NGM NGM Biopharmaceuticals Inc.
Upcoming Catalysts
| Drug | Stage | Catalyst Date |
|---|---|---|
|
NGM621 (CATALINA)
Geographic atrophy
|
Phase 2
Phase 2
|
Premium membership is required to view catalyst dates, analyst ratings, earnings dates and cash burn data. Click here to unlock and sign up to a 14-day FREE TRIAL.
|
Drug Pipeline
| Drug | Stage | Notes |
|---|---|---|
|
NGM120, GEMZAR (gemcitabine) and ABRAXANE (nab-paclitaxel)
Pancreatic Cancer
|
Phase 2
Phase 2
|
Phase 1b data had all 6 patients demonstrated disease control, 3 patients had partial responses (PR), and 3 stable disease (SD). 2 patients discontinued early due to gemcitabine/Nab-paclitaxel toxicity and/or progression of the underlying disease. Phase 1a monotherapy cohort reported 3 patients (30%) in the 30 mg dosing and 2 patients (20%) in the 100 mg dosing had stable disease (SD), September 16, 2021. Phase 2 trial initiated March 2021.
|
|
NGM831
Solid tumors
|
Phase 1
Phase 1
|
First in-human testing to commence 1H 2022.
|
|
Aldafermin (NGM282) - (ALPINE 4)
NASH cirrhosis
|
Phase 2b
Phase 2b
|
Phase 2b trial ongoing.
|
|
NGM707 and KEYTRUDA (pembrolizumab)
Solid Tumors
|
Phase 1
Phase 1
|
Phase 1 trial initiation announced July 7, 2021.
|
|
Aldafermin (NGM282) - ALPINE 2/3
Non-alcoholic steatohepatitis (NASH)
|
Phase 2b
Phase 2b
|
Phase 2b top-line data released May 24, 2021. Primary endpoint not met.
|
|
NGM438
Oncology
|
Phase 1
Phase 1
|
Phase 1 trial to be initiated 4Q 2021.
|
Latest News
-
View Full Article Hide Full Article
- 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 26th 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 1About 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.
Investor Contact:
Kristin Hilton
ir@ngmbio.comMedia Contact:
Liz Melone
media@ngmbio.com1 = Assessed using the RECIST Version 1.1 criteria
- NGM120 is a novel antagonist antibody that binds GFRAL and inhibits GDF15 signaling for the potential treatment of cancer
-
View Full Article Hide Full Article
- Publication describes NGM's discovery of ILT3's functional ligand, fibronectin, a key component of the tumor stroma
- ILT3-fibronectin interactions within the tumor microenvironment may form a stromal checkpoint that actively suppresses myeloid cell function and inhibits antitumor immunity
- NGM831 is designed to block ILT3's interaction with fibronectin, as well as with other ligands
- NGM plans to initiate first-in-human testing of NGM831 in the first half of 2022
- NGM's extensive research efforts focused on tumor stroma biology and myeloid reprogramming have yielded a portfolio of oncology product candidates designed to enhance antitumor immunity
SOUTH SAN FRANCISCO, Calif., Aug. 23, 2021 (GLOBE NEWSWIRE) -- NGM Biopharmaceuticals, Inc. (NGM) (NASDAQ:NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, today disclosed its fourth oncology development candidate, NGM831, an antagonist antibody designed to block the interaction of ILT3 with fibronectin, as well as with other ligands. The announcement coincides with a publication in Cancer Immunology Research, a journal of the American Association for Cancer Research,1 describing NGM's discovery of ILT3's functional ligand, fibronectin, an extracellular matrix protein that forms a fibrillar network within the tumor stroma. This discovery enabled the development of NGM831, which joins NGM's growing portfolio of wholly owned oncology antibody programs, including NGM120 (anti-GFRAL), NGM707 (anti-ILT2/ILT4) and NGM438 (anti-LAIR1).
NGM is a leader in research elucidating the central role that myeloid cells play in creating a suppressive environment around many solid tumors that restricts antitumor immunity. Myeloid cells often represent the most abundant tumor-associated immune cells and, in some tumors, myeloid cells alone account for more than half of the tumor mass2. Through systematic screening, NGM was able to identify the suppressive receptors that are most highly enriched in myeloid cells, including four members of the LILR family: ILT2, ILT3, ILT4 and LAIR1. These receptors may play a central role in establishing the immune suppressive state of the tumor microenvironment3-6.
"The work we published on the ILT3-fibronectin pathway and our unveiling of NGM831 is yet another proof point of our robust in-house capabilities to deeply interrogate biology and rapidly translate our discoveries into investigational medicines designed to bring hope and meaningful change to patients with cancer and other serious diseases," said David J. Woodhouse, Ph.D., Chief Executive Officer at NGM. "With oncology programs now targeting ILT2/ILT4, ILT3 and LAIR1, we have constructed a comprehensive myeloid reprogramming strategy that is directed at multiple and distinct targets. Our planned biomarker strategy across the NGM707, NGM831 and NGM438 clinical development programs will help inform target patient populations for each product candidate."
