GFRAL

SOUTH SAN FRANCISCO, CA, USA I February 24, 2025 I NGM Biopharmaceuticals, Inc. (NGM Bio), a privately held biotechnology company focused on discovering and developing transformative therapeutics for patients, today announced that it has dosed the first participant in its EMERALD Phase 2 clinical study of NGM120, a GFRAL antagonist designed to block GDF15 activity, for the treatment of hyperemesis gravidarum (HG), a rare, debilitating condition of pregnancy. The leading cause of hospitalization in early pregnancy, HG 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 typically recurs in subsequent pregnancies. There are no approved therapies that target the underlying cause of HG. “We are proud to advance NGM120 into the clinic to evaluate its potential to address hyperemesis gravidarum, or HG, by targeting a major underlying cause of this debilitating condition,” said Wendy Yeh, M.D., Chief Medical Officer at NGM Bio. “Unfortunately, the severity and impact of HG are often underappreciated. At NGM, we understand how devastating this condition is, and we hear the pleas of women who experience the physical and mental toll of HG for an effective therapeutic solution. By inhibiting the activity of GDF15, NGM120 may potentially help reduce symptoms associated with HG, and, thereby, mitigate the impact and significant risks this condition can present during pregnancy.” 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. NGM120 has been generally well-tolerated in over 140 non-pregnant participants treated in clinical trials to date. To learn more about NGM120 as a potential treatment for HG, link here . About the Randomized, Placebo-Controlled EMERALD Phase 2 Study The randomized, placebo-controlled EMERALD study is designed to assess the safety and tolerability of NGM120 in addition to standard of care and supportive care. Eligible pregnant participants diagnosed with HG who are enrolled in the study will receive a single subcutaneous dose of NGM120 or placebo on the first day of the assigned study period, which lasts seven days. Participants assigned to the NGM120 arm and participants assigned to the placebo arm will also receive the following: intravenous (IV) fluids with multivitamins on several days prior to and throughout the seven-day study period as supportive care; IV multivitamins according to the standard of care at each study center; and 4 mg ondansetron (a prescription medicine that counteracts nausea and vomiting) three times daily, per standard of care. The EMERALD study is enrolling participants in the United Kingdom ( ISRCTN76681798 ) and Australia (ACTRN12624001421527). To learn more, please visit the following clinical trial listings: United Kingdom (Link here ) Australia (Link here ) About NGM Bio NGM Biopharmaceuticals, Inc. (NGM Bio), a wholly owned subsidiary of NGM Bio Holdings, Inc., a privately held biotechnology company, is focused on discovering and developing novel, life-changing medicines for people whose health and lives have been disrupted by disease. NGM Bio’s biology-centric drug discovery approach aims to seamlessly integrate interrogation of complex disease-associated biology and protein engineering expertise to unlock proprietary insights that are leveraged to generate promising product candidates, enable their rapid advancement into proof-of-concept studies and address high unmet patient need. NGM Bio has three clinical-stage programs: NGM120, a GFRAL antagonist designed to block the activity of GDF15, in development for hyperemesis gravidarum and for cancer cachexia, and aldafermin, an engineered analog of the human hormone FGF19, in development for primary sclerosing cholangitis. Visit us at http://www.ngmbio.com for more information. Abbreviations FGF19 = fibroblast growth factor 19; GDF15 = growth differentiation factor 15; GFRAL = glial cell-derived neurotrophic factor receptor alpha-like SOURCE: NGM Bio

