NASDAQ:NRBO
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Business Update
Pre-Clinical MASH Data for DA-1241 to be Presented at EASL Congress 2024
On May 22, 2024, NeuroBo Pharmaceuticals, Inc. (NASDAQ:NBRO) announced that preclinical data suggests DA-1241, the company’s novel G-protein coupled receptor 119 (GPR119), in combination with semaglutide (Wegovy®) improves liver fibrosis in an additive manner in models of metabolic dysfunction-associated steatohepatitis (MASH). The data is being presented in two posters at the EASL Congress 2024, which is taking place June 5-8 in Milan, Italy. The posters will be available following their presentation on June 6, 2024.
Additive Hepatoprotective Effects of DA-1241, a Novel GPR119 Agonist, in Combination with Semaglutide in the GAN Diet-Induced Obese and Biopsy-Confirmed Mouse Model of MASH
In this study, C57BL/6JRj mice were fed the GAN (Gubra-Amylin NASH) diet (40% saturated fat, 22% fructose, 2% cholesterol) for 36 weeks. Mice were then biopsied to confirm MASH (steatosis score = 3; locular inflammation score ≥2, fibrosis stage F2-F3) and stratified to treatment groups (n=14-15 per group). Mice received once daily treatment of vehicle, DA-1241 (100 mg/kg, PO), semaglutide (30 nmol/kg, SC), or combination of DA-1241 and semaglutide for 8 weeks. Results showed that DA-1241 did not impact weight while semaglutide treatment reduced body weight by approximately 25% and improved hepatomegaly with or without combination treatment. Plasma transaminase and liver cholesterol levels were both positively impacted by each monotherapy and combination therapy provided further improvement.
The following image on the left shows that DA-1241 and semaglutide monotherapy both improved NAS by ≥2-point in 21% of mice, while combination therapy improved NAS by ≥2-point in 80% of mice and by ≥1 point in all mice. The reduction in NAS was driven by reduction in steatosis and lobular inflammation scores (image on the right).
The company also reported that while no treatments significantly influenced quantitative markers of fibrosis, DA-1241 and semaglutide monotherapies both lowered -SMA levels, with further improvements in combination. Lastly, liver transcriptome analysis showed a significant increase in the number of differentially expressed genes, particularly in lipid metabolism, chemokine signaling, and fiber proteins following combination therapy when compared with monotherapies.
DA-1241, a GPR119 Agonist, Combined with Semaglutide Synergistically Improved Liver Fibrosis in Mice with CCl4 Induced Liver Fibrosis
In this study, liver fibrosis was generated in mice through feeding a Western diet in addition to twice weekly CCl4 injections for three weeks. Mice with elevated ALT levels were entered into the study and received DA-1241, semaglutide, or combination treatment for four weeks. Similar to the other experiment, semaglutide therapy resulted in a reduction in weight loss by approximately 17% (P<0.05 vs. vehicle control) while DA-1241 reduced body weight by only 2.8%. The following image shows the percentage of fibrosis in each treatment group. Both DA-1241 (17.8%) and semaglutide (17.1%) alone decreased collagen-positive areas compared to vehicle control (25.8%, P<0.05). Combination therapy further reduced the collagen-positive area to 6.05% (P<0.05), which was statistically significant compared to each treatment group alone.
In addition, the company reported that hepatic hydroxyproline content and gene expression of various collagen subtypes (Col1a1, Col3a1, Col5a1, Col6a1) were also altered, which supports the beneficial combination effects against liver fibrogenesis. Expression of Hedgehog-interacting protein (Hhip), which is a suppressor of hepatic stellate cell division, was lower in mice with liver fibrosis compared to normal mice and treatment with either DA-1241 or semaglutide increased its expression while combination therapy fully restored its expression. Lastly, the expression of multiple inflammatory cytokines (Tnfa, IL1b, Ccl2, Cxcl10) were significantly reduced by either DA-1241 or semaglutide and combination therapy reduced both Tnfa and Cxcl10 more than monotherapy.
