Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder with an estimated birth prevalence of ~1 in 3,500–5,000 live male births, characterized by onset of muscle weakness in early childhood, loss of ambulation around 9–13 years without effective disease-modifying therapy, and premature death from respiratory and cardiac failure in late teens to 20s.

ADA-SCID is an ultra-rare primary immunodeficiency with estimated incidence between roughly 1 in 200,000 and 1 in 1,000,000 live births. Classic disease presents in early infancy with severe, recurrent opportunistic infections, failure to thrive, and non-immune manifestations; without definitive treatment, most infants die within the first year or two (PAPER-01, PAPER-10). Newborn screening for SCID in many high-income regions enables presymptomatic diagnosis within weeks of life, shifting the therapeutic window earlier (PAPER-02, PAPER-10).

Ultra-rare neurodevelopmental disorder with several hundred to a few thousand diagnosed individuals worldwide; onset in neonatal/infant period with profound, lifelong disability and global distribution concentrated in tertiary pediatric neurology/genetics centers.

X-linked SCID accounts for approximately 40-50% of severe combined immunodeficiency cases worldwide; incidence of all SCID is roughly 1 in 50,000 to 1 in 100,000 births, with higher detection in regions with newborn screening.

Genetic (inherited) prion diseases, including inherited CJD, account for about 10–15% of all human prion diseases (PAPER-01, BIOMNI-07). Overall prion disease incidence is well below 1 per 100,000 person-years, qualifying as ultra-rare (WEB-07). Inherited CJD is an autosomal dominant disorder caused by pathogenic PRNP variants (WEB-01, WEB-02, BIOMNI-07). Onset is typically in mid- to late-adulthood, but many mutation carriers remain presymptomatic for decades (PAPER-04, PAPER-05).

Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder with a birth prevalence around 1 in 3,500–5,000 live male births worldwide. Affected boys typically present in early childhood with delayed motor milestones and proximal weakness, lose independent ambulation around 10–12 years of age, and, despite optimized multidisciplinary care, often die in early adulthood from respiratory failure or cardiomyopathy. The disease burden is concentrated in regions with specialized neuromuscular centers and registries but cases are globally distributed.

SCID overall incidence is about 1/50,000–1/58,000 live births in high-income settings, with higher frequencies reported in consanguineous or isolated populations. X-linked IL2RG defects account for around 30% of SCID in Western cohorts; other monogenic causes include ADA, JAK3, IL7R, DCLRE1C (Artemis), RAG1/2 and others. Without treatment, most affected infants die from severe infections within the first 1–2 years of life.

Beta-thalassemia (ORPHA:848) is an autosomal recessive disorder caused by reduced (β+) or absent (β0) synthesis of the β-globin chains of adult hemoglobin. Orphanet reports a global prevalence on the order of 1–9 per 1,000,000 in the general population, but carrier frequencies are much higher (up to 10–20%) in high-prevalence regions such as the Mediterranean, Middle East, South and Southeast Asia. Clinically, three main types are recognized—minor, intermedia, and major—corresponding broadly to carrier, non–transfusion-dependent (NTDT), and transfusion-dependent (TDT) phenotypes. TDT typically presents in infancy or early childhood with severe anemia requiring lifelong regular transfusions to maintain hemoglobin around 9–10 g/dL, and is associated with substantial morbidity and premature mortality unless optimally managed.

Exceptionally rare autosomal recessive disorder with incidence ~0.6-1 per 1,000,000 newborns worldwide; presents in neonates with severe unconjugated hyperbilirubinemia and high risk of kernicterus.

Canine hemophilia B is a rare X-linked bleeding disorder reported in multiple breeds (e.g., Hovawart family with Leyden-like phenotype, experimental colonies). Large, population-based incidence data for pet dogs are lacking. Human severe hemophilia B affects ~1 in 25,000–30,000 male births, with persistent excess mortality and morbidity despite modern care (PAPER-07, BIOMNI-05).

Extremely rare, with an estimated incidence of ~1 in 20 million births and global prevalent population on the order of 100–200 children alive at any time, with cases concentrated in countries with access to molecular diagnosis and registries (North America, Europe, selected other regions) [WEB-04, WEB-07].

