alive and kicking
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Discussion starts:
“2.5. Resistance
As with any other antiviral, resistance can be either basal or treatment-emergent.
Mutations in Mpro causing resistance to nirmatrelvir are already found in circulating SARS-CoV-2 viruses (Table 1 and Figure 1)…”
Hu et al identified in GISAID sequences 66 prevalent Mpro mutations located at the nirmatrelvir binding site, 11 of them (including S144M/F/A/G/Y, M165T, E166Q, H172Q/F, and Q192T/S/V) showing <10-fold change in enzymatic activity and resistance to nirmatrelvir (Ki > 10-fold increase) [53]. Sasi et al identified 5 mutations (N142L, E166M, Q189E, Q189I, and Q192T) that reduce the potency of nirmatrelvir: in particular, the IC50 of nirmatrelvir was reduced by 24-fold against E166M [54]. Dias Noske et al reported that N/R retained most of its in vitro activity against most of 14 naturally occurring polymorphism close to the binding site, with only G143S and Q189K linked to higher resistance.
In addition to in vitro data, nirmatrelvir can restrict viral infection in the respiratory organs of hamsters infected with BA.2 [41]. However, a pharmacokinetically human-equivalent dose of N/R did not significantly reduce shed SARS-CoV-2 titers in ferrets and failed to block virus transmission to untreated direct-contact ferrets, whereas transmission was fully suppressed in a group of animals treated with a human-equivalent dose of molnupiravir. Prophylactic administration of molnupiravir to uninfected ferrets in direct contact with infected animals blocked productive SARS-CoV-2 transmission, whereas all contacts treated with prophylactic N/R became infected[42].
It also doesn't hurt that in slide 21, in vitro cell culture data for live virus showed EDP-235 was more potent against omicron than either delta or alpha.
ENTA finally back over $50. First time since early October.
cheynew, what a misery that a super company like HALO goes down based on what analysts THINK HALO should achieve.
What a GREAT MINIPULATION TOOL if you can make the public believe that when a company does a super performance but less than what analysts projected it should go down.
Considering that Enanta owns the patent on Paxlovid, they should be able to make their own clinical trial supply if necessary.
Is the stock going to go up now?
RVNC is now up 13% after hours! After hours trading can be quite misleading and with the weekend upon us we will have a few days to find out if this rise is the real thing and the start of something big. Have a good weekend!
They wait until Friday after hours? Must think it’s bad news
• Slide 21 has new info about EDP-235’s live-virus potency against Omicron and other strains.
• Slide 22 has new preclinical EDP-235 info from a ferret model, including data on viral transmission from animal to animal.
IMO, it’s reasonable to surmise that ENTA is unwilling to dedicate much effort to finding a second HBV agent, and is prepared out-license EDP-514 on suitable terms.
• Presents New Preclinical In Vivo Data Demonstrating EDP-235’s Efficacy and Prevention of COVID-19 Transmission
In fact the half-hearted PFE trial in vaccinated patients failed to show a benefit and was abandoned. It seems a bit contradictory to tell us that vaccines significantly reduce hospitalization yet at the same time promote the use of Paxlovid in the vaccinated, which presumes they are at high risk.
Pfizer said Tuesday that a much-watched study of its antiviral Paxlovid in patients who have Covid but don’t have risk factors for severe disease failed to show a benefit in speeding alleviation of Covid symptoms, but did seem to prevent doctor’s visits and hospitalizations. Additionally, because of the small number of hospitalizations overall in the study, it failed to produce a statistically significant finding on whether patients who had previously been vaccinated against Covid were hospitalized less often if they received Paxlovid.
It seems a bit contradictory to tell us that vaccines significantly reduce hospitalization yet at the same time promote the use of Paxlovid in the vaccinated, which presumes they are at high risk. Maybe Pax and vaccines are additive.
Because they spent billions on a drug that doesn't, in this scenario work, buying the drug and handing it out like very expensive candy to a population on which it wasn't tested, without insisting on a randomized trial in a real world population.
The same trial is also testing Paxlovid. The trial is in a population that has largely been vaccinated. Cf. the trials that lead to US approval for Paxlovid and Molnupiravir, where vaccinated people were excluded.
The study has been published as a preprint and has not yet been peer reviewed.....On the secondary endpoint, the observed median time to first self-reported recovery was six days shorter in the molnupiravir group (nine days v 15 days). In other analyses of the Panoramic trial, clinical recovery was three to four days faster with molnupiravir. However, Hill said that the Panoramic study was open label and that recovery could be quite subjective.
If the Paxlovid arm fails in Panoramic, the FDA and Biden administration are going to look pretty bad, given how vigorously they have been touting use of Paxlovid in the vaccinated population.
This after doing a decent job of holding things together for a long period thru a nasty bear biotech market.
On your last buy post - didn't want to be smartest guy in room, but your buying more based on logic of it's down so much a bottom must be close, to be worrisome. The 50 day and 200 day averages have been obliterated in impressive fashion, (big deal to traders, which makes things worse short term), suggesting more short term downside risk.
