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Re "different unrelated third parties"
So could be 'unrelated' to each other, i.e., multiple 3rd parties that are unrelated to each other.
Or it could mean 'unrelated' to NW and its principals. this would mean unrelated to LP, Toucan, etc.
It is likely both of these. I'm not sure if this would cover entities cooperating on trials, such as companies with CI's; I would guess these would be unrelated, as I think the meaning is unrelated financially, but I'm not sure.
I'm still at first steps on the SEC filings from the screening halt to now, but (IMO without the research) the Catch 22 here is that NW is in this dire financing situation because LP has so far chosen not to solve the issues with the SEC, Woodford, etc, while providing emergency financing at egregiously favorable terms for her (discounted conversion price, large warrant coverage). From pre-2015 knowledge, my guess is she is reluctant to give up control, so the company stays in purgatory.
Hi Flip, good to interact again.
Re PFS, just marketing VP (which I was) judgment that non-inclusion means not as powerful a story. Plus remember in 2014 trial was modified to change PFS endpoint to 4 months advantage vs 6 months originally, with expanded enrollment, so IMO has been a brewing issue all along.
Re OS, I'm going by the PR of the 19th, where 3 yr OS is 46% for methylated and 11% for unmethylated (2017 data). So clearly methylated is a dominant factor. I acknowledge both are better than SoC, as is the 23 mo overall ITT OS (which is why I have confidence that efficacy will be agreed by the FDA).
Re approval dynamics, of course PFS will have to be evaluated since it is the primary endpoint. But now that I have seen many AdComm's for other companies on the way to PDUFA decisions, I just think it will be a distant second consideration to OS, which is the gold standard for cancer treatments.
And the FDA over recent years has been diaplaying a very welcome use of common sense, even approving some of the label for the CI's (Opdivo, Keytruda) using just PhI data; and as well, that was even with the very dangerous SAE profile of those drugs - and the CAR-T drugs. The extremely benign safety profile of DCVax will also be viewed very favorably IMO.
The net net for me on efficacy is that I think the FDA will be satisfied on the efficacy of DCVax-L.
Thanks VuBru - very useful.
IMO it is likely scenario 3 or 4. Why?
- Lack of PFS data in data released so far likely indicates an issue.
- Methylation status looks to be the dominant prognostic indicator, and not whether ndGBM or rGBM. And there will be methylated patients in both initial DCVax and crossover cohorts.
- The insistence on getting the long tail OS data is likely being done to be able to have this powerful data to carry the day for approval.
Also, PFS was always a surrogate endpoint for OS. The original reason to use it as primary was so the trial could end earlier without having to wait for the OS data to mature, especially given the long tail of DCVax in PhI. Now that the OS data will be there, including the long tail, PFS becomes almost a non-issue (IMO).
Thanks Senti, Highway. I hope the deck is available at some point; I want to see all the updated data.
For me, there are 2 categories of consideration for NWBO in making a decision: 1) efficacy / approvability, and 2) investibility.
Re 1), the data from ASCO and the SNO update demonstrate efficacy (IMO), with the long tail seen in the PhI present again. And IMO NWBO will be able to figure out a SAP to show it, though it will be complicated to deal with the crossover effect on data.
Re 2), this is where the issues are for me now. The SEC investigation and delisting are major red flags that something is amiss in corp governance. IMO this is what is holding the pps to penny levels. I'm trying to wade through the SEC filings to see if I can get a handle on it. Exacerbating this is mgmt.'s perennial opacity / lack of communication. I'll post ideas as I work through the filings. One thing for sure, though, is that the issues need to be remedied, and a reverse split in the 1-for-10 to 1-for-25 range needs to be done to make the stock investible for institutional investors and for pps thereby to get to a rational valuation for a company with such a groundbreaking drug.
Hello all, does anyone know if Dr. Liau's pres from SNO is available online somewhere? Apologies if already posted - I've been trying to catch up since Saturday but so many posts!
I've been out of the stock since the screening hold happened; evaluating now whether to get back in.
Thanks Fox
Hello All. I have not been following NW closely for the past few months. Question: Has NW submitted the data yet that regulators are looking for in order end the PhIII screening suspension?
Thanks in advance for saving me from doing the research.
Hi Flip. Hope all is well with you and yours.
