Complete atrioventricular block

Direct evidence that BRII-179-induced functional antibody responses can contribute to increased and sustained HBsAg loss rate New insight in utilizing BRII-179 to enriching patients with intrinsic humoral immune responses for higher HBsAg loss or HBV functional cure rates New data support progression to late-stage clinical development with data expected to inform curative treatment approaches in chronic Hepatitis B DURHAM, N.C. and BEIJING, Nov. 13, 2023 /PRNewswire/ -- Brii Biosciences Limited ("Brii Bio" or the "Company", stock code: 2137.HK), a biotechnology company developing therapies to improve patient health and choice across diseases with high unmet need, today shared three posters at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting® in Boston, MA, two of which were accepted as late-breakers providing new data from two Phase 2 assets, BRII-179 (VBI-2601) and BRII-835 (VIR-2218), within the chronic hepatitis B (CHB) clinical program. "We are pleased to share these data at The Liver Meeting that demonstrate the versatility of our HBV portfolio and critical insight in our search for a cure for HBV," said David Margolis, MD, Chief Medical Officer of Brii Bio. "The important connection between HBsAg loss and antibody response provides a clear direction in further improving the functional cure rate and identifying patients who will most likely respond to curative treatments. Our goal is to develop the right treatment regimen for the right patient in the broadest possible populations, while sparing patients from the expensive or less tolerated treatment option that may not benefit them." In a late-breaking poster presentation, Brii Bio announced additional interim data that were unblinded at the cohort level from a randomized, placebo-controlled and double-blinded Phase 2 study of BRII-179, in combination with pegylated interferon-alpha (PEG-IFNα) in patients with CHB infection. Findings from this presentation include: BRII-179 add-on therapy to existing PEG-IFNα treatment was generally safe and tolerated, with adverse events similar to those associated with PEG-IFNα treatment and BRII-179 as previously reported. At Week 36 (12 weeks after end-of-treatment [EOT]), BRII-179 + PEG-IFNα combination group achieved higher HBsAg loss rate compared to Placebo + PEG-IFNα group (Full Analysis Set (FAS): 24.6% vs.14.0%, Per Protocol Set (PPS): 31.8% vs.14.9%). The difference in HBsAg loss rate was observed at Week 24 (EOT) and maintained through Week 36. The clinical study also found that the combination group had significantly higher HBsAg seroconversion rates than Placebo + PEG-IFNα group (FAS: 15.8% vs. 1.8%, p=0.016; PPS: 19.6% vs. 2.0%, p=0.0058) at Week 24 (EOT). The addition of BRII-179 induced robust and functional HBsAg antibody responses, participants in BRII-179 + PEG-IFNα combination group achieved significantly higher hepatitis B surface antibody (HBsAb) response rate than those in Placebo + PEG-IFNα group both at Week 24 (FAS: 38.6% vs. 14.0%, p=0.0052; PPS: 39.1% vs. 13.7%, p=0.0054) and Week 36 (FAS: 33.3% vs. 12.3%, p=0.0131; PPS: 34.1% vs. 10.6%, p=0.0105). The HBsAb titer was significantly associated with HBsAg loss at Week 24 and 36. 4 out 5 patients who rebounded had no detectable antibody responses. The data from this proof-of-concept study demonstrated that the addition of BRII-179 induced functional immune responses that could improve the rate and duration of HBsAg loss in CHB patients who receive PEG-IFNα treatment, thereby increasing the CHB functional cure rate. In a second late-breaking poster presentation, Brii Bio presented translational research data from BRII-179-001 and BRII-179-835-001 studies, indicating the distinct HBsAg antibody responses induced by BRII-179 observed only in a subset of CHB subjects, suggesting that intrinsic immune responses against HBV in some patients may be more profoundly impaired. Additionally, researchers found: BRII-179 in combination with BRII-835 (VIR-2218) was generally well tolerated when administered up to 9 monthly doses, with no treatment related adverse events > Grade 2. In CHB participants on nuceos(t)ide reverse transcriptase inhibitors (NrtI) therapy, BRII-179, alone or in combination with BRII-835, induced substantial HBV specific T cell responses, while significant HBsAg antibody responses were elicited in some but not all chronic HBV participants even after 9 doses of vaccination in combination with BRII-835, an