Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
The video doesn’t appear using the app but does when I use the website.
There’s a difference between cryptocurrency, for which pet rock seems a reasonable analogy and using blockchain to track trades or contracts or real estate deeds or whatever other use they find for it.
<<As to the flu vaccines, most of them are grown in eggs.>>
Novovax uses moth cells. They get the genetic code for the spike virus into those cells, which produce spike protein. Steps are outlined in this:
https://www.novavax.com/science-technology/vaccine-pipeline/covid-19-investigational-vaccine
The "harvesting" of the spike protein requires purification and different batches may have different levels of purrty, that adds complexity and time as vinmantoo has pointed out. And this isn't being done by a Genentech-level company.
I think Novovax management would take 3 months to make a batch of soup from a can of Campbell’s (spoken as a bitter former shareholder).
<<only need 2-3 months to get out an updated vaccine - that is hard for any other platform to match>>
Why is that? In practice you are clearly correct and I've read this before but I'm not sure why.
Simplistically speaking, mRNA COVID vaccines and the NVAX COVID vaccine are similar in that that both introduce the spike protein into the body; while the mRNA vaccine does so by introducing mRNA into the body, where it is translated into spike protein, NVAX produces the spike protein in production using mRNA and then the spike protein is injected into patients. I assume, in both cases, that the relevant mRNA is produced using modified DNA, so to change the spike protein/antigen, you need to change the DNA in some way so as to appropriately modify the mRNA (which is then injected directly or used to produce the spike protein).
<<A friend of mine told me to get the NVAX booster.>>
I’m curious- merits aside, has anyone ever seen the NVAX booster offered? I searched for my daughter— she lives in Portland Maine — and couldn’t find any place offering it. Also looked for myself, I live in Westchester, NY, couldn’t find it. Admittedly didn’t try that hard. Ended up with the Pfizer bivalent (and COVID 6 weeks later).
<<As far as EDP-235, it is a different chemical entity than Paxlovid so it is highly unlikely any mutants resistant to it will exhibit cross-resistance to EDP-235.>>
Indeed, that was my assumption and partly for that reason I added to my ENTA position today.
At the same time, resistance to Paxlovid is claimed to be developing. https://www.sciencedirect.com/science/article/pii/S0924857922002400
Discussion starts:
“2.5. Resistance
As with any other antiviral, resistance can be either basal or treatment-emergent.
Mutations in Mpro causing resistance to nirmatrelvir are already found in circulating SARS-CoV-2 viruses (Table 1 and Figure 1)…”
<<I don’t know the source of Califf’s 10% figure, but I find the datum believable based on the posts I’ve read about COVID vaccines on various iHub boards.>>
Sounds like a classic case of selection bias to me.
Thanks, that’s exactly what I meant. Changes to the study description, not protocol. If you choose
https://clinicaltrials.gov/ct2/history/NCT05011513?A=1&B=12&C=merged#StudyPageTop
you see they added two exclusions, vaccination within 12 months and “Has at least one underlying medical condition associated with an increased risk of developing severe illness from COVID-19.”
Notwithstanding the change, they had in fact enrolled 721 vaccinated patients with risk of progression, that’s how they ended up with data on vaccinations patients with risk factors in a trial that ended up recruiting only unvaccinated (within 12 months) and no risk of progression.
And Happy New Year to you too and everyone else.
<<You are confused. The trial where Paxlovid failed involved patients with no risk factors.>>
The EPIC-SR trial changed. In fact it started out enrolling vaccinated patients with risk factors and then changed, with the permission of the FDA. At one point I may have linked to a blackline of the clinicaltrials.gov information on the trial but I can't find that and I'm not sure how to run a comparison of changes to the protocol -- someone on Twitter did that 6 months ago.
You can see this discussed in the article you linked to:
<<at least if you want your health care insurance company to pay for it>>
Insurance doesn't pay so far as I know. The US government has purchased $12 billion of it and provides it for free. That may change at some point.
Trials don’t happen randomly. They happen because someone requires it. The FDA or the US government could have insisted that Pfizer run such a trial. Instead the US spent $12 billion on a drug with a EUA based on a trial in an unvaccinated population and didn’t require or even encourage Pfizer to run a trial showing it works in the real world. In fact the half-hearted PFE trial in vaccinated patients failed to show a benefit and was abandoned. It seems a bit contradictory to tell us that vaccines significantly reduce hospitalization yet at the same time promote the use of Paxlovid in the vaccinated, which presumes they are at high risk. Maybe Pax and vaccines are additive. But we don’t know and are going to find out soon, but months and $billions later than we would have had the trial been run in the US as soon as it was possible. It’s not like Paxlovid is free of side effects or cheap.
