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ALGS CEO: “ENTA’s [EDP-235] data were informative and good”:
https://wsw.com/webcast/jeff281/algs/1840410
Listen at the 20:00 mark, right after the comment that PRDS’ COVID drug was too weak.
ALGS has its own SARS-CoV-2 protease inhibitor, but it has not yet started phase-1.
Please see my reply in #msg-172089455.
I listened the talk Jeffries today. It was very uplifting to me. Jay Luly stated that there is sufficient EDP-235 for phase 3 trials, which is reassuring. He also explained a big difference in the Shionogi trial and the EDP-235 trial. For the Shionogi trial the number of nucleocapsid positive patients (i.e. previously Covid infected) was in the single digits whereas it was some 70%-80% in the EDP-235 trial. That would explain why an overall virus decline was seen in the overall population in the Shionogi trial and was also seen in the new analysis from ENTA in nucleocapsid negative population in the EDP-235. Looking at only nucleocapsid negative population in the EDP-235 trial is an apples to apples comparison, and should remove any doubt that EDP-235 has potent anti-viral activity. Well, the statistically significant improvement in symptoms for EDP-235, which Paxlovid failed to show in a standard risk population, should have already made that crystal clear. Still it is nice confirmatory bit of data to see even though the FDA wouldn't base any approval on viral reduction in nasal swabs.
The Jeffries interview was fair but tough and pointed. He made it clear that EDP-235 showed symptom relief and Luly reiterated that Paxlovid failed to do so even with a mostly nucleocapsid low population. They talked about IC90 and Luly pointed out the bar has been raised for new drugs as EDP-235 has reaches a much higher drug level with regards to IC90 than Paxlovid, and that likely explains symptom relief. Yes the Jeffries interviewer/host pressed about timelines not only for EDP-235 but for RSV drugs. There was some ballpark figures about the cost of 2 large phase 3 trials for Covid and it was $100-$200 million. Luly did point out the China was experiencing a major surge in Covid cases. Luly refused to get drawn in and make specific comments. Obviously there are no guarantees, but overall I came away more confident about ENTA and about EDP-235 and ENTA.
Thanks for that confirmation!
Post-hoc analyses cannot be statistically significant in a rigorous sense because the hypotheses being tested were not prespecified. (That’s why ENTA did not show p-values for the new analyses.)
Thanks. Are these new results statistically significant?
ENTA reports additional post-hoc EDP-235 analyses_from_ phase-2_trial—details_in_new_corporate_slide_set:
https://www.sec.gov/ix?doc=/Archives/edgar/data/0001177648/000095017023026739/enta-20230607.htm
Thanks. I appreciate your response.
As a classic layman I often find myself not knowing.
But I also see approval agencies struggling with trial design, trying to determine what to measure.
With COVID we really didn't have the luxury of much time, history, and the virus kept shape shifting.
All this against the backdrop of a far more weaponized political thumb on the scales imposing new dynamics in public health and on drug approvals.
COVID will be one for the textbooks.
Having said that, I think that in the face of so much uncertainty the logical response is to NOT have a strong opinion.
Well..... an opinion is OK, but not opinion that is dressed up as fact.
In that regard, like you I DO appreciate reading the bear view on my stock picks.
It's a great opportunity to learn something I might easily overlook, a flaw in my reasoning, opposing data, a better informed or seasoned investor will know and see things that I don't.
But I've also got to tell you that your feedback has also been very very helpful since I only know what I think and I have no formal background to know if I'm right or wrong.
Hahahah, but I'm not alone there, particularly in the area of COVID.
I replied since you wanted more current data on China covid.
I provided it. It is still into a second wave with an impressive amount of infection.
You have no response to that, when you yourself have at least twice that you expect new variants.
I point out several of your contradictions in your own writings, where you actually lay out your thoughts but you don't or cant explain the error, contradiction or weakness in your argument.
Instead, you change the subject with pure whataboutism.
You write that a phase 3 can't happen cause "seropositivity" as though one word is an answer, yet you warn us that the Pfizer next gen is coming as though - somehow - that molecule won't be subject to the same issues that Enanta's covid candidate faces.
You seem to suggest that it's viral decline that is the bar for approval when all evidence is that it is NOT the metric. You seem able to hold that thought when the Pfizer next gen candidate has not yet provided any such data in their phase 1 trial (have they even dosed participants yet?).
You seem to allege that where it is difficult to contrast viral load declines in dosed versus healthies as undercutting the efficacy of the drug but I suspect that you are aware that if it were in a more impaired group than healthies, or with a nastier variant like Delta or a lesser seropositive cohort the results would be more differentiated.
