Moonsoon Briefing Thurs 20 April, page-92

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Agent-86

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02/12/23

09:53

Post #: 71232124
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Originally posted by ashgood123: ↑

Why is NNZ 2591 the jewel in the crown? here is a good read from Karst Peak Capital research:

We see the positive results of trofinetide as de-risking Neuren’s other key asset, NNZ-2591, because of the overlapping mechanism of action. NNZ-2591’s primary mechanism of action is to maintain or normalise the levels of IGF-1 in the brain by ‘freeing’ IGF-1 from its binding protein, which prevents IGF-1 from binding to its receptor. NNZ-2591 is a smaller and simpler molecule than trofinetide thus reducing manufacturing complexity. Neuren has also shown that NNZ-2591 has 100% oral bioavailability. Thus theoretically, the dose of NNZ-2591 will be significantly lower than trofinetide and may not have the same level of gastrointestinal side effects seen with trofinetide.

Normally, we would not put much confidence in mouse models of neurological diseases. The difference in this case is that these diseases are all caused by a known gene mutation that can be replicated in mice. In contrast, diseases such as depression or anxiety are challenging to replicate in mice, and therefore mouse models are not very predictive.

Looking at Phelan-McDermid as an example, Neuren conducted a trial in mice where the SHANK3 gene has been deleted (called ‘Knock Out’ or KO mice). The results below show a consistent benefit with NNZ-2591 across various measures of disease.

Seizures as a measure is particularly important as it is an objective measure and is a symptom in humans with Phelan-McDermid. This measure has limited subjectivity in its measurement, either the mouse has a seizure or it does not. The incidence of seizures drops from 60% in the KO + vehicle (i.e. placebo) to 10% in the two highest doses. This coupled with all the other measurements strongly indicates that NNZ-2591 should be trialled in humans.

Similarly positive results have been seen across the other three diseases the company is targeting. While we will not conduct a deep dive into the preclinical results in this wire, all the information regarding the preclinical package can be found on Neuren’s website.

We have had conversations with experts who are KOLs in translational science of neurodevelopmental disorders and the role IGF-1 in these disorders. The feedback has been consistently positive. Experts noted that NNZ-2591 has a clearly understood mechanism of action and the bioavailability means that dosing is convenient and when given orally the drug will reach the required target. These experts also noted that, while mouse models are not perfect, models in these diseases are relevant given the clear aetiology of the diseases under research.

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Thanks @ashgood123 for posting. Provides a good explanation. GLTA

NEU Price at posting: $16.09 Sentiment: Buy Disclosure: Held
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Moonsoon Briefing Thurs 20 April, page-92

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Moonsoon Briefing Thurs 20 April, page-92

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