Designed for highly stable, site-specific conjugation, overcoming the inherent limitations of conventional conjugation
Our most advanced internal candidate is ARX788, an anti-HER2 ADC currently being studied broadly in breast cancer, gastric/GEJ cancer and other solid tumor clinical trials. The United States Food and Drug Administration (FDA) has granted Fast Track Designation for ARX788 in HER2+ metastatic breast cancer and Orphan Drug Designation for ARX788 in gastric cancer.
ARX788 is a homogeneous and highly stable ADC, which targets the HER2 receptor and contains two AS269 cytotoxic payloads site-specifically conjugated to a trastuzumab-based antibody. ARX788 was designed to maximize potential anti-tumor activity by optimizing the number and position of the payloads and the chemical bonds that conjugate the payloads to the antibody. AS269, our proprietary payload, is a tubulin inhibitor specifically designed to form a highly stable covalent bond with our SAAs and kill tumor cells only upon entry into the cell when aided by the conjugated targeting antibody, thereby limiting off-target effects on healthy tissue.
Our lead internal asset ARX517 targets the prostate-specific membrane antigen (PSMA) expressed on prostate cancer cells. PSMA is a clinically validated target and important biomarker of prostate cancer which is highly over-expressed in metastatic castration-resistant prostate cancer (mCRPC), as well as in solid tumors (such as pancreatic, non-small cell lung cancer (NSCLC) and ovarian). Prostate cancer represents a significant unmet medical need with 1.4 million annual new cases worldwide and a $9.9 billion treatment market (2020). ARX517 has the potential to be the first PSMA-targeted ADC. We initiated a Phase 1 clinical trial for ARX517 and anticipate interim Phase 1 safety data in 2H 2023.
ARX305 targets CD70 on cancer cells. CD70 is overexpressed in a broad range of solid and hematologic tumors such as nasopharyngeal cancers, multiple myeloma, non-Hodgkin’s lymphoma and acute myeloid leukemia (AML). CD70 expression is 70% in RCC, providing a great opportunity to assess safety and efficacy of ARX305.
The IND application for ARX305 received clearance from the FDA and we intend to advance to a Phase 1 clinical trial in 2023, subject to positive data from our development partner NovoCodex Biopharmaceuticals that will inform our internal trial.
IOC therapies harness the power of the body’s immune system to treat cancer. Unlike ADCs that use an antibody to deliver a cytotoxic payload to a cancer cell, IOCs modulate and direct the immune system, triggering a cascade reaction that kills cancer cells. We believe our IOC product candidates are complementary and synergistic to our ADC franchise for treating cancer.
Our IOC franchise is comprised of a preclinical program: ARX102, a long-acting “alpha-off” smart IL2 cytokine. We anticipate submitting an IND to the FDA in 2024, subject to positive data from our development partner Sino Biopharmaceuticals that will inform our internal trial.
Ambrx has a long track record of partnering with leading pharmaceutical companies to apply its technology platform to create Engineered Precision Biologics for broad therapeutic applications. Ambrx evaluates partnership opportunities for its ADC and IOC programs and platform with biopharmaceutical companies possessing complementary capabilities. For more information, please contact firstname.lastname@example.org.
In August 2013, we entered into a collaborative license agreement with the California Institute for Biomedical Research (which later merged with The Scripps Research Institute) that secured a license to CCW702, a bispecific targeting prostate cancer cells. TSRI subsequently licensed the global rights to develop CCW702 to Abbvie in an option agreement.
In June of 2013 Ambrx entered into a collaboration with Zhejiang Medicine Co., Ltd., which was transferred to NovoCodex, to develop and commercialize ARX788, Ambrx’s most advanced internally developed site-specific ADC targeting HER2-positive breast cancer. Under the agreement, Ambrx and ZMC will continue the development of ARX788. ZMC received commercial rights in China while Ambrx retained commercial rights outside of China and receives royalties on sales of the product in China.
In January 2020, Ambrx entered into a co-development and license agreement with Sino Biopharmaceutical for two Engineered Precision Biologics. Sino Biopharmaceutical was granted rights for development and commercialization of the two programs in China and specific additional territories, and Ambrx retains rights for the rest of the world.
In March 2019, Ambrx entered into an agreement with BeiGene focused on advancing next-generation biologic therapeutics. The partnership combines Ambrx’s technologies for site-specific modification of proteins and incorporation of non-natural amino acids into proteins with BeiGene’s expertise in innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer.