Our agenda is expertly curated by an experienced team of producers with an expansive global network.
The Festival of Biologics is your opportunity to hear from industry leaders, global regulators and world-renowned academics at the forefront of innovation. Join us for 3 days of cutting-edge insights into the latest industry developments.
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Biosimilars are transforming the healthcare landscape by stimulating competition, reducing drug acquisition costs, increasing access, and promoting reinvestment in future biologic treatments. Despite the numerous benefits they offer, their long-term sustainability is under threat. The current market presents several challenges to achieving this sustainability. Pfizer is committed to the future of biosimilar medicines, recognizing that achieving biosimilar sustainability hinges on the commitment of all stakeholders. Explore the challenges to fostering a sustainable biosimilars market through this presentation.
· Data from our first 16 patients
· Our move to increase the dose and add checkpoint inhibitors
· Translational data on INF-g,andCytokines
·Reviewing the current field of bispecific and ADC therapies
·Challenges: engineering difficulties, toxicity, immunogenicity
·Next generation therapies: comparing and contrasting novel bispecifics/multispecifics and next generation ADCs (novel payloads, linkers and multiple payloads)
Past, Present, Future Data: Challenges in the Evolution of Clinical Data Management
· Investigating TAAxCD28 plus aPD-1 combination strategy in solid tumors
· Investigating TAAxCD28 plus TAAxCD3 combination strategy in heme malignancies
Antibody discovery remains one of the most challenging aspects in antibody therapeutic development. Novel proteomics-based approaches to antibody discovery offer a promising strategy to overcome roadblocks often associated with other discovery technologies. With REpAb technology, antibody discovery with mass spectrometry enables the exploration of the natural immune repertoire with unparalleled antibody diversity and creates a pathway for the discovery of novel antibodies from human serum
Traditional antibody discovery relies on analytical instruments that require significant hands-on time, quantities of sample, capital equipment, and specialized expertise. In this presentation, we will demonstrate how the Alto® Digital SPR™ system is an ideal platform for antibody characterization at every step of the discovery process and for a broad range of applications. From only 2 µL of crude sample, see how it's possible to perform screening, quantitation, kinetics, and binning to fully characterize and select the best antibodies.
A limitation of biologics is their inability to cross the cell membrane. Conversely, small molecules readily cross cell membranes, but many intracellular proteins lack pockets for small molecule binding. We developed a method to deliver antibodies and proteins into the cytosol, which enabled us to inhibit the cancer-associated proteins, multidrug resistance Protein 1 and NFκB as well as conventionally-undruggable targets, Ras and Myc. More recently, we showed that we can also deliver BioPROTACs intracellularly, enabling the specific degradation of target proteins.
Key findings from Cardinal Health’s 2024 Biosimilars Report including biosimilar awareness and educational needs, as well as inventory management strategies for optimization.
Senior Representative, Amgen
Early developability screens are used to predict the downstream biophysical characteristics and manufacturability of candidate drug biologics, to screen out difficult to manufacture molecules during the discovery phase. Such developability screens are run in medium to high throughput and require very little protein (typically ≤100ug of antibody). Published analyses of developability datasets consisting of clinical stage antibodies have shown a negative correlation between the number of flags in early developability screens and clinical progression. Less is known about the correlations between specific early developability screens and downstream biophysical attributes. To study such correlations, we have produced an extensive dataset consisting of 250 antibodies. However, whereas many developability dataset studies to date have focused on clinical stage or approved antibodies, we have constructed our developability dataset to include a large number of “misbehaving” antibodies that showed a high number of developability flags during discovery. This set of antibodies underwent extensive experimental and in silico characterization. This talk will present our dataset construction strategy alongside insights gained into correlations between early developability assays and downstream analytical characterizations.
Scale-up productions of the viral protein faced many challenges, including issues revolving around protein aggregation, degradation, and yield instability. Thus, we need to optimize different cultures, transfection, purification conditions and key parameters to facilitate large-volume scale-up production.
Using an in-house developed efficient vector expression platform, different proprietary reagents, high-density cell culture technology, controlled culture conditions and the addition of anti-aggregation agents, with refined SEC-HPLC and buffer optimization, we were able to optimize the expression and scale-up production of viral proteins.
We introduce GV20-0251, a first-in-class antibody drug designed to disrupt the novel immune checkpoint IGSF8. Our research, driven by CRISPR screens, unveiled the presence of IGSF8 on cancer cells and its potent inhibitory effects on the innate immune system, particularly natural killer (NK) cells. While IGSF8 is typically expressed in neuronal tissues and not considered essential in in vitro or in vivo settings, its overexpression in various malignancies has been linked to reduced antigen presentation, diminished immune infiltration, and unfavorable clinical outcomes.
Leveraging artificial intelligence, we systematically scoured patient tumor data to pinpoint anti-IGSF8 antibodies, ultimately leading to the discovery of our lead candidate, GV20-0251. Our studies have demonstrated that GV20-0251 effectively disrupt the IGSF8-NK receptor interaction, thereby potentiating NK cell-mediated cytotoxicity against cancer cells in vitro. Furthermore, GV20-0251 augments antigen presentation and unleash NK cell-mediated cytotoxicity pathways in in vivo models.
Our preclinical evaluations, conducted across multiple syngeneic tumor models, have revealed that GV20-0251 has single-agent efficacy and is synergistic with anti-PD1 in controlling tumor growth. Given the potential of anti-IGSF8 to activate innate immunity, we have initiated a Phase 1 clinical trial (NCT05669430) to investigate GV20-0251 in patients with advanced or metastatic solid tumors.
Ex vivoantigen loadingof antigens into dendritic cells (DC)bypasses the need forin vivoantigen uptake and processing by endogenous DC to initiate an adaptive immune response.Ex vivoloading ofautologous tumorantigens(ATA)into autologous DCyields a uniquelypersonalvaccine. Peripheral blood mononuclear cells are differentiated intoDCin vitro; thenIncurrent methods,DC areincubated witha lysate of irradiated tumor cells from a short-term cell linederived from surgically resected tumor, andestablished under conditions that favorself-renewal of tumor initiating cells (TICs) including cancer stem cells and early progenitor cells while eliminating extraneous hematopoietic and stromal cells.Personal therapeutic DC-ATA cancer vaccines have been manufacturedandtested inclinicaltrials inpatients witha variety ofadvancedcancers, but especiallymelanoma,glioblastoma, ovarian, renal cell,andhepatocellular cancers.Feasibility, safety,enhancedimmune responses, and suggestion of efficacy have been demonstrated. In this presentation, the methods for manufacturing these personal DC-ATAvaccines and available clinical and immune response data will be reviewed.
