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Teaser, summary, work performed and final results

Periodic Reporting for period 1 - L2L (Leap-to-Lead platform for expanding Drug Discovery beyond its current limits)


Development of new drugs represents very high costs, for example, a single drug development can cost up to 2-5 billion USD in up to 15 years in time. In the early stage of drug discovery, about 10,000 compounds can be tested for a single target, from which about 250...


Development of new drugs represents very high costs, for example, a single drug development can cost up to 2-5 billion USD in up to 15 years in time. In the early stage of drug discovery, about 10,000 compounds can be tested for a single target, from which about 250 preclinical lead substances are selected. From these 250 lead molecules only about 5 compounds reach clinical trial phase. About 27 million USD is estimated to be lost on trials of unsuccessful drug candidates per each approved new drug. Key reasons for drug failures result from off-target toxicology, lack of target efficacy, and poor solubility or bioavailability.

We have developed and patented the Leap-to-Leadâ„¢ (L2L) concept for expanding early stage drug discovery beyond its current limits. Application of Leap-to-Leadâ„¢ substantially extends synthetic chemical space to include proprietary candidate molecules with the potential to interact with previously undruggable targets. In addition, our process results in leads with superior pharmaceutical properties that can lower the risk of downstream development and shorten the timeline needed to validate newly uncovered biological pathways. Leap-to-Leadâ„¢ consists of two major components: 1. The Comprehensive Fragment Library (CFL), which is a proprietary collection of available fragments with computational connections to a designed set of 850,000 related molecules that are selected using strict quality and pharmaceutical value criteria; 2. Then Syntheverseâ„¢ (SVS), which is a compound database of >500 Billion molecules using pre-coded feasible reaction schemes and curated reagent sets.

Work performed

In this Phase 1 project, we examined the feasibility of our approach. From technology point of view, to fully operate the Leap-to-Leadâ„¢ platform and exploit its full potential for drug discovery, we need to expand the diverse 3D physical fragment library from its current size to better cover possible interactions with biological targets. Compounds in the CFL are unique and highly diverse; thus, their synthesis needs individually tailored approaches. To meet this synthetic challenge, in this Phase 1 project, we demonstrated the applicability of photochemical processes for the expansion of our CFL. To demonstrate the business feasibility of platform utilization for collaborative drug discovery, we made a detailed market study by interviews with key stakeholders (potential clients, CEOs and CSOs of drug discovery focused companies). Based on the results, we developed 3 main business scenarios and developed our collaborative business offer. Furthermore, we examined the potential risks of our project and developed mitigation plans for each risk identified.

As results of the actions, we updated our business plan and defined main points of a subsequent Phase 2 application: work packages, objectives, tasks, and resources were defined.

Final results

Most of the current, state-of the art fragment libraries contain commonly available fragments, based on some thematic selections, such as number of heavy atoms, Florine Fragment library, Bromine-Based Fragment Library, Fsp3-enriched Fragment Library, Fragment Library with Experimental Solubility Data, etc.. The typical size is few thousand compounds and there are only few libraries using 3D data (e.g., Shape Signatures). However, in all cases, suppliers are providing subsets of the library containing multiple closely related alternatives for a given fragment scaffold. On the other hand, the Leap-to-Lead™ Comprehensive Fragment Library (CFL) will provide a 3D physical library of ca. 500 diverse compounds where each molecule represents 1000’s of novel CFL analogues. This concept, as such, is new and revolutionary.

In one hand, the L2L project will be highly beneficial for the pharmaceutical industry, as it will make possible fast, appropriate, and cost-effective selection of high quality lead compounds as starting points of drug discovery. On the other hand, the success of the project will impact our company by enhancing our profitability and growth. Beside the scientific and business impacts of the project, the widespread usage of L2L method will result in accelerated drug discovery, as the lead molecule will be found in less steps and in shorter time. As consequence, drug discovery activities will produce less waste. The faster and cheaper synthesis of drug candidates will lead, eventually, to less costly drugs, which will be an overall societal benefit. Furthermore, the more efficient selection of drug candidates from a broadly represented chemical space may contribute to find drugs for important and yet unmet chronic diseases.

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