Ethambutol Hydrochloride

Enrollment concluded in the Phase 2a proof-of-concept clinical trial evaluating SPR720 in nontuberculous mycobacterial pulmonary disease (NTM-PD); preliminary data expected in 4Q 2024New SPR720 in-vitro resistance data to be presented at IDWeek 2024 conference in OctoberCompany announces departure of Chief Medical Officer Kamal Hamed, MD, MPH, MBA; Appoints Board member and Chair of Development Committee John C. Pottage, Jr., M.D., as Special Advisor to oversee medical function; search ongoing for a new CMOCash balance of $63.5 million as of June 30, 2024; reiterate expected cash runway into late 2025Conference call and webcast at 4:30pm ET today CAMBRIDGE, Mass., Aug. 05, 2024 (GLOBE NEWSWIRE) -- Spero Therapeutics, Inc. (Nasdaq: SPRO), a multi-asset clinical-stage biopharmaceutical company, focused on identifying and developing novel treatments for rare diseases and multi-drug resistant (MDR) bacterial infections, today announced financial results for the second quarter ended June 30, 2024, and provided a business update. “Spero’s pipeline of both wholly-owned and partnered clinical-stage programs continues to advance as planned this year,” said Sath Shukla, President and Chief Executive Officer of Spero. “We recently concluded enrollment in the Phase 2a trial of SPR720 in treatment-naive and treatment-experienced non-refractory NTM-PD patients, and we anticipate reporting data in the fourth quarter of 2024. In addition, we remain on track with enrollment in the ongoing global Phase 3 PIVOT-PO clinical trial with tebipenem HBr. We are hopeful that both SPR720, with the potential to be the first approved oral agent in NTM-PD, and Tebipenem, with the potential to be the first oral carbapenem for complicated urinary tract infection (cUTI) and acute pyelonephritis (AP), could become meaningfully differentiated treatment options for patients and expand treatment choice for providers.” Pipeline Update SPR720 SPR720 is an investigational novel, oral, first-line treatment for NTM-PD. Enrollment has concluded, with 25 patients enrolled in the Phase 2a proof-of-concept clinical trial evaluating SPR720 in NTM-PD. The last patient received the first dose in July 2024. Preliminary data on SPR720’s early bactericidal activity, as assessed by the change in NTM bacterial load over the treatment course of 56 days, are expected in 4Q 2024. The rate of change in log10 Colony Forming Units per milliliter (CFU/mL), which is the trial’s primary endpoint, is being measured, along with the rate of change in Time to Positivity, which is a key secondary endpoint. The double-blinded, placebo-controlled, trial enrolled treatment-naïve and treatment-experienced patients with non-refractory NTM-PD due to Mycobacterium avium complex in 3 treatment groups (placebo, SPR720 500 mg and SPR720 1000 mg dosed QD). Additional secondary endpoints include assessments of pharmacokinetics and safety and tolerability. For more information on the trial, see ClinicalTrials.gov identifier NCT05496374.Dosing completed in two Phase 1 clinical studies evaluating SPR720 in healthy volunteers: 1) a bronchoalveolar lavage (BAL) study assessing intrapulmonary PK (epithelial lung fluid and alveolar macrophage) of SPR719, the active moiety of the prodrug SPR720 (NCT05955586), and 2) a study evaluating changes in plasma PK when SPR720 is co-administered with azithromycin and ethambutol (NCT05966688). Topline results from both studies are also expected to be disclosed in 4Q of 2024. Upcoming Presentation Data from in vitro evaluation of the development of microbial resistance against SPR720 have been accepted for presentation at IDWeek, taking place October 16 to 19, 2024 in Los Angeles, CA. Tebipenem HBr Tebipenem HBr is an investigational oral carbapenem antibiotic being developed for the treatment of cUTI including acute pyelonephritis (AP) to help patients avoid hospitalizations or reduce duration of in-patient therapy. Spero granted GSK an exclusive license to commercialize tebipenem HBr in all territories, except certain Asian territories. Enrollment on track in PIVOT-PO, the global Phase 3 clinical trial of tebipenem HBr in patients with cUTI. This randomized, double-blinded trial compares oral tebipenem HBr with intravenous imipenem cilastatin, in hospitalized adult patients with cUTI/AP. The primary endpoint is overall response (a combination of clinical cure and favorable microbiological response) at the Test-of-Cure (TOC) visit. Target enrollment for the trial is approximately 2,648 patients, with enrollment completion expected in the second half of 2025. For more information on PIVOT-PO, refer to ClinicalTrials.gov ID NCT06059846. SPR206 SPR206 is an investigational, intravenously administered next-generation polymyxin that has shown antibiotic activity against MDR Gram-negative pathogens, including carbapenem-resistant Enterobacterales, Acinetobacter baumannii and Pseudomonas aeruginosa in preclinical studies. The U.S. Food and Drug Administration (FDA) cleared the Company's IND for a Phase 2 trial in participants with hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP). The Company maintains its guidance to initiate the