glucagon

WVE-007 (INHBE GalNAc-siRNA for obesity) is on track to initiate a clinical trial in 1Q 2025; new preclinical data for WVE-007 demonstrate opportunities for monotherapy, for synergistic use with GLP-1s, and for maintenance to avoid rebound weight gain following cessation of GLP-1s Recent proof-of-mechanism data for WVE-006 unlocked Wave’s best-in-class RNA editing capabilities; three new wholly owned RNA editing programs targeting PNPLA3, LDLR and APOB are first-in-class approaches to address significant unmet needs in cardiometabolic diseases Wave plans to have five GalNAc-RNA editing or GalNAc-siRNA programs in the clinic by 2026 Wave’s clinically validated platform continues to lead on the improvement of intracellular delivery using novel chemistry, including PN backbone chemistry modifications CAMBRIDGE, Mass., Oct. 30, 2024 (GLOBE NEWSWIRE) -- Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health, today announced updates across its growing pipeline, which were also discussed during the company’s virtual analyst and investor Research Day (link to webcast). Updates included new preclinical data for Wave’s GalNAc-small interfering RNA (siRNA) approach for obesity, WVE-007, which is on track to initiate a clinical trial in the first quarter of 2025. Wave also introduced new, wholly owned GalNAc-RNA editing programs and demonstrated its leadership in oligonucleotide chemistry innovation. “This year, we showed through multiple positive clinical datasets that our leading RNA medicines platform is opening up new possibilities for the treatment of human disease. Next to the clinic will be our WVE-007 program, which reimagines obesity treatment with a mechanism that directly impacts fat cells – particularly visceral fat – and which could be used as monotherapy, add-on to GLP-1s, or for maintenance post-GLP-1 cessation,” said Paul Bolno, MD, MBA, President and Chief Executive Officer at Wave Life Sciences. “Additionally, we are excited to introduce three new programs for mRNA correction and upregulation to treat cardiometabolic diseases with significant unmet needs. These programs have substantial, well-defined patient populations, strong support from human genetics, efficient paths to proof-of-concept in the clinic, and offer the opportunity to meaningfully change health outcomes for millions of people. This truly is an exciting time for Wave and for patients as we unlock new biology and build our high-value and innovative pipeline.” Key Highlights from Today’s Virtual Research Day WVE-007: INHBE GalNAc-siRNA and potential best-in-class obesity therapeutic approaching the clinic WVE-007 is Wave’s GalNAc-siRNA that targets INHBE as a novel approach to treat obesity. The approach is based on human genetics, where individuals who have a protective loss-of-function mutation in the INHBE gene have a healthier cardiometabolic profile, including less unhealthy visceral fat, lower triglycerides, and lower risk of type 2 diabetes and cardiovascular disease.Silencing of INHBE in vivo directly impacts adipocytes (fat cells) and induces lipolysis (fat burning), which is different from GLP-1s’ centrally acting mechanism that involves the digestive system and central nervous system to decrease appetite.New preclinical data in diet induced obese (DIO) mice demonstrate the potential of WVE-007 to be used across the treatment continuum, including as monotherapy, as an add-on to GLP-1s, and for maintenance to prevent weight regain and weight cycling after discontinuing GLP-1s.Wave is on track to initiate a Phase 1 clinical trial for WVE-007 in adults living with overweight or obesity in the first quarter of 2025. The trial is planned to assess safety, tolerability, pharmacokinetics, and Activin E lowering (a biomarker for target engagement), as well as body composition. New GalNAc-RNA editing programs designed to optimally address high-impact cardiometabolic diseases Building on Wave’s recent achievement of the first-ever therapeutic RNA editing with WVE-006 in alpha-1 antitrypsin deficiency, the company today announced three new, wholly owned RNA editing programs that are on track for candidate selection in 2025. Like WVE-006, these programs leverage GalNAc conjugation and have efficient clinical paths to proof-of-concept. These new programs include: PNPLA3 (mRNA correction): Homozygous PNPLA3-I148M patients are at high risk for a variety of liver diseases and there are more than 9 million impacted individuals in the US and Europe. Wave’s RNA editing approach aims to achieve at least 50% correction to restore the heterozygous phenotype with low risk of liver disease, similar to the approach with WVE-006.LDLR (mRNA upregulation) and APOB (mRNA correction): High unmet needs remain among familial hypercholesterolemia (FH) patients, with approximately half of patients not reaching goal LDL-c levels with available therapies. Wave’s AIMers to upregulate LDLR and correct APOB have potential to be first-in-class treatment approaches for best-in-class effects to reach target LDL-c levels in Heterozygous FH (HeFH) patients. Combined, LDLR and APOB AIMers would address ~1 million HeFH patients in the US and Europe. LDLR upregulation also offers significant expansion opportunities in patients with statin