SCID comprises a group of at least 20 monogenic primary immunodeficiencies including familial forms; infants typically present in the first months of life with severe, recurrent and opportunistic infections and failure to thrive, and the disease is uniformly fatal without treatment. X-linked IL2RG-SCID and ADA-SCID are among the more frequent subtypes, but each genetic subtype remains rare.

Ultra-rare primary monoamine neurotransmitter disorder with only dozens to a few hundred diagnosed patients worldwide; founder variants cause higher prevalence in some East Asian populations; substantial underdiagnosis likely (WEB-03, WEB-08, PAPER-03, PAPER-06, PAPER-09).

Approximately 60,000 symptomatic beta-thalassemia births annually worldwide, with highest prevalence in the Mediterranean, Middle East, South and Southeast Asia; beta-thalassemia major presents in infancy with severe anemia and is universally transfusion-dependent without curative therapy.

Incidence approximately 1 in 200,000-250,000 live births with higher prevalence in consanguineous populations; over 50% of ARO due to TCIRG1, 10-15% due to CLCN7, smaller fractions due to OSTM1, CA2 and others.

Autosomal recessive 5q spinal muscular atrophy has an incidence of roughly 1 in 10,000–11,000 live births with carrier frequency about 1 in 50; SMA type 1 is the most common and severe form, with onset before 6 months and historically death or permanent ventilation before age 2 without treatment.

Neuronal ceroid lipofuscinoses (NCLs) are ultra-rare, autosomal recessive, fatal pediatric neurodegenerative lysosomal storage disorders with an overall prevalence around 1 in 100,000 live births, with higher incidence in founder populations such as Finland (CLN1 about 1 in 20,000) [WEB-01, WEB-11, PAPER-01]. Infantile CLN1 disease typically presents between 6 and 18 months with rapid psychomotor regression and early death, while late-infantile CLN2 disease presents around 2–4 years with seizures and language delay followed by rapid loss of motor and cognitive function and death in late childhood if untreated [PAPER-08, PAPER-09]. Congenital-onset NCL is rarer but represents the extreme of this spectrum with symptom onset at birth or in the first months of life [WEB-01, WEB-10, PAPER-01].

Dravet syndrome is a rare, severe developmental and epileptic encephalopathy with onset in the first year of life, most often due to de novo heterozygous loss-of-function variants in SCN1A. Population-based data from the United States indicate that SCN1A-positive Dravet syndrome is more common than previously estimated, and Orphanet categorizes Dravet as an ultra-rare disease with prevalence below approximately 1 in 50,000, consistent with several hundred to a few thousand patients in high-income regions. Diagnostic delay is substantial: claims-based analyses of 770 individuals show a median age at diagnosis around 4.2 years despite seizure onset in infancy, implying a multi-year window of uncontrolled disease and missed early-intervention opportunities.

Fanconi anemia (all subtypes) is an ultra-rare inherited bone marrow failure and cancer predisposition syndrome with an estimated incidence of roughly 1–5 per 1,000,000 individuals. Registry and review data indicate that the cumulative incidence of bone marrow failure exceeds 50% by age 40 years, with approximately 20% risk of acute myeloid leukemia and around 30% risk of solid tumors (especially head and neck and gynecologic squamous cell carcinoma). Most patients develop bone marrow failure in the first decade of life. FANCT/UBE2T is an extremely rare complementation group with only a small number of families and case reports, but affected individuals show classic FA features including congenital anomalies, early-onset cytopenias, and progression to pancytopenia or AML in childhood.

Executed all paper-assigned subtasks from plan.jsonl for Hb Bart's hydrops fetalis / alpha-thalassemia major. For severity/urgency (S1-S3, U1-U2), collected cohort and registry data on survival, neurodevelopment, organ damage, healthcare utilization, and chronic transfusion/chelation burden, plus regional prevalence/incidence. For therapeutic strategies (F1-F5), reviewed HSCT, intrauterine and postnatal transfusion programs, emerging maternal–fetal stem cell transplantation, and lentiviral HSC gene therapy and gene-editing approaches targeting HBA1/HBA2 or compensatory pathways. For pathophysiology/targets and genotype–phenotype thresholds, synthesized reviews and guidelines on alpha-thalassemia molecular mechanisms, Hb Bart's fetal hydrops pathogenesis, and correlations between number of functional alpha-globin genes, HbH disease, and Hb Bart's. DALY/QALY estimates specific to Hb Bart's remain unavailable; burden is inferred from global hemoglobinopathy burden and severe thalassemia cohorts. In‑utero gene editing data specific to alpha-thalassemia are still preclinical or extrapolated from related hemoglobinopathies; no mature clinical trials yet.

