Investigator Initiated Research (IIR) Program is a grant from Takeda Pharmaceutical Company Limited that funds innovative clinical and basic science studies addressing important medical and scientific questions related to Takeda's compounds and therapeutic areas of interest, with the goal of improving patient care and advancing science.

Priority areas include maribavir effectiveness in immunocompromised patients, studies on cytomegalovirus infection, and health-related quality of life outcomes. Eligible applicants include academic, private, or governmental investigators, organizations, and institutions — such as universities, medical schools, hospitals, academic medical centers, physician groups, and government agencies.

Award amounts vary by project scope; support may include funding, products, or both.

Investigator Initiated Research Opportunities | Takeda Pharmaceuticals Investigator Initiated Research Opportunities | Takeda Pharmaceuticals Investigator Initiated Research # Investigator Initiated Research We, along with our partner network, are committed to improving patient care through support of scientific advances in medicine and increasing understanding of important diseases.

Our Investigator Initiated Research (IIR) program supports innovative clinical and basic science studies that address important medical and scientific questions related to our compounds and therapeutic areas of interest. We, along with our partner network, are committed to improving patient care through support of scientific advances in medicine and increasing understanding of important diseases.

Our Investigator Initiated Research (IIR) program supports innovative clinical and basic science studies that address important medical and scientific questions related to our compounds and therapeutic areas of interest.

Studies exploring maribavir effectiveness and safety in the real-world setting including: Immunocompromised patients with high-risk of Cytomegalovirus (CMV) infection Longer term impact, early treatment (e.g., preemptive, 1st line therapy/treatment) Diverse demographic populations (e.g., racial, ethnic) Studies focusing on effectiveness of maribavir following letermovir use or combination therapy Studies examining the impact of maribavir on Health Related Quality of Life Measures (HRQoL) and Patient Reported Outcomes (PROs) among thoracic (heart/lung) transplant patients with CMV infection Real-world studies exploring the role of maribavir in CMV management: 1) In post-transplant subpopulations with high unmet needs (e.g. the paediatric population, those with myelosuppression/immuno-dysfunction/renal dysfunction, and those intolerant or at risk of intolerance to other anti-CMV antivirals) 2) Patterns of use (e.g. treatment duration, use with adjunctive therapy, earlier treatment initiation) and impact on patient responses (e.g. informed by immunologic recovery) and outcomes 3) In immunocompromised patient populations (e.g. bi-specific antibodies, CAR-T cell therapy recipients) Real-world studies exploring antiviral treatment patterns and outcomes in immunocompromised populations (e.g. EBV) #### Maribavir - U.S. Only * Studies exploring maribavir effectiveness and safety in the real-world setting including: * Immunocompromised patients with high-risk of Cytomegalovirus (CMV) infection * Longer term impact, early treatment (e.g., preemptive, 1st line therapy/treatment) * Diverse demographic populations (e.g., racial, ethnic) * Studies focusing on effectiveness of maribavir following letermovir use or combination therapy * Studies examining the impact of maribavir on Health Related Quality of Life Measures (HRQoL) and Patient Reported Outcomes (PROs) among thoracic (heart/lung) transplant patients with CMV infection * Real-world studies exploring the role of maribavir in CMV management: * 1) In post-transplant subpopulations with high unmet needs (e.g. the paediatric population, those with myelosuppression/immuno-dysfunction/renal dysfunction, and those intolerant or at risk of intolerance to other anti-CMV antivirals) * 2) Patterns of use (e.g. treatment duration, use with adjunctive therapy, earlier treatment initiation) and impact on patient responses (e.g. informed by immunologic recovery) and outcomes * 3) In immunocompromised patient populations (e.g. bi-specific antibodies, CAR-T cell therapy recipients) * Real-world studies exploring antiviral treatment patterns and outcomes in immunocompromised populations (e.g. EBV) Hereditary Angioedema (HAE) ### Hereditary Angioedema (HAE) Hereditary Angioedema (HAE) Approaches to facilitating diagnosis and decreasing diagnostic delay Impact of treatment switching between new treatment options and TAKHZYRO (Lanadelumab) Data from the pediatric population around efficacy/effectiveness and safety of TAKHZYRO, prevalence, diagnostic pathways and treatment patterns, burden of disease and QoL Long-term, real-world effectiveness and safety data of TAKHZYRO across the disease activity spectrum, particularly in patients with lower disease activity, including the impact on QoL Data from pregnancy/post-pregnancy and breastfeeding/post-breastfeeding population treated with TAKHZYRO Understanding treatment during paediatric – adolescent – adult patient transition, including dosing, patient journey and care pathway #### Hereditary Angioedema (HAE) * Approaches to facilitating diagnosis and decreasing diagnostic delay * Impact of treatment switching between new treatment options and TAKHZYRO (Lanadelumab) * Data from the pediatric population around efficacy/effectiveness and safety of TAKHZYRO, prevalence, diagnostic pathways and treatment patterns, burden of disease and QoL * Long-term, real-world effectiveness and safety data of TAKHZYRO across the disease activity spectrum, particularly in patients with lower disease activity, including the impact on QoL * Data from pregnancy/post-pregnancy and breastfeeding/post-breastfeeding population treated with TAKHZYRO * Understanding treatment during paediatric – adolescent – adult patient transition, including dosing, patient journey and care pathway Gastroenterology, Immunology and Nephrology ### Gastroenterology, Immunology and Nephrology Ulcerative Colitis (UC), Crohn’s Disease (CD) and Inflammatory Bowel Diseases (IBD) Characteristics (including biomarkers) of optimal patients for Vedolizumab (VDZ) treatment Utilization of Vedolizumab- Clinical Decision Support Tool (VDZ-CDST), including a) characterizing intermediate responders; b) understanding the impact of previous biologic exposure on Entyvio outcomes; and c) differentiating Entyvio from other biologics Efficacy of VDZ in novel patient-reported outcomes (e.g. bowel urgency) Real-world transmural healing with VDZ in CD Disease modification by VDZ in CD and UC Real-world disease clearance by VDZ in UC VDZ utilization in patients with new moderately active CD/endoscopic CD with mild symptoms Real-world data on subcutaneous (SC) VDZ (including efficacy, safety, switching patterns from IV to SC and vice versa, different SC dosing regimens, SC induction, and dose optimization, including de-escalation) Data on patient preferences (route of administration) and willingness to switch treatments Data on health equity, health disparities and social determinants of health in patients with IBD Efficacy and safety of VDZ in combination with advanced therapeutic agents in CD and UC Understanding biological mechanisms (including omics/histology) of combining different mechanism of actions with VDZ Areas of high unmet need for which the VDZ mechanism of action can be of potential benefit (e.g. proof-of-concept studies) Sequencing of advanced therapy Data on the burden of pediatric IBD Adoption of new methods and technologies to diagnose and manage patients with celiac disease: use of video capsule endoscopy (VCE) tools for diagnosing and monitoring CeD and its role in clinical guidelines tools and studies objectively assessing real world gluten exposure Biomarkers of the future when monitoring CeD Disease burden in special populations with highest unmet need (pediatric, adolescents, elderly) Correlation of histology/serology/symptoms/other risk factors with disease progression/complications Humanistic burden and patient / healthcare professional (HCP) preferences Disease pathophysiology (especially advances in immunology) Optimization of gluten-free diet (GFD) when managing CeD New modalities and development targets in CeD New indications with relevance to gluten sensitivities/wheat allergy Pilot studies in Functional Gastrointestinal Diseases with rationale for prokinetic use Safety and efficacy of prucalopride in secondary causes of constipation Real world, retrospective studies of prucalopride in adults with chronic idiopathic constipation Alpha-1 Antitrypsin Deficiency (AATD) Liver Disease Studies focusing on identification and validation of non-invasive methods for assessment of liver fibrosis in AATD Studies exploring predictors of disease progression in AATD liver disease or for the development and or progression of liver disease in patients with or without AATD lung disease Studies exploring novel markers for the early identification of patients with AATD-LD and diagnostic characterization of disease stage Studies evaluating correlations between intrahepatic globule accumulation, patient-centered outcomes and/or clinical outcomes Eosinophilic Esophagitis (EoE) – US Only Identification of non-invasive, or minimally invasive diagnostic and monitoring techniques in EoE Development and validation of symptom monitoring tools implementable for patient care Impact of disease severity on EoE treatment outcomes Development of tools (questionnaires, artificial intelligence tools, etc.) to improve EoE patient identification across the multidisciplinary team Further understanding into ways to improve diagnosis rates and engagement with healthcare in under-represented populations within the EoE community Real-world evidence of safety and efficacy with budesonide oral suspension Predictors of response to EoE therapy, with special focus on predictors of response to budesonide oral suspension Immune Thrombocytopenia (ITP) Characterize CD38-mediated mechanism of action (MoA) in ITP, including investigating effects on autoantibody secreting cells, T cell subsets, and NK cells Describe and quantify current treatment burden, treatment goals, optimal treatment, remaining unmet need by line of therapy, including combination therapy Understand definitions and difference between remission, sustained response off treatment (SROT), disease modification and cure, as well as rates of these by disease duration Characterize CD38-mediated mechanism of action (MoA) in other autoimmune diseases Understand the IgAN mechanism of disease, specifically the role of plasma cells Evaluate the role of novel and exploratory biomarkers and risk prediction tools for IgAN to stratify patients, guide treatment selection, monitor disease progression and predict outcomes Understand definitions of early diagnosis, remission, treatment response, sustained response off-treatment and disease modification, as well as rates of these by disease duration, severity and treatment choice Evaluate the role of non-invasive biomarkers to support early diagnosis of IgAN Characterize the epidemiology of IgAN globally, regionally and locally #### Ulcerative Colitis (UC), Crohn’s Disease (CD) and Inflammatory Bowel Diseases (IBD) * Characteristics (including biomarkers) of optimal patients for Vedolizumab (VDZ) treatment * Utilization of Vedolizumab- Clinical Decision Support Tool (VDZ-CDST), including a) characterizing intermediate responders; b) understanding the impact of previous biologic exposure on Entyvio outcomes; and c) differentiating Entyvio from other biologics * Efficacy of VDZ in novel patient-reported outcomes (e.g. bowel urgency) * Real-world transmural healing with VDZ in CD * Disease modification by VDZ in CD and UC * Real-world disease clearance by VDZ in UC * VDZ utilization in patients with new moderately active CD/endoscopic CD with mild symptoms * Real-world data on subcutaneous (SC) VDZ (including efficacy, safety, switching patterns from IV to SC and vice versa, different SC dosing regimens, SC induction, and dose optimization, including de-escalation) * Data on patient preferences (route of administration) and willingness to switch treatments * Data on health equity, health disparities and social determinants of health in patients with IBD * Efficacy and safety of VDZ in combination with advanced therapeutic agents in CD and UC * Understanding biological mechanisms (including omics/histology) of combining different mechanism of actions with VDZ * Areas of high unmet need for which the VDZ mechanism of action can be of potential benefit (e.g. proof-of-concept studies) * Sequencing of advanced therapy * Data on the burden of pediatric IBD #### Celiac Disease (CeD) * Adoption of new methods and technologies to diagnose and manage patients with celiac disease: * use of video capsule endoscopy (VCE) tools for diagnosing and monitoring CeD and its role in clinical guidelines * tools and studies objectively assessing real world gluten exposure * Biomarkers of the future when monitoring CeD * Disease burden in special populations with highest unmet need (pediatric, adolescents, elderly) * Correlation of histology/serology/symptoms/other risk factors with disease progression/complications * Humanistic burden and patient / healthcare professional (HCP) preferences * Disease pathophysiology (especially advances in immunology) * Optimization of gluten-free diet (GFD) when managing CeD * New modalities and development targets in CeD * New indications with relevance to gluten sensitivities/wheat allergy #### Prucalopride - US Only * Pilot studies in Functional Gastrointestinal Diseases with rationale for prokinetic use * Safety and efficacy of prucalopride in secondary causes of constipation * Real world, retrospective studies of prucalopride in adults with chronic idiopathic constipation #### Alpha-1 Antitrypsin Deficiency (AATD) Liver Disease * Studies focusing on identification and validation of non-invasive methods for assessment of liver fibrosis in AATD * Studies exploring predictors of disease progression in AATD liver disease or for the development and or progression of liver disease in patients with or without AATD lung disease * Studies exploring novel markers for the early identification of patients with AATD-LD and diagnostic characterization of disease stage * Studies evaluating correlations between intrahepatic globule accumulation, patient-centered outcomes and/or clinical outcomes #### Eosinophilic Esophagitis (EoE) – US Only * Identification of non-invasive, or minimally invasive diagnostic and monitoring techniques in EoE * Development and validation of symptom monitoring tools implementable for patient care * Impact of disease severity on EoE treatment outcomes * Development of tools (questionnaires, artificial intelligence tools, etc.) to improve EoE patient identification across the multidisciplinary team * Further understanding into ways to improve diagnosis rates and engagement with healthcare in under-represented populations within the EoE community * Real-world evidence of safety and efficacy with budesonide oral suspension * Predictors of response to EoE therapy, with special focus on predictors of response to budesonide oral suspension #### Immune Thrombocytopenia (ITP) * Characterize CD38-mediated mechanism of action (MoA) in ITP, including investigating effects on autoantibody secreting cells, T cell subsets, and NK cells * Describe and quantify current treatment burden, treatment goals, optimal treatment, remaining unmet need by line of therapy, including combination therapy * Understand definitions and difference between remission, sustained response off treatment (SROT), disease modification and cure, as well as rates of these by disease duration * Characterize CD38-mediated mechanism of action (MoA) in other autoimmune diseases #### IgA Nephropathy (IgAN) * Understand the IgAN mechanism of disease, specifically the role of plasma cells * Evaluate the role of novel and exploratory biomarkers and risk prediction tools for IgAN to stratify patients, guide treatment selection, monitor disease progression and predict outcomes * Understand definitions of early diagnosis, remission, treatment response, sustained response off-treatment and disease modification, as well as rates of these by disease duration, severity and treatment choice * Evaluate the role of non-invasive biomarkers to support early diagnosis of IgAN * Characterize the epidemiology of IgAN globally, regionally and locally Narcolepsy and Idiopathic Hypersomnia Characterize the pathophysiological mechanisms underlying narcolepsy type 2 and idiopathic hypersomnia Explore the involvement of the orexin system in functions extending beyond sleep-wake regulation Describe the natural course of narcolepsy and IH in untreated individuals, such as disease progression, mortality, clinical and functional outcomes and quality of life Advance knowledge of the diverse phenotypic expressions in narcolepsy and idiopathic hypersomnia Identify early signals/predictors of narcolepsy and idiopathic hypersomnia #### Narcolepsy and Idiopathic Hypersomnia * Characterize the pathophysiological mechanisms underlying narcolepsy type 2 and idiopathic hypersomnia * Explore the involvement of the orexin system in functions extending beyond sleep-wake regulation * Describe the natural course of narcolepsy and IH in untreated individuals, such as disease progression, mortality, clinical and functional outcomes and quality of life * Advance knowledge of the diverse phenotypic expressions in narcolepsy and idiopathic hypersomnia * Identify early signals/predictors of narcolepsy and idiopathic hypersomnia Studies examining the cost efficiency of recombinant Antihemophilic Factor (ADVATE) and PEGylated –recombinant Antihemophilic Factor (ADYNOVATE/ADYNOVI) with or without myPKFiT Studies examining the relationship between FVIII levels and the occurrence of bleeds at varying physical activity levels with or without the use of the myPKFiT mobile app Studies to investigate changes in adherence and quality of life (QoL) in patients using recombinant Antihemophilic Factor (ADVATE) and the myPKFiT patient app Real World Evidence on use of PEGylated -recombinant Antihemophilic Factor (ADYNOVATE/ADYNOVI), an extended half-life rFVIII (EHL rFVIII), in clinical practice with or without myPKFiT (including safety, efficacy, utilization, QoL, adherence, patient satisfaction etc.) Studies on other non-coagulation effects of Factor VIII Studies looking at the GOAL-HEM (Goal Attainment Scaling for Life – Hemophilia) as a patient-centered reported outcome measure to monitor clinical progress Non-clinical studies on Polyethylenglycol (PEG) safety Role of PEGylated -recombinant Antihemophilic Factor (ADYNOVATE/ADYNOVI) for tolerization or in previously tolerized/partially tolerized patients Studies to investigate appropriate assessment of joint health and prevention/management of all bleeds including subclinical Studies to investigate benefit of FVIII replacement therapy vs. non-factor therapy in optimising bleed outcomes Recombinant-porcine Antihemophilic Factor and Acquired Hemophilia (AHA) Prospective or retrospective studies that provide insights on first-line use, loading dose, dosing over time, FVIII:c and anti-drug antibodies Explore efficacy and safety of recombinant-porcine Antihemophilic Factor in patient subpopulations (i.e. post-partum or patients with specific comorbidities) with AHA Relationship between treatment effectiveness, FVIII level and anti-pFVIII inhibitor titer in subjects with AHA receiving recombinant-porcine Antihemophilic factor Development/validation of dosing algorithms for recombinant-porcine Antihemophilic factor, initial and follow-on, when the anti-porcine FVIII titers are unknown.

