Phase 1/2 Study of REGN5458 in Adult Patients With Relapsed or Refractory Multiple Myeloma

Key Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

2. Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma WorkingGroup (IMWG) diagnostic criteria

3. Patients must have myeloma that is response-evaluable according to the 2016 IMWGresponse criteria as defined in the protocol.

• Phase 1, Part 1 (Dose Escalation): Patients with MM who have exhausted alltherapeutic options that are expected to provide meaningful clinical benefit,either through disease relapse, treatment refractory disease or intolerance ofthe therapy and including either:a. Progression on or after at least 3 lines of therapy, or intolerance oftherapy, including a proteasome inhibitor, an Immunomodulatory agent (IMiD),and an anti-CD38 antibody, OR b. Progression on or after an anti-CD38 antibodyand have disease that is "double refractory" to a proteasome inhibitor and anIMiD, or intolerance of therapy. The anti-CD38 antibody may have beenadministered alone or in combination with another agent such as a proteasomeinhibitor (PI). Refractory disease is defined as lack of response or relapsewithin 60 days of last treatment.

• Phase 1, Part 2 (SC Administration): Patients with MM whose disease meets thefollowing criteria:a. Progression on or after at least 3 prior lines of therapy including a(n) PI,IMiD, and anti-CD38 antibody, OR b. Patients must be triple-refractory, definedas being refractory to prior treatment with at least 1 anti-CD38 antibody, aproteasome inhibitor, and an IMiD.

• Phase 2 (Cohorts 1 and 2): Patients with MM whose disease meets the following criteria: a. Progression on or after at least 3 prior lines of therapy including a(n) PI,IMiD, and anti-CD38 antibody, OR b. Patients must be triple- refractory, defined asbeing refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38antibody.

• Phase 2 (Cohort 3): Patients with MM whose disease meets the following criteria:

1. Progression on or after at least 3 prior lines of therapy including a(n) PI,IMiD, and anti-CD38 antibody, OR

2. Patients must be triple- refractory, defined as being refractory* to priortreatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody.

• Refractory disease is defined as progression during treatment or within 60days after completion of therapy, or <25% response to therapy. AND, for ALL patients, if they have relapsed after a BCMA-directed CAR-T cellulartherapy then:

• Treatment with a CAR-T must have been associated with a response of PR or better,and

• If CAR-T cellular therapy was the most recent prior therapy, excludingcorticosteroids, then treatment must have been a minimum of 60 days prior totreatment with REGN5458.

Key Exclusion Criteria:

1. Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis, (excluding myeloma-associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly,endocrinopathy, monoclonal protein, and skin changes) 2. Patients with known MMbrain lesions or meningeal involvement 3. Cardiac ejection fraction <40% byechocardiogram or multi-gated acquisition scan (MUGA) 4. Prior treatment withBCMA-directed immunotherapies, including BCMA bispecific antibodies and BiTEs. Note:BCMA antibody-drug conjugates are not excludedand BCMA-directed CAR-T treatment isnot excluded in Phase 2 Cohort 3.

2. History of allogeneic stem cell transplantation at any time, or autologous stem celltransplantation within 12 weeks of the start of study treatment

Note 1: Other protocol defined inclusion / exclusion criteria apply Note 2: US enrollment completed