Replies to post #795634 on NorthWest Biotherapeutics Inc (NWBO)

[dennisdave]

Eh, if that's true, this application should be backlogged and counting against MHRA's performance metrics. We don't see that. That pretty patently disproves this theory. I'm not saying the RFI's aren't complete, but if they are it wasn't "months" ago. Plus if you look at NWBO's own estimations of the process, the Flaskworks unit still shouldn't be ready for approval. We'll find out more on that in the 10Q in 2 weeks, but I don't think that's approvable quite yet.

I think the aspect of Eden/flaskworks manufacturing is well enough decoupled from the MAA. My estimate is they are going to approve the MAA on artisan, then over the next (few?) months, Eden manufacturing will be ready/approved, then the NICE application will be submitted for Eden and not artisan.

Actually, the MHRA backlog metric doesn’t really apply here.
Those performance stats only track standard chemical or biologic applications not complex ATMPs that involve ongoing GMP validation. ATMP reviews routinely fall outside those public “performance metrics” because those metrics measure clock days, and MHRA pauses the clock whenever the sponsor is completing regulatory tasks (like Flaskworks validation data).

So the absence of a “backlogged” entry doesn’t disprove anything, it just means this review remains active with supplementary data pending, which is completely normal for ATMPs.

On the Artisan vs Flaskworks issue:
MHRA could technically approve DCVax-L on the existing manual (Artisan) process first, but that would make little sense operationally. Flaskworks validation was initiated after the MAA submission and has been progressing in parallel under Advent’s GMP license.Once that validation data are ready, it’s far more efficient for MHRA to synchronize the two decisions the MAA for DCVax-L and the separate authorization to use Flaskworks for production rather than approve the manual process first and issue a replacement license a few months later.

The “manual production plans” mentioned in earlier filings are exactly that plans on paper, not real build-outs. They serve as regulatory insurance to keep the MAA technically valid while Flaskworks validation runs in parallel. NWBO never suggested those manual cleanrooms would actually be installed and used long-term; they’re there to satisfy MHRA’s requirement that a fallback process exists on record. The latest 10-Q confirms it:

“Building upon the design and engineering work in preceding months, the Company and Advent developed an improved design and configuration for the simplified Grade C lab. The Company and Advent also negotiated the construction arrangements and undertook preparations to enable construction to begin in the third quarter.”

That reads like paper planning, not physical construction essentially the regulatory equivalent of a “children’s trial” to keep MHRA comfortable that a validated manual option exists, even though Flaskworks will replace it.

NWBO’s 10-K ties it all together:

“Production of the GMP-grade units will be timed to coincide with the timing for build-out of Grade C labs in the Sawston facility. When the GMP-grade units are delivered, Advent BioServices will undertake qualification and validation of those units, conduct engineering runs and collect data, and apply to regulators for approval to use the system to produce DCVax-L for patients.”

That’s exactly what you’d expect if MHRA and NWBO are coordinating a single decision covering both DCVax-L and the new Flaskworks manufacturing platform. If the next 10-Q shows that GMP units are now being qualified or validation runs are underway, it would fit perfectly with an integrated approval timeline not two separate sign-offs.

Just my two cents

[kabunushi]

My thoughts on when they absolutely need to have Eden in commercial production are as follows. I have no idea how Eden might tie in to MAA approval; however, on a business and cash flow basis, if NWBO can max out their current Artisan capacity of ~1000 patients in the first year, that would be a fantastic commercialization success, imo. Even with rGBM greatly increasing the possible patient pool beyond 3500 annual nGBM patients, that might not seem to be a huge penetration of the market; but I think that will be a huge success if they can do close to that in the first year. Some longs might think that NW can go from 0% to filling 100% of artisan capacity in less than a year but I'm guessing that is unrealistic. I'm very open to hearing other opinions if they are backed by reasonable analysis.

If the economics are even close to $100k per customer at 50% GM (both are probably in the ballpark IMO), then given they will have a bit of extra existing and maybe new 3rd party revenue from Advent, and slightly lower costs per patient dose due to absorbing Advent in-house, 1000 customers will get NW to cash flow break even or at least close. To break into much more impressive per share gross profits, they need to treat much more of the total annual UK GBM patient population and/or get approved and get sales going in the EU or in the USA. But IMO doing 1000 patients in the first year would be a blow-out success in every sense. And that means that Eden while might be needed asap for regulator purposes or to put a lower production price tag and/or higher margins, it's hard for me to imagine they absolutely will need Eden to meet the patient demand sooner than 1 year post approval. I will mean huge success with commercialization if they did reach the limit of artisan capacity in that timeframe Admittedly I'm taking a WAG on artisan production cost and the revenue per patient, but I don't think I'm making absurd assumptions of what might be possible in practice. Reaching actual good margins in practice will depend on ramping up the patient numbers, but if once they get to 50-100 patients per month, they should be well beyond making their fixed production costs. That sounds like a heck of lot of patients to get to, starting out from 0; I'm just trying to make a WAG about how soon we can imagine NW exceeding the artisan production limit in actual practice, hence having a timeline to when they might absolutely need to have Eden approved for commercial production.