Enanta Pharmaceuticals Inc (ENTA)

[vinmantoo]

ENTA finally back over $50. First time since early October.

[DewDiligence]

CFO, Paul Mellett exercised-and-held ~$135K of stock from options that were about to expire:

https://www.sec.gov/Archives/edgar/data/1177648/000106299323000800/xslF345X03/form4.xml

[DewDiligence]

SRNE encounters some safety questions in phase-1b trial of SARS-CoV-2 protease inhibitor:

https://www.globenewswire.com/news-release/2023/01/09/2585304/0/en/Sorrento-Releases-Positive-Results-from-a-Phase-1b-Study-in-China-in-COVID-19-Patients-and-is-Ready-for-Pivotal-Phase-3-trials-with-OVYDSO-STI-1558-an-Oral-Mpro-Inhibitor-as-a-Stan.html

A total of 12 subjects reported an AE in the SAD portion of the study, with one AE of elevated blood thyroid-stimulating hormone (TSH) deemed related to STI-1558 in the 2000 mg cohort.

…In the MAD portion of the study in COVID-19 patients, 20 subjects from a total of 46 subjects reported AEs, with only four subjects experiencing STI-1558-related events. These four AEs included two subjects with mild or moderate liver enzyme elevation (ALT/AST) without bilirubin elevation in the 300 BID and 800 BID cohorts, one subject with mild hyperuricemia in the 600 mg BID cohort and one subject with mild rash in the 800 mg BID cohort.

This trial was conducted entirely in China.

[DewDiligence]

Addendum—The latest slide set addresses some issues posters have raised on this board about EDP-235’s animal data and in vitro potency assays.

[DewDiligence]

Additions/changes in ENTA’s most recent slide set:

• Slides 17-18 have info on the new program for dual inhibition of hMPV and RSV.

• 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.

• Slide 25 has a graphic on the design of the (in-progress) phase-2 trial for EDP-235.

• Slide 27 has info on the new program to develop a papain-like protease inhibitor for SARS-CoV-2.

• Slide 35 has a list 2023 catalysts.

[DewDiligence]

It would be a big deal if EDP-235 was shown to limit transmission of Covid.

Agreed.

[vinmantoo]

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.

It might have been different if EDP-235 had already been approved or already showed stellar phase 3 data but sometimes you have to deal with fiscal reality and corporate capabilities. A bit disappointing but not unexpected.

• Presents New Preclinical In Vivo Data Demonstrating EDP-235’s Efficacy and Prevention of COVID-19 Transmission

It would be a big deal if EDP-235 was shown to limit transmission of Covid.

[DewDiligence]

What ENTA will be discussing at JPM:

https://ir.enanta.com/news-releases/news-release-details/enanta-pharmaceuticals-provide-updates-its-research-and-3

• Progresses Phase 2 SPRINT Trial of EDP-235, an Oral, 3CL Protease Inhibitor for COVID-19, With Data Expected in 1H 2023

• Presents New Preclinical In Vivo Data Demonstrating EDP-235’s Efficacy and Prevention of COVID-19 Transmission

• Expands Robust COVID-19 Antiviral Portfolio With a New Research Program Developing SARS-CoV-2 Papain-Like Protease Inhibitors—[Note: This is a different target from EDP-235, which impedes the SARS-CoV-2 “main” protease—Dew.]

• Introduces New Research Program Targeting Human Metapneumovirus (hMPV) and Respiratory Syncytial Virus (RSV) with a Single Agent; Clinical Candidate Selection Targeted for 4Q 2023

[Emphasis added.] Alas, no update on a new HBV candidate to combine with EDP-514, although the above PR contains one paragraph (at the bottom) reiterating ENTA’s purported interest in HBV. 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.

[DewDiligence]

ENTA’s new corporate slide set—(1/6/23):

https://ir.enanta.com/static-files/0b9a9564-339c-4501-8c98-eab636846bf4

[willyw]

Nearly half of passengers from China to Milan have COVID: Italian officials
https://thehill.com/policy/healthcare/3790837-nearly-half-of-passengers-from-china-to-milan-have-covid-italian-officials/?fbclid=IwAR0TtDHh2TmPlQtODvyfI2u0nd9yB6eJNf7DqB7iI2OzV1dD6VHtnjbjiMg

Gosh! Who could have foreseen that?!

In other news J. Luly ENTA CEO, recently characterized the pandemic as moving towards endemic -- but the pandemic part may yet be with us yet a few more years.

[vinmantoo]

ENTA FY4Q22 CC transcript:

Thanks Dew for the ENTA info and for all the great information you provide on so many topics. 2023 could be the transformative year ENTA shareholders have been waiting for.