Relationship between treatment effectiveness and recombinant-porcine Antihemophilic factor dosing in subjects with AHA Explore the potential use of recombinant-porcine Antihemophilic factor as treatment for breakthrough bleeds in patients treated with non-factor therapies [i.e. Emicizumab] Studies intended to develop flexible and tailored dosing regimens for recombinant-porcine Antihemophilic Factor Investigate effectiveness, safety and treatment outcomes of the continuous infusion of recombinant-porcine Antihemophilic Factor Collect long term data on treatment for patients with AHA Clinical outcomes of Anti-Inhibitor Coagulant Complex for treatment of AHA patients Measures to evaluate outcomes with hemophilia gene therapy (clinical, humanistic, quality of life, economic, biomarkers, etc.) Thrombotic Thrombocytopenic Purpura (TTP) Understand the role of ADAMTS13 activity on disease outcomes Assess quality of life, healthcare resource utilization and disease and treatment burden of patients with TTP (including those with neurological conditions, renal failure, or severe organ damage) and their caregivers Identify clinical signs, biomarkers, and laboratory values to stratify iTTP by severity, relapse risk, and treatment response Description of patient characteristics that guide treatment decisions and management of cTTP, including identification of clinically relevant biomarkers, acute/subacute events, isolated manifestations/non-overt symptoms and silent organ damage Explore the epidemiology of cTTP, e.g. prevalence of pathogenic mutations von Willebrand Disease (VWD) Studies analyzing real-world use of rVWF (including by bleed location, bleed prediction, PK-guided dosing etc.) and its impact on effectiveness and safety Comparative studies of pdVWF versus rVWF in the treatment or prevention of mucosal bleeds (epistaxis, HMB, GI) and joint bleeds Studies exploring the relationship between rVWF unique characteristics (half-life, multimeric profile, absence of FVIII) and its clinical efficacy and safety or impact on disease progression (ex.

