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Anti-alpha2 antiplasmin antibody is being studied in patients with deep vein thrombosis to assess its potential as a thrombolytic Anti-alpha2 antiplasmin antibody might also provide potential treatment options in indications of high medical relevance BERLIN, Germany I February 20, 2024 I Bayer announced today the start of a Phase II clinical trial (SIRIUS study) with BAY3018250, an investigational first-in-class anti-alpha2 antiplasmin (anti-α2ap) antibody in patients with deep vein thrombosis (DVT). The results of this study might provide evidence of anti-α2ap antibody's potential as a treatment option in indications of high medical relevance. "We are excited to advance our anti-α2ap antibody to the next stage of clinical development in patients with deep vein thrombosis," said Christian Rommel, Member of the Executive Committee of Bayer AG's Pharmaceuticals Division and Head of Research and Development. "This study will also help to better understand if the anti-α2ap antibody is suitable as a thrombolytic to treat patient in indications of high medical relevance. By targeting alpha2 antiplasmin, we will have a more precise approach to modulate plasmin to break down thrombotic blood clots." Following the successful first-in-human trial, the goal of the randomized, double-blind, placebo-controlled, multi-center Phase II study (SIRIUS study) is to assess the efficacy and safety of BAY3018250 in patients with symptomatic proximal deep vein thrombosis. BAY3018250 is designed to target alpha2 antiplasmin. α2ap's primary function is to inhibit the enzymatic activity of plasmin and thereby balance the formation and dissolution of blood clots. About Bayer's Commitment in Cardiovascular Diseases Bayer is a leader in cardiology and is advancing a portfolio of innovative treatments in cardiovascular (CV) diseases of high unmet medical need. The strategy is to unlock the strong potential of the future CV market by transforming Bayer's portfolio into precision cardiology, addressing the high CV disease burden, and driving the long-term growth. Bayer's portfolio in the field of cardiovascular diseases already includes a number of innovative products and compounds in various stages of preclinical and clinical development. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2022, the Group employed around 101,000 people and had sales of 50.7 billion euros. R&D expenses before special items amounted to 6.2 billion euros. For more information, go to www.bayer.com . Find more information at https://pharma.bayer.com Follow us on Facebook: http://www.facebook.com/bayer SOURCE: Bayer

Pictured: Eli Lilly headquarters in Indianapolis/iStock, jetcityimage A first-in-human Phase I trial showed that Eli Lilly’s investigational oral lipoprotein(a) inhibitor muvalaplin was safe and could elicit sharp reductions in concentrations of the cholesterol formation. The study, published Monday in the medical journal JAMA, demonstrated that the pill lowered Lp(a) levels within 24 hours of the first administration. Subsequent muvalaplin doses led to further Lp(a) reductions. The placebo-adjusted decrease in Lp(a) reached a maximum of 63% to 65% in the muvalaplin arm. Of the 114 participants, more than 90% achieved plasma Lp(a) levels lower than 50 mg/dL. These promising signals of efficacy did not come with worrying safety signals, according to the JAMA study. Muvalaplin also did not significantly alter plasminogen levels or activity. “Muvalaplin is the first oral agent specifically developed to lower levels of Lp(a) by disrupting its formation,” the study’s authors wrote, adding that the drug candidate also represents a novel treatment option for targeting Lp(a). Lilly has taken muvalaplin into Phase II assessments, according to its website, and is developing the small molecule Lp(a) for cardiovascular diseases. In atherosclerotic cardiovascular diseases, there sometimes remains a residual likelihood of cardiovascular events despite optimally suppressed levels of low-density lipoprotein (LDL) cholesterol. This points to the need of addressing other risk factors and potentially related biomarkers, among them Lp(a). A variant of LDL cholesterol, Lp(a) that carries an apolipoprotein(a) molecule covalently bound to apolipoprotein(B). According to the Centers for Disease Control and Prevention, high Lp(a) levels have been tied to worse risks of heart attack or stroke, particularly in people with family histories of these conditions. Lp(a) also plays a role in the narrowing of the aortic valve. Muvalaplin, an oral small molecule inhibitor of Lp(a), works by disrupting the covalent bond between apolipoprotein(a) and apolipoprotein(B), thereby preventing the formation of the complete Lp(a) molecule. “This drug is a gamechanger in more ways than one. Not only do we have an option for lowering an elusive form of