Enanta's EDP-323 meets Phase 2a endpoints in respiratory syncytial virus

Enanta Pharmaceuticals announced positive topline results from a Phase 2a human challenge study of EDP-323 in healthy adults infected with respiratory syncytial virus - RSV -. 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, a 97-98% reduction in infectious viral load AUC by viral culture, and a 66-78% reduction of total clinical symptoms score AUC vs. placebo. EDP-323, which received Fast Track designation from the FDA, is a novel L-protein inhibitor in development as a once-daily oral treatment for RSV. EDP-323 demonstrated a rapid and sustained antiviral effect. EDP-323 demonstrated favorable pharmacokinetics, supportive of once-daily dosing. Overall, EDP-323 demonstrated a favorable safety profile over a 5-day dosing period and through 28 days of follow-up. Adverse events were similar between EDP-323 dosing groups and placebo. There were no serious adverse events, no severe adverse events, and no adverse events leading to treatment discontinuation or study withdrawal.

Read more at:
https://thefly.com/n.php?id=3988864

JNJ

https://endpts.com/jj-folds-cardiovascular-and-metabolic-drug-unit/

BIOA IPOs 12.65M* shares @$18.00:

https://www.globenewswire.com/news-release/2024/09/26/2953430/0/en/BioAge-Labs-Announces-Pricing-of-Upsized-Initial-Public-Offering.html

Fortunately, PFE’s acquisition of GBT is not a total bust. PFE still has GBT-601 (a/k/a Osivelotor), which is in a phase-2/3 trial (https://www.clinicaltrials.gov/study/NCT05431088).

PFE- Withdrawing OXBRYTA from the market. Pfizer acquired Oxbryta as part of its $5.4 billion takeover of Global Blood Therapeutics (GBT), which closed in October 2022. The drug had $328 million in 2023 full year sales and was one of the places PFE was looking to for growth. (Original Peak sales estimates were for $2B)

Pfizer Voluntarily Withdraws All Lots of Sickle Cell Disease Treatment OXBRYTA® (voxelotor) From Worldwide Markets

Thanks so obviously some patients have still not seen resolution off drug (yet?)
Nothing here is a deal breaker to get to market IMO, but certainly could have implications commercially. It's possible intermittent dosing could alleviate some of these AEs without much drop off in efficacy if the AEs reverse faster than mast cells replenish

CLDX says, “Most events were grade-1, mechanism-related, and expected to be reversible” [emphasis added; from slide #14 from slide set linked in #msg-175137124]. So, it sounds like reversibility is in question to some degree.

was it reversible? if so not as big a deal IMO
It's odd that THRD is not tanking, but the ability to fine tune the dose with an oral drug must be off setting the on target tox here

The hair-color changes tell us that skin hypopigmentation, which is harder to mask cosmetically, is apt to be an issue for this drug.

The devil is going to be in the details. If things like hair color are mild and reversible and not a primary cause of dropout then perahps not a big deal
PBO adjusted dropout rate was 9%. I view this as disappointing because with such good efficacy you would think patients would want to stay on study through some AEs. Of course if you are in a CR for many months already and drop out towards the end then that is somewhat mitigating
looks like the Q4 week regimen had less AEs than Q8 weeks so if this is indeed the regimen that emerges as best then a negative for CLDX
*I do think this opens the door for oral drugs because of the fast on off to manage AEs in general so mildly bullish for THRD, BPMC and ENTA despite the AE concerns related to the target (so perhaps why THRD etc are relatively flat and not down along w CLDX now)
I will have to listen to the cc at some point

CLDX—(-20%)—reports phase-2 CSU data_for barzolvolimab—25%_dropout_rate_and hair-color changes _in_6_patients:

https://finance.yahoo.com/news/celldex-therapeutics-presents-landmark-52-144500144.html

CC slides (slide #6 contains AE info):
https://ir.celldex.com/static-files/104cb8ec-550b-42d3-aef6-3c9d9c9d9fdb

p.s. ENTA is pursuing small-molecule treatments for CSU.

