Enanta Pharmaceuticals Inc (ENTA) Options

Pls tell Baby Flo to fix this mess!

Baby FLO has been prescribed PROZAC for the Kennedy nomination.

At this rate we are going to be the least prepared developed country if a health crisis emerges
That is an understatement.

Pls tell Baby Flo to fix this mess!

Maybe too busy with partnership discussions ;)

And many of the future plan and expenses are based on the outcome of those discussions so my hope remains

Will see if they update guidance.

I think 5 Feb is correct. One or more companies in your portfolio will announce earnings as below
- ENTA declaring Q1 '25 earning on 05-FEB-2025 AfterClose. Consensus EPS: -1.27 Revenue: 18.0 M

I also think the decision not to have an earnings CC is a misstep, all considered.

Where you got the info?

And the cdc website with updates on virus activity has no active resources at the moment with this notification:

“CDC’s website is being modified to comply with President Trump’s Executive Orders.”

At this rate we are going to be the least prepared developed country if a health crisis emerges

Ok thx

Now 2/7.  

I believe earnings 2/10

This morning the Senate Finance Committee advanced Robert F. Kennedy Jr.'s nomination Tuesday, moving forward with his confirmation to lead the Department of Health and Human Services.

They have always given a week's notice before a cc, so w earnings slated for end of this week (I didn't realize it was tomorrow) a PR would have come out by Friday last week. So yeah no cc

Earning release is tomorrow after market?
Don't see a PR from ENTA, but my broker has notification that said it's tomorrow. So I guess no CC this year.

Enanta Pharmaceuticals, Inc. v. Pfizer Inc.

Monday, February 03, 2025
399 appeal Notice of Appeal to the Federal Circuit Mon 02/03 4:16 PM
NOTICE OF APPEAL to the Federal Circuit as to398 Judgment,393 Memorandum & ORDER, by Enanta Pharmaceuticals, Inc. Filing fee: $ 605, receipt number AMADC-10820732 Fee Status: Filing Fee paid. US District Court Clerk to deliver official record to Court of Appeals by 2/24/2025. (Fiacco, Barbara)

398 order Judgment Mon 02/03 9:59 AM
Judge Denise J. Casper: ORDER entered. JUDGMENT (LMH)

397 order Order on Motion for Extension of Time Mon 02/03 9:58 AM
Judge Denise J. Casper: ELECTRONIC ORDER entered granting396 Pfizer's Motion for Extension of Time to File Motion for Attorneys Fees in connection with the Final Judgment to fifteen days after the earlier of (1) expiration of the time for appeal (if no appeal is filed) or (2) receipt by the Clerk of the mandate from the appellate court. (LMH)

yes I think the push to move 323 forward sooner than later is there now that there is a drug at a similar stage from a competitor, especially since that mechanism might prove superior to 938. So if moving 323 is dependent on a partner, then I would think both ENTA and a prospective partner would make concessions to accelerate a deal and in particular not wait on adult HR data - that can always be handled as a development milestone like a healthy sum for start of an adult phase 3 which would by definition be predicated on good HR data

Fair assumption so the key advantage here is Enta is further ahead and have combo optionality, I hope Enta would partner up soon and move into phase 3 with both single and combo asap. They would maximize the chance of its approval and commercial success

If they wait for adults data in q3, they would burn much of the lead time they have now.

Personally, hope to hear about a partnership before their annual meeting

yes, but the baseline assumption is that they are on par, but like you said there is room to be 10% worse, which in and of itself may or may not transfer clinically
the rationale for how they may be worse is that they may not be at the top of the dose repsonse as per my last post, and if not that might mean worse virology than the 97-98% in culture ENTA had which frankly is about as good as it gets

I also personally wouldn't describe culture data as "nearly identical" if there was a 8-10% greater difference in VL drop relative to PBO so with the risk of reading too much into this I would say the possibility of worse VL reduction than ENTA by culture to me has increased slightly from last week after seeing this response from their IR dept

Nearly identical gives them wiggle room so as not to provide the actual data. We don't know for sure, but if it were better they would likely have spelled it out.

