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Https://www.fiercebiotech.com/biotech/roche-bets-700m-upfront-nurixs-late-phase-btk-degrader-set-lilly-showdown

Scancell ran an earlier Phase 1/2 clinical trial of its DNA vaccine SCIB1 alone in resected patients, with 14 out of 16 stage 4 patients (89%) surviving for more than 5 years following vaccination.

This 89% survival rate is significantly better than 5 year survival rate of 52% seen in the nivolumab+ ipilimumab double treatment, as also the 44% / 26% survival rates respectively in the stand-alone nivolumab or ipilimumab treatments.

It is off the shelf immediately available , cheaper etc.

iScib-1 should be even better in resected patients.

iSCIB1+ estimated: $3bn Market (Neoadjuvant/Adjuvant disease) for iSCIB1+ estimated $6-9bn

Https://youtu.be/Dl7nZtPK8e0

Https://x.com/i/status/2061103390562673120

All 8 programs are early-stage therapies based on antibodies, including antibody-drug conjugates (ADCs) and multi-specific antibodies that can engage the immune system

Pfizer will make a $650 million upfront payment and offer up to $9.85 billion in development, regulatory and commercial milestones.

Pfizer will have an exclusive worldwide license to four, while its ownership over the other four will apply only outside the Greater China region. The pharma will be the major funder of all eight programs.

https://www.biospace.com/business/pfizer-bets-up-to-10-5b-in-12-candidate-cancer-collab-with-chinas-innovent?utm_campaign=33719445-2026%20%7C%20Daily%20Social&utm_content=379015240&utm_medium=social&utm_source=twitter&hss_channel=tw-21793154

Plus we may not need all the data;

Pre-Planned Interim Analysis (The "50% Data" Threshold)

For a trial to stop early and seek approval based on partial data, the trial protocol must include a pre-specified interim analysis.

The Mechanism: An Independent Data Monitoring Committee (IDMC) will review unblinded data once a set milestone is reached—typically when 50% of the patient events (progressions) or enrollments have occurred.

The Rule: If the data shows "overwhelming clinical benefit" that surpasses a strict statistical threshold (proving it would be unethical to keep giving the control group the standard treatment), the IDMC can recommend halting the trial early for efficacy.

3. Current Strength of the Data

The likelihood of an early Phase 3 halt is bolstered by its strong Phase 2 SCOPE trial data:

iSCIB1+ combined with standard immunotherapy (ipilimumab/nivolumab) demonstrated a 77% PFS rate at 20 months in target patients.

This represents a massive 34-percentage-point improvement over the historical standard-of-care baseline (43% PFS at 20 months from the CheckMate-067 trial).

If this substantial 30%+ efficacy delta holds up during the interim review of the global Phase 3 trial (expected to initiate in late 2026), iSCIB1+ would be a prime candidate for an early trial stoppage and subsequent rapid FDA approval

NHS Cancer Vaccine Launch Pad (CVLP)

Data from the initiative indicates the CVLP could drastically accelerate standard Phase 3 timelines through several mechanisms:

1. Significant Recruitment Acceleration

Traditional global Phase 3 oncology trials of this scale typically take 2 to 3 years just to complete patient enrollment. However, national figures show that the CVLP/VIP infrastructure has driven a 500% increase in patient recruitment speed across participating trials.

2. High Pre-Screening Efficiency

In early-stage deployments, the Launch Pad seamlessly referred over 550 bowel and skin cancer patients to active vaccine trials in just a matter of months. Because the upcoming iSCIB1+ trial targets specific inherited genetic markers (HLA tissue types) that represent 80% of all melanoma cases, the CVLP’s rapid DNA/RNA screening will allow investigators to identify and register eligible patients immediately upon diagnosis.

3. Proof of Speed in Phase 2

The impact of this framework was already proven during Scancell’s Phase 2 SCOPE trial. While the initial iSCIB1+ cohort (Cohort 3) took roughly 14 months to fully recruit using standard methods, the subsequent Launch Pad-supported cohort (Cohort 4) began dosing in June 2025 and saw significantly compressed enrollment timelines

Australia: Australia is highly competitive for Phase 3 recruitment. Because of its diverse, treatment-naïve population, fast regulatory turnaround (via the TGA), and generous government R&D tax incentives, Australia often achieves faster per-site patient recruitment rates than both the UK and Germany

Germany: As one of Europe's top hubs for clinical trials, Germany is generally faster at site activation than the UK, offering robust trial infrastructure.

United States: The USA leads in clinical trial speed, boasting the fastest median turnaround time

Https://www.linkedin.com/posts/erik-scalfaro_super-proud-to-spotlight-our-collaboration-activity-7401614552758505472-T7eh/

The Regulatory Precedent

Melanoma immunotherapy trials have a history of being stopped early. For example, trials evaluating sequential immunotherapy vs. targeted therapy have been halted ahead of schedule when the survival curves showed definitive, undeniable separation.

