Biotech Values

[sab63090]

Dew: FYI
I see that Biotech Jim added to his apparently long position in $VKTX yesterday....

[jbog]

Vin

2023 had the big fintech write down.

The 1st quarter had a estimate of ($ 0.59) 3 months ago, ($ 0.61) 2 months ago and now is at ($ 0.75) . Wrong way

[vinmantoo]

Take a look and the following analysis for a clue, not only are loss estimates increasing but they are increasing with with more shares on the market.

jbog,

Not sure what you are looking at but that link you gave had analysts estimates for EPS declining and projected revenues increasing. For EPS, the average predicted EPS for 2024 is -2.3 compared to -3.83 for 2023, and their estimates for 2025 EPS are -1.06. For revenues, they predict $281.7 million for 2024 compared to $234 million sales in 2023 and their prediction for 2025 is $382 million in sales.

[jbog]

Biowatch

Please, you tell me why it keeps hitting new lows

Wall Street knows what's going on. I'm sure they have channel checks to evaluate sales. Take a look and the following analysis for a clue, not only are loss estimates increasing but they are increasing with with more shares on the market.

https://finance.yahoo.com/quote/RVNC/analysis

[vinmantoo]

No, but this one seems to be. Please, you tell me why it keeps hitting new lows. I don’t know.

Obviously more people are selling than buying, as well as substantial short positions driving the price down. There is an average of 2.6 million shares traded per day, and with the price at $3.30 that comes to less than $10 million per day, making it an easy stock to manipulate. Is it going on now? How the hell would I know?

Do you own RVNC? I try not to figure out the motives of the market because you can't. Obviously I would prefer the stock be much higher but I have been able to do some tax loss selling then buying back to increase my shares. Making lemonade out of lemons if you will. I will likely do the same later in the year.

[DewDiligence]

Sorry Dew, I’ve never used Botox so don’t have your experience.

If I didn’t have first-hand knowledge of how much better Daxxify is, I would be concerned about my investment.

[WorstLuck]

Please, you tell me why it keeps hitting new lows. I don’t know.

I have no idea what price RVNC should be at right now. I do know that they need better sales numbers and, at some point, profits. Whether or not they have the best BoTN on the market is irrelevant if they don't sell enough of it.

FWIW, I think the selling has gone a bit too far. But that doesn't mean it can't go lower. Q1 sales are probably priced in. Q2 will be interesting. Early CD sales may be informative, or not. I feel no rush to put on a position for the long term. Buying downtrends isn't what I want to do.

[Biowatch]

So do you feel that all stocks with cosmetic products should be selling off?

No, but this one seems to be. Please, you tell me why it keeps hitting new lows. I don’t know.

I watched wild market gyrations when I owned and followed IMCL before they were bought out, but an effective cancer drug is more likely to have a steady market than this “we are better than Botox” company has so far.

[vinmantoo]

RVNC hits $3.28.

Now I don't feel so bad about selling some last week for a tax loss as I will might be able to buy back those shares at a lower price after the wash rule time has passed.

Someone knows something I don’t, or perhaps I’m ignoring the obvious.

Lots of people make foolish mistakes believing that.

Hate to be the curmudgeon, but this, aside from CD, is a cosmetic surgery company, and that market can be fickle.

So do you feel that all stocks with cosmetic products should be selling off?

[Biowatch]

RVNC hits $3.28. Someone knows something I don’t, or perhaps I’m ignoring the obvious.

Great, it will prove itself in the long term, but it seems to be fading away into the twilight.

Sorry Dew, I’ve never used Botox so don’t have your experience.

Hate to be the curmudgeon, but this, aside from CD, is a cosmetic surgery company, and that market can be fickle.
———
It hit $3.23 today if you believe Yahoo Finance, but perhaps some people covered their short sales, bringing it back up.

[DewDiligence]

This unorthodox anti-obesity candidate may not warrant inclusion in your table, but here it is anyhow:

https://www.globenewswire.com/news-release/2024/04/25/2869629/0/en/Aphaia-Pharma-Provides-Enrollment-and-Protocol-Update-for-Phase-2-Trial-in-Individuals-with-Obesity.html

https://www.clinicaltrials.gov/study/NCT05385978

Aphaia Pharma is private.

[DewDiligence]

Thanks, dewo—much appreciated!

