Putting Research to the Test

Inclusion Criteria

• Clinically stable, mild atopic asthma (FEV1 ≥70% predicted)
• Established allergy confirmed by positive skin prick test at screening
• Willing and able to perform lung function tests and other study-related procedures
• Participants of childbearing potential must consent to use a method of highly-effective contraception in addition to a condom during the study and for at least 90 days following the end of study or last investigational product administration, whichever is later

Inclusion Criteria

• Age ≥50 years
• Lp(a)≥ 200 nmol/L during screening
• Multiple atherosclerotic cardiovascular disease risk factors, and/or evidence of atherosclerosis

Inclusion Criteria

• Willing to follow diet counseling as per Investigator judgment based on local standard of care
• Specific fasting TG, LDL-C, and non-high density lipoprotein cholesterol levels at Screening
• Participants of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of the study or last dose of study drug, whichever is later; participants must not donate sperm or eggs during the study and for at least 90 days following the end of the study or last dose of study drug whichever is later

Inclusion Criteria (All Participants)

• Body mass index between 18.0 and 35.0 kg/m^2 at Screening
• Not pregnant or breast-feeding
• Able and willing to provide written informed consent prior to the performance of any study specific procedures
• Participants of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of the study or last dose of study drug, whichever is later; participants must not donate sperm or eggs during the study and for at least 90 days following the end of the study or last dose of study drug whichever is later

Inclusion Criteria (Alzheimer's Disease)

• Adults aged 50 to 75 years of age with a clinical diagnosis of early AD and plasma, CSF, or imaging biomarkers consistent with the diagnosis
• On stable doses of AD-related medications for at least 8 weeks prior to Screening Visit and throughout the Screening period until Day 1

Inclusion Criteria

• Obesity, defined as BMI between 30-50 kg/m2, inclusive, with weight at Screening not to exceed 159 kg (350 lbs)
• At least one self-reported, unsuccessful attempt at weight loss with lifestyle modification
• No abnormal finding of clinical relevance at Screening that could adversely impact participant safety during the study or adversely impact study results
• Participants of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of the study or last dose of study drug, whichever is later. Participants must not donate sperm or eggs during the study for at least 90 days following the end of the study or last dose of study drug, whichever is later

Inclusion Criteria

• Age ≥12 years, non pregnant, non lactating, do not plan to become pregnant during the study
• Body weight ≥35 kg at Screening as patients could theoretically be <35 kg as the study continues.
• HoFH based on a supportive genetic test or a clinical diagnosis (total cholesterol >500 mg/dL OR treated LDL-C concentration of ≥ AND both parents with documented total cholesterol >250 mg/dL OR cutaneous or tendinous xanthoma before 10 years of age)
• LDL-C ≥70 mg/dL (1.8 mmol/L)
• Hemoglobin A1c (HbA1c) ≤9.5%
• Total bilirubin <2xULN, unless in previously confirmed cases of Gilbert's syndrome
• Alanine aminotransferase or aspartate aminotransferase <3×ULN
• On standard of care, maximally tolerated lipid-lowering therapy

Inclusion Criteria

• Obesity, defined as Body Mass Index (BMI) between 30 to 50 kg/m2 at Screening
• At least one self-reported, unsuccessful attempt at weight loss with lifestyle modification
• Willing, able and motivated to comply with all study assessments and adhere to the protocol schedule, including adherence to a stable diet and exercise routine for the duration of the study
• No abnormal finding of clinical relevance at Screening that, in the opinion of investigator, could adversely impact subject safety or adversely impact study results
• Participants of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of the study or last dose of study medication whichever is later
• Participants must not donate sperm or eggs during the study and for at least 90 days following the end of the study or last dose of study medication whichever is later