Viking's oral VK2735 a potential candidate for OTC status, says Oppenheimer

VKTX Following "disappointing results" from competitors' oral obesity drugs, Oppenheimer analyst Jay Olson tells investors that the firm views the black box warning assigned to GLP1 drugs as "a hangover from earlier GLP1's" and suspects a relatively safe oral GLP1, like Viking Therapeutics' VK2735, could eventually become a candidate for a prescription to over-the-counter, or OTC, switch. In that context, the firm says its survey of 40 high GLP1 prescribing primary care providers, or PCPs, for opinions on oral GLP1 if it were OTC found that almost half were unconditionally in favor of an oral GLP1 drug going OTC.

The firm, which believes oral VK2735 is a potential candidate for OTC status based on existing clinical data and looks forward to Obesity Week updates, suspects the potential for Rx to OTC switch is "top of mind for larger partners seeking a valuable entrant into the obesity space with potential for an extended life-cycle." OpCo maintains an Outperform rating and $138 price target on Viking shares.

Read more at:
https://thefly.com/n.php?id=3988596

Peer Reviewed Paper Published today on IceCure Cryogenics Platform for Breast Cancer.
https://ir.icecure-medical.com/news-events/press-releases/detail/145/icecures-ice3-5-year-trial-results-published-in-the-peer-reviewed-annals-of-surgical-oncology-journal-prosense-cryoablation-without-excision-for-early-stage-low-risk-breast-cancer-demonstrates-96-3-recurrence-free-rate

$ICCM

Typo in #msg-175130495—There are two case d) entries (oops). Let's refer to them as case d1 and case d2.

That scenario probably falls within my case e), LOL.

Another possibility -- this would require the cooperation all the various parties, Crown, Teoxane, and to a lesser extent, RVNC. This is, allow Teoxane to continue on as a shareholder in Crown/Revance post acquisition. It is not uncommon for management or other significant or strategic shareholders to continue to hold their shares after an acquisition target is acquired by a PE fund or porfolio company of a PE fund (one well-known example, Prince Alaweed and Twitter, see https://www.forbes.com/sites/mattdurot/2022/10/31/saudi-prince-alwaleed-becomes-twitters-second-largest-shareholder/) Here it would be more complicated because RVNC would be combined with Crown, so Crown and Teoxane would have to agree on a value for the combined Crown/RVNC business. I don't see why RVNC would care, all other shareholders get bought out at the agreed on price. For Crown, yes, they would own stock of a private company, but it is a private company owned by PE funds which will be sellers at some point, typically PE funds have limited lives, 10 or 12 years. In that regard, note that the owner of Crown, Hildred Capital, raised cash in a "continuation fund," allowing their investors in an older Hildred fund to get liquidity without having to sell their entire portolio. https://www.hildred.com/news/hildred-capital-announces-close-of-multi-asset-continuation-fund-with-capital-commitments-in-excess-of-750-million

“Interesting” commentary on Yahoo! RVNC community board:

One possible reason for a maximum supply level would be for Teoxane to retain control over who sells their product.

… in the event that the relationship is terminated.

Probabilities of various RVNC outcomes, IMHO….

The cutoff date for all cases listed below is 12/31/24. (The 12/31/24 date is arbitrary, but I must have a time limit in order to define the cases.)

a) Crown buyout closes on the original terms: 46%.

b) Crown’s tender offer either doesn’t happen or it fails to garner a majority of RVNC’s shares, and hence there is no RVNC buyout at this time: 29%.

c) Crown raises its offer and the buyout closes on the new terms: 9%.

d) Crown raises its offer but the tender still fails (and hence there is no buyout at this time): 2%.

d) A White Night bests Crown’s offer and a bidding war ensues: 8%.

e) The situation remains unresolved as of 12/31/24, possibly tied up in court: 6%.

I do not have a case for RVNC’s accepting a lowered buyout offer from Crown (or another party) because I consider the probability of this to be negligible.

Metsera - Another GLP1 drug reporting good phase 1 results without much info on AE's. A couple of twists as this is a peptide and dosing was weekly without titration but they are targeting monthly dosing due to long half-life. N was 125 so a larger Ph1 trial. Metsera is private.

Metsera Reports Highly Competitive Results from Ongoing Trial of Novel, Potential Once-Monthly Injectable GLP-1 Receptor Agonist MET-097

One thing I need to correct is that the allegation Toexane is making about stocking. The SEC filing says

Why are you so sure they would give up their jobs immediately? Why not wait and see what happens?

Of course sales reps should be updating their resumes as part of the process of seeking new employment if or when they lose their current RVNC job. Do you think Crown has a crack sales team ready to jump in and start selling Daxxify so they will fire all the RVNC sales reps ASAP?

I'd have to assume that Revances Reps hit the road right after the merger became public. A decent portion of their income is tied to stock and to see not only their income get strained but all the stock they bought through the employee programs hopelessly underwater, Dermal Sales probably fell through the floor.

Yes- I assume it is a simple matter to buy more inventory as that is a hard and fast number. The other allegation of time spent on promotion is a lot more nebulous and often subject to interpretation.

When I was involved with ":exclusive distributor terminations" - multiple meetings were held regarding "sales effort". Things discussed included targets for sales call engagements(quantity metric), conversions (quality metric), customer satisfaction (surveys/interviews), market share penetration (using 3rd party numbers) seminar requirements, etc. The paperwork was onerous on both sides and again a lot of things were subject to interpretation. Time frames for improvement were made in months. The ones I was involved with took about 6 mos. from time notice was served till final actual distributor termination.

The Revance - Teoxane deal may have hard targets and it may not. Hard to say because as you point out, it's heavily redacted. I can't really say its the same as what I was involved with would have the same metrics.

The bottom line as I see it is if the supplier wants out of a exclusive distribution agreement, there is a very high probability the supplier is going to get out it eventually and make the distributors life miserable in the interim. Crown must have some pause regarding this if Teoxane is making threats.

As you seem to be saying, the buffer stock requirement doesn't seem that significant, presumably it's just a matter of buying some additional inventory. As to the required efforts to promote, the agreement appears to be quite specific but all of the key language is redacted. I assume there are numerical requirements relating to amounts that have to be spent on promotion, with rules for determining how to compute that. From the license (which you provided a direct link to):

I don’t think the change in control clause the route Teoxane is going to terminate the agreement. Todays 8-K says:

Re: Teoxane, Revance, change of contol

Well, I agree with that. Merger/sale, doesn't matter. It's all a change in ownership as defined. But it's all irrelevant unless you believe Crown is a competitor.

Well add me to the camp that says Teoxane isn't happy with Crown being their distributor or their RVNC stock performance.

Exclusive distribution agreements are complex. Both the supplier and distributor have rights by US Law. Distributors (in this case RVNC) make investments to often sell products which require a certain level of skill to sell so a supplier can't just say "you're fired". Suppliers have rights too and they can make demands on the "distributor" that if they aren't met can allow the supplier to terminate the agreement.

Here is a link to the Jan 2010 Revance - Teoxane agreement filed as an Exhibit to the 10-Q on Jan 10, 2020

https://www.sec.gov/Archives/edgar/data/1479290/000147929020000042/fy1910-kexhibit1043teo.htm#s1DFC4791AADBD4C4BDBE7F318C55CA31

Many years ago, I worked in sales for a major manufacturer who used exclusive distribution in the US. I can tell you it was always a love hate relationship and it is just human nature. On a couple of occasions, we as the supplier terminated a distributor and it wasn't easy. It took time and a lot of effort (need to follow a process) You needed to do it legally to not get sued by the distributor. In each case where management wanted the distributor terminated, we got it done.The outcome during the process was always crystal clear to mostly everyone involved.

