Cizzle Biotech

We're in the endgame now.

Good Morning Team.

I’ve been invested in Cizzle Biotechnology Holdings for years. Unlike many of my investments, I haven’t spoken too much about it.

Why?

Because until they could long-run patent, manufacture and sell their early-stage lung cancer test, the entire thesis lived in the land of theory, both in terms of financial and life-saving returns.

Well guess what?

We’re there.

Let’s dive in.

I’m going to assume readers know nothing - so those of you familiar with the basics, bear with me.

Cizzle is a UK-based diagnostics developer with a single, highly focused mission: to bring the world’s first blood-based single biomarker test for early-stage lung cancer to the global market.

The company has spent years transitioning from pure research and development into a commercial-stage business.

Days ago, it crossed what may prove to be the most consequential threshold in its history - the beginning of clinical use for the CIZ1B biomarker test in the United States.

For context, this milestone signifies that the test is authorised for use within a CLIA and COLA accredited laboratory (it’s important to distinguish this from FDA pre-market approval, which is not applicable to the lab-developed test).

This achievement marks the formal start of the company's commercial operations, providing a regulated, validated pathway to deliver this diagnostic technology to healthcare providers and their patients.

With a current market capitalisation of approximately £10 million, Cizzle is priced as a small, speculative biotech. The market does not yet understand that the company is no longer speculative in the conventional sense.

It has a commercially validated test, a federally approved lab route to market in the world’s largest healthcare economy, guaranteed contractual royalty revenues already flowing, a clinical partnership with one of America’s top cancer centres, a letter of intent with an NHS partner, granted patents in the US, Canada and Europe, and a licensing structure that means Cizzle takes no operational risk for the US rollout whatsoever.

But before we get to that, let’s rewind.

Why early stage lung cancer detection matters

Lung cancer is the leading cause of cancer-related death worldwide, and by a significant margin.

It kills more people each year than breast, prostate and colorectal cancers combined. In the United States alone, more than 234,000 new cases are diagnosed annually. Globally that figure exceeds 2.2 million.

The disease accounts for roughly 5,000 deaths every single day.

The reason lung cancer is so lethal is not because it is biologically more aggressive than other cancers, though it can be.

The core problem is detection timing.

Because the disease typically produces no symptoms until it’s advanced, the overwhelming majority of patients — around 75% globally — are diagnosed at a late stage when curative treatment is no longer possible.

At that point, five-year survival rates can be as low as 10%. Contrast that with Stage I detection, where five-year survival can reach 90%.

The difference between catching this disease early and catching it late is, undeniably, the difference between life and death.

Sadly, the lion’s share of investor attention for oncology work lies in clinical trials for late-stage cancers. There’s a certain joy to be found in bringing hope to the hopeless - but in mathematical terms, early-stage prevention does more good overall.

And is more profitable.

The existing gold standard for lung cancer screening in the United States and United Kingdom is the low-dose CT scan, known as LDCT. The US Preventive Services Task Force (USPSTF) now recommends annual LDCT screening for approximately 14.5 million Americans — adults aged 50 to 80 with a history of smoking.

This was an 81% expansion of the eligible population when updated guidelines came into force in 2021. But there’s a big problem.

Uptake.

Despite these guidelines, and despite insurance coverage for the scan being mandated, actual screening rates remain critically low. Depending on the study, fewer than 6% of eligible Americans are getting screened, with some data points from major health systems showing annual completion rates below 1%.

The barriers are numerous — awareness, access, convenience, physician inertia and patient anxiety about radiation — but the outcome is the same: millions of at-risk people are not being screened, and thousands who could be saved not being diagnosed in time.

This is both awful in terms of human cost, but also very expensive for insurers who are shelling out for later-stage treatments. Inevitably, that additional cost is passed on to the general population’s insurance premiums (and in the case of the UK, your tax bill. The NHS is taxpayer-funded, not free).

The LDCT scan itself carries a further problem - a high false positive rate. Studies have shown that CT scanning in lung cancer produces false positive results (findings that look suspicious but turn out not to be cancer) at a rate that even approaches 90% of flagged scans in some series.

This generates a significant downstream burden, and also goes some way to explaining patient reticence.

Patients undergo unnecessary invasive procedures, experience significant anxiety, consume clinical resources and are exposed to further radiation.

For reference, most people have some kind of benign growth somewhere in their body.

