We are a biotechnology company developing novel small molecule therapeutics to treat diseases across several therapeutic areas, including central nervous system (“CNS”) disorders, lysosomal storage disorders (“LSDs”), metabolic disorders, and other diseases that can be targeted through protein degradation, such as oncology.
−Removed: GT-02287 - our lead product candidate:
−Removed: for the treatment of GBA1 Parkinson’s disease and other synucleinopathies
−Removed: Our clinical stage product candidate, GT-02287, is being developed for the treatment of GBA1 Parkinson’s disease.
+Added: GT-02287 - our lead product candidate, for the treatment of Parkinson’s disease, is currently being evaluated in a Phase 1b study in people with Parkinson’s disease with or without a GBA1 mutation.
We have generated an extensive preclinical data package providing evidence of the mechanism of action and safety of GT-02287.
−Removed: In preclinical models of GBA1 Parkinson’s disease, GT-02287 has been shown to restore glucocerebrosidase, or GCase, function in the lysosome, reduce toxic lipid substrates and toxic forms of alpha-synuclein, improve survival of dopaminergic neurons, increase dopamine levels, completely restore locomotor function, and reduce plasma-based neurodegeneration maker, neurofilament light chain, or NfL, back to the level of healthy animals.
−Removed: In September 2023, we initiated in Australia the first-in-human Phase 1 clinical trial to assess the safety, tolerability, pharmacokinetics, and food effect of GT-02287 in healthy participants.
−Removed: The study design includes a single ascending dose part during which the study participants receive one dose of GT-02287 at different dose levels, and a multiple ascending dose part during which the study participants receive one daily dose of GT-02287 for 14 days at different dose levels.
−Removed: In February 2024, we initiated the multiple ascending dose part of this Phase 1 clinical trial, which we anticipate completing in the second quarter of 2024, with the availability of the quality assurance audited interim report in the third quarter of 2024.
−Removed: We are planning to expand the scope of this Phase 1 clinical trial by amending the study protocol to include a cohort of 12-15 patients with Parkinson’s disease.
−Removed: These patients will be treated for a period of three months to evaluate safety, tolerability, and pharmacokinetics in patients, as well as to assess the effect of GT-02287 on certain biomarkers of the GCase disease cascade.
−Removed: In preparation for the treatment of Parkinson’s disease patients, in September 2023, we initiated the sub chronic (13 weeks treatment) preclinical toxicity study.
−Removed: The in-vivo phase of the preclinical toxicity study was concluded in January 2024 with the final, quality assurance audited, report expected by the beginning of the second quarter of 2024.
−Removed: In addition, we are planning to initiate the chronic (6 months in rodents and 9 months in non-rodents) preclinical toxicity study in the second half of 2024, enabling the conduct of clinical studies in patients with a GT-02287 treatment duration beyond three months.
+Added: In preclinical models of GBA1 and idiopathic Parkinson’s disease, GT-02287 has been shown to restore glucocerebrosidase, or GCase, function in the lysosome, improve mitochondrial health, reduce toxic lipid substrates and toxic forms of alpha-synuclein, reduce neuroinflammation, improve survival of dopaminergic neurons, increase dopamine levels, completely restore locomotor function and improve cognition, and reduce plasma-based neurodegeneration maker, neurofilament light chain (NfL) back to the level of healthy animals.
+Added: In September 2024, we reported results from a first-in-human Phase 1 clinical trial completed in Australia to assess the safety, tolerability, pharmacokinetics, and food effect of GT-02287 in healthy participants.
+Added: The study enrolled 72 healthy volunteers and included a single ascending dose part during which the study participants (n=40) received one dose of GT-02287 at different dose levels, and a multiple ascending dose part during which the study participants (n=32) received one daily dose of GT-02287 for 14 days at different dose levels.
+Added: Review of the unblinded data after database lock confirmed that single and multiple doses of GT-02287 were safe and generally well tolerated up to and including the highest planned dose levels across all age groups (approximately 15% of which were over the age of 50 years).
+Added: The single and multiple dose levels tested were safe and generally well tolerated, with no serious adverse events or Grade 3 (severe) adverse events observed, and no other safety signals detected.
+Added: The PK profile of GT-02287 was linear across the tested dose ranges, and plasma exposures at daily doses of 7.7 mg/kg and above were within the projected therapeutic range.
+Added: GT-02287 was measurable in cerebrospinal fluid (CSF) at levels in line with rodent levels at effective doses from our preclinical models, demonstrating CNS exposure.
+Added: Notably, GCase activity in dried blood spots increased approximately 53% in subjects who received 13.5 mg/kg GT-02287 (the highest dose cohort and the only dose cohort analyzed for GCase activity) but not in those who received placebo, demonstrating target engagement and modulation of GCase enzyme.
+Added: GCase activity continued to increase 12 hours post-dose at 14 days, the furthest time point analyzed in the study.
+Added: We believe these results support the continued development of GT-02287 and its potential as a biology-modifying treatment for Parkinson’s disease.
+Added: Importantly, the favorable safety and tolerability profile at oral dose levels that resulted in therapeutic plasma levels, CNS exposure, and target engagement further strengthens GT-02287’s potential to be a lead treatment for Parkinson’s disease in patients with or without a GBA1 mutation.
+Added: In December 2024, we received approval in Australia to initiate a Phase 1b trial for GT-02287 in people with Parkinson’s disease with or without the GBA1 mutation.
+Added: We are working with local Parkinson’s disease (PD) advocacy groups in Australia to support enrollment and expect enrollment to complete in the summer of 2025 with interim data from the study expected by mid-2025.
+Added: The Phase 1b open-label trial will assess the safety and tolerability of 13.5 mg/kg/day of GT-02287 for three months in patients with GBA1-PD or idiopathic Parkinson’s disease.
+Added: Secondary endpoints include pharmacokinetics, GCase modulation, levels of GCase substrates, and other biomarkers in plasma and cerebrospinal fluid.
+Added: The primary goal of the Phase 1b trial is to assess the safety and tolerability of GT-02287.
+Added: Upon successful completion we expect to begin planning a Phase 2 study during the second half of 2025.
+Added: In preparation for the treatment of Parkinson’s disease patients, we initiated a chronic (6 months in rodents and 9 months in non-rodents) preclinical toxicity study in July 2024, enabling the conduct of clinical studies in patients with a GT-02287 treatment duration beyond three months.
+Added: The 6- and 9-month studies will be completed in the second quarter of 2025 and the third quarter of 2025, respectively.
Our Magellan™ Platform
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and the ability to identify small molecules with more favorable drug-like properties.
−Removed: The Magellan™ drug discovery platform is an evolution of its predecessor SEE-Tx®, or Site-Directed Enzyme Enhancement Therapy.
−Removed: Magellan™ integrates and adds to the foundational models of SEE-Tx® with proprietary AI and machine learning tools that enable the screening of over 50 billion compounds.
Discovering and targeting novel allosteric sites with our platform not only reduces traditional drug discovery timelines but enables rational drug design and offers the potential for superior small molecule drugs that are highly specific and that can penetrate hard to reach tissues and cross the blood-brain barrier.
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Allosteric Binding Site Identification
−Removed: Using the three-dimensional structure of proteins that have been experimentally derived or generated or predictive protein structures from AI-powered databases such as Alphafold, our Magellan™ platform applies various computational methods and proprietary algorithms to identify and map previously uncharacterized clusters of binding hotspots on the protein surface where a small molecule can potentially bind.
+Added: Using the three-dimensional structure of proteins that have been experimentally derived or generated or predictive protein structures from AI-powered databases such as Alphafold, our Magellan™ platform applies various computational methods and proprietary algorithms to identify and map previously uncharacterized clusters of binding
+Added: hotspots on the protein surface where a small molecule can potentially bind.
The number, density, nature and quality of these hotspot clusters determine the druggability of the protein, which refers to whether drug-like small molecules can effectively bind to the particular site on the target protein with an appropriate potency.
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Current therapeutic approaches to address misfolded enzymes have inherent limitations.
−Removed: Drugs that binds to the active site of the enzyme or other target protein impair the protein’s function to some degree by competing with the active substrate, decreasing efficacy and potentially leading to selectivity issues.
+Added: Drugs that bind to the active site of the enzyme or other target proteins impair the protein’s function to some degree by competing with the active substrate, decreasing efficacy and potentially leading to selectivity issues.
Other treatments such as enzyme replacement therapy, or ERT, in which new functional enzymes are infused into the patient, are not suitable for treating neurological conditions because currently available ERTs cannot cross the blood-brain barrier.
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GCase Enzyme-Related Neurodegenerative Diseases and LSDs
−Removed: GCase is a lysosomal enzyme encoded by the GBA1 gene that is needed to break down fatty chemicals, in particular glucosylceramide and glucosylsphingosine, into sugar and fat.
