PCI Biotech Holding ASA - An innovative and versatile platform technology for therapeutic enhancement and vaccination
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Unlocking the potential of innovative medicines PCI Biotech Holding ASA An innovative and versatile platform technology for therapeutic enhancement and vaccination Investor presentation December 2014
Important notice and disclaimer (1:2) ABOUT THIS PRESENTATION By reading this investor presentation (the “Presentation”), or attending any meeting or oral presentation held in relation thereto, you (the “Recipient”) agree to be bound by the following terms, conditions and limitations. This Presentation has been produced by PCI Biotech Holding ASA (the “Company”) solely for use at presentations to potential investors in connection with establishing a guarantee consortium for a contemplated rights offering of shares by the Company. The managers for establishing the guarantee consortium and the contemplated rights issue are DNB Markets, a part of DNB Bank ASA and Fondsfinans AS (collectively the “Managers”). The Presentation is for information purposes only. The information contained in this Presentation does not constitute or form part of, and should not be construed as, an offer or invitation to subscribe for or purchase, or a solicitation of an offer to buy any securities of the Company in any jurisdiction. Prospective guarantors (if and when a consortium is to be established) are required to read the offering material and other relevant documentation which is released in relation thereto for a description of the terms and conditions of the guarantee. Neither this Presentation nor any part of it shall form the basis of, or be relied upon in connection with any offer, or act as an inducement to enter into any contract or commitment whatsoever. CONFIDENTIALITY This Presentation and its contents are strictly confidential. Distribution of this Presentation to any person other than the Recipient and any person retained to advice the Recipient with respect to the guarantee consortium or the contemplated rights offering is unauthorized, and any disclosure of any of the contents of this Presentation, without the prior written consent of the Company or the Managers, is prohibited. FORWARD LOOKING STATEMENTS This Presentation contains certain forward-looking statements relating to the business, financial performance and results of the Company and/or the industry in which it operates. Forward- looking statements concern future circumstances and results and other statements that are not historical facts, sometimes identified by the words “believes”, expects”, “predicts”, “intends”, “projects”, “plans”, “estimates”, “aims”, “foresees”, “anticipates”, “targets”, and similar expressions. The forward-looking statements contained in this Presentation, including assumptions, opinions and views of the Company or cited from third party sources are solely opinions and forecasts which are subject to risks, uncertainties and other factors that may cause actual events to differ materially from any anticipated development. None of the Company or any of its subsidiary undertakings or any such person’s officers or employees provides any assurance that the assumptions underlying such forward-looking statements are free from errors nor does any of them accept any responsibility for the future accuracy of the opinions expressed in this Presentation or the actual occurrence of the forecasted developments. The Company assumes no obligation, except as required by law, to update any forward-looking statements or to conform these forward-looking statements to our actual results. RISK FACTORS An investment in the Company involves significant risk, and several factors could adversely affect the business, legal or financial position of the Company or the value of its securities. The Recipient should carefully review the chapter “Risk Factors” in the Presentation for a description of certain of the risk factors that will apply to an investment in the Company’s securities. Should one or more of these or other risks and uncertainties materialise, actual results may vary significantly from those described in this Presentation. An investment in the Company is suitable only for investors who understand the risk factors associated with this type of investment and who can afford a loss of all or part of their investment. 2
Important notice and disclaimer (2:2) NO REPRESENTATION OR WARRANTY / DISCLAIMER OF LIABILITY None of the Company or the Managers or any of their respective parent or subsidiary undertakings or affiliates, or any directors, officers, employees, advisors or representatives of any of the aforementioned (collectively “Representatives”) make any representation or warranty (express or implied) whatsoever as to the accuracy, completeness or sufficiency of any information contained herein, and nothing contained in this Presentation is or can be relied upon as a promise or representation by the Managers or any of its Representatives. None of the Managers or any of their Representatives shall have any liability whatsoever (in negligence or otherwise) arising directly or indirectly from the use of this Presentation or its contents or otherwise arising in connection with the guarantee consortium or the contemplated rights offering, including but not limited to any liability for errors, inaccuracies, omissions or misleading statements in this Presentation. Neither the Company nor the Managers have authorised any other person to provide investors with any other information related to the guarantee consortium, the contemplated rights offering or the Company, and neither the Company nor the Managers will assume any responsibility for any information other persons may provide. NO UPDATES This Presentation speaks as at the date set out on herein. Neither the delivery of this Presentation nor any further discussions of the Company or the Managers with the Recipient shall, under any circumstances, create any implication that there has been no change in the affairs of the Company since such date. Neither the Company nor the Managers assume any obligation to update or revise the Presentation or disclose any changes or revisions to the information contained in the Presentation (including in relation to forward-looking statements). NO INVESTMENT ADVICE The contents of this Presentation shall not be construed as financial, legal, business, investment, tax or other professional advice. The Recipient should consult with its own professional advisers for any such matter and advice. CONFLICT OF INTEREST The Managers and/or their employees may hold shares, bonds, options or other securities of the Company and may, as principal or agent, buy or sell such securities. The Managers may have other financial interests in transactions involving such securities. DISTRIBUTION AND SELLING RESTRICTIONS None of the Company or the Managers, or any of their respective Representatives, has taken any actions to allow the distribution of this Presentation in any jurisdiction where action would be required for such purposes. The Presentation has not been registered with, or approved by, any public authority, stock exchange or regulated market. The distribution of this Presentation, as well as any subscription, purchase, sale or transfer of securities of the Company may be restricted by law in certain jurisdictions, and the Recipient should inform itself about, and observe, any such restriction. Any failure to comply with such restrictions may constitute a violation of the laws of any such jurisdiction. None of the Company or the Managers, or any of their respective Representatives, shall have any responsibility or liability whatsoever (in negligence or otherwise) arising directly or indirectly from any violations of such restrictions. GOVERNING LAW AND JURISDICTION This Presentation is subject to Norwegian law, and any dispute arising in respect of this Presentation is subject to the exclusive jurisdiction of Norwegian courts. 3
Risk factors
Investing in the shares (the "Shares") of the Company involves inherent risks. Before deciding whether or not to invest in the Shares, a prospective investor should consider carefully all
of the information set forth in this Presentation and otherwise available.
Below is a brief summary of the most relevant risk factors that may affect the Company and/or the value of the Company's Shares. The summary must be read in conjunction with the
chapter "Risk Factors" in the appendix of this presentation, which provides for a more detailed description of certain of the risk factors that will apply to an investment in the Company's
Shares.