Inclusion Criteria

• Non-pregnant, non-lactating
• Diagnosis of symptomatic SCA2 and ≥33 CAG repeats in the ATXN2 gene based on source verifiable medical records or genetic testing at Screening
• Scale of Assessment and Rating of Ataxia (SARA) score ≤14
• Coagulation parameters within normal ranges at Screening
• Subjects of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of the study or last dose of study drug whichever is later.
• Subjects must not donate sperm or eggs during the study and for at least 90 days following the end of the study or last dose of study drug whichever is later

Inclusion Criteria

• Established diagnosis of hypertriglyceridemia (HTG) and prior documented evidence (medical history) of mean fasting TG level ≥150 mg/dL (≥1.69 mm/L) and ≤499 mg/dL (≤5.64 mmol/L)
• Mean fasting TG level ≥150 mg/dL (≥1.69 mmol/L) and ≤499 mg/dL (≤5.64 mmol/L) collected at 2 separate and consecutive visits at least 7 days apart and no more than 17 days apart during the screening period
• Fasting low density lipoprotein-cholesterol (LDL-C) ≤ 130 mg/dL (≤3.37 mmol/L) at screening
• Screening HbA1c ≤8.5%
• Willing to follow diet counseling and maintain a stable low-fat diet
• Must be on standard of care lipid-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator)

Inclusion Criteria

• Established diagnosis of severe hypertriglyceridemia (SHTG) and prior documented evidence (medical history) of fasting TG levels of ≥ 500 mg/dL (≥5.65mmol/L)
• Mean fasting TG level ≥500 mg/dL (≥5.65 mmol/L) collected at 2 separate and consecutive visits at least 7 days apart and no more than 17 days apart during the screening period
• Fasting low density lipoprotein-cholesterol (LDL-C) ≤130 mg/dL (≤3.37 mmol/L) at screening
• Screening HbA1C ≤8.5%
• Willing to follow diet counseling and maintain a stable low-fat diet
• Must be on standard of care lipid-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator)

Inclusion Criteria

• Established diagnosis of severe hypertriglyceridemia (SHTG) and prior documented evidence (medical history) of fasting TG levels of ≥500 mg/dL (≥5.65 mmol/L)
• Mean fasting TG level ≥500 mg/dL (≥5.65 mmol/L) collected at 2 separate and consecutive visits at least 7 days apart and no more than 17 days apart during the screening period
• Fasting low density lipoprotein-cholesterol (LDL-C) ≤130 mg/dL (≤3.37 mmol/L) at screening
• Screening HbA1C ≤8.5%
• Must be on standard of care lipid-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator)

Inclusion Criteria

• Healthy volunteers must be willing to be vaccinated with a meningococcal and pneumococcal vaccine. IgAN participants must have been vaccinated or willing to undergo vaccination
• Body Mass Index (BMI) between 18.0 and 35.0 kg/m2
• Must be willing to be vaccinated or have a history of vaccination for Haemophilus influenzae type B
• No abnormal finding of clinical relevance at the Screening evaluation that, in the opinion of the Investigator, could adversely impact participant safety or adversely impact study results.

Inclusion Criteria

• Genetically confirmed FSHD1 based on Screening evaluation or source verifiable medical record
• Clinical severity score between 3 and 8 (scale, 0 to 10)
• Must have eligible lower extremity muscle for biopsy as determined from MRI by a central reader
• A 12-lead electrocardiogram (ECG) at Screening with no abnormalities that may compromise participant's safety in the study
• Participants of childbearing potential and their partners must use highly effective contraception during the study and for at least 12 weeks following the end of study or last dose of study medication, whichever is later. Males must not donate sperm during the study from Day 1 until at least 12weeks following the end of study or last dose of study medication, whichever is later

Inclusion Criteria

• Key Inclusion Criteria for Participants with Hepatic Impairment and Participants with Normal Hepatic Function can be found on clincialtrials.gov
• Key Inclusion Criteria for Participants with Hepatic Impairment can be found on clincialtrials.gov
• Key Inclusion Criteria for Participants with Normal Hepatic Function can be found on clincialtrials.gov