NGM plans to initiate first-in-human testing of NGM831 in the first half of 2022. In July 2021, NGM announced the initiation of a Phase 1/2 study of NGM707 when given alone or in combination with KEYTRUDA® (pembrolizumab) in patients with advanced solid tumors, which is anticipated to enroll 180 patients. NGM also plans to initiate a Phase 1 study of NGM438 in advanced solid tumors in the first half of 2022.
As detailed in the publication, ILT3 is a fibronectin-binding inhibitory immune receptor that receives signals from the extracellular matrix to directly promote myeloid cell suppression. ILT3 is expressed specifically on tumor-associated myeloid cells, with particularly high expression on tolerogenic dendritic cells (DCs), myeloid-derived suppressor cells and M2 macrophages. This receptor is upregulated in several tumor types and is associated with poor survival7,8. Moreover, fibronectin has been shown to be upregulated in multiple cancers and associated with tumor progression9,10. For tumors in which both ILT3 and fibronectin are upregulated, the ILT3-fibronectin pathway may act as a stromal checkpoint to repress myeloid cell function.
Designed to inhibit ILT3 interactions with fibronectin and other ligands, NGM831 is expected to reprogram tolerogenic DCs into stimulatory cells with enhanced Fc receptor activity as well as to enhance T cell infiltration and activation. The findings published today are the latest research underpinning NGM's growing oncology portfolio focused on tumor stroma biology and myeloid reprogramming to enhance antitumor immunity.
"NGM has a strong track record of identifying important ligand-receptor interactions, thereby opening the door to impactful therapeutics," said Alex DePaoli, M.D., Chief Translational Officer at NGM Bio. "We are pleased to showcase how our team of scientists identified ILT3's functional ligand, fibronectin, and subsequently designed an antibody specifically tailored against the target. By inhibiting ILT3's interaction with fibronectin, NGM831 represents another potential approach to mobilize a patient's own immune system to fight tumors by shifting myeloid cells from a suppressive state to a stimulatory state and promoting antitumor immunity."
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)
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 1About 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 "may," "will," "efforts," "plans," "planned," "believe," "expected," "designed to," "anticipated," "aspire," "potential" 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 therapeutic potential and potential benefits of NGM831, including NGM831's potential ability to block ILT3's interactions with fibronectin and other ligands; NGM's research efforts to develop a portfolio of oncology product candidates designed to enhance antitumor immunity; the potential of ILT3-fibronectin interactions to form a stromal checkpoint that actively suppresses myeloid cell function and inhibits antitumor immunity; NGM's myeloid reprogramming strategy; the potential for NGM to translate its discoveries into investigational medicines; the potential of NGM's planned biomarker strategy to inform target patient populations; planned initiations of Phase 1 studies of NGM831 and NGM438 and the anticipated timing thereof; anticipated enrollment in NGM's Phase 1/2 study of NGM707; 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 NGM707, NGM120, NGM438 and/or NGM831 are not tolerable and effective treatments for cancer patients or that the effects of inhibiting ILT3-fibronectin interactions are otherwise different than anticipated, and the risk that success in preclinical studies does not ensure that clinical trials evaluating NGM831 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 NGM707, NGM120, NGM438, NGM831 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.
Investor Contact:
Kristin Hilton
ir@ngmbio.comMedia Contact:
Liz Melone
media@ngmbio.com1 = Paavola et al, Cancer Immunology Research, 2021
2 = Zhang et al, PNAS 2019
3 = Siu et al, ESMO Virtual Congress 2020
4 = Carosella et al, Cell 2021
5 = Singh et al, Molecular Cancer Research, 2021
6 = Peng et al, Nature Communications, 2020
7 = L de Goeje et al, OncoImmunology 2015
8 = Liu et al, Pathology - Research and Practice, 2018
9 = Saito et al, Molecular Medicine Reports, 2008
10 = Niknami et al, EXCLI Journal, 2017
-
View Full Article Hide Full Article
- Completed enrollment in 320-patient Phase 2 CATALINA study of NGM621, an anti-complement C3 antibody, for the treatment of geographic atrophy; topline data expected in second half of 2022
- Initiated a Phase 1/2 clinical trial of NGM707, an ILT2/ILT4 dual antagonist antibody, in patients with advanced solid tumors
- Amended collaboration with Merck to focus primarily on advancing novel medicines for retinal and cardiovascular and metabolic diseases; NGM gained worldwide rights to its disclosed oncology portfolio as well as additional assets falling outside of the amended collaboration's narrower scope
- $390.6 million in cash, cash equivalents and marketable securities as of June 30, 2021
SOUTH SAN FRANCISCO, Calif., Aug. 05, 2021 (GLOBE NEWSWIRE) -- NGM Biopharmaceuticals, Inc. (NGM) (NASDAQ:NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, today provided business highlights and reported financial results for the period ending June 30, 2021.
