Urinary Tract Infections

SAN DIEGO, March 19, 2024 /PRNewswire/ -- Blacksmith Medicines, Inc. (Blacksmith), a leading biopharma dedicated to discovering and developing medicines targeting metalloenzymes, announced today that it will present a talk and poster highlighting its novel chemistry technology platform for metalloenzyme inhibitors of LpxC for the treatment of infections caused by multidrug-resistant Gram-negative bacteria at the New Antibacterial Discovery and Development Gordon Research Conference (GRC): Innovative Approaches in Antibacterial Research and Development to Fight the Antibiotic Resistance Crisis being held March 17-22, 2024, in Ventura, CA. "We are looking forward to attending the GRC and presenting an overview of Blacksmith's discovery platform along with a progress update on our novel class small-molecule antibacterial targeting LpxC," said Andrew Tomaras, Ph.D., Senior Vice President of Blacksmith. "Our lead candidate, currently undergoing IND-enabling studies, has demonstrated activity against susceptible and multidrug-resistant Gram-negative organisms included on the WHO and CDC bacterial threat lists, and is currently being pursued using both IV and oral routes of administration for indications such as UTI." Talk Presentation Details: Title: "Anti-Infective Candidates with Novel Targets Using the Blacksmith Discovery Platform" Category: Discovery Pipelines, Hits, Leads and Candidates Date and Time: Tuesday, March 19 at 11:05am – 11:25am Pacific Poster Presentation Details: Title: "Advanced preclinical in vitro and in vivo characterization of a novel, non-hydroxamate-based LpxC inhibitor for the intravenous and oral treatment of multidrug-resistant Enterobacterales" Date and Time: Thursday, March 21 at 4:00pm – 6:00pm Pacific Poster Board Number: 13 More information can be found on the meeting website at 2024 New Antibacterial Discovery and Development GRC and, following the presentation, a version of the poster will be made available on the Blacksmith Medicines website About LpxC LpxC, a zinc hydrolase, is an attractive and highly sought-after antibiotic target – it is conserved across Gram-negative bacteria and not found in Gram-positive bacteria or human cells. Inhibiting LpxC results in potent killing of Gram-negative bacteria with the benefit of sparing Gram-positive bacteria such as those residing in the protective microbiome of the gut which help to deter opportunistic C. difficile infections. Other LpxC inhibitors have been evaluated by biopharma in the past but chemistry limitations (e.g. hydroxamic acid) have yielded ineffective compounds that suffer from poor drug-like properties. Thus, there are no approved therapeutics targeting LpxC. Blacksmith, using its proprietary chemistry platform, has developed novel non-hydroxamate inhibitors of LpxC that are safe and effective in animal models of Gram-negative infection and are able to kill Gram-negative 'superbugs' where other antibiotics are ineffective. About metalloenzymes and the Blacksmith platform Metalloenzymes utilize a metal ion cofactor in the enzyme active site to perform essential biological functions. This diverse class of targets has historically been difficult to drug due to small molecule chemistry limitations that have plagued the industry. The Blacksmith metalloenzyme platform has solved this problem by leveraging the following: A large proprietary fragment library of metal-binding pharmacophores (MBPs); A comprehensive database containing a full characterization of the metalloenzyme genome including functions, metal cofactors, and associations to disease; A first-of-its-kind metallo-CRISPR library of custom single guide RNAs; An industry-leading metalloenzyme computational toolkit for docking, modeling and structure-based drug design; and A robust and blocking intellectual property estate covering bioinorganic, medicinal, and computational chemistry approaches for metalloenzyme-targeted medicines. About Blacksmith Medicines At Blacksmith Medicines, we are developing medicines targeting metal-dependent enzymes. Over 30% of known enzymes are metalloenzymes, covering all major enzyme classes: oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. Metal ions, including magnesium, zinc, iron, manganese and copper, are the essential ingredient in these metalloenzymes. We recognized a large unmet need for new chemical matter and innovative approaches to drug this important class of enzymes. Our purpose-built platform for metalloenzyme-targeted medicines combines, for the first time in industry, a focused library of metal-binding pharmacophores with proprietary computational modeling approaches to rapidly and rationally design small molecule inhibitors that interact with key metal ions in the enzyme's active site. Our comprehensive knowledge of the metal environment and key active site interactions enables Blacksmith to rapidly build potent and selective inhibitors in a stepwise and predictable manner. Blacksmith has executed strategic drug discovery collaborations with Basilea Pharmaceutica International Ltd., Cyteir Therapeutics Inc., Eli Lilly and Company (Lilly), Hoffmann-La Roche Ltd., and Zoetis LLC., and has been awarded non-dilutive Federal funding agreements with CARB-X and NIH/NIAID. Blacksmith investors include Lilly, Evotec A.G., MP Healthcare Partners, MagnaSci Ventures, and Alexandria Venture Investments. For further information, please visit the company's website and LinkedIn. Media Contact: Amy Conrad Juniper Point [email protected] 858-366-3243 SOURCE Blacksmith Medicines