Inclusion Criteria

• The participant enrolling in this open-label extension (OLE) study will have participated in a previously qualifying study, and will be considered for eligibility based on the study-specific criteria found on clincialtrials.gov

Inclusion Criteria

• The participant must have a diagnosis of the Z allele homozygotes (PiZZ) genotype AATD. PiZZ diagnosis from source verifiable medical records is permitted. Otherwise, participants must undergo PiZZ confirmatory testing (genotyping for PiS and PiZ alleles) at screening. PiMZ or PiSZ genotypes are not permitted
• The participant's liver biopsy core sample collected should meet the requirements of the protocol
• The participant has evidence of METAVIR stage F2, F3, or F4 liver fibrosis, evaluated by a centrally read baseline liver biopsy during the screening period; or confirmed as meeting all the entry criteria by central reading of a previous biopsy conducted within 6 months before the estimated enrollment date using an adequate liver biopsy and slides as defined in the study laboratory manual
• It must be confirmed that the participant does not have HCC. Participants will be screened for HCC with alpha-fetoprotein (AFP) and abdominal ultrasound. If the participant has any of the following, they will be required to have contrast-enhanced CT or MRI imaging to exclude HCC before randomization
• In adult participant must have a body mass index (BMI) between 18.0 and 39.0 kilograms per meter square (kg^m2), inclusive
• The participant is a nonsmoker for at least 12 months before screening

Inclusion Criteria

• In the opinion of the investigator, the participant is capable of understanding and fully complying with the protocol requirements and adhering to the protocol schedule
• The participant is able to read, understand, and complete the study questionnaires electronically per the investigator's judgment
• The participant signs and dates a written Informed Consent Form (ICF). Any required privacy authorization should also be signed before the initiation of any study procedures
• The participant must have a diagnosis of the protease inhibitor Z mutation (PiZZ) genotype AATD. A diagnosis of PiZZ from source-verifiable medical records is permitted. Otherwise, participants must undergo PiZZ confirmatory testing (genotyping for PiS and PiZ alleles) at screening. PiMZ or PiSZ genotypes are not permitted
• The participant's liver biopsy core samples should be collected as per protocol requirements
• The participant has evidence of METAVIR stage F1 liver fibrosis, evaluated by a centrally read baseline liver biopsy during the screening period; or confirmed as meeting all the entry criteria by central reading from a previous biopsy conducted within 1 year before the screening period using an adequate liver biopsy and slides as defined in the study laboratory manual
• Visit clinicaltrials.gov to see the full inclusion criteria

Inclusion Criteria

• Diagnosis of AATD
• Women of childbearing potential must have a negative pregnancy gest, cannot be breast feeding, and must be willing to use contraception
• Willing to provide written, informed consent and to comply with study requirements
• Non-smoker for at least 1 year
• No abnormal findings of clinical relevance at screening

Inclusion Criteria

• Genetically confirmed diagnosis of DM1
• Clinician-assessed signed of DM1 including clinically apparent myotonia
• Onset of DM1 symptoms occurred after the age of 12 years
• Walk for at least 10 meters independently at Screening
• Subjects of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of study or last dose of study drug, whichever is later. Subjects must not donate sperm or eggs during the study and for at least 90 days following the end of study or last dose of study drug whichever is later

Inclusion Criteria

• Age 18 to 80 years
• Lipoprotein (a) > 150 nmol/L
• Evidence of atherosclerotic cardiovascular disease

Inclusion Criteria

• Age 18 to ≤ 85 years
• Lp(a)≥ 200 nmol/L during screening
• History of ASCVD as evidenced by history of either: Myocardial infarction (presumed type 1 event due to plaque rupture/erosion) and/or Coronary revascularization with percutaneous coronary intervention AND at least 1 additional risk factor