"With six disclosed pipeline programs, five of which are in the clinic, and additional undisclosed preclinical and research programs, we continue to make meaningful progress towards achieving our mission to translate complex powerful biology with urgency and rigor to deliver life-changing medicines for patients," said David J. Woodhouse, Ph.D., Chief Executive Officer at NGM Bio. "In our sizable oncology portfolio alone, we continue to advance multiple programs that we believe have the potential to benefit patients with a variety of solid tumors. We were pleased to dose our first patient with NGM707 in a Phase 1/2 study this quarter and look forward to presenting interim results from our Phase 1a/1b dose-finding study of NGM120 at ESMO later this quarter."
"We also continued to make important strides in ophthalmology, with the recent completion of enrollment in our Phase 2 CATALINA study exactly one year after initiation. Our strong balance sheet positions us well to continue progressing our ambitious clinical and research efforts."
Key Second Quarter and Recent Highlights
Retinal diseases
- Completed enrollment in the Phase 2 CATALINA study of NGM621 in patients with geographic atrophy. NGM completed enrollment in the Phase 2 CATALINA study, a multi-center, randomized, double-masked, sham-controlled clinical trial to evaluate the safety and efficacy of intravitreal, or IVT, injections of NGM621 every four weeks or every eight weeks in 320 patients with geographic atrophy in one or both eyes secondary to age-related macular degeneration. The primary efficacy endpoint is the rate of change in geographic atrophy lesion area, as measured by fundus autofluorescence, or FAF, imaging, over 52 weeks of treatment. NGM anticipates reporting topline data from the CATALINA study in the second half of 2022. Upon completion of a proof-of-concept study in humans, Merck has a one-time option to license NGM621 and its related molecules as well as the additional one-time option to license NGM621 and its related molecules together with all other ophthalmology compounds included within the scope of our ongoing collaboration with Merck.
Cancer
- Continued enrollment in a Phase 2 placebo-controlled component of the ongoing Phase 1/2 PINNACLES study testing NGM120 as a first-line treatment in combination with gemcitabine and Abraxane® (paclitaxel protein bound) in patients with metastatic pancreatic cancer. In March 2021, NGM initiated a multi-center, randomized, single-blind (sponsor unblinded), placebo-controlled component of NGM120 in combination with gemcitabine and Abraxane as a first line treatment in patients with metastatic pancreatic cancer as part of the ongoing Phase 1/2 trial. This Phase 2 component of the Phase 1/2 study is designed to enroll approximately 60 patients and will assess the efficacy, safety and tolerability of NGM120 or placebo in combination with gemcitabine and Abraxane against both cancer and cancer-related cachexia endpoints. The Phase 1a/1b dose-finding portion of the study is still ongoing, and NGM expects to report interim results from that portion of the study at the European Society for Medical Oncology in the third quarter of 2021.
- Initiated the Phase 1 portion of a Phase 1/2 Study of NGM707 for the treatment of advanced solid tumors. The Phase 1 portion (n≅60) of the study includes a monotherapy dose escalation arm (Part 1a) and a dose-finding arm in combination with KEYTRUDA® (pembrolizumab) (Part 1b). The Phase 2 portion (n≅120) of the study will employ a basket design that will include expansion cohorts of patients treated with NGM707 monotherapy (Part 2a) or NGM707 in combination with KEYTRUDA (Part 2b).
Liver and metabolic diseases
- Reported topline data from the Phase 2b ALPINE 2/3 study of aldafermin in patients with NASH and liver fibrosis stage 2 or 3, or F2 or F3, in May 2021. The 24-week study assessed the efficacy, safety and tolerability of 0.3 mg, 1 mg and 3 mg doses of aldafermin compared to placebo. The primary objective of the ALPINE 2/3 study was to evaluate a dose response on liver fibrosis improvement by ≥ 1 stage with no worsening of steatohepatitis at week 24. The study did not meet its primary endpoint evaluating a dose response at 24 weeks on liver fibrosis improvement by >1 stage with no worsening of NASH (p=0.55), analyzed using a dose response-driven statistical analysis plan (Multiple Comparison Procedure Modeling, or MCP-Mod). The study achieved statistical significance versus placebo on certain secondary endpoints, including NASH resolution (at the 3 mg dose) and multiple non-invasive measures of NASH, including liver fat content reduction by MRI-PDFF, ALT, AST and Pro-C3 (at the 1 mg and 3 mg doses). Aldafermin was generally well tolerated with an overall safety profile similar to placebo. As previously disclosed, NGM plans not to pursue Phase 3 clinical development of aldafermin in F2/F3 NASH.