Any tool that can symbiotically complement LDCT by either helping identify patients who warrant a scan or, crucially, by clarifying whether a suspicious nodule found on scan represents cancer or a benign tumour, has enormous clinical and economic value.

There is currently no approved blood-based biomarker test available within the NHS, and no widely adopted blood test available in the US, for diagnosing early-stage lung cancer.

This is the unmet clinical need that Cizzle Biotechnology exists to address.

What is CIZ1B and what does it do?

The CIZ1B biomarker test is the product of more than two decades of academic research led by Professor Dawn Coverley and her team at the University of York.

Coverley is a world-leading expert on the CIZ1 protein — a naturally occurring cell nuclear protein involved in the preservation of DNA and the stabilisation of epigenetic patterns in normal cells and tissues.

Her research established that CIZ1 normally functions as part of the nuclear structures that dampen the expression of certain genes.

When CIZ1 is altered or absent, cells lose this control, becoming epigenetically unstable (the cell’s gene regulatory mechanisms are disrupted without altering the underlying DNA sequence itself), and this instability is strongly linked with the early stages of cancer.

The key discovery, published in the Proceedings of the National Academy of Sciences in 2012, was that a specific variant of the CIZ1 protein — called CIZ1B — is produced by lung cancer cells and released into the bloodstream, where it can be detected even in patients with early-stage tumours that would not yet be identifiable by symptoms.

Even where an LDCT might not spot it.

What makes CIZ1B particularly useful as a diagnostic target is the mechanism by which it survives in the blood.

CIZ1B lacks a small segment present in the parent CIZ1 protein, which creates a unique epitope (molecular fingerprint) that’s specific to the variant.

Critically, once in the bloodstream, CIZ1B binds to fibrinogen, a protein involved in blood clotting. This fibrinogen effectively acts as a protective carrier, stabilising CIZ1B in plasma and allowing it to be measured at detectable concentrations even when the underlying tumour is small.

Let’s fast-forward a little.

In 2024, Cizzle finally succeeded in producing proprietary monoclonal antibodies that specifically recognise CIZ1B in blood plasma.

These antibodies are manufactured to ISO 13485 standards by BBI Solutions, the world’s largest independent producer of immunodiagnostic reagents.

The commercial test format is a fibrinogen-capture sandwich ELISA — enzyme-linked immunosorbent assay — a tried and tested laboratory method that can be run on equipment already present in most hospitals and labs.

This is mission critical because it means that the test doesn’t require specialist machinery or new capital investment from laboratory partners.

It slots into existing workflows. Patients have no problem with a blood test - especially when they’re being drawn from anyway.

Which makes it easy (read not expensive) to adopt.

The clinical performance data published to date is compelling.

Extensive earlier studies using the initial research version of the assay demonstrated an impressive 95% sensitivity for Stage I lung cancer detection and a 96% negative predictive value, but these results were merely the foundation.

Having now achieved the crucial regulatory milestone of clinical availability for its validated commercial assay, Cizzle is moving swiftly to build a comprehensive real-world dataset.

It appears confident that the high performance metrics established during the development phase will serve as the benchmark for the clinical value the CIZ1B test will deliver as an essential adjunctive tool in the fight against lung cancer.

For context, a 96% negative predictive value means that if the test is negative, a patient has a 96% probability of not having early-stage lung cancer — an important reassurance tool for stratifying patients presenting with indeterminate CT findings.

A 95% sensitivity for Stage I disease is exceptional, given that this is the stage at which other detection methods most commonly fail.

Crucially, CIZ1B takes a fundamentally different approach from multi-cancer early detection tests such as those being developed or commercialised by Illumina’s Grail (Galleri) or Guardant Health.

Those tests work by detecting circulating tumour DNA bearing mutation or methylation signals. CIZ1B detects a stable tumour-associated protein biomarker.

This protein-based approach offers distinct advantages:

1. Proteins are typically more stable in blood than ctDNA.

2. The test doesn’t require next-generation sequencing equipment.

3. The cost structure is substantially lower.

4. Cizzle’s test uses ELISA technology available in virtually every hospital laboratory on earth. The potential for global scalability, including in lower-resource settings, is therefore significantly greater than for DNA-based alternatives.

Recent commercial history

Take a moment to consider a chronological account of the milestones that have brought the company to commercial launch.

The foundations were laid over two decades at the University of York, supported by grant funding from Yorkshire Cancer Research and other UK research bodies.

The company was incorporated by Professor Coverley in 2005 and floated on the London Stock Exchange Main Market in May 2021.