[dewophile]

I was able to listen midway and the audio was pretty bad, but the slides are up and could be interesting
They do list the profile of their candidate and it has high potency, selectivity and potential for QD dosing. The latter may differentiate from THRD bc at least their earlier candidate was BID. If this is a drug given chronically this could be important (I don't really know if companies are thinking for flares only or chronic for prophylaxis)
clearly this is going to be an important 3rd company with an oral kit inhibitor in the space. There are a lot of potential clinical avenues to pursue so there could be room for more than one drug here but I think this is one where ENTA would want to partner up early to move into multiple indications quickly assuming all the oral drugs end up progressing - it could be that one carves out an indication prior to another depending on development path
I did find the slide of mast cell expression in various tissues somewhat interesting bc one area of differentiation could be how well you hit a specific tissue - ENTA seems to have been able to tune other molecules to hit certain tissues and spare others so if they can get good skin uptake for urticaria, or good GI uptake for eosiniphilic esophagitis that could be a way to set apart from the competition
looks like BPMC is going to file this Q and enter clinic later this year so a few months behind THRD and then ENTA is going to be a few months behind BPMC
What was notable by omission in the slides was any preclinical liver related tox-avoidance. This is what sidetracked THRD's first candidate, and ENTA does mention it iin their slide deck "no GSH adducts in human liver microsome incubation", THRD certainly talks about it - perahps this was brought up during Q&A in this talk but that seems perhaps notable by omission although I give the benefit of the doubt to BPMC given they have success in the kit arena already with non-wild type inhibitors

[DewDiligence]

“Less than half of veterinary professionals feel their profession is appreciated…”

https://www.globenewswire.com/news-release/2024/04/25/2869326/0/en/Less-than-half-of-veterinary-professionals-feel-their-profession-is-appreciated.html

I’d be willing to bet that the animals appreciate the service!

[DewDiligence]

Keytruda sold_at_a $28B(!) annualized_rate_in 1Q24, +24% YoY in_constant_currency:

https://www.businesswire.com/news/home/20240425889273/en

It’s going to be tough for MRK to replace this revenue when Keytruda goes off-patent in 2028, although a subcutaneous formulation of Keytruda could blunt some of the erosion.

[DewDiligence]

Private company developing AMD tri-specific that_hits VEGF-A/VEGF-C/Ang-2:

https://www.prnewswire.com/news-releases/revopsis-secures-16-5-million-seed-funding-to-advance-first-in-class-tri-specific-therapy-for-neovascular-amd-treatment-302127081.html

[DewDiligence]

The short answer to your questions is yes, but “phase-2 and “phase-2b” are not precisely defined terms—i.e. the devil is in the details.

[ggwpq]

DewD, is there any precedent of clinical trials proceeding directly to phase-3 without running a phase-2b, especially in the GLP-1 field? TIA.

[DewDiligence]

VKTX—Not sure why they wouldn't have a normal end of phase-2 meeting with FDA on the obesity drug.

Based on today’s 1Q24 CC Q&A session, it seems that VKTX wants a type-C meeting with the FDA regarding VK2735 to ascertain whether they can proceed directly to phase-3 without running a phase-2b.

[Whalatane]

In 2013, after the publication of the updated recommendations, however, the percentage of atorvastatin prescriptions began to grow regularly from 26% until it reached the highest point at 52% (p = 0.000) in 2019

I think Lipitor ( atorvastatin ) still dominates . Considered the most patient friendly ( best tolerated ) of the high intensity statins .
Simavastatin is the most popular low intensity Statin and Crestor ( generally considered the strongest Statin ) more for the " hard core ".

Kiwi ...baseline LDL cholesterol at 312 mg/dl !!!
Got as low as 20 mg/dl on Repatha , max dose Crestor with some Vascepa thrown in ......312 down to 20 took many years .

[Fred Kadiddlehopper]

George S. Kaufman

[Fred Kadiddlehopper]

Nein!

[zipjet]

I agree with all of that.

GLP-1's look like the class could become the biggest selling class of drug with MANY branded versions.

In that, it reminds me of the statins which became the biggest selling class of drug, with 16 branded versions.

[DewDiligence]

Henry Kissinger?

[Fred Kadiddlehopper]

OT: In answering your question, I just realized that iHub removed my longstanding avatar photo. He's back now and hopefully will remain undisturbed.
Bonus points if you can ID him.
PS, agreed about Denmark ultimately supporting Wegovy. There's really no reason not to. (Well, except that it might perhaps rub up against their national self-image as that of a nation of fit and trim people.)

