Background EVT401, Evotec’s P2X7 receptor, is an ATP-gated ion channel and may provide a novel approach for the treatment of inflammatory conditions. The compound was completely developed in-house. Phase I results in 2009 showed a very good safety profile and confirmed on-target activity. In May 2012, Evotec started an alliance with CONBA, one of the largest pharmaceutical companies in China. The agreement grants CONBA exclusive rights to develop and commercialise the compound for the Chinese market for human indications with the exception of ophthalmological, chronic obstructive pulmonary disease (COPD) and endometriosis.
Status In the first half of 2014, as requested by SFDA, CONBA completed in vivo efficacy studies for EVT401 which demonstrated that EVT401 is effective against experimental arthritis in non-human primates. Development of a clinical formulation is ongoing for use in clinical trials.
Pre-clinical and discovery stage
Beyond its partnered clinical-stage partnered product pipeline, Evotec has a broad and deep pipeline of partnered product opportunities at pre-clinical and discovery stages.
In April 2014, Evotec entered into a research collaboration and licensing deal (TargetCanMet) with Debiopharm Group™ Lausanne, Switzerland. The objective of this collaboration is to identify and develop novel compounds having the potential to treat multiple forms of solid tumours and leukaemias with defined genetic alterations. Discovery and pre-clinical development efforts are driven by Evotec, whilst Debiopharm will manage clinical development. Evotec receives R&D funding and significant double-digit total payments triggered by clinical, regulatory and commercial milestones, plus royalties on sales of resulting commercial products.
Effective 29 April 2014, Janssen Pharmaceuticals decided to end the partnership on beta cell regeneration. CureBeta, the alliance between Harvard and Evotec, will continue and Evotec will try to identify alternative partners. Effective in April 2014, Evotec acquired the German-based company Bionamics GmbH (“Bionamics”), an asset management company that focuses on the translation of academic innovations into attractive assets for the biotech and Pharma industry. Bionamics brought to EVT Innovate a portfolio of funded projects that bear considerable upside for Evotec. In October 2014, Boehringer Ingelheim decided not to pursue EVT070 further in the disease area of diabetes. The compound has been returned to Evotec and is now being investigated in other indications.
Milestone achievements within existing alliances
In April 2014, Evotec reported the successful achievement of a milestone in its biomarker alliance with Roche. The milestone was achieved on the decision by Roche to use a response prediction marker, identified using Evotec’s Proteome Profiling platform, in an extended phase I oncology trial. This is the first milestone achieved under the collaboration and licence agreement between Evotec and Roche, signed in 2011, which is part of the m4 Munich Biotech Cluster Personalized Medicine and Targeted Therapies initiative. Evotec is eligible for further success-based payments upon clinical companion diagnostics development.
In June 2014, Evotec disclosed that its research alliance with Boehringer Ingelheim had reached a milestone triggering revenues of € 1.0 m for
Clinical
EVT3021) Alzheimer’s disease Roche
EVT201 Insomnia JingXin
Somatoprim Acromegaly Aspireo
EVT100 CNS diseases Janssen
EVT401 Inflammation CONBA
ND2) Oncology Boehringer Ingelheim
ND2) Oncology Roche
Pre-clinical
ND2) Pain Novartis
ND2) Oncology Boehringer Ingelheim
Various Endometriosis Bayer
EVT770 Diabetes – type 2/1 MedImmune/AstraZeneca
ND2) Pain Boehringer Ingelheim
Discovery
Various Inflammation UCB
Various Diabetes – type 2/1 MedImmune/AstraZeneca Various Diabetes – type 2/1 Harvard
Various Kidney disease AstraZeneca
Various Oncology Debiopharm Group
Various Alzheimer’s disease Johnson & Johnson Innovation
Various CNS/MS Neu2
Molecule Indication Partner Discovery Pre-clinical Phase I Phase II Phase III
1) RO4602522 2) Not disclosed
Large portfolio of product opportunities with significant upside
Evotec. The milestone was for the transition of a back-up compound from a respiratory programme into pre-clinical development.
In September 2014, Evotec reached an important milestone in its multi- target collaboration with Bayer for the transition of a molecule into pre-clinical development for the treatment of endometriosis. In December 2014, Evotec announced that this collaboration with Bayer had achieved additional important milestones for the transition of certain molecules into pre-clinical development for the treatment of endometriosis. The goal of this collaboration is to develop three clinical candidates during the five-year alliance.
In July, September and December 2014, Evotec achieved milestones in its TargetAD collaboration with Janssen Pharmaceuticals, Inc. (“Janssen”) for the identification and selection of targets from the TargetAD database. These target selections were achieved under the agreement between Evotec and Janssen, facilitated by the Johnson & Johnson Innovation Center in California, signed in November 2013. Under the terms of the agreement, Janssen and Evotec are collaborating to identify new drug targets for the discovery of novel treatment approaches to Alzheimer’s disease. Janssen has the option to internalise selected targets and therapeutic candidates and progress them into pre-clinical and clinical development. Janssen funds target drug discovery research via a combination of defined research payments and progress-related milestones.
Unpartnered product opportunities – Cure X and Target X initiatives in 2014
Cure X and Target X initiatives are carefully selected discovery stage projects that are either pursued as internal R&D projects or in collaboration with leading academic laboratories or biotech companies. Cure X and Target X initiatives that are carried out in collaboration with academia or biotech predominantly work on the principle of risk and reward sharing, i.e. both partners contribute to the project and share potential financial rewards according to the respective contributions.
The focus is on developing product opportunities with first-in-class potential in indications of high, unmet medical need and significant markets. Preferably, these initiatives pursue drug product opportunities with disease-modifying properties, i.e. mechanisms that may slow or even reverse progression of disease. The aim is to advance and partner these projects at tangible value inflection points and thereby expand Evotec’s proprietary pre-clinical and clinical pipeline.
Cure X and Target X initiatives require access to highly innovative biology and extensive disease area expertise. To complement and expand Evotec’s internal expertise and capabilities, Evotec partners with leading academic institutions in the USA (Harvard, Yale, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, etc.), in Europe (Fraunhofer Institute, UKE, University of Berlin) as well as emerging biotech companies (Apeiron, Haplogen, Aspireo, etc.).
Clinical 1,033 2,512 516 106 116 Discovery 1,804 1,897 2,972 5,246 9,027 Platform R&D 868 1,101 1,942 1,754 742 Overhead R&D 2,411 2,927 2,910 2,558 2,519 Total R&D 6,116 8,437 8,340 9,664 12,404 Funded R&D 3,878 1,648 554 425 703 in T€ 2010 2011 2012 2013 2014
Development of R&D expenses
The goal of EVT Innovate is to grow aggressively through additional Cure X and Target X projects and partnerships. Many projects have been initiated in 2013 and 2014 and the current pipeline of opportunities is shown below.
management capabilities and its market presence to identify drug candidates in these novel approaches to tackle MS and to commercialise those later on. Current MS treatments mostly constitute symptomatic approaches while more specific, well-differentiated disease-modifying treatment modes are eagerly looked for by the industry.
In December 2014, Evotec announced a research collaboration with the laboratories of Prof. Roger Briesewitz at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. The objective of the collaboration is to progress a novel mechanism for engaging the KRas target discovered at The Ohio State University using Evotec’s technology platform and broad expertise in drug discovery and pre-clinical development, thereby validating and progressing novel leads into pharmaceutically developable candidates.
1) Today at least partly progressed under commercial partnership
R&D projects initiated within EVT Innovate
CureNephron1) (Harvard, BWH, USC,
AstraZeneca) TargetSP (Internal) TargetASIC1) (BMBF/undisclosed Pharma partner) Somatoprim (Aspireo) TargetPicV (Haplogen) TargetCanMet1) (Debiopharm)
CureBeta (Harvard Stem Cell Institute) TargetImmuniT (Apeiron)
TargetDBR (Yale) TargetFX (Internal) TargetPGB (Harvard)
TargetKDM (Dana-Farber, Belfer) CureMN (Harvard) TargetEEM (Harvard) TargetAD1) (NBB/J&J) TargetSX (Internal) TargetBCD (Internal) TargetDR (Internal) TargetColCan (Internal) TargetKX (Internal) TargetCytokine (DRFZ) Undisclosed (Fraunhofer) ...