Understanding the Role of CEACAM6 in Hard-to-treat Cancers

April is Bowel Cancer Awareness Month—an occasion to draw attention to the growing global burden of colorectal cancer, the screening methods that can potentially prevent cancer from developing, and the evolving treatment landscape for those already facing a diagnosis. 

Colorectal cancer (CRC) has emerged as the second leading cause of cancer death worldwide, with CRC-related deaths expected to increase by 73% by 2040—to 1.6 million deaths per year.1 What is especially worrying is that colorectal cancer is becoming increasingly common in younger adults. Known as early-onset CRC, since the mid-1990s, incidence rates in adults aged 20 to 39 years have consistently been increasing (by 2% each year), with one in five patients diagnosed today being under the age of 55.2 Early-onset CRC is often diagnosed at a more advanced stage compared to patients with later-onset CRC (Stage III-IV), stealing away some of their most productive and creative years of life.3 Though no one knows for certain why there is an uptick in early-onset CRC, generational differences in diet, lifestyle factors (from sedentary lifestyles and obesity, to smoking and alcohol use), and environmental and genetic factors have all been associated with the disease.4  

There are four early warning signs, each of which significantly increases the likelihood of being diagnosed with the early-onset form of CRC:5 

  1. Abdominal pain
  2. Rectal bleeding
  3. Diarrhea or changes in bowel patterns
  4. Iron deficiency anemia

The belief that CRC typically affects older adults is still widespread, meaning younger adults are more likely to ignore early signs of the disease. This belief needs to change; younger adults experiencing these symptoms persistently should seek medical attention immediately. 

If caught early, CRC is highly treatable and often curable if it is limited to the bowel. Approximately 50% of patients are cured with surgery alone.6 However, colon and rectal cancers can return within months or years of treatment—either locally in the bowel (locoregional recurrence) or as a metastasis somewhere else in the body (systemic recurrence), most commonly in the liver. Occurring in 4-12% of patients who have undergone curative resection surgery, locoregional recurrence is often more difficult to diagnose, while liver metastases can occur in up to 50% of patients after curative CRC treatment.7 Much of this ordeal be avoided with timely screening. Colonoscopy remains the gold standard of CRC screening and can, in fact, prevent precancerous polyps or lesions from becoming malignancies. Official guidelines recommend that both men and women of average risk should get colonoscopy screenings every 10 years starting at the age of 45.8

Recent breakthroughs have provided a glimmer of hope for those already facing a diagnosis, with innovative approaches including antibody-drug conjugates (ADCs), non-coding RNA-based strategies, and oncolytic viral therapies that have the potential to enhance treatment specificity and overcome drug resistance.9 Notably, in a recent Phase II study, the immune checkpoint inhibitor, Dostarlimab (JEMPERLI), achieved a remarkable complete remission in 100% of patients with specific types of rectal cancer.10 However, these successes are currently limited to select patient subgroups, and there is a lot of work ahead of us to address the global rise in colorectal cancer effectively. In this evolving landscape, targeting biomarkers like CEACAM6 offers a novel approach to broaden therapeutic impact and bridge current treatment gaps.

Understanding CEACAM6’s Biology and Overexpression

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is far more than a diagnostic marker – it is a potent driver of tumor aggressiveness.11 This immunoglobulin superfamily protein is normally present on epithelial surfaces and certain immune cells, but in many aggressive cancers, its expression increases dramatically. Overexpression of CEACAM6 is closely linked to several key processes that fuel cancer progression:

  • Inhibition of Apoptosis: CEACAM6 helps cancer cells evade programmed cell death, allowing them to survive beyond their normal lifespan.
  • Promotion of Invasion and Metastasis: Elevated levels of CEACAM6 facilitate the breakdown of cell adhesion and extracellular matrix components, enabling cancer cells to migrate and form secondary tumors.
  • Enhancement of Drug Resistance: By activating survival pathways and modulating cell signaling, CEACAM6 contributes to a tumor’s ability to withstand conventional therapies.

High levels of CEACAM6 expression are correlated with poorer overall survival and disease-free survival in cancers such as lung, breast, colorectal, and pancreatic malignancies.12 A detailed understanding of CEACAM6’s role not only underscores its value as a diagnostic marker but also positions it as a promising therapeutic target, paving the way for precise interventions using advanced technologies.

How We’re Targeting CEACAM6 with RDC and ADC Technology

Building on a robust scientific foundation, our approach at Helix BioPharma has evolved through extensive experience with CEACAM6-targeted treatments. Our work with L-DOS47, an antibody-enzyme conjugate that targets CEACAM6 and neutralizes the pH of the tumor microenvironment, has provided crucial insights into effective tumor targeting. We’ve used this experience to further the development of our next-generation oncology therapies.

