Enanta Pharmaceuticals Inc (ENTA)

[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.

[Jake2234]

1) you know nothing about making a drug
2) you know nothing about clinical trials
3) long time listener, first time caller

[vinmantoo]

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.

That's your big example? Bbbbwwaaa hhhhaaaa. Nobody has YET shown ANY mechanism which can be used to successfully block or limit RSV in humans to prevent illness. In stark contrast, inhibiting the Covid protease is an ESTABLISHED mechanism of blocking Covid replication has been shown to be HIGH EFFECTIVE in HUMANS. That drug is Paxlovid. Are you going to dispute that? The levels of EDP-235 far exceed what is needed to inhibit Covid by the same mechanism as Paxlovid.

Remember, this is a phase 2 in standard risk, highly seropositive population with a safety primary endpoint. A very hesitant step, you must agree.

So? ENTA isn't a large pharma so they are spending less money on a phase 2 trials so they can partner for the phase 3. Would I prefer a phase 2/3? As an investor who wants to make money sooner rather than later, yes.

Just trying to be objective. And I’m not short anything.

You created an alias 3 days ago and all you have done is make a series of posts that are very questionable attacks on ENTA and you justify it with irrelevant comparisons to RSV. Either you never heard of Paxlovid and that its inhibition of the Covid protease is effective in humans. Well, either that or you have an agenda, i.e. a short.

[Jake2234]

For laughs? Not trying to laugh. Just trying to be objective. And I’m not short anything.

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.

Yes this is a validated MoA. But, they are not showing their full hand. Again- where is the animal efficacy data? They must have it. Everyone else has shown this. If someone was buying, they would have already bought it. Certainly cheap enough here.

[vinmantoo]

Yes, rodent PK has been shown. But why not the efficacy? If I had a dime for every drug that had good absorption and tissue distribution I would be a rich man.

Just for laughs, tell us all the anti-viral drugs with well defined MOAs for specific well-studied viruses, such Covid-19, where drug levels far exceeded the level needed to inhibit viral replication but that failed miserably. Please exclude viruses that integrate into the host's DNA. That should be a very long list as you said it would take only take a dime for each example to make you a rich man. I mean, at $0.10 a pop you would need 10 million examples to get to a mere $1 million.

You don't seem to grasp that Covid is a virus that has been extensively studied and the protease that EDP-235 target whose activity is indispensable for viral replication. Inhibiting that protease has been proven to provide excellent efficacy. The EDP-235 concentration needed to inhibit Covid has been assessed and the bioavailability in animals as well as in humans from the phase I trial makes it crystal clear that EDP-235 greatly exceeds that concentration. The only concern I have is potential safety issues. However, such concerns are lessened greatly by the good phase I safety data and the fact treatment is a once-daily dosage over only for 5 days and doesn't requite a drug pump inhibitor like Paxlovid does. I urge you to short away.

Possibly inspired by the success of HIV protease inhibitors, of which eleven drugs are FDA approved, multiple SARS-CoV-2 main protease inhibitors are under develop- ment. One protease inhibitor candidate drug with FDA fast track designation, EDP-235 (Enanta Pharmaceuticals), is currently in a phase 2 clinical trial. Unlike Paxlovid and Mol- nupiravir, which require twice-daily doses, EDP-235 is targeted as a once-daily oral drug that does not require co-administration of Ritonavir18. Interestingly, Glecaprevir, a com- ponent of the hepatitis C drug Mavyret (identified jointly by Enanta and AbbVie), is a high affinity macrocyclic inhibitor of SARS-CoV-2 main protease19. As such, is EDP-235 repurposed macrocyclic Glecaprevir that is being developed as an antiviral drug against SARS-CoV-2? This is not unreasonable, since Enanta has two issued compound owner- ship (COM) US patents (8,648,037; and 9,220,748). More likely EDP-235 is a macrocyclic spiropyrrolidine derived structure cited in US patent 11,319,325 and assigned this year to Enanta for treatment of coronavirus infection. A confounding factor regarding little infor- mation about the structure of EDP-235 may be a patent infringement suit concerning Paxlovid, filed by Enanta June 21, 2022 against Pfizer and prompted by Enanta's US patent 11,358,953, issued June 14, 2022.