Angiodysplasia) Studies assessing the need for long-term management and prophylaxis with rVWF and its impact on quality of life (QoL), healthcare resource utilization (HCRU), and/or patient-reported outcomes (PROs) * Studies examining the cost efficiency of recombinant Antihemophilic Factor (ADVATE) and PEGylated –recombinant Antihemophilic Factor (ADYNOVATE/ADYNOVI) with or without myPKFiT * Studies examining the relationship between FVIII levels and the occurrence of bleeds at varying physical activity levels with or without the use of the myPKFiT mobile app * Studies to investigate changes in adherence and quality of life (QoL) in patients using recombinant Antihemophilic Factor (ADVATE) and the myPKFiT patient app * Real World Evidence on use of PEGylated -recombinant Antihemophilic Factor (ADYNOVATE/ADYNOVI), an extended half-life rFVIII (EHL rFVIII), in clinical practice with or without myPKFiT (including safety, efficacy, utilization, QoL, adherence, patient satisfaction etc.) * Studies on other non-coagulation effects of Factor VIII * Studies looking at the GOAL-HEM (Goal Attainment Scaling for Life – Hemophilia) as a patient-centered reported outcome measure to monitor clinical progress * Non-clinical studies on Polyethylenglycol (PEG) safety * Role of PEGylated -recombinant Antihemophilic Factor (ADYNOVATE/ADYNOVI) for tolerization or in previously tolerized/partially tolerized patients * Studies to investigate appropriate assessment of joint health and prevention/management of all bleeds including subclinical * Studies to investigate benefit of FVIII replacement therapy vs. non-factor therapy in optimising bleed outcomes #### Recombinant-porcine Antihemophilic Factor and Acquired Hemophilia (AHA) * Prospective or retrospective studies that provide insights on first-line use, loading dose, dosing over time, FVIII:c and anti-drug antibodies * Explore efficacy and safety of recombinant-porcine Antihemophilic Factor in patient subpopulations (i.e. post-partum or patients with specific comorbidities) with AHA * Relationship between treatment effectiveness, FVIII level and anti-pFVIII inhibitor titer in subjects with AHA receiving recombinant-porcine Antihemophilic factor * Development/validation of dosing algorithms for recombinant-porcine Antihemophilic factor, initial and follow-on, when the anti-porcine FVIII titers are unknown.

