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ENTA hasn't disclosed whether there is a backup RNA-destabilizer in the pipeline, but I think it's pretty likely there is. The question, of course, is whether the safety problem seen with EDP-721 is compound-specific or class-specific.
The hit to the share price ought to be pretty modest inasmuch as EDP-721 was only in phase-1.
I assume ENTA will take a hit in stock price tomorrow. Do you think they have another destabilized in process or will this approach be a dead end. I assume the upcoming conference call will provide some information
ENTA new corporate slide set—updated for discontinuation of EDP-721 (HBV RNA destabilizer)—also new slide #19 with in vitro data on COVID protease inhibitor EDP-235:
https://s22.q4cdn.com/306858242/files/doc_presentations/2021/11/Enanta-Corporate-Presentation-Final-11-18-21.pdf
Note: The new slide #19 is different from #19 in the previous version of the slide set, which also coincidentally had new data on EDP-235.
Re: ENTA EDP-721
Discontinuing a compound is always a letdown, but it’s much better to find a safety problem in phase-1 than later on.
ENTA will need to find a second oral compound to complement EDP-514 (the lead HBV compound), which could either be another RNA destabilizer or a compound with a different MoA. The company’s drug-discovery engine is up to the task, IMO.
Enta terminates edp-721 on safety issues…..
First off, I am unaware of any study where HBV viral DNA and RNA were reduced so completely in such a high percentage of trial participants. It's proper to note this is a tiny group and so obviously it needs to be verified in larger studies.
I theorized it like this; if 28 days of monotherapy could virtually eradicate HBV RNA and DNA, that with a nuc you could have the potential for viral eradication - if it weren't for the pesky surface antigen that EDP-721 (Oral Hepatitis B Virus RNA Destabilizer) was designed to attack. "HBV RNA was undetectable at Day 28 in 11 patients in the three EDP-514 cohorts as compared to none in placebo." That's including the 200mg arm that is probably not quite sufficient dosing. That's impressive.
I think I would say that as small as these cohorts were they validate Enanta's approach, their prowess with anti-virals and that success with EDP-514 may foreshadow similar success with EDP-721.
ENTA reports final data from two phase-1b studies of EDP-514 (including 800mg cohorts):
https://www.enanta.com/investors/news-releases/press-release/2021/Enanta-Pharmaceuticals-Reports-Positive-Final-Data-from-its-Phase-1b-Studies-of-EDP-514-a-Novel-Hepatitis-B-Virus-Core-Inhibitor/default.aspx
In the nuke-suppressed phase-1b trial, HBV DNA at baseline is either very low or undetectable in all patients, but HBV RNA is detectable in some patients. However, in the 800mg cohort, 5 of the 6 patients happened to have very low or undetectable HBV RNA at baseline, making the HBV RNA change from baseline to day-28 a meaningless calculation.
In the viremic phase-1b trial, there was a nice dose response in the reduction of HBV DNA from baseline to day-28: -2.9 logs in the 200mg arm; -3.3logs in the 400mg arm; and -3.5 logs in the 800mg arm.
All told, the 400mg dose looks like it provides sufficient pressure on the virus, and it is the most likely dose for ENTA to advance into phase-2, IMO.
I still plan to post the AASLD poster presentations on both phase-1b studies when I obtain them from IR.
I'll post the two poster presentations when I get them from IR. As far as I know, only registered AASLD attendees can access the posters on their own.
That's great!
I wonder if the abstracts will be updated and where they will be visible? Or since it is a teleconference whether they can be viewed?
Thanks, Dew!
The actual poster presentations, which will be available tomorrow, should have the 800mg data. I'm getting copies of them from IR.
Thanks Dew and Willyw. I guess I am not crazy, well at least for for thinking the 800mg dose data would be out soon.
Really, their corporate slides had the same data more or less.
They did win an award for one abstract.
https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.32188 (page 505) abstracts 822 and 823
AASLD presidential poster of distinction
I held back a post where I wrote what I thought it all meant, but felt like you know enough to correctly interpret the data.
My main point hinged on in the 6 each who got active EDP-514 in the 200 and 400 mg cohorts- 8 of the 12 had viral RNA clearance- which to me means 2/6 probably cleared in the 200mg cohort and that the 800mg arm may be less important.
