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If you’d like to be involved, please contact Derek Cavanagh derek.cavanagh@terrapinn.com or +44 (0)207 092 1297
Senior Representative, FUJIFILM Diosynth
The discussion will focus on the importance of data and digital in biopharma R&D, what works and what does not, and current trends. We would like to present diverse approaches across a spectrum of biopharma and biotech companies with a focus on best practices and emerging ways of working with information.
·Digitalization strategies–challenges & successes
·Automation - instrument integration, workflow and process automation
·Enabling collaboration & innovation through digitalization
·Future trends and AI approaches
Understanding the necessity for pharma to adopt AI
The challenges of implementing new technologies
Which pharma companies are ahead?
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Senior Representative, FUJIFILM Diosynth
Senior Representative, Instadeep
Antibodies are an integral part of the adaptive humoral immune response and interact with a variety of immune receptors enabling functions beyond target binding.
Deep molecular understanding of antibody-Fc interactions with different Fc receptors allows finetune and expansion of therapeutic efficacy in the clinic.
Beyond finetuning hIgG1 by Fc function enhancing or silencing further Isotypes such as IgA are in focus. The round table likes to exchange on the latest developments for selecting antibody isotype or Fc-engineering strategies to achieve maximal therapeutic efficacy.
- MSC sources, output and availability
- Cell therapies with MSC - status and outlook
- Case studies of Clinical trials of MSC based Cell Therapies
Senior Representative, Carterra Bio
If you’d like to be involved, please contact Derek Cavanagh derek.cavanagh@terrapinn.com or +44 (0)207 092 1297
Senior Representative, AbCellera
Senior Representative, Genovac
Senior Representative, PALL
Senior Representative, FUJIFILM Diosynth
Novel digital measures
Decentralized clinical trial components
Collaboration generated resources
Recombinant proteinproduction can cause severe stress on cellular metabolism, resulting in limitedtiter and product quality. To investigate cellular and metaboliccharacteristics associated with these limitations, oneukaryotic cells as aresult of various product genes, a panel of human secreted proteins (N=24),non-secreted proteins and bispecific antibodies were explored as stable ortransient cultures in CHO and/or HEK293 andanalysed by transcriptomics.Additionally the effect on HEK293 cells upon producing high versus low amountsof either erythropoietin (EPO) (secretory) or GFP (non-secretory), revealedsignificantly higher metabolismand oxidative phosphorylation in EPO producerscompared with parental and GFP cells. In addition, ribosomal genes exhibitspecific expression patterns depending on the recombinant protein and theproduction rate.
In short wereport on:1. Systemsbiology comparison of a panel of humansecreted proteins in HEK293 and CHO as host2. Cellularanalysis of aggregation of bispecific antibodies during stable expression inCHO3. Increasedenergy need and shift in ribosomal structure for secreted proteins
If you’d like to be involved, please contact Derek Cavanagh derek.cavanagh@terrapinn.com or +44 (0)207 092 1297
Senior Representative, Pipe Bio
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Senior Representative, Abzena
- the CD47-SIRPα myeloid immune checkpoint in cancer
- BYON4228 preclinical characterization
- clinical development of BYON4228
A generic strategy for the generation of trispecifc common light chain antibodies was established. The technology is based on chicken immunization and antibody discovery by yeast display. It was applied to the isolation of a two-in-one antibody, where the VL/VH combination simultaneously targets EGFR and PD-L1. In combination with a CD16 binding module that mediates enhanced NK cell engagement, potent antibodies were generated that display high tumor selectivity.
Antibody combination therapies have become viable therapeutic treatment options for certain severe diseases such as cancer. The co-formulation production approach is intrinsically associated with more complex drug product variant profiles and creates more challenges for analytical control of drug product quality. In addition to the various individual quality attributes, those arising from interactions between the antibodies also potentially emerge through co-formulation. In this study, we describe the development of a widely applicable mD-LC-MS/MS method for antibody homo- versus hetero-aggregate characterization. The co-formulation of trastuzumab and pertuzumab was used, a challenging model system, comprising of two mAbs with very similar physicochemical properties. The data presented demonstrates the high stability of the co-formulation, where only minor aggregate formation is observed upon product storage and accelerated temperature or light-stress conditions. The results also show that the homo- and hetero-aggregates, formed in low and comparable proportions, are only marginally impacted by formulation and product storage conditions. No preferential formation of hetero-aggregates, in comparison to the already existing pertuzumab and trastuzumab homo-aggregates, was observed.