* Relationship between treatment effectiveness and recombinant-porcine Antihemophilic factor dosing in subjects with AHA * Explore the potential use of recombinant-porcine Antihemophilic factor as treatment for breakthrough bleeds in patients treated with non-factor therapies [i.e. Emicizumab] * Studies intended to develop flexible and tailored dosing regimens for recombinant-porcine Antihemophilic Factor * Investigate effectiveness, safety and treatment outcomes of the continuous infusion of recombinant-porcine Antihemophilic Factor * Collect long term data on treatment for patients with AHA * Clinical outcomes of Anti-Inhibitor Coagulant Complex for treatment of AHA patients #### Hemophilia Gene Therapy * Measures to evaluate outcomes with hemophilia gene therapy (clinical, humanistic, quality of life, economic, biomarkers, etc.) #### Thrombotic Thrombocytopenic Purpura (TTP) * Understand the role of ADAMTS13 activity on disease outcomes * Assess quality of life, healthcare resource utilization and disease and treatment burden of patients with TTP (including those with neurological conditions, renal failure, or severe organ damage) and their caregivers * Identify clinical signs, biomarkers, and laboratory values to stratify iTTP by severity, relapse risk, and treatment response * Description of patient characteristics that guide treatment decisions and management of cTTP, including identification of clinically relevant biomarkers, acute/subacute events, isolated manifestations/non-overt symptoms and silent organ damage * Explore the epidemiology of cTTP, e.g. prevalence of pathogenic mutations #### von Willebrand Disease (VWD) * Studies analyzing real-world use of rVWF (including by bleed location, bleed prediction, PK-guided dosing etc.) and its impact on effectiveness and safety * Comparative studies of pdVWF versus rVWF in the treatment or prevention of mucosal bleeds (epistaxis, HMB, GI) and joint bleeds * Studies exploring the relationship between rVWF unique characteristics (half-life, multimeric profile, absence of FVIII) and its clinical efficacy and safety or impact on disease progression (ex.

Angiodysplasia) * Studies assessing the need for long-term management and prophylaxis with rVWF and its impact on quality of life (QoL), healthcare resource utilization (HCRU), and/or patient-reported outcomes (PROs) ### Rare Metabolic Diseases Lysosomal Storage Disorders Assess the clinical impact of the immunogenic profile of agalsidase alfa in the management of Fabry disease Explore clinical outcomes of agalsidase alfa in specific patient subpopulations like late-onset disease (e.g. cardiac and neurological phenotypes), pediatrics and females Generate data to assess optimal time for treatment initiation and provide evidence of long-term clinical outcomes with agalsidase alfa Evaluate the impact of agalsidase alfa on Lyso-Gb3 levels in patients with Fabry disease, and its association with clinical outcomes Identify the most relevant factors associated with patients’ changes in treatment plan from chaperone to agalsidase alfa, and analyse the impact that these factors have on clinical outcomes of patients with Fabry disease Understand the impact of self-infusion with agalsidase alfa on patient health-related quality of life (HRQoL) Establish the clinical impact of velaglucerase alfa on bone manifestations (e.g. osteonecrosis) in Gaucher disease and the optimal way to assess clinical outcomes on bone health (e.g. bone mineral density, bone marrow burden, bone biomarkers) Assess safety and efficacy/effectiveness of velaglucerase alfa in specific patient subpopulations with Gaucher disease (e.g. early paediatric [below 4 years of age], female patients, use during pregnancy) Assess safety and effectiveness of velaglucerase alfa in addressing somatic manifestations inpatients with Gaucher disease type 3 Understand the impact of higher dosing and frequency of administration of velaglucerase alfa in severe phenotypes of Gaucher disease Generate local epidemiology data for patients with Gaucher disease type 3 Hunter/ Mucopolysaccharidosis Type II (MPSII) Assess the impact of treatment with idursulfase in patients under 16 months of age on clinical and humanistic burden of disease Explore biomarkers that would correlate with disease progression and help predict neuronopathic involvement in MPS II Assess alternative dosing of idursulfase, including higher or variable dosing, on somatic and neurological symptoms of patients with MPS II Generate local epidemiology data to account for increased newborn screening of MPS II Understand the impact of home infusion with idursulfase on patient health-related quality of life (HRQoL) Assess the clinical impact of the immunogenic profile of idursulfase in the management of MPS II.