Inclusion Criteria

• Body Mass Index (BMI) ≥25 kilogram per meter square (kg/m^2) (all ethnic origins) except for Asian participants who qualify for the study with BMI ≥23 kg/m2 at Screening
• In the opinion of the investigator, there are features of metabolic syndrome and NAFLD is the most likely cause of liver disease. Metabolic syndrome may include type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and hypertension
• A liver biopsy at baseline showing NAFLD Activity Score (NAS) >=4 with at least 1 point each in steatosis, inflammation and ballooning and Fibrosis CRN score of 3
• Able and willing to comply with all study assessments, including a liver biopsy at Week 52

Inclusion Criteria

• Participant must be 18 to 75 years of age
• Participant must be capable of giving signed informed consent which includes compliance with the requirements and restrictions listed for the study
• Participants who have proven diagnosis of NASH or suspected NASH based on defined study criteria
• Participants must meet predefined stable use requirements of concomitant medications based on study criteria

Inclusion Criteria

• Chronic hepatitis B virus (HBV) infection, hepatitis B e Antigen (HBeAg) positive or negative with suppressed viral replication under nucleos(t)ide analogue treatment for at least 6 months prior to screening
• Medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening
• Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
• Must have serum HBsAg greater than (>) 100 international units per milliliter (IU/mL) at screening, as assessed by quantitative HBsAg assay
• Must have a fibroscan stiffness measurement less than or equal to (<=) 9.0 Kilopascal (kPa) at screening

Inclusion Criteria

• Must have stable renal function defined as a less than (<) 20 percent (%) change in serum creatinine concentrations between screening and Day -1
• Concomitant medications should be stable for the previous 1 month and throughout the duration of the study
• Women, except for postmenopausal women, must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and urine (beta-hCG) pregnancy test on Day -1
• Must sign an informed consent form (ICF) indicating they understand the purpose of, and procedures required for the study and are willing to participate in the study
• Participants with kidney disease without dialysis using benzodiazepines, tricyclic antidepressants, and prescription opiates with a positive urine test for drugs prescribed by their physician may be included following prior discussion with the sponsor

Inclusion Criteria

• Medically stable based on physical examination, medical history, vital signs, laboratory values, and 12-lead Electrocardiogram (ECG) at screening
• Currently not treated chronic hepatitis B virus (HBV) infection with alanine transaminase (ALT) less than (<) 2* upper limit of normal (ULN) at screening and HBV deoxyribonucleic acid (DNA) greater than or equal to (>=) 20,000 international units per milliliter (IU/mL)
• Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
• Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than or equal to (<=) 9 Kilopascal (kPa) at screening

Inclusion Criteria

• For all participants: Body mass index (BMI) between 18.0 and 38 kilogram per meter square (kg/m^2), (extremes included), and a body weight not less than 50 kilograms (kg) at screening; Woman of childbearing potential must not be pregnant; Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential; Non-smoker or light smoker as defined per protocol
• For Healthy Participants with Normal Hepatic Function and No Liver Cirrhosis: Demographically comparable to the study groups with hepatic impairment with respect to sex, age (+/-10 years), and body weight (+/-10 kg); Participants must be in good health clinically and biologically as defined per protocol
• For Participants with Liver Cirrhosis and Moderate or Mild or Severe Hepatic Impairment: Must have a total Child-Pugh score of 5 or 6, inclusive (mild); or 7 to 9, inclusive (moderate); or 10 to 15, inclusive (severe) as determined by the investigator; Must have liver cirrhosis with fibro scan readout greater than (>) 12.5 Kilopascal (kPa) as cut-off at screening
• Participants with controlled hypertension, with problems directly associated with the primary diagnosis of hepatic impairment may be included. Participants may have concurrent stable medical conditions and may be included in the study if the investigator and the sponsor consider that the condition(s) will not introduce an additional risk factor and will not interfere with the study objectives and the procedures (that is, participants with mild degenerative joint disease, controlled diabetes, controlled thyroid conditions, other conditions addressed on a case by case basis)
• Concomitant medications to treat underlying disease states or medical conditions related to hepatic impairment are allowed

