Presentations Incuron, 2012

1. Incuron, LLC
Development, preclinical investigations and
clinical trials of innovative medicines for
treatment of cancer and auto-immune
diseases, based on Curaxins - a novel class of
chemical structures
2012

2. Applicant’s Characteristics
CEO – Andrey A. Leonov, PhD
Deputy General Manager– Roman V. Ivanov, PhD.
Director of pre-clinical programs – Ramiz M. Salimov, D. Sci.
Clinical Operations Manager – Polina A. Shpigotskaya, PhD.
Scientific Manager –Andrei V. Gudkov, prof., D.Sci.
Project Manager – Ludmila V. Khristoforova, PhD
Persons providing assistance to Applicant in implementing Innovation Project:
Bioprocess Capital Partners managing company provides assistance to Incuron LLC project with GR/PR issues and regulatory procedures in Russia
Медицинский Совет компании, состоящий из ведущих врачей-онкологов России и США:
Andrei Vladimirovich Gudkov – Sc.D., Professor, Senior Vice-President, Abstract Science; Head, Department of Cell Stress Biology, Roswell
Park.
Sergey Alekseevich Tjulandin – MD, Professor, Deputy Director, Head, Department of Clinical Pharmacology and Chemotherapy, Russian
Oncological Scientific Research Center under the Russian Academy of Medical Sciences
Vladimir Mikhailovich Moiseenko – MD, Professor, Honoured Doctor of the RF; Deputy Director for Science; Head, Department of
Biotherapy and Bone Marrow Transplantation, Prof. Petrov Oncology Research Institute under Federal Agency of Health and Social
Development of the RF
Valeriy Georgievich Savchenko – MD, Professor, corresponding member, Russian Academy for Medical Sciences; Deputy Director for
Science, Haematological Research Center; Director, BMT and Molecular Haematology Research Institute; Scientific Adviser, Department
of Chemotherapy for Hemoblastosis, Hematopoiesis depression and BMT
Alex Adjei – MD, Professor, Senior Vice-President for Clinical Research; Chief, Department for Clinical Research Phase I, Roswell Park,
member of medical expert councils at many BigPharma large Western Companies.
Preet Chaudhary – MD, Professor, Deputy Director, University of Relaying Research at Pitsburg Cancer Institute; Director of Haematology
Programs at Pitsburg University, USA

3. Innovation project overview
The aim of the project is to become a global pharmaceutical company which
develops and bring to the Russian and international markets novel anti-cancer
medicines
Curaxins – small molecules with potentially wide spectrum of therapeutic use as pharmaceuticals
which showed efficacy against various malignant tumors, autoimmune diseases, also demonstrated anti-
inflammatory activity
Advances technologies developed by American Company Cleveland Biolabs, Inc.
Existing curaxins are represented by two classes of chemical compounds:
―Based on aminoacridine structure (innovative by their use)
―Based on carbazole structure (innovative by chemical class of molecules)
Curaxin’s uniqueness is based on their ability to repair the abnormal activity of three key signaling
pathways simultaneously in tumor cells, providing selective anti-tumor activity (through inhibition of
chromatin protein complex FACT)
Highly potent and selective pharmaceuticals against several types of malignant tumors
Curaxins potentially could also be developed into novel pharmaceuticals against some autoimmune
diseases and inflammatory conditions

4. Product and (or) technology description
 The ultimate goal of the Project is the use of breakthough biomedical technologies of the Clevеland Biolabs, Inc.
for development and launch on the Russian markets (5 years) and USA (7 years) of fundamentally novel effecient
anticancer medicines with the unique effect mechanism.
 Curaxins are synthetic small molecules with previously unknown properties. Their structure is patentable.
 Animal tests demonstrated favorable toxicological and pharmacological characteristics of curaxins.
 Their anti-tumor activity was proven by preclinical studies of mouse models and of human tumor xenograft
models performed in Russian Federation and in the USA.
 Structural analysis resulted in establishing an algorithm predicting with high degree of accuracy the functionality
of Curaxin-like molecules. These data show that the structure of DNA is not damaged by curaxins.
Curaxin
Active compounds Doxorubicin
No DNA damage by Curaxins
Inactive compounds DNA binding

