Science Pool

Date: 29 August - 2 September 2022

Venue: University of Copenhagen, Copenhagen, Denmark

Attendees: Sneha Kumar and Frederic Somny (on-site), Steve England (virtual)

If you wish to meet with us in Denmark, get in touch via the form below, we will be happy to arrange a meeting.

Learn more about ARDD 2022.

Date: 5-6 October 2022

Location: Hotel Movenpick Amsterdam City Centre, Piet Heinkade 11, 1019 BR Amsterdam, Netherlands

Attendees: Anna Kerins and Marta Koszyczarek

Learn more about 3rd European Biotransformation Workshop

Date: 2 - 3 October 2022

Location: Park Plaza Victoria Amsterdam, Damrak 1-5, 1012 LG Amsterdam, Netherlands

Attendees: Basile Khara 

Learn more about Peptide and Oligonucleotide ADME Workshop 2022 (POW22)

Date: 24-26 October, 2022

Venue: Leipzig Messe, Leipzig, Germany

Attendees: 

Werner Lanthaler, Chief Executive Officer
Matthias Evers, Chief Business Officer
Thomas Hanke, Executive Vice President, Head of Academic Partnerships
Ryan Brady, Executive Vice President, Head of Global Discovery Business Development
Friedrich Scheiflinger, Executive Vice President, General Manager Evotec Gene Therapy
Bernd Muehlenweg, Senior Vice President, Global Business Development
Christelle Dagoneau, Senior Vice President, Business Development
Jason Brown, Senior Vice President, Business Development
Sneha Kumar, Director, Business Development
Christine Guenther, Entrepreneur in Residence, Medical Director Cell Therapy
Dara Henry, Entrepreneur in Residence
Insa Hartmann, Associate, Global Business Development

Evotec will be a sponsor at BIO-Europe 2022 in Leipzig and will be at booth #82c.

Our CEO, Werner Lanthaler, and SVP, Global Business Development, Bernd Muehlenweg, will speak at the event.

Werner Lanthaler Chief Executive Officer, Evotec	Opening plenary session: Opportunities created by a bear market - There IS a silver lining	Monday, 24 October 2022 10:45 - 11:45 CET/CEST Location: Level 1, Hall 1
Bernd Muehlenweg Senior Vice President, Global Business Development	Panel session: Global dealmaking in a global indication: oncology partnering in 2022	Tuesday, 25 October 2022 09:00-10:00 CET/CEST Location: Multi-purpose room 3

Talk to us about:

• Biologics
• iPSC based Cell Therapy
• Panomics
• Integrated R&D

We look forward to meeting all the biopharma community in Leipzig!

If you wish to arrange a one-on-one meeting with us in Leipzig, you can request a meeting via the BIO-Europe PartneringONE platofrm or get in touch via the form below, we will be happy to arrange a meeting. 

Learn more about Bio Europe.

Watch the webinar to learn more about recent updates in CYP induction!

About the Webinar

Cytochrome (CYP) P450 induction is a well-established mechanism for increased prevalence of DDIs. Whilst its study in vitro has been described in regulatory guidance for over 20 years, data interpretation methods and details for study design have evolved and the best approaches for study of small molecules and other therapeutics are still being discussed within CROs, pharma and biotechs.

In this webinar our expert, Katie Plant, describes the most recent updates in CYP induction. By reviewing and consolidating literature and recent perspectives from Innovation and Quality Induction Working Group (IQ IWG) alongside the regulatory guidance, this provides a comprehensive overview and outlines the recommended approach to assess CYP induction in vitro. When supported by well-designed in vitro assays and batch qualification using a known set of CYP3A4 inducers, relative induction score (RIS) correlation analysis serves as a useful tool enabling the magnitude of clinical CYP3A4 induction to be predicted and used to support decision-making for investigating potential DDI risk.

About the Speaker

Katie Plant Principal Scientist | Cyprotex Discovery Ltd Katie Plant is a Principal Scientist in the Drug Metabolism group at Cyprotex, UK, responsible for operational delivery of high-throughput screening assays covering metabolic stability, enzyme inhibition and induction, alongside supporting clients in designing and interpreting DDI studies to support regulatory submission, supporting R&D and bespoke studies and driving continuous improvement projects.

Watch the webinar to learn more!

