Novel, orally available immune modulator MP1032 with anti-SARS-CoV-2 and anti-cytokine activity

Project Information

iMPact

Grant agreement ID: 101046182

DOI

10.3030/101046182

Project closed

EC signature date 16 November 2021

Start date 1 August 2021

End date 30 April 2023

Funded under

• Health

Total cost

€ 7 988 724,50

EU contribution

€ 7 988 724,25

Coordinated by

METRIOPHARM AG
Switzerland

Periodic Reporting for period 2 - iMPact (Novel, orally available immune modulator MP1032 with anti-SARS-CoV-2 and anti-cytokine activity)

Reporting period: 2022-08-01 to 2023-04-30

Summary of the context and overall objectives of the project

The global pandemic caused by SARS-CoV-2 has resulted in significant health and socio-economic challenges worldwide. Early intervention in COVID-19 is crucial to prevent severe disease and mortality.

To reduce the disease burden and alleviate strain on healthcare systems, it is vital to halt the progression of COVID-19 in its early stages. Recently, small-molecule antiviral drugs have been approved for high-risk patients, particularly for early-stage treatment following SARS-CoV-2 infection. However, these drugs have side effects and may lead to drug resistance due to viral mutations. Therefore, there is an urgent need to develop prophylactic and safe therapeutic agents that are widely available and effective against various strains of SARS-CoV-2.

The iMPact project focuses on demonstrating the potential of the drug candidate MP1032 for early intervention in COVID-19 patients. MP1032 is a first-in-class drug that targets cellular oxidative stress and reduces inflammatory markers associated with COVID-19, such as TNF-alpha, IL-6, and IL-12. It offers several unique advantages:

• Dual mode of action: MP1032 acts as an immune modulator and antiviral agent, addressing key disease mechanisms in the early stages of COVID-19 and potentially preventing disease progression.
• Unique self-regulation mechanism: The drug does not suppress the immune system, allowing it to continue fighting the virus and its consequences.
• Excellent safety profile: MP1032 can be used in high-risk patients.
• Broad antiviral activity: MP1032 is likely effective against current and future SARS-CoV-2 variants, as well as other SARS viruses.
• Potential for long-COVID treatment and prophylactic use after initial approval for early intervention.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Key achievements of the project include the completion of a Phase IIa clinical trial with 132 enrolled patients, demonstrating the drug's safety and efficacy. In vitro studies showed MP1032's antiviral activity against different SARS-CoV-2 variants. The drug exhibited both therapeutic and prophylactic efficacy when administered during or before infection. Combinational treatment with MP1032 and other antiviral drug candidates showed strong synergistic antiviral activity.

The project also made progress in the scale-up of the active pharmaceutical ingredient (API) production. Further, a new investigational medicinal product (IMP) prototype suitable for automated capsule filling was developed.

In terms of regulatory strategy, steps were taken to evaluate the nonclinical data package for inclusion of women of childbearing potential and to prepare a Pediatric Investigational Plan (PIP) for authorization in pediatric patients. MetrioPharm engaged with the European Medicines Agency for scientific advice on the future development program.

Website: http://covidimpact.eu/.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

In the iMPact project, the consortium advanced MP1032, a novel COVID-19 therapeutic, towards Phase IIb/Phase III clinical trials. MP1032 is an enrichment of the current portfolio of COVID-19 therapeutics because it is the first-in-class auto-regulated drug targeting reactive oxygen species, which play an important role in both the mild and moderate stages of COVID-19. MP1032 does not suppress the immune system due to its unique self-regulating ability and is therefore a promising addition to the existing portfolio of drugs. Furthermore, MP1032 has broad and comparable antiviral activity against all SARS-CoV-2 variants of concern appeared so far. Hence, it could be effective in treating SARS-CoV-2 infections regardless of current and potential future variants, which is a major advantage over other drugs on the market.

Besides the direct contribution of the iMPact project to the treatment of COVID-19 patients, there was also a lot of scientific knowledge generated. Firstly, on the disease progression from moderate to severe and critical COVID-19 stages. By closely monitoring hospitalized COVID-19 patients, we will now be able to better understand and predict in which patients the disease will progress, and which patients will be cured quickly. This is especially important in relation to specific co-morbidities, which increase the risk of disease progression and even mortality.

Since the patients in this study received MP1032 plus standard of care (SoC), the results showed also that drug-drug interactions of MP1032 with other anti-viral drugs or corticosteroids, mostly given as SoC, are very unlikely and no significant side effects in this direction were reported. Those findings clearly support the potential of MP1032 also in combination with e. g. corticosteroids as an effective treatment of several infectious diseases, not limited to SARS-CoV-2. As MP1032 has shown a favorable safety profile, it would also potentially be more suitable for older and multi-morbid patients with a wide range of comorbidities and medications. Altogether, the findings and the easy intake of MP1032 makes the molecule also interesting for early intervention and prevention of symptomatic disease in non-hospitalized patients.

By engaging with at least one large European trial network (RECOVER or EU-RESPONSE), we ensure that all data and knowledge gained from the iMPact project will benefit the scientific community and can be used to deepen our understanding of the development of COVID-19 in the future.