When it all began: from consulting to medicine
The story of Gurus began in 2005, when Igor Teterin,
"The two fastest growing and profitableThe industry now is IT and biotech. IT simply did not interest me, but medicine attracted by its social significance, Igor Teterin recalls. - Each discovery in this area is either someone’s life saved or a significant contribution to people's health. I wanted not only to earn money, but also to leave something really great behind me, to contribute to the development of national science. It is no secret that many talented scientists are leaving, but I would like the works of Russian scientists not to remain in the table, as is usually the case, but would be of practical use. All these motives attracted me to the medical field. ”
Igor Teterin. Photo: Vlad Shatilo / "Hightech"
Pharmaceutical industry in Russia, beingone of the most important elements of the health care system, is on the verge of fundamental change. To the greatest extent, these changes are related to the formation of the innovation component, the development of import substitution and the growth of labor productivity. The domestic medical market is beginning to actively absorb innovative solutions and adapt to human needs. Biotech investors have higher returns than venture capital funds in other sectors: 26.8% vs. 21.8%. For 2017, the growth of investment in European biotech companies amounted to 29%. All this pays close attention of potential investors to biomedicine. But there are huge drawbacks, consisting in the long-term nature of the investment, usually exceeding five years, and high risk: 90.4% of all clinical studies of the first phase do not achieve successful registration and entry into the market.
Return on investment in innovation from variousspheres (IT, medicine, new materials, etc.) - 400% growth in seven years. Yield on yield only biomedical innovation, but with a large margin from all other indices. Source: Thomson Reuters Venture Capital Indices
Initially, the company was engaged in the evaluation of innovativemedical projects. And Teterin himself specialized in raising financing for the development of enterprises, conducting marketing research on the pharmaceutical market, evaluating investment targets.
"By 2008, I had accumulated a goodhands-on marketing experience. I wanted to use it in more important, developing industries, ”says Igor Teterin. - In my opinion, medicine and pharmaceuticals were exactly like that.
With the future co-founder, Igor Lyubimov, wemet in April 2011 by chance - on the plane, on the way to Tomsk to the conference “Medicine of the Future”. We sat in neighboring places, talking about the development of medicine in our country and the world. And quickly found a common language. Since I was acutely aware that I was missing a partner in medicine, I suggested that Igor work together - to lead research, development, and later all the medical activities of the company. ”
Igor Teterin - co-founder of Gurus BioPharm. He received an economic education, has an MBA in marketing, graduated from the University of California. In 1991 he received a mathematical education. Since 2011, he has been an expert in biomedical technologies at the Skolkovo Foundation, and has led over 100 examinations. More than 20 years in management positions.
Igor Lyubimov - CEO and co-founder of Gurus BioPharm. He graduated from the medical institute in the specialty "immunologist". He completed a postgraduate course in biology and received a PhD in biological sciences. With his participation more than 100 examinations on the creation of innovative medicines were conducted. The businessman has experience in management and research in the field of applied pharmacology. For a long time participated in the development of biomedical projects. Before joining Gurus BioPharm, Lyubimov was a member of the research institute (STS SBB).
At the end of 2011 in the work of Gurus BioPharmthere was a medical focus associated with the pharmaceutical industry. The first project was the development of an innovative medicine for the treatment of asthma in 2015, investments in which amounted to 44 million rubles. The next major development, a medicine for the treatment of critical limb ischemia, required as much investment in 2016. Both drugs are not yet ready for sale, and clinical trials are ongoing.
Igor Lyubimov. Photo: Vlad Shatilo / "Hightech"
The company is a resident of the IC “Skolkovo”, onthe basis of which conducts research. The laboratory of the company with high-precision equipment purchased at its own expense is located in Skolkovo. The company employs about 15 people. The main staff consists of scientists - chemists and biologists, employees of various research institutes, which Teterin and Lyubimov selected individually for their projects. Research activities are conducted in two directions: the development of innovative products for aesthetic medicine and the creation of innovative medicines.
