Strategy
In line with end-customers and professional users expectations regarding food production we present an innovative and revolutionary approach to plant protection, which will allows to substitute currently used (in excessive way) fungicides and other pesticides, for much more environmentally friendly solution (at extremely low dosages) which through its action will not influence the ecosystem but only allow the plants to become more resistant to infections by pathogens.
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Challenge and solution
The ever growing demand for food is a major pushing factor for increasing the efficiency of methods of crops cultivation. However, modern intensified cultivation methods often lead to problems related to exposure of plants to factors that drastically reduce the crops yields (pathogens, insects or other pests). Now, influence of those factors is reduced by using chemical plant protection products (pesticides) with high efficacy but big negative impact on environment and human health examined both in world and Europe. As reported by the Eurostat current use of PPP is at the level of ~200 000 tons per year in EU alone. This amount gives on average, the dosage of PPP at the level of ~2.3kg of active substances/ha. Due to this fact EU implemented new directives which will cause withdrawn of the most harmful but at the same time the most effective pesticides from the market. New EU Directive 2009/128/EC constitutes new directions in plant protection in EU and emphasizes that the applied pesticides shall be as specific as possible and have the least side effects on organisms and the environment concentrating on non-toxic and eco-friendly analogues of currently used agrochemicals. Moreover Commission Implementing Regulation (EU) 2015/408 of 11 March 2015 lists active ingredients of common PPPs to be removed from the market. According to reports by Klefman Group and BayerCropScience, as a result of those regulations up to 75 of approved active ingredients in PPPs will be banned from the market resulting in withdrawn from for example Polish market 900 from 1800 available PPPs. Such limitation of available PPPs will drastically increase the cost of plant protection (e.g. wheat by 100-250 Euro/ha), decrease in crop yield (e.g. corn by 5-30%) and decrease in quality (e.g. potatoes by 10-70%). Lack of effective alternatives for plant protection without those pesticides is a huge pain point for farmers and other crop producers. Thus, challenges facing modern agriculture demonstrate a need for newer, safer and more sophisticated methods of plant protection, among which plants resistance induction is one possibility.
Chart presented shows total number of fungicidal PPPs available on the Polish market by top 20 manufacturers. Each column is divided into 2 groups: number of compounds that will remain on the market after implementation of European legislation (blue) and products which will be removed (red). Besides of consequences for final customers also pesticides manufacturers will feel the effects of implemented regulations. Whole Polish market will be reduced by ~600 products (from fungicides only). The portfolio of the largest companies will be reduced from 10% (Dow Agro Science) to even more than 50% (Rotam, Syngenta and Sharda). These reductions will result in searching for new solutions, among which our product is located. In our opinion market will be pushed to more eco-friendly products to fulfil formed gap – it is the best moment to introduce ILAGRO product to the market.
Chart presented shows total number of fungicidal PPPs available on the Polish market by top 20 manufacturers. Each column is divided into 2 groups: number of compounds that will remain on the market after implementation of European legislation (blue) and products which will be removed (red). Besides of consequences for final customers also pesticides manufacturers will feel the effects of implemented regulations. Whole Polish market will be reduced by ~600 products (from fungicides only). The portfolio of the largest companies will be reduced from 10% (Dow Agro Science) to even more than 50% (Rotam, Syngenta and Sharda). These reductions will result in searching for new solutions, among which our product is located. In our opinion market will be pushed to more eco-friendly products to fulfil formed gap – it is the best moment to introduce ILAGRO product to the market.
Business need and market opportunity
Being aware the dangers that overuse of pesticides can bring, better and effective utilization of pesticides is currently one of key aspects of IPM (Integrated Pest Management) - new European policy implemented in all EU countries. IPM emphasizes the growth of a healthy crop with the least possible disruption to agro-ecosystems. But, opportunity has been created not only by law regulations for safer and healthier crops to be produced with use of as little as possible pesticides but also important are growing expectations of conscious customers, which more frequently start to expect from their food suppliers (markets, stores) safer and pesticide-free vegetables, fruits, or other plant products. In this specific case law and society pressure has created a niche, which is an opportunity for ILAGRO (plant resistance inducer).
Implementation of ILAGRO allow (1) lowering the amount (by up to 100%) and cost (by up to 50%) of conventional pesticides used for plants cultivation, (2) decreasing the amount of pesticides in the environment and in crop products (by up to 90%) (3) improving the quality and safety of food, free of conventional pesticides. Moreover, ILAGRO product is simple in use, user-friendly and does not require implementation of new plant treatments techniques or even worker training as its application can be adopted to current methods and equipment in used agriculture.
