PIK3R5

12 Abstracts and one Symposium further support potential of ensifentrine,a first-in-class, selective, dual inhibitor of PDE3 and PDE4 Conference call May 23 at 4:00 p.m. EDT / 9:00 p.m. BST LONDON and RALEIGH, N.C., May 02, 2023 (GLOBE NEWSWIRE) -- Verona Pharma plc (Nasdaq: VRNA) (“Verona Pharma” or the “Company”), a clinical-stage biopharmaceutical company focused on respiratory diseases, announces 12 abstracts, including a mini symposium, and a clinical trials symposium, on additional analyses from its successful Phase 3 ENHANCE studies with ensifentrine for the treatment of chronic obstructive pulmonary disease (“COPD”) have been accepted by the American Thoracic Society International Conference (“ATS”) 2023. An overview of the ENHANCE trial results will be presented as part of the clinical trials symposium ‘Breaking News: Clinical Trial Results in Pulmonary Medicine’ reserved for highlighting new breakthroughs. The abstracts are published on the ATS website and in the publication, American Journal of Respiratory and Critical Care Medicine. Verona Pharma will host a webcast and conference call on Tuesday, May 23, 2023, to review these data. The abstracts include subgroup data and pooled analyses from the ENHANCE-1 and ENHANCE-2 trials, first reported by the Company on December 20, 2022, and August 9, 2022, respectively, covering exacerbations, use of rescue medication and healthcare utilization. Abstracts highlight reductions in the rate and risk of exacerbations with ensifentrine in pooled sub-group analyses of ENHANCE-1 and ENHANCE-2 and a mini symposium discussing the improvements in lung function and reductions in exacerbation rate and risk demonstrated in ENHANCE-2. Antonio Anzueto, MD, Professor of Medicine and Section, Chief of Pulmonary at South Texas Veterans Healthcare System, commented: “These additional analyses from the ENHANCE studies further demonstrate ensifentrine’s potential to become a first-in-class bronchodilator and non-steroidal anti-inflammatory therapy for COPD. The reduction in the rate and risk of exacerbations across subgroups is exciting. Combined with the significant improvements in lung function, symptom and quality of life measures, as well as the favorable safety profile, these data confirm ensifentrine’s potential to change the treatment paradigm for COPD patients.” David Zaccardelli, Pharm. D., Verona Pharma’s President and Chief Executive Officer, said: “We are looking forward to providing additional analyses of the positive results from the Phase 3 ENHANCE trials that highlight key areas of interest for physicians. These data further support the potential for ensifentrine to provide a much needed treatment for the millions of symptomatic COPD patients.” Conference Call and Webcast Information Verona Pharma will host an investment community webcast and conference call at 4:00 p.m. EDT / 9:00 p.m. BST on Tuesday, May 23, 2023, to discuss the Phase 3 ENHANCE data presented at ATS 2023. To participate, please dial one of the following numbers and ask to be placed into the Verona Pharma investor call: +1-833-816-1396 for callers in the United States+1-412-317-0489 for international callers A live webcast will be available on the Events and Presentations link on the Investors page of the Company's website, www.veronapharma.com, and the audio replay will be available for 90 days. Details of Verona Pharma’s abstracts and the symposia are listed below and linked to the ATS website. Clinical Trials Symposium: Effect of Ensifentrine, a novel PDE3 and PDE4 inhibitor, on lung function, symptoms and exacerbations in patients with COPD: The ENHANCE TrialsParticipant: Antonio Anzueto, MD, Professor of Medicine and Section Chief of Pulmonary at South Texas Veterans Healthcare SystemSession: B13 – Breaking News: Clinical Trial Results in Pulmonary Medicine Mini Symposium: Ensifentrine, a Novel Dual Phosphodiesterase (PDE) 3 and 4 Inhibitor, Improves Lung Function and Reduces Exacerbation Rate and Risk in Phase 3 ENHANCE-2 TrialParticipant: Antonio Anzueto, MD, Professor of Medicine and Section Chief of Pulmonary at South Texas Veterans Healthcare SystemSession: C15 – Emerging COPD Diagnostics and Treatments Abstract: P101 – Twice-daily, Nebulized Ensifentrine Produced Significant Improvement in Week 12 Lung Function: Subgroup Analysis in the Phase 3 Trial ENHANCE-2Participant: Kathleen Rickard, Chief Medical Officer, Verona PharmaSession: B22 – New Treatments and Novel Targets for COPD and Alpha-1 Abstract: P102 – Ensifentrine Reduced Healthcare Resource Utilization in Subjects With COPD: Results From ENHANCE-2, a Phase 3 Trial of Ensifentrine, a Dual PDE3/4 InhibitorParticipant: Igor