- Continued enrollment in Phase 2b ALPINE 4 study of aldafermin in patients with compensated NASH cirrhosis (liver fibrosis stage 4, or F4). The 48-week study is designed to enroll approximately 150 patients and will assess the efficacy, safety and tolerability of 0.3 mg, 1 mg and 3 mg doses of aldafermin compared to placebo. The primary objective of the ALPINE 4 study is to evaluate a dose response at 48 weeks on liver fibrosis improvement by ≥ 1 stage with no worsening of steatohepatitis.
- Merck continued enrollment in its Phase 2b study of MK-3655 in patients with NASH and F2 or F3 liver fibrosis. In November 2020, Merck initiated a global Phase 2b multicenter study of MK-3655 for the treatment of patients with F2 or F3 NASH. The 52-week randomized, double-blind study is designed to enroll approximately 320 patients and will assess the efficacy, safety and tolerability of 50 mg, 100 mg and 300 mg once monthly doses of MK-3655 compared to placebo. The primary objective of the Phase 2b study is NASH resolution without worsening of fibrosis after 52 weeks. Merck licensed MK-3655 following NGM's completion of a proof-of-concept study. NGM retains an option, at the initiation of the first Phase 3 clinical trial for MK-3655, to either receive milestone and royalty payments or to co-fund development and participate in a global cost and revenue sharing arrangement of up to 50% for MK-3655.
Corporate
- Announced appointment of Roger M. Perlmutter to Board of Directors. On June 8, 2021, NGM announced that the stockholders of the company elected Roger M. Perlmutter, M.D., Ph.D. to the company's board of directors. Dr. Perlmutter brings decades of expertise and renowned leadership in drug discovery and development with global healthcare companies including Merck and Amgen. Dr. Perlmutter is currently Chairman, President and Chief Executive Officer at Eikon Therapeutics, Inc.
- Amended collaboration with Merck. In June 2021, NGM and Merck announced that they will continue their research, discovery and development collaboration with a narrower scope, focused primarily on retinal and cardiovascular and metabolic (CVM) targets of interest to Merck. Merck will continue to advance MK-3655, which is currently in a global Phase 2b clinical trial in patients with F2 or F3 NASH. Merck retains its option to license NGM621 and its related molecules, which is currently in the NGM-led Phase 2 CATALINA clinical study in patients with geographic atrophy. Merck will provide approximately $120 million in research and development, or R&D, funding to NGM through March 2024, plus additional potential license option payments. NGM gained worldwide rights to its disclosed oncology portfolio, including NGM120, NGM707 and NGM438, as well as all undisclosed preclinical and research assets falling outside of the amended collaboration's narrower scope.
Second Quarter 2021 Financial Results
- NGM reported a net loss of $36.7 million for the quarter ended June 30, 2021, compared to a net loss of $25.6 million for the same period in 2020.
- Related party revenue from our collaboration with Merck was $16.8 million for the quarter ended June 30, 2021, compared to $19.8 million for the same period in 2020. Related party revenue decreased $3.0 million in the quarter ended June 30, 2021 as compared to the prior year due to the derecognition of a $4.6 million contract asset that was associated with our previous collaboration agreement with Merck.
- R&D expenses were $43.6 million for the quarter ended June 30, 2021, compared to $38.5 million for the same period in 2020. R&D expenses increased $5.1 million in the quarter as compared to the prior year, primarily due to increases in external expenses driven by our ongoing clinical studies of NGM621 and NGM120 and preclinical studies of NGM438, and increases in personnel-related and internal and unallocated R&D expenses. These increases were partially offset by decreases in expenses for our manufacturing activities and our clinical trials of aldafermin and in external expenses related to our other development programs.
- General and administrative expenses were $9.8 million for the quarter ended June 30, 2021, compared to $6.8 million for the same period in 2020. The $3.0 million increase in general and administrative expenses in 2021 was primarily attributable to increases in personnel-related expenses driven by increased headcount, as well as external expenses to support our operations.
- Cash, cash equivalents and short-term marketable securities were $390.6 million as of June 30, 2021, compared to $295.2 million as of December 31, 2020.
About NGM Biopharmaceuticals, Inc.