The company develops new molecules, conductspreclinical and clinical trials, which include tests for safety and efficacy. Such work may take more than eight years and includes the following steps:
- Intellectual design. The company's scientists are investigating a certain class of substances (for example, prostaglandins) and put forward hypotheses about what the chemical structure of the molecule should be in order for it to have a given therapeutic activity (in particular, for the treatment of asthma). Creating a library of compounds - according to the hypothesis, 10–20 connections are being made.
- Preclinical research. This includes studies on cellular and biological models. In studies on cellular models (dropping the substance on the cells), toxicity is checked and the mechanism of action is investigated. Further studies are conducted on biological models. The cost of preclinical studies is 30–45 million rubles, the duration is two years.
- Clinical studies consisting of three phases. Substance is tested on humans (volunteers). The first phase is testing on healthy volunteers in order to understand how the substance affects the body (disintegration time and route of withdrawal). The second phase is testing for patient volunteers to identify the optimal effective and safe dose. The third phase - assessment of the effectiveness of patients with volunteers. Patients in the second or third phase can be invited to participate in clinical trials only by the attending physician, they do not participate in the first phase.
- Commercialization and market entry.
Prostaglandins - physiologically active substances related tolipid group. Formed in the body by fermentation of arachidonic acid. They contain a carbon chain of 20 members. They have been known since 1935, when they were first isolated from the seminal fluid by the Swedish physiologist Ulf von Euler. The name comes from the Latin word prostata - “prostate gland”.
The precursor of all prostaglandins arepolyunsaturated fatty acids, in particular, arachidonic acid, which, after release from phosphoglycerins (phospholipids) of the biomembrane, gives rise to prostaglandins and leukotrienes.
Prostaglandins have a variedphysiological activity, active in low concentrations. They are involved in maintaining the homeostasis of the body, acting on pain receptors, regulating the immune response, in labor, keep the thoracic duct open during pregnancy, cause contraction (prostaglandins F) or expansion (prostaglandins E) of the bronchi and trachea. In addition, prostaglandins cause an increase in body temperature, have a sedative and tranquilizing effect, stimulate the secretion of pancreatic enzymes, inhibit gastric secretion, can mediate and modulate the action of other biological stimuli, act as synergists or antagonists.
Due to its wide distribution intissues and high and versatile biological activity of prostaglandins (and prostanoids in general) are becoming more widely used in medical practice as drugs. These circumstances stimulate further research both in the search for new prostanoids and in the chemical synthesis of their modified analogues with protected functional groups that are more active and stable when introduced into the body.
Prostaglandins are used in obstetrics, gynecology, treatment of peptic ulcer, rheumatoid arthritis and diseases of the blood coagulation system.
"The development was done by talented chemists -partners of the company, who have dedicated their lives to working with this group of substances, specifically with natural bioregulators, - said Igor Teterin. - They know prostaglandins very well, they have done thousands of experiments. Therefore, they obtained a substance that showed a very high activity in the treatment of asthma and critical ischemia. In any case, smooth muscle relaxation occurs. In the first case, these are smooth muscles of the trachea, which allow breathing air in a state of asthmatic spasm with a wide chest. And in the case of critical limb ischemia, the smooth muscles of the arteries and arterioles expand. This allows the tissues to receive blood, the lack of which is a sign of ischemia. "
Igor Lyubimov. Photo: Vlad Shatilo / "Hightech"
“All our developments are connected with one groupmolecules derived from arachidonic acid - prostaglandins. They are synthesized from it, and it turns out a whole set of different substances. Seven or eight key molecules are formed from this set. We work with three, ”adds Igor Lyubimov.
The hard way
Study of any drugalways causes difficulties: it is necessary to determine the components, to create a suitable research design for a specific dosage form. The activity is regulated by the highest authorities, in Russia the Ministry of Healthcare is also involved in this. The patenting process contains many pitfalls.
"Either you will be given a positive decision, or not,- Igor Teterin admits. - For example, we were denied a patent in China. In this country, it was considered that the previous patent obtained by chemical scientists before they came to Gurus BioPharm duplicates an innovative medicine for asthma. They recognized innovation throughout the world, but not in China. ”
China has its own patent policy. The Russian company sells its product in China, makes a profit, and taxes go to Russia. Oh wow! Any country does not want this. Any country resists granting patents to non-residents of their country. Simply, China is doing it especially aggressively.