<<Not sure why the Biden administration would look bad.>>
Because they spent billions on a drug that doesn't, in this scenario work, buying the drug and handing it out like very expensive candy to a population on which it wasn't tested, without insisting on a randomized trial in a real world population.
Merck's COVID-19 Molnupiravir therapy fails to reduce hospitalization in randomized UK trial (Panoramic).
https://www.bmj.com/content/379/bmj.o2441
The drug did reduce symptoms by about 24 hours.
The same trial is also testing Paxlovid. The trial is in a population that has largely been vaccinated. Cf. the trials that lead to US approval for Paxlovid and Molnupiravir, where vaccinated people were excluded. I would expect the Paxlovid results soon, I don't see a reason why that arm would take materially longer than the Molnupiravir arm.
If the Paxlovid arm fails in Panoramic, the FDA and Biden administration are going to look pretty bad, given how vigorously they have been touting use of Paxlovid in the vaccinated population.
Not sure if this is significant, but the patient website, https://daxxify.com, uses language that is a bit less precise than what I believe is the healthcare provider site, https://daxxify.revanceaesthetics.com/
EOLS is down about 26% over the same period (10/6/2021, date of the RVNC high, to current). High beta, low revenue, story stocks have not done well over the last few months.
MGDL collateral effects:
what about ENTA, down a bit more than the market, their website lists EDP-305 (their FXR agonist) as available for outlicensing so perhaps that minimal value has decreased.
Also, Revance has said that they will offer remote training in the future. From the transcript of the latest quarterly call, “As we move from PrevU to broader commercial launch, we will offer a variety of live and virtual training options …”
Re Tesla — Is "con" item #4 true?
As true as the rest of the email, which is, mostly BS. We’ve owned two Tesla Model S’s since 2013, maybe three damaged tires, at least two repaired by third parties. In fact Tesla would not repair a simple puncture for us, went to a tire shop.
As to range, we don’t drive at 100 mph, that affects mileage. Our range is generally fairly close to the Tesla estimated range. We drive around 10,000 miles a year and have gone on some reasonably long trips, eg, this summer, from Westchester to Toronto. Most superchargers are in shopping centers and sometimes you have to spend a few minutes looking for it but in 10 years I’ve never failed to find a supercharger the car directed us to.
Most of the time we charge at home, paid maybe $500 to get a 40 amp outlet installed in the garage. My sister paid less than that to install one at our mother’s house. We pay about $.22 per kw hour, all in.
We’ve driven in some harsh conditions, zero degree snowstorm to Lake Placid and never ran out of juice. I have, however, run out of gas twice in German luxury cars when the gas gauge got stuck and gave a false reading.
This is probably our last Tesla, fit and finished is just not impressive for a luxury car, our Tesla sedan is noisier than my convertible sports car because of wind leaking through the windows. Worse, seats are barely ok for me, unacceptable for my 5 foot tall wife - she needs a booster seat and back. Seat is just not as adjustable as a high end auto should be. And the whole enhanced/full auto pilot experience had been disappointing, to say the least. Borderline or beyond misleading - we were lied to about upgrades etc.
The point, I thought, of the double dose canard, is that doubling the dose increases adverse side effects, otherwise Allergan would tell you to do it. That the rate of adverse side effects in thousands of treated Daxxify trial patients is similar to, or perhaps lower than, Botox, has to be explained— maybe it’s because it’s a clinical trial with especially skilled injectors, maybe there’s fraud, not sure how the fairy tail continues…. But actually doubling the dose likely would increase ptosis etc.
Note this, not that we have doubts, still nice to see this stated:
“Dr. Peredo’s site enrolled 50 patients with moderate to severe wrinkles in the glabella area. Patients received 40 units of Daxxify, which contained 0.18ng of core active neurotoxin. This amount is equal to the amount of core active neurotoxin in a 20U Botox Cosmetic dose (0.18ng).”
<<Data are expected in 1H23.>>
Seems awfully slow for a five day trial that shouldn’t take long to enroll.
Hyperdilution - here’s a relatively recent study of the efficacy of hyperdilution. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570655/
RVNC - equity purchase at 80 percent of fmv.
I’m not seeing this in the proxy statement, discussion of equity comp starts in page 44. https://www.sec.gov/Archives/edgar/data/1479290/000147929022000048/rvncfy21proxystatementdef1.htm#i7f269223b3d049af92690f686780c342_112
Where is this 20 discount described?
