This study is researching a treatment combination with two experimental drugs called pozelimab and cemdisiran referred to as "study drugs". Researchers are looking for a better way to treat Paroxysmal Nocturnal Hemoglobinuria (PNH).

The aim of the study is to see how well the pozelimab and cemdisiran combination works to lower hemolysis in participants whose PNH has been not well controlled even after taking other complement component 5 (C5) inhibitors, eculizumab/eculizumab biosimilar, ravulizumab or crovalimab.

The study is looking at several other research questions, including:

• What side effects may happen from taking the study drugs?
• How much of the study drugs are in the blood at different times?
• Whether the body makes antibodies against the study drug (which could make the study drugs not work as well or could lead to side effects)

The treatment period has two parts, a Treatment Period (TP, 28 weeks) and an Extension treatment Period (EP, 52 weeks).

Key Inclusion Criteria:

1. Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
2. Currently treated with marketed eculizumab, ravulizumab, or crovalimab at the labeled dose for at least 6 months
3. LDH persistently > 1.5 × Upper Limit of Normal (ULN) in the previous 6 months that the Principal Investigator (PI) attributes is due to intravascular hemolysis
4. At least 2 screening LDH values from different visits as described in the protocol
5. Willing and able to comply with clinic/remote visits and study-related procedures, including completion of the full series of meningococcal vaccinations required per protocol and agreement to continue to remain up to date with these vaccinations during the study

Key Exclusion Criteria:

1. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplants
2. Body weight <40 kilograms at screening visit
3. Patients with a known or suspected C5 mutation that is refractory to their current C5i treatment as described in the protocol
4. Any active or ongoing infection within 2 weeks of screening or during the screening period or any recent infection as described in the protocol
5. Known hereditary complement deficiency

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf