Extensively Drug-Resistant Tuberculosis

BV100 Phase 2 preliminary results suggest BV100 is generally safe and well tolerated and showed strong initial signs of efficacy in VABP patientsStrategic investment from GIBF and launch of BV100 clinical program in ChinaSecond lead asset, alpibectir Phase 2a trial completed in April showing human proof of concept in tuberculosis BASEL, Switzerland, Oct. 16, 2024 (GLOBE NEWSWIRE) -- BioVersys AG, a multi-asset, clinical stage biopharmaceutical company focusing on research and development of novel antibacterial products for serious life-threatening infections caused by multi-drug resistant ("MDR") bacteria, announced today the completion of the last patient's last visit in the Phase 2 clinical trial with its lead asset BV100, the company's novel formulation of rifabutin suitable for intravenous administration. The Phase 2 multicenter, open label, randomized, active controlled study evaluated the pharmacokinetics, efficacy and safety of BV100 in adult patients with ventilator associated bacterial pneumonia (VABP) suspected or confirmed to be due to Carbapenem Resistant Acinetobacter baumannii (CRAB). Preliminary analysis of the data shows that the primary endpoint was met. BV100 is generally safe and well tolerated, met the expected pharmacokinetic targets and showed strong signs of efficacy in VABP patients with confirmed CRAB infection. In Part A of the study, the 14- and 28-day all-cause mortality (ACM) for BV100 was 12.5% and 25% respectively compared to the best available therapy control arm with 40% and 60% ACM respectively in patients with carbapenem resistant Acinetobacter infections. Similar trends in the test of cure and microbiological endpoints were seen. Full top line results from the trial are expected in early 2025 once analysis of the data has been finalized. BV100 is based on the newly identified mode of action for the active uptake of rifabutin into Acinetobacter baumannii-calcoaceticus complex and is being developed for hospital infections caused by Acinetobacter baumannii, including CRAB strains. There is a serious lack of effective and safe treatment options for CRAB infections and mortality rates in hospitals can be as high as 50%. CRAB has been designated a priority pathogen by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC). Due to the high unmet need and based on the current carbapenem resistance rates in Acinetobacter baumannii, we estimate in excess of 1 million hospital treated patients across the United States, Europe, the Middle East and China that could benefit from BV100. BioVersys is committed to advancing the clinical development of BV100 in a global Phase 3 registration trial, which it expects to initiate in the second half of 2025. To date, BV100 has been administered to over 230 subjects, at doses of up to 900 mg and over periods of up to 14 days in Phase 1 and 2 clinical trials and was considered generally safe and well tolerated. The strong clinical data package comprising the first in human studies, the Phase 2 in VABP patients, two drug-drug interaction studies, studies in renally and hepatic impaired patients and a bronchoalveolar study provides the foundation for progressing BV100 into the final clinical Phase. Dr. Glenn E. Dale, Chief Development Officer of BioVersys: "We are making great progress with our clinical evaluation of BV100, and we are very pleased to have met this latest milestone with the final visit of our last patient in the Phase 2 trial, with BV100 demonstrating strong signs of efficacy. We are now looking forward to finalizing the data ahead of our planned readout early next year, which we expect will build on the promising safety profile that BV100 demonstrated in Phase 1 and provide a further basis for our planned Phase 3 study." Prof. David Paterson: "BV100 could bring a much-needed solution for patients with an unmet need due to carbapenem resistant infections caused by Acinetobacter. Its safety profile and ease of use in an ICU setting, together with the strong signs of efficacy seen in the Phase 2 trial, make BV100 a compelling treatment option to be tested in a pivotal Phase 3 trial of VABP patients with confirmed CRAB infection.” In addition to the progress of BV100, the company's second clinical asset, alpibectir a first in class molecule for tuberculosis which is developed in partnership with GSK, completed a Phase 2a clinical trial earlier this year. Alpibectir delivered a proof of concept in patients and was also shown to be generally safe and well tolerated. Alpibectir will continue to be developed in close partnership with GSK. In May 2024, BioVersys announced the expansion of the strategic collaboration with GSK and the extension of the Series C round by CHF 14.7 million. This was complemented by the strategic investment of the investment firm Guangzhou Sino-Israel Bio-Industry Investment Fund 2 LLP (GIBF) of US$ 6 mio (approximately CHF 5.17 mio) announced in September 2024. This investment provides a strategic partnership to extend our development of BV100 to China as well as adding additional flexibility to our cash position. BV100 Phase 1 study in China is expected to start in 1H 2025 as part of our preparation for a global Phase 3 registration study. Dr. Marc Gitzinger, Chief Executive Officer and founder of BioVersys: "BioVersys has made significant progress during 2024 on multiple fronts. Our lead asset BV100 holds a lot of promise towards treating patients with very severe, drug-resistant bacterial infections, with limited or no treatment options. We are now looking forward to engaging with regulatory authorities to expedite the Phase 3 development of our lead asset in order to make this drug available as soon as possible to patients in need. Besides our clinical assets, BV100 and alpibectir, we are also very happy with the progress our pre-clinical pipeline in the form of BV200 and BV500, which is also moving forward. On the business side, we have extended our collaboration with GSK and we recently announced the investment from GIBF that will enable us to extend our clinical development to China. We remain committed to bringing new treatment options for drug resistant infections to patients in dire need and take great encouragement from the headway we are making towards that goal." About BV100BV100 is a novel formulation of rifabutin suitable for intravenous administration, with a recently discovered novel mode of action showing an active uptake of rifabutin into the Gram-negative bacterial species, Acinetobacter baumannii. For the first time, the lead candidate allows for the targeting of the RNA-polymerase enzyme in Gram-negative bacteria with a human-suitable dose. BV100 is being developed for the treatment of infections caused by Acinetobacter baumannii calcoaceticus complex (ABC), including Carbapenem-Resistant ABC (CRAB) in critically important indications of ventilator associated bacterial pneumonia (VABP), hospital-acquired bacterial pneumonia (HABP) and bloodstream infections (BSI). BV100 was granted QIDP Designation by the U.S. FDA in May 2019 for use in the treatment of VABP, HABP and BSI, making BV100 eligible for priority FDA review, Fast Track designation, and a five-year extension of market exclusivity upon approval of the first QIDP indication. About Acinetobacter baumanniiAcinetobacter baumannii calcoaceticus complex (ABC) are Gram-negative bacteria found in the environment (e.g., in soil and water) and an opportunistic pathogen in humans, typically infecting critically ill and immunocompromised patients, that can result in severe pneumonia and bloodstream infections in addition to affecting other parts of the body. ABC is considered a significant worldwide threat in the healthcare setting given its ability to survive for prolonged periods on surfaces, combined with its ability to develop or acquire resistance to standard of care antibiotics, e.g. carbapenems. Carbapenem-resistance as well as multidrug-resistance (MDR) rates for ABC are among the highest recorded for any bacteria in current times (The Lancet 2022; 399: 629–55). Incidence and resistance rates for ABC are trending upwards and COVID-19 has exacerbated this significantly. BioVersys forecasts the annual number of carbapenem-resistant A. baumannii infections in hospitals to have surpassed one million globally and due to the limited treatment options, such infections come with high (up to 50%) mortality rates. About alpibectirAlpibectir is a first in class small molecule acting on a transcriptional regulator protein in Mycobacterium tuberculosis (TB). Alpibectir rejuvenates the existing drug ethionamide (Eto), by both potentiating the activity of Eto and restoring the antibacterial activity of Eto towards Eto-resistant TB. The resulting fast bactericidal effect of alpibectir/Eto at low and safe doses offers the potential to replace Isoniazid (INH) in future TB drug regimens for MDR/XDR-TB but also in TB-meningitis patients or INH-mono-resistant patients. Alpibectir is being co-developed with our long-term partner GSK and the molecule originates form a very successful public-private partnership with the Pasteur Institute Lille and the University of Lille. The program was supported by several grants from the Wellcome Trust, EU IMI joint undertaking and EDCTP. Alpibectir in combination with Eto has the orphan drug designation (ODD) and QIDP designation from the US FDA. About tuberculosis (TB) Tuberculosis (TB) is one of the leading causes of death worldwide. Its causative agent is the bacterial pathogen Mycobacterium tuberculosis (Mtb). Worldwide, an estimated 10.6 million people developed TB in 2022 and an estimated 1.30 million died from TB. The WHO estimates that there were 410’000 new cases with resistance to rifampicin – the most effective first-line drug – most of them were multi-drug resistant (MDR). MDR-TB remains a public health crisis and a health security threat. Worldwide, only 63% of MDR-TB patients are currently