−Removed: If GCase is dysfunctional or not available at sufficient levels, these fatty chemicals start to aggregate and eventual become toxic to the cells, leading to cell death.
−Removed: Our clinical-stage lead product candidate GT-02287 has been shown to restore enzymatic function of GCase in the lysosome, which may be useful as a treatment for Parkinson’s disease, or PD, neuronopathic Gaucher disease, or nGD, an LSD, and other neurodegenerative diseases, including dementia with Lewy bodies and Alzheimer’s disease.
+Added: GCase is a lysosomal enzyme encoded by the GBA1 gene that is needed to break down fatty substrates, in particular glucosylceramide and glucosylsphingosine, into sugar and fat.
+Added: If GCase is dysfunctional or not available at sufficient levels, these fatty substrates start to accumulate and eventually become directly toxic to the cells, as well as initiating a disease cascade including lysosomal and mitochondrial dysfunction and accumulation of aggregated proteins associated with neurodegenerative diseases such as alpha synuclein and phospho-tau leading to neuroinflammation and neuronal cell death.
+Added: Our clinical-stage lead product candidate GT-02287 has been shown to restore enzymatic function of GCase in the lysosome, which may be useful as a treatment for Parkinson’s disease, or PD, Gaucher disease, oGD, an LSD, and other neurodegenerative diseases, including dementia with Lewy bodies and Alzheimer’s disease.
Overview of GBA1 Parkinson’s Disease
−Removed: Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease.
−Removed: Death of dopaminergic neurons in the brain causes dopamine levels to drop, leading to the symptoms of Parkinson's disease, which often start with a tremor in one hand and other symptoms including slow movement, stiffness and loss of balance, and progresse to a severely debilitating disease that eventually requires full-time home care or a transfer to a skilled nursing facility.
GBA1 Parkinson’s disease is associated with heterozygous mutations in the GBA1 gene, which leads to the expression of misfolded and dysfunctional GCase.
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Aggregated alpha-synuclein accumulation and GCase deficiency are thought to act in a debilitating cycle.
−Removed: GCase deficiency can cause the accumulation of glucosylceramide and glucosylsphingosine substrates, which has been reported to directly affect the accumulation and aggregation of alpha-synuclein.
+Added: GCase deficiency can cause the accumulation of glucosylceramide and glucosylsphingosine substrates, which has been reported to directly affect the accumulation and aggregation of alpha-
In addition, increased aggregated alpha-synuclein levels can lead to less GCase activity, which in turn can lead to more aggregated alpha-synuclein accumulation.
Parkinson’s disease is reported to affect more than ten million people worldwide.
−Removed: Up to 15% of patients with Parkinson’s disease carry GBA1 mutations, making it the largest genetic risk factor for the disease, and this rate is higher in certain ethnic populations.
+Added: Around 10% of patients with Parkinson’s disease carry GBA1 mutations, making it the largest genetic risk factor for the disease.
At present, there is no effective cure for Parkinson’s disease.
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The benefits of these types of treatments diminish over time as the disease progresses, and these therapies do not impact the non-motor symptoms such as cognitive decline or the progression of the disease.
−Removed: As the disease progresses, the non-motor symptoms, such as dementia and cognitive impairment, can lead to severe morbidity and mortality.
+Added: As the disease progresses, the non-motor symptoms, such as cognitive impairment and dementia, can lead to severe morbidity and mortality.
Overview of Gaucher Disease
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People with Gaucher disease type 3 may survive into adulthood with a wide variety of signs and symptoms, including seizures, skeletal irregularities, eye movement disorders, cognitive and coordination problems as well as enlarged liver and spleen, respiratory problems, and blood disorders.
−Removed: Gaucher disease is caused by mutations of the GBA1 gene, which leads to the expression of misfolded and dysfunctional GCase.
−Removed: Partial or complete loss of GCase activity can cause the buildup of glucosylceramide and glucosylsphingosine in the lysosomes of macrophages, and the accumulation of these lipid substrates in neuronal cells can result in neurological symptoms.
+Added: Loss of GCase activity can cause the buildup of glucosylceramide and glucosylsphingosine in the lysosomes of macrophages, and the accumulation of these lipid substrates in neuronal cells can result in neurological symptoms.
The prevalence of Gaucher disease type 1 (non-neuronopathic Gaucher disease) is reported as 1:57,000 to 75,000 people worldwide.
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In DLB, deposits of the protein alpha-synuclein aggregate in neuronal cells and form inclusions called Lewy bodies.
−Removed: GT-02287 has been shown to reduce alpha-synuclein aggregation in preclinical models.
−Removed: In Alzheimer’s disease, the main pathophysiology involves the development of amyloid plaques and neurofibrillary tangles.
−Removed: Lysosomal dysfunction has been shown to play a role in aggregation of Tau and development
−Removed: of amyloid plaques.
−Removed: GT-02287 has been shown to reduce tau hyperphosphorylation and neuronal death in response to aggregated amyloid-beta in preclinical models.
+Added: GT-02287 has been shown to reduce alpha-synuclein aggregation and to improve cognitive ability in preclinical models.
+Added: In Alzheimer’s disease, the main pathophysiology involves the development of amyloid plaques and neurofibrillary tangles which contain aggregated amyloid beta and Tau protein, respectively.
+Added: Lysosomal dysfunction has been shown to play a role in aggregation of Tau and development of amyloid plaques.
+Added: GT-02287 has been shown to reduce tau hyperphosphorylation in response to aggregated amyloid-beta and neuronal cell death in response to aggregated tau in preclinical models.
Preclinical Characterization of Lead Compound GT-02287 for the Treatment of GBA1-Related Diseases
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GT-02287 also has shown GCase enzyme enhancement in an extended panel of patient-derived cells representative of the most frequent and pathogenic GBA1 mutations related to GBA1 PD and nGD.
−Removed: In addition, we reported that GT-02287 increased GCase enzyme levels, co-localization of GCase with lysosomes, reduced GlcCer accumulation as well as phosphorylated and aggregated a-synuclein accumulation in cells derived from L444P/RecNcil and L444P/L444P patients .
+Added: In addition, we reported that GT-02287 increased GCase enzyme levels, co-localization of GCase with lysosomes, reduced GlcCer accumulation as well as phosphorylated and aggregated alpha-synuclein accumulation in neurons derived from patients carrying GBA1 mutations .
Pharmacokinetics
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In-Vivo Pharmacology in PD Animal Models
−Removed: In mice administered the irreversible GCase inhibitor CBE (conduritol beta epoxide) to simulate the effects of reduced GCase activity seen in GBA1 Parkinson’s disease and GD, GT-02287 was orally administered once a day, at doses of 30, 60 90 and 120 mg/kg.
−Removed: The data generated in this study showed statistically significant reduction of aggregated alpha-synuclein, reduced microgliosis, or neuroinflammation, as measured by Iba-1 staining, increased survival of dopaminergic neurons in the substantia nigra, as measured by tyrosine hydroxylase staining, increased dopamine levels in the striatum, increased survival of cortical neurons, and decreased levels of NfL (neurofilament light chain), an emerging neurodegeneration biomarker, in the plasma.
−Removed: These biological effects were accompanied by a dose-dependent behavioral effect shown by improved neuromotor strength as measured by the wire hang test and increased coordination as measured by the beam walk test.
−Removed: GT-02287 increases dopaminergic and cortical neuronal survival, decreases NfL in plasma, and improves motor function in the CBE Mouse Model
−Removed: In a therapeutic paradigm in a model in which mice were administered with low levels of CBE every second day and received an injection of alpha-synuclein preformed fibrils directly into the brain to mimic GBA1 Parkinson’s disease, GT-02287 completely restored motor function in the wire hang test even following a delayed administration of the drug candidate after the initial toxic insult.
−Removed: Rescue of locomotor impairment was reflected in the complete reversal of plasma levels of NfL, the emerging neurodegeneration biomarker, to the level of the control arm in the study, which also suggests a neuroprotective effect of GT-02287.
−Removed: GT-02287 displays neuroprotection and restores motor function in preclinicaltherapeutic models of Parkinson’s disease.
+Added: Mice were administered low levels of irreversible GCase inhibitor CBE and received an injection of alpha-synuclein preformed fibrils (PFFs) directly into the brain to mimic reduced GCase activity and alpha-synuclein accumulation seen in GBA -PD, or PFFs only to mimic idiopathic Parkinson’s disease.
+Added: GT-02287, orally administered once a day after the mice has started to show deficits in motor function, showed statistically significant improvements in GCase activity, restoration of markers of lysosomal and mitochondrial integrity, reduction of aggregated alpha-synuclein, reduced neuroinflammation, increased survival of dopaminergic neurons in the substantia nigra, increased dopamine levels in the striatum, increased survival of cortical neurons, and decreased levels of NfL (neurofilament light chain), an emerging neurodegeneration biomarker, in the plasma, in both the GBA1 and idiopathic PD models.
