Development of the scientific-technical platforms in a

field of biomedicine

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Author:

Academician Genrikh Sofronov

Speakers:

Prof. Anton Orlov

Prof. Youry Scherbuk

• Single product development

• Complex vehicle

Ideology:

Development of founded platforms will lead to wide-front breakthrough in

technologies creation and implementation

Scientific-technical platforms as mainstream approach for effective

innovative development

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Developing Platforms:

Nosological

group

Technological

group

Oncology

Autoimmune diseases

Recombinant

vaccines

Scientific-research centers

Clinical centers

Healthcare system - Implementation

- Clinical studies

- Invention & development

Ap

pro

ac

hes

alt

ern

ati

ve

Experimental-industrial

production

Education centers - Education

- Test output

Institute of Experimental Medicine (IEM)

of the North-West Branch

of Russian Academy of the Medical Sciences

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• 7 academicians, members of RAMS;

• 24 professors;

• 53 doctors of sciences (Dr.Sc);

• 102 PhDs.

An investigation of molecular mechanisms of

dysfunctions of the human organs and systems

and search of the ways for their correction

Major goal of the studies

conducted in IEM:

Over 120-years history (since 1890)

The most authoritative center of the biomedical science in Russian Federation

•

•

Staff: more than 600 employees, including:

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- diagnosis, study, treatment and prophylaxis of human diseases

• Mass-spectrometers,

• Real time PCR equipment,

• Confocal microscopy,

• Microarray systems,

• Sequencers,

• Cytofluorymeters, etc.

International cooperation:

USA, Sweden, Slovakia, Vietnam, Germany, Australia, Italy, Poland, Hungary,

China, Czech Republic, Japan and others

Research

facilities

Institute of Experimental Medicine (IEM)

of the North-West Branch

of Russian Academy of the Medical Sciences

11 research

departments

Clinic

Structure include:

Educational

unit

Scientific-

practical centers

Sustainable development of new clinical capacities

Unique facilities for initial founding of scientific-technological platforms of a

State/Federal value

Modern Clinical facilities of Saint-Petersburg

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Saint-Petersburg State Healthcare complex

RAMS

Scientific

capacity

•

International

Scientific

capacity

Outstandingly equipped

clinical complexes• oncology;

• cardiology;

• infections;

• multi profile;

• others

Sustainable city Expenses on top-class equipment

•

•

Bases to implement

breakthrough technologies and methodics

Launched – feb 2010

Clinical complex of a top level in Russia relevant to a worldwide level

Modern Clinical facilities of Saint-Petersburg

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Saint-Petersburg clinical scientific & practical center (oncological)

Technical capacity:

• Multispiral computed tomography 128

• combined PET-CT,

• MRT 3Tesla,

• Intraoperational MRT,

• Dual-head CT gamma camera,

• Dual-source CT angiograph,

• US complexes of expert and premium class,

• Digital X-Ray complexes.

14 beam therapy complexes, including:

• LEA 20 MeV complexes,

• Brahitherapy complexes,

• Intraoperational X-Ray complexes.

Properties:78 000 sq.m. area

23 units

14 surgeries GMP laminar coatings

Diagnostics Beam therapy

Bright example of one of nosological

platform Participant

Personnel – 1 200 employees.

Clinical capacity – 600 beds

Research & Development of the facilities for

personified diagnostics and treatment of

oncological diseases

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Scientific-technical platform #1

Project Participants

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Saint-Petersburg State University

Institute of Experimental Medicine of the North - West

Branch of the Russian Academy of the Medical Sciences

Saint-Petersburg clinical scientific & practical center (oncological)

IEM

SPbSU

CSPC

• The risk group identification, via genetic diagnostics of the oncology

predisposition

• General diagnostics of oncology

• Noninvasive extracting of tumor cells

• Differential diagnostics with optimal for therapy tumor cell surface

antigens recognizing

• R&D and production of medicines made of genetically engineered

complexes

• Target therapy of multiple origin tumors

Project structure:

First case in Russia of full-stages united system to be created: from diagnostics to

personified therapy

Research & Development tools for personified diagnostics and

treatment of oncological diseases

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1

2

2,5 mln

patients

490 000 new

cases

290 000

patients

Under monitoringAnnually

detected new casesAnnual

deaths

29 % growth

in 10 years

11 % growth

in 5 years

0 % growth

Russia: the disease rate increase

• Cancer– the second in value cause of country population mortality

• While peoples life length is growing the following growth of disease rate is estimated

Medicine therapy

required

Medicine

therapy

provided

Deathes due to the

absence of medicine

therapy

Lung tumor 65% 10% >50%

Breast tumor 95% >50% >30%

Ovary tumor 95% >50% >30%

Low medicine consumption rate in Russia

65-70% of cancer patients need to be treated with medicines on multiple desease stages

• Indexes show medicines demand unavoidable growth in close future

Ве

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9 г

.

Ста

тисти

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Project actuality

10

• The risk of hereditary cancer development is near 90%.

• The hereditary breast cancer occurs mostly due to genes BRCA1 and BRCA2 mutations.

• Most frequently noted is the 5382 ins C mutation, which is responsible for breast cancer cases and 40% ovary

cancer cases. Also were found some other mutations associated with tumors of several types development.

• The risk of cancer development in young aged mutations holders is 10 times higher.

• It is reasonable to run tests on mutations presence (PCR, sequenation, restriction analysis) firstly for women of

families with breast or ovary cancer, and for all women from 20 to 50 years old, as routine healthcare campaign.

Over 90% of patients with determined tumors of breast in due time are able to run a valid life.

