Cefepime hydrochloride

DSMC has reviewed the safety and pharmacokinetic data from Cohort 2 and recommended that the study proceed to enroll patients into Cohort 3ROCKVILLE, Md., Oct. 03, 2024 (GLOBE NEWSWIRE) -- Theriva™ Biologics, Inc. (NYSE American: TOVX), (“Theriva” or the “Company”), a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, today announced a positive outcome from the Data and Safety Monitoring Committee (DSMC) review of results from the second Cohort of its Phase 1b/2a randomized, double-blinded, placebo-controlled clinical trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant (HCT) recipients for the prevention of acute graft-versus-host-disease (aGVHD). Cohort 2 enrolled 19 patients who received at least 1 dose of study drug (SYN-004 or Placebo randomized 2:1). Eighteen (18) patients received at least one dose of intravenous (IV) piperacillin/tazobactam and 12 of these patients completed sufficient doses of IV piperacillin/tazobactam to be evaluable towards the study endpoints. The study is ongoing and remains blinded; however, key findings from blinded data for Cohort 2 are included below: Adverse events (AEs) and serious adverse events (SAEs) observed in Cohort 2 were typical of those observed in allo-HCT patients and no AEs or SAEs were determined by the investigators to be related to study drug treatment. A total of 15 SAEs were reported among 10 patients, with the most common SAE being infections and infestations, including sepsis.No patients died within the 30-day follow-up period after the last dose of study drug; 1 patient died 95 days and another 211 days after the last dose of study drug due to cancer relapse and pneumonia respectively (not related to study drug). Consistent with the findings from Cohort 1 and previous studies of SYN-004 in healthy volunteers, no patient blood samples were positive for SYN-004 at any timepoint.The pharmacokinetics of piperacillin, which can be metabolized by SYN-004, were as expected for this patient population. Based on a review of the safety and pharmacokinetic data, the DSMC has recommended that the study proceed to enroll Cohort 3, in which study drug (SYN-004 or placebo) will be administered in combination with the IV beta-lactam antibiotic cefepime. Steven A. Shallcross, Chief Executive Officer of Theriva Biologics, commented, “These encouraging data support the clinical advancement of SYN-004 and build on the growing data that underscore its therapeutic potential. The first 2 cohorts have shown that active SYN-004 is not found in the blood of allo-HCT patients after repeated oral doses, in part alleviating the concern that SYN-004 might be absorbed in patients with poor intestinal barrier function and potentially interfere with IV antibiotics. We are very grateful for the tremendous support from Dr. Dubberke and his team at Washington University as we pursue additional funding to enable the conduct of the third cohort and continue with the goal of improving standard treatment for these highly susceptible patients by overcoming existing limitations of broad-spectrum IV beta-lactam antibiotics.” About the Phase 1b/2a Clinical Trial The ongoing randomized, double-blinded, placebo-controlled Phase 1b/2a clinical trial is being conducted at Washington University School of Medicine in St. Louis. The trial is designed to evaluate the safety, tolerability, and potential absorption of oral SYN-004 (150 mg QID for a maximum of 28 days) into the systemic circulation of allogeneic HCT recipients who receive an IV antibiotic. To mitigate risk, Cohort 1 of the study administered meropenem as the study-assigned antibiotic. Meropenem is a carbapenem antibiotic that is not metabolized by SYN-004. Patients in Cohorts 2 were administered piperacillin/tazobactam and Patients in Cohort 3 will be administered cefepime. Both piperacillin and cefepime can be metabolized by SYN-004. The trial is also designed to evaluate potential protective effects of SYN-004 on the gut microbiome as well as generate preliminary information on potential therapeutic benefits and patient outcomes of SYN-004 in allogeneic HCT recipients. The trial is expected to enroll up to 36 participants with three sequential cohorts, each evaluating a different study-assigned IV beta-lactam antibiotic. Safety and pharmacokinetic data for each Cohort will be reviewed by an independent Data and Safety Monitoring Committee that will make a recommendation on whether to proceed to the next IV antibiotic. More information on the study is available here (NCT04692181). About SYN-004 (ribaxamase) SYN-004 (ribaxamase) is an oral prophylactic therapy designed to degrade certain IV beta-lactam antibiotics within the GI tract and maintain the natural balance of the gut microbiome for the prevention of Clostridioides difficile infection (CDI), overgrowth of pathogenic organisms, the emergence of antimicrobial resistance (AMR) and acute graft-versus-host-disease (aGVHD) in allogeneic hematopoietic cell transplant (HCT) recipients. Allogeneic HCT recipients routinely receive long courses of IV beta-lactam antibiotics to treat infection following conditioning therapy. Antibiotic-mediated damage of the gut microbiome in allogeneic HCT recipients may lead to adverse outcomes including CDI, VRE colonization and potentially fatal bacteremia and aGVHD. A previously completed placebo-controlled Phase 2b clinical trial of 412 patients demonstrated SYN-004 protected the gut microbiome from antibiotic-mediated dysbiosis. Patients who received SYN-004 also demonstrated significantly better maintenance and recovery of the gut microbiome as well as lower incidences of new colonization by opportunistic and potentially pathogenic microorganisms such as VRE. About Theriva™ Biologics, Inc. Theriva™ Biologics (NYSE American: TOVX), is a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need. The Company is advancing a new oncolytic adenovirus platform designed for intravenous (IV), intravitreal and antitumoral delivery to trigger tumor cell death, improve access of co-administered cancer therapies to the tumor, and promote a robust and sustained anti-tumor response by the patient’s immune system. The Company’s lead candidates are: (1) VCN-01, an oncolytic adenovirus designed to replicate selectively and aggressively within tumor cells, and to degrade the tumor stroma barrier that serves as a significant physical and immunosuppressive barrier to cancer treatment; (2) SYN-004 (ribaxamase) which is designed to degrade certain commonly used IV beta-lactam antibiotics within the gastrointestinal (GI) tract to prevent microbiome damage, thereby limiting overgrowth of pathogenic organisms such as VRE (vancomycin resistant Enterococci) and reducing the incidence and severity of acute graft-versus-host-disease (aGVHD) in allogeneic hematopoietic cell transplant (HCT) recipients; and (3) SYN-020, a recombinant oral formulation of the enzyme intestinal alkaline phosphatase (IAP) produced under cGMP conditions and intended to treat both local GI and systemic diseases. For more information, please visit Theriva Biologics’ website at www.therivabio.com. Forward-Looking Statement This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases forward-looking statements can be identified by terminology such as “may,” “should,” “potential,” “continue,” “expects,” “anticipates,” “intends,” “plans,” “believes,” “estimates,” and similar expressions, and include statements regarding the encouraging data supporting the clinical advancement of SYN-004 and building on the growing data that underscore its therapeutic potential, SYN-004 improving standard treatment for the highly susceptible patients by overcoming existing limitations of broad-spectrum IV beta-lactam antibiotics, the potential protective effects of SYN-004 on the gut microbiome and generating preliminary information on potential therapeutic benefits and patient outcomes of SYN-004 in allogeneic HCT recipients, the Company’s ability to find additional funding to support Cohort 3, and the trial enrolling up to 36 participants with three sequential cohorts, each evaluating a different study-assigned IV beta-lactam antibiotic. These forward-looking statements are based on management's expectations and assumptions as of the date of this press release and are subject to a number of risks and uncertainties, many of which are difficult to predict that could cause actual results to differ materially from current expectations and assumptions from those set forth or implied by any forward-looking statements. Important factors that could cause actual results to differ materially from current expectations include, among others, the ability of SYN-004 to improve standard treatment for the highly susceptible patients by overcoming existing limitations of broad-spectrum IV beta-lactam antibiotics, the ability to enroll the anticipated number of patients in the Phase 1b/2a clinical trial, the Company’s ability to reach clinical milestones when anticipated, the Company’s ability to find additional funding to support Cohort 3, as well as results that are consistent with prior results; the ability to complete clinical trials on time and achieve the desired results and benefits, continuing clinical trial enrollment as expected; the ability to obtain regulatory approval for commercialization of product candidates or to comply with ongoing regulatory requirements, regulatory limitations relating to the Company’s ability to promote or commercialize their product candidates for the specific indications, acceptance of product candidates in the marketplace and the successful development, marketing or sale of Synthetic Biologics' and VCN's products, developments by competitors that render such products obsolete or non-competitive, the Company’s ability to maintain license agreements, the continued maintenance and growth of the Company’s patent estate, the ability to continue to remain well financed, and other factors described in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023 and its other filings with the SEC, including subsequent periodic reports on Forms 10-Q and current reports on Form 8-K. The information in this release is provided only as of the date of this release, and Theriva Biologics undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law. For further information, please contact:Investor Relations: Chris CalabreseLifeSci Advisors, LLCccalabrese@lifesciadvisors.com917-680-5608 Source: Theriva Biologics, Inc.