Enrollment Complete in Part 1 of Phase 2a Trial of DA-1241
On April 1, 2024, NeuroBo announced the completion of enrollment of Part 1 of the two-part, Phase 2a clinical trial of DA-1241 for the treatment of metabolic dysfunction-associated steatohepatitis (MASH; formerly NASH). This follows the news in March 2024, in which NeuroBo announced that the Safety Review Committee (SRC) recommended that the two-part Phase 2a trial of DA-1241 continue without modification following a blinded safety review of the first six months of study conduct. We anticipate topline data from the trial in the second half of 2024.
The Phase 2a trial of DA-1241 is designed to be a 16-week, multicenter, randomized, double blind, placebo controlled study to evaluate the efficacy and safety of the compound in subjects with presumed MASH. Part 1 is exploring the efficacy of DA-1241 compared to placebo and enrolled approximately 49 subjects, who were randomized in a 1:2:1 ratio into three cohorts: DA-1241 50 mg, DA-1241 100 mg, or placebo. Part 2 will explore the efficacy of DA-1241 in combination with sitagliptin compared to placebo. Approximately 37 subjects will be randomized in a 2:1 ratio into two treatment groups: DA-1241 100 mg/sitagliptin 100 mg or placebo.
First Patient Dosed in Phase 1 Trial of DA-1726
On April 18, 2024, NeuroBo Pharmaceuticals, Inc. (NRBO) announced the first patient was dosed in the Phase 1 clinical trial of DA-1726 for the treatment of obesity. DA-1726 is a novel oxyntomodulin (OXM) analogue that functions as a dual agonist of the GLP-1 receptor (GLP-1R) and the glucagon receptor (GCGR). Part 1 of the trial is a single ascending dose (SAD) study that is expected to enroll approximately 45 obese but otherwise healthy participants randomized into one of five planned cohorts. Each cohort will be randomized in a 6:3 ratio of DA-1726 or placebo. Part 2 of the trial is a multiple ascending dose (MAD) study this is expected to enroll approximately 36 obese but otherwise healthy participants into four planned cohorts, with each to receive four weekly administrations of DA-1726 or placebo, randomized in a 6:3 ratio. The primary endpoint will assess the safety and tolerability of DA-1726 with secondary endpoints examining the pharmacokinetics (PK) of DA-1726. Exploratory endpoints include the effect of DA-1726 on metabolic parameters, cardiac parameters, fasting lipid levels, body weight, waist circumference, and body mass index. Topline results from Part 1 of the study are anticipated in the third quarter of 2024 while topline results from Part 2 are expected in the first quarter of 2025.
Financial Update
On May 9, 2024, NeuroBo announced financial results for the first quarter of 2024. As expected, the company did not report any revenues in the first quarter of 2024. R&D expenses for the first quarter of 2024 were approximately $4.9 million compared to approximately $0.6 million for the first quarter of 2023. The increase was primarily due to increased expenditures for investigational drug manufacturing costs, non-clinical and preclinical services, clinical trials, consulting, and employee compensation. G&A expenses were approximately $2.0 million for the first quarter of 2024 compared to $1.9 million for the third quarter of 2023. The increase was primarily due to higher non-cash stock-based compensation partially offset by lower legal and professional fees.
As of March 31, 2024, NeuroBo had approximately $16.0 million in cash and cash equivalents. We anticipate the company has sufficient capital to finance operations into the fourth quarter of 2024. As of May 6, 2024, NeuroBo had approximately 4.9 million shares outstanding and, when factoring in stock options and warrants, a fully diluted share count of approximately 5.1 million.
Conclusion
The data to be presented at EASL is very encouraging and shows the potential for DA-1241 to positively influence a number of factors involved in MASH development, including hepatic steatosis, inflammation, and fibrosis. While the ongoing Phase 2 trial of DA-1241 includes a combination arm with sitagliptin, the data showing a combination effect between DA-1241 and semaglutide is important as GLP-1 agonists are becoming an important part of the MASH treatment landscape. We look forward to data from the ongoing Phase 2 study of DA-1241 in the fourth quarter of 2024. In addition, we anticipate topline data from Part 1 of the Phase 1 trial of DA-1726 in the third quarter of 2024 and topline data from Part 2 of the trial in the first quarter of 2025. With no changes to our model our valuation remains at $25 per share.
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