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 Portfolio
Pipeline
Robust Pipeline of Conditionally Active Biologic (CAB) Based Therapeutics
CAB Program
Target
Indications
IND Enabling
Phase 1
Phase 2
Anticipated Milestones
CAB-ADCs
BA3011
Mecbotamab Vedotin
AXL
- STS & Bone Sarcoma
- NSCLC
- Ovarian Cancer*
- Submitted Exposure-Response analysis to medical meeting (1H)
- Enrolling more frequent dosing regimens in NSCLC as part of Phase 2, part 1 (1H)
- Initiated UPS Phase 2, part 2 potentially registrational study (1H)
- Request FDA feedback re: Phase 2, part 2 NSCLC potentially registrational study design (1H)
- Receive FDA feedback re: Phase 2, part 2 NSCLC (2H)
- Initiate Phase 2, part 2 NSCLC potentially registrational study (2H)
- Phase 2 IIT interim data ovarian (2H)
BA3021
Ozuriftamab Vedotin
ROR2
- NSCLC
- Melanoma
- SCCHN
- Ovarian Cancer*
- FPI SCCHN Phase 2 (1H)
- Initiated NSCLC Phase 2 more frequent, dose intensive regimens (1H)
- Prioritize registration indications (2H)
- Phase 2 IIT interim data ovarian (2H)
BA3361
Next Gen
Nectin-4
- Multiple tumor types**
- IND submission 2023 / 2024
BA3151
Next Gen
B7-H4
- Multiple tumor types**
- IND submission TBD
CAB I/O
BA3071
CTLA-4
- Multiple tumor types**
- Phase 1 data (2H)
- Initiate Phase 2 (2H)
CAB-Bispecifics
BA3182
EpCAM & CD3
- Adenocarcinoma**
- Multiple tumor types**
- Phase 1 IND clearance (1H)
- Initiate Phase 1 (1H)
BA3142
B7-H3 & CD3
- Multiple tumor types**
- IND submission 2024
BA3311
EGFR & CD3
- Multiple tumor types**
- IND submission TBD
MABs
& ADCS
& ADCS
Other
Programs
Programs
Immuno-
oncology
oncology
Bispecifics
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.
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.
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-HER2-CAR-T
HER2 is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family. Amplification or over-expression of this oncogene has been shown to play an important role in the development and progression of certain aggressive types of breast cancer. In recent years the protein has become an important biomarker and target of therapy for approximately 30% of breast cancer patients. Amplification, also known as the over-expression of the ERBB2 gene, occurs in approximately 15-30% of breast cancer. It is strongly associated with increased disease recurrence and a poor prognosis; however, drug agents targeting HER2 in breast cancer have significantly positively altered the otherwise poor-prognosis natural history of HER2-positive breast cancer. Over-expression is also known to occur in ovarian, stomach, adenocarcinoma of the lung and aggressive forms of uterine cancer, such as uterine serous endometrial carcinoma, e.g. HER2 is over-expressed in approximately 7-34% of patients with gastric cancer and in 30% of salivary duct carcinomas.
With its elevated receptor copy number and relatively homogeneous expression following gene amplification, HER2 represents an attractive antigen to target via CAR-T; unfortunately, severe toxicity related to off-tumor binding of traditional CAR-T's to HER2 present in normal tissue may limit the use of traditional HER2 CAR-T therapy, To circumvent this issue Exuma developed a "logic-gated" HER2-targeted CAR-T based upon a HER2 CAB that preferentially recognizes HER2 in the tumor microenvironment, thereby limiting on-target toxicity of low HER2 levels expressed in normal tissue.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.
BA3142
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-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.
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.
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