Congenital or early-onset severe-to-profound sensorineural hearing loss with auditory neuropathy phenotype (absent ABR, preserved otoacoustic emissions). OTOF mutations account for a substantial subset of auditory neuropathy spectrum disorder cases in several populations; congenital severe-to-profound hearing loss overall occurs in ~1:500–1:2000 newborns, with hereditary causes in >50% of prelingual cases.

MELAS is a rare mitochondrial encephalomyopathy caused most often by MT-TL1 m.3243A>G; carrier prevalence may be as high as 1 in 400 in some populations, but clinically overt MELAS is much rarer, with onset typically in childhood or early adulthood and high mortality within ~17 years of neurologic onset (WEB-01, WEB-03, PAPER-07, PAPER-08, PAPER-09, BIOMNI-05).

Mitochondrial complex I deficiency is the most common primary mitochondrial disorder and Leigh syndrome is a frequent clinical presentation. Nuclear type 4 due to NDUFS4 is an autosomal recessive subtype within the complex I deficiency phenotypic series (OMIM PS252010). Precise prevalence for NDUFS4-related disease is unknown but is considered ultra-rare; Leigh syndrome overall is estimated at roughly 1 in 40,000–100,000 live births based on cohort and registry data (WEB-02, WEB-07). Affected children typically present in infancy or early childhood with progressive neurodegeneration, lactic acidosis, and characteristic MRI brainstem/basal ganglia lesions (WEB-01, WEB-03, WEB-04, WEB-08).

Congenital myotonic dystrophy (CDM1) is the most severe form of myotonic dystrophy type 1, typically presenting at birth with hypotonia and respiratory failure. Birth prevalence estimates from Orphanet and registries suggest DM1 overall around 1:8,000, with congenital forms a small subset, often clustering in families with very large maternal CTG expansions.

~24 reported sFI cases worldwide, all PRNP 129MM, PrPSc type 2; ultra-rare sporadic prion disease with middle-age onset.

Affects approximately 200 million people worldwide, prevalence increasing to 288 million by 2040. Higher prevalence in European ancestry populations with 30-40% carrying risk allele.

1 in 12,000-20,000 live births (~500,000 globally), no gender preference, affects males and females equally

Hemophilia A is an X-linked congenital bleeding disorder caused by deficiency or dysfunction of coagulation factor VIII and accounts for ~80% of hemophilia cases. Birth prevalence in males is ~24.6 per 100,000, and overall prevalence is ~1 in 5,000 live male births (WEB-01, WEB-11). Severe disease (FVIII <1% activity) leads to spontaneous joint, muscle, and internal bleeding; moderate (1-5%) and mild (6-40%) disease bleed mainly after trauma or surgery (WEB-01). U.S. DALY burden was estimated at ~110,000 DALYs in 2007, highlighting substantial population-level impact (WEB-06).

Ultra-rare inherited bone marrow failure syndrome with fewer than 100 reported cases worldwide and estimated prevalence <1/1,000,000; most cases present in the neonatal period with severe thrombocytopenia and progress to pancytopenia and marrow failure in early childhood (WEB-01, WEB-03, WEB-09, PAPER-01, PAPER-05).

IL2RG-related X-SCID accounts for ~40–50% of SCID cases and presents in early infancy with severe, often fatal infections without curative therapy (WEB-02, BIOMNI-01). Classical SCID birth prevalence in developed settings is around 1/40,000–1/60,000 live births (WEB-05).

Bilateral renal agenesis is a rare, typically lethal congenital anomaly with reported birth prevalence around 1 in 8,000-10,000 births, including live births, fetal deaths, and terminations (EUROCAT BRAHD data and Orphanet registry). Most cases present with oligohydramnios/anhydramnios and Potter sequence; perinatal or early neonatal mortality is historically near 100% without experimental fetal intervention.

Global birth prevalence of PAH-deficient PKU is ~1:16,000–1:24,000 newborns, with higher rates in certain countries (e.g., up to ~1:4,000 in parts of the Middle East) and routine newborn screening in most high-income regions.