Senior Representative, Fyion Bio
Characterization workflows using mass spectrometric detection and quantitation of biopharmaceutical quality attributes is used extensively in biopharmaceutical development and increasingly for cGMP testing. At Symphogen challenges are regularly observed with conventional MS-based characterization strategies, such as trypsin-based MAM workflows based on LC MS. Here, case studies highlighting challenges encountered during biopharmaceutical development, and potential solutions using alternative approaches, will be presented and discussed.
Lonza has applied 35 years’ of CMC experience in Biologics development to deliver a 13 month end-to-end DNA to IND strategy for bispecific molecules. Case studies highlighting key approaches and technologies for vector, process, analytical and formulation development, which enable acceleration of bispecific antibody pre-clinical development, will be presented.
Mass photometry provides insights into the mass distribution of biomolecules in their native state within minutes without the need for labelling, surface immobilization or big sample quantities. Its ease of use and single-molecule resolution make mass photometry the perfect tool for rapid assessments of sample purity, binding affinities or structural integrity across biomolecules ranging from differently sized proteins to DNA and even small viruses, such as AAVs
Motivating example
Estimands: a framework to align statistical analyses with the clinical question of interest
Illustrating a hypothetical estimand with a case study
- introduction of major immune microenvironment players in glioblastoma
- overview on current strategies to modulate microglia/macrophages
- presentation of novel approaches that potentially translate into clinical application
iCIEF was investigated in combination with orthogonal techniques for the characterization of biologics in the context of
· Check point inhibitors targeting PD-1 have shown unprecedented clinical efficacy in several cancer indications and therefore have, revolutionized the standard of care. However, despite this advancement, only ~20-30% of the patients derive durable benefit from such a treatment.
· One of the suggested reasons for this limited success is the expression/activation of compensatory inhibitory pathways such as LAG-3 on tumor-reactive T cells. Therefore, it is envisioned that simultaneous antagonism of PD-1 and LAG-3 receptors would overcome this adaptive resistance mechanism and allow a more profound reinvigoration of tumor-reactive T cells.
· However, blockade of LAG-3 on regulatory T cells (Tregs) increases their suppressive function and, therefore may off-set its benefit on the reinvigoration of tumor-reactive T cells.
· We therefore developed a 1+1 PD1-LAG3 bispecific antibody (BsAb) with a higher affinity for PD-1 than for LAG-3, allowing an avidity driven selectivity gain to PD-1 and LAG-3 double positive T cells like tumor-reactive T cells rather than Tregs due to different expression patterns of PD-1 and LAG-3 on these two T cell types. This preferential targeting provides increased in vitro T cell effector functions even in the presence of Tregs, and superiror in vivo tumor control/eradication in several mouse models compared to combination of monospecific anti-PD1 and anti-LAG3 antibodies
If you’d like to be involved, please contact Derek Cavanagh derek.cavanagh@terrapinn.com or +44 (0)207 092 1297
Senior Representative, Benchling
Utilizing its proprietary DNA technology to write synthetic libraries, Twist Biopharma provides end-to-end antibody discovery libraries including both (1) highly diverse synthetic naïve antibody phage display libraries and (2) target class specific antibody phage display libraries against difficult-to-drug targets. In this talk, Aaron Sato, CSO, will present on how Twist uses our libraries coupled with Machine Learning to discover 1) antibody sequences from NGS sequencing of our successive panning rounds and 2) optimize existing leads derived from traditional screening.
New biotherapeutics and evolving clinical and commercial needs are putting new demands on protein expression platforms and manufacturing strategies. Also, there is a heightened awareness in the industry about the need for novel therapeutic development paradigms that are more agile and effective in dealing with situations like our recent COVID pandemic, where time to clinic and to market, have been completely re-imagined for some medicines.