#### Lysosomal Storage Disorders * Assess the clinical impact of the immunogenic profile of agalsidase alfa in the management of Fabry disease * Explore clinical outcomes of agalsidase alfa in specific patient subpopulations like late-onset disease (e.g. cardiac and neurological phenotypes), pediatrics and females * Generate data to assess optimal time for treatment initiation and provide evidence of long-term clinical outcomes with agalsidase alfa * Evaluate the impact of agalsidase alfa on Lyso-Gb3 levels in patients with Fabry disease, and its association with clinical outcomes * Identify the most relevant factors associated with patients’ changes in treatment plan from chaperone to agalsidase alfa, and analyse the impact that these factors have on clinical outcomes of patients with Fabry disease * Understand the impact of self-infusion with agalsidase alfa on patient health-related quality of life (HRQoL) * Establish the clinical impact of velaglucerase alfa on bone manifestations (e.g. osteonecrosis) in Gaucher disease and the optimal way to assess clinical outcomes on bone health (e.g. bone mineral density, bone marrow burden, bone biomarkers) * Assess safety and efficacy/effectiveness of velaglucerase alfa in specific patient subpopulations with Gaucher disease (e.g. early paediatric [below 4 years of age], female patients, use during pregnancy) * Assess safety and effectiveness of velaglucerase alfa in addressing somatic manifestations inpatients with Gaucher disease type 3 * Understand the impact of higher dosing and frequency of administration of velaglucerase alfa in severe phenotypes of Gaucher disease * Generate local epidemiology data for patients with Gaucher disease type 3 #### Hunter/ Mucopolysaccharidosis Type II (MPSII) * Assess the impact of treatment with idursulfase in patients under 16 months of age on clinical and humanistic burden of disease * Explore biomarkers that would correlate with disease progression and help predict neuronopathic involvement in MPS II * Assess alternative dosing of idursulfase, including higher or variable dosing, on somatic and neurological symptoms of patients with MPS II * Generate local epidemiology data to account for increased newborn screening of MPS II * Understand the impact of home infusion with idursulfase on patient health-related quality of life (HRQoL) * Assess the clinical impact of the immunogenic profile of idursulfase in the management of MPS II.

### Plasma Derived Therapies Chronic inflammatory demyelinating polyneuropathy (CIDP) Real world studies on effectiveness and safety of facilitated subcutaneous immunoglobulin 10% (fSCIG 10%) in CIDP maintenance therapy Studies looking at fSCIG 10% use and outcomes in CIDP patients switching from prior therapies (including rationale to switch, patient preference and satisfaction) Studies exploring use and impact of patient preferred/flexible dosing schedules, accelerated ramp-up/no ramp-up in fSCIG 10% Studies addressing humanistic burden of disease in CIDP patients and caregivers Research that intends to identify biomarkers for diagnosis or to predict disease progression and treatment outcome Studies intended to improve patient care, for example using digital solutions for monitoring CIDP symptoms/disease Secondary Immunodeficiency (SID) Studies aimed at understanding the course of infections in pediatric or adult patients with hematological and non-hematological (autoimmune) diseases who develop secondary immunodeficiency (SID) due to treatment with B-cell-directing therapies (e.g. bispecific antibodies, chimeric antigen receptor [CAR] T-cell therapy, anti-CD19, anti-CD20, anti-CD38, or other new modalities or combinations of the above), as well as after hematopoietic stem cell transplant (HSCT), solid organ transplantation (SOT) or experiencing antibody mediated rejection (AMR).