With machine-learning we have built a pan-cancer single-cell RNA atlasplatform (scTx)comprisingdata fromover25 millioncells,enablingustodissect how the composition of the tumor microenvironment correlates with patient outcomes and target biology.Using ourscTxplatform, we identify a specific CAF subtype associated with immune-exclusion and therapeutic resistance, with CTHRC1 being the most upregulated target of this pathogenic cell type while also being expressed on tumor epithelial cells. Candidate therapeuticmAbswe developed against CTHRC1that demonstrate significant staining of both CAFs and tumor cells, with high selectivity confirmed through in vivo biodistribution studies. CTHRC1mAbswere further engineered as targeting arms for CD3 bispecific antibodies and demonstrate anti-tumor activity in vitro and in vivo. Together, we show thatourscTxplatformenablesunprecedented dissection of tumor microenvironment biologycapable of identifying novel biology and targets for therapeutic development.
The biosimilars market has significantly grown and matured over the past decade. Biosimilars are projected to save more than $180B in healthcare costs in the US from 2023 to 2027, and yet the future of biosimilars may be threatened due to existing market dynamics. In this session, we will assess the current state of biosimilar sustainability, identify key barriers that exist to maintaining a viable future, and discuss potential strategies to thwart these threats to the future of biosimilars.
It is critical that all stakeholders collectively ensure that the viability of the biosimilars market is protected to continue to deliver on its promise of savings.
Biologics development organizations are faced with challenges to accelerate the biologics development process, speed up the development timeline to clinic. Optimal Cell Line Development (CLD) process is a key technology driver in drug development programs. Samsung Biologics’s S-CHOice technology platform provides streamlined workflow solutions to tackle heavy CLD workflow limitations while improving manufacturing cost, efficiency and quality.
-Examine how Immune-Stimulating Antibody Conjugates (ISACs) harness the mechanisms of the innate immune response and lead to prolonged adaptive immune responses, effectively “teaching” the immune system to recognize and eliminate cancer cells.
-Present clinical data with first generation payloads and how those learnings inform design of next generation payloads
The growing complexity of protein therapeutics requires a greater understanding and evaluation of their stability issues throughout the entire drug development process. Bispecific antibodies, in particular, pose notable challenges in terms of their diverse structural variations and intricate mechanism of action, resulting in significant chemical and physical liabilities. Here, we will share bioanalytical strategies for in vitro characterization and in vivo pharmacokinetic assessment of this new drug modality using a variety of chromatography and mass spectrometry (LCMS)-based assays during the pre-clinical drug development phase. Additionally, we will discuss the benefits of opting for a multiplex hybrid LCMS-based PK assay and challenges associated with assay development
A multibody is a symmetrical IgG antibody that can bind more than one target in each of its arms. Thus, multibodiesare essentially programmable switches that can execute “and” or “or” functions in living biologicalsystems.In this talk I will explain what makes multibodies so powerful and give a few examples. Next I will describeBiolojic Design'sAI-basedcomputational platform formultibodies design. Specifically, we use high throughput experimental technologiesto generate large data sets of measurementsof antibodies properties. Then, relying on pretrainedproteinLarge Language Models (LLMs) we train multi property-specific models. I will show how such generative models allow the de-novo design of multibodies with the desired specificities, affinities and developability profile.
IgA antibodies are involved in various inflammatory and autoimmune diseases and are reported to be prognostic markers for disease severity. Monomeric IgA complexed on either tissue or soluble (auto)antigens acts as a potent activator of myeloid cells through CD89. Most notably, the neutrophil is more potentially activated by IgA-complexes when compared to IgG, underlining the observed relation between serum IgA and disease severity. With no commercially available treatments for IgA-CD89-mediated inflammation, there is a high unmet need for patients suffering from IgA-driven disease. JJP-1212 is a potential first-in-class IgG4 CD89 antagonist that inhibits binding and subsequent activation of CD89-positive myeloid cells by IgA. Additionally, JJP Biologics is developing serum-IgA-based companion diagnostics to stratify patients to provide them with a truly personalized treatment.
Demonstrating the potency of a biopharmaceutical is critical to drug development and ultimately drug marketability. Potency assessment is indeed important not only in terms of CMC as a tool to assess product quality and consistency, but also as a link to product clinical efficacy and establishment of the dose. However there are a lot of challenges of potency assay as it is time-consuming, complex, variable and low throughput. Here we will share how to use different detection procedure, alternative readout based on mechanisms of action to improve potency assay efficiency and reduce cost. Also we will discuss about using genetically modified cell line and well-prepared and characterized assay ready cell bank to reduce assay variation and time. Furthermore, automation of cell-based assay significantly improves assay throughput while gives us accurate, precise and reproducible data.
Antibody has evolved as one of the most successful classes of protein therapeutics with
broad application, high specificity and strong potency. Due to the complexity of disease
biology, which often involves multiple targets, pathways and cells, bispecific and
multispecific antibodies have emerged as attractive platforms to achieve enhanced
efficacy and hence become the focus of development in both preclinical and clinical
settings. The effort of developing multispecific alternative format antibody (Altibody) and
its utility will be discussed in this presentation.
GITR is a member of TNFR superfamily implicated in various autoimmune and inflammatory conditions. GITR signaling in T cells is mediated by ligand trimer mediated clustering. We identified GITR antagonist antibody with novel allosteric non-competitive MoA that promotes extended inactive receptor conformation incompatible with signaling complex. Hybridoma campaign followed by humanization, sequence optimization and affinity maturation by structure/machine learning/phage display methods led to sub-nanomolar antibody with potent GITR antagonism in primary human cells and excellent biotherapeutic like-biophysical properties.
1. Distinguish CHCs from other types of healthcare organizations
2. Learn from a grant that surveyed 41 CHCs nationwide about their perceptions and needs related to clinical trials. The grant title: Building Clinical Trial and Health Research Access for People of Color via Community Health Centers
3. Evaluate options for CHCs to be involved with supporting clinical trials and diverse enrollment
The development of biologics for human use is a challenging enterprise that requires a wide variety of skills. Notably, biologics require complex, qualified assays to ensure that manufacturing lots are produced to specifications. The production methods are also complex, requiring specialized equipment and the control of hundreds of parameters across multiple unit operations over a period of weeks. Traditionally, assays are developed by analytical scientists and scalable production methods are developed by process development scientists. And although it is well known that analytical results are necessary to assist with process development efforts, it is not always the case that these teams work closely together as one. In our experience, a close and strong collaboration between analytical and process development scientists yields reduced development cycle times, identifies potential pitfalls early and generally improves development outcomes. This talk will present several case studies illustrating the benefits of this collaboration.
· Synthetic biology holds promise for tackling global health and sustainability challenges.
· The fast and reliable synthesis of longer nucleic acid constructs, without sequence limitations, is critical to drive the next generation of discovery.
