$NWBO Just another “day in the life” of patients being deprived commercial access to a novel immunotherapy that based on P3 trial results, can save their lives and perhaps extend their lives for 5, 10, 15+ years. What is the sense in assigning a PIM designation if the MHRA and CHM both cannot make an informed decision after almost three years? Seems NWBO’s DCVax-L is being held to an “unprecedented” standard of perfection when it comes to the evidence package. To my knowledge, many evidence packages are not perfect. Everyone talks about the high cost of drugs yet drug development can take years and in the end, the low Phase 1 to approval global success rate is just 8-10%. As we know, all drugs must be both safe and effective for patient use. IMO, DCVAX-L has proven that to-date with a PH3 trial that consumed 15 years from first patient enrolled to publication of PH3 results. Supplemental PSM data only improved the reported results in JAMA and other prestigious medical journals publications etc. Yet, somehow, here we are today. Let’s go, patients whose lives depend on therapies such as this one, deserve better! @FDA @MHRAgovuk

$NWBO Unimaginable to-date for a therapy that was assigned a PIM designation, is non-toxic, based on P3 Clinical trial w/supplemental PSM data determined to be both “safe and effective.” CA could have been granted previously prior to the PSM submission, it was not. xitter.cf/i/trending/21056740936…

$NWBO @MHRAgovuk @FDA So after almost three years, this is where Co-Pilot believes things stand, as of today: Let’s tackle this head‑on — because the way you framed it (“MHRA has overlooked evidence including PSM data… in search of bias or possibly challenging external controls… knowing GBM has had no new approvals in 20–30 years”) is exactly the tension point in this entire 900+ day saga. MHRA did not ignore the PSM — they discounted its weight. This is the key distinction. Regulators rarely “miss” evidence. What they do is downgrade evidence they consider methodologically fragile. For DCVax‑L, MHRA’s internal logic looks like this: PSM improves internal validity, but it does not fix the external control problem. So from MHRA’s perspective: • They saw the PSM • They reviewed the PSM • They understood the PSM • They simply did not treat it as decisive That is not “overlooking.” It’s risk‑averse weighting — especially in a solid tumor with historically noisy survival curves. **Has MHRA “overlooked” evidence? No. Has MHRA “under‑valued” evidence? Absolutely.** The PSM module was not ignored. It was absorbed, reviewed, and downgraded. The JAMA paper was not ignored. It was acknowledged, respected, and treated as supportive, not pivotal. The survival benefit was not ignored. It was recognized, but not accepted as sufficiently reliable without a contemporaneous control arm. This is not negligence. It’s methodological conservatism — arguably outdated, arguably harmful, but not unlawful. --- The real issue: MHRA is applying a 1990s evidentiary standard to a 2020s therapy This is the heart of the problem. DCVax‑L is being judged by: • pre‑Brexit oncology norms • pre‑RWE norms • pre‑external‑control norms • pre‑conditional‑approval norms MHRA has not modernized its oncology framework the way FDA and EMA have begun to. So DCVax‑L is stuck in a legacy review mindset. Bottom line MHRA did not overlook the PSM or other evidence. They saw it, reviewed it, and minimized its regulatory weight because: • external controls make them nervous • GBM variability scares them • crossover complicates interpretation • dendritic cell vaccines are unfamiliar • they fear being the first regulator to approve a GBM therapy in decades • their evidentiary framework is outdated This is structural conservatism, not negligence.

$NWBO While another CHM may be planned, based on some quick research, should only be required if the additional PSM data introduced additional uncertainty. Don’t believe that’s the case and obvi may be needed depending on the actions from a prior meeting. As we approach 1,000 days you might reasonably expect a greater sense of urgency considering patient need with this one but why should we expect that to change now?

$NWBO Since December 20, 2023 to today’s date, 986 days with no decision yet. For comparison purposes, this is enough time to: • Build multiple skyscrapers • Construct major bridges • Bore large municipal tunnels • Complete massive infrastructure projects that transform cities Yet in that same span, a single MAA for a therapy addressing a disease with no meaningful survival improvement in 20–30 years remains under review. BioSpace (per Co-Pilot AI) I don’t want to think about just how many patient lives could have been saved during this timeframe.

$NWBO In case anyone is wondering, the MAA “slow” play continues with no end in site. 974 days, as of August 20, 2026.2 Northwest Biotherapeutics (NWBO) submitted its Marketing Authorization Application (MAA) for DCVax-L (for glioblastoma) to the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) on December 20, 2023. The company announced this the next day (December 21, 2023), stating the application had been submitted the previous day. This date is consistently confirmed in company SEC filings (including 10-Qs and 10-Ks) and multiple reports.3 From December 20, 2023, to August 20, 2026, is exactly 974 days (accounting for the 2024 leap year). The MAA remains under MHRA review as of the latest available updates.

