GFRAL

--Enrollment ongoing for patients with microsatellite stability (MSS) colorectal cancer (CRC) in Phase1/2 trial of NGM707, a dual ILT2/ILT4 antagonist antibody product candidate, in combination with KEYTRUDA® (pembrolizumab) with expected completion of enrollment in the second quarter of 2024-- --Announced ongoing toxicology activities intended to support initiation of a potential proof-of-concept study of NGM120, a GDF15/GFRAL antagonist, for the treatment of hyperemesis gravidarum (HG) by the end of 2024-- --Ongoing discussions with regulators on the design of a potential registrational trial of aldafermin, an engineered FGF19 analog, for the treatment of primary sclerosing cholangitis (PSC), a rare liver disease, using surrogate endpoints-- --Reported $144.2 million in cash, cash equivalents and marketable securities as of December 31, 2023-- --On February 26, 2024, announced that it had entered into the Agreement and Plan of Merger with Atlas Neon Parent, Inc., and Atlas Neon Merger Sub, Inc.-- SOUTH SAN FRANCISCO, Calif., March 11, 2024 (GLOBE NEWSWIRE) -- NGM Biopharmaceuticals, Inc., (NGM Bio) (Nasdaq: NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, today provided recent business highlights and reported financial results for the fourth quarter and full year ended December 31, 2023. “In 2023, we made significant progress in patient enrollment in trials of our solid tumor drug candidates. Most notably, we are encouraged by the signals of activity observed in our NGM707 Phase 1b trial, particularly among MSS CRC patients whose lesions are typically unresponsive to immuno-checkpoint therapies. We also made progress in our discussions with the FDA regarding the design of a potential registrational Phase 2 study of aldafermin in PSC using a primary endpoint composed of surrogate biomarkers of PSC progression and obtained orphan drug designation from the agency for aldafermin for the treatment of PSC,” said David J. Woodhouse, Ph.D., Chief Executive Officer at NGM Bio. “In 2024, we are focused on completing patient enrollment for NGM707 with a potential interim Phase 1b trial readout in the middle of the year, initiating a potential Phase 2 proof-of-concept trial of NGM120 in HG by the end of 2024, and, provided we have the financial resources and agreement on trial design, initiating a registrational Phase 2 trial of aldafermin in PSC patients. Our priority remains to seek licensing and other business development partners across all our wholly-owned product candidates and to allocate our resources to the programs that we believe have the greatest potential both in the near- and long-term.” Key Fourth Quarter and Recent Highlights Solid Tumor Oncology Disclosed in January 2024 encouraging findings in a Phase 1 Part 1b cohort of the ongoing Phase 1/2 trial evaluating NGM707 in combination with pembrolizumab for the treatment of patients with advanced or metastatic solid tumors, including MSS CRC patients. 46 patients were enrolled as of the November 6, 2023 data-cutoff and, of the 37 response-evaluable patients (those completing at least one on-treatment scan), there were four confirmed partial responses across multiple indications, including one pathological complete response, and 12 patients with stable disease (11% overall response rate and 43% disease control rate). The combination of NGM707 and pembrolizumab was generally well-tolerated at all four doses (200, 600, 1200, 1800 mg) of NGM707. The maximum tolerated dose was not reached. NGM Bio expects to complete enrollment in the Phase 1 Part 1b cohort in the second quarter of 2024 and anticipates providing an update in mid-2024 on the fully enrolled cohort and subsequent next steps, including, provided sufficient financial resources, the potential for additional cohorts, which NGM Bio expects will include MSS CRC patients. Completed enrollment in the Phase 1 Part 1b cohorts of the Phase 1/1b trials evaluating NGM831, an ILT3 antagonist antibody product candidate, and NGM438, a LAIR1 antagonist antibody product candidate, in combination with pembrolizumab in patients with advanced solid tumors. NGM831 and NGM438, alone and in combination with pembrolizumab, have been generally well-tolerated and there have been no dose limiting toxicities noted to date. Initiated an ongoing Phase 1, Part 1c dose finding cohort evaluating the triplet combination of NGM831, NGM438 and pembrolizumab. This cohort is anticipated to complete enrollment in the first half of 2024. Hyperemesis Gravidarum Announced in January 2024 potential development of NGM120 for the treatment of HG. NGM120, a GFRAL antagonist antibody, is designed to block GDF15 signaling, the central cause of HG and, thereby, may potentially have therapeutic benefit for treating pregnant women suffering from HG. HG is a rare, serious condition that affects approximately 100,000 – 150,000 women in the United States each year during pregnancy and is characterized by intractable nausea and vomiting, which then results in dehydration, weight loss and malnutrition. HG has a significant physical and psychosocial impact on patients and leads to overall higher rates of fetal loss, preeclampsia, preterm birth, low birth weight and fetal malnutrition. HG is the second leading cause of hospitalization in pregnancy (second to preterm labor) and typically recurs in subsequent pregnancies. There are currently no FDA-approved therapies for this condition. Research1 has shown that GDF15 levels increase steadily in early pregnancy and, on average, are higher in women who experience nausea and vomiting in pregnancy and HG. The research also