The above quote is from unreviewed preprint that has just been submitted but it does provide good information.

https://www.preprints.org/manuscript/202211.0221/v1

[DewDiligence]

What kind of rodent “efficacy” data would you want to see?

This thread is a red herring, IMHO.

[Jake2234]

Yes, rodent PK has been shown. But why not the efficacy? If I had a dime for every drug that had good absorption and tissue distribution I would be a rich man.

What kind? The same kind Pardes and Shionogi have shown.

[Jake2234]

Thanks for the thoughtful reply. Indeed HCV had a great outcome. This was realized in a collab with Abbvie, not solo. Completely different game now. Others, including Shionogi and Pardes, have shown rodent efficacy data. Why none from Enanta? Also (as Dew expressed earlier) it is strange that they are running a Phase 2 and not a 2/3 registrational trial. To boot, safety is the primary endpoint! They are setting up for a “positive” P2 result no matter what (standard risk patients), by doing this.

[DewDiligence]

All we have seen is cellular potency.

That’s not entirely true. See slide #18 in the latest slide set (https://ir.enanta.com/static-files/0b9a9564-339c-4501-8c98-eab636846bf4 ):

– Good oral bioavailability (95% in rats) and long half-life (16 hours)

– Good target tissue distribution (e.g. lung to plasma AUC ratio >4)

Cellular assays don’t have lungs.

Also see the footnotes to slide #20.

[willyw]

That's trials. : ) Each step you only get a little more clear view of safety, efficacy. If there were animal studies posted you can still correctly assert that it's no proof it will work on people.

Years ago Gilead bought a whole company just to acquire rights to a Hep C drug; a nuke. They hypothesized that another company was having good results in trials using 4 antivirals to treat Hep C. Gilead thought; lets combine the nuke with another competitors drug; an NS5a antiviral - Daclatasvir.

Gilead thought that the nuke and NS5a in combination could work as well as the other HCV pioneering partnership's treatment- Abbott (now Abbvie) and Enanta's. (that was about 2010 or 11)

Gilead paid about 11 billion for the compound and the reaction was similar to yours; it's too much money and it's not proven. I was in that final Phase 3 registration study in 2014 where Gilead was still proving dosing and duration in the middle of the decade. Conventional wisdom was that Gilead had lost it's mind and overpaid........ and was soon proven soundly incorrect.

In the case of Enanta, it was some unknown tiny company, but it did what JNJ, Merck, BMY, Roche, Sherring-Plough, Boehringer Ingelheim, et al couldn't do.
AND Enanta did it twice, in two successful launches of Hep C treatments.

There was a time that conventional wisdom said that a "nuke was necessary" to treat Hep C. And yet this small company in a partnership w/ Abbvie created a pan-genotypic Hep C 2 drug treatment with protease inhibitors they created in each - without the use of a nuke.

How many companies tried to create a Covid antiviral? Who will have the best? That same small company seems to have some of the best data I've seen. Yes, it's still early and things are not yet proven to your satisfaction. We won't have that long to wait for data.
Enanta has demonstrated *proficiency* with protease inhibitors with great success in the past.

[vinmantoo]

All we have seen is cellular potency.

Please feel free to short away.

[DewDiligence]

ENTA’s updated corporate slide set (11/21/22):

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

[Jake2234]

They have not released any animal efficacy data (as others have). Go ahead and link to the data since you say they have released it. All we have seen is cellular potency.

“Caveat Emptor”

[vinmantoo]

How do you know it removes coronavirus infection in patients? Cellular potency data?