successfully treated.1 In the modern world of global travel, and ease with which infections spread, it is very worrying to note that two-thirds of the global total of TB cases was in eight countries: India (27%), Indonesia (10%), China (7.1%), the Philippines (7.0%), Pakistan (5.7%), Nigeria (4.5%), Bangladesh (3.6%) and the Democratic Republic of the Congo (3.0%). Furthermore, 3.3% of all new and 17% of reoccurring TB cases were MDR/RR-TB. About BioVersysBioVersys AG is a multi-asset, clinical stage biopharmaceutical company focused on identifying, developing and commercializing novel antibacterial products for serious life-threatening infections caused by multi-drug resistant (“MDR”) bacteria. Derived from the company’s two internal technology platforms (TRIC and Ansamycin Chemistry), candidates are designed and developed to overcome resistance mechanisms, block virulence production and directly affect the pathogenesis of harmful bacteria towards the identification of new treatment options in the antimicrobial and microbiome fields. This enables BioVersys to address the high unmet medical need for new treatments against life-threatening resistant bacterial infections and bacteria-exacerbated chronic inflammatory microbiome disorders. The company’s most advanced research and development programs address nosocomial infections of Acinetobacter baumannii (BV100, Phase 2), and tuberculosis (alpibectir, Phase 2a, in collaboration with GlaxoSmithKline (GSK) and a consortium of the University of Lille, France). BioVersys is located in the biotech hub of Basel, Switzerland. BioVersys contact Sylvia Mundt, Tel. +41 61 633 22 50; Mail: IR@bioversys.com www.bioversys.com https://twitter.com/Bioversyshttps://www.linkedin.com/company/bioversys-ag 1 Global Tuberculosis Report 2023 WHO

Research achievements enabled by a combination of advanced AI platforms, research capabilities, and drug discovery technologies SEOUL, South Korea, April 4, 2023 /PRNewswire/ -- Standigm, a company using artificial intelligence (AI) technology for drug discovery and development, and Korean non profit research institute Institut Pasteur Korea announced that they have jointly developed new lead compounds effective in treating resistant tuberculosis (TB). The two organizations conducted a technology acceleration grant project supported by the Right Foundation from 2021 to 2022. They achieved encouraging results by combining their core competencies of artificial intelligence (AI) platforms, infectious disease research capabilities and drug discovery technologies. This breakthrough demonstrates that AI technology can effectively address unmet medical needs for low and middle-income countries that tend to have higher than normal rates of resistant TB. Standigm, the project's lead organization, utilized its drug design artificial intelligence platform, Standigm BEST™, with a scaffold-based molecular generation model and a deep learning prediction model that learned the features of three-dimensional molecular structures. The collaborating institute, Institut Pasteur Korea, utilized its drug discovery platform in a biosafety level 3 laboratory to evaluate the efficacy of new compounds against drug-sensitive and multi-drug-resistant TB (MDR-TB)/extensively drug-resistant TB (XDR-TB) and incorporated the compound information and efficacy evaluation results into Standigm BEST™. In particular, the researchers designed and synthesized various new compounds based on the compounds' structure-activity relationship (SAR) analysis and continuously provided high-quality anti-TB efficacy evaluation results, which Standigm utilized to enhance its AI platform. The two organizations have successfully identified lead compounds for resistant TB through this AI-based drug discovery research collaboration. Standigm and Institut Pasteur Korea have been collaborating on TB drug discovery since 2020. On September 29, 2021, they signed a memorandum of understanding to develop AI-based infectious disease drugs to accelerate their joint research. "There is no vaccination that can guarantee complete protection against TB," said Dr. Sangok Song, co-founder and chief research officer of Standigm. "The BCG vaccination is the only vaccination against TB, and even if antibodies are developed, the lifetime protection rate is only 19% to 27%. We believe that artificial intelligence technology will play an important role in discovering new, low-cost, and effective treatments for TB and other diseases in low- and middle-income countries." TB often spreads in enclosed, poorly ventilated, multi-use facilities where many people stay for long periods, but it is one of the most urgently needed vaccines and treatments in medically underserved countries because of its high prevalence in socio-economically disadvantaged populations and the resistance issues from prolonged use of currently available TB drugs. "Through this collaboration with Standigm, we have presented a complementary and advanced drug