Even payment of patent fees by many countries.rejected. Because sanctions. For example, we pay a fee in Brazil, but the money that is sent to a Brazilian bank is returned. They are not accepted by the bank. And it is clear that the internal financial policy is that they support sanctions against Russia. Do not even accept payments from here. Because they come from the side of our bank VTB. And we also came across this in Australia. ”
Igor Teterin. Photo: Vlad Shatilo / "Hightech"
Today, Gurus BioPharm already has tenpatents worldwide: in Russia, USA, Japan, Australia and European countries. The company has twice become a participant and winner of competitions from the Ministry of Education and Science - in 2016–2018 and in 2015–2017. These were programs of preclinical studies of drugs for the treatment of asthma and ischemia of the extremities. Thanks to the victory in the competition, the company received 33 million rubles for preclinical studies. This amount covered 75% of all costs. Another 11 million rubles were invested in preclinical studies from the company's own funds.
Ability to breathe
For people with asthma, Gurus BioPharmdevelops the drug GUR-501, the mechanism of action of which differs from the usual principle of operation of aerosols, which relieve asthmatic symptoms. At the moment, GUR-501 is ready for clinical trials.
Old asthma drugs have a number of side effects.effects, as well as many of them are addictive. Currently, drugs for only two types of receptors involved in the regulation of bronchial tone have been developed to relieve acute attacks of bronchial asthma. These are β-adrenomimetics (alupent, ventolin, salbutamol, berotok and others), relaxing bronchi, and M-anticholinergic blockers (atropine and its analogs), blocking spasm. However, the use of β-adrenomimetics is often accompanied by serious side effects - severe tachycardia, headache, dizziness, muscle tremors, pulmonary edema, and others. And with prolonged use or overdose, loss of receptor sensitivity develops. This situation is deadly for the patient. M-holinoblokatory cause multiple side effects and do not apply independently, often with β-adrenomimetikami.
"There is a third, not used before thistime type of receptors for the regulation of bronchial tone. This is the prostanoid EP4 receptor (for prostaglandin E2), which we develop and use to create drugs, - says Igor Lyubimov. - The relaxing effect of prostaglandin E2 on the smooth muscles of the bronchi is as strong as that of β-adrenomimetics, but at the same time, the side effects are much less, since it is the body's natural bioregulator.
Use of natural prostaglandin E2(contained in the body of people and animals - "High-tech") for the relief of bronchospasm is impossible because of the strong cough it causes. This restriction is overcome in our proposed hybrid preparation containing only natural components: prostaglandin E2, glycerin and associated nitric oxide, which, when released, significantly enhances the bronchorelaxant effect. In the new structure, it was possible not only to eliminate the effect on cough receptors, but also to increase its activity by 20 times compared with natural prostaglandin. This led to a significant reduction in therapeutic dose and additional safety for patients: the impossibility of overdose and the absence of serious side effects.
Photo: Vlad Shatilo / "Hightech"
Significant expansion of the scopeThe proposed drug is possible with its complex use with β-adrenomimetics and inhalation glucocorticosteroids used in the clinic. Such complex drugs will be especially in demand for relief of severe attacks of asthma. The proposed drug may be the only effective means for patients with a long history of asthma, who have developed an addiction to existing bronchodilators. "
Ability to walk
Another drug, GUR-201, was created totreatment of critical limb ischemia. With currently existing methods of treating this disease, the number of patients undergoing leg amputation is 25%. The emergence of a new drug based on prostaglandins will help to avoid heavy surgery. This drug has also been preclinically tested and is ready for clinical studies.
Prostaglandin molecule, based on whichthe molecule is made for critical limb ischemia, it acts on vascular smooth muscle to improve blood supply. It happens that vessels suffer, namely smooth muscles and connective tissues. They begin to collapse, narrow, small vessels begin to suffer greatly, the capillaries are even stronger. And there is such a condition as peripheral tissue hypoxia. To prevent necrotic phenomena, people are injected substance. It expands the capillaries and blood vessels, restores tissue nutrition. And a person is actually saved a leg or an arm. The molecule Gurus BioPharm differs in that it includes two components. The first acts as a foreign molecule, the second compensates for the function of damaged vessels.