An investment in the Company's Shares are suitable only for investors who understand the risk factors associated with this type of investment and who can afford a loss of all or part of
the investment. If any of the risks described below or in the chapter "Risk Factors", individually or together with other circumstances, they may have a material adverse effect on the
Company’s business, financial condition, results of operations and cash flow, which may cause a decline in the value and trading price of the Shares that could result in a loss of all or
part of any investment in the Shares. The actual results of the Company could differ materially from those anticipated as a consequence of many factors, including the following:
Risks related to the company and its business • Most of the Company’s expenses have since inception been related to research and
• The Company is in an early stage of development and the Company’s clinical development and accordingly, the Company has accumulated substantial net losses
studies may not prove to be successful and expects such losses to continue as it continues product and clinical development
• Obtaining regulatory approvals is required for commercialisation of the and with the aim to obtain regulatory marketing authorisation of products derived from
Company’s products its technology
• The financial success of the Company requires obtaining acceptable price and • The Company is exposed to commercial risk
reimbursement • The Company may face competition from low-cost generic products
• The success, competitive position and future revenues will depend in part on the • The Company is exposed to risks related to changes in regulatory environment
Company’s ability to protect intellectual property and know-how • The Company’s results may be affected by changes in public sentiment
• The Company operates in a highly competitive industry • The Company’s business involves use of chemicals and is thus exposed to
• The Company relies, and will continue to rely, upon third-parties for clinical trials environmental risks
and manufacturing
• The Company may not be able to develop new product candidates Risks related to the shares
• There may be limited alternative use of the photochemical internalisation • The Company is listed on a regulated market place with a inherent risk of limited
platform liquidity for securities issued by the Company
• The Company may not be able to enter into partner agreements • The price of the Shares may fluctuate significantly
• The proceeds of the rights offering are not expected to fund the Company until a • Future issuances of Shares or other securities in the Company may dilute the holdings
commercial stage has been reached of shareholders and could materially affect the price of the Shares
• The Company’s ability to raise additional capital to satisfy future liquidity • Investors in the United States may have difficulty enforcing any judgment obtained in
requirements, operations and projects the United States against the Company or its directors or executive officers in Norway
• The Company faces an inherent business risk of liability claims in the event that • The transfer of the Shares may be subject to restrictions on transferability and resale in
the use or misuse of the compounds results in personal injury or death certain jurisdictions
• The Company may not receive full, or any, VAT refunds • Shareholders outside of Norway are subject to exchange rate risk
• The Company is reliant on key personnel and the ability to attract new, qualified • Investors may not be able to exercise their voting rights for Shares registered in a
personnel nominee account
• The Company’s results will be exposed to exchange rate and interest rate risks
4
Agenda
1. Introduction
2. The PCI technology platform
3. An innovative localised cancer treatment concept
Head & neck cancer
Bile duct cancer
4. Unlocking the true potential of new treatment paradigms
Immunotherapy
Macromolecules
5. Commercial strategy and key financials
6. Organisation and shareholders
5
Key company highlights
Unique drug Effective localised targeted delivery of a range of therapeutics, from small to macromolecules
enhancement
technology
Strong IP and unique patented technology
Innovative localised Targeting cancers with high unmet medical need and significant market potential
cancer treatment
Strong clinical effects proven for head and neck cancer – currently in clinical Phase II
concept with proven
effects Proven pre-clinical effects for bile duct cancer – an orphan indication currently in clinical Phase I/II
Unlocking the true Opening a pipeline of pre-clinical partnership opportunities
potential of new Immune-potentiating technology to enhance key immune cell response of partners’ cancer vaccines
treatment paradigms Effective localised delivery of partners’ innovative macromolecules
Experienced team
with strong support
Experienced management team and board, backed by a solid shareholder base
Attractive timing Company is approaching key data readouts and potential partnering agreements
6
PCI Biotech at a glance
A listed (PCIB:NO) cancer-focused biotech company
PCI induces endosomal escape through illumination
Photochemical internalisation (“PCI”) technology,
originating from the Norwegian Radium Hospital
Technology platform for a delivery system of molecules
into cells; Enables targeted delivery of chemotherapy
into cancer cells activated by illumination
Promising phase I results with the PCI-inducing
photosentisizer Amphinex® for head & neck cancer
Entering clinical Phase II with Amphinex® for two
indications;
Head & neck cancer
Bile duct cancer
PCI
Pre-clinical program for enhancement of therapeutic
vaccination:
CTL*-induction technology that provides significant
enhancement of the needed cellular immune response to
vaccines
7 *Cytotoxic T Lymphocyte
Key achievements and milestones to date
2008-2010 2011 2012 2013 2014
PCI Biotech listed Phase I completed, Initiated the Redesigned the First patient treated
on the Oslo Stock demonstrating that ENHANCE study, a Phase II study in in the Phase I/II
Exchange (2008) Amphinex induced Phase II study with head & neck cancer study in inoperable
PCI of bleomycin is Amphinex induced to optimise intra- bile duct cancer
Enabling PCI well tolerated, and PCI of bleomycin in tumour illumination
technology platform exhibiting early recurrent inoperable Treatment evaluation
signs of promising head & neck cancer Amphinex induced of the first two intra-
Identification of efficacy PCI of gemcitabine tumour optimisation
product candidates Selection of locally Phase I/II study on groups in the Phase
for PCI treatment In-depth assessment advanced inoperable bile duct cancer II study in head &
of clinical indications bile duct cancer as initiated neck cancer
Focus on and products for PCI second clinical completed
demonstrating development indication Promising pre-
proof-of-concept clinical vaccination Safety evaluation of
and commercial Selection of Regulatory pathway results and IP the first treatment
attractiveness recurrent head & for Amphinex in generation – focus cohort in the Phase
neck cancer as first head & neck cancer on vaccination I/II bile duct study
Amphinex Phase I clinical indication in EU clarified amplified completed
study with PCI of
bleomycin initiated Thorough trial design Pre-clinical program Initiated discussions
discussions with key in vaccination with the FDA on the
opinion leaders and initiated head & neck cancer
expert groups program
8
Use of proceeds and value inflection points
2015 Mid-2016
• The company expects
Complete proof of concept for intra-
that the contemplated Head and tumour illumination and initiate
NOK 70 million rights neck expansion of the Phase II ENHANCE Phase II ENHANCE study ongoing
study
issue will provide the cancer
Open IND* and initiate US sites
company with sufficient *Investigational New Drug
funding until mid-2016
Complete clinical Phase I dose- Orphan drug designation
Bile duct escalation part and initiate Phase II
cancer Bile duct cancer Phase II study
randomised study
ongoing
Document immune-potentiation in
relevant animal models and
Vaccines & strengthen products/IP Strategic collaboration to facilitate
Macro- Position PCI in second generation
further vaccine product development
molecules in pre-clinical testing
cancer immunotherapy regimen
Strategic R&D alliances and licensing
9
Agenda
1. Introduction
2. The PCI technology platform
3. An innovative localised cancer treatment concept
Head & neck cancer
Bile duct cancer
4. Unlocking the true potential of new treatment paradigms
Immunotherapy
Macromolecules
5. Commercial strategy and key financials
6. Organisation and shareholders
10PCI technology – enable drugs to cover additional
areas of unmet medical need
Existing & innovative treatments PCI enhancement technology
Cells Active ingredient Photosensitiser Light source
(trapped in endosome) (Amphinex)
Small molecules
siRNA/mRNA
Antibody targeted
Cancerous cell Red light
drugs TPCS2a
Peptides
Antigens
Blue light
Dendritic cell
Endosomal escape
Release of drug in cells
11PCI technology – enabling drugs to reach
intracellular therapeutic targets
STEP 1:
• TPCS2a (S) and the active molecule (D) are injected into the body and The active molecule
carried by the blood stream to the cell - Anticancer agent, e.g.