Barjaktarevic, MD, Medical Director, COPD Program, UCLA Division of Pulmonary & Critical Care MedicineSession: B22 – New Treatments and Novel Targets for COPD and Alpha-1 Abstract: P166 – Treatment With Ensifentrine, a Dual PDE3 and PDE4 Inhibitor, Significantly Reduced Exacerbation Rate and Risk in Subjects With COPD: Sub-group Results from the Phase 3 Trial, ENHANCE-2Participant: Antonio Anzueto, MD, Professor of Medicine and Section Chief of Pulmonary at South Texas Veterans Healthcare SystemSession: C40 – Clinical Trials and Novel Interventions in COPD Abstract: P167 – Ensifentrine, a Dual Inhibitor of PDE3 and PDE4, Reduces the Risk of Exacerbation Regardless of Background Medication Use: A Sub-group Analysis of ENHANCE-2, a Phase 3 TrialParticipant: Gary T. Ferguson, MD, Director of the Pulmonary Research Institute of Southeast MichiganSession: C40 – Clinical Trials and Novel Interventions in COPD Abstract: P168 – Ensifentrine, a Novel Dual Phosphodiesterase (PDE) 3 and 4 Inhibitor, in Moderate and Severe COPD: Symptoms, Quality of Life and Health Status From the Phase 3 Trial ENHANCE-2Participant: Tara Rheault, Senior Vice President, R&D, Verona PharmaSession: C40 – Clinical Trials and Novel Interventions in COPD Abstract: P171 – Safety Results From Dual PDE3/4 Inhibitor Ensifentrine: Gastrointestinal and Cardiovascular Safety From a 24-week Phase 3 Trial, ENHANCE-2Participant: Thomas Siler, MD, President at Midwest Chest ConsultantsSession: C40 – Clinical Trials and Novel Interventions in COPD Late-breaking Abstract: P172 – Twice-daily, Nebulized Ensifentrine Significantly Improves Lung Function: Sub-group Analysis in the Phase 3 Trial, ENHANCE-1Participant: Thomas Siler, MD, President at Midwest Chest ConsultantsSession: C40 – Clinical Trials and Novel Interventions in COPD Late-breaking Abstract: P173 – Ensifentrine, a Novel Dual Phosphodiesterase (PDE) 3 and 4 Inhibitor, Improves Lung Function, Symptoms, Quality of Life and Reduces Exacerbation Rate and Risk in Patients With COPD: Results From Replicate Phase 3 TrialsParticipant: Frank Sciurba, MD, University of Pittsburgh Medical CenterSession: C40 – Clinical Trials and Novel Interventions in COPD Late-breaking Abstract: P174 – Ensifentrine, a Novel Dual Phosphodiesterase (PDE) 3 and 4 Inhibitor, Improves Lung Function, Symptoms, Quality of Life and Reduces Exacerbation Rate and Risk in the ENHANCE-1 Phase 3 Trial of Ensifentrine in COPDParticipant: Frank Sciurba, MD, University of Pittsburgh Medical CenterSession: C40 – Clinical Trials and Novel Interventions in COPD Late-breaking Abstract: P175 – Ensifentrine, a Novel Dual Phosphodiesterase (PDE) 3 and 4 Inhibitor, Significantly Improves COPD Symptoms and Quality of Life in the Phase 3 ENHANCE-1 TrialParticipant: Frank Sciurba, MD, University of Pittsburgh Medical CenterSession: C40 – Clinical Trials and Novel Interventions in COPD Late-breaking Abstract: P176 – Ensifentrine, a Novel Dual Phosphodiesterase (PDE) 3 and 4 Inhibitor, Significantly Reduces Annualized Exacerbations and Delays the Time to First Exacerbation in COPD: Pooled Sub-Group Analyses of ENHANCE-1 and ENHANCE-2 Phase 3 TrialsParticipant: Igor Barjaktarevic, MD, Medical Director, COPD Program, UCLA Division of Pulmonary & Critical Care MedicineSession: C40 – Clinical Trials and Novel Interventions in COPD For further information please contact: Verona Pharma plcUS Tel: +1-833-417-0262UK Tel: +44 (0)203 283 4200Victoria Stewart, Senior Director of Investor Relations and CommunicationsIR@veronapharma.comArgot Partners(US Investor Enquiries)Tel: +1-212-600-1902verona@argotpartners.comOptimum Strategic Communications(International Media and European Investor Enquiries)Tel: +44 (0)203 882 9621verona@optimumcomms.comMary Clark / Richard Staines / Zoe Bolt About Ensifentrine Ensifentrine (RPL554) is an investigational, first-in-class, selective dual inhibitor of the enzymes phosphodiesterase 3 and 4 that combines bronchodilator and anti-inflammatory activities in one compound. In Phase 2 clinical studies in COPD, ensifentrine has shown significant and clinically meaningful improvements in lung function, symptoms and quality of life as a monotherapy or added onto a maintenance bronchodilator. In the Phase 3 ENHANCE-1 and ENHANCE-2 clinical trials, ensifentrine showed significant and clinically meaningful improvements in lung function measures and reduced the rate of COPD exacerbations. Ensifentrine has been well tolerated in clinical trials involving approximately 3,000 subjects to date. About Verona Pharma Verona Pharma is a clinical-stage biopharmaceutical company focused on developing and commercializing innovative therapies for the treatment of chronic