If the 800mg arm had equal results to the 400mg those who experienced clearance of viral RNA in 28 days would be
2 (200mg) +6 (400mg) +6 (800mg)=14/18.
Now that the abstracts are out, the data was pretty much already out there- maybe Enanta will provide more commentary.
The 800mg (highest dose) data from both phase-1b trials of EDP-514 (nuke-supressed and viremic) should be in ENTA's two poster presentations this weekend at AASLD (https://www.enanta.com/investors/news-releases/press-release/2021/Enanta-Pharmaceuticals-Announces-Data-Presentations-at-AASLDs-The-Liver-Meeting-2021/default.aspx ).
I contacted IR to find out how to access these presentations. I'll post again when I get an answer.
The trading liquidity is very low, so ENTA has oversized swings from day to day (and hour to hour). Regardless, the good news is that ENTA is no longer considered a mere royalty play in HCV.
Sold some $46 shares today. Love the prospects but not the time to get greedy in this market.
The stock was in the $40’s a few months ago. I’m okay with $80’s…..
Easy come, easy go as ENTA is about back to where it was before the PFE COVID pill data was announced.
To which I would add- the PFE protease inhibitor also is prescribed w/ (ritonavir) RTV q12h (not terrible, but sub-optimal).
The Enanta compound could be more efficacious, fewer drug interactions, fewer pills fewer times per day.
Once (ha; and IF) approved it may be hard to beat.
And anti-virals will likely play a key part in ending the pandemic.
They will reduce viral shedding, reduce recovery time, probably reduce longer term inflammation damage. They will help make it safer to reopen hospitals, schools and work -thereby getting the economy back closer to normal.
So the value of a great covid anti-viral cannot be overstated.
One other thing that could change all results is (as J. Luly has said) getting the antiviral to patients sooner will likely improve the response success.
Quote:Pfizer to Seek U.S. Nod for Covid Pill After Strong Results
By Robert Langreth
November 5, 2021, 6:45 AM EDT Updated on November 5, 2021, 6:53 AM EDT
Drug reduced Covid hospitalizations by 89% in clinical trial
Covid pill race is heating up with Merck awaiting approval
Jbog, provided this Bloomberg article on the Biotech values web site. https://www.bloomberg.com/news/articles/2021-11-05/pfizer-to-seek-u-s-nod-for-covid-pill-after-strong-results?sref=XLA0GJqR
Two relevant passages from that from that link follow
Quote:
The drug, Paxlovid, binds to an enzyme called a protease to stop the virus from replicating itself. Some drugs for HIV work in a similar way.
The viral protease is the same target ENTA is attacking with EDP-235, which validates that approach.Quote:
The Pfizer drug works to block a crucial enzyme that the Covid-19 virus needs to replicate. It is taken twice a day for five days and used in combination with a second medicine called ritonavir that helps the Pfizer compound stay in the bloodstream longer.
So it is a twice a day combination oral drug whereas EDP-235 is a single oral drug and expected to be a once a day treatment regimen. The PFE drug will be a really nice advance but there is still plenty of room for EDP-235, well assuming it does well in trials.
DewDiligence corrected my dosing regimen comment for the PFE drug as it will required 6 pills a day.
You can see a comparison of the ENTA's drug vs the PFE drug for in vitro cell line data form the ENTA corporate presentation. See slide #19. The first column is ENTA's drug, EDP-235. The second column is the PFE drug. ENTA's drug looks a lot better, but keep in mind ENTA is behind as EDP-235 is slated to begin human trials in the beginning of next year.
https://s22.q4cdn.com/306858242/files/doc_presentations/2021/10/v2/Enanta-Corporate-Presentation-Final-10.19.21.pdf
Roth Capital analyst Zegbeh Jallah keeps a Buy rating on Enanta Pharmaceuticals (ENTA) with a $107 price target after the company data for EDP-235, its oral protease inhibitor of SARS-CoV2. While Merck's (MRK) oral antiviral drug molnupiravir is expected to receive Emergency Use Authorization, EDP-235, specifically developed for SARS-CoV2, is "naturally more potent and could offer a lower pill burden" than the eight daily pills required for molnupiravir, Jallah tells investors in a research note. The analyst says EDP-235 has nanomolar potency against SARS-CoV2 and its variants, ranging from IC50 2.0 - 5.8 nM. She looks forward to EDP-235 entering the clinic in 2022.
