KORTUC Helping cancer patients live longer by increasing the effectiveness of radiotherapy
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KORTUC
Helping cancer patients live longer
by increasing the effectiveness of radiotherapy
Kazuyuki Matsuda, CEO
in Tokyo Japan
The challenge of radiotherapy
n Radiotherapy (RT) is established cancer treatment
n However, RT efficacy is far from satisfactory due to hypoxia（low level
of oxygen）in tumor
Progression Free Survival (PFS*) for 5yrs
Cervical Cancer case
Non-hypoxic 83%
Hypoxic 27%
3x higher PFS for non-hypoxic patients
KORTUC
Source: Fjeldbo et al 2020 2 LIMITED DISTRIBUTION
*PFS An indicator to evaluate oncology product that shows the length of time during and after the treatment of a disease
KORTUC changes tumor radioresistant to radiosensitive
n KORTUC offers a fundamental solution to hypoxia
n KORTUC is comprised of Hydrogen peroxide solution and sodium
hyaluronate directly injected into the tumor
Radioresistant Radiosensitive
tumor tumor
KORTUC Radiation
Eliminate hypoxia
KORTUC
3 LIMITED DISTRIBUTION
Background story of KORTUC
Dr Ogawa, a professor at local small university in Japan with limited
financial resources found the most basic and simple solution
Dr. Yasuhiro Ogawa, Dr. John Yarnold,
Inventor of KORTUC Emeritus Professor
at The Institute of Cancer Research,
The Royal Marsden Hospital in the UK
KORTUC
4 LIMITED DISTRIBUTION
Mechanism of KORTUC
Please see Video
https://vimeo.com/574688871
KORTUC
5 LIMITED DISTRIBUTION
Proprietary patented prefilled injection device
n Offers user-friendly onsite operation, allowing to mix hydrogen peroxide
and sodium hyaluronate with specific precise ratio
n Protected by usage patents and product patents
KORTUC Kit
KORTUC
6 LIMITED DISTRIBUTION
In vitro study: Significant increase in RT effect
H2O2 increased RT effect 3x, better than non-hypoxic tumor
Cancer Cell Death
30.7% 32.8%
9.9%
+H2O2
X-ray X-ray X-ray
Non-hypoxic Hypoxic tumor Hypoxic tumor
tumor + H2O2
KORTUC
7 LIMITED DISTRIBUTION
Source: Kariya S et al (2009)
In the animal model: Synergetic effect with RT
Tumor size of RT + KORTUC method was 60% smaller than the size of
RT Only after 60 days from single RT shot
Tumor Volume (RT vs. RT + KORTUC method)
6,000
Volume (mm3)
4,000
60% smaller
2,000
RT Only RT + KORTUC method
60 days after single treatment
(mouse with squamous epithelium cancer cell line)
KORTUC
8 LIMITED DISTRIBUTION
Source: Akima et al, Jpn J Clin Radiol. 2009; 54: 1683–88 (In Japanese)
Records of many effective cases in clinical sites
n Over 1,000 patients were treated by RT + KORTUC method as
Investigator initiated clinical research in Japan for various solid cancers
n No safety concerns have been reported and showed meaningful efficacy
Breast cancer lymph node metastasis
Report 2017a 2016 2010 2011 2015-16 2010 2017b
Local-
Stage 4 2A-3C 1A-2A 1A-2A 1A 1A
recurrent
RT dose (Gy) 57-71 57-67 57 71 71 71 66
71% 79% 100% 100% 99% 100% 100%
cCR%*
(5/7) (19/24) (17/17) (10/10) (71/72) (14/14) (15/15)
KORTUC
9 LIMITED DISTRIBUTION
Source: 8 publications for Breast Cancer (Ogawa 2015, Aoyama 2017 etc.) * cCR% clinical Complete Response rate
Completed Phase 1 study for breast cancer in UK
n Demonstrated excellent safety in locally advanced/recurrent Breast
Cancer
n Most patients showed > 80% volume reduction
n Results were published on Red Journal* in 2020
% Tumor volume reduction in 12 months
Open label study, n=12
KORTUC
10 LIMITED DISTRIBUTION
* Int J Radiation Oncol Biol Phys, Vol. 108, No.4, pp.1019-1029, 2020Clinical Development Strategy
Pivotal studies of Breast Cancer is ongoing and Cervical and Rectal
cancers will start in 2022
Breast Cancer Cervical Rectal
Local Control Curative therapy Curative Therapy
Phase 2b-3 Phase 2b-3 Phase 1-2a
Ongoing Starts in 2022 Starts in 2022
2020-2024
RT effective rate is very low RT does not work for Only 20% patients
for late-stage patients 40% patients mainly due completely recover with
to hypoxia neoadjuvant RT
→ Improve Progression → Decrease the needs
Free Survival rate of surgery
KORTUC
11 LIMITED DISTRIBUTIONFuture Milestone
