Date: 19-20/10/2021
Location: The Exhibition Centre, ACC, Liverpool
Attendee: Oksana Nikolayenko
Date: 19-20/10/2021
Location: The Exhibition Centre, ACC, Liverpool
Attendee: Oksana Nikolayenko
Molecular profiling of cancer patients is a great success story: A single test can analyse a patient’s genome to identify genetic alterations from the four main classes that are known to drive cancer growth: base mutations, gene insertions and deletions, copy number alterations, and rearrangements or fusions. In addition to retrieving information on these common oncogenic drivers, it is also possible to obtain new information on complex or rare biomarkers from the same test. Based on this knowledge, oncologists can select the most suitable cancer therapy, often a combination of increasingly targeted drugs that address a specific cancer mechanism. As a result, molecular profiling approaches have been integrated to mainstream clinical oncology, and targeted therapies have become standard of care for patients known to express certain mutations in their tumours.
Molecular profiling – suitable for many indications
This success has fueled interest in the molecular profiling of other complex indications as well and has also expanded the profiling process: not only the sequence is analysed, but also methylation and expression patterns. The profiling toolbox also includes proteomics to analyse the proteins expressed in a cell or tissue and metabolomics to study the metabolism of diseased cells, tissue, organs, and patients.
The wealth of data generated by these approaches is now being analysed by artificial intelligence linking these data to individual patient information to identify biomarkers that provide insights into the genesis and course of the disease and that may help to stratify patients, predict outcome, and select therapies. The goal of these efforts is the development of precision medicines for complex diseases not only in cancer, but also in autoimmune or other chronic diseases – a clear departure from the old paradigm of “one-drug-fits-all.”
By systematically integrating data science across its discovery and development platform, Evotec aims to lead this paradigm change towards highly effective personalised medicine of the future. It has industrialised the generation of genomics, transcriptomics, proteomics and metabolomics data with its EVOpanOmics platform and has built a strong complementary data analytics platform driven by artificial intelligence and machine learning with EVOpanHunter. This platform makes use of molecular patient databases, bioinformatics and the data generated by EVOpanOmics.
Integrated approach
The company is in a unique position as these platforms are complemented by Evotec’s multimodality expertise spanning from small molecules and chemistry to biologicals, antisense molecules to cell and gene therapy. Moreover, with its iPSC platform Evotec’s scientists can design and test patient-derived disease models for comprehensive compound profiling in the treatment development process, focusing on disease relevance throughout the entire pre-clinical and clinical steps.
Already, Evotec has closed a number of collaborations in this field. In 2020, it joined forces with Indivumed GmbH for the discovery and development of first-in-class therapeutics for the treatment of non-small cell lung cancer (NSCLC). The collaboration combines Evotec’s bioinformatics, advanced analytics and AI capabilities as well as its small molecule and antibody discovery platforms, with the NSCLC cohort of Indivumed’s multi-omics cancer database “IndivuType.”
In the same year, Evotec closed a partnership with the University of Oxford, gaining access to biospecimens from the biobank Quality in Organ Donation (QUOD), an initiative of the university’s Nuffield Department of Surgical Sciences (NDS) in close collaboration with the National Health Service Blood and Transplant (NHSBT) organisation in the UK. QUOD is providing blood, urine and tissue samples from heart, lung, liver and kidney from consented organ donors for researchers with anonymised integrated medical records. Evotec at present is investigating first samples from 1,000 individuals using a comprehensive multi-omics approach (genomics, transcriptomics, proteomics, metabolomics) to complement its existing patient database. The goal is to enable a better understanding of disease mechanisms across indications, i.e. cardiovascular, kidney, and liver diseases.
A particular focus of Evotec is chronic kidney disease (CKD). CKD is an impending public healthcare challenge, and the traditional diagnostic biomarkers, e.g. creatinine, have low sensitivity and specificity. Therefore, novel diagnostic and prognostic biomarkers for patients at high risk of early-stage progression are urgently needed. They may not only provide information about the etiology and mechanisms underlying CKD progression, but may also enable early diagnosis and the selection of appropriate therapies, thereby personalising therapy. Evotec closed a strategic partnership with the University Hospital of Erlangen for the molecular analysis of biospecimens from the German Chronic Kidney Disease (GCKD) cohort study initiated by the university. GCKD is the world’s largest cohort study on chronic kidney disease, enabled by scientists from eleven universities and more than 150 practicing nephrologists that monitor more than 5,000 patients with CKD. The study comprises sampling of biospecimens, clinical data and multiple interviews. The collaboration aims to better understand the various kidney disease etiologies, their respective disease mechanisms, progression, and potential complications. Together with Evotec’s existing molecular patient database, this systematic integrated exploitation of the GCKD biobank is expected to provide novel starting points for drug discovery and the identification of biomarkers, enabling precision medicine approaches for highly effective treatment options for clearly defined patient populations.