respiratory diseases with significant unmet medical needs. If successfully developed and approved, Verona Pharma’s product candidate, ensifentrine, has the potential to be the first therapy for the treatment of respiratory diseases that combines bronchodilator and anti-inflammatory activities in one compound. The Company has evaluated nebulized ensifentrine in its Phase 3 clinical program ENHANCE (“Ensifentrine as a Novel inHAled Nebulized COPD thErapy”) for COPD maintenance treatment. Ensifentrine met the primary endpoint in both ENHANCE-1 and ENHANCE-2 trials demonstrating statistically significant and clinically meaningful improvements in lung function. In addition, ensifentrine significantly reduced the rate and risk of COPD exacerbations in pooled analysis from ENHANCE-1 and ENHANCE-2. Verona Pharma expects to submit a New Drug Application (“NDA”) to the US Food and Drug Administration (“FDA”) in the second quarter of 2023. Two additional formulations of ensifentrine have been evaluated in Phase 2 studies for the treatment of COPD: dry powder inhaler (“DPI”) and pressurized metered-dose inhaler (“pMDI”). Ensifentrine has potential applications in cystic fibrosis, asthma and other respiratory diseases. For more information, please visit www.veronapharma.com. Forward-Looking Statements This press release contains forward-looking statements. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, but not limited to, statements regarding the development of ensifentrine and plans to release data from the ENHANCE trials at ATS 2023, planned regulatory submissions and timing thereof, including the timing of submission of an NDA for ensifentrine, the potential for ensifentrine to be the first therapy for the treatment of respiratory diseases to combine bronchodilator and non-steroidal anti-inflammatory benefits in one compound, the potential of ensifentrine to change the treatment paradigm for COPD patients, and the potential of ensifentrine in the treatment of cystic fibrosis, asthma and other respiratory diseases, as well as the potential of the DPI and pMDI formulations of ensifentrine. These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from our expectations expressed or implied by the forward-looking statements, including, but not limited to, the following: our limited operating history; our need for additional funding to complete development and commercialization of ensifentrine, which may not be available and which may force us to delay, reduce or eliminate our development or commercialization efforts; the reliance of our business on the success of ensifentrine, our only product candidate under development; economic, political, regulatory and other risks involved with international operations; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; serious adverse, undesirable or unacceptable side effects associated with ensifentrine, which could adversely affect our ability to develop or commercialize ensifentrine; we may not be successful in developing ensifentrine for multiple indications; our ability to obtain approval for and commercialize ensifentrine in multiple major pharmaceutical markets, including the US; misconduct or other improper activities by our employees, consultants, principal investigators, third-party service providers and licensees; our inability to realize the anticipated benefits under licenses granted by us to third parties to develop and commercialize ensifentrine, our future growth and ability to compete depends on retaining our key personnel and recruiting additional qualified personnel; material differences between our “top-line” data and final data; our reliance on third parties, including clinical research organizations, clinical investigators, manufacturers and suppliers, and the risks related to these parties’ ability to successfully develop and commercialize ensifentrine; lawsuits related to patents covering ensifentrine and the potential for our patents to be found invalid or unenforceable; lawsuits related to our licensing of patents and know-how with third parties for the development and commercialization of ensifentrine; changes in our tax rates, unavailability of certain tax credits or reliefs or exposure to additional tax liabilities or assessments could affect our profitability, and audits by tax authorities could result in additional tax payments for prior periods; and our vulnerability to natural disasters, global economic factors, geo-political actions and unexpected events may adversely impact our business. These and other important factors under the caption “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2022, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.