Merry Christmas to those who celebrate and Happy Holidays to everyone else. Here's hoping 2023 will be a great year.

[DewDiligence]

ENTA FY4Q22 CC transcript:

https://www.insidermonkey.com/blog/enanta-pharmaceuticals-inc-nasdaqenta-q4-2022-earnings-call-transcript-1100664/?singlepage=1

[DewDiligence]

Typo: FY3Q22—>FY4Q22.

[vinmantoo]

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.

[vinmantoo]

Thanks. How concerning is the possibility of protease mutations that would diminish EDP-235 efficacy?

We can worry about this after EDP-235 has been approved and garnered $20 billion in sales in the first year or two. :)

Even if some resistance is generated to Paxlovid, EDP-235 is a different molecule based on patent filings making it less likely to have cross-resistance.

[biocqr]

Thanks.

[DewDiligence]

As a concern for ENTA shareholders, this is way down on the list. The subject has been discussed several times on ENTA's CCs.

[biocqr]

Thanks. How concerning is the possibility of protease mutations that would diminish EDP-235 efficacy?

Impact of SARS-CoV-2 3CL Protease Mutations on Nirmatrelvir Inhibitory Efficiency. Computational Insights into Potential Resistance Mechanisms

[DewDiligence]

ENTA has undoubtedly run the tests you are referring to, but this doesn’t warrant a press release or a new version of the corporate slide set. The additional info should be in the next version of the slide set, which will presumably be released in time for the JPM conference in January.

[biocqr]

BQ.1.1 has been around since Sept and the slide deck was posted on Nov 21 and now we're almost into 2023 with no update. Why is it taking so long for ENTA to run a test and update their slide deck or make an announcement?

[DewDiligence]

It shouldn’t be a problem insofar as the main protease (what EDP-235 inhibits) is highly conserved across SARS-CoV-2 variants.

[biocqr]

Since Omicron variant BQ.1.1 is resistant to all treatments and is now >57% of all cases in the U.S. and there's no assay listed on slide 19 for BQ.1.1 is that something to be concerned about?

New COVID Subvariant Resistant to All Therapeutic Antibodies

Omicron variant BQ.1.1 found to be resistant to all monoclonal antibody treatments

[vinmantoo]

I am getting whiplash watching ENTA's day to day fluctuations. For some reason the upswings feel a lot better than the downswings. :)

[DewDiligence]

Jay Luly exercised and held $620K of stock today:

https://www.sec.gov/Archives/edgar/data/1177648/000106299322024173/xslF345X03/form4.xml

The options in question did not expire until Dec 2023. Moreover, Luly paid the tax due from the exercised shares in cash rather than in forfeited shares, which makes the exercise-and-hold action mathematically equivalent to an open-market purchase in terms of bullishness.

Note: This exercise-and-hold action was not triggered by Luly’s 10b5-1 plan.

[willyw]

Much of what I am looking at is in the red today.
Further, some Enta (-6.3%) similar small caps are down; AGIO -5.5%. PRDS -13.8%, and ABUS -10.7%. A sea of red.

It seems to me that this December selling is quite common for Enanta. I've also seen large gains also in the New Years period.

FWIW I at one time held MDGL but got impatient and years earlier sold the few shares I had; It was a win in a way cause they were no longer a distraction. The Enanta covid program OTOH has a relatively near time frame readout that very well could distinguish itself from other antivirals.

[vinmantoo]

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.

[DewDiligence]

More_on_the_same_story—Paxlovid sales in China:

https://finance.yahoo.com/news/3-china-meheco-distribute-pfizers-180624462.html

[vinmantoo]

Pavlovid sales are ramping up in China:

I guess it is about time I bought some PFE. China could also be a major market for ENTA's EDP-235. Fingers crossed!!

[DewDiligence]

Pavlovid sales are ramping up in China:

https://finance.yahoo.com/news/1-china-health-app-starts-093451036.html

[DewDiligence]

So they claim it is much more potent than EDP-235 but they don't know if it needs ritonavir.

Ha!

[vinmantoo]

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.

Looks like China is still pushing treatments originating in China in their ultraNationalism fervor driven by Xi rather than taking steps to protect its citizens.

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.

So they claim it is much more potent than EDP-235 but they don't know if it needs ritonavir. The only thing I m jealous of is they are talking about a phase 2/3 trial already whereas ENTA is conducting a phase 2 only.

[rwwine]

Ascletis Pharma (OTCPK:ASCLF) said China's National Medical Products Administration (NMPA) approved its investigational new drug (IND) application to start a trial of oral drug ASC11 for COVID-19.