Read more at:
https://thefly.com/n.php?id=3389716
ENTA EDP-235 vs competition—for those too lazy to scroll through the slides :- )
$ENTA $AVIR $PFE $MRK $GILD https://t.co/Wax5QGU8NK pic.twitter.com/gNYZITkISK
— M (@bio_clouseau) October 19, 2021
ENTA—New corporate slides—(with EDP-235/COVID update):
https://s22.q4cdn.com/306858242/files/doc_presentations/2021/10/v2/Enanta-Corporate-Presentation-Final-10.19.21.pdf
The new info on EDP-235 is on slide #19.
New_preclinical_data_for EDP-235—the SaRS-CoV2 protease_inhibitor:
https://www.enanta.com/investors/news-releases/press-release/2021/Enanta-Pharmaceuticals-Presents-New-Data-for-EDP-235-its-Lead-Oral-Protease-Inhibitor-Designed-for-the-Treatment-of-COVID-19-at-the-ISIRVWHO-Virtual-Conference-2021/default.aspx
They have Aegis underwriting them with 23 mil in financing , and a protease inhibitor finishing mice trails , pretty sure they are going to be a competitor.
SBFM is essentially insolvent—here’s the 6/30/21 balance sheet:
https://www.sec.gov/ix?doc=/Archives/edgar/data/1402328/000168316821003345/sbfm_i10q-20210630.htm#a_003
Not a serious competitor to ENTA, IMO.
Has anyone heard of sunshine Biopharma ? Ticker SBFM. Great website to browse through. They have Aegis underwriting them to try and get to Nasdaq . COVID/ antiviral pill , Cancer cure and mRNA .
Good point about market cap and share price.
And in contrast to Merck look at Moderna
Moderna's market cap in 2018 - $5b --- 2019 - $6.5b ---2020 - $41. b
and 2021 - $137b
Moderna was tiny (but still 4X ENTA's market cap) and increases to it's market cap caused large elevations in share price; the past years share price range was $65.49 - $497.49.
SO.... if Enanta's Hep B asset alone does well the company will see huge increases in share price.
One would think that the covid asset would also raise it dramatically as well.
And I think other investors are seeing it the same way; hence the recent rise in share price.
I also agree w/ you on the Nash being shelved. The money is far better spent elsewhere.
I am pretty certain Enanta's Hep B franchise will get a lot of attention leading up to and culminating at AASLD mid November.
Congrats! I started adding in March, then share price dropped again which was a bonus. I closed another position in order to add.
Then the Hep B data came out, then covid- which seemed to validate my feelings.
Much of Enanta's pipeline will come into greater focus next year. So like you I rather wished it would stay down a bit longer.
At issue with covid- there are still huge numbers who aren't or won't get vaccinated AND data is showing the need for boosters, increasing proof that immunity isn't forever, etc.
So the need for an antiviral/theraputic is great.
What I am seeing is that the Pfizer PI has some issues (twice daily w/ R boosting), and the Merck is also not free of risk-regardless of the recent positive buzz. Do I think ENTA can create a superior PI to Pfizer's? Yes.
The ATI/Roche compound looks good/interesting and they say their nuke will be resistant to mutation vrs a PI, but we are looking at a 5-7 day treatment- so resistance may not be an issue. It may be more possible/likely to create a successful PI than a nuke but we will see.
IF the Hep B data gets digested and holds in trials the Jeffrie's 95 dollar target will be low.
I cannot imagine Enanta's market cap w/ a successful drug(s) in HBV, Covid and RSV; well over $95, I'd wager.
Finally got into this yesterday. Good timing.