To design drugs that stall the growth of aggressive cancers, it helps to know the structures of the proteins that are revving the cancers' engines. In a series of three papers published in Proceedings of the National Academy of Sciences, Scripps Research scientists have illuminated the three-dimensional structure of phosphoinositide 3-kinase alpha (PI3K), a protein often mutated in cancer cells. Moreover, the research team shed light on how that structure changes with the cancer-associated mutations, paving the way for drugs that could target only the mutated versions. "We hope that these detailed structural findings lead to the discovery of drugs that affect cancer cells but not healthy cells," says senior author Peter Vogt, PhD, a professor in the Department of Molecular Medicine at Scripps Research. "That could potentially eliminate the side effects associated with current PI3K drugs." PI3K plays a central role in cell survival and growth. In healthy cells, the protein is flipped on and off as needed. But in numerous types of cancer - including breast, colorectal, endometrial and brain - mutations in PI3K make it active all the time, encouraging the unchecked growth of the tumors. Current drugs that aim to put the brakes on PI3K bind to a section of the protein that rarely changes between healthy and mutated versions; this means all the PI3K in the body is shut off. Because of that, these PI3K inhibitors carry a long list of side effects and toxicities. "To solve this problem, you have to make inhibitors that only recognize the mutated versions of PI3K," says Vogt. "But to do that, you need structural information about what differentiates mutated, overactive PI3K from normal PI3K." This is no easy feat: PI3K is a particularly flexible, "wiggly" protein, so it's difficult to get a single snapshot of its structure. Vogt's group, however, discovered that when PI3K was bound to one of the existing inhibitors, it became more stable. In PNAS papers published in November 2021 and September 2022 , they used a type of imaging technique known as cryogenic electron microscopy (cryo-EM) to work out the three-dimensional structure of PI3K. With this knowledge, they first examined the structure of PI3K attached to the inhibitor. Then, to visualize the protein without the inhibitor, they used cross-linking molecules to attach different parts of PI3K to itself, stabilizing the most flexible parts of the protein. More recently, the research team used the same cryo-EM toolbox to piece together the structure of two mutated versions of PI3K often found in cancer cells. That work, published last month in PNAS , showed how some segments of the mutated PI3K resemble the activated form of PI3K. "There are quite dramatic structural changes," says Vogt. "And in the end, the changes essentially mimic the normal activated form of the protein, with the only difference being that it's always in this active structure." The findings point toward ways to use drugs to shut off this always-on version of PI3K in cancer cells, without turning off healthy PI3K. The key, Vogt says, is that the drugs will need to bind to a different part of the PI3K protein than where the existing PI3K inhibitors bind - a part that varies structurally between the healthy and mutated versions of the protein. His lab group is following-up on this research with additional studies revealing how current drugs change the structure of PI3K. Liu X, Yang S, Hart JR, Xu Y, Zou X, Zhang H, Zhou Q, Xia T, Zhang Y, Yang D, Wang MW, Vogt PK. Cryo-EM structures of PI3K reveal conformational changes during inhibition and activation. Proc Natl Acad Sci U S A. 2021 Nov 9;118(45):e2109327118. doi: 10.1073/pnas.2109327118