bleomycin,
gemcitabine
- Oligonucleotide, e.g.
siRNA
STEP 2: - Protein, e.g. antibody-
drug conjugate
• TPCS2a (S) and the active molecule (D) are taken up by the cell, but D - Peptide: e.g. antigen
is unable to reach the target (T), as it is encapsulated in an endosome
• S is washed away from the cell membrane, but trapped in endosomes
S
The PCI component
STEP 3: - Light sensitive
• Light activates TPCS2a (S) in the membrane of the endosome component
- Amphinex - TPCS2a
• The membrane integrity is affected and the active molecule released
STEP 4: The target
- Target for the active
• The active molecule (D) can now bind to its target (T) and initiate the molecule
therapeutic response - E.g. DNA, mRNA,
enzyme, microtubuli
PCI mechanism of action – triggered endosomal escape through illumination
12PCI technology and IPR
• PCI Biotech is the world leader in photochemical internalisation – an innovative technology
platform for localised targeted endosomal escape
• PCI Biotech has several patents covering all potential business areas across the PCI platform, as
well as business area specific technology and use patents
• The company follows an active patenting strategy to solidify and enhance the proprietary PCI
platform, including all interesting and potentially valuable medical applications
• PCI Biotech is currently particularly active in the emerging field of immunotherapy, where several
new patent applications have been filed the last years to build a robust IP estate for PCI as a
powerful CTL-induction technology for therapeutic vaccination
Platform & business
area patents
Vaccination platform
and technology area
patent applications
13Agenda
1. Introduction
2. The PCI technology platform
3. An innovative localised cancer treatment concept
Head & neck cancer
Bile duct cancer
4. Unlocking the true potential of new treatment paradigms
Immunotherapy
Macromolecules
5. Commercial strategy and key financials
6. Organisation and shareholders
14Head & neck cancer – introduction and motivation
Introduction to head & neck cancer Why target head & neck cancer?
Cancer affecting the cell lining of mouth
and throat
Large patient population with high unmet medical need
The sixth most common cancer with a
worldwide incidence of ~650,000 Cancer metastasises late, but local recurrence is common
Five-year survival rate of 40-50% Adverse effects of existing local treatments affect quality of life
HPV induced cancer is increasing, A field with historic lack of innovations
affecting younger people
Need of new functional and cosmetic benign treatments
Recurrent disease mainly given palliative treatment
Quality of life and locoregional control considered most important
Treatment options often limited to palliative systemic therapy
High unmet medical need for better localised treatment
15Head & neck cancer – a substantial market
potential
Sizeable immediate target market Head & Neck cancer
Incidence:
Incidence is stable, close to 200,000 across Europe and the US Europe: 140,000
North America: 50,000
Immediate target is inoperable recurrent patients 33% of patients 66% of patients
Almost 40,000 assumed to be eligible for PCI treatment* Stage I Stage II Stage III Stage IV
Substantial upside potential earlier in the treatment algorithm
Surgery and/or Surgery and/or Combined stage III and IV
Attractive price potential radiotherapy radiotherapy
alone alone >50% $1.8 billion in 2012 (~40% estimated to be in H&N) 80% complete 60% complete
remission remission
Average total price / patient close to $70k in US and $40k in EU
Surgery and Other
radiotherapy treatments
High potential market penetration
50%
Anticipated benefits of PCI with Amphinex Recurrence
Greater efficacy 30%
Less systemic side effects Distant metastases
Source: Datamonitor Stakeholder Opinions: Head and Neck Cancer (2004),
Better cosmetic and functional outcome, with improved quality of life GLOBOCAN (www-dep.iarc.fr, accessed March 2010)
16
* Source: Market assessment from BridgeheadAmphinex Phase I summary – well tolerated and
promising early signs of efficacy
Summary of Study Design
Key findings
Cutaneous and subcutaneous Very promising early signs of tumour response across a
Cancer type
malignancies range of Amphinex dose levels
Phase I Apparent strong selectivity for cancer in several patients
Photosensitiser Amphinex (PCIB) Well tolerated with appropriate pain control and
Drug Bleomycin (single dose) anaesthesia
Light source Red laser, 652 nm (PCIB) Dose limiting toxicities (“DLT”) at highest dose due to skin
photosensitivity and wound infection
Fixed variables Bleomycin and light dose
Variables Amphinex dose
Assess safety and tolerance of
Purpose of study
Amphinex
Patients with cutaneous and/or
subcutaneous tumours. Majority of Baseline Day 14
Patient description
patients had Squamous cell
carcinoma of the head & neck
22 patients treated across 5 dose
Patient sample size
groups
Treatment modality Surface illumination Day 28 Day 90
Complete Response following treatment of malignant skin adnexal tumour
17Amphinex Phase II ENHANCE head & neck
cancer study – addressing a clear unmet need
Summary of study design Current status and plans
Squamous cell carcinoma of the head
Cancer type
and neck
The intra-tumour illumination introduced in Phase II
resulted in too strong and undesired treatment effects
Phase II
Intra-tumour illumination is therefore optimised in a
Photosensitiser Amphinex (PCIB)
separate light-dose escalation part of the study; second
Drug enhanced Bleomycin (single dose) light-dose cohort (3 pts) concluded Q3-2014
Light source Red laser 652 nm (PCIB) So far no serious safety concerns in the light-dose
Amphinex, Bleomycin and surface escalation part and clear indications of tumour
Fixed variables
light dose response; three more patients will be included at the
Intra-tumour light dose (in run-in same light dose before final light dose selection
Variables
optimisation part of the study)
Interim/PoC analysis after 12 patients treated with intra-
Assess safety and efficacy of a single tumour illumination at the selected light dose
Purpose of study treatment of Amphinex induced PCI
of Bleomycin
Recurrent head and neck squamous
cell carcinoma, with or without
Patient description
metastasis, unsuitable for
radiotherapy and surgery
Surface and/or intra-tumour
Treatment modalities
illumination
Patient sample size Up to 80 patients
Primary endpoint: Progression Free Survival at 6 months
18Bile duct cancer – introduction and motivation
Introduction to bile duct cancer Why target bile duct cancer?
