MAM01 / Atreca, Bill & Melinda Gates Foundation - LARVOL DELTA

The promise of monoclonal antibody interventions in malaria: A narrative review. (PubMed, Clin Microbiol Infect) - "Current evidence indicates that long-acting monoclonal antibodies have the potential to complement existing malaria control strategies by providing rapid, highly effective, and durable protection, particularly for populations at greatest risk of infection, including young children, pregnant women and individuals in seasonal transmission settings. Continued optimization of antibody potency, durability, delivery platforms, together with the identification of robust immune correlates of protection, will be critical for integrating monoclonal antibodies into future malaria control programs."

Journal • Review • Infectious Disease • Malaria

Engineered antibodies preserve structural and functional recognition of Plasmodium falciparum circumsporozoite protein. (PubMed, Protein Sci) - "Recently, two highly protective human mAbs 224 (IGHV3-49/IGLV1-40) and 7088 (IGHV3-33/IGKV1-5), encoded by distinct germline genes, were re-engineered and renamed MAM01 and MS-1805, respectively, to extend serum half-life and enable low-cost, large-scale manufacturing in alignment with WHO guidelines...Structural comparisons demonstrated that engineered antibodies retained key molecular and hydrogen-bond interactions without significant conformational changes, thereby maintaining antigen recognition and preserving binding affinity. These findings demonstrate that targeted framework engineering can enhance therapeutic potential while preserving structural integrity and function, providing insights for next-generation antibody-based interventions against malaria."

Journal • Infectious Disease • Malaria

Study To Evaluate Safety, Tolerability, and Pharmacokinetics of MAM01 in African Population (clinicaltrials.gov) - P1 | N=125 | Completed | Sponsor: Gates Medical Research Institute | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Malaria

Study To Evaluate Safety, Tolerability, and Pharmacokinetics of MAM01 in African Population (clinicaltrials.gov) - P1 | N=125 | Active, not recruiting | Sponsor: Gates Medical Research Institute | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2026 ➔ Jun 2026 | Trial primary completion date: Jan 2026 ➔ Jun 2026

Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease • Malaria

Efficacy and safety of Monoclonal Antibodies in Malaria Protection and Prevention of Transmission: A Systematic Review. (PubMed, Clin Ther) - "Antimalarial mAbs show promise as scalable tools for malaria prevention and transmission reduction. Subcutaneous delivery and prolonged protection enhance their feasibility for integration into the public health system for wider implementation in community settings. Further large-scale trials assessing long-term efficacy, operational feasibility, and cost-effectiveness in diverse settings, including children and pregnant women, are required and will govern the feasibility of its use in wider community settings."

Journal • Review • Fatigue • Infectious Disease • Malaria • Pain

Pharmacokinetic-Pharmacodynamic (PKPD) Characterization of MAM01, an investigational Monoclonal Antibody with extended half-life Targeting Plasmodium falciparum Sporozoites, Using a Controlled Human Malaria Infection Model (CHMI) (ASTMH 2025) - "Establishing the relationship between the EC80 and protection under field-relevant mosquito exposure is an important next step. A phase 1b age de-escalation trial in Ugandan adults and children aged 3 months to 5 years to assess safety and PK is ongoing."

Late-breaking abstract • PK/PD data • Infectious Disease • Malaria

Human monoclonal antibody MAM01 for protection against malaria in adults in the USA: a first-in-human, phase 1, dose-escalation, double-blind, placebo-controlled, adaptive trial. (PubMed, Lancet Infect Dis) - P1 | "MAM01 was well tolerated, met safety targets, and showed clinical proof-of-principle by eliciting protection in malaria-naive adults using the controlled human malaria infection model. Progress driving down the cost of goods coupled with dose selection within target populations will dictate the feasibility of malaria monoclonal antibody deployment."