intolerance or prior cardiovascular events (~30 million patients in the US and Europe). Chemistry innovation enhancing intracellular delivery Today, Wave shared data demonstrating how its proprietary chemistry results in marked improvements in five key areas of intracellular delivery: 1) cellular uptake; 2) endosomal release; 3) cellular residency; 4) nuclear uptake; and 5) target engagement.Wave shared how it is using PN variants and modifications to physicochemical properties to achieve best-in-class siRNA silencing and RNA editing in a variety of extrahepatic tissues.Wave also highlighted novel chemistry used in its AIMers, including proprietary N-3-uridine chemistry (N3U), which substantially enhances RNA editing efficiency. This novel chemistry was the subject of a recent Nucleic Acids Research publication. An archived webcast of the event can be accessed by visiting “Investor Events” on the investor relations section of the Wave Life Sciences website: https://ir.wavelifesciences.com/events-publications/events. About Wave Life SciencesWave Life Sciences (Nasdaq: WVE) is a biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health. Wave’s RNA medicines platform, PRISM®, combines multiple modalities, chemistry innovation and deep insights in human genetics to deliver scientific breakthroughs that treat both rare and prevalent disorders. Its toolkit of RNA-targeting modalities includes editing, splicing, RNA interference and antisense silencing, providing Wave with unmatched capabilities for designing and sustainably delivering candidates that optimally address disease biology. Wave’s diversified pipeline includes clinical programs in Duchenne muscular dystrophy, Alpha-1 antitrypsin deficiency and Huntington’s disease, as well as a preclinical program in obesity. Driven by the calling to “Reimagine Possible”, Wave is leading the charge toward a world in which human potential is no longer hindered by the burden of disease. Wave is headquartered in Cambridge, MA. For more information on Wave’s science, pipeline and people, please visit www.wavelifesciences.com and follow Wave on X (formerly Twitter) and LinkedIn. Forward-Looking StatementsThis press release contains forward-looking statements concerning our goals, beliefs, expectations, strategies, objectives and plans, and other statements that are not necessarily based on historical facts, including statements regarding the following, among others: the anticipated initiation, site activation, patient recruitment, patient enrollment, dosing, generation and reporting of data and completion of our clinical trials, including interactions with regulators and any potential registration based on these data, and the timing and announcement of such events; regulatory submissions and timing for regulatory feedback; the protocol, design and endpoints of our clinical trials; the future performance and results of our programs in clinical trials; our expectations with respect to how our clinical data successes to date may predict success for our future therapeutic candidates, future clinical data readouts and further validate of our platform; ongoing and future preclinical activities and programs; the potential of our preclinical data to predict the behavior of our compounds in humans; our identification and expected timing of future product candidates and their therapeutic potential; the anticipated benefits of our therapeutic candidates and pipeline compared to our competitors; patient population estimates related to our therapeutic candidates and the potential addressable market that our therapeutics may address; our ability to design compounds using various modalities and the anticipated benefits of that approach; the breadth and versatility of our PRISM drug discovery and development platform; the expected benefits of our stereopure oligonucleotides compared with stereorandom oligonucleotides; the potential benefits of our RNA editing capability, including our AIMers, compared to others; the benefits of RNA medicines generally; the potential for certain of our programs to be best-in-class or first-in-class; the potential benefits that our “edit-verse” may provide us, including identifying new RNA editing targets; our ability to translate genetic insights into high impact medicines; the status and progress of our programs relative to potential competitors; the progress and potential benefits of our collaborations; ;and the anticipated duration of our cash runway and our ability to fund future operations. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual results to differ materially from those indicated by these forward-looking statements as a result of these risks, uncertainties and important factors, including, without limitation, the risks and uncertainties described in the section entitled “Risk Factors” in Wave’s most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as amended, and in other filings Wave makes with the SEC from time to time. Wave undertakes no obligation to update the information contained in this press release to reflect subsequently occurring events or circumstances. Investor Contact:Kate Rausch+1 617-949-4827krausch@wavelifesci.com Media Contact:Alicia Suter+1 617-949-4817asuter@wavelifesci.com

