A Phase 2 Trial to Evaluate the EBA, Safety and Tolerability of Ethionamide Alone and in Combination With BVL-GSK098 Administered Orally to Adults With Newly Diagnosed, Rifampicin- and Isoniazid-Susceptible Pulmonary Tuberculosis

To evaluate the 7-day early bactericidal activity (EBA), pharmacokinetics (PK), safety and tolerability of ethionamide (Eto) with or without BVL-GSK098 in participants with rifampicin- and isoniazid-susceptible pulmonary TB.

Start Date06 Dec 2022

Sponsor / Collaborator

TASK Applied Science

NCT04654143 / CompletedPhase 1

A Phase I, Double-blind, Randomized, Placebo-controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics and Food Effect of BVL-GSK098 Administered as Single and Multiple Oral Doses to Healthy Volunteers

This is a phase I single-center, double-blind, randomized, placebo-controlled study to investigate the safety, tolerability and pharmacokinetics and food effect of BVL-GSK098 administered as single and multiple oral doses to healthy volunteers

Start Date02 Dec 2020

Sponsor / Collaborator

BioVersys AG

100 Clinical Results associated with Alpibectir

100 Translational Medicine associated with Alpibectir

100 Patents (Medical) associated with Alpibectir

Literatures (Medical) associated with Alpibectir

01 Aug 2024·DRUG METABOLISM AND DISPOSITION

Alpibectir: Early Qualitative and Quantitative Metabolic Profiling from a First-Time-in-Human Study by Combining¹⁹F-NMR (Nuclear Magnetic Resonance),¹H-NMR, and High-Resolution Mass Spectrometric Analyses

Article

Author: Pieren, Michel ; Boyle, Gary W ; Weston, Daniel J ; Thomas, Steve

Alpibectir (also known as BVL-GSK098 and GSK3729098) is a new chemical entity (NCE) with a novel mechanism for the treatment of tuberculosis. The disposition of alpibectir was determined in subjects from a first-time-in-human trial after a single oral dose of 40 mg and after 7 days repeat dosing at 30 mg. Here we present a combined approach of ¹⁹F-NMR (nuclear magnetic resonance), ¹H-NMR, and high-resolution mass spectrometry (HRMS) to confidently determine the human metabolic fate of alpibectir. Utilizing multiple sites of fluorination in the molecule, it was possible to fractionate human urine and plasma to confidently detect and quantify the metabolite responses using ¹⁹F-NMR. Qualitative detection and structural characterization of F-containing NMR fractions were performed using complementary high-resolution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) analyses to further add confidence to the metabolite responses in these fractions. Subsequent ¹H-NMR then provided unequivocal standard-free structural confirmation for key metabolites, which would not be possible with conventional radioactivity detection and LC-MS/MS techniques. Alpibectir was shown to undergo extensive hydrolysis of the central amide moiety, where the resultant N-dealkylated amine and trifluorobutyric acid products were detected initially by unbiased ¹⁹F-NMR detection along with major downstream biotransformations to form a carbamoyl glucuronide conjugate and trifluoroacetic acid, respectively. Parallel UHPLC-MS/MS analyses provided confirmatory or additional structural characterization only where relevant. These concerted data allowed for the qualitative metabolic profile and quantitative determination of drug-related material (DRM) in urine and plasma, along with the percentage of dose excreted in urine, to be reported in a comprehensive, efficient, and data-led manner. SIGNIFICANCE STATEMENT: Combining the selectivity of ¹⁹F-NMR (nuclear magnetic resonance) for unfractionated samples as first-intent, data-led sample fractionation prior to ¹⁹F-NMR and structure-rich ¹H-NMR detection, along with the sensitivity of high-resolution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS), a novel alternative for time-efficient detection and quantification of drug-related material (DRM) in human without use of radiolabeled drug is reported. This allowed more complete data rationalization of human metabolism, permitting early risk assessment and progression of the development of antitubercular agent, alpibectir.