[hs-form id="f0365c7a-f5d3-411a-a11b-097b618db7a5" show="hide on login" url="https://news.evotecsciencepool.com/hubfs/Sciencepool/Videos%20and%20Webinars/Cyprotex%20webinars%20and%20videos/cyp-induction-webcast-on-demand-july2022.mp4"]

Gene therapy based on adeno-associated virus (AAV) has come a long way and has been used for more than 20 years in over 2,000 patients. While AAV based gene therapy is regarded as generally safe, the field has experienced several setbacks recently: some trials were halted for safety reasons and product approvals were delayed.

The reasons for these developments are complex, but gene therapy is nowadays not only applied to a narrow spectrum of rare diseases with no other treatments available but is also beginning to be used as a therapeutic option in more common diseases. Consequently, many more patients are being treated and several limitations have surfaced:

• The quality of the clinically used vector material is often, despite cGMP manufacturing requirements, insufficient to prevent adverse events
•  For difficult to access tissues, site-specific administration and delivery of gene therapy vectors can be an important barrier
• The database to demonstrate long lasting therapeutic effects in clinical trials is often thin and the interpretation of results can be difficult
• Patients experience serious adverse events after escalating to high AAV doses

The lack of AAV materials with high and reproducible quality, particularly the presence of substantial amounts of empty capsids is, at times, making the interpretation of controlled clinical trials difficult. Insufficient product quality in combination with very high AAV vector doses often leads to a massive presence of capsids in the liver, causing inflammatory responses and raising safety concerns. In addition, AAV vectors with a desired tropism towards specific tissues or organs and a high yield manufacturability are scarce, thereby limiting the applicability of AAV gene therapy. Yet another complication is that current AAV-based gene therapy technology cannot offer a once in a lifetime treatment in many cases, requiring a repeated dosing (if feasible) in case of therapeutic effects diminishing over time.

Adding to these issues is the fact that about 50 percent of the population already has some immunity to AAV so that not all affected patients will benefit from AAV-based gene therapies.

How to improve AAV-based therapies?

Evotec has identified and addressed a number of issues which were presented in our recent webinar titled “AAV Gene Therapy: Closing the Translational Gap”. According to Hanspeter Rottensteiner, VP, Head of In Vitro Gene Therapy of Evotec Austria, the most important needs are to:

1. Improve the delivery vectors by developing capsids with better tissue tropism and translating into improved efficacy and safety. Also, promoters and the respective transgene need to be optimized to improve cell-type specificity, controllability, and durability
2. Gain better insights into the effects of gene therapy by developing better biomarkers

Improve tracking and analyzing of side effects, for instance by tracking protein expression and metabolic fluxes with proteomic and metabolomic platforms and via high-throughput sequencing of RNA and DNA in target and non-target tissue and cells

Improved specificity

Dirk Grimm, Professor for Viral Vector Technologies at Heidelberg University, explains in the webinar that - thanks to new powerful technologies - knowledge about the host factors that influence AAV vector transduction has increased tremendously. In addition, many new technologies allow for the rational design of next-generation AAV capsids. These novel vectors not only avoid neutralizing anti-AAV antibodies circulating in the human population but also outperform wild-type capsids in terms of potency and / or specificity. Grimm demonstrated as an example that rationally designed myotropic AAV capsids with a tropism exclusively for muscle cells did not accumulate in the liver at all. They demonstrate a substantial improvement in terms of specificity as compared to capsids in use today. The latest technology advancement – barcoding of capsids and nucleic acids - allows for tracking capsids not only to specific organs and tissues but can also tell whether a functional transduction has taken place. Grimm added that the increased use of artificial intelligence will also make animal experiments largely obsolete. In his view, it will be possible in the future to design capsids tailormade to individual patients and their disease.

Filling the gaps

Werner Höllriegl, VP, Head of In Vivo Gene Therapy at Evotec GT GmbH, detailed in the webinar the current gaps in translational efficacy and safety that Evotec is addressing when preparing first-in-human trials. Great efforts are made to assess toxicity in liver, cardiovascular and nervous systems, but also for evaluation of potential oncogenic effects.
Höllriegl also mentioned gaps that cannot be filled by Evotec alone but require a concerted effort by the gene therapy community. Among them are lacking industry standards for AAV titers and dose assessments and guidance from the regulatory agencies on the design of preclinical studies that can best inform IND decisions.
He stressed, however, that even more research at basic and translational science level is needed to tackle specific efficacy or safety issues.