Rather than answering any of these contradictions you pivot.
If no partnership has been announced you must be right.
We will see what happens- nobody knows until it happens or it doesn't happen.
These things take time- as I suspect that you know.
Is there/has there been a market for Remdesivir? Was that approval based on viral decline?
The same for Paxlovid?
You see, I had thought that approval was based on outcomes.
Are further Phase 3 trials for covid possible? Pfizer and others seem to think so.
Should I believe Pfizer or you?
Your usual pattern is to scare, cast aspersions, create doubt.
Who do you like? Where have you plunked down your money? I don't recall having read that.
Yet many of us have been straightforward in that area with you but you only seem to be able to dish it.
Are you that insecure in your beliefs?
Dew posted to you in Biotech values but you answer with word salad.
"No deal, high seropositivity, Pfizer 2nd gen… going to be a rough road there."
---For a brilliant guy you don't express yourself very well. It's not even a sentence and where you were called for an explanation, here too you pivoted, avoided "The second post I was actually posing the question to you" or answered with more word salad without any clarification; "For the first point, I never commented on viral load reduction but actually antiviral effects".
--that's an explanation?
A guy with more confidence would explain clearly their position and be prepared to defend their thesis.
I don't see that happening in your posts.
It's just mostly about throwing stones.
I probably have the least amount of technical background in biotech compared to many others here.
I'm straight from the trenches; a guy who was infected and cured through his involvement in biotech- cured in a Gilead HVC registration trial.
I suspect that you have a deeper understanding of some of the technical aspects than I do.
So, here's my question.
Why don't you just share your views, explain them clearly and attempt to validate them?
I would find that helpful.
Thanks for the reply. Why do you think everyone has passed on EDP-235?
Thanks for pointing out the NPR link was 5.5 months old. In haste to post I mixed that big initial wave with the current. I am unable to alter the post. Here is a more current article. (from May 26 2023) You will notice that the dates have changed but Covid is still very much present in China. Such as it is with Covid, you have a peak which is then followed by waves.
As in the earlier link it's still serious in China it appears;
"BEIJING — China is bracing for a new wave of Covid infections that could see as many as 65 million cases per week by the time the surge peaks at the end of June."
https://www.nbcnews.com/news/world/china-covid-second-wave-xbb-variant-omicron-rcna86171
As it pertains to the link I posted, the newer link somewhat addresses the results of that wave;
"During China’s first omicron wave in December and January, a different omicron variant was infecting millions of people every day, overwhelming hospitals and crematoriums in cities across the country. Store shelves were emptied of fever medications and schools were shut down.
About 80% of China’s 1.4 billion people were infected during that wave, Wu Zunyou, chief epidemiologist at the Chinese Center for Disease Control and Prevention, said in January. But immunity may have waned in the months since, raising the risk of reinfection."
I appreciate the feedback for the sake of accuracy.
======
I remain skeptical that covid is over.
I remain in the opinion that more covid registration trials can still happen.
The fact that Pfizer is attempting an improved antiviral to replace Paxlovid is ample proof of that- not only that there is a future market, that there is a path forward to getting an improved drug approved, or that a drug can be shown to be non- inferior to Paxlovid.
I've mentioned months before that the bar to approval is very low, which I think you may agree since you seem to have a low opinion of Paxlovid's efficacy.
And in that you seem to feel that the next gen Pfizer drug has great potential I infer you must also agree. What I cannot grasp is how in your mindset that approval is possible for competitors, but also somehow impossible for Enanta's EDP 235.
But as they say, that's what makes a market.
Your NPR article is wildly outdated. You should amend the emphasis.
Yes, I was recently reading on this uptick- interest in how it pertains to ENTA and it's pipeline- and in it's ability to perform trial work.
https://www.forbes.com/sites/brucelee/2023/05/29/human-metapneumovirus-hmpv-has-surged-around-36-higher-in-2023/?sh=f17dc2d71455
Meanwhile in China?
https://www.npr.org/sections/goatsandsoda/2022/12/15/1143002538/china-appears-to-be-facing-what-could-be-the-world-s-largest-coronavirus-outbrea
"COVID spreading faster than ever in China. 800 million could be infected this winter"
I keep hoping that the mechanics of running a Paxlovid non-inferiority study will be rather simple and prescribed. I hope that this translates into action.
hMPV—>“…the most important virus you’ve never heard of”:
https://www.cnn.com/2023/05/29/health/human-metapneumovirus-explainer-wellness
Paxlovid receives full-fledged FDA approval—with boxed warning for DDIs:
https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-antiviral-treatment-covid-19-adults
Good to see ENTA starting to rebound as it breaks $28/share. Obviously a long way to go but eventually the impulsive moves that cause market over-reactions, like the drop ENTA suffered, are countered by cold hard and rational assessment.
