Cdibb, you’ve made an important point, one which I was also intending to make.
Jon Pilcher has made it quite clear that any further development by Neuren of NNZ-2591 will be limited to orphan neurodevelopmental disorders. For the reasons you have mentioned. That rules out previously mentioned indications for NNZ-2591 such as TBI, Parkinson’s disease, MS, Alzheimer’s, stroke or ASD. But Jon Pilcher has also made it clear that Neuren is “actively exploring” further potential indications.
While there is a long list of potential orphan neurodevelopmental disorders, I think Jon Pilcher might have come to regret mentioning that it's 100+. Not that that figure is incorrect but because the majority of these disorders, imo, won’t meet other criteria for development.
If Neuren sticks to the playbook established with its first 6 clinical candidates, it will limit itself to monogenic disorders, not because NNZ-2591 specifically addresses the mutant gene, but because these disorders come with a clearly identifiable, diagnosable population.
Any new indication can’t have too large a population, because it wouldn’t qualify as an orphan indication, but very rare disorders with tiny patient populations are probably also not suitable from a commercial perspective.
The disorder would need to feature symptoms that can benefit from NNZ-2591. For example, some neurodevelopmental disorders have a predominantly physical development component with little impact on the brain.
Some neurodevelopmental disorders are so devastating that lifespan is sadly reduced to just a few years, ruling them out as well.
Any new indication would need to address a serious need. Some neurodevelopmental disorders present with predominantly mild symptoms.
From a commercial perspective, it would be preferable that the disorder doesn’t have already approved treatments or treatments in late-stage development. Ideally, one aims to be first-in-class.
Finally, the disorder should have an established patient advocacy group to work with.
As for which disorders might qualify, within the NNZ-2591 patent, Tuberous sclerosis complex and CDLK5 mutations are mentioned.
Some other examples of rare neurodevelopmental disorders which might qualify are: 18q syndrome, 18p syndrome, Smith-Magenis syndrome, Mowat-Wilson syndrome, Lennox-Gastaut syndrome and Dravet syndrome.
Lennox-Gastaut syndrome, Dravet syndrome and Tuberous sclerosis complex do already have a dedicated approved treatment, but it only addresses the symptom of epilepsy.
GW Pharma’s CBD therapy, Epidyolex, was approved in the first two of these indications in 2018 and in the third indication in 2020. Lennox-Gastaut and Dravet syndrome were approved together under the one NDA with 2 Phase 3 trials conducted in each. The third indication, Tuberous sclerosis complex, was approved under an sNDA (supplemental NDA) on the basis of data from a single Phase 3 trial. Once a drug is approved in one indication, approval in further indications is possible under an sNDA with potentially just a single Phase 3 trial conducted.
GW Pharma, by the way, went on to expand its Epidyolex pipeline with multiple other indications but was acquired by Jazz Pharma in 2021 for US$7.2bn.
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