A Serious Disease Impacting Pregnant Women

Hyperemesis Gravidarum (HG), also known as extreme pregnancy sickness, is a serious disease characterized by intractable vomiting and nausea in pregnancy. Often minimized as ‘just’ morning sickness in the past, there is now growing awareness of the gravity of HG and its impact during pregnancy. In addition, a recent scientific breakthrough has identified genetic variants of the protein GDF15 as a root cause of HG.

NGM is advancing NGM120 as a potential treatment to address this root cause and deliver an effective therapeutic solution for this debilitating condition.

100-150K pregnant patients with HG in the US each year
300-400K ER visits due to HG¹ in the US each year
>750K of pregnant women experience severe nausea and vomiting in pregnancy
~45% of pregnant women take antiemetics¹ in the 1st trimester to treat nausea and vomiting

1 anti-emetics = anti-nausea medications

Source: Total pregnancies in the US (CDC, 2019); Einarson et. al., J Popul Ther Clin Pharmacol. 2013; Fiaschi et al.. BJOG 2019; Mansour et. al., Am J Obstet Gynecol 2023

The Underappreciated Severity and Impact of HG

HG is characterized by intractable nausea and vomiting (as frequent as 10 to 15 times per day), which results in dehydration, debility, weight loss and malnutrition. Many HG patients are undiagnosed or misdiagnosed, especially in early pregnancy.

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, and fetal malnutrition and depression, of which some patients have suicidal ideation. This condition is the second leading cause of hospitalization in pregnancy (second to preterm labor) and typically recurs in subsequent pregnancies.

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2nd leading cause of hospitalization during pregnancy

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Higher risk of HG in subsequent pregnancies

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Current treatments are weak and ineffective

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Higher rates of fetal loss and termination, preterm birth, low birth weight and suicidal ideation

Scientific Breakthrough in Understanding HG: Higher Levels of GDF15 Identified as a Risk Factor

Recent research published by an international team that included Marlena Fejzo, Ph.D., Clinical Assistant Professor of Population and Public Health Sciences in the Center for Genetic Epidemiology at the University of Southern California, and Sir Stephen O’Rahilly, M.D. FRS FMedSci, Professor of Clinical Biochemistry and Medicine at the University of Cambridge, found that GDF15 levels increase steadily in early pregnancy and are higher in women who experience nausea and vomiting in pregnancy and hyperemesis. The research uncovered that women with GDF15 genetic variants associated with lower levels of GDF15 in a non-pregnant state are predisposed to hyperemesis.

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Source: Fejzo et al. Nature Communications 2018

NGM’s Opportunity to Treat HG: Targeting the root cause by blocking GDF15’s activity

With higher levels of GDF15 now identified as a risk factor for HG and severe nausea/vomiting during pregnancy, NGM is advancing NGM120 as a novel approach to treat this condition. NGM120, a GFRAL antagonist antibody discovered by NGM scientists through the company’s Biologics Discovery Engine, is designed to block GDF15 activity by preventing the interaction of GDF15 and GFRAL, the only cognate receptor of GDF15, and, as a result, may have a therapeutic benefit for women suffering from HG.

NGM120 is being developed as a single injection. Antiemetics typically require multiple pills daily or intravenous administration.

Supportive Clinical Data and Development Status

NGM120 has been generally well-tolerated in over 140 patients (non-pregnant) treated in clinical trials to date. NGM is currently planning a proof-of-concept Phase 2 study in pregnant women suffering from HG.