discovery research model that combines the accumulated know-how of our researchers with cutting-edge technologies and next-generation artificial intelligence, said Dr. Byung-Kwon Lim, director of the Institut Pasteur Korea." We will accelerate the subsequent development of new drug candidates derived from this research collaboration and contribute to the global effort to end TB." About Institut Pasteur Korea Institut Pasteur Korea is a non-profit research organization that focuses on infectious disease research and development with the goal of improving global public health, and was founded in 2004 based on Korea-France science and technology cooperation. Utilizing its core research capabilities, including innovative screening platforms, the institute is leading the way in understanding the mechanisms of development and accelerating the development of new drugs for emerging infectious diseases such as MERS, Zika, and COVID-19, as well as diseases that threaten humanity today, such as viral hepatitis, tuberculosis, antibiotic-resistant bacterial infections, neglected diseases, and cancers. As a member of the Pasteur Network of 33 laboratories in 25 countries across five continents, the institute plays a key role in leading early drug discovery research within the network. By providing original technologies and promoting multidisciplinary global projects that link Korean and international biomedical sciences, the institute contributes to Korea's scientific, knowledge, and technological resources and helps prepare for and respond to global infectious diseases. () About Standigm Standigm was founded in 2015 to revolutionize drug discovery with artificial intelligence (AI) technology. It's AI technologies cover the entire drug discovery lifecycle (target discovery, hit identification, hit-to-lead, and lead optimization) to continuously develop first-in-class and best-in-class drug discovery projects. Standigm's leading AI platforms include Standigm ASK™, which identifies novel and promising disease targets, and Standigm BEST™, which generates novel chemical structures. By combining the Standigm ASK™ and Standigm BEST™ platforms, Standigm has completed Standigm Magic, a workflow AI that can be completed in an average of seven months from target discovery to lead compound series. Standigm works on various first-in-class and best-in-class drug candidate development projects in collaboration with leading domestic and international pharmaceutical companies and research institutes. For more information about the company, please visit . Press Inquiries Kim Ji-Eun, Head of External Relations, Institut Pasteur Korea [email protected] +82-31-8018-8041 Kyungmoon Kim, Head of Operations at Standigm [email protected] +82-2-501-8118 Gabriella Perez-Silva, PR for Standigm [email protected] 714-875-6424 SOURCE Standigm

GSK plc (LSE/NYSE: GSK) announced positive results from a Phase IIa study demonstrating that GSK3036656, a first-in-class investigational antitubercular agent, was well tolerated and showed early bactericidal activity with a low, once-daily oral dose after 14 days of treatment in participants with drug-susceptible pulmonary tuberculosis. These results demonstrate the potential for GSK3036656 to be a component of simpler treatment regimens in the future which could help address the TB epidemic. A selection of these data was presented in an oral late breaker session at the Union World Conference on Lung Health on 11 November. The TB epidemic is one of the most pressing public health challenges: over the last decade TB was the leading cause of death due to an infectious disease globally, causing approximately 1.5 million deaths annually. Earlier this year, GSK made a commitment to invest 1bn over the next decade to accelerate R&D on infectious diseases, including TB, that disproportionately impact lower-income countries. David Barros-Aguirre, Head of Global Health Medicines R&D, GSK, said: Existing treatments for TB can be complicated, of long duration and have serious side effects which significantly impact the lives of patients with TB around the world. Todays encouraging data provide a good foundation from which to investigate GSK3036656 in different combinations in Phase IIb/c studies, with the aim of contributing to shorter, simpler and better tolerated treatment regimens for patients with TB. Anti-mycobacterial activity was demonstrated both in terms of reducing the number of viable TB cells which are able to multiply (colony forming units - CFU), and an increase in the time to detect bacterial growth in culture (time to positivity - TTP). In addition, PET CT imaging of the lungs showed a reduction in TB disease over 14 days in all participants taking GSK3036656 30mg. Prof. Andreas Diacon, Chief Scientific Officer, TASK, said The data show that GSK3036656 is a potential new antibiotic for tuberculosis that can be used in low, once daily doses. This can help reduce side effects and is an important characteristic of any new