· Ansa Biotechnologies enzymatic nucleic acid synthesis platform enables this paradigm shift, leading to innovations in healthcare and beyond.
In all biological products, distinguishing aggregated API from other particle types matters for understanding the root cause of instability. Until now, subvisible particle characterization methods have been unreliable, slow, require significant sample volume, and have been difficult to use across different therapeutics. Here we present Aura, a USP 1788 compatible, low-volume, high throughput particle imaging system that can rapidly size, count, and characterize biological particles and identify them as proteins, non-proteins, cellular aggregates, or other types of molecules. In this talk, we will present 3 case studies: identifying protein aggregates and distinguishing them from degraded polysorbate components, determining subvisible particle content of AAV formulations at low volumes, and gaining key insights on how DNA leakage plays a role in subvisible particle formation and product instability, and characterizing cellular therapy products including cell aggregation, viability, and product impurities including residual Dynabeads
Monoclonal antibodies (mAbs) account for 80% of the biotherapeutics' class approved by FDA in 2023. To date, this class of biotherapeutics is fueling the biopharma industry. With inflation being an important concern for patients' health accessibility, and high competition among biopharma companies, price and timeline are scrutinized for mAb programs. In the meantime, patient's safety should never be put at risk with poor quality products. In this talk, we explain how SUREmAb™ streamlines mAb programs from Cell Line Development to Drug Substance Conditional Release in 11 months with cost-efficiency and uncompromised quality.
The oral delivery of protein therapeutics offers numerous advantages for patients, but also presents significant challenges in terms of development. Currently, there is limited knowledge available regarding all aspects of the CMC development of oral biologics, including analytical methods, formulation, stability and shelf-life. To solve the problem, we developed various advanced analytical technologies in characterizing the solid dosage form protein therapeutics. These innovative analytical approaches enhance our understanding in the structure and function of the oral dosage protein and help the team to mitigate various risks identified in the CMC development of the oral protein formulations.
· Identify trends within the therapeutic development market
· Highlight challenges in the geopolitical landscape
· Introduce tools to streamline and accelerate insourced synthesis and screening
WORKSHOP: Investing in Women’s Health, Hosted by Aquillius
Panel Discussion: Investing in Women’s Health
· Phong Tran, Cimable
· Navin Govind, Founder and CEO, Aventyn
· Jay Wadia, Head, Search and Evaluation, Ferring Pharmaceuticals
· Lindsey Mignano, Co-Founder and Shareholder, SSM
· Meganne Houghton-Berry, Investor and Advisory Board Member, Angel Academe
· Moderator: Amy Duncan, Director, The Brink SBDC, University of San Diego
Start Up Pitches:
· Timeless Biotech
· Azura Bio
· Avira Health
· Concarlo Therapeutics
· MeCo Diagnostics
· Altin Biosciences
· Advanced Prenatal Therapeutics, Inc.
Hosted by:
MyPhuong Le, President, Aquillius & Leah Villegas, Managing Partner, Aquillius (Confirmed)
The team at Wheeler Bio, an antibody CDMO located in Oklahoma City, OK, spent the last three years standing up a purpose-built, boutique CDMO to better serve the needs of preclinical and clinical stage antibody companies needing early CMC development and cost-effective material supply services that better align with current fundraising challenges. With a digital-first approach to platform development that fully embraced modern bioprocess design, bioprocess modeling, machine learning, and integrated automations, Wheeler has built an open-source platform called Portable CMC® with proven scalability and cost-effectiveness. Efforts to integrate early CMC development with late discovery workflows have led to collaborative partnerships with coastal discovery CROs, including Alloy Therapeutics and Charles River Laboratories, that further distinguish Wheeler’s unique value proposition to biotechs. In this presentation, Dr. McNaull will share an overview of the platform development strategy and current performance metrics and describe how Wheeler better integrates programs from discovery to CMC development and early clinical supply.
ProtIQ is a machine learning-based suite of tools that aggregates protein target information from a variety of sources, where available, and annotates and analyzes proteins when information is lacking. The tool was developed to address the global hypothetical proteome and is therefore not biased to any one protein type. Through structural modeling and protein language transformer models, protein sequences are inputted to derive protein design and process development in silico to improve the likelihood of success in the protein development cycle. ProtIQ puts the protein expert at your fingertips
Establishing a control system strategy is necessary to ensure consistent product quality is achieved. For ADC’s this is more involved than just for monoclonal antibodies. This talk will go over why a strategy is need, what is a control system strategy entails, focusing on establishing specifications for antibody intermediate, drug substance, and Drug product with some case studies.
Antibody-based therapeutics have transformed drug development, providing precise and potent treatments. GenScript is committed to empowering therapeutic antibody development through our comprehensive portfolio of advanced tools and services for every stage of the process. Discover our innovative solutions developed for high-throughput automated purification platforms, optimizing your workflows. Additionally, explore our custom services for antibody development and optimization, ensuring the generation of high-quality antibodies with unparalleled specificity and efficacy. Join us in elevating your development efforts and shaping the future of precision medicine with GenScript.
The pharmacy stakeholder is one of the only driving forces for biosimilar adoption. As Health Systems have evolved to encompass more diverse locations, they must adapt to new evaluation processes that support the complexities of the biosimilar market in the outpatient setting, compared to inpatient formulary management for lowest cost. Hear about the Mayo Clinic’s successful adoption of biosimilars over time and how this can inform processes at Health Systems that have a more open system with the help of Vizient resources and partnership.
HCAb Harbour Mice® of Nona Biosciences is the first fully human heavy chain only antibody (HCAb) transgenic mice platform in history. It is optimized, clinically validated with global patent protection. HCAb Harbour Mice® efficiently produces high affinity, and functional HCAbs with excellent biophysical characteristics.Fully human heavy chain only antibodies are the ideal antibody format to generate a multitude of next-generation therapeutic modalities including bispecific/multispecific antibodies, CART, ADC, and mRNA therapy.
We recently discovered a new functional B7 immune checkpoint molecule called HHLA2 (HERV–H LTR Associating 2) and its two functionally opposite receptors including the costimulatory receptor TMIGD2 (transmembrane and Ig domain containing 2) and the coinhibitory receptor KIR3DL3 (killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 3). We found that HHLA2 was widely expressed in a broad spectrum of human cancers, particularly in PD-L1 negative tumors. KIR3DL3 was mainly expressed on CD56dim NK and terminally differentiated effector memory CD8 T (CD8 TEMRA) cells, whereas TMIGD2 was mainly expressed on naïve T and NK cells. The HHLA2-KIR3DL3 pathway inhibited immune function, whereas the HHLA2-TMIGD2 pathway stimulated immune function. I will discuss our results from discoveries to novel therapies to clinical trials.