Generalized pustular psoriasis (GPP) is a rare, chronic, heterogenous neutrophilic inflammatory disease associated with skin and systemic symptoms, such as fever, pain, and fatigue1,2,3,4 In China, SPEVIGO®’s expanded approval adds the reduction of occurrences of GPP in pediatric patients aged 12 and above weighing ≥40 kg, and adults5 The US FDA’s approval expands the use of SPEVIGO® to include the treatment of GPP in adults and pediatric patients aged 12 and above weighing ≥40 kg, making it the first targeted therapy that addresses the need for acute and chronic treatment for GPP patients6 SPEVIGO® is currently approved in 48 countries7 Boehringer Ingelheim today announced that the US Food and Drug Administration (FDA) has approved SPEVIGO® (spesolimab-sbzo) injection for the treatment of generalized pustular psoriasis (GPP) in adults and pediatric patients aged 12 and above weighing ≥40 kg.5 This approval follows the Chinese National Medical Products Administration’s (NMPA) recent approval of SPEVIGO® for the reduction of occurrence of generalized pustular psoriasis (GPP) in adolescents from 12 years of age with a body weight ≥40 kg and adults. SPEVIGO® is a novel, humanized selective IgG1 antibody that binds to interleukin-36 receptor (IL-36R), a key part of a signaling pathway within the immune system shown to be involved in the cause of GPP.8,9,10,11,12 The regulatory authorities’ decisions are majorly based on the positive results of the EFFISAYIL® 2 clinical trial, a 48-week clinical trial that showed that SPEVIGO® significantly reduced the risk of GPP flares by 84%, compared with placebo. In the trial with 123 patients, no flares were observed after week 4 of SPEVIGO® subcutaneous treatment in the high-dose group (n=30).13,14,15,16 In the Effisayil® 2 trial, SPEVIGO® was associated with an increased incidence (≥9 cases per 100 patient-years) of injection site reaction, urinary tract infection, arthralgia, and pruritus compared to placebo. “Until now, people living with GPP have not had any approved options to treat their disease,” said Bruce Strober, MD, PhD, Clinical Professor, Dermatology, Yale University and Central Connecticut Dermatology. “SPEVIGO® has the potential to redefine the treatment options for the patients we serve.” Distinct from plaque psoriasis, GPP is a rare, chronic, heterogenous, inflammatory neutrophilic disease associated with painful skin manifestations and systemic symptoms, such as fever, pain, and fatigue.1-4 GPP varies widely between individuals living with the condition, with symptoms presenting on a continuum, which means that it can present in either a persistent or a relapsing course.2-4 GPP often requires emergency care and can lead to life-threatening complications, such as multi-organ failure and sepsis.17 GPP’s unpredictable nature can potentially have significant long-term impacts on quality of life for people living with it, and may cause fear and anxiety over the disease course.3,18 “SPEVIGO®’s new approvals constitute a fundamental change for people living with GPP, addressing their huge need for acute and chronic treatment,” said Carinne Brouillon, Member of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim. “Experiencing GPP can be mentally and physically devastating, leaving those affected with uncertainty and fear of the next episode. Therefore, expanding the treatment of GPP is a critical step towards addressing patients’ needs.” About SPEVIGO® SPEVIGO® is a novel, humanized, selective antibody that specifically blocks the activation of the IL-36R, a signaling pathway within the immune system shown to be involved in the pathogenesis of several autoinflammatory diseases, including GPP.7-11 It is the first targeted therapy for the treatment of GPP and has been evaluated in the largest clinical program specifically for the treatment of patients with GPP.10,19 What is SPEVIGO®? SPEVIGO® is a prescription medicine used to treat generalized pustular psoriasis (GPP) in adults and children 12 years of age and older who weigh at least 88 pounds (40 kg). It is not known if SPEVIGO® is safe and effective in children under 12 years of age or who weigh less than 88 pounds. Important Safety Information Do not receive SPEVIGO® if you or your child have had a severe or life-threatening allergic