Looks like the biggest piece of news is update on the RSV peds study which has more granularity they have enrolled >70 of the 90 total, and they hope to wrap up enrollment in time to report by end of year now (vs Q3 originally)
The other is cash runway which is 1 quarter less, which is about 3 years of cash. Seems like the burn is going to have to drop for this to happen, but not unrealistic once they wrap up the RSV studies in the next few quarters, but I have to think this does not factor in any phase 3 development for RSV or significant phase 2s for immunology (not sure if this was asked on the call)
otherwise fairly ho hum ? I didn't catch the call but nothing doing after hours right now

correct PFE completed their phase 2 months ago - it is still listed in their pipeline so it has not been formally killed, and data could just be under wraps for competitive reasons

Yeah for a study that most think will be positive I too am starting to think they may have a miss or at least some mixed data. We will probably know more in the coming days w their earnings
The long Covid endpoints are at 24 weeks in the trial listing but they said more than once they plan to unblind data at 12 weeks so??

Not sure but I wasn’t surprised by paxlovid sales and think they are lowballing guidance still. They are still the only game in town in western countries although most people think ensitrelvir will be on the market here by early 2025 (although the odds went down a bit IMO when they missed their own guidance for reporting top line data)

This is what Shionogi said on their call Jan 31:

https://www.shionogi.com/content/dam/shionogi/global/investors/ir-library/presentation/2023/3q/e20240202.pdf

“we have completed the enrollment of over 2,000 cases in December 2023. For the primary endpoint, the time to resolution of all COVID-19-related symptoms, all 15 symptoms, was determined after consultation with the FDA.
In addition, we have obtained data on the suppression of the incidence of Long COVID, so-called sequelae, at 12 weeks, and we are verifying this as well in SCORPIO-HR trial. We are keeping the data up to three months under blind, so we expect to be able to present our results to you in April on these results as a topline after a three-month follow-up starting in December.”

April came and went with no PR. You would think an outright hit or miss would be a straightforward readout so perhaps they are doing some post hoc data mining? Could also be they decided to keep the trial blinded out to 24 weeks who knows

Enta also said on a call in the past that this patent dispute doesn’t affect 235 at all which is distinct enough that it has entirely different IP filed

PIGF is a ligand for VEGFr so they probably hit this family with one of the 3 moieties then target ang-2 and il6 w the 2 others so my guess is they have a tripartite drug that hits more than 3 targets Bc at least one of the “tri specific “ parts has pleiotropic activity
Just my guess and if this is the case I agree that calling it “trispesific” is misleading

The case is farmed out to a high profile MA based firm. The in house counsel is not actively managing the case at all
Even Pfizer uses outside counsel to manage a case like this which requires specific expertise which they simply don't keep in house

I was able to listen midway and the audio was pretty bad, but the slides are up and could be interesting
They do list the profile of their candidate and it has high potency, selectivity and potential for QD dosing. The latter may differentiate from THRD bc at least their earlier candidate was BID. If this is a drug given chronically this could be important (I don't really know if companies are thinking for flares only or chronic for prophylaxis)
clearly this is going to be an important 3rd company with an oral kit inhibitor in the space. There are a lot of potential clinical avenues to pursue so there could be room for more than one drug here but I think this is one where ENTA would want to partner up early to move into multiple indications quickly assuming all the oral drugs end up progressing - it could be that one carves out an indication prior to another depending on development path
I did find the slide of mast cell expression in various tissues somewhat interesting bc one area of differentiation could be how well you hit a specific tissue - ENTA seems to have been able to tune other molecules to hit certain tissues and spare others so if they can get good skin uptake for urticaria, or good GI uptake for eosiniphilic esophagitis that could be a way to set apart from the competition
looks like BPMC is going to file this Q and enter clinic later this year so a few months behind THRD and then ENTA is going to be a few months behind BPMC
What was notable by omission in the slides was any preclinical liver related tox-avoidance. This is what sidetracked THRD's first candidate, and ENTA does mention it iin their slide deck "no GSH adducts in human liver microsome incubation", THRD certainly talks about it - perahps this was brought up during Q&A in this talk but that seems perhaps notable by omission although I give the benefit of the doubt to BPMC given they have success in the kit arena already with non-wild type inhibitors