HBV-targeting siRNA lowering immunosuppressive viral antigens such as HBsAg. Immunological analysis suggests that BRII-179 may offer a unique opportunity to enrich CHB patients who are able to elicit the necessary HBsAg antibody response in achieving higher functional cure rate in some patients while sparing others from unnecessary treatments. In a poster presentation, Brii Bio highlighted the multiple dose pharmacokinetics (PK) of BRII-835 (VIR-2218) in patients with chronic HBV infection from Phase 1b/2 and Phase 2 clinical trials, and the impact of regional or ethnic background may have on the PK of the drug. Highlights include: The PK characteristics of BRII-835 in patients with chronic HBV infection are generally similar to those in healthy volunteers. At doses of 50 and 100 mg, dose dependent increases in systemic exposures were observed. There was no apparent accumulation in plasma after a second dose given four weeks later. Similar PK profiles between patients enrolled in the Asia-Pacific region and mainland China demonstrate that Chinese ethnic background from mainland China has no apparent impact, which could serve as a bridge to support mainland China's participation in future global trials for further evaluation of BRII-835. As part of Brii Bio's unique approach to develop a functional cure for HBV, the Company and its partners are progressing multiple ongoing phase 2 studies, including BRII-835 and BRII-179 combination, BRII-179 and PEG-IFN⍺ combination, BRII-835, BRII-877 (VIR-3434) with or without PEG-IFN⍺. In addition, Vir Biotechnology, Inc. ("Vir") is also investigating VIR-2218 and/or VIR-3434 for the treatment of HBV/HDV co-infection. About Hepatitis B Hepatitis B viral infection is one of the world's most significant infectious disease threats with more than 290 million people infected globally.1 Chronic HBV infection is the leading cause of liver disease and an estimated 820,000 people die of complications from chronic HBV each year.1 HBV is of exceptional concern in China, where 87 million people are infected.2 About BRII-179 BRII-179 (VBI-2601) is a novel recombinant protein-based HBV immunotherapeutic candidate that expresses the Pre-S1, Pre-S2, and S HBV surface antigens, and is designed to induce enhanced and broad B-cell and T-cell immunity. BRII-179 is currently being investigated in two Phase 2 clinical trials in combination with BRII-835 or PEG-IFNα as part of a potential functional cure regimen for the treatment of chronic HBV infection. Brii Bio licensed BRII-179 from VBI Vaccines, Inc. ("VBI") in December 2018, providing Brii Bio with commercial rights to BRII-179 in the licensed territories of China, Hong Kong, Macau, and Taiwan. The exclusive license for BRII-179 has been extended to worldwide markets since July 2023. About BRII-835 BRII-835 (VIR-2218) is an investigational subcutaneously administered HBV-targeting siRNA that has the potential to stimulate an effective immune response and has direct antiviral activity against HBV. It is the first siRNA in the clinic to include Enhanced Stabilization Chemistry Plus (ESC+) technology to enhance stability and minimize off-target activity, which potentially can result in an increased therapeutic index. Brii Bio licensed exclusive rights to develop and commercialize BRII-835 for the greater China territory from Vir Biotechnology, Inc. ("Vir") in 2020. About BRII-877 BRII-877 (VIR-3434) is an investigational subcutaneously administered HBV-neutralizing monoclonal antibody designed to block entry of all 10 genotypes of HBV into hepatocytes and also to reduce the level of virions and subviral particles in the blood. BRII-877 (VIR-3434), which incorporates Xencor's Xtend™ and other Fc technologies, has been engineered to potentially function as a T-cell vaccine against HBV in infected patients, as well as to have an extended half-life. Brii Bio licensed exclusive rights to develop and commercialize BRII-877 for the greater China territory from Vir Biotechnology, Inc. ("Vir") in 2022. About Brii Bio Brii Biosciences Limited ("Brii Bio", stock code: 2137.HK) is a commercial stage biotechnology company developing therapies to address major public health challenges where patients experience high unmet medical needs, limited choice and significant social stigmas. With a focus on infectious and central nervous system diseases, the Company is advancing a broad pipeline of unique therapeutic candidates with lead programs against hepatitis B viral infection (HBV), postpartum depression (PPD), and major depressive disorder (MDD). The Company is led by a visionary and experienced leadership team and has operations in key biotech hubs, including Raleigh-Durham, the San Francisco Bay Area, Beijing and Shanghai. For more information, visit . 1 World Health Organization. (June 2022). Hepatitis B. World Health Organization. Retrieved from 2 World Health Organization. Hepatitis. World Health Organization. Retrieved from . SOURCE Brii Biosciences Limited