Typo correction:
Some more observations on why viral RNA levels in the nose aren't a good metric for anti-Covid efficacy. I also point to data from the Shionogi's drug trial isn't as impressive as they would like you to believe or some ENTA critics here assert.
The link to the Shionogi presentation (provided by dewophile). If you notice on slide 9 there is once again is NOT a dose dependent response as the 250mg dose is LESS effective in reducing viral titer than the 125mg dose. In fact, by day 6 the 250mg dose is no better than placebo.
https://www.shionogi.com/content/dam/shionogi/global/investors/ir-library/presentation/2022/ECCMID%20Ph2b%20presentation%20final2.pdf
The same is true for slide 12, total symptom change from baseline as the 250mg dose was LESS effective than the 125mg dose. Something weird is happening, and it sure doesn't inspire confidence.
In slide 14 the middle panel assesses systemic symptoms. It looks like the 250mg dose is essentially a placebo and the 125mg dose had at best a minor effect. Once again NOT a dose dependent response. The only one is a clear separation was respiratory symptoms but not digestive symptoms.
Some last thoughts about the disconnect between viral levels in nasal swabs. The first a general one that people often keep testing positive for RNA long after their symptoms are gone. The second is the issue of the faster viral clearance in the placebo arm in the ENTA study (see slide 22 of the ENTA presentation for SPRINT below). For placebos at day 3, the Shionogi phase 2b study showed maybe a 0.8 log decline but for SPRINT is was already 1.5 log decline. By day 5, the Shionogi phase 2b study showed a 2 log decline whereas the ENTA placebo had a 3.5 log decline. If the decline of viral RNA in the nasal swab correlates with symptom improvement, then the placebo group in the SPRINT study should have reduced their symptoms faster than in the Shionogi phase 2b study.
However, look at slide 17 of the ENTA presentation. The left side is ENTA's SPRINT data and the right side is Shionogi phase 2b study. By 3 days, total symptom score in Shionogi's placebo is down just over 4 log (~4.5 log) whereas in SPRINT, there is a bit less than a 4 log drop. By 4 days, total symptom score in Shionogi's placebo is down 6 logs as is in the SPRINT study. So it sure looks like the more rapid clearance in the SPRINT trial doesn't correlate with more rapid patient symptom improvement. This once again points to nasal swabs not being a good metric for drug efficacy.
https://ir.enanta.com/static-files/c9eca2f1-296c-4a0c-9ce4-d668229f1ec5
Thank you for outlining the EV presently. Added to my position this morning 10,000 at $24.00. Fascinating story and interesting to watch the developments the balance of 2023/2024.
ENTA’s EV at the current share price ($24.64)=~$190M, based on 26.16M fully-diluted shares (#msg-171925301) and $454M of pro forma cash (#msg-171925391).
The $190M EV is down from ~$1.1B three months ago and ~$1.4B none months ago. Note that the EV decline is slightly exaggerated by the fact that ENTA’s (retained) Mavyret royalty stream is now worth less than it was three months ago.
ENTA’s pro forma cash @3/31/23=$454M—an increase of $166.4M* since 12/31/22. The $454M figure consists of:
• $239.0M of net current assets on the 3/31/22 balance sheet (https://www.sec.gov/ix?doc=/Archives/edgar/data/0001177648/000095017023019842/enta-20230331.htm#consolidated_balance_sheets );
• $15.0M of marketable securities on the 3/31/23 balance sheet designated as long-term (e.g. bonds with a time to maturity greater than one year) (ibid); and
• $200M proceeds from partial monetization of the Mavyret royalty stream (#msg-171766236), which was announced on 4/25/23 and hence was not reflected in the 3/31/23 balance sheet.
*Excluding the $200M proceeds from the Mavyret royalty monetization, ENTA pro forma cash at 3/31/23 declined by $33.6M relative to $12/31/22.
ENTA’s fully-diluted share count @3/31/23=26.16M—an increase of 0.03M since 12/30/22.
The 26.16M figure above consists of: 21.05 basic shares on the 3/31/23 balance sheet (https://www.sec.gov/ix?doc=/Archives/edgar/data/0001177648/000095017023019842/enta-20230331.htm#consolidated_balance_sheets ); and 5.11M options and unvested restricted-stock equivalents (whether or not exercisable) (ibid, p.9).
Clearly, the most troubling COVID symptoms are not those in the upper respiratory tract. If there were an easy way to measure viral load in the lung and other organs, the conversation we’re having would likely be very different.
Apropos to ENTA's royalty monetization: #msg-171904228.
I have had the chance to go over the data from the published phase 2 data of Shionogi's anti-Covid drug Ensitrelvir and somethings stand out that just don't make sense, but provides some hope for ENTA's EDP-235. We see that a dose dependence effect for Ensitrelvir doesn't read true and that there isn't a correlation between viral tier in the nose and symptom relief. Keep in mind that Ensitrelvir failed to show a significant relief of Covid-19 symptoms.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110269/pdf/ciac933.pdf
Figure 2 compares viral changes in placebo and drug (125mg in blue & 250mg in red). In 2B (viral titer decrease log10), the day 4 and day 6 improvement is greater in the 125mg arm than the 250mg arm.
Table 2 shows the same, the lower dose was better.
Table 3 shows patients with treatment related AEs were higher in the 250mg arm (22.1%) than the 125mg arms (13.6%) vs placebo (5.0%). That means the higher dose is doing something, but not doing something beneficial. Still, it provides confidence they didn't mis-label the graphs from Figure 2 or in the supplemental figures following.
Supplementary Figure 1. Mean total symptom changes (A) and change form baseline (B). Keep in mind that Ensitrelvir failed to show a significant relief of Covid-19 symptoms. In looking at the data from B, the 250mg arm looks identical to placebo until 48hrs. The 250mg arm did worse than the 125mg arm until 72hrs then goes back to being worse. None of this is statistically significant but it looks puzzling to me and or shows the weakness of the drug in improving symptoms.
Supplementary Figure 2. Graph of the percentage of patients positive for viral titer in nasal swabs. This is where Ensitrelvir really shines but a disconnect between nasal viral levels and symptom relief becomes clear. By day 4, 54% of patients in the placebo arm are still positive for viral titer. Positive titers are found in only 2% of patients in the 125mg arm and in 6% in the 250mg arm. The difference between the drug arms are likely meaningless but it follows the pattern where dose dependence doesn't follow. However, the major point I am making and that is clear is that a drop in viral titer from nasal swabs does NOT correlate with symptom relief/improvement.
Taking this all to its logical conclusion, if nasal viral titer is NOT a metric for a drug's ability to serve as a anti-covid treatment, then it isn't such a stretch to accept that EDP-235 showed a dose dependent statistical improvement in symptom relief despite not showing a viral reduction in nasal swabs. While not a guarantee, it is food for thought. ENTA will almost certainly present the full data set parsed out in far more detail in a future conference than they did in the press releases. That will be something to look forward to analyzing.
ENTA updated corporate slide set (5/8/23):
https://ir.enanta.com/static-files/0b9a9564-339c-4501-8c98-eab636846bf4
The main difference between the 5/8/23 corporate slide set and the previous version (dated 4/18/23) is three new slides containing data from the EDP-235 phase-2 SPRINT trial. Specific changes in the slide set:
• New Slide 22 has essentially the same info as old Slide 22, but the wording has been shuffled a bit. (The bullet point re 95% bioavailability in rats is gone.)
• Slide 25 is the same as old Slide 26; Slide 26 is the same as old Slide 27; and Slide 30 is the same as old Slide 25.
• Slides 27-29, which contain results from the EDP-235 phase-2 SPRINT trial, replace old Slide 28. (See https://ir.enanta.com/static-files/c9eca2f1-296c-4a0c-9ce4-d668229f1ec5 for the complete slide set for the SPRINT trial.)
• Slides 31-40 are the same as old Slides 29-38 — i.e. subtract “2” from the new slide number to get the corresponding old slide number.
• Slides 37-38, which contain updated financial data, supersede old slides 35-36. Slide 37 has an error of omission insofar as it doesn’t mention the partial monetization of Mavyret royalties starting in 3Q23.
I too was enticed to add 1000 shares @24.00. Never got filled at a < price.
cl
Dewophile made great post on the Biotech values board that fits with my thinking. I will add in that the phase I data for EDP-323 in RSV should be out in a month or so. It is worth the read.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=171872796
The other reason 235 has no chance:
https://clinicaltrials.gov/ct2/show/NCT05580003
Not going to beat them. If a new variant comes along and seropositivity goes for naught, I believe Pfizer will win with this new compound.
