I get the point you are trying to make but 2 months in early stage patients vs the patient population in the BEACON trials is an entirely different beast. I think there is a high probability NKTR-102 would/will do wonders in the patient population where the tumors are still more chemo sensitive. I understand why NKTR went after patient populations where nothing else works, but there is plenty of room to question their development strategy why even do the OC work half way. IMO Klaus is right about one thing NKTR-102 is special. 12B special ? No that's just nonsense, but a cytotoxic with greatly attenuated toxicity and improved potency still has a significant place in the treatment of multiple cancers especially if the potential in combination therapies pans out.
The clowns showing up to trash NKTR are also right about one thing NKTR management does not deserve a free pass on their historical execution, not when they reward themselves so generously. 2 CMOs have been shown the door in recent history at some point you have to blame to people making the hiring decisions.
"Lastly, we’ve now completed dosing for all patients in the Phase III clinical trial for BAX 855. To-date we have no reports of inhibitors or drug related series to adverse events. We look forward to sharing the top line data in the third quarter and continue to expect to file in the U.S. before the end of the year." $11 THANK YOU!!!!! the couple thousand shares I picked up will be a wonderful gift in a few months.
Of course arguing against that ~7M shorts still need to cover and if my speculative scenario plays out that might give them an opportunity to get off the hook with minimal damage. I'd be very nervous being short in the Sept-Dec timeframe.
I was thinking of doing something similar, but I didn't pull the trigger yet. Honestly I was/am hoping bad news from FDA for SLXP/PGNX might happen, and be misinterpreted as bad news for NKTR as well.
IMO people are clearly confused about the adcom recommendations, and what it means for all involved. In the short term I think a lot of people might panic if FDA delivers bad news for Relistor, and think 118/Naloxegol/Movantik is in the same boat. If there is a big dip on such news, then I'll pull the trigger on a purchase, otherwise I own enough already.
Their approach is really interesting, but this news will unfortunately pummel their stock. Oh well we only recently found out about this collaboration and it's potential benefit to NKTR, so it's not one that was factored into my premise for being here. Mind you we still don't know what is going on here at all, but what seems like an unusual action on the safety front will have investors jumping to the "where there's smoke there is fire" line of though, and I can't say it gives me a warm fuzzy feeling about the candidate or the prospects of the technology in general at this point. Best case these reactions aren't attributable to drug (we have no idea how many or any details to my knowledge), if they are rare and risk factors can be identified then they would have to look at the relative benefit of the drugs reversibility vs the risk of these reactions. In any case at the very least it means the safety data will be run through with a fine tooth comb.
A couple points: There is not really anything new in the data, and it's pretty much standard for companies to publish at this point in time. Good PR but mostly a feather in the cap for all involved to add one more publication in a high quality journal to their CVs
As for the clown suggesting there is ANYTHING in the data that would indicate an advantage for Relistor this just isn't the case. It's tough to know what to make of Relistor data, SC= who cares, and as stated here before oral has a long road ahead of it. If they don't want to believe that I really couldn't care less. But just looking at the dosages they are an order of magnitude higher due to poor oral availability. The potential issue with this comes with potential variability in patients, E.G. somebody could absorb much more than the average, and this could obviously cause problems. That's just one potential question, I can't believe FDA will say the data generated to date is adequate
"I thought the CLR was entirely about CV issues and not about the general long term safety issues. It's hard to run trials when the end game keeps changing."
While your statement is true enough in the end it doesn't matter. The argument that FDA advised us this would likely be ok when we set out years ago doesn't hold any weight. To modify a line from Unforgiven "fair has got nothing to do with it" I saw this first hand at Magainin/Genaera with their Locilex trials years ago. FDA can walk away from agreement on trial design whenever they see fit.
Fair enough on the who is to blame front. SLXP can't be blamed for what they inherited, but IMO they also have not been upfront on the extend of the clinical work that needs to be done. There are several layers of issues here that seem to be confusing people.
First off there is SC Relistor's status. From a commercial perspective who cares, but FDA will likely provide their judgement on whether the clinical work done to date is adequate. IMO it isn't the adcom was clear on what should be expected, and I don't get this "for future candidates" argument FDA doesn't grandfather in lack of safety requirements even if you say they agreed on this in the past.