reaction to spesolimab-sbzo or any of the ingredients in SPEVIGO®. What is the most important information I should know about SPEVIGO®? SPEVIGO® may cause serious side effects, including: Infections. SPEVIGO® may lower the ability of your or your child’s immune system to fight infections and may increase your or your child’s risk of infections. Your healthcare provider should check you or your child for infections and tuberculosis (TB) before starting treatment with SPEVIGO® and may treat you or your child for TB before you begin treatment with SPEVIGO® if you have a history of TB or have active TB. Your healthcare provider should watch you or your child closely for signs and symptoms of TB during or after treatment with SPEVIGO®. Tell your healthcare provider right away if you or your child have an infection or have symptoms of an infection during or after treatment with SPEVIGO®, including: fevers, chills, or sweats muscle aches cough shortness of breath blood in your phlegm (mucus) burning when you urinate urinating more often than normal Allergic reactions and infusion-related reactions. Serious allergic reactions may happen during or after your or your child’s SPEVIGO® injection. If you or your child have a serious allergic reaction, your healthcare provider will stop treatment with SPEVIGO®. If you or your child are given SPEVIGO® in a vein (intravenously) and have an infusion- related reaction, your healthcare provider will stop your or your child’s SPEVIGO® infusion and treat your or your child’s symptoms and may restart SPEVIGO® at a slower infusion rate. Tell your healthcare provider or get emergency medical help right away if you or your child get any of the following symptoms during or after your or your child’s SPEVIGO® injection: feeling faint, dizzy, or lightheaded swelling of your face, eyelids, lips, mouth, tongue, or throat trouble breathing or throat tightness fever mouth sores chest tightness hives or skin rash that is different than the rash from generalized pustular psoriasis (GPP) itching swollen lymph nodes Before you or your child receive SPEVIGO®, tell your healthcare provider about all of your medical conditions, including if you or your child: have an infection that does not go away or that keeps coming back. have TB or have been in close contact with someone with TB. have recently received or are scheduled to receive an immunization (vaccine). You or your child should not receive live vaccines during and for at least 16 weeks after treatment with SPEVIGO®. You or your child should be brought up to date with all vaccines before starting SPEVIGO®. are pregnant or plan to become pregnant. It is not known if SPEVIGO® can harm your or your child’s unborn baby. are breastfeeding or plan to breastfeed. It is not known if SPEVIGO® passes into your breast milk. Talk to your healthcare provider about the best way to feed your or your child’s baby during treatment with SPEVIGO®. Tell your healthcare provider about all the medicines you or your child take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What are the possible side effects of SPEVIGO®? The most common side effects of SPEVIGO® given in a vein (intravenously) for GPP flare treatment include: feeling tired or weak nausea and vomiting headache itching or itchy bumps a collection of blood under the skin at the infusion site or bruising urinary tract infection The most common side effects of SPEVIGO® when given under the skin (subcutaneously) for treatment of GPP when not experiencing a flare include: redness, pain, swelling, hardening, hives, or warmth at the injection site joint pain urinary tract infection itching These are not all of the possible side effects of SPEVIGO®. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1‐800‐FDA‐1088. Please see full Prescribing Information, Medication Guide, and Instructions for Use. CL-SPG-100004 03.18.2024 About the EFFISAYIL® clinical trial program The EFFISAYIL® clinical trial program evaluated the largest and broadest population of GPP patients in trials of a therapy specifically targeting the IL-36 pathway for GPP:10,18 EFFISAYIL® 1: A Phase II study that demonstrated treatment with a single intravenous dose of spesolimab significantly improved signs and symptoms of GPP in patients experiencing a flare, including rapid pustular and skin clearance. These results supported the approval of spesolimab as the first specific treatment for GPP flares in adults in major markets10,20 EFFISAYIL® 2: A Phase IIb study that showed spesolimab significantly reduced the risk of GPP flares by 84% over 48 weeks compared to placebo. In the trial with 123 patients, no flares were observed after week 4 of spesolimab SC treatment in the high-dose group (n=30)12–15 EFFISAYIL® ON: An open-label extension study to evaluate the long-term safety and efficacy of spesolimab in patients with GPP who have completed previous spesolimab trials21 About generalized pustular