cpamtm

Management Consulting and Advisory

[cpamtm @cpamtm]

@975TheFanatic @BillColarulo Totally agree, never saw anything like this at any Philly sports event in 50+ years - Eagles, Flyers, Phillies, Sixers, Union etc. Disgraceful, embarrassing and don’t want to hear about Eagles fans throwing snowballs at Santa in ‘68 anymore!

[cpamtm @cpamtm]

Inexcusable for a product that has demonstrated strong safety and efficacy to-date. While the end to end manufacturing supply chain is critical, unsure why the MHRA could not have made an informed decision six months ago. Those that want to see the company fail can talk about bias or crossover all they want but when you have patients living beyond 5, 10, 15 years, the results speak for themselves.

[cpamtm @cpamtm]

@SouthernDrive21 Thanks for confirming. That’s what I assumed based on the language used. Interestingly, AI wasn’t certain given all of the false narratives out there.

[cpamtm @cpamtm]

@alphavestcap One of the dumbest posts I have seen to-date. Someone let Zadie know, ATMP’s like this one take time.

[cpamtm @cpamtm]

$NWBO While a $1 pt is well above where this one continues to trade due all the negative forces, including the on going litigation, believe it should trade much higher on favorable news.

This is what Grok had to say about atmp buyouts to-date:

Valuations vary widely based on stage (preclinical vs. near-approval), platform tech, and pipeline breadth—often with heavy milestone components. These are primarily for companies/platforms rather than individual assets. For the latest or specific deals, values can include CVRs (contingent value rights) tied to milestones.Major buyouts/acquisitions for CAR-T and related oncology cell/immunotherapies (ATMPs) have been driven by Big Pharma's push into cell and gene therapies, especially autologous CAR-T initially, then shifting toward allogeneic, in vivo, and manufacturing platforms.alacrita.comHere are the most notable deals to date, focused on oncology immunotherapies (primarily CAR-T):Foundational/High-Value CAR-T Acquisitions (2017–2018)
Gilead Sciences acquired Kite Pharma (Yescarta/autologous CD19 CAR-T) for $11.9 billion ($180/share) in 2017. This was a landmark deal establishing commercial CAR-T https://t.co/xWAogKarbc
Celgene acquired Juno Therapeutics (lisocabtagene maraleucel/liso-cel, now Breyanzi) for $9 billion ($87/share) in 2018. BMS later acquired Celgene (~$74B in 2019, incorporating Juno assets).biopharmadive.comThese two deals totaled ~$21B and set early valuation benchmarks for the field.Recent/Platform-Focused Deals (2023–2026)The focus has shifted to in vivo CAR-T, allogeneic platforms, manufacturing improvements, and autoimmune expansions, with many deals including upfront payments + milestones (total potential value shown):
Gilead/Arcellx (anito-cel CAR-T for multiple myeloma): $7.8 billion (2026).biospace.com
Eli Lilly/Kelonia Therapeutics (in vivo CAR-T): up to $7 billion (including $3.25B upfront, 2026).stocktitan.net
AbbVie/Capstan Therapeutics (in vivo targeted LNP for CAR-T/mRNA): up to $2.1 billion (2025).biopharmadive.com
Eli Lilly/Orna Therapeutics (circular RNA-LNP for in vivo CAR-T): up to $2.4 billion (recent).alacrita.com
AstraZeneca/Gracell Biotechnologies (FasTCAR autologous manufacturing platform): up to $1.2 billion (closed 2024).alacrita.com
BMS/Orbital Therapeutics (circular RNA for in vivo CAR-T/immunotherapies): $1.5 billion (2025).pharmaceutical-technology.com
Roche/Poseida Therapeutics (allogeneic CAR-T, e.g., P-BCMA-ALLO1): up to $1.5 billion (~$1B upfront, 2024).linkedin.com
AstraZeneca/EsoBiotec (in vivo CAR-T): up to $1 billion (2025).theguardian.com
Gilead (Kite)/Interius BioTherapeutics (in vivo lentiviral): $350 million (2025).bioinformant.com
BMS/2seventy bio (Abecma CAR-T commercialization/manufacturing): $286 million (2025).regmednet.comOther Notable Mentions
Smaller or manufacturing-focused deals (e.g., Novartis acquisitions of manufacturing sites or partnerships) are often undisclosed or https://t.co/K0QTCL2hYn
Bluebird bio (gene therapy, with some CAR-T overlap historically) was acquired privately for a low ~$29–50 million in 2025 due to financial challenges (far below prior peak valuations).fiercepharma.comTrends: Early ex vivo CAR-T deals commanded massive premiums due to first-mover advantage and approved products. Recent activity (2024–2026) emphasizes in vivo platforms to simplify manufacturing/delivery, allogeneic approaches, and expansion beyond oncology (e.g., autoimmune). Total deal values for in vivo CAR-T platforms exceeded $6–7B in https://t.co/62XTO2RPSL

[cpamtm @cpamtm]

Makes no sense. Container/closure systems and their materials/components must be qualified and controlled through the supplier and pharma manufacturer. Supplier, materials/components must be qualified, receipts must be inspected/sampled/tested and primary packaging subject to leachable and extractable testing/studies. Unless there is a supplier/component quality/performance issue, not sure why the stopper/cover would be a focus.

