RBC Bioscience Corp.

CBeyond™ will assess nimacimab’s ability to safely induce weight loss, and will also evaluate a combination of a GLP-1 receptor agonist plus nimacimab SAN DIEGO, CA, USA I August 22, 2024 I Skye Bioscience, Inc. (Nasdaq: SKYE) (“Skye”), a clinical-stage biopharmaceutical company focused on unlocking new therapeutic pathways for metabolic health, has started screening patients for a Phase 2 clinical trial ( CBeyond TM ) of its novel peripheral CB1 inhibitor, nimacimab, a negative allosteric modulating antibody. The study will assess the ability of nimacimab as a next-generation weight loss therapeutic to safely and effectively reduce weight in patients with obesity. It will assess parameters increasingly viewed as important to the long-term quality and/or sustainability of weight loss, including gastrointestinal tolerability (GI) and lean mass retention. “There is clearly a need for alternative mechanisms of action that can provide physicians and patients with improved overall health outcomes in the pursuit of weight loss beyond those achieved with GLP-1 and GIP drugs. We believe that peripheral CB1 inhibition, and nimacimab, a unique biologic drug within the class, have attributes that may help provide such outcomes, and we look forward to our goals of reporting interim data from this Phase 2 obesity trial in Q2 of 2025 and final data in Q4 of 2025,” said Punit Dhillon, Chief Executive Officer of Skye. “CB1 inhibition research has shown its potential to directly promote energy expenditure and fat breakdown 1 , improve leptin sensitivity 2 , and peripherally modulate hunger and satiety 3 . We are pleased to be assessing nimacimab as a monotherapy but to also undertake a preliminary evaluation of our peripheral CB1 inhibitor in combination with a GLP-1 drug.” “As we evaluate CB1 inhibition as a possible alternative mechanism for weight loss, we believe it is important to consider health outcomes beyond GI intolerance and muscle loss, such as neuropsychiatric adverse events, that may compromise the long-term use of these drugs that is necessary for sustainable results,” added Tu Diep, Chief Development Officer of Skye. “The first-generation CB1 inhibitor, rimonabant, was a small molecule that acted on the CNS. While showing efficacy in reducing weight 4 , it also indicated dose-related psychiatric adverse events 5 including anxiety, depressed mood, depression and suicidality. Current second-generation CB1 inhibitors, small molecules that may be more peripherally restricted than rimonabant, continue to show accumulation in the brain 6 in preclinical models, which suggest a potential lingering safety issue with this approach. Nimacimab, a monoclonal antibody (large molecule), is significantly more restricted from the brain 7 and there were no psychiatric adverse events in our preclinical studies 7 or Phase 1 study 7 in patients with nonalcoholic fatty liver disease (NAFLD). We believe that nimacimab’s positive safety and tolerability profile places Skye at a competitive advantage over small molecule CB1 inhibitors.” “We are most honored to participate in this study of nimacimab as an adjunct therapy for the treatment of obesity. This innovative approach, targeting the CB1 receptor, is a logical next step following the results in promising early trials,” said Harold Edward Bays, MD, Medical Director/President of Louisville Metabolic and Atherosclerosis Research Center/Your Body Goal. “We hope investigations into this additional mechanism of action will ultimately broaden the treatment options for patients living with obesity.” CBeyond TM Phase 2 Clinical Trial Design The clinical trial protocol for this Phase 2 study of nimacimab consists of the following elements: 1 Ruiz de Azua et al., J Clin Invest. 2017 2 Tam et al., JCI. 2010; Tam et al., Cell Metabolism 2012 3 Tam et al., JCI. 2010; Tam et al., Cell Metabolism 2012 4 RBC Capital Markets (February 2024); Després et al., NEJM. 2005 5 FDA Briefing Document, NDA 21-888, Zimulti (rimonabant) Tablets, 20 mg, Sanofi Aventis, Advisory Committee – June 13, 2007 6 Liu et al., ACS Pharmacol Transl Sci. 2021. 