S-337395 PCR vs culture data

per Shionogi IR: "We have also assessed it [viral loads] using viral culture, and the results are nearly identical"

That means their live culture assay could be 10% worse than EDP-323.

More musings on Shionogi vs ENTA data
One likely difference between the two data sets is that ENTA was clearly at the top of the dose response curve, while Shionogi may not have been. ENTA had comparable viral responses in the two doses they disclosed, with the lower dose having 2% greater reduction vs placebo on PCR compared w the higher dose, but 1% lower VL reduction in culture vs higher dose - all noise and not that surprising since both were many many multiples above the EC90
Shionogi stated at the highest dose 89% reduction, so that suggests lower doses (I think they had 4 doses in their challenge study) had lower viral responses. So the 89% on PCR is excellent, but we really don't know they were at the very top of their dose response if the next lowest dose was meaningfully lower

Added 58,800 shares this morning on overall market weakness. Total now at 92,000 shares and counting.

No if they are on par or better than ENTA I don't see how keeping that close to the vest would help competitively bc the best thing for them as you say would be to dissuade rapid progression of 323 by ENTA and a partner. The only rationale is to hold the data for a scientific meeting, and perhaps their modus operandi in general is to only give data in PRs for primary outcomes - I don't follow them to know what is typical for top line PRs. Certainly if they were worse than ENTA on culture virology or symptoms it is to their benefit to keep the data under wraps. I should note that disclosing symptom data and culture data shouldn't preclude presentation at a medical meeting - there is plenty of other detail to include in a peer review setting. I also personally wouldn't describe culture data as "nearly identical" if there was a 8-10% greater difference in VL drop relative to PBO so with the risk of reading too much into this I would say the possibility of worse VL reduction than ENTA by culture to me has increased slightly from last week after seeing this response from their IR dept

Logic says if they were better than ENTA, they would have presented it? Presenting it would 1) to discourage others to partner with Enta 2) please their shareholders, not like they would be looking to this out. Do you see how keeping that piece of data would serve any competitive advantage ?

might be neck and neck if they define nearly identical as +/- 10% difference, or the culture data is a tad worse than ENTA which is in part why they didn't include it in the PR
The ability to combine drugs might give ENTA the edge in some populations who knows
It does seem like a 2 horse race

Seems pretty much neck to neck on the challenge data. The combo optionality with both L and N might well end up to be a differentiator?

S-337395 PCR vs culture data

per Shionogi IR: "We have also assessed it [viral loads] using viral culture, and the results are nearly identical"

I guess you think they should have progressed into phase 3 alone. If a partner didn't want it then they probably made the correct decision, but I do agree from all we know it seemed like a very promising asset, and one that had a distinct advantage over ensitrelvir as well as paxlovid when it came to drug interactions

Going it alone would have indeed been risky. Maybe they could have made a bigger push for partnership, even at less favorable terms for ENTA, would have been good. Nobody knows how much effort ENTA pushed into a partnership or if theee was any interest even at a really backloaded way. In any event, it is water under the bridge now.

Agree. The sentiment is so bad, everything got discounted to zero or less, including even the cash assets.

The good news is volume is normalizing, so those who wanted out seems mostly out by now

I bet this would slip through - enta has no prospects according to the market, there is no market now for rsv antivirals anyway, they could argue they want the flexiblity of combining 938 with their own drug and or 323 to try and get anythign across the finish line
so yeah i think shionogi could get away w it

point taken
because PCR can pick up dead viral antigens though by PCR I don't think differences, especially small differences, matter even when you look at results from this other POV. for example if there were 11% remaining virus for the shionogi drug at 89% reduction versus 13% for ENTA with 87%, is the relative difference of 15% meaningful? absolutely not IMO bc of what I already mentioned there is variability in assay, variability in the placebo comparator, and the difference could be in dead virus only so clinically meaningless. I think most would say 87% or 89% or 85% are all roughly comparable - I mean every cohort was relatively small like 25 patients so you have to account for some noise

that makes me feel ENTA really dropped the ball on EDP-235

I guess you think they should have progressed into phase 3 alone. If a partner didn't want it then they probably made the correct decision, but I do agree from all we know it seemed like a very promising asset, and one that had a distinct advantage over ensitrelvir as well as paxlovid when it came to drug interactions
Maybe the one case of liver tox turned off possible partners and it wasn't just the regulatory environment? I mean PFE and shhionogi are continuing development and it is still a multibillion dollar opportunity.