Top-line 48-week results from the MOMENTUM Phase 2 obesity trial expected Q4 2023 Pemvidutide granted Fast Track designation for the treatment of non-alcoholic steatohepatitis (NASH) Top-line results from the Phase 2 trial of HepTcell™ in chronic hepatitis B (CHB) expected Q1 2024 Webcast to be held today, November 7, 2023, at 8:30 am EST GAITHERSBURG, Md., Nov. 07, 2023 (GLOBE NEWSWIRE) -- Altimmune, Inc. (Nasdaq: ALT), a clinical-stage biopharmaceutical company, today announced financial results for the three months ended September 30, 2023, and provided a business update. “The next few months will be important as we receive the data from our 48-week MOMENTUM trial of pemvidutide in subjects with obesity as well as the results of our Phase 2 trial of HepTcell in CHB,” said Vipin K. Garg, Ph.D., President and Chief Executive Officer of Altimmune. “The rapidly expanding obesity market needs differentiated products that address not only excess body weight, but also risk factors for cardiovascular comorbidities, including elevated LDL-cholesterol and excess liver fat. We also were very pleased to receive Fast Track designation for our pemvidutide program in NASH, which demonstrates the unmet need for this critical liver disease. We believe that our liver fat reduction is class-leading and could result in unprecedented reductions of fibrosis and measures of NASH.” Recent Highlights and Anticipated Milestones Pemvidutide Top-line data readout from 48-week MOMENTUM Phase 2 obesity trial expected in Q4 2023 Patient dosing (last subject last dose) was completed in September 2023.Dr. Louis Aronne, Professor of Metabolic Research and Professor of Clinical Medicine, Weil Cornell Medical School, a leading authority in obesity and obesity clinical trials, is serving as the Principal Investigator.391 subjects with obesity or overweight and without diabetes were randomized 1:1:1:1 to 1.2 mg, 1.8 mg, 2.4 mg pemvidutide or placebo administered weekly for 48 weeks in conjunction with diet and exercise.In an interim 24-week data readout in March 2023, subjects receiving pemvidutide achieved robust reductions in body weight, waist circumference, serum lipids and blood pressure without arrhythmias, clinically meaningful heart rate increases or other safety signals.Top-line data readout at 48 weeks will include subject disposition, weight loss, serum lipids, vital signs, adverse events and glycemic control. Enrollment commenced in IMPACT Phase 2b NASH trial Informed by the positive results of the Phase 1b randomized, placebo-controlled trials of pemvidutide in subjects with non-alcoholic fatty liver disease (NAFLD), the FDA granted pemvidutide Fast Track designation for the treatment of NASH.This Phase 2b biopsy-driven NASH trial is being conducted at approximately 60 sites in the U.S., with Dr. Stephen Harrison, Medical Director, Pinnacle Research, and Adjunct Professor of Medicine, Oxford University, serving as the principal investigator.Approximately 190 subjects with and without diabetes are planned to be randomized 1:2:2 to 1.2 mg, 1.8 mg pemvidutide or placebo.The key endpoints will be NASH resolution and fibrosis improvement after 24 weeks of treatment, with subjects followed for an additional 24 weeks for assessment of safety and additional biomarker responses.Top-line results after 24 weeks of treatment are expected in the first quarter of 2025. HepTcell™ Top-line data from Phase 2 clinical trial expected in Q1 2024 The multicenter clinical trial, which is being conducted at 26 sites in North America, Europe and Southeast Asia, enrolled approximately 80 previously untreated subjects with inactive CHB and low levels of hepatitis B surface antigen (HBsAg).Subjects were randomized 1:1 to HepTcell or placebo to receive six monthly administrations.The primary endpoint is virological response, defined as a 1-log or greater reduction or clearance of HBsAg; secondary endpoints include changes in the levels of hepatitis B virus (HBV) DNA, pre-genomic RNA and