Ultra-rare autosomal recessive congenital liver disease characterized by severe unconjugated hyperbilirubinemia presenting in the neonatal period; precise prevalence is unknown but considered extremely low.

JNCL/CLN3 disease is the most common form of neuronal ceroid lipofuscinosis, with incidence estimates ranging from ~0.02 to 4.8 per 100,000 worldwide and overall Batten disease prevalence around 1 in 100,000 live births (PAPER-01, WEB-01). Onset typically occurs at 5-7 years with rapid progression and death in the late teens to 20s (PAPER-09, WEB-03).

Leigh syndrome (ORPHA:506) is a rare, early-onset mitochondrial encephalomyelopathy with an estimated birth prevalence around 1 in 36,000–40,000. Onset is typically in infancy (median ~7 months), and over half of patients die within the first few years of life. Cardiac involvement, particularly hypertrophic cardiomyopathy and conduction disease, is a recognized complication and is associated with worse prognosis in mitochondrial disease cohorts, including Leigh syndrome.

Complex I deficiency is the most common childhood respiratory chain disorder, frequently presenting as Leigh or Leigh-like syndrome with high early mortality; NDUFS2 mutations explain a subset of nuclear-encoded complex I cases.

Executed all subtasks assigned to web in plan.jsonl: (1) characterized SMA phenotypes and care pathways with focus on prenatal/infantile onset using Orphanet-style disease overviews, payer policies and SMA newborn-screening practice data; (2) quantified severity and economic/market aspects via HTA reports (NCPE) and ICER draft scope for SMA therapies; (3) mapped current and pipeline therapies (nusinersen, onasemnogene abeparvovec, risdiplam, apitegromab) and stages through ClinicalTrials.gov and payer monographs, annotating modalities; (4) aggregated epidemiology and patient-flow data from US newborn screening and NBS practice surveys; (5) compiled regulatory and ethical context for early gene therapy/editing using FDA gene therapy guidance listings and analysis of CBER expectations for long-term follow-up. Phenotype-specific data for "prenatal-onset SMA with congenital bone fractures" per se remain sparse and were approximated using SMA type 0/1 and SMABF2 literature (not fully accessible via web tools), which is noted as a gap.

Autosomal recessive hemoglobinopathy prevalent in individuals of African, Middle Eastern, and Indian descent; A allele frequency ~0.10 in African ancestries (BIOMNI-08).

RPE65-LCA is an ultra-rare autosomal recessive inherited retinal dystrophy causing severe early-onset vision loss and progressive retinal degeneration; inherited retinal diseases overall affect about 1 in 4000 people with substantial national economic burden.

Myotonic dystrophy type 1 (DM1, Steinert disease) has an overall prevalence between ~1/2,300 and 1/8,000 in many populations, with regional clusters [WEB-02, WEB-09]. Congenital-onset DM1 represents the most severe end of the spectrum and is relatively rare but captured in pediatric DM1 registries [PAPER-01, WEB-09]. Congenital cases typically arise from maternal transmission of very large CTG expansions (>2000 repeats) [WEB-03, BIOMNI-02, BIOMNI-05].

Rett syndrome is a rare X-linked neurodevelopmental disorder, almost exclusively affecting girls, with prevalence around 1 in 10,000 female births. Onset follows 6–18 months of apparently normal development, after which regression leads to severe intellectual disability and lifelong care needs.

Canine mucopolysaccharidosis VII (MPS VII) is a rare, autosomal recessive lysosomal storage disease reported in multiple dog breeds and also in cats and mice as spontaneous models. Genetic summaries indicate that spontaneous canine and feline models faithfully recapitulate human MPS VII with residual GUSB activity typically below 2% of normal and widespread storage vacuoles in many tissues, including brain ganglion cells (BIOMNI-08, BIOMNI-09). Precise breed-specific incidence and prevalence figures are not well established; available data come from research colonies and isolated breed reports, so the overall patient population is small and geographically scattered but clustered in referral/academic centers.