Cancer affecting the cell lining of the bile
duct (Medical term: Cholangiocarcinoma) Patient population with high unmet medical need
Rare disease – incidence rate of 1-2 per Most patients die of unrelieved biliary obstruction
100,000 in the western world
Resection only potential cure, but only possible in ~30%
Five-year survival rate of less than 5%,
Remarkable resistance to chemotherapy – none approved
and 0% when inoperable
Gemcitabine + cisplatin is becoming standard treatment
Incidence and mortality rates are
increasing worldwide Medical need for better local treatment methods
Orphan indication represents a distinct market opportunity
A range of development and market incentives
About one third of orphan drugs have sales > $1b
Orphan market totaled $50b in 2011 (~6% of pharma sales)
Easy access with light through routine endoscopic methods
Attractive due to orphan benefits and absence of satisfying treatments
19Bile duct cancer – an orphan indication with a
sizeable market potential
Immediate target market is as first line treatment
Bile duct cancer
Incidence is close to 15,000 across Europe and the US Incidence*:
Europe: 6-8,000
USA: 5-6,000
Immediate target is inoperable patients with local disease
Approximately 3,000 assumed to be eligible for PCI treatment 45% of patients 55% of patients
Possible upside potential in metastatic disease
Local disease Metastatic disease
Stenting and
High price potential 50% 50%
chemotherapy
Lack of approved medicinal treatment options
Orphan indication implies a high price
Operable disease Inoperable disease
Surgery and Stenting and
chemotherapy chemotherapy
Potential significant majority share of the market
Anticipated benefits
No competing marketable treatment alternatives *Source; Khan et al, Lancet 2005; 366:1303
Gatta et al, Eur J Cancer 2011; 47:2493
Bragazzi et al, Transl Gastrointest Cancer 2012; 1:21
Greater efficacy due to local chemotherapy boost
Easy light access through established standard procedures
20Pre-clinical data – PCI enhances the effect of
gemcitabine in vitro and in vivo
PCI enhances the effect of gemcitabine PCI enhances the effect of gemcitabine
in bile duct cancer cells in vitro in animal cancer in vivo model
Cancer cell survival (% of untreated cells)
TFK-1 cells
EGI-1 cells
Light exposure time (sec)
21Amphinex Phase I/II study in bile duct cancer
– an orphan indication without approved drugs
Summary of Study Design Current status and plans
Cancer type Bile duct (Cholangiocarcinoma)
Phase I/II Safety driven Phase I
Photosensitiser Amphinex (PCIB)
First dose cohort (3 pts) concluded Q2-2014 – no
Drug enhanced Gemcitabine (single dose) safety concerns
Light source Red laser 652 nm (PCIB)
Inclusion into second cohort ongoing
Gemcitabine PCI dose and systemic
Fixed variables
cisplatin/gemcitabine dosing regimen 5:2 randomisation in Phase II, 35 pts in total
Variables Amphinex and/or light dose
Open-label, multi-centre study to
assess the safety and efficacy of a
single treatment of Amphinex
induced PCI of gemcitabine, followed
Purpose of study by systemic cisplatin/ gemcitabine.
All patients are stented. Phase I to
find light and Amphinex dose.
Phase II randomized to compare PCI
vs. stenting alone
Locally advanced inoperable bile
Patient description
duct cancer
Treatment modality Intraluminal illumination
Patient sample size Up to 45 patients
Primary endpoint: Progression free survival
22PCI for localised head & neck- and bile duct
cancer treatment – advantages and competitors
Advantages Competitors
Current chemotherapies can kill cancer cells, but Chemotherapy
lack of tumour selectivity requires highly toxic dose • Historic lack of innovations for these cancers
levels. PCI treatment may: • None approved for bile duct cancer and weak pipeline
target chemotherapy to localised cancer cells • Limited head & neck cancer pipeline
make reduced dosing efficacious Radiation therapy
• Long-lasting treatment courses with frequent visits
avoid most systemic adverse reactions
• Lack of tumour selectivity
• Limited treatment repeatability of recurrences
PCI may also provide important advantages
• New technologies are complex and expensive
compared to other localised cancer treatments:
Radiofrequency ablation
single treatment
• Lack of tumour selectivity and ambiguous safety data
improved tumour selectivity
Photodynamic therapy
repeatable upon recurrence • Limited tumour selectivity and treatment depth
benign cosmetic and functional outcome • Limited approval / ambiguous efficacy data
• Historic lack of innovations and weak pipeline
23Agenda
1. Introduction
2. The PCI technology platform
3. An innovative localised cancer treatment concept
Head & neck cancer
Bile duct cancer
4. Unlocking the true potential of new treatment paradigms
Immunotherapy
Macromolecules
5. Commercial strategy and key financials
6. Organisation and shareholders
24Unlocking the true potential of new treatment
paradigms
Enhancement of therapeutic vaccination and delivery of macromolecules
• PCI is a clinically proven endosomal escape
technology that may realise the true
therapeutic benefit of innovative medicines
• Strong preclinical efficacy evidence
Potentiation of responses considered key
for effective therapeutic vaccination
Effective localised delivery of a range of
macromolecules
• Value will be captured through licensing deals
and strategic R&D alliances – currently in
discussion with potential partners
PCI may realise additional therapeutic potential of innovative medicines and
increase their coverage of unmet need in certain disease areas
25An opportunity to play a key role in the second
generation cancer immunotherapy paradigm
PCI
Second generation
cancer immunotherapy
PCI technology
• Make it possible to achieve Cytotoxic
T Lymphocyte (CTL) response with
protein/peptide vaccines
• Can solve a fundamental challenge for
several existing vaccine approaches
26Cancer therapeutic vaccines – substantial
development pipeline and expected market growth
Development pipeline Market size forecast
Therapeutic Cancer Vaccines Market, Global, Development Therapeutic Cancer Vaccines Market, Global,
Pipeline, Candidates by Indication, 2012-2019 Revenue Forecast ($bn), 2013-2019
Source: GBI Research’s Proprietary Pipeline Products database; GLOBOCAN 2008 Source: GBI Research’s Proprietary Pipeline Products Epidemiology and Market Size Databases
• “Provenge” currently the only marketed therapeutic
cancer vaccine (annual global sales of approx. $200
million)
• “233 companies plus partners are today developing 275 cancer
• Therapeutic cancer vaccine market could grow to a
vaccine drugs in 600 developmental projects in cancer across
value of $7.6 billion by 20192
161 different targets” 1
• All therapeutic cancer vaccines will need immune-
• Top 5 indications: Breast, Colorectal, Lung, Prostate, Melanoma
potentiating technologies to be effective
1 BioseekerGroup; Cancer Vaccines Drug Pipeline Update 2014
27 2 GBIResearch, March 2013
*France, Germany, Italy, Spain, UKCancer therapeutic vaccines – PCI as a powerful
CTL-induction technology
1 An effective immune-potentiator, 2 that works in synergy with state-of-the-art vaccine technologies
PCI in vivo vaccination in mouse model
PCI with technology A and B in mouse model
Antigen-specific CD8+ T-cells (% of total
PCI
Antigen specific killer T-cells (% of
25
16
20
totall killer T-cells)
12
CD8+ T-cells)
15
8
10
4
5
0
0 Untreated OVA 10 OVA 100 OVA 10 OVA 10 PCI / PCI / PCI /
Untreated Vaccine alone Vaccine + PCI µg µg µg + A µg + B OVA 10 OVA 10 OVA 10
µg µg + A µg + B
3 and translates into therapeutic effect in disease models.
