Bi-specific humanized antibody against Endosialin and LGALS3BP

Endosialin (aka TEM1 and CD248) is a protein expressed by pericytes of tumor blood vessels and directly on a subset of malignant cells. Blocking Endosialin with antibodies has been shown to inhibit tumor growth and metastasis.

LGALS3BP is a a protein secreted at large amounts by the vast majority of tumor cells, which plays an important role in cell-cell and cell-extracellular matrix adhesion and, recently, as a pro-angiogenic factor.

Use of a bi-specific antibody against Endosialin and LGALS3BP may result in a greater anti-angiogenic and anti-tumor effect than either antibody alone.

HER3-ADC Antibody-Drug Conjugate

MediaPharma’s scientists have generated a novel anti-HER-3 Antibody-Drug Conjugate (HER3-ADC). It consists of a humanized anti-HER3 monoclonal antibody (EV20) conjugated to highly potent payloads by means of a linker. In HER3 expressing cancer cell lines, this HER3-ADC shows a picomolar, specific and target-dependent killing activity. Administration of  HER3-ADC was effective in inducing a long lasting tumor growth inhibition of several tumor cell line-based xenografts.

Indications in oncology:

Cancers overexpressing HER-3 arising from breast (including those resistant to Trastuzumab and T-DM1), stomach, prostate, ovary, lung,  head & neck, ovary, pancreas, colorectum. melanoma and neuroblastoma.

Endosialin (TEM1) Antibody-Drug Conjugate

The Endosialin/TEM1/CD248 receptor is expressed in the cell surface of tumor-associated stroma cells, as well as in sarcoma and neuroblastoma cells. This receptor is emerging as an attractive molecule in diagnostics and therapeutics because of its expression across the stroma of many human tumors, the low to absent expression in normal tissues and accessibility from the vascular circulation.

MediaPharma’s scientists have generated a novel anti-Endosialin Antibody-Drug Conjugate (ENDOS-ADC). It consists of a humanized anti-Endosialin monoclonal antibody (E.8-3) conjugated to a highly potent duocarmycin derivative by means of a linker. In TEM-1 expressing cancer cell lines, this ENDOS-ADC shows a powerful, specific and target-dependent killing activity. Aministration of  ENDOS-ADC was effective in inducing a long lasting tumor growth inhibition of cell line-based models of human sarcoma.

Indications in oncology:

Sarcoma, melanoma, neuroblastoma, colorectal carcinoma

EV20 labeled with ⁸⁹Zr

Preclinical proof of activity established: in vivo localization of HER3+ human tumor xenografts.

Indications in Oncology
In vivo localization of HER3-expressing cancer by immuno-PET.

Humanized bispecific antibody against HER3 and LGALS3BP

• Humanized bispecific antibody against HER3 and LGALS3BP
• Preclinical proof of efficacy established: inhibition of HER3 activation/downstream signaling in various tumor cell lines and inhibition of capillary-like structures in HUVEC
• Indications in Oncology: cancers whose growth and progression depend on HER3 and LGALS3BP-promoted angiogenesis, including but not limited to those arising from breast, prostrate, ovary, lung, pancreas, stomach and melanoma.

Humanized Anti-Gal-3 BP Antibody-Drug Conjugate

MP-1959 is the humanized version of the murine monoclonal antibody SP-2 which recognizes Gal-3 BP (also known as LGALS3BP, 90K or Mac-2 BP), a glycoprotein secreted in large amounts by the majority of tumor cells, which plays an important role in cell-cell and cell-extracellular matrix adhesion and tumor invasion. In addition, Gal-3 BP functions as a pro-angiogenic factor through a dual mechanism, i.e by induction of tumor VEGF and stimulation of endothelial cell tubulogenesis, which is inhibited by MP-SP2/1959.

MediaPharma’s scientists have generated a non-internalizing anti-Gal-3 BP Antibody-Drug Conjugate (LGS-ADC). It consists of a humanized, engineered anti-Gal-3 BP monoclonal antibody (1959-sss) directly conjugated to highly potent maytansinoids (DM3 & DM4) via a disulfide bond to residual cysteine of the antibody light chain.  Administration of  LGS-ADC was effective in inducing a long lasting tumor shrinkage of tumor cell line-based melanoma xenografts.

Indications in Oncology: cancers overexpressing Gal-3 BP, including those arising from breast, prostrate, ovary, pancreas, lung. melanoma, glioblastoma and neuroblastoma

Humanized Anti HER-3 Antibody

EV-20 is a humanized monoclonal antibody against HER3 (human epidermal growth factor receptor 3,
also known as ErbB-3).

EV-20 inhibits both ligand-dependent/-independent HER3 activation and downstream signaling as well as formation of HER3/HER2 dimers; it rapidly and efficiently internalizes into HER3 expressing tumor cells following receptor binding.

EV20 treatment  (10 mg/Kg) leads to a long lasting tumor growth delay of several cell line-based xenografts models.

Indications in Oncology: cancers whose growth and progression depend on HER3, including those arising from breast, stomach, pancreas, ovary, prostate, lung, colorectum, head and neck and melanoma.