Plan to launch in 2026 for Cervical cancer in the US then in EU and
Breast Cancer in the US and the EU
2022 2023 2024 2025 2026 2027
Indications
(cost till launch)
P2 Study in UK EU US
Breast Approval
Launch Launch
($6mm)
Accelerated US EU
P2/3 Study in US
Cervical Approval Launch Launch
($6.5mm)
P2 pilot study Accelerated US/EU
P3 study in US and EU
Rectal EU Approval Launch
($19mm)
IMP* Manufacturing
($10mm)
CMO Line Registration
Commercial Product Selection setup Batch
Stability Test
($6mm)
KORTUC
12 LIMITED DISTRIBUTION
*IMP Investigational Medicinal ProductFurther Potential with Immunotherapy/RT
n As the fourth pillar of Cancer treatment, immunotherapy is projected to expand to
about USD 130 billion globally by 2026
HOWEVER,
n Only 20-40% of patients respond to immunotherapy
n RT is expected to improve efficacy of cancer immunotherapy
n KORTUC could further enhance efficacy of immunotherapy with RT
n The company has initiated a pre-clinical animal study and expected to announce the
result in 2022
KORTUC
13 LIMITED DISTRIBUTIONStaged approach for the large addressable markets
KORTUC can potentially treat as many as 1.5m+ cancer patients globally
RT/Immunotherapy
Combination
Africa/Asia
For 9 Indications
1mm
US/EU
+ 6 Indications*
400k
US/EU
Initial 3 Indications
100k patients
TOTAL # of Patients 1.5mm
KORTUC
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*Additional 6 indications Breast Cancer for early stage, Prostate, Melanoma, Esophageal, Head and Neck, Soft Tissue SarcomaPotential competitor
KORTUC directly and safely resolves the fundamental problems of RT
KORTUC Nanobiotix
KORTUC Kit (Hydrogen peroxide &
Product Hensify (nanoparticles, hafnium oxide)
Hyaluronic acid)
Resolves underlying issues, hypoxia and
Physically activates RT
Mode of Action excessive antioxidase through hydroxy
(yields high energy of ionizing radiation)
radical
Safety P1 exempt ( > 1,000 use cases) P1 required (300 use cases)
Cervical Cancer, Rectal Cancer, Breast
Main Indications Head and Neck Cancer, Soft Tissue Sarcoma
Cancer
KORTUC
15 LIMITED DISTRIBUTIONEfficient marketing due to the market characteristics
n Treatment decision maker is Radiation Oncologists
Small Doctorʼs (RO)
Community n The number of RO is approximately only 4,000 in the
US and 5,000 in EU
n All targeted cancer patients concentrates on large
High Patients hospitals
Concentration n For example, covering 10% of ROs enables to
reach about 50% of all Breast Cancer patients
n Only few pharmaceutical players focus on ROs as
Less Competitive
their target customer
Market
n No direct substitutes of KORTUC
KORTUC
16 LIMITED DISTRIBUTIONSale Projection: 3 Initial indications in the US/EU
In 3 years after the launch, sales is projected to reach over $500mm based on a
competitive price of $30k per patient
USD MM 600
544
500
Rectal
Cancer
400
300
232 Breast
Cancer
200
100 Cervical
52 Cancer
0
2026 2027 2028
KORTUC
17 LIMITED DISTRIBUTIONExperienced Team
Management Clinical Development
Kazu Matsuda Minako Koga Hiroyuki Suda
Founder, CEO R&D Head
Finance Product Business Development
Yukiko Sawa Masaya Ishibashi Shogo Yamashita Kazuhiko Tawara
CFO
KORTUC
18 LIMITED DISTRIBUTIONScientific Experts
Inventor/Advisor of KORTUC Clinical Experts
Dr Yasuhiro Ogawa Bob Kneller MD Michihiko Wada, MD
Emeritus Professor Emeritus Professor Professor at Keio University
Kochi University University of Tokyo
UK Clinical Trial Leads
Dr John Yarnold Dr Navita Somaiah
Emeritus Professor at The Team Leader, Translational Breast Radiobiology
Institute of Cancer at The Institute of Cancer Research, London
Research Clinical oncologist at The Royal Marsden
Hospital
KORTUC
19 LIMITED DISTRIBUTIONFunding Ask
Our ask
n $60mm Series C (runway to Oct 2024)
l $18.5mm raised from AXA Insurance and SBI Investment
n 36 months of runway to proceed with
l clinical studies for breast and cervical cancers
l clinical studies of P2 for rectal
l commercial product development
We have raised
n $8mm from 2017-2019
l Nissay Capital
l Fenox Venture (Pegasus Tech Ventures)
l Sparx Group
l JST (Japan Science and Technology Agency) etc.