other markers of virologic response.Data readout is expected in the first quarter of 2024 after all subjects complete the 6-month course of treatment. Financial Results for the Three Months Ended September 30, 2023 Cash, cash equivalents and short-term investments totaled $140.8 million as of September 30, 2023.Research and development expenses were $18.4 million for the three months ended September 30, 2023, compared to $20.3 million in the same period in 2022. The expenses for the quarter ended September 30, 2023 included $10.4 million in direct costs related to development activities for pemvidutide and $1.6 million in direct costs related to development activities for HepTcell.General and administrative expenses were consistent period-over-period at $4.5 million for the three months ended September 30, 2023 and 2022.Interest income for the three months ended September 30, 2023 was $1.9 million as compared to $1.1 million in the same period in 2022, primarily due to an increase in interest income earned on cash equivalents and short-term investments.Net loss for the three months ended September 30, 2023 was $20.7 million, or $0.39 net loss per share, compared to a net loss of $23.5 million, or $0.48 net loss per share, in the same period in 2022. Conference Call Information: Date: Tuesday, November 7, 2023Time: 8:30 am ESTWebcast: To listen, the conference call will be webcast live on Altimmune’s Investor Relations website at https://ir.altimmune.com/investors.Dial-in: To participate or dial-in, register here to receive the dial-in numbers and unique PIN to access the call. Following the conclusion of the call, the webcast will be available for replay on the Investor Relations page of the Company’s website at www.altimmune.com. The Company has used, and intends to continue to use, the IR portion of its website as a means of disclosing material non-public information and for complying with disclosure obligations under Regulation FD. About Pemvidutide Pemvidutide is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist in development for the treatment of obesity and NASH. Activation of the GLP-1 and glucagon receptors is believed to mimic the complementary effects of diet and exercise on weight loss, with GLP-1 suppressing appetite and glucagon increasing energy expenditure. Glucagon is also recognized as having direct effects on hepatic fat metabolism, leading to rapid reductions in levels of liver fat. Pemvidutide incorporates the EuPort™ domain, a proprietary technology that increases its serum half-life for weekly dosing while likely slowing the entry of pemvidutide into the bloodstream, which may improve its tolerability. About HepTcell HepTcell is a novel, investigational, immunotherapeutic comprised of nine synthetic peptides representing conserved T-cell epitopes on key HBV antigens formulated with IC31®, a TLR9-based adjuvant from Valneva SE. The HBV-directed peptides are designed to drive T cell responses against all HBV genotypes towards a functional cure for chronic HBV in patients of diverse genetic backgrounds. About Altimmune Altimmune is a clinical-stage biopharmaceutical company focused on developing innovative next-generation therapeutics for the treatment of patients with liver diseases and obesity. The Company’s lead product candidate, pemvidutide, is a GLP-1/glucagon dual receptor agonist that is being developed for the treatment of obesity and NASH. In addition, Altimmune is developing HepTcell™, an immunotherapeutic designed to achieve a functional cure for CHB. For more information, please visit www.altimmune.com. Follow @Altimmune, Inc. on LinkedInFollow @AltimmuneInc on Twitter Forward-Looking Statement Any statements made in this press release relating to future financial or business performance, conditions, plans, prospects, trends, or strategies and other financial and business matters, including without limitation, the timing of key milestones for our clinical assets, and the prospects for the utility of, regulatory approval, commercializing or selling any product or drug candidates, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In addition, when or if used in this press release, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to Altimmune, Inc. may identify forward-looking statements. The Company cautions that these forward-looking statements are subject to numerous assumptions, risks, and uncertainties, which change over time. Important factors that may cause actual results to