cholesterol, but being able to deliver it in an oral tablet means it will be more accessible for patients,” Stephen Nicholls, director of Monash University’s Victorian Heart Institute who led the trial, said in a statement. Beyond muvalaplin, Lilly has also started working on other Lp(a)-directed therapies. In October 2018, the company signed a licensing and research collaboration deal with Dicerna Pharmaceuticals to develop RNA interference-based treatments for cardiometabolic indications. This partnership gave rise to lepodisiran, a siRNA candidate whose Investigational New Drug application was approved in May 2021. Lepodisiran is now currently in Phase II development for diabetes and obesity. In June 2023, Lilly signed another collaboration contract, this time with Verve for a one-time gene editing program targeting Lp(a). Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

On Friday, clinical-stage Canadian biotech NervGen announced the peer-reviewed publication of a preclinical study, which showed that its proprietary drug NVG-291-R could repair the nervous system after a stroke in rodents —even when it was administered seven days after the episode. The data, published Tuesday in Cell Reports, showed that in a mouse model of severe ischemic stroke, treatment with NVG-291 strongly and significantly improved learning and memory outcomes. In the Barnes Maze Test, mice who had suffered a stroke but were treated with NervGen’s drug found the correct exit much quicker and with fewer errors than those who were given placebo. Researchers from the University of Cincinnati and Case Western Reserve University, who conducted the study, traced these profound symptomatic improvements back to better plasticity. Treatment with NVG-291, it turned out, helped neurons create new connections among themselves after a stroke. The drug’s effect was found to be significantly better than the vehicle control. “We are very excited about the data showing significant improvement in motor function, sensory function, spatial learning, and memory, even when treatment was initiated as late as 7 days after stroke onset,” Dr. Agnes (Yu) Luo, associate professor at the Department of Molecular Genetics and Biochemistry at the University of Cincinnati, and senior author of the paper said in a statement. “If these results translate to the clinic, NVG-291 would be a substantial breakthrough in the treatment of stroke patients for multiple reasons because the only current FDA-approved drug for treatment of stroke does not repair damage and must be administered within 4.5 hours of stroke onset,” she added. NVG-291 also promoted the migration of neuronal stem cells into the damaged site after the stroke episode and then helped these stem cells differentiate into neurons, demonstrating what Luo called “robust neuroreparative effects.” NVG-291 is currently undergoing Phase I assessments in healthy volunteers and is set to enter Phase Ib/II trials for Alzheimer’s, multiple sclerosis and spinal cord injury. NervGen holds the exclusive worldwide rights to NVG-291. Currently, there is only one drug approved by the U.S. FDA for ischemic stroke: Genentech’s Activase (alteplase), an intravenously administered tissue plasminogen activator. By converting the largely inert plasminogen to the proteolytic enzyme plasmin, Activase can help dissolve the clots that block blood vessels. However, for it to work, Activase has to be administered within mere hours of the stroke episode. This is because Activase cannot repair damage from the stroke but only prevents the situation from worsening by restoring blood flow. According to Luo, other drugs in development suffer from a similar problem and need to be administered very soon after a stroke. The ischemic stroke space is ripe for a big shake-up. Activase was given the go-ahead for stroke treatment in 1996 and has remained unchallenged. Unfortunately, there doesn’t seem to be much promise on the horizon, with trial failures marking drug development in this field. Earlier this month, DiaMedica Therapeutics announced that it was putting its Phase II/III ReMEDy2 trial on hold following several cases of worrying low blood pressure in patients after being treated with the company’s candidate DM199. In May, MultiStem cell (invimestrocel), put forward by the partnership between Athersys and Healios, failed to meet the primary endpoint of the TREASURE trial. NervGen's president and CEO, Paul Brennan who is enthusiastic about the findings said "While we remain committed to developing NVG-291 in our core indications of spinal cord injury, Alzheimer’s and multiple sclerosis, this paper provides a very strong argument to undertake a stroke study with NVG-291. Given this compelling new preclinical data, we believe there is a solid opportunity to secure non-dilutive funding to advance the program through a partnership, either with industry or government.”