MUNICH--( BUSINESS WIRE )-- CatalYm today announced new findings from its ongoing Phase 1/2a study as well as preclinical research, highlighting the therapeutic potential of its lead drug candidate, visugromab, to mitigate cancer cachexia by neutralizing the Growth Differentiation Factor 15 (GDF-15). Cachexia, a condition affecting a significant number of advanced cancer patients, leads to severe weight loss, muscle wasting, and reduced quality of life, often limiting the ability to tolerate cancer therapies. The data were presented at the 17 th International Conference on Sarcopenia, Cachexia & Wasting Disorders (SCWD). Preclinical and clinical data from the CatalYm’s ongoing GDFATHER Phase 1/2a study ( GDF -15 A ntibody-media T ed H uman E ffector T Cell R elocation Phase 1/2a Trial; NCT04725474 ) demonstrate that visugromab, a humanized monoclonal antibody targeting GDF-15, can significantly counteract the effects of cachexia. By neutralizing GDF-15, visugromab inhibits the activation of the GFRAL pathway in the brainstem, a key driver of weight loss and appetite suppression in cancer patients. Beyond its immuno-oncology benefits in overcoming resistance to checkpoint inhibitors, visugromab shows potential to improve the overall treatment experience and quality of life for cancer patients. “Cachexia is one of the most challenging complications in advanced cancer with GDF-15 being one of its most important drivers,” commented Christine Schuberth-Wagner, Chief Scientific Officer at CatalYm. “Elevated GDF-15 levels promoting cachexia development can result from GDF-15-producing tumors or standard of care treatments like chemotherapy. In addition to blocking GDF-15 mediated immunosuppression within tumor, our latest data demonstrate visugromab’s strong potential to counteract cachexia development.” “Cachexia is significantly affecting patients’ quality of life and ability to undergo intensive anticancer treatment regimen,” added Eugen Leo MD PhD MBA, Chief Medical Officer at CatalYm . “Our latest clinical data show that GDF-15 neutralization with visugromab not only enhances immune response but also alleviates the symptoms of cachexia, offering a dual benefit for patients, which we aim to further investigate in our broad Phase 2 clinical development program.” Key findings include : Clinical impact : A distinct subgroup of patients in the GDFATHER Phase 1/2a trial that entered the trial with manifest cachexia and elevated GDF-15 levels experienced meaningful weight gain during combination treatment of visugromab and nivolumab. Preclinical evidence : In xenograft mouse models with GDF-15 overexpression, visugromab effectively inhibited the GFRAL/Erk1/2 pathway, reversing weight loss and restoring normal food intake. Dual benefit in cancer care : The findings reinforce visugromab’s potential to address both immune suppression and cachexia, establishing it as a promising therapeutic option to improve patient outcomes and quality of life. About Cancer cachexia and GDF-15 Cancer cachexia is a complex and debilitating syndrome that affects up to 80% of patients with advanced cancer. The condition is closely linked to elevated GDF-15 levels, which drive severe and progressive weight loss, muscle wasting, reduced appetite, and metabolic disturbances through activation of the GFRAL receptor in the brainstem. Unlike starvation, cachexia cannot be fully reversed with nutritional support alone, as it is driven by a combination of systemic inflammation, tumor-derived factors, and metabolic dysregulation. This condition significantly diminishes the quality of life for cancer patients and severely impacts their ability to tolerate and respond to treatment, often leading to poorer outcomes and increased mortality. About Visugromab (CTL-002) Visugromab is a monoclonal antibody that neutralizes the tumor-derived Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant fostering immunotherapy resistance. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by re-enabling immune cell activation, proliferation and Interferon-γ signature induction. Visugromab has demonstrated a good safety profile and potent and durable anti-tumor efficacy in combination with anti-PD-1 treatment in advanced cancer patients The antibody will now be investigated in Phase 2b studies in multiple solid tumor indications. About CatalYm CatalYm has identified GDF-15 as a key cancer therapy resistance mechanism and is developing it as safe and efficacious immune therapy for solid tumors. GDF-15 is an immunosuppressant that is hijacked by cancer cells to evade immune system attack. Visugromab, CatalYm’s lead antibody, has demonstrated durable anti-tumor efficacy with long-lasting objective responses in relapsed and refractory metastatic solid tumor patients in combination with anti-PD-1 treatment. CatalYm is now advancing to Phase 2b studies to confirm visugromab as a new class of cancer immunotherapy in a broad range of anti-cancer regimens.

