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.
CAB Portfolio
Pipeline
Robust Pipeline of Conditionally Active Biologic (CAB) Based Therapeutics
CAB Program
Target
Indications
IND Enabling
Phase 1
Phase 2
CAB-ADCs
BA3011
Mecbotamab Vedotin
AXL
- UPS
- NSCLC
BA3021
Ozuriftamab Vedotin
ROR2
- Melanoma
- SCCHN
CAB I/O
BA3071
Evalstotug
CTLA-4
- Melanoma
- NSCLC
- Carcinomas
CAB-Bispecifics
EpCAM & CD3
- Adenocarcinomas
Next Gen CAB-ADC
Nectin-4
- Multiple tumor types
ADCs
Next-Gen
CAB-ADC
CAB-ADC
Immuno-
oncology
oncology
Bispecifics
Pipeline
Antibody Drug Conjugates
Mecbotamab Vedotin
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. BA3011 is being evaluated both as monotherapy and in combination with a PD-1 inhibitor (nivolumab) in patients with AXL-expressing sarcoma, non-small cell lung cancer (NSCLC) and ovarian cancer.
Ozuriftamab Vedotin
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.
BioAtla's CAB anti-ROR2 ADC is engineered to selectively bind tumor cells expressing the ROR2 protein and avoid binding to normal tissue expressing this protein. BA3021 is being evaluated both as monotherapy and in combination with a PD-1 inhibitor (nivolumab) in patients with ROR2-expressing melanoma, non-small cell lung cancer (NSCLC) and ovarian cancer.
Next Gen CAB-ADC
BioAtla©'s NextGen CAB antibody drug conjugates (CAB ADCs) combine the advantages of a tumor-targeting, conditionally active antibody with an ultra-stable, glycosidase cleavable linker. The attachment group of the linker is inert to transfer to another molecule (retro-Michael addition). The glycosidase-based cleavage maximizes payload release in the tumor. This powerful new combination of our CAB technology with our novel linker technology takes ADCs to the next level, making them safer and more effective.
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.
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.
BA3071
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.
BA3182
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.
Robust Pipeline of Conditionally Active Biologic (CAB) Based Therapeutics
Program
Target
IND Enabling
Pre-Clinical
Phase 1
Clinical
Phase 2
Lead Indications
BA3011
Mecbotamab Vedotin
AXL
- STS & Bone Sarcoma
- NSCLC
- Ovarian Cancer*
(Mono & Combo w/ PD-1)
BA3021
Ozuriftamab Vedotin
ROR2
- NSCLC
- Melanoma
- HNC
- Ovarian Cancer*
(Mono & Combo w/ PD-1)
BA3071
Naked Antibody
CTLA-4
- RCC
- NSCLC / SCLC
- HCC
- Melanoma
- Bladder
- Gastric
- Cervical Cancer
BA3182
Bispecific
EpCAM & CD3
- Colorectal
- NSCLC / SCLC
- Ovarian
- Prostate Cancer**
- TNBC
BA3142
Bispecific
B7-H3 & CD3
- HNC
- Melanoma
- NSCLC / SCLC
- Pancreatic
- Prostate Cancer**
- Sarcoma
BA3361
2nd Gen ADC
Nectin-4
- Coloractal Cancer**
- HNC
- NSCLC
- Pancreatic
- TNBC
BA3151
2nd Gen ADC
B7-H4
- Breast
- Colon
- Kidney
- Ovary
- Prostate
BA3311
Bispecific
EGFR & CD3
- Bladder
- Pancreatic Cancer**
- TNBC
*Ph2 investigator-initiated trial for Ovarian Cancer** Anticipated indications based upon tumor target expression
Abbreviations: STS = Soft Tissue Sarcoma, NSCLC = Non-small Cell Lung Cancer, RCC = Renal Cell Carcinoma, SCLC = Small Cell Lung Cancer, HCC = Hepatocellular Carcinoma, TNBC = Triple-Negative Breast Cancer, HNC = Head and Neck Cancer
