Skyler

[Skyler @XC_Crypto]

@HOThomasWPhelps Is removing the 400mg just housecleaning? As long as 1 participant demonstrated positive response, then the trial moves to 200mg Stage 2 and never needs to escalate dosage. Is that result something that typically results in a trial description update, like seen here?

[Skyler @XC_Crypto]

$ETON If ETON management hits their goal of $500M+ revenue by 2030 and improvement to gross margins from 60 to 75% it'll do fantastic things to the share price.

[Skyler @XC_Crypto]

@tradingsssss My hesitation is then there is a cohort of only placebo, and that didn't align with how CRVS structured previous trials. It is however a parallel trial, while the others were sequential. I messaged Conrad in December since I couldn't get the # to tie out without a placebo cohort.

[Skyler @XC_Crypto]

Here's what the new $CRVS Phase 2 AD Trial design for #SIERRA1 should look like. Corrections welcome.

[Skyler @XC_Crypto]

@tradingsssss That aligns with Q3 CC when Miller says that "patients will be randomized equally into 4 cohorts, 50 patients each, receiving soquelitinib 200 milligrams once per day, 200 milligrams twice per day, 400 milligrams once per day, or placebo.

[Skyler @XC_Crypto]

$ETON PDUFA date of Feb 25 for ET-600 is key to Eton achieving $500MM+ annual sales.

[Skyler @XC_Crypto]

@epickram @plainyogurt21 @Archimedes20311 I wonder how much AZD5462, which they're moving forward still, played into the decision to cut AZD3427.

[Skyler @XC_Crypto]

@FWCStocks I'm presuming the current ~30% increase is from AZD5462. Depending on how much detail AZ provides for AZD3427, we could see a big jump, or the more modest 25%. Counting down the days until Feb 10.

[Skyler @XC_Crypto]

@honzaskaroupka Would they kill one of the drugs, even if they would likely target different lines? I would imagine that AZD5462 would be used first, and then AZD3427? There's cannibalization, but I would think AZD3427 is more escalation and targeted to a specific subgroup.

[Skyler @XC_Crypto]

@tradingsssss So where does TECX fit in all of this?

[Skyler @XC_Crypto]

@liteupthedark1 I don't think you go through that many patients in Cohort 1-3 only to end up with bad data in Cohort 4; I'd give a much lower probability of bad data than 50%. There's too much literature that SQL works in Th2 diseases for that high likelihood for a single cohort to bomb.

[Skyler @XC_Crypto]

@HOThomasWPhelps @DanielJacobsbio With positive data, I would like to see CRVS sell/partner, with a primarily upfront payment, Cifo. 818 is the primary focus for the company, and using non-core assets to bolster their long-term cash position makes sense to me.

[Skyler @XC_Crypto]

Relatively low N (for Phase 2) is selected to balance preliminary data that Ph3 would be successful with <1 year trial. Aim here is to prove that #soquelitinib works in IL-17 diseases and reinforce safety/dosing data that crosses over between all CPI-818 trials.

[Skyler @XC_Crypto]

Here's how I would structure a Phase2 psoriasis trial, if I were $CRVS. Trial objectives is confirm dosing is in-line with AD (IL-17) and PTCL, then move to use optimal dosing (expecting 400mg) for straightforward two-cohort trial. N=60 shortens trial. YYMV, not my field.

[Skyler @XC_Crypto]

@HOThomasWPhelps The biomarker activity is interesting, since DICE identified reduction of IL-17 in the trial. CRVS from their press release saw "reductions in serum cytokine levels were seen for IL-5, IL-9, IL-17, IL-31, IL-33, TSLP and TARC" which I'll classify as meets or exceeds the DICE data

[Skyler @XC_Crypto]

@HOThomasWPhelps Honestly, comparing DICE's DC-806 results of the Phase 1 to CRVS, unless I'm missing something, CRVS is further along significantly.

DICE key takeaways are:
1/ Clean safety profile
2/ Convenient dosing
3/ Biomarker indication
4/ 4-week improvement

[Skyler @XC_Crypto]

@HOThomasWPhelps DICE's goals in Phase 2 are:
1/ Explore QD/BID dosing to obtain optimal dosing
2/ Efficacy and Safety at 12-weeks

CRVS has a significantly more robust safety data that meets DICE's AE profile.
CRVS also has convenient dosing.

[Skyler @XC_Crypto]

@semodough Pretty smart actually. Use data from an ongoing trial, convince the FDA to accept those results for an Orphan Drug & pediatric indication to support a similar population size approval. They basically double their addressable market for a n=16 open-label trial.

[Skyler @XC_Crypto]

@semodough This really should read "FDA concurs that ersodetug registrational data from sunRIZE trial in congenital HI supports ersodetug approval in tumor HI".

FDA agreed to simplify one trial based on RZLT convincing the FDA that results from sunRIZE are also applicable.

[Skyler @XC_Crypto]

@HOThomasWPhelps Although, notably, the total patients in each trial is a decent size of each total population. sunRIZE n=56, which is ~4% of addressable population and upLIFT n=-16 is ~1%.

Ersodetug has Breakthrough Therapy, Orphan Drug, and Pediatric Rare Disease designations by the FA.

[Skyler @XC_Crypto]

@HOThomasWPhelps It's not exactly apples to oranges as upLIFT is only half of the trial data, with the "FDA also confirmed that Rezolute’s pivotal sunRIZE trial... would serve as confirmatory clinical evidence".