More info on RSV competitor S-337395 from Shionogi

https://www.shionogi.com/content/dam/shionogi/jp/investors/ir-library/presentation-materials/fy2024/%EF%BC%93q/E_FY2024_3Q%20financial%20results_.pdf


Dewophile, thanks for the link. The Shionogi slide presentation has a lot about their Covid drug Ensitrelvir (slides 18-22). The mention the US market alone for oral therapeutics was $4.3 billion from Jan to Sept 2024. Man, that makes me feel ENTA really dropped the ball on EDP-235.

It would be surprising if they top lined what is probably a secondary endpoint assessing VL by culture versus PCR

I wasn't making a judgement about what Shionogi was reporting. My point was that there are different ways of analyzing data which can provide more information and clarity. That was why I said oyu can analyzing results based on reduction in viral load, or calculating how much active virus remains.

I suspect so, but does FTC care as much about phase 2 drugs?

$125M, give or take. Lower interest rates (compared to when the OMERS deal was inked) reduce the discount rate and thereby increase the NPV of future receipts.

not sure if the FTC would allow that, but yeah there really is no one else
Ark is running a second phase 3 peds trial for their F inhibitor using the same Wang bronchiolitis endpoint as the first trial in China only, small 180 pateints IIRC - the listing is on ct.gov, but again doesn't look like they are moving forward ex-China right now

So if Shionogi buy ENTA or partner its RSV program, it will pretty much be the monopoly as it seems no other competitors are close.

Just a thought.

Dew, if you don't mind, given the -6% YoY decline what is the NPV of remaining 45% royalty revenue stream? Thanks.

More info on RSV competitor S-337395 from Shionogi

https://www.shionogi.com/content/dam/shionogi/jp/investors/ir-library/presentation-materials/fy2024/%EF%BC%93q/E_FY2024_3Q%20financial%20results_.pdf

slide 24: endpoint is VL AUC by PCR. with 88.9% reduction in their highest dose cohort. ENTA's L-inhibitor had 84.9 and 87.48% reductions by PCR in their two cohorts. I view this as comparable - you can see my post yesterday about the variability in even placebo VL AUCs in the same trial same strain same center (edp-938 NEJM paper). VL decline by culture for ENTA was also 97% and 98% respectively for low and high dose cohort in their challenge trial so hard for anyone to beat that frankly.
They will present full data at future medical meeting so we will get to see rapidity of decline, culture data, and symptom data.
Per slide 25 next step is "Adult Verification trial start (FY25)", so no mention of plans in peds yet but we may know more once the transcript of the earnings call is available in coming days.
At this point I think it's safe to assume they probably have a carbon copy of 323 given same MOA and comparable top line VL suppression by PCR, although omitting the top line symptom data is curious. Like I said yesterday I think this pushes ENTA to partner up quickly so 323 can keep pace while progressing 938. Shionogi has a slide on the size of the market and it is substantial and certainly room for 2 players. If Shionogi is interested in progressing a very similar compound to 323 in this space I don't see why ENTA can't find a similarly interested party to partner up

ABBV 4Q24 Mavyret sales=$291M, -4% QoQ, -6% YoY:

https://finance.yahoo.com/news/abbvie-reports-full-fourth-quarter-123600846.html

Mavyret’s sales decline continues at a gradual pace.