indicated that women with GDF15 genetic variants associated with lower levels of GDF15 in a non-pregnant state are predisposed to HG. NGM Bio’s goal is to initiate a Phase 2 proof-of-concept study of NGM120 for the treatment of HG by the end of 2024. NGM Bio is in the process of producing a toxicology package to submit to regulatory authorities in Australia or the United Kingdom that we hope will support initiation of the trial. Aldafermin Presented positive Phase 2b results from the ALPINE 4 trial of aldafermin in compensated cirrhosis (F4) due to NASH at AASLD The Liver Meeting in November 2023. In January 2024, announced U.S. Food and Drug Administration (FDA) granted orphan drug designation to aldafermin, an engineered FGF19 analog, for the treatment of PSC. NGM Bio plans to further develop aldafermin for the treatment of PSC, a rare liver disease that irreparably damages the bile ducts, leading to bile acid dysregulation, which, ultimately, results in serious liver damage. There are currently no FDA-approved therapies for PSC. NGM Bio is continuing discussions with the FDA regarding the design of a potential registrational trial of aldafermin in PSC, including on the proposed utilization of a primary endpoint composed of surrogate biomarkers with the goal of obtaining accelerated approval from the FDA. NGM Bio plans to continue working towards the goal of initiating a potential registrational trial contingent upon further discussion with the FDA on trial design and obtaining the additional capital necessary to conduct the study. Corporate On February 26, 2024, NGM Bio announced that it had entered into the Agreement and Plan of Merger (Merger Agreement) with Atlas Neon Parent, Inc. (Parent) and Atlas Neon Merger Sub, Inc., a wholly-owned subsidiary of Parent (Merger Sub). The Merger Agreement provides for, among other things, (i) the acquisition of NGM Bio by Parent through a cash tender offer (the Offer) by Merger Sub for each issued and outstanding share of NGM Bio’s common stock (other than certain rollover shares) for $1.55 per share (the Offer Price), and (ii) the merger of Merger Sub with and into NGM Bio (the Merger), with NGM Bio surviving the Merger as a privately held company. Subject to the terms of the Merger Agreement, the Offer Price will be paid subject to any applicable tax withholding and without interest. Pursuant to the Merger Agreement, on March 8, 2024, Parent commenced the Offer. Additional details can be found in NGM Bio’s recent filings with the United States Securities and Exchange Commission (SEC). NGM Bio anticipates that the Offer and the Merger contemplated under the Merger Agreement will be consummated in the second quarter of 2024. However, closing of the Merger is subject to customary closing conditions, and there can be no assurance that the Offer and the Merger contemplated by the Merger Agreement will be completed. If the Merger is effected, NGM Bio’s common stock will be delisted from The Nasdaq Stock Market LLC and NGM Bio will be privately held. Fourth Quarter and Full Year 2023 Financial Results NGM Bio reported a net loss of $27.7 million and $142.4 million for the quarter and year ended December 31, 2023, respectively, compared to a net loss of $36.4 million and $162.7 million for the same periods in 2022. Related party revenue from the collaboration with Merck Sharp & Dohme LLC, or Merck, was $0.2 million and $4.4 million for the quarter and year ended December 31, 2023, respectively, compared to $18.2 million and $55.3 million for the same periods in 2022. The collaboration with Merck ends on March 31, 2024. Research and development expenses were $21.9 million and $118.0 million for the quarter and year ended December 31, 2023, respectively, compared to $46.7 million and $181.1 million for the same periods in 2022. General and administrative expenses were $7.9 million and $37.8 million for the quarter and year ended December 31, 2023, respectively, compared to $9.8 million and $40.5 million for the same periods in 2022. Cash, cash equivalents and short-term marketable securities were $144.2 million as of December 31, 2023. About NGM Biopharmaceuticals, Inc. NGM Bio is focused on discovering and developing novel, life-changing medicines for people whose health and lives have been disrupted by disease. The company’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 and enable their rapid advancement into proof-of-concept studies. As explorers on the frontier of life-changing science, NGM Bio aspires to operate one of the most productive research and development engines in the biopharmaceutical industry. All therapeutic candidates in the NGM Bio pipeline have been generated by its in-house discovery engine, always led by biology and motivated by unmet patient need. Visit us at for more information. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Abbreviations (in Alphabetical Order) F4=fibrosis stage 4; FGF19=fibroblast growth factor 19; GDF15=growth differentiation factor 15; GFRAL=glial cell-derived neurotrophic factor receptor alpha-like; HG=hyperemesis gravidarum; NASH=nonalcoholic steatohepatitis; ILT2=immunoglobin-like transcript 2; ILT3=immunoglobin-like transcript 3; ILT4=immunoglobin-like transcript 4; LAIR1=leukocyte-associated immunoglobulin-like receptor 1 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 “encouraged”, “will,” “could,” “expect,” “expected,” “promising,” “aspires,” “aims,” “hope” 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 of NGM Bio’s product candidates; NGM Bio’s continued pipeline development, including identification and engagement of third-party partners for potential future business development arrangements, or the BD Arrangements, across all NGM Bio’s wholly-owned product candidates and to allocate its resources to the programs that it believes have the greatest potential both in the near- and long-term and; research and development and discovery engine output; the expected timing of completion of enrollment of NGM Bio’s ongoing Phase 1 Part 1b cohort of the Phase1/2 trial of NGM707 in combination with KEYTRUDA® (pembrolizumab) and timing of anticipated updates on the completed cohort and subsequent next steps, including the potential for additional cohorts; timing of the potential start of NGM120 in a proof-of-concept study for the treatment of HG; the design and initiation of a potential registrational trial for aldafermin for the treatment of PSC using surrogate endpoints; timing of completion of enrollment of NGM Bio’s ongoing Phase 1, Part 1c dose finding cohort evaluating the triplet combination of NGM831, NGM438 and pembrolizumab; the potential therapeutic benefit of NGM120 for treating pregnant women suffering from HG; the ability of NGM Bio and Atlas Neon Parent, Inc., a Delaware corporation (Parent), and Atlas Neon Merger Sub, Inc., a Delaware corporation and a wholly-owned subsidiary of Parent (together with Parent, the Purchaser) to complete the transactions contemplated by the Merger Agreement, including the parties’ ability to satisfy the conditions to the consummation of the Offer and the other conditions set forth in the Merger Agreement, statements about the expected timetable for completing the transactions, NGM Bio’s and Purchaser’s beliefs and expectations and statements about the benefits sought to be achieved by Purchaser’s proposed acquisition of NGM Bio, the possibility of any termination of the Merger Agreement, estimates relating to NGM Bio’s past, current or future financial condition; and other statements that are not historical fact. Because such statements deal with future events and are based on NGM Bio’s current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of NGM Bio 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; 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 preclinical or clinical trials to date may not be indicative of results obtained in future trials; the lack of regulatory clarity regarding acceptable surrogate endpoints for PSC and related development uncertainty; the vulnerable patient population experiencing HG and risks associated with clinical trials on such patient population; uncertainties inherent in the preclinical development process of NGM120 in HG, including that NGM120 in HG may never reach clinical development; NGM Bio’s ability to identify, attract and engage third-party partners for BD Arrangements for its wholly-owned programs; the time-consuming and uncertain regulatory approval process; NGM Bio’s reliance on third-party manufacturers for its product candidates and the risks inherent in manufacturing and testing pharmaceutical products; the sufficiency of NGM Bio’s cash resources and expected cash runway, including the risk that NGM Bio could utilize its available capital resources sooner than it currently expects and its need for additional capital; macroeconomic conditions (such as the impacts of global geopolitical conflict, global economic slowdown, increased inflation, rising interest rates and recent and potential future bank failures); the timing of the Offer and the subsequent Merger; uncertainties as to how many of the unaffiliated stockholders will tender their shares in the Offer; the risk that competing offers or acquisition proposals will be made; the possibility that various conditions to the consummation of the Offer and the subsequent Merger may not be satisfied or waived; the occurrence of any event, change or other circumstance that could give rise to the termination of the Merger Agreement, including in circumstances which would require NGM Bio to pay a termination fee; the effects of disruption from the transactions contemplated by the Merger Agreement; the risk that stockholder litigation in connection with the Offer or the Merger may result in significant costs of defense, indemnification and liability; and other risks and uncertainties affecting NGM Bio and its development programs, including those discussed in the section titled “Risk Factors” in NGM Bio’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 filed with the SEC on November 2, 2023 and future filings and reports that NGM Bio makes from time to time with the SEC. Except as required by law, NGM Bio 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: ir@ngmbio.com Media Contact: media@ngmbio.com 1 Fejzo, M., Rocha, N., Cimino, I. et al. GDF15 linked to maternal risk of nausea and vomiting during pregnancy. Nature (2023). NGM BIOPHARMACEUTICALS, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (In thousands, except per share amounts) (Unaudited) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022* Related party revenue $ 165 $ 18,181 $ 4,417 $ 55,333 Operating expenses: Research and development 21,890 46,722 118,040 181,067 General and administrative 7,938 9,756 37,840 40,515 Total operating expenses 29,828 56,478 155,880 221,582 Loss from operations (29,663 ) (38,297 ) (151,463 ) (166,249 ) Interest income, net 2,041 2,030 9,322 3,714 Other expense, net (48 ) (170 ) (234 ) (132 ) Net loss $ (27,670 ) $ (36,437 ) $ (142,375 ) $ (162,667 ) Net loss per share, basic and diluted $ (0.33 ) $ (0.45 ) $ (1.73 ) $ (2.03 ) Weighted average shares used to compute net loss per share, basic and diluted 82,803 