PRE-CONFERENCE WORKSHOPS (pm only) and TRAINING COURSE (full day)Sunday, 15 December 2024 - PT (Pacific Time, GMT-08:00)

Prominent among challenges faced in the immunotherapeutics field across a spectrum of platforms is the need for improved understanding of the complex mechanisms involved in their operation at multiple levels of the immune system. We have been working to address one aspect of this challenge with respect to immune cell signaling networks, aiming to construct comprehensive yet actionable models for their how they govern effectiveness of immunotherapeutic modalities. This presentation will describe certain new findings, including in applications to antibody glycosylation and to chimeric antigen receptor T cells.

Pancreatic ductal adenocarcinoma (PDAC) is an immunologically cold disease. Increasing immune cell trafficking and activation in PDAC are therefore important for understanding response to immune checkpoint therapies (ICT). Mathematical modeling of the tumor microenvironment (TME) allows us to elucidate the features of PDAC that can determine responsiveness to ICT. By integrating mathematical models with spatial data from patients, we can identify the specific mechanisms in the TME that regulate immune cell trafficking during ICT treatment.

ADCs are a rapidly expanding class of therapeutics with 7 new approvals in the past 6 years. However, they have a long history with many failures in the clinic. This presentation will use a quantitative systems pharmacology approach to highlight the major delivery challenges with ADCs in solid tumors, and how recent successes can be used to inform the design of the next wave of clinical approvals.

The unique cell-to-cell crosslinking action of T-cell engagers (TCEs) poses challenges for in vitro to in vivo translation. Recent advances in QSP models of TCEs capture key biophysical details of crosslinking, enabling rational techniques for first-in-human dose selection and efficacious dose prediction from in vitro potency assays and preclinical animal studies. This talk will review these developments and explain how QSP models can support and accelerate TCE development.

Bispecific antibody clinical development remains rife with challenges, including nuanced pharmacology, limited translatability of preclinical findings, frequent on-target toxicity, and convoluted dosing regimens. Here we argue that trimer formation on the molecular level are but a proxy for the actual driver of pharmacology. The formation of immunological synapses between tumor cells and T cells involves a coordinated cascade of molecular and cellular interactions that extend beyond the initial antigen-binding event. This cascade includes the survey of potential target cells within the tumor microenvironment, the slowing of T-cell movement upon identification, and the establishment cell-to-cell adhesion. Incorporating these cellular mechanisms into bsTCE QSP models offers promise for predicting long-term efficacy, resistance, and relapse in solid tumors.

This talk will present ADC QSP bystander models incorporating both antigen-positive and antigen-negative cells. These models demonstrate that ADC modality may offer limited response durability if antigen-positive and antigen-negative cells grow independently. However, this limitation could potentially be overcome by stromal-targeting ADCs, as stromal cells are recruited to the tumor. Additionally, we will discuss the optimal ADC properties that balance efficacy across both cell populations.

While some of the best selling drugs of all time are biologics, several other modalities have been propelled into the limelight by continued innovations that have the potential to outcompete biologics. My talk will focus on the exciting new areas in biologics development through the lens of early-stage therapeutics investing.

Protecting antibody innovations globally faces increasing challenges, both due to different laws in different countries as well as evolving legal standards, particular in the US and Europe. My talk will focus on potential strategies to a) cover products, b) throw patent obstacles in front of biosimilars and c) generate third party licenses for platform technologies.

Key considerations in starting and investing in companies focused on antibody- based therapeutics include the importance of choosing the right target, molecule attributes and format, clinical indication, investors and team. I will also discuss the differences in drug discovery at large biotech/pharma versus at a smaller company including portfolio considerations.

Early-stage biotech companies must walk a fine line between innovation and risk management. For some companies, this means working with a clinically validated MOA and differentiating from first movers based on target and indication selection or significant functional improvements. As part of the highly active T-cell engager field, our team has successfully created multiple differentiated platforms.

As a new addition this year, we're excited to announce this Early Career Scientists session taking place on the morning of December 15, the day before the main conference. Are you within 10 years of completing your Master’s or Ph.D. and under the age of 35? If so, unlock a range of exclusive benefits by selecting the "Early Career Scientist" pass when you register. This session will spotlight short, novel research presentations from early career scientists in the antibody engineering and therapeutics community. You’ll also hear an inspiring career journey from a distinguished mid-career scientist, plus enjoy the opportunity to connect and network with peers. You’ll also receive free admission to the afternoon pre-conferences workshops on December and the opportunity to present a free poster during the main conference. Please Note: Access to the early career scientists session is only available to those who register for the main conference by selecting the “Early Career Scientist” pass. All passes subject to approval by conference organizers.

To be considered for a short oral presentation in this session, or for general information about this session, please contact Michael Keenan at Michael.keenan@informa.com

If you are interested in sponsoring this session, please contact Blake Shuka at Blake.Shuka@informa.com