Missing the Marker: Clinical Consequences of Incomplete Biomarker Testing

The Testing Gap: A Persistent Problem

Comprehensive molecular profiling is a foundational requirement in the management of advanced non-small cell lung cancer (NSCLC). In practice, this typically means next-generation sequencing (NGS) panels assessing multiple genomic alterations alongside immunohistochemistry (IHC).

This is because NSCLC is not a single disease, but a collection of molecularly distinct subtypes, each with different therapeutic vulnerabilities and clinical trajectories. Without this information, treatment decisions are inherently limited, increasing the likelihood of suboptimal therapy selection.

In principle, this makes comprehensive profiling a baseline requirement for care; in practice, however, implementation is far less consistent. Part of this gap reflects real-world complexity: obtaining sufficient tumor tissue is not always straightforward; additional procedures can be clinically challenging, time-sensitive, and burdensome for individuals who are often already in a fragile state. However, system-level factors, ranging from access to NGS and reimbursement limitations to workflow inefficiencies, remain significant drivers of uneven adherence.

Across all stages of NSCLC, biomarker testing is underutilized. Even among patients with metastatic disease:

• 61.8% do not receive guideline-concordant testing (≥5 gene testing plus IHC)
• 7.8% receive no biomarker testing at all.
• 54% undergo IHC alone, without comprehensive genomic profiling

In effect, a substantial proportion of patients begin treatment without a complete molecular understanding of their disease.

Testing rates are higher among certain groups: patients under 65, those of Asian ethnicity, never-smokers, and individuals with adenocarcinoma histology or advanced-stage disease. But these patterns reflect probability, rather than eligibility.[1][2]

Survival Is Directly Affected

Patients who never undergo biomarker testing face a 30% higher adjusted risk of death compared with those who do (HR 1.30, 95% CI 1.24–1.37). Even when testing is simply delayed beyond first-line treatment, mortality risk increases by 12% (HR 1.12).

The impact becomes even more pronounced in biomarker-positive disease. When actionable alterations are present but not matched with appropriately targeted therapies, mortality risk rises by 25% (HR 1.25).[1][2]

By contrast, comprehensive testing changes outcomes:

• NGS is associated with a 13% reduction in three-year mortality risk (adjusted HR 0.87).
• In stage IV NSCLC, mortality risk is reduced by 24% (HR 0.76).

The implication is straightforward: understanding tumor biology changes survival.[1][2]

Treatment Decisions Depend on Testing

Therapeutic strategy in NSCLC is only as precise as the data informing it. Patients who receive comprehensive biomarker testing (≥5 genes plus IHC) are:

• More likely to receive targeted therapies
• More appropriately matched to immunotherapy
• Less likely to receive chemotherapy alone

Without this information, treatment decisions may default to broader, less effective options, even when more precise alternatives exist.

The limitations of this approach are stark; in EGFR-mutated NSCLC, immunotherapy alone has demonstrated response rates approaching zero. Without molecular profiling, patients may receive treatments with minimal benefit while missing therapies that could significantly extend survival.[3][2]

Timing also plays a critical role. When test results are delayed beyond 2–3 weeks, 37–59% of patients begin non-targeted therapy before results are available. Once treatment begins, course correction becomes more complex, both clinically and logistically.

Testing late is often equivalent to not testing at all.

Disparities in Access

Access to comprehensive testing, and the therapies it enables, is not evenly distributed.

Higher rates of testing and targeted treatment are observed among:

• Patients with higher socioeconomic status
• Patients in urban settings
• Commercially insured populations

Lower rates are seen among:

• Patients aged ≥75
• Rural populations
• Lower socioeconomic groups
• Certain racial and ethnic minorities
• Patients treated in community settings

These disparities translate directly into differences in care. For example, individuals from higher socioeconomic backgrounds have 67% greater odds of receiving targeted therapy than those from lower SES groups.[2]

Barriers Behind the Gap

The gap in testing is driven by a combination of practical and systemic constraints:

• Limited tissue availability from small biopsies
• Sequential single-gene testing that exhausts samples
• Delays in turnaround time
• Reimbursement and insurance challenges
• Variability in payer coverage
• Limited access to NGS in some community settings
• Educational gaps among providers

Individually, each of these barriers are manageable; collectively, they result in missed opportunities for optimal care. As precision oncology advances, however, incomplete molecular data becomes increasingly difficult to justify.