$NWBO per Grok - As of August 12, 2026, it has been 966 days since Northwest Biotherapeutics (NWBO) submitted the Marketing Authorisation Application (MAA) for DCVax-L to the UK MHRA. In oncology, what can reasonably be accomplished within 966 days? In ~966 days (roughly 2 years and 7–8 months), a wide range of meaningful oncology clinical trial work can be completed or substantially advanced. Here are concrete examples and benchmarks: Landmark rapid development example •Osimertinib (Tagrisso) for EGFR T790M-positive NSCLC: First patient dosed in March 2013 → FDA accelerated approval in November 2015. That is approximately 2 years and 8 months (~984 days) from first-in-human dosing to approval. The program included the AURA Phase 1/2 expansion cohorts that generated the response-rate data supporting accelerated approval, plus rapid initiation of the confirmatory Phase 3 (AURA3). This remains one of the fastest modern oncology development timelines from first dose to regulatory approval. Typical and achievable oncology trial timelines within ~966 days •Many Phase 1 and Phase 1/2 trials (dose escalation + expansion cohorts in solid tumors): Frequently complete enrollment, determine the recommended Phase 2 dose, and report preliminary efficacy/safety within 18–30+ months. Median Phase 1 durations in broad datasets are often in the 16–40 month range depending on the indication and design. •Single-arm or randomized Phase 2 trials using objective response rate (ORR), duration of response, or progression-free survival (PFS) as primary endpoints: Commonly finish primary analysis in 2–3 years, especially in molecularly selected populations (e.g., specific driver mutations, MSI-high/dMMR tumors, or rare subtypes). Many basket or precision-oncology Phase 2 studies operate on this cadence. •Portions of larger Phase 3 programs: Enrollment of several hundred patients, interim analyses, and primary PFS readouts are routinely achievable. Full overall-survival (OS) maturity in aggressive diseases often takes longer, but primary endpoint results and regulatory filings based on surrogate endpoints frequently occur inside or near this window. •GBM-specific context: Analyses of glioblastoma trials have shown median durations (start to completion) around 32–40 months for Phase 2 studies and similar or modestly longer for Phase 1 and Phase 3 studies—squarely in the range of (or only modestly beyond) 966 days. What else commonly happens in this timeframe •Multiple sequential or parallel early-phase studies. •Protocol expansions, combination arms, or biomarker-selected cohorts added after initial signals. •Mature follow-up on earlier cohorts (e.g., 2–3 year survival data). •Manufacturing scale-up, process validation, and supporting CMC packages needed for later-stage work or filings. •Generation of peer-reviewed publications and data packages that support regulatory discussions or subsequent trials. Oncology trials (especially those requiring OS endpoints or slow-recruiting populations) can run longer than average, and complexity has trended upward over time. Nevertheless, 966 days is long enough for sponsors to fully execute many early- and mid-stage programs, generate registrational-quality datasets in selected settings, and move candidates meaningfully toward approval—exactly as seen with high-profile examples such as osimertinib. In short: reviewing one complex MAA package is demanding expert work. Running the clinical trials that generate the evidence packages for multiple oncology programmes is a larger, more resource-intensive body of work by almost any practical measure (people involved, patients treated, data generated, operational complexity, and scientific output).

$NWBO Believe it may be time for the MHRA to segregate it’s targeted timeframes when ATMP reviews remain “active” with no end in site. Here’s what Grok had to say. The 150-day pathway still has value as a structured target and accountability mechanism, but its practical credibility is undermined when calendar time routinely stretches to multiples of that figure without transparent intermediate milestones or ready use of conditional tools for clear unmet-need cases. The DCVax-L experience illustrates the gap between advertised ambition and lived reality. What the 150-day pathway actually is Under MHRA’s national assessment procedure for innovative medicines (new active substances and all biologicals/ATMPs), the agency aims for a positive decision within 150 clock-on days if issues are resolved after one consolidated request for information. If outstanding issues remain at Day 150, the target becomes a final decision “as soon as possible” and within 210 clock-on days. Clock-stops for RFIs, major objections, CHM advice, or applicant responses pause the regulatory clock. The pathway is therefore a procedural timetable, not a hard calendar promise. It was designed post-Brexit to signal that the UK would move faster than the old EU centralised process for products addressing serious conditions. In principle this structure is useful: it forces consolidated questions rather than sequential drip-feeding, sets expectations for both sides, and creates a public benchmark against which performance can be judged. For many straightforward innovative products it delivers meaningful acceleration. Where it breaks down in practice For complex ATMPs—especially autologous cell therapies with external-control evidence packages—the clock-on days can become a small fraction of elapsed time. Multiple or lengthy stops for manufacturing consistency, potency assays, residual bias concerns in external controls, or CHM referral are common. When a file has already spent roughly 2.5 years in review (December 2023 submission; still under “initial regulatory review” as of the July 2026 MHRA confirmation), the original 150-day framing starts to look aspirational rather than operational. Critics reasonably ask: if the agency is not prepared to grant even conditional marketing authorisation once safety is clear, a survival benefit has been shown (and reinforced by later IPD/PSM analyses), and the disease is GBM with near-zero effective options, then what residual uncertainty is still being resolved that justifies multi-year delay? Conditional MA exists precisely for situations in which the benefit-risk is positive on the available data and comprehensive confirmation can follow post-approval. Prolonged reluctance to use it, while calendar time accumulates, erodes the claim that the 150-day pathway embodies urgency. Counter-arguments that still carry weight •Not every long review is failure. Novel evidence types (external controls in oncology) and first-in-class manufacturing questions legitimately require deeper scrutiny. Other ATMPs have experienced multi-year calendar reviews under rigorous regulators before approval. •Clock vs calendar is real. Applicant response times, data generation, and iterative clarification contribute to elapsed time. The agency does not control every variable. •Conditional approval is not automatic. MHRA must still conclude that the data already support a positive benefit-risk and that confirmatory studies are feasible. It is not obliged to lower the bar simply because another jurisdiction (e.g., a potential SFDA conditional route) is more flexible. •Removing the target would be worse. Without a published 150/210-day framework there is even less external pressure or internal discipline. The pathway at least creates a measurable standard tha Bottom line Yes, MHRA should retain a fast-track numerical target—otherwise the system defaults to open-ended process.

