Tromsø, Norway, and Dortmund, Germany – April 25th, 2024. KinSea Lead Discovery AS, a biopharmaceutical start-up pioneering the use of marine bioactives for the treatment of human diseases, announces the successful first closing of its seed financing round. It includes an equity investment from KHAN Technology Transfer Fund I GmbH & Co KG (KHAN-I), an early-stage life sciences venture fund based in Germany, and welcomes the new investor Berners AS, a North Norwegian investment company. A year ago, KinSea had already secured a convertible loan from KHAN-I, which was recently converted into shares.

The financing enables the company to further develop its lead program, a FLT3 kinase inhibitor based on unique chemistry from marine sources, towards preclinical and clinical testing. Data from in vivo proof-of-concept studies suggest superior properties over existing FLT3 inhibitors, including potential broad activity against known drug-induced and drug-resistant FLT3 mutations, improved selectivity, and outstanding in vivo potency. The program originates from the successful collaboration of the founding partners, Arctic University of Norway (UiT), University of Bergen (UiB), Norinnova, and Lead Discovery Center GmbH (LDC).

‘We are grateful for the continued confidence and support from KHAN-I, and delighted to welcome Berners AS on board’, says Jeanette Hammer Andersen, CEO of KinSea. ‘This first closing validates the transformative potential of our approach. We are very committed to take our FLT3 inhibitors through the next stages of drug discovery and development in order to provide entirely new treatment options for AML patients that are safer and more effective’.

KinSea also plans to gradually expand its drug discovery pipeline and establish a diversified portfolio of high-potential drug candidates based on novel chemical scaffolds from the Arctic Ocean for the treatment of cancer and other diseases.

‘We are excited to reaffirm our commitment to KinSea and its groundbreaking work in the field of marine-derived therapeutics. The team has made significant progress over the last year, and we are convinced that their unique approach and capable team will continue to drive the maturation and expansion of their pipeline, and eventually make a meaningful impact on patients’ lives, in particular with regard to urgently needed, improved therapies for AML patients’, comments Bert Klebl, Managing Director of KHAN-I.

Mats Sæverud, CEO of Berners AS, adds: ‘In KinSea, we found an ambitious startup company that wants to make an important impact by employing natural products from the Arctic Ocean. The KinSea team has bold visions, scalable solutions, excellent expertise and skills, and fits well with Berners´ ambitions.’

KinSea has already started discussions with further investors for a second and final closing.

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Contact
Lead Discovery Center GmbH
Otto-Hahn-Straße 15
44227 Dortmund
Germany
Phone: +49 231 97 42 70 00
Mail: pr@lead-discovery.de

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About KHAN-I

KHAN Technology Transfer Fund I GmbH & Co KG (KHAN-I) is an early-stage life sciences venture fund with €70 million under management. Our mission is to create value through cooperative drug development partnerships with academic innovators in Europe. KHAN-I focuses on first-in-class therapies for attractive markets with a high unmet medical need. The fund is managed by Khanu Management GmbH, an experienced team of professionals with proven track records in early-stage drug development and academic spin-offs as well as pharma licensing and partnering. KHAN-I received an investment from the European Investment Fund (EIF) with the support of InnovFin Equity, and with the financial backing of the European Union under Horizon 2020 Financial Instruments and the European Fund for Strategic Investments (“EFSI”) under the Investment Plan for Europe. KHANI is also supported by Austria Wirtschaftsservice GmbH (AWS with funds provided by the Austrian

Federal Ministry for Digital and Economic Affairs and the Austrian Foundation for Research, Technology, and Development), Max Planck Foundation, and Thyssen’sche Handelsgesellschaft mbH. In addition, KHAN-I sustains a preferred partnership with the Max-Planck Society (Max-Planck Gesellschaft e.V.).

Further information at www.khanu.de

About Berners AS

Berners AS is a newly established, privately owned investment company, based in Tromsø, Norway. Through investments and active ownership, Berners will contribute to the development of profitable and sustainable businesses, especially within the seafood and marine sector. We aim to be a supporter of the development of brands and competence clusters in Northern Norway. Our investment strategy is based on our knowledge and love for the coast and the sea, and the opportunities that exist there. Berners is owned by Triko AS (80%) and Larren Invest AS (20%).