+Added: These effects on disease markers were accompanied by a dose-dependent behavioral effect shown by improved neuromotor strength as measured by the wire hang test and increased coordination as measured by the beam walk test as well as an improvement in nest building which is a complex behavior involving an element of cognitive function.
+Added: Withdrawal of the compound resulted in a reduction in GCase activity as expected but improvement in disease markers and on motor and cognitive function were maintained for at least 9 days, suggesting a disease slowing effect of GT-02287.
Nonclinical Toxicology and Safety Studies
−Removed: The GLP in vivo safety pharmacology and general toxicity studies have been successfully concluded, thus enabling the initiation of the first-in-human clinical trial in September 2023.
−Removed: In September 2023, we also initiated the 13 weeks GLP toxicology studies, completing the in vivo phase in January 2024.
−Removed: The final, quality assurance audited report, is expected in the beginning of the second quarter of 2024.
−Removed: The availability of the 13-weeks GLP study results enables us to continue the clinical development by treating patients with GT-02287 for the same duration, i.e.
−Removed: To further extend our clinical development plan with GT-02287, we are planning to initiate the chronic toxicity study (6 months in rodents and 9 months in non-rodents) in the second half of 2024, enabling the conduct of clinical studies in patients with a GT-02287 beyond 12 months treatment duration.
+Added: The sub-chronic GLP general toxicity studies in both rodents and non-rodents were successfully completed in the second quarter of 2024, without any delays, which allows for the treatment of patients over a three-month period.
+Added: To further advance our clinical development plan for GT-02287, we initiated a chronic toxicity study—lasting six months in rodents and nine months in non-rodents during the second half of 2024.
+Added: This will enable clinical studies involving GT-02287 in patients for treatment durations exceeding twelve months.
+Added: The in-vivo phase of the chronic toxicity study in rodents was completed in February 2025, and the final quality assurance audited report is anticipated by May 2025.
+Added: The completion of the in-vivo phase in non-rodent species is expected by the second quarter of 2025.
+Added: Additionally, a comprehensive mass-balance study using radiolabeled GT-02287 in rats was concluded in 2024, demonstrating the distribution of the compound within the central nervous system.
Clinical Study
In September 2023, we initiated the first-in-human Phase 1 clinical trial to assess the safety, tolerability, pharmacokinetics, and food effect of GT-02287 in healthy participants.
−Removed: The study design includes a single ascending dose part during which the study participants receive one dose of GT-02287 at different dose levels, and a multiple ascending dose part during which the study participants receive one daily dose of GT-02287 for 14 days at different dose levels.
−Removed: In February 2024, we initiated the multiple ascending dose part of this Phase 1 clinical trial, which we anticipate completing in the second quarter of 2024, with the availability of the quality assurance audited interim report in the third quarter of 2024.
−Removed: We are planning to expand the scope of this Phase 1 clinical trial by amending the study protocol to include a cohort of 12-15 patients with Parkinson’s disease.
−Removed: These patients will be treated for a period of three months to evaluate safety, tolerability, and pharmacokinetics in patients, as well as to assess the effect of GT-02287 on certain biomarkers of the GCase disease cascade.
+Added: The study design included a single ascending
+Added: dose part during which the study participants receive one dose of GT-02287 at different dose levels, and a multiple ascending dose part during which the study participants received one daily dose of GT-02287 for 14 days at different dose levels.
+Added: The study was completed in July 2024 and the quality assurance audited interim report was finalized in the third quarter of 2024.
+Added: In the ongoing Phase 1b study, participants with Parkinson’s disease will receive GT-02287 for a period of three months to evaluate safety, tolerability, pharmacokinetics, and the effect of GT-02287 on certain biomarkers of the GCase disease cascade
Pipeline Programs in Research and Discovery Phases
−Removed: In addition to our clinical-stage lead program for Parkinson’s disease, we are planning to progress additional programs in the research and discovery phases, including our programs for alpha-1 antitrypsin deficiency, GM1 gangliosidosis, Krabbe disease, and two active programs in oncology, in conjunction with academic and industry collaborations as well as with non-dilutive grant funding as we have already received under a Eurostars grant for our alpha-1 antitrypsin deficiency program.
−Removed: GALC Enzyme-Related Disorders:
−Removed: Krabbe Disease
−Removed: Krabbe disease is a severe neurological condition that is part of a group of disorders which result from the loss of myelin (demyelination) in the CNS.
−Removed: Myelin is the protective covering around neurons that ensures the rapid transmission of neural signals.
−Removed: The most common form of Krabbe disease, the infantile form, usually begins before the age of one.
−Removed: Initial symptoms typically include irritability, muscle weakness, feeding difficulties, episodes of fever without any sign of infection, stiff posture and delayed mental and physical development.
−Removed: As the disease progresses, muscles continue to weaken, affecting the infant’s ability to move, chew, swallow and breathe.
−Removed: Affected infants also experience vision loss and seizures.
−Removed: Because of the severity of the condition, individuals with the infantile form of Krabbe disease rarely survive beyond the age of two.
−Removed: The less common forms, those that have a later onset, begin in childhood, adolescence, or adulthood.
−Removed: Vision problems and walking difficulties are the most common initial symptoms in these late-onset forms of the disorder, however, signs and symptoms vary considerably among affected individuals.
−Removed: Individuals with late-onset Krabbe disease may survive many years after the condition begins.
−Removed: Krabbe disease is an inherited LSD caused by mutations in the gene GALC.
−Removed: In affected individuals, GALC substrate psychosine accumulation can trigger a neuroinflammatory response, a loss of myelin forming cells and a progressive demyelination of the central and peripheral nervous systems.
−Removed: The prevalence of Krabbe disease is reported as about 1 in 100,000 to 1 in 250,000 live births worldwide.
−Removed: At present, there is no effective cure or disease-modifying treatment for Krabbe Disease.
−Removed: Treatment of a child who is symptomatic before six months of age is supportive and focused on improving quality of life and avoiding complications.
−Removed: For older individuals, treatment with HSCT is individualized based on disease burden and manifestations, but it serves to delay disease progression and is not an effective cure.
−Removed: We are investigating the restoration of GALC function as a treatment for Krabbe disease.
−Removed: GALC is an enzyme in lysosomes needed to breakdown galactolipids, which are fats primarily found in the nervous system and kidneys.
−Removed: Among the galactolipids that GALC breaks down are galactosylceramide, which is an essential component of neuronal myelin, and psychosine, which is formed during myelin production and is toxic to cells.
−Removed: The misfolding of GALC can result in the toxic accumulation of galactosylceramide, inhibiting myelin production, and of psychosine, leading to demyelination of cells and ultimately to Krabbe disease.
−Removed: There is no available cure for Krabbe disease.
−Removed: Current developments in invasive procedures such as bone marrow transplants have not been shown to provide significant neurological improvements, and most developments in gene therapy treatments are still in the preclinical stages.
−Removed: GLB Enzyme-Related Disorders:
−Removed: GM1 Gangliosidosis
−Removed: GLB is an enzyme found in lysosomes, which are compartments within cells that degrade and recycle different types of molecules, including toxic molecules.
−Removed: GLB is essential for the breakdown of GM1 and keratan sulfate, which serve important functions in the brain and other tissues.
−Removed: Misfolding of GLB allows these substrates to build up to toxic levels and leads to the diseases GM1 Gangliosidosis.
−Removed: GM1 gangliosidosis is a rare and often life-threatening LSD in infants (type 1), juveniles (type 2) and adults (type 3).
−Removed: It manifests in a continuum of clinical severity by type.
−Removed: In type 1 or the infantile form, the onset is observed earlier and is a more severe and rapidly progressive disease.
−Removed: Type 2 and 3 are less severe manifestations and have slower progression with a juvenile or adult onset.
−Removed: The infantile form of the disease is characterized by onset in the first year of life with symptoms including hypotonia (reduced muscle tone), progressive CNS dysfunction that can lead to deafness, blindness, enlarged liver and spleen rigidity, and progressive skeletal dysplasia that can result in restrictive lung disease and aspiration pneumonia.
−Removed: The disease rapidly progresses, with a life expectancy of two to four years.
−Removed: Juvenile GM1 manifests between 18 months and five years of age with a slower progression compared to infants.
−Removed: The average life expectancy for type 2 GM1 is typically 10 years.
−Removed: Adult GM1 has an onset age between three and 30.
−Removed: While it is less severe and progresses at a slower rate than infantile or juvenile GM1, adult GM1 causes debilitating symptoms, including muscular atrophy, corneal clouding and dystonia.
−Removed: The prevalence of GM1 is approximately 1:100,000 to 200,000 live births worldwide.
−Removed: Currently, there is no effective cure for GM1, and symptomatic treatment options, including substrate reduction therapy, ERT, bone marrow transplantation, stem cell transplantation and gene therapy are limited or still under development.