EDP-235 is a very potent inhibitor of Covid. The data from in vitro data and animal models is quite clear on what level is needed to inhibit Covid. The phase I trials provided crystal clear data showing that EDP-235 reaches levels many times higher than needed to inhibit Covid, and maintains it for several days after administration stops. This isn't an oncology trial where MOA is unknown or where animal model often doesn't predict what happens in humans. I can't rule out that some unexpected safety issue will crop up in the phase 2 trial.

[Jake2234]

How do you know it removes coronavirus infection in patients? Cellular potency data?

[vinmantoo]

They have an exorbitant spend and no indication that this drug even works. A very tricky clinical development path.

Two lies in one post! Impressive. There is strong evidence that EDP-235 robustly inhibits Covid and the amount of money needed to get it through phase 2 trials isn't very high.

I notice your alias was just made today and that was nonsensical post is your only post. Short alert, short alert.

[Jake2234]

They have an exorbitant spend and no indication that this drug even works. A very tricky clinical development path.

[DewDiligence]

ENTA will presumably seek some up-front cash when they partner EDP-235 following phase-2 (assuming the data are positive).

[vinmantoo]

So with expenses going up $50-75MM and revenue weak, it is possible for $175-200MM (or higher) loss in next 12 months. Sounds like they might need to raise more money sooner than later.

The markets seems to agree with you. The long projected timeline for EDP-235 and no announcement on a second anti-HBV drug may also be weighing on ENTA stock price.

[Rocky3]

So with expenses going up $50-75MM and revenue weak, it is possible for $175-200MM (or higher) loss in next 12 months. Sounds like they might need to raise more money sooner than later.

[DewDiligence]

FY3Q22* financials—9/30/22_pro_forma_cash=$307.2M (including $28.7M tax refund due from IRS):

https://ir.enanta.com/news-releases/news-release-details/enanta-pharmaceuticals-reports-financial-results-its-fiscal-33

FY4Q22 royalty revenue was $20.3M, up from $19.5M in FY2Q22 (#msg-169620050). FY2022* (12m) royalty revenue was $86.2M, down from $97.1M in FY2021.

FY2022 (12m) R&D expenses were $164.5M, inline with ENTA’s guidance of $150-170M. FY2022 (12m) SG&A expenses were $45.5M, slightly above ENTA’s guidance of $35-41M.

For FY2023*, ENTA today issued guidance of $210-230M of R&D expenses and $46-52M of SG&A expenses.

*ENTA’s fiscal years end on September 30.

[DewDiligence]

Feature story on EDP-235 in today's Boston Globe:

https://twitter.com/DewDiligence/status/1590639173970538497

[vinmantoo]

ENTA starts phase-2 trial of EDP-235 in non-hospitalized, standard-risk COVID patients:......Data are expected in 1H23. I had been hoping for a pivotal phase-2/3 trial. but either ENTA or the FDA evidently didn’t like that idea.

I was hoping the same. Maybe ENTA decided they didn't have the experience to run a phase 3 or they didn't want to risk the money. If the phase 2 data is good they will seek a partnership. Hell, they may have an interested suitor waiting in the wings to see what happens.

[DewDiligence]

ENTA starts phase-2 trial of EDP-235 in non-hospitalized, standard-risk COVID patients:

https://finance.yahoo.com/news/enanta-pharmaceuticals-initiates-sprint-phase-120000085.html

The randomized, double-blind, placebo-controlled study will enroll approximately 200 non-hospitalized, symptomatic patients with mild to moderate COVID-19, who are not at increased risk for developing severe disease. Patients will be eligible to participate if they have had symptoms for five days or less and have not received a SARS-CoV-2 vaccine or been infected with SARS-CoV-2 within 90 days of enrollment.

Patients will receive EDP-235 orally at a dose of 200mg or 400mg or placebo once daily for five days. The primary objective of the study includes evaluation of safety and tolerability, and secondary objectives include the evaluation of virologic endpoints, clinical symptoms and outcomes, and pharmacokinetics.

