On November 20, 2022 Elpiscience Biopharmaceuticals, Inc. ("Elpiscience"), a clinical-stage biopharmaceutical company focused on developing next-generation immunotherapies to benefit cancer patients worldwide, reported positive studies for its innovative immunotherapeutic molecules at the SITC (Free SITC Whitepaper) 2022 Annual Meeting, including anti-SIRPα monoclonal antibody ES004, PD-L1/SIRPα bispecific antibody ES019, anti-LILRB2 monoclonal antibody ES009, anti-SIGLEC15 antibody ES012, and anti-LAG3 monoclonal antibody ES005 (Press release, Elpiscience, NOV 20, 2022, View Source [SID1234624262]).
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Study highlights:
1. Title: Treatment of anti-SIRPα in combination with anti-TAA exerts superior anti-tumor activity
Abstract No.: 793
SIRPα is an inhibitory receptor expressed mainly on myeloid cells and dendritic cells. Ligation of CD47 to SIRPα delivers a "don’t eat me" signal to suppress macrophage phagocytosis. Tumor cells frequently overexpress CD47 to evade macrophage-mediated destruction. Anti-SIRPα mAb ES004 potently potentiates antibody dependent cellular phagocytosis (ADCP) activity of antibodies against tumor associated antigens (TAAs) in vitro and in vivo.
Highlights:
ES004 recognizes pan-allele human SIRPα with high affinity
ES004 binds to a unique epitope on the CD47 binding domain of SIRPα
ES004 potently blocks CD47-SIRPα interaction and CD47 induced SIRPα signaling
ES004 effectively potentiates pan-allelic macrophage phagocytosis of tumor cells
ES004 has no negative impact on T cell activation
ES004 enhances anti-tumor activity in combination with anti-Claudin18.2 in MC38/hCLDN18.2 syngenetic tumor model
ES004 has demonstrated favorable PK, full target occupancy and excellent safety profile in cynomolgus monkeys.
2. Title: Dual targeting of innate and adaptive immune checkpoints with a PD-L1/SIRPα bispecific macrophage engager to promote anti-tumor activity
Abstract No.: 1211
The anti-PDL1/SIRPα bispecific antibody ES019, designed for tumor cell and immune cell dual targeting, is capable of reactivating macrophages and T cells to kill cancer cells with the potential to overcome the limitations of traditional anti-PD1 therapies and has demonstrated significantly enhanced tumor therapeutic efficacy and specificity versus combo or monotherapies.
Highlights:
ES019 phagocytosis activity is corrected with PD-L1 level on tumor cells
ES019 leads to better phagocytosis capability of tumor cells by M2-like than M1-like macrophage
ES019 activates T cells without induction of phagocytosis of T cells
ES019 shows favorable PK in mouse model
ES019 demonstrates single agent anti-tumor efficacy in animal model
3. Title: ES009, a LILRB2-specific blocking antibody, reprograms myeloid cells into pro-inflammation phenotype and potentiates T cell activation
Abstract No.: 1062
LILRB2 is predominantly expressed in myeloid lineage cells. Human LILRB2 broadly binds to multiple ligands and contributes to immune suppression in the tumor microenvironment (TME). Anti-LILRB2 mAb ES009 has demonstrated superior effects in converting immunosuppressive myeloid cells into pro-inflammation phenotypes in in vitro and ex vivo models.
Highlights:
ES009 specifically binds human LILRB2 with high affinity
ES009 binds to a unique epitope on D1 domain of LILRB2
ES009 potently blocks LILRB2 binding to multiple ligands
ES009 promotes monocytes and monocytes derived DCs into a pro-inflammatory status
ES009 effectively reprograms human monocyte derived M2 macrophages into pro-inflammation M1 phenotypes
ES009 effectively relives T cells from M2 macrophages mediated suppression
ES009 converts primary macrophages in malignant ascites in ovarian cancer patients into a pro-inflammatory status
4. Title: SIGLEC15 induces monocyte apoptosis and an SIGLEC15 antibody ES012 reverses myeloid cells driven immunosuppression
Abstract No.: 1401
SIGLEC15 is a glycan-recognition proteins belonging to the SIGLEC family and is highly expressed on TAM and many tumor cells. It’s reported that SIGLEC15 inhibits T cell activity via its binding to an unknown receptor on T cells. Elpiscience has identified a novel function of SIGLEC15 that SIGLEC15 can induce monocyte apoptosis and its inhibitory effect on T cell function is indirect. Based on this newly discovered SIGLEC15 biology, we have developed a potent, functional anti-SIGLEC15 mAb ES012 that has great potential to reverse immune suppression in TME to promote anti-tumor immunity.
Highlight:
SIGLEC15 induces monocyte apoptosis, which is dependent on sialic acid binding and mediated via caspase-3
SIGLEC15 inhibits T cell function via myeloid cells but not by directly binding to T cells
ES012 is a high affinity anti-SIGLEC15 monoclonal antibody.
ES012 can rescue monocyte apoptosis and inhibit T cells by SIGLEC15.
ES012 showed superior anti-tumor efficacy and better PK profile than benchmark antibody in preclinical model
5. Title: ES005, a high affinity anti-LAG3 monoclonal antibody, inhibits the interactions between LAG3 and multiple ligands and enhances anti-tumor activity of T cells in preclinical models
Abstract No.: 426
LAG3 plays an important role in regulating immune homeostasis with multiple biological activities related to T cell functions. Anti-LAG3 mAb ES005 has demonstrated significant tumor growth inhibition in in vivo mouse tumor models, and showed excellent PK and safety profile in NHPs, indicating great potential to be used as next-generation immune checkpoint inhibitor in cancer treatment.
Highlights:
ES005 is a high affinity and cynomolgus reactive anti-LAG3 mAb
ES005 binds to a unique epitope on LAG3 D1 domain
ES005 potently blocks LAG3 binding to multiple ligands including FGL-1
ES005 effectively upregulates NFAT reporter gene transcription via blocking LAG3/MHC-II interaction
ES005 effectively reverses LAG3 driven inhibition of T cell activation
ES005 monotherapy potently inhibits tumor growth in EMT6 syngeneic tumor model
ES005 was well tolerated in cynomolgus monkeys with favorable PK Profile