The Revance - Teoxane relationship may be fixable or it maybe beyond the point of repair. If Teoxane has a will to get out, my guess is they will find a way to do it legally over time. I doubt this gets resolved easily and putting a time limit for resolution of Oct 4th (new tender deadline) sounds like a stretch.

What this all means is anyone's guess. I think the deal for Crown to buy Revance is not going to happen. I don't believe Crown will tender with the threat of Teoxane leaving if the deal happens and I suspect that this will go to court on who owes who for the breakup fee.

If the Crown deal doesn't go through, Teoxane may still follow through with taking away the line from Revance because they are just not happy. They may have already written off their stock investment. Revance never filed for European DAXXIFY approval which is something that at one point Teoxane wanted but who knows now given the RVNC struggles in the US/time frame for approval. This would be a scorched earth move by Teoxane, but we just don't know if they think the loss on the stock they own outweighs their desire to sell in the all their products in the US market directly or with someone else.

Full disclosure, I have no current position in RVNC.

You still maintain that the change of control triggers a termination right (applicable only if the change is to a competitor, as broadly but specifically defined in the Teoxane license) even though (i) Crown represented in the merger agreement that it is not a competitor, using language tracking the competitor definition in the Teoxane license and (ii) the 8-K filed this morning, listing a variety of grievances that Teoxance asserted two days after the merger agreement was filed, failed to mention the change of control provision?

With respect to Teoxane's Change of Control provision, it's immaterial whether the Crown-RVNC deal is characterized as a merger or an acquisition. Regardless, the deal plainly involves a change of control.

Dew

16.4. Termination in case of a Change of Control

The Supplier shall have the right, but not the obligation, to terminate, with a

Teoxane is private, so we don't know its financial resources. Your hypothetical seems unlikely but it's not crazy, IMO.

jbog:

I bet they aren’t happy with losing money on buying RVNC stock.

No way would he fit into that costume.

Pumpkin spice season is here.

Is the rumor true that Foley is planning to go to a Halloween party disguised as a competent CEO?

I get the feeling Teoxane isn't happy with Crown being their U,S, Distributor

Revance Therapeutics plunges as Crown Labs tender offer delayed amid Teoxane dispute
RVNC -0.68%Sep. 23, 2024 7:47 AM ET
Revance Therapeutics (NASDAQ:RVNC) dropped 12% in premarket trading after the company said Crown Laboratories tender offer has been delayed until at least Oct. 4 amid a dispute with Teoxane.

Revance (RVNC) disclosed that on Aug. 16 it received a notice to remedy alleged material breaches, including breaches of the maximum levels of buffer stock and required efforts to promote and sell Teoxane products, under the company’s exclusive distribution agreement with Teoxane, according to an 8-K filing on Monday. The company denies the alleged material breaches asserted in the notice, does not believe that the asserted allegations constitute material breaches under the terms of the distribution agreement, and intends to defend itself vigorously. Revance is engaged in discussions with Teoxane regarding the notification.

In light of the discussion, on Sept. 19, Revance (RVNC) and Crown Labs agreed to extend the date where Crown Labs has to start its tender offer to Oct. 4 or such other date as may be mutually agreed to between the company and the buyer parties, according to the filing.

"The Company’s ongoing discussions with Teoxane and the Buyer Parties could result in delays to the consummation of the Offer or in the Company or the Buyer Parties seeking remedies in accordance with the terms of the Merger Agreement.," the company said in the 8-K.

Revance (RVNC) also disclosed that the HSR waiting period for the sale to Crown Labs expired on Thursday.

The disclosures come after Revance (RVNC) shares fell 9% last Monday after Crown Laboratories failed to start a tender offer for the company by a deadline.