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 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.

Pfizer's (PFE) Paxlovid consists of (nirmatrelvir and ritonavir).

"The IND approvals of ASC11 from both China NMPA and U.S. FDA mark a great recognition to our in-house R&D capabilities," said Ascletis Founder, Chairman and CEO Jinzi Wu.

Ascletis added that ASC11 has potent antiviral activity against several Omicron variants such as BA.1 and BA.5. In the animal model with infectious SARS-CoV-2, ASC11 also showed potent antiviral activity, according to the company.

[DewDiligence]

PFE enlists Clear Creek Bio (private) to develop an oral inhibitor of the SARS-CoV-2 papain-like protease (which is distinct from the SARS-CoV-2 “main” protease that is targeted by Paxlovid):

https://finance.yahoo.com/news/pfizer-clear-creek-bio-collaborate-114500791.html

This collaboration is a tacit admission by PFE that Paxlovid is far from an ideal answer to the question of how endemic COVID should be treated.

Financial terms were not disclosed.

[vinmantoo]

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.

Apparently, I am much more of a gambler than you are. I don't gamble just to gamble, I prefer to do it when I have an edge. For example, when I go to Las Vegas to gamble, I count cards and play blackjack. You can still lose counting cards, but you shift the odds in your favor and pays over the long run. I consider Biotech stocks in that same way, and I really like my chances with ENTA. FWIW, I nibbled and bought a little bit more ENTA this morning at just above $40.

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).

My IRAs from work are in various mutual funds, much of it low load in TIAA-CREF. I also have a separate money in my personal account where I focus on Biotech with some of that in dividend producing stocks you live like ABBV and BMY. I did diverge and add some APPL and NFLX in July and have a small loss for APPL and a nice gain from NFLX.

[Rocky3]

ENTA's EV at the current share price ($41.58)=~$750M—down sharply from ~$1.4B three months ago.

If there's a better $750M-EV biotech stock out there, I don't know what it is.

Part of the the EV decrease is from the loss for 3 months (~$25MM), and they have guided for another $175MM+ loss in the next 12 months. 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).

[biolover]

Makes sense , thanks Dew. It’s not a trading vehicle for me.

[DewDiligence]

The selloff during the past three months was triggered, in part, by Biden saying (prematurely) that the pandemic was over.

Day-to-day movements in the share price are almost meaningless (unless you're trading them) because the volume is so low.

[biolover]

Agree . Any particular reason it got sold off lately? Healthcare overall doing ok. Really surprised by the reaction. I am a shareholder of ENTA. I mean 7 percent drop on holiday weekend ? For no reason !!

[DewDiligence]

ENTA's EV at the current share price ($41.58)=~$750M—down sharply from ~$1.4B three months ago.

If there's a better $750M-EV biotech stock out there, I don't know what it is.

[DewDiligence]

ENTA’s fully-diluted share count @9/30/22=25.2M—an increase of 0.5M since 6/30/22 (#msg-169621216).

The 25.2M figure above consists of: 20.8M basic shares on the 9/30/22 balance sheet (https://www.sec.gov/ix?doc=/Archives/edgar/data/0001177648/000095017022025667/enta-20220930.htm#consolidated_balance_sheets ); and 4.4M options and unvested restricted-stock equivalents (whether or not exercisable) (ibid, page F-13).

[vinmantoo]

There will be no phase 3 in high risk pts.

I never imagined there was any sure thing in investing but our resident board Kreskin Jake2234 apparently feels there are sure things. First he said that EDP-235 will fail its phase 2 trial. Now he say even if it succeeds that won't be a phase 3 trial. Amazing! So why does he say the latter?

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.

Bbbwwaaa hhaaa, looks like the FDA didn't consult with Kreskin, uh Jake, as there are a series of drugs to combat Covid in phase 3 trials. Apparently, our modern day Kreskin Jake doesn't know that Paxlovid isn't readily available everywhere the world, or that clinical trials can be conducted outside the US.

Phase 3 trial.

https://ir.ateapharma.com/news-releases/news-release-details/atea-advance-global-phase-3-registrational-study-bemnifosbuvir


Phase 3 trial.

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00215-6/fulltext


Phase 3 trial.

https://www.fiercepharma.com/pharma/gilead-touts-veklury-resilience-against-mutated-coronavirus-plots-phase-3-new-covid-oral


Phase 3 trial.

https://www.shionogi.com/global/en/news/2022/09/20220928.html


Phase 3 trials.

https://pharmaceutical-journal.com/article/feature/everything-you-need-to-know-about-the-covid-19-therapy-trials


There is a regulatory framework.

https://www.fda.gov/drugs/coronavirus-covid-19-drugs/coronavirus-treatment-acceleration-program-ctap

[Jake2234]

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.