Senior Representative, Vincerx
Bispecific T-cell engager (BiTE)-based cancer therapies that activate T cells of a patient’s own immune system have had success in the treatment of hematological malignancies, but so far only limited efficacy in targeting solid tumors has been observed. Here, I will discuss the development of BiTE-sialidase fusion proteins that enhance the susceptibility of solid tumors to BiTE-mediated cytolysis by T cells via targeted desialylation at the T cell-tumor cell interface
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Antibody therapeutics have been very successful in the clinic and many new modalities are currently emerging. Many challenges still exist and three main challenges will be addressed in this talk:
1) The fast generation of well-behaved antibodies
2) Modality selection
3) Efficient antibody optimization for biological efficacy
Senior Representative, Bioelectronica
Senior Representative, PipeBio
Neutralizing antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to protect against infection and prevent COVID-19 disease progression, especially among the immune-compromised patient population. However, as highly mutated variants of concern (VoCs) emerge over time, antibody neutralization potency can be lost and break through infections occur. One strategy to combat VoCs is to re-engineer previously discovered antibodies such that they bind to new VoCs. AZD3959 is a SARS-CoV-2 RBD binding antibody discovered from patients infected with the Beta variant. AZD3959 potently neutralized all previously circulating SARS-CoV-2 variants, but lost efficacy against Omicron variant XBB.1. Using a co-crystal structure of AZD3959 Fab and BA.1 RBD, we sought to re-design AZD3959 to restore neutralization against XBB.1 while simultaneously maintaining potency against previous SARS-CoV-2 variants, such as BQ.1.1. We used free energy perturbation (FEP) calculations to screen 252 rationally designed AZD3959 point mutations in silico for retained thermostability and improved antigen binding. A total of 53 AZD3959 modified antibodies were generated as purified mAbs for in vitro testing, with 17 mAbs showing binding to XBB.1 as good or better than the parental AZD3959. Two of the designed mAbs exhibited broad neutralization of all tested SARS-CoV-2 VoCs, including XBB.1 (up to 32-fold increase) with IC50 <20 ng/mL while maintaining <10 ng/mL IC50 potency to past variants, such as BA.1. This talk will focus on the use of a rapid in silico screening approach to design and test modified antibodies that lead to enhanced affinity and neutralization potency.
The discovery of functional antibodies against G-protein coupled receptors (GPCRs) and their downstream engineering to improve potency remain longstanding challenges. Affinity maturation via yeast display is a common antibody engineering strategy that is facilitated by the availability of soluble antigens. The solubilization and purification of GPCRs in the presence of detergents can generate antigens for yeast display, but the detergents can lead to reduced stability and loss of conformational relevance of the purified receptor. Here I present how GPCR incorporation into nanodiscs and styrene-maleic acid lipid particles enabled antibody affinity maturation and identification of antibodies with functional potencies matching that of a small molecule with demonstrated clinical efficacy.
Triple transient transfection of HEK293 cells is a common method used in cell and gene therapy to generate rAAV. Transfection parameters, such as the mass ratios of the three plasmids used, can be manipulated to impact the vector genome titer and product quality at harvest. This presentation will consider the results of plasmid mass ratio DOEs using multiple GOIs that were input into platforms that differed in cell bank, DNA concentration, and transfection reagent.
· CDM Communication and Coordination Across All Sectors for Quality Data
· What is MedDRA and Medical Coding and Its Role in Study Inception
mAbs produced in fed-batch mode by CHO cell lines have a low risk profile. Streamlined platform technology and infrastructure allow for rapid CMC development and manufacture. However, the current and future multiple modality pipeline is stretching the classic mAb platform paradigm, necessitating new modular approaches to development and manufacturing. How do we balance complexity with simplicity to meet current market trends and business drivers such as market growth, demand uncertainty, new product classes, cost-of-goods reduction, increased speed, quality and agility, and improved sustainability? In this presentation, we describe our CMC and development approaches, which include the application of advanced processing technologies in engineering biology, high-throughput analytical technologies and integrated continuous biomanufacturing to meet the market and business challenges of a diverse mAb, multi-specific and therapeutic protein pipeline.
Engineering of biologic drug candidates to optimize desirable properties or to dial down unwanted characteristics often involves laborious experimentation. This presentation will highlight recent advances in computational structure-based methods grounded in physics and describe their role in accelerating candidate optimization. Some of the common challenges faced in antibody engineering that will be covered include the accurate prediction of antibody-antigen binding affinities, improvement of structural stability, as well as the identification and mitigation of developability risks. The presentation will illustrate the incorporation of the resulting workflows into a collaborative biologics discovery informatics platform that integrates experimental data with strong computational modeling execution, delivery, and analysis capabilities with the goal to expedite and improve decision making by having all critical information in one centralized hub.
The receptor for advanced glycation end products (RAGE) is a multi-ligand, cell surface receptor of the immune globulin superfamily. The ligand recognizes damage-associated molecular patterns (DAMPs), which include advanced glycation end products (AGE), HMGB1, members of the S100 protein family, amyloid proteins and others. There is no defined canonical ligand binding site on the receptor and different ligands lead to distinct down-stream signaling. Persistent over-activation and upregulation of RAGE has been associated with several disease conditions, including certain cancers, diabetic complications and Alzheimer’s disease.
To further evaluate RAGE as a drug target and to understand mechanistic details of RAGE signaling, we partnered with Genovac to launch a multi-species discovery campaign to develop a broad panel of anti-RAGE antibodies. The presentation will discuss results of the antibody generation and development process along with approaches to identify ligand specific RAGE antagonistic antibodies.
· Recombinant viral vectors haveemerged as prominent gene delivery vehicles for gene therapy.
· Viralvector proteins playimportant roles in gene delivery to the nucleus of target cells.
· Characterization of viral vector proteins can provide valuable and important information for gene therapy development.
Rabbits produce robust antibody responses and have unique features in their antibody repertoire, but the frequent occurrence of a non-canonical disulfide bond between CDRH1 and CDRH2 is often seen as a liability for therapeutic antibody development. Here we describe sequence, structure and ML-guided protein engineering approaches to recover the affinity loss upon removal of this non-canonical disulfide bond in a human-mouse cross-reactive anti-PD-1 monoclonal rabbit antibody. Our case study indicates that while the non-canonical inter-CDR disulfide bond found in rabbit antibodies does not necessarily constitute an obstacle to therapeutic antibody development, combining structure- and ML-guided approaches can provide a fast and efficient way to improve antibody properties and remove potential liabilities.