We will present how gene editing can be effectively used to design new functionalities in host cell lines. We will discuss how gene editing workflows can be structured to maximise precision and efficiency, particularly when multiple concurrent edits are required
We will finally discuss how cell host gene editing modifications, combined with new vector transposon technologies, can help, amongst other things in optimising the behaviour of cells in bioreactor cultures, increase process robustness and simplify and accelerate process development.
Senior Representative, Evotec
Senior Representative, Oxford Biomedica
We have implemented a pipeline for Machine Learning (ML) model generation and property prediction for antibodies/VHHs to evaluate sequences and 3D structures/models with regard to their diversity and developability properties, such as liabilities, Post-Translational Modifications (PTMs), immunogenicity risks, pharmacokinetics (PK) properties and compatibilities with formulations. This pipeline does not only allow to select sequences from high-throughput screening approaches, but is also utilized for sequence optimization towards the desired overall developability profile
Senior Representative, Abveris: A Division of Twist Bioscience
Senior Representative, Maxcyte
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Models
Data
Infrastructure
Biologics research and development present unique challenges in data management and analytics. Complex logistics, massive data streams from unique HT processes, and diverse modalities such as antibodies and bispecifics, cell and gene therapies, and RNA-based therapeutics and vaccines require on-going advancement of fit-for-purpose digital technology and automation approaches. Digital innovation can significantly accelerate biologics research and development and it is increasingly seen as a competitive differentiator. We present use cases showing how biopharma and biotech organizations digitalize and automate their biologics workflows today and how they leverage having full traceability and data integrity for data sciences and machine learning.
Tumor-associated macrophages (TAMs) affect tumor biology and immune escape. TAMs are in constant transition between M1 (anti-tumor) and M2 (pro-tumor) phenotypes because of high plasticity, which requires a fast change of translational activity. FKBP51 is an immunophilin encoded by FKBP5 gene that supports NF-κB and STAT1 transcriptional activities, essential features of M1 macrophages. FKBP5 alternative splicing occurs on M2 polarization. The splicing protein is unable to support NF-κB and STAT1 activation, but it upregulates PD-L1 expression
Advanced technology that uses sensory instruments to track and record
AI and Remote Patient Monitoring - Working together for higher Quality Care and How AI can be a powerful tool in Drug Development and Discovery
Improved Patient Outcomes; Personalized Care
Increased Revenue and Reduced Healthcare Costs
Human-derived antibodies are advantageous as they target disease-relevant proteins and epitopes
We have applied our human antibody discovery pipeline to identify anti-allergen antibodies that are able to prevent allergic reaction and anaphylaxis in preclinical models of peanut allergy.
We have screen >50,000 patients to identify rare autoantibodies against neurological targetsBayer has a long history of developing small molecule drugs for the treatment of various cardiovascular diseases and in the recent years has also expanded to include Biologics as a modality option.In the case study to be presented here, antibody lead finding and screening strategies relying only on target-expressing cells are presented to address a complex cardiovascular target with multiple functions and epitopes of interest.In addition,several important lessons were learned along the way regarding the choice of isotype, translatability between preclinical species and human and ultimately what defines a "good" antibody target.
Senior Representative, EurekaBio
Therapeutic antibody producing Chinese Hamster Ovary (CHO) cell lines have been pushed to their limit, leaving developability and formulation groups to stabilise biologics that were not designed with aggregation in mind. Aura+ is the first instrument designed to characterise antibody stability as early as cell line development (CLD). Aura enables low volume, high throughput subvisible particle imaging, counting, sizing, and identification. It easily handles and analyses the biologically complex cellular and protein samples present in CLD to characterize protein stability at the point of production, following release from CHO cell lines. In this talk, we will show how Aura+ quickly and accurately characterizes secreted antibody stability during CHO CLD in unfiltered cell line samples and using the same antibody labeling protocols established by the innovators to characterise protein titre to rank cell lines according to the physical stability of secreted antibodies using volumes as low as 40 µL per sample.In addition,the Aura+ brings with it the capability to rapidly assess different formulation strategies and, for the first time, distinguish polysorbate degradants from other protein aggregates through the application of a novel fluorescent workflow.