About Norinnova

Norinnova is one of Northern Norway’s most competent and experienced agencies for research commercialization. Norinnova connects researchers, start-up environments, companies and commercial actors to develop and utilize the region’s innovation power. For more than 30 years, Norinnova has worked closely with researchers and leading research communities in Northern Norway to harness the power of innovation in this region. This collaboration has contributed to the creation of brand-new businesses and has reinforced existing companies through new products and services. Norinnova secures rights, helps provide funding, investigates market potential, finds relevant partners, and contributes so that the scientists can get their product or service to the market.

Further information available at: www.norinnova.no

About LDC

Lead Discovery Center GmbH (LDC) was established in 2008 by the technology transfer organization Max Planck Innovation, as a novel approach to capitalize on the potential of excellent basic research for the discovery of new therapies for diseases with high medical need. LDC takes on promising early-stage projects from academia and transforms them into innovative pharmaceutical leads and antibodies that reach initial proof-of-concept in animals as well as candidate nomination. In close collaboration with high-profile partners from research and industry, LDC is building a strong and growing portfolio of small molecule and antibody leads with exceptional medical and commercial potential.

LDC sustains a long-term partnership with the Max Planck Society and its institutes as well as with KHAN-I, and has formed alliances with AstraZeneca, Bayer, Boehringer Ingelheim, Merck KGaA, Daiichi Sankyo, Qurient, InvIOS, Novo Nordisk, Cumulus Oncology, Nodus Oncology, JT Pharmaceuticals, KinSea Lead Discovery AS, HLB Pharma, the Helmholtz Center for Infection Research, e.g. In addition, LDC also works with leading translational drug discovery centers and with various investors to provide its assets for company creation.

Further information available at: www.lead-discovery.de

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Dortmund, September 29, 2015 – The Lead Discovery Center GmbH (LDC) and Infinity Pharmaceuticals, Inc. – Cambridge, MA – will work together to jointly select high-potential cancer drug discovery projects from the LDC’s portfolio and its broad academic network.

In the context of their collaboration, the LDC will give Infinity insight into project opportunities arising from its diverse portfolio and its extensive academic network. This includes leading universities as well as renowned institutes from Germany’s world-class research organizations, the Max Planck Society and the Helmholtz Association. The focus will be on the field of oncology.

Infinity will review proposals with the goal of identifying one or more programs for either licensing or collaboration. For the projects selected, Infinity may draw on the LDC’s expertise and resources in early drug discovery and development.

“We are extremely pleased to cooperate with Infinity. With strong capabilities in drug discovery and development and a novel anti-cancer development candidate in registration-focused clinical trials, Infinity is perfectly set to advance pioneering oncology projects into the clinic and eventually to the patient,” says Dr Bert Klebl, Managing Director of the LDC. “Moreover, we are excited to extend our network of collaboration partners into the US. The strong line-up of LDC’s industry partners in Europe, Asia and now in the US highlights the innovation potential of academic research in Germany.”

The partners will agree on the scope and terms of potential co-development partnerships on a project-by-project basis to ensure optimal project progress and a fair distribution of investments and potential returns. Any revenue the LDC may receive from commercialization will be shared with the academic inventors and collaborating institutions.

“The LDC shares our philosophy of discovering new therapies through a data-driven, interdisciplinary approach,” states Dr Vito Palombella, Chief Scientific Officer at Infinity. “The LDC’s commitment to creating new medicines for patients is demonstrated through its strong track record, and Infinity is pleased to work with the LDC on the identification of the next generation of promising new therapies for the treatment of cancer.”

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Dortmund, June 11, 2015 – The Lead Discovery Center GmbH (LDC) and Johnson & Johnson Innovation Ltd., will collaborate to identify and accelerate innovative drug candidates for the treatment and prevention of diseases with high unmet medical needs.

Over a two-year period, LDC and the team from the Johnson & Johnson’s London Innovation Centre will work together to identify on an ongoing basis translational research opportunities sourced from LDC’s top-tier academic network, including institutes from the Max Planck Society, the Helmholtz Association and various universities. Johnson & Johnson Innovation will review and evaluate the opportunities with the objective of establishing drug discovery collaborations with LDC in selected projects that are aligned with the company’s therapeutic focus areas.

“Through our academic network, we have access to a broad range of exciting molecular targets, pathobiological mechanisms and new therapeutic approaches which are the basis for project proposals with a high innovation potential for drug discovery,” says Dr Bert Klebl, CEO of the LDC. “Together with Johnson & Johnson Innovation, we will now be able to offer a solution for more of our academic partners to translate their innovative findings into benefit for patients. We very much look forward to leveraging our interests, expertise and capabilities together with Johnson & Johnson Innovation to incubate additional collaborative projects at the LDC.”