Hello All,
Regards to all; have not had time to be on the board, but saw something today that is significant. Sorry if already posted.
See the 13d filed today: Woodford now owns 20.46m shares, having spent $149m so far to acquire them. That is commitment!
Combined with the 13g filed on Sep 9, where 14.2m shares were owned as of Aug 7, Woodford has acquired an additional 6.2m shares in the last month.
It's not clear to me if the shares came from the company, which would be welcome given the need for a new capital raise, or were purchased on the open market.
No argument from me - I would also like to see a complete look at Direct data. The last patient should be receiving their last injection within the past few weeks, and many should have had many months since the last injection. The Direct data release issue is (IMO) an outcome of the AF-induced sh*tstorm of last year when the first data points were released; they look to have decided that only with MDA agreement will any data come out.
Interesting that Robert Prins of UCLA (DCVax-L developer along with Linda Liau) is listed on the Direct poster. That gives additional legitimacy/impact IMO.
Final April 7 Call Update:
As of Friday close, there were still approx. 12,700 contracts OI, with Friday volume of only 450 or so. That means approx. 12,300 contacts were exercised, or 1.23m shares were purchased at 7 (up until expiration, IMO the daily April 7 volumes were from people trading in and out of the options, with no shares purchased). This is likely a bullish indicator, but it should be noted that these remaining calls may or may not have been from the original large 20k contract buy.
Interesting that 23k July 6 puts are still OI. IMO indicates a very savvy investor, with a large margin capacity of course. I doubt we will see the puts exited before the bid goes below .1 since the investor has held them this long.
IMO this is likely all from the same investor, selling the puts ("sell to open") to pay for the calls ("buy to open". And this investor made the investment with inside information on NW's intention to present in late March and in April at the various conferences (a co. does not sign up to present unless they have something positive to say). The investment happened a few days before NW showed up on the agendas of the conferences. Because of the "illegal" timing, I do not think it was Woodford.
This has been a very successful trade. I did something similar when I saw these positions opened and after NW showed up on the agendas, yielding the 'light bulb' that this was a low-risk, high-reward trade due to the likely pps runup into the conferences. In my case, I sold April 6 puts for .85, and bought April 7 calls for .25 in a 3-1 ratio with the puts. Worst case I buy shares at 5.15. Both legs of course ended up great: I banked the put money last Friday as they expired worthless, and sold the calls at various times for an average of 1.3 (first sell was just after LPs March pres, fearing the next cap raise, and last batch sold was last week), so approx. 5x return on someone else's money, which I also kept. The seller of the July puts will make even more money due to the higher extrinsic value of July vs April.
Overall, just pointing out an example of how money can be made on short term judgments while waiting for the long term home run.
So Pyrr, are you no longer a 'patient long'? I thought you had the right of it with that strategy as regards having a core holding of NW.
That is what I am doing with shares and 2017 leaps, with some additional shorter term trading of shares and options around the somewhat predictable swings caused by conference presentations/posters (upward) and funding needs (downward).
As you previously wrote, and which I agree with then and now, the real data from the L PhIII and the Direct PhI and PhII's will be determinative. IMO NW will still see success with those outcomes.
I always value your opinions, even if negative at the time being, and even if I disagree.
Posters are available on nwbio.com front pg.
I don't see much new news on either, except DCVax-L PhIII psPD arm is 32 patients; IMO fully enrolled (not specified).
Re Direct SAEs, remember that the PhI tested 3 dose levels: 2m, 6m, and 15m DCs/injection. Likely the 1 SAE happened with the 15m dose level. From the MDA site, seems the PhII's will use 2m.
And 1/40 (2.5%) is a much safer SAE profile than either Keytruda or Opdivo.
This (IMO) looks like a typical immunotherapy characteristic: as dose potency is increased, at some point the immune response becomes large enough that SAE consequences become possible. The Duke PhI had this same profile.
Senti, thanks for clearing up the April Call / July Put scenario. I never thought to simply call the Schwab options desk. 'Buy to Open' calls, and "Sell to Open' puts are both bullish plays.
Hi Jeff, the reason for the focus on understanding the analytics is that the FDA/PEI/MHRA are made up of analytic personalities and all use the stat analysis to make the approval decisions.
I agree common sense says DCVax works and works extremely well by historical standards, but the stat analysis must back it up for NW and DCVax to be successful.