28Cancer therapeutic vaccines – competitive
advantages and user-friendly PCI solutions
Safety – TPCS2a tested in Phase I study (i.v. inj.) at much
higher doses than what will be used for vaccination
Stability – TPCS2a can be autoclaved and is stable
at room temperature, also in solution
Innovation – Unique mode of action; indication that
TPCS2a provides CTL-induction by MHC class I antigen
presentation in dendritic cells and macrophages
Cost effectiveness – Simple and cost effective synthesis of TPCS2a
Broad applicability – Peptide and protein antigens as well as particulate antigen formulations;
Prophylactic & therapeutic vaccination, in vivo & ex vivo
Clinical safety and preclinical efficacy evidence, combined with a comprehensive
patent estate on PCI-mediated CTL-induction (products, uses and devices)
29Macromolecules – endosomal escape of a range
of products, pre-clinical data
1 Intracellular delivery of immunotoxin – in vivo 2 Intracellular delivery of siRNA
3 Intracellular delivery of gene therapy – in vivo 4 Intracellular delivery of mRNA
• Therapeutic
gene (p53)
• Head & neck - PCI +PCI
• EGFP mRNA
tumours (p53
mutated)
• Local injection
Ndoye et al. (2006) Mol. Ther. 13:1154-1162 Bøe, S et al. (2010) Oligonucleotides 20:1-
30 6Agenda
1. Introduction
2. The PCI technology platform
3. An innovative localised cancer treatment concept
Head & neck cancer
Bile duct cancer
4. Unlocking the true potential of new treatment paradigms
Immunotherapy
Macromolecules
5. Commercial strategy and key financials
6. Organisation and shareholders
31Development and commercial strategy;
Execution plan and future milestones
2014 - 2015 2016 - 2017
Complete proof of concept for intra-tumour
illumination and initiate expansion of the Complete the Phase II ENHANCE study
Head and neck
Phase II ENHANCE study and initiate potential market approval
cancer
process and/or licensing
Open IND* and initiate US sites
*Investigational New Drug
Orphan drug designation
Complete clinical Phase I dose-escalation
Bile duct cancer Complete bile duct cancer Phase II study
part and initiate Phase II randomised study
and initiate licensing
Document immune-potentiation in relevant
animal models and strengthen products/IP Strategic collaboration to facilitate further
Vaccines & vaccine product development in pre-
Position PCI in second generation cancer clinical testing
Macromolecules
immunotherapy regimen
Enter clinical Phase I with partner
Strategic R&D alliances and licensing
Focus on research leadership and licensing of the unique proprietary PCI technology
32Development and commercial strategy;
A flexible partnering strategy
H&N and bile duct cancer Therapeutic vaccination Macromolecules
• Successful Phase II • High failure rate in clinical • Many potential partners, as
studies are important development linked to low the technology works with
value-enhancing efficacy makes PCI an most macromolecules
milestones attractive licensing asset
• Opportunistic approach;
• PCI Biotech will maintain a • High deal activity, with a use existing pre-clinical
flexible licensing strategy, large number of pre-clinical data to attract partners
but licensing agreements deals and alliances
based on Phase II data is • Aim is to license to several
assumed to maximise the • Aim is to license to several partners for use with
ROI for shareholders partners for use in different different macromolecular
disease areas and/or with technologies in different
different technologies disease areas
Retain rights and actively participate in the commercialisation of PCI
33Key financials – 2013 and Q3 2014 (IFRS)
Profit & Loss Balance sheet items Long term financing
2014-Q3
(NOK 1,000) 2013
YTD
(NOK 1,000) 2013 2014-Q3 Equity
Total operating revenue 6 681 5 755 Total fixed assets 18 15
Has raised a total of NOK 150,4m
in equity since 2008 – NOK 60m
R&D expenses 32 789 29 622 Short term receivables 6 123 7 642 (IPO) in 2008, NOK 90m in 2010
and NOK 0,4m in 2013 through
Cash and cash
Other operating expenses 3 217 2 340
equivalents
46 595 19 645 employees exercise of stock
options
Total operating
36 006 31 962 Total current assets 52 718 27 288
expenses Non-dilutive cash
Operating results -29 325 -26 208 Has received a total of NOK 50m
Total equity 43 396 19 021
in non-dilutive cash since 2008 –
Net financials 1 717 574
research grants and support
Tax 0 0
Total non-current
118 0 schemes
liabilities
Net income -27 608 -25 634 Total current liabilities 9 222 8 282
More than NOK 30m per year in R&D Yearly burn rate of NOK 22-27m in recent
expenses years
Around NOK 7m per year in research Yearly burn rate will increase as the
grants and support schemes clinical studies progress with patient
inclusion, after the dose escalation parts
are completed in 2014-2015
34Agenda
1. Introduction
2. The PCI technology platform
3. An innovative localised cancer treatment concept
Head & neck cancer
Bile duct cancer
4. Unlocking the true potential of new treatment paradigms
Immunotherapy
Macromolecules
5. Commercial strategy and key financials
6. Organisation and shareholders
35An experienced management team
CEO CFO CSO CBDO
Per Walday Ronny Skuggedal Anders Høgset Gaël L’Hévéder
Pic Pic Pic Pic
PhD from the Institute of Biology at MSc Economics and Business PhD from the Institute of MSc Bioorganic Chemistry
University of Oslo Administration from the Norwegian Biochemistry at the University of
>20 years of international
School of Economics (NHH), Master Oslo
Previously held the position of Global pharmaceutical experience in US
of Professional Accountancy from BI, > 10 years experience with and EU in major pharmaceutical
Head of Project Management at GE
State Authorised Public Accountant academic research at the companies (Aventis, Baxter,
Healthcare
in Norway University of Oslo (Medical Roche), including research,
>20 years of senior management Faculty) and The Norwegian regulatory affairs and >10 years in
> 10 years experience from auditing
experience in pharmaceutical Radium Hospital business development functions
and advisory services, serving clients
industry; Nycomed, Amersham including market intelligence and
ranging from Norwegian SME to > 10 years Industrial experience
Health, GE Healthcare licensing
large international and PE structured from Nycomed and PCI Biotech,
Experienced in pharmaceutical clients as Senior Scientist, Project Experience in leading clinical-
development, from preclinical Leader, Research Director and stage licensing transactions on
Experience from several M&As and
research to registration and CEO (PCI Biotech) buy side more recently with Roche
exits, and as management for hire in
commercialization of new products in Basel, Switzerland as
post M&A phase for international Co-author on some 60 scientific
Extensive international network and company Partnering Director
papers and 9 patents/patent
thorough understanding of critical applications. Extensive C-level global network
Served as Director at PwC prior to
success factors in drug development
joining PCI Biotech
36Board of Directors with extensive network
and broad experience
Chairman
Mr. Øverland holds a Master Degree from the Norwegian School of Economics and Business Administration. He has extensive
and broad experience in business, finance and marketing from several corporate leadership positions in Statoil, including five
years as CFO and several years as EVP for downstream operations. He has served four years as President and Chairman of
Erling Øverland, MBE the Confederation of Norwegian Enterprise (NHO). He serves as Chairman of The Norwegian NOx Fund and as Board
member of the University of Stavanger and Sparebank 1 SR-Bank ASA. Mr. Øverland has been Chairman of the Board of PCI
Biotech Holding ASA since 2008.