trial, contingent on availability of non-dilutive funding. Corporate Update Kamal Hamed, MD, MPH, MBA, Chief Medical Officer, is departing the Company, effective August 29, 2024.John C. Pottage, Jr., M.D., a member of Spero’s Board of Directors since August 2018, with over 20 years of experience advancing therapeutics for infectious diseases, has been appointed Special Advisor to oversee the Company’s medical function, effective immediately, and will assume responsibility for oversight of Spero’s pipeline programs, including the ongoing clinical studies for SPR720 and Tebipenem HBr. Dr. Pottage has served as Senior Vice President and Chief Scientific and Medical Officer of ViiV Healthcare, where he oversaw research and development, regulatory, safety and medical affairs. Prior to that, Dr. Pottage served as Senior Vice President and Head of the Infectious Disease Medicine Development Center at GSK (formerly GlaxoSmithKline), and prior to that, as Vice President of Global Clinical Development of Antivirals at GSK. Earlier in his career he held senior clinical development roles at Achillion Pharmaceuticals and Vertex Pharmaceuticals, as well as various academic/ clinical positions at Rush University Medical Center. In connection with this appointment, Dr. Pottage has stepped aside from the Company’s audit committee, as he will not meet the independence requirements for service on the audit committee while serving as a Special Advisor to the Company. Mr. Shukla added, “We wish to thank Kamal for his significant contribution to the development and advancement of Spero’s three clinical programs over the last two years. At the same time, we are pleased that our clinical programs will be under the extremely capable oversight of Dr. Pottage while we continue our ongoing search for a new Chief Medical Officer.” Second quarter 2024 Financial Results Spero reported a net loss of $17.9 million, or ($0.33) per share of common stock, basic and diluted, for the second quarter ended June 30, 2024, compared with a net loss of $11.9 million, or ($0.23) per share of common stock, basic and diluted, for the second quarter ending June 30, 2023.Total revenue for the second quarter of 2024 was $10.2 million, compared with total revenue of $2.7 million for the second quarter of 2023. The revenue increase for the second quarter of 2024 was primarily due to an increase in collaboration revenue related to our agreement with GSK for tebipenem HBr and an increase in grant revenue related to our BARDA contract for tebipenem HBr, partially offset by a decrease under our NIAID agreement relating to SPR206 and collaboration revenue related to our agreement with Pfizer for SPR206.Research and development expenses for the second quarter of 2024 were $23.7 million, compared to $9.5 million of research and development expenses for the same period in 2023. The increase in research and development expenses year-over-year was primarily due to higher direct costs related to the pivotal Phase 3 trial for tebipenem HBr and the Phase 2a clinical trial for SPR720, partially offset by lower direct expenses related to SPR206 and lower R&D personnel-related costs.General and administrative (G&A) expenses for the second quarter of 2024 were $5.5 million, compared to $6.1 million of general and administrative expenses for the same period in 2023. This year-over-year decrease was primarily due to a decrease in G&A personnel-related costs, partially offset by increases in professional and consulting fees and facility-related expenses.As of June 30, 2024, Spero had cash and cash equivalents of $63.5 million. Based on its current operating plans, Spero expects that its cash and cash equivalents, together with other non-dilutive funding commitments, will be sufficient to fund its operating expenses and capital expenditure requirements into late 2025. For further details on Spero’s financials, refer to Spero’s Quarterly Report on Form 10-Q, filed with the U.S. Securities and Exchange Commission (SEC) today. Conference Call and Live Webcast Spero will host a conference call and live audio webcast today at 4:30 p.m. to report its second quarter 2024 financial results and provide an update on its business and pipeline. To access the call, please dial 1-877-269-7751 (domestic) or 1-201-389-0908 (international) and refer to conference ID 13747505, or click on this link and request a return call. The audio webcast can be accessed live on this link and also on the “Investor Relations” page of the Spero Corporate Website at https://sperotherapeutics.com. The archived webcast will also be available on Spero’s website for 30 days following the call. About Spero TherapeuticsSpero Therapeutics, headquartered in Cambridge, Massachusetts, is a multi-asset clinical-stage biopharmaceutical company focused on identifying and developing novel treatments for rare diseases and MDR bacterial infections with high unmet need. For more information, visit www.sperotherapeutics.com Government Agency Research Support The views expressed in this press release are those of the authors and may not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government. Tebipenem HBr Research SupportSelect tebipenem HBr studies have been funded in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, under contract number HHSO100201800015C. Department of Defense Select SPR206 studies have been supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Joint Warfighter Medical Research Program under Award No. W81XWH 19 1 0295. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. National Institute of Allergy and Infectious Disease Select SPR206 studies have been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93021C00022. Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the timing, progress and results of Spero's preclinical studies, clinical trials and research and development programs; the potential benefits of any of Spero’s current or future product candidates in treating patients; and Spero’s strategy, goals and anticipated financial performance, milestones, business plans and focus. In some cases, forward-looking statements may be identified by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could," "intent," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue," the negative of these terms or other similar expressions. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of important risks, uncertainties and other factors that may cause actual results to differ materially from those indicated by such forward looking statements, including whether tebipenem HBr, SPR720 and SPR206 will advance through the clinical trial process on a timely basis, or at all, taking into account the effects of possible regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, clinical trial design and clinical outcomes; whether the results of such trials will warrant submission for approval from the FDA or equivalent foreign regulatory agencies; whether the FDA will ultimately approve tebipenem HBr and, if so, the timing of any such approval; whether the FDA will require any additional clinical data or place labeling restrictions on the use of tebipenem HBr that would delay approval and/or reduce the commercial prospects of tebipenem HBr; whether a successful commercial launch can be achieved and market acceptance of tebipenem HBr can be established; whether results obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials; Spero's reliance on third parties to manufacture, develop, and commercialize its product candidates, if approved; Spero's need for additional funding; the ability to commercialize Spero's product candidates, if approved; Spero's ability to retain key personnel; Spero's leadership transitions; whether Spero's cash resources will be sufficient to fund its continuing operations for the periods and/or trials anticipated; and other factors discussed in the "Risk Factors" set forth in filings that Spero periodically makes with the SEC. The forward-looking statements included in this press release represent Spero's views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Spero explicitly disclaims any obligation to update any forward-looking statements. Investor Relations Contact:Shai Biran, PhDSpero Therapeutics IR@Sperotherapeutics.com Media Inquiries: media@sperotherapeutics.com Spero Therapeutics, Inc.Condensed Consolidated Balance Sheet Data(in thousands)(Unaudited) June 30, December 31, 2024 2023Cash, cash equivalents and marketable securities $63,527 $76,333Other assets 86,354 106,057Total assets $ 149,881 $ 182,390 Total liabilities 69,381 75,496Total stockholder's equity 80,500 106,894Total liabilities and stockholders' equity $ 149,881 $ 182,390 Spero Therapeutics, Inc.Condensed Consolidated Statements of Operations(in thousands, except share and per share data) (unaudited) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Revenues: Grant revenue $4,180 $1,928 $9,243 $3,258 Collaboration revenue - related party 5,903 519 9,967 1,036 Collaboration revenue 114 269 254 492 Total revenues 10,197 2,716 19,464 4,786 Operating expenses: Research and development 23,725 9,510 41,057 18,489 General and administrative 5,533 6,096 11,450 13,413 Total operating expenses 29,258 15,606 52,507 31,902 Loss from operations (19,061) (12,890) (33,043) (27,116)Other income (expense) 1,199 976 2,512 1,936 Net loss $(17,862) $(11,914) $(30,531) $(25,180)Net loss per share attributable to common shareholders per share, basic and diluted $(0.33) $(0.23) $(0.57) $(0.48) Weighted average shares outstanding, basic and diluted: 53,957,766 52,571,813 53,740,901 52,549,538