In the years following the IPO the company focused on developing its proprietary monoclonal antibodies, validating the assay format and building international partnerships.

A commercial agreement for China was executed in early 2022 with the International Co-Innovation Centre for Advanced Medical Technology, providing a 10% royalty on Chinese sales.

The pace of development accelerated materially in 2024.

In July 2024 Cizzle signed a manufacturing agreement with BBI Solutions for its first order of commercial-grade proprietary monoclonal antibodies — to support up to 5,000 assays — manufactured in ISO 13485-certified facilities.

This was the critical industrial step that transformed the test from a research-grade assay into a product ready for commercial deployment.

In September 2024 Cizzle announced a collaboration with the Moffitt Cancer Center in Florida — the only National Cancer Institute-designated Comprehensive Cancer Centre in Florida and the best cancer hospital in the south-east United States — to evaluate the CIZ1B biomarker in patients with suspicious indeterminate lung nodules.

This was the first time the test was being used in a real-world prospective clinical setting at a major cancer centre, and represented a significant endorsement of the tech.

October 2024 brought the cornerstone commercial event: the execution of an exclusive licensing and partnership agreement with Cizzle Bio Inc, a US-based corporation, for the CIZ1B biomarker test throughout the USA and Canada.

The terms included an initial upfront royalty payment of $300,000 and guaranteed minimum royalty payments totalling $2 million over the following 30 months, on top of a $100,000 exclusivity fee already paid during the MoU period.

Cizzle also received the right to an equity stake in BIO — 10% for no cash consideration — providing additional upside on any future realisation of BIO’s value. Under the structure, BIO funds all costs of clinical evaluation, accreditation and marketing in North America.

Cizzle takes no cash risk on the US rollout.

In December 2024 the North American territory was extended to include 14 Caribbean sovereign states plus the Cayman Islands, with the same 10% royalty structure. This extension was driven by BIO investor relationships within the Caribbean healthcare sector and triggered early royalty payment commitments to Cizzle of an additional $500,000.

January 2025 saw Coverley appointed as Chief Scientific Officer in an executive capacity, reducing her teaching commitments at York to devote more time directly supporting licensing partners through the commercialisation phase.

The same announcement confirmed completion of the technical programme to determine the optimal, most cost-effective and scalable version of the CIZ1B assay — an ELISA format demonstrating equivalence with earlier manual laboratory tests, with sensitivity consistent with published CIZ1B lung cancer studies.

In March 2025 BIO appointed its first accredited laboratory partner, iGenomeDX, a COLA-accredited and CLIA-certified specialist oncology lab, as a pathfinder facility to establish the operating and quality systems required for CLIA LDT accreditation.

April 2025 brought the first Caribbean hospital contract: BIO signed a laboratory services agreement with Doctors Hospital (Chrissie Tomlinson Memorial Hospital) in the Cayman Islands, triggering the early royalty payments.

August 2025 was another inflection point.

BIO moved its accreditation and market launch strategy from the pathfinder laboratory to a significantly larger multi-site clinical diagnostics group — OmniHealth Diagnostics — which operates COLA and CLIA accredited laboratories with a national expansion strategy covering Texas, New York, California, South Carolina, Tennessee and Florida.

This reorientation reflected the scale of the commercial opportunity BIO was seeing and its decision to pursue a coordinated national rollout rather than a lab-by-lab gradual build.

Simultaneously, a revised royalty payment schedule was agreed, with all remaining advance royalties of $1.875 million to be received by Cizzle by end of 2026 rather than April 2027.

By September 2025 Cizzle had received payments totalling $525,000 from BIO and its Executive Chairman had attended the Prevent Cancer Foundation 40th Anniversary and Gala in Washington DC alongside BIO, further cementing the commercial relationships being built in the US cancer screening community.

November 2025 brought confirmation of the UK strategy: a Letter of Intent was signed with a leading unnamed UK medical diagnostic services provider acting in partnership with the NHS, for the verification and validation of the CIZ1B test with an NHS Foundation Trust partner.

The unnamed provider — confidential for commercial reasons — could potentially become the exclusive UK supplier of the CIZ1B test.

They could be the big gun that buys this thing out.

This plan aligns directly with the NHS long-term cancer plan that aims to improve cancer survival by diagnosing 75% of cancers at stages 1 and 2 by 2028, an ambition intended to save 55,000 additional lives per year.