03 Jun 2024·The Journal of antimicrobial chemotherapy

First-in-human study of alpibectir (BVL-GSK098), a novel potent anti-TB drug

Article

Author: Davy, Maria ; Martínez-Martínez, María S ; Husband, Lisa ; Pefani, Eleni ; Antonijoan Arbós, Rosa María ; Dale, Glenn E ; Vlasakakis, Georgios ; Penman, Sophie L ; Davila, Myriam ; Abáigar Gutiérrez-Solana, Ana ; Boyle, Gary W ; Zeitlinger, Markus ; Gitzinger, Marc ; Remuiñán, Modesto J ; Mazarro, Dolores Ochoa ; Pieren, Michel

Abstract:

Background:

The clinical candidate alpibectir augments the activity of, and overcomes resistance to, the anti-TB drug ethionamide in vitro and in vivo.

Objectives:

A Phase 1, double-blind, randomized, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics (PK) and food effect of alpibectir administered as single and multiple oral doses in healthy volunteers (NCT04654143).

Methods:

Eighty participants were randomized. In single ascending dose (SAD), a total of six dose levels of alpibectir (0.5 to 40 mg) were tested under fasted and fed (10 mg) conditions as single daily doses in sequential cohorts. In multiple ascending dose (MAD), repeat doses (5 to 30 mg) were administered once daily for 7 days in three sequential cohorts.

Results:

No serious adverse event was reported. Thirteen participants across groups experienced a total of 13 mild or moderate treatment-emergent adverse events. Alpibectir showed rapid absorption after single dose (mean Tmax range of 0.88 to 1.53 h). Food affected the PK of alpibectir, characterized by a slower absorption (mean Tmax 3.87 h), a lower Cmax (−17.7%) and increased AUC0–t (+19.6%) compared with the fasted condition. Following repeat dosing, dose proportionality was shown for both Cmax and AUC0–tau. Accumulation of alpibectir was observed across all doses, with a more profound effect on AUC during a dosing interval (AUC0–tau) compared with Cmax (1.8- and 1.3-fold on average), respectively. Steady state was considered to have been achieved by Day 7 of dosing.

Conclusions:

Alpibectir was generally well tolerated, and no clinically relevant safety findings were identified in the participants treated during SAD or MAD. The PK is dose-proportional and affected by food.

01 Nov 2018·European journal of medicinal chemistryQ1 · MEDICINE

Efficient analoging around ethionamide to explore thioamides bioactivation pathways triggered by boosters in Mycobacterium tuberculosis

Q1 · MEDICINE

Article

Author: Sournia-Saquet, Alix ; Baulard, Alain R ; Frita, Rosangela ; Probst, Nicolas ; Prieri, Marion ; Déprez, Benoit ; Willand, Nicolas ; Bourotte, Marilyne

Ethionamide is a key antibiotic prodrug of the second-line chemotherapy regimen to treat tuberculosis. It targets the biosynthesis of mycolic acids thanks to a mycobacterial bioactivation carried out by the Baeyer-Villiger monooxygenase EthA, under the control of a transcriptional repressor called EthR. Recently, the drug-like molecule SMARt-420, which triggers a new transcriptional regulator called EthR2, allowed the derepression a cryptic alternative bioactivation pathway of ethionamide. In order to study the bioactivation of a collection of thioisonicotinamides through the two bioactivation pathways, we developed a new two-step chemical pathway that led to the efficient synthesis of eighteen ethionamide analogues. Measurements of the antimycobacterial activity of these derivatives, used alone and in combination with boosters BDM41906 or SMARt-420, suggest that the two different bioactivation pathways proceed via the same mechanism, which implies the formation of similar metabolites. In addition, an electrochemical study of the aliphatic thioisonicotinamide analogues was undertaken to see whether their oxidation potential correlates with their antitubercular activity measured in the presence or in the absence of the two boosters.

News (Medical) associated with Alpibectir

26 Oct 2024

·www.globenewswire.com

BioVersys Joins EU-Funded RespiriNTM Programme to Accelerate Development of Its Broad-Spectrum Drug Candidates Against NTM Pulmonary Diseases

Oct. 22, 2024 (GLOBE NEWSWIRE) -- RespiriNTM Programme allows BioVersys’ NTM project to access up to €2 million of non-dilutive funding BioVersys taps into key expertise of the established RespiriNTM consortium members and will lead development of its candidates through preclinical and clinical studies BioVersys’ NTM candidates are derived from the company’s proprietary Ansamycin Chemistry platform and are being developed to address difficult-to-treat Mycobacterium avium complex (MAC) and Mycobacterium abscessus subspecies (MAB) infections 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 that it has joined the EU-funded RespiriNTM programme, an 8-year journey exploring multiple approaches to determine new targets for anti-mycobacterial compounds, define and optimize novel inhibitors and move these through the process of hit-to-lead up until the First-in-Human trials. BioVersys’ in-house non-tubercular mycobacteria (NTM) project will have access to up to approximately €2 million in non-dilutive funding from the original IMI2 RespiriNTM grant of approximately €5.7 million, and to key capabilities of established consortium partners to develop novel candidates to address NTM pulmonary disease (NTM-PD). NTM-PD is estimated to affect more than 86,000 people in the US according to the American Lung Association and antimicrobial resistance (AMR) is a major global health threat with currently available therapeutics becoming more and more obsolete due to AMR.1 This is of greatest concern when addressing NTM-PD, as chronic antibiotic treatments of 12-24 months required for these infections often lead to the development of antibiotic resistance. Due to the lack of effective treatment options, current cure rates for NTM-PD are as low as 30-50%.2 Particularly vulnerable to NTM-PD are people who suffer from structural airway diseases such as cystic fibrosis, COPD and bronchiectasis. BioVersys’ NTM program is derived from the company’s proprietary Ansamycin Chemistry platform. The BioVersys’ research team is developing a novel and highly potent broad-spectrum anti-NTM ansamycin, suitable for oral or inhalation therapy that is devoid of cross-resistance with other therapeutic classes. Since NTM-PD patients are often on multi-drug regimens, the company focuses on developing molecules that do not show any significant potential for drug-drug interactions. Meindert H. Lamers, Associate Professor, Leiden University Medical Center & RespiriNTM Project Coordinator: "Working together with BioVersys on the RespiriNTM project is a unique opportunity. Their powerful ansamycin class of inhibitors have the potential to provide an effective and highly needed treatment option for NTM infections, which fits perfectly with the aims of the RespiriNTM project. BioVersys’ strong drive to deliver a novel NTM antibiotic has invigorated the RespiriNTM project. Our collaboration to date has been very stimulating and I am very much looking forward to deepening our collaboration with BioVersys over the coming years." Dr. Sergio Lociuro, Chief Scientific Officer of BioVersys: “Following on from the recent successes of TRIC-TB, we are very pleased to have the opportunity to join a second IMI2 JU funded programme, which is tackling another area of high unmet medical need. RespiriNTM is a strong consortium of many expert partners with valuable experience in the field of antimicrobial resistance. We aim to develop our broad-spectrum NTM candidates into effective treatments against these difficult to treat pulmonary diseases to positively impact patients' lives.” Mycobacterium avium complex (MAC) and Mycobacterium abscessus subspecies (MAB) cause several hundreds of thousands of infections worldwide each year. Unlike the well know related species M. tuberculosis, there are currently limited and poor treatment options to address these pathogens with significant levels of relapse and unacceptably high mortality rates, approaching 45%.3 Therefore, there is an urgent need for antibiotics that can treat the debilitating diseases that are caused by the Non-Tuberculous Mycobacteria (NTM), M. avium complex and M. abscessus. The RespiriNTM project aims to develop novel antibiotics that target the RNA transcription machinery that is required for protein production in the cell. Through this work we aim to develop desperately needed antibiotics that work against M. avium and M. abscessus that form an increasing threat to global health. RespiriNTM is part of the IMI AMR Accelerator Programme. Non-tuberculous Mycobacteria (NTM) are ubiquitous environmental bacteria whose common clinical manifestation is pulmonary disease (NTM-PD) caused most frequently by Mycobacterium avium complex (MAC) and Mycobacterium abscessus subspecies (MAB).4 NTM-PD affects approximately 250,000 people per year, predominantly in North America and Asia.4 Treatment of NTM infections is challenging due to variable intrinsic bacterial susceptibility, acquired resistance to commonly used antimicrobial agents, length of therapy (at least 12 months) and adverse effects associated with current treatment options. Macrolide-based, triple drug regimens, plus aminoglycosides for chronic/relapsing infections5 are considered only moderately effective for treating MAC, whereas no therapy of predictable efficacy exists for the treatment of M. abscessus, a pathogen associated with up to 50% mortality.6 People with predisposed conditions, including cystic fibrosis (CF), other lung diseases and immune-compromised patients are more easily colonised. Alarmingly, the incidence of NTM infections among people living with CF has increased from 3.3% to 22.6%, with MAB becoming a very prominent pathogen.7 Statements or views expressed in this release are of those of the respective organizations or persons and the IMI2 JU is not responsible for any use of the information contained herein. The RespiriNTM project has received funding from the Innovative Health Initiative 2 Joint Undertaking (JU) under grant agreement No 853932. This Joined Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The Innovative Medicines Initiative (IMI) IMI is a partnership between the European Union and the European pharmaceutical industry, represented by the European Federation of Pharmaceutical Industries and Associations (EFPIA). It was set up to improve health by speeding up the development of, and patient access to, the next generation of medicines, particularly in areas where there is an unmet medical or social need. It works by facilitating collaboration between the key players involved in healthcare research, including universities, pharmaceutical companies, other companies active in healthcare research, small and medium-sized enterprises (SMEs), patient organisations, and medicines regulators. This approach has proven highly successful, and IMI projects are delivering exciting results that are helping to advance the development of urgently-needed new treatments in diverse areas. IMI projects are now managed by the Innovative Health Initiative (IHI), which builds on the successes of IMI and is a cross-sectoral public-private partnership involving a wider range of health industries. BioVersys 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. 1 Lancet, Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis, VOLUME 399, ISSUE 10325, P629-655, FEBRUARY 12, 2022 2 Wang et al., 2022; Novosad et al., 2017; Lee et al., 2021; Mourad et al., 2021 3 The Impact of Nontuberculous Mycobacteria Species on Mortality in Patients with Nontuberculous Mycobacterial Lung Disease. Wang et al, 2022, Frontiers in Microbiology. doi:10.3389/fmicb.2022.909274 4 Hamed KA & G. Tillotson “A narrative review of nontuberculous mycobacterial pulmonary disease: microbiology, epidemiology, diagnosis, and management challenges” Ex. Rev. Resp. Med. (2023), 17 (11), 973 - 988 https://doi.org/10.1080/17476348.2023.2283135 5 Daley CL et al. “Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline” Eur. Resp. J. (2020), 56, 2000535; https://doi.org/10.1183/13993003.00535-2020; Griffith DE et al. “An Official ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases” Am. J. Respir. Crit. Care Med. (2007), 175, 367–416; https://doi.org/10.1164/rccm.200604-571ST 6 Jhun BW et al. “Prognostic factors associated with long-term mortality in 1445 patients with nontuberculous mycobacterial pulmonary disease: a 15-year follow-up study” Eur. Resp. J. (2020), 55, 1900798; https://doi.org/10.1183/13993003.00798-2019 7 Degiacomi G. et al. “Mycobacterium abscessus, an Emerging and Worrisome Pathogen among Cystic Fibrosis Patients” Int. J. Mol. Sci. (2019), 20, 5868; doi: 10.3390/ijms20235868 The content above comes from the network. if any infringement, please contact us to modify.