MicuRx showcased the latest research progress on their pipeline products, MRX-5 and MRX-8, at the 7th World Bronchiectasis Conference Three significant study results further support the potential of MRX-5 and MRX-8 in treating Nontuberculous Mycobacteria (NTM) lung disease and Pseudomonas aeruginosa infections DUNDEE, Scotland, July 18, 2024 /PRNewswire/ -- Shanghai MicuRx Pharmaceutical Co., Ltd. ("MicuRx"，688373.SH) presented the latest research progress on their novel antibiotic pipeline products, MRX-5 and MRX-8, at the 7th World Bronchiectasis Conference (WBC) held in Dundee, Scotland, from July 4 to 6, 2024. These research results provide new hope for the future treatment of Nontuberculous Mycobacteria (NTM) lung disease and Pseudomonas aeruginosa infections. Conference Background Continue Reading The World Bronchiectasis Conference is a leading global academic conference focused on the research and treatment of bronchiectasis. This conference brings together top scientists and clinical experts from around the world to discuss the latest research developments, clinical management strategies, and the development of new therapies for bronchiectasis. Research Highlights As a biopharmaceutical company dedicated to developing innovative anti-infective drugs, MicuRx presented three significant research results in poster presentation at the conference. These studies further support the potential of MRX-5 and MRX-8 in the treatment of specific infections： In Vitro and In Vivo Activity of A Novel Leucyl-tRNA Synthetase Inhibitor Against Mycobacterium Abscessus The active drug MRX-6038 was very potent against M. abscessus clinical isolates in vitro with MIC90 0.5 mg/L while the control drug clarithromycin MIC90 was 4 mg/L. MRX-6038 greatly reduced the resistance frequency of standard of care drugs (Ethambutol, Clarithromycin, Rifabutin, Clofazimine, Amikacin, Imipenem, Ciprofloxacin) by more than 10 to 100,000 folds, demonstrating the potential for combination with the background therapy. Oral prodrug MRX-5 was tested in mice with lung infections due to M. abscessus isolates, and efficacy was demonstrated against infections with both clarithromycin-sensitive and clarithromycin non-susceptible isolates. In Vitro Activity of Novel Leucyl-tRNA Synthetase Inhibitor Against Mycobacterium Avium Complex MRX-6038, the major activedrug of MRX-5, has demonstrated potent in vitro activity against Mycobacterium avium clinical isolates including isolates not susceptible to clarithromycin. When MRX-6038 was combined with Clarithromycin, Rifabutin, Amikacin, and Ethambutol, the resistance frequency of these standard of care drugs was greatly reduced to below 6.5×10-11. Further studies are warranted for the evaluation of MRX-6038 for the treatment of Mycobacterium avium pulmonary disease. In Vitro and In Vivo Activity of A Novel Antibiotic In The Polymyxin Class Against Pseudomonas Aeruginosa MRX-8 demonstrated potent in vitro activity against P. aeruginosa including tobramycin and amikacin resistant clinical isolates. In mouse models with P. aeruginosa lung infections of both tobramycin-sensitive and tobramycin-resistant isolates, nebulized MRX-8 treatment significantly decreased bacterial load in the lung tissues, demonstrating bactericidal activity. About MRX-8 MRX-8 is a novel polymyxin antibiotic developed by MicuRx, primarily used to treat severe infections caused by multidrug-resistant Gram-negative bacteria. Traditional polymyxins are limited in clinical use due to nephrotoxicity and neurotoxicity. Through meticulous structural design, MRX-8 not only maintains or enhances therapeutic efficacy but also significantly improves safety by reducing these potential toxic risks. In 2022, MRX-8 completed Phase I clinical trials in the United States. In 2023, it completed Phase I enrollment in China, with primary study results released in June 2024. These trial results indicated that MRX-8 achieved the desired therapeutic levels in the human body at the expected clinical doses for infections caused by Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. Besides systemic administration, the company plans to explore the development of an inhaled formulation of MRX-8 to uncover its clinical and commercial value in targeted treatment of chronic lung infections. About MRX-5 and NTM MRX-5 is a novel benzoxaborole antibiotic developed by MicuRx for infections caused by NTM. NTM is a common pathogen causing bronchiectasis. In recent years, the incidence of NTM diseases has rapidly increased, becoming a significant public health issue. [1] Among diseases caused by NTM, Mycobacterium avium complex and Mycobacterium abscessus complex account for 70%-95% of NTM diseases. [2] The main clinical symptoms of NTM pulmonary infections include persistent cough, sputum production, chest pain, shortness of breath, fatigue, weight loss, and malaise. [1] Preclinical data indicates that MRX-5 has good antibacterial activity against most common NTM pathogens and has demonstrated good safety in animal studies. Additionally, its characteristics of minimal drug interactions, low resistance potential, and oral availability make it an ideal candidate for the treatment of chronic infections. Currently, MRX-5 is undergoing Phase I clinical trials, offering a promising new treatment option for patients with NTM diseases. About Shanghai MicuRx Pharmaceutical Co., Ltd. MicuRx is a biopharmaceutical company focusing on novel therapeutics for infectious diseases. With global independent intellectual property and competitiveness, we are committed to the discovery, development, and commercialization of innovative drugs for unmet medical needs. Since the company was founded in 2007, MicuRx has adhered to the principle of "Better therapy through superior medicine", focusing on the increasingly serious problem of global antimicrobial resistance. For more information, please visit our website at References： SOURCE MicuRx Pharmaceutical