Powerful biology, transformative impact.

Hyperemesis Gravidarum (HG), a rare, debilitating condition of pregnancy, is characterized by intractable nausea and vomiting, which can be as frequent as 10 to 15 times per day and results in dehydration, debility, weight loss and malnutrition. HG has a significant physical and psychosocial impact on patients and leads to overall higher rates of fetal loss and termination, preeclampsia, preterm birth, low birth weight, fetal malnutrition, maternal depression, and in some cases, suicidal thoughts. HG is the leading cause of hospitalization in early pregnancy and typically recurs in subsequent pregnancies. There are no approved therapies that target the underlying cause of HG.

Although GDF15 is a hormone that everyone produces, levels of GDF15 are higher in pregnant women and can be even higher in women with HG. The extremely high levels of GDF15 are believed to cause the nausea and vomiting that are hallmarks of HG. NGM120 is an antibody designed to bind to the receptor (known as GFRAL) for GDF15. This binding blocks the interaction of GDF15 with GFRAL, which, in turn, inhibits the activity of GDF15, potentially alleviating HG symptoms.

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NGM120 has been generally well-tolerated in over 200 participants treated in clinical trials to date.

GDF15 = growth differentiation factor 15
GFRAL = glial cell-derived neurotrophic factor receptor alpha-like

Defined by >5% weight loss, cachexia is a complex, multifactorial, multi-organ complication of cancer and several other chronic diseases. Up to 80% of advanced cancer patients are cachectic, and 30% of cancer deaths list cachexia as the primary cause. Cachexia may be a key factor for cancer treatments being ineffective or intolerable to patients.

GDF15 is a hormone that everyone produces, but elevated levels of GDF15 have been identified as the top risk factor associated with cachexia. The GDF15 pathway has been clinically validated as a potential therapeutic approach for patients with this condition. There are no approved therapies for treating cancer cachexia in the US or Europe.

NGM120 is an antibody designed to bind to the receptor (known as GFRAL) for GDF15. This binding blocks the interaction of GDF15 with GFRAL, which, in turn, inhibits the activity of GDF15. Thus, NGM120 has the potential to be a novel treatment targeting an underlying cause of cancer cachexia.

NGM is enrolling patients in a Phase 2 proof-of-concept study of NGM120 as a treatment for cancer cachexia.

United States

GDF15 = growth differentiation factor 15
GFRAL = glial cell-derived neurotrophic factor receptor alpha-like

Antibody drug conjugates (ADCs) – comprising a tumor-associated antigen (TAA)-directed antibody joined to a cytotoxic payload through a chemical linker – are an increasingly important anti-cancer therapeutic class.

For many cancer types, including gastrointestinal and thoracic cancers, the identification of optimal TAAs has been challenging. Numerous TAAs that are highly expressed in these tumors have shown limited efficacy as ADC targets due to poor internalization which, in turn, hampers payload delivery.

NGM’s proprietary, next-generation ADC program – RI-ACT™ – combines the power of ADCs with bispecific antibodies to enhance anti-cancer activity through improved internalization efficiency.

Rapidly internalized receptors (RIR) are trafficked between the cell surface and endocytic vesicles, which are responsible for transporting molecules into a cell. Our Bispecific RI-ACTs first bind to the TAA arm (i.e., the “address” for the cancer cell) and then bind to the RIR arm, which pulls the ADC into the cell, improving cytotoxic payload delivery.

In preclinical studies, our RI-ACTs have demonstrated enhanced internalization efficiency, tumor cell killing and in vivo efficacy relative to clinical benchmarks.

NGM936 is a bispecific T cell engager targeting ILT3 (LILRB4), a highly restricted marker of monocytic acute myeloid leukemia (AML). ILT3 is also expressed on malignant and autoantibody-producing plasma cells and may have therapeutic application for the treatment of multiple myeloma (MM) and other autoantibody-driven autoimmune diseases. NGM936 was engineered to induce potent T cell-dependent cytotoxicity while minimizing cytokine release. 

NGM936 shows potent depletion of tumor cells and autoantibody-secreting plasma cells in humanized mouse models of AML, MM, and autoimmune disease. 

A novel dual antagonist antibody inhibiting ILT2 and ILT4, NGM707 is being advanced by NGM with the goal of improving patient immune responses to tumors.

NGM completed enrollment in a Phase 1/2 study of NGM707 for the treatment of advanced solid tumors.