To Evaluate Efficacy, Safety, Tolerability and PK of Intravenous Cipargamin in Participants With Severe Plasmodium Falciparum Malaria

Inclusion Criteria:

• Cohort 1: Participants aged ≥ 12 years with moderately severe malaria as defined in (prostration and/or repeated vomiting) without presence of other signs of severemalaria (and with high P. falciparum parasitemia (60,000-250,000 parasites per µl)

• Subsequent Cohorts 2 to 5: Participants diagnosed with severe malaria asdefined in modified version of WHO criteria and P. falciparum parasite count of ≥ 5000 per µl

• Cohort 2: Participants aged ≥ 12 years

• Cohort 3: Participants aged 6 - < 12 years

• Cohort 4: Participants aged 2 - < 6 years

• Cohort 5: Participants aged ≥ 6 months - < 2 years

Exclusion Criteria:

Exclusion criteria applying to all Cohorts 1 to 5:

• Mixed Plasmodium infections

• Treatment with quinine or artemisinin derivative or any other antimalarial drug orany antibiotic with known antimalarial activity within 12 hours of screening.

• Signs/symptoms of severe malnutrition in general accordance with WHO guidelines:

1. Under 18 years: <-3 Z-scores of WHO growth standard forweight-for-height/length (in children < 5 years) or BMI for age (5-18 years),or very low mid-upper arm circumference (MUAC < 115 mm in children < 12 years, < 160mm 12-18 years), or bilateral pitting edema

2. Over 18 years: BMI < 16 kg/m2 or MUAC < 160mm or bilateral pitting edema

• Known underlying illness, surgical or medical condition, which is not related toongoing event of severe malaria and which might jeopardize the participant's healthin case of participation in the study or which might alter the distribution,metabolism or excretion of study treatment. For example:

1. neurological or neurodegenerative disorders,

2. cardiac, renal, or hepatic disease, diabetes,

3. epilepsy, cerebral palsy,

4. known or suspected to be HIV-1 positive and/or receiving antiretroviraltreatment

5. malignancy of any organ system (other than localized basal cell carcinoma ofthe skin or in situ cervical cancer), treated or untreated, within the past 5years, regardless of whether there is evidence of local recurrence ormetastases

6. known or suspected cases of active infections or concurrent febrile illnesssuch as TB, Typhoid, COVID-19 etc.

Additional exclusion criteria are as follows:

Exclusion criteria for Cohort 1:

• ALT > 5 x the upper limit of normal range (ULN), regardless the level of totalbilirubin

• Total bilirubin is > 3 mg/dL

• Body weight of < 35 kg or >75 kg

Exclusion criteria for Cohort 2:

• Body weight of < 35 kg or >75 kg

• Participants diagnosed as moderately severe malaria due to repeated vomiting withoutpresence of any of the symptoms of severe malaria

Exclusion criteria for Cohorts 3 to 5:

• Body weight of < 5 kg

• Participants diagnosed as moderately severe malaria due to repeated vomiting withoutpresence of any of the symptoms of severe malaria