Our lead discovery candidate is a radionuclide drug conjugate (RDC) targeting CEACAM6. RDCs represent an innovative strategy that uses precision targeting to deliver a radioactive payload directly to tumors. In RDCs, tumor antigen-specific antibodies or nanobodies are linked to radioisotopes,  facilitating targeted radiotherapy by directing radiation precisely to the tumor site and minimizing exposure to healthy tissues.13 Recent studies in colon cancer have highlighted the need to improve the precision of targeting, addressing challenges such as the accumulation of nanoparticles in non-target tissues.14

Based on our clinical experience with L-DOS47, we now have the know-how to select nanobodies that minimize these risks. This precision targeting not only enhances the safety profile but also innovates from strength by delivering an established treatment modality, radiotherapy, with unprecedented accuracy. Research has consistently shown that CEACAM6 is overexpressed in colorectal tumors, where it drives progression and metastasis.15 This makes colorectal cancer a prime candidate for our CEACAM6-targeted RDC.

The Role of AI in Optimizing Targeting

Innovation at Helix BioPharma isn’t limited to conventional research but is also powered by cutting-edge artificial intelligence. We’re using AI to refine our antibody constructs, ensuring high binding affinity and optimal manufacturing yields. By analyzing the amino acid sequences that determine binding characteristics, our AI tools help us avoid problematic residues that cause aggregation, they help us streamline production, and enhance overall efficacy. This integration of AI-driven optimization not only accelerates our development timelines but also ensures that our CEACAM6-targeted therapies are as precise and effective as possible.

A New Paradigm in Precision Oncology

CEACAM6 is emerging as a central player in the battle against aggressive cancers, and at Helix BioPharma, we are at the forefront of transforming this knowledge into breakthrough treatments. By combining state-of-the-art RDC technology with AI-driven optimization, we are turning a once-overlooked biomarker into a powerful therapeutic target. This approach testifies to our commitment to innovating from strength, purposefully pushing the boundaries of proven science to deliver real-world impact for those who need it most. Together, we can turn the tables on cancer, paving the way for a future where even the most prevalent or aggressive cancers are rendered vincible. 

But an even better outcome is to stop the cancer before it starts. It’s easy to put off, but if you’re eligible for a colonoscopy, penciling it in could be one of the most important appointments that you make.   

References:

1 https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer
2 https://www.cancerresearch.org/blog/march-2025/colorectal-cancer-awareness-month
3 https://pmc.ncbi.nlm.nih.gov/articles/PMC7994182/
4 https://www.yalemedicine.org/news/colorectal-cancer-in-young-people
5 https://www.cancer.gov/news-events/cancer-currents-blog/2023/colorectal-cancer-young-people-warning-signs
6 https://www.cancer.gov/types/colorectal/hp/colon-treatment-pdq
7  https://jgo.amegroups.org/article/view/40709/html
8 https://www.mdanderson.org/cancerwise/why-are-more-young-adults-getting-colorectal-cancer-what-to-know.h00-159385890.html
9 https://pmc.ncbi.nlm.nih.gov/articles/PMC10190721/
10 https://www.targetedonc.com/view/dostarlimab-shows-remarkable-100-clinical-response-rate-in-dmmr-rectal-cancer
11 https://pmc.ncbi.nlm.nih.gov/articles/PMC5765285/
12 https://link.springer.com/article/10.1007/s12672-024-01053-6
13 https://pmc.ncbi.nlm.nih.gov/articles/PMC10908151/
14 https://pmc.ncbi.nlm.nih.gov/articles/PMC11859487/
15 https://www.pnas.org/doi/10.1073/pnas.2319055121

One Reply on “Understanding the Role of CEACAM6 in Hard-to-treat Cancers”

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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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Christof Boehler

Chief Business Development Officer

Dr. Christof Boehler is a commercially oriented scientist with a proven track record in building and leading teams that successfully commercialize products and services in the life science industry. His core competencies are in technology transfer, business development and corporate governance with a focus on technology scouting, preclinical and clinical R&D, licensing, sales, capital raising and M&A.

Mr. Boehler is also a strategic advisor to Takeda.

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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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Praveen Kumar

V.P. Drug Development

Praveen has experience working in the pharmaceutical industry for more than 25 years and has expertise in the development of drug products for small and macro-molecules using various dosage forms. He was involved in projects comprising the formulation development of generic drug products and their production and developed a novel transdermal drug product containing a protein-based drug (interferon alpha 2b) for the treatment of HPV infections.

Presently as a V.P. he manages the CMC-related activities (drug product formulation, technology transfer, quality, stability testing and interaction with regulatory agency) for the development of L-DOS47 drug product, an antibody drug conjugate, for the treatment of various cancers. He has a Ph.D. in Pharmaceutical sciences and he completed his post-doctoral fellowship in gene regulation. He was the author of multiple peer-reviewed published articles, a book chapter, and patents.

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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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