psoriasis (GPP) GPP is a chronic, heterogenous, neutrophilic inflammatory disease associated with skin and systemic symptoms that is distinct from plaque psoriasis. GPP is recognized as a separate clinical entity from other forms of psoriasis, with the IL-36 pathway being a key driver of GPP and triggering response to treatment.1 Prevalence of GPP is low and varies considerably across geographical regions, ranging from 1.76 to 124 patients per million persons in reports from key countries, including France, Japan, Sweden, and South Korea.2 GPP can become life-threatening (mortality rates ranging from 2% to 16%) due to severe complications, such as multisystem organ failure and sepsis requiring urgent hospital care; many GPP patients also suffer from various comorbidities, which contribute to the ongoing burden for the patient and healthcare systems.2,16,17 GPP symptoms appear unpredictable and present on a continuum, which greatly impacts a patient’s quality of life, and may cause fear and anxiety over the disease course, as well as long-term impacts on quality of life related to work/school, emotional health, social activities, and finances.2,3,4 About Boehringer Ingelheim Boehringer Ingelheim is working on breakthrough therapies that transform lives today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units, Human Pharma and Animal Health. Learn more at . March 2024 MPR-CRP-100327, MPR-US-102903 References: 1Marrakchi S, Puig L. Pathophysiology of generalized pustular psoriasis. Am J Clin Dermatol. 2022;23:13–19. 2Prinz JC, Choon SE, Griffiths CEM, et al. Prevalence, comorbidities and mortality of generalized pustular psoriasis: A literature review. J Eur Acad Dermatol Venereol. 2023;37:256–273. 3Reisner DV, Johnsson FD, Kotowsky N, et al. Impact of generalized pustular psoriasis from the perspective of people living with the condition: Results of an online survey. Am J Clin Dermatol. 2022;23:65–71. 4Gooderham MJ, Van Voorhees AS, Lebwohl MG. An update on generalized pustular psoriasis. Expert Rev Clin Immunol. 2019;15:907–919. 5National Medical Products Administration. Drug approval document release, March 11 2024. 2024年03月11日药品批准证明文件送达信息发布 (nmpa.gov.cn) (Accessed 14 March 2024) 6Record on file. 7Record on file. 8Bassoy EY, Towne JE, Gabay C. Regulation and function of interleukin-36 cytokines. Immunol Rev. 2018;281:169–178. 9Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365:620–628. 10Ganesan R, Raymond EL, Mennerich D, et al. Generation and functional characterization of anti-human and anti-mouse IL-36R antagonist monoclonal antibodies. MAbs. 2017;9:1143–1154. 11Bachelez H, Choon SE, Marrakchi S, et al. Trial of spesolimab for generalized pustular psoriasis. N Engl J Med. 2021;385:2431–2440. 12Bachelez H, Choon SE, Marrakchi S, et al. Inhibition of the interleukin-36 pathway for the treatment of generalized pustular psoriasis. N Engl J Med. 2019;380:981–983. 13Boehringer Ingelheim. Spesolimab prevented generalized pustular psoriasis flares in Effisayil™ 2 trial. 2023. . (Accessed 14 March 2024). 14Morita A, Strober B, Burden AD, et al. Efficacy and safety of subcutaneous spesolimab for the prevention of generalised pustular psoriasis flares (Effisayil 2): an international, multicentre, randomised, placebo-controlled trial. Lancet. 2023;402:1541–1551. 15Gordon KB, Lebwohl M, Barker J, et al. Effect of spesolimab on achieving sustained disease remission in patients with generalized pustular psoriasis: Results from the Effisayil 2 study. European Academy of Dermatology & Venereology Congress; 2023; Berlin, Germany. Abstract P0731. 16Strober B, Augustin M, Tada Y, et al. Effect of high-dose subcutaneous spesolimab on skin manifestations: Results from the pivotal Effisayil 2 trial of flare prevention in generalized pustular psoriasis. European Academy of Dermatology & Venereology Congress; 2023; Berlin, Germany. Abstract 1732. 17Choon SE, Navarini AA, Pinter A. Clinical course and characteristics of generalized pustular psoriasis. Am J Clin Dermatol. 2022;23:21–29. 18Burden D, Mrowietz U, Skalicky AM, et al. Symptom experience and content validity of the Psoriasis Symptom Scale (PSS) in patients with generalized pustular psoriasis (GPP). Dermatol Ther (Heidelb). 2022;12:1367–1381. 19Choon SE, Lebwohl MG, Marrakchi S, et al. Study protocol of the global Effisayil 1 Phase II, multicentre, randomised, double-blind, placebo-controlled trial of spesolimab in patients with generalized pustular psoriasis presenting with an acute flare. BMJ Open. 2021;11:e043666. 20Navarini A, Prinz JC, Morita A, et al. Spesolimab improves patient- reported outcomes in patients with generalized pustular psoriasis: Results from the Effisayil 1 study. J Eur Acad Dermatol Venereol. 2022; 37:730–736. 21Effisayil™ ON: A study to test long-term treatment with spesolimab in people with generalized pustular psoriasis who took part in a previous study. . (Accessed 14 March 2024).