[DewDiligence]

For some reason, I never appreciated it until now.

[DewDiligence]

I checked Jim’s X account (@JamesEKrause), and the last time he posted about VKTX was Jun 2023.

[Fred Kadiddlehopper]

OT:

p.s. When did you adopt adopt your iHub signature line?

Oh, my! It must have been when I created the account. That feels like another lifetime ago.
What piqued your interest there?

[DewDiligence]

I’ll catch the replay.

I'd appreciate your comments on it when you have a chance to listen. TIA

[DewDiligence]

I doubt that obesity is much of a problem in Denmark.

In that case, the national healthcare system would incur relatively little risk by covering Wegovy. I predict that they will cover it, in due course.

p.s. When did you adopt adopt your iHub signature line?

[Fred Kadiddlehopper]

I doubt that obesity is much of a problem in Denmark. When I visited the country, it was easy to spot the Americans in Copenhagen for obvious reasons. But, yes, you'd think they would show some support for their largest company, if only for international PR reasons.

[DewDiligence]

I would argue that the two MoAs are more different than similar. Excision Bio’s approach of editing the cccDNA does not rely on the immune system—or on any host response whatsoever.

[DewDiligence]

Irony? Denmark’s national healthcare system does not reimburse for Wegovy.

[dewophile]

No I have procedures that day
I’ll catch the replay

[DewDiligence]

Are you planning to tune in?

[dewophile]

re CSU

BPMC has targeted an IND filing this quarter for an oral kit inhibitor for csu
they have an investor day focused on csu/mast cell therapeutics this thursday

https://ir.blueprintmedicines.com/news-releases/news-release-details/blueprint-medicines-host-webcast-and-conference-call

[dewophile]

HBV
Reminder that IMCR has a program targeting a functional cure similarly by hitting infected hepatocytes
Here is a PR of some initial clinical data from the program:

https://ir.immunocore.com/news-releases/news-release-details/immunocore-announces-presentation-initial-data-phase-1-immtavr

They are also looking at the drug in HBV infected patients w HCC now

[DewDiligence]

Will this work?

https://www.globenewswire.com/news-release/2024/04/23/2867508/0/en/Regeneration-Biomedical-Doses-First-Patient-in-a-First-in-Human-Phase-I-Clinical-Trial-of-Stem-Cell-Therapy-delivered-directly-into-the-brain-of-Patients-with-Alzheimer-s-Disease.html

Wnt-activated, autologous, expanded, adipose-derived stem cells administered directly into lateral ventricles of the brain via Ommaya reservoir implanted under the scalp to bypass blood brain barrier

The company, Regeneration Biomedical, is private.

[DewDiligence]

UBX—Beware when a company increases the statistical power of a clinical trial in midstream:

https://www.globenewswire.com/news-release/2024/04/23/2867620/0/en/UNITY-Biotechnology-Announces-Extension-of-Phase-2b-ASPIRE-Clinical-Study-Evaluating-UBX1325-in-DME.html

UNITY Biotechnology…today announced that the ongoing Phase 2b ASPIRE study of UBX1325 has been extended from 24 to 36 weeks to assess potentially greater durability compared to aflibercept. In addition, the study is being upsized from 40 to 50 patients to increase the statistical power. The ASPIRE study is designed to evaluate the safety, efficacy, and long-term durability of UBX1325 as a monotherapy compared head-to-head to aflibercept in patients with diabetic macular edema (DME).

This phase-2b trial should not have been conducted, IMO (#msg-171758374).

[sab63090]

I know that Biotech Jim has followed MDGL for many years, not sure how he stands on VKTX which has been very strong this year. He has posted here recently and it would be interesting to see his thoughts on this...congrats for your excellent coverage on VKTX.

[Mufaso]

The fact that new corporate entrants will emerge to challenge the NVO/LLY duopoly means that prices will decline. The market size will still increase because of wider adoption and increased manufacturing capacity.

Most new entrant may have only niche marketability. The degree to which any drug has significant success in this space will be measured by how well in competes with Zepbound for tolerability and weight loss (in that order).This is why I believe VKTX's VK2735 will be a major player.

[Mufaso]

VKTX- VK2809 in NASH should read out ph2a 52 week biopsy (Fibrosis and NASH Resolution) data very soon. I'm modifying my best guess of when to be tomorrow Wednesday April 24th after the close to coincide with the VKTX earnings release.

