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.

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

@cpamtm LP was asking for 150 days review. I wonder what happened.

$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. --- 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. --- 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. --- 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. --- 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. --- 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.

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.

It seems to me like the MHRA has a lot of red tape, & in my opinion the DCVax works. Patients are dying, & they’re concerned about one form that NWBO didn’t submit in a certain timeframe… It really screams of Big Pharma & possibly Market Manipulation. @TomBaxers @peter_brit @kshaughnessy2 @NorthwestBio @JackAWynn

#dcvax $nwbo #gbm interesting Gemini AI Analysis of DCVax eligibility evaluation: The launch of the MHRA-NICE Aligned Pathway on April 1, 2026, is a highly relevant development for DCVax-L. This pathway is specifically designed to eliminate the "90-day gap" between a drug getting its license and getting NHS funding approval. Based on the criteria and current status of DCVax-L, here is an evaluation of its eligibility: 1. High Eligibility for the "Innovation" Criteria The pathway is intended for medicines that address unmet clinical needs and are transformative. DCVax-L fits these criteria exceptionally well: Unmet Need: Glioblastoma (GBM) has had no major new standard-of-care treatments in nearly two decades. Innovation: As a personalized immunotherapy using a patient’s own dendritic cells, it is exactly the kind of "step-change" technology the government’s 10-Year Health Plan aims to fast-track. 2. Status of the NICE Appraisal (ID836) DCVax-L is already in the NICE system (Project ID836). According to the new pathway rules: Automatic Transition: Since October 2025, topics submitted to NICE for scheduling can follow the aligned pathway. Current Progress: NICE updated the DCVax-L project page as recently as April 2025, indicating the evaluation is "In Progress." Because the appraisal is active but a final decision has not yet been published, it is a prime candidate for this "simultaneous decision" model. 3. Requirements for Eligibility To fully utilize this specific pathway, Northwest Biotherapeutics (NW Bio) would need to meet certain administrative milestones: UK PharmaScan: The manufacturer must have registered the product on UK PharmaScan (the database for upcoming medicines). Early Engagement: The pathway encourages "Integrated Scientific Advice" 2 to 5 years before marketing authorization. While DCVax-L is already in the late stages, the new pathway allows for parallel processing where NICE committee meetings happen in public before the MHRA even grants the license.+1 Simultaneous Publication: If eligible, the goal would be for the MHRA to grant the license and NICE to publish its "Green Light" for NHS funding on the exact same day. 4. Synergy for the Platform Technology If DCVax-L (the "L" for Lysate) is successfully processed through this aligned pathway, it creates a "regulatory blueprint" for the rest of the DCVax platform: DCVax-Direct: Future variations of the platform could use the Integrated Scientific Advice service mentioned in the blog to align trial endpoints with what NICE requires for cost-effectiveness from the start. UK as a Hub: The pathway is part of a broader strategy to make the UK the "most attractive place to invest in life sciences." For a company like NW Bio, which has invested heavily in UK infrastructure (the Sawston facility), this pathway justifies that investment by providing a faster route to revenue. Conclusion Yes, DCVax-L is highly eligible. In fact, it is the exact type of "complex, high-impact" medicine the MHRA-NICE Aligned Pathway was built to handle. The main hurdle is whether the manufacturer has provided enough "timely notification" and data to NICE to keep pace with the MHRA review. If they have, patients could see DCVax-L available on the NHS 3 to 6 months sooner than under the old system. (Gemini AI Analysis)

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.

x.com/joeretired41/s… @alphavestcap

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.

$nwbo @alphavestcap

@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.

@d_stock07734 @FatboyChan74370 Did Citadel help the author write the article.

Big news. Target price $1 within 12 months NWBO😍 markets.ft.com/data/announce/…

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.

$nwbo @alphavestcap @BrianEgolf2 @ATLnsider @SchlangDaddy x.com/Siobhain_Mc/st… $NWBO @MHRAgovuk @wesstreeting @Keir_Starmer @InstituteGC @smith348572: "Dear Dame McDonagh, to be honest, your message really bothers me. Every time a public figure dies from glioblastoma, the same line comes back: “We need to find a cure.” But you have #DCVax right in your backyard, a therapy that saves lives and yet it still isn’t approved. The application is lost in a never-ending regulatory labyrinth. Meanwhile, the 5 year overall survival for the current SOC is about 5%, while the personalized vaccine #DCVax shows ~13% 5-year survival, more than double! And yet the decision keeps dragging on, even for a therapy with virtually no toxicity. Unbelievable. To go further, the UK already has some of the worst survival rates in Europe for brain cancer (See chart). But here’s the real question: why hasn’t the approved #DCVax yet? It has already been over two years under review… At this stage, it’s not #GBM killing patients, it’s bureaucracy."

