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First Patient Expected to be Randomized in the Second Quarter of 2024 CAMBRIDGE, Mass., Feb. 29, 2024 /PRNewswire/ -- NeuroBo Pharmaceuticals, Inc. (Nasdaq: NRBO), a clinical-stage biotechnology company focused on transforming cardiometabolic diseases, today announced that it has received first site Institutional Review Board (IRB) approval for Alexander Prezioso, M.D., Investigator, Clinical Pharmacology of Miami, in Hialeah, FL, to proceed with the Phase 1 clinical trial of DA-1726, a novel, dual oxyntomodulin (OXM) analog agonist that functions as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR), for the treatment of obesity. The company expects to randomize the first patient in the second quarter of this year. "With this first site IRB approval, we have achieved another significant milestone in the development of DA-1726, bringing the program one step closer to the clinic," stated Hyung Heon Kim, President and Chief Executive Officer of NeuroBo. "This promising cardiometabolic asset may have a better tolerability profile than currently available GLP-1 agonists due to its balanced activation of GLP1R and glucagon receptors. As previously reported, in mouse models, DA-1726 showed superior weight loss compared to semaglutide (Wegovy®), and its administration resulted in similar weight reduction while consuming more food compared to tirzepatide (Zepbound™). We look forward to working closely with our contract research organization (CRO) partner and our investigators, such as Dr. Prezioso, to start randomizing patients in the second quarter of this year. We expect to report top-line data from the single ascending dose (SAD) Part 1 in the first half of 2025 and the multiple ascending dose (MAD) Part 2 in the second half of 2025." The Phase 1 trial is designed to be a randomized, placebo-controlled, double-blind, two-part study to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple ascending doses of DA-1726 in obese, otherwise healthy subjects. Part 1 will be a single ascending dose (SAD) study, expected to enroll approximately 45 participants, randomized into one of 5 planned cohorts. Each cohort will be randomized in a 6:3 ratio of DA-1726 or placebo. Part 2 will be a multiple ascending dose (MAD) study, expected to enroll approximately 36 participants, who will be randomized at the same 6:3 ratio into 4 planned cohorts, each to receive 4 weekly administrations of DA-1726 or placebo. The primary endpoint will assess the safety and tolerability of DA-1726 by monitoring adverse events (AEs), serious adverse events (SAEs), treatment emergent adverse events (TEAEs) and AEs leading to treatment discontinuation. Secondary endpoints include the PK of DA-1726, assessed via serum concentrations over time and metabolite profiling at the highest doses of DA-1726. Exploratory endpoints will include the effect of DA-1726 on metabolic parameters, cardiac parameters, fasting lipid levels, body weight, waist circumference and body mass index (BMI), among others. For more information on this clinical trial, please visit: NCT06252220. About DA-1726 DA-1726 is a novel oxyntomodulin (OXM) analogue functioning as a GLP1R/GCGR dual agonist for the treatment of obesity and NASH that is to be administered once weekly subcutaneously. DA-1726 as a dual agonist of GLP-1 receptors (GLP1R) and glucagon receptors (GCGR), leading to weight loss through reduced appetite and increased energy expenditure. DA-1726 has a well understood mechanism and, in preclinical mice models, resulted in improved weight loss compared to semaglutide and cotadutide (another OXM analogue). About NeuroBo Pharmaceuticals NeuroBo Pharmaceuticals, Inc. is a clinical-stage biotechnology company focused on transforming cardiometabolic diseases. The company is currently developing DA-1241 for the treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Type 2 Diabetes Mellitus (T2DM), and is developing DA-1726 for the treatment of obesity. DA-1241 is a novel G-protein-coupled receptor 119 (GPR119) agonist that promotes the release of key gut peptides GLP-1, GIP, and PYY. In preclinical studies, DA-1241 demonstrated a positive effect on liver inflammation, lipid metabolism, weight loss, and glucose metabolism, reducing hepatic steatosis, hepatic inflammation, and liver fibrosis, while also improving glucose control. DA-1726 is a novel oxyntomodulin (OXM) analogue that functions as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR) dual agonist. OXM is a naturally-occurring gut hormone that activates GLP1R and GCGR, thereby decreasing food intake while increasing energy expenditure, thus potentially resulting in superior body weight loss compared to selective GLP1R agonists. For more information, please visit . Forward Looking Statements Certain statements in this release may be considered forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "believes", "expects", "anticipates", "may", "will", "should", "seeks", "approximately", "intends", "projects," "plans", "estimates" or the negative of these words or other comparable