[vinmantoo]

There is no phase 3 trial for EDP-235. It is in a standard risk phase 2.

Wow, you are a genius and an amazing detective to be able to find out something that is obvious.

This won’t work (again, see real clinical results from the Paxlovid trial) and won’t get to phase 3.

You don't understand what the phase 2 trial is about. The phase 2 trial does not have a primary end point regarding patient outcome. It is primarily a safety and dosage assessment trial. You are delusional to think there won't be a phase 3 trial involving the elderly and high risk patients if safety and plasma distribution data are as good in the pase 2 trial as was indicated in the small phase I trial. You also don't seem to understand the advantages of EDP-235 over Paxlovid. EDP-235 doesn't require a drug pump inhibitor and 6 pills a day as Paxlovid does. Rather, EDP-245 will be a one pill a day treatment and NO drug pump inhibitor. You short use all your assets to short ENTA as you are so certain of failure.

[Jake2234]

Thanks for the reply. 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.

Did I miss anything there?

[vinmantoo]

The Paxlovid standard risk population trial did not meet its endpoint with statistical significance.

Yes, but that won't be the target population for EDP-235 in phase 3. EDP-235 will be going the high risk population and the elderly, you know, the population where Paxlovid is racking in $20 billion in 2022 alone. By the way, Paxlovid's failure in the standard risk population represents an unmet need.

[Jake2234]

The Paxlovid standard risk population trial did not meet its endpoint with statistical significance.

[willyw]

Paxlovid does not work in standard risk patients. Check your data. EDP-235 won’t work either.

Ask yourself; what is the bar to approval?
According to you it seems to be incredibly low if Paxlovid doesn't work.

https://www.globaldata.com/media/pharma/top-selling-covid-19-drug-paxlovid-see-sales-decrease-2023-following-second-booster-says-globaldata/

"Although many pharmaceutical companies have launched therapeutic drugs for COVID-19, Pfizer’s Paxlovid takes the top spot as market leader. The drug has expected peak sales of $30.7 billion in 2022 and total generated sales of $81 billion between 2021 and 2028, according to GlobalData, a leading data and analytics company."

So..... if Enanta's compound were better, more efficacious, once a day without boosting it would seem approval would be simple since the bar is so incredibly low.

[vinmantoo]

Paxlovid does not work in standard risk patients.

Good to see you have moved on to a different meaningless approach.

What do you mean by Paxlovid doesn't work in standard risk patients?

Do you know that Paxlovid has massive sales in the elderly and in treating high risk patients?

[Jake2234]

Paxlovid does not work in standard risk patients. Check your data. EDP-235 won’t work either.

[vinmantoo]

Deflectors on maximum.

1) you know nothing about making a drug

It is irrelevant whether or not I know how to make a drug.

2) you know nothing about clinical trials

It is irrelevant whether or not I know a lot about clinical trials.

3) long time listener, first time caller

If you say so but personally I think you a recent first time arrival. I suggest you read more about Covid, Paxlovid and EDP-235 so you can get up to speed and raise reasonable issues.

Back to your irrelevant comparison to RSV. There has never been a drug that has been clinically proven to inhibit RSV enough to help infected people enough to get FDA approval. That means we don't yet no how much inhibition of RSV in vivo is needed to sufficiently improve patient prognosis, nor do we know which RSV target would work best or even work well. ENTA's EDP-938 showed real promise in a challenge trial but while it lowered viral titer in infected people, it didn't statistically reduce symptoms. ENTA is testing it in high risk patient. We will see.

In stark contrast, Paxlovid works quite well in patients. We know how much drug is needed to improve prognosis of infected patients. We also knows that Paxlovid targets the Covid protease. EDP-235 targets the same protease but inhibits at much lower drug levels. Unlike Paxlovid, EDP-235 also doesn't need a drug pump inhibitor, making it better (safer?) for patients who are on other drugs. We know from the phase I trial of EDP-235 that its plasma levels are several fold high than needed to inhibit Covid, and its ~1 day half-life means EDP-235 should remain at inhibitory concentrations for several days after treatment stops. That may make it better at preventing Covid rebound than Paxlovid. There are no guarantees. I did mention potential safety issues could crop up in any trial, and that goes for EDP-235 even though the safety data looked good in the small phase I safety trial. I also stated the short treatment period, 5 days, makes safety issues less likely.

I have covered this issue sufficiently so I am done with this thread.