Periodic Reporting for period 2 - sbli-ant3310 (A novel combination treatment effective against all multidrug-resistant pathogens deemed as a critical priority by the WHO)
Berichtszeitraum: 2024-03-01 bis 2025-03-31
Antibiotic resistance is a growing global public health crisis, with major implications:
-Epidemiological: projected 10 million deaths annually by 2050.
-Medical: jeopardizes standard treatments like chemotherapy, surgery, and transplants.
-Economic: estimated cost to healthcare systems of 100,000 billion dollars/year.
In 2019, 1.27 million deaths were directly caused by antibiotic resistance, with 4.95 million associated(1). The WHO's 2022 report(2) highlighted the lack of sufficient antibacterial agents in the development pipeline and the challenges of bringing effective solutions to market. Efforts from the EU and other bodies aim to incentivize innovation and access to such therapies.
In this context, ANTABIO's mission is to develop innovative solutions to treat severe infections caused by antibiotic-resistant gram-negative bacteria, recognized as first priority by the WHO. MEM-ANT3310 is the combination of a well-known antibiotic, the meropenem(MEM), and Antabio’s innovative and proprietary serine-beta-lactamase inhibitor ANT3310. ANT3310 represents a significant breakthrough as it completely inhibits a broad range of beta-lactamases, including the Klebsiella pneumoniae carbapenemases(KPC) and oxacillin-hydrolysing(OXA) type enzymes found in Carbapenem-Resistant Enterobacterales(CRE) and Carbapenem-Resistant Acinetobacter baumannii(CRAB), and restores meropenem activity against these deadly pathogens. This is critical for the treatment of polymicrobial infections such as those causing hospital-acquired pneumonia(HAP) and ventilator-associated pneumonia(VAP) and complicated Urinary Tract Infection(cUTI).
Antabio SAS has entered into a grant agreement with the European Innovation Council and European SMEs Executive Agency(EISMEA) in February 2023 in relation to the project “A novel combination treatment effective against all multidrug-resistant pathogens deemed as a critical priority by the WHO”(sbli-ant3310). The objective of the project is to bring Antabio’s lead program, MEM-ANT3310, to market with a strong clinical package and identifying a pharmaceutical partner for commercialization of MEM-ANT3310.
In May 2023, Antabio launched a Phase 1 First-in-Human(FIH) trial (not funded by the EIC) to evaluate safety, tolerability, and pharmacokinetics(PK) via SAD, MAD, and DDI cohorts. The study concluded successfully in Q3 2024, providing a strong foundation for continued development under the EIC grant.
In September 2024, the FDA endorsed Antabio’s proposal to skip Phase 2 and proceed directly to Phase 3 based on FIH results and preclinical data. The agency also approved the lung PK study design.
By March 2025, Antabio had finalized preparations for a Phase 1 lung PK study in Epithelial Lining Fluid (ELF), including IND approval and clinical site setup. Supported by the EIC (WP2), the trial is scheduled to start in Q2 2025.
(1)Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Murray et al. The Lancet (2022)/
(2)https://www.who.int/publications/i/item/9789240047655
-Epidemiological: projected 10 million deaths annually by 2050.
-Medical: jeopardizes standard treatments like chemotherapy, surgery, and transplants.
-Economic: estimated cost to healthcare systems of 100,000 billion dollars/year.
In 2019, 1.27 million deaths were directly caused by antibiotic resistance, with 4.95 million associated(1). The WHO's 2022 report(2) highlighted the lack of sufficient antibacterial agents in the development pipeline and the challenges of bringing effective solutions to market. Efforts from the EU and other bodies aim to incentivize innovation and access to such therapies.
In this context, ANTABIO's mission is to develop innovative solutions to treat severe infections caused by antibiotic-resistant gram-negative bacteria, recognized as first priority by the WHO. MEM-ANT3310 is the combination of a well-known antibiotic, the meropenem(MEM), and Antabio’s innovative and proprietary serine-beta-lactamase inhibitor ANT3310. ANT3310 represents a significant breakthrough as it completely inhibits a broad range of beta-lactamases, including the Klebsiella pneumoniae carbapenemases(KPC) and oxacillin-hydrolysing(OXA) type enzymes found in Carbapenem-Resistant Enterobacterales(CRE) and Carbapenem-Resistant Acinetobacter baumannii(CRAB), and restores meropenem activity against these deadly pathogens. This is critical for the treatment of polymicrobial infections such as those causing hospital-acquired pneumonia(HAP) and ventilator-associated pneumonia(VAP) and complicated Urinary Tract Infection(cUTI).
Antabio SAS has entered into a grant agreement with the European Innovation Council and European SMEs Executive Agency(EISMEA) in February 2023 in relation to the project “A novel combination treatment effective against all multidrug-resistant pathogens deemed as a critical priority by the WHO”(sbli-ant3310). The objective of the project is to bring Antabio’s lead program, MEM-ANT3310, to market with a strong clinical package and identifying a pharmaceutical partner for commercialization of MEM-ANT3310.
In May 2023, Antabio launched a Phase 1 First-in-Human(FIH) trial (not funded by the EIC) to evaluate safety, tolerability, and pharmacokinetics(PK) via SAD, MAD, and DDI cohorts. The study concluded successfully in Q3 2024, providing a strong foundation for continued development under the EIC grant.
In September 2024, the FDA endorsed Antabio’s proposal to skip Phase 2 and proceed directly to Phase 3 based on FIH results and preclinical data. The agency also approved the lung PK study design.
By March 2025, Antabio had finalized preparations for a Phase 1 lung PK study in Epithelial Lining Fluid (ELF), including IND approval and clinical site setup. Supported by the EIC (WP2), the trial is scheduled to start in Q2 2025.