TB drug. GSK3036656 is of a completely new class of antibiotics which makes the chance of drug resistance very low. I am looking forward to evaluating GSK3036656 in shorter and better tolerated combinations with other new agents to bring about a new era of tuberculosis treatment. The investigational antitubercular agent will be tested in Phase IIb/c studies in different drug regimens to determine the appropriate partner agents to complement its anti-TB action and the optimal regimen durations. The aim is to identify a GSK3036656-containing regimen with sufficient tolerability, efficacy and short enough duration to progress to Phase III with a high probability of success. These innovative studies will be conducted in collaboration with industry and academic partners and will be co-funded by the European Unions IMI2 programme. GSK works in partnership to develop new TB medicines and vaccines, focusing efforts on research and early development, and partnering with world-leading organisations and funders on late development, manufacturing and access to maximise impact for patients. About the trial Study 201214 was a single centre, Phase IIa, open-label study to investigate the early bactericidal activity (EBA), safety, and tolerability of GSK3036656 in participants with drug-sensitive pulmonary tuberculosis. The study had four cohorts, with 12 to 20 participants in each cohort. The participants were randomized in a 3:1 ratio to receive either GSK3036656 at doses 1 mg, 5 mg, 15 mg, and 30 mg or standard-of-care (SoC) regimen for drug sensitive TB (i.e. Rifafour e-275 or equivalent generic alternative), respectively. The primary endpoint was to determine the rate of change in log10colony forming units (CFU) per mL direct respiratory sputum samples over the period baseline to Day 14 (EBA CFU0-14). A key secondary outcome was the rate of change in time to sputum culture positivity (EBA TTP) over the time period baseline to Day 14 (EBA TTP0-14). GSK3036656 doses of 5 mg to 30 mg showed bactericidal activity as evidenced by both endpoints after 14 days. GSK3036656 30 mg had the highest bactericidal activity: A decline in CFU of -0.138 log10CFU/mL (95% CI: -0.167, -0.109) An increase in TTP of 0.22 log10CFU/mL (95% CI: 0.019, 0.024) GSK3036656 was generally well tolerated with no serious adverse events (SAEs) identified in the study. The percentage of participants reported with adverse events was similar between SoC and GSK3036656 and no large differences between GSK3036656 and SoC or GSK3036656 dose related trends were observed. The trial was conducted as part of the anTBiotic project, a consortium which consists of GSK Global Health Medicines R&D (Spain), the University of Troms (Norway), Forschungszentrum Borstel (Germany), the University of Cape Town (South Africa) and the TASK Foundation (South Africa). The project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 733079. About tuberculosis Tuberculosis is the leading cause of death due to an infectious disease globally, other than COVID-19, causing approximately 1.5 million deaths annually. It is caused by a bacterium called Mycobacterium tuberculosis and mainly affects the lungs, although it can affect any part of the body. Current treatment options are often inadequate for patients with TB: long and complicated courses of treatment with serious side effects mean many people struggle to adhere to the full course. As a result, the bacteria are developing resistance to existing medicines making treatment less effective. New treatments are urgently needed: the ambition is to find shorter, simpler and better tolerated treatments for TB to reduce the burden on patients and increase adherence to treatment thereby preventing further selection of resistant strains. However, developing new TB treatment regimens is challenging as they involve a combination of more than three different compounds often from multiple organisations. A collaborative approach is required to ensure researchers can access the compounds at an early stage of development to understand how they work in combination. About GSK3036656 GSK3036656 is a first-in-class investigational antitubercular agent which is being developed for the treatment of tuberculosis as part of a future combination regimen. It suppresses protein synthesis in Mycobacterium tuberculosis (Mtb) by inhibiting the enzyme leucyl t-RNA synthetase (LeuRS). GSK3036656 has demonstrated activity not only against laboratory strains of Mtb, but also against a selection of Drug Sensitive TB (DS-TB), Multi Drug Resistant TB (MDR-TB) and Extensively Drug Resistant TB (XDR-TB) clinical isolates. Animal models of TB infection have shown that GSK3036656 is potent in vivo. The compound is the result of a collaboration between GSK and Anacor Pharmaceuticals which led to the identification of GSK3036656 as a selective anti-mycobacterial agent that is inactive against other respiratory pathogens. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together.