−Removed: We believe current approaches are unable to address both the neuronal and systemic symptoms because current treatment options cannot cross the blood-brain barrier or reach other hard-to-treat organs, such as bone.
−Removed: We have identified novel STAR molecules targeting GLB through our Magellan™ platform and conducted our initial studies on these compounds.
−Removed: Binding of two of these compounds to the GLB target has been confirmed using a biophysical assay.
−Removed: Preclinical studies indicate that our STARs help mutated GLB escape premature degradation and travel to the lysosome where it can perform its catalytic activity.
−Removed: These preliminary studies were conducted in vitro using cells that carried the GLB1 mutation.
−Removed: In addition, one compound showed clearance of the toxic GM1 ganglioside accumulation in GM1-affected canine cells.
−Removed: Based on the data generated to date, we have selected a lead series for further characterization and development.
−Removed: A priority patent application was filed in November 2023.
−Removed: Serpina Related Disorder:
−Removed: alpha-1 Antitrypsin (A1AT) Deficiency
−Removed: We are investigating the stabilization of alpha-1 antitrypsin (AAT) as a potential treatment for rare lung and/or liver disorder.
−Removed: If A1AT is stabilized, then we believe the molecule would prevent the toxic gain of function of aggregated AAT in the liver and loss of function in the lung.
−Removed: We have identified one allosteric site and identified a hit chemical series that inhibits polymerization of A1AT protein.
−Removed: A priority patent application was filed in February 2023.
−Removed: On March 21, 2023, we announced that that Eurostars with Innosuisse have awarded a grant in the aggregate amount of €1.2 million to a consortium led by Gain Therapeutics which includes the Institute for Research in Biomedicine, Newcells Biotech and the University of Helsinki.
−Removed: This grant supports a research project to develop novel small molecule allosteric regulators against Alpha-1 Antitrypsin (AAT) Deficiency, a rare genetic condition that can result in serious lung and liver diseases.
−Removed: Allosteric Regulators in Oncology
−Removed: Allosteric regulators are molecules able to modify the activity of a protein binding to a site topographically distinct from the site of the protein, called the active site, in which the activity characterizing the protein is carried out and in oncology usually involves the binding of receptors.
−Removed: Targeting allosteric sites may provide greater specificity and selectivity of activity and allow for a better efficacy and safety profile.
−Removed: An allosteric site is more specific to an individual protein, potentially leading to safer and more efficacious medicines.
−Removed: The allosteric-targeted therapies also introduce the possibility of fine-tuning a protein’s activity in new ways—one modulator may shift a protein into a conformation that shuts it down entirely, while another might under the right condition potentiate activity, and others may result in activity levels in between.
−Removed: Allosteric drugs open the door to identifying drug targets that are inaccessible to traditional active-site inhibitors.
−Removed: Allosteric drugs also may provide a new foundation for combining oncolytic agents, to achieve important additive and synergistic effects, and to prevent or overcome drug-resistance to traditional orthosteric anti-cancer agent.
−Removed: Targets have been selected based on the potential mechanism of action (with an initial focus on allosteric inhibition), unmet medical needs such as immune resistance, metastatic resistance, non satisfactory response to current standard of care, level of innovation and availability of preclinical tools.
−Removed: We have two active oncology projects underway in which we are identifying STARs that are designed to destabilize target proteins by binding to allosteric sites on the proteins and rendering them inactive.
−Removed: Thus far we have identified allosteric binding sites and run virtual screens to identify virtual hits which have been characterized further in biochemical and cell-based assays.
+Added: In addition to our clinical-stage lead program for Parkinson’s disease, we are planning to progress additional programs in the research and discovery phases in conjunction with academic and industry collaboration.
The biotechnology and pharmaceutical industries are characterized by the rapid evolution of technologies and understanding of disease etiology, intense competition, and a strong emphasis on intellectual property.
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Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.
−Removed: These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient
−Removed: enrollment in clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.
+Added: These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient enrollment in clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.
As a result, our competitors may discover, develop, license, or commercialize products before or more successfully than we do.
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Prevail Therapeutics, which is evaluating a potential gene therapy candidate in a Phase 1/2 clinical trial, and Voyager Therapeutics.
−Removed: There are also a number of companies with alpha-synuclein specific approaches ranging from all stages of clinical development but these are distinct from us as they only aim to deplete a specific protein rather than affecting the root cause of the disease at the start of the disease cascade.
−Removed: For Krabbe disease, companies such as Chiesi, Ranedis, Passage Bio, MediciNova and Polaryx are all developing potential therapies, which we believe are in the preclinical stage.
−Removed: We may also face competition from large pharmaceutical and biotechnology companies, academic research institutions, government agencies and public and private research institutions with genetic medicine and other therapeutic approaches.
Additionally, new or advanced technologies developed by our competitors may render our current or future product candidates uneconomical or obsolete, and we may not be successful in marketing our product candidates against competitors.
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We have entered into a license agreement, dated December 20, 2017 (the “Minoryx License Agreement”), with Minoryx Therapeutics, S.L., a company organized under the laws of Spain (“Minoryx”), pursuant to which we obtained exclusive worldwide license rights from Minoryx to use and exploit its intellectual property (“IP”), including certain components of its computational drug discovery platform Magellan™ for the identification of non-competitive pharmacological chaperones and exclusive worldwide sublicense rights to certain IP licensed by Minoryx from the University of Barcelona and the Institució Catalana de Recerca i Estudis Avançats.
−Removed: Under the terms of the Minoryx License Agreement, we have an exclusive, worldwide, royalty-bearing, assignable, transferable license, including the right to license through multiple tiers of sublicense, to Minoryx’s IP to make, have made, use, import, export, offer to sell, have sold, copy, modify, perform, display, create derivative versions of products in the licensed field or otherwise to exploit Minoryx’s IP in the field.
+Added: Under the terms of the Minoryx License Agreement, we have an exclusive, worldwide, royalty-bearing, assignable, transferable license, including the right to license through multiple tiers of sublicense, to Minoryx’s IP to make, have made, use, import, export, offer to
+Added: sell, have sold, copy, modify, perform, display, create derivative versions of products in the licensed field or otherwise to exploit Minoryx’s IP in the field.
Minoryx’s IP includes certain components of the Magellan™ drug discovery platform, certain proprietary Minoryx compounds acting as pharmacological chaperones, all patents and pending applications related thereto and Minoryx’s Know-How.
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Khalid Islam, the Chairman of our board of directors and one of our founders, is currently the Chairman of the board of directors of Minoryx.
−Removed: As consideration for the license grant from Minoryx, we have agreed to pay Minoryx royalties on a product-by-product basis based on the licensed IP used by us, ranging from a high single digit to low single digit percentage
−Removed: of net revenues of products during the royalty term commencing on the effective date of the Minoryx License Agreement and continuing until the 10th anniversary of the first product commercialization.
+Added: As consideration for the license grant from Minoryx, we have agreed to pay Minoryx royalties on a product-by-product basis based on the licensed IP used by us, ranging from a high single digit to low single digit percentage of net revenues of products during the royalty term commencing on the effective date of the Minoryx License Agreement and continuing until the 10th anniversary of the first product commercialization.
Upon the expiration of the royalty term for a product or service in a country, the license with respect to the product or service, as the case may be, shall become royalty-free, fully-paid, irrevocable and perpetual.
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Our policy is to seek to protect our proprietary position by, among other methods, pursuing and obtaining patent protection in the United States and in jurisdictions outside of the United States related to our proprietary technology, inventions, improvements, platforms and our product candidates that are important to the development and implementation of our business.
−Removed: As of February 2024, our patent portfolio consisted of one patent granted in Europe, five international PCT applications in national phase stage and two international PCT applications which will be published in 2024.
+Added: As of February 2025, our patent portfolio consisted of two patents granted in the U.S., Europe, and Japan.
+Added: three international PCT applications in national phase stage, two international PCT applications published in 2024 and entering national phase in 2025, and two international PCT applications to be published in 2025.
In regard to our computational drug discovery platform Magellan™, we in-licensed the European patent under the Minoryx License Agreement, which is owned by UB/ICREA and has claims directed to a method of binding site and binding energy determination by mixed explicit solvent simulations.
This patent is expected to expire in 2032.
−Removed: In regard to our GLB program, we in-licensed from Minoryx pursuant to the Minoryx License Agreement, a patent family with a pending European patent application with claims directed to composition of matter and eight foreign patent applications pending in such jurisdictions such as Canada, Australia, Japan, Europe, and China.
−Removed: These patents applications, if issued, are expected to expire in 2037, not giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.
−Removed: In regard to our GBA program, we in-licensed from Minoryx pursuant to the Minoryx License Agreement, a patent family with a pending European patent application with claims directed to composition of matter and eight foreign patent applications pending in such jurisdictions such as Canada, Australia, Japan, Europe, and China.