Molecular Profiling Must Become the Standard

Metastatic NSCLC is a spectrum of molecularly distinct subtypes. Tumors that appear identical under a microscope may behave very differently depending on their genomic drivers.

Comprehensive molecular profiling enables:

• Identification of actionable alterations
• Alignment of first-line therapy with tumor biology
• Avoidance of ineffective treatments
• Improved survival outcomes

The evidence increasingly supports comprehensive biomarker testing not as an adjunct to care, but as its foundation.[3][2]

At Helix BioPharma, we believe that molecular clarity should not be conditional. Precision oncology can only deliver on its promise if access to comprehensive biomarker testing is consistent, timely, and equitable. Closing the testing gap is a clinical imperative because in NSCLC, missing the marker means missing the opportunity to treat the disease as it truly is.

References:

1. Penault-Llorca F, Kerr KM, Garrido P, et al. Expert opinion on NSCLC small specimen biomarker testing – Part 2: Analysis, reporting, and quality assessment. Virchows Arch. 2022;481(3):351-366. doi:10.1007/s00428-022-03344-1

2. Stanford A, Boykin S, Desai K, Ohaegbulam K, Karia PS. Real-world insights on biomarker testing patterns and implications for mNSCLC therapy selection. Am J Manag Care. 2026;32(suppl 3):S27-S37. doi:10.37765/ajmc.2026.89765

3. Mileham KF, Basu Roy UK, Bruinooge SS, et al. Physician concern about delaying lung cancer treatment while awaiting biomarker testing: results of a survey of U.S. oncologists. J Clin Oncol. 2021;39(15_suppl):9067. doi:10.1200/JCO.2021.39.15_suppl.9067

Jacek Antas

Chief Executive Officer

Jacek Antas is a shareholder of the Company, has spent more than 25 years in the financial services industry holding various positions in sales and consulting.

Mr. Antas obtained a master’s degree from the Warsaw School of Economics and has served as a board member of various
companies throughout his career.

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James B. Murphy

Chief Financial Officer

Mr. Murphy is a certified public accountant with over thirty years of experience in finance and operations management. He is currently a consultant with Danforth Advisors LLC (“Danforth”), a leading provider of outsourced strategic and operational specialists across functions in the life sciences industry. While at Danforth, Mr. Murphy has served over fifteen private and publicly held life sciences companies as CFO and CFO Advisor, helping them secure over USD 0.5 billion in financing and successfully execute pivotal asset transactions. Mr. Murphy functions as a consultant to Helix pursuant to a consulting agreement between the Company and Danforth.

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Thomas Mehrling

Medical Adviser

Thomas Mehrling (PhD in Pharmacology and MD) has over 20 years’ experience in multinational Pharma companies developing novel oncology compounds from preclinical research through to registration. Prior to entering the industry, he spent 13 years as an MD at the University Hospital in Frankfurt, working on preclinical and translational projects. He served as Director of European Oncology at Mundipharma International (2003–2013), building the company’s first European oncology business from the ground up out of Cambridge, UK, and completing the clinical development, registration and launch of two major products in Europe, DepoCyte® and Levact® (Ribomustin® and Treanda®). In 2013, he led the establishment of the Mundipharma Group’s start-up, Mundipharma EDO, developing anti-cancer therapeutics for solid tumours out of Basel, Switzerland.

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Kim Gaspar

Director Quality Assurance

Kim is the Director of Quality Assurance at Helix BioPharma Corp. An experienced quality assurance professional with expertise in Canadian, US, and EU regulations, she has been involved in all aspects of Phase I/II biopharmaceutical product development over the years, including regulatory submissions, QC laboratory compliance, tech transfer and third-party oversight of CMC activities, clinical QA, and bioanalytical data analysis. Kim joined Helix in 2000, transitioning into QA in 2003. She holds a B.Sc in Biochemistry and a Ph.D in Veterinary Physiological Sciences, both from the University of Saskatchewan.