Investing in biotech can be risky so you have to have some diversity, and I do and also advise others who ask me to do the same. I made more than >3x as much on IMGN as I lost on ENTA this morning, RVNC has also been doing well and SGEN is getting bought out at a big premiums, so April and May and 2023 have been very good to me.
Back to ENTA, the fact remains that EDP-235 showed a statistically significant reduction in Covid symptoms in a healthy young population, something Paxlovid failed to do in a trial several fold larger that the SPRINT. This was even though the population in the SPRINT trial ENTA just ran.
One question that was asked in the CC was the market for anti-Covid drugs now that Covid is essentially endemic. The market fro such drugs are ~$10 billion in 2023. PFE estimated $8 billion for 2023 but reported $4 billion for Q1. The market is still quite big and will remain so for quite some time.
There is no hiding that is it painful to see an investment drop as much as ENTA did today. I did buy more ENTA this morning at $24.15. I will probably keep buying over the next few days. In a month or two I will likely sell some as I need a tax loss to reduced my capital gains from the SGEN buyout. Still, my goal is to have more shares of ENTA than I did before the SPRINT trial data was released. I am not telling everyone they should do this. That is my plan and you have to weigh what to do yourself.
Good luck to you and other ENTA investors as we move through this challenging time.
Apparently we have a sensitive little fellow on this board who likes to talk smack but can't handle a little himself.
“Vin”, it’s good. Stay optimistic.
If you buy enough shares today, maybe it will go green. You can do it! Rooting for you
The after hours trades means lots of pain tomorrow. However, there is also opportunity possible. I have made some nice cash picking up shares after a drop, as long as you think the drop is unwarranted.
I listened to the CC and the key points, at least to me were.
Enough cash to take ENTA into 2026. This doesn’t model ENTA running their own phase 3 and they aren’t looking to do so. The goal is now and has always been to partner. Looking for partnership for phase 3 as their plan has never been to run their own phase 3. Mentioned phase 2 for long Covid but that will likely be self-funded and run but nothing is set right now.
FDA doesn’t approve Covid drugs aren’t based on viral load changes. It is symptom relief, reduction of hospitalizations and deaths.
Why would symptoms improve with EDP-235 but not really viral load? They speculated that EDP-235 has a higher tissue distribution levels (EC50 & EC90) than Paxlovid but measurements only in the nasal cavity. Effect of EDP-235 on different viral compartments, lung, heat etc could explain systemic symptoms improved with EDP-235 without showing better viral clearance in nasal swabs. It would be difficult to assess these other compartments. Also talked about the much more rapid viral clearance in the nasal swabs in placebo. Nasal swabs only measure viral RNA levels, not active virus that can trigger inflammation.
Question about viral rebound. The analyses haven’t been completed.
Question about EDP-514. looking at other data sets, external assets. No mention of another internal drug.
EDP-323 polymerase inhibitor for RSV. Phase I data safety, tolerability and pharmacokinetics due next month. Challenge study would be next assuming positive data.
Yeah… the market just tanked this thing and you’re still buying. Nice. You’re getting rolled.
Now you are coming around! Great job.
Please don’t buy the “long Covid” bull that they will try to feed you. Viral damage has already been done unfortunately and it’s not coming back from 235.
My agenda is to speak the truth. Anyone here listening yet?
Well, you deny that your bullish thesis was incorrect and grossly overstated. You denied that the placebo arm reality was significant.
Now you deny. Wow. Buying more shares… for what exactly? You’re going to lose all of your money.
Now trading at $24. I suppose your opinion was incorrect “Vin”
“Key secondary endpoints evaluating virologic effect were not met. No difference was observed between patients treated with EDP-235 and placebo in viral RNA decline or infectious viral load, likely due to the rapid viral decline in the placebo arm of this trial’s seropositive, standard risk population. “
Let’s see how long this management team can milk that $450M for.
ENTA FY2Q23* financials—3/31/23_pro_forma_ cash=$454M†:
https://ir.enanta.com/news-releases/news-release-details/enanta-pharmaceuticals-reports-financial-results-its-fiscal-35
FY2Q23 royalty revenue was $18.7M.
FY2Q23 R&D expenses were $43.5M, somewhat below the run rate for ENTA’s FY2023 guidance of $210-230M.
FY2Q23 SG&A expenses were $13.8M, slightly above the run rate for ENTA’s FY2023 guidance of $46-52M.
†Including $200M from partial monetization of Mavyret royalties and a $28.7M tax refund due from IRS.
*ENTA’s fiscal years end on September 30.
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