Breakthroughs for Innovative Products Going Overseas with Global Operation Capabilities Continuing to Strengthen SHANGHAI, Aug. 28, 2024 /PRNewswire/ -- On August 27, Shanghai Fosun Pharmaceutical (Group) Co., Ltd. ("Fosun Pharma" or "the Group"; Stock Code: 600196.SH; 02196.HK), announced its operating performance for the first half of 2024 (the "Reporting Period"). During the Reporting Period, Fosun Pharma achieved revenue of RMB20.46 billion, an increase of 5.31% YoY after excluding COVID-related products. The net profit attributable to owners of the parent of the Group after deducting extraordinary gain or loss amounted to RMB1.3 billion. In the second quarter of 2024, the net profit attributable to owners of the parent of the Group after deducting extraordinary gain or loss was RMB646 million, a quarter-on-quarter increase of RMB37 million. As a global innovation-driven pharmaceutical and healthcare industry group, Fosun Pharma continuously advance its innovation transformation and the development and commercialization of innovative products. In the first half of 2024, Fosun Pharma's revenue from key innovative products in pharmaceuticals business grew steadily, exceeding RMB3.7 billion. In 2024, Fosun Pharma continued to boost operational efficiency and profitability, laying the foundation for long-term sustainable development. During the Reporting Period, the gross margin minus the selling and distribution expense ratio increased by 1.72 percentage points YoY; excluding the impact of newly acquired companies, the management expense decreased by about RMB0.2 billion. During the Reporting Period, Fosun Pharma ensured stable free cash flow through measures including optimizing operating cash flow, supply chain management, and controlling capital expenditures, achieving operating cash flow of RMB1.9 billion, a period-on-period increase of 5.36%, exceeding the growth of operating profit. In addition, the Group continued to optimize asset structure and improve asset efficiency. Since 2024, the cash inflow from asset disposals and the expected cash inflow from contracts signed by Fosun Pharma exceeded RMB2 billion in aggregate. Revenue from innovative products maintains steady growth, with a further focus on innovative drugs and high-value devices In the first half of 2024, Fosun Pharma further focused on innovative drugs and high-value devices. Four key innovative products with a total of 9 indications, independently developed and licensed-in by the Group, were approved for launch domestically and internationally. In addition to the key innovative products, Fosun Pharma also had 38 generic drug varieties approved for launch domestically and internationally. In the first half of 2024, Fosun Pharma's pharmaceutical manufacturing segment achieved revenue of RMB14.7 billion. The innovative drug business achieved breakthroughs in core therapeutic areas such as solid tumors, hematologic tumors and immunity inflammation, and realized multiple innovative achievements in hematologic tumors, breast cancer and lung cancer, benefiting patients worldwide. Han Si Zhuang (serplulimab injection), Fosun Pharma's first self-developed biopharmaceutical innovative drug, as well as the world's first anti-PD-1 monoclonal antibody (mAb) approved for the first-line treatment of small cell lung cancer (SCLC), was commercialized in the domestic market in March 2022. Up to now, it has been approved for 4 indications, broadly covering high-incidence tumours including lung cancer and gastrointestinal cancer, benefiting over 75,000 patients globally. Additionally, the 5th NDA of Han Si Zhuang for the first-line treatment of non-squamous non-small cell lung cancer (nsNSCLC) has been accepted by the National Medical Products Administration (NMPA) in China. During the Reporting Period, Fosun Pharma's self-developed biosimilar Han Da Yuan (adalimumab injection) received 4 new indications approval from the NMPA. It has now been approved for eight indications in China, covering all indications of originator adalimumab in China, providing more treatment options for adult and pediatric patients with autoimmune diseases. Fosun Pharma adheres to an open innovation strategy, and actively expands its pipelines through BD in addition to independent R&D. In June 2024, Su Ke Xin (avatrombopag malate tablets), which is exclusively commercialized by Fosun Pharma, received approval in Chinese mainland for a second indication for the treatment of adult patients with chronic primary immune thrombocytopenia (ITP) who have shown poor response to prior treatment, further benefiting ITP patients in China. Additionally, certain domestic innovative drugs licensed-in by the Group such as Bei Wen (keverprazan hydrochloride tablets) and Pei Jin (telpegfilgrastim injection), were officially included in the National Medical Drugs Catalogue in January 2024. This significantly enhanced the accessibility of drugs for relevant diseases within Chinese mainland and practically reduced the burdens of drugs on patients, aiming to improve the living and life quality of patients through regulated therapies. In the field of vaccines, Fosun Pharma has