Given that iSCIB1+ is tracking a 77% PFS rate at 20 months compared to just 43% for standard care, the margin of improvement is wide enough that an early stoppage for overwhelming efficacy is a distinct possibility if these numbers replicate in the larger Phase 3 cohort

When Could It Happen? (Estimated Timeline)

If Scancell embeds an interim readout for Progression-Free Survival (PFS) into the study design, an early stop would likely fall into the 2027 to 2028 window:

Late 2027 (Earliest Efficacy/Futility Check):

This would occur after a pre-determined percentage of patients (e.g., 50%) are enrolled and monitored for a minimum timeframe. An Independent Data Monitoring Committee (IDMC) looks at unblinded data. If the 30%+ PFS advantage seen in Phase 2 holds up perfectly, the IDMC could recommend halting the trial early due to overwhelming clinical benefit.

2028 (Pre-planned Interim Readout): A typical milestone where interim PFS curves diverge enough to prove statistical significance. If stopped here, Scancell could immediately use the data to trigger its Fast Track Accelerated Approval pathway with the FDA.

The First Primary Endpoint Landmark (PFS Interim Analysis)

The Timing: Likely around 12 to 16 months into the Phase 3 trial.

What Happens: This is the earliest point where the primary endpoint of Progression-Free Survival (PFS) is formally evaluated. An Independent Data Monitoring Committee (IDMC) will review the unblinded data.

Can it stop the trial?

Yes.

If the data mirrors the Phase 2 SCOPE trial—where iSCIB1+ showed a massive 74% to 77% PFS compared to the standard of care's historical ~50%—the statistical significance might cross what is known as an O'Brien-Fleming stopping boundary. If the p-value indicates it is mathematically unethical to keep giving control patients the inferior standard of care, the IDMC will halt the trial early due to "overwhelming efficacy" so all patients can transition to the vaccine.

The Timeline Impact: By doubling the eligible patient pool, clinical trial sites can screen and enroll patients twice as fast. This vastly accelerates the recruitment phase compared to the previous program.

2. The Patient Enrichment Biomarker

The Discovery: During the Phase 2 SCOPE trial, Scancell identified a specific translational selection marker linked to patient response.

The Strategy: The upcoming Phase 3 trial will use this selection biomarker to intentionally enrich the trial pool by pre-screening for patients most likely to respond to the vaccine.

The Timeline Impact: Enrichment drastically reduces statistical noise. Because the drug is concentrated in patients with a higher likelihood of clinical benefit, a smaller overall patient sample size (N) is needed to mathematically prove a 50% improvement over the standard of care. Fewer required patients directly shortens the enrollment timeline.

3. Adaptive Trial Design

The Strategy: The FDA-cleared Investigational New Drug (IND) application utilizes an adaptive trial protocol.

The Timeline Impact: An adaptive approach allows the trial to seamlessly expand or adjust enrollment sizes based on early data looks without needing to stop, close, and restart a brand new trial protocol.

4. Smooth Control Group Transition

The Strategy: Because the standard of care combination (nivolumab plus ipilimumab) captures about 65% to 70% of the market share in the US, the trial mirrors what doctors already prescribe.

The Timeline Impact: Setting the control arm as the exact real-world standard of care makes it highly attractive to oncology sites and patients. Investigators do not have to convince patients to try an obscure control drug, which significantly lowers patient refusal rates during recruitment

Trish described it as a "no-brainer" to join the trial of this drug created by pharmaceutical company Scancell Holdings. She said: "I decided to jump right in, and I'm really pleased I did."

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Her tumour is now half the size it was when Trish started taking the vaccine in September last year. Trish, who has a new grandson, George and another on the way, said: "The progress has been amazing.

"To have this kind of effect over such a short space of time gives you a lot of hope - and hope that this treatment can be there and be even better for people in the future.

"Although I was a nurse, I was community-based so did not get involved with clinical trials. So the whole process has been new to me. But everything was explained so thoroughly and I understood what was going to happen to me.

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"I feel absolutely brilliant – it is the easiest treatment I've ever had. There have been no real side-effects. And this is one of the remarkable things, that it has been a total breeze compared to other cancer treatments, such as chemotherapy and radiotherapy.

"When I was a paediatric nurse, I saw the effects that chemotherapy had on children. To think that this new treatment could become standard is really amazing.

