20 Years of Modernizing
Drug Discovery

Origenis was founded in October 2005 through a management buy-out of former Morphochem AG’s technology platform. Michael Almstetter, Dr. Michael Thormann, and Dr. Andreas Treml decided to continue their research programmes together with the drug discovery team they had built up. Two collaboration partners, Probiodrug (now Vivoryon) in the CNS field, and Alcon in the Ophthalmology fields supported this decision with continued trust and financial support. Both collaborations sought small molecules that would show sufficient exposure at the target tissue, passing through barriers that the brain and the eye have perfected to protect themselves.

 

To achieve these ambitious goals, we focused our investments in technology. The core was the evolutionary, intelligent, prospective synthesis planning with virtual assessment of drug-likeness combined with high-troughput in silico screening with MolMind® (similar to the MasterMind strategic game). The next step is performed then by MOREsystem®, which performs the chemically synthesis of the virtual compounds in the lab in an automated fashion. This way, an almost infinite number of combinations is possible to create new compounds and take them through the design, synthesis, and screening quickly to enable a straightforward optimization.

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Through Origenis’ long year collaboration with Biotech and Pharma companies, it became clear that the traditional development of small molecule drugs is plagued by a high attrition, and efforts often produce an inverse effect: the necessary optimization of one property (side effects) if often related to deterioration of efficacy.

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Here, BRAINstorm® helps through the measurement of important physicochemical properties very early in the characterization process, to predict the distribution of the compound in the body with high accuracy. The combination of these three technologies speeds up the transition from the computer to the chemical lab, such that lead compounds can be generated very quickly. In addition, Origenis has built the Cippix® platform, one of the largest proprietary chemistry-centric patent databases, that extracts all chemical and non-chemical information from patents since 1970, such that the lead compound series are checked for novelty and nearby IP, to ensure patentability of our drugs.

Business development and financing

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Through the last couple of years, Origenis orientation has been evolving. While the drug discovery platform was initially used to fill our clients’ pipelines, we used grants and supportive financing since 2012 from BMBF (German Bundesministerium für Bildung und Forschung) and the Bavarian Ministry of Economy to focus more and more on our internal research with a special focus on CNS-penetrating protein kinase inhibitors. “While the therapeutic use of protein kinase inhibitors has become a great success story, we at Origenis tried to transfer and adapt this knowledge with our Small Molecule Technology to the field of neurodegenerative diseases”, said Michael Almstetter. We doubled our efforts with blood-brain-barrier penetrating compounds against LRRK2 (Leucine rich repeat kinase 2) for the treatment of Parkinson’s Disease, as well as inhibitors of other kinases for the treatment of Frontotemporal Dementia.

From its inception, the our company was self-financed and got support from High Net Worth Individuals from Germany and Switzerland to build out the company step-by-step. Currently, Origenis has 28 full time employees. In 2016/2017, the granting process of our patents required a larger investment, that would strained the revenue stream. In order to maintain financial and operative independency, and not to become economically dependent from any Pharma company, we thought to found a novel “CNS company”.

 

Heading towards the USA

The main idea of this new company was to build a counterweight against the much hyped idea of therapeutic antibodies, which were thought to revert protein deposits in the brain. Rather Origenis’ kinase inhibitors should open up a new avenue for CNS therapies: With five complementary therapeutic programs, it should become possible to modulate both, the primary disease itself and the devastating neuroinflammation that accompanies the primary disease. Michael Almstetter and his partners believe that this novel therapeutic approach will delay the different forms of neurodegeneration substantially.

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This would have a large positive impact on the patients and the health care sector. Unfortunately, the echo in Europe amongst investors and potential Pharma licensors war week, as the programs were still in relatively early state. This is why we decided to seek investment in the USA, the propagated “Land of Limitless Opportunities”. Here, the community was already much more knowledgeable and open for such novel approaches in the CNS field. Furthermore, the entire capital market and stock market valuation play in a different league, have much larger cash reserves and risk capital, such that a follow-up financing becomes more feasible.

A dream come true

All these reasons supported the decision to found together a new company at the West Coast together with a US partner, which jump-starts with five programs. In parallel, the financing was secured to develop the drugs into the clinics. Since 2018, a new team is built there on site, that is supported and advised by Origenis. This way, Origenis also built a new collaboration partner. That allows both to progress the most advanced programs, and to provide a running start to our US partners. As the biotech landscape in the USA offers very different chances for drug and company development, Michael Almstetter expects a significant headway for Origenis in Europe. The successful built of a US-based CNS company will shed a very different light on the German company. Further expansion as well as an IPO are possible future scenarios for Origenis, which “wants to remain a German company”, underlines Michael Almstetter.

 

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After and with permission of Nicole Unger. Original German text:  https://www.goingpublic.de/life-sciences/eine-ki-basierte-wirkstoffplattform-sorgt-fuer-furore