Inclusion Criteria

• Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
• Chronic hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening
• Hepatitis B e (antigen) (HBeAg)-negative on stable nucleotide analogue (NA) treatment for at least 24 months prior to screening
• Hepatitis B surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening
• Body mass index (BMI) between 18.0 and 35 kilogram per meter square (kg/m^2), extremes included
• Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
• Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than (<) 9 Kilopascal (kPa) at screening

Inclusion Criteria

• Participant must be a Japanese participant who has resided outside Japan for no more than 10 years and whose parents and grandparents are Japanese, as determined by participant's verbal report
• Participant must have a body mass index (BMI; weight in kilogram [kg] divided by the square of height in meters) of 18.0 to 30.0 kilogram per square meter (kg/m^2) extremes included, and body weight not less than 45.0 kg
• Participant must be healthy on the basis of physical examination, clinical laboratory tests, medical history, and vital signs performed at screening. In case of abnormalities (except for those listed in the exclusion criteria) a participant may be included after all if the investigator judges the abnormalities not clinically significant or appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator
• A female participant of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and a negative urine pregnancy test on Day -1
• A male participant must agree not to donate sperm after enrollment (Day 1) in the study until at least 90 days after receiving the study drug

Inclusion Criteria

• Medically stable on the basis of physical examination, medical history, vital signs, and triplicate 12-lead electrocardiogram (ECG) performed at screening
• Hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening: participants be either currently not treated with HBeAg positive status or virologically (nucleos[t]ide analog [NA]) suppressed with HBeAg negative status
• Hepatitis B surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening
• Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
• Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
• Fibroscan liver stiffness measurement less than and equal to (<=) 9 Kilopascal (kPa) within 6 months prior to screening or at the time of screening

Inclusion Criteria

• Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
• Chronic hepatitis B virus (HBV) and hepatitis D virus (HDV) co-infection with documentation at least 6 months prior to screening
• For Part 1: hepatitis D RNA (HDV RNA) greater than or equal to (>=) 1000 international units per milliliter (IU/mL) at screening. For Part 2: must have HDV RNA values >= 500 IU/mL, and must have hepatitis B surface antigen (HBsAg) values less than or equal to (<=) 10000 IU/mL at screening or HDV RNA values at screening are <= 100000 IU/mL
• Alanine aminotransferase (ALT) greater than upper limit normal (ULN) but less than 10 times (ULN)
• Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
• Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
• Non-cirrhotic participants and participants with compensated cirrhosis (Child Pugh class A) at screening (Part 1) and participants must have absence of cirrhosis and platelet count of >= 140000 per deciliter (dL) for enrollment into Part-2

Inclusion Criteria

• Participant must be healthy based on physical examination, laboratory assessment, vital signs and electrocardiogram (ECG) at screening
• A female participant of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [hCG]) pregnancy test at screening and a negative urine pregnancy test on Day -1
• A male participant must agree not to donate sperm after enrollment (Day 1) in the study and a female participant must agree not to donate eggs (ova, oocytes) during the study until at least 90 days after receiving the study drug
• Participant must not use nicotine-containing substances including tobacco products for at least 3 months prior to screening until completion of the study
• Participant must have suitable veins for cannulation and/or repeated venipuncture

Inclusion Criteria

• Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
• Chronic hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening
• Hepatitis B surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening
• Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
• Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
• Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than (<) 9 Kilopascal (kPa) at screening

Inclusion Criteria

• The subjects voluntarily participate in this study who are able to read, understand, and sign the ICF before participation; and have a full understanding of the content, process and possible adverse reactions of the study and are able to complete the study in accordance with the requirements of the protocol.
• Healthy male and female subjects aged between 18 and 55 years (both inclusive) at the time of informed consent.
• Body mass index (BMI) = weight (kg)/height (m)2, within the range of 19.0-30.0 kg/m2 (both inclusive), and body weight no less than 50 kg.
• In good general health and without clinically significant abnormalities as judged by the investigator, based on medical history, physical examination, vital signs, 12-lead ECG, and laboratory results.
• Negative serum pregnancy test within 72 h prior to initiation of study treatment in all premenopausal females and females who have been amenorrheic for less than 12 months. (Serum pregnancy test is not required for females who have undergone surgical sterilization, such as hysterectomy and/or bilateral oophorectomy, or those who have not experienced menses for 12 consecutive months and are judged to be postmenopausal based on factors such as age and castration therapy).
• Subjects and their partners must agree to use adequate contraceptive methods prior to initiation of study treatment, during the study, and for at least 3 months after discontinuation of study treatment.
• Fasting serum TGs >80 mg/dL (>0.903 mmol/L) at screening.