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 six 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 "focused," "towards," "anticipates," "believe," "look forward to," "will," "designed to," "potential," "aspire," "continue," "expects," "plans" 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 NGM's mission to translate complex powerful biology with urgency and rigor to deliver life-changing medicines for patients; NGM's belief that it is advancing multiple programs that have the potential to benefit patients with a variety of solid tumors; the design of NGM's and Merck's clinical trials of NGM's product candidates; the availability and anticipated timing of topline data from Phase 2 CATALINA study of NGM621 in patients with geographic atrophy; the availability and anticipated timing of the interim results from the Phase 1a/1b dose-finding portion of the Phase 1/2 PINNACLES study testing NGM120; NGM plans not to pursue Phase 3 clinical development of aldafermin in F2/F3 NASH; anticipated activities under NGM's amended collaboration with Merck and the amount of development funding under, and potential option payments to NGM under, the amended collaboration; the potential receipt of milestone and royalty payments by NGM under the amended collaboration with Merck; the therapeutic potential of NGM's product candidates; 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 biopharmaceutical product development process and the uncertainty of clinical success, including risks related to failure or delays in successfully initiating, enrolling, reporting data from or completing clinical studies, as well as the risks that results obtained in clinical trials to date may not be indicative of results obtained in ongoing or future trials and that NGM's product candidates may otherwise not be tolerable and effective treatments in their planned indications; NGM's ability to maintain its amended collaboration with Merck, including the risk that if Merck were to breach or terminate the amended collaboration or Merck's development funding obligations, NGM would not obtain all of the anticipated financial and other benefits of the amended collaboration, and the development and/or commercialization of NGM's product candidates within the scope of the amended collaboration could be delayed, perhaps substantially; 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 clinical trials; the time-consuming and uncertain regulatory approval process; NGM's reliance on third-party manufacturers for aldafermin and its other product candidates; the sufficiency of NGM's cash resources, including to fund programs that fall outside of the amended collaboration's narrower scope, and NGM's need for additional capital; and other risks and uncertainties affecting NGM and its development programs, including those discussed in the section titled "Risk Factors" in NGM's quarterly report on Form 10-Q for the quarter ended March 31, 2021 filed with the United States Securities and Exchange Commission (SEC) on May 6, 2021 and future filings and reports that NGM makes from time to time with the SEC. 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.
Investor Contact:
Alex Schwartz
ir@ngmbio.comMedia Contact:
Liz Melone
media@ngmbio.comNGM BIOPHARMACEUTICALS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS
(In thousands, except share and per share amounts)
(Unaudited)Three Months Ended
June 30,Six Months Ended
June 30,2021 2020 2021 2020 Related party revenue $ 16,773 $ 19,755 $ 38,348 $ 44,119 Operating expenses: Research and development 43,570 38,494 84,269 76,933 General and administrative 9,823 6,794 18,544 13,389 Total operating expenses 53,393 45,288 102,813 90,322 Loss from operations (36,620 ) (25,533 ) (64,465 ) (46,203 ) Interest income, net 115 388 229 1,563 Other expense, net (187 ) (471 ) — (91 ) Net loss $ (36,692 ) $ (25,616 ) $ (64,236 ) $ (44,731 ) Net loss per share, basic and diluted $ (0.48 ) $ (0.38 ) $ (0.84 ) $ (0.66 ) Weighted average shares used to compute net loss per share, basic and diluted 77,096,416 68,305,056 76,568,217 67,850,640 NGM BIOPHARMACEUTICALS, INC.
CONDENSED CONSOLIDATED BALANCE SHEETS
(In thousands)
(Unaudited)June 30,
2021December 31,
2020*ASSETS Current assets: Cash and cash equivalents $ 99,403 $ 147,017 Short-term marketable securities 291,147 148,139 Related party receivable from collaboration 3,586 333 Related party contract asset — 6,100 Prepaid expenses and other current assets 8,993 6,837 Total current assets 403,129 308,426 Property and equipment, net 12,790 14,526 Restricted cash 1,499 1,499 Other non-current assets 5,593 4,592 Total assets $ 423,011 $ 329,043 LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities: Accounts payable $ 5,141 $ 9,663 Accrued liabilities 31,891 29,945 Deferred rent, current 3,048 2,975 Contract liabilities 4,963 — Total current liabilities 45,043 42,583 Deferred rent, non-current 4,893 6,417 Total liabilities 49,936 49,000 Commitments and contingencies Stockholders' equity: Preferred stock, $0.001 par value; — — Common stock, $0.001 par value; 77 71 Additional paid-in capital 735,860 578,599 Accumulated other comprehensive income 5 4 Accumulated deficit (362,867 ) (298,631 ) Total stockholders' equity 373,075 280,043 Total liabilities and stockholders' equity $ 423,011 $ 329,043 ___________
* Derived from the audited consolidated financial statements. - Completed enrollment in 320-patient Phase 2 CATALINA study of NGM621, an anti-complement C3 antibody, for the treatment of geographic atrophy; topline data expected in second half of 2022
-
View Full Article Hide Full Article
- Geographic atrophy is a progressive, irreversible retinal degenerative disease that can lead to blindness, with no currently approved treatments
- NGM621 is a monoclonal antibody against complement C3, a protein implicated in the pathophysiology of geographic atrophy, and is engineered with the goal of potently inhibiting the central component of the complement cascade by blocking all of its initiating pathways to reduce disease progression
- Multicenter, randomized, double-masked, sham-controlled study enrolled 320 patients
- NGM anticipates Phase 2 CATALINA study topline data readout in the second half of 2022
SOUTH SAN FRANCISCO, Calif., July 22, 2021 (GLOBE NEWSWIRE) -- NGM Biopharmaceuticals, Inc. (NGM) (NASDAQ:NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, today announced it has completed enrollment in the Phase 2 CATALINA study, which is evaluating the safety and efficacy of intravitreal (IVT) injections of NGM621 in patients with geographic atrophy secondary to age-related macular degeneration. Geographic atrophy is characterized by progressive retinal cell loss that results in irreversible loss of vision, and the disease affects approximately 1 million patients in the U.S. and 5 million patients globally. There are no approved treatments for geographic atrophy.