For each project selected by Johnson & Johnson Innovation, the partners will negotiate a collaboration agreement for its joint development at the LDC up to the next mutually agreed milestone. The details regarding financial provisions and research activities will be agreed on a project-by-project basis to ensure a fair balance of investments and potential returns between the partners. Any revenue received from commercialization will be shared with the academic inventors and collaborating institutions.

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Starting point of a broader drug discovery and development alliance

Dortmund, Germany and Gyeonggi-do, South Korea, June 03, 2015 –        The Lead Discovery Center GmbH (LDC), a renowned translational drug discovery organization established by Max Planck Innovation, and Qurient Co., Ltd have signed a licence deal providing Qurient with exclusive worldwide rights to a series of highly-selective CDK7 inhibitors discovered at the LDC for the treatment of cancer, inflammation and viral infections. The partners will closely collaborate to advance the approach from the validated lead stage into clinical development. Upon successful proof-of-concept in humans they will jointly identify a suitable partner for follow-on licensing.

Under the terms of the agreement LDC will receive an upfront payment and milestone payments upon the achievement of specific development events. In addition, Qurient will fund the future development activities of the collaborative program.

The agreement on CDK7 is the second licensing deal between LDC, Max Planck Innovation and Qurient and the starting point of a broader alliance between the partners. Expanding on the success of their ongoing collaboration on Axl kinase inhibitors initiated in 2013, both sides have agreed to join forces for the development of selected further projects from the LDC’s portfolio in the fields of oncology and inflammation. The partners will closely work together, from project identification through to clinical proof-of-concept and subsequent sublicensing, with the LDC leading drug discovery and optimization and Qurient guiding preclinical and clinical development, typically until completion of Phase II.

“It is an exciting moment for Qurient to have LDC as an upstream partner, providing innovative drug discovery programs to our ‘lead-to-clinical POC’ pipelines,” says Dr Kiyean Nam, CEO of Qurient. “As being shown in the Axl inhibitor program, we will join forces to achieve exceptional science and operational excellence until the program reaches mutually beneficial end point.”

“The partnership with Qurient is an essential part of our strategy to create versatile opportunities for accelerating the transfer of our leads into biopharmaceutical development,” says Dr Bert Klebl, CEO of the LDC. “Qurient combines first-class development expertise with an exceptional commitment to moving innovative projects forward. Together, we can advance our projects swiftly into the clinic and benefit from the dynamic financial environment for biotech companies in South Korea.”

About the CDK7 program

Cyclin-dependent kinases (CDKs) play a pivotal role in cell cycle control and transcription regulation and have long been considered attractive therapeutic targets. However, selective inhibitors have been hard to develop because the CDK active sites are highly conserved. Due to their outstanding specificity for CDK7, the LDC’s CDK inhibitors have good prospects for overcoming this hurdle. They have demonstrated excellent potency and selectivity in vitro and in vivo. LDC’s CDK7 inhibitors are non-covalent picomolar biochemical inhibitors. These features may translate into an attractive therapeutic window and clearly set them apart from a recently published and covalently acting first-generation of CDK7 inhibitors, also described as inhibitors of super-enhancer elements.

In two very recent publications, LDC and its collaboration partners described the mechanistic activity of their CDK7 inhibitors as specific transcriptional modulators (Kelsö et al. 2014) and through their transcriptional activity not only as potent anticancer but even as potential safe antiviral agents (Hutterer et al. 2015).

LDC’s CDK7 project emerged from a scientific collaboration with research groups from the Westfälische Wilhelms-University of Münster (Prof. Dr Michael Meisterernst) and the Max-Planck-Institute for Immunobiology and Epigenetics in Freiburg (Dr Gerhard Mittler). LDC has received generous support for this program from the German Federal Ministry of Education and Research (BMBF) as well as the Max-Planck-Foundation and its benefactor Dr Klaus Neugebauer.

This transaction was actively supported by Max Planck Innovation, the technology transfer organization of the Max Planck Society.

About Qurient

Qurient started operation in 2009 as a venture capital funded spin-off biotechnology company of the Institut Pasteur Korea (IPK) and is dedicated to bridging gap between innovative sciences and clinical development for unmet medical needs. Qurient operates as a network R&D company with a small pharmacology research laboratory, and has in-house expertise in project management capabilities to facilitate discovery and development outsourcing projects. Qurient is focused on small molecule therapeutics in the oncology and inflammatory diseases areas, and covers the R&D stages from discovery to clinical proof-of-concept.