Preclinical data from ex vivo human islet experiments showed that icovamenib (BMF-219) was able to enhance the activity of glucagon-like peptide-1 (GLP-1)-based therapies, potentially leading to increased insulin secretion and improved glycemic control in patients with diabetesPhase II study (COVALENT-211), combining icovamenib with a GLP-1-based therapy, planned to begin in 2025BMF-650, an investigational next-generation, oral small-molecule GLP-1 receptor agonist (GLP-1 RA), demonstrated positive early preclinical activity, including improved glucose-stimulated insulin secretion, reduction in blood glucose concentration, and appetite suppression in cynomolgus monkeys REDWOOD CITY, Calif., Oct. 30, 2024 (GLOBE NEWSWIRE) -- Biomea Fusion, Inc. (“Biomea” or “the Company”) (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing oral covalent small molecules to improve the lives of patients with diabetes, obesity, and genetically defined cancers, today presented preclinical data showing icovamenib enhanced the activity of GLP-1-based therapies, along with early preclinical efficacy and pharmacokinetic data for BMF-650, a next-generation, oral small-molecule GLP-1 RA candidate. “Menin plays a central role in the pancreas, not only impacting the proliferation of beta cells but also the expression of GLP-1 receptors. We observed that icovamenib, when combined with either of the two most commonly used GLP-1-based therapies, tirzepatide or semaglutide, enhanced the responsiveness of human islets to the GLP-1-based therapy, leading to substantial insulin secretion under hyperglycemic conditions. The dose-dependent improvements, where glucose-stimulated insulin secretion more than doubled, are highly promising,” stated Juan Pablo Frias, MD, Biomea Fusion’s Chief Medical Officer. “Additionally, we believe the results we’ve seen with our own GLP-1 RA product candidate, BMF-650, highlight a strong potential as a next-generation, oral GLP-1 RA for both diabetes and obesity. We believe these findings open exciting new avenues for treatment.” Icovamenib (BMF-219) in Combination with a GLP-1-Based TherapyKey Highlights: Preclinical studies evaluated insulin secretion by GLP-1-based therapies (tirzepatide and semaglutide) using human islets cultured ex vivo under hyperglycemic conditions, with and without icovamenib treatment.We hypothesized that menin inhibition would enhance the effectiveness of GLP-1-based therapies and showcased functional data, indicating stronger insulin responses with both tirzepatide and semaglutide when combined with icovamenib treatment.Further studies with orforglipron also indicated that icovamenib pretreatment improved insulin secretion, approximately doubling the effect-size depending on the dose.Additionally, BMF-650, Biomea’s next-generation, oral small molecule GLP-1 RA product candidate, used alone or in combination with icovamenib, yielded even further improved results supporting the potential for therapeutic benefits.The initiation of a Phase II study, COVALENT-211, to evaluate the combination of icovamenib with a GLP-1-based therapy, is planned for 2025. In addition, the Company announced additional details about its investigational, next-generation, oral small-molecule GLP-1 RA candidate, BMF-650. BMF-650 - an Investigational, Next-Generation, Oral Small Molecule GLP-1 Receptor Agonist - Key Highlights: We conducted preclinical studies to evaluate the properties of BMF-650 in comparison to a leading oral GLP-1 RA. BMF-650 exhibited higher bioavailability and a less variable pharmacokinetic profile, which may translate to improved tolerability and support successful dose escalation in patients. The estimated human dose will be approximately 100 mg once daily.In human donor islet studies, BMF-650 significantly enhanced glucose-stimulated insulin secretion.In cynomolgus monkey studies, BMF-650 showed significant improvements in glucose stimulated insulin secretion, in line with findings from the human donor islet experiments. BMF-650 also demonstrated superior glucose control.Appetite suppression studies revealed that daily oral BMF-650 dosing significantly reduced food intake during peak drug concentration, with sustained effects throughout the day for a six-day study period.These findings highlight BMF-650’s potential as an oral treatment for diabetes and obesity. “Our preclinical findings about the inhibition of menin in the GLP-1 pathway, announced today, may support the profile of icovamenib as a potential combination agent for GLP-1-based therapies. With the combination of icovamenib, less GLP-1 RA dosing may be required, which may support the overall benefits of these therapeutics. We believe, icovamenib may contribute to improved efficacy, tolerability and adherence, which ultimately will lead to more patients having longer benefits from these agents. We plan to clinically evaluate icovamenib as an adjunct to GLP-1-based therapies,” stated Thomas Butler, Biomea Fusion’s Chief Executive Officer and Chairman of the Board. “We are equally excited with the early results of our newest asset, BMF-650, which demonstrated clear advantages, including when compared to a leading GLP-1 RA in our preclinical studies. BMF-650 has shown superior insulin secretion, better glucose control, a