5. Technical description of the product
 As transforming to malignant tumors cancer cells undergo changes in
the main signaling cascades responsible for survival. Among cascades
the functioning of which is disturbed almost in all cells of malignant
tumors, the most significant is the cascade of tumor suppress p53
(depressed), NF-κB and heat shock proteins cascades (activated). Live tumor cell Dead tumor cell
Curaxins
 Curaxins enable to activate p53 cascade and simultaneously suppress
NF-κB and HSF-1 cascades(which induce heat shock cascade). High activator Drugs exist
frequency of deregulation of those cascades in different oncological
diseases suggests that significant proportion of tumors are treatable inhibitor Drugs exist
by combinational Curaxins. Drugs under development
inhibitor but not on the market yet
Description Curaxin CBL0102 Curaxin CBL0137
Class of compound Aminoaсridines Carbazoles
Novelty of the molecule Have been applied for treatment of malaria First-in-class molecule
during many years
Suggested molecular effect 1) Activation р53 1) Activation p53
mechanism 2) Inhibition NF-kB 2) Inhibition NF-kB
3) Inhibition HSF1 3) Inhibition HSF1
Distribution in organism Predominantly accumulates in the liver Predominantly accumulates in lungs, spleen,
thymus, kidneys
Relative anticancer activity on ** ***
animals

6. Project finance.
1 tranche 2 tranche 3 tranche
175 570 thousand 194 000 thousand 179 927 thousand
rubles rubles rubles.
34 000 thousand 116 000 thousand
rubles rubles
(grant of Skolkovo) (grant of Skolkovo)
 Preclinical studies CBL0137 to Carry out of Phase 1 of Clinical trials Phase 2 of Clinical Trials (RF)
obtain a permit for phase 1B of of CBL0137 Phase 1 of Clinical Trials in
Clinical Trials in Russia Completion of R&D RF and US as a monotherapy
 Research and Development of Preclinical Trials of CBL0137 in and as a complex
CBL0137 and its analogs complex Phase 1 of Clinical trials of
 Phase 1B of Clinical Trial of Preclinical Trial of one of the analogs of
 CBL0102 in Russia intravenous formulation of CBL0137 in CBL0137 (carbazolic
US compound) for further
Completion of Phase 1B of Clinical investigations of autoimmune
trials of CBL0102 diseases and cancer
Start of Phase 2 of Clinical trials of
CBL0102
The study of carbazolic analogs for
several indicators, including Preclinical
and Clinical trials of hit compounds 6

7. Method of commercialization and competitive
advantages, reasons for the interest of consumers in
the product and (or) technology
• Competitive advantages of the product:
―Curaxin’s property to target several key pathways simultaneously in cancer cells that decreases the potency of
tumor cells to form drug resistance and increases anti-tumor efficacy (it was proven experimentally).
―As opposed to conventional anti-cancer drugs, curaxins combine high efficacy and safety
―As opposed to conventional anti-cancer drugs, curaxins do not induce DNA damage
Market of state procurement (Russia)
Commercialization
Medical insurance market (USA)
• Reasons for the interest of consumers in the product:
―Innovative medicines against several types of cancer including orphan disease – nephroma and auto-immune
disease – systemic lupus erythematosus; that gives specific social status to the developed medicines
―The novel class of medicines that fundamentally differ by effect mechanism and efficiency from the current and
developing by other companies

8. Project progress
2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
CT 1 (RF) CT 1 (RF)
CT 2 (RF) CT 2 (RF)
CBL0102
CT 3 (RF) CT 3 (RF) Sales (RF)
CT 1 (USA) CT 1 (USA)
CT 2 (USA) CT 2 (USA)
CT 3 (USA) CT 3 (USA) Sales (USA)
Pre-CT (RF)
Pre-CT (RF)
CT 1 (RF)
CT 1 (RF)
CT 2 (RF) CT 2 (RF)
CBL0137
CT 3 (RF) CT 3 (RF)
Sales (RF)
Pre-CT (USA) Pre-CT (USA)
CT 1 (USA) CT 1 (USA)
CT 2 (USA)
CT 2 (USA)
CT 3 (USA) CT 3 (USA)
Sales (USA)
SRD (RF) SRD (RF)
Analogues
Pre-CT (RF) Pre-CT (RF)
CBL0137
CT 1 (RF) CT 1 (RF)
CT 2 (RF) CT 2 (RF)
CT 3 (RF) CT 3 (RF) Sales (RF)
194 mln. RUR
110,7 mln. RUR
116 mln. RUR
( Skolkovо ) 69,2 mln. RUR.
Approval