[cpamtm @cpamtm]

As of May 21st, MAA under review for 883 days since submission or 805 days since validation. Regardless of the reason(s), far too long for patients/families, healthcare professionals, investors etc. imo given the initial DCVax-Direct Phase I started in 2013-2014 and Phase III (enrollment from ~ 2007 onward).

[cpamtm @cpamtm]

$NWBO Another day longer for patients, I asked Grok the greater MHRA concern - DCVAX-L efficacy or manufacturing:

Manufacturing consistency (part of the “quality” pillar in MHRA’s safety/quality/efficacy assessment).86
MHRA is currently reviewing Northwest Biotherapeutics’ Marketing Authorisation Application (MAA) for DCVAX-L (submitted December 2023, with a request for the rapid 150-day pathway for serious unmet needs like glioblastoma). As of late 2025, the agency has publicly confirmed it is actively assessing the application “rapidly for safety, quality, and efficacy” with no backlog issues, but it cannot comment on specifics during review.8662
No public MHRA statement singles out one area as the “greatest” concern (regulators keep application details confidential). However, the nature of DCVAX-L as a personalized autologous dendritic cell ATMP (Advanced Therapy Medicinal Product) makes manufacturing/quality the heavier lift compared with efficacy:
•Efficacy data is already strong and aligned with MHRA’s evolving frameworks. The Phase 3 trial (331 patients) showed statistically significant and clinically meaningful survival extensions vs. matched contemporaneous external controls (published in JAMA Oncology). MHRA has issued guidance supporting real-world data (RWD) and externally controlled arms (ECAs) for rare/unmet-need indications like GBM, and investor/regulatory analyses note this aligns with what NICE and MHRA have accepted previously.3010 There is no indication in public MHRA responses, parliamentary records, or company filings that the clinical data itself is the primary blocker.
•Manufacturing consistency/quality is the well-documented challenge for ATMPs like this. DCVAX-L uses a complex, patient-specific “living” process (leukapheresis + autologous tumor lysate-loaded dendritic cells, produced in ~8 days per batch with strict GMP, comparability, and release testing). For biologics/cell therapies, “the process is the product”—reproducibility, comparability, and control of individualized batches are core to the quality dossier. MHRA requires detailed GMP inspections of facilities, processes, quality systems, and validation as a prerequisite for MA.896
◦MHRA granted (and has renewed/expanded) GMP/Manufacturing and Import Authorisation (MIA) licenses for the key Sawston (Advent BioServices) UK facility specifically for DCVAX-L cell therapy production.187
◦Delays in ATMP reviews frequently stem from CMC (Chemistry, Manufacturing, and Controls) questions, comparability data, and manufacturing inspections—exactly as seen with other complex therapies (e.g., a BioMarin hemophilia A gene therapy faced a 180-day clock stop on manufacturing consistency; similar patterns appear in MHRA ATMP timelines).4885
◦Investor and analyst discussions consistently flag manufacturing comparability and decentralized/point-of-care scaling (e.g., via automated systems) as the key ongoing focus area for this personalized product.85
In short, the clinical efficacy evidence enabled the MAA submission and is being reviewed under modernized ECA/RWD pathways, while the personalized manufacturing process triggers the most intensive scrutiny, inspections, and potential clock stops typical of ATMPs. This is why manufacturing consistency is MHRA’s greatest (practical) concern for DCVAX-L approval. The review remains ongoing with no rejection or major efficacy red flags reported.

[cpamtm @cpamtm]

@patrickwalsh14 IDK but to think LP’s 150 day request is now 800+ days later, obvi processes are broken.

[cpamtm @cpamtm]

$NWBO

Per Co-Pilot AI when asked “What is the longest MHRA MAA review and approval ever?”

Here’s the clearest, evidence‑based answer you can get from public regulatory history — and it’s actually pretty fascinating.

There is no single officially published “record holder,” because MHRA does not maintain a public leaderboard of longest assessments. But we can answer this by looking at:

• Statutory timelines
• Historical outliers
• Known cases where reviews stretched far beyond the norm
• First‑in‑class or highly complex products that required multiple CHM cycles

And when you put those together, a pattern emerges.

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MHRA statutory timelines vs. real-world extremes

Standard statutory limit:

• 210 days for a national UK marketing authorisation (excluding clock stops) RAPS
• 150 days for priority or high‑quality dossiers (target, not guaranteed) RAPS

But these clocks stop during RFIs, company responses, CHM re‑reviews, and major scientific issues. That’s where extreme cases arise.

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Documented long-duration MHRA reviews (multi‑year)

While MHRA doesn’t publish a “longest ever,” several categories of products have historically taken 2–4+ years from initial submission to approval due to scientific complexity, manufacturing issues, or repeated CHM cycles.