KORTUC
20 LIMITED DISTRIBUTIONThank you!
Kazuyuki Matsuda, CEO
kazu.matsuda@kortuc.com
KORTUC
21 LIMITED DISTRIBUTIONAppendix
KORTUC
22 LIMITED DISTRIBUTIONExecutive Summary
– a beautiful solution to improve cancer radiotherapy efficacy –
1. KORTUC is the only solution in the world which resolves tumor hypoxia to overcome
radio-resistance.
2. KORTUC first targets 100k radiotherapy patients for 3 indications in the US/EU
markets, with additional upsides in combination with radiotherapy and
immunotherapy, additional indications and Asian /African markets.
3. Late Stage Program
l In the UK, currently a phase 2/3 registrational study is ongoing in locally
advanced/recurrent breast cancer. (NDA in 2025, Launch in 2026)
l In the US, meetings with FDA were held in 2020-2021. The IND filing is planned for
advanced cervical cancer in 2022.
l In EU, a phase 2 pilot study in rectal cancer is planned in 2022.
l In Japan, KORTUC has been used over 1,000 patients with various types of solid
tumor in clinical researches.
4. Seasoned management team with successful track record of building/exiting biotech
startups with highly experienced medical collaborators recognized in global oncology
arena with leading academic publication track record.
KORTUC
23 LIMITED DISTRIBUTIONOriginal data of slide #2
The challenge of radiotherapy
Large difference of Progression Free
The more a malignant tumor grows, the Survival (PFS)
radiotherapy become less effective due
Hypoxic vs Non-Hypoxic
to:
(Cervical Cancer example)
l Hypoxia (reduced oxygen level)
in tumor cell creating resistance to
radiotherapy
83％ patients with less hypoxic
survive 60 months without
progression while only 27%
patients with more hypoxic
KORTUC
24 LIMITED DISTRIBUTION
Source: Fjeldbo et al 2020Original data of slide #7
In vitro study, KORTUC showed significant increase in RT effect
H2O2 increases RT effect 3x (9.9% to 32.8%) in hypoxic condition which is same level as
RT effect in normoxic condition.
Hypoxic Condition Radiation
(7.6 mmHg) H 2 O2 (10 Gy)
(0.1 mM)
Cell Apoptosis
Analysis
PC-3 cells
(human prostate cancer cell line)
X-ray only
control (normoxic condition)
H2O2 + X-ray
(hypoxic condition)
X-ray only
(Hypoxic condition) H2O2 only
KORTUC
25 LIMITED DISTRIBUTION
Source: Kariya S et al (2009)Original data of slide #8
In the animal model, KORTUC showed synergetic effect with RT
In animal model, with KORTUC, the tumor volume size growth was about 1/3 compared to
radiation alone
Tumor Volume change over 60 days
Mouse with squamous epithelium cancer cell line
No Radiation
Radiation Only
KORTUC
Measure Tumor
volume
SCCVII cells bearing mouse
model (mouse squamous H2O2 (0.5%) + Radiation
epithelium cancer cell line) sodium hyaluronate (30 Gy, single dose)
KORTUC
26 LIMITED DISTRIBUTION
Source: Akima et al, Jpn J Clin Radiol. 2009; 54: 1683–88 (In Japanese)KORTUC makes radioresistant tumor to radiosensitive tumor
Mechanism of KORTUC Please see Video
https://vimeo.com/574688871
KORTUC
27 LIMITED DISTRIBUTIONThe world first patented prefilled injection device
n Unique pre-filled device for intra-tumoral injection
l The injection can be performed by a radiologist under ultrasound guidance with no
specific training
l The kit allows to mix hydrogen peroxide and sodium hyaluronate with specific precise
ratio
n Usage and product patents granted/being filed
l 2 use patents for radiation sensitizer: granted in US, UK, Germany, Japan and others
l 4 product patents for device: granted in Japan and being filed in other countries
KORTUC kit includes:
• One pre-filled syringe of hydrogen peroxide
• One pre-filled syringe of sodium hyaluronate
• Other parts of injection device
• (syringe socket to insert two pre-filled syringes
and rod connector)
Any needles can be attached with universal luer lock of
syringe socket.