Second there is the oral formulation. From the commercial perspective this is the more important issue. IMO additional clinical work is also still required based on same argument, adcom was clear LT controlled safety trial for all canidates should be required. People don't seem to grasp controlled= adequate placebo arm. History of SC Relistor on the market does not help meet this requirement.
Third there seems to be this SC data should be transferable to oral clinical body of work. While it's the same compound and superficially seems safer that doesn't preclude the need for the LT controlled safety trials for the oral version. The drug was dosed SC for a reason, poor availability. E.G. If part of the way this was fixed was formulation and a larger dose assuming poor availability can you assume there wont be a subset of patients where substantially more drug is absorbed? We will have the answer soon enough, but I would be VERY surprised if Relistor SC or oral sees approval for chronic use before 2016.
The Salix pill isn't what is on the 30 day timetable that is for a response to the appeal of the CRL for the SC trial. If the response is negative it's doubtful SLXP would continue development for SC Relistor for chronic use. They would almost certainly shift focus to oral and leave SC as is. The key question is what lies in front of oral Relistor I and some others here believe they have a lot more work ahead of them then they are claiming. In 30 days the tone the FDA takes with them on the SC product will likely tell us where the FDA stands even though there are 2 separate issues they are intertwined. If they have not run controlled trials of the size and scope FDA wants it will be a much longer wait for oral Relistor to show up as competition.
A lot of people seem to be seeing the adcom results as smooth sailing for all parties IMO they misinterpret the reality. yes the candidate killing pre approval CVOTs will not be required, but controlled safety studies (now preferably enriched to look for CV risk signals) are required. I actually wonder if FDA rules against the SLXP will people actually assume that's a negative for NKTR (it isn't) simply because they don't understand the core issues.
I listened to the same call. The CEO admits additional trials might be required, but spins the situation as he believes this unlikely. FDA doesn't give free passes, only new candidates have to meet this standard? Believe what you want to believe. You will have an answer from FDA soon enough, and I would bet real money the verdict wont be what you are hoping for. ($100 to the charity of the winners choice?)
If I had a nickel for everytime a biotech CEO misrepresented to situation with FDA only to blame the agency later. We have 30 days to hear back from FDA on the CRL and likely their general stance on where Relistor stands.
"it was his belief that the AdComm rec for a controlled safety trial would apply only to new PAMORAs and not the ones currently before the FDA"
There were clear questions about whether the SLXP clinical plan was adequate before all of the CV storm kicked up. SLXP is thinking they will get a pass on safety trials why? The adcom didn't dismiss all safety concerns if anything the message was essentially: there isn't enough signal to warrant prohibitively large expensive and not necessarily informative pre approval CV trials, but its worth continued observation to see if there is a modest real signal. And that only touches the CV issue chronic use oral Relistor needs to be examined for any other safety issues that might be there. Even if there were adequate long term controlled safety studies for chronic use of SC relistor (and there aren't), the oral version would still need examination. Honestly I think the SLXP management knows they screwed up, but can't admit that. They will likely just shift to blame the FDA mode if things don't work out the way they hope. It's one shining argument for the value of a partner like AZ with the resources and experience to navigate the clinical process with a candidate like this. It also argues for some careful consideration if NKTR should look at a partner for candidates like 181 we already have a PII one could easily argue was botched costing us time and money.
What are you talking about Corona? Nobody here has suggested there is any doubt re pre approval CV studies. I think you are missing the point being discussed. The panel was crystal clear a controlled long term safety study should be required for all candidates in the class. The Movantik/Naloxegol trials are almost certainly adequate to move ahead with approval in Sept. Relistor is another story SLXP has not run comparable safety trials to those run by AZ hoping to "piggback" oral chronic use on the SC work. I'll bet real money they need to do more trials. This is good news for NKTR as the competition is effectively set back at least a year IMO.
I'm genuinely surprised there seems to be confusion on this point, clearly enough people understand and are in agreement, and that is why we see NKTR responding positively post adcom and PGNX has effectively stalled out. I really wonder if SLXP would even recoup their PIII trial expenses if the argument is correct that oral relistor is 2nd to market with Movantik having a 12 month plus lead.
I thought the advisory panel was pretty clear while no pre approval CV outcomes study is required the controlled safety data should be required for all candidates. I think some people took the outcome to mean no further trials required, this is far from the reality. I'm not sure how much this has held up the Cubist candidate, but I'll wager Relistor doesn't even have much of a time lead on that additional competition.