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 @GoneGoodguy @ThomasOwenMcCa1 Of course not, and what does what I want have to do with the trial design? Also, placebo group in cnacer therapies doesn't mean saline - they just get standard of care, as in case of any cancer trial. External control is not a gold standard, these trials are exceptions

It's only annoying if you are reading "imminent approval" posts and ignoring MHRA's (and #NWBO's) actions. My claim of imminent MHRA approval is based on unassailable FACTS. How/why you find this 'annoying' beats the hell out of me! I am excited to no end! Go $NWBO!!!

@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.

@GoneGoodguy @ThomasOwenMcCa1 The results were superb. So now, think. What might be the problem. It's not novelty of therapy itself. It's flawed trial design that undermines these superb results. The same results with the proper design with placebo group would have gotten us approval 2 years ago

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

@sanderhamburger @Dino3442 @cpamtm The better question: Do you think #NWBO's DCVax will be approved?

@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.

@kshaughnessy2 @metacollectiveG @AllaireMar73316 @biggercapital $NWBO Time will tell but had we known it would take more than 700 days to reach a decision on #DCVAX, I’m not sure the UK would have been the first choice for submission. Considering the Phase 3 results, along with unpublished data from the combination work with Keytruda (see chart below), it’s difficult to understand why a decision would require years rather than months. 1/ Here are the key statistics published in JAMA Oncology. 2/ Newly Diagnosed GBM (nGBM) Median Overall Survival: • 19.3 months (DCVax-L) • 16.5 months (control) ➡️ +2.8 months HR ~0.80 p ~0.002 3/ Long-term survival (where it matters most): • 48 months: 15.7% vs 9.9% • 60 months: 13.0% vs 5.7% ➡️ More than DOUBLE the 5 year survival rate. That’s a meaningful survival tail effect. 4/ MGMT Methylated Subgroup Median OS: • 30.2 months (DCVax-L) • ~21 months (control) Substantial benefit in a key biological subgroup. 5/ Recurrent GBM (rGBM) Median Overall Survival: • 13.2 months (DCVax-L) • 7.8 months (control) ➡️ +5.4 months HR ~0.58 p < 0.001 6/ 24-Month Survival (Recurrent): • 20.7% vs 9.6% Again, more than double. 7/ Safety Profile • No significant systemic toxicity • No cytokine storm • Comparable serious adverse events to standard care Immunotherapy without classic chemo toxicity. 8/ First Phase 3 systemic treatment in 17 years to significantly extend survival in nGBM. First Phase 3 in 27 years to significantly extend survival in rGBM.

I secured a debate on brain tumours, which are the biggest cancer killer of children and adults under 40. 3 years after my sister, Margaret, passed away from a Glioblastoma brain tumour, the search for a cure remains painfully slow. We need a shake-up of the system.

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

@cpamtm The vast majority of those long reviewed applications also have potentially significant long-term risks associated with them. DC-Vax-L does not, since the actual GBM risk is virtually 100% certain death in 5 years. Thus, the logic of long-term analyses for this is ridiculous.

There are a few AI posts more recently with April ‘26. Unfortunately, I cannot repost a link - “The "April 2026" Regulatory Cliff A major factor in the current timing is the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025, which are set to become a legal requirement on April 28, 2026. Synchronization: Regulators and companies are currently in a "transition window." The MHRA is updating its entire approach to how data is validated, specifically shifting toward ICH E6 (R3) standards. These standards emphasize "Quality by Design" and data integrity over the entire trial lifecycle.+1 The RWE Guidance: The MHRA is currently finalizing its refined framework for Real-World Evidence (RWE) and "Rare Therapies," with consultations active in early 2026. Since DCVax-L relied heavily on external control arms (a form of RWE) rather than a concurrent placebo group, the MHRA may be ensuring their decision aligns perfectly with these new, more flexible—but technically rigorous—licensing models.”

@cpamtm Who is posting April?