81,787 82,496 79,950 ___________ * Derived from the audited consolidated financial statements. NGM BIOPHARMACEUTICALS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS (In thousands) (Unaudited) December 31, 2023 December 31, 2022* ASSETS Current assets: Cash and cash equivalents $ 55,816 $ 73,456 Short-term marketable securities 88,369 198,036 Related party receivable from collaboration 58 7,580 Prepaid expenses and other current assets 9,202 9,787 Restricted cash 2,999 — Total current assets 156,444 288,859 Property and equipment, net 7,033 8,496 Operating lease right-of-use asset — 2,096 Restricted cash 2,455 3,954 Other non-current assets 2,936 3,997 Total assets $ 168,868 $ 307,402 LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities: Accounts payable $ 2,982 $ 8,453 Accrued liabilities 17,099 33,638 Operating lease liability, current — 5,385 Contract liabilities — 366 Total current liabilities 20,081 47,842 Other non-current liabilities 149 — Total liabilities 20,230 47,842 Commitments and contingencies Stockholders' equity: Preferred stock, $0.001 par value — — Common stock, $0.001 par value 83 82 Additional paid-in capital 872,545 841,413 Accumulated other comprehensive income (loss) 18 (302 ) Accumulated deficit (724,008 ) (581,633 ) Total stockholders' equity 148,638 259,560 Total liabilities and stockholders' equity $ 168,868 $ 307,402 ___________ * Derived from the audited consolidated financial statements.

Encouraging findings in heavily pretreated patients in multiple solid tumor indications, including MSS colorectal cancer (CRC), in ongoing Phase 1 Part 1b study evaluating NGM707, a dual ILT2/ILT4 antagonist antibody, in combination with KEYTRUDA® (pembrolizumab) Aldafermin, an engineered FGF19 analog, has been granted Orphan Drug Designation by the FDA for the treatment of primary sclerosing cholangitis (PSC), a rare liver disease Initiating design of a potential registrational trial of aldafermin in PSC and in discussion with the FDA on utilizing proposed surrogate endpoints with the goal of obtaining accelerated approval Large body of clinical data, including from NGM Bio’s prior Phase 2 study in PSC, supports aldafermin’s differentiated potential to address the bile acid dysregulation underpinning PSC NGM120, a GDF15/GFRAL antagonist, has strong biologic rationale for the treatment of hyperemesis gravidarum Discussing design of an acceptable toxicology package to support clinical trials in hyperemesis gravidarum patients in ongoing dialogue with the FDA Recent evidence suggests this rare, devastating condition is linked to higher levels of, and greater sensitivity to, GDF15 during pregnancy NGM Bio is a long-time pioneer in elucidating GDF15 biology, including identifying its cognate receptor, GFRAL SOUTH SAN FRANCISCO, Calif., Jan. 09, 2024 (GLOBE NEWSWIRE) -- NGM Biopharmaceuticals, Inc. (NGM Bio) (Nasdaq: NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, today announced encouraging new data from an ongoing Phase 1 Part 1b study evaluating NGM707, a dual ILT2/ILT4 antagonist antibody product candidate, in combination with KEYTRUDA® (pembrolizumab). NGM Bio also outlined its strategy to evolve clinical development of its product candidates aldafermin and NGM120 to focus on rare conditions characterized by significant unmet need. “Our priorities for 2024 center on directing our efforts and investing our resources as efficiently and effectively as possible toward select development activities that we believe have the greatest potential to deliver nearer-term impact and value creation while being fully aligned with our mission to deliver life-changing medicines for patients with significant unmet needs,” said David J. Woodhouse, PhD, Chief Executive Officer at NGM Bio. Dr. Woodhouse continued, “Our focus on the combination of NGM707 and pembrolizumab stems from encouraging responses observed in heavily pretreated patients with very advanced disease, including MSS CRC, that has been largely unresponsive to anti-PD-1/L1 monotherapy. Our interest and efforts in aldafermin in PSC are based on data that we believe supports aldafermin’s differentiated potential as an engineered FGF19 analog to address the bile acid dysregulation underpinning this rare liver disease, including our prior Phase 2 study in PSC, as well as our positive clinical study in NASH F4 patients and data from other PSC trials supporting the use of biomarkers of fibrosis, such as ELF, to predict clinical outcomes. Finally, our potential exploration of NGM120, a GDF15/GFRAL antagonist, in a proof-of-concept study for the treatment of hyperemesis gravidarum is rooted in our decade-long efforts advancing the understanding of GDF15 biology and exploring its therapeutic application in a number of disease areas. Recent landmark genetic research confirmed the link between this rare, devastating condition experienced during pregnancy to higher levels of GDF15. Given our deep expertise in GDF15 biology, we believe we are well positioned to potentially pursue this indication for NGM120. As we concurrently pursue these important development efforts, exploring partnering opportunities across our full product candidate and research portfolio, all wholly owned by NGM, remains an important priority for us in 2024.” Key Pipeline Updates NGM707 in Advanced Solid Tumors Announced encouraging new findings from the Phase 1 Part 1b dose escalation cohort of the ongoing Phase 1/2 trial evaluating NGM707 in combination with pembrolizumab for the treatment of patients with advanced or metastatic solid tumors. The combination of NGM707 and pembrolizumab was generally