Previously Viking readout 12 week top line data that was considerably better than MDGL rezdiffra (resmetirom). I expect VK2809 data to again be better than rezdiffra.

[Whalatane]

LS. as a follow up . Renvela is also swallowed but most require 2 pills ( fairly large ) with each meal.
OLC ( Lanthanum ) is far more effective at lowering serum pho
https://unicycive.com/wp-content/uploads/2023/05/Renazorb-Phosphate-Binders-Daily-Medication-Volume-Poster.pdf

Kiwi

[Whalatane]

LS. good question
My wife prescribes a lot of Sevelamer (Renvela® or Renagel®) largely because its what the issuers will cover . Her patients hate the drug and most are nowhere near serum pho goal .
Those who absolutely refuse Sevelamer , she will go thru the prior authorization hurdles for them to get Fosrenol ( which I believe costs more ) .
If a brand pho binder that patients will take ...1 small pill with meals , swallowed , is approved and the copay is affordable , the thinking is that more Nephrologists and patients will push for it.
The current SOC re pho binders is a failure . 85% of the roughly 400,000 US dialysis patients on these SOC binders are nowhere near pho goal because of pill burden and taste .
Note ...the existing Fosrenol generic is CHEWED ( or in powder form ) Patients hate the taste. The OLC bio equivalent is SWALLOWED .
I don't have a clear idea on pricing , rebates etc except they need to make the copay affordable ...something ARDX did not do with their Xphazoh.

But first they need their final " tolerability " trial to succeed.
Kiwi

[DewDiligence]

B-I has_a fusion protein_for NASH that_hits GLP-1/FGF21:

https://www.genengnews.com/news/boehringer-ingelheim-yuhan-launch-up-to-870m-nash-collaboration/

Could be an alternative to combination therapy.

[LS89]

UNCY questions...

I don't know the space, but have a few questions?

1) Fosrenol and other serum pho binders are generic? And these are the current SOC?
2) If question 1 is true, then why would PBM's cover a bioequivalent version of a generic without a significant (>70%) rebate?

[DewDiligence]

Addendum—This program is very early, but if the MoA works it would rid hepatocytes of HBV cccDNA and thereby cure the disease.

[DewDiligence]

Private company attacking HBV via CRISPR-based editing_of_viral_DNA:

https://www.globenewswire.com/news-release/2024/04/22/2867238/0/en/Excision-BioTherapeutics-Announces-Oral-Presentation-Highlighting-Positive-Data-from-its-HBV-Program-EBT-107-at-the-Upcoming-ASGCT-2024-Annual-Meeting.html

[DewDiligence]

ABEO—(-53%/AH)—receives CRL due to CMC issues:

https://finance.yahoo.com/news/abeona-therapeutics-provides-regulatory-pz-200500676.html

[Biowatch]

diffusion rates will be the same if the volume injected is the same.

That is a misleading statement because it is the concentration gradient of the active ingredient that matters, not the volume of the inert carrier, e.g., saline.

It doesn't matter if is 1ug, 2ug, 4ug or 10ug toxin, the rate of diffusion will be the same. That means the concentration at various points away from the injection site will be HIGHER for the higher dose at ALL areas.

That seems more accurate.
————

Diffusion describes the net movement of molecules from an area of high concentration toward areas of lower concentration. The greater the concentration gradient, the faster the rate of diffusion that will occur.

https://open.baypath.edu/bio109biology1introductiontobiology/chapter/diffusion/

Drugs given IV enter the systemic circulation directly. However, drugs injected IM or subcutaneously must cross one or more biologic membranes to reach the systemic circulation. If protein drugs with a molecular mass > 20,000 g/mol are injected IM or sc, movement across capillary membranes is so slow that most absorption occurs via the lymphatic system. In such cases, drug delivery to systemic circulation is slow and often incomplete because of first-pass metabolism (metabolism of a drug before it reaches systemic circulation) by proteolytic enzymes in the lymphatics.

https://www.msdmanuals.com/professional/clinical-pharmacology/pharmacokinetics/drug-absorption#Oral-Administration_v43449621

FDA Approval Date: Jeuveau received FDA approval for cosmetic use in 2019.
Molecular Weight: Jeuveau has a molecular weight of approximately 900 kDa.
Recommended Dose: The recommended dose for Jeuveau is typically 20 units for glabellar lines.

https://modernaestheticsmd.com/med-spa-blog/neurotoxins-comparison-botox-dysport-jeuveau-xeomin-and-daxxify