"Patients living with geographic atrophy, like those enrolled in CATALINA, may face significant and progressive vision loss that has far-reaching implications, including a loss of independence, depression and an increased risk of falls and fractures. Completing enrollment in CATALINA is an important milestone for NGM and the patients with geographic atrophy that we hope to serve. NGM621, as a monoclonal antibody with a high potency targeting C3 and the potential for every-eight-week dosing, may offer an innovative treatment option for this underserved patient population," said Hsiao D. Lieu, M.D., Chief Medical Officer at NGM. "We are highly encouraged by the program's progress to date and for the potential of NGM621 to change the disease trajectory for geographic atrophy patients."
The Phase 2 CATALINA study enrolled a total of 320 patients with geographic atrophy, more than the originally planned 240 patients. Patients were enrolled and randomized to receive IVT injections of NGM621 or sham every four or eight weeks. The primary efficacy endpoint is the rate of change in geographic atrophy lesion area, as measured by fundus autofluorescence (FAF) imaging, over 52 weeks of treatment. NGM621 Phase 1 study results, which were first presented at the American Academy of Ophthalmology in November 2020, supported the advancement of the drug to the ongoing Phase 2 study.
"Building upon encouraging Phase 1 results demonstrating that NGM621 was well-tolerated and had an acceptable safety profile, the CATALINA study will provide additional safety information and will inform whether NGM621 may slow disease progression in patients with geographic atrophy," said Arshad M. Khanani, M.D., M.A., Managing Partner, Director of Clinical Research, and Director of Fellowship at Sierra Eye Associates and Clinical Associate Professor at the University of Nevada, Reno School of Medicine. "Complement inhibition continues to be a promising approach for the treatment of geographic atrophy, a disease that represents a major unmet need in ophthalmology, affecting millions of people around the world. As a retina specialist, it is extremely difficult to watch my geographic atrophy patients' disease worsen without being able to intervene effectively. I look forward to seeing top-line results from the CATALINA study next year, as we continue to strive for meaningful medical advancements for these patients."
About NGM621 and Complement C3 Inhibition
NGM621 is a humanized IgG1 monoclonal antibody engineered to potently inhibit complement C3. The therapeutic is delivered via intravitreal (IVT) injection and is being evaluated with dosing intervals of every four and eight weeks. NGM621 Phase 1 study results showed single and multiple IVT injections appeared to be safe and well tolerated (clinicaltrials.gov identifier: NCT04014777). In preclinical models, NGM621's high affinity binding to C3 has demonstrated the potential for potent C3 inhibition, and NGM's pharmacokinetics/pharmacodynamics modeling has shown sufficient drug coverage for potential every-eight-week dosing. The company's preclinical data also suggest that NGM621, unlike PEGylated molecules, may not exacerbate choroidal neovascularization (CNV); the human translation of this observation is being investigated in the Phase 2 CATALINA clinical trial.
C3 is a key component of the complement system, which helps orchestrate the body's response to infection and maintains tissue homeostasis. The complement cascade can be activated through its three distinct pathways – classical, lectin and alternative – all of which converge to activate C3. When this cascade is dysregulated, the immune response may lead to the development and progression of geographic atrophy. Inhibition of C3 represents a promising therapeutic approach that broadly inhibits downstream effector functions triggered by the excessive activation of C3, including inflammation, activation of the adaptive immune system, opsonization (the marking of a pathogen to be destroyed by phagocytes, a type of immune cell), phagocytosis and cell lysis (cell death).
NGM621 was discovered by NGM under its strategic collaboration with Merck.