Inclusion Criteria

• Healthy male or female subjects, 18-55 years of age
• Be a non-smoker

Inclusion Criteria

• Male or female, 18-55 years of age, inclusive
• Able to provide written informed consent
• BMI between 19.0 and 35.0 kg/m2, inclusive
• 12-lead ECG at Screening and pre-dose with no clinically significant abnormalities
• Highly effective, double barrier contraception (both male and female partners) during the study and for 3 months following the dose of ARC-520
• Willing and able to comply with all study assessments
• Suitable venous access for blood sampling
• Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and creatinine levels in the normal range
• No abnormal finding of clinical relevance

Inclusion Criteria

• Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception
• Willing to provide written informed consent and to comply with study requirements
• Non-smoker for at least one year
• Normal lung function
• No abnormal finding of clinical relevance at Screening
• Normal AAT level at Screening visit

Inclusion Criteria for Parts A & B

• Women of childbearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use contraception.
• Willing to provide written informed consent and comply with study requirements

Additional Inclusion Criteria for Part B

• Diagnosis of chronic HBV infection
• HbsAg at screening > or = 50 IU/mL
• Liver Elastography score < or = 10.5

Inclusion Criteria

• Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding and must be willing to use contraception
• Willing to provide written informed consent and to comply with study requirements
• On a stable diet for at least 4 weeks with no plans to significantly alter diet or weight over course of study
• Normal electrocardiogram (ECG) at Screening

Inclusion Criteria

• Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding and must be willing to use contraception
• Willing to provide written informed consent and to comply with study requirements
• Histologically confirmed locally advanced or metastatic clear cell renal cell carcinoma that has progressed during or after at least two prior therapeutic regimens which must include vascular endothelial growth factor (VEGF)-targeted therapy and checkpoint inhibitor therapy or that has otherwise failed such therapies, is measurable disease per RECIST 1.1 criteria, is biopsy accessible
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Estimated life expectancy of longer than 3 months
• Adequate organ function at screening

Inclusion Criteria

• Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding and must be willing to use contraception
• Willing to provide written informed consent and to comply with study requirements
• On a stable diet for at least 4 weeks with no plans to significantly alter diet or weight over course of study
• Normal electrocardiogram (ECG) at Screening
• No abnormal finding of clinical relevance (other than NASH, suspected NASH in patients) at Screening that could adversely impact subject safety during the study or adversely impact study results

Inclusion Criteria

• Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding and must be willing to use contraception
• Willing to provide written informed consent and to comply with study requirements
• Normal electrocardiogram (ECG) at screening
• Hypertriglyceridemic patients must have a history of fasting serum triglycerides of at least 300 mg/dL (3.38 mmol/L) at screening or verifiable diagnosis of FCS

Inclusion Criteria

• Diagnosis of AATD
• Liver biopsy at Screening indicating liver fibrosis (score less than F4); a patient with no fibrosis may participate based on a previous biopsy conducted within one year
• Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception
• Willing to provide written informed consent and to comply with study requirements
• Non-smoker for at least 1 year
• No abnormal finding of clinical relevance at Screening

Inclusion Criteria

• Based on medical history, evidence of TG ≥ 500 mg/dL and ≤ 4000 mg/dL at Screening
• Fasting TG ≥ 500 mg/dL at Screening
• Willing to follow diet counseling per Investigator judgment based on local standard of care
• Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception
• Willing to provide written informed consent and to comply with study requirements

