A Study to Investigate the Safety and Efficacy of RO7204239 in Combination With Risdiplam (RO7034067) in Participants With Spinal Muscular Atrophy

Inclusion Criteria:

• Age at screening: Part 1 Cohorts A (ambulant participants), B (ambulantparticipants), and D (non-ambulant participants): 5-10 years, inclusive; Part 1Cohort C (ambulant participants): 2-4 years, inclusive; Part 2 (ambulantparticipants): 2-25 years, inclusive

• Participants who have a confirmed genetic diagnosis of 5q-autosomal recessive SMA

• Symptomatic SMA disease, as per investigator's clinical judgement

• Participants who have received previous SMA disease-modifying therapies may beincluded provided that: Onasemnogene abeparvovec was received at least 90 days priorto screening. Participants should be tapered off steroids prior to receivingrisdiplam. In addition, participants should have normal levels of liver functiontests, coagulatory parameters, platelets, and troponin-I at 90 days afteradministration of onasemnogene abeparvovec or at least 1 month after tapering offcorticosteroids, whichever comes later; Nusinersen last dose was received at least 90 days prior to screening; Risdiplam is switched to the investigational medicinalproduct (IMP) provided by the site

Inclusion Criteria for Part 1 Cohorts A, B, and C and Part 2 only:

• Participants who are ambulant, where ambulant is defined as able to walk/rununassisted (i.e., without the use of assistive devices such as canes, walkingsticks, crutches, walkers, person/hand-held assistance, braces, orthoses, over themalleoli insoles or any other type of support) 10 meters in ≤ 30 seconds as measuresby the Timed 10-Meter Walk/Run Test [10MWRT] at screening

Inclusion Criteria for Part 1 Cohort D only:

• Participants who are able to sit, defined by: A score of 3 on Item 9 of the MFM32 (sitting without upper limb support while maintaining contact between the two handsfor 5 seconds); A score of at least 2 on Item 10 of the MFM32 (while seated, leaningforward to touch a tennis ball and sitting back again, either with or without upperlimb support)

• Participants who are able to raise a standardized plastic cup with a 200g weight init to the mouth, using both hands if necessary, defined by a score of 3 on the entryitem of the Revised Upper Limb Module (RULM)

Exclusion Criteria:

• Concomitant or previous participation in any investigational drug or device studywithin 90 days prior to screening or 5 half-lives of the drug whichever is longer,with the exception of those who have completed a risdiplam study, or participated ina nusinersen or onasemnogene abeparvovec study

• Receiving or have received previous administration of anti-myostatin therapies

• Any history of cell therapy

• Hospitalization for a pulmonary event within the last 2 months or plannedhospitalization at the time of screening

• Past surgery for scoliosis or hip fixation in the 6 months preceding screening orplanned within the next 9 months (Part 1) or 21 months (Part 2)

• Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular systemdiseases considered to be clinically significant

• Clinically significant ECG abnormalities at screening from average of triplicatemeasurement, abnormal findings at echocardiography, or cardiovascular diseaseindicating a safety risk for participants at the time of screening

• Any major illness within 1 month before screening

• Received any multidrug and toxin extrusion (MATE1/2K) substrates within 2 weeksbefore screening

• Hereditary fructose intolerance

• Used any of the following medications within 90 days prior to screening: riluzole,valproic acid, hydroxyurea, sodium phenylbutyrate, butyrate derivatives, creatine,carnitine, growth hormone, anabolic steroids, probenecid, acetyl cholinesteraseinhibitors, agents that could potentially increase or decrease muscle strength, andagents with known or presumed histone deacetylase (HDAC) inhibitory effect

• Clinically significant abnormalities in laboratory test results at the time ofscreening

• Ascertained or presumptive hypersensitivity to RO7204239 or risdiplam, or to theconstituents of its formulations

• Clinically relevant history of anaphylactic reaction requiring inotropic support

• Any abnormal skin conditions, pigmentation or lesions in the area intended for SCinjection (abdomen) and that would prevent visualization of potential injection sitereactions to RO7204239

• Immobilization, surgical procedures, fracture, or trauma to the upper or lower limbswithin 90 days prior to screening

Exclusion Criteria for Part 1 Cohorts A and B only:

• Participants with contraindications for MRI scan (including, but not restricted to,claustrophobia, pacemaker, artificial heart valves, cochlear implants, presence offoreign metal objects in heart or body, including spinal rods, intracranial vascularclips, insulin pumps, etc.), difficulties maintaining a prolonged supine position,or any other clinical history or examination finding that would pose a potentialhazard in combination with MRI

Exclusion Criteria for Part 1 Cohort D only:

• Participants who are unable to adopt the correct position to endure adequate qualityof DXA scan acquisition, as determined by the DXA scan technologist

• Participants who have contractures at screening that would interfere with DXA scanacquisition or functional assessments, as confirmed by the DXA scan technologist andclinical evaluator

• For participants able to take steps only: Able to walk unassisted (i.e., without theuse of assistive devices such as canes, walking sticks, crutches, walkers,person/hand held assistance, braces, orthoses, over the malleoli insoles or anyother type of support) 10 meters in ≤ 30 seconds as measured by the timed 10MWRT atscreening

• Participants who have severe scoliosis (curvature > 40°) at screening based on theparticipant's most recent X-ray as performed per standard of care or scoliosis thatwould interfere with functional assessments, as confirmed by the clinical evaluator.An X-ray is not required if it is not clinically indicated (e.g., in participantswith mild scoliosis)

• Participants who require invasive ventilation, tracheostomy, or the use ofnoninvasive ventilation (e.g., bilevel positive airway pressure) during the daytime