Bioversys: Last patient in clinical trial on ventilator associated bacterial pneumonia

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 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 BV100
BV100 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 baumannii
Acinetobacter 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 alpibectir
Alpibectir 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.

References
[1] Global Tuberculosis Report 2023 WHO