SOUTH SAN FRANCISCO, CA, USA I July 17, 2024 I NGM Biopharmaceuticals, Inc. (NGM Bio), a privately held biotechnology company focused on discovering and developing transformative therapeutics for patients, today announced a $122 million Series A financing led by TCG with participation from a select group of investors. NGM Bio will use the proceeds from the Series A financing to initiate a planned registrational trial of aldafermin, an engineered FGF19 analog, for the treatment of PSC, and to complete a planned Phase 2 trial of NGM120, a GDF15/GFRAL antagonist, for the treatment of HG. Both trials are expected to begin in the fourth quarter of 2024. “At the beginning of this year, we unveiled our strategy to advance clinical development efforts for two serious, rare conditions characterized by significant unmet patient need. This Series A capital strengthens our financial position, enabling us to progress our planned registrational trial of aldafermin in primary sclerosing cholangitis and to evaluate NGM120 in a proof-of-concept study for hyperemesis gravidarum,” said David J. Woodhouse, PhD, Chief Executive Officer at NGM Bio. “Having just completed a take-private transaction in April to bolster our efficiency and flexibility as a company, we’re grateful to TCG and our new investors for their support of these important programs, and we look forward to sharing more details on both trials in the coming months.” “The Column Group has long championed NGM’s mission to turn extraordinary scientific discoveries into meaningful therapeutics. NGM continues to show remarkable resilience and persistence in its pursuit of life-saving medicines while maintaining the highest level of scientific rigor. With this Series A investment, TCG is delighted to extend our investment in NGM and support the compelling opportunities presented by aldafermin and NGM120 as potential treatments for PSC and HG, respectively,” said Peter Svennilson, Founder and Managing Partner of TCG. Concurrent with the Series A financing, Mr. Svennilson joined NGM Bio’s Board of Directors. Aldafermin as a Potential Treatment for PSC PSC is a rare disease that irreparably damages the bile ducts, leading to bile acid dysregulation, which ultimately can result in end-stage liver disease, liver failure and bile duct cancer. NGM Bio’s advancement of aldafermin as a potential treatment for PSC is based on a large body of clinical data that supports its differentiated potential to address the bile acid dysregulation underpinning the disease, including NGM Bio’s prior Phase 2 study in PSC. NGM Bio anticipates that the registrational trial for aldafermin in PSC will utilize proposed surrogate endpoints with the goal of obtaining accelerated approval. Learn more about aldafermin as a potential treatment for PSC here . NGM120 as a Potential Treatment for 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. 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. This condition is the second leading cause of hospitalization in pregnancy (second to preterm labor) and typically recurs in subsequent pregnancies. Development of NGM120 as a potential treatment for HG is rooted in NGM Bio’s decade-long efforts to advance the understanding of GDF15 biology and explore its therapeutic application in a number of disease areas. Recent genetic research confirms the link between HG and higher serum levels of GDF15. NGM120 is an antibody designed to block GDF15 signaling through its cognate receptor, GFRAL, in cells at the base of the brain involved in triggering nausea and vomiting and, thereby, may have therapeutic benefit for treating patients suffering from HG. Learn more about NGM120 as a potential treatment for HG here . Aldafermin and NGM120 were both discovered through NGM Bio’s in-house discovery engine. Abbreviations (in alphabetical order) FGF19 = fibroblast growth factor 19; GDF15 = growth differentiation factor 15; GFRAL = glial cell-derived neurotrophic factor receptor alpha-like About NGM Bio NGM Biopharmaceuticals, Inc. (NGM Bio), a wholly owned subsidiary of NGM Bio Holdings, Inc., a privately held biotechnology company, is focused on discovering and developing novel, life-changing medicines for people whose health and lives have been disrupted by disease. NGM Bio’s biology-centric drug discovery approach aims to seamlessly integrate interrogation of complex disease-associated biology and protein engineering expertise to unlock proprietary insights that are leveraged to generate promising product candidates, enable their rapid advancement into proof-of-concept studies and address high unmet patient need. Visit us at http://www.ngmbio.com for more information. SOURCE: NGM Biopharmaceuticals