−Removed: These patent applications, if issued, are expected to expire in 2037, not giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.
+Added: In regard to our GLB program, we in-licensed from Minoryx pursuant to the Minoryx License Agreement, a patent family granted in U.S., Europe and Japan with claims directed to composition of matter.
+Added: These patent applications are expected to expire in 2037, not giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.
+Added: In regard to our GBA program, we in-licensed from Minoryx pursuant to the Minoryx License Agreement, a patent family granted in U.S., Europe and Japan with claims directed to composition of matter.
+Added: These patent applications are expected to expire in 2037, not giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.
Individual patents extend for varying periods depending on the date of filing of the patent application or the date of patent issuance and the legal term of patents in the countries in which they are obtained.
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● completion of extensive non-clinical studies in accordance with applicable regulations, including studies conducted in accordance with good laboratory practice, or GLP, requirements;
−Removed: ● submission to the FDA of an IND application, which must become effective before clinical trials may begin;
+Added: ● submission to the FDA of an Investigative New Drug, or IND, application, which must become effective before clinical trials may begin;
● approval by an institutional review board, or IRB, or independent ethics committee at each clinical trial site before each trial may be initiated;
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The conduct of preclinical studies is subject to federal and state regulations and requirements, including GLP requirements for safety/toxicology studies.
−Removed: The results of the preclinical studies, together with manufacturing information and analytical data must be submitted to the FDA as part of an IND.
+Added: The results of the preclinical studies, together with manufacturing information and analytical data, must be submitted to the FDA as part of an IND application.
An IND is a request for authorization from the FDA to administer an investigational product to humans and must become effective before clinical trials may begin.
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Submission of an IND may result in the FDA not allowing clinical trials to commence or not allowing clinical trials to commence on the terms originally specified in the IND.
−Removed: The clinical stage of development involves the administration of the product candidate to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance with GCP requirements, which include the requirement that all research patients provide their informed consent for their participation in any clinical trial.
+Added: The clinical stage of development involves the administration of the product candidate to healthy volunteers or patients under the supervision of qualified investigators.
+Added: These investigators are generally physicians not employed by or under the trial sponsor’s control, in accordance with GCP requirements, which also includes the requirement that all research patients provide their informed consent for their participation in any clinical trial.
Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria and the parameters and criteria to be used in monitoring safety and evaluating effectiveness.
Each protocol, and any subsequent amendments to the protocol, must be submitted to the FDA as part of the IND.
−Removed: Furthermore, each clinical trial must be reviewed and approved by an IRB for each institution at which the clinical trial will be conducted to ensure that the risks to individuals participating in the clinical trial are minimized and are reasonable related to the anticipated benefits.
−Removed: The IRB also approves the informed consent form that must be provided to each clinical trial subject or his or her legal representative, and must monitor the clinical trial until completed.
+Added: Furthermore, each clinical trial must be reviewed and approved by an IRB for each institution at which the clinical trial will be conducted to ensure that the risks to individuals participating in the clinical trial are minimized and are reasonable in relation to the anticipated benefits.
+Added: The IRB also approves the informed consent form that must be provided to each clinical trial subject or his or her legal representative and must monitor the clinical trial until
The FDA, the IRB or the sponsor may suspend or discontinue a clinical trial at any time on various grounds, including a finding that the patients are being exposed to an unacceptable health risk.
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● Phase 1 —Phase 1 clinical trials involve initial introduction of the investigational product into healthy human volunteers or patients with the target disease or condition.
−Removed: These studies are typically designed to test the safety, dosage tolerance, absorption, metabolism and distribution of the investigational product in humans, excretion the side effects associated with increasing doses, and, if possible, to gain early evidence of effectiveness.
+Added: These studies are typically designed to test the safety, dosage tolerance, absorption, metabolism and distribution of the investigational product in humans, excretion of the side effects associated with increasing doses, and, if possible, to gain early evidence of effectiveness.
● Phase 2 —Phase 2 clinical trials typically involve administration of the investigational product to a limited patient population with a specified disease or condition to evaluate the preliminary efficacy, optimal dosages and dosing schedule and to identify possible adverse side effects and safety risks.
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Progress reports detailing the results of the clinical trials, among other information, must be submitted at least annually to the FDA.
−Removed: Written IND safety reports must be submitted to the FDA and the investigators fifteen days after the trial sponsor determines the information qualifies for reporting for serious and unexpected suspected adverse events, findings from other studies or animal or in vitro testing that suggest a significant risk for human volunteers and any clinically important increase in the severity or rate of a serious suspected adverse reaction over that listed in the investigator brochure.
+Added: Written IND safety reports must be submitted to the FDA and the investigators fifteen days after the trial sponsor determines that the information qualifies for reporting for serious and unexpected suspected adverse events, findings from other studies or animal or in vitro testing that suggest a significant risk for human volunteers and any clinically important increase in the severity or rate of a serious suspected adverse reaction over that listed in the investigator brochure.
The sponsor must also notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction as soon as possible but in no case later than seven calendar days after the sponsor’s initial receipt of the information.
Concurrent with clinical trials, companies usually complete additional laboratory and animal studies and must also develop additional information about the chemistry and physical characteristics of the product candidate and finalize a process for manufacturing the drug product in commercial quantities in accordance with cGMP requirements.
−Removed: The manufacturing process must be capable of consistently producing quality batches of the product candidate and manufacturers must develop, among other things, methods for testing the identity, strength, quality and purity of the final drug product.
+Added: The manufacturing process must be capable of consistently producing quality batches of the product candidate.
+Added: Manufacturers must develop, among other things, methods for testing the identity, strength, quality and purity of the final drug product.
Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.
Special Protocol Assessment
−Removed: The FD&C Act directs FDA to meet with sponsors, pursuant to a sponsor’s written request, for the purpose of reaching agreement on the design and size of clinical trials intended to form the primary basis of an efficacy claim in an NDA or a Biologic Licensing Application (BLA).
+Added: The FD&C Act directs the FDA to meet with sponsors, pursuant to a sponsor’s written request, for the purpose of reaching an agreement on the design and size of clinical trials intended to form the primary basis of an efficacy claim in an NDA or a Biologic Licensing Application (BLA).
If an agreement is reached, the FDA will reduce the agreement to writing and make it part of the administrative record.
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Exceptions include public health concerns emerging that were unrecognized at the time of the protocol assessment, identification of a substantial scientific issue essential to the safety or efficacy testing that later comes to light, a sponsor’s failure to follow the protocol agreed upon or the FDA’s reliance on data, assumptions or information that are determined to be wrong.
+Added: Disclosure of Clinical Trial Information
+Added: Sponsors of clinical trials of FDA-regulated products, including biological products, are required to register and disclose certain clinical trial information on the website www.clinicaltrials.gov.
+Added: Information related to the product, patient population, phase of investigation, trial sites and investigators and other aspects of a clinical trial are then made public as part of the registration.
+Added: Sponsors are also obligated to disclose the results of their clinical trials after completion.
+Added: Disclosure of the results of clinical trials can be delayed in certain circumstances for up to two years after the date of completion of the trial.
+Added: Competitors may use this publicly available information to gain knowledge regarding the progress of clinical development programs as well as clinical trial design.
Marketing Approval for Drugs
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The marketing application may include both negative and ambiguous results of preclinical studies and clinical trials, as well as positive findings.
−Removed: Data may come from company-sponsored clinical trials intended to test the safety and efficacy of a product’s use or from a number of alternative sources, including studies initiated by investigators.
−Removed: marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the investigational product to the satisfaction of the FDA.
+Added: Data may come from company-sponsored clinical trials intended to test the safety and efficacy of a product’s use or from a number of alternative sources.
+Added: These sources include studies initiated by investigators.
+Added: To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the investigational product to the satisfaction of the FDA.
FDA approval of an NDA must be obtained before a drug may be marketed in the U.S.
The FDA reviews all submitted NDAs before it accepts them for filing and may request additional information rather than accepting the NDA for filing.
−Removed: The FDA must make a decision on accepting an NDA for filing within 60 days of receipt, and such decision could include a refusal to file by the FDA.
+Added: The FDA must make a decision on accepting an NDA for filing within 60 days of receipt.
+Added: Such decision could include a refusal to file by the FDA.
Once the submission is accepted for filing, the FDA begins an in-depth substantive review of the NDA.
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In most cases, the FDA requires two adequate and well-controlled Phase 3 clinical trials to demonstrate the efficacy of the drug.
−Removed: A single trial may be sufficient in some instances, including (1) where the study is a large multicenter trial demonstrating internal consistency and a statistically very persuasive finding of a clinically meaningful effect on mortality, irreversible morbidity or prevention of a disease with a potentially serious outcome and confirmation of the result in a second trial would be practically or ethically impossible or (2) when there is one adequate and well-controlled clinical investigation plus other confirmatory evidence.