IMO any individual stock biotech investor is well served to acquire at least a rudimentary understanding of how the analysis is done (and what the analysis results are for a given treatment) when a BLA/NDA is submitted.
Koman, re your PFS question:
Koman, NW's summary was (from my notes, I think I captured it correctly):
20 ePD: mOS 15.3 mo
1 psPD: mOS 30 mo and counting (still alive)
25 indeterminate: 21.5 mOS
5 unclassified due to missing images
15 are still alive with OS of 26-40 months
Classification was done by an independent image review company
So looks quite good to me. Hope NW publishes the slide deck.
BTW, Note the DCVax-L rGBM AACR Abstract (Liau, Prins, Bosch et al) uses Rano criteria. Perhaps due to the Recist issues discussed over the last several days.
Hi Pyrr, thanks for the Recist 1.1 summary. I was generally aware, but did not realize the 5 tumor aspect.
Curious then that the apparent PhII protocol will be for only 3 tumors. It would seem (IMO) that NW would be wise to either change the protocol to at least 5 tumors injected, or use an inclusion criteria of only 3 measurable tumors allowed in. Perhaps we have not yet seen the final protocol.
A bit more on the Opdivo NSCLC approval. Keep it in mind for upcoming Direct and (later) L data releases.
From the FDA PR:
H2R, yes I put GBM in that category. Further, Sarcoma and pancreatic cancer would also qualify, raising the possibility of an AA for Direct after the PhII's - if the PhII's are large enough. Opdivo and Keytruda each received their first approvals with 21 and 24 responding patients providing the data so hopefully NW designs the trials to produce at least that number.
Hey Mav, just saw your post. I've got many things going on right now so don't have time to read every post.
Re April 7 calls, approx. 25k volume the past week, with OI increasing approx. 3k to 25k. So lots of profit taking on the spike to 7.5+ a few days ago with the 20k+ day, which is smart options behavior, as >100% profit was made from the original big buys in Jan (could have been bought at .2-.25; sold at .6-.7). The 3k increase in OI, though, says that even more new positions were opened. The net net for me on the April options is that they indicate that the March Direct update is expected to be a significant catalyst. If this was not going to be positive news, IMO LP does not mention it at the last conference.
The bigger picture is that the next 12 months should be transformative - if the schedules are met - as we will see Direct data with most patients having received the full regimen, enrollment complete and topline data on L, and the HE program actually rolling with revenue generation. if these data points confirm the earlier results, institutions and the big Inv Bank analysts will come on board in a major way.
Opdivo (BMY PD-1 CI) approved for lung cancer today. Immunotherapies are on a roll - FDA has fundamentally changed from the days of issuing the CRL on Provenge in 2007.
Bodes well for DCVax (IMO).
Very welcome to finally see confirmation of what Luna has been uncovering.
April 7 Call update: today is another large day: 22,000 contracts, with 21,479 OI. We'll see tomorrow how much of this is a net add or if some of the 21,479 are taking profits from buying in past weeks at .2-.3 (today's spread is .5-.6).
Re UCLA, it also could be that a condition Liau insisted on to be PI on the PhIII is to not have a limit on enrollment at UCLA. Or it could be that the UCLA quota is simply quite high given Liau's preeminence with DCVax.
April 7 call update: yesterday was another 10k contract day (10,700 approx.). Today reveals a net gain in OI to ~21,800 contracts from ~15,800 yesterday. So yesterday approx. 8,350 contracts were new positions and 2,350 were exits of previous. Most of the transactions I saw (I can't see all of them without sitting on that screen all day, which I can't do) were at the ask, indicating bullish positions.
Today an additional 2180 contracts traded. The trades I saw were at the ask also; tomorrow's OI will tell the further tale.
Net net (IMO) the bullish expectation for the March updates at the conferences is still building.
Thanks RK. Looks like lots of good data there; I'm starting the digging out process today;)
It would be great if down the road, differential versions of DCVax could be created based on different markers to enhance efficacy for each of the subtypes.
Flip, left you a PM on IV.
Hi RK, yes, it is quite unfortunate. Flip is a passionate and sensitive person. He has gotten fed up and taken a sabbatical previously in the same scenario of trying to address posts from relentlessly negative/attacking people who offer no new or useful information. Hopefully, he will take some time, get back to a good place and come back, as he has much knowledge to contribute on NW.