Four healthy subjects dosed with RECCE® 327 at 3,000mg over 20 minutes Data received from this cohort will support preparations for a Phase II trial SYDNEY, Australia, March 19, 2024 (GLOBE NEWSWIRE) -- Recce Pharmaceuticals Ltd (ASX: RCE, FSE: R9Q), (the Company), the Company developing a new class of synthetic anti-infectives, today announced it completed dosing healthy subjects in the latest cohort of its Phase I/II trial, evaluating its lead candidate, RECCE® 327 (R327), at fast infusion rates. “Completing dosing of our latest cohort marks another milestone in our journey toward advancing R327 as a potential frontline treatment for patients with UTIs or urosepsis,” said James Graham, Chief Executive Officer of Recce Pharmaceuticals. “We are dedicated to delivering impactful solutions to combat infectious diseases and improve global health outcomes.” An Independent Safety Committee will now review and evaluate the comprehensive data from the 4-subject cohort. Recruitment for the next cohort is underway. Data from this trial is expected to pave the way for a Phase II trial to establish the potential of R327 as a frontline treatment for patients with UTIs or urosepsis. The administration of antibiotics via rapid intravenous infusions is a proven safe and effective method of administration, impacting patient treatment, wait times, and nursing workloads globally. More information on this trial can be found at the Australia New Zealand Clinical Trial Registry under the trial ID ACTRN12623000448640. About Recce Pharmaceuticals Ltd Recce Pharmaceuticals Ltd (ASX: RCE, FSE: R9Q) is developing a New Class of Synthetic Anti-Infectives designed to address the urgent global health problems of antibiotic-resistant superbugs and emerging viral pathogens. Recce’s anti-infective pipeline includes three patented, broad-spectrum, synthetic polymer anti-infectives: RECCE® 327 as an intravenous and topical therapy that is being developed for the treatment of serious and potentially life-threatening infections due to Gram-positive and Gram-negative bacteria including their superbug forms; RECCE® 435 as an orally administered therapy for bacterial infections; and RECCE® 529 for viral infections. Through their multi-layered mechanisms of action, Recce’s anti-infectives have the potential to overcome the hypercellular mutation of bacteria and viruses – the challenge of all existing antibiotics to date. The FDA has awarded RECCE® 327 Qualified Infectious Disease Product designation under the Generating Antibiotic Initiatives Now (GAIN) Act – labelling it for Fast Track Designation, plus 10 years of market exclusivity post approval. Further to this designation, RECCE® 327 has been included on The Pew Charitable Trusts Global New Antibiotics in Development Pipeline as the world’s only synthetic polymer and sepsis drug candidate in development. RECCE® 327 is not yet market approved for use in humans with further clinical testing required to fully evaluate safety and efficacy. Recce wholly owns its automated manufacturing, which is supporting present clinical trials. Recce’s anti-infective pipeline seeks to exploit the unique capabilities of its technologies targeting synergistic, unmet medical needs. Corporate Contact James Graham Recce Pharmaceuticals Ltd +61 (02) 9256 2571 James.graham@recce.com.au Media & Investor Relations (AU) Andrew Geddes CityPR +61 (02) 9267 4511 ageddes@citypublicrelations.com.au Media (USA) Michael Fitzhugh LifeSci Communications mfitzhugh@lifescicomms.com Investor Relations (USA & EU) Guillame van Renterghem LifeSci Advisors gvanrenterghem@lifesciadvisors.com