Financing

16 Oct 2024

·www.globenewswire.com

Bioversys Announces Last Patient Last Visit in BV100 Phase 2 Clinical Trial in Ventilator Associated Bacterial Pneumonia (VABP) and Provides a Business Update

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

Phase 2Fast TrackPhase 3Orphan DrugClinical Result

24 Sep 2024

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Nature Reviews Highlights Significant Successes of Antibiotic Collaboration and Calls for Sustainable R&D Funding Schemes

BASEL, Switzerland, Sept. 24, 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, in collaboration with its partners in the AMR Accelerator programme, call for sustainable investment in antimicrobial research and development. Antibiotic resistance is a threat to modern healthcare. Nine European research projects have published in Nature Reviews Drug Discovery an article emphasizing the need to maintain expertise and capability for developing new treatments for infectious diseases, such as those exemplified in the successful European Union’s IMI2 funded TRIC-TB programme. TRIC-TB, successfully reached key milestones, delivering a Phase 2-ready tuberculosis clinical candidate, alpibectir, that is being jointly developed by BioVersys and GSK. The funding that BioVersys as the product developer received, enabled the translation of this exciting new TB therapy into Phase 2a in patients in South Africa. This program now seeks funding to address deadly TB meningitis infections, which predominantly and severely affect children. Together, the nine projects of the AMR Accelerator call on government leaders, the private sector and other stakeholders to invest in the development of new antibiotics and research on antimicrobial resistance (AMR), to secure a sustainable future for large-scale efforts. Dr. Marc Gitzinger, Chief Executive Officer and founder of BioVersys: “The continued innovation for developing new antibiotics fighting AMR is crucial for modern medicine, in high- and low-income countries. There is simply no way around appropriate funding and market incentives for new antibiotics. Efforts led by the European Union, such as the IMI2 programme should continue and be expanded. However, even more important is to act on adequate reimbursement mechanisms for antibiotics, which are life-saving medicines. We hope that successful projects like TRIC-TB demonstrate the success that adequate funding can deliver.” Dr. David Barros-Aguirre, VP and Head of Global Health Medicines R&D Unit, Global Health R&D, GSK: “Now more than ever, there is a need for sustainable funding mechanisms to combat antimicrobial resistance (AMR), which disproportionately impacts people living in lower income countries. We have witnessed the positive impact of pooled procurement mechanisms in supporting equitable access to new vaccines, building resilience into supply chains and contributing to the development of healthy markets. Yet, these mechanisms do not currently exist for many AMR innovative treatment opportunities.” Antimicrobial resistance is recognised as one of the greatest global challenges of our time, undermining healthcare systems that rely heavily on antibiotics to prevent and treat infections. The need for new antibiotics is well-recognized, and on 26 September, the United Nations General Assembly will spotlight this issue in a high-level meeting on AMR. However, the low return on investment in this area has caused many large pharmaceutical companies to leave the field. This has led to a decline in the rate of development of new drugs and therapies for bacterial infections. The broad scope sets the AMR Accelerator apart from other large-scale efforts: the projects have received funding from the European Commission via the Innovative Medicines Initiative (IMI) and pharmaceutical companies that are members of EFPIA. With a total budget of €479 million, the AMR Accelerator has progressed 44 antibacterial programmes over the past 5 years. So far, the effort has resulted in 16 preclinical and clinical candidates, two completed Phase 1 studies, and five ongoing Phase 1 and 2 studies. The continuing success of the AMR Accelerator demonstrates the value of public-private partnerships, replenishing the antibiotics pipeline and providing tools and infrastructure for the global research community. “In TRIC-TB, we combined an agile, fast-moving SME (BioVersys) with the experience and capabilities of a big industry partner (GSK), to develop an anti-TB drug with an entirely new concept. The small consortium size allowed us to move with speed and agility. In 3½ years TRIC-TB completed CTA-enabling and Phase 1 studies allowing the start of a Phase 2a trial despite the impact of the COVID-19 pandemic”, says Michel Pieren, the TRIC-TB project coordinator, from BioVersys. The AMR Accelerator has created critical mass and synergies that have allowed the transfer of assets, knowledge, and expertise between projects. The