February 2026 brought the patent news - the Canadian Intellectual Property Office granted patent protection for the core two-step test format — Use of a Fibrinogen Capture Agent to Detect a CIZ1B Variant.

A similar patent application was confirmed as likely to be granted by the USPTO in due course.

Simultaneously, Cizzle updated shareholders on the commercial progress, confirming BIO was in the final stages of CLIA accreditation, expected to submit the application in Q2 2026, and announcing a further commitment from BIO - an additional minimum $3.5 million in guaranteed royalty payments as part of a contract extension to 2031, equivalent to at least $500,000 per year, on top of the existing $2.4 million to be paid by end of 2026.

The total minimum contract value across the full term was confirmed at $5.9 million in guaranteed payments, representing advances against the 10% royalty on gross sales.

June 2026 (as in, now) delivered two headline announcements, and brought me out of hibernation.

First, on 12 June, the USPTO granted the patent covering the core methods used to measure the CIZ1B biomarker — the fibrinogen capture sandwich ELISA format that is the commercial test.

This granted US patent, alongside the existing European Patent Office protection and the newly granted Canadian patent, gives Cizzle a robust three-jurisdiction patent shield around its core commercial product in its three most important markets.

Second, on 16 June, Cizzle announced that the CIZ1B biomarker test had received CLIA accreditation for clinical use in the United States at OmniHealth Diagnostics in Dallas, Texas.

The test is now commercially live and available to licensed US healthcare providers.

US commercial launch and what CLIA means for the investment case

CLIA — the Clinical Laboratory Improvement Amendments — is the federal regulatory framework that governs laboratory testing on human specimens in the United States, regulated by the Centers for Medicare and Medicaid Services (CMS).

CLIA accreditation is a rigorous, multi-stage process that evaluates a lab’s testing procedures, quality control systems, personnel qualifications and patient safety protocols. The CIZ1B test has now passed this process at OmniHealth Diagnostics.

What this means in practical terms is that any licensed US healthcare provider can now order the CIZ1B test. It’s now a real commercial product available to real doctors for real patients today.

CLIA compliance is also a mandatory prerequisite for a lab to receive Medicare and Medicaid reimbursements — meaning the pathway to the largest government healthcare payers in the country is now open.

OmniHealth Diagnostics, the approved laboratory, is a CLIA-certified, COLA-accredited facility based in Richardson, Texas, and is part of the Katharos Health family of laboratories. Its services span genetic testing, molecular diagnostics, clinical laboratory testing, toxicology and pharmacogenomics. It’s not a small operation, and national expansion is underway.

Importantly, OmniHealth’s validation of the CIZ1B test establishes the template for national rollout.

For context, even though CIZ1B is offered as a Laboratory Developed Test, each additional CLIA-certified laboratory wishing to perform the assay must complete its own validation. But the hard technical work — the Standard Operating Procedure, the quality systems documentation, the analytical performance proof — has now been done and can be transferred.

OmniHealth’s existing national presence and acquisition programme means the infrastructure for nationwide coverage is either in place or being assembled.

OmniHealth and BIO have also stated their intent to engage a progressive marketing campaign working closely with patient advocacy groups and to pursue CPT codes — Current Procedural Terminology codes — to allow Medicare and Medicaid reimbursement.

CPT codes are the mechanism by which commercial scale becomes possible in the US system. Private pay testing is the entry point; insurance reimbursement is the mass market.

And this is about to launch.

US money is different to UK money.

Speaking of money…

How Cizzle makes money

Cizzle’s commercial model is a licensing business. The company does no manufacturing at scale, conducts no clinical trials at its own expense in North America and maintains no US commercial infrastructure.

All of those costs are borne by BIO. Cizzle receives royalties and guaranteed minimum payments in exchange for its IP.

Pretty clean.

The current contracted financial terms are as follows:

The North American and Caribbean licence carries a 10% royalty on gross sales after applicable taxes. This is a fair royalty rate for a diagnostics product, reflecting the proprietary nature and differentiation of the technology.

Guaranteed minimum advance royalty payments totalling $2.4 million were agreed to be paid to Cizzle by BIO by end of 2026. As of February 2026 Cizzle had received $590,000 of this total. The remaining $1.81 million has been confirmed as on schedule for receipt before end of 2026.

Beyond 2026, as part of a contract extension agreed in early 2026, BIO committed to a further minimum of $3.5 million in guaranteed royalty payments across the seven years following the 2031 agreement extension, equivalent to at minimum $500,000 per year.