smoother pharmacokinetic profile and higher bioavailability; all of which point to the potential for a greater therapeutic window and support our plans to evaluate BMF-650 as a next-generation oral treatment for diabetes. The appetite suppression results were particularly exciting, as they signal a new and impactful profile which we believe may support an impact on obesity.” Conference Call and Webcast DetailsWebcast, and related presentation, of Biomea’s investor update on Wednesday, October 30 at 4:30 pm ET will be available to registered attendees under the Investors and Media section of the company’s website at https://investors.biomeafusion.com/news-events/events. A replay of the presentation will be available on Biomea’s site following the event. About ObesityObesity is a chronic disease necessitating long-term management, associated with diminished life expectancy and a spectrum of severe health complications. These include metabolic disorders such as type 2 diabetes and non-alcoholic fatty liver disease; cardiovascular diseases like heart attack, stroke, and hypertension; and increased risks of chronic kidney disease, certain cancers, and chronic inflammation. The CDC estimates that over 40% of adults in the U.S. are considered obese, contributing to a significant burden on public health and healthcare systems. Globally, over 650 million adults are living with obesity, and these numbers are steadily rising. About GLP-1 Receptor AgonistsGlucagon-like peptide-1 (GLP-1) is a naturally occurring incretin hormone that plays a vital role in glucose homeostasis and appetite regulation. GLP-1 receptor agonists (GLP-1 RAs) are a class of medications that bind to and activate GLP-1 receptors, mimicking the effects of native GLP-1. These agents have demonstrated robust clinical efficacy in improving glycemic control, promoting weight loss, and enhancing insulin sensitivity in individuals with type 2 diabetes and obesity. About Biomea FusionBiomea Fusion is a clinical-stage biopharmaceutical company focused on the discovery and development of oral covalent small molecules to improve the lives of patients with diabetes, obesity, and genetically defined cancers. A covalent small molecule is a synthetic compound that forms a permanent bond to its target protein and offers a number of potential advantages over conventional non-covalent drugs, including greater target selectivity, lower drug exposure, and the ability to drive a deeper, more durable response. We are utilizing our proprietary FUSION™ System to discover, design and develop a pipeline of next-generation covalent-binding small-molecule medicines designed to maximize clinical benefit for patients. We aim to have an outsized impact on the treatment of disease for the patients we serve. We aim to cure. Visit us at biomeafusion.com and follow us on LinkedIn, X and Facebook. Forward-Looking Statements Statements we make in this press release may include statements which are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact, including statements regarding the clinical and therapeutic potential of our product candidates and development programs, programs and their potential relative to approved products marketed by third parties; our research, development and regulatory plans, the progress of our ongoing and upcoming clinical trials, the progress and timing of pre-clinical development in our programs; the anticipated enrollment of patients and availability of data from our clinical trials, anticipated milestones, and the timing of such events may be deemed to be forward-looking statements. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. Any forward-looking statements in this press release are based on our current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including the risk that preliminary or interim results of preclinical studies or clinical trials may not be predictive of future or final results in connection with future clinical trials and the risk that we may encounter delays in preclinical or clinical development, patient enrollment and in the initiation, conduct and completion of our ongoing and planned clinical trials and other research and development activities. These risks concerning Biomea Fusion’s business and operations are described in additional detail in its periodic filings with the U.S. Securities and Exchange Commission (SEC), including its most recent periodic report filed with the SEC and subsequent filings thereafter. Biomea Fusion explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law. Contact: Investor & Media RelationsRamses Erdtmannre@biomeafusion.com