(1)Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Murray et al. The Lancet (2022)/
(2)https://www.who.int/publications/i/item/9789240047655
During the second reporting period, Antabio carried out key R&D activities to prepare for the Phase 1 lung pharmacokinetic(PK) study of MEM-ANT3310, scheduled for 2025. This study will use bronchoalveolar lavage fluid(BALF) to evaluate pulmonary penetration, aiding dose selection and efficacy predictions.
A stable isotope-labeled internal standard (C13/N15) of ANT3310 produced during the first period was used for bioanalytical method development and clinical sample analysis (Task 1.4). These methods were completed in September 2024 and will enable BALF sample evaluation during the upcoming study.
Process improvements across the supply chain (Task 1.2) included a new synthesis route for ANT3310 Drug Substance (DS), eliminating a toxic reagent and increasing yield. A lyophilization process enhanced Drug Product(DP) stability, and the co-administration of MEM and ANT3310 was simplified into a single infusion bag, addressing practical concerns noted in the FIH trial (where separate bags resulted in excessive volume).
A new GMP batch of ANT3310 DP was successfully manufactured for the lung PK study. The Certificate of Analysis confirmed that the batch met all specifications (Task 1.3).
To initiate the Phase 1 lung PK study, an Investigational New Drug (IND) application was submitted on November 18, 2024, and approved by the U.S. Food and Drug Administration(FDA) on December 16, 2024 (Task 2.1). Ethics committee approval was granted on March 12, 2025 (Task 2.2). These approvals allow the study to begin in the USA in Q2 2025, concluding by Q4 2025.
A susceptibility study (Task 1.6) confirmed MEM-ANT3310’s strong activity against Gram-negative clinical isolates, including carbapenem-resistant Enterobacterales and Acinetobacter baumannii. Results align with Clinical and Laboratory Standards Institute(CLSI) and European Committee on Antimicrobial Susceptibility Testing(EUCAST) guidelines, reinforcing MEM-ANT3310’s potential against resistant infections.
A stable isotope-labeled internal standard (C13/N15) of ANT3310 produced during the first period was used for bioanalytical method development and clinical sample analysis (Task 1.4). These methods were completed in September 2024 and will enable BALF sample evaluation during the upcoming study.
Process improvements across the supply chain (Task 1.2) included a new synthesis route for ANT3310 Drug Substance (DS), eliminating a toxic reagent and increasing yield. A lyophilization process enhanced Drug Product(DP) stability, and the co-administration of MEM and ANT3310 was simplified into a single infusion bag, addressing practical concerns noted in the FIH trial (where separate bags resulted in excessive volume).
A new GMP batch of ANT3310 DP was successfully manufactured for the lung PK study. The Certificate of Analysis confirmed that the batch met all specifications (Task 1.3).
To initiate the Phase 1 lung PK study, an Investigational New Drug (IND) application was submitted on November 18, 2024, and approved by the U.S. Food and Drug Administration(FDA) on December 16, 2024 (Task 2.1). Ethics committee approval was granted on March 12, 2025 (Task 2.2). These approvals allow the study to begin in the USA in Q2 2025, concluding by Q4 2025.
A susceptibility study (Task 1.6) confirmed MEM-ANT3310’s strong activity against Gram-negative clinical isolates, including carbapenem-resistant Enterobacterales and Acinetobacter baumannii. Results align with Clinical and Laboratory Standards Institute(CLSI) and European Committee on Antimicrobial Susceptibility Testing(EUCAST) guidelines, reinforcing MEM-ANT3310’s potential against resistant infections.
During the second reporting period, significant advancements were made in the development of the MEM-ANT3310 project, further strengthening its potential impact in combating carbapenem-resistant infections. The project has achieved key milestones in:
-Drug formulation and the Phase 1 lung PK clinical study preparation, including: a) The successful synthesis of a stable isotopically labelled standard of ANT3310, enabling accurate bioanalytical method development and clinical samples analysis; b) Optimization of the DS and DP production processes and c) The successful manufacture of a clinical batch of ANT3310 under GMP conditions;
-Regulatory approvals, as both the IND application to the FDA and the ethics committee approval allowed the Phase 1 lung PK clinical study to begin;
-Antimicrobial efficacy assessment, as MEM-ANT3310 demonstrated strong activity against carbapenem-resistant clinical isolates, aligning with CLSI and EUCAST guidelines.
Through the Phase 1 lung PK clinical study of MEM-ANT3310 and the evaluation of its pulmonary penetration and distribution, this project is positioned to support dose selection and efficacy predictions for treating carbapenem-resistant infections, highlighting its significance in addressing critical respiratory infections.
-Drug formulation and the Phase 1 lung PK clinical study preparation, including: a) The successful synthesis of a stable isotopically labelled standard of ANT3310, enabling accurate bioanalytical method development and clinical samples analysis; b) Optimization of the DS and DP production processes and c) The successful manufacture of a clinical batch of ANT3310 under GMP conditions;
-Regulatory approvals, as both the IND application to the FDA and the ethics committee approval allowed the Phase 1 lung PK clinical study to begin;
-Antimicrobial efficacy assessment, as MEM-ANT3310 demonstrated strong activity against carbapenem-resistant clinical isolates, aligning with CLSI and EUCAST guidelines.
Through the Phase 1 lung PK clinical study of MEM-ANT3310 and the evaluation of its pulmonary penetration and distribution, this project is positioned to support dose selection and efficacy predictions for treating carbapenem-resistant infections, highlighting its significance in addressing critical respiratory infections.