terminology (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements are predictions, projections and other statements about future events that are based on current expectations and assumptions and, as a result, are subject to risks and uncertainties. Many factors could cause actual future events to differ materially from the forward-looking statements in this release, including, without limitation, those risks associated with NeuroBo's ability to execute on its commercial strategy; the timeline for regulatory submissions; ability to obtain regulatory approval through the development steps of NeuroBo's current and future product candidates, the ability to realize the benefits of the license agreement with Dong-A ST Co. Ltd., including the impact on future financial and operating results of NeuroBo; the cooperation of our contract manufacturers, clinical study partners and others involved in the development of NeuroBo's current and future product candidates; potential negative interactions between our product candidates and any other products with which they are combined for treatment; NeuroBo's ability to initiate and complete clinical trials on a timely basis; our ability to recruit subjects for its clinical trials; whether NeuroBo receives results from NeuroBo's clinical trials that are consistent with the results of pre-clinical and previous clinical trials; impact of costs related to the license agreement, known and unknown, including costs of any litigation or regulatory actions relating to the license agreement; effects of changes in applicable laws or regulations; effects of changes to NeuroBo's stock price on the terms of the license agreement and any future fundraising; and other risks and uncertainties described in our filings with the SEC. Forward-looking statements speak only as of the date when made. NeuroBo does not assume any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Contacts: NeuroBo Pharmaceuticals Marshall H. Woodworth Interim Chief Financial Officer +1-857-299-1033 [email protected] Rx Communications Group Michael Miller +1-917-633-6086 [email protected] SOURCE NeuroBo Pharmaceuticals, Inc.

Boehringer is also investigating survodutide’s efficacy in obesity in five clinical trials. Credit: Michael Vi via Shutterstock. Boehringer Ingelheim’s glucagon/GLP-1 receptor dual agonist survodutide has demonstrated efficacy for metabolic dysfunction-associated steatohepatitis (MASH), a liver disease connected with other cardiovascular, renal, and metabolic conditions. The Phase II trial (NCT04771273) met its primary endpoint, wherein 83% of patients treated with survodutide saw significant biopsy-proven improvement in MASH without the worsening of their fibrosis stages, compared to 18.2% of patients who took the placebo. Boehringer Ingelheim’s candidate stands out from other GLP-1 receptor agonists in that it also targets the hormone glucagon. Simultaneously activating these two key gut hormone receptors could potentially produce more efficacious results than the current single-hormone agonists, such as Novo Nordisk ’s Wegovy and Eli Lilly’s Zepbound, the two main players for obesity. In the Phase II trial, secondary endpoints evaluating reduced liver fibrosis and lower liver fat content, as measured by a specific magnetic resonance imaging (MRI) techniques were also met. Boehringer, in partnership with the Danish biotech Zealand , is investigating survodutide in five clinical trials for obesity, including three—SYNCHRONIZE-1, SYNCHRONIZE-2 and SYNCHRONIZE-CVOT—which were kicked off in May 2023. See Also: Amneal signs agreement with Zambon for Parkinson’s disease therapy Biogen receives EMA CHMP recommendation for ALS drug Qalsody The booming obesity market is forecast to reach $37.1bn in the seven major markets (US, France, Germany, Italy, Spain, UK and Japan) in 2031, according to a report on GlobalData’s Pharma Intelligence Center. GlobalData is the parent company of Pharmaceutical Technology. In June 2021, the US Food and Drug Administration (FDA) granted fast track designation for survodutide, with the European Medicines Agency (EMA) following suit, granting access to the Priority Medicine (PRIME) scheme for MASH with fibrosis in November 2023. The scheme enables earlier access to treatments that targets conditions with an unmet medical need. In the 26 February announcement accompanying the data, head of human pharma at Boehringer Carinne Brouillon said: “These MASH results show survodutide has potential to become a best-in-class treatment, and we believe its true differentiator is the action of the glucagon receptor agonism which works directly on the liver.” Earlier this year, Boehringer reinforced its interest in MASH entering into a multi-target collaboration with Suzhou Ribo Life Science and Ribocure Pharmaceuticals (Ribo) targeting the condition in a deal worth $2bn. This collaboration comes six years after Boehringer joined forces with Dicerna Pharmaceuticals to discover and develop new therapeutics using Dicerna’s GalXC technology platform, for the treatment of liver diseases including MASH.