“I don't think I'd been here now if I was not on this clinical trial - I've felt like all the planets aligned for me. The Clatterbridge team have been so supportive. They never make you feel like you have been left alone."

https://liverpoolhealthpartners.org.uk/retired-nurse-given-lifeline-by-clinical-research-trial/

The specific market sizes, commercial positionings, and value drivers for each indication include:

1. Head and Neck Cancer (SCCHN)

Total Market Size: The global Head and Neck Squamous Cell Carcinoma market is projected to reach $8.1 billion by 2031.

The Target Population: Scancell is specifically targeting HPV-negative SCCHN. This represents the majority of head and neck cancer cases, carries a notoriously poor prognosis (median survival of only ~1 year), and responds poorly to standard therapies.

Commercial Positioning: Modi-1 would market itself as an essential first-line combination booster. By increasing the Objective Response Rate (ORR) of standard pembrolizumab from ~19% to 43%, a successful Modi-1 would become the standard-of-care add-on for newly diagnosed patients.

Neoadjuvant Market Expansion: Scancell is also testing Modi-1 in the neoadjuvant setting (given to patients before curative surgery). Success here opens up an entirely new, highly lucrative early-stage market aimed at preventing tumor recurrence rather than just treating advanced disease.

2. Renal Cell Carcinoma (RCC)

Total Market Size: The global Renal Cell Carcinoma (kidney cancer) market is projected to reach $12.7 billion by 2032.

The Target Population: Advanced or metastatic RCC patients. Metastatic RCC has a bleak 5-year survival rate of just 12%, creating an urgent commercial demand for better frontline therapies.

Commercial Positioning: Modi-1 is positioned to be paired with doublet CPI therapy (e.g., combining Opdivo and Yervoy) as a first-line treatment. Because doublet therapy is highly toxic, Modi-1’s exceptionally clean safety profile (no dose-limiting toxicities) gives it a unique market advantage. It can be layered onto aggressive treatments to prevent relapse without adding to the patient's symptom burden.

Strategic and Platform Value to Big Pharma

For an off-the-shelf vaccine platform like Moditope, the true commercial value lies in licensing deals and acquisition potential.

Low Cost of Goods (COGs): Unlike personalized mRNA or CAR-T therapies that must be custom-made for every individual patient, Modi-1 is a standardized, scalable peptide formulation. This gives it very high profit margins.

CPI Combination Synergies: Pharmaceutical giants (like Merck, Bristol Myers Squibb, or AstraZeneca) face massive "patent cliffs" on their multi-billion-dollar CPIs. A successful vaccine that doubles the efficacy of an existing checkpoint inhibitor allows Big Pharma to defend its market share, justify premium pricing, and extend patient treatment durations.

Financially, analysts (such as Trinity Delta) heavily weight Scancell’s risk-adjusted net present value (rNPV) on the clinical progression of these cohorts. Success in SCCHN and RCC validates an "off-the-shelf" (non-personalized) vaccine platform. This drastically reduces manufacturing costs &complexity compared to personalized CAR-T or mRNA therapies, making it a prime, highly valuabl

In the Phase 1/2 ModiFY basket trial, clinical data for the ovarian cancer (HGSOC) and triple-negative breast cancer (TNBC) cohorts differ primarily in their trial designs, clinical settings, and reported milestones:

1. High-Grade Serous Ovarian Carcinoma (HGSOC)

Treatment Regimen: Evaluated strictly as a monotherapy. Because there are currently no approved checkpoint inhibitors (CPIs) for standard-of-care ovarian cancer, patients received Modi-1 on its own.

Patient Status: Fully recruited cohort of 16 patients. All participants had advanced disease, had exhausted standard lines of treatment, and were actively progressing upon trial entry.

Efficacy Results: Demonstrated a 44% Disease Control Rate (DCR) (7 out of 16 patients achieved stable disease). Stability lasted at least 8 weeks, with several patients maintaining disease control for 4 to 6+ months.

Strategic Next Steps: The strong single-agent DCR provides a clinical rationale for moving this cohort into combination therapies with CPIs to turn "stable disease" into active tumor shrinkage.

2. Triple-Negative Breast Cancer (TNBC)

Treatment Regimen: Evaluated as both a monotherapy and in combination with CPIs (like pembrolizumab), depending on the patient's eligibility for standard-of-care checkpoint blockade.

Patient Status: Enrolled as a parallel advanced-stage solid tumor expansion cohort.

Efficacy Results: In the monotherapy dose-expansion phase, early data highlighted prolonged disease control, with Scancell reporting that at least one advanced TNBC patient achieved stable disease extending past the 8-week mark.

Strategic Next Steps: TNBC is a notoriously immunosuppressive ("cold") tumor microenvironment. The focus for this cohort revolves heavily around evaluating Modi-1’s ability to generate cytotoxic CD4 T-cells to enhance the efficacy of checkpoint inhibitors.