-Describe the real-world experience of using monoclonal antibodies for treatment and prevention of COVID-19 at a major academic medical center
-Strategies for allocation of scarce resources of monoclonal antibodies during pandemic surges
-Challenges with access and administration of monoclonal antibodies
-Assessment of effectiveness of long-acting monoclonal antibodies for prevention of infection in high-risk populations
Engineered proteins empower molecular therapeutics, diagnostics, and fundamental biology. Engineering precise mechanisms of action, as well as biophysical robustness (‘developability’), is required for practical use. This presentation will discuss several advances in pursuit of efficient protein therapeutic discovery including a platform for developability engineering, the interplay of developability and functionality, and case studies in therapeutic discovery of miniprotein ligands.
Despite the therapeutic promise of cytokines for cancer treatment, their clinical utility is hampered by toxicity from systemic administration. To address this challenge, we present a novel methodology for precision engineering of cytokine therapeutics using the AlphaSeq platform, which quantitatively measures protein-protein interactions at scale by reprogramming yeast mating. Using IFNA2 and IL-21 as two test cases, we developed extensive mutational libraries of each cytokine and measured their binding against second libraries that included the human wild-type receptor, species orthologs, and off-target receptors. Using AlphaSeq, we simultaneously discovered detuned variants with a wide affinity range for both human and mouse receptors. Affinity de-tuned cytokine variants were then produced as Fc fusion proteins and their affinities and signaling potencies measured orthogonally using biolayer interferometry and an in vitro human PBMC phosflow assay. Promising cytokines were fused to anti-CD8 antibodies, some displaying 1000-fold or greater increased signaling potency in targeted cell populations versus non-targeted ones. Our results demonstrate the AlphaSeq platform's ability to accurately quantitate thousands of cytokine variant affinities simultaneously against multiple relevant receptors, enabling the selection of candidate immunocytokine antibody fusion proteins with exquisite cell population specificity. We have extended this approach to a diverse panel of cytokines and localizing antibodies, enabling a broad therapeutic matrix to address a wide range of indications across immuno-oncology.
Luminary will show data outlining engineered gamma delta cells expansion rates of 3,000 + fold from post electroporation.Estimated cost models will be explored in a GMP setting. Simulated distribution models demonstrating new forms ofaccessibility.
In vivo CRISPR editing is an emerging new therapeutic approach to make genetic and epigenetic alternations in a patient’s own body in organs such as the liver. Base editing and epigenome editing are particularly advantageous because they can function efficiently without the need for double-strand breaks. I will discuss the use of mRNAs to encode editors along with synthetic guide RNAs to alter genes involved in cardiovascular and metabolic diseases—namely, the inactivation of the PCSK9 gene via genome editing or epigenome editing for the treatment of hypercholesterolemia and atherosclerotic cardiovascular disease, and the correction of pathogenic variants in the PAH gene for the treatment of phenylketonuria. The strategies can be applied to a broad set of monogenic and complex diseases.
AAV vectors used for some disorders at ≥ 1014 viral genomes (vg)/kg have resulted in serious adverse events (SAE) or even deaths demonstrating that AAV vector doses that can safely be injected into patients are limited and for some indications below the therapeutic dose. Some of the SAEs, such as myocarditis and thrombotic microangiopathy (TMA) are immune mediated while the etiology of others remains unknown. Currently used immunosuppressive drugs have not prevented the SAEs indicating that it may be prudent to treat patients with repeated transfer of moderate doses rather than a single injection of high doses of AAV vectors. The former approach has been avoided as AAV vectors elicit neutralizing antibodies (Abs) (NAs) that prevent successful reapplication of serologically cross-reactive vectors. Drugs that target crucial steps of B cell activation signaling cascades used alone or in combination should be explored for their ability to inhibit neutralizing antibody responses to AAV. AAV capsid binds to complement factor C3 products such as iC3b. This allows for deposition of AAV particles onto complement receptors on follicular dendritic cells (FDCs), which in turn are essential to drive activation of germinal center (GC) B cells. It also allows for binding of the iC3b- AAV complexes to CD21 on the surface of B cells, which amplifies B cell receptor signaling. Blocking this interaction provides an additional avenue to dampen B cell responses to AAV capsid.
Upstream process development requires a large array of screens to identify a bioreactor process that is robust, productive, and manufacturing friendly. The models used must be both representative of at-scale bioreactors, and capable of sufficient throughput to investigate a large design space. In this talk, the Sartorius AMBR systems will be investigated as tools to accelerate upstream process development and increase the screening capacity at early phases of development.
The Notch pathway is conserved in all metazoans, but safely drugging this target has remained an elusive challenge. Herein we describe the discovery and characterization of a Jag-ligand selective anti-Notch2 antibody that binds an unique epitope on Notch2. We demonstrate this selectivity via systemic administration of this antibody, which causes selectivetransdifferentiation of the guinea pig airway without causing DLL-dependent
Existing methods for biologics discovery offer complementary advantages but each come with their drawbacks. We present Immune Replica, a microfluidics-based discovery engine to generate, enrich and screen natively-paired libraries, thereby combining the strengths of B cell and display-based platforms. The IR platform has been extensively used to rapidly isolate potent antibodies from millions of human and mouse B cells without the need for additional maturation. These antibodies have shown value across therapy areas and modalities, including some that are now entering the clinic.
-The small size and limited chemical diversity of nanobodies enables distinct conjugation approaches
-Repertoire analyses identify sites of conserved chemically addressable residues and potential tolerated substitutions
-Mutation of conserved chemically addressable residues permits selective functionalization of naturally-occurring or engineered reactive groups
Therapeutics in inflammatory indications often are limited in their efficacy, either in the proportion of patients that can be treated successfully or in the degree of mitigation of symptoms. Combining blockade of multiple pathways in the same indication is a way to enhance the efficacy and benefit to patients. We describe the engineering of trispecific antibodies that are able to neutralize three cytokines simultaneously. Design factors to be discussed include arrangement of binding domains, strategies for driving correct chain pairing, and optimizing for expression, stability, and developability.
CD270 has three known ligands, of which both CD160 and BTLA are co-inhibitory, whereas LIGHT is co-stimulatory to T cells. High expression of the CD270 on tumors strongly correlates with poor survival and an immunosuppressive TME. Anti-CD270 antibodies were selected that specifically inhibit the interaction with immune suppressive ligands CD160 and BTLA but do not inhibit the immune stimulating CD270-LIGHT interaction
In this talk, we'll demonstrate AI approaches that automate some of the more tedious tasks in biometrics and data management. We'll walk through specific use-cases, starting with AI-based data-quality assessments, moving on to automated biometrics, where we'll show how AI can code data, perform the appropriate biostatistics, and then write up the results in complaint reports. The goal is to demonstrate the huge cost and time savings of AI, in real scenarios, while explaining how these techniques can plug directly into existing day-to-day clinical trial operations, without adding extra burden.
