« Normogen » – antitumor preparation of the future

1. «Normogen» – antitumor preparation of the future Slide presentation Real Med Company Ltd, Almaty, Kazakhstan All rights reserved

2. Conception: Preparation “Normogen” – a new direction for creation of selective antitumor drugs. Main steps: 1. Creation of the oncogenesis theory (1994-2006) 2. Production of the “Normogen” preparation in the medicinal form for intravenous injection (2003-2006)

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

4. Validation of the oncogenesis theory scientific conception 1. Certificate of the member of the II world-widecongress on immunopathology and respiratory allergy (Russia, Moscow, May 14-17, 2004). 2. Certificate of the winner of the II world-widecongress on immunopathology and respiratory allergy (Russia, Moscow, May 14-17, 2004).

5. Proofs of novelty of the technical problems solution 1. Patent of the Republic of Kazakhstan 2. Eurasian patent. 3. Registered trademark

6. Mechanism of action of the “Normogen” preparation Mechanism of action of the “Normogen” preparation All cells have special structures - AFP receptors (ReAFP), which are located on their surfaces (they are marked by red color in the figures).Cells usually have a low density of ReAFP as itshowed in the first figure. The ReAFP density on the surfaces of the dividing cells is very high (second figure). At low density of ReAFP the “Normogen” preparation blocks ReAFP and prohibit obtaining of the unsaturated fatty acids by cell that results in stoppage of cell division. At high density of ReAFP the “Normogen” preparation stimulates destruction of the transformed cells by perforation of their cell walls with activation of the complement (serum protein), causing their death due to complement-mediated lysis as it is shown on the last figure.

7. Preclinical trials of the “Normogen” preparation Use of the “Normogen” preparation for prevention of cancer : 1. Control set: Lungs of rats with the tumors induced by intravenous introduction of cancer cells 2. Action of the “Normogen” preparation (about 60% of the rats lungs are free from tumors); 3. Action of the “Normogen” preparation in combination with exogenous complement (serum protein) - about 90% of the rats lungs are free from induced tumors.

8. Preclinical trials of the “Normogen” preparation action on the spontaneous tumors Action of the “Normogen” preparation on the spontaneous tumors: 1. A dog with a name “Verna”, of 12 years old; 2. Two kinds of tumors are identified in the dog: a) Adenocarcinoma of the mammary gland (98 cm3); b) Tumor in the vagina wall (Ǿ = 4 cm) 3. The tumor in the vagina wall disappeared on the third day of the treatment. The volume of the mammary gland on the 15-th day reduced to 45 cm3 (in two times)

9. Report of the Institute of Oncology on the preclinical trials of the “Normogen” preparation. • The “Normogen” preparation is absolutely nontoxic even if it is used in high dosages • “Normogen” provides a high antitumor action (80,0%, in some cases – 100%) • The antitumor “Normogen” preparation shows high antimetastasis activity that reaches 90,5%, and in some cases – 100% • The “Normogen” preparation is effective against cancer cells regardless of type or localization of tumor • Preliminary introduction of the “Normogen” preparation reduces the possibility of the induced tumors appearance more than by 90.0% • The best way of the “Normogen” preparation introduction is the intravenous introduction • The “Normogen” preparation shows its maximal antitumor activity at presence of excess quantity of the complement

10. 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 investigations was 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

11. 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).

12. 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.

13. A commercial advantage of the “Normogen” program The program of production and application of the “Normogen” preparation is attractive to investors and socially significant for the State. Availability of the raw material and Relatively simple technology provide the Economic efficiency over 1000% (relatively to world prices on the existing antitumor preparations).