Iatrogenic Creutzfeldt-Jakob disease (iCJD) is an acquired prion disease caused by medical procedures that transmit infectious prions. Major sources include cadaveric human growth hormone, dura mater grafts, and to a lesser extent contaminated neurosurgical instruments, corneal grafts, and other pituitary-derived products. CDC reviews report 226 growth hormone–associated cases with incubation periods of 5–42 years (mean ~17 years) and attack rates up to ~6% in some national cohorts [WEB-02]. Dura mater graft–associated series from Japan identify over 140 cases with median incubation ~13 years and long latency after neurosurgical procedures [PAPER-03]. Overall, iCJD accounts for roughly 1–5% of all CJD cases [PAPER-01], and CJD as a whole has an incidence of ~1 case per million population per year worldwide [WEB-10]. iCJD cases cluster in countries that historically used cadaver-derived growth hormone or specific dura products (e.g., France, UK, USA, Japan) [WEB-01, PAPER-03].

LCA overall prevalence is approximately 1/33,000-1/50,000 live births and accounts for around 5% of inherited retinal dystrophies and 20% of childhood blindness; GUCY2D is one of the more common molecular causes but exact LCA7 subtype prevalence is uncertain. Patients typically present in infancy with nystagmus, extinguished ERG, and severe visual impairment, with relatively preserved retinal structure on OCT into childhood and even midlife (WEB-01, WEB-02, WEB-03, PAPER-01, PAPER-02).

RAG1/2 defects account for roughly 10-20% of SCID cases; cohort data from Slavic countries suggest a minimal RAG deficiency incidence of ~1:180,000-1:300,000 live births (PAPER-01, WEB-08, WEB-09).

Rare primary immunodeficiency (SCID subtype) with estimated birth prevalence on the order of 1 in 50,000–100,000 births; represents one of the most common genetically defined SCID forms detected by TREC-based newborn screening.

Over 500,000 infants are born with sickle cell disease annually worldwide, with high prevalence and mortality concentrated in sub-Saharan Africa, India, and the Middle East; approximately 100,000 affected individuals live in the United States (PAPER-04, WEB-01).

IL10RA-deficient very-early-onset IBD is an ultra-rare autosomal recessive monogenic form of inflammatory bowel disease, typically presenting in the first months of life with severe enterocolitis, perianal disease, and failure to thrive. Cohort and regional data suggest that monogenic VEO-IBD constitutes a minority of pediatric IBD (often <5–10% overall), with IL10RA/B defects representing a small subset, but with very high morbidity and mortality without definitive treatment (PAPER-01, PAPER-04, WEB-02).

Perinatal-lethal Gaucher disease (PLGD) is an extremely rare, most severe end of the type 2 (acute neuronopathic) Gaucher disease spectrum. It typically presents prenatally or in the neonatal period with non-immune hydrops fetalis, collodion-baby/ichthyotic skin, arthrogryposis, respiratory failure, hepatosplenomegaly, cytopenias, and early neurologic involvement, leading to death in utero or within weeks to a few months despite intensive care (WEB-02, PAPER-01, PAPER-02, PAPER-04, PAPER-08, BIOMNI-03, BIOMNI-06). Overall Gaucher disease incidence is ~1:40,000–1:100,000 live births, but neuronopathic forms (types 2 and 3 combined) are much rarer, roughly 1:100,000–300,000; perinatal-lethal cases may be at least as frequent as classic type 2 yet substantially under-recognized because many affected fetuses die before or soon after birth without specific diagnosis (WEB-08, PAPER-02, PAPER-04). Registries and case series confirm that survival for type 2 Gaucher remains under 2 years despite modern supportive care (PAPER-03, PAPER-08, PAPER-11, PAPER-13).

RAG1/2-related T-B- NK+ SCID is an ultrarare autosomal recessive primary immunodeficiency. Orphanet describes severe combined immunodeficiency due to complete RAG1/2 deficiency with prevalence 1–9 per 100,000 for SCID as a group (WEB-01), while a multicentre cohort of 82 RAG-deficient patients from Slavic countries estimated a minimal annual incidence of RAG deficiency of roughly 1 in 180,000–300,000 live births in that region (PAPER-01). RAG2 deficiency contributes a minority of overall SCID cases but is enriched in certain populations with founder variants.