About the NGM621 Phase 2 CATALINA Study
The Phase 2 CATALINA study enrolled 320 patients diagnosed with geographic atrophy in one or both eyes. The primary objectives of this multicenter, randomized, double-masked, sham-controlled study are to evaluate the efficacy and safety of NGM621 IVT injections compared to sham control. Patients will be randomized to one of four treatment groups to receive IVT injections of NGM621 or sham every four- or eight-weeks for a total of 52 weeks, and monitored for an additional four weeks upon treatment completion. The primary efficacy endpoint is the rate of change in geographic atrophy lesion area, as measured by fundus autofluorescence (FAF) imaging, over 52 weeks of treatment. The primary safety endpoints will evaluate the incidence and severity of ocular and systemic adverse events from treatment with NGM621 compared to sham control.
For more information, please visit the study listing on clinicaltrials.gov (identifier: NCT04465955).
About NGM Biopharmaceuticals, Inc.
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 six 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 "with the goal of," "engineered to," "anticipates," "may," "suggest," "potential," "will," "look forward," "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: NGM's strategy to deliver transformative medicines for patients across a range of therapeutic areas through the clinical development of NGM621 and other product candidates; the design, timing and potential results of NGM's Phase 2 CATALINA study of NGM621; the availability of Phase 2 CATALINA study topline data readout in the second half of 2022; the ability of NGM621 to serve as an innovative treatment option for patients with geographic atrophy; the potential for every-eight-week dosing of NGM621 and the suggestion that NGM621 may not exacerbate CNV; the potential of NGM621 to change disease trajectory and slow disease progression for geographic atrophy patients; the potential therapeutic effects, benefits and dosing schedule of NGM621 and the role of NGM621 as a potential potent C3 inhibitor engineered with the goal of inhibiting the central component of the complement cascade by blocking all of its initiating pathways and that may have the effect of reducing disease progression in patients with geographic atrophy; 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 forward-looking statements in this press release. These risks and uncertainties include, 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 receiving regulatory clearance and the risk that CATALINA study and future studies in humans may show that NGM621 is not a safe and effective treatment for patients with geographic atrophy; the risk that the results obtained to date in NGM's clinical trials may not be indicative of results obtained in pivotal or other late-stage trials; the evolving effects of the COVID-19 pandemic, which may significantly impact (i) our business and operations, including activities at our headquarters in the San Francisco Bay Area and our clinical trial sites, as well as the business or operations of our manufacturers, contract research organizations or other third parties with whom we conduct business, (ii) our ability to access capital and (iii) the value of our common stock; the time-consuming and uncertain regulatory approval process; NGM's reliance on third-party manufacturers for NGM621 and its other product candidates; the sufficiency of NGM's cash resources and need for additional capital; and other risks and uncertainties affecting NGM and its development programs, including those described under the caption "Risk Factors" in NGM's quarterly report on Form 10-Q for the quarter ended March 31, 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.
Investor Contact:
Alex Schwartz
ir@ngmbio.comMedia Contact:
Liz Melone
media@ngmbio.com -
View Full Article Hide Full Article
--NGM707, a ILT2/ILT4 dual antagonistic antibody, is engineered to reverse myeloid suppression with the goal of improving patient immune responses to tumors--
--Study to evaluate potential of NGM707 in patients with tumor types with elevated expression of ILT2 and ILT4 as a monotherapy and in combination with KEYTRUDA® (pembrolizumab)--
--Approximately 180 patients expected to be enrolled in the Phase 1/2 Study--SOUTH SAN FRANCISCO, Calif., July 07, 2021 (GLOBE NEWSWIRE) -- NGM Biopharmaceuticals, Inc. (NGM) (NASDAQ:NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, announced it has dosed the first patient in a Phase 1/2 study to evaluate the efficacy, safety and pharmacokinetics/pharmacodynamics of NGM707 when given alone or in combination with KEYTRUDA® (pembrolizumab), an anti- PD-1 antibody. NGM707 is a novel dual antagonist antibody that inhibits the Immunoglobulin-like Transcript 2 (ILT2) and Immunoglobulin-like Transcript 4 (ILT4) receptors. NGM707 originated from NGM's in-house discovery engine. The program follows NGM120, a glial cell-derived neurotrophic factor alpha-like (GFRAL) antagonistic antibody, which is currently in a Phase 2 study in patients with metastatic pancreatic cancer, as the second NGM wholly owned oncology candidate in the clinic.
"NGM707 is designed to improve tumor responses in cancer patients by both reprogramming immuno-suppressive myeloid cells through ILT4 inhibition and by further stimulating the activity of myeloid and lymphoid cells through ILT2 inhibition. As ILT4 inhibition continues to gain interest as a potentially important oncology strategy, our research suggests that NGM707's novel dual blockade of ILT4 and ILT2 may yield enhanced anti-tumor activity," said Alex DePaoli, M.D., Senior Vice President, Chief Translational Officer at NGM. "As a result, we believe NGM707 offers a potentially compelling treatment profile and could represent an important therapeutic advancement for patients with cancer."