In this drug discovery environment, the drug discovery community faces numerous challenges bringing a new biologic to patients who need them. Time is a critical factor that contributes heavily on the probability of the success of a new biologic drug. Cost is another critical factor as small and medium companies with capital constraints are the major innovative engine in discovery phase. Alloy Therapeutics is a drug discovery partner that is expediting the path to the clinic through continuous innovation and partnerships. Alloy recently launched SeqImmune, a high-velocity antibody drug discovery workflow dramatically reducing optimized around Alloy’s ATX-Gx human transgenic mouse platform now now includes the use of ATX-GKH human transgenic hyperimmune mouse offering fast, robust response, and a deeper diversity that is ideal for any target. In partnership with Alloy’s Translational Research team and Wheeler Bio for Portable CMC(™), a partner has the potential to reach IND much faster. In this talk, we’ll highlight some of the key innovations that enables such a rapid path through discovery, reveal strategies for maximizing diversity with ATX mouse strains and highlight the partnerships and case studies to demonstrate the value of engaging a true drug discovery partner. Let’s move drug discovery further, faster.
The extracellular RNAs (exRNAs) from human biofluid have recently been systematically characterized. However, the correlations of biofluid exRNA levels and human diseases remain largely untested. Here, considering the unmet need for presymptomatic biomarkers of sporadicAlzheimer's disease (AD), we leveraged the recently developed SILVER-seq (small-input liquid volume extracellular RNA sequencing) technology to analyze exRNA from a longitudinal collection of human plasma samples. When we required statistical significance with multiple testing adjustments, phosphoglycerate dehydrogenase (PHGDH) was the only gene that exhibited consistent upregulation in AD brain transcriptomes from 3 independent cohorts and an increase in AD plasma as compared to controls. We validatedPHGDH's serum exRNA and brain protein expression increases in AD by using 5 additional research cohorts. Furthermore, human hippocampalPHGDHprotein expression level is reversely correlated with the person's cognitive ability. These data suggest the potential utilities of plasma exRNA levels for screening sporadic AD.
This presentation explores the transformative role of generative AI within pharmacology and clinical trials, with its potential to revolutionize molecular discovery, clinical trial design, and unstructured document processing. It explores cutting-edge technologies, including generative AI and machine learning, to outline how AI can generate synthetic data, enhance document analysis, and improve data labeling processes. By examining practical examples and methodologies, such as prompt engineering and the use of LLMs, the presentation provides insights into current capabilities and future directions in AI-driven pharmacological research and clinical trial management.
Cluster of differentiation 47 (CD47) is a transmembrane protein highly expressed on tumor cells that interacts with signal regulatory protein alpha (SIRPα) and triggers a “don’t eat me” signal to the macrophage, inhibiting phagocytosis and enabling tumor escape from immunosurveillance. The CD47-SIRPα axis has become an important target for cancer immunotherapy. To date the advancement of CD47-targeted modalities is hindered by the ubiquitous expression of the target, often leading to rapid drug elimination and hematologic toxicity including anemia. To overcome those challenges a bispecific approach was taken. CC-96673, a humanized IgG1 bispecific antibody co-targeting CD47 and CD20, is designed to bind CD20 with high affinity and CD47 with optimally lowered affinity. As a result of the detuned CD47 affinity, CC-96673 selectively binds to CD20-expressing cells, blocking the interaction of CD47 with SIRPα. This increased selectivity of CC-96673 over monospecific anti-CD47 approaches allows for the use of wild-type IgG1 Fc, which engages activating fragment crystallizable gamma receptors (FcγRs) to fully potentiate macrophages to engulf and destroy CD20+ cells, while sparing CD47+CD20- normal cells. The combined targeting of anti-CD20 and anti-CD47 results in enhanced anti-tumor activity compared to anti-CD20 targeting antibodies alone. Furthermore, preclinical studies have demonstrated that CC-96673 exhibits acceptable pharmacokinetic (PK) properties with a favourable toxicity profile in non-human primate. Collectively, these findings define CC-96673 as a promising CD47xCD20 bispecific antibody that selectively destroys CD20+ cancer cells via enhanced phagocytosis and other effector functions.
In the proposed talk, we will highlight our work on going from DNA to protein to functional validation within a day to characterize membrane bound proteins as well as affinity reagents of interest. We focus on micro-encapsulation to compartmentalize cell-free protein production, followed by functional assessment using fluorescent correlation spectroscopy. fluorescent correlation spectroscopy can provide information on protein production rate, size, binding and discern solubility as well as aggregation. This workflow requires small volumes and low concentrations of solutes, while reducing the cost and time to generate and study multiple protein/small molecule interactions in parallel.
Nearly half of all pregnancies in the U.S. are unintended, and most occur in women who are not using contraceptives. Inadequate user adherence is a major driver of failures in contraception, and underscore the sore need for methods that can afford sustained contraceptive activity. Here, we engineered a monoclonal antibody (mAb) that can efficiently agglutinate and trap sperm, and thereby block sperm from swimming through mucus to fertilize eggs. We further developed a versatile capsule-intravaginal ring (IVR) system that enable precise release of our contraceptive antibody, enabling both rapid release as well as sustained release of mAb over 30 days into vaginal fluid simulants in vitro, while fully preserving activity and stability. In vivo, our IVR resulted in comparable sustained release, leading to nearly instantaneously agglutination of all human sperm introduced into the sheep vagina at different times over 22 days, a period that covers the fertility window in most women. We are also developing combinatorial multipurpose prevention technologies (MPT) that additionally would prevent sexually transmitted disease (STDs) and bacterial infections. Overall, our results underscore our capsule-IVR as a promising sustained non-hormonal contraceptive method, and the use of such platform to enable use of biologics to reinforce female reproductive health.
The XpressCF+® platform is Sutro Biopharma’s proprietary technology enabling efficient, flexible, and scalable cell-free protein production at manufacturing scale. Furthermore, XpressCF+® can incorporate non-native amino acids efficiently and site-specifically for designed therapeutic conjugate products like antibody-drug conjugates (ADCs). The platform is made possible by XtractCF®, an E. coli extract of the cellular components required to produce proteins. XtractCF® can be produced and stored in advance of the protein production, and it can be used for the production of many different products. XtractCF® includes all the necessary biochemical components for energy production, transcription and translation and can be used to support cell-free protein synthesis by the addition of plasmids containing specific DNA sequence for the desired protein. In this study, we leverage the power of definitive screening design to optimize the performance of the XpressCF+® process for an antibody intermediate toward ADC production. The results reveal a significant improvement in productivity with comparable or superior product quality. Furthermore, we successfully demonstrate the scalability of this optimized process through production at 1000 L scale. The study also provides valuable insights into the productivity and quality impacts of various process parameters, enhancing our understanding of the XpressCF+® process.
