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, an Advanced Form of Age-Related Macular Degeneration
The Unmet Need
Age-related macular degeneration, or AMD, remains the leading cause of vision loss and blindness in people 65 years of age and over in the US. Prevalence of AMD increases with age, and it is estimated that approximately 3 million people 40 years of age and older will be affected by AMD in the US by 2020.
AMD is a gradually progressive disease that involves the damage and degeneration of cells under the retina and, in the advanced stages, patients can develop either or both the wet and dry form of AMD.
Geographic atrophy, or GA, is an advanced form of dry AMD characterized by deposits under the retina and damage and dysfunction of retinal cells. This results in single or multiple regions that become impaired in the central area of the retina called the macula. These patches of GA gradually enlarge to cause permanent loss of central vision.
GA is prevalent in about 1 million people in the US and over 5 million people worldwide in 2017 and occurs bilaterally, or in both eyes, in approximately 50% of patients within seven years of diagnosis.
There are currently no approved treatments for dry AMD and GA.
There are multiple modalities and classes of therapies under investigation for GA, including intravitreal injections that are administered once monthly or once every two months by retinal specialists, consistent with the current administration of treatments for wet AMD.
Given the significant unmet medical need and the importance of dosing convenience for GA patients, we believe that NGM621 has the potential to provide a desirable treatment option with improved efficacy with respect to slowing the rate of disease progression and less frequent dosing. We have advanced NGM621 to Phase 1 clinical study for the potential treatment of dry 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."