First-in-human • Journal • P1 data • Infectious Disease • Malaria

Study To Evaluate Safety, Tolerability, and Pharmacokinetics of MAM01 in African Population (clinicaltrials.gov) - P1 | N=139 | Recruiting | Sponsor: Bill & Melinda Gates Medical Research Institute | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Malaria

Safety, Tolerability, Pharmacokinetics and Protective Efficacy of MAM01 in Healthy Adults (clinicaltrials.gov) - P1 | N=61 | Completed | Sponsor: Bill & Melinda Gates Medical Research Institute | Trial completion date: Jun 2025 ➔ Dec 2024 | Recruiting ➔ Completed

Trial completion • Trial completion date • Infectious Disease • Malaria

Pharmacokinetics and efficacy of MAM01, anti-circumsporozoite protein (CSP) monoclonal antibody, in mice (ASTMH 2024) - "In this study MAM01 demonstrated dose-dependent protection (up to 100%) in both models. Clinical studies with MAM01 are ongoing."

Late-breaking abstract • PK/PD data • Preclinical • Infectious Disease • Malaria • AVEN

190 - Clinical Development of Monoclonal Antibodies that Target Malaria Sporozoites (ASTMH 2024) - "The aim of this symposium is to bring together leaders in the field to present results from Phase 2 trials of L9LS in Mali and Kenya, and a Phase 1 Challenge Study in the US for MAM01. Each presenter will provide an overview on prior experience exploring some of these concepts in prior and current projects, but also will discuss important concepts to explore in future mAb clinical trials. Ample time will be provided at the end of the symposium to promote Q&A and discussion from the audience."

Clinical • Infectious Disease • Malaria

MAM01: Safety, PK and Preliminary Efficacy of a new 1st gen CSP Monoclonal Antibody (ASTMH 2024) - No abstract available

Clinical • Infectious Disease • Malaria

Study To Evaluate Safety, Tolerability, and Pharmacokinetics of MAM01 in African Population (clinicaltrials.gov) - P1 | N=139 | Not yet recruiting | Sponsor: Bill & Melinda Gates Medical Research Institute | N=264 ➔ 139 | Trial completion date: May 2026 ➔ Jan 2026 | Initiation date: Sep 2024 ➔ Jan 2025 | Trial primary completion date: May 2026 ➔ Jan 2026

Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date • Infectious Disease • Malaria

Safety, Tolerability, Pharmacokinetics and Protective Efficacy of MAM01 in Healthy Adults (clinicaltrials.gov) - P1 | N=61 | Recruiting | Sponsor: Bill & Melinda Gates Medical Research Institute | Trial primary completion date: Mar 2025 ➔ Dec 2024

Trial primary completion date • Infectious Disease • Malaria

Study To Evaluate Safety, Tolerability, and Pharmacokinetics of MAM01 in African Population (clinicaltrials.gov) - P1 | N=264 | Not yet recruiting | Sponsor: Bill & Melinda Gates Medical Research Institute

New P1 trial • Infectious Disease • Malaria • Pediatrics

A candidate antibody drug for prevention of malaria. (PubMed, Nat Med) - "However, the first malaria vaccine recommended by the World Health Organization (WHO) for pediatric use, RTS,S/AS01 (Mosquirix), has modest efficacy. We engineered the variable domains (Fv) of both antibodies to enable low-cost manufacturing at scale for distribution to pediatric populations, in alignment with WHO's preferred product guidelines. The engineered clone with the optimal manufacturing and drug property profile, MAM01, was advanced into clinical development."

Journal • Infectious Disease • Malaria • Pediatrics

Safety, Tolerability, Pharmacokinetics and Protective Efficacy of MAM01 in Healthy Adults (clinicaltrials.gov) - P1 | N=61 | Recruiting | Sponsor: Bill & Melinda Gates Medical Research Institute

Trial completion date • Trial primary completion date • Infectious Disease • Malaria

Prophylactic malaria monoclonal antibody MAM01 showed extensive binding breath to Circumsporozoite protein repeat region epitopes (ASTMH 2023) - "MAbs such as CIS43LS and L9LS are in development for malaria prevention in multiple clinical use cases...Overall, MAM01 demonstrated a broad range of cross-reactivity to CSP epitopes and a strong Fc effector function in vitro. Further determination of clinical significance of MAM01 can help expand prophylaxis options for malaria treatment."

