F I N A N C I A L I N F O R M A T I O N M A J O R S H A R E H O L D E R S ( A p r i l )
Shareholder %
Avanza Pension 8,97%
Nasdaq Stockholm: IMMU.ST Nordnet Pension Insurance 5,73%
Market cap: $75 M / SEK 726 M
Fourth Swedish National Pension Fund 4,88%
Price (9-May-2019): $0.83 / 8 SEK Gladiator 4,06%
Shares: 92,257,531 Martin Lindström 3,62%
Holger Blomstrand Byggnads AB 3,23%
Cash (31-03-2019): $41 M / SEK 393 M Second Swedish National Pension Fund 2,71%
Skandinaviska Enskilda Banken S.A 2,63%
Raised to date: $92 M / SEK 826 M Nordic Cross Asset Management 2,60%
Runway: towards end 2021 BNP Paribas Sec Serv Luxembourg 1,95%
BNP Paribas Asset Management 1,95%
Theodor Jeansson 1,73%
17Key value-inflection points in next 12 months
SEK 351M ($39M) Phase II RCC MERECA
raised on Nasdaq study top-line results
Stockholm on overall survival
2018 2019 2020
Q4 Q1 Q2 Q3 Q4 Q1
Merck KGaA & Phase I/II GIST
Pfizer collaboration top-line results
Phase Ib/II ILIAD study Phase Ib/II ILIAD study
with checkpoint inhibitors with checkpoint inhibitors
First Patient In initial safety and dosing results
18Immunicum’s market: Immuno-Oncology
• Immuno-Oncology global market size expected to reach $76 billion in 20221
• Big Pharma racing to find combination therapies with their in-house checkpoint inhibitors, including BMS,
Merck, and J&J with recent high-value transactions
Source: (1) Radiant Insights - Global Cancer Immunotherapies Market to 2022, 2016. (2) Financial Times 29 May 2015
19Management team experienced in drug & business development (1/2)
- Carlos de Sousa is a medical doctor by training, having earned his degree at School of Medicine, University of Lisbon and
Carlos de Sousa holds an Executive MBA from the Stern School of Business, New York University.
Chief Executive Officer
- Dr. de Sousa has more than 25 years of senior level experience in the global pharmaceutical and biotech industry, including
M.D., Executive MBA business development, mergers & acquisitions, global marketing and clinical development.
- Prior to joining Immunicum, Dr. de Sousa held senior positions at Nycomed/Takeda, Pfizer, Novartis, BBB Therapeutics,
Newron Pharmaceuticals and, most recently, as Chief Business Officer at Zealand Pharma in Denmark.
- Michaela Gertz holds a MSc in Business and Economics from Uppsala University including a course of study at the
Michaela Gertz Katholieke Universiteit in Leuven, Belgium.
Chief Financial Officer
- Ms. Gertz most recently was CFO & Investor Relations Manager at PledPharma AB, a drug development company based in
MSc. in Business and Stockholm. She was instrumental in PledPharma’s IPO in 2011 and subsequent fund-raising efforts.
Economics
- Prior to that, Ms. Gertz spent three years as Head of Investor Relations and Financing at Accelerator Nordic AB. Before
joining the life sciences industry, Ms. Gertz worked in finance and private equity at ITP Invest AB and Handelsbanken.
Alex Karlsson-Parra - Adjunct Professor Karlsson-Parra has over 20 years of experience working in the field of transplantation immunology and is
Founder, Chief Scientific Officer former chairman of the Swedish Expert Group for Clinical Immunology.
M.D., Ph.D. Adjunct Professor in - He was awarded the Athena Prize, the Swedish healthcare’s most prestigious award for clinical research, in 2014.
Clinical Immunology, Uppsala
University - He was formerly Associate Professor and chief physician at the Department of Clinical Immunology at Sahlgrenska University
Hospital, Gothenburg.
- Peter Suenaert is gastroenterologist – oncologist by training (Leuven University, Belgium, McGill University, Canada, Institute
Peter Suenaert Gustave-Roussy, France) and holds a PhD in gut barrier function related to inflammatory bowel diseases from Leuven
Chief Medical Officer University.
M.D., Ph.D. Digestive - Prior to joining Immunicum Dr. Suenaert served as Global Clinical Program Lead of Glenmark Pharmaceuticals for the oncology
Oncologist unit (immune oncology assets) from start-up stage to being fully operational phase I/II protocol development.
- Dr. Suenaert has held several leading positions within global clinical development and research e.g. a Clinical Research
Development leader in global early cancer immunotherapeutics development at GlaxoSmithKline Vaccine in Belgium.
20Management team experienced in drug & business development (2/2)
Sharon Longhurst - Sharon Longhurst holds a Ph.D. in Virology from the University of Warwick, UK.
Head of CMC - Dr. Longhurst has more than 15 years of experience in leading CMC efforts in small and medium sized organizations.
Ph.D. in Virology - Prior to joining Immunicum, she was Senior CMC Manager at Akari Therapeutics, where she was responsible for all aspects
of CMC. Before Akari, she spent 5 years as Principal Consultant of CMC at Parexel Consulting, and 6 years as
Pharmaceutical Assessor at MHRA in London.