differ materially from the results discussed in the forward looking statements or historical experience include risks and uncertainties, including risks relating to: delays in regulatory review, manufacturing and supply chain interruptions, access to clinical sites, enrollment, adverse effects on healthcare systems and disruption of the global economy; the reliability of the results of studies relating to human safety and possible adverse effects resulting from the administration of the Company’s product candidates; the Company’s ability to manufacture clinical trial materials on the timelines anticipated; and the success of future product advancements, including the success of future clinical trials. Further information on the factors and risks that could affect the Company's business, financial conditions and results of operations are contained in the Company’s filings with the U.S. Securities and Exchange Commission, including under the heading “Risk Factors” in the Company’s most recent annual report on Form 10-K and our other filings with the SEC, which are available at www.sec.gov. Investor Contact:Rich EisenstadtChief Financial OfficerPhone: 240-654-1450reisenstadt@altimmune.com Media Contact:Danielle CanteyEvoke CanalePhone: 619-826-4657danielle.cantey@evokegroup.com ALTIMMUNE, INC.CONSOLIDATED BALANCE SHEETS(In thousands, except share and per-share amounts) September 30, December 31, 2023 2022 (Unaudited) ASSETS Current assets: Cash and cash equivalents $86,855 $111,097 Restricted cash 41 34 Total cash, cash equivalents and restricted cash 86,896 111,131 Short-term investments 53,924 73,783 Accounts receivable 876 173 Income tax and R&D incentive receivables 3,653 2,368 Prepaid expenses and other current assets 7,615 5,358 Total current assets 152,964 192,813 Property and equipment, net 765 1,081 Indefinite-lived intangible asset 12,419 12,419 Other assets 425 615 Total assets $166,573 $206,928 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable $3,046 $4,804 Accrued expenses and other current liabilities 8,825 12,250 Total current liabilities 11,871 17,054 Other long-term liabilities 4,305 4,581 Total liabilities 16,176 21,635 Commitments and contingencies (Note 10) Stockholders’ equity: Common stock, $0.0001 par value; 200,000,000 shares authorized; 52,858,920 and 49,199,845 shares issued and outstanding as of September 30, 2023 and December 31, 2022, respectively 5 5 Additional paid-in capital 590,206 568,399 Accumulated deficit (434,690) (377,884)Accumulated other comprehensive loss, net (5,124) (5,227)Total stockholders’ equity 150,397 185,293 Total liabilities and stockholders’ equity $166,573 $206,928 ALTIMMUNE, INC.CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS(In thousands, except share and per-share amounts) Three Months Ended Nine Months Ended September 30, September 30, 2023 2022 2023 2022 Revenues $362 $2 $389 $42 Operating expenses: Research and development 18,388 20,262 48,890 51,359 General and administrative 4,514 4,492 13,805 13,329 Total operating expenses 22,902 24,754 62,695 64,688 Loss from operations (22,540) (24,752) (62,306) (64,646)Other income (expense): Interest expense (29) (64) (33) (191)Interest income 1,884 1,053 5,387 1,402 Other income (expense), net 14 50 146 185 Total other income (expense), net 1,869 1,039 5,500 1,396 Net loss before income taxes (20,671) (23,713) (56,806) (63,250)Income tax expense (benefit) — (197) — (197)Net loss (20,671) (23,516) (56,806) (63,053)Other comprehensive income — unrealized gain (loss) on short-term investments 56 (143) 103 (263)Comprehensive loss $(20,615) $(23,659) $(56,703) $(63,316)Net loss per share, basic and diluted $(0.39) $(0.48) $(1.10) $(1.37)Weighted-average common shares outstanding, basic and diluted 53,633,354 49,286,535 51,495,957 45,881,547

Results presented at TCT 2023 in San Francisco KADIMA, Israel and SAN FRANCISCO, Oct. 26, 2023 /PRNewswire/ -- The US Early Feasibility Study of Magenta Medical's Elevate™ System, designed to provide temporary mechanical circulatory support during high-risk percutaneous coronary intervention (HR-PCI) procedures, has successfully met its objectives. Elevate™ is the smallest and most powerful percutaneous Left Ventricular Assist Device (pLVAD) in the world. Continue Reading Image of the Magenta Elevate™ Pump, the smallest and most powerful pLVAD. (PRNewsfoto/Magenta Medical) The results were presented by Dr. Perwaiz M. Meraj, Director of the Cardiac Catheterization Laboratory at North