KORTUC
28 LIMITED DISTRIBUTIONPatent Portfolio
Priority Expirat Countries（underline:
Patent Title
date ion granted）
Radiation sensitizer or anti-cancer JPN, UK, FRA, DEU, CHN,
9/21/2007 2027
chemotherapy sensitizer*1 AUS, CAN and US
Use Radiation/chemotherapy sensitizer to be used
patent for intratumoral local injection and for JPN, UK, FRA, DEU, ITA,
2/14/2014 2034
controlled release of hydrogen peroxide with CHE, TUR, US
hydrogel as carrier
Syringe suitable for hydrogen peroxide
solution and kit thereof 11/16/2018 2038 JPN
Product Syringe suitable for hydrogen peroxide JPN, PCT application*2,
6/21/2019 2039
(KORTUC solution and kit thereof ARG, BGD, PAK, TWN
kit）
Holder for administrating radiation or anti-
5/31/2019 2039 JPN, PCT application*3
cancer chemotherapy sensitizer
Oil composition to store hydrogen peroxide
3/29/2019 2039 JPN
stably
Hydrogen peroxide solution-prefilled syringe
JPN, PCT application*2,
Others with excellent hydrogen Peroxide preservation 4/16/2019 2039
ARG, BGD, PAK, TWN
due to silicone oil included in oil composition
*1: Exclusive license from Kochi University
*2: 55 countries including US, UK, EU countries、China、India
*3: US, UK, FRA, DEU, CAN, MEX, BRA, CHN, IND, ISR, AUS, ZAF
KORTUC
29 LIMITED DISTRIBUTIONKORTUC is in a late clinical stage
Early stage Late stage
Area Indication Regimen Sponsor
(Ph1-2a) (P2b-3)
The Institute of
Breast Completed Ongoing
With RT Cancer Research,
Cancer
UK
Cervical Preparing
With RT KORTUC
Cancer
Universitair
Rectal Preparing
With RT Ziekenhuis
Cancer
Brussel, Belgium
Completed
Various Solid Clinical
With RT
Tumors Researches
> 1,000
Preparation patients
KORTUC
30 LIMITED DISTRIBUTIONDetails of ongoing registrational Phase 2/3 study (Breast Cancer)
Randomized phase II trial testing the efficacy of intratumoral KORTUC as a radiosensitizer in patients with locally
Title
advanced/recurrent breast cancer
Multi-center, non-blinded randomized open-label trial with two groups comparing radiotherapy with/without
Design
KORTUC
Patients with poorly controlled symptoms of primary or recurrent locally advanced breast cancer requiring high
Subject
dose radiotherapy for lifetime control of moderate or severe morbidities
184 subjects (92 in each randomized group). This provides 80% power to detect a 20% difference in complete
Pts No. response at 12 months, assuming a 65% rate in the control group, 2-sided α=0.05, and allowing for 10%
unevaluable at 12 months.
Study RT1: 49.5 Gy in 18 daily fractions of 2.75 Gy with/without sequential boost in 3-5 daily fractions of 2.75 Gy
Treatment RT2: 36.0 Gy in 6 twice-weekly fractions of 6.0 Gy
Primary Endpoint
Endpoint
Complete tumor response 12 months post-radiotherapy assessed by MRI
RT1 or RT2
+ KORTUC starting week 2
Random Follow Up 3 monthly
Screen ization up to 24 months
RT1 or RT2
MHRA agreed to file MAA with one registrational study.
KORTUC
31 LIMITED DISTRIBUTIONRecords of efficacy in breast cancer at clinical investigation
Breast Cancer: Comparison of Response Rate with/without KORTUC
RT only RT + KORTUC
Ogawa
Mukai
Miyatake Hitomi Tsuzuki 2015/ Aoyama Aoyama Aoyama
Report 2013
2010 2010 2011 Aoyama 2016 2017a 2017b
2016
20
n 108 17 14 10 72 7 15
(24 lesions)
Stage Stage Stage Stage Stage Local- Stage Stage
Stage
1A-3A 2A-3C 1A 1A-2A 1A-2A recurrent 4 1A
RT dose
55 57 71 71 71 57-67 57-71 66
(Gy)
Outcome: 43% 100% 100% 100% 99% 79% 71% 100%
cCR rate (46/108) (17/17) (14/14) (10/10) (71/72) (19/24) (5/7) (15/15)
RT only: RT was used as neo-adjuvant setting and CR was estimated at 12 weeks after RT (before surgery)
Stage: UICC 8 th edition
KORTUC
32 LIMITED DISTRIBUTION
Source: 8 publications for Breast Cancer (Ogawa 2015, Aoyama 2017 etc.)You can also read
