Pipeline

Designed to overcome the inherent limitations of conventional conjugation approaches

Our pipeline consists of differentiated Engineered Precision Biologics (EPBs) discovered and developed using our proprietary expanded genetic code technology platform. EPBs can be designed to treat a broad range of diseases and disorders, with our initial internal focus on antibody drug conjugates (ADCs) and immuno-oncology conjugates (IOCs) for potential treatment of cancers with a high unmet medical need.

Ambrx ADC Oncology Programs

Anti-HER2 ADC (ARX788) — Oncology
Anti-PSMA ADC (ARX517) — Oncology
Anti-CD70 ADC (ARX305) — Oncology

Ambrx Immuno-oncology Programs

PEG-Cytokines (IL-2)
Anti-CD3 Folate Bi-Specific
TLR-agonist Antibody Conjugates
Bi-Specific Platform

ARX788

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.

ARX517

ARX517 targets the prostate-specific membrane antigen (PSMA) expressed on prostate cancer cells. PSMA is a clinically 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). We received clearance of our investigation new drug (IND) application for ARX517 from the FDA and plan to advance into clinical investigation.

ARX305

ARX305 targets CD70 on cancer cells. CD70 is overexpressed in a broad range of solid and hematologic tumors such as renal cell carcinoma (RCC), nasopharyngeal cancers, multiple myeloma, non-Hodgkin’s lymphoma and acute myeloid leukemia (AML). We are currently conducting IND-enabling studies to support potential future clinical investigation.

Our Immuno-Oncology Conjugates (IOC) Programs

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 three preclinical programs: ARX102, a long-acting “alpha-off” smart IL2 cytokine; ARX822, a CD3 bispecific directed towards the folate receptor of cancer cells; and our TLR7/8 ISAC program that stimulates the immune system. ARX102 and ARX822 are in IND-enabling studies. Our TLR7/8 ISAC program is in lead development, with a clinical candidate expected to be nominated this year.

Partnered Programs

Ambrx has a long track record of partnering with leading pharmaceutical companies, including Bristol Myers Squibb, AbbVie and Eli Lilly’s Animal Health. In addition to providing opportunities to validate our technology, these agreements provide non-dilutive capital through upfront and milestone payments. Ambrx will continue to evaluate partnership opportunities for its ADC and IOC programs on a case-by-case basis with biopharmaceutical companies possessing complementary capabilities.

BMS-986036 (Pegbelfermin) is a long-acting fibroblast growth factor 21 (FGF21) partnered with Bristol Myers Squibb and currently advancing in clinical development for potential treatment of metabolic conditions, including non-alcoholic fatty liver disease (NASH).

BMS-986259 is a next-generation version of Relaxin partnered with Bristol Myers Squibb and currently advancing in clinical development for potential treatment of acute heart failure.

CCW702 is a bispecific antibody targeting prostate cancer cells partnered with The Scripps Research Institute, and is subject to an option agreement with Abbvie.

Ambrx and Eli Lilly’s Animal Health division have a partnership to discover, develop and commercialize protein-based animal health products. Eli Lilly’s Animal Health division has marketed Imrestor™ for treatment of clinical mastitis in dairy cows, and is repurposing the product for additional indications.

Collaboration Programs (Partners are driving these programs)

PEG-FGF21 (BMS-986036) - NASH
FA-Relaxin (BMS-986259) – Acute Heart Failure
CD3-DUPA (CCW702) – Prostate Cancer
BeiGene Collaboration (multiple projects)
Sino Biopharmaceutical Collaboration (multiple projects)

Partners

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 bd@ambrx.com.

Bristol Myers Squibb

In September of 2011, Ambrx entered into a worldwide collaboration with Bristol Myers Squibb to develop and commercialize product candidates surrounding the Fibroblast Growth Factor 21 (FGF-21) protein, for potential use in treating metabolic condidtions, and the Relaxin hormone, for potential use in treating heart failure. Derivatives of FGF-21 and Relaxin were developed using Ambrx’s unique platform technology to modify the native proteins with amino acid building blocks beyond the 20 naturally occurring amino acids. Both programs are currently being evaluated in clinical development programs. Bristol Myers Squibb and Ambrx also entered into research collaborations for both programs, which focus on engineering enhanced versions of the two target proteins for therapeutic use. In May of 2013, Ambrx entered into a collaboration agreement with Bristol Myers Squibb for the discovery and development of novel antibody drug conjugates.

TSRI and Abbvie

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.

Zhejiang Medicine/NovoCodex

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.

Sino Biopharmaceutical

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.

BeiGene

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.