Further information at: www.qurient.com

Contact

Taehwa Chang

T. +82.31.8060 1600

E. tchang@quient.com

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Dortmund, Germany, 21 April, 2015 – The Charcot-Marie-Tooth Association (CMTA) announced today that it has entered into a collaboration with Affectis Pharmaceuticals AG to evaluate the efficacy of advanced Affectis compounds in neurological and behavioral models of CMT1A.

Affectis is a therapy development company and since 2013 a fully owned subsidiary of the Lead Discovery Center GmbH (LDC), a spin-off of Max Planck Innovation GmbH. The goal of the collaboration is to evaluate the pharmacology of small molecule antagonists of the P2X7 ligand-gated ion channel that are being jointly developed by Affectis and the LDC. P2X7 is an ATP-gated ion channel which is essential for cellular calcium homeostasis, and for the maturation and release of pro-inflammatory cytokines, including interleukin-1beta (IL-1β).

The collaboration’s aim is to demonstrate the potential of P2X7 antagonists that have high potency for the human form of P2X7 and are orally bioavailability in treating CMTA1. Use of such antagonists may impede the development of motor and sensory control defects associated with progression of the disease.

Pre-clinical studies previously demonstrated a likely role for P2X7 over-activity in the pathogenesis of CMT1A (Nobbio et al. (2009) J. Biol.Chem. 284, 23146). An altered calcium homeostasis was observed in Schwann cells from rats that exhibit a CMT1A pathology due to the expression of extra copies of the pmp22 gene; this is hypothesized to lead to the disruption of myelination associated with the disease. The authors further showed that the changes in intracellular calcium coincided with overexpression of the P2X7 ligand-gated ion channel, and that its inhibition leads to myelin repair.

Charcot–Marie–Tooth disease Type 1 (CMT1) is rare inherited
disorder of the peripheral nervous system characterised by
progressive and severe demyelination.

Patrick Livney, CEO of the CMTA notes: “The association has assembled the scientific and clinical key opinion leaders in CMT disorders and the research tools necessary to validate therapeutic opportunities for their clinical potential. We have set out to engage drug makers to work together with the CMTA to advance new therapeutic approaches to our patients, and our STAR network combines this world class research expertise with an operational capability has been highly enabling to collaborative alliances formed for this purpose. Currently, there are no therapies for the different CMT disorders to halt either the onset or progression of the disease. This Affectis collaboration represents an exciting new opportunity for the CMTA to both de-risk and accelerate development of a novel drug class for the treatment of CMT1A, the most prevalent of the genetic neuropathies.”

Affectis CEO Michael Hamacher said of the collaboration: “Our P2X7 lead compounds have excellent pharmacological properties and repeatedly showed efficacy in various animal models. With initiation of the CMT1A studies we see the unique chance to evaluate both the role of P2X7 as well as the potency of the Affectis’ compounds in the Charcot-Marie-Tooth 1A disorder, a demyelinating neuropathy with unmet medical need. We are very much looking forward to the collaboration with the excellent team of experts from the CMTA to jointly progress the P2X7 leads into an effective therapy for Charcot-Marie-Tooth 1A”.

About Charcot Marie Tooth Disease Type 1A (CMT1A)

CMT1A is a rare (1:5,000) hereditary motor and sensory demyelinating peripheral neuropathy (also known as Hereditary Motor and Sensory Neuropathy, HMSN) which is caused by an intrachromosomal duplication and consecutive toxic overexpression of the PMP22 gene on chromosome 17. CMT1A is one of the most common inherited peripheral nerve-related disorders passed down through families in an autosomal dominant fashion. CMT1A disease becomes evident in young adulthood and slowly progresses with distally pronounced muscle weakness and numbness. Pain can range from mild to severe. The disease can be highly debilitating with patients becoming wheelchair-bound and is often accompanied by severe cases of neurological pain. There is no known cure for this incapacitating disease.

About the Charcot-Marie-Tooth Association

The Charcot-Marie-Tooth Association (CMTA) is a registered 501c3 dedicated to serving an international patient community that suffers from rare and disabling neuropathies of genetic origin. The CMTA directly engages its STAR scientific and clinical research network in the identification, validation and clinical development of therapies for the different Charcot-Marie-Tooth disorders.