It would be surprising if they top lined what is probably a secondary endpoint assessing VL by culture versus PCR

dewphile, granted we can't really compare the L protein inhibitor from Shionogi and ENTA giving the paucity of data in the Shionogi press release. Just for an exercise let's assume they are measuring the same thing, active virus in a cell culture assay. The difference between viral reduction of 88% and 98% is only 10%, which seems small, but it is actually bigger if you flip the data around. What I mean is that at a viral reduction of 88% means that 12% of the live virus remains present. At 98% reduction, only 2% of the active virus remains. That means 98% reductions leaves 6-fold less active virus (2%) than an 88% decrease (12%).

The real upside lies in RSV and Enanta’s shift toward becoming an immunology-focused company. Mavyret remains a factor, but the real potential comes from these strategic moves. If executed well, this could be a great setup—we’ll see how it unfolds in the next few quarters.

The waiting sucks but the upside is there

shionogi and enta / partner can share the market for all I care if the Ls prove better than 938 in some or all populations. In the near term Shionogi advancing a similar compound in RSV is a reminder 323 has value in the eyes of some pharmas.
I don’t really care if Mavyret (45%) is worth 80M or 130M at this point

As you state, difficult to handicap the relative success. Obviously there is a race to the finish line. I wouldn’t be surprised to see EDP-323 getting a boost here, especially w/ a partnership. How should we handicap MAVYRET sales going forward? ENTA’s revenue stream will be impacted by slumping sales.

I agree culture trumps PCR in terms of importance because the latter can pick up dead virus
However I do think the Shionogi data was probably PCR because these challenge studies are very standardized, so they probably use the same primary endpoint which is PCR VL
note that there is no listing for their trial that I could find so I cannot confirm this, but I bet the numbers of centers that perform an RSV challenge trial is very limited and they all probably follow the same or identical protocols. That said AUC for placebo even using the same viral strain and protocol can vary enough to throw VL data off by a few percent. EDP-938 VL placebo AUC in part 1 by PCR for example was 790, which was lower than VL AUC in part 2 (879) in the same challenge trial. By CBI assay the percent difference in AUC of viral load between the two placebo groups in the 938 study on a relative basis was even greater 185 vs 244. All of this highlights the significant noise that is inherent in these studies even under the most controlled of circumstances. That is why it would be nice to see the full Shionogi data. How quickly the VL dropped (it was faster for 323 than 938), culture data, symptoms, etc. Because the MOA is the same and the top line number is comparable all the other data are probably also similar, but at this point we just don't know bc they only released the one data point with just qualitative info on symptoms

https://www.nejm.org/doi/full/10.1056/NEJMoa2108903

I think both challenge data were conducted the same way, where you have to confirm RSV infection by PCR and then start study drug or placebo. I just think the shionogi PR is vague. It doesn't mention if it was PCR or viral culture (probably PCR), and it doesn't mention the percent reduction in symptoms

That is the key point about vial load, was it via qRT-PCR or infectious viral load. The latter measure is more important. The fact they didn't specify could be an honest mistake or a deliberate action because they know their data on infectious viral load worse that EDP-323. Below is the EDP-323 data from ENTA's challenge trial.

These data demonstrated that EDP-323 was generally safe and well-tolerated and achieved an 85-87% reduction in viral load area under the curve (AUC) by qRT-PCR (p

well partnership discussions sometimes lead to buyout discussions
The fact Shionogi had good challenge data was expected IMO - good mechanism from a company with a good track record in ID, and they telegraphed they were progressing the compound by starting a peds RSV observational study last month.
We may have more color after Shionogi earnings. I would think if the symptom reduction were better they would have put that in the top line PR data and in general I still think ENTA in a strong position but now w more urgency to progress the programs which likely moves up deal making IMO

I am so ready for a partnership or even better, a nice buyout as result of such discussions.

Really hard to understand how this can continue to trade at such huge discount to pretty much any possible valuation scenarios.

Eventually, we will get there but the wait isn’t fun

A couple more thoughts
1. Shionogi is running a peds observational study. Having competition is not necessarily all bad - both companies can use endpoints in peds from these types of studies and newer tools.
2. I initially thought ENTA would wait for the adult HR data to partner, but now I think they may look to partner right away to be prepared to move 323 ASAP for competitive reasons, and the HR data and progression to phase 3 in adults would just be built in as a milestone