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More likely contingent on what (if any) information is requested by MHRA after the first phase. This will give any good RA department the likelihood of approval IMO.
I know it's not apples to apples, but the FDA eSTAR submission process has evolved a bunch even in the last two years. They've gotten to the point where the system asks questions and you select answers via drop down menus which guide you to other short answer questions and where to upload files. As you complete sections, the fields, they turn from red to green on the left side of the page. (This is a much longer and involved process than I'm describing but essentially the same red to green principals apply) Once everything is green, you hit submit and as long as they have your money, they send confirmation of receipt. Just two years ago, the system was subtly different, where someone would have to physically check that all fields were present and you completed your check list. That took about a week or two. Maybe the MHRA system is similar?
Per the guidance, once the clock starts (Validation or "Acceptance") Assessment phase I will be completed within 80 days. During this period, eligibility for grant of orphan status is also determined. If there are issues requiring clarification (RFI), the clock turns off and RFI should be address within 60 days. NWBO can request an extension of an additional 60 days, but these are granted only for exceptions (not common).
Once RFI is addressed and sent to MHRA, clock turns back on and they have 70 days to provide a decision on approvability.
Max time: 80-Phase I+60-RFI+60-RFI Extension+70 = 270 days - > September 30th approval
Min time: Either no RFI (improbable) or RFI for simple things -> Approval a few weeks after CHM meeting scheduled for March 21 & March 22.
I think there is a possibility that we are approved by MHRA by the end of March, early April. The MHRA knows the treatment well, has been through the manufacturing facility several times, and the safety profile of the treatment has an excellent benefit/risk profile.
If NWBO has had a QSub meeting with the FDA (which they've most certainly had by now) and the FDA has recommended additional trials, that would be material, no? I'm not buying the political influence excuse. Maybe 10 years ago, but not anymore, as the FDA is now 65 percent funded by user fees, vs around 10 percent funded by user fees 10 years ago (see below).
I think they either think that a lucrative deal awaits (or was loosely inked) upon approval anywhere, or they are using one of the collaborative pathways that hits multiple RAs using minimal effort (UK, Canada, Australia, etc.) The UK seems to be the path of least resistance to get a foot in the door, especially if they approve while the FDA has a BLA on their desk under review.
https://www.google.com/url?sa=t&source=web&rct=j&opi=89978449&url=https://crsreports.congress.gov/product/pdf/R/R44576%23:~:text%3DThe%2520FY2022%252Denacted%2520appropriation%2520provides,%25242.881%2520billion%2520in%2520user%2520fees.&ved=2ahUKEwi3hNCJxqCDAxUVFjQIHSQGAq8Q5YIJegQIJBAA&usg=AOvVaw1iiEPWg-gI-TwBXLG0In5p
Gary -
Can we do this again for 2024? Like mid year estimate?
Thanks!
We won't go until we get some!
Figgy pudding
At least. Her and les share 98 million that are part of the blocker letter. She additionally has 173 million options, also part of the blocker.
Not selling
The million pages was just the clinical master file (and is continuing to grow because patients are still living). They do not have to submit it, just make sure it is in auditable shape if anyone cares to inspect it. I don't think a submission of 700k+ pages is unheard of for something like this though. It is all electronically filed and can be put together over time before submission. They would essentially fill out forms within the system (application and discussion) and attach supplemental information where necessary (i.e. reports, risk documentation, label drafts, etc.).
Les suggested something like 26 modules were being prepared on the big biz show, whereas, UK only has 6 or so (i could be off in this). The theory was the 26 modules could be the separate packages for multiple jurisdictions.
It was also discussed that his reference to the 26 modules could have meant sub modules, or subsections within each module.
X posted on reddit:
Within the guidance, they say that the company "should tell us the intended date of submission of the dossier". The press release states that NWBO completed the prerequisite of the "required formal notification to the MHRA of the upcoming MAA".