The total confirmed minimum payment stream across the full contract term is $5.9 million, representing guaranteed advances against the 10% royalty on gross sales — with further royalty payments only becoming due once cumulative earned royalties exceed that guaranteed minimum.

CIZ also receives revenue from the sale of the proprietary antibodies to BIO in addition to the royalties.

Additionally, Cizzle holds a SAFE (Simple Agreement for Future Equity) in BIO with a value of just over $1 million, received for no cash consideration.

Based on BIO's first-round valuation of circa $10 million, this would equate to approximately 10% equity upon conversion. The SAFE can be converted into equity at the time of a future financing round, or Cizzle can elect a cash settlement upon a sale of BIO — meaning Cizzle is positioned to participate in any future realisation of value.

Given BIO is now a commercially live US entity with a validated diagnostic product in the world’s largest healthcare market, this equity position is not immaterial.

Separately, the UK LoI, if converted to a full partnership agreement, would likely generate further royalty or revenue-share income from NHS and private UK markets, and potentially from a European rollout beyond.

The company has also received funding support from existing and very supportive shareholder Frazer Lang through convertible loan notes — £150,000 in May 2025 and up to £250,000 in April 2026 — which have supported cash flow during the pre-revenue build phase.

Market opportunity - size of the prize?

The addressable market for the CIZ1B test is humongous.

Starting with the United States alone:

As noted above, the USPSTF estimates approximately 14.5 million Americans are eligible for annual lung cancer screening. Actual LDCT screening uptake remains critically low — national studies put the rate at roughly 6% on average, with some regional data as low as 1%.

This represents both a challenge and an opportunity: the market is enormously underpenetrated, and any tool that makes screening more accessible, more actionable and less dependent on specialist imaging infrastructure has powerful tailwinds.

Consider even a conservative penetration scenario.

If 5% of the 14.5 million eligible US patients were to use CIZ1B in any given year, that would represent approximately 725,000 tests annually.

Comparable US laboratory diagnostic tests in oncology typically price at $100-$500 per test. At even the lower end of pricing — say $150 per test — 725,000 tests would generate revenues of approximately $109 million per year in the US alone.

Cizzle’s 10% royalty on that would be $10.9 million annually, more than the company’s current entire market capitalisation in a single year’s royalties from one territory at modest penetration.

At meaningful penetration — say 15-20% of the eligible population over time, which is still well below the penetration rates seen for other cancer screening tests with insurance coverage — the numbers become substantially larger.

The broader lung cancer diagnostics market context underlines the scale of the opportunity. Multiple market research sources project the global lung cancer diagnostics market at $13.3 billion in 2025, growing to $28 billion by 2035 at a CAGR of approximately 7.7%.

The cancer biomarkers market specifically, in the US alone, is projected to grow from $3.88 billion in 2025 to over $11 billion by 2034, at a CAGR approaching 12.5%.

The segment of blood-based biomarker tests for cancer (where CIZ1B sits) is described across dozens of research reports as the fastest-growing sub-segment, driven by demand for non-invasive, cost-effective, scalable diagnostic solutions.

In the UK, Cizzle’s technology is aligned with the NHS cancer plan’s stated objective of diagnosing 75% of cancers at Stage 1 or 2 by 2028 — an objective that requires exactly the kind of accessible, low-cost, primary-care-deliverable early detection tool that the CIZ1B test represents.

There is currently no NHS-approved blood-based biomarker test for early-stage lung cancer. The LoI with the NHS-linked diagnostic provider is the first step in what could become a commercially significant UK and European licensing stream.

Adding the Caribbean territory — 45 million people across 14 sovereign states plus the Cayman Islands — and the potential of China, Europe and other markets that Cizzle retains rights to, the global picture is of a technology positioned at the intersection of an enormous unmet clinical need and multiple large, growing market segments.

Patent protection

A licensing business is only as valuable as the intellectual property it licenses. Cizzle’s patent position has been much strengthened during 2025 and 2026.

The company now holds granted patent protection from the European Patent Office for its core CIZ1B detection methods. The Canadian Intellectual Property Office granted the patent for the fibrinogen capture agent test format in February 2026. The USPTO allowed the patent application for the same core methods in June 2026 — the most recent and perhaps most significant addition to the portfolio, given that the US is the primary commercial market.

The US patent — Use of a Fibrinogen Capture Agent to Detect a CIZ1B Variant — protects the specific two-step test format that BIO is deploying commercially through OmniHealth.

This means the commercial launch is now backed by granted IP protection in the US, Canada and Europe simultaneously. Any competitor seeking to replicate the exact commercial approach now faces a direct patent barrier in all three of Cizzle’s most important markets.

Professor Coverley’s team at the University of York continues to publish foundational research on the CIZ1 protein family and epigenetic instability in cancer, generating ongoing data that reinforces the scientific validity of the biomarker and may support additional IP protection and clinical utility claims in future.

Clinical validation — the Moffitt study and NIH engagement

Commercial credibility in the diagnostics sector requires ongoing clinical validation - you want more deals, you need continued data build.

Cizzle is progressing on multiple fronts.

The collaboration with the Moffitt Cancer Center — an NCI-designated Comprehensive Cancer Centre and the top cancer facility in Florida and the south-east United States — is the most significant clinical partnership to date.

Under the collaboration, patients presenting with suspicious indeterminate lung nodules at Moffitt’s Lung Cancer Early Detection Centre are providing blood samples for CIZ1B testing, analysed in Professor Coverley’s laboratory in York.

This is a prospective real-world clinical evaluation, not a retrospective study on banked samples.

The results, when published, will provide new sensitivity and specificity data for the CIZ1B biomarker in a contemporary US clinical population, directly relevant to the test’s intended use case: helping clinicians determine whether a lung nodule found on CT is malignant.

The Moffitt study also highlights the clinical logic of CIZ1B’s positioning.

Dr Lary Robinson, Director of Moffitt’s Lung Nodule Clinic, has articulated three specific clinical scenarios where a highly accurate blood test would be of potential benefit:

• Determining whether an indeterminate lung nodule found on CT is cancer

• Using the test as a primary blood screening tool for lung cancer in high-risk populations

• Long-term surveillance for recurrent disease after curative treatment

Each of these scenarios represents a distinct commercial application for the CIZ1B test, broadening its potential use well beyond a single entry point.

In July 2025 Cizzle Bio submitted a grant application to the National Institutes of Health (NIH) in partnership with top-tier research institutions to support a two-year validation study of the CIZ1B biomarker.

NIH grant applications involving clinical diagnostic tools are highly competitive, and submission alone reflects the scientific credibility of the programme. A successful grant award would provide additional non-dilutive funding for validation work and further strengthen the evidence base for the test.

BIO has also been building relationships with multiple National Cancer Institute-designated cancer centres across the United States, creating a pipeline of clinical evaluation opportunities that will generate the ongoing real-world evidence base necessary to drive physician adoption and insurance reimbursement.

Beyond lung cancer?

One aspect of the Cizzle story that is frequently underappreciated is the potential for the CIZ1B platform technology to expand beyond lung cancer detection.

The scientific basis of the test — the ability to detect a stable plasma protein biomarker at very early stages of disease — is a platform capability, not a single-indication product.

This brings Cizzle from a simple 10x stock to Blue Sky potential.

Coverley’s laboratory is actively investigating the utility of CIZ1B in detecting other cancer types. Research published in the Journal of Cell Biology in 2025 described epigenetic deprogramming linked to CIZ1 in early-stage breast cancer, opening the possibility that similar biomarker detection approaches could be applied to breast cancer screening.

The 2023 publication in BMC Biology on epigenetic instability and cancer transformation provides further foundational evidence that the CIZ1 pathway is not lung-cancer specific.

Furthe, BIO — Cizzle’s US partner, has already expanded beyond lung cancer. BIO holds a worldwide exclusive licence for the DEX-G2 biomarker test for gastric cancer, a test developed from research by Ajay Goel at the City of Hope Comprehensive Cancer Center, based on a dual-action combination of cell-free and exosomal microRNAs.

DEX-G2 has been validated in a major clinical study published in JAMA Surgery, with an AUC of 96% for early-stage gastric cancer detection.

Gastric cancer causes around 2,500 deaths per day globally and is the third most lethal cancer worldwide. BIO’s positioning as a multi-cancer early detection company with a portfolio of validated blood tests — rather than a single-product business — significantly increases its commercial attractiveness and the value of Cizzle’s 10% equity stake in BIO.

The point-of-care development pathway for CIZ1B also deserves a mention.

The current ELISA format requires a clinical laboratory. A point-of-care version — suitable for use in a GP surgery, pharmacy or primary care setting — has been identified as a future development goal.

If achieved, this would transform the addressable market for the test, enabling use at the very front line of healthcare and in lower-resource settings globally.