No I have procedures that day
I’ll catch the replay

re CSU

BPMC has targeted an IND filing this quarter for an oral kit inhibitor for csu
they have an investor day focused on csu/mast cell therapeutics this thursday

https://ir.blueprintmedicines.com/news-releases/news-release-details/blueprint-medicines-host-webcast-and-conference-call

HBV
Reminder that IMCR has a program targeting a functional cure similarly by hitting infected hepatocytes
Here is a PR of some initial clinical data from the program:

https://ir.immunocore.com/news-releases/news-release-details/immunocore-announces-presentation-initial-data-phase-1-immtavr

They are also looking at the drug in HBV infected patients w HCC now

I never considered a data leak on the RSV drug, but there could be a leak on ensitrelvir data (run by NIH and they have data in hand so could be more leaky than if was strictly managed by shionogi I think) or some happenings in the court case. Most likely of course is that the recent drop is just due to inherent volatility

ENTA mentioned that they will have to go to the southern hemisphere for the RSVHR study so enrollment won't be completed for this study in the 2024 northern hemisphere season, but could still be completed this calendar year after the southern hemisphere season
I don't recall if ENTA had as much detail on the CSU program, but they did mention during the last presentation they have been working on it for a long time (over a year), so I am hoping they are not too far behind THRD (which incidentally has a higher valuation w their CSU program being the lone asset and cash through 2026 vs 2027 for ENTA)

I agree they won't run a registrational trial, and I doubt they sink any meaningful money into this program for now
My guess is the entire double dose strategy was not to make money on a longer duration formulation per se, but rather for competitive reasons to upend any perception that daxi was special or unique

Net bad news for the stock need for a booster would have far outweighed any new barrier to competing vaccines that this creates

Just calling it the way I see it - ENTA does have a potential stake in paxlovid
PFE has been totally silent on their next gen PI for covid - the phase 2 was completed months ago

https://clinicaltrials.gov/study/NCT05799495?term=PF-07817883&rank=5

The market is upset they are allocating the cost of a plane ticket to Spain and hotel for the presentation. It's a few thousand added burn ;)
Joking aside nice to see the data will be presented - it's the right thing to do even on what seems to be a defunct asset
235 could be revived if ensitrelvir doesn't post positive phase 3 data this month. Regardless negative ensitrelvir data would still be bullish for ENTA because it is bullish for paxlovid which would make any potential settlement in the lawsuit more valuable (and vice versa of course if the ensitrelvir data are good)

The timing of this presentation should coincide with data from the Shionogi drug. They announced completion of enrollment in December but said the trial would be kept blinded for 3 months to get 12 week data on symptoms for a look on drug effect on long covid (they are planning to follow patients for 6 months total).

Nice try. Panuwat knew about plans for PFE to acquire the company before it was public. Sure the public knew that the company had a for sale sign after the failed SNY bid to acquire the company, but that was already baked into the share price at the time.

No worries north I can get access through my academic institution just a hassle but I should get a new password anyway

I didn't have access to full text either but certainly from the abstract impressive albeit early/small numbers data

i agree harder to do after the fact. GSK and PFE doubled their proposed pricing for RSV vaccines once 2 year efficacy data came out. It's not going to be as easy to do a step change in pricing on the off chance the vaccines will show good efficacy in year 3 (this data will be out soon in fact). However I do think if you suddenly have a 3 year vaccine when you thought you were pricing for a 2 year vaccine you can make an argument to CMS et al. for some larger than typical increase.
RVNC may end up in such a situation if in fact the lower dosing for CD ends up being employed in the real world than expected based on dosing in trials as I am hearing, and you then also start looking at the value proposition. ACIP didn't think GSK was predatory in their pricing when they argued the initial models were for an annual vaccine and were then doubled because of biennial dosing
However you also have pharmas being their own worst enemy on occasion and that might end up the case here too. Abbie for example completely underpriced Mavyret IMO. They could have taken market share from GILD with far less an aggressive price discount (they now had at least a comparable product or better on duration) and now both companies are probably making 50% less than they could have been off the hep c franchises.

