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Victoria Yan Profile picture
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Jan 1 • 3 tweets • 2 min read
I have wondered why ph2/3 #VV116 trials exclude participants with eye disease (super specific imo)

From study protocol: Conjunctiva and cornea changes were noted in dogs treated at 250 mpk

A VV116-specific effect or also applicable to #GS441524 prodrugs @GileadSciences?
nejm.org/doi/full/10.10…
I am reminded of the FDA-approved ocular drugs that are ester prodrugs. Added lipophilicity + esterase expression in cornea might explain preclinical ocular tox with VV116 in dogs.

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More from @victoriacyanide

Victoria Yan Profile picture
Dec 28, 2022
When did @GileadSciences decide that #GS441524 hypothesis was valid? Clues in patent history🔍

While Gilead bashed GS-441524 in 2020, they quietly worked on oral prodrugs

Could we have had an oral COVID pill in late '20/early '21? 💊

I think YES 🧵1/16
worldwide.espacenet.com/patent/search?…
Patent on oral GS-441524 prodrugs has 1st priority filing on AUGUST 27, 2020. So they did not think the '524 hypothesis was worthless in 2020. 2/16
statnews.com/2020/05/14/gil…
Context: @Muller_Lab & I published an Opinion in @statnews urging Gilead to pursue dev of #GS441524 in May 2020 (above)

On June 24, 2020, we first met w Gilead science leadership, who indicated they were not interested. 3/16
medium.com/@victoriacyani…
Read 16 tweets
Victoria Yan Profile picture
Nov 29, 2021
BIG NEWS: deuterated #GS441524 tri-iBu ester (#VV116) is in clinical trials in Uzbekistan for #COVID19. Trials in China 🔜. Developed by the one and only *Wuhan Institute of Virology*. Deuterium was added to bypass @GileadSciences 💊 1/4
@ncats_nih_gov
shine.cn/news/nation/21… Image
Official article published in @cell_res in September 2021 by the folk at Wuhan Institute of Virology. Original @biorxivpreprint was published in November 2020. 2/4
nature.com/articles/s4142…
Chinese patent by the WIV first filed in Sept 2020. WO patent filed in April 2021. Gilead's 2009 patent on 524 and the 2016 patent on #remdesivir do not include any of the compounds described in the WIV patent. Does Gilead actually own any of these WIV compounds?? 3/4 ImageImage
Read 5 tweets
Victoria Yan Profile picture
Apr 9, 2021
First-in-Woman Safety, Tolerability, and Pharmacokinetics of Orally Administered #GS441524: A Broad-Spectrum Antiviral Treatment for #COVID19. A 🧵1/7 osf.io/am5s8/
Part 1 of the study: 750 mg GS-441524 was orally administered as a solution QD for 7 days. D1-5 were performed in the fasted state. D6-7 in the fed state. There was a slight food effect that seemed to hamper drug absorption. Cmax ~2.4-3 uM. AUC ~26-33 uM. 2/7
No AEs or lab abnormalities were observed in Part 1 of the study. Blood chemistry was normal. 3/7
Read 7 tweets
Victoria Yan Profile picture
May 14, 2020
Fun fact: #remdesivir is almost certainly not the species that reaches #COVID19 patients' lungs! Its nucleoside #GS441524 is. Wrote this piece for @statnews explaining this! @GileadSciences consider aerosolizing GS-441524 prophylaxis. Pls read and RT! 1/x

bit.ly/3dIc0Au
I've been reading a lot of general audience/science articles on #remdesivir. Many of these articles seem to confuse nucleoSIDES with nucleoTIDES. Here's the difference, feat. important figures. 2/x
#remdesivir is a nucleoTIDE monophosphate analogue. #GS441524 is a nucleoSIDE analogue. 3/x
Read 10 tweets

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