ANGPTL4

Positive topline results from Phase 2a study of MAR001 demonstrate clinically meaningful reductions in remnant cholesterol and triglycerides; Phase 2b study expected to initiate in First Half 2025 Second Lead Program announced, MAR002, a growth hormone receptor (GHR) antagonist for the treatment of acromegaly; Phase 1 study expected to initiate in Second Half 2025 Marea to present at 43rd Annual J.P. Morgan Healthcare Conference on Wednesday, January 15 SAN FRANCISCO, CA, USA I January 09, 2025 I Marea Therapeutics, Inc., a clinical-stage biotechnology company harnessing the latest advances in human genetics to develop first-in-class, next-generation medicines for cardio-endocrine diseases, today provided an update on the company’s recent progress and upcoming milestones for 2025 in advance of the J.P. Morgan 43 rd Annual Healthcare Conference, taking place from January 13-16, 2025 in San Francisco, CA. “Since our launch in June 2024, Marea has made excellent progress across a number of areas,” said Josh Lehrer, M.D., M.Phil., FACC, chief executive officer of Marea. “Based on positive results from our Phase 2a study that demonstrate clinically meaningful reductions in remnant cholesterol and triglycerides, we are preparing to advance MAR001 into Phase 2b clinical development in the first half of 2025. These data demonstrate the potential of MAR001 to address the untreated lipid and metabolic drivers of cardiovascular disease in high-risk patients. In addition, we announced our second lead pipeline program for the treatment of acromegaly with clinical development expected to initiate in the second half of 2025. Our strong pipeline progress, further fueled by the recent expansion of our management team and board of directors, positions us for an important 2025 as we seek to accelerate a new generation of medicines for cardiometabolic and endocrine diseases.” Positive Phase 2a Topline Results for MAR001 “These clinical data, coupled with the remarkable human genetic validation of ANGPTL4, the target for MAR001, establishes MAR001 as one of the most promising candidates advancing into late-stage development for treating residual cardiovascular risk in the patients who remain at highest risk despite aggressive standard of care therapies,” said Ethan Weiss, M.D., chief scientific officer of Marea. Second Lead Pipeline Program Announced: MAR002 for the Treatment of Acromegaly MAR002 is a potential first-in-class anti-growth hormone receptor (GHR) antibody being developed for acromegaly. Acromegaly is a life-shortening disease where much of the morbidity is caused by insulin resistance, lipotoxicity, and cardiovascular events. Current therapies for acromegaly are associated with suboptimal disease control. It is estimated there are more than 30,000 patients with acromegaly in the U.S. Marea expects to initiate a Phase 1 clinical trial with MAR002 in the second half of 2025. Other Corporate Highlights Presentation at the 43 rd Annual J.P. Morgan Healthcare Conference Management will participate in the 43 rd Annual J.P Morgan Healthcare Conference. In addition to hosting meetings, management will present an overview of the Company on Wednesday, January 15, at 11:30 a.m. PT in San Francisco. About Marea Therapeutics Marea Therapeutics is a clinical-stage biotechnology company harnessing the latest advances in human genetics to develop first-in-class, next-generation medicines for cardio-endocrine diseases. The company’s lead program, MAR001, is in Phase 2 clinical development for adults with metabolic dysfunction and high risk for cardiovascular disease. The company is also advancing MAR002 for the treatment of acromegaly. To learn more, please visit www.mareatx.com and follow us on LinkedIn and X . SOURCE: Marea Therapeutics

Marea Therapeutics on Friday posted some encouraging results with its lead program, a triglyceride-lowering medicine for cardiovascular disease, that could give an indication of whether the investors in its $190 million raise in June spent their money wisely. Actual data from the Phase 2a trial of MAR001, however, are thin. Marea said in the release that the antibody dosed at 300 mg and 450 mg cut patients’ remnant cholesterol levels by around 50% on a placebo-adjusted basis at three months. It said that this predicted “meaningful” clinical benefit. Reductions in remnant triglycerides were also “meaningful,” though no figures were given. Remnant cholesterol and triglycerides are associated with worse outcomes for cardiovascular disease patients. MAR001 was licensed from Novartis and targets ANGPTL4, a protein expressed on adipose cells. Marea said it could be a first-in-class therapy. The Swedish biotech Lipigon Pharmaceuticals pushed its own anti-ANGPTL4 RNA drug Lipisense into Phase 2 in November. Lipigon’s trial will enroll patients with moderate to severe hypertriglyceridemia and type 2 diabetes. Marea’s Phase 2a trial randomized patients with hypertriglyceridemia 2:1 to MAR001 or placebo. A 150 mg dose was also tested, but Marea did not give data for this group. There were no deaths or serious adverse events, and no subjects discontinued the drug because of side effects. Marea intends to release more data at a medical conference and will start a Phase 2b trial in the next six months. The biotech also unveiled its second program, a growth hormone receptor antagonist intended to treat acromegaly. A Phase 1 study of MAR002 is expected to start in the second half of 2025.

TUESDAY, Nov. 5, 2024 -- Current treatments sometimes fail to help people with “wet” age-related macular degeneration -- and researchers now think they know why. Wet AMD is caused by an overgrowth of blood vessels in the retina, the light-sensing tissue at the back of the eye. The vessels leak fluid or bleed, damaging the retina and causing vision loss. To combat this, doctors prescribe medications that slow the growth of new blood vessels, called anti-VEGF (vascular endothelial growth factor) drugs. Unfortunately, these anti-VEGF drugs might actually hamper vision improvements by triggering the over-expression of a second blood-vessel-related protein, researchers have discovered. This second protein, ANGPTL4, also can stimulate overproduction of abnormal blood vessels in the retina, researchers reported Nov. 4 in the Proceedings of the National Academy of Sciences . These findings could explain why fewer than half of patients who receive monthly anti-VEGF eye injections wind up showing any major improvements in their vision, researchers said. “We have previously reported that ANGPTL4 was increased in patients who did not respond well to anti-VEGF treatment,” said researcher Dr. Akrit Sodhi , an associate professor of ophthalmology at the Johns Hopkins University School of Medicine, in Baltimore. “What we saw in this paper was a paradoxical increase of ANGPTL4 in patients that received anti-VEGF injections -- the anti-VEGF therapy itself turned on expression of this protein,” Sodhi said in a Hopkins news release. For the study, researchers compared VEGF and ANGPTL4 levels in the eye fluid of 52 patients with wet AMD, all of whom were receiving anti-VEGF treatments. After anti-VEGF treatment, their VEGF levels decreased but their ANGPTL4 levels rose. Such ANGPTL4 activity could promote more damaging blood vessel overgrowth, researchers said. The team then investigated ways to limit ANGPTL4 levels, using an experimental drug on mice with wet AMD. The drug decreases levels of a third protein, HIF-4, known to be involved in wet AMD by promoting VEGF production. The drug also decreased VEGF and ANGPTL4 levels in mice, and limited overgrowth of blood vessels, researchers found. Combining the experimental drug with existing anti-VEGF meds proved more effective than either drug alone in mice, results showed. “This work exposes a way to improve anti-VEGF therapy for all patients and potentially help a subset of patients with wet AMD who still lose vision over time despite treatment,” Sodhi said. “Our hope is that this [project] will further the three goals we have related to wet AMD: make current therapies as effective as possible, identify new therapies and prevent people from ever getting wet AMD." Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.