1 Risk groups identification

Genetical diagnostics of hereditary cancer predisposition

The predisposition to breast and ovary cancer was explored

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IEM

re

se

arc

hes

Researches held

Original Methodics

2012-2013 г.

• PCR with reverse transcription

(cDNA, detection on transcriptase level);

• ELISA

(detection on proteomics level).

2 General diagnostics via tumor markers

Universal tumor genes are found which are proposed as base for

diagnostics.

Reverse transcription PCR analysis of these markers (cDNA)

shows sensibility up to 95% and specificity – 95%.

ELISA with purified proteins for antibodies used in blood

detection shows sensibility up to 94%, specificity – 98%

Methods

Base

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Start-up №1original methodics

2012-2013

Registration of medicines,

certification of methodics,

launch on market

• The fraction of tumor cells in blood determination via stream cytologic fluorimetry

• Concentration of tumor cells via monoclonal antibodies based sorter

• Test of tumor cells RNA function of specific surface antigen encoding

3 Extraction of tumor cells via non-invasive technique

Method

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Advantages:

• Biopsy avoidance

• High promptnessOriginal methodic

2012-2013

• for monoclonal antibodies (МАb) and target-medicines created on their base

• for medicine resistance determination and its neutralization vehicles switching on

• for immunotherapy efficiency increasing

4 Differential diagnostics

Method: Reverse transcription – real time PCR

Antigens specification – as targets for each individual case

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Start-up №2original methodics

2012-2013

Medicines registration,

Methodics sertification,

Product launch

• Specified linking to the transmembrane antigenes, expressed on the surfaces of tumor cells (onco-markers)

• Initiate a cascade of immunological reactions of the humans organism which leads to a lysis of onco-markers

expressing cells

• Fundamental difference of MAb opposite to chemo-medicines is its specificity of damage action on target-cells causing

minimal harmful influence on normal tissues and organs of host

• Nowadays in Russia some of himeric and humanized monoclonal antibodies (MAb) medicines which are totally foreign

made are approved for clinical implementation

- Monoclonal antibodies (MAb)

5 Developing of biotechnological medicines based on genetically

engineered complexes

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receptor

MAb

Invention 2 original MAb worldwide exclusive

Particularly based on stage №4 achievements

(Definition of universal tumor markers)

Therapeutic efficiency studies using cell-models and

clinical samples

Methodics of application studies

IEM

Conventional MAb

action illustration:

Start-up №3MAb pharmaceuticals

2013 г.

Clinical studies,

Pharmaceuticals registration,

Methodics certification,

Product launch

- Single-chain antibodies (mini-MAb)

• Single-chains are genetically engineered atnibodies consisting of only

Fv and Sc fragments of ordinary monoclonal antibodies.

Their size is 5 times less than that of ordinary antibodies (up to 20nm).

• Action mechanism is equivalent to one of ordinary MAb

• Small size allows it to penetrate the areas unreachable for МАb

5 Developing of biotechnological medicines based on genetically

engineered complexes

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Start-up №3single-chain MAb

pharmaceuticals

2013

Clinical studies, Pharmaceutical registration,

Methodics certification,

Product launch

- MAb conjugated with cytostatic agents (A-MAb)

• Complexes of MAb molecules (as nano carrier) conjugated with chemotherapy cytostatic molecules

• Action principles based on MAb’s ability to specifically conjugate with onco-markers expressed on tumor cells

surface

• Due to implementation of MAb as nano-carrier it allows to deliver cytostatic agents directly to cells expressing

onco-markers.

Nucleus

Clathrine

Clathrine-banded

vesicle

5 Developing of biotechnological medicines based on genetically

engineered complexes

17

Start-up №3conjugated MAb

pharmaceuticals

2013

Clinical studies, Pharmaceutical registration,

Methodics certification,

Product launch

1. Risk groups identification

4. Differential diagnostics

2. General diagnostics

6. Developed pharmaceuticals

appliance to cancer therapy

Targeted R&D achievements

5. Development of genetically-

egineered pharmaceuticals

Field

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3. Non-invasive tumor cells

extraction

Investigation of additional reasonable

mutations;

Population studies

Original methodics;

Base for diagnosticums development

and commercialization

Extended studies of proposed

tumor-specified genes

Studies of additional reliable tumor-

specified genes

Extended studies and proving the

precision of proposed method ,

relevant to all types of tumors

Original methodics;

Matter Target

Base for unified diagnosticums

development and

commercialization/

Original methodics

In framework of following start-up

development

Technologies of synthesis

of 4 original pharmaceuticals.

Lab Protocols of

efficiency studies

Base for unified diagnosticums for

onco-markers development and

commercialization.

Original methodics

Developing new 4 genetically-

engineered medicines: technology

of synthesis, therapeutic efficiency

studies

Start-

up

Start-

up

Start-

upExtended studies and proving the

precision of proposed method

relevant to all types of tumors

Project result

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Creation of technologies and tools for Russia’s first united full-stage

system in treatment of oncological diseases: from risk groups

identification to personified diagnostics and therapy, relevant to top

worldwide class

Creation of technologies for national innovative pharmindustry of

general and differential diagnostics facilities and target-therapy

pharmaceuticals for treatment of oncological diseases. Creation of

original treatment methodics.

This will lead to competence for developing start-ups purchased with

more than 7 original oncologic medicines of top worldwide level

Creation of scientific-technological platform aimed to facilitate quick

spinoff of start-ups for development and to put into healthcare

practice a new highly innovative pharmaceuticals and treatment

methodics in a field of oncology

Within 5 years following aims will be reached: