Main Conference Day 3Wednesday, 17 December 2025 - PT (Pacific Time, GMT-08:00)

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.

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.

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.

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.

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.