7 Skye data. About Nimacimab Nimacimab is a first-in-class humanized monoclonal antibody that acts as a negative allosteric modulator to inhibit CB1 signaling in the periphery. Inhibition of CB1 has shown anti-fibrotic, anti-inflammatory, and metabolic mechanisms of action with potential to address a broad range of diseases with unmet medical needs such as obesity, chronic kidney disease, and metabolic dysfunction-associated steatohepatitis (MASH). In July 2024 Skye conducted an Obesity KOL event with key opinion leaders and Skye management which highlighted the mechanisms of peripheral CB1 inhibition and the attributes and potential role of nimacimab in the obesity therapeutic landscape. The presentation and a replay of the call are available on the Company’s website . About Skye Bioscience Skye is focused on unlocking new therapeutic pathways for metabolic health through the development of next-generation molecules that modulate G-protein coupled receptors. Skye’s strategy leverages biologic targets with substantial human proof of mechanism for the development of first-in-class therapeutics with clinical and commercial differentiation. Skye is conducting a Phase 2 clinical trial in obesity for nimacimab, a negative allosteric modulating antibody that peripherally inhibits CB1. This study is also assessing the combination of nimacimab and a GLP-1R agonist (Wegovy ® ). For more information, please visit: https://www.skyebioscience.com. Connect with us on X and LinkedIn . SOURCE: Skye Bioscience

The Biden administration struck a triumphant tone on Thursday in rolling out the first drug price cuts negotiated by Medicare, a new authority granted by the Inflation Reduction Act. But the industry and investment communitys response to the long-awaited announcement was mixed, signaling a level of uncertainty as to the laws true impact on drugmakers going forward.The industry lobbying group PhRMA warned of the potentially dire consequences Medicares new powers may levy on drug research and access. In a statement, the group claimed the threat of lower prices may cause private funding to dry up, research incentives to shift, and Medicare premiums to climb.The ironically named Inflation Reduction Act is a bad deal being forced on American patients: higher costs, more frustrating insurance denials and fewer treatments and cures for our loved ones, PhRMA said in its statement.Investors had a more muted response to the announcement. Two stock indexes associated with the sectors health rose slightly. Multiple Wall Street analysts expressed relief and described the financial hit on drugmakers as manageable. Many of the 10 drugs involved a mix of blood thinners, diabetes treatments and a cancer pill were already heavily rebated, making their newly discounted prices not much lower than the net prices Medicare currently pays, they said.Additionally, some of the soon-to-be-discounted medicines are no longer increasing in sales and will soon reach the end of their market exclusivity, meaning theyll face generic competition shortly after the new prices take effect in 2026.The likely already substantial [price] discounts given to Medicare could help somewhat reduce the impact of these and future negotiated prices, wrote RBC Capital Markets analyst Brian Abrahams in a note to clients. With several of these initial 10 drugs already approaching their patent cliffs anyway, biopharma companies may have given more concessions to build goodwill in future negotiations.Leerink Partners David Risinger added that the discounts were not as bad as anticipated earlier this year, and noted that many pharmaceutical executives have telegraphed on earnings calls that they can weather the financial repercussions. He also wrote that the only cancer drug on the list, AbbVie and Johnson & Johnsons Imbruvica, had the lowest price cut, a marginal positive for the perception of the threat to future oncology medicines.The price cuts ranged from 38% to 79% lower than the drugs wholesale acquisition cost, or list price. The actual savings are smaller when compared to the net prices already negotiated between pharmaceutical companies and the private Medicare insurance plans that contract with the federal government to cover drugs.Still, had those prices been in place in 2023, taxpayers would have saved $6 billion, according to the Centers for Medicare and Medicaid Services. Net prices would have also been roughly 22% lower, which some see as a sign of progress in lowering drug costs.I am encouraged to see that they were able to negotiate real discounts off of the net prices, said Stacie Dusetzina, a health policy professor at the Vanderbilt University School of Medicine, in an email. Thats good news for the