This suggests to me that NWBO and MHRA both know the date of dossier submission. Here are some scenarios with my opinion of likelihood of each:
1. They've submitted and are waiting until day 45 to announce, just in case they get acceptance or expect to get acceptance. (20%)
2. They've submitted and are timing announcement with something else (partnership, flaskworks, manufacturing expansion) (15%)
3. They communicated the 45 day date to MHRA and are bound to the date or it just took that long. (60%)
4. The application was not accepted or they ran into an issue submitting and will be late. (5%)
Another scenario that I would place low likelihood:
5. Access consortium where they simultaneously apply to UK, Australia, Canada, Singapore and/or Switzerland. The guidance suggests that the simultaneous applications go out within a 2 week period, which may explain the time window given by NWBO when the submission date would otherwise have already been chosen.
Are all briefs written in such a pompous and condescending tone? I've scanned through the latest and am amazed that this is how the defense wants to convey their position. (I come from the science and engineering world)
"The Company believes that it has now completed all of the remaining prerequisites for such an application, including certain steps related to implementation of the approved Pediatric Investigation Plan and submission of the required formal notification to the MHRA of the upcoming MAA".
According to the guidance
"We recommend you email AcceleratedandRollingReview@mhra.gov.uk before you intend to submit an application. You should tell us the intended date of submission of the dossier and whether the MAA is to be submitted to UK, Great Britain (England, Scotland and Wales) only, or Northern Ireland only".
Therefore, both NWBO and MHRA knows the date of submission. I am OK with that.
LP said herself that most of the documents (Master Trial Data) only needs to be inspection ready. They would not need to submit the data, only have it ready if a regulator needs to examine a part of it.
With the electronic submission options that MHRA and FDA uses, the actual uploading of data is really quite simple compared to how it was done in the past. To be clear: they are not uploading 1.7m pages anywhere.
Looks like the FUD argument that LL is distancing herself from NWBO is now dispelled. Are there even any more FUD arguments left at this point?
Here are my thoughts based on today's PR.
This was an important element: "The Company believes that it has now completed all of the remaining prerequisites for such an application, including certain steps related to implementation of the approved Pediatric Investigation Plan and submission of the required formal notification to the MHRA of the upcoming MAA".
According to the guidance
"We recommend you email AcceleratedandRollingReview@mhra.gov.uk before you intend to submit an application. You should tell us the intended date of submission of the dossier and whether the MAA is to be submitted to UK, Great Britain (England, Scotland and Wales) only, or Northern Ireland only".
Therefore, both NWBO and MHRA knows the date of submission. It would be silly if they didn't make the September 25th deadline.
Within 80 days from submission acceptance (also loosely coinciding with the December 21/22 meeting) they could be issued a request for further information, or they could approve.
Additional information would be gathered in a 60 day clock off period, followed by the 70 day remainder for final approval.
That means there still is a decent probability of approval by the end of the year. If not, a decision would likely be in by the end of April if no extension is requested by NWBO to respond to the RFI.
I feel like I'm watching an episode of Scooby Doo.
They weren't as of June 30. We don't know if they have since completed the work.
I'm guessing it's non- dilutive finding contingent on monetary settlement of the lawsuit. Not sure about what happens if the case is dismissed.
They mentioned it I think...
Since there are still patients living, the master file continues to be updated.
I knew it was part of the strategy for 2023, but first time seeing it in a q.
On another note, are all of those gain contingencies set up around the lawsuit? I hadn't seen that in previous q's either.
"The Company is in active discussions in regard to certain combination treatment regimens, and is planning for certain strategic trials with such combination treatments."
Silver lining
From LP's AOL account. Just gotta remember where the floppy disk is. Hey, maybe that's the hold up!
My theory FWIW is that they are double checking for consistency across modules, as they likely had multiple consultant groups working on various parts of the overall package. Fringe theory is that they had different groups working on modules pertaining to different regulatory bodies, which comes from LG's big biz talk a few weeks ago. We do know he likes to embellish where they are at though.