Late-breaking abstract • Infectious Disease • Malaria

MAM01 Mechanism of Action: Inhibition of Parasite Motility & Displacement (ASTMH 2023) - "An evaluation of net displacement and speed on motile sporozoites in the skin of naïve and MAM01 immunized mice displayed a threshold effect whereby doses ≥ 30 µg had a statistically significant lower net displacement (30 µg = 8.10 µm) and a lower speed (30 µg = 1.01 µm/sec) as compared to the 10 µg (displacement, 30 µg = 10.64 µm; speed 30 µg = 1.67 µm/sec) and naïve group (displacement, 30 µg = 10.89 µm; speed 30 µg = 1.73 µm/sec), but there was not a clear dose-response beyond the 30 µg dose. While a dose-response was not obtained from these experiments, the data support MAM01's mechanism of action to be alteration of sporozoite motility."

Late-breaking abstract • Infectious Disease • Malaria

MAM01 Demonstrates Protection Against Plasmodium falciparum (Pf) Malaria in Humanized Mouse Model (ASTMH 2023) - "Although a definitive relationship between antibody levels and protection was not established due to dosing errors, antibody levels as low as 10.6 µg/m L at the time of challenge were protective. This is a similar level of antibody that provided protection in a recent controlled human infection model clinical study for anti-Pf CSP antibody L9LS, supporting further development of MAM01."

Late-breaking abstract • Preclinical • Hepatology • Infectious Disease • Malaria

Peptide Cross-Reactivity has Functional Potential for MAM01 Efficacy (ASTMH 2023) - "The percentage inhibition of liver burden after sporozoite challenge was measured by bioluminescence in an IVIS Spectrum imager and expressed as flux readings 42 hours post infection. Our data show MAM01 is equally active against parasites expressing the full repeat region, eight NANP repeats, or the NVDPNANP containing minor repeat region suggesting peptide cross-reactivity has functional potential."

Clinical • Late-breaking abstract • Infectious Disease • Malaria

MAM01 and L9LS Demonstrate Equipotent Protection Against Plasmodium falciparum (Pf) Malaria Infection in Mice (ASTMH 2023) - "The efficacy of MAM01 was compared to two comparator antibodies L9LS and CIS43LS. In the liver burden assay, which has a continuous readout, approximately 40 µg/m L of MAM01 provided 95% protection from infection; similar levels of protection in the parasitemia assay, which has a binary readout (infected or protected), required a higher concentration (approximately 140 µg/m L). The equipotency of MAM01 with L9LS, which recently conferred protection in a human challenge model supports further development of MAM01."

Late-breaking abstract • Preclinical • Infectious Disease • Malaria

MAM01: The Development for Seasonal Passive Immunization Intervention (ASTMH 2023) - No abstract available

Infectious Disease • Malaria

51 - Clinical Development of Monoclonal Antibodies that Target Malaria Sporozoites (ASTMH 2023) - "The aim of this symposium is to bring together leaders in the field to present results from pivotal phase 2 trials of CIS43LS and L9LS in Mali and Kenya, and to review progress in the development of the MAM01 mAb. The symposium will provide a forum for the community to discuss next steps in the clinical development and registration of mAbs including potential targeted populations. Each presenter will provide an overview on prior experience exploring some of these concepts in prior and current projects, but also will discuss important concepts to explore in future mAb clinical trials."

Clinical • Infectious Disease • Malaria

Safety, Tolerability, Pharmacokinetics and Protective Efficacy of MAM01 in Healthy Adults (clinicaltrials.gov) - P1 | N=61 | Recruiting | Sponsor: Bill & Melinda Gates Medical Research Institute | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Malaria