Cambridge Healthtech Institute’s Inaugural

Modality Selection for Next-Gen Biotherapeutics

The State of the Science, Clinical Considerations, and Challenges in Biotherapeutic Drug Products

September 17 - 18, 2020 ALL TIMES EDT

As the industry gains more experiences with biotherapeutics, the concept of an agnostic approach to modality selection is becoming more common in early discovery, with the premise of automatically moving a target into a given product format and giving way to a comprehensive examination of alternatives. New screening assays and technologies and a trend toward pushing functional studies earlier in the process are blending with an increasing range of options for achieving desired specificity, MOA and safety. DOT's Modality Selection for Next-Gen Biotherapeutics conference considers the state of the science for complex antibody formats, expanding applications of cell and gene therapies, and clinical perspectives on the use of biotherapeutics in patients. The program also examines options for unique circumstances including receptor agonism, alternate routes of administration, and delivery to the brain and CNS.

Thursday, September 17

PLENARY KEYNOTE PROGRAM

12:20 pm

PLENARY KEYNOTE: Tackling Undruggable Oncoproteins: Lessons from the VHL Tumor Suppressor Protein

William G. Kaelin, Jr., MD, 2019 Nobel Laureate; Professor, Medical Oncology, Dana-Farber Cancer Institute; Investigator, Howard Hughes Medical Institute; Co-Founder, Cedilla and Tango Therapeutics

VHL tumor suppressor protein (pVHL) inactivation is common in kidney cancer and upregulates the HIF2 transcription factor. PT2977/MK-6482 is an allosteric HIF2 inhibitor now in Phase 3 testing. Thalidomide-like drugs (IMiDs) bind to cereblon which, like pVHL, is the substrate-binding unit of a ubiquitin ligase. IMiDs redirect cereblon to destroy the myeloma oncoproteins, IKZF1 and IKZF3. We have developed new assays for identifying drugs that can destabilize oncoproteins of interest.

12:45 pm LIVE Q&A:

Plenary Keynote Discussion

Panel Moderator:
Stewart Fisher, PhD, CSO, C4 Therapeutics, Inc.
Panelist:
William G. Kaelin, Jr., MD, 2019 Nobel Laureate; Professor, Medical Oncology, Dana-Farber Cancer Institute; Investigator, Howard Hughes Medical Institute; Co-Founder, Cedilla and Tango Therapeutics
12:55 pm LIVE PANEL AND Q&A:

Plenary Keynote Discussion: De-Risking Early Drug Discovery

Panel Moderator:
Nadeem Sarwar, PhD, Founder & President, Eisai Center for Genetics Guided Dementia Discovery, Eisai, Inc.
  • Data Sciences
  • ​Novel Chemical Modalities
  • Investment and Partnering Models
  • COVID-19 Progress as Examples of Successful Partnerships
Panelists:
Anthony A. Philippakis, PhD, Chief Data Officer, Data Sciences & Data Engineering, Broad Institute; Venture Partner, GV
Stephen A. Hitchcock, PhD, Head, Research, Takeda Pharmaceuticals, Inc.
1:35 pm Lunch Break - View Our Virtual Exhibit Hall

THE STATE OF THE SCIENCE FOR BIOTHERAPEUTIC MODALITIES

2:05 pm KEYNOTE PRESENTATION:

Multifunctional Antibody and Cell-Based Therapeutics; the Last Frontier

Lakshmi Krishnan, PhD, Director General, Human Health Therapeutics Research Center, National Research Council, Canada

Monoclonal antibodies have come of age as efficacious and ‘precise’ therapeutics that have captured significant markets. NRC is harnessing the power of next-generation single domain and monoclonal antibodies to develop a pipeline of multifunctional antibodies, cell and gene therapeutics targeting cancer, neurodegenerative disease and emerging infections, to improve therapeutic potency, precision, and cost. These efforts will pave the way for affordable and accessible biologic therapies for the future.

2:25 pm AAV Capsid Evolution, Applications for Targeted Delivery
Benjamin E. Deverman, PhD, Director, Vector Engineering, Broad Institute

AAV vectors are now used in multiple FDA-approved gene therapies and hold tremendous promise as a modality for treating genetic diseases. However, the application of these vectors remains constrained by delivery inefficiencies, dose-limiting adverse effects, and manufacturing challenges. In this talk, I will discuss our ongoing efforts to expand the impact of gene therapy through the development of AAV capsids with novel capabilities using data-driven protein engineering methods.

2:45 pm Challenges and Opportunites in the Treatment of Hematological Malignancies with Engineered Cellular Therapies
Challice L. Bonifant, MD, PhD, Assistant Professor, Oncology, Johns Hopkins University

We will focus on clinical treatment of pediatric patients with hematological malignancies using engineered cellular therapies. An overview of the current state-of-the art will be presented, with specific highlights on the therapeutic issues. We will add our data on development and testing of engineered cell products against AML.

3:05 pm

High Prophylactic and Therapeutic Efficacy of Human VH-Fc and IgG1 in Animal Models of SARS-CoV-2

Dimiter Dimitrov, PhD, Professor and Director, Center for Antibody Therapeutics, University of Pittsburgh; Executive Vice President and CSO, Abound Bio

We identified an IgG1 and a VH-Fc which bound with high affinity/avidity to SARS-CoV-2 S glycoprotein and mutants found in patients. They potently and specifically neutralized SARS-CoV-2 in hACE2 expressing transgenic mice and hamsters as well as mouse ACE2 adapted SARS-CoV-2 in wide type BALB/c mice at doses as low as 2 mg/kg which in combination with their good developability suggests their potential use for prophylaxis and therapy of COVID-19.

3:25 pm LIVE Q&A:

Session Wrap-Up Panel Discussion

Panel Moderator:
Dimiter Dimitrov, PhD, Professor and Director, Center for Antibody Therapeutics, University of Pittsburgh; Executive Vice President and CSO, Abound Bio
Panelists:
Challice L. Bonifant, MD, PhD, Assistant Professor, Oncology, Johns Hopkins University
Benjamin E. Deverman, PhD, Director, Vector Engineering, Broad Institute
Lakshmi Krishnan, PhD, Director General, Human Health Therapeutics Research Center, National Research Council, Canada
3:45 pm Happy Hour - View Our Virtual Exhibit Hall
4:15 pm Close of Day

Friday, September 18

CLINICAL DEVELOPMENT OF BIOTHERAPEUTIC MODALITIES

10:00 am

Monoclonal Antibodies 45 Years Later: Current Landscape of Antibodies and Antibody-Related Molecules

William Strohl, PhD, President & Owner, BiStro Biotech Consulting LLC

This year marks the 45th anniversary of the first publication on monoclonal antibodies. This presentation provides insight to how far we have come in that time, presenting an overview of current, publicly available clinical stage antibodies, Fc fusion proteins, and chimeric antigen receptor (CAR) constructs, the combination of which there are currently over 1,000 examples. Different strategies for addressing the 300-plus unique target antigens will be compared and contrasted.

10:20 am Integration of Discovery with Clinical Translation in Biologics and Cell Therapy
Dongxing Zha, PhD, Institute Head, ORBIT Platform, MD Anderson Cancer Center

The ORBIT is a paradigm-shift platform in academic institute dedicated to discover and develop therapeutic biologics and cell therapy. We want to harness our strengths on clinical science and basic cancer research to identify novel targets and translate such scientific knowledge into first-in-class therapeutic antibodies, and quickly advance these agents into clinical trials. Examples will be discussed on how we could accelerate early discovery into clinical development.

10:40 am New Biotherapeutic Approaches for Targeting PCSK9
Robert Giugliano, MD, SM, Cardiovascular Medicine, Brigham & Womens Hospital, Professor Medicine, Harvard Medical School

PCSK9 inhibitors represent the third proven class of medications (following statins and ezetimibe) to reduce LDL-cholesterol and prevent cardiovascular events. The first two PCSK9 inhibitors approved for clinical use were monoclonal antibodies, but other approaches, including antisense oligonucleotides and small interfering RNAs, have been studied in humans. Mimetic peptides, LDL-receptor antagonists, small molecules, vaccines, and gene silencing approaches are in earlier stages of development.

11:00 am LIVE Q&A:

Session Wrap-Up Panel Discussion

Panel Moderator:
Dongxing Zha, PhD, Institute Head, ORBIT Platform, MD Anderson Cancer Center
Panelists:
Robert Giugliano, MD, SM, Cardiovascular Medicine, Brigham & Womens Hospital, Professor Medicine, Harvard Medical School
William Strohl, PhD, President & Owner, BiStro Biotech Consulting LLC
11:20 am Session Break
11:40 am Coffee Break - View Our Virtual Exhibit Hall
11:55 am Session Break
Larry Green, Ph.D., CEO, Ablexis, LLC
John "Lippy" Lippincott, Ph.D., Vice President, Research, AlivaMab Discovery Services, LLC

AlivaMab Discovery Services produces low picomolar, neutralizing, development-ready human antibodies against even toxic targets in exceptionally fast timelines. Combining Ablexis' AlivaMab Mouse with ADS' proprietary AMMPD immunizations and direct-to-function screening puts projects on the fastest, most de-risked path from discovery through development and to market.

Panel Moderator:
Larry Green, Ph.D., CEO, Ablexis, LLC
John "Lippy" Lippincott, PhD, Vice President, Research, AlivaMab Discovery Services, LLC
12:40 pm Session Break

ISSUES AND CHALLENGES

12:55 pm New Therapeutic Modalities in Immunotherapy
Paul D. Rennert, PhD, President & CSO, Aleta Biotherapeutics

Two cell therapy and T cell engager technologies are advancing for diverse cancer indications. We developed novel proteins designed to complement and extend the functionality of cell therapeutics called bridging proteins. These can be considered CAR-T cell engagers by MOA. We present examples of the creation and evaluation of these proteins, for delivery to the patient as a biologic for injection or for delivery within the CAR T cell itself.

1:15 pm How Uncertainty in Patentability Will Impact Modality Selection for Biotherapeutics
John M. Conley, PhD, William Rand Kenan Jr. Professor, Law, University of North Carolina

The law is in chaos with respect to the patentability of medical diagnostics and therapies, DNA, RNA, and proteins. The PTO and courts are acting inconsistently. Last year Congress seemed close to passing clarifying legislation, but that effort died. This presentation addresses such questions as: Are existing patents that seem to restrict research really valid? Are new therapies likely to be patentable? If not, can they attract necessary capital?

R&D TOOLS AND WORKFLOWS

1:35 pm Structure of CD20 in Complex with the Therapeutic Monoclonal Antibody Rituximab
Lionel Rougé, PhD, Principal Scientific Researcher, Structural Biology, Genentech Inc.

CD20 is a B cell marker of unknown function targeted by monoclonal antibodies (such as Rituximab) for the treatment of B cell disorders. We obtained a structure of CD20 in complex with Rituximab, revealing CD20 as a dimer bound by two Fabs; each Fab engages a composite epitope and an homotypic Fab:Fab interface. Our data suggest that Rituximab crosslinks CD20 into circular assemblies, leading to a model for complement recruitment.

1:55 pm

Efficient Discovery of Antibodies against GPCRs by Combining Single B Cell Cloning with a Yeast-Based Expression Platform

Noel T. Pauli, PhD, Senior Scientist, Antibody Discovery, Adimab LLC

Integral membrane proteins represent a major class of therapeutic targets currently underserved by antibody-based drugs. Using a combination of immunization, single B cell isolation, and yeast-based cloning and expression, we have developed a high-throughput method to discover antigen-specific antibodies to a variety of membrane protein target classes. Here, we demonstrate the efficient and large-scale isolation of high-affinity antibodies against membrane protein targets, including CCR8, a class-A GPCR.

2:15 pm Screening Strategies for Discovery of Functional Biologics
Anna Yarilina, MD, PhD, Senior Scientist, AbbVie Bioresearch Center

Successful biologic discovery requires development of comprehensive screening funnel. Introduction of functional assays early in the screening process enables effective selection of biologics with a desired mode of action and improves understanding of drug biology. This presentation will highlight benefits of the early implementation of functional assays into biologics screening funnel.

2:40 pm LIVE Q&A:

Session Wrap-Up Panel Discussion

Panel Moderator:
John M. Conley, PhD, William Rand Kenan Jr. Professor, Law, University of North Carolina
Panelists:
Paul D. Rennert, PhD, President & CSO, Aleta Biotherapeutics
Lionel Rougé, PhD, Principal Scientific Researcher, Structural Biology, Genentech Inc.
Anna Yarilina, MD, PhD, Senior Scientist, AbbVie Bioresearch Center
3:00 pm Close of Conference





Submit a Speaker Proposal