Here is a snapshot of the Sandstone reference. BACKGROUND ON...

Here is a snapshot of the Sandstone reference.


BACKGROUND ON INDICATIONS

Neuren’s Trofinetide - two potential neurological indications:
(1) Rett Syndrome (in market, branded as ‘DAYBUE’: A progressive X-linked chromosomal disorder that is associated with severe neurological disability. It mainly affects girls with an incidence estimated to be between 1 in 10k and 1 in 15k female births worldwide. It is significantly rarer in males. Symptoms present from 6-12mths with developmental regression resulting in the onset of a variety of effects, including motor or movement impairment, loss of acquired language, intellectual disability, seizures and anxiety.
(2) Fragile X Syndrome: An inherited mutation of the X chromosome, causes a range of developmental problems including learning disabilities and cognitive impairment. It is more common and more severe in males with an incidence of 1 in 4k to 1 in 7k while the incidence in girls averages at 1 in 6k to 1 in 11k with about half of the girls suffering symptoms. It is the most common inherited cause of intellectual disabilities and highest cause of autism. Other symptoms include anxiety, mood instability, seizures, intellectual disability with delayed speech and language development.
Neuren’s NNZ-2591 is aiming to tackle six neurological indications incl Rett and Fragile X syndrome.
The other syndromes are:
(1) Phelan-McDermid (PMS) Syndrome: The prevalence of Phelan-McDermid Syndrome (PMS) has been estimated to be between 1 in 8k and 1 in 15k with both males and females equally affected. Symptoms usually appear in early childhood with patients displaying developmental delay, intellectual disability, and absent or severely delayed speech. Other common symptoms include autism, low muscle tone, breathing difficulties, poor motor control, seizures, and epilepsy. Some children present with heart or kidney defects. The patients share facial and body characteristics.
(2) Angelman Syndrome: Angelman syndrome (AS) is estimated to affect between 1 in 12k and 1 in 24k people. It is a complex genetic disorder that causes an array of symptoms that primarily affect the nervous system. Patients present with delayed development, intellectual impairment, speech and balance problems, seizures and ataxic movement. Common physical characteristics include a small head.
(3) Pitt Hopkins Syndrome: Pitt Hopkins syndrome (PTHS) is estimated to affect between 1 in 11k and 1 in 41k PTHS is characterized by severe intellectual disability and development delay with poor or no speech and distinctive facial features with a small head. Breathing problems, epilepsy and autism are common. It also plays a role in the maturation of cells to carry out specific functions (cell differentiation).
(4) Prader-Willi Syndrome: A genetic disease that causes neurological impacts both males and females of all racial backgrounds. The prevalence of Prader-Willi Syndrome is between 1 in 10k and 1 in 30k. Symptoms include intellectual disability and constantly craving food which leads to health conditions such as obesity, diabetes and heart disease.
RISKS TO INVESTMENT VIEW

Clinical Trial Risks: NNZ-2591 has received Orphan Drug designation and Investigational New Drug (IND) approval for Angelman, Phelan-McDermid, Pitt-Hopkins, and Prader-Willi syndromes. Phase 2 trials are ongoing or completed, following positive Phase 1 safety results. However, potential delays, patient dropout, and study design modifications could impact forecasts and valuation.
Regulatory Risk: The FDA approval of trofinetide in March 2023 reduces regulatory risk, though new safety information could lead to re-evaluation. Failure to secure approvals in other regions may also affect forecasts.
Competitor Risks: Currently, no other therapies are approved for Rett Syndrome. Early-stage gene therapies are in development but pose a minor risk to DAYBUE, which could potentially be used in combination with new treatments.
Reliance on Acadia: Acadia's focus on trofinetide for Rett Syndrome is critical, but exploring additional indications like Fragile X syndrome could influence forecasts based on the timing and choice of these indications.
Figure 3: Summary of Neuren target indications and addressable market/patient sizes and current trial progress

Source: Company Reports, Sandstone Insights
Figure 4: With Phase 2 trials looking more promising, future opportunites are becoming priced in. NEU can deliver significant operating leverage given its business model.