Data are expected in 1H23. I had been hoping for a pivotal phase-2/3 trial. but either ENTA or the FDA evidently didn’t like that idea.

[procqw2]

Guessing if P2 turns out great, it doesn't matter it isn't 2/3? eom

[randychub]

I would think so. RVNC is sliding with an approved drug. If everything runs perfectly how long until approval? Like RVNC unless the company is sold the market turns around it will linger

[vinmantoo]

Is ENTA going to keep sliding until they announce their phase 2 or phase 2/3 trial of EDP-235 for Covid, or won’t that even stop it?

[willyw]

“It all has a very COVID-esque feel to it,” said Dr. Meghan Bernier, the medical director of the pediatric intensive care unit at the children’s center. “This is the pediatrician’s COVID. This is our March 2020.”

https://www.yahoo.com/news/march-2020-childrens-hospitals-overwhelmed-183549189.html

[DewDiligence]

RSV is surging, just as Jay Luly predicted:

https://www.npr.org/2022/10/24/1130764314/childrens-hospitals-rsv-surge

"This year, parents are sending their children to daycare and school for the first time following two years of the pandemic. ... Children who haven't been previously exposed to respiratory viruses are getting sick…"

[vinmantoo]

ENTA doses the first person in a phase I safety study of their new RSV L-protein inhibitor EDP-323.

https://finance.yahoo.com/news/enanta-pharmaceuticals-doses-first-subject-110000022.html

[vinmantoo]

Both the RSV and Covid programs are short treatments and expedited approval processes.
It has been hard to be patient, I must say.

You and me both, willyw, you as me both. As they say, patience is a virtue so we have to be extremely virtuous.

[willyw]

"Right now, we're in a huge spike of RSV," said Dr. Frank Esper, an infectious diseases expert at the Cleveland Clinic. RSV often affects babies but can also be problematic in adults with underlying lung problems, such as asthma and chronic obstructive pulmonary disease.

Esper said that cases of RSV are usually seen in December and January, but for the past two years, the typical RSV season has come earlier, during summer and early autumn. Rhinoviruses and enteroviruses are also circulating earlier than usual. This is because measures to curb Covid spread didn't allow other viruses to spread as they historically have.

"Flu off to an early start as CDC warns about potentially severe season"
https://www.yahoo.com/news/flu-off-early-start-cdc-235915662.html
==================================

With some luck the trials will be filled with greater ease than during Covid restrictions.

Both the RSV and Covid programs are short treatments and expedited approval processes.
It has been hard to be patient, I must say.

[vinmantoo]

MRK—Lagevrio misses_primary_endpoint_in_large_Oxford_U_trial:

Yet for some reason ENTA dropped today. Welcome to today's stock market. Oh well, another chance to add more ENTA at a lower price.

[DewDiligence]

MRK—Lagevrio misses_primary_endpoint_in_large_Oxford_U_trial:

https://ca.finance.yahoo.com/news/merck-ridgeback-biotherapeutics-clinical-non-235000071.html

The PANORAMIC study, a UK-based clinical trial sponsored by the University of Oxford, included 25,783 participants who were randomized to open label treatment with LAGEVRIO plus usual care (n=12,821) or usual care alone (n=12,962); mean age of participants was 56.6 years. Primary outcome data were available in 25,000 (97%) participants. Nearly all (>98%) participants were vaccinated, with approximately 95% receiving three or more doses of a SARS-CoV-2 vaccine.

In the preliminary analysis, the primary endpoint of reduction of hospitalizations and deaths within 28 days of randomization, compared to usual care, was not met; 0.8% of patients in both the LAGEVRIO group (n=103/12,516) and the usual care group (n=96/12,484) were hospitalized or died in the first 28 days.