Inclusion Criteria

• Based on medical history, evidence of TG ≥ 150 mg/dL but ≤ 499 mg/dL
• Fasting levels at Screening of LDL-C ≥ 70 mg/dL OR non-HDL-C ≥ 100 mg/dL after at least 4 weeks of stable diet and stable optimal statin therapy
• Mean fasting TG ≥ 150 mg/dL and ≤ 499 mg/dL during Screening collected at two separate and consecutive visits and at least 7 days apart and not more than 17 days apart
• Willing to follow diet counseling and maintain a stable diet per Investigator judgment based on local standard of care
• Participants of childbearing potential must agree to use highly-effective contraception during the study and for at least 24 weeks from last dose of study medication
• Women of childbearing potential must have a negative pregnancy test and cannot be breastfeeding
• Women of childbearing potential on hormonal contraceptives must be stable on the medication for ≥ 2 menstrual cycles prior to Day 1
• Men must not donate sperm during the study and for at least 24 weeks following the last dose of study medication
• Able and willing to provide written informed consent and to comply with study requirements

Inclusion Criteria

• Based on medical history, evidence of TG ≥ 150 mg/dL but ≤ 499 mg/dL on more than one occasion
• Fasting levels at Screening of non-HDL-C ≥ 100 mg/dL OR LDL-C ≥ 70 mg/dL after at least 4 weeks of stable diet and stable optimal statin therapy
• Mean fasting TG ≥ 150 mg/dL and ≤ 499 mg/dL during Screening collected at two separate and consecutive visits and at least 7 days apart and not more than 14 days apart
• Willing to follow diet counseling as per Investigator judgment based on local standard of care
• Participants of childbearing potential (males & females) must use highly-effective contraception during the study and for at least 24 weeks following the last dose of study medication. Males must not donate sperm and females must ot donate eggs during the study and for at least 24 weeks following the last dose of study medication.
• Women of childbearing potential must have a negative pregnancy test at Screening and cannot be breastfeeding
• Women of childbearing potential on hormonal contraceptives must be stable on the medication for ≥ 2 menstrual cycles prior to Day 1
• Willing to provide written informed consent and to comply with study requirements

Inclusion Criteria

• Willing to provide written informed consent and to comply with study requirements
• Female participants must be non-pregnant/non-lactating
• Healthy volunteers must be willing to be vaccinated with a meningococcal and pneumococcal vaccine. C3G and IgAN participants must have been vaccinated or willing to undergo vaccination
• All participants must be willing to be vaccinated or have a history of vaccination for Haemophilus influenzae
• Body Mass Index (BMI) between 18.0 and 35.0 kg/m2
• 12-lead electrocardiogram (ECG) at Screening with no abnormalities that may compromise participant's safety at discretion of investigator
• Participants of childbearing potential must use highly effective contraception during the study and for at least 12 weeks following the end of the study or last dose of study drug, whichever is later. Males must not donate sperm during the study and for at least 12 weeks following the end of the study or last dose of study drug, whichever is later.
• No abnormal finding of clinical relevance at the Screening evaluation that, in the opinion of the investigator, could adversely impact participant safety or study results

Inclusion Criteria

• Fasting TG ≥ 10 mmol/L (≥ 880 mg/dL) at screening refractory to standard lipid lowering therapy
• Diagnosis of FCS
• Willing to follow dietary counseling as per investigator judgement based on local standard of care
• Participants of childbearing potential (males & females) must use highly-effective contraception during the study and for at least 24 weeks following the last dose of study medication. Males must not donate sperm during the study and for at least 24 weeks following the last dose of study medication
• Women of childbearing potential must have a negative pregnancy test at Screening and cannot be breastfeeding
• Women of childbearing potential on hormonal contraceptives must be stable on the medication for ≥ 2 menstrual cycles prior to Day 1

