««NormogenNormogen»» – – antitumor antitumor

preparation preparation of the futureof the future

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Real Med Company Ltd, Almaty, KazakhstanReal Med Company Ltd, Almaty, Kazakhstan

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Preparation “Normogen” – a new direction for Preparation “Normogen” – a new direction for creation of selective antitumor drugs.creation of selective antitumor drugs.

Main steps:Main steps:

1. Creation of the oncogenesis theory 1. Creation of the oncogenesis theory

(1994-2006)(1994-2006)

2. Production of the “Normogen” preparation in the 2. Production of the “Normogen” preparation in the medicinal form for intravenous injection medicinal form for intravenous injection

(2003-2006)(2003-2006)

Conception:Conception:

Oncogenesis theoryOncogenesis theory

Females “pump in” special proteins–immunoglobulins – Females “pump in” special proteins–immunoglobulins – into fetus serum through placenta. There are antiidiotypical into fetus serum through placenta. There are antiidiotypical antibodies to alfa-fetoprotein (AtAFP) antibodies to alfa-fetoprotein (AtAFP) among the maternal immunoglobulins. among the maternal immunoglobulins. Presence of the maternal AtAFP in the Presence of the maternal AtAFP in the fetus blood defends it from cancer. fetus blood defends it from cancer. Low concentration or narrow spectrum Low concentration or narrow spectrum of AtAFP leads to development of the of AtAFP leads to development of the tumor diseases. tumor diseases. ““Normogen” preparation contains essential spectrum of Normogen” preparation contains essential spectrum of antiidiotypical antibodies to alfa-fetoproteinantiidiotypical antibodies to alfa-fetoprotein.. Introduction of such antibodies into organism provides Introduction of such antibodies into organism provides prophylactics and treatment of tumor diseases. prophylactics and treatment of tumor diseases.

Validation of the oncogenesis theory Validation of the oncogenesis theory scientific conceptionscientific conception

1. 1. Certificate of the member Certificate of the member of the II world-wideof the II world-wide congress on congress on immunopathology and respiratoryimmunopathology and respiratory allergy allergy (Russia, Moscow, May 14-17, 2004).(Russia, Moscow, May 14-17, 2004).

2. 2. Certificate of the winner of Certificate of the winner of the II world-widethe II world-wide congress on congress on immunopathology and respiratoryimmunopathology and respiratoryallergy allergy (Russia, Moscow, May 14-17, 2004).(Russia, Moscow, May 14-17, 2004).

Proofs of novelty of the technical Proofs of novelty of the technical

problems solutionproblems solution

1. 1. Patent of the Patent of the

Republic of KazakhstanRepublic of Kazakhstan

2. Eurasian patent.2. Eurasian patent.

3. Registered trademark3. Registered trademark

Mechanism of action of the “Normogen” preparationMechanism of action of the “Normogen” preparation

Mechanism of action of the “Normogen” preparationMechanism of action of the “Normogen” preparationAll cells have special structures - AFP receptorsAll cells have special structures - AFP receptors(ReAFP), which are located on their surfaces (they(ReAFP), which are located on their surfaces (theyare marked by red color in the figures).Cells usuallyare marked by red color in the figures).Cells usuallyhave a low density of ReAFP as ithave a low density of ReAFP as it showed in the showed in the first figure. first figure.

The ReAFP density on the surfaces of the dividingThe ReAFP density on the surfaces of the dividingcells is very high (second figure). At low density of cells is very high (second figure). At low density of ReAFP the “Normogen” preparation blocks ReAFP ReAFP the “Normogen” preparation blocks ReAFP and prohibit obtaining of the unsaturated fatty acidsand prohibit obtaining of the unsaturated fatty acidsby cell that results in stoppage of cell division.by cell that results in stoppage of cell division.

At high density of ReAFP the “Normogen” preparationAt high density of ReAFP the “Normogen” preparationstimulates destruction of the transformed cells bystimulates destruction of the transformed cells byperforation of their cell walls with activation of theperforation of their cell walls with activation of thecomplement (serum protein), causing their death due complement (serum protein), causing their death due to complement-mediated lysis as it is shown on the to complement-mediated lysis as it is shown on the last figure.last figure.

Preclinical trials of the Preclinical trials of the “Normogen” preparation“Normogen” preparation

Use of the “Normogen” preparation forprevention of cancer :

1. 1. Control set: Lungs of rats with theControl set: Lungs of rats with thetumors induced by intravenous tumors induced by intravenous introduction of cancer cellsintroduction of cancer cells

2. Action of the “Normogen”2. Action of the “Normogen”preparation (about 60% of the rats preparation (about 60% of the rats lungs are free from tumors);lungs are free from tumors);

3. 3. Action of the “Normogen” preparation Action of the “Normogen” preparation in combination with exogenousin combination with exogenouscomplement (serum protein) - about 90%complement (serum protein) - about 90%of the rats lungs are free from inducedof the rats lungs are free from inducedtumors.tumors.