Why can’t they raise prices as therapeutics comes online to levels that are still acceptable to payers (especially if duration Pam’s out saving md visits etc) and then just provide coupons to spas etc and take a modest hot to aesthetics share (but maintain especially if duration pans out for a certain percentage of patients )

Link to the NEJM publication

https://www.nejm.org/doi/full/10.1056/NEJMoa2312323

Small trial, but the slight improvement in the tx arm vs decline in the control arm translated to a p-value of.007.
a small molecule glp-1 would probably get through the BBB more efficiently and have better efficacy (or similar efficacy w better tolerability bc can dose it lower systemically)

“It was odd that he chose to address a market which could be addressed just as well more mature technology.”

Agree. There will be skeptics even if they make it through approval given the track record in this class to date.

I was not suggesting they promote off label at all. Rather run trials and get a label for frontalis, or if that is too costly (money and time), at least get more data and publish it where injectors can learn what differences if any there might be for daxi in these other areas of the face
The presumption I am sure was that all these muscles (at least in the face) are comparable and it would not be worth the money and time to run them, but there was a hint that daxi may perform differently in different muscle groups from the CD trial where you didn't need double the botox dose for efficacy
again hindsight is 20/20 but they were dealing with a fundamentally new drug unlike evolus which is basically a botox biosimilar

In hindsight not fleshing out the proper dosing and technique for other areas of the face was also a mistake - it sounds like many injectors knew what to do for glabella but not frontalis, lateral canthal, etc. which affected results
That though should get sorted out through real world experience over time

good one!
I don't follow the company but the CEO sounds like a straight shooter. However he also didn't say the preclinical signal was not there for the second generation so I still think it would have been worth an ask, but it could have been implied. Regardless they have clean data on the 75 patients that have already received LNP2 which bodes well (and yes I assume these patients had the identical delivery w liver targeting moiety but it wasn't expressly stated IIRC)
good luck!

I listened thanks
One of the reasons they think it was the LNP was because they saw dose dependent liver effects preclinically (presumably at doses higher than what they thought they would need in humans).
It would have been nice if Brad Loncar simply asked him if they saw the same liver effects preclinically in the next generation system. Seems like an obvious follow up question to have asked
The company did mention their confidence in the second generation LNP because it has been tested by others in about 75 patients, but he also mentioned they also modified it with a proprietary GALNAc liver targeting moiety. It would have been nice to know if the outlicensed LNP had this modification or was an LNP without the GALNAC attached

Here is what the company said about coverage in therapeutics, whether they have first line use as toxin for CD, need for step edits, and potential for off label use. Sounds to me they have been doing well on the access side of things. From the last cc:

Exactly
Except it’s time consuming. If you can get references for the answers from searches that would be an improvement bc then you can judge the trustworthiness of the sources
We all know there is misinformation out there and my understanding is that current generation of AI can’t always distinguish good from bad sources. Chatgpt could be correct here but If it’s garbage in then it’s garbage out

How do you know chatgpt is correct?

Here’s the paper.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10246135/

Thanks I’ll check out the study. The typical confounders in observational cohort trials like this are really controlled for here so it sounds like this could be pretty compelling data

Speaking of Martin Shkreli he had a cameo on this board right when his news started swirling IIRC

“The outgoing CEO of AlmataBio (the private company AVTX is acquiring) is Patrick Crutcher, who used to be a co-moderator of this message board.”

Very cool. Sounds like he is going to make out quite well. The company is due 7.5 M in cash now and 5M upon dosing the first patient into phase 2 which is a near certainty, along with stock valued at 15M. Another 15M (cash and or stock ) if it makes it to phase 3. Good for him.

We might get a more definitive answer to this now that GSK might be incentivized to bear the cost of a large trial. The upside to their Shingrix franchise would be very significant if positive.

A corollary here is that if you have a small molecule drug with lower efficacy but very clean safety and distinct MOA (i.e. combinable with a GLP-1 backbone) it might be written off by analysts due to efficacy when in fact it could have tremendous value in combination. That would be an entry I might eye in this area bc right now I’m late to the party and valuations are sky high. I have no idea what regimens will ultimately win the day but at least that would be an under appreciated entry

VKTX up 20%, enta up 17% riding its coattails (just kidding i have no clue why enta also up today could be something on the legal front but nothing obvious that I can find https://www.pacermonitor.com/public/case/44980990/Enanta_Pharmaceuticals,_Inc_v_Pfizer_Inc)