$NWBO For those now posting April ‘26 for possible approval of DCVax-L, while there are other options available that arguably are more patient focused, the question is “Why hasn’t this pathway been a viable option to-date?” The Medicines and Healthcare products Regulatory Agency (MHRA) in the UK offers several pathways to accelerate access to medicines that address unmet medical needs, particularly for serious, life-threatening, or debilitating conditions. These include schemes like the Early Access to Medicines Scheme (EAMS), Conditional Marketing Authorisation (CMA), Rolling Review, and the Innovative Licensing and Access Pathway (ILAP). The MHRA does not strictly require a fully scaled commercial supply chain (i.e., large-scale, validated commercial manufacturing) at the point of initial approval or early access for these accelerated/unmet needs pathways. Instead, it allows flexibility with interim or development-stage manufacturing arrangements to enable faster patient access, provided quality, safety, and consistency standards are met. Key examples: •Early Access to Medicines Scheme (EAMS): This voluntary scheme provides pre-marketing authorisation access to promising unlicensed medicines for unmet needs. Applicants must demonstrate they can “manufacture, or secure the manufacturing of, the product to a consistent quality standard and in compliance with good manufacturing practice (GMP)”. Supply occurs under schemes like this before full marketing authorisation, often using existing manufacturing licences (e.g., Manufacture/Importation Authorisation (MIA), MIA for Investigational Medicinal Products (MIA(IMP)), or for unlicensed “specials”). This supports interim supply chains, as the medicine is provided free of charge to the NHS during the EAMS period (typically at least 6 months before full authorisation), without needing full commercial-scale production upfront. •Conditional Marketing Authorisation (CMA): For medicines fulfilling unmet needs where comprehensive data aren’t yet complete (but will be soon), the MHRA grants authorisation if the benefit of immediate availability outweighs risks from incomplete data. Manufacturing must comply with GMP and quality standards, but this aligns with accelerated timelines rather than mandating fully scaled commercial supply chains at approval. Post-authorisation commitments (e.g., confirmatory data) apply, and supply can start with validated but not necessarily maximally scaled production. •Rolling Review and Other Accelerated Pathways: These allow modular data submission and faster assessment for innovative medicines with unmet needs. Manufacturing requirements focus on quality assurance and GMP compliance rather than full commercial scale at the outset. In all cases, the emphasis is on ensuring consistent quality and GMP-compliant production to support safe supply, even if it’s not yet at full commercial scale. This enables faster market entry for patients while full validation or scaling occurs (often post-approval via variations or commitments). Full commercial-scale supply chains are typically expected for long-term, post-approval sustainability, but interim arrangements suffice to accelerate initial access in unmet needs scenarios. For official details, refer to MHRA guidance on EAMS and Conditional Marketing Authorisations.

@SportsRadioWIP As a 20 year season ticket holder, good luck in ‘26 with new coaches for the OL, OC and QB. Agree with Slay, “Stoutland was the best coach in the building!” Where is Sirianni’s accountability for the team’s “one and done” playoff run this past season?

Joe DeCamara says losing Jeff Stoutland is a "disaster" for the Eagles: "This is a disaster. And it's a tremendously mismanaged situation. And it's bad leadership...It should not have come to this."

@JohnKincade @Eagles @975TheFanatic Sirianni utlimately needs to be held accountable. If I were Lurie or Roseman, I am doing all I can to keep him. Agree with Slay, "best coach in the building!" @bigplay24slay

The decision to hire Kevin Patullo is like a game of dominos where things continue to fall all off of that one horrendous decision. Much, not all, of this falls at the feet of the Head Coach. Buckle up because I don’t think the ride is getting smoother. @Eagles @975TheFanatic

@RichFairgrieve @Siobhain_Mc @wesstreeting @NIHRresearch @CR_UK @MHRAgovuk At this point, considering it is non-toxic, safe and effective, the silence is deafening. Perhaps just waiting for NWBO to withdrawal its MAA. There has never been a sense of urgency with unmet patient needs in mind, in my opinion.

@Siobhain_Mc @wesstreeting @NIHRresearch @CR_UK And to think the @MHRAgovuk has been in possession of an MAA from $NWBO for $DCVax-L to treat one of the deadliest forms of cancer, GBM, for over 2 years and still hasn't approved it. $DCVax is a safe and effective treatment yet languishes in a government morass. Shameful.

We come 27th out of 29 comparative countries in treatment of Rare Cancers. Just shameful.Thank you to @wesstreeting and team for tackling this shocking situation but questions need to be asked of @NIHRresearch @CR_UK Why have people been let down so badly. How will they change?

You called it John! I was hopeful you were wrong. Felt like the offense would find a way to pull out a win. Obvi, what we saw throughout the season (penalties, ineffective play calling, inability to sustain drives and special teams) is what we saw in the Wildcard game. Not to mention, SF, as depleted as they were, were more intense each and every play.

Jon Ritchie was stunned by the Eagles' last play of the game against the 49ers: "Our coaches, it felt like they just said, 'hey, guys, just go run and get open!' It felt like what I used to do in fourth grade at Hampton Elementary School when I'm playing all-time quarterback out at recess, just go run."

@49ersSportsTalk @RSherman_25 Eagles will show up and win this game. Injuries are part of the game as we know. The Eagles have beaten playoff teams at full strength in the past and have also beaten playoff teams with back ups and won the SB. Go Birds!

Richard Sherman absolutely cooking Eagles fans and giving them a reality check. Appreciate the straight facts, @RSherman_25 🔥 He’s not lying 👀⬇️ #FTTB #49ers