Shore University Hospital (Northwell System), at the Transcatheter Cardiovascular Therapeutics (TCT) conference, the annual scientific symposium of the Cardiovascular Research Foundation in San Francisco. The presentation also included a case study of one of the patients enrolled in the trial. Mechanical circulatory support is often necessary for high-risk patients with coronary artery disease undergoing a catheterization procedure to open blockages in the arteries feeding the heart to improve quality of life and reduce the risk of heart attacks. Since the duration of support for this indication is relatively short (up to 6 hours), with patients ambulatory soon following the procedure, it is particularly important to limit the insertion profile of the device in order to minimize vascular access complications. Magenta Medical's Elevate™ Pump addresses this unmet clinical need. STUDY RESULTS Fifteen patients were treated in the study at The Mount Sinai Hospital, St. Francis Hospital and Heart Center, and North Shore University Hospital. Investigators include Drs. Samin K. Sharma, Richard A. Shlofmitz, Ziad Ali, Allen Jeremias, Rajiv Jauhar, Perwaiz M. Meraj, Margaret B. McEntegart, and Ajay J. Kirtane. All 15 patients (mean age of 65) underwent a HR-PCI, with Left Ventricular Ejection Fraction (EF) of 35 ± 10% at baseline and 45 ± 11% at discharge. Key findings: Performance: No hypotensive episodes – in all patients, mean arterial pressures were maintained well above 60 mmHg while on support Technical Success: Uneventful delivery and extraction of all pumps No device stoppage or replacement No device-related complications Safety: No new or worsening aortic regurgitation No meaningful hemolysis All discharged alive and well, and completed the 30-day follow-up visit No Major Adverse Cardiac and Cerebrovascular Events (MACCE) at 30 days Usability: Highly rated ease-of-use Access Site and Closure: 10Fr commercially available femoral sheaths Access site closure using a variety of pre- and post-closure techniques CASE STUDY A 71-year-old male, with severe generalized atherosclerosis, an abdominal aortic aneurysm, 3-vessel coronary artery disease, and severely depressed left ventricular function, was referred to a HR-PCI procedure. With a pre-existing bi-fascicular block and a known prior episode of syncope, the patient developed complete AV-Block with ventricular asystole early in the procedure. Elevate™ Pump flow was increased (mean of 5.7-5.9 L/min), allowing placement of a trans-venous temporary pacemaker under stable hemodynamic conditions. As a result, mean arterial pressures were normal and stable throughout the procedure, the patient remained conscious and communicative for the duration, and the extensive revascularization plan (stenting, rotational atherectomy, and intravascular lithotripsy) was fully achieved in less than one hour. The complete AV-Block subsided upon arrival at the ICU, and the pacemaker lead was removed. About Elevate™ The Elevate™ percutaneous Left Ventricular Assist Device (pLVAD) is a miniaturized heart pump that fits an 8 Fr delivery system. The ElevateTM Pump can be inserted over a guidewire, using a 10 Fr commercially available femoral introducer sheath, providing the smallest crimping profile in the industry. The flow of the pump is adjusted based on the clinical circumstances of the patient and can exceed 5 L/min of mean flow. This makes it the most powerful device of its kind. Elevate™ is an investigational device, limited by federal law to investigational use only. The technology was awarded Breakthrough Device Designation from the US Food and Drug Administration (FDA) for two indications: high-risk percutaneous coronary intervention (HR-PCI) and cardiogenic shock. About Magenta Medical Magenta Medical Ltd. is a privately-held company dedicated to the development of miniaturized blood pumps intended to provide minimally-invasive support to the native heart during acute episodes of dysfunction that could lead to dangerously low blood pressure and compromised perfusion of vital organs. Magenta's Elevate™ percutaneous Left Ventricular Assist Device (pLVAD) is currently in clinical trials to be evaluated for at least two indications: patients undergoing high-risk coronary interventions (HR-PCI) and patients with cardiogenic shock. For more information, please visit Media Contact Marjie Hadad General Manager Must Have Communications [email protected] +972 (54) 536-5220 Photo - SOURCE Magenta Medical