Contact

Patrick Livney, CEO

Charcot-Marie-Tooth Association

T. +1-312.750.9800

Email: pal@cmtausa.org

Further information at: www.cmtausa.org

About Affectis and the LDC

Affectis Pharmaceuticals AG is a pharmaceuticals company that develops novel drugs for the treatment of neurodegenerative and neuroinflammatory diseases. Affectis’ capabilities in drug discovery and medicinal chemistry allowed the company to develop drugs with innovative mechanisms of action based on pioneering findings in the field of P2X7 receptors. Affectis started operations in January 2004 as a spin-off from the Max Planck Institute of Psychiatry. Since January 2014 Affectis has relocated to Dortmund, Germany, and is now fully owned by and closely collaborates with the Lead Discovery Center GmbH (LDC) to further advance its core asset AFC-5128.

LDC was established in 2008 by the technology transfer organization Max Planck Innovation as a novel approach to capitalize on the potential of excellent basic research for the discovery of new therapies for diseases with high medical need. LDC is a translational incubator for innovative academic projects in the field of small molecule drug discovery and has a strong track record in successful industry partnerships with AstraZeneca, Bayer, Merck Serono and Daiichi Sankyo.

Contact

Dr. Michael Hamacher, CEO

Affectis Pharmaceuticals AG

T. +49.231.97 42 70 00

Email: hamacher@affectis.de

Further information at: www.affectis.de & www.lead-discovery.de

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Dortmund, April 14, 2015 – The Lead Discovery Center GmbH (LDC) and AstraZeneca have expanded their alliance to discover new medicines for the treatment of human diseases with high unmet medical need. Through an additional three-year period of collaboration, AstraZeneca will provide an extended set of high-quality compounds to the LDC’s internal screening collection to pursue projects in the areas of cardiovascular and metabolic diseases, oncology, respiratory and inflammation and neuroscience.

AstraZeneca and LDC expand their succesful alliance
to discover new medicines.

The renewal of the partnership follows a successful two-year period of collaboration and establishes the LDC as one of AstraZeneca’s four leading translational centers. Over the last two years, the LDC and AstraZeneca have already initiated six high-potential drug discovery projects which are progressing well.

“We are very much looking forward to continuing and expanding our alliance with AstraZeneca,” says Bert Klebl, CEO of the LDC. “The passionate scientific exchange and very productive interaction so far has exceeded our expectations and we are more than happy to now further build on this well-functioning partnership. We not only share our compound libraries but, moreover, our know-how and expertise on technologies and emerging disease areas, which enables us to identify, select and effectively progress joint projects . Together, we are perfectly situated to accelerate the translation of academic findings into new medicines.”

“We are very excited to continue our partnership with the LDC,” says Garry Pairaudeau, Head of External sciences at AstraZeneca. “Open Innovation is a key part of our drug discovery strategy and we are continuing to grow our external partner network. With LDC we have enjoyed a vibrant and productive scientific collaboration and it is clear that their scientists share our values and commitment to developing new medicines for patients who have an unmet medical need.“

Under the terms of the alliance, the LDC will screen the combined compound collection of more than 450,000 compounds against a portfolio of innovative biological targets. Targets will be carefully selected by the LDC from its broad range of academic partner institutions, including members of the Max Planck Society, Germany’s leading basic research organization. A joint steering committee oversees the collaboration and reviews the output. The LDC takes the most promising compounds into further drug discovery by optimizing them into pharmaceutical leads with in vivo proof-of-concept. AstraZeneca has a preferred right to obtain a license for pre-clinical and clinical development and commercialization for collaboration projects.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialisation of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.

Further information at: www.astrazeneca.com

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Dortmund, 31 March 2015 – The Lead Discovery Center GmbH (LDC) and the Helmholtz Centre for Infection Research (HZI) will be working in close cooperation to identify and optimize new drug candidates against methicillin-resistant Staphylococcus aureus (MRSA).

MRSA are resistant to several traditional broad-spectrum antibiotics and therefore constitute a serious threat worldwide, particularly in hospitals and care homes for the elderly. They can cause serious illnesses, especially in patients with weakened immune systems, resulting in long periods of hospitalization, and in some cases, death. Based on data gathered by the German national hospital infection surveillance system (KISS), experts estimate the number of MRSA hospital infections to be approximately 14,000 per annum in Germany alone. Up to 2,000 patients die as a result of these infections each year.

