Approximately USD 8 Million Investment for New Vaccine and Drug Development Against Malaria in Sumitomo Pharma, Mitsubishi Tanabe Pharma and New Product Development in NTDs

Project Title

Towards the clinical development of the new asexual blood-stage malaria vaccine candidate PfRipr5 (PfRipr5-PD)

Collaboration

Partners

1. Ehime University (Ehime)
2. Sumitomo Pharma Co., Ltd. (Sumitomo Pharma)

3. European Vaccine Initiative e.V. (EVI e.V.)

4. Instituto de Biologia Experimental e Tecnologica (iBET)

Disease

Malaria

Intervention

Vaccine

Stage

Pre-Clinical Development

Awarded Amount

¥572,951,478 (US$3.9 million)

Status

Continued project

Summary

[Project objective]

This project will build on the established successful collaboration between the partners to further advance the development of the PfRipr5 malaria vaccine candidate. The main objectives are to:

1. Establish a process for PfRipr5 production compliant with current Good Manufacturing Practice (cGMP)

2. Produce PfRipr5 for safety-toxicology study according to cGMP

3. Perform a safety-toxicology study to evaluate PfRipr5 formulated with the SA-1 adjuvant

4. Prepare the dossier for Phase I/IIa clinical trial

[Project design]

The project workplan has been structured according to the four research objectives defined above. In objective 1, the production and purification processes of PfRipr5 will be fine-tuned using the optimal expression system identified in the previous project (T2018-151) funded by the GHIT Fund. In objective 2, the established manufacturing process will be transferred to the selected CDMO, where PfRipr5 will be produced in accordance with cGMP. PfRipr5 will be formulated with SA-1 and further evaluated in a pre-clinical GLP safety-toxicology study (objective 3). Finally, under objective 4, the clinical trial documentation will be prepared for subsequent ethical and regulatory approval to conduct a Phase I/IIa clinical trial.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/210/en

Project Title

Development of Enzyme Inhibitors as a SERCAP for Relapsing Malaria

Collaboration

Partners

1. Mitsubishi Tanabe Pharma Corporation (MTPC)

2. Medicines for Malaria Venture (MMV)

3. University of Georgia (UGA)

Disease

Malaria

Intervention

Drug

Stage

Lead Optimization

Awarded Amount

¥334,238,778 (US$2.3 million)

Status

Continued project

Summary

[Project objective]

The ultimate objective of the project will be to deliver a preclinical candidate, with a novel mode of action, with the potential for single dose treatment and/or prophylaxis of malaria. The 2-year project will aim to identify 1-3 Late Lead compounds, as defined by MMV's progression criteria, within 18 months and then to profile them in the subsequent 6 months to select a compound which meets MMV's late lead criteria suitable to progress into preclinical candidate profiling.  As an additional objective, the project will endeavor to confirm the proposed mode of action against P. vivax hypnozoites.  The project will also assess the potential of the late lead(s) to be developed as a SERCAP for relapsing malaria, which do not cause hemolysis, and thus not requiring G6PD testing.

[Project design]

A multi-disciplinary drug discovery approach will be used by the project, utilizing the inputs and diverse skills and experiences of medicinal chemists, molecular modelers, parasitologists, pharmacokineticists, toxicologists, formulation and scale-up chemistry.  Starting with the identified Lead Series, rational and systematic modifications of the leading compounds will be undertaken to further improve their pharmacological, physicochemical, pharmacokinetic and toxicological properties, based on state-of-the-art capabilities and data generated at MMV, MTPC, UGA and our partners.  As the putative target of these molecules is an enzyme that is essential to the growth of the malaria parasite, and structural information is available from analogous bacterial proteins, a structure-based drug design (SBDD) approach will be applied, supported at MTPC. This will provide the opportunity to rapidly and rationally design compounds with a higher likelihood of inhibiting the enzyme potently and selectively and achieving the project goals.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/211/en

Project Title

A Highly Sensitive and Specific Serological Rapid Diagnostic Test to Support WHO's Schistosomiasis Monitoring and Evaluation (M&E) Programs

Collaboration

Partners

1. Medical & Biological Laboratories Co., Ltd.

2. Drugs & Diagnostics for Tropical Diseases (DDTD)

Disease

Schistosomiasis

Intervention

Diagnostics

Stage

Product Design

Awarded Amount

¥55,712,697 (US$0.3 million)

Status

New project

Summary

[Project objective]

The overarching project goal is to deliver a Rapid Diagnostic Test (RDT) to detect exposure to Schistosoma mansoni, one of the main pathogens responsible for schistosomiasis. The RDT will meet the sensitivity and specificity requirements of the WHO TPP. At the end of this project, the test will be ready to be evaluated in the field. This test could be a standalone solution, or could be part of a total solution, in which people would be prescreened with the RDT at the point of contact, and positive results would later be confirmed in a laboratory using stool examination or molecular techniques.

