Clinical Research Directory

Inclusion Criteria Participants must meet all of the following criteria: 1. Age: * 18 to 80 years, inclusive, at the time of informed consent. 2. Diagnosis of ALS: * Diagnosis of amyotrophic lateral sclerosis according to revised El Escorial criteria or equivalent, confirmed by a qualified neurologist. 3. GREM2-Positive Status: * Evidence of elevated GREM2 at screening, defined as: * CSF GREM2 above a pre-specified threshold OR * Plasma GREM2 above a pre-specified threshold with supportive evidence of astrocytic or TGF-β pathway activation (e.g., elevated GFAP or TGF-β-responsive biomarker). * Biomarker thresholds will be defined prospectively in the protocol and laboratory manual. 4. Disease Duration: * Time from first ALS-related symptom onset ≤ 24 months at screening. 5. Functional Status: * ALS Functional Rating Scale - Revised (ALSFRS-R) total score ≥ a protocol-defined minimum (e.g., ≥ 25) at screening, sufficient to allow detection of functional change. 6. Respiratory Function: * Slow vital capacity (SVC) or forced vital capacity (FVC) ≥ 50% of predicted at screening. 7. Stable Background ALS Therapy: * If receiving riluzole and/or edaravone, participants must be on a stable dose for ≥ 30 days prior to screening and willing to maintain the regimen throughout the study. 8. Ability to Consent: * Ability to understand and provide written informed consent personally or via a legally authorized representative, in accordance with local regulations. 9. Contraception: * Women of childbearing potential and men with partners of childbearing potential must agree to use effective contraception during the study and for a defined period after the last dose. Exclusion Criteria Participants will be excluded if any of the following apply: 1. Non-ALS Motor Neuron Disease: * Diagnosis of primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), or other non-ALS motor neuron disorders. 2. Advanced Respiratory Insufficiency: * Requirement for invasive mechanical ventilation at screening or anticipated need within the immediate study period. 3. Clinically Significant Hepatic Disease: * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 × upper limit of normal (ULN) at screening. * Known cirrhosis or active chronic liver disease. 4. Clinically Significant Cardiac Disease: * Uncontrolled arrhythmia, recent myocardial infarction, unstable angina, or clinically significant cardiac dysfunction that may increase risk with study participation. 5. Active or Uncontrolled Infection: * Active systemic infection requiring treatment at screening or known chronic infection that could interfere with immune or biomarker assessments. 6. Immunocompromised State: * History of organ transplantation, active malignancy requiring systemic therapy, or chronic immunosuppressive therapy (excluding stable low-dose corticosteroids, if allowed by protocol). 7. Prior Exposure to TGF-β Pathway Inhibitors: * Previous treatment with galunisertib or other direct TGF-β or ALK5 inhibitors within a protocol-defined washout period. 8. Recent Investigational Therapy: * Participation in another interventional clinical trial or receipt of an investigational drug within 30-60 days prior to screening (exact window defined in protocol). 9. Concomitant Medications with High Interaction Risk: * Use of strong CYP modulators or medications known to significantly interfere with galunisertib or nerandomilast metabolism, unless safely discontinued. 10. Pregnancy or Breastfeeding: * Pregnant or breastfeeding women. 11. Other Medical Conditions: * Any medical, neurological, or psychiatric condition that, in the investigator's judgment, could: * Interfere with study participation or compliance, * Confound interpretation of efficacy or biomarker outcomes, * Increase risk to the participant.