Implementation of ILAGRO allow (1) lowering the amount (by up to 100%) and cost (by up to 50%) of conventional pesticides used for plants cultivation, (2) decreasing the amount of pesticides in the environment and in crop products (by up to 90%) (3) improving the quality and safety of food, free of conventional pesticides. Moreover, ILAGRO product is simple in use, user-friendly and does not require implementation of new plant treatments techniques or even worker training as its application can be adopted to current methods and equipment in used agriculture.
Our innovation
People associate plant protection only with substances and methods acting directly on pathogens by eliminating them. Substances acting this way have to be very effective and use in high dose to achieve planned effect. Being aware of that, research of our scientific group focused on different approach. We started from question: Why should we focus on particular pathogens instead of straightening plants? Thus our innovative and revolutionary approach focuses on using Systemic Acquired Resistance (SAR) induction which proves, that plants have their own immune system (like animals). This immunity could be strengthen by using elicitors – special compounds interacting with plants and stimulating them to be more resistant to all types of pathogens. Moreover those biostimulants could be used in very small doses (because they interact with plants on the molecular level) which in result would allow to substitute currently used dangerous pesticides, with more environmentally and human friendly products. Our ILAGRO product is based on discovered by PhD Smiglak active substance BTHWA which is the most effective elicitor designed, synthesized and evaluated by our group. Plants stimulated by ILAGRO product will survive in such unfavorable conditions as they will be strengthened from the inside.
Current development stage of innovation
Beginnings (2013-2014 TRL1-TRL3):
We have started research on plant resistance inducers in early 2013 as a research group of Poznan Science and Technology Park (PSTP) supported by funds from Foundation for Polish Science. Thanks to this funding we have created over 30 potential substances and started to test it in the greenhouse environment on the model plant-pathogen model. This work allowed to narrow down the target molecules to just few with the biggest potential. All tests were performed with reference to best know plant resistance inducers on the market (BION™-not registered in most EU countries). Tests show better performance than competitive products.
Prototype development and tests (2015-2016 TRL4-TRL5):
After selection of target molecule we have started development work on proving wide application potential of new product. Further development we have carried thanks to another two research projects obtained from national funding. This founding allowed us to widen the range of tests (greenhouse and field tests) on various crops including tomato, potato, wheat, barley, tobacco, zucchini, ash. At the same time we have started to work on the synthesis optimization and initial formulation of ILAGRO product. At the same time we have filed for patent protection initially in Poland and later (July 2016) filed PCT application. We have started to search for the industrial partner among polish agrochemical companies and research institutes and entered research and development collaboration with 2 companies and 4 institutes. In 2016 we have carried coordinated field and greenhouse test on final ILAGRO product in order to determine best application methods and scope of action.
Current status (2017- TRL6):
We are working on final development stages of the product ILAGRO, its registration and commercialization. The year 2017 was dedicated to filed and greenhouse test using application conditions selected from tests performed in 2016. The tests must be repeated at least over 2 years period to be validated. Currently, technology is at the stage of the national filing for patent protection in 26 countries. We are continuously conducting talks with industrial partners regarding future commercialization and sale of license.
We have started research on plant resistance inducers in early 2013 as a research group of Poznan Science and Technology Park (PSTP) supported by funds from Foundation for Polish Science. Thanks to this funding we have created over 30 potential substances and started to test it in the greenhouse environment on the model plant-pathogen model. This work allowed to narrow down the target molecules to just few with the biggest potential. All tests were performed with reference to best know plant resistance inducers on the market (BION™-not registered in most EU countries). Tests show better performance than competitive products.
Prototype development and tests (2015-2016 TRL4-TRL5):
After selection of target molecule we have started development work on proving wide application potential of new product. Further development we have carried thanks to another two research projects obtained from national funding. This founding allowed us to widen the range of tests (greenhouse and field tests) on various crops including tomato, potato, wheat, barley, tobacco, zucchini, ash. At the same time we have started to work on the synthesis optimization and initial formulation of ILAGRO product. At the same time we have filed for patent protection initially in Poland and later (July 2016) filed PCT application. We have started to search for the industrial partner among polish agrochemical companies and research institutes and entered research and development collaboration with 2 companies and 4 institutes. In 2016 we have carried coordinated field and greenhouse test on final ILAGRO product in order to determine best application methods and scope of action.
Current status (2017- TRL6):
We are working on final development stages of the product ILAGRO, its registration and commercialization. The year 2017 was dedicated to filed and greenhouse test using application conditions selected from tests performed in 2016. The tests must be repeated at least over 2 years period to be validated. Currently, technology is at the stage of the national filing for patent protection in 26 countries. We are continuously conducting talks with industrial partners regarding future commercialization and sale of license.
Safe and Efficient
The active substance BTHWA in ILAGRO product is a molecule discovered during research performed in years 2013-2014. Results of studies on BTHWA have shown that in provocative conditions tested compound can act as a strong plants resistance inducer (e.g >99% resistance to infection on tobacco plant with TMV virus (Fig 1) and can activate plants immunity system thus preventing plant infections much more effectively than commercial Bion™(the most effective commercial plants resistance inducers) (82% effectiveness). Moreover the induced resistance effect was found to last for over 25 days after just single application of BTHWA. Also under greenhouse conditions tomato plants treated with ILAGRO were effectively protected (>95%) against powdery mildew (Fig 2) and bacterial infection (Pseudomonas syringae pv. tomato). A crucial aspect which lead to implementation our product to the market is low environmental footprint. Moreover observed resistance induction is effective against various types of pathogens at the same time. Field tests included two year/season tests on potatoes and barley. In case of potatoes application of BTHWA allowed to limit spread of the virus transmitted by aphids and the number of plants infected by the PVY virus by 50%. As a result of application of ILAGRO through spraying on the spring barley, at very low dosage of 8g/ha only 18% of corps were found to be infected by fungi Pyrenophora teres, which is comparable to the effect obtained for fungicide Orius Extra 250EW (16% of crops infected) (active substance tebuconazole – common pesticide). Our product, based on the stimulation of natural plants response can be used in “homeopathic” doses (as low as 8 g per hectare), which is more than 50 times less than dose of common pesticides. Currently the prototype is being tested on 7 different crops in various locations in Poland (TRL 6).
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Enviromental Benefits
The main benefit for the professional user (crop producers) will be access to new, safe, environmentally neutral, and highly effective (preventing plant diseases up to 100%) plant protection product used at extremely low dosage 8g/ha (20-500x less than common PPPs, usually 250-1000g/ha) that fulfils EU directives and falls within current trends in the market, which seeks pesticide-free crops cultivation methods. In addition, due to the low cost of treatment per hectare of cultivar (as a result of low dose), ILAGRO product is likely to access very poor countries that do not use pesticides of high purity due to their high production costs. In case of commercial application of proposed resistance inducer present in ILAGRO product it is possible that due to its broad scope of action: prevention of fungal, bacterial and viral infections in plants at the same time (contrary to specific action of pesticides against particular pathogens or groups), it will become universal and ultimate plant protection agent. The product of such broad spectrum of activity, especially acting against viruses (no PPP acts directly on viruses) will revolutionize agriculture by satisfying farmers and consumers. The current state of technology includes a properly functioning prototype in a resembled study.
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Our Plan For Future
The entire research project is set to investigate application potential of N-methoxy-N-methyl-1,2,3-benzothiadiazole-7-carboxamide (BTHWA) (the best from our compounds and already tested on few plant-pathogen models) in inducing the resistance in economically important plant species toward their common diseases under greenhouse and field conditions. Until recently, thanks to the funding available from Foundation for Polish Science (projects HOMING PLUS and IMPULS) we were performing initial “prove of concept” experiments (TRL 1-5). Now we need to move to perform more advanced tests (TRL 6-8), including tests on (i) new varieties of plants (cultivated in greenhouses and on the fields) and (ii) determination of particular conditions of treatment such as application period, frequency and optimal dosage). Only then when results of more advanced tests will be available it will be possible to fully involve large industrial partners (for example Ciech and Synthos Agro companies) as they expect more ready solution before testing it in its final form under operational conditions (TRL 9) and later investing in it. We are certain that the discovered compound, when finally available to farmers will be a great support to currently overused pesticide programs and we hope that through the innovative approach that the plants resistance inducers offer, they will become the major method in future plant protection.
The work in the project will be divided into 4 main objectives with 17 major tasks (Fig 3) set out in the way that after completion of the project, the full overview of the best performing plant resistance inducer BTHWA, in terms of its synthesis, formulation, effectiveness and potential environmental issues, will be available (TRL 8). As it can be seen from the scheme below, the work will be organized starting from efforts in the design and optimization of synthesis method of BTHWA, including scale-up, from commercially available starting materials (Objective 1). As a result of the development of the synthetic pathway toward BTHWA, it is anticipated that the new derivatives of benzothiadiazole will also be formed and additionally evaluated toward their plant resistance induction properties in Objective 3 (Task 3.6). In Objective 2 attempts will be made to prepare prototype formulations of targeted substance (formulations – concentrates of the active ingredient mixed with additives used for e.g. increasing bioavailability and solubility). Prepared formulations will be evaluated toward their physical properties, long term stability and compatibility with working solution to be applied onto the plants, etc. The best formulation will be used in performing broad biological tests set out in Objective 3 (tasks 3.1-3.5). In Objective 3 all possible tests on plants are planned to be performed, including greenhouse and field tests on various economically important plants (e.g. tomato, cucumber, pepper, zucchini, rapeseed, strawberry, apple trees, rhododendron, tulip, ash, papaya, tamarillo) exposed to their most harmful naturally occurring pathogens (viruses, bacteria and fungi). This will allow to determine (i) the plant-pathogen scope of effectiveness, (ii) the longevity of the SAR induction effect after single or multiple applications of active substance. (iii) plant specific application requirements (dosage, frequency, mean of application) tested in provocative or natural conditions in greenhouse and field tests. Moreover, in parallel to experiments in Objective 3, in Objective 4 the investigation of the distribution and persistence of the active substance in plants will be determined. Such experiments are curtail in establishing the grace period between the last application of the substance and harvesting, as some of envisioned applications of SAR inducers would be in cultivating vegetables that are ready-to-eat right after being harvested and where use of common pesticides is strictly prohibited. Moreover in Objective 4 work will be performed in order to determine (i) potential ecotoxicity, biodegradability and bioaccumulation of new plant resistance inducer, (ii) the effect of SAR induction on beneficial microorganisms and (iii) possible synergistic effect of SAR induction and biological methods of plant protection. Only having such broad overview of the potential of our new SAR inducer, its possible interactions and influence on the environment such compound can be further commercialized and in future submitted for the registration procedure for use on plants.