Core Metrics Summary

Feature Ovarian Cancer Cohort (HGSOC) Triple-Negative Breast Cancer Cohort (TNBC)

Primary Arm Monotherapy expansion Monotherapy & CPI combination

Cohort Size 16 patients (Fully Recruited) Enrolled in parallel adaptive cohorts

Key Clinical Data 44% DCR (7/16 patients with stable disease) Early data showing stable disease >8 weeks

Safety Profile No dose-limiting toxicities No dose-limiting toxicities

Both cohorts validate that the Moditope platform can successfully trigger an immune response against citrullinated stress proteins (vimentin and enolase) without causing autoimmune toxicity

If successful, Scancell’s Modi-1 would enter two rapidly growing oncology markets with a combined value projected to exceed $20 billion within the next decade. Because Modi-1 acts as a "plug-and-play" combination treatment rather than a standalone replacement, its addressable market is directly tied to expanding and protecting the market share of major blockbuster checkpoint inhibitors (CPIs) like Keytruda.

If successful, Scancell's Modi-1 therapeutic vaccine holds immense clinical and commercial value because it addresses the severe immunosuppressive tumor microenvironments that cause current standard-of-care treatments to fail in head & neck cancer (SCCHN) and renal cell carcinoma (RCC).

Instead of targeting traditional CD8 T-cell pathways, Modi-1 utilizes Scancell's proprietary Moditope platform to stimulate cytotoxic CD4 T-cells. These cells target stress-induced post-translational modifications (specifically citrullinated proteins), effectively stripping away the tumor's natural defenses.

The value profile of Modi-1 in these two specific indications breaks down as follows:

1. Value in Head & Neck Cancer (SCCHN)

Modi-1’s primary value in HPV-negative head and neck squamous cell carcinoma is its ability to more than double the efficacy of standard checkpoint inhibitors (CPIs):

BioIndustry Association | BIA

Clinical Breakthrough: Early Phase 2a data from the ModiFY study demonstrated a 43% Objective Response Rate (ORR) when Modi-1 was combined with pembrolizumab (Keytruda).

Beating the Benchmark: This significantly outperforms historical benchmarks, where pembrolizumab alone achieves only a 19% ORR and nivolumab yields just 13%.

Commercial Appeal: Because it passed its non-futility hurdles (Simon Stage 1), it has massive commercial value as a "plug-and-play" combination booster. It could extend the patent life or market dominance of existing multi-billion-dollar CPI blockbusters by rescuing patients who would otherwise not respond to checkpoint therapy.

Neoadjuvant Potential: Scancell is also exploring its value in the neoadjuvant setting (administered before surgery). If successful, it could trigger early T-cell infiltration to prevent tumor recurrence, opening up a highly lucrative early-stage market.

2. Value in Renal Cell Carcinoma (RCC)

In advanced/unresectable kidney cancer, Modi-1’s value lies in its synergy with double checkpoint inhibitor therapy:

Overcoming Resistance: Advanced RCC is traditionally treated with aggressive double CPI regimens (like ipilimumab plus nivolumab). However, many patients eventually relapse or remain unresponsive. Modi-1 targets citrullinated vimentin and enolase—two stress proteins heavily upregulated in renal tumors.

Clean Safety Margin: A major barrier to combining oncology treatments is toxicity. Modi-1 has consistently shown an exceptionally clean safety and tolerability profile with no dose-limiting toxicities. This allows it to be safely layered on top of intense double-CPI regimens without exacerbating severe side effects.

Out of an estimated 40,000 to 50,000 total advanced, unresectable melanoma cases diagnosed globally each year, only about 25,000 to 30,000 patients have full, reliable access to modern systemic treatments like immunotherapy and targeted therapy.

We will move into adj/neo adj

An estimated 315,000 to 320,000 melanoma patients undergo surgery globally each year.

I thought that too Ray

Looks like the committee members have made calls to their stockbrokers 😂

How impressive is our Phil?

Fantastic

Https://parliamentlive.tv/event/index/bedc34d8-d481-46c3-89c3-5ccd4ff8189c

A phase 3 trial of Regeneron’s LAG-3 inhibitor has missed its primary endpoint, leaving the biopharma reeling from the second failure of a key late-stage program in the past year.

The trial assessed fianlimab in combination with Regeneron’s PD-1 inhibitor Libtayo as a first-line treatment for unresectable locally advanced or metastatic melanoma. Progression-free survival (PFS) on the drug combination was statistically no better than on Merck & Co.’s PD-1 inhibitor Keytruda, causing the trial to miss its primary endpoint.

Median PFS was numerically longer on the fianlimab combination, coming in at 11.5 months on the high dose compared to 6.4 months on Keytruda.

Https://committees.parliament.uk/event/27266/formal-meeting-oral-evidence-session/