−Removed: Under the goals and polices agreed to by the FDA under the Prescription Drug User Fee Act, or PDUFA, the FDA targets ten months, from the filing date, in which to complete its initial review of a new molecular entity NDA and respond to the applicant, and six months from the filing date of a new molecular entity NDA for priority review.
+Added: A single trial may be sufficient in some instances, including (i) where the study is a large multicenter trial demonstrating internal consistency and a statistically very persuasive finding of a clinically meaningful effect on mortality, irreversible morbidity or prevention of a disease with a potentially serious outcome and confirmation of the result in a second trial would be practically or ethically impossible or (ii) when there is one adequate and well-controlled clinical investigation plus other confirmatory evidence.
+Added: Under the goals and polices agreed to by the FDA under the Prescription Drug User Fee Act, or PDUFA, the FDA targets ten months from the filing date to complete its initial review of a new molecular entity NDA and respond to the applicant and six months from the filing date of a new molecular entity NDA for priority review.
The FDA does not always meet its PDUFA goal dates for standard or priority NDAs and the review process is often extended by FDA requests for additional information or clarification.
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The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.
−Removed: Additionally, before approving an NDA, the FDA may inspect one or more clinical trial sites to assure compliance with GCP and other requirements and the integrity of the clinical data submitted to the FDA, and one or more sites where non-clinical testing was conducted to assure compliance with GLP and other requirements.
+Added: Additionally, before approving an NDA, the FDA may inspect one or more clinical trial sites to assure compliance with GCP and other requirements and the integrity of the clinical data submitted to the FDA as well as one or more sites where non-clinical testing was conducted to assure compliance with GLP and other requirements.
After evaluating the NDA and all related information, including the advisory committee recommendation, if any, and inspection reports regarding the manufacturing facilities and clinical trial sites, the FDA may issue an approval letter, or in some cases, a complete response letter.
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An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.
−Removed: Even if the FDA approves a product, depending on the specific risk(s) to be addressed it may limit the approved indications for use of the product, require that contraindications, warnings or precautions be included in the product labeling, require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess a
−Removed: drug’s safety after approval, require testing and surveillance programs to monitor the product after commercialization or impose other conditions, including distribution and use restrictions or other risk management mechanisms under a REMS, which can materially affect the potential market and profitability of the product.
+Added: Even if the FDA approves a product, depending on the specific risk(s) to be addressed, it may limit the approved indications for use of the product, require that contraindications, warnings or precautions be included in the product labeling, require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess a drug’s safety after approval, require testing and surveillance programs to monitor the product after commercialization or impose other conditions.
+Added: These other conditions include distribution and use restrictions or other risk management mechanisms under a REMS that can materially affect the potential market and profitability of the product.
The FDA may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs.
1 unchanged sentence
Orphan Drug Designation and Exclusivity
−Removed: Under the Orphan Drug Act of 1983, the FDA may grant orphan designation to a drug intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals in the U.S., or if it affects more than 200,000 individuals in the U.S., there is no reasonable expectation that the cost of developing and making the product available in the U.S.
+Added: Under the Orphan Drug Act of 1983, the FDA may grant orphan designation to a drug intended to treat a rare disease or condition, a disease or condition that affects fewer than 200,000 individuals in the U.S., or if it affects more than 200,000 individuals in the U.S., there is no reasonable expectation that the cost of developing and making the product available in the U.S.
for the disease or condition will be recovered from sales of the product.
Orphan designation must be requested before submitting an NDA.
−Removed: Orphan designation does not convey any advantage in or shorten the duration of the regulatory review and approval process, though companies developing orphan products are eligible for certain incentives, including tax credits for qualified clinical testing and waiver of application fees.
+Added: Orphan designation does not convey any advantage in or shorten the duration of the regulatory review and approval process though companies developing orphan products are eligible for certain incentives such as tax credits for qualified clinical testing and waiver of application fees.
If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to a seven-year period of marketing exclusivity during which the FDA may not approve any other applications to market the same therapeutic agent for the same indication, except in limited circumstances such as a subsequent product’s showing of clinical superiority over the product with orphan exclusivity or where the original applicant cannot produce sufficient quantities of product.
Competitors, however, may receive approval of different therapeutic agents for the indication for which the orphan product has exclusivity or obtain approval for the same therapeutic agent for a different indication than that for which the orphan product has exclusivity.
−Removed: Orphan product exclusivity could block the approval of one of our products for seven years if a competitor obtains approval for the same therapeutic agent for the same indication before we do, unless we are able to demonstrate that our product is clinically superior.
+Added: Orphan product exclusivity could block the approval of one of our products for
+Added: seven years if a competitor obtains approval for the same therapeutic agent for the same indication before we do unless we are able to demonstrate that our product is clinically superior.
If an orphan designated product receives marketing approval for an indication broader than what is designated, it may not be entitled to orphan exclusivity.
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The FDA maintains several programs intended to facilitate and expedite development and review of new drugs to address unmet medical needs in the treatment of serious or life-threatening diseases or conditions.
−Removed: These programs include Fast Track designation, Breakthrough Therapy designation, Priority Review and Accelerated Approval, and the purpose of these programs is to either expedite the development or review of important new drugs to get them to patients earlier than under standard FDA development and review procedures.
+Added: These programs include Fast Track designation, Breakthrough Therapy designation, Priority Review and Accelerated Approval.
+Added: The purpose of these programs is to either expedite the development or review of important new drugs to get them to patients earlier than under standard FDA development and review procedures.
A new drug is eligible for Fast Track designation if it is intended to treat a serious or life-threatening disease or condition and demonstrates the potential to address unmet medical needs for such disease or condition.
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Breakthrough Therapy designation provides all the features of Fast Track designation in addition to intensive guidance on an efficient drug development program beginning as early as Phase 1 and FDA organizational commitment to expedited development, including involvement of senior managers and experienced review staff in a cross-disciplinary review, where appropriate.
−Removed: Any product submitted to the FDA for approval, including a product with Fast Track or Breakthrough Therapy designation, may also be eligible for additional FDA programs intended to expedite the review and approval
−Removed: process, including Priority Review designation and Accelerated Approval.
+Added: Any product submitted to the FDA for approval, including a product with Fast Track or Breakthrough Therapy designation, may also be eligible for additional FDA programs intended to expedite the review and approval process, including Priority Review designation and Accelerated Approval.
A product is eligible for Priority Review if it has the potential to provide a significant improvement in safety or effectiveness in the treatment, diagnosis or prevention of a serious disease or condition.
−Removed: Under Priority Review, the FDA must review an application in six months compared to ten months for a standard review.
+Added: Under Priority Review, the FDA must review an application within six months, compared to ten months for a standard review.
Additionally, products are eligible for Accelerated Approval if they can be shown to have an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit or an effect on a clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality which is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity or prevalence of the condition and the availability or lack of alternative treatments.
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For example, the FDA may require post-market testing, including Phase 4 clinical trials, and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization.
−Removed: In addition, drug manufacturers and their subcontractors involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMP, which impose certain procedural and documentation requirements upon us and our contract manufacturers.
+Added: In addition, drug manufacturers and their subcontractors involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and certain state agencies and are subject to periodic, unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMP.
+Added: These impose certain procedural and documentation requirements upon us and our contract manufacturers.
Failure to comply with statutory and regulatory requirements can subject a manufacturer to possible legal or regulatory action, such as warning letters, suspension of manufacturing, product seizures, injunctions, civil penalties or criminal prosecution.
There is also a continuing, annual prescription drug product program user fee.
−Removed: Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information, requirements for post-market studies or clinical
−Removed: trials to assess new safety risks, or imposition of distribution or other restrictions under a REMS.
+Added: Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information, requirements for post market studies or clinical trials to assess new safety risks, or imposition of distribution or other restrictions under a REMS.
Other potential consequences include, among other things:
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Manufacturing, sales, promotion and other activities of product candidates following product approval, where applicable, or commercialization are also subject to regulation by numerous regulatory authorities in the U.S.
−Removed: in addition to the FDA, which may include the Centers for Medicare & Medicaid Services, or CMS, other divisions of the Department of Health and Human Services, the Department of Justice, the Drug Enforcement Administration, the Consumer Product Safety Commission, the Federal Trade Commission, the Occupational Safety & Health Administration, the Environmental Protection Agency and state and local governments and governmental agencies.
+Added: addition to the FDA.
+Added: These authorities may include the Centers for Medicare & Medicaid Services, or CMS, other divisions of the Department of Health and Human Services, the Department of Justice, the Drug Enforcement Administration, the Consumer Product Safety Commission, the Federal Trade Commission, the Occupational Safety & Health Administration, the Environmental Protection Agency and state and local governments and governmental agencies.