VANCOUVER, Wash., Oct. 30, 2024 (GLOBE NEWSWIRE) -- CytoDyn Inc. (OTCQB: CYDY) ("CytoDyn" or the "Company"), a biotechnology company developing leronlimab, a CCR5 antagonist with the potential for multiple therapeutic indications, announced today that Dr. Melissa Palmer, M.D., has been engaged as Lead Consultant in Hepatology. In this role, Dr. Palmer will drive the Company’s strategy for research and development in Hepatology, leveraging her expertise to further CytoDyn’s clinical evaluation of leronlimab in treating liver conditions, including MASH and liver fibrosis. This engagement follows the recent breakthroughs with SMC Laboratories (“SMC”). In addition, the Company announced that following promising initial results from its preclinical study with SMC, it has commissioned the lab to conduct two follow-up studies to confirm and extend the observation of fibrosis reversal observed in the study concluded in September 2024. Both follow-up studies are underway, with results expected in early 2025. An internationally renowned hepatologist, Dr. Palmer brings more than three decades of deep research experience to the CytoDyn team. She has held leadership positions at several biotech and pharmaceutical companies, including serving as Chief Medical Officer of Gannex/Ascletis and Head of Liver Disease at Takeda Pharmaceutical Company. She has also worked as a hepatology consultant with over 60 biotech and pharmaceutical companies since 1991 and previously served as interim Chief Medical Officer of CytoDyn. In addition to consulting, Dr. Palmer has been the primary investigator for numerous clinical trials in MASH and other liver diseases. Her work has been published in over 100 publications, abstracts, manuscripts, books and book chapters, including several guidelines she co-authored with colleagues from the FDA and EMA concerning drug-induced liver injury among patients in clinical trials evaluating potential drugs to treat MASH and other liver diseases. She also maintained a solo medical practice treating patients with liver disease for over 20 years. Dr. Palmer will work with the CytoDyn team to oversee the two follow-up studies with SMC. These studies will again compare leronlimab alone and in combination with other therapies, including both resmetirom, the only approved treatment for MASH, and a GLP-1 agonist in an increased number of mice evaluated in both a proprietary STAM model of MASH which includes T2DM (previously studied), as well as a second model of liver fibrosis driven by CCL4 toxicity that is independent of fat deposition. “As we continue to capitalize on our momentum and push forward the path of scientific discovery here at CytoDyn, we are pleased to welcome Dr. Palmer to the team,” said Dr. Jacob Lalezari, CEO. “Dr. Palmer’s robust research and consulting background, and past familiarity with CytoDyn, will provide the tailored expertise we need to maximize opportunities to pursue breakthroughs in new treatment paths for MASH and liver fibrosis.” Dr. Palmer added, “This is an exciting time in liver health research, as scientific innovation paves the way for improved treatments for conditions like MASH and liver fibrosis. I look forward to collaborating with the CytoDyn team to advance clinical evaluations of leronlimab, including the studies in motion, and explore new treatments that have the potential to truly transform patient outcomes.” Dr. Palmer trained in Hepatology at Mount Sinai School of Medicine, where she also received her M.D. degree. She also holds a B.S. from Columbia University and is a Fellow of the American Association for the Study of Liver Diseases. About CytoDyn CytoDyn is a clinical-stage biotechnology company focused on the development and commercialization of leronlimab, an investigational humanized IgG4 monoclonal antibody (mAb) that is designed to bind to C-C chemokine receptor type 5 (CCR5), a protein on the surface of certain immune system cells that is believed to play a role in numerous disease processes. Leronlimab is being studied for oncology and inflammation, as well as other potential indications, including but not limited to HIV and MASH. About SMC Laboratories SMC Laboratories, Inc. is a CRO, with a focus on conducting the non-clinical research necessary for the drug development process. As a global consulting company that designs studies according to customer requests, it supports cutting-edge non-clinical pharmacological studies. The company owns a variety of mouse models for inflammation and fibrosis in various organs, centered on the innovative STAM™ mouse' animal model of liver cancer derived from MASLD (metabolic dysfunction-associated steatotic liver disease). This patented mouse model was developed by SMC Laboratories as a worldwide-first model based on MASLD. We offer non-clinical pharmacological studies using the model mouse. Please check the company's website for further details. Note Regarding Forward-Looking StatementsThis news release contains forward-looking statements relating to, among other things, product development, market position, future operating and financial performance, and business strategy. The reader is cautioned not to rely on these statements, which are based on current expectations of future events. For important information about these statements and our Company, including the risks, uncertainties and other factors that could cause actual results to vary materially from the assumptions, expectations and projections expressed in any forward-looking statements, the reader should review our Annual Report on Form 10-K for the fiscal year ended May 31, 2024, including the section captioned “Forward-Looking Statements” and in Item 1A. CytoDyn Inc. does not undertake to update any forward-looking statement as a result of new information or future events or developments. Media Contacts CytoDynRiyaz LalaniGagnier CommunicationsCytoDyn@gagnierfc.com