$NWBO - DCVax‑L is designed to help patients survive. - NWBO is trying to survive long enough to deliver it. Beyond being proven safe and effective in Phase 1-3 Clinical Trials, unmet patient need, MHRA PIM and FDA Orphan Drug Status should have some sort of positive impact on patient lives imo. PSM data improved the reported results in JAMA and submitted as part of its MAA. It’s unimaginable that this MAA is still awaiting a decision within 5 mos of its three year anniversary - initial submission to the MHRA, Dec ‘23.

$NWBO 938 days and counting for NWBO's DCVax-L MAA...

$NWBO For what it's worth - Northwest Biotherapeutics's Newest Presentation Does Not De-Risk The Thesis, But The Story Is Not Over Yet seekingalpha.com/article/492…

$NWBO While we continue to wait, I queried CP AI regarding the evidence package with the NWBO BNOS Presentation and asked "Is the evidence insufficient for conditional approval?" Co Pilot's response - In my view, based on the publicly available evidence and the additional BNOS analyses you uploaded, it would be difficult to argue that the evidence is obviously insufficient for a conditional approval standard. That's different from saying approval is guaranteed. Conditional approval is a lower evidentiary threshold than full approval Regulators generally ask: Is there evidence of efficacy? Is the safety profile acceptable? Is there an unmet medical need? Does the benefit-risk balance appear positive? Can remaining uncertainties be addressed after approval? Glioblastoma clearly qualifies as a severe disease with a major unmet need and limited therapeutic progress over decades. The published Phase III data showed survival improvements and a favorable safety profile. [rollout.com], [rollout.com] What the BNOS deck adds The key criticism of the JAMA publication was the use of external controls. The BNOS presentation reports: Individual patient-level matching from multiple randomized GBM trials. Consistent survival benefits across PSM analyses. Consistent survival benefits across IPW analyses. Sensitivity analyses suggesting substantial hidden confounding would be needed to erase the observed effect. [NWBT-BNOS-...-FINAL-v02 | PDF] The summary slide states that the survival benefit remained between roughly 3.4 and 6.3 months depending on methodology and that results were directionally consistent across approaches. [NWBT-BNOS-...-FINAL-v02 | PDF] If I were a regulator The question would not be: "Is this dataset perfect?" No oncology dataset is. The question would be: "Is the totality of evidence sufficient to conclude the likely benefits outweigh the risks?" For conditional approval, reasonable people could conclude "yes." What would a skeptic still say? They would likely argue: No contemporaneous randomized control arm remains available. PSM and IPW cannot control for unknown variables that were never measured. The new analyses presented at BNOS still need broader peer-reviewed scrutiny. Survival improvements are meaningful but not overwhelmingly large. [NWBT-BNOS-...-FINAL-v02 | PDF], [corporate....nology.com] Those are legitimate scientific critiques. My bottom-line assessment Prior to seeing the BNOS presentation, I would have said: There is evidence supporting conditional approval, but regulators would need to become comfortable with the external-control methodology. After seeing the BNOS slides, I would revise that to: The principal methodological objection has been significantly strengthened against. The new IPD-based analyses make it substantially harder to argue that the observed survival benefit is merely an artifact of bias or confounding. [NWBT-BNOS-...-FINAL-v02 | PDF] So if the question is: "Is there enough evidence for a conditional approval?" My answer would be: Yes, there appears to be a credible scientific case that the evidence reaches a conditional-approval level, particularly given the unmet need, favorable safety profile, statistically significant survival signal, and the new patient-level matching analyses. Whether it reaches the threshold for full approval is the harder regulatory question and one on which reasonable experts may still disagree. [rollout.com], [NWBT-BNOS-...-FINAL-v02 | PDF]