Healthcare Reform
+Added: The containment of health care costs is a priority of federal, state and foreign governments, and the prices of drugs have been a focus in this effort.
In March 2010, Congress passed the Affordable Care Act, or the ACA, a sweeping law intended to broaden access to health insurance, reduce or constrain the growth of health spending, enhance remedies against fraud and abuse, add new transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional policy reforms.
−Removed: The ACA, for example, contains provisions that subject products to potential competition by lower-cost products and may reduce the profitability of products through increased rebates for drugs reimbursed by Medicaid programs;
−Removed: address a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, increase the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program and extends the rebate program to individuals enrolled in Medicaid managed care organizations;
+Added: The ACA, for example, contains provisions that subject products to potential competition by lower-cost products and may reduce the profitability of products through increased rebates for drugs reimbursed by Medicaid programs, addresses a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, increase the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program and extends the rebate program to individuals enrolled in Medicaid managed care organizations;
establish annual fees and taxes on manufacturers of certain branded prescription drugs;
and create a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 50% (increased to 70% pursuant to the Bipartisan Budget Act of 2018, or BBA, effective as of 2019) point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D.
−Removed: Since its enactment, there have been judicial, administrative, executive and Congressional legislative challenges to certain aspects of the ACA, and we expect there will be additional challenges and amendments to the ACA in the future.
+Added: Since its enactment, there have been judicial, administrative, executive and Congressional legislative challenges to certain aspects of the ACA.
+Added: We expect that there will be additional challenges and amendments to the ACA in the future.
For example, on June 17, 2021, the U.S.
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The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program.
−Removed: It is unclear how any additional challenges and healthcare reform measures of the Biden administration will impact the ACA and our business.
+Added: It is unclear how any additional challenges and healthcare reform measures of the Trump administration will impact the ACA and our business.
Other federal health reform measures have been proposed and adopted in the U.S.
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government has passed legislation requiring pharmaceutical manufacturers to provide rebates and discounts to certain entities and governmental payors to participate in federal healthcare programs.
−Removed: Further, in July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs.
−Removed: In response to Biden’s executive order, on September 9, 2021, the U.S.
−Removed: Department of Health and Human Services (“HHS”), released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles.
−Removed: In addition, the IRA, among other things, (i) directs HHS to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare, and subject drug manufacturers to civil monetary penalties and a potential excise tax by offering a price that is not equal to or less than the negotiated “maximum fair price” for such drugs and biologics under the law, and (ii) imposes rebates with respect to certain drugs and biologics covered under Medicare Part B or Medicare Part D to penalize price increases that outpace inflation.
+Added: In addition, the IRA, among other things, (i) directs the U.S.
+Added: Department of Health and Human Services (“HHS”) to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare, and subject drug manufacturers to civil monetary penalties and a potential excise tax by offering a price that is not equal to or less than the negotiated “maximum fair price” for such drugs and biologics under the law, and (ii) imposes rebates with respect to certain drugs and biologics covered under Medicare Part B or Medicare Part D to penalize price increases that outpace inflation.
The IRA permits HHS to implement many of these provisions through guidance as opposed to regulation for the initial years.
−Removed: These provisions will take effect progressively starting in fiscal year 2023, although they may be subject to legal challenges.
+Added: These provisions will progressively take effect beginning in fiscal year 2023, although they may be subject to legal challenges.
It is currently unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry.
−Removed: Further, the Biden administration released an additional executive order on October 14, 2022, directing HHS to submit a report on how the Center for Medicare and Medicaid Innovation can be further leveraged to test new models for lowering drug costs for Medicare and Medicaid beneficiaries.
+Added: Further, the Biden administration released an additional executive order on October 14, 2022 directing HHS to submit a report on how the Center for Medicare and Medicaid (“CMS”) Innovation can be further leveraged to test new models for lowering drug costs for Medicare and Medicaid beneficiaries.
It is unclear whether this executive order or similar policy initiatives will be implemented in the future.
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Other Healthcare Laws and Regulations
−Removed: If we obtain regulatory approval of our products, we may be subject to various federal and state laws targeting fraud and abuse in the healthcare industry.
+Added: If we obtain regulatory approval of our products, then we may be subject to various federal and state laws targeting fraud and abuse in the healthcare industry.
These laws may impact, among other things, our proposed sales and marketing strategies.
−Removed: In addition, we may be subject to patient privacy regulation by both the federal government and the states in which we conduct our business.
+Added: In addition, we may be subject to patient privacy regulations by both the federal government and the states in which we conduct our business.
These laws include, without limitation, state and federal anti-kickback, fraud and abuse, false claims, privacy and security and physician sunshine laws and regulations.
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A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.
−Removed: In addition, many states have adopted laws similar to the federal Anti-Kickback Statute, some of which apply to the referral of patients for healthcare items or services reimbursed by any source, not only government programs.
+Added: In addition, many states have adopted laws similar to the federal Anti-Kickback Statute, some of which apply to the referral of patients for healthcare items or services reimbursed by not only government programs, but any source.
Additionally, the civil False Claims Act (the “FCA”) prohibits knowingly presenting or causing the presentation of a false, fictitious or fraudulent claim for payment to the U.S.
2 unchanged sentences
Manufacturers can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims.
−Removed: The federal government continues to use the FCA, and the accompanying threat of significant liability, in its investigations and prosecutions of pharmaceutical and biotechnology companies throughout the U.S.
+Added: The federal government continues to use the FCA and the accompanying threat of significant liability in its investigations and
+Added: prosecutions of pharmaceutical and biotechnology companies throughout the U.S.
Such investigations and prosecutions frequently involve, for example, the alleged promotion of products for unapproved uses and other sales and marketing practices.
3 unchanged sentences
Federal government price reporting laws require manufacturers to calculate and report complex pricing metrics to government programs.
−Removed: federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, includes a fraud and abuse provision referred to as the HIPAA All-Payor Fraud Law, which imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program, or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items or services.
+Added: federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, includes a fraud and abuse provision referred to as the HIPAA All-Payor Fraud Law.
+Added: This provision imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items or services.
Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.
We may also be subject to federal transparency laws, including the federal Physician Payment Sunshine Act, which was part of the ACA and requires manufacturers of certain drugs and biologics, among others, to track and disclose payments and other transfers of value they make to U.S.
−Removed: physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners), and teaching hospitals, as well as ownership and investment interests in the manufacturer held by such
−Removed: physicians and their immediate family members.
+Added: physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners), and teaching hospitals, as well as ownership and investment interests in the manufacturer held by such physicians and their immediate family members.
This information is subsequently made publicly available in a searchable format on a CMS website.
9 unchanged sentences
If any of the physicians or other healthcare providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to significant criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.
−Removed: Ensuring business arrangements comply with applicable healthcare laws, as well as responding to possible investigations by government authorities, can be time- and resource consuming and can divert a company’s attention from the business.
+Added: Ensuring business arrangements comply with applicable healthcare
+Added: laws, as well as responding to possible investigations by government authorities, can be time- and resource consuming and can divert a company’s attention from the business.
Data Privacy and Security
7 unchanged sentences
In addition, the CPRA expanded the CCPA’s requirements.
−Removed: Additionally, European data privacy and security laws (including the EU GDPR and UK GDPR) impose significant and complex compliance obligations on companies that are subject to those laws, notably with respect to the processing of health-related data from EEA or UK-based individuals.
+Added: Additionally, European data privacy and security laws (including the EU GDPR and UK GDPR) impose significant and complex compliance obligations on companies that are subject to those laws, notably with respect to the processing of health-related data from the European Economic Area (“EEA”) (comprised of the 27 EU Member States plus Iceland, Liechtenstein and Norway) or UK-based individuals.
Coverage and Reimbursement
1 unchanged sentence
Third-party payors decide which therapies they will pay for and establish reimbursement levels.
−Removed: Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own coverage and reimbursement policies.
+Added: Third-party payors often rely upon the Medicare coverage policy and payment limitations in setting their own coverage and reimbursement policies.
Additionally, a third-party payor’s decision to provide coverage for a therapy does not imply that an adequate reimbursement rate will be approved.
7 unchanged sentences
To market any product outside of the U.S., we would need to comply with numerous and varying regulatory requirements of other countries regarding safety and efficacy and governing, among other things, clinical trials, marketing authorization, manufacturing, commercial sales and distribution of our products.
−Removed: To obtain a Marketing Authorization, or MA, for a product in the European Economic Area, or the EEA (comprised of the 27 EU Member States plus Iceland, Liechtenstein and Norway), for example an applicant must be established within the EEA.
−Removed: The applicant must submit a Marketing Authorization Application, or MAA, either under a centralized procedure administered by the EMA or one of the procedures administered by competent authorities in the EEA countries
−Removed: (decentralized procedure, national procedure or mutual recognition procedure).