Comprehensive safety assessment

Evotec also brings its already long-established strong expertise in prediction of drug-induced liver injury to the table – an experience gained with small molecules, as explained by Rüdiger Fritsch, Principal Scientist, Metabolic Diseases at Evotec. Among other safety assessments, the Company uses a wealth of technologies and expertise to identify transcriptomic fingerprints and applies its proprietary and continuously growing database of tox-related data from hundreds of tested compounds. AI-based modeling can predict mechanisms and probabilities for AAV-induced liver toxicity. Moreover, using single nucleic RNA-sequencing tools, Evotec can study and profile the expression and activity of the transgene at single cell level – not only in liver cells and organoids but in a growing portfolio of tissues from brain, muscle, lung, heart, and kidney. Evotec thereby is successfully translating its toxicology expertise from the small molecule space to gene therapy research and development, offering a 21st century omics-approach to provide for safe and efficacious gene therapy vectors.

Stream the webinar

Date: 13-16 September, 2022

Venue: Messe und Congress Centrum Halle Münsterland, Münster, Germany

Attendees: Matthias Renz (VP Innovative Strategic Initiatives) and Sandra Lubitz (SVP iPSC Drug Discovery)

Evotec will be sponsoring this year’s GSCN conference  as well as showcasing its research on site in Münster.

C10- Revolutionizing drug discovery for neurological disorders through precision medicine

Sandra Lubitz, SVP iPSC Drug Discovery at Evotec, will be presenting within the industry talk session on Thursday, 15th September, from 11:45am - 12:00am. 

If you wish to meet with us in Münster, get in touch via the form below, we will be happy to arrange a meeting.

Learn more about the 10th GSCN Conference & 20 years of Stem Cell Network NRW.

Date: 6th-8th September, 2022

Location: Burleigh Court, Loughborough

Attendees: David Whitlock, Brigita Simanskaite & Beth Raper

Learn more about DMDG - Fundamentals of DMPK

About the Webinar

• At Evotec we discover, develop and manufacture novel medicines for hard-to-treat diseases through efficient partnerships with academia, biotechs and pharma
• For antibody-based modalities, Evotec has developed an integrated discovery platform ranging from target validation, antibody discovery and optimization, in vitro/in vivo pharmacology, PK, and toxicology to select the best clinical candidates
• We apply both humanized, mouse-derived hybridoma and phage display (from immune and synthetic antibody libraries) coupled to automated HTS antibody screening and AI/ML-based optimization, antibody hits are selected to best fit their intended modality, (e.g. mAbs, ADCs, bispecifics)
• A particular emphasis is placed on integrating good manufacturing properties for the selected antibody sequence

About the Speaker

Thierry Wurch SVP, Integrated Biologics Discovery | Evotec Thierry joined Evotec in May 2022 as SVP Integrated Biologics Discovery. He has more than 22 years of expertise in the antibody R&D space primarily in Oncology and immune-oncology. Thierry held positions of growing strategic importance from head of an antibody discovery and engineering department (Pierre Fabre, 2003-2011), head of immunotherapy discovery research activities (Servier, 2011-2017) then moving to BD-oriented activities and heading external innovation for Oncology (Servier, 2017-2020 and Ipsen 2020-2022). Thierry is also Chairman of the antibody sub-committee at NC-IUPHAR, member of the Editorial board of mAbs Journal and Distinguished Advisor of The Antibody Society.

[hs-form id="052874a9-75e5-4960-9b82-931f9dd753b7" show="hide on login" url="https://player.vimeo.com/video/719092289"]

Novel phosphodiesterase 10A inhibitor drugs, through a distinct mechanism on striatal dopamine receptors, could raise the possibility of producing an augmented pharmacological antipsychotic effects by a combination therapy with the standard antipsychotic drug.

TAK-063 is a novel phosphodiesterase 10A inhibitor which has been evaluated for this hypothesis. Results show that the use of TAK-063 can produce augmented antipsychotic-like activities in combination with antipsychotics without alteration of plasma prolactin levels and catalepsy

In this collaborative paper with Takeda, we demonstrate that:

• Combined treatment with TAK-063 and either haloperidol or olanzapine leads to a significant increase in phosphorylation of glutamate receptor subunit 1 in the rat striatum.
• TAK-063 enhances N-methyl-D-aspartic acid receptor mediated synaptic responses in rat cortical striatal slices in both direct and indirect pathway MSNs to a similar extent.
• Co-administration of TAK-063 with haloperidol or olanzapine additively activated the indirect pathway, but not the direct pathway.
• Combined treatment with TAK-063 and either haloperidol or olanzapine at subeffective doses produced significant effects on methamphetamine- or MK-801-induced hyperactivity in rats and MK-801-induced deficits in prepulse inhibition in mice.
• TAK-063 did not affect plasma prolactin levels and cataleptic response from antipsychotics in rats.

DOWNLOAD