Main Conference Day 3 - PT (Pacific Time, GMT-08:00)
- Paul Parren, PhD - Founder and CSO, Gyes BV
- Mitchell Ho, PhD - Senior Investigator, Laboratory of Molecular Biology, NIH NCI
We will discuss the pros and cons of bispecific T-cell engagers (TCEs) relative to CAR-T cell therapies as well as protein-engineering strategies that can be employed to address limitations of TCEs for cancer therapy.
- Yvonne Chen - Professor, University of California, Los Angeles
- Dan Rock, PhD - Chief Scientific Officer, Cartography Biosciences
- Peyton Greenside, Ph.D. - Chief Scientific Officer and Co-founder, BigHat Biosciences
- Pamela Holland, PhD - Senior Vice President, Biology, InduPro
- Gail Lewis, PhD - Distinguished Scientist, Discovery Oncology, Genentech
We are developing dual-payload ADCs that enable delivery of two different payloads simultaneously to the tumor with the goal of enhancing therapeutic efficacy and overcoming resistance mechanisms. Leveraging our cell-free platform, we precisely control payload placement and ratio to optimize efficacy. Preclinical data demonstrate superior efficacy in vitro and in vivo over single-payload ADCs, with favorable pharmacokinetics, stability, and safety.
- Daniel Calarese, PhD - Executive Director of Research Innovation, Sutro Biopharma
PIP is a versatile targeting peptide that binds selectively to multiple tumor-associated targets, a unique feature enabling payload delivery to virtually any solid tumor. This presentation focuses on the development of PIP-Drug Conjugates, their efficacy and safety, and how PIP’s multi-specific targeting overcomes resistance seen with conventional single-antigen targeting ADCs.
- Caitlyn Miller - Researcher, Stanford University
Radiotherapy remains a cornerstone of cancer treatment, yet its efficacy is often limited by normal tissue toxicity and tumor resistance. This talk will highlight a translational strategy to enhance radiotherapy by leveraging antibody-drug conjugates (ADCs) for targeted delivery of cytotoxic agents. I will present preclinical data demonstrating how ADCs directed against radiation-inducible tumor antigens potentiate tumor response, offering a precision-based approach to improve outcomes in solid tumors.
- Vaishali Kapoor - Assistant Professor, Radiation Oncology, Washington University School of Medicine
Using an entirely original strategy, we have developed a novel platform that uses dual-binding antibodies to generate therapeutics with targeted, conditional activity only when bound to a selected marker. We are currently applying this Antibody Controlled Therapeutic technology to multiple targets, including PD1, LAG3, ATP, and LRRC15 and to multiple effectors including IL-2, IFN-a, IL-12 and TGFb inhibition.
- Diane Hollenbaugh, PhD - Chief Scientific Officer, Bonum Therapeutics
While IL-2 has been shown to be key cytokine for the promotion of T-cell proliferation and effector function, its clinical use for cancer immunotherapy has been limited by severe toxicities. This talk describes the pre-clinical development of REGN10597, a PD-1 targeted receptor masked wild type IL-2 that demonstrates potent in vitro and in vivo activity when targeted to PD-1 expressing T cells but lowered systemic activity in the absence of targeting.
- Eric Smith - Executive Director - Bispecifics, Regeneron Pharmaceuticals
Targeted therapy with covalent inhibitors of oncoprotein KRAS(G12C) are initially effective but typically lack durability due to cancer cell resistance. MHC presentation of the covalently modified KRAS(G12C) peptides on the cell surface creates synthetic neoantigens that can be stabilized and targeted by antibodies across HLA restriction. Conversion to T-cell engagers affords a unique combination of targeted and immune therapy.
- Christoph Rader - Chief Technology Officer, Aethon Therapeutics
We are investigating unique payloads by exploring agents that target cancer cell dependencies/vulnerabilities, or that have known or assumed safety liabilities or poor physicochemical properties that would benefit from delivery via antibodies. We will discuss early achievements in the development of these more targeted ADCs.
- Gail Lewis, PhD - Distinguished Scientist, Discovery Oncology, Genentech
- Marco Lobba, PhD - CEO & Co-Founder, CatenaBio
- Sharsti Sandall, PhD - Executive Director, ADC Biology, Pfizer
- Brandon DeKosky, Ph.D. - Associate Professor of Chemical Engineering, MIT and The Ragon Institute
- Jamie Spangler, PhD - Associate Professor, Johns Hopkins University
My group engineers genetic systems that dramatically accelerate the speed of mutation and gene evolution in vivo so that we can drive the rapid evolution of new biomolecular functions and prospectively watch (and systematically manipulate) the course of long gene evolutionary processes on laboratory timescales. I will share recent developments in the use of our continuous evolution system, orthogonal DNA replication system (OrthoRep), to evolve antibodies. I will discuss our efforts to affinity mature antibodies at scale along with the intersection of computational antibody design and evolution, including work focusing on prioritizing sequence space exploration to generate data for training computational models.
- Chang Liu, PhD - Professor and Chancellor's Fellow, Biomedical Engineering, UC Irvine
We developed a novel functional screening method using hyperphage display platform that allows rapid discovery of potent antiviral single domain antibodies. We benchmarked RASP against established phage ELISA and deep sequencing methods. RASP can be used either as a standalone platform or seamlessly integrated with conventional screening methods to accelerate the discovery of antiviral VHHs.
- Manpreet Kaur, PhD - Staff Scientist, Dept of Microbiology & Immunology, Albert Einstein College of Medicine
We present JAM, a protein design system capable of designing antibodies de novo with therapeutic-grade affinities, function, and early-stage developability for soluble and multipass membrane protein targets. For GPCRs, we show de novo designed antibodies have single-digit nM to picomolar binding affinities, and while most are functional antagonists, remarkably, a subset are agonists -- marking an important milestone in the field.
- Surge Biswas, PhD - Co-founder & CEO, Nabla Bio
- James Larrick, MD, PhD - Managing Director and Chief Medical Officer , Panorama Research Institute
- Vaughn Smider, MD, PhD - President, The Applied Biomedical Science Institute
The ion channel Kv1.3 is well known to be important in the activation of effector-memory T cells. We have developed a unique ultralong CDR3 antibody based on the cow scaffold that potently inhibits Kv1.3 activity. Surprisingly, this reagent was also found to inhibit important immune functions in monocytes and macrophages, revealing a novel role for Kv1.3 in the innate immune system.
- Vaughn Smider, MD, PhD - President, The Applied Biomedical Science Institute
Inflammation and tissue fibrosis co-exist and are causally linked to organ dysfunction. However, the molecular mechanisms driving immune-fibroblast crosstalk remain unexplored, and there are currently no approved treatments that directly target cardiac fibrosis. Using human tissues and mouse models, we delineate the functions of FAP+ fibroblasts within the heart and define immune cell crosstalk and transcriptional events that govern their differentiation. From a broader perspective, we show that bispecific T-cell engaging antibodies targeting FAP+ fibroblasts suppress cardiac fibrosis and have similar effects in other organs. These findings highlight the therapeutic potential of cell specific targeting of defined fibroblasts subsets.
- Kory Lavine, PhD - Professor of Internal Medicine, WashU Medicine
We have previously demonstrated that an IgG3 agonistic TLR4/MD2 antibody reversed acute murine Type 1 Diabetes (T1D) through induced immune tolerance. To translate this work to humans we developed novel human TLR4 agonistic antibodies, demonstrated that the IgG3 isotype and enhanced multivalency are necessary for their TLR4 signaling, and demonstrated their tolerogenic potential for treating inflammatory diseases.
- Luke Heuer, Ph.D. - Postdoctoral Researcher, University of California, Davis
Therapeutic protein engineering has been transformed by the incorporation of big data and AI/ML techniques. An emerging challenge for this field is how to efficiently leverage the right data and the best models to drive meaningful results and resolve long-standing bottlenecks. Amgen has incorporated a generative biology approach to tackle complex engineering problems, aiming to deliver better, more effective molecules across every therapeutic program.
- M. Jack Borrok, PhD - Director, Protein Therapeutics, Rare Disease, Amgen
- Dima Kozakov, PhD - Professor, Stony Brook University
This talk will share updates from the AIntibody competition, a benchmarking initiative engaging the biotech, pharma, academia, and AI communities to use AI and other informatic methods to design or identify developable antibodies with high affinities, from curated NGS datasets. Results will compare the properties of these antibodies with those derived using experimental methods, providing insights into the value of AI in antibody discovery. AIntibody announcement manuscript: Erasmus, M. F. et al. Nat Biotechnol 42, 1637-1642 (2024).
- Andrew Bradbury, MD, PhD - Chief Scientific Officer, Specifica
We leverage our discoveries which show that blockade of innate immune regulatory pathways can halt and even reverse lung fibrosis. We aim to develop novel, multivalent Ab constructs that simultaneously block the activity of these profibrotic pathways.
- Gerlinde Wernig, PhD - Associate Professor, Stanford Medicine
The inability of diverse biomolecules to readily penetrate the blood-brain barrier is a key limitation to their use in research, diagnostic, and therapeutic applications. We are developing bispecific antibodies that engage either CD98hc or transferrin receptor, and efficiently transport biomolecules into the CNS. We will discuss our recent work on protein delivery to the CNS, including cytokines for modulating the immune environment in the brain for therapeutic applications.
- Peter Tessier, PhD - Albert M. Mattocks Professor, Departments of Pharmaceutical Sciences, Chemical Engineering and Biomedical Engineering, University of Michigan
Natriuretic peptide receptor 1 (NPR1) is a membrane-bound guanylate cyclase and activated by atrial (ANP) and brain (BNP) natriuretic peptide and NPR1 agonism alters blood pressure via regulation of intravascular volume, vasorelaxation, natriuresis and diuresis. We have isolated fully human antibodies from VelocImmune® mice that either agonize or antagonize NPR1 activity and are developing as potential treatment of cardiac diseases such as heart failure and hypovolemic/hypotensive disorders.
- Jee Kim, PhD - Executive Director of Therapeutic, Regeneron Pharmaceuticals
Degeneration of retinal neurons in mammals leads to irreversible vision loss. We discovered that Prox1, a homeobox protein, is transferred from neurons to Müller glia (MG) to suppress regeneration. Blocking this transfer with our Anti-PROX1 therapy reactivates MG’s regenerative potential. This approach successfully delayed vision loss in disease model mice, offering a promising strategy to treat retinal degenerative conditions by restoring the intrinsic repair capacity of the mammalian retina.
- Jin Woo Kim, PhD - Professor, Department of Biological Sciences, KAIST