AREAS OF FOCUS
Uncovering novel biologic insights for a spectrum of diseases
Since our founding in 2008, we have uncovered novel biological insights underlying several therapeutic areas including cardio-metabolic, liver, oncologic and ophthalmic diseases. We have already advanced several candidates to the clinic and continue to progress myriad research programs.
Our Areas of Focus
Cardio-Metabolic and Liver Diseases
Initial Diseases of Focus: NASH, Type 2 Diabetes and Obesity
The Unmet Need
Cardio-metabolic and liver diseases are among the largest unmet medical needs globally and represent a leading cause of morbidity and mortality and a significant burden for healthcare systems. They also represent areas of underinvestment by the pharmaceutical industry, driven in part by the biological complexity of the diseases and the substantial costs necessary to develop new therapeutics.
Metabolic syndrome is exhibited by 34% of adults in the US and is believed to be at the center of this health epidemic. Metabolic syndrome comprises a constellation of co-morbid conditions, including type 2 diabetes, obesity, high blood pressure, poorly regulated lipids and non-alcoholic fatty liver disease, or NAFLD, a precursor to non-alcoholic steatohepatitis, or NASH.
We have spent the last decade discovering and developing a portfolio of clinical stage drug candidates that target various forms of cardio-metabolic and liver diseases, including NASH, type 2 diabetes and obesity.
Each of these drug candidates stem from novel insights we have made in understanding hormone pathways that regulate cardio-metabolic processes and liver function.
We have identified multiple hormone pathways of interest. Our most advanced programs focus on:
- Fibroblast growth factor 19, or FGF19, which plays a critical role in controlling bile acid, lipid and glucose metabolism
- Fibroblast growth factor receptor 1c-beta-klotho, or FGFR1c/KLB, which regulates insulin sensitivity, blood glucose and liver fat
- Growth differentiation factor 15, or GDF15, which drives profound metabolic activity by regulating fuel flux.
Based on our novel insights, we believe these hormone pathways work through distinct mechanisms and play an important role in metabolic regulation.
Case StudyFGF19: Powerful Biology to Rapidly and Directly Impact Fibrosis
Initial Disease of Focus: Cancer and Cancer Anorexia/Cachexia Syndrome (CACS)
The Unmet Need
CACS is the uncontrolled wasting of both skeletal muscle and fat that is a common co-morbidity of cancer. CACS is associated with increased hospitalization and shortened survival compared to cancer patients who do not exhibit the syndrome. While CACS can occur in all types of cancer, particularly high incidence rates are observed in pancreatic, gastric, colorectal and esophageal cancers, as well as non-small cell lung cancer.
Current therapeutics targeting CACS are primarily directed toward increasing appetite. However, there are limited approved treatments that address the muscle-wasting associated with CACS, and no approved treatments that address the altered energy metabolism.
NGM scientists previously made several seminal discoveries related to growth differentiation factor 15 (GDF15), including de-orphaning its cognate receptor, glial cell-derived neurotrophic factor receptor alpha-like (GFRAL).
NGM’s preclinical research suggests the central role of the GDF15/GFRAL pathway in promoting tumor-associated appetite suppression and weight loss. In addition, GDF15 levels are elevated in numerous tumor types and increased serum GDF15 levels are associated with worse prognosis in prostate, colorectal, esophageal and ovarian cancers, based on available scientific literature.
We are currently in Phase 1a/1b clinical development with NGM120, a first-in-class antagonistic antibody that binds GFRAL and inhibits GDF15 signaling, for the potential treatment of cancer and CACS. In preclinical studies of NGM120, we have demonstrated that blocking the interaction between GFRAL and GDF15 is able to both reduce tumor-associated weight loss and slow tumor growth and could potentially provide a novel treatment for CACS and cancer.
Case StudyGDF15/GFRAL: Novel Biologic Insights to Help Address Cancer Anorexia/Cachexia Syndrome
Initial Disease of Focus: Geographic Atrophy, a Progressive, Irreversible Neurodegenerative Disease
The Unmet Need
Age-related macular degeneration, or AMD, is a leading cause of vision loss and blindness in people 65 years of age and over in the US and other industrialized countries. The two advanced stages of the disease are called neovascular (wet) AMD and geographic atrophy, or GA.
GA is a progressive retinal degenerative disease associated with irreversible loss of vision, diminished quality of life and eventual blindness. GA is estimated to impact about 1 million people in the US and over 5 million people worldwide.
In patients with GA, single or multiple areas in the macular region of the retina become atrophic, forming distinct lesions that expand and coalesce over time. Enlargement of these lesions can lead to loss of vision and irreversible blindness. GA is often bilateral, meaning it occurs in both eyes.
While there are approved treatments for wet AMD, there are currently no approved treatments for GA.
Dysregulated activation of the complement system, a key component of the immune system, has been implicated in the onset and progression of GA. NGM621 is a humanized IgG1 monoclonal antibody engineered to potently inhibit activity of complement C3 with the treatment goal of reducing disease progression in patients with GA, and with the potential for every eight week dosing.
We are currently underway with a Phase 2 Catalina study, a multicenter, randomized, double-masked, sham-controlled clinical trial to evaluate the safety and efficacy of intravitreal injections of NGM621 in patients with GA secondary to AMD.
"NGM is a company that's very nimble and very flexible. We can respond to different, hot areas and quickly pivot. The exposure we get to new and interesting fields makes things very exciting. The mentality that’s important to have here is that you want to be part of something bigger than yourself and working toward the common goal of making the company successful and benefiting patients."