These studies could explore factors such as the timing, frequency, type, and severity of infections, as well as their impact on patient outcomes and treatment. Studies that aim to establish or validate existing predictive models or to identify biomarkers that could help to select patients at high risk of developing infections in cancer-related and treatment-related SID.

Studies with a focus on understanding who would benefit the most from prophylactic or on-demand immunoglobulin (IG) therapy as well as studies defining the optimal IgG threshold for initiating IG replacement therapy (IGRT) to ensure the best possible protection for SID patients.

Analyses that quantify and qualify the impact of SID and/or impact of IG therapy (prophylactic and on-demand—especially [facilitated] subcutaneous immunoglobulin [(f)SCIG]) vs standard of care (SOC) on clinical and patient-related outcomes (e.g. efficacy, long-term safety, quality of life [QoL], personalized health, perceived health, health care resource utilization [HCRU], and continuity of cancer treatment).

Studies investigating the impact of treatment with B-cell-depleting therapies on the induction of hypogammaglobulinemia (HGG) across hematologic malignancies, autoimmune diseases, and transplant indications, with the goal of understanding the incidence of HGG for each indication and drug, the rate and severity of associated infections, and the potential protective role of IGRT in these settings.

Studies investigating the impact of IGRT on the underlying disease outcomes (i.e. cancer, autoimmune disorders, transplant) and treatment effects (in addition to its role in SID).

Primary Immunodeficiency (PID) Real-world evidence studies that provide insights into usage and administration parameters of subcutaneous immunoglobulin (SCIG) products, particularly in special populations not yet sufficiently studied (e.g. patients who are underweight, patients with certain comorbidities) Studies that assess and evaluate quality of life (QoL), personalized health and perceived health for IG replacement therapy Studies that explore novel or validate existing approaches in support of earlier PID diagnosis – especially those that could have global impact Studies with a focus on understanding the full presentation of PID including the impact of comorbidities on PID and/or vice versa Studies that assess and evaluate the application of new device or digital health concepts in the management of PID Clinical outcomes of long-term albumin treatment of patients with decompensated liver cirrhosis Clinical and analytical studies related to the concept of functional albumin Clinical experience with Flexbumin in patients with liver disease, and patients managed in intensive care units (ICUs) Central line-associated bloodstream infections (CLABSIs): Burden of illness, pharmacoeconomic impact and evaluations of prevention strategies Clinical outcomes of hyperoncotic (25% albumin) Flexbumin in patients with liver cirrhosis and critical care Impact of closed infusion system in albumin therapy on albumin storage, preparation, and handling Identification of biomarkers for albumin treatment of consequences or complications of liver diseases and in critically ill patients Alpha1-antitrypsin (AAT) deficiency (AATD) and AAT Augmentation Therapy: AATD pathogenesis, mechanisms, and biomarkers AATD clinical, humanistic, and economic burden of illness and co-morbid conditions Characterization of MZ patients Impact of early diagnosis and screening AAT Augmentation Therapy: for example, but not limited to: Adherence in AATD patients with emphysema/chronic obstructive pulmonary disease (COPD) AAT deficient patients in specific populations, (i.e. young adults/adolescents/older/post lung-transplant/forced expiratory volume (FEV) 1 35% Predicted) Exploratory research on anti-inflammatory, immunomodulatory, and tissue protective effects of AAT therapy in non-AATD individuals (i.e. graft vs host disease, autoimmune, rheumatoid arthritis, cardiac) C1-esterase inhibitor in Hereditary Angioedema (HAE) Real-world data (RWD) on effectiveness and safety of on demand use, as well as pre-procedural treatment, short- and long-term prophylaxis with C1-esterase inhibitor in HAE patients Understand dosing of C1-esterase inhibitor in the real-world setting Switching from oral HAE medications to C1-esterase inhibitor (including, but not limited to, reasons and patients’ perception/preferences/reported outcomes) RWD on C1-esterase inhibitor use in special patient populations like children, pregnant or breastfeeding women For disease related, non-product specific areas of interest please visit Hereditary Angioedema (HAE) section of the website (see above).

Activated prothrombin complex concentrate (aPCC) in Congenital Hemophilia A and B with Inhibitor (CHAWI) or Acquired Hemophilia (AHA) Preclinical and clinical studies examining the interaction between