Also in kidney disease, Evotec is collaborating with Novo Nordisk to jointly identify and develop novel targets based on comprehensive medical and molecular data sets of thousands of chronic kidney disease patients, and with Chinook Therapeutics to identify, characterise and validate novel mechanisms and discover and develop precision medicines.
All collaborations leverage the EVOpanOmics and EVOpanHunter platforms with the overarching goal to develop disease-modifying therapies for the targeted treatment of patients with unmet medical needs.
Date: 25th -28th October 2021
Location: Virtual event
Evotec is a sponsor of BIOEurope 2021 - View the event agenda and register to the on-demand sessions to listen from our experts:
Interview | On Demand | Cord Dohrmann, Evotec CSO
How to build an innovative pipeline
Business Development Stream
Panel Discussion | On Demand | Bernd Muehlenweg - SVP, Innovate Strategic Initatives at Evotec
The speed of life science innovation
Technologies such as CRISPR and mRNA have been hailed as 'new science' but these therapies are the result of long lab hours, years of clinical development, and intensive research by solo scientists and collaborative teams. This session will consider the fundamental character of the lifescience discovery process. Are there tools that have emerged that that ease the 25-year discovery process to something shorter? What role does collaboration and communication play in facilitating advancements? And what modalities emerging now could be the breakthroughs of the future?
Biotech Ecosystem Stream
Presentation | On Demand | Thomas Hanke, Evotec Head of Academic Partnerships at Evotec
Diversifying your funding options is key to startup success
What type of funding is best suited to you? VC's are not always the perfect fit and the right route to take when looking for funding sources to start a successful company. This panel will explore alternative funding sources.
Business Development Stream
Don't miss Evotec's showcase on cell and gene therapy published in the EBR's annual BIO-Europe 2021 Supplement: "Next Generation Treatments to Cure Chronic Diseases"
Connect via PartneringOne to meet with them and all our experts at BioEurope or email us at info@evotec.com
Our team at BioEurope 2021
Cord Dohrmann, Bernd Mühlenweg, Thomas Hanke, Adam Stoten, Margit Wissenbach, Fred Somny, Daniel Ozanne, Sneha Kumar
P2X3 receptors play an important role in the sensitisation of nerve fibres and pain pathways. Involvement in pathways triggering cough and contribution to the pathophysiology of endometriosis and overactive bladder have also been reported. Development of P2X antagonists have been hampered by off‑target effects which include severe taste disturbances associated with blocking the P2X2/3 receptor heterotrimer.
In this publication, we focus on:
Tags: Neuroscience, Articles & Whitepapers, In vitro Biology, In vivo Pharmacology
The key to de-risking and expediting the development and approval of new antimicrobials lies in the detailed understanding of the PK/PD relationship. Understanding this relationship informs the development of optimal human dosing, maximising efficacy while minimising the potential to antimicrobial resistance.
This white paper describes and appraises today's most versatile in vitro system for the determination of in vitro PK/PD relationships between antimicrobial compounds and bacteria, fungi and viruses - the Hollow Fibre Infection Model (HFIM)
Tags: Articles & Whitepapers, In vitro Biology, Anti-Infectives
Mass spectrometry (MS)-based ubiquitinomics allows a system-level understanding of ubiquitin signalling.
In this publication, we focus on:
Tags: Oncology, Articles & Whitepapers, Proteomics, Metabolomics & Biomarkers
Alastair Parkes, Ph.D, Group Leader, Discovery Chemistry, Evotec UK
As part of our ongoing efforts at Evotec to tackle AMR through the design of novel antibiotics we have been working with Boston-based X-Biotix in a collaboration focussed on targeting priority Gram-negative pathogens. We are now able to share the story of our work on inhibitors of UDP-N-Acetylglucosamine Acyltransferase (LpxA), a key enzyme in the biosynthetic pathway of the outer membrane lipopolysaccharide of Gram-negative bacteria. Building on hit-finding work at X-Biotix we put together a multi-disciplinary team including Medicinal Chemistry, Computational Chemistry, Structural Biology and DMPK at our Abingdon UK site, in vitro and in vivo Microbiology and PK at our Alderley Park UK site, and in vitro Biology at our site in Hamburg, Germany. Through structure and property-based optimisation we were able to design highly potent inhibitors of Pseudomonas aeruginosa LpxA that were active against multi-drug resistant clinical isolates. To our knowledge, this is the first reported LpxA inhibitor series with selective activity against P. aeruginosa bacteria. In our paper in the Journal of Medicinal Chemistry we share the optimisation story, along with a significant quantity of activity data that we hope will be useful for other teams working on small molecule strategies to tackle P. aeruginosa and other Gram-negative bacteria.
