Enterin announced interesting results of their Phase 2b randomized, placebo-controlled, double-blind KARMET study of ENT-01 (a derivative of squalamine)
Following a 2-week baseline, participants were stratified to high dose or low dose depending on baseline constipation severity & randomized to receive ENT-01 or placebo. 25-day treatment period, then all placed on placebo for 2 weeks + 4-week wash-out
ENT-01 again looks to be safe & well tolerated, AEs primarily gastro in nature - similar to the RASMET study results
The main result: Primary endpoint (change in complete spontaneous bowel movement from baseline to the end of the 3-week treatment period) was met - bowel movement was significantly better in the treatment group compared to placebo (p=0.0001). Note some maintenance in washout
All bowel-related secondary endpoints improved
Interestingly, there was a reduction in levels of psychosis (as measured by SAPS-PD) during 3 week study period, & effect persisted out to 6 weeks post termination of treatment (small numbers in this result, but trend is present)
UPDRS was conducted - mainly for safety sake (study was too short for any efficacy measures) - and the results indicate no worsening of motor symptoms
No announcements on future study plans beyond "More details on future plans will be announced in coming weeks"
Encouraging results though!
p.s. ENT-01 is a synthetic version of squalamine, a molecule originally discovered in the liver and gall bladder of the dogfish shark.
Another experimental small molecule targeting alpha synuclein that is in clinical testing at the moment is ENT-01, which is being developed by the biotech company Enterin Inc.
ENT-01 is a synthetic version of squalamine, a molecule originally discovered in the liver and gall bladder of the dogfish shark.
Squalamine has a wide range of antimicrobial activities, but in 2017 researchers discovered that it is also a potent inhibitor of alpha synuclein protein aggregation:
Enterin Inc. was foundered and between 2017-2018, the company conducted the RASMET study, which was a Phase I safety clinical trial of ENT-01 (Click here for the details about this trial and click here to read a SoPD post on this topic). The issue with ENT-01 compared to other molecules targeting alpha synuclein is that it does not cross the blood brain barrier. Thus, Enterin are focusing their clinical trial on Parkinson’s-associated constipation – can this drug reduce alpha synuclein aggregation in the gut and alleviate complaints like constipation.
The results of the Phase I RASMET study have been published (Click here to read them and click here to read the press release), and the company has very recently announced the results of their Phase IIb ‘KARMET’ clinical study of ENT-01 (Click here to read more about this study).
KARMET was a randomized, placebo-controlled, double-blind study of ENT-01 involving 150 individuals with Parkinson’s. Following a 2-week baseline period, participants were stratified to high dose or low dose depending on baseline constipation severity & randomized to receive ENT-01 or placebo. They were treated and monitored for a 25-day period, then all placed on placebo for 2 weeks before going through a 4-week wash-out. ENT-01 was again found to be safe & well tolerated, with common adverse events being primarily gastrointestinal in nature.
The primary endpoint in the study – change in complete spontaneous bowel movement from baseline to the end of the 3-week treatment period – was met. The researchers observed that bowel movement was significantly better in the ENT-01 treatment group compared to placebo (p=0.0001). It is interesting to note that there was some maintenance of this effect in the washout phase:
In addition, all of the bowel-related secondary endpoints improved in the ENT-01 treatment group. Interestingly, there was a reduction in levels of psychosis (as measured by SAPS-PD) during 3 week study period, & effect persisted out to 6 weeks post termination of treatment (small numbers in this result, but trend is present)
Motor scores (as determined by UPDRS III) were measured, but this was mainly done for safety reasons (the 3 week study was too short for any meaningful efficacy measures). The results indicated that there was no worsening of motor symptoms during the study for either treatment group. Enterin is yet to announce what the next steps are in terms of clinical testing of ENT-01 for Parkinson’s, and they may now be seeking guidance from the FDA regarding next steps.
Enterin has also been assessing ENT-01 in Parkinson’s Disease Dementia in a Phase I open label study (Source). This study was scheduled to complete in mid-2021, so we will hopefully also learn the results of this study in 2022.
In addition to ENT-01 which does not cross the blood brain barrier, Enterin has a strong patent position around another molecule called Trodusquemine which does get into the brain. It is very similar to ENT-01 (also known as squalamine):
The assumption here at SoPD HQ is that the company is conducting preclinical evaluations of trodusquemine (or a derivative of it) with the goal of taking it forward for Phase I clinical testing. We hope to learn more about this in 2022.
ent-01
Very interesting -
@ParkinsonsUK
are investing £2M in Enterin's Phase 2 clinical trial of its drug ENT-01 - a potential treatment for #Parkinsons dementia; They plan to launch a placebo-controlled Phase 2b study in the UK & US in 2023
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