NGM Bio Presents Preliminary Findings from Ongoing Phase 1a/1b Dose Escalation Study of NGM120 in Patients with Advanced Solid Tumors at the ESMO Virtual Congress 2021

• NGM120 is a novel antagonist antibody that binds GFRAL and inhibits GDF15 signaling for the potential treatment of cancer
  
• NGM120 has been well tolerated to date in patients in the Phase 1a/1b study with no dose-limiting toxicities
• All six evaluable metastatic pancreatic cancer patients in the Phase 1b combination cohort (NGM120 + gemcitabine + Nab-paclitaxel) demonstrated disease control at 16 weeks, with three partial responses (PR) and three stable disease (SD)
• Four metastatic pancreatic cancer patients in Phase 1b cohort continued to exhibit PR/SD beyond 36 weeks at the July 26^th data cut-off

SOUTH SAN FRANCISCO, Calif., Sept. 16, 2021 (GLOBE NEWSWIRE) -- NGM Biopharmaceuticals, Inc. (NGM) (Nasdaq: NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, today announced that preliminary findings from its ongoing, open-label Phase 1a/1b dose escalation study of NGM120, a novel GFRAL antagonist antibody, in patients with advanced solid tumors are being presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2021, being held September 16 - 21. These preliminary results demonstrated that treatment with the drug was well tolerated to date in the study with no dose-limiting toxicities and provided encouraging initial signals of anti-cancer activity in patients with metastatic pancreatic cancer.

The poster titled “Initial results of a phase 1a/1b study of NGM120, a first-in-class anti-GDNF family receptor alpha like (GFRAL) antibody in patients with advanced solid tumors” (ePoster 550P) is available to conference attendees for the duration of the ESMO Congress and will be archived on the ‘Presentations and Publications’ page of NGM’s website here.

“We are pleased to share these initial findings from our ongoing Phase 1a/1b dose escalation study of NGM120, which give us an early understanding of the drug’s clinical profile," said Alex DePaoli, M.D., Senior Vice President, Chief Translational Officer at NGM. “While still preliminary, these findings mark an important milestone for NGM as we work to advance our oncology portfolio, now four programs strong, focused on targeting largely untapped and potentially important disease-driving biology to enable more cancer patients to respond to treatment and achieve better outcomes.”

The poster’s first author, Rishi Jain, M.D., Assistant Professor, Department of Hematology/Oncology, Fox Chase Cancer Center, commented, “Pancreatic cancer is associated with notoriously poor outcomes due to lack of treatment response. To that end, the preliminary disease control results observed with NGM120 in combination with gemcitabine/Nab-paclitaxel in the Phase 1b cohort warrant attention. Historic median progression-free survival in this patient population is approximately 24 weeks. While a small sample size, seeing several patients in this cohort exhibit either stable disease or partial response beyond 36 weeks is promising. I look forward to further clinical study of NGM120.”

NGM120 Phase 1a/1b Preliminary Findings

Design, Safety and Tolerability

The primary endpoint of the ongoing Phase 1a/1b multi-site, open-label, dose escalation clinical study is the safety and tolerability of NGM120 30 mg and 100 mg as monotherapy in patients with advanced solid tumors (Phase 1a, n=20) or in combination with gemcitabine + Nab-paclitaxel (Phase 1b, n=8) in patients with metastatic pancreatic cancer. Patients are dosed once every three weeks in the Phase 1a cohort and once every four weeks in the Phase 1b cohort. Secondary endpoints include pharmacokinetics (PK), overall response rate¹, progression-free survival (PFS) and changes in lean body mass and body weight. Entry criteria for both cohorts included elevated serum levels of GDF15. Both the Phase 1a and 1b cohorts are fully enrolled.

Overall, treatment with NGM120 showed no dose-limiting toxicities in the Phase 1a/1b study data presented at ESMO. The PK exposure of NGM120 in both the Phase 1a and Phase 1b cohorts increased with dose. In the Phase 1a monotherapy cohort, most adverse events were Grade 1-2 with no serious adverse events attributed to NGM120. The Phase 1b combination cohort showed a safety profile consistent with gemcitabine/Nab-paclitaxel treatment, with two patients discontinuing early due to gemcitabine/Nab-paclitaxel toxicity and/or progression of the underlying disease.

Phase 1a Cohort Clinical Activity

In the Phase 1a monotherapy cohort, three patients (30%) in the Phase 1a 30 mg arm and two patients (20%) in the Phase 1a 100 mg arm had stable disease¹, although no objective response was observed. Four patients experienced increases in lean body mass greater than 3.5% at Week 8. As of the July 26, 2021 data cut-off, one patient in the Phase 1a cohort remained on drug. At the time of this announcement, this patient remains on drug.

Phase 1b Cohort Clinical Activity

In the Phase 1b combination cohort, all six evaluable patients with metastatic pancreatic cancer showed disease control at 16 weeks, including three with partial responses (PR) and three with stable disease (SD), with four of those six patients exhibiting PR/SD beyond 36 weeks, as of the July 26, 2021 data cut-off. At the time of this announcement, three of those four patients remain on drug, exhibiting PR (two patients) and SD (one patient) beyond 44 weeks. In addition, all six CT-evaluable patients showed a 4% average maximal increase in lean body mass, and four of the six evaluable patients exhibited greater than 5% maximum body weight gain.

NGM plans to report final results from the Phase 1a and Phase 1b cohorts once all patients have completed treatment and follow-up per protocol.

