CAB Portfolio

MABs
& ADCS
Other
Programs
Immuno-
oncology
Bispecifics
cab-portfolio-wheel-panel-icon
Pipeline
Naked mAbs & Antibody Drug Conjugates
CAB-ADC antibodies aim to address the inherent limitations of current ADC antibody technology by actively binding to antigens expressed on cancer cells, but not to the same antigens expressed on normal cells in non-diseased tissues. This approach allows the preferential targeting of tumor tissues by ADCs, thereby increasing the efficacy to toxicity ratios (Therapeutic Index) of CAB-ADCs relative to their conventional counterparts. The use of CAB antibodies as payload delivery vehicles could dramatically increase the safety and number of tumor-associated antigens that are addressable with ADC technology.

Naked monoclonal antibodies or mAbs bind to specific epitopes or target molecules on cells.  Therapeutic uses of mAbs have been limited by several factors, including cancer cell specificity, tumor penetration, as well as manufacturing issues.  BioAtla’s human CAB mAbs are optimized and expressed in our proprietary CIAO! system.  CAB mAbs have a high Therapeutic Index because they are only active under the physiological conditions associated with disease.  This unique capability enables development of therapeutics for targets that are also expressed on healthy tissues, while minimizing undesirable side effects. 

CAB-AXL
AXL is a receptor tyrosine kinase and oncogene involved in the stimulation of cell proliferation and associated with a variety of cancers including pancreatic, colon cancer, melanoma, CML and others. Like many cancer targets AXL is over-expressed in cancer but can also be found in some normal tissues, which would cause toxicity if treated with conventional Antibody Drug Conjugates (ADC’s). BioAtla’s CAB anti-AXL ADC however specifically targets the tumor microenvironment, reducing toxicity in normal tissue.
Representative Cancer Indications
  • NSCLC
  • Breast
  • Pancreatic
  • Ovarian
  • Prostate
  • Esophageal
  • Liver
  • AML
CAB-ROR2
ROR2 is a receptor tyrosine kinase involved in Wnt signal transduction and thus in embryonic development and cancer. It is associated with cancers including osteosarcoma, melanoma, renal cell carcinoma, gastrointestinal stromal tumor (GIST), colorectal cancer, pancreatic ductal adenocarcinoma, and NSCLC. In many cancer types expression of ROR2 correlates with advanced stage of disease or poor prognosis.
Representative Cancer Indications
  • Osteosarcoma
  • Melanoma Renal Cell
  • Carcinoma
  • Gastrointestinal Stromal
  • Tumor (GIST)
  • Colorectal
  • Pancreatic
  • NSCLC
Other Programs
BioAtla’s partner Exuma Biotechnology is developing conditionally active Chimeric Antigen Receptor-T cell (CAR-T) therapies engineered by grafting single-chain variable fragments (scFv) from a Conditionally Active Biologic (CAB) antibody to a proprietary T cell signaling domain. These fusion molecules trigger T cell recognition and killing of cells expressing the cancer target in the tumor microenvironment. We believe the improved tumor specificity of these CAB-based CAR-Ts will improve their safety profile and ultimately help enable CAR-T treatment of solid tumors.
CAB-AXL-CAR-T
AXL is a receptor tyrosine kinase and oncogene involved in the stimulation of cell proliferation and associated with a variety of cancers including pancreatic, colon cancer, melanoma, CML and others. Like many cancer targets AXL is over-expressed in cancer but can also be found in some normal tissues, which could cause toxicity if treated with a conventional AXL-CAR-T therapy. The CAB-AXL portion of F1 Oncology’s CAB-AXL-CAR-T however will enable specific targeting of AXL in the tumor microenvironment, and enhanced therapeutic window.
CAB-ROR2-CAR-T
ROR2 is a receptor tyrosine kinase involved in Wnt signal transduction and thus in embryonic development and cancer. It is associated with cancers including osteosarcoma, melanoma, renal cell carcinoma, gastrointestinal stromal tumor (GIST), colorectal cancer, pancreatic ductal adenocarcinoma, and NSCLC. In many cancer types expression of ROR2 correlates with advanced stage of disease or poor prognosis.
Immune Checkpoint Inhibitors
BioAtla®’s CAB immune Checkpoint inhibitors and stimulators (CAB-C’s) are engineered to target either immune cells or tumor cells. CAB-C’s are active in selected microenvironments within the body and prevent tumor cells from inhibiting immune cells, thereby enabling the body's immune cells to remain activated. These activated immune cells can shrink the tumor, individually or in combination with other drugs, and may eradicate the cancer.
CAB-CTLA4