results are tangible: better and more efficient science, a strengthening of the antibiotic pipeline, and a legacy of research infrastructures that can support the global fight against antibiotic resistance: these include, standardized infection models, non-clinical assays, clinical trial protocols and regulatory compliant processes. However, the key challenge for all nine projects is to ensure the long-term sustainability of assets, infrastructures and expertise. Which in turn requires a commitment from governments and the pharmaceutical industry to long-term investment in antimicrobial research and antibiotics development. Read the article: https://www.nature.com/articles/d41573-024-00138-9 and DOI: 10.1038/d41573-024-00138-9 About the AMR AcceleratorAMR Accelerator programme was launched in 2019, with the aim to accelerate the development of medicines for patients suffering from infections with drug-resistant Mycobacterium tuberculosis, Nontuberculous mycobacteria (NTM), and Gram-negative bacteria, and build capability for antibiotics research and development. The programme is funded by the Innovative Medicines Initiative (IMI). The AMR Accelerator programme includes nine projects: AB-Direct, COMBINE, ERA4TB, GNA NOW, PriMAVeRa, RespiriNTM & RespiriTB, TRIC-TB, and UNITE4TB. Together, the projects have a €479 million budget. The 98 partners represent key stakeholders from academia, industry, small- and medium-sized companies, patient organisations, regulators, and Health Technology Assessment. IMI projects are public-private partnerships, funded in equal parts by the European Union’s Horizon 2020-programme and the pharmaceutical companies that are members of EFPIA. More information: www.amr-accelerator.eu AMR Accelerator portfolio: https://amr-accelerator.eu/amr-accelerator-project-portfolio/ The AMR Accelerator has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Grant Agreements No 853967 I 853989 I 853979 I 853932 I 853800 I 853903 I 853976 I 101007873 I 101034420. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. ERA4TB receives additional support from Global Alliance for TB Drug Development, Bill & Melinda Gates Foundation and University of Dundee. UNITE4TB receives additional support from Deutsches Zentrum für Infektionsforschung e. V. (DZIF), and Ludwig-Maximilians-Universität München (LMU). EFPIA/AP contribute to 50% of funding, whereas the contribution of DZIF and the LMU University Hospital Munich has been granted by the German Federal Ministry of Education and Research. Disclaimer: This text reflects the author’s view. Neither IMI nor the European Union, EFPIA or any other third parties are responsible for any use that may be made of the information contained herein. The COMBINE project has a coordinating role in the AMR Accelerator programme. For more information, please contact Anders Karlén, Professor of Computer-Aided Drug Design, Uppsala University & project coordinator, COMBINE. E-mail: anders.karlen@uu.se or Marie Olliver, Alliance manager COMBINE, Uppsala University. E-mail: marie.olliver@uu.se. About TRIC-TBTRIC-TB successfully completed the Phase 1 study with alpibectir (BVL-GSK098), a small molecule potentiating the activity of ethionamide. It is hoped alpibectir would allow lower doses of ethionamide thus minimizing dose-dependent side effects and, it is hoped, improving patient compliance. In laboratory tests, the combination of alpibectir/ethionamide (AlpE) is rapidly bactericidal, overcomes MDR and Eto-resistance, and shows the potential to become an important building block in novel regimens in TB endemic countries. AlpE is currently tested in a Phase 2a proof-of-concept study (NCT05473195). TRIC-TB has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Grant Agreement No 853800. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA companies’ in-kind contribution. For more information, please contact Michel Pieren, Clinical Program Team Leader, BioVersys & TRIC-TB project coordinator. E-mail: michel.pieren@bioversys.com About GSKGSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com 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, Executive Assistant to CEO, Tel. +41 61 633 22 50 ; Mail : IR@bioversys.com Website: www.bioversys.com https://twitter.com/Bioversyshttps://www.linkedin.com/company/bioversys-ag

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Indication	Highest Phase	Country/Location	Organization	Date
Pulmonary Tuberculosis	Phase 2	ZA	TASK Applied Science	06 Dec 2022
Tuberculosis	Phase 2	ZA	BioVersys AG	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04654143 (Pubmed) Manual	Phase 1	-	80	Alpibectir 0.5 mg	ivxzxugfqi(tnuwkyptgf) = No serious adverse event was reported. Thirteen participants across groups experienced a total of 13 mild or moderate treatment-emergent adverse events lroogvzoky (klsfsrsmdy ) View more	Positive	24 Apr 2024
				Alpibectir 40 mg

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