The NHS opportunity

In the UK, Cizzle is pursuing a parallel commercial track that, if successful, could be highly strategically valuable independent of the US revenue stream.

The November 2025 LoI with the leading NHS-linked diagnostic services provider established a formal validation pathway.

Under the terms, the partner — unnamed for commercial reasons but believed by some informed investors to be a major UK reference laboratory group with existing NHS Foundation Trust contracts — will immediately carry out a validation exercise with Professor Coverley’s involvement.

Success criteria, if met, will lead to negotiation of a full Partnership Agreement in which the provider may become the exclusive UK supplier of the CIZ1B test.

The regulatory pathway in the UK is UKCA/CE marking and potentially HIE (Healthcare In-vitro diagnostic Exemption) routes.

The UK’s Health Research Authority clinical trial reforms that came into force in April 2026 — the biggest such reforms in over 20 years — may create accelerated pathways for diagnostic tools that have already been validated internationally, particularly where equivalent data can be leveraged rather than requiring entirely new UK-specific safety datasets.

The political alignment could not be stronger. The UK government’s NHS cancer plan explicitly targets diagnosing 75% of cancers at Stage 1 or 2 by 2028, with an ambition to save 55,000 additional lives per year.

There is currently no blood-based biomarker test for lung cancer anywhere in the NHS. The CIZ1B test, if validated and approved, would be the only such tool available to NHS clinicians — a unique proposition.

The scale of the NHS as a single procurement entity means that a successful UK partnership could generate serious volume extremely quickly in a way that’s simply not possible elsewhere.

Management matters

Professor Dawn Coverley — Founder and Chief Scientific Officer.

Coverley is the world’s leading authority on the CIZ1 gene, the scientist who discovered CIZ1B and its association with early-stage lung cancer, and the person who has led the lab work at the University of York that produced the commercial test.

Her appointment as CSO in an executive capacity at the start of 2025, reducing her teaching load to devote more direct time to the company’s commercial programme, was a material positive.

She provides irreplaceable scientific leadership and hands-on technical support to laboratory partners going through CLIA accreditation.

The company has also published a substantial body of peer-reviewed scientific literature — six papers are referenced in the company’s own science materials, spanning 2012 to 2025 — which independently validates the scientific rationale for the test and serves as a barrier to replication.

Allan Syms — Executive Chairman.

Syms has led the commercial development of the company’s licensing strategy, negotiated and executed the North American agreement with BIO, overseen the Caribbean extension, the UK LOI, and the delivery of the guaranteed royalty payment schedule.

He has been consistently engaged with the US commercial programme, including attending key industry events alongside BIO to build clinical awareness.

Bill Behnke — Founder and CEO of Cizzle Bio Inc.

Based in the United States, Behnke is the architect of BIO’s commercial strategy. He has built the clinical relationships with major cancer centres, selected and onboarded OmniHealth as the commercial launch laboratory, assembled BIO’s leadership team and driven the royalty payment schedule.

BIO’s positioning — as a multi-cancer early detection company also advancing the DEX-G2 gastric cancer test — suggests a management team thinking about long-term platform value, not just a one-product launch.

Valuation estimate

Valuing early commercial stage diagnostics companies is inherently uncertain.

But what I can do is frame the opportunity and compare the current market capitalisation to the contracted revenue streams and plausible upside scenarios.

Current market capitalisation at approximately £10 million. The company has contracted minimum revenues from BIO of $5.9 million over the contract term in guaranteed payments alone, the bulk of which ($2.4 million) is due by end of 2026 with a further $1.81 million of that remaining to be received. These are contracted minimum obligations from a commercial partner that has consistently made payments and recently strengthened its commitments.

The 10% running royalty on gross US sales is the more transformative element. As framed in my market opportunity section, even a modest penetration of the 14.5 million eligible US screening population generates royalty revenues that dwarf the current market capitalisation.

If CIZ1B achieves just 1% penetration of the eligible US population at say $200 per test, that is 145,000 tests generating $29 million in revenues for BIO and $2.9 million per year in royalties for Cizzle — a sum greater than 20% of the company’s current market cap, every year, from a 1% penetration scenario in a single territory.

If this works, it could penetrate 50%.

I’ll let you do the maths. Add in the UK, Europe, the rest of the world…and the blue sky potential to apply this platform to tohers cancers…

Comparable diagnostic licensing businesses with approved products in the US market, contracted royalty streams, and genuine platform technology trade at multiples of revenues that would imply a Cizzle market cap of many times its current level.