Ischaemic heart disease, predominantly coronary artery disease (CAD), is the leading cause of death worldwide and accounts for ~23.5% of DALYs among non-communicable diseases; DALYs due to ischaemic heart disease increased by ~28% from 2005 to 2015 [PAPER-01]. Elevated lipoprotein(a) affects tens of millions: ~64 million people in the US have Lp(a) ≥60 mg/dL and ~3 million have ≥180 mg/dL, conferring very high coronary risk [WEB-09]. Monogenic and oligogenic dyslipidaemias such as familial hypercholesterolaemia (LDLR, APOB, PCSK9) and genetically elevated Lp(a) (LPA) drive premature CAD in high-risk subgroups [WEB-04, BIOMNI-02, BIOMNI-03].

Dystrophin-deficient muscular dystrophy has been reported in at least 15 dog breeds (BIOMNI-07), including Golden Retrievers, Beagles (DE50-MD), Cavalier King Charles Spaniels, Welsh corgis, Rottweilers, Cocker spaniels, Tibetan terriers, German shorthaired pointers and others (BIOMNI-06). These cases are rare and typically confined to research or familial colonies, mirroring the X-linked recessive inheritance and early-onset progressive course of human DMD (BIOMNI-05, PAPER-06).

Inherited epidermolysis bullosa overall has a prevalence around 11 per million; DEB subtypes ~3.3 per million, with roughly similar prevalence of dominant and recessive forms. Disease is ultra-rare but present worldwide, with patients concentrated in specialized centers and registries.

Extremely rare neonatal-lethal laminopathy with prevalence <1/1,000,000 and only a few dozen cases reported worldwide; cases are globally scattered and usually identified in tertiary perinatal centers (Orphanet ORPHA:1662 and clinical case series).

~100,000 affected individuals in the US and millions worldwide; highly prevalent in sub-Saharan Africa, India and the Middle East, with carrier frequencies >10% and birth prevalence >1% in some regions.

PLA2G6-associated neurodegeneration (PLAN/NBIA2A) is an ultra-rare, autosomal recessive neurodegenerative disorder with an estimated prevalence around 1 per million, presenting as a spectrum that includes infantile neuroaxonal dystrophy (onset 6–36 months), atypical childhood-onset neuroaxonal dystrophy, and adult-onset PLA2G6-related dystonia-parkinsonism. Cohort and registry data indicate small, geographically dispersed patient numbers with cases reported worldwide.

Global prevalence of all hemophilia B is ~3.8/100,000 males and severe hemophilia B ~1.1/100,000 males, implying ~289,000 severe cases worldwide; disease is concentrated in countries with established registries and hemophilia treatment centers.

Extremely rare, with only a few reported infants with combined saposin (prosaposin, PSAP) deficiency worldwide; presentations are typically neonatal or very early infantile with severe neurovisceral storage disease and death within months. Overall PSAP-related spectrum (isolated saposin deficiencies causing Gaucher-like or metachromatic leukodystrophy-like phenotypes) remains ultra-rare, with only scattered case reports and small series.

Fanconi anemia overall has an estimated prevalence between 1 in 100,000 and 1 in 350,000 live births, with higher incidences in certain founder populations (WEB-04). It is usually inherited in an autosomal recessive manner with more than 20 genes implicated including BRCA2/FANCD1 (WEB-04). BRCA2/FANCD1 represents a rare but extremely severe subset; a leukemia-focused review reports that FANCD1/BRCA2 patients have a cumulative incidence of cancer of approximately 97% by age 7 years, with acute myeloid leukemia, brain tumors, and Wilms tumor predominating (PAPER-01). Broader Fanconi anemia cohorts show cumulative risks by age 40 years exceeding 50% for bone marrow failure, 20% for acute myeloid leukemia, and 30% for solid tumors (PAPER-02, PAPER-03, WEB-02).

Frontotemporal dementia (FTD) is an early-onset dementia with a prevalence of roughly 10–15 per 100,000 and accounts for 5–10% of all dementias, often presenting before age 65 [WEB-01, PAPER-03]. Amyotrophic lateral sclerosis (ALS) has an incidence of about 1–3 per 100,000 person-years and a prevalence of 4–6 per 100,000, with median survival 3–5 years from symptom onset [WEB-02, PAPER-04]. Familial forms (often due to C9orf72, SOD1, GRN, MAPT and other genes) represent around 10% of ALS and a substantial fraction of familial FTD [PAPER-04, PAPER-05, BIOMNI-01–BIOMNI-04].