Board members
Dr. Stenberg holds a Ph.D. degree from the Karolinska Institute, Sweden, and has 25 years experience from management
positions in R&D and global research alliances & licensing with AstraZeneca. He is the founder and served as CEO of Combio
Kjell Göran Stenberg, A/S in Denmark, and has held CSO positions in CePeP AB and Orexo AB. He was COO of BioMS Medical Corp. and
Ph.D. Investment Manager at Medwell Capital, Canada. He is currently a board member of Galecto Biotech and Novation Pharma,
and of PCI Biotech Holding ASA since 2013.
Dr. Steineger holds a PhD in Biochemistry from University of Oslo, Norway. Currently Head of Innovation Mgmt at
Hilde Hermansen Pronova/BASF and previously VP IR & Communications, Pronova BioPharma. Held positions as Sr. Associate at Neomed
Mgmt and equity analyst at Kreditkassen (now part of Nordea), Oslo/Copenhagen. She has also worked as independent
Steineger, Ph.D. advisor for Life Science start-ups, and in clinical research and international marketing in Nycomed. She is Board member of
Cortendo AB, Weifa AS and Inven2 AS, and of PCI Biotech Holding ASA since May 2014.
Dr. Taskén is Professor of Medicine at the University of Oslo (UiO) since 2001. He is also Director of the Biotechnology Centre
Professor Kjetil Tasken, of Oslo, UiO, and of Centre for Molecular Medicine Norway, Nordic EMBL Partnership, UiO. He is co-founder and Board
member of Lauras AS, now Lauras Immuno AS, where he also was VP R&D for almost 10 years. Dr. Taskén has previously
M.D., Ph.D. served as Board member of Biomedical Innovation AS, siRNAsense AS and ChemLex AS. He has been a Board member of
PCI Biotech Holding ASA since 2008.
Ms. Comiskey Olsen is an Attorney-at-Law (USA) in private practice through the Comiskey Olsen law firm. She has >20 years
of experience in the pharmaceutical/life sciences field, with special emphasis on negotiating and drafting international licensing
Theresa Comiskey agreements. Ms. Comiskey Olsen was previously General Counsel and Company Secretary of the Nycomed Group. She is
Olsen, B.A., J.D. currently Board member of Calpro AS and Nordic Nanovector AS, and has been a Board member of PCI Biotech Holding ASA
since 2008.
37Largest shareholders Largest shareholders as of 24.11.2014 Name No of shares % PHOTOCURE ASA 1 483 339 19.2 % RADIUMHOSPITALETS FORSKNINGSSTIFT. 859 853 11.1 % STOREBRAND VEKST 590 576 7.6 % FONDSAVANSE AS 449 138 5.8 % VICAMA AS 389 973 5.0 % MP PENSJON PK 379 375 4.9 % KLP AKSJE NORGE VPF 325 000 4.2 % KOMMUNAL LANDSPENSJONSKASSE 305 000 3.9 % LGJ INVEST AS 265 285 3.4 % OTHER 2 678 851 34.7 % Total number of shares 7 726 390 100.0 % Fully diluted no of shares (incl. outstanding options) 8 371 890 Employee options as of 30.09.2014 Expiry date Exercise price No of options 2015 - Q2 6.47 174 000 2015 - Q3 37.24 90 000 2016 - Q3 19.02 170 000 2017 - Q3 37.02 86 500 2018 - Q3 19.63 85 000 2018 - Q3 18.64 40 000 Total number of options 645 500 38
Key company highlights
Unique drug Effective localised targeted delivery of a range of therapeutics, from small to macromolecules
enhancement
technology
Strong IP and unique patented technology
Innovative localised Targeting cancers with high unmet medical need and significant market potential
cancer treatment
Strong clinical effects proven for head and neck cancer – currently in clinical Phase II
concept with proven
effects Proven pre-clinical effects for bile duct cancer – an orphan indication currently in clinical Phase I/II
Unlocking the true Opening a pipeline of pre-clinical partnership opportunities
potential of new Immune-potentiating technology to enhance key immune cell response of partners’ cancer vaccines
treatment paradigms Effective localised delivery of partners’ innovative macromolecules
Experienced team
with strong support
Experienced management team and board, backed by a solid shareholder base
Attractive timing Company is approaching key data readouts and potential partnering agreements
39Enquiries PCI Biotech Fondsfinans AS DNB ASA Holding ASA CFO Ronny Skuggedal Johan Aaserud Thomas Hoftvedt Cell phone: + 47 94 00 57 57 Cell phone: + 47 95 43 79 20 Cell phone: + 47 97 52 55 76 Telephone: +47 67 11 54 03 Telephone: +47 23 11 30 28 Telephone: +47 23 26 80 57 E-mail: rs@pcibiotech.com E-mail: ja@fondsfinans.no E-mail: thomas.hoftvedt@dnb.no CEO Per Walday Rolf Henning Lem Inga Rakauskaite Cell phone: +47 91 79 34 29 Cell phone: +47 97 74 88 45 Cell phone: +47 41 08 84 89 Telephone: +47 67 11 54 02 Telephone: +47 23 11 30 47 Telephone: +47 23 26 80 59 E-mail: pw@pcibiotech.com E-mail: rhl@fondsfinans.no E-mail: inga.rakauskaite@dnb.no 40
Appendix
Patent Overview
Platform and business area patents
41Appendix –
Platform and business area patents
Granted and Pending
No Patent title Priority date Brief patent description Expiry
This is the first photochemical internalization (PCI) method case
Transfer of molecules into the cytosol of
0 08.09.1994 describing the general method of internalizing molecules by the 2015
cells
PCI technology
The photosensitizer TPCS2a and similar compounds.
