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KDDF-201812-23 Development of B7-H3 Targeting Antibody-Drug Conjugate in Non-Small-Cell Lung Cancer(Oncology, Protein) [2019-06-24]

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Ongoing Project
Section Lead
Generation
Lead
Optimization
Preclinical Phase I Phase II Phase III

Development and Market Objectives

B7-H3 is a newly discovered immune checkpoint target which is overexpressed in many solid cancers and linked to poor prognosis, metastasis, resistance to therapy, and decreased overall survival.

Anti PD-1 immunotherapy improves survival in NSCLC, but some cases are refractory to treatment, thereby requiring alternative strategies. B7-H3 expression is evident in 74% of NSCLCs and correlated critically with non-responsiveness to anti-PD-1 immunotherapy. NSCLCs lacking B7-H3 expression were highly susceptible to anti-PD-1 therapy.

Antibody-drug conjugates (ADCs), a novel therapeutic application, combine specificity of mAbs and potent cell killing activity of small molecule drugs. A novel B7-H3 ADC will be generated and optimized using OHPAS technology, a proprietary linker platform developed by IntoCell. Preclinical candidate of B7-H3 ADC will be selected after exploring its NSCLC targeting potential.

Unmet Medical Need & Target Patients

Lung cancer has the highest incidence rate and 85% of lung cancer patients are classified as NSCLC. The 10-year survival rate of lung cancer patients is less than 10%.

Current first-line treatment decisions for advanced NSCLC are based on the presence of genetic aberrations, such as sensitizing mutations of EGFR and translocations of ALK. However, most patients with NSCLC do not harbor these oncogenic drivers, and for these patients, treatment options are limited cytotoxic chemotherapy.

Anti-PD-1 and anti-PD-L1 antibodies produced durable responses in approximately 20% of unselected patients with advanced NSCLC. They only benefit a fraction of patients and there is urgent need for novel NSCLC treatments.

Status

Novel B7-H3 targeting antibodies were developed by Y-Biologics, a joint research company.

Novel B7-H3 ADCs were generated by conjugating lead antibody to various drug payloads with OHPAS linker technology.

The resulting ADCs showed very potent activity against B7-H3 positive cancer cells.

In vivo POC of B7-H3 ADCs was confirmed in human breast cancer mouse xenograft model (JIMT-1, B7-H3 overexpressed).

Intellectual Property

Patent applications were submitted for novel OHPAS linker and benzodiazepine payloads.

Key OHPAS patent has been published in Korea as of January 2019 and has been filed in USA, PCT (Application No. KR 10-2018-0076708 ; PCT/IB2018/000847 ; US 62/597,226).

B7-H3 ADC patent will be applied after lead ADCs are selected.

Competitive Advantages

Novel self-immolative OHPAS linker and ultra-potent benzodiazepine payload technologies are employed in B7-H3 ADCs.

  - highly stable in chemical and biological environment

  - efficiently liberating appended payload in target cancer cells and demonstrating excellent potencies in vivo

  - possibly able to broaden the therapeutic window by avoiding premature payload release in circulation

  - Site-specifically drug conjugated

Contact & Company Overview

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