[Project design]

Different assay formats will be generated and compared in terms of their performance. Great care will be given to demonstrating matrix equivalence between serum and whole blood, given that the test will be developed and validated with serum/plasma samples but eventually used with fingerstick blood, as required by the TPP. In addition to this, the TPP calls for a shelf life of minimally 18 months, and ideally 24 months, at 2–40°C and a relative humidity of 75%. Since stability studies are inherently long and intricate, we will commence them already at this very early stage and dedicate a significant amount of work to them. The antigen(s), or antigen combination, providing the best overall test performance in terms of sensitivity and specificity, as well as matrix equivalence and thermal stability, will be selected for further development.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/212/en

Project Title

Supporting WHO Onchocerciasis Elimination Programs: Progressing a Highly Sensitive and Ultra-specific Rapid Diagnostic Test to Commercialization Readiness

Collaboration

Partners

1. Medical & Biological Laboratories Co., Ltd.

2. Drugs & Diagnostics for Tropical Diseases (DDTD)
3. Big Eye Diagnostics, Inc. (BEDx)

Disease

Onchocerciasis

Intervention

Diagnostics

Stage

Product Design, Development and Validation

Awarded Amount

¥66,870,532 (US$0.4 million)

Status

New project

Summary

[Project objective]

The project team proposes a rapid diagnostic test (RDT) to detect exposure to Onchocerca volvulus, the pathogen responsible for onchocerciasis. Built in a biplex format, the team's test detects IgG4 antibodies specific for two O. volvulus antigens. Our RDT was shown by the CDC to be sensitive and specific enough to meet both WHO TPPs, with a specificity of >99.8% even at the lower bound 95% CI. GHIT and NIH funding will be used to generate the critical biological materials in ISO-13485 grade, and to transition test production from a low-throughput card-to-card format to a high-throughput, manufacturing-friendly reel-to-reel system, under ISO-13485 standards. Test performance will be validated in a laboratory setting by the CDC, and in regional laboratories of targeted onchocerciasis-endemic countries by the TFGH/USAID.

[Project design]

Given the demand forecast of up to 1 million tests/year, it will be critical to

- ensure constant product quality by minimizing the variability between different production lots, compliant with ISO13485 standards

- replace the current, low-throughput card-to-card production process with a high-throughput, manufacturing-friendly reel-to-reel process.

The team will send the final candidate test to CDC for advanced testing to ensure that sensitivity and specificity criteria defined in the TPPs are met. The team will then organize a round-table meeting involving all key stakeholders (CDC/TFGH/USAID/NIH/BMGF/WHO/GHIT) with the goal to ensure alignment and accelerate the path towards a WHO recommendation to use the test for onchocerciasis elimination mapping and, depending on the test's exact performance profile, for potential additional clinical applications.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/213/en

Project Title

Engagement of people affected by leprosy in the LepVax Clinical Trial

Collaboration

Partners

1. Sasakawa Health Foundation (SHF)
2. American Leprosy Missions, Inc. (ALM)
3. Oswaldo Cruz Institute (IOC/Fiocruz)

Disease

Leprosy

Intervention

Vaccine

Stage

Clinical Phase 1b/2a

Awarded Amount

¥150,379,601 (US$1.0 million)

Status

New project

Summary

[Project objective]

LepVax clinical research is advancing the mission of interrupting transmission and eliminating leprosy disease. This project is a pivotal phase 1/2 safety study in a leprosy-endemic region of Brazil to demonstrate safety and immunogenicity of a defined subunit vaccine, LepVax, in healthy individuals and leprosy patients. A pioneering component of these clinical trials is the engagement of people affected by leprosy. We will work closely with the members of the organization of people affected by leprosy in Brazil, called MORHAN (Movement to Reintegrate Persons Affected by Hansen's Disease), to bring their perspectives and insight in the investigation, with the goal of realizing quality leprosy services and uptake of interventions in Brazil. Together, we can increase leprosy awareness and clinical opportunities leading to elimination of leprosy.  This trial serves as a critical stage-gate for further development of LepVax for therapeutic and prophylactic indications.

[Project design]

Phase 1b and 2a trials are double-blind, randomized, placebo-controlled clinical trials designed to evaluate the safety, tolerability, and immunogenicity of LEP-F1 + GLA-SE study in healthy adult participants and leprosy patient adult participants, respectively.  The phase 1b trial will evaluate a low dose of LEP-F1 antigen (2 µg) or high dose of LEP-F1 (10 µg) combined with GLA-SE adjuvant (5 µg) compared to saline placebo.  There will be 18 participants per group.  A dose selection of LEP-F1 is proposed for testing in paucibacillary (PB) and multibacillary (MB) leprosy patients.  Outcome measures of the phase 1b trial are local and systemic reactions of each study injection and number of participants spontaneously reporting adverse events. LEP-F1 IgG antibody and specific T cell responses based on cytokine secretion will be evaluated as a secondary outcome. Biomarker immune modulation are exploratory outcomes.  Outcome measures of the phase 2a trial will also include measurements of inactive lesions, bacillary load, frequency and intensity of leprosy reactions, and neurological function for potential reactogenicity effect of the vaccine.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/214/en