Cytotoxic T Lymphocyte Associated Protein-4 (CTLA-4) is a receptor on the surface of helper T cells that binds CD80 and CD86 on antigen presenting cells, transmitting an inhibitory signal to T cells. By reversing this inhibition anti-CTLA-4 antibodies have been shown to have great benefit in treating cancer, but can also cause toxicity by activating T cells generally, especially in combination with other immune checkpoint antibodies. BioAtla’s CAB-CTLA4 antibody helps target this activation to the tumor microenvironment, reducing on-target toxicity and enabling more powerful and safer combination therapies.
Representative Cancer Indications
  • Non Small Cell Lung Cancer (NSCLC)
  • Melanoma
Bispecifics
We have also leveraged our CAB technology to develop bispecific antibodies, which bind both a tumor-specific antigen and a T cell receptor using CAB antigen-binding domains. A bispecific antibody is a type of engineered antibody that can simultaneously bind two separate and unique antigens, unlike conventional monospecific antibodies that only bind to one type of target. This is a powerful approach to harness cytotoxic T cells to directly kill tumor cells with reduced toxicity. We have shown in preclinical experiments that our CAB bispecific molecules meet or exceed the activity of conventional bispecifics and reduce systemic activation of potentially fatal immune responses.
CAB-EpCAM
Epithelial Cell Adhesion Molecule or EpCAM is highly expressed in adenocarcinomas in the lung, colon, ovaries, prostate and breast. Epithelial cell proliferation is driven through EpCAM signal transduction. EpCAM is also expressed in virtually all epithelia containing tissues. Loss of function in these tissues causes significant pathology and morbidity, thus a lack of selectivity would make EpCAM a difficult target for traditional antibodies or ADC’s, but an ideal target for a CAB bispecific.
CAB-B7-H3
B7-H3 is a member of the B7/CD28 superfamily of immune checkpoint molecules. Overexpression of B7-H3 in numerous cancer types has been shown to be correlated with advanced tumor stage and high tumor grade. B7-H3 has possible roles in regulating cancer metabolism, protein regulation, cell proliferation, and epithelial-mesenchymal transition. There is high expression of B7-H3 across many different solid tumors including head and neck, lung, melanoma, pancreatic, prostate and sarcoma. B7-H3 is overexpressed on many solid cancers and seems to display high tumor-versus-normal tissue binding differential. B7-H3 overexpression has been correlated with disease severity and poor outcome in many cancer types.
CAB-EGFR
The EGFR RPTK is a validated target in colon and lung cancers. Current modalities include naked antibodies and TKI’s, with CAR-T and bispecifics in development. There is resistance to EGFR inhibitors due to mutations in KRAS and BRAF signal transduction. Over 50% EGFR positive cancers are not addressed by currently approved EGFR inhibitors. EGFR is ubiquitously expressed on normal epithelial tissues, including the skin and gastrointestinal mucosa. Traditional EGFR inhibitors cause skin and GI toxicity. A CAB Bispecific approach will address this unmet medical need.
CAB-Nectin4
Nectins and Nectin-like molecules (Necl) are families of cellular adhesion molecules involved in Ca2+-independent cellular adhesion. Nectins are ubiquitously expressed and have adhesive roles in a wide range of tissues such as the adherens junction of epithelia or the chemical synapse of the neuronal tissue. Nectin4 is a significant prognostic predictor and may play a mechanistic role in pancreatic cancer progression. Nectin4 is a target for adenocarcinomas in general.
Robust Pipeline of Antibody Based Therapeutics
CAB Program Target Initial Indications Discovery IND Enabling Phase 1 Pivotal Upcoming Milestones
BA3011
(AXL-ADC)
AXL Positive STS & Bone Sarcoma, Lung, Ovarian
(Mono & Combo w/PD-1)
  • Ph2 interim data 2021
  • Ph2 registration data 2022
BA3021
(ROR2-ADC)
ROR2 Positive Lung. Melanoma
(Mono & Combo w PD-1)
  • Ph2 interim data 2021
  • Ph2 registration data 2022
BA3071
(CTLA4)
CTLA4 Liver, Renal, Lung, Melanoma, Bladder, Gastric, Cervical (Mono & Combo w/PD-1)
  • Ph1 dose-escalation initiated 2020
  • Ph1 data 2021
BA3182
(EpCAM-Bispecific)
EpCAM/CD3 Lung, Colon, Ovarian, Prostate, Breast
  • Potential US IND 2H 2021
B7-H3
(Bispecific)
B7-H3/CD3 Lung, Head & Neck, Melanoma, Sarcoma, Pancreatic, Prostate
  • Potential US IND 2022
EGFR
(Bispecific)
EGFR/CD3 Lung, Head & Neck, Pancreatic, Breast, Colon
  • Potential US IND 2022
Nectin-4
(Bispecific)
Nectin-4/CD3 Bladder, Breast, Pancreatic
  • Potential US IND 2022