Using the amber suppression-based mutagenesis, noncanonical amino acids that contain chemical functionalities for direct binding to epigenetic proteins are incorporated into phage display peptide libraries. These noncanonical amino acids serve as anchors for directing phage display peptides to the active site of target proteins leading to the quick enrichment of potent inhibitors. Successful applications have been demonstrated on targets including histone deacetylases, bromodomains, and YEATS domains. Most identified ligands display nanomolar to sub-nanomolar potency.
Novelcell-basedtherapies are currently being developed for the treatment of solid tumors. However, the hostile tumor microenvironmentand immune check-point receptorscontinue to pose major challenges to the successful translationof these therapies.To overcome these challenges, we havedeveloped acord blood derived NK celltherapy(CB-NK),thatcombineseditingofCytokine Inducible SH2 containing protein (CIS)proteinwhich isacheckpointof IL-15cytokinesignalingpathway,together witheditingTGFβRIIonCB-NK cells to overcome the immunosuppressive effects of TGF-β on NK cellfunctionality. ThedualCISHKnockoutTGFβRIIKnockoutCB-NKis furthergeneticallyengineered tosecretesoluble IL-15which can promote NK cell activation andproliferation. Our goal is to combinetheseCB-NK engineered cells withstandard of care monoclonal antibodiesor NK cell engagers.This combination approachwould represent a keydevelopmenttowards our goalofimprovingcellularimmunotherapyfor solidtumors.
The Pioneer Antibody Discovery Platform is Bio-Rad’s new service for biotherapeutic discovery. The Pioneer Platform comprises a new antibody phage display library engineered to have optimal properties for the selection of therapeutic candidates, including the reduction of CDR-located posttranslational modification sites for improved developability. With 92% of the clones (VH and VL combined) encoding functional antibodies, the Pioneer Antibody Library encodes 2.25x1011 unique antibodies. Pioneer takes advantage of SpyDisplay, a novel selection system based on SpyTag technology and gives access to SpyLock, a novel prototyping tool for screening ofbispecific antibodies. Herein, we demonstrate that the Pioneer Platform delivers diverse high-affinity antibody lead candidates. Using anti-TIGIT antibodies, we show that the performance of our lead candidates is comparable with antibodies undergoing clinical trials.
Diabetes Mellitusis a global health challenge, affecting over 500 millionpeople. In 2021 alone, it claimed 6.7 million lives. Shockingly, there’s a projected increase of more than 670%in diabetes cases among individuals under 20 years oldin the next two decades. Despite this alarming situation, insulin remains unaffordablefor a significant portion of the world’s population.
To address this critical issue, scientists have ingeniously engineered a solution: proinsulin produced in plant cells. Let’s delve into the details:
1. Gene Stability and Expression:
o The proinsulin gene was stably maintained across subsequent generations of plant cells even after removing the antibiotic-resistance gene. This was confirmed through techniques like PCR, Southern blot, and western blot.
o Proinsulin expression reached impressive levels, with up to 12 mg/g DW(dry weight) or 47.5%of total leaf protein.
2. Long-Term Stability:
o Freeze-dried plant cells containing proinsulin remained stable for up to one yearat ambient temperature.
o These results met the FDA regulatory requirementsfor uniformity, moisture content, and bioburden.
3. GM1 Receptor Binding:
o The GM1 receptor, crucial for uptake via gut epithelial cells, was confirmed by the pentameric assembly of CTB-Proinsulin.
4. Oral Delivery vs. Insulin Injections:
o Insulin injections (without C peptide) in STZ miceled to rapid blood glucose reduction followed by hepatic glucose compensation.
o Interestingly, oral proinsulin (with a 15-minute lag period for gut transit) showed blood sugar regulation kinetics similar to naturally secreted insulin in healthy mice (both containing C-peptide), without rapid hypoglycemia.
o Eliminating expensive fermentation, purification, and cold storage/transportation could significantly reduce costs and enhance the health benefits of plant fibers.
5. Promising Outlook:
o The recent FDA approval for plant cell delivery of therapeutic proteins and the approval of CTB-ACE2for phase I/II human clinical studies bode well for advancing oral proinsulin to clinical use.
This groundbreaking research holds immense potential to revolutionize diabetes management and make life-saving insulin more accessible globally.
· CAR T-cell function promotes in combination with anti-PD-1 agent.
· CAR T-cell intrinsic PD1DNR (Dominant Negative Receptor) can prolong CAR T-cell functional persistence.
· Our recent data showed that PD1DNR shed from CAR T cell was effective on non CAR T-cell as well
Glycol immunology represents a new frontier of immune regulation, playing vital roles in cancer and inflammation. We have developed a human sialidase-based EAGLE platform to overcome these challenges. The EAGLE platform has demonstrated robust antitumor activity as a single-agent treatment and a broad safety margin in preclinical animal models. Furthermore, phase I clinical trials have established EAGLE’s safety and proof-of-mechanism in cancer patients. EAGLE offers a promising novel immunomodulatory approach to cancer therapy.
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TFF is a standard unit operation included in platform processes across many therapeutics. For AAV manufacture, TFF is useful to concentrate crude vector lysate prior to subsequent capture chromatography steps to provide shorter processing time. However, there are many complications that can occur when transferring from process development scale up to Pilot and GMP scales including TMP control and skid processing capabilities. This presentation will share case studies of various pitfalls during TFF scale-up regardless of filter type (Hollow Fiber Filter vs. Cassette) or transfer facility (internal vs. external). The lessons learned here provide considerations applicable across the field for future successful AAV processes scale-up and transfer.
Describe organisms, bioreactors and bioprocesses for scientific, engineering and business professionals with some prior biological science experience. Explore upstream and downstream processes development, optimization, control, monitor, and analysis based on biological principles behind microbial/cell culture/transgenic plants selection, physiology, growth, rDNA technology. Will also discuss separation science principles involved in cell harvesting, chromatography, and filtration and discuss strategies enabling improved accessibility of biosimilars by optimizing bioprocess performance and costs.
A panel discussion to review and compare T-Cell Therapies (such asCART and TIL) with T-Cell Engagers (such asIL-2, anti-PD-1, bifunctional antibodies, and cancer vaccines)
Arrhythmogenic cardiomyopathy (ACM) is a fatal inherited cardiac disease with prevalent mutations in the cardiac desmosomal mechanical anchoring gene, plakophilin-2 (PKP2).
LX2020 effectively restored PKP2 expression and improved cardiac anchoring and physiological function with long-term efficacy, including extended lifespan in preclinical ACM mouse models
LX2020 demonstrated safety in non-human primates and illustrated the use of an AAV to address long-term ACM deficits at remarkably lower doses in disease states, setting a new standard in the field.