2022
1 Sulfonated Chlorins as Photosensitizer 30.08.2001 Pharmaceutically acceptable salts. Use in photochemical
USA 2025
internalization and photodynamic therapy
2 Chitosan-photosensitiser conjugates 15.05.2012 Chitosans 2034
3 Soluble photosensitisers 14.08.2009 Soluble photosensitisers 2030
Photochemical Internalization for Delivery Methods of PCI in which application of the transfer molecule to
4 29.11.2000 2021
of Molecules into the Cytosol the cells occurs at the same time or after illumination of the cells
Photochemical Internalization for Virus-
Methods of PCI in which the transfer molecule is attached to a
5 Mediated Molecule Delivery into the 29.11.2000 2021
viral carrier
Cytosol
6 TKI-PCI 30.06.2008 The use of PCI for transfer of kinase inhibitors into cells 2029
7 SIRNA-PCI 11.07.2006 The use of PCI for transfer of siRNA molecules into cells 2027
Method of expressing antigens on the
Use of the PCI method to achieve cell surface presentation of
8 surface of antigen presenting cells by 15.03.1999 2020
antigens, e.g. for vaccination
photochemical internalization
42Appendix - Detailed trial summaries
Supportive Data from Phase I and Phase I Extension
43Appendix – Key Phase I data Phase I study Amphinex® dose escalating study (0,25 mg/kg, 0,50 mg/kg, 1,0 mg/kg and 1,5 mg/kg) Total 19 patients included, 13 SCC, including H&N , 4 breast cancer patients and 2 other metastatic patients DLTs at the highest dose (1,5 mg/kg) Tumour response in all dose groups Apparent tumour selectivity in several patients Phase I Extension study An extension to the Phase I study was initiated with recruitment to a lower dose of Amphinex® (0,125mg/dose) Total 3 patients included in the extension part of which all where SCC including H&N. Tumour response was less obvious Overall conclusion Phase I studies Same safety conclusion for all 22 patients; Well tolerated with appropriate analgesia and anesthesia Amphinex® dose selected for further studies: 0,25 mg/kg 44
Appendix –
Phase I Patient Demographics
19 patients
Amphinex Dose Group (mg/kg)
0.25 0.5 1.0 1.5
N=4 N=9 N=3 N=3
Number (%) of Patients
Sex, n (%):
Male 4 (100%) 2 (22%) 2 (67%) 1 (33%)
Female 0 (0%) 7 (78%) 1 (33%) 2 (67%)
Age, years:
mean (SD) 69.8 (12.1) 56.4 (12.8) 49.7 (19.1) 72.0 (7.8)
(range) (55–82) (39–74) (34–71) (67–81)
Ethic group, n (%):
Caucasian 4 (100%) 8 (89%) 2 (67%) 3 (100%)
Asian (Oriental) 0 (0%) 0 (0%) 1 (33%) 0 (0%)
Asian (Indian) 0 (0%) 1 (25%) 0 (0%) 0 (0%)
Skin type, n (%):
I 2 (50%) 2 (22%) 0 (0%) 0 (0%)
II 0 (0%) 4 (44%) 1 (33%) 2 (67%)
III 2 (50%) 2 (22%) 0 (0%) 1 (33%)
IV 0 (0%) 1 (11%) 2 (67%) 0 (0%)
Diagnosis, n (%)
Squamous cell carcinomas, including head
and neck 3 (75%) 6 (67%) 2 (67%) 2 (67%)
Breast cancer metastasis, cutaneous/local
recurrence 0 (0%) 3 (33%) 1 (33%) 0 (0%)
Other metastases 1 (25%) 0 (0%) 0 (0%) 1 (33%)
Data Source: Section 14, Tables 14.1.2.1.1 and 14.1.2.1.2
45Appendix –
Phase I Safety
Adverse Events
Overview of Adverse Events
Amphinex Dose Group (mg/kg)
0.25 0.5 1.0 1.5
N=4 N=9 N=3 N=3
Number (%) of Patients
Any AE 4 (100%) 8 (89%) 3 (100%) 3 (100%)
Treatment related1 AEs 3 (75%) 7 (78%) 2 (66%) 3 (100%)
SAEs 0 (0%) 6 (67%) 2 (67%) 2 (67%)
Severity of AEs2:
Mild 3 (50%) 6 (66%) 1 (33%) 3 (100%)
Moderate 0 (0%) 3 (33%) 2 (67%) 3 (100%)
Severe 3 (75%) 6 (66%) 2 (67%) 2 (67%)
Intensity of treatment-related AEs by CTC grade2:
Number (%) of AEs
Grade 1 3 (50%) 16 (70%) 1 (50%) 25 (81%)
Grade 2 0 (0%) 2 (9%) 1 (50%) 4 (13%)
Grade 3 3 (50%) 4 (17%) 0 (0%) 2 (6%)
Grade 4 0 (0%) 1 (4%) 0 (0%) 0 (0%)
1 Adverse events considered unlikely, possibly or probably related
2 Patients could have AEs of more than one severity or intensity
Data Source: Section 14, Tables 14.3.1.1.1, 14.3.1.1.2, 14.3.1.1.3, 14.3.1.2b and Appendix 16.2, Listing16.2.7.3
46Appendix –
Phase I Safety
Serious Adverse Events
Serious Adverse Events (SAE)
Time between
Treatment
Patient Event term Amphinex dose Causality Outcome
group
and onset (days)
205 0.5 Pneumonia 22 Not related Death
Thrombocytopenia 15 Unlikely Death
208 1.0 Acute renal failure 6 Unlikely Resolved
Upper GI bleed 32 Not related Resolved
Nausea 32 Not related Resolved with residual effects
Vomiting 32 Not related Resolved with residual effects
210 1.0 Respiratory failure 25 Not related Death
211 0.5 Respiratory failure 73 Not related Death
212 1.5 Swelling to hands 34 Probable Resolved
Blisters to back of hands 26 Probable Resolved
213 1.5 Infection to wound site 28 Probable Resolved
215 0.5 Pain to left arm 9 Not related Ongoing
216 0.5 Potential airway threat from oedema of tongue 6 Probable Resolved
218 0.5 Subject’s death (due to oral squamous cell carcinoma) 75 Not related Death
219 0.5 Surgical emphysema 14 Not related Resolved
Data Source: Appendix 16.2, Listing 16.2.5.1 and Listing 16.2.7.4
47Appendix –
Phase I Efficacy Safety Population
19 patients
Investigator Evaluation of Response of the Target Lesion according to RECIST
Amphinex Dose Group (mg/kg)
0.25 0.5 1.0 1.5
Number (%) of Patients
Day 28 (unconfirmed) N=4 N=9 N=3 N=3
Complete response 4 (100%) 4 (44%) 2 (67%) 1 (33%)
Partial response 0 (0%) 0 (0%) 0 (0%) 2 (67%)
Stable disease 0 (0%) 2 (22%) 0 (0%) 0 (0%)
Progressive disease 0 (0%) 1 (11%) 0 (0%) 0 (0%)
Missing 0 (0%) 2 (22%) 1 (33%) 0 (0%)
Last Visit (confirmed) N=2 N=6 N=1 N=2
Complete response 2 (100%) 2 (33%) 0 (0%) 1 (50%)