A Boehringer Ingelheim drug in development for weight loss now has data from a separate mid-stage clinical trial showing dramatic reductions across several measures of a fatty liver disease whose severe problems can lead up to requiring a liver transplant. In preliminary Phase 2 clinical trial results announced Monday, 48 weeks of treatment with the experimental drug, survodutide, led to 83% of patients showing statistically significant improvement in the disease, metabolic dysfunction-associated steatohepatitis, or MASH. By comparison, 18.2% of patients met that main study goal. The results were determined by liver biopsy, which showed improvement from the treatment was achieved without worsening of fibrosis, the liver scarring that is characteristic of the chronic liver disorder. Specific details were not provided, but Boehringer Ingelheim said its drug met all secondary goals, including a statistically significant improvement in liver fibrosis. These are preliminary data. The privately held German company said full data will be presented in coming months. Survodutide comes from the labs of publicly traded Zealand Pharma, which struck up a research collaboration with Boehringer in 2011 focused on developing therapies for type 2 diabetes, obesity, and non-alcoholic steatohepatitis (NASH), which is now referred to as MASH. The drug simultaneously activates two gut hormone receptors. Targeting the receptor for GLP-1 decreases appetite and increases satiety; hitting the glucagon receptor offers the potential to increase energy expenditure, which the company said potentially contributes to fibrosis improvement. Last June, Boehringer Ingelheim presented data showing its drug met the main goal of its Phase 2 test in obesity. A Phase 3 study in obesity is underway. The Phase 2 test of survodutide in MASH enrolled 295 participants. This study is evaluating three doses of the drug, administered once weekly by injection. In addition to preliminary results reported Monday showing improvement in the disease at all three doses, Boehringer said the drug did not show any unexpected safety or tolerability issues. Survodutide is a potential competitor to Eli Lilly’s tirzepatide, which activates two gut hormone receptors: GLP-1 and GIP. Earlier this month, Eli Lilly reported preliminary Phase 2 data for tirzepatide in MASH, with results showing 74% of study participants who received the highest dose achieved the study goal compared to 12.6% of those given placebo. Tirzepatide was first approved for type 2 diabetes and has become a blockbuster seller in that indication, marketed under the brand name Mounjaro. Last fall, the FDA approved the drug for chronic weight management, where it’s marketed as Zepbound. While Lilly’s MASH results show its drug led to “clinically meaningful” improvement on the fibrosis secondary endpoint, Boehringer said survodutide met all of its secondary endpoints, including demonstrating statistically significant improvement in liver fibrosis. Boehringer Ingelheim contends this result positions its drug to top its rivals. “These MASH results show survodutide has potential to become a best-in-class treatment, and we believe its true differentiator is the action of the glucagon receptor agonism which works directly on the liver,” Carinne Brouillon, head of human pharma, Boehringer Ingelheim, said in a prepared statement. Financial analysts are more cautious. In a note sent to investors, Leerink Partners analyst Thomas Smith said there are limitations in interpreting the Boehringer data, including the trial’s enrollment of a broader population of patients that includes those with mild fibrosis. Without knowing the proportion of the patient enrollment this group represents, it’s unclear whether or how much these patients contributed to the overall fibrosis improvement or whether this benefit holds only in those in more advanced stages of fibrosis, he said. It’s also unclear whether the analyses represent the drug taken as advised or a more real-world situation in which patients may take the drug irregularly or stop taking the medication. Smith also noted a lack of detail on the drug’s safety and tolerability. “We view these as key details needed to properly contextualize the topline results, and expect these data will be featured as a late breaking presentation at the upcoming European Association for the Study of the Liver (EASL) Congress in June,” Smith said. The MASH field could have its first therapeutic product by then. The FDA set a March 14 target date for a regulatory decision on Madrigal Pharmaceuticals’ drug candidate, resmetirom. The once-daily oral small molecule is designed to bind to and activate thyroid hormone receptor beta. This receptor plays a role in multiple pathways associated with liver health.