established an independent R&D system centered on two major technical platforms: bacterial vaccines and viral vaccines. In March 2024, the rabies vaccine (Vero cell) for human use (freeze dried), which is independently developed by the Group, has been approved for launch in Chinese mainland. The production line has also passed the GMP compliance inspection. Research progress on various pipelines develops rapidly to secure innovative development To meet the unmet clinical needs, through diversified and multi-level cooperation models such as independent R&D, co-development, license-in and industrial investment, Fosun Pharma continues to enrich its innovative product pipeline and focus on differentiated product R&D with high-tech barriers, to continuously enhance the value of its pipeline. In the first half of 2024, Fosun Pharma's total R&D expenditure amounted to RMB2.7 billion, with R&D expenses totaling RMB1.9 billion. The R&D expenditure in the pharmaceutical manufacturing segment amounted to RMB2.4 billion, accounting for 16.4% of the segment's revenue. In particular, R&D expenses were RMB1.6 billion, accounting for 10.7% of the segment's revenue. In the first half of 2024, 4 innovative drugs/biosimilars with a total of 9 indications independently developed, co-developed and licensed-in by the Group had entered the pre-launch approval/critical clinical stage. The pharmaceutical manufacturing segment of the Group submitted 124 patent applications, including 2 American patents applications, 8 PCT applications, and the Group has obtained 37 licensed invention patents authorization. During the Reporting Period, the New Drug Application (NDA) of self-developed selective MEK1/2 inhibitor (project code: FCN-159) for two indications was accepted by NMPA in May and June 2024, both of which were included in the priority review procedure. The Marketing Authorization Application (MAAs) for five indications of the self-developed denosumab biosimilar HLX14 (recombinant anti-RANKL fully human monoclonal antibody injection) was accepted by the European Medicines Agency (EMA). Additionally, during the Reporting Period, the Phase 3 clinical trials for its self-developed Han Si Zhuang (serplulimab injection), in combination with bevacizumab and chemotherapy for the first-line treatment of metastatic colorectal cancer (mCRC) patients, had commenced in the Chinese mainland. The combination dosing of OP0595 and cefepime or aztreonam, developed by Fosun Pharma in collaboration with Meiji Seika Pharma Co., Ltd., for the treatment of adults infected by aerobic gram-negative bacteria with limited options, had commenced two phase III clinical trials in China. During the Reporting Period, clinical data from multiple pipeline products and marketed products of Fosun Pharma were presented at global industry conferences, including the American Society of Clinical Oncology (ASCO), American Association for Cancer Research (AACR), and the European Hematology Association (EHA), further demonstrating the Group's innovative R&D capabilities on the international stage. In addition to independent R&D, Fosun Pharma actively practices an open R&D model, engaging in the incubation and investment of R&D projects through initiatives such as the establishment and management of industrial funds, ensuring the sustainability of its innovation pipeline. During the reporting period, Fosun Pharma successfully completed the establishment and filing of Shenzhen Biopharma Industrial Fund with fundraising size of RMB5.0 billion Continues to enhance global operation capabilities and gains international recognition for innovative products Fosun Pharma continues to uphold the internationalization strategy in multiple dimensions, such as innovative R&D, two-way license, production and operations as well as commercialization to enhance operational efficiency and strengthen global market layout while covering major overseas markets, including the United States, Europe, Africa, India, and Southeast Asia. As at the end of the Reporting Period, the Group had formed an overseas commercialization team of approximately 1,000 employees. For the first half of 2024, overseas revenue reached RMB5.5 billion, an increase of 15.13% YoY, accounting for 26.93% of total revenue. During the Reporting Period, Fosun Pharma's self-developed Han Qu You (trastuzumab injection, trade name: HERCESSI™ in the U.S., Zercepac® in Europe) received the U.S. FDA approval for three indications covering the treatment of breast cancer and gastric cancer, becoming the first domestic biosimilar approved for launch in China, the EU and the United States. Additionally, through collaboration with global renowned pharmaceutical companies, Fosun Pharma has established a presence in Europe, the United States, Canada, and numerous emerging markets. Up to date, Han Qu You has been approved in 48 countries and regions, benefiting 200,000+ patients, bringing affordable and high-quality treatment options to breast cancer and gastric cancer patients worldwide. Self-developed biopharmaceutical innovative drug of Fosun Pharma, Serplulimab Injection (anti-PD-1 monoclonal antibody, Chinese trade name: Han Si Zhuang) completed the first international shipment in January 2024, making it the first Chinese anti-PD-1 mAb approved for launch in Southeast Asia. The marketing authorization application (MAA) of Han Si Zhuang has been accepted in March 2023 and its head-to-head bridging trial comparing to first-line standard of care with Atezolizumab for extensive-stage small cell lung cancer (ES-SCLC) had entered clinical enrollment stage in the United States. At the same time, Fosun Pharma has established an innovative drug team in the United States to advance the commercialization of Serplulimab Injection. Fosun Pharma actively introduces leading international technologies and products into the Chinese market to benefit more patients. During the Reporting Period, the Headquarters Industrial Base of the joint venture Intuitive Fosun officially opened and was put into operation in Shanghai Zhangjiang International Medical Park. The base integrates R&D, production and training, and its operation will further accelerate the localization process of the Da Vinci Surgical System. As at the end of June 2024, the accumulated total installation volume of the Da Vinci Surgical Robot in Chinese mainland and Hong Kong S.A.R.and Macau S.A.R. was over 380 in more than 300 hospitals. More than 540,000 patients had benefited from the Da Vinci Surgical Robot's precise treatment and returned to normal life. During the Reporting Period, Fosun Pharma's joint venture with Insightec, Fosun Insightec, made steady progress in the commercialization, clinical application and research of magnetic resonance-guided focused ultrasound treatment system for neurological diseases (MRgFus brain therapy system) in Chinese mainland, Hong Kong S.A.R and Macao S.A.R.. As a global pharmaceutical and healthcare industry group, Fosun Pharma continues to promote the building of production system with international quality standard, with its quality management system and production capabilities recognized by leading international certification authorities, laying a solid foundation for the overseas distribution of preparations. As at the end of the Reporting Period, all production lines of the domestic subsidiaries under the pharmaceutical manufacturing segment of the Group obtained domestic GMP certifications and 10 production lines had passed GMP certification in major regulatory markets such as the U.S. and the EU. "Guided by the 4IN strategy (Innovation, Internationalization, Intelligentization, and Integration), Fosun Pharma consistently focuses on unmet clinical needs, prioritizes innovative R&D, adheres to technology-driven and product-driven approach, and strengthens global operation capabilities, ensuring steady and sustainable development." Wu Yifang, Chairman of Fosun Pharma, said, "Looking forward, Fosun Pharma's internal operation will be further improved in quality and efficiency, continuing to enhance its leading position in hematologic tumors, breast cancer, lung cancer and other fields while expanding footprint in immunity inflammation, chronic diseases and central nervous system. We will also intensify industry-university-research strategic cooperation with world-class universities and research institutions to capture innovative products at an early stage. At the same time, we will actively promote the overseas export of high-quality products and promote global simultaneous development, aiming to become the global leading integrator of pharmaceutical and healthcare innovation." About Fosun Pharma Founded in 1994, Shanghai Fosun Pharmaceutical (Group) Co., Ltd.* ("Fosun Pharma"; stock code: 600196.SH, 02196.HK) is a global innovation-driven pharmaceutical and healthcare industry group. Fosun Pharma directly operates businesses including pharmaceuticals, medical devices, medical diagnosis, and healthcare services. As a shareholder of Sinopharm Co., Ltd., Fosun Pharma expands its areas in the pharmaceutical distribution and retail business. Fosun Pharma is patient-centered and unmet clinical needs-oriented. Through diversified and multi-level cooperation models such as independent research and development, cooperative development, license-in, and industrial investment, the company continues to enrich its innovative product pipeline and focus on differentiated product R&D with high-tech barriers, to continuously enhance the value of its pipeline. Fosun Pharma's innovative products focus on core therapeutic areas such as solid tumors, hematologic tumors and immunity inflammation. It also strengthens core technology platforms such as antibodies/ADC, cell therapy, and small molecules. Guided by the 4IN strategy (Innovation, Internationalization, Intelligentization, and Integration), Fosun Pharma adheres to the business philosophy of "Innovation for Good Health", continues to promote innovative transformation, actively deploys internationalization, strengthens business focus by product lines, promotes integrated operations and efficiency improvement, and is dedicated to being the global leading integrator of pharmaceutical and healthcare innovation. For more information, please visit our official website: SOURCE Fosun Pharma