The Biocytogen team concluded a successful SITC 2023 event this past weekend, after presenting 9 drug asset posters, 7 genetically engineered mouse model posters, and connecting with current and prospective clients at booth 223. Summarized below are the highlights presented from each product/research area:
Bispecific ADC Assets
Advantages of BsADCs
Biocytogen’s R&D team developed a series of fully human bispecific antibodies (bsAbs) with multi-species cross reactivity from our proprietary fully human common light chain antibody RenLite® mice. These bsAbs were subsequently assembled into bispecific ADCs (bsADCs), which have distinct advantages over monoclonal ADCs, including enhanced internalization, improving payload enrichment in heterogeneous tumors and achieving broader killing of tumors with varying levels of dual-target expression.
Introduction of a proprietary payload
In addition to prior work evaluating vcMMAE-conjugated bsADCs, SITC 2023 posters disclosed the most recent data of Biocytogen’s proprietary novel DNA topoisomerase I inhibitor payload and cleavable linker system (BLD1102). Preclinical research indicated that BLD1102 has excellent hydrophilicity, good in vivo and in vitro stability, efficient intratumoral payload release, broad tumor killing capacity, and powerful bystander killing. Many BLD1102-conjugated bsADCs exhibited strong tumor killing effects in a variety of solid tumor models, including Dxd and MMAE-resistant models. All of the above results indicate that the BLD1102 bsADCs could be next-generation ADC therapeutics that provide new treatment options for many types of solid tumors.
BsADC Asset Posters:
Poster 1152: *DM001, a novel TROP2xEGFR bispecific ADC, demonstrates potent tumor growth inhibition in preclinical models and favorable safety profile in cynomolgus monkey
The poster characterized the novel BLD1102 linker/payload system in DM001 bsADC. By targeting pan-cancer TAAs of TROP2 and EGFR, DM001 demonstrated potent in vivo and in vitro tumor killing capabilities in a number of solid tumor PDX models, especially for gastric cancer and both EGFRm and EGFRwt NSCLC xenografts. Pilot toxicity study showed that DM001 is well tolerated in non-human primates. DM001 is under preclinical investigation for IND filing.
Poster 1165: Preclinical evaluation of fully human bispecific antibody-drug candidates targeting HER3 and the juxtamembrane region of MUC1
HER3 and MUC1 targeting ADC drugs have limited clinical effectiveness. Dual targeting of HER3 and MUC1-C are expected to improve anti-tumor activity and avoid the drug neutralization by shed MUC1. DM002-vcMMAE is effective in HER3-low PDX models and DM002-BLD1102 showed effective tumor killing in DM002-vcMMAE/DM002-Dxd resistant PDX models. In addition, DM002-BLD1102 showed excellant anti-tumor activity in refractory colorectal PDX models.
Poster 1150: *DM005, an EGFR х MET bispecific antibody-drug conjugate with a novel DNA
topoisomerase I inhibitor payload, showed robust anti-tumor activity in preclinical models
DM005 is a bsADC targeting EGFR and MET conjugated with BLD1102. Preclinical in vivo studies demonstrated DM005’s potent tumor killing effects in multiple NSCLC (regardless of EGFRm or EGFRwt) and head & neck cancer CDX and/or PDX models. DM005 is under preclinical investigation for IND filing.
Poster 1164: BSA01, a bispecific antibody-drug conjugate targeting EGFR and membrane-bound MUC1-C, exhibits anti-tumor efficacy in vivo
BSA01’s MUC1 arm targets the unique epitope of MUC1 that enhance tumor cell binding and avoid being neutralized by shed MUC1. The EGFR arm was selected to have good tumor selectivity to reduce the toxicity on EGFR expressing normal tissues. BSA01 is effective in EGFR/MUC1 double positive CDX models regardless of their expression levels. In addition, they demonstrated superior anti-tumor activities then benchmark ADCs in multiple PDX models, including NSCLC, ampullary and pancreatic cancers. BSA01 is under CMC development.
Poster 1153: BCG022: A HER3×MET bispecific antibody-drug conjugate (BsADC) targeting key mechanisms of bypass resistance in multiple tumor types
HER3 overexpression can lead to the resistance of EGFR and HER2 targeted therapies. MET overexpression is also one of the bypass mechanisms of EGFR-TKI therapy. Dual targeting of HER3 and MET may overcome the resistance and provide new treatment options. BCG022-BLD1102 showed stronger anti-tumor activity than benchmark ADC in gastric cancer PDX.
Poster 1163: A novel bispecific antibody-drug conjugate targeting PTK7 and TROP2, BCG033, demonstrates preclinical efficacy against triple-negative breast cancer xenografts
As an emerging TAA, PTK7 is overexpressed in multiple solid tumors similar to TROP2. BCG033-vcMMAE candidates target PTK7 and TROP2. They showed more potent anti-tumor activity in TNBC and NSCLC PDX models. BCG033-BLD1102 are effective in benchmark ADC resistant colorectal cancer PDX model. BCG033 is expected to be a new treatment option for PTK7/TROP2 co-expressing solid tumors. BCG033-BLD1102 is under further development.
Fully human TCR-mimic antibody assets
Using our novel RenMice-based RenTCR-mimicTM platform, we screened out KRAS G12V7-16 fully human antibodies complexed with different HLA types. KRAS G12V/HLA-A03 antibodies have excellent specificity and the bispecific T cell engager assembled with CD3 nanobodies showed good in vitro killing activity. In another project, we screened out highly specific NY-ESO-1/HLA-A02 fully human antibodies which demonstrated good in vitro and in vivo anti-tumor activity when assembled into TCRm-T cell therapy.
Fully Human TCRmimic Asset Posters:
Poster 1168: Identification of fully human TCR-mimic antibodies targeting the KRAS G12V/HLA complex generated in HLA-transgenic RenMabTM mice
Poster 356: Preclinical application of a fully human TCR-mimic antibody developed to target NY-ESO-1/HLA-A02
Fully human monoclonal antibody asset poster
Our TIGIT blocking fully human IgG1 antibodies generated from RenMab mice have unique binding epitopes, good physiochemical properties and superior in vivo efficacy when compared to a benchmark antibody.
Poster 479: Fc-competent fully human anti-TIGIT blocking monoclonal antibodies demonstrated potent anti-tumor efficacy in preclinical models
Several exciting new animal models were introduced at SITC that can be used for testing novel immunotherapies:
Off-the-Shelf Mouse Models - Humanized Mice
Mouse models: B-hCD98HC
Poster titles13: Development of a preclinical CD98HC mouse model for therapeutic studies
Mouse models: B-hGARP/hTGFB1
Poster titles18: Generation and validation of humanized GARP/TGFB1 mice for testing novel anti-human GARP antibodies
Mouse models: B-hCD200/hCD200R
Poster titles12: Humanized CD200/CD200R mice as a tool for evaluating novel therapeutics
Mouse models: B-hICOS
Poster titles11: Humanized ICOS mice as a novel tool for predicting and monitoring T-cell-mediated immunotherapy response
Poster titles17: Humanized NKP46 mouse models for testing novel NK cell-based immunotherapies
Poster titles19: Preclinical CD3-based mouse models for evaluation of bi-specific T-cell engager antibodies
Off-the-Shelf Mouse Models - Immunodeficient Target Humanized Mice
Mouse models: B-NDG B2m plus/hIL15 mice
Poster titles16: A novel B2m-deficient immunodeficient model expressing human IL-15 for preclinical evaluation of T cell and NK cell-based therapies
For more information, contact us:
Antibody assets: BD-Licensing@biocytogen.com
BioMice modes: email@example.com