For myself, I have just put such posters on ignore. Makes for a much more pleasant and efficient experience.
With all the March activity on new information coming out, the large April 7 call open interest that has come into being over the last 6-8 weeks is perhaps not random. Now at 14000+ contracts.
Items of significance I heard:
DCVax-L
- There will be an announcement within 1 month of an 'expansion'; given this gravitas, I would guess that means a 3rd EU country
- HE negotiations expected to last through 1H 2015
- Enrollment completion still expected this year
- 1st interim " " "
DCVax-Direct
- There may be 'news' in late March at a German conference
- PhII dosing will be 'a couple weeks apart'
- the first PhII is expected to start Mar / Apr
~80m shares outstanding
Largely the same slide deck as previously, but with a nice '2015 catalysts slide'
Obuhz, agree that the open label PhI data will be shared freely with BPs in discussing combo trials.
My comment was about when we, the retail shareholders, will see the next data update - this is based on the brouhaha last year orchestrated by AF and participated in by MDA.
Jim, re partnering with BP CI's, it depends upon the terms. It could be that BP pays for the trial, but gets no rights to DCVax.
The negotiation from NW might be something like:
- DCVax is on a path to being SoC for all solid tumor cancers; your CI is not.
- So the benefit is to you more than us.
- So you pay.
In actuality, the benefit to NW is the perception enhancement from the endorsement of BP, which should result in pps trading in a higher range after the announcement, decreasing dilution in all subsequent cap raises.
I could see the possibility of a strategic investment from a BP as the next capital raise (with no product rights) as part of a trial deal; that would boost the pps even more. If I were BP, though, I would want to see the next data update on -Direct before deciding on such an investment / trial deal, so we may not see a joint trial occur (if it does at all) until after ASCO.
Agreed, and wrt PhII's, the treatment regimen will be much faster than the PhI (from LPs latest talk). For a full regimen of 6 doses (remember there is a dose at time=0):
- every 2 weeks is 10 weeks total
- every 3 weeks is 15 weeks total
- first 3 1 week apart then every 2 weeks is 8 weeks.
If enrollment takes 4 months, treatments could be complete in 6-8. If they get started soon, topline data could come in before the DCVax-L PhIII topline.
Well Sid, I guess we'll just have to agree to disagree then. I think the reason was the BSSR outcome; very cut and dried stat calc based on slower event rate and longer accrual than assumed in the initial design.
BTW, I do agree that getting the long tail effect into the outcome analysis is highly desirable, and it is there already in 2 ways (3 if your reasoning is correct), so there would be no need IMO to add events to the endpoint for that:
1. The trial has been going for quite a long time; patients treated since 2007 (when it was a randomized, blinded PhII) are in the data set. This will provide excellent long term data.
2. Part of the data package will be % of patients unevented, and % patients alive at annual boundaries, i.e., % unevented at 1yr, 2yr, 3yr, etc. This will be very revealing of long tail effects, as it was in the PhI's.
Flip, thanks for that FDA doc reference on adaptive trial design. There are several passages directly applicable to the PhIII:
Section: "III.A. Definition and Concept of an Adaptive Design Clinical Trial"
Luna, can you give larger context as to what this is a list of?
The entry does not mention 'lysate', so could be other GBM DC vaccines / could be the total of all GBM-targeted DC vaccines perhaps .... or not.
The definition of status 4 makes it seem it is not DCVax as NW has said the HE is in place from Feb 2014 and now it is reimbursement levels that are in negotiation. Status 4 seems to be before a decision is made and that info is insufficient.
Actually, it was the announcement of the resizing that happened in Aug. The German trial site had 348 shown for many months before that. I and others thought that was clerical error, until some very thorough poster (don't remember who, sorry to say) read the additional detail on that same pg of the new endpoint event numbers, which legitimized the data on the German site for most of us, revealing something was going on.
I would guess the decision to resize was made almost right away from when the BSSR was run (and that was when LP started using the language of 'a strength of the trial design ... etc'), but the announcement was being held off until all regulators had given formal approval. Recall NW only announced when the German site came to light, and the PR said the PEI gave 'preliminary' approval, or some other weasel word, to indicate the process there was not complete at that time.