Preclinical trials of the “Normogen” Preclinical trials of the “Normogen” preparation action on the spontaneous tumorspreparation action on the spontaneous tumors

Action of the “Normogen” preparation on Action of the “Normogen” preparation on the spontaneous tumors:the spontaneous tumors:

1. A dog with a name “Verna”, of 12 years old;1. A dog with a name “Verna”, of 12 years old;

2. Two kinds of tumors are identified in the dog:2. Two kinds of tumors are identified in the dog:aa)) Adenocarcinoma of the mammary gland (98 cm Adenocarcinoma of the mammary gland (98 cm33););b) Tumor in the vagina wall (b) Tumor in the vagina wall (ǾǾ = 4 cm) = 4 cm)

3. 3. The tumor in the vagina wall disappeared on theThe tumor in the vagina wall disappeared on thethird day of the treatment. The volume of the third day of the treatment. The volume of the mammary gland on the 15-th day reduced to 45 cmmammary gland on the 15-th day reduced to 45 cm33

(in two times)(in two times)

Report of the Institute of Oncology on the Report of the Institute of Oncology on the preclinical trials of the “Normogen” preparation.preclinical trials of the “Normogen” preparation.

The “Normogen” preparation is absolutely nontoxic The “Normogen” preparation is absolutely nontoxic even if it is used in high dosageseven if it is used in high dosages ““Normogen” provides a high antitumor action (80,0%, Normogen” provides a high antitumor action (80,0%, in some cases – 100%)in some cases – 100%) The antitumor “Normogen” preparation shows high The antitumor “Normogen” preparation shows high antimetastasis activity that reaches 90,5%, and in someantimetastasis activity that reaches 90,5%, and in somecases – 100%cases – 100% The “Normogen” preparation is effective against cancerThe “Normogen” preparation is effective against cancercells regardless of type or localization of tumorcells regardless of type or localization of tumor Preliminary introduction of the “Normogen” preparation Preliminary introduction of the “Normogen” preparation reduces the possibility of the induced tumors appearancereduces the possibility of the induced tumors appearancemore than by 90.0%more than by 90.0% The best way of the “Normogen” preparation introduction The best way of the “Normogen” preparation introduction is the intravenous introductionis the intravenous introduction The “Normogen” preparation shows its maximal antitumorThe “Normogen” preparation shows its maximal antitumoractivity at presence of excess quantity of the complementactivity at presence of excess quantity of the complement

Clinical trial of the “Normogen” preparation (1st phase).Clinical trial of the “Normogen” preparation (1st phase).

The tested group was comprised of 15 patients with 12 diagnosis of cancer in the advanced form: Pleura mesothelioma – 1; Primary, multiple cancer (sigmoid intestine, thyroid gland, breast cancer) – 1; Cancer of the cardioexophageal part of stomach, cancer of esophagus,

stomach cancer – 2; Cancer of lung – 1; Breast cancer – 3; Salivary gland cancer – 1; Cancer of kidney – 1; Rectal cancer – 1; Urinary bladder carcinoma – 1; Testicle cancer – 1; Ovarian carcinoma – 1; Spinal chondrosarcoma –1.The patient did not undergo immune-histological selection or any other typing.

Participation of the patients with such different diagnoses in the clinical investigationswas provided with two purposes: Checking the safety of the preparation and determination of the dosage relationship Preliminary assessment of the “Normogen” preparation spectrum of action against

differently localized tumors and determination of the effective therapeutic dosages

Changes in the patients’ quality of life after application of the “Normogen” preparation.

66.7% of the patients after treatment with the “Normogen” preparation Felt

themselves noticeably better. Their aches considerably reduced or completely

disappeared, their appetites got better. 20% of the patients did not notice any

improvements in their states. 13.3% of the patients complained of their state

worsening. The dynamics of changes in the patients’ quality of life is showed

in the table. Parameters of the patients’ quality of life that are marked by the

1st degree of the World Health Organization rose from 53.3% to 66.7% (in

1.2 times), and the states of the patients with the 2nd and 3rd degrees changed

in the same way (in 1.9 and 1.2 accordingly).

Observations Observations

stagesstagesNumber ofNumber of

patientspatients

WHO WHO

(in degrees)(in degrees)

00 11 22 33 44

By Karnovski By Karnovski (in %)(in %)

100100 80 - 9080 - 90 7070 60 - 4060 - 40 --

Before theBefore the

treatmenttreatment

1515 88

53,3%53,3%

22

13,3%13,3%

55

33,4%33,4%

--

After of theAfter of the

treatmenttreatment

1515 1010

66,7%66,7%

11

6,7%6,7%

44

26,6%26,6%

--

Clinical presentations of the “Normogen” preparation action.Clinical presentations of the “Normogen” preparation action.

On the 3-4 day from the beginning of treatment with the “Normogen” preparation

most of the patients had: Significant reduction or complete disappearance of aches, improvement in appetites,

improvement in state of health and mood; Temperature normalization; Reduction and complete resolution of lymphostases, which have place, for example, at

the breast cancer; Blood parameters normalization; Rehabilitation of the natural activity of the patient’s excretory systems; Improvement in the motion activity.

Reductions in the dimensions of the tumors and lymphatic nodes were registered

by instrumental methods (roentgen, ultrasonic scanning etc).

On the background of the improvement in quality of life the progress of the tumor

disease were registered at 26.66% of the patients. Total antitumor activity of the

“Normogen” preparation in the mode of monotherapy reaches 73.34%.

None of the immunobiological preparations that are used in the oncology

practice has such an antitumor activity and broad spectrum of action.

A commercial advantage of the A commercial advantage of the “Normogen” program“Normogen” program

The program of production and application The program of production and application

of the “Normogen” preparation is attractive of the “Normogen” preparation is attractive

to investors and socially significant for theto investors and socially significant for the

State. Availability of the raw material andState. Availability of the raw material and

Relatively simple technology provide theRelatively simple technology provide the

Economic efficiency over 1000% (relatively Economic efficiency over 1000% (relatively

to world prices on the existing antitumorto world prices on the existing antitumor

preparations).preparations).