A review of the current landscape for measuring adherence in clinical research (industry guidance, traditional methods for monitoring and the efficacy of such methods, real-life examples of the prevalence of non-adherence in trials)
Exploring the link between medication adherence and dose selection (discuss post-marketing dose reductions and drug forgiveness) – refer to ICH E9.
Discuss where smart packaging and corresponding real-time analytics are increasingly being used to inform dose selection
If you’d like to be involved, please contact Derek Cavanagh derek.cavanagh@terrapinn.com or +44 (0)207 092 1297
The Specifica Generation3 Library Platform is based on highly developable clinical scaffolds, into which natural CDRs purged of sequence liabilities have been embedded. The platform uses phage and yeast display to directly yield highly diverse, high affinity, developable, drug-like antibodies, which in a recent Covid campaign were as potent as antibodies from immune sources. This talk will outline the Generation 3 concept and its application to antibody and VHH libraries, as well as affinity maturation.
Understanding how nanobodies interact with their target antigens at the atomic level is essential for successful engineering of better binders. The prerequisite is to have an accurate 3D model of the nanobody, especially in the CDR regions. We used comparative modelling approaches, as well as Machine Learning algorithms, to predict 3D structures of several nanobodies that target Glutamate receptors. To identify the correct epitopeswe used protein-protein docking algorithms that use physics based and knowledge based approaches, and refined the complexes with molecular dynamics simulations in an explicit membrane-water environment. Deep Learning models were also used to predict the poses and score them.
We assessed the quality of our predictions with experimental mutagenesis and compared the different methods used.
During the last years, significant advancement has been made in the clinical application of cancer immunotherapies. Molecules directed against immune checkpoints and other agonists show great promise for the treatment of a variety of malignancies. Next to CTLA-4 and PD-1 blockade, a wide range of therapeutics with the potential to reverse the tumor-induced suppression are under development. Here, we review our current understanding of immune checkpoint pathways and methods used to measure the activity of antibodies and other biologics drugs designed to target immune checkpoint receptors. We show a portfolio of immune checkpoint bioassays that can be used for antibody screening, characterization, potency, and stability studies.
Senior Representative, Waters
Treg cells play a key role in tumor immunity by accumulating and suppressing effector responses and, by contrast, are defective in many autoimmune diseases. Treg cells constitutively express CD25, the alpha chain of the IL-2 receptor and are vitally depending on IL-2 signaling through the trimeric alpha-beta-gamma receptor. In contrast, effector T cells and NK cells can benefit from IL-2 signaling through the dimeric beta and gamma receptor. Two novel IL-2 muteins have been designed, that bind to CD25 and either block or stimulate STAT-5 signaling through the beta/gamma chains, respectively presenting IL-2 starving or IL-2 signaling activities. They differentiate from other IL-2 muteins by selectively docking to CD25 and therefore preferentially impacting Treg cells. For indications in oncology, Egle Therapeutics developed immunocytokines combining Treg IL-2 starvers with Treg-directed antibodies and demonstrated Treg selective depletion in vitro and in vivo, resulting in the increase of the ratio of CD8+ T cells to Treg cells. For indications in autoimmunity, selective Treg boosters have been designed in the form of Fc-fused homodimers of the Treg-selective muteins, which demonstrated selective Treg activation and expansion in vitro and in vivo. These IL-2 muteins constructs represent novel therapeutic modalities with potential to breaks through the immunological barriers that are keeping current treatments from achieving better performances.
More than 110 antibodies approved by the FDA are therapeutic monoclonals involved in treatment of cancer with more than 30 different targets.
We developed an antibody against proangiogenic Olfactomedin-like 3 (Olfml3), an extracellular matrix related molecule with matricellular properties. Gene knock-out of Olfml3 reduced embryonic development by partial blocking of angiogenesis due to reduced endothelial cell-pericyte interaction, PDGF-B signaling in pericytes and BMP4 signal transduction in endothelial cells. In cancer patients, Olfml3 expression was upregulated in a series of tumor cells and in the tumor vasculature. Particularly in colorectal carcinoma (CRC), expression correlated with shorter relapse free survival and tumor grade. Blocking of Olfml3 by the monoclonal antibody reduced tumor angiogenesis, pericyte coverage and CRC tumor growth. It also increased the number of NKT innate immune cells in tumors and it improved the antitumor efficacy of anti-PD-1 checkpoint inhibitor immune therapy. The in vivo experiments in mice became possible as the antibody cross-reacts between human and mouse tissue. Taken together, anti-Olfml3 antibodies are novel candidates for CRC therapy with multiple anti-tumor effects.