Inclusion Criteria

• Fasting LDL-C >100 mg/dL at Screening
• Weight of ≥ 40 kg and body mass index ≥ 18.5 and ≤ 40 kg/m2
• Diagnosis of HoFH based on a supportive genetic test or clinical diagnosis
• On stable maximally tolerated lipid lowering therapy
• Willing to abide by stable low-fat, low-cholesterol, heart-healthy diet for at least 4 weeks prior to Day 1
• Participants of childbearing potential (males & females) must agree to use highly-effective contraception during the study and for at least 24 weeks from the last dose of study medication.
• Women of childbearing potential must have a negative pregnancy test and cannot be breastfeeding
• Women of childbearing potential on hormonal contraceptives must be stable on the medications for > 2 menstrual cycles prior to Day 1
• Willing to provide written informed consent and to comply with study requirements

Inclusion Criteria

• Normal pulmonary function tests at Screening (NHVs only)
• Confirmed diagnosis of asthma based on source verifiable medical record (asthma patients only)
• No abnormal finding of clinical relevance at Screening (other than asthma for asthma patients)
• Stable dose of asthma controller medications for at least 4 weeks prior to Screening (asthma patients only)
• Non-smoking
• Able to produce an induced sputum sample at Screening
• Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception. Males must not donate sperm during the study and for at least 12 weeks following the last dose of study drug
• Willing to provide written informed consent and to comply with study requirements

Inclusion Criteria

• Normal pulmonary function tests at Screening (NHVs only)
• Confirmed diagnosis of asthma or COPD based on source verifiable medical record (asthma and COPD patients only)
• No abnormal finding of clinical relevance at Screening (NHVs only)
• Stable dose of asthma controller medications for at least 28 days prior to Screening (asthma patients only)
• Documented treatment with an inhaled corticosteroid and at least 1 additional maintenance asthma controller medication for at least 3 months prior to Screening (asthma patients only)
• Non-smoking (NHVs and asthma patients)
• Current smoker or ex-smoker with smoking history of ≥ 10 pack-years (COPD patients only)
• All COPD treatments have been stable for at least one month prior to Screening (COPD patients only)
• Able to produce an induced sputum sample at Screening
• Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception. Males must not donate sperm during the study and for at least 12 weeks following the last dose of study drug
• Willing to provide written informed consent and to comply with study requirements

Inclusion Criteria

• Adults who are nonpregnant, nonlactating and do not plan to become pregnant during the study
• Able and willing to provide written informed consent
• Completed the 48-week study treatment period in the parent study

Inclusion Criteria

• Normal pulmonary function tests at Screening prior to sputum induction
• Normal 12-lead electrocardiogram (ECG) at Screening
• Non-smoking
• Able to produce an induced sputum sample at Screening
• Participants of child-bearing potential (male and female) must use highly effective contraception and cannot donate sperm or eggs during the study or for at least 12 weeks following the end of the study or last dose of study drug, whichever is later. Women must have a negative pregnancy test and cannot be breastfeeding
• Willing to provide written informed consent and to comply with study requirements

Inclusion Criteria (NHVs)

• Normal pulmonary function tests at Screening
• Normal electrocardiogram (ECG) at Screening
• Non-smoking
• Female participants cannot be pregnant or lactating
• Male and female participants of childbearing potential must agree to use highly effective contraception and must not donate eggs/sperm during the study and for at least 90 days following end of study or last dose of study drug, whichever is later.

Inclusion Criteria (IPF Participants)

• Age ≥ 45 years at Screening
• Clinical diagnosis consistent with IPF based upon established criteria confirmed by review of high-resolution computed tomography (HRCT) and surgical lung biopsy findings (if available)
• Safely able to undergo bronchoscopy
• Stable IPF disease at Screening with minimum life expectancy of ≥ 12 months from Screening
• Female participants cannot be pregnant or lactating
• Male and female participants of childbearing potential must agree to use highly effective contraception and must not donate eggs/sperm during the study and for at least 90 days following end of study or last dose of study drug, whichever is later.