The goals of the project will be realized through four distinct research objectives:
Objective 1: Design and optimization of synthesis of BTHWA, including scale-up, from commercially available starting materials
Objective 2: Preparation of prototype formulations of targeted substance and evaluation of physical properties, long term stability and compatibility with working solution
Objective 3: Biological efficacy assessment and application requirements of prepared formulations on various plant-pathogen models including greenhouse and field tests
Objective 4: Evaluation of substance accumulation in plants and possible environmental footprint that tested substance could have on the ecosystem and other organisms
The work in the project will be divided into 4 main objectives with 17 major tasks (Fig 3) set out in the way that after completion of the project, the full overview of the best performing plant resistance inducer BTHWA, in terms of its synthesis, formulation, effectiveness and potential environmental issues, will be available (TRL 8). As it can be seen from the scheme below, the work will be organized starting from efforts in the design and optimization of synthesis method of BTHWA, including scale-up, from commercially available starting materials (Objective 1). As a result of the development of the synthetic pathway toward BTHWA, it is anticipated that the new derivatives of benzothiadiazole will also be formed and additionally evaluated toward their plant resistance induction properties in Objective 3 (Task 3.6). In Objective 2 attempts will be made to prepare prototype formulations of targeted substance (formulations – concentrates of the active ingredient mixed with additives used for e.g. increasing bioavailability and solubility). Prepared formulations will be evaluated toward their physical properties, long term stability and compatibility with working solution to be applied onto the plants, etc. The best formulation will be used in performing broad biological tests set out in Objective 3 (tasks 3.1-3.5). In Objective 3 all possible tests on plants are planned to be performed, including greenhouse and field tests on various economically important plants (e.g. tomato, cucumber, pepper, zucchini, rapeseed, strawberry, apple trees, rhododendron, tulip, ash, papaya, tamarillo) exposed to their most harmful naturally occurring pathogens (viruses, bacteria and fungi). This will allow to determine (i) the plant-pathogen scope of effectiveness, (ii) the longevity of the SAR induction effect after single or multiple applications of active substance. (iii) plant specific application requirements (dosage, frequency, mean of application) tested in provocative or natural conditions in greenhouse and field tests. Moreover, in parallel to experiments in Objective 3, in Objective 4 the investigation of the distribution and persistence of the active substance in plants will be determined. Such experiments are curtail in establishing the grace period between the last application of the substance and harvesting, as some of envisioned applications of SAR inducers would be in cultivating vegetables that are ready-to-eat right after being harvested and where use of common pesticides is strictly prohibited. Moreover in Objective 4 work will be performed in order to determine (i) potential ecotoxicity, biodegradability and bioaccumulation of new plant resistance inducer, (ii) the effect of SAR induction on beneficial microorganisms and (iii) possible synergistic effect of SAR induction and biological methods of plant protection. Only having such broad overview of the potential of our new SAR inducer, its possible interactions and influence on the environment such compound can be further commercialized and in future submitted for the registration procedure for use on plants.
The goals of the project will be realized through four distinct research objectives:
Objective 1: Design and optimization of synthesis of BTHWA, including scale-up, from commercially available starting materials
Objective 2: Preparation of prototype formulations of targeted substance and evaluation of physical properties, long term stability and compatibility with working solution
Objective 3: Biological efficacy assessment and application requirements of prepared formulations on various plant-pathogen models including greenhouse and field tests
Objective 4: Evaluation of substance accumulation in plants and possible environmental footprint that tested substance could have on the ecosystem and other organisms
Fig. 3. Schematic representation of research Objectives, individual tasks and relation between Objectives.
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