well tolerated at all four dose levels of NGM707. The maximum tolerated dose was not reached. The Phase 1 Part 1b cohort enrolled 46 patients as of a November 6, 2023 data-cutoff. Of 37 response-evaluable patients (those completing at least one on-treatment scan), there were four confirmed partial responses (PRs) across multiple indications, including one pathological complete response (CR), and 12 stable disease (SD) (11% overall response rate [ORR] and 43% disease control rate [DCR]). The pathological CR patient had significant target lesion reduction that allowed subsequent surgical resection of all gross residual disease, resulting in a confirmed pathological CR with no active tumor cells and ctDNA below detection. Three of the four responders had active liver metastases at baseline; patients with liver metastases, which are associated with immune suppression and lower survival rates, tend to have a reduced response to immunotherapy. Eight of the 37 response-evaluable patients had MSS CRC; two of these MSS CRC patients were among the confirmed PRs, including the patient with a pathological CR, and two had SD (25% ORR and 50% DCR). Anti-PD-1/L1 monotherapies have shown low or no benefit in MSS CRC patients. NGM Bio is completing enrollment in the Phase 1 Part 1b cohort and anticipates providing an update in mid-2024 on the completed cohort and subsequent next steps, including the potential for additional cohorts, which may include MSS CRC patients. Aldafermin in Primary Sclerosing Cholangitis (PSC) Announced planned further development of aldafermin for the treatment of PSC, a rare liver disease that irreparably damages the bile ducts, leading to bile acid dysregulation, which, ultimately, results in serious liver damage. There are currently no FDA-approved therapies for PSC. NGM Bio recently met with the FDA regarding the design of a potential registrational trial, including the utilization of proposed surrogate primary endpoints. NGM Bio plans to continue working with the FDA to reach agreement on a trial design in the coming months, with the goal of initiating trial enrollment by the end of 2024, contingent upon reaching agreement with the FDA on trial design and additional capital availability. NGM Bio’s decision to pursue the potential further clinical development of aldafermin as a treatment for PSC was informed by a large body of clinical data. Over 800 patients across multiple indications have been treated with aldafermin, which has repeatedly demonstrated powerful bile acid suppression in patients with PSC and NASH, and thus, NGM Bio believes aldafermin has the differentiated potential to directly address the underlying biology of PSC. NGM Bio previously reported data from a randomized, double-blind, placebo-controlled Phase 2 study of aldafermin for the treatment of PSC. While that Phase 2 study did not meet its primary endpoint of statistically significant change in alkaline phosphatase, an exploratory biomarker of PSC disease progression, from baseline to week 12, aldafermin demonstrated both statistically significant improvements in biomarkers of hepatic injury and fibrosis, as well as statistically significant reductions in biomarkers of bile acid synthesis and serum bile acids, consistent with past studies of aldafermin in other liver diseases. The Phase 2 study met the secondary endpoints and was generally well tolerated by patients. NGM120 in Hyperemesis Gravidarum Announced potential development of NGM120 for the treatment of hyperemesis gravidarum (referred to colloquially as hyperemesis), subject to the outcome of ongoing discussions with the FDA. Hyperemesis, a rare, serious condition that affects approximately 100,000 – 150,000 women in the United States each year during pregnancy, is characterized by intractable nausea and vomiting, which then results in dehydration, weight loss and malnutrition. Hyperemesis has a significant physical and psychosocial impact on patients and leads to overall higher rates of fetal loss, preeclampsia, preterm birth, low birth weight and fetal malnutrition. Hyperemesis is the second leading cause of hospitalization in pregnancy (second to preterm labor) and typically recurs in subsequent pregnancies. There are currently no FDA-approved therapies for this condition. Research published by an international team that included Marlena Fejzo, Ph.D., Clinical Assistant Professor of Population and Public Health Sciences in the Center for Genetic Epidemiology at the University of Southern California, and Sir Stephen O'Rahilly, M.D. FRS FMedSci, Professor of Clinical Biochemistry and Medicine at the University of Cambridge, found that GDF15 levels increase steadily in early pregnancy and are higher in women who experience nausea and vomiting in pregnancy and hyperemesis. The research uncovered that women with GDF15 genetic variants associated with lower levels of GDF15 in a non-pregnant state are predisposed to hyperemesis. NGM120, a GFRAL antagonist antibody, is designed to block GDF15 signaling and, thereby, may have therapeutic benefit for treating patients suffering from hyperemesis. Dr. Fejzo, who experienced hyperemesis in her own pregnancies and subsequently dedicated her professional life to uncovering the biology underpinning the condition, is serving as an advisor to NGM Bio. Key 2023 Highlights Solid Tumor Oncology Continued enrollment in a Phase 1 Part 1b cohort of the ongoing Phase 1/2 trial evaluating NGM707 in combination with pembrolizumab for the treatment of patients with advanced or metastatic solid tumors. This cohort is anticipated to complete enrollment in the first