Separately, in a retrospective study based on electronic medical records of high-risk patients in Israel, Lagevrio showed a benefit in reducing hospitalizations and death in the patients age 65+ but not in patients age 40-64.

Bottom line: Legevrio (molnupiravir) remains a poor choice for treating COVID. It is being prescribed only when Paxlovid is either unavailable or contra-indicated due to drug-drug interactions (from ritonavir).

[vinmantoo]

ENTA starts phase-2b trial_of EDP-938 in high-risk adults:

Good to see EDP-938 moving forward. Now if we can only hear about the start of the phase 2 or phase 2/3 trial of EDP-235 in high risk people infected with Covid.

[DewDiligence]

ENTA starts phase-2b trial_of EDP-938 in high-risk adults:

https://finance.yahoo.com/news/enanta-pharmaceuticals-initiates-phase-2b-110000822.html

The Phase 2b, randomized, double-blind, placebo-controlled, multi-center, global study is designed to evaluate the effect of EDP-938 compared with placebo on the progression of RSV infection by assessment of clinical symptoms. Approximately 180 patients will be treated with 800 mg of EDP-938 or placebo for 5 days and evaluated for 28 days thereafter.

The study will include non-hospitalized adult subjects with up to 72 hours of respiratory tract infection symptoms who test positive for RSV and negative for influenza virus and SARS-CoV-2. Patients will be considered high risk for complications after RSV infection if they have at least one of the following risk factors: age 65 years or older, congestive heart failure, COPD or asthma.

The primary endpoint of the study is time to resolution of RSV lower respiratory tract disease symptoms as assessed by the Respiratory Infection Intensity and Impact Questionnaire (RiiQ) symptom scale through Day 33. Secondary endpoints include additional clinical efficacy measures and antiviral activity compared to placebo, pharmacokinetics, and safety of EDP-938.

The prior phase-2b trial of EDP-938 that missed its primary endpoint was in low-risk adults, who recovered well enough on their own to make EDP-938 non-statsig relative to placebo.

[DewDiligence]

PRDS vs ENTA phase-2 dosing:

https://twitter.com/DewDiligence/status/1570156764741632000

[vinmantoo]

EDP-235 as possible treatment for long COVID?

A Key to Long Covid Is Virus Lingering in the Body, Scientists Say

Virus remaining in some people’s bodies for a long time may be causing longer-term complications, recent research suggests

That indication might require a longer period of treatment than 5 days and so could require a longer trial. Given Paxlovid needing a drug pump inhibitor, that would seem to make it a less preferred drug and could favor EDP-235.

[DewDiligence]

Yes, that's an additional opportunity for EDP-235.

[biocqr]

EDP-235 as possible treatment for long COVID?

A Key to Long Covid Is Virus Lingering in the Body, Scientists Say

Virus remaining in some people’s bodies for a long time may be causing longer-term complications, recent research suggests

Sept. 8, 2022 12:01 am ET

The virus that causes Covid-19 can remain in some people’s bodies for a long time. A growing number of scientists think that lingering virus is a root cause of long Covid.

New research has found the spike protein of the SARS-CoV-2 virus in the blood of long Covid patients up to a year after infection but not in people who have fully recovered from Covid. Virus has also been found in tissues including the brain, lungs, and lining of the gut, according to scientists and studies

The findings suggest that leftover reservoirs of virus could be provoking the immune system in some people, causing complications such as blood clots and inflammation, which may fuel certain long Covid symptoms, scientists say.

A group of scientists and doctors are joining forces to focus research on viral persistence and aim to raise $100 million to further the search for treatments. Called the Long Covid Research Initiative, the group is run by the PolyBio Research Foundation, a Mercer Island, Wash., based nonprofit focused on complex chronic inflammatory diseases.