- Margareth Jorvid holds an MSc. Pharm from Uppsala University, Sweden, a MSc MTRA from Cranfield University, UK, and
Margareth Jorvid an MBA from Stockholm School of Economics, Sweden.
Head of Regulatory and QA
- Ms. Jorvid has over 30 years of Regulatory Affairs experience and has worked at the regulatory side at the Medical Products
Agency (MPA) in Sweden, and in large and small pharmaceutical companies such as Roussel Nordiska and Neopharma.
MSc. in Pharmacology, MBA - Since 2006, she is consultant in regulatory affairs and quality assurance as CEO of Methra Uppsala AB, LSM group, and is
fellow and Honorary Life Member of TOPRA - The Organisation for Professionals in Regulatory Affairs.
- Sijme Zeilemaker holds an MSc. in Biomedical Sciences - Management from Leiden University, the Netherlands, which
Sijme Zeilemaker included an exchange program with Karolinska Institutet, Sweden.
Senior Director Business
Development - Mr. Zeilemaker had various business development positions at preclinical and clinical oncology biotech companies, being
responsible for pharma/biotech partnering, licensing technologies, non-dilutive funding, and corporate communication.
MSc. in Biomedical Sciences -
Management - He was formerly Director Business Development at InteRNA Technologies, Head of Business at 2-BBB Medicines and
Business Development Manager at to-BBB technologies in the Netherlands.
21Immunicum: corporate highlights
Unique Positioning Advanced Stage
Innovative immune primer Phase II fully enrolled
Off-the-shelf cell therapy Safety in >90 patients
Backbone therapy Robust manufacturing
Experienced Team Growth Opportunity
Pharma & Biotech Immuno-Oncology market
Founder as CSO SEK 351 M capital raise
CMC & Regulatory Value-inflection data in 2019
22Immunicum Establishing a unique immuno-oncology approach by developing allogeneic, off-the-shelf, cell-based therapies
Strong patent protection until at least 2031
Patent family Country Filing Date Expir. date Title Status
BE, BR, CH, CN, DE, DK,
ES, FR, GB, HU, IE, IT, JP, 2031-02-10 Improved composition for inhibiting Granted: all other
Ilixadencel 2011-02-10
KR, NL, PL, RU, SE, SI, TR, 2031-08-16 (US) tumor cell proliferation Pending: BR
US
AU, BE, BR, CA, CH, CN, Granted: BE, CH, DE, DK, ES, FR, GB,
DE, DK, ES, FR, GB, HU, 2033-12-18 Co-differentiation of monocytes from HU, IE, IT, MX, NL, US
Production 2013-12-18
IN, IE, IT, ID, JP, KR, MX, 2034-01-28 (US) allogeneic donors
NL, PL, RU, SE, SI, TR, US Pending: all other
CH, DE, DK, ES, FR, GB, 2002-06-06 (SE) 2022-06-06 New method and composition for
IMM-2 Granted: all
HU, IE, IT, NL, SE, SI, US 2003-06-05 2023-12-19 (US) producing cellular allogenic vaccine
Hexon tat-ptd modified adenovirus and
IMM-2 adenovirus US 2013-05-13 2033-05-33 Granted: US
uses thereof
2017-09-20 (EP) Improved allogeneic dendritic cells for
IMM-2 EPO, WO ~2038 Pending
2018-09-19 (WO) use in cancer treatment
Method for proliferation of
IMM-3 CN, EPO, HK, JP, US 2010-10-13 2030-10-13 Granted: CN, HK, JP, US
antigen-specific T cells
IMM-3 antiviral EPO, US 2012-04-12 2032-04-12 Method for priming of T cells Granted: US, EPO
Method for proliferation of
IMM-3 CN, EPO, JP, US 2012-04-12 2032-04-12 Granted: CN, US, JP
antigen-specific T cells
Additional potential protection
ü Additional 7-10 years of protection for Orphan Drug designation possible depending on regulatory authority
ü Additional 5 years of protection possible through Supplementary Protection Certificate (SPC)
ü Manufacturing process and regulatory landscape increase complexity and barriers to entry
24Ilixadencel as backbone therapy in the cancer immunity cycle:
“pushing the gas” to turn cold tumors into hot tumors for immunotherapy
4 Trafficking of CD8+ “killer” T cells to cancer tissue
Priming and activation of CD8+ T cell
3 BL 5 Infiltration of T cells into cancer tissue
immune response to neoantigens OO
LY D
MP VE
HN SS
OD EL
E
OR
TUM
Transport of neoantigens by ILIXADENCEL
2 INJECTION 6 Recognition of cancer cells by T cells
dendritic cells to lymph nodes
Release of tumor neoantigens and Killing of cancer cells
1 7
recruitment of dendritic cells
PUSH THE GAS: RELEASE THE BRAKE:
ACTIVATE THE IMMUNE SYSTEM BLOCK CANCER IMMUNE SUPPRESSION
and/or KILL CANCER CELLS
Immunicum’s ilixadencel primes and checkpoint inhibitors (Keytruda®/Opdivo®)
activates the immune system to tyrosine kinase inhibitors (sunitinib)
recognize and find cancer cells chemotherapies (gemcitabine)
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