−Removed: An MA may be granted only to an applicant established in the EEA.
+Added: To obtain a Marketing Authorization, or MA, for a product in the EEA, for example, an applicant must be established within the EEA.
+Added: The applicant must submit a Marketing Authorization Application, or MAA, either under a centralized procedure administered by the European Medicines Agency (the “EMA”) or one of the procedures administered by competent
+Added: authorities in the EEA countries (decentralized procedure, national procedure or mutual recognition procedure).
The centralized procedure provides for the grant of a single MA by the European Commission that is valid for all EEA countries.
23 unchanged sentences
Innovative products that target an unmet medical need and are expected to be of major public health interest may be eligible for a number of expedited development and review programs, such as the Priority Medicines, or PRIME, scheme, which provides incentives similar to the breakthrough therapy designation in the U.S.
−Removed: PRIME is a voluntary scheme aimed at enhancing the EMA’s support for the development of medicinal products that target unmet
−Removed: medical needs.
−Removed: Eligible products must target conditions for which there is an unmet medical need (there is no satisfactory method of diagnosis, prevention or treatment in the EU or, if there is, the new medicinal product will bring a major therapeutic advantage) and they must demonstrate the potential to address the unmet medical need by introducing new methods of therapy or improving existing ones.
+Added: PRIME is a voluntary scheme aimed at enhancing the EMA’s support for the development of medicinal products that target unmet medical needs.
+Added: Eligible products must target conditions for which there is an unmet medical need (there is no satisfactory method of diagnosis, prevention or treatment in the EU or, if there is, the new medicinal product will bring
+Added: a major therapeutic advantage) and they must demonstrate the potential to address the unmet medical need by introducing new methods of therapy or improving existing ones.
Benefits accrue to sponsors of product candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements and potentially accelerated MAA assessment once a dossier has been submitted.
11 unchanged sentences
These circumstances may arise in particular when the intended indications are very rare and, in the state of scientific knowledge at that time, it is not possible to provide comprehensive information, or when generating data may be contrary to generally accepted ethical principles.
−Removed: Like a conditional MA, an MA granted in exceptional circumstances is reserved to medicinal products intended to be authorized for treatment of rare diseases or unmet medical needs for which the applicant does not hold a complete data set that is required for the grant of a standard MA.
+Added: Like a conditional MA, an MA granted “under exceptional circumstances” is reserved to medicinal products intended to be authorized for treatment of rare diseases or unmet medical needs for which the applicant does not hold a complete data set that is required for the grant of a standard MA.
However, unlike the conditional MA, an applicant for authorization in exceptional circumstances is not subsequently required to provide the missing data.
22 unchanged sentences
Orphan designation in the EU
−Removed: The criteria for designating an “orphan medicinal product” in the EEA are similar in principle to those in the U.S.
−Removed: In the EEA a medicinal product may be designated as orphan if (1) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition;
−Removed: (2) either (a) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the EU to justify investment;
−Removed: and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU, or if such a method exists, the product will be of significant benefit to those affected by the condition.
+Added: The criteria for designating an “orphan medicinal product” in the EEA is similar in principle to that in the U.S.
+Added: In the EEA, a medicinal product may be designated as orphan if (i) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition;
+Added: (ii) either (a) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the EU to justify investment;
+Added: and (iii) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU, or if such a method exists, the product will be of significant benefit to those affected by the condition.
Orphan medicinal products are eligible for financial incentives such as reduction of fees or fee waivers and are, upon grant of a marketing authorization, entitled to ten years of market exclusivity for the approved therapeutic indication.
5 unchanged sentences
or (iii) the applicant cannot supply enough orphan medicinal product.
−Removed: Similar to the United States, the various phases of non-clinical and clinical research in the European Union are subject to significant regulatory controls.
+Added: Similar to the U.S., the various phases of non-clinical and clinical research in the EU are subject to significant regulatory controls.
Conduct of clinical trials in the EU
In the EU, clinical trials are governed by the Clinical Trials Regulation (EU) No 536/2014, or CTR, which entered into application on January 31, 2022, repealing and replacing the former Clinical Trials Directive 2001/20, or CTD, and related national implementing legislation of EU Member States.
−Removed: The CTR is intended to harmonize and streamline clinical trial authorizations, simplify adverse-event reporting procedures, improve the supervision of clinical trials and increasing their transparency.
+Added: The CTR is intended to harmonize and streamline clinical trial authorizations, simplify adverse-event reporting procedures, improve the supervision of clinical trials and increase their transparency.
Specifically, the Regulation, which is directly applicable in all EU Member States, introduces a streamlined application procedure through a single-entry point, the "EU portal", the Clinical Trials Information System, or CTIS;
7 unchanged sentences
Individual EU Member States retain the power to authorize the conduct of clinical trials on their territory.
−Removed: The extent to which on-going clinical trials will be governed by the CTR will depend on the duration of the individual clinical trial.
−Removed: For clinical trials in relation to which application for approval was made on the basis of the CTD before January 31, 2022, the CTD will continue to apply on a transitional basis for three years.
−Removed: If authorized, those clinical trials will be governed by the CTD until January 31, 2025.
−Removed: By that date, all ongoing trials will become subject to the provisions of the CTR.
−Removed: The CTR will apply to clinical trials from an earlier date if the clinical trial has already transitioned to the CTR framework.
−Removed: Since January 31, 2023 all new requests for approval of clinical trials must be based on the CTR.
Should we utilize third-party distributors, compliance with such foreign governmental regulations would generally be the responsibility of such distributors, who may be independent contractors over whom we have limited control.
3 unchanged sentences
The Annex provides a framework for the recognition of Good Manufacturing Practice, or GMP, inspections and for the exchange and acceptance of official GMP documents.
−Removed: The regime does not, however, extended to procedures such as batch release certification.
+Added: The regime does not, however, extend to procedures such as batch release certification.
As part of the TCA, the European Union and the UK will recognize Good Manufacturing Practice inspections carried out by the other party and the acceptance of official GMP documents issued by the other party.
1 unchanged sentence
Among the areas of absence of mutual recognition are batch testing and batch release.
−Removed: The UK has unilaterally agreed to accept European Union batch testing and batch release However, the European Union continues to apply European Union laws that require batch testing and batch release to take place in the European Union territory.
+Added: The UK has unilaterally agreed to accept European Union batch testing and batch release.
+Added: However, the European Union continues to apply European Union laws that require batch testing and batch release to take place in the European Union territory.
This means that medicinal products that are tested and released in the UK must be retested and re-released when entering the European Union market for commercial use.
−Removed: As regards marketing authorizations, Great Britain has a separate regulatory submission process, approval process and a national marketing authorization.
+Added: In regard to marketing authorizations, Great Britain has a separate regulatory submission process, approval process and a national marketing authorization.
Northern Ireland will, however, continue to be covered by the marketing authorizations granted by the European Commission.
2 unchanged sentences
The MHRA has been updating various aspects of the regulatory regime for medicinal products in the UK.
−Removed: These include:
−Removed: introducing the Innovative Licensing and Access Procedure to accelerate the time to market and facilitate patient access for innovative medicinal products;
−Removed: updates to the UK national approval procedure, introducing a 150-day objective for assessing applications for marketing authorizations in the UK, Great Britain and Northern Ireland and a rolling review process for marketing authorization applications (rather than a consolidated full dossier submission).
+Added: These include introducing the Innovative Licensing and Access Procedure to accelerate the time to market and facilitate patient access for innovative medicinal products, updates to the UK national approval procedure, introduction of a 150-day objective for assessing applications for marketing authorizations in the UK, Great Britain and Northern Ireland and a rolling review process for marketing authorization applications (rather than a consolidated full dossier submission).
Orphan designation in Great Britain following Brexit is, unlike in the EU, not available pre-marketing authorization.
Applications for orphan designation are made at the same time as an application for a marketing authorization.
−Removed: The criteria to be granted an orphan medicinal product designation or essentially identical to those in the EU but based on the prevalence of the condition in Great Britain.
+Added: The criteria to be granted as an orphan medicinal product designation is essentially identical to those in the EU but is based on the prevalence of the condition in Great Britain.
The UK regulatory framework in relation to clinical trials is derived from existing EU legislation (as implemented into UK law, through secondary legislation).
19 unchanged sentences
Employees and Human Capital Resources
−Removed: As of December 31, 2023, we had twenty-nine full-time employees and three part-time employees.
−Removed: Of these thirty-two employees, twenty-three were engaged in research and development activities and nine were engaged in finance, business development, administrative support and general management.
+Added: As of December 31, 2024, we had twenty-three full-time employees and two part-time employees.
+Added: Of these twenty-five employees, seventeen were engaged in research and development activities and eight were engaged in finance, business development, administrative support and general management.
We have a branch office in Barcelona, Spain.
14 unchanged sentences
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.