Jeffries initiates with a $95 price target
WATERTOWN, Mass.--(BUSINESS WIRE)-- Enanta Pharmaceuticals, Inc. (NASDAQ:ENTA), a clinical stage
biotechnology company dedicated to creating small molecule drugs for viral infections and liver diseases, today
announced that new preclinical data for EDP-235, its lead oral protease inhibitor specically designed for the
treatment of COVID-19, will be presented at the International Society for Inuenza and Other Respiratory Virus
Diseases (ISIRV)-World Health Organization Virtual Conference (WHO): COVID-19, Inuenza and RSV: SurveillanceInformed Prevention and Treatment. The conference is being held virtually on October 19 – October 21, 2021.
Poster Presentation:
Date: October 19, 2021
Time: 8:00 a.m. CET
Poster #120: “EDP-235, A Potential Oral, Once-Daily Antiviral Treatment and Preventative for COVID-19”
Presenter: Li-Juan Jiang, Ph.D.
ENTA new corporate slide set (updated for NASH discontinuation):
https://s22.q4cdn.com/306858242/files/doc_presentations/2021/10/Enanta-Corporate-Presentation-10.4.21.pdf
ENTA discontinues NASH program:
https://www.businesswire.com/news/home/20211004005192/en
ENTA’s EDP-305 (first-generation FXR) wasn’t going anywhere due to an unacceptably high rate of pruritis, as was previously discussed on iHub (#msg-152426231). The new news in today’s PR is that EDP-297, the follow-on FXR compound, was no better than EDP-305.
The market was ascribing zero value to ENTA’s NASH program, so I don’t expect today’s news to be a market-moving event one way or the other.
Today's jump goes under the heading of "oh what a beautiful morning, oh what a beautiful day".
Today's rise is a mere shadow of what is in store when/if either the NASH data, the Hep-B drug data or he as yet not in trials Covid drug data comes back looking really good.
Similar article from Business Insider:
https://www.businessinsider.com/covid-19-antiviral-pills-results-coming-impacting-the-pandemic-2021-9
$ENTA is the only one of the mentioned companies that is developing a SARS-CoV-2 oral antiviral from the ground up, as far as I know. That's a distinction worth noting.
— Roy Friedman (@DewDiligence) September 30, 2021
ENTA 9/13/21 (latest) corporate slide set:
https://s22.q4cdn.com/306858242/files/doc_presentations/2021/09/Enanta-Corporate-Presentation-9.13.21.pdf
Thank you for the copy and paste. I often read them a few times so this is convenient.
The best insight into the covid program is here in the most recent presentation; from about the 6 minute mark to 14 minute mark.
https://kvgo.com/baird-2021-global-healthcare-conference/enanta-pharmaceuticals-sept
Before that I believe during the recent Q3 earnings call they also announced the covid candidate. In the following Q and A someone asked if they wanted to compare their covid asset EDP-235 to the others which had been in development. Luly passed on talking about the competition, but mentioned that Enanta was pretty aware of the other theraputics/antivirals in development before releasing theirs.
https://seekingalpha.com/article/4446932-enanta-pharmaceuticals-inc-s-enta-ceo-jay-luly-on-q3-2021-results-earnings-call-transcript
I got the impression that they were confident about their asset, and that they were not going to release a sub-par candidate. It may not be the first, but I think it likely superior to a repurposed or rushed compounds further in trials. My hope is that Enanta's expertise and extra time spent in development will mean a seat at the sars-covid table.
Interesting read on Reuters today featuring Enanta and Jay Luly regarding EDP-235 for COVID:
"Reuters
COVID-19 pill developers aim to top Merck, Pfizer efforts
By Deena Beasley
September 28, 2021
(Reuters) - As Merck & Co and Pfizer Inc prepare to report clinical trial results for experimental COVID-19 antiviral pills, rivals are lining up with what they hope will prove to be more potent and convenient oral treatments of their own.
Enanta Pharmaceuticals, Pardes Biosciences, Japan’s Shionogi & Co Ltd and Novartis AG said they have designed antivirals that specifically target the coronavirus while aiming to avoid potential shortcomings such as the need for multiple pills per day or known safety issues.
Infectious disease experts stressed that preventing COVID-19 through wide use of vaccines remains the best way to control the pandemic. But they said the disease is here to stay and more convenient treatments are needed here.