Partial response 0 (0%) 1 (17%) 0 (0%) 1 (50%)
Stable disease 0 (0%) 2 (33%) 0 (0%) 0 (0%)
Progressive disease 0 (0%) 1 (17%) 1 (100%) 0 (0%)
Data Source: Section 14, Tables 14.2.1.1.2 and 14.2.1.1.4
Note: Patients 210, 215 and 218 did not attend the Day 28 visit. Patients 201, 203, 205, 209 and 213 attended the last
visitAppendix –
Phase I Efficacy Per Protocol Population
12 of 19 patients
Investigator Evaluation of Response of the Target Lesion according to RECIST
Amphinex Dose Group (mg/kg)
0.25 0.5 1.0 1.5
Number (%) of Patients
Day 28 (unconfirmed)
N=4 N=4 N=1 N=3
Complete response
4 (100%) 4 (100%) 1 (100%) 1 (33%)
Partial response
0 (0%) 0 (0%) 0 (0%) 2 (67%)
Last Visit (confirmed)
N=2 N=3 N=0 N=2
Complete response
2 (100%) 2 (67%) 0 (0%) 1 (50%)
Partial response
0 (0%) 1 (33%) 0 (0%) 1 (50%)
Data Source: Section 14, Table 14.2.1.1.2 and 14.2.1.1.4
49Appendix –
Phase I Extension Patient Demographics
3 patients
Study Population
• Three Caucasian patients were enrolled in the study. Mean age was 58.0 years (range 51 to 65 years).
Two patients were male. Mean height was 169.7 cm (range 160 to 175 cm), mean weight was 71.07 kg
(range 66.6 to 75.5 kg). ECOG performance score at baseline was 0 in one patient and 1 in two patients
• Total 3 patients treated with 0,125 mg/kg Amphinex; two patients where re-treated with 0,5 mg/kg
• All three patients had squamous cell carcinoma of the head and neck.
Summary of Safety
• Two patients out of 3 patients treated reported a total of 13 adverse events (AEs), nine of which were
reported after treatment with 0.125 mg/kg Amphinex and the other four of which were reported after re-
treatment with 0.5 mg/kg Amphinex. Six AEs were considered unrelated and seven AEs were considered
related to treatment.
• There was one episode of photosensitivity reaction reported as an AE.
• Two AEs where Serious Adverse Events
Efficacy Results
• The unconfirmed responses in the target lesions at Day 28 were complete response in one patient, partial
response in one patient, and stable disease in one patient
50Appendix – Preclinical data
Preclinical data
CTL-induction for therapeutic vaccination
Intracellular delivery of macromolecules
51Appendix –
PCI may solve a key challenge for many
innovative medicines today – endosomal escape
Therapeutic vaccination Macromolecules
The overall concept is to modulate the activity Many innovative targeted medicines are
of the antigen processing machinery to enhance macromolecules, i.e. large complex
and direct the presentation of antigens to the molecules
necessary target for effective cancer treatment
These innovative medicines include classes
Stimulation of Killer (i.e. CD8+) T-cells is such as antibody-drug-conjugates (ADCs),
needed to recognize and destroy diseased cells oligonucleotides (e.g. siRNA and miRNA),
(e.g. tumor or virus infected cells) gene therapy, and different types of nano-
medicine
This effect can be achieved by proper
presentation of antigen on MHC I molecules on Macromolecules with intracellular targets are,
the surface of antigen presenting cells; the by the sole factor of their size, inherently
action of PCI is to significantly enhance such difficult to deliver in large enough payloads to
presentation give an effective therapeutic response
PCI has the potential to be used in combination Macromolecules are in most cells taken up
with a wide variety of antigens with different efficiently by endocytosis, but then trapped in
physical characteristics: peptides, proteins, and endosomes
various forms of particulate antigen formulations
The PCI endosomal escape platform can
The PCI immune-potentiating platform can be provide locally targeted delivery of
applied to antigens from infectious pathogens, macromolecules in diseases where there is a
as well as tumor antigens for cancer vaccines need of improved localised therapy
52Appendix –
PCI – an innovative and versatile platform for
CTL-induction and macromolecule delivery
• “…for a cancer vaccine to be optimally • “The safe, selective, and efficient delivery of
efficacious, it must induce antigen-specific CD8+ siRNA is a key challenge to the broad
cytolytic T cells…” application of siRNA therapeutics in humans”
− Schlom, J Natl Cancer Inst, 2012 – Dong et al., PNAS, 2014
• “Adjuvants are crucial components of all cancer • “The translation of siRNA-based cancer
vaccines…” “…the primary lymphocyte therapeutics to the clinic is hindered by several
population that is widely recognized to be the challenges associated with the cargo (siRNA)
necessary target for effective cancer therapeutic and the delivery system, including inability to
vaccine strategies is the CD8+ T cells.” escape endosomes and release into the
− Tefit & Serra, Expert Rev Vaccines, 2011 cytosolic compartment for an RNAi-mediated
effect…”
• “…compelling evidence that CD8+ T cells are – Seth et al., Therapeutic Delivery, 2012
key players in the immune response to
intracellular infections and tumours…” • “…they [siRNA] are potentially superdrugs. We
“…level and type of costimulation may play a have to figure out how to get them into cells
considerable part in boosting T cells…” better.”
− Appay et al, Nature Medicine, 2008 – Judy Lieberman, Immune Disease Institute,
Harvard Medical School, 2009
PCI Biotech - unlocking the potential of new treatment paradigms
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