Biotransformation (e.g., deamidation, oxidation) can contribute to decreased efficacy/potency, poor pharmacokinetics, and/or toxicity/immunogenicity for protein therapeutics. Identifying and characterizing such liabilities in vivo are emerging needs for biologics drug discovery. In vitro stress assays, (e.g. PBS for deamidation or AAPH for oxidation) are commonly used to predict liabilities in manufacturing and storage, and are sometimes considered a predictive tool for in vivo liabilities. In this talk, I will discuss the use of mass spectrometry to characterize in vivo biotransformation in pharmacokinetically relevant compartments for diverse protein therapeutic modalities, as well as their correlation with in vitro stresses.
T cells in the tumor microenvironment require TCR/MHC engagement and costimulatory receptor engagement to achieve optimal activation. Solid tumor cells lack expression of CD28 ligands, so we hypothesized that activation of CD28 signaling at the T cell/tumor cell interface could enhance anti-tumor activity. We generated tumor-associated antigen (TAA) x CD28 bispecific antibodies that conditionally provide CD28 costimulation only in the presence of TAA and TCR engagement, and show that they provide enhanced activity over traditional bispecifics.
A team of experts across industry and the Food and Drug Administration have been working together for the last six years on a series of white papers aimed at streamlining the immunogenicity testing and reporting included in regulatory filings. The first white paper1 focusing on anti-drug antibodies was published in 2022 and has been accessed over 13,000 times. It has since been recognized by FDA reviewers as having significantly reduced health authority queries. The second white paper2, addressing neutralizing antibodies was published in July 2023 and was accessed over 14,000 times in the first two weeks. This continued collaboration between global industry leaders and health authorities has proved useful in proactively aligning expectations and decreasing the time and cost associated with filing query resolution and post marketing commitments.
1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8816448/
2 https://link.springer.com/article/10.1208/s12248-023-00830-5
- Introduction to biosafety testing
- Cell bank & Virus Seed Biosafety & Characterisation, including a brief overview of
o Identity Testing
o Genetic Stability
o Purity (freedom from bacteria, fungi and mycoplasma)
o Virus Safety
- Regulations and Guidelines
- Testing strategies
The next generation of medicines will rely heavily upon our ability to quickly assess the structures and stabilities of protein-based biotherapeutics, including degradation products, engineered constructs, and antibody-antigen complexes. Such endeavours are both slow and challenging using standard biophysical tools. In this presentation, I discuss recent developments surrounding collision induced unfolding (CIU) methods that aim to bridge this technology gap. CIU uses ion mobility-mass spectrometry (IM-MS) to measure the stability and unfolding pathways of gas-phase proteins, without the need for covalent labels or tagging, and consuming 10-100 times less sample than almost any other label-free technology. Recent developments in high-throughput CIU screening methods, their ability to track alterations in biomolecular structure as a function of stress, and software developments that seek to enhance CIU information content will be discussed.
Protein therapeutics have numerous critical quality attributes (CQA) that must be evaluated to ensure safety and efficacy, including the adoption and retention of the correct structural fold without formation of unintended aggregates. The entirety of structural elements from primary sequence to quaternary interactions is termed the ‘higher order structure’ (HOS) of the therapeutic, and the development of analytical techniques for HOS characterization throughout the lifecycle of a protein therapeutic, from development to manufacture, has emerged as a major priority in the pharmaceutical industry. To address this measurement need, I will describe nuclear magnetic resonance (NMR) spectroscopy methods that can provide high-resolution spectral 'fingerprints' of the HOS of protein therapeutics in formulated drug products at atomic resolution. Using measurements on an IgG1k NIST reference mAb (NISTmAb), and mAbs from biopharma partners, I will show how NMR spectral fingerprints can be used to quantitatively assess and classify variations in the HOS of formulated protein therapeutics and how these fingerprints can be correlated with other biophysical and functional data.
· Targeted 2D-LC-MS/MS enabled quantification of biotherapeutics and biomarkers down to pg/mL range without the need of custom antibody reagents
· Hybrid immunoaffinity enrichment with targeted 2D-LC-MS/MS provides the most direct approach for understanding KRAS G12C target engagement
· Understanding target engagement at the site of action in tumor tissues provides critical insights for drug development
Targeted cytokine (TaCk) therapies are attractive therapeutic strategies to augment or modulate existing immune responses, with the goal of enhancing specificity, safety, and efficacy over first-generation, non-targeted cytokine administration. In this talk, we share our strategic approach for the design, production, and selection of a PD1-targeted IL-15 agent from a panel of closely related glycoforms. Additionally, we highlight the contributions of glycan identity and occupancy on potency assessments in vitro as well as in vivo, and propose a mechanism for glycan-mediated clearance based on the findings from a PK mouse model.
GRIP Display (Gluing RNA to Its Protein) enables rapid screening of vast protein libraries (~10^13 unique variants) against a target of interest, with minimal genetic swapping, significant selection enrichment, and one-step simple experimental protocol. This talk showcases its effectiveness in: 1) optimizing the binding tunnel of HaloTag protein (HTP) for enhanced ligand capture (HTL), and 2) developing high-affinity orthogonal HTP/HTL pairs with minimal cross-reactivity.
Rapid, high throughput measurements of biomolecular interactions are essential across medicine and bioscience. Traditional methods for affinity-screening proteins require a long and costly process involving cell-based expression, purification, and titration of multiple concentrations to arrive at a binding curve. In contrast, we have developed a fast and cheap approach that yields a wealth of information about the expression of the protein and its binding characteristics, all in a “one-pot reaction” and done in under several hours. The method uses cell-free lysate to produce the protein of interest in the presence of its binding partner, while simultaneously using fluorescence correlation spectroscopy to measure the increasing concentration of the protein and its binding to the binding partner. This lays the foundation for a platform aimed at production and in situ affinity screening of thousands of different proteins.
Since its founding two decades ago, Alliance for Cancer Gene Therapy has become a catalytic force in shaping entirely novel approaches to curing cancer by identifying, funding, and advancing the most innovative and impactful translational research in cancer cell and gene therapies; effective, efficient, less toxic cancer therapies that use the body’s own cells and genes as medicine.
Building on our breakthrough successes in funding CAR T cell therapy research for blood cancers, through grant funding of Dr. Carl June and Dr. Michel Sadelain, ACGT now focuses on solid tumors and hard-to-treat cancers including brain, pancreatic, sarcoma, and rare pediatric tumors.
As we build alliances, fund new research, and see innovative therapeutic approaches move through clinical trials, we are enabling immunotherapy experts to join forces with cancer cell biology experts to change the outlook for cancer patients.
Hear from Chief Program Officer on Alliance for Cancer Gene Therapy’s mission to advance new curative therapies for cancer.
This panel will explore challenges around access and patient centric development across the value chain
· Meeting patient needs in development: personalised and precision medicine
· Access considerations in translational and clinical development
· Delivering the therapy to patients: patient involvement in bringing a product to market