If you’d like to be involved, please contact Derek Cavanagh derek.cavanagh@terrapinn.com or +44 (0)207 092 1297
If you’d like to be involved, please contact Derek Cavanagh derek.cavanagh@terrapinn.com or +44 (0)207 092 1297
In the past years biopharmaceutical companies have searched for new biological entities (NBE’s) as a follow-up of the very successful monoclonal antibodies. One of the most promising new lines of NBE’s are the Antibody Drug Conjugates. Antibody Drug Conjugates (ADC’s) are new biotherapeutic medicines consisting of a drug (chemotherapeutic agent), a (non-)cleavable linker and a monoclonal antibody. The mechanism of action consists of the recognition of a specific receptor on the cells by monoclonal antibodies, the complete ADC is internalized into the cell and the cytotoxic agent is released in the cell by cleaving the linker and the monoclonal antibody from the ADC so that the cytotoxic agent is able to block cellular processes followed by cell death. Since the approval of the first ADC brentuximab vedotin (Adcetris®) in 2017 more new ADCs have reached the market.
The current progress on the development of the conjugation and purification processes for ADCs with Duocarmycin as toxic payload, using (site-directed) SH groups for the conjugation strategy, will be explained. Moreover, detailed characterization of the ADC’s with physicochemical/biochemical studies will be presented and the precautions taken to perform conjugations and purifications of the ADC’s to final drug substance as cytotoxic agents are being used as drug.
If you’d like to be involved, please contact Derek Cavanagh derek.cavanagh@terrapinn.com or +44 (0)207 092 1297
Senior Representative, Bio-Techne
Senior Representative, Sino Biological
I will present an end-to-end automated MS analytics workflow developed at Roche Innovation Center Munich. It covers all aspects of the protein MS analytics, starting with sample registration, wet lab processing and measurement, as well as data analysis, data management, and results reporting. It is part of a comprehensive digital and lab workflow ecosystem and is routinely applied on heterogeneous antibody-based drug candidate samples at all stages of the research and early development process.
PoC studies applying mammalian libraries for both antibody optimization (screening for manufacturability and selectivity) as well as microfluidics-assisted high throughput cellular binding or functional screening exemplify the versatility and powerful options when combining these two emerging technologies.
In recent years there have been many advances in technology that allow techniques previously limited to small numbers of molecules to be applied to large numbers of samples. Applying such techniques in parallel to the early stages of the antibody discovery process enables determination of high throughput kinetics and biophysical screening of hundreds of antibodies. This can facilitate rapid selection of high affinity antibodies with acceptable early stage developability characteristics. A deeper insight into the data can be achieved by applying enhanced analytics capabilities such as artificial intelligence and machine learning. During this talk I will discuss implementation and application of some of the methods and data workflows which enable characterisation of more molecules with less material and in less time, and give greater breadth of characterisation, to accelerate decision making while improving opportunities for data reuse.
Targeted small molecules have significantly improved outcomes for a number of cancer types
- The impact of such therapies on the anti-cancer immune response is often poorly understood
- A better understanding of how therapeutics impact the anti-tumour immune response will aid the design of biologically rational combination therapies
The legal and ethical frameworks for innovation in data acquisition and transfer
Federated data, blockchain, and quality assurance
Developing instruments for improving data utility in clinical trials
Ichnos’ BEAT® platform (Bispecific Engagement by Antibodies based on the TCR) facilitates design of multispecific antibodies using efficient heavy chain heterodimerization and a common light chain. ISB 1442, a first-in-class 2+1 biparatopic BEAT® 2.0 bispecific (CD38xCD47) antibody, demonstrates higher potency and tumor growth inhibition preclinically relative to daratumumab. A Phase 1 study in hematologic malignancies is planned for mid-2022.