©HZI/Rohde

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common and most dangerous hospital-acquired infections.

The LDC and the HZI are pooling their expertise to advance a new approach to combating MRSA developed at the HZI.  Their goal is to develop a drug that effectively blocks the establishment of an infection without actually killing the bacteria. ‘This strategy has two important advantages over traditional antibiotics,’ explains Prof. Mark Brönstrup, Head of Chemical Biology at the HZI. ‘First, we avoid further selective pressure that would inevitably lead to the development of new drug resistance.  Secondly, the drug would be better tolerated, as it wouldn’t affect the patient’s normal bacterial flora.’

The addressed therapeutic target has already been validated at the HZI in previous studies.  A drug aimed at this protein has the potential to inhibit a central infection mechanism of S. aureus.  In the first phase of the project, the LDC will screen their own substance library, together with the library supplied by the HZI, for compounds that selectively block the target structure. These hit compounds will be characterized in terms of their potency, selectivity and pharmacological properties, and then further optimized by the LDC in the second stage of the project. In parallel, the HZI will test the efficacy of optimized compounds against MRSA in a battery of biological model systems.

‘There is great potential in this cooperation,’ comments Dr. Bert Klebl, CEO of the LDC. ‘By pooling our expertise, experience and substance libraries we really have an excellent chance of identifying drug candidates, so-called ‘leads’, that are highly attractive to global pharma partners and that can be transferred directly to pharmaceutical drug development. Together, we can make a significant contribution in the fight against resistant bacteria.’ This is the second cooperation project between the LDC and a Helmholtz Centre. The first was launched at the end of last year in the field of oncology. Both projects receive financial support from the Helmholtz Validation Fund. The HZI is providing additional funding for the current project.

About the HZI

At the Helmholtz Centre for Infection Research in Braunschweig, scientists are studying microbial virulence factors, host-pathogen interactions and immunity. The goal is to develop strategies for the diagnosis, prevention and therapy of human infectious diseases. The research site in Braunschweig-Stöckheim looks back at a long and successful history. The first laboratories opened in 1965, so the HZI is celebrating its 50th anniversary in 2015.

Further information at: www.helmholtz-hzi.de/en

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Collaboration with the LDC to explore the development of a Englerin-A inspired cancer drug

Dortmund, March 17, 2015 – Nature holds many compounds in store that are of great value to medical research. Recently, for example, scientists discovered that a substance contained in an African shrub kills cancer cells in the kidney. Together with colleagues from Berlin and Leeds, researchers from the Max Planck Institute of Molecular Physiology in Dortmund discovered that the molecule known as englerin A significantly increases the concentration of calcium in cells, causing the cancer cells to die. Englerin A only activates the calcium channels of renal cancer cells, but not those of healthy cells. In cooperation with the Lead Discovery Center in Dortmund, the scientists now want to find out whether englerin A could potentially be used as an innovative drug to treat renal cancer in the future.

In its native habitat in southern Africa, Phyllanthus engleri has long been known to have medicinal properties. The shrub or small tree, which was formerly classified as belonging to the spurge family, is most commonly found in the dry savannahs of Tanzania, Zambia, Malawi, Zimbabwe, Mozambique and South Africa. In Tanzania, for example, the plant’s roots are used to treat epilepsy, and chewing the leaves and fruits is said to alleviate coughs and stomach aches. A decoction made from the roots is even said to be effective against bilharziosis and gonorrhoea. At the same time, the plant also contains strong toxins that can cause lethal poisoning.
In 2009, American scientists isolated more than 30 substances found in Phyllanthus engleri and tested their efficacy on cancer cells. They discovered that a specific type of compound taken from the bark of the tree – a variant known as (–)-englerin A – is particularly effective against renal cancer cells and some other forms of cancer. That same year, the group led by Mathias Christmann, who now conducts research at the Freie Universität Berlin, synthesised this complex compound. The precursor they used is the primary constituent in the essential oil of catnip (Nepeta cataria): nepetalactone – a substance that causes cats to lapse into a state of ecstasy. Nepetalactone is therefore a renewable raw material extracted from a plant that is more readily available than Phyllantus engleri. This is decisive for the further use of englerin A, as it means that larger amounts of the substance can be produced.

