Elpiscience products

ES104 is a bispecific antibody that simultaneously blocks Delta-like ligand 4/Notch (DLL4) and vascular endothelial growth factor A (VEGF-A) signaling pathways, which are critical to angiogenesis and tumor vascularization. VEGF also plays an important role in creating an immune suppressive TME. Pre-clinical and early clinical data of ES104 show that blocking both pathways provides robust anti-tumor activity across several solid tumors, including colorectal, gastric, cholangiocarcinoma, pancreatic, and non-small cell lung cancer. Partial responses to ES104 as a monotherapy have been observed in heavily pre-treated cancer patients, who were resistant to currently approved anti-VEGF therapies. Positive interim ES104 Phase 2 data in combination with paclitaxel in patients with biliary tract cancers (BTC) was also reported in May 2022.

ES101 is a first-in-class tetravalent bispecific antibody targeting 4-1BB and PD-L1. It has a unique  mechanism of action as 4-1BB activation is dependent on PD-L1 binding. 4-1BB is a T cell co-stimulatory receptor and is a compelling immune checkpoint target. 4-1BB targeting antibodies being developed by multinational companies have exhibited dose-dependent liver toxicity in clinical trials, thereby limiting dose-escalation and ultimately their efficacy.

OX40, also known as CD134, is a member of the tumor necrosis factor (TNF) receptor family and is an important co-stimulator of T cell responses. Typically for TNF receptor family members, 3 molecules of OX40 bind to the trimeric OX40 ligand-protein, activating downstream NF-κB, PI3K, and AKT pathways, which lead to increased cytokine production. Activation of OX40 enhances T-cell expansion, differentiation, and the generation of memory T-cells. OX40 antibodies have been clinically tested to expand activated T cells and suppress regulatory T cells in the treatment of cancer.

ES002’s dual ATP-adenosine mechanism is a potentially powerful TME regulator and transformative cancer immunotherapy. In preclinical studies ES002 demonstrated significant single agent anti-tumor activity as well as an excellent tolerability profile. ES002 has also shown superior enzymatic inhibition and binding affinity.

ES014 is a first-in-class anti-CD39xTGF-β bispecific antibody (bsAb) that simultaneously targets the adenosine and TGF-β pathways, two major immunosuppressive mechanisms in the tumor microenvironment (TME). Solid tumors frequently express TGF-β, which suppresses T cell activation and induces CD39 expression, the rate-limiting enzyme in the ATP-adenosine pathway. The anti-CD39 target is designed to selectively direct ES014 to the TME where the anti-TGF-β activity promotes effector T cell function and immune activation, while avoiding or minimizing systemic immunotoxicity. ES014’s anti-CD39 activity further aims to reverse TME immunosuppression by reducing suppressive adenosine, while maintaining high levels of immune-stimulatory extracellular ATP.

LAG3 is an immune checkpoint receptor known to suppress T cell activation. We designed ES005  to block  LAG3 ligands, including  MHC class II and FGL1. Through unique epitope binding, ES005 is able to recognize human LAG3 with high affinity. In preclinical studies, ES005 inhibited tumor growth both as a monotherapy and in combination with a PD-1 blocker.

ES004 is a potentially best-in-class antibody targeting pan-allele signal-regulatory protein alpha (SIRPα). SIRPα is an inhibitory receptor expressed only on myeloid cells and dendritic cells. Binding of CD47 to SIRPα delivers a “don’t eat me” signal to suppress phagocytosis. Tumor cells frequently overexpress CD47 to evade macrophage-mediated destruction. To overcome this issue, ES004 stimulates potent macrophage-mediated phagocytosis against multiple tumor cells by blocking SIRPα. Unlike agents targeting CD47, targeting SIRPα is designed to avoid anemia and thrombocytopenia and improve the therapeutic window.

ES009: A Potential Best-in-Class Antibody Targeting LILRB2. ES009 is a potential best-in-class monoclonal antibody targeting LILRB2 designed to reprogram inhibitory myeloid cells to create an immune favorable TME. LILRB2 is an inhibitory receptor that suppresses myeloid cell activation. Blocking LILRB2 reverses immunosuppression by reprograming tumor-associated macrophages (TAMs) from M2 (pro-tumor) to M1 (anti-tumor) phenotype, leading to immune responses including myeloid cell activation and pro-inflammatory cytokine release.

ES028 is a potential first-in-class SIRPα/CLDN18.2 bsAb developed using our Bispecific Macrophage Engager (BiME®) platform. The SIRPα antibody blocks the “don’t-eat-me” signal while the TAA antibody provides an “eat-me” signal through Fc receptor engagement. ES028 and the BiME platform are designed for potent activation of phagocytosis and directly kill tumor cells for treatment of solid tumors. We expect to develop ES028 as a monotherapy to provide an “eat-me” signal that can induce full activation of macrophage phagocytosis towards CLDN18.2-expressing tumors, which include gastric cancer and pancreatic cancer. Additionally, ES028 has the potential to be combined with chemotherapy in earlier lines of therapy.