Brain uptake of therapeutic antibodies has been reported using different experimental systems and diverse methodologies, but the precise measurement of drug levels in all relevant brain compartments is often hampered by technical difficulties. We present the comprehensive characterization of a Brain Shuttle anti-amyloid antibody in Cynomolgus monkey, including modeling-supported plasma and brain pharmacokinetics, and provide first evidence for brain uptake in human.
Immunoglobulin G antibodies are well established as central players in all aspects of life science, from assays in the lab, to diagnostic tests, to cancer therapy in the clinic. The general notion is that antibodies bind to a target surface through bivalent interactions that dramatically increase their apparent binding affinity. This decades-old view, however, needs revision, as studies in recent years have shown surprisingly complex interactions of these supposedly simple molecules.In this talk, I will present our biophysical approaches to characterize the interactions and structural dynamics of antibodies and complement proteins on the single-molecule level, and how these are linked to antibody effector functions. We therefore combine methods such as high speed atomic force microscopy (HSAFM), single molecule force spectroscopy (SMFS), and quartz crystal microbalance (QCM) to directly visualize and characterize dynamic structural changes and interactions of unlabeled functioning biological molecules in physiological solutions, at sub-second time- and sub-molecular spatial resolution. Based on these data we further develop kinetic models of these processes that give further insights into the molecular limiting factors that finally govern antibody effector functions.
In the past, data was siloed and fragmented across Research which made Biologics discovery and scientific decision-making a cumbersome task..Therefore, at Novartis Research we aim to digitalize our Biologics discovery processes and workflows to improve and speed up decision making and to support the digital transformation of our organization. We aim to achieve this by implementing a state-of-the-art data and workflow platform. This platform will be comprised of a central data management solution integrated with a set of diverse tools and applications ensuring a seamless integration into NIBR’s existing IT landscape, helping the uninterrupted flow of data within the organization, and providing the data layer for data science and AI based applications.In this presentation we will present the approach we took, the challenges we faced and the solutions we developed to create our Research Biologics Platform, covering organizational, scientific, IT and operational aspects.
If you’d like to be involved, please contact Derek Cavanagh derek.cavanagh@terrapinn.com or +44 (0)207 092 1297
Cleavable linkers have become the subject of intense study in the field of chemical biology, particularly because of their applications in the construction of antibody-drug conjugates (ADC), where they facilitate lysosomal cleavage and liberation of drugs from their carrier protein. Due to lysosomes’ acidic nature, acid-labile motifs have attracted much attention, leading to the development of hydrazone and carbonate linkers, among several other entities. In this context, we here present a family of cyclic acetals that exhibit excellent plasma stability and acid lability, notably in lysosomes. Incorporated in ADC, they led to potent constructs with picomolar potency in vitro and similar in vivo efficacy as the commercially available ADC Kadcyla in mouse xenograft models.
The Berkeley Lights’ Opto™ Plasma B Discovery (OPBD) 4.0 workflow enables recovery of 1000s of hits by screening up to 100,000 plasma cells, down-selection of lead candidates by functional screening, and sequencing and re-expression of >1000 functionally characterized antibodies in one week. By maximizing the diversity of antibodies through direct functional profiling of plasma cells, the OPBD 4.0 workflow allows users to tackle even the most challenging targets.
At Alchemab we harness the power of the human immune system to counter complex diseases. Using a combination of antibody repertoire deep sequencing, serum proteomics, computational biology and machine learning, we identify antibodies associated with patient resilience. Selected antibodies are characterised by their biological activity and targets. We have analysed many samples from diverse patient cohorts, and antibodies to novel targets are progressing towards the clinic. This talk will highlight examples of our work to discover novel antibodies and targets from patients with neurodegenerative diseases.