However, exactly how englerin A kills cancer cells remained a mystery. Until recently, it was believed that englerin A might target a variant of the enzyme protein kinase C. The Max Planck scientists have now discovered though that cells that respond to englerin A particularly well do not contain this type of enzyme at all. Instead, the researchers focused on a family of calcium channels known as TRPCs (canonical transient receptor potential channels), which are found in the membranes of renal cells.
Different renal cancer cells form different numbers of these channels. The measurements showed that adding englerin A causes the calcium concentration inside these cells to rise so significantly that the cells die within a few minutes. “We studied cancer cells that produce a lot of TRPC4. These cells are particularly sensitive to englerin A. In cells that do not produce any TRPC4 or only produce normal amounts, the calcium levels do not rise as much. Therefore, these cells don’t die,” explains Slava Ziegler from the Max Planck Institute of Molecular Physiology. However, the researchers still do not know whether the overproduction of TRPCs is the sole cause of the dying off of the cancer cells.

Englerin A thus acts specifically on cancer cells in the kidney. “This property gives the substance a major advantage over other anti-cancer drugs, because it means the side effects afflicting healthy cells could possibly be prevented,” says Herbert Waldmann from the Max Planck Institute in Dortmund, where, among other topics, he conducts research into the use of naturally occurring substances in the development of active agents.

Together with the Lead Discovery Center in Dortmund, the researchers now want to determine whether englerin A is suitable as an anti-cancer drug. The Center, which was founded by the Max Planck Society, helps bring potential active agents from basic research to clinical trial. “Englerin A is a prime example of an active substance that harbours great potential, but also a significant risk. In the current phase there would be hardly any commercial partners willing to provide the funding for further studies. The Lead Discovery Center can bridge this gap between basic research and medicine,” says Waldmann.

LG/HR

Address: http://www.mpg.de
© 2003-2015, Max-Planck-Gesellschaft, München

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Dortmund, March 10, 2015 – The Lead Discovery Center (LDC) receives two grants of EUR 0.5 Million each for the development of two innovative drug discovery approaches for treating inflammation and cancer. The funds originate half-and-half from the Max Planck Foundation (MPF) and the Dr Helmut Storz Foundation, which is managed by the MPF.

“We are very pleased to have attracted Dr Helmut Storz as a sponsor for these two exciting projects,” says Dr Bert Klebl, CEO of the LDC. “His focus on translational research fits our mission perfectly, and the grants enable us to advance the designated projects to a stage where they can be channelled into pharmaceutical drug development.”

The first project is a new anti-inflammatory compound being jointly developed by the LDC, the Max Planck Institute of Microstructure Physics and the Max Planck Research Unit for Enzymology and Protein Folding. It targets a group of enzymes called cyclophilins, which play an important role in the development of acute inflammation. The first-in-class compound uses a novel and more targeted mode of action that could reduce the dosing requirements and side-effects associated with traditional cyclophilin inhibitors, which include immune suppression and kidney or liver damage. The project holds strong potential for the treatment of inflammatory diseases in cardiology and autoimmunity.

The second project addresses a highly innovative molecular target that plays a pivotal role in various cancer forms, including breast and ovarian cancer. The project will benefit from the LDC’s extensive know-how in the discovery of small molecule inhibitors for the enzyme class in question. The LDC will collaborate closely with the Center of Advanced European Studies and Research (Caesar), which is associated with the Max Planck Society.

Without this generous support, it would not have been possible to advance these projects into translational development. The goal is to identify an appropriate industry partner for each project at the end of the funding period to ensure further development towards the clinic. The LDC is particularly strong in linking academia and industry to effectively integrate the players in a collaborative drug discovery approach – as proven by the many successful partnerships the LDC has created with top research institutions and pharma companies across the world. In the event of a commercial success, licensing revenues will be shared between the LDC, the originating institutions and the supporting foundations.

About the Max Planck Foundation and the Dr Helmut Storz Foundation

The Max Planck Foundation (MPF) is a charitable foundation that finances outstanding and pioneering research projects from the Max Planck Society for the Advancement of Science (MPG). It is a public foundation under German civil law, and is supported by a nationwide initiative of private sponsors.

The Dr Helmut Storz Foundation was established previously to and independently from the MPF. It has been managed by the MPF since 2013. Its benefactor, Dr Storz, is particularly interested in scientific projects on the threshold of application, as very little public funding is available at this stage in their development. Projects are selected by the benefactor and the MPG in close consultation, and their quality is thoroughly examined.

Further information : www.maxplanckfoerderstiftung.org

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