1. Advanced Therapy Medicinal Products (ATMPs)

Cell therapies, gene therapies, and autologous products often undergo:

• Multiple rounds of RFIs
• Manufacturing comparability reviews
• CHM re‑referrals
• Benefit–risk reassessments

Several ATMPs in the 2010s–2020s took 3–4 years from initial submission to final approval (publicly traceable through EMA-era UK participation and MHRA post‑Brexit national procedures).

2. Oncology products with novel mechanisms

Historically, some oncology submissions required 2–3 CHM meetings, stretching total review time to 2–3 years.

3. Products requiring major manufacturing remediation

When MHRA identifies CMC or GMP deficiencies, the review can extend well beyond 2 years.

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So what’s the longest?

Based on all publicly traceable cases:

The longest MHRA review durations on record fall in the ~3–4 year range.

These involve:

• ATMPs
• First‑in‑class immunotherapies
• Products requiring multiple CHM cycles
• Applications paused for major CMC remediation

There are no publicly documented MHRA approvals exceeding ~4 years from initial submission to final authorisation.

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Where does DCVax‑L fit in this context?

You’ve been tracking this closely, so here’s the strategic interpretation:

• DCVax‑L is a first‑in‑class autologous dendritic cell therapy
• It is exactly the type of product that historically falls into the longest MHRA review category
• A 2‑year review is not unusual for ATMPs
• Several ATMPs have taken longer (3–4 years) before approval
• There is no signal of refusal or appeal (which would be public)

So DCVax‑L is not approaching any historical “limit.”
It is still well within the range of long but normal ATMP review timelines.

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Bottom line

The longest MHRA drug reviews ever documented are ~3–4 years, almost always involving complex ATMPs or first‑in‑class oncology products requiring multiple CHM cycles.

A 2‑year review is not unprecedented, not a negative signal, and not outside MHRA norms for this class of therapy.

[cpamtm @cpamtm]

For as long as NWBO’s MAA has been under MHRA review, while it’s great to know the processes will now be aligned for the MHRA and NICE to work more closely together (perhaps should have been done long ago), the reality is that NWBO’s patients continue their journey 835 days since submission, without a formal DCVax-L decision (proven to be non-toxic, safe and effective), as of today. This wasn’t exactly what LP expected when deciding to submit to the UK first.

[cpamtm @cpamtm]

Assuming a CMA is the most likely favorable decision, as this MAA seems to drag on endlessly, the question will be why couldn't they have issued a CMA a year ago? Obvi, safety and efficacy front and center but for a product that is non-toxic and has had success extending lives, the risk/benefit shouldn't have changed.

[cpamtm @cpamtm]

FB research may be comprehensive but the price target of $1 appears to be nothing more than a placeholder imo. If MHRA issues a positive decision in the very near future, it would be expected that other markets will soon follow given GBM patient needs. Should DCVax-L become more of a platform for all solids tumors, coupled with urgency to cover synthetic positions, safe to say the PPS should be well above $1/ps. Shorts have “unlimited” loss potential which often times gets overlooked.

[cpamtm @cpamtm]

@patrickwalsh14 @d_stock07734 @FatboyChan74370 Authored by someone who is obviously grossly disconnected from the history of the company, trial results / potential of the product pipeline and the possible significant counterfeit share position that may exist as a result of many years of off the radar activity.

[cpamtm @cpamtm]

So true, based on the trial results - DCVax-L has been proven to be safe, effective and non-toxic. Based on the results alone, it is proven to work based on OS results regardless of the comparative data used and the inherent bias that may or may not exist. MHRA has most likely scrutinized the external control design so perhaps manufacturing still a work in process. Who knows?Although AI notes for ATMP’s with manufacturing innovation (CAR-T, gene therapies and complex cell therapies), 15-30 mos to decision.

[cpamtm @cpamtm]

The SAP and endpoints were prespecified and submitted to regulators before unblinding, if your issue is with the placebo arm only receiving SOC + placebo until recurrence to allow DVax-L to extend patient lives, external controls were accepted by MHRA for DCVax-L whether you or others have an issue with it.

[cpamtm @cpamtm]

@WojciechSmann2 @GoneGoodguy @ThomasOwenMcCa1 Times have changed, would you want to be in that placebo group if your life depended on it? I will answer for you. “Not a chance!” Stop with the nonsense, DCVAX-L is safe, effective and non-toxic based on the trial results. End of story.

[cpamtm @cpamtm]

@whiddFD03 @sanderhamburger @Dino3442 Don't think it's "if", simply a question as to "when".

[cpamtm @cpamtm]

@smith348572 @Siobhain_Mc @kshaughnessy2 @metacollectiveG @AllaireMar73316 @biggercapital Agree, UK MHRA MAA would not have been NWBO's first choice for submission. At the time, it was believed an expedited review and approval might be possible.

[cpamtm @cpamtm]

@TerryRo84010346 Agree, I have addressed exactly this point in the past. Yet, for some reason, NWBO/GBM patients still awaiting approval +2yrs later.