Phase 2 PINNACLES Study of NGM120 in Metastatic Pancreatic Cancer

NGM initiated a Phase 2 randomized, single-blind (investigator-blinded), placebo-controlled, multi-center expansion study (PINNACLES) in March 2021 to evaluate NGM120 as a first-line treatment in 60 patients with metastatic pancreatic cancer. In the ongoing study, patients will be randomized to either NGM120 or placebo in combination with gemcitabine/Nab-paclitaxel. The study will evaluate the effects of NGM120 on both cancer and cancer-related cachexia.

About NGM120

NGM120 is an antagonist antibody that binds glial cell-derived neurotrophic factor receptor alpha-like (GFRAL) and inhibits growth differentiation factor 15 (GDF15) signaling. NGM scientists have made several important discoveries related to GDF15, including identification of its cognate receptor, GFRAL. GFRAL is expressed in a specific region of the hindbrain, partially outside the blood brain barrier, and is believed to initiate signaling through multiple pathways, including the autonomic nervous system. Evidence has shown that serum levels of GDF15 are elevated in patients with a number of tumor types, including non-small cell lung cancer, melanoma, pancreatic, prostate, colorectal, gastric, esophageal and ovarian cancer, and are associated with a worse prognosis in multiple cancers.

About NGM’s Oncology Portfolio

NGM’s currently disclosed oncology product candidates are all derived from the company’s in-house discovery engine and are wholly owned by NGM. These oncology programs include: NGM120, a GFRAL antagonist antibody in a Phase 2 study for the treatment of metastatic pancreatic cancer; NGM707, an ILT2/ILT4 (LILRB1/LILRB2) dual antagonist antibody in a Phase 1/2 study for the treatment of advanced solid tumors; NGM831, an ILT3 (LILRB4) antagonist antibody, planned to enter into a Phase 1 study in advanced solid tumors in the first half of 2022; and NGM438, a LAIR1 antagonist antibody, also planned to enter into a Phase 1 study in advanced solid tumors in the first half of 2022.

Abbreviations (in Alphabetical Order)
GDF15= Growth/Differentiation Factor 15; GFRAL=Glial Cell-Derived Neurotrophic Factor Receptor Alpha-Like; ILT2=Immunoglobin-Like Transcript 2; ILT3=Immunoglobin-Like Transcript 3; ILT4=Immunoglobin-Like Transcript 4; LILR= Leukocyte Immunoglobin-Like Receptor [ILT2 = LILRB1, ILT3=LILRB4, ILT4=LILRB2] LAIR1=Leukocyte-Associated Immunoglobulin-Like Receptor 1

About NGM

NGM is a biopharmaceutical company focused on discovering and developing novel therapeutics based on scientific understanding of key biological pathways underlying retinal diseases, cancer and liver and metabolic diseases. We leverage our biology-centric drug discovery approach to uncover novel mechanisms of action and generate proprietary insights that enable us to move rapidly into proof-of-concept studies and deliver potential first-in-class medicines to patients. At NGM, we aspire to operate one of the most productive research and development engines in the biopharmaceutical industry. All of our therapeutics have been generated by our in-house discovery engine; today, we have seven disclosed programs, including four in Phase 2 or 2b studies, across three therapeutics areas. Visit us at www.ngmbio.com for more information.

Forward Looking Statements

Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “preliminary,” “potential,” “promising,” “encouraging,” “enable,” “work to,” “look forward,” “plans,” “planned,” “believed,” “will,” “further,” “aspire” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These statements include those related to: the preliminary findings in the Phase 1a/1b study of NGM120 providing encouraging signals of anti-cancer activity; the potential of NGM120 for the treatment of cancer; NGM working to advance its oncology portfolio; NGM’s plans to report final results from the Phase 1a/1b study of NGM120; planned initiations of Phase 1 studies of NGM831 and NGM438 and the anticipated timing thereof; and other statements that are not historical fact. Because such statements deal with future events and are based on NGM’s current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of NGM could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including, without limitation, risks and uncertainties associated with the costly and time-consuming pharmaceutical product development process and the uncertainty of clinical success, including risks related to failure or delays in successfully initiating, enrolling or completing clinical studies, the risk that NGM’s ongoing or future clinical studies in humans may show that NGM120, NGM707, NGM438 and/or NGM831 are not tolerable or effective treatments for cancer patients, the risk that preliminary results from clinical studies may not be predictive of the final results of such studies, and the risk that success in earlier-stage clinical studies does not ensure that later clinical trials evaluating NGM120 or NGM’s other product candidates will generate the same results or otherwise provide adequate data to demonstrate the effectiveness and safety of such product candidates; the ongoing COVID-19 pandemic, which has adversely affected, and could materially and adversely affect in the future, NGM’s business and operations, including NGM’s ability to timely supply, initiate, enroll and complete its ongoing and future clinical studies; the time-consuming and uncertain regulatory approval process; NGM’s reliance on third-party manufacturers for NGM120, NGM707, NGM831, NGM438 and its other product candidates; the sufficiency of NGM’s cash resources, including to fund its wholly owned programs, and its need for additional capital; and other risks and uncertainties affecting NGM and its development programs, as well as those discussed in the section titled “Risk Factors” in NGM’s quarterly report on Form 10-Q for the quarter ended June 30, 2021 and future filings and reports that NGM makes from time to time with the United States Securities and Exchange Commission. Except as required by law, NGM assumes no obligation to update these forward-looking statements or to update the reasons if actual results differ materially from those anticipated in the forward-looking statements.

1 = Assessed using the RECIST Version 1.1 criteria