Tags: Antibacterial, Medicinal Chemistry, Articles & Whitepapers, ADME/DMPK, In vitro Biology, In vivo Pharmacology, Anti-Infectives, Antimicrobial resistance
Arthralgia (persistent pain or stiffness of the joints) is a common symptom of chikungunya virus infection which can persist for many months following the disease. This condition is associated with significant disability and reduced quality of life. In order to manage individual clinical expectations and long term burden on the population following a chikungunya virus infection epidemic, it is critical to know the expected duration of the post infection arthralgia.
In this publication, we focus on:
Following chikungunya virus infection, chronic rheumatological symptoms are similar to those observed with rheumatoid arthritis. To further evaluate this, a comparison was made between the relevance of joint counts and symptoms between the two conditions.
In this publication, we focus on:
Dendritic Cells (DCs) are very efficient antigen-presenting cells and have long been considered as attractive candidates for cancer immunotherapy. They are obtained from the patient and loaded in vitro with tumour antigens and additional maturation stimuli and subsequently, infused back into the patient. However, after more than 200 clinical trials involving thousands of patients, clinical responses have been disappointing so far.
While the treatment is safe and well-tolerated and often elicits anti-tumour immunity in both patients with advanced stages of disease and those with minimal residual disease following tumour resection, only a minority of patients demonstrates objective response rates. There are several reasons why the results are disappointing, and while scientists have been able to address problems such as active immune suppression and evasion mechanisms of the tumour, some DC therapy-related aspects contributing to the limited clinical efficacy of DC therapy remain to be solved: the choice of the antigen, the method of loading, and, above all, the type of DCs used. Access to the full spectrum of DCs is limited and many subsets known to be very effective simply are not accessible as they can be derived from the patients only in very low quantities.As a result, sentiment has switched to approaches viewed as more promising, such as checkpoint inhibitors or chimeric antigen receptor (CAR)-T cells.
Exciting advances with iPSCs
However, thanks to the recent advances made with induced pluripotent stem cells (iPSCs) interest in these vaccines has been renewed. iPSCs can be induced to produce dendritic cells and this provides an opportunity for the rational design of DC vaccines displaying additional functionality via genetic engineering technologies. As iPSCs also open up the possibility for the mass production of large numbers of high-quality iPSC-derived DCs, it is now possible to design next generation DC vaccines from engineered DCs.
Moreover, iPSCs also allow for the production of DC subsets that are not accessible as yet for therapeutic development because sufficient quantities could not be obtained. Examples are DCs facilitating anti-viral responses and a certain subset called CD141+ specialised on cross-presentation of antigens. The CD141+ subset, which is found in very low abundance in vivo, is of particular interest for cancer therapy as it induces optimal cytotoxic T lymphocyte (CTL) responses. Thanks to iPSC, these subsets now can be produced under cGMP conditions in bulk quantities.
Off-the-shelf cancer vaccines?
All in all, these advances may provide the opportunity to design off-the-shelf DC products suitable for cancer vaccines.
Evotec therefore has invested in British immune oncology company OXvax Ltd., a spin-out from the University of Oxford focused on the development of an advanced next-generation dendritic cell vaccine platform for the treatment of solid cancers. The company is pioneering the use of iPSCs as a novel source of CD141+ dendritic cells (DC) and is based on intellectual property from the Fairchild laboratory at the Sir William Dunn School of Pathology. OXvax’s technology addresses, among others, the low cross-presentation and the T-cell activation problems of past DC-based cancer treatments. The platform enables the manufacture at scale of an off-the-shelf, highly potent vaccine which addresses the major limitations that have frustrated cancer vaccine development in the past. If the approach is successful in oncology, it can also be expanded to other therapeutic areas, e.g. viral infections.
Tags: Oncology, immuno-oncology, Blog, Biologics