Senior Representative, Evotec
Autoantigen-specific IgA autoantibodies closely correlate with symptoms severity in a subgroup of patients in multiple autoimmune diseases. Beyond the value of these IgA autoantibodies as biomarkers, the presence of excessive IgA/autoantigen immune complexes results in continuous CD89 (FcαRI)-mediated activation of myeloid cells, leading to severe tissue damage. Activation of myeloid cells - especially of neutrophils - is a highly underappreciated and untargeted hallmark of autoimmune diseases. Enabling a personalized medicine approach, high autoantigen-specific IgA serum levels will serve as companion diagnostic to stratify patients for personalized treatment with our antagonist humanized anti-CD89 antibody (JJP-1212). Interfering with the IgA/CD89 axis by JJP-1212, resolves IgA/autoantigen-induced inflammation and subsequent tissue damage in a variety of autoimmune diseases.
Can data-based machine learning techniques suggest developable drugs depending on the business situation of each pharmaceutical company?
Evolving scenario of big data and Artificial Intelligence (AI) in drug discovery
A new generation of AI-enhanced drug discovery companies
Creating value from next-generation real-world evidence
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Reserved for Spark Therapeutics
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Development and production of innovative biotherapeutics demands bioprocesses that consistently yield a high-quality product. However, current methods to determine product quality do not necessarily capture the actual mix of product and related impurities in cell culture supernatant, but rather what can be captured after purification. We developed a highly-sensitive method that can be applied to the detailed characterization of cell culture supernatants from bioreactors without a falsifying pre-purification step.
Antibody-cytokine conjugates (Immunocytokines) have been shown to selectively accumulate at the site of disease with a residence time of several hours or evendays. A clear dose dependence has been reported for the efficacy ofimmunocytokinetherapies.
Immunocytokine-driven toxicities are typically observed at early time points, correlating with the peak serum concentration of the molecule, which limits escalationto higher and potentially more effective dose levels.Carefully chosen small organic inhibitors of cytokine signaling with a rapid pharmacokinetic profile can block immunocytokine-related side effects systemically. Due to the fast clearance and lack oftumoraccumulation of the small molecule, the anti-tumoractivity of theimmunocytokineis preserved, while systemic sideeffects are efficiently inhibited. Thus, combination of tumor-targeted cytokines with small molecule inhibitors may allow dose escalation beyond the maximum tolerated dose of theimmunocytokine alone.
If you’d like to be involved, please contact Derek Cavanagh derek.cavanagh@terrapinn.com or +44 (0)207 092 1297
The costimulatory immune receptor CD137 has been recognized for its potential as a drug target alongside checkpoint inhibitors, but this promise has not been realized for patients due to toxicity and limited efficacy of current biologic-based therapies. Bicycles are small, structurally constrained peptides discovered via phage display and optimized using medicinal chemistry. We have developed BT7480, a multifunctional molecule that induces Nectin-4-dependent agonism of CD137 that leads to complete tumor regressions and subsequent resistance to tumor re-challenge in syngeneic mouse models. BT7480 entered clinical evaluation in November 2021 and is currently in Phase 1 dose escalation. The preclinical characterization and mechanism of action of BT7480 will be discussed.
If you’d like to be involved, please contact Derek Cavanagh derek.cavanagh@terrapinn.com or +44 (0)207 092 1297
The market of biologics in Biopharma companies is in constant evolution and moved away in the last few years from classical monoclonal antibody to proteins that are more difficult to analyze, such as therapeutics proteins, Antibody drug/molecule conjugates and even in the cell and gene therapy space with Adeno Associated Viruses for example. With all these new modalities, state of the art analytics must be developed to characterize them in details and mass spectrometry is a major player in this arena. Native MS applied to heterogeneous biotherapeutics like ADC and other complex format is heavily used. More recently Charge Detection Mass Spectrometry (CD-MS) on commercially available UHMR Orbitrap has been developed and applied on Biotherapeutics Beasts in the half Megadalton to 3-4 MDa range to measure AAV Full:Empty genome ratio. In this talk, data will be presented featuring new ways of using Orbitrap UHMR, which includes native-MS and CD-MS.
·The impurities of therapeutic monoclonal antibody is classified as product-related and process-related.
·The potential process-related impurities of monoclonal antibody therapeutics are originated from raw material, cell banking, upstream/downstream bioprocess, fill finish, and dosing regimen.
·This presentation focuses on analytical procedures to detect, characterize and quality control (QC) potential process contaminants and impurities to safeguard patients