half of 2024. Completed enrollment in Phase 1 Part 1b cohorts of Phase 1/1b trials evaluating NGM831 and NGM438, respectively, in combination with pembrolizumab in patients with solid tumors. NGM831 is an ILT3 antagonist antibody product candidate, and NGM438 is a LAIR1 antagonist antibody product candidate. Initiated an ongoing Phase 1 Part 1c dose finding cohort evaluating the triplet combination of NGM831, NGM438 and pembrolizumab. This cohort is anticipated to complete enrollment in the first half of 2024. Completed a Phase 2 randomized, single-blind (investigator-blinded), placebo-controlled, multi-center expansion trial of NGM120 in combination with gemcitabine and Nab-paclitaxel as a first-line treatment in patients with metastatic pancreatic cancer (referred to as the PINNACLES trial). NGM120 was well tolerated in the trial. A clear signal of response was not detected, and further development of NGM120 in oncology has been paused. Liver and Metabolic Diseases Presented positive, comprehensive results from the Phase 2b ALPINE 4 trial of aldafermin in patients with compensated cirrhosis (liver fibrosis stage 4 or F4) due to NASH at AASLD The Liver Meeting® in November 2023. ALPINE 4 met its primary endpoint, with aldafermin 3 mg demonstrating a statistically significant reduction in ELF score compared to placebo at 48 weeks of treatment. Although ALPINE 4 was not statistically powered for the secondary endpoint of histological fibrosis improvement of ≥1-stage (NASH Clinical Research Network, or CRN, criteria), a dose-dependent trend in fibrosis improvement was observed. Announced positive data from a Phase 2 investigator-sponsored trial of aldafermin for the treatment of patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and bile acid malabsorption (BAM) in May 2023 at Digestive Disease Week 2023. Aldafermin demonstrated statistically significant reductions in serum 7αC4 (a marker of bile acid synthesis) and fecal bile acids versus placebo in patients with idiopathic BAM with IBS-D. Key 2024 Priorities and Anticipated Milestones Complete enrollment in the Phase 1 Part 1b cohort evaluating the combination of NGM707 and pembrolizumab; provide an update in mid-2024. Continue discussions with the FDA on the design of a potential registrational trial of aldafermin for the treatment of PSC and provide an update in the first half of 2024; plan to initiate enrollment by the end of 2024, contingent upon reaching agreement with the FDA on trial design and additional capital availability. Plan to initiate a reproductive toxicology study of NGM120 for the treatment of hyperemesis in 2024, subject to ongoing discussions with the FDA. Continue exploring partnering opportunities across the full NGM Bio product candidate and research portfolio. NGM Bio may further develop other product candidates in its pipeline, pending partnering and/or the availability of additional capital. NGM Bio plans to post an updated corporate presentation on the Investor Relations section of NGM Bio’s website at . About NGM Bio NGM Bio 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 and enable their rapid advancement into proof-of-concept studies. All therapeutic candidates in the NGM Bio pipeline have been generated by its in-house discovery engine, always led by biology and motivated by unmet patient need. Visit us at for more information. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA Abbreviations (in Alphabetical Order) F4=Fibrosis stage 4; ILT2=Immunoglobin-Like Transcript 2; ILT3=Immunoglobin-Like Transcript 3; ILT4=Immunoglobin-Like Transcript 4; LAIR1=Leukocyte-Associated Immunoglobulin-Like Receptor 1; MSS=Microsatellite stable; NASH=nonalcoholic steatohepatitis 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 “support”, “aims,” “anticipates,” “believe,” “may,” “plans,” “potential,” “promising,” “proposed” 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 Bio’s evolved strategy for aldafermin and NGM120 and focus on rare conditions with unmet needs, and NGM Bio’s belief that this strategy has the greatest potential to deliver nearer-term impact and value creation; discussions with the FDA regarding the design of a potential registrational trial of aldafermin in PSC, including the proposed use of surrogate endpoints for potential accelerated approval; NGM Bio’s belief that the large body of clinical data supports aldafermin’s differentiated potential to address the bile acid dysregulation underpinning PSC; the potential of aldafermin as an engineered FGF19 analog to address the bile acid dysregulation underpinning PSC; the potential of biomarkers of fibrosis, like ELF, to predict clinical outcome in patients with PSC; the potential of NGM120 to treat hyperemesis; NGM Bio’s potential exploration of NGM120 in a planned proof-of-concept study for the treatment of hyperemesis, including ongoing discussions with the FDA on an acceptable toxicology package; the therapeutic potential of, potential indications for and/or planned and continued development of the product candidates in NGM Bio’s pipeline, including NGM707, aldafermin, NGM120, NGM831 and NGM438; the planned timing of initiation, enrollment, data readouts and results of NGM Bio’s clinical trials; NGM Bio’s continued pipeline development, including identification and engagement of third-party partners for potential future business development arrangements (“BD Arrangements”) to determine further development of programs across the full NGM Bio product candidate and research portfolio; and other statements that are not historical fact. Because such statements deal with future events