The SC Relistor well was never very deep but it's likely to run dry soon, and I'd be shocked if SLXP did not have to conduct safety trials comparable to those run by AZ if they want to be in the market for chronic use. Will they move forward at all is a legitimate question IMO.
Point to the long terms safety studies you are referring to. They don't exist. I know the history very well and if Relistor wants to enter the chronic use arena with their oral product uncontrolled short term usage with the SC product does not make the case.
People seem to be misinterpreting what the adcom results mean, don't listen to me get SLXP or PGNX to comment on the path forward, and the timing. No pre approval CV outcomes study does not mean you get a pass on controlled PIII studies comparable to what AZ conducted for Naloxegol/Movantik. Don't want to take my word for it, then don't. Talk to IR, get PGNX and or SLXP to give you some clarity on the path forward now that the adcom is in the rearview mirror. Honestly I'd love to hear what they have to say on the issue.
Fantasy! Relistor has additional studies to perform to meet the standards the adcom recommended. Not having to do a pre approval CV outcomes study does not mean what SLXP has done to date is in any way adequate. How far from completion of an adequate controlled long term PIII with oral Relistor is SLXP?, and what does being second (assuming Cubist doesn't also pass SLXP) to market with an inferior compound mean?
WIth AZ's marketing muscle behind Movantik I wouldn't even bother burning the money to advance Relistor if I were SLXP. The market seems to have figured this out, and that is why you see NKTR up 10%+ while PGNX languishes post adcom.
I wouldn't be at all surprised to see a PR in the near future re one of the other candidates moving forward. E.G. I didn't expect NKTR to move ahead with 181 PIII until there was some certainly that they could count on the milestone payments.
Even with the milestones 102 PIII plus 181 PIII plus everything else is a whole lot of burn. That's why I still think another financing is possible/likely. While I have raged against dilution in the past I have no problem with raising money to advance a promising pipeline as long as it's in the context of people paying the appropriate premium to jump on the bandwagon at a late time point with a lot of the risk off the table. It's always best to raise money when you really don't need to. Deep pockets to fund R&D when you have a tech platform that shows this kind of promise is an ideal situation EG I would hate to see a candidate like 214 languish in preclinical limbo for lack of funds. (I'm not saying I think that's the case w/214, but I think the point I'm trying to make is clear)
DCX Are you planning on buying back in at any point or holding to the sidelines just out of curiosity?
It was definitely a bit tense listening at times. There were definitely a few zealots on the panel with an attitude of there's always a way to do the study, and I don't care what it costs that's on the invesigators tab. A smaller panel with a different makeup and a bit more questionable data, and you could see how an ultra conservative stance could have been the majority opinion. I don't think they grasp there is a trade off in developing new drugs at some point zero risk= no new drugs or HUGE healthcare cost burdens to a system already under cost strain.
I agree that the ultimate size of this market is still very debatable, and perceived CV risks real or imagined still need to be dealt with, but for me Movantik was never the pot of gold at the end of the rainbow. The milestones are the key IMO. Buying dilution free time (or at least much less painful dilution) until other candidates cross the finish line is what I'm seeing.
I also wonder if DCX is going to tell us he got back in in time to avoid paying the premium having this result in the rear view mirror will result in.
Hijacked in the big picture I think Movantik/AZ/NKTR is the clear winner coming out of all of this (assuming FDA does the expected and goes with the adcom recommendation).
It seems to me like it's pretty much smooth sailing for NKTR to get their milestones without any penalty from having to re-negotiate the AZ deal terms. While the competition was set way back, waiting for the outcome here. Relistor (and particularly Relistor oral) likely needs to run PIII trials comparable to what AZ has done as a starting point. Cubist likely held up their progress waiting to see the outcome here. In the end Movantik will likely be first to market as an oral peripheral opiod antagonist, and the gap in timing between Movantik and the competition was dramatically increased by all of this confusion.
I'm not really sure why the people over at PGNX are so happy about this result. IMO they have already lost. A distant second to market with an inferior compound only to go toe to toe with AZ marketing? The downside for NKTR was arguably having to raise money at a reduced price in the shadow of this confusion, but outside of that all of this has played out in NKTR's favor in a big way IMHO.
actually 4A 5B 15C with corrections is my count but they likely will leave it as 7A since they just commented vs a revote, but even so you are effectively at 7 to 17 (or 4 to 20 with changes) most being in favor of post approval studies of various flavors in either case