The disconnect between the current valuation and the commercial reality may reflect the market’s historical scepticism of small-cap biotech timelines — Cizzle has experienced delays relative to early targets, as is common in this sector — combined with limited analyst coverage and low liquidity.

The share price has already rerated materially from its 52-week low of approximately 1.2p, reaching highs of around 3.75-3.8p in May 2026, before settling back toward 2-3p in recent weeks. The 52-week performance substantially outpaces the FTSE All Share.

But even at 3.75p — the recent peak — the market cap barely exceeds £15 million for a company that is now commercially live in the United States, holds granted patents across three major jurisdictions, has a validated clinical product, contracted revenues, an NHS validation pathway and a pipeline that includes gastric cancer detection.

It’s a 10x. With ease.

(Risks apply, as ever. Not financial advice)

Near-term catalysts

The following events have the potential to drive a re-rate, imho:

1. First commercial sales in the United States. BIO has stated it expects immediate uptake following CLIA approval, based on patient requests for early access. The first announcement of commercial revenue — even a small initial figure — would represent a watershed moment in market perception.

2. Moffitt study data. The results of the prospective clinical evaluation at Moffitt Cancer Center will be closely watched. Strong sensitivity and specificity data in a real-world US population would substantially strengthen the evidence base for the test, accelerate physician adoption conversations, and support CPT code and reimbursement applications.

3. Additional laboratory validations. Each additional CLIA-certified laboratory that validates the CIZ1B test for its own accreditation extends national coverage and demonstrates scalability. OmniHealth’s national expansion across New York, California, South Carolina, Tennessee and Florida provides the platform for multiple such announcements.

4. CPT code application outcome. The pathway to Medicare and Medicaid reimbursement is through CPT codes. Any progress on this front — submission, acceptance in principle, or formal code award — would be a very significant catalyst for projected volumes and revenues.

5. UK partnership announcement. Conversion of the LOI into a full Partnership Agreement with the NHS-linked diagnostic provider, or announcement of successful validation data, would open a major new commercial territory and introduce a second parallel revenue stream.

6. NIH grant award. A successful NIH grant award for the two-year validation study submitted by BIO in July 2025 would provide non-dilutive funding, scientific credibility and access to additional clinical datasets.

7. BIO equity realisation. The 10% equity stake Cizzle holds in BIO, received for no cash consideration, has a notional value that is currently ascribed a zero in any conservative valuation (in that it’s unreliasable paper until it’s not). If BIO attracts institutional investment, a strategic partner, or moves toward any form of liquidity event, the value of this stake could become very significant.

8. European or Asian licensing announcement. Cizzle retains rights to all markets outside North America and the Caribbean. The company is actively exploring licensing partnerships in the UK, Europe and Asia. Any announcement of a new territory licence would expand the revenue base and demonstrate global commercial momentum.

The bottom line

Cizzle is not the typical speculative small-cap biotech.

It’s not for a drug to work in a trial. I have enough of these.

It has a validated diagnostic test, commercially approved in the United States, built on 30 years of peer-reviewed science from a world-leading research institution, protected by granted patents in the US, Canada and Europe, and generating contractually guaranteed revenues from a well-funded US commercial partner.

The core clinical problem the test addresses — the absence of any blood-based test for early-stage lung cancer despite 234,000 US diagnoses and 2.2 million global diagnoses per year, the vast majority too late for curative treatment — is one of the most pressing unresolved challenges in oncology.

The size of the market that would benefit from a solution is enormous.

The performance characteristics of the CIZ1B test - low cost, standard lab equipment, non-invasive blood draw — are differentiated.

The risk profile as of June 2026 is fundamentally different from the risk profile of six months ago.

The test is approved.

The route to market is open.

The revenue stream is contracted.

The patents are granted.

The NHS pathway is active.

The £10 million market cap prices Cizzle as if these milestones have not yet occurred, or as if they will not translate into meaningful commercial outcomes.

The gap between what the market perceives and what is, is where the money is made.

I am not going to pretend there are not risks here. Things can and do go wrong. This is not a major. Diversify and manage your risk.

But for investors willing to take a considered view on a company with a validated product, real revenues, contracted minimum payments, IP protection, clinical validation underway at one of America’s top cancer centres and a global market of considerable scale — at a market cap that appears to substantially undervalue the sum of those parts — Cizzle is one to consider.

And with just 5ml blood - a Calpol syringe’s worth - it might even save your life.