Being someone who has interacted with the FDA and OUS regulatory bodies, and has aided in the preparation of these types of documents (albeit on the device side), they have exceeded my maximum estimate for how long it should take to submit. That being said, if they are trying to get through without any further requests for information or questions, it does take time to make it perfect. You never know what a reviewer will cling to as far as inconsistency, omissions or errors. Taking the extra time now would be paid in spades if the submission(s) cruise through without any additional requests.
All IMHO
My TD account got converted to Schwab over memorial day (Midwest region). The Schwab app does not have level 2. I have been disappointed, to say the least, in the conversion.
They do have a professional app that has additional functionality, and may be offering think or swim in the future. If I had the time I would switch broker's.
Thanks ATL for the info.
I don't doubt they could easily get the data and even use it in a submission if they wanted to. I would just assume that a deal would be in place prior to using in a submission if their expectation was to combine it with someone else's drug.
For the record, I do hope that you are correct, and they include combo data in submissions, but my impression has been that this workstream will occur (not begin) once the first round of submission(s) have gone out.
Trial Master File + Case Report Forms + Batch Manufacturing Records = ~1M Pages + Rest of Application Package(s)? Not sure it would add up to 1.7M, but its a lot of information.
Remember, the MIA was not delayed due to flaws in the submission. It was because they added scope to the submission.
The issue I see is that NWBO is not a sponsor of the trial, therefore, the data is not theirs. In order for them to be able to use the data, there would have to be a deal of some sort for them to be able to use the data in any marketing application.
I think the simplest explanation is that they are moving forward with the phase 3 data as is, and will use the phase 2 combo data to form partnerships in the future (as LP stated in the ASM).
I also do know from talking with the company that they are not formulating marketing application(s) in a vacuum, and the consultants they are using to prepare and submit are in constant communication with regulatory authorities. They will include with any submission what is needed to get the product to market fastest (i.e. reducing review time by making sure everything submitted is perfect).
Smitty -
Have you seen transactions that were not held in escrow? It appears the $3M is already in NWBO's coffers.
If they received this as a result of a LOI or JDA, do you know what the disclosure rules are or do they not need to disclose until a material agreement is signed?
Yeah, we really should be listening to the poly sci major.
The beatings will continue until morale improves.
-Management
Hey I agree with you man. I was just trying to emphasize that even if she did say 1.5M (which she didn't) the verification process of documents should have been done mid March.
Moot point.
It's been 149 business days since mid September. Even at 12k pages per day they should have processed 1.788M pages. They should be done with that work stream and be putting the finishing touches on the package for submission, if they haven't submitted already.
And just the work that we did, for example, from mid-September to the first week of December this fall, while everything else was going on that you already know, we went through a process of scanning and processing close to 0.5 million pages of trial master file, 12,000 to 15,000 pages a day for months. right? That's the scale of what's involved in putting this together.
From ASM-
So there's a trial master file. And there are case report forms that contain the patient data. There are batch manufacturing records from each individual product that's been manufactured. Overall, the documents could be in the range of 1 million pages. And these pages have to be gone through by humans and they have to be checked and checked for any gaps, inconsistencies, anything so that this body of documents, some of which will go in the application package and some of which will be supportive and have to be inspection-ready, all have to be up to snuff and pass muster with inspection by regulators.
Thanks!
I was referring to this article that I don't have access too to see why they are referencing the jama article (#63).
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00005-0/fulltext#back-bib63
The JAMA article is also listed in the references, as well as the Wick and Van den Bent retort. I do not have access to the full article.
The update to their website also happens to be 90 days ago. Coincidentally, that is the recommended timing around planning a pre-submission meeting with MHRA and NICE before submission.
That could be, however, one would think they would time the PR for website release. If there isn't a PR tonight, I am hopeful for something big tomorrow at open.
What's more interesting to me is that the MHRA website is providing the update. For the clinical manufacturing approval, the company issued the PR on December 21st, 2021 and the website wasn't updated until February 21, 2022. Obviously, that timing doesn't make sense here, but the point being that it would be impossible that the company did not have the MIA approval information several days ago, yet no PR. I wonder what they are waiting for?