and are based on NGM Bio’s current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of NGM Bio 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 shift in NGM Bio’s strategy and investor perception thereof; the costly and time-consuming pharmaceutical product development process and the uncertainty of clinical success; 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 preclinical or clinical trials to date may not be indicative of results obtained in future trials and that interim topline and preliminary results of clinical trials may change as more participant data becomes available and are subject to audit and verification procedures, which could result in material changes in the final data and such interim topline and preliminary results may not be predictive of final results or results obtained in future trials; the lack of regulatory clarity regarding acceptable surrogate endpoints for PSC and related development uncertainty; the vulnerable patient population experiencing hyperemesis and risks associated with clinical trials on such patient population; uncertainties inherent in the preclinical development process of NGM120 in hyperemesis, including that NGM120 in hyperemesis may never reach clinical development; NGM Bio’s ability to identify, attract and engage third-party partners for BD Arrangements; the time-consuming and uncertain regulatory approval process; NGM Bio’s reliance on third-party manufacturers for its product candidates and the risks inherent in manufacturing and testing pharmaceutical products; the sufficiency of NGM Bio’s cash resources and anticipated cash runway, including the risk that NGM Bio could utilize its available capital resources sooner than it currently expects, and its need for additional capital to pursue further development of its product candidates, including the additional capital necessary for NGM Bio to pursue further development of aldafermin in PSC and NGM120 in hyperemesis; macroeconomic conditions (such as the impacts of global geopolitical conflict, global economic slowdown, increased inflation, high interest rates and recent and potential future bank failures); and other risks and uncertainties affecting NGM Bio and its development programs, including those discussed in the section titled “Risk Factors” in NGM Bio’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 filed with the United States Securities and Exchange Commission (“SEC”) on November 2, 2023 and future filings and reports that NGM Bio makes from time to time with the SEC. Except as required by law, NGM Bio 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: Media Contact: ir@ngmbio.com media@ngmbio.com

In mouse experiments with the weight-loss-driving molecule GDF15, weight loss plateaued in the untreated group after 14 days in spite of their still-restricted diet. But the treated group continued to shed kilograms for another four weeks. It’s a conundrum well-known to scientists and dieters alike: When one loses weight, the body’s metabolism slows, making it harder to keep the pounds off even with continued calorie restriction. But despite being documented for more than 50 years, researchers haven’t yet figured out a way to outsmart the phenomenon, known as adaptive thermogenesis. “We know people are very good at losing weight in the short term,” Gregory Steinberg, Ph.D., a researcher at McMaster University, told Fierce Biotech Research in an interview. “But if you lose 10% of your body weight, your metabolism will slow down by 200 to 300 calories a day. The mechanisms behind that aren’t really well understood.” Steinberg and his lab have unlocked new knowledge in the quest for the ultimate solution: A weight loss drug that doesn’t just help patients lose pounds, but does so without slowing their metabolism. In the results of a new study published June 27 in Nature (sponsored in part by Novo Nordisk), his team of international collaborators described how they discovered that the protein growth/differentiation factor 15, or GDF15, induces weight loss by stimulating muscle cells to burn more energy. Their findings also shed light on the mystery of how losing weight drives down one’s metabolism. While GDF15’s potential to induce weight loss has been established in preclinical models for a while—drugs that stimulate its receptor, GFRAL, have even made it to clinical trials—this is the first time a research team has characterized its mechanism of action. Steinberg and his team were building on previous work that suggested the appetite-suppressing effects of the diabetes drug metformin depended on GDF15, levels of which increased in response to the drug. But back then, it wasn’t clear how or why. “This was a really bizarre finding to us because when we looked at what the heck GDF15 is and why it was going up, we saw that it was a biomarker indicating that, basically, you were going to die,” Steinberg recalled. Indeed, high GDF15 levels are associated with cancer, heart attacks, strokes and death in general—the opposite of what you’d expect to see from taking metformin, which some research has linked to longevity. As the scientists were scratching their heads, new papers began to emerge showing a link between GDF15 and weight loss. The molecule appeared to be responsible for appetite suppression in cancer patients—a quality that Big Pharma was already eyeing, according to Steinberg. But he and his team wondered if GDF15 might be doing something more.“We were really intrigued by the idea that it might be controlling metabolism independently of its impact on appetite,” he said.  