program.The IRAs impact on drug prices could grow in the coming years. The act will subject 15 medicines to Medicare price negotiations in 2027 and 2028, and 20 per year in 2029 and beyond. Medicare will announce the list of the next 15 drugs eligible for pricing talks on Feb. 1, a date some analysts are predicting as worrisome for the sector regardless of the outcome of the November election.With politics very much front and center right now, we do worry that another very large shoe is likely to drop on Feb. 1, or even sooner as both parties seem to view the pharmaceutical industry as an adversary to be defeated, rather than a force for good, wrote Piper Sandler analyst Christopher Raymond, in a note to clients.John Stanford, executive director of the Incubate Coalition, a venture capital advocacy group, also predicted the IRAs effects on innovation will deepen with time as it will begin impacting drugs that arent as significantly rebated.This year was kind of a freebie year because these products were already heavily discounted, he said. But in the aggregate, its not manageable.Dusetzina, though, believes those concerns may be overblown. Prices are nowhere near the cost of producing these drugs, she wrote. That is helpful for ensuring that companies still see Medicare as a profitable place to invest in drug development. '

Dive Brief:Gilead Sciences has won Food and Drug Administration approval to sell Livdelzi, a new medicine for a rare liver disease known as primary biliary cholangitis.The FDA clearance covers patients who cant tolerate a commonly used treatment called ursodeoxycholic acid or those whose disease doesnt respond well enough to the older medicine alone. For the latter group of patients, the regulatory clearance specifies combination use of Livdelzi and ursodeoxycholic acid, Gilead said Wednesday.Livdelzis approval comes just a few months after Gilead spent $4.3 billion to buy CymaBay Therapeutics, the company that developed the drug, then known as seladelpar. Analysts at RBC Capital Markets expect the medicine to reach peak sales of more than $650 million a year.Dive Insight:Gilead has spent much of the last few years focused on building up its oncology business. In 2020, the company paid $4.9 billion to buy immunotherapy specialist Forty Seven and then followed it up with a $21 billion deal to buy cancer drugmaker Immunomedics.But disappointments have followed those purchases. Myriad delays and clinical setbacks have prompted Gilead to rethink the future of the experimental medicineat the center of the Forty Seven deal. Trodelvy, the medication developed by Immunomedics, has also stumbled in a few key trialsand hasnt yet met analysts lofty sales expectations. With Livdelzi, Gilead is focusing on a treatment area thats more of a comfort zone. The company has a strong portfolio in hepatitis drugs and has a sales force that executives estimate is already covering 80% of the doctors who treat primary biliary cholangitis.Gilead also believes Livdelzi will stand out among the competition in the market because of clinical research showing the drugs effects on a key symptom of the disease called pruritus, debilitating itching that often occurs at night. The approved label for Livdelzi refers to that data and also carries fewer warnings about safety issues than rival treatments.Overall, Livdelzis cleaner label and its itch relief benefits should provide a competitive edge, RBC Capital Markets analyst Brian Abrahams wrote in a note to clients.The commercial list price for Livdelzi is $12,606 for a 30-day supply, a Gilead spokesperson said. That represents a 10% premium over Ipsens recently approved Iqirvo and a 30% premium over another rival called Ocaliva, potentially representing upside to our estimates and consensus, Leerink Partners analyst Thomas Smith wrote in a note to clients.U.S. regulators gave Livdelzi an accelerated approval, based on data that showed it could help normalize levels of an enzyme in the body thats a predictor of liver transplant and death. Continued approval may be contingent on Gilead proving clinical benefits in the future.Intercept Pharmaceuticals, owned by Alfasigma, is trying to satisfy similar requirements for Ocaliva, with an FDA advisory committee meeting set for September. In Europe, regulators in June recommendedthat Ocaliva be removed from the market, saying the medications benefits no longer outweighed its risks. '