"Our drug allows you to compensate for the functionendothelium, which with such pathologies is completely destroyed, - said Igor Lyubimov. - The difference of our substance is that it can act in more severe stages, when the vascular endothelium is already badly damaged. Older drugs are effective only in the early stages, when endothelial functionality is still preserved. ”
Hair Growth Serum
Another area that Gurus BioPharm actively deals with is the development and production of products for aesthetic medicine.
“In the field of aesthetic medicine, we provide a full cycle: from the creation of a substance to mass production, market launch and sales,” says Igor Teterin.
Regeus serums that stimulate hair growth,eyelashes and eyebrows are finished products. Despite the fact that the idea of such a serum came to the partners of the company in 1995, research continues to this day. The formula improves, interactions with other preparations are investigated. An innovative tool solves a difficult problem from the field of aesthetic medicine: hair loss, rare and weak eyelashes and eyebrows. Regeus is already available for purchase, and its cost is comparable with similar products in the industry.
Innovative Molecules nitrolipins - active ingredient serum Regeus. Nitrolipins are natural substances derived from arachidonic acid. The composition of nitrolipins includes two components:
- Prostaglandins. Prostaglandins E1, E2 and F2-alpha are contained in the human body and regulate many biological processes, including the activity of the hair follicle and its blood supply.
- NO donors. NO is a small regulatory molecule contained in the human body. Promotes relaxation of blood vessels and better absorption of oxygen by the cells of tissues, which is necessary for hair growth.
Due to the unique chemical structure, nitrolipins penetrate deep into the dermis up to the level of the location of the vessels and hair follicles and act on them.
Nitrolipin E1 improves rheological propertiesblood in the growth papilla of the follicle by reducing platelet aggregation. Thus, nitrolipin E1 not only restores the narrowed diameter of the “pipeline system” of arterioles - capillaries to normal, but also cleans it from microthrombi. The restoration of the patency of the arteriole capillaries brings the blood supply to the hair follicles closer to the state of the blood supply to the young skin.
Nitrolipin E2 stimulates the division anddifferentiation of hair follicle stem cells, activates vascular endothelial growth factors (which leads to the formation of new microvessels), reduces the local activity of pro-inflammatory cytokines, prevents the transition of hair follicles to telogen (resting) phases.
Nitrolipin F activates a group of specialhair bulb receptors that promote the regeneration of hair follicle cells and their transition from the telogen phase (dormancy) to the anagen phase (active hair growth).
Normally, these molecules are produced in the bodyon their own. They act only locally - in the lower layers of the skin, where the hair bulbs are located, and do not penetrate deeper, because they are neutralized by special enzymes. Serum Regeus also functions in the same way: the active substances reach the follicles, physiologically and carefully affect them, then are removed from the body without causing adverse reactions. The serum contains no hormones. But tests have shown that serum prevents intense hair loss, activates the growth of hair, eyelashes, eyebrows and thickens hair, making it stronger and darker by several tones.
"Means for growth of hair, eyebrows, eyelashesdeveloped on the basis of prostaglandin derivatives. Active substances help solve the problem of baldness in men and women, - said Igor Teterin. “Serum is bought by women who have lost hair, and men who do not want to lose their hair with age.”
Photo: Vlad Shatilo / "Hightech"
The main channel to attract customers -Internet advertising and social networks. The serum based on nitrolipins was released in 2018, investment in products amounted to about 6 million rubles, but has not yet paid off. Sales of funds began six months ago.
Biomedical technology - new, but fasta growing industry that allows you to help a large number of people. The company's plans include preclinical studies on glaucoma and clinical studies on asthma and critical limb ischemia.
"We will continue to study serum forhair growth. Perhaps we will create new products in this area. For example, serum for beard growth, - adds Igor Lyubimov. - We are also working on bringing our products to new, foreign markets. Our principles are based on the use of mechanisms created by nature itself and already existing in our body. This is the most ideal thing we can have. We help the body to restore its own functions and thus get rid of pathologies. ”