“We need to have oral alternatives for suppression of this virus. We have people who aren’t vaccinated getting sick, people whose vaccine protection is waning, and people who can’t get vaccinated,” said Dr. Robert Schooley, an infectious diseases professor at UC San Diego School of Medicine.
Pfizer and Merck, as well as partners Atea Pharmaceuticals and Roche AG have all said they could seek emergency approval for their COVID-19 antiviral pills this year.
Rivals are at least a year behind. Pardes began an early-stage trial last month, Shionogi plans to start large-scale clinical trials by year-end, Enanta aims to start human trials early next year and Novartis is still testing its pill in animals.
Enanta Chief Executive Jay Luly said re-purposing drugs originally developed for other viral infections is not an unreasonable approach. But it is not known how potent they will be against COVID-19 or how well they can target lung tissue, where the virus takes hold.
The risk is “if it’s not a great effort ...you’ll end up losing time,” Luly said.
Antivirals are complex to develop because they must target the virus after it is already replicating inside human cells without damaging healthy cells. They also need to be given early to be most effective.
Currently, intravenous and injected antibodies are the only approved treatments for non-hospitalized COVID-19 patients.
An effective, convenient COVID-19 treatment could reach annual sales of over $10 billion, according to a recent Jefferies & Co estimate. Merck has a contract with the U.S. government that implies a price of $700 for a course of treatment with its antiviral molnupiravir.
SEARCH FOR AN EASY TREATMENT
Several classes of antiviral drugs are being explored. Polymerase inhibitors such as Atea’s drug - first developed for hepatitis C - aim to disrupt the ability of the coronavirus to make copies of itself. There are also protease inhibitors, like Pfizer’s pill, which are designed to block an enzyme the virus needs in order to multiply earlier in its lifecycle.
We are trying to halt the processes “that allow the virus to set up a replication factory,” said Uri Lopatin, CEO at Pardes, which is also developing a COVID-19 protease inhibitor.
Merck’s molnupiravir, developed with Ridgeback Biotherapeutics, was at one point envisioned as a flu drug and works by introducing errors into the genetic code of the virus.
“The broad spectrum activity of molnupiravir against RNA viruses, including other respiratory viruses, suggests that it should be a durable, useful molecule,” said Jay Grobler, who oversees infectious disease and vaccines at Merck.
Merck said data shows the drug is not capable of inducing genetic changes in human cells, but men in its trials have to abstain from heterosexual intercourse or agree to use contraception.
Until reproductive toxicology study results are available, “we don’t know if there’s any potential effect of drug on sperm,” said Merck research executive Nicholas Kartsonis.
Both molnupiravir and Pfizer’s pill are taken every 12 hours for five days. Pfizer’s drug must be combined with older antiviral ritonavir, which boosts the activity of protease inhibitors but can cause gastrointestinal side effects and interfere with other medications.
“It is a nuisance to add a drug you don’t need to have a drug you want to take be effective,” Schooley said.
Pfizer said a low dose of ritonavir will help its protease inhibitor remain in the body longer and at higher concentrations.
Enanta, which gets most of its revenue from a hepatitis C deal with AbbVie Inc, scanned its library of antiviral compounds early in 2020. It instead chose to design a new protease inhibitor that targets an enzyme vital to the ability of the coronavirus, and its variants, to replicate.
The drug will be tested at once daily dosing with no ritonavir boosting, Luly said.
Lopatin said Pardes is assessing once- and twice-a-day dosing and whether its drug needs to be combined with ritonavir. “We do not anticipate that we will need to use a booster,” he said.
Pardes received funding from Gilead Sciences, which gave up on an inhaled version of its remdesivir, an intravenous polymerase inhibitor approved for hospitalized COVID-19 patients.
Gilead is still working an oral remdesivir, which was also first developed for hepatitis C and is currently the only antiviral approved for treating COVID-19.
This story corrects name to Ridgeback Biotherapeutics."
Indeed sir. I nibbled a little last week. Admittedly surprised how quickly this moved north….
Happy Labor Day weekend to you all!
Some serious under the radar accumulation of ENTA seems to be happening as the stock price has risen from the low $40s to over $58 in about a month.
HBV competitor, ASMB can’t get anything right:
#msg-165734953
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