“We really want to understand what’s at the root of [long Covid] and we want to focus on that,” says Amy Proal, a microbiologist at PolyBio and the initiative’s chief scientific officer. Dr. Proal has devoted her career to researching chronic infections after developing myalgic encephalomyelitis/chronic fatigue syndrome, an illness that shares similar symptoms with long Covid, in her 20s.

Three long Covid patients, frustrated at the lack of answers and treatments, have helped connect researchers.

“Long Covid is this really incredible emergency,” says Henry Scott-Green, one of the patients, a 28-year-old in London who says brain fog, extreme fatigue and other debilitating long Covid symptoms prevented him from resuming full-time work as a product manager, though he plans to return soon. “We’re really trying to run really efficiently and cut out as many layers of bureaucracy as possible.”

So far, the group says it has received a pledge of $15 million from Balvi, an investment and direct giving fund established by Vitalik Buterin, the co-creator of the cryptocurrency platform Ethereum.

Among the strongest evidence of viral persistence in long Covid patients is a new study by Harvard researchers published Friday in the journal of Clinical Infectious Diseases. Researchers detected the spike protein of the SARS-CoV-2 virus in a large majority of 37 long Covid patients in the study and found it in none of 26 patients in a control group.

Patients’ blood was analyzed up to a year after initial infection, says David R. Walt, a professor of pathology at Brigham and Women’s Hospital in Boston and Harvard Medical School and lead researcher of the study. Dr. Walt isn’t currently involved with the long Covid initiative.

A year after infection, some patients had levels of viral spike protein that were as high as they did earlier in their illness, Dr. Walt says. Such levels long after initial infection suggest that a reservoir of active virus is continuing to produce the spike protein because the spike protein typically doesn’t have a long lifetime, he adds.

Dr. Walt plans to test antivirals such as Paxlovid or remdesivir to see if the drugs help clear the virus and eliminate spike protein from the blood. He says it’s possible that for some people, the normal course of medication isn’t enough to clear the virus. Such cases may require “a much longer exposure to these antivirals to fully clear,” says Dr. Walt.

One of the research group’s goals is to find a way for people to identify whether they continue to have the virus in their bodies. There is no easy way to determine this now.

New studies offer clues about who may be more susceptible to long Covid, a term for lingering Covid-19 symptoms. WSJ breaks down the science of long Covid and the state of treatment. Illustration: Jacob Reynolds for The Wall Street Journal
Long Covid patients experience such a wide range of long-term symptoms that scientists think there is likely more than one cause, however. Some cases may be fueled by organ damage, for instance.

Yet consensus is growing around the idea that lingering virus plays a significant role in long Covid. Preliminary research from immunologist Akiko Iwasaki’s laboratory at Yale University documented T or B cell activity in long Covid patients’ blood, suggesting that patients’ immune systems are continuing to react to virus in their bodies. Dr. Iwasaki is a member of the new initiative.

In a 58-person study published in the Annals of Neurology in March, University of California, San Francisco researchers also found SARS-CoV-2 proteins circulating in particles in long Covid patients’ blood, especially in those with symptoms such as fatigue and trouble concentrating.

Now, the group is completing a study using imaging techniques and tissue biopsies to detect persistent virus or reactivation of other viruses in tissue. It also is looking at T-cell immune responses in tissues and whether they correlate with symptoms.

Some people may harbor the virus and don’t have long-term symptoms, says Timothy Henrich, an associate professor of medicine at UCSF involved with the study and a member of the long Covid initiative. For others, lingering virus may produce problems.

“I think there’s a real amount of mounting evidence that really suggests that there is persistent virus in some people,” says Dr. Henrich.

Write to Sumathi Reddy at [e-mail]

[willyw]

https://ir.enanta.com/news-releases/news-release-details/new-preclinical-data-edp-235-enantas-oral-coronavirus-protease

For me this seems one more step validating EDP-325. As J.Luly Enanta CEO addressed some of the potential differences between the Enanta antiviral and it's Pfizer competitor Paxlovid we may soon see some of those differences quantified in a medical conference in about 6 weeks.