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Brenda Lee

Director Clinical Operations

Brenda is the Clinical Operations Director at Helix Biopharma Corp. A clinical research operations professional with 25 years of experience managing clinical trials, ranging from early Phase I to late Phase IIIb/IV studies, she brings experience in clinical study protocol writing and development, trial start-up and vendor management, and a proven track record in planning and managing clinical trials to quality standards, timelines and budget. Brenda joined Helix Biopharma Corp. in 2018, working to advance the clinical program of L-DOS47. She holds B.Sc and M.Sc. degrees from the University of Toronto, specializing in Nutritional Sciences and Human Biology.

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Jerzy Leszczynski

Director

Jerzy Leszczynski is a shareholder of the Company, has spent more than 35 years developing businesses and has served in the capacity of board member of various real estate development companies. Mr. Leszczynski obtained his Master of Science in Chemistry from the Warsaw Institute of Technology.

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Janusz Grabski

Director, Chair of Audit Committee

Janusz (John) Grabski is a lawyer specialized in corporate and real estate law with over twenty years of experience.

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Malgorzata Laube

Director

Malgorzata Laube has over 19 years of experience in nuclear medicine. In her last role with Alberta Health Services, she was the Department Supervisor, Nuclear Medicine at Royal Alexandra Hospital. Ms. Laube obtained a MSc degree in Environmental Engineering from the Warsaw University of Technology and is based in Edmonton, Alberta, Canada.

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Jacek Antas

Chairman of the Board

Jacek Antas is a shareholder of the Company, has spent more than 25 years in the financial services industry holding various positions in sales and consulting.

Mr. Antas obtained a master’s degree from the Warsaw School of Economics and has served as a board member of various
companies throughout his career.

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Jonathan Davis

Advisor, ADC Discovery

Jonathan Davis received his Ph.D. from University of California, San Francisco, where he studied protein structure and function using NMR. After a post-doc at Harvard Medical School exploring RNA selection and structure in the labs of Jack Szostak and Gerhard Wagner, he went to work at EMD Serono, where his work involved improving antibody-based therapeutics, inventing a platform technology for generating heterodimeric Fcs as a basis for multifunctional molecules, and developing a novel scaffold based on an artificially-designed protein from David Baker’s lab. In 2008 he took a job at Bristol-Myers Squibb in Waltham/Cambridge MA, working on antibody discovery and platform development in a wide range of therapeutic areas, with a particular focus on multispecific therapeutics. He moved to Madison, WI in 2019 to take on the role of VP of Innovation and Strategy at Invenra, a biotech focused on bispecific antibodies, and where he is currently head of the Scientific Advisory Board. In early 2024 he left the corporate world to found Creative Antibodies, a consulting firm that helps guide companies to successful antibody discovery and development projects, from mAbs to multispecifics, ADCs, and other formats. Outside of science, Jonathan is a conservatory trained cellist, plays numerous other instruments, and founded the UCSF Orchestra (now Symphony Parnassus) in San Francisco, where he was Music Director for six years.

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Davide Guggi

Advisor, CMC

Davide graduated as a pharmacist and received his PhD in Pharmaceutical Technology and Biotechnology from the University of Vienna. He has over 20 years of experience in the pharmaceutical industry, principally in the field of oncology. At the beginning of his career, Davide led oncology business units and commercial departments at Mundipharma and Gilead across Austria and Eastern Europe. Since over 10 years he has been working as a CMC expert, covering operational and regulatory CMC functions on behalf of over 20 different small- and medium-sized biotech companies across the world. He has served as CMC Director and CSO/CTO for several years, developing both small molecules and biologics (mABs, Fab, ADCs and Radio-immuno-conjugates) from early discovery to NDA/BLA in the US, EU and Canada, with a focus on First-in-Human and Phase I/II studies in oncology indications.

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