The researchers took two groups of mice, injected one with the unmodified GDF15 protein, and then over the course of two weeks fed them according to what’s called caloric matching or pair feeding: However much the treated group ate, the untreated group was fed the same amount. As expected, both groups lost weight—the same amount, in fact, about 5% of their starting body weight. “This was exactly what other groups had shown before, which led to the conclusion that GDF15 was primarily causing weight loss by suppressing appetite,” Steinberg explained. But unlike in earlier studies, his team extended the experiment out another four weeks. Over that period, weight loss plateaued in the untreated group in spite of their still-restricted diet. Meanwhile, the treated group continued to shed kilograms, with the group that received a lower dose of the drug dropping to about 85% of their starting weight and the one that received a higher dose falling to 76%. What the researchers observed in the untreated mice “is consistent with dieting—you can stick with the same diet, but you don’t just keep losing weight,” Steinberg said. “Eventually, your metabolism slows down and the weight loss doesn’t happen at the same rate.” That wasn’t the case for the mice treated with GDF15, however, indicating that something must be keeping their metabolism revved. Experiments on genetically-altered mice lacking the GDF15 receptor in the brain confirmed that the molecule’s presence there was essential for energy expenditure, but they didn’t explain the connection between the brain and the body. That sent the team on a bit of a hormone goose chase. Was the protein-altering thyroid hormone levels? Nope. Cortisol? Not that, either. A light bulb began to glow when the researchers found that mice with a gene mutation that impaired sympathetic nervous system (SNS) activity didn’t lose weight after being injected with GDF15. At first, the researchers thought SNS stimulation might be activating a process called futile cycling in brown fat. Futile cycling is when two metabolic pathways run simultaneously, producing and reusing each others’ metabolites, with no net product other than burned energy. “But we looked at this for over a year and found absolutely no evidence that it was increasing energy burning [in brown fat],” Steinberg recalled. “And then we got to thinking, ‘Well, maybe it’s muscle.’” Additional studies confirmed that idea. By stimulating the sympathetic nervous system, GDF15 was upregulating calcium release in the muscle. The muscle cells were using it up through futile cycling, releasing energy in the process, Steinberg explained. “[The process] required more ATP to get that calcium back under control,” he said. “And of course, if you’re using more ATP, then you need to burn more calories to keep those levels constant.” The effects of this were apparent when the researchers compared the muscle mass of GDF15-treated mice with the ones on a calorie-restricted diet alone. As expected, the untreated mice lost muscle function—dieting causes you to lose not just fat, but muscle mass. But the ones in the GDF15 group preserved it. This is a key difference from GLP-1 agonists, Steinberg noted. Rapid muscle loss is one of the maligned side effects of drugs like Ozempic and Wegovy; in the STEP1 trial on semaglutide, a drop in lean muscle mass accounted for nearly 40% of total weight loss. The same results were seen in the SUSTAIN 8 trial, which also found that 40% of weight loss could be contributed to shrunken muscle mass, even with lower doses. “This is really important because this is one of the things that people don't like about the GLP-1 receptor agonists,” Steinberg said. “But it seemed like GDF15 was maintaining muscle function better than if you just restricted the calories.” It’s unclear right now how GDF15 will fit into the wider world of weight loss drugs. Clinical trials on modified forms of the protein have produced disappointing results Lilly, for instance, reported in February that a phase 1 test of its long-acting GDF15 receptor agonist showed that despite attenuating appetite and being well-tolerated, the drug had little effect on participants’ weight. “These results demonstrate that agonism of the [GDF15-GFRAL receptor system] can modulate energy balance in humans, though the decrease in body weight is surprisingly modest, suggesting challenges in leveraging the GDF15 system for clinical weight loss applications,” the researchers concluded. Those lackluster results aren’t necessarily a reason to stop pursuing GDF15 as a weight loss aid, Steinberg said, especially given what scientists are learning about its mechanism of action. It could be that the best results will come from combining GDF15 and GLP-1 receptor agonists, or that unmodified GDF15 itself is the ticket to efficacy in humans. No one so far has tried injecting people with native GDF15, as far as Steinberg knows. And in any case, scientists spent decades trying to develop a GLP-1 agonist that could work for weight loss in humans, he pointed out. “The initial GLP-1 receptor agonist didn’t induce this huge weight loss that we see today—it took 20 years of refining them to get where we are now,” Steinberg said. “It didn’t just happen overnight. It’s easy to say that this is just a mouse study that didn’t translate, but I think it’s too early to say that.” For his team, there are a couple of items next up on the to-do list. One is animal studies putting weight loss drugs with GDF15 to see whether combination therapies might be effective. Another is human research analyzing how levels of the protein change after the pounds come off.