So institutions suddenly start paying attention to the "real" financial outlook, but only AFTER approval and subsequent launch is underway. Huh, interesting. Wow. They know a lot about odds of success long prior to approval, launch, IMO.
The MRK-SGEN deal reputed to be nearly done last summer (#msg-169332904) can probably be dismissed after MRK’s ADC collaboration with China’s Kelun-Biotech today:
ENTA FY4Q22 CC transcript:
I'm moving 70% of my assets to Cash, Silver and Gold and having all of my bank accounts set up as Joint accounts with my wife so I am covered up to $500K FDIC for each account...'
Will also have 10% in Crypto and have 5% cash in a safe or safety deposit box and the rest in real estate and tangible assets.
I'm afraid we are going the way of Japan, they have been in a bear mkt since 1990....down 80% for 30 years......
The consequences of the Feds stupidity are already happening with China, Russia and others not buying our bonds and using other currency to purchase oil from Saudi Arabia.
Is this really about a slow ramp up, bad market, lost faith in management, or combination of all of the above? Beats me. We're trading as if approval never happened, and it's really hard to understand why. Even slow launch seems hard to back as a reason because market is always forward looking, One possibility, which I hope is untrue, is that my assumptions about company aren't true/realistic, someone else already knows this now based on launch feedback, but tragically, I won't until later
jmkobers,
I just bought some more RVNC at $19.13.
No update by ENTA about a second molecule for HepB. I thought ENTA was targeting year end for such a molecule or a combination with a drug from another company.
I wonder when the RSV data for EDP-938 is due for high risk patients and young children. There must have been a large population available for the trial given the RSV surge this year.
Thanks. How concerning is the possibility of protease mutations that would diminish EDP-235 efficacy?
I am getting whiplash watching ENTA's day to day fluctuations. For some reason the upswings feel a lot better than the downswings. :)
So buying, as you suggested you would in earlier post? People always think they will, but when it gets lower than they ever thought it would, it's really hard to pull the trigger.
Acting really recently as if a decent sized player wanted out, and quickly, must not have thought much of acceptance bump
I doubt anyone was ascribing non-zero value to ENTA's NASH program, which is why I didn't list ENTA along with the other NASH companies.
Low volume trading but a big drop in RVNC today on no news. It must be tax loss selling. I never expected a drop below $20 after FDA approval. Looks like yet another buying opportunity for longs.
Low volume trading but a big drop in ENTA today on no news. It must be tax loss selling. With the news that China is easing up on their zero Covid policy and that Covid infections are rising dramatically, China would represent a great market opportunity for EDP-235, well if it ever gets approved.
Pavlovid sales are ramping up in China:
Pavlovid sales are ramping up in China:
A win for both patients and physicians!
I love people who think short-term and overreact. Yesterday I added more CDMO and more RVNC.
The Chinese company said that in antiviral cellular assays with infectious SARS-CoV-2, ASC11 showed much higher potency against the virus than other 3CLpro inhibitors including nirmatrelvir, Shionogi's (OTCPK:SGIOF) (OTCPK:SGIOY) oral drug S-217622, Pardes Biosciences' (PRDS) oral therapy PBI-0451, and Enanta Pharmaceuticals' (ENTA) oral medicine EDP-235.
The goal of the phase 1 trial, which is expected to be completed within Q1 2023, is to identify a safe and efficacious dose for the pivotal phase 2/3 in patients with COVID-19.
In addition, the phase 1 study will determine if ASC11 needs to be boosted by ritonavir or not.
The market is a discounting mechanism, and one where each person makes a bet of one kind or another. Your bet is that something will happen to produce income in the future.
I am not prepared to make that bet yet (though not willing to bet against it either). I prefer bets that MRK, BMY, GILD, and ABBV will continue to produce income longer than the market is saying today (plus they are paying me while I wait).
There will be no phase 3 in high risk pts.
Due to the availability of molnupiravir and Paxlovid, it is unethical for a physician to give a placebo to a high risk patient. There is no regulatory framework for this.
There is no phase 3 trial for EDP-235. It is in a standard risk phase 2.
This won’t work (again, see real clinical results from the Paxlovid trial) and won’t get to phase 3.
The Paxlovid standard risk population trial did not meet its endpoint with statistical significance.
Paxlovid does not work in standard risk patients.
Deflectors on maximum.
1) you know nothing about making a drug
2) you know nothing about clinical trials
3) long time listener, first time caller
A good example for you is any of the RSV therapeutics- all failed. Great exposures and great potencies - no translation. My point is that just because something is potent and has good PK, that doesn’t mean it will translate into a cure for an acute infection.
Remember, this is a phase 2 in standard risk, highly seropositive population with a safety primary endpoint. A very hesitant step, you must agree.
Just trying to be objective. And I’m not short anything.