Cortexyme is now Lighthouse; Cue Party Music!

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
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J11
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Cortexyme is now Lighthouse; Cue Party Music!

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J11 here! Great great news!

Cortexyme has reemerged as Lighthouse. I had been unhappy that Cortexyme seemed to just vanish after the Gain phase 2/3 trial. I was worried that that was that. But, no! It has returned.

This is fantastic news! Cor 388 was an oral medication that targeted mouth bacteria that was found to cause Alzheimer effects in the brain. Problem with Cor 388 was it caused liver problems at high doses. They went back to the drawing board and invented Cor 588 which appears to have avoided these problems in a phase 1/2 dose escalation study. They are now all ready to start up a phase 2 trial to see what it can do in AD. The phase 2 study design is all set to be presented tomorrow!

This research would seem to be a win for AD clinical medicine as it could continue to narrow the patient population to more homogeneity. AD is perhaps one of the last wild west type illnesses where there is a very large pool of largely non-differentiated patients. The biggest division besides patient stage is probably e4 versus non e4. Adding in more refinement of patient definition possibly could help reduce the trial noise and possibly increase the topline results.
Last edited by J11 on Mon May 29, 2023 5:32 pm, edited 2 times in total.
J11
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Re: Cortexyme is now Lighthouse; Cue Party Music!

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Atuzuginstat.PNG
Gain.PNG
Periodontal 1.PNG
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Last edited by J11 on Mon May 29, 2023 5:22 pm, edited 2 times in total.
J11
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Re: Cortexyme is now Lighthouse; Cue Party Music!

Post by J11 »

As we can see periodontal illness is associated with rapid AD progression. Periodontal disease has a fairly large effect on AD progression. This does make me wonder about the mab trials: would patients with untreated periodontal disease be allowed into an AD clinical given the above evidence? I wonder if a patient with any treatable medical problem would be given access to a treatment with a retail cost of ~$25,000+ per year without first attaining basic control over comorbidities?

Above is the result from Gain with COR 388 using different measures of presence of bacteria; this analysis was pre-specified. The unselected topline missed. DS in the top left of the top figure is Detected in Saliva-- so there is some easily measurable and non-invasive method of finding the responder class. The company probably has this biomarker in development for commercialization. Cor 388 is an oral medication without risk of ARIA, though it did have problems with liver tox. In Gain there was a problem with the ADCS-ADL it did not confirm the ADAS-cog result. It is not entirely clear why the function test did not show the benefit seen with the cognitive test.
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