[vinmantoo]

willyw,

Thanks for that excellent post.

[willyw]

I've seen a few articles that make it seem that the USA wants to try harder to be ahead of the curve with covid (and or other possible emerging health threats) The CDC has recently spoken to reorganizing, in part based on perceived past failures in covid.
And Fauci really never stopped lamenting our covid response;
https://www.aol.com/fauci-u-covid-response-theres-140731132.html

When I factor in that both Joe and Jill Biden experienced covid/paxlovid viral breakthroughs I have to wonder if EDP-325 might experience a more rapid green lighting of the EDP-325 approval process. Exactly how common is breakthrough? J.Luly Enanta CEO in the recent August earnings report gave a few reasons as to how EDP-325 could be superior to Paxlovid.

EUA? Rolling approval? Some grant or other assistance?
I feel the current climate is that they are not going to make the world wait for a better covid antiviral.

Enanta CEO J.Luly has mentioned that the phase 2 work should be within Enanta's capacity without outside partnership.
The ATM aspect may reassure investors, the government or potential partners that the Phase 2 (or 2/3) IS going forward. This itself could streamline the work of setting up the next stages of trial work.

In gaining a partner to potentially take the trials to phase 3, larger enrollment and world wide to be in a superior bargaining position Enanta may almost need to demonstrate that they don't need a partner. The ATM could ensure Enanta a stronger bargaining position in order to achieve a more lucrative financial agreement with a potential partner.

A final point worth noting is that potentially the patent issue with Pfizer could be decided- either in an legal decision or a settlement.
IF Enanta saw an encouraging legal patent decision the potential EDP-325 collaboration could become even more attractive.

Whether they touch the ATM or not, it seemed responsible to me to make sure that they can move forward in the approval and de-risking process of EDP-325.

[DewDiligence]

I concur. If ENTA inks a partnership deal for EDP-235, the ATM will probably not get used.

[vinmantoo]

ENTA had ~$330M of pro forma cash at 6/30/22 (#msg-169621212), so the ATM looks like a backup contingency in case ENTA decides to conduct the phase-2(/3) EDP-235 trial without a partner.

It sounds like some good long-term planning by ENTA.

[DewDiligence]

ENTA opens $100M ATM with Jefferies:

https://www.sec.gov/Archives/edgar/data/0001177648/000119312522231299/d396056d424b5.htm

ENTA had ~$330M of pro forma cash at 6/30/22 (#msg-169621212), so the ATM looks like a backup contingency in case ENTA decides to conduct the phase-2(/3) EDP-235 trial without a partner.

p.s. ENTA has never raised capital as a public company apart from its 2013 IPO. HCV milestones and royalties from ABBV have been sufficient to fund ENTA's operations.

[vinmantoo]

There are two ways of looking at this from ENTA’s perspective. The bearish take is that COVID antivirals aren’t needed in adults under age 65 lacking major risk factors, limiting the addressable market for EDP-235. The bullish viewpoint is that Paxlovid isn’t potent enough to help low-risk patients, but a superior drug such as EDP-235 could find an opening where Paxlovid has been shown to be ineffective.

The market seems to agree with the bearish take, as least for today.

I scanned the paper and chances for hospitalization for those under 65 and not immunized was greatly reduced by Paxloid treatment. That means the market is broader than just the over 65. By the way, the over 65 with risk factors is still a pretty high market.

[DewDiligence]

Reason for today’s ENTA selloff: #msg-169786228.

[DewDiligence]

FDA wants PFE to_test Paxlovid in_relapse_cases:

https://finance.yahoo.com/news/1-fda-asks-pfizer-test-201939904.html

The U.S. Food and Drug Administration (FDA) has ordered Pfizer Inc to test the effects of an additional course of its antiviral Paxlovid among people who experience a rebound in COVID-19 after treatment, the regulator said on Friday.