Is there similar data for Botox, i.e., where the measured duration of effect is based on that EITHER the patient’s self-assessment or the investigator’s assessment was none or mild? Or put another way, how large of a duration advantage does Daxxify have using an apples to apples comparison.
CLF — 10 percent down on those result seems overdone. I am going to modestly add to my position.
That’s why they emphasize how large the first booster market is (in theory):
“According to CDC data, almost 50 percent of adults who received their primary series have yet to receive their first booster dose.1 Offering another vaccine choice may help increase COVID-19 booster vaccination rates for these adults. Novavax is also conducting ongoing trials further exploring the immunogenicity and safety of the Novavax COVID-19 Vaccine, Adjuvanted to expand its use as a booster.”
I don’t think they ever started the upper limb phase 3, they truncated the phase 2. However the 2/22/2021 press release says they got enough data to inform dosing for phase 3:
“Although we reduced the subject enrollment size in response to COVID-19 concerns, we were able to generate sufficient data to inform our dosing strategy for our Phase 3 program, while also demonstrating a long duration profile that is consistent across our therapeutic and aesthetic clinical programs. Our next step is to schedule an end-of-Phase 2 meeting with the FDA prior to finalizing a Phase 3 program. I want to thank the patients, investigators, CROs and the Revance team for their time and commitment in making this trial possible.”
https://investors.revance.com/news-releases/news-release-details/revance-announces-positive-topline-phase-2-data-supporting
That’s not shocking given the degree of control and skill required to inject into the eye and perform procedures such as a needle revision to a trabeculectomy.
Later they project some modest (pitiful?) revenue from therapeutic indications.
For cerivcal dystonia, they project "2025/2030 unadjusted sales of $22mn/$39mn and apply a 70% POS."
For upper limb spasticity, about the same, $24 million in 2025 and $82 million in 2030.
It's a long (8 page) discussion, part of an 67 page analysis of 7 mid-cap stocks. This is part of the discussion:
Plus antibody response is in “the majority of patients dosed,” consistent with little or no response in, say, 40 percent of patients.
“Significant antibody response (2-6 fold over baseline) as measured by multiple markers of immune response to VLP vaccine antigens observed in majority of the patients dosed”
Oops, left out a “not”.
It seems the injector does NOT gave to learn a new technique.
Comparing the package inserts for Botox and Daxxify, the actual injection procedure for glabellar lines looks the same, 5 injections of the reconstituted liquid, 0.1 ml per injection in a similar pattern. I suppose that’s good, since the injector does have to learn a new technique but it surprises me since I thought there is a bit less “spread” with Daxxify.
I don't know but in any event I don't think you can compare what happens in a placebo controlled randomized clinical trial to what happens in a Miami Botox injector's office. This was a placebo controlled trial with lots of patient and investigator evaluation and other monitoring, including hooking patients up to 12 lead ECG at initial visit and 4 weeks.
https://clinicaltrials.gov/ProvidedDocs/35/NCT03014635/Prot_000.pdf
Re Revance rollout: those 2700 patients (who received 4200 injections) were treated as 61 different sites, in about 20 different states. How many people actually did the injections, 200? Not much of a rollout if limited to that.
Starts at 47:43.
His main thesis is that Daxify achieves its result doubling the toxin dose. I thought that been argued before but is just wrong.
If it were correct, why limit his criticism to the aesthetic market, which is what he does. For therapeutic market if you can get the same result by doubling the dose, why don’t people do exactly that with Botox and why would Daxi have any advantage.
OCUL: there are a number of reasons why the comparison is not valid, but I can't resist pointing out that the difference between the OCUL wet AMD data and Eylea (even the high dose) is similar to the difference between RVNC's Daxi and Botox. Fewer injections, 6 or 7 month efficacy (or longer) for the newcomer v. half that for the established brand. Granted, the Daxi data is just a bit more robust and they have an approved product.... But in both cases, the challenger is pinning their hopes on the belief that patients will prefer to have needles stuck in them something like 50% less frequently.
Me too. I speak from experience. Haven’t been injected for AMD but I’ve been “needled” more times than I remember for my glaucoma and an eye injection is better than a poke in the eye with a sharp stick - no, that’s what it is. It seems entirely believable to me when OCUL claims that many (perhaps the majority) of patients don’t come for the frequent injections. Layer in that ophthalmologist offices seem worse than other doctors in making you wait, not a pleasant experience at all.