ILT2 and ILT4 are receptors overexpressed on myeloid cells in the tumor microenvironment. These receptors are implicated in suppressing anti-tumor immune responses and may represent myeloid checkpoints that enable certain tumors to evade immune detection. NGM707 was designed with the goal of improving patient immune responses to tumors by inhibiting both the ILT2 and ILT4 receptors. In preclinical studies of NGM707, NGM has demonstrated that blockade of ILT4 reverses myeloid cell immune suppression, while blockade of ILT2 promotes natural killer (NK) and CD8+ T-cell killing of tumor cells and activates macrophage phagocytosis of tumor cells. Furthermore, preclinical studies of NGM707 have shown that the dual blockade of ILT2 and ILT4 may be more effective than blockade of either receptor alone in reversing suppression of Fc receptor signaling. In addition, preclinical work has shown that NGM707 in combination with pembrolizumab acts additively to increase T-cell activation and cytokine secretion.
"As we continue to look for novel agents applicable to a broad range of solid tumors and approaches with stronger anti-tumor immune responses, a therapeutic that addresses key myeloid checkpoint resistance mechanisms could represent a significant advancement for cancer patients," said Patricia LoRusso, DO, Professor of Medicine (Medical Oncology); Associate Cancer Center Director, Experimental Therapeutics, Yale University. "NGM707, by reversing myeloid and lymphoid checkpoints, is a promising approach that can potentially help these patients. We look forward to enrolling patients in this Phase 1/2 study and understanding how NGM707's preclinical benefits may translate to patients in the clinical setting."
About the NGM707 Phase 1/2 Study Design
The Phase 1 portion (n=60) of the study includes a monotherapy dose escalation arm (Part 1a) and a dose-finding arm in combination with KEYTRUDA (Part 1b) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and recommended Phase 2 dose of NGM707 alone and administered in combination with KEYTRUDA. Parts 1a and 1b may also provide the opportunity to identify preliminary efficacy signals. The Phase 2 portion (n=120) of the study employs a basket design that will include expansion cohorts of patients treated with NGM707 monotherapy (Part 2a) or NGM707 in combination with KEYTRUDA (Part 2b) to evaluate the efficacy, safety and tolerability of NGM707 alone or in combination with KEYTRUDA. Preliminary evidence of anti-tumor response in the Phase 2a portion will be evaluated using objective response rate, duration of response and progression free survival, while the Phase 2b portion will also evaluate overall survival. Both the Phase 1 and Phase 2 portions of the study will provide the opportunity to evaluate correlations between biomarker changes and clinical outcomes.
This study will enroll adult patients with advanced or metastatic solid tumors with elevated expression of ILT2 and ILT4, including patients with non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), renal cell carcinoma (RCC), mesothelioma, glioblastoma, melanoma, pancreatic, gastric, biliary duct, breast, ovarian, cervical, endocervical, colorectal and esophageal cancer.
For additional information about the study, please click here to visit the listing on clinicaltrials.gov.
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, GFRAL antagonistic antibody in Phase 2 study for the treatment of metastatic pancreatic cancer; NGM707, an ILT2/ILT4 (also known as Immunoglobulin-Like Receptor subfamily B (LILRB1/LILRB2)) dual antagonist antibody in a Phase 1/2 study for the treatment of advanced solid tumors; and NGM438, a Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) antagonist antibody, planned to enter into a Phase 1 study in advanced solid tumors in the first half of 2022.
About NGM Biopharmaceuticals, Inc.
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 six 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 "may," "could," "will," "planned," "believe," "expected" "promising," "opportunity," "look forward," "goal," "designed to," "suggests," "aspire," "potential," "potentially" 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 therapeutic potential and potential benefits of NGM707, including NGM707's potential in patients with tumor types with elevated expression of ILT2 and ILT4 and NGM's belief that NGM707 could represent an important therapeutic advancement for patients with cancer; the potential of NGM707's novel dual blockade of ILT4 and ILT2 to yield enhanced anti-tumor activity and be more effective than blockade of either receptor alone in reversing suppression of Fc receptor signaling; expected enrollment in the Phase 1/2 Study of NGM707; the design of the Phase 1/2 Study of NGM707; the planned initiation of a Phase 1 study of 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 NGM707, NGM120 and/or NGM438 are not tolerable and effective treatments for cancer patients or that the effects of inhibiting both the ILT2 and ILT4 receptors are otherwise different than anticipated, and the risk that success in preclinical studies does not ensure that clinical trials evaluating NGM707 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 NGM707, NGM120, 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 March 31, 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.
Investor Contact:
Alex Schwartz
ir@ngmbio.comMedia Contact:
Liz Melone
media@ngmbio.com