Helix BioPharma’s Strategic Vision for Next-Generation Cancer Therapies

Unlike most visions for the future, Helix BioPharma’s is focused on the near term, with longer-term goals shaped by the success and learning that come from acting now. The reason is simple: time is a luxury that many of us don’t have; while the science is advancing, outcomes are not keeping pace with the real, immediate needs of those facing a diagnosis today. Innovation takes time, especially in oncology, where cancer is not a single disease but a complex group of more than 200 distinct types, each with its own biology, behavior, and response to treatment.

The incidence of cancer is projected to increase by 77% by 2050, meaning that for every person diagnosed with cancer today, there will soon be nearly two. This trend raises serious concerns about whether turning innovation into widely adoptable, effective therapies can keep up with this growing, global emergency for humanity. Meeting the needs of a larger population affected by cancer in the future hinges on our ability to meet the needs of people living with cancer today; and these patients have already waited long enough for better treatment options. At Helix, next-generation cancer therapies are exactly that: what comes next, not what comes years down the line.

That’s why our focus is on turning proven science into near-term, high-impact solutions. We do this by taking a pragmatic approach to innovation (innovating from strength): selecting high-potential candidates where we can deliver difference, rather than investing valuable time and resources in proving premise; developing therapies designed to elevate and fit seamlessly into existing care algorithms; and leveraging insight and know-how to identify value-based opportunities and strategically accelerate their development, to bring urgently-needed therapies to those who need them most.

Our recent acquisition of LEUMUNA™ and GEMCEDA™ reflects this strategy in action: two next-generation candidates that address hard-to-treat cancers, build on proven science, and offer a direct path to meaningful impact.

i) LEUMUNA™

LEUMUNA™ (LR 09, ulodesine hemiglutarate) is a novel, patented, oral immune checkpoint modulator with the potential to significantly extend progression-free survival for patients relapsing with leukemia after allogeneic stem cell transplantation (allo-SCT). Allo-SCT is a physically and emotionally taxing, often life-threatening procedure, which patients willingly endure because it represents the only potentially curative treatment for acute leukemia and other hematological malignancies. If the procedure is successful, patients with hematological cancers have a 20% to 30% chance of relapsing within 24 months, delivering a devastating blow to morale and a grim prognosis of just four months. In this scenario, the treatment landscape is fragmented and options are largely ineffective, with most offering limited durability and few achieving long-term remission in specific patient subsets, making leukemia relapse a hard-to-treat cancer, today.

In preclinical models of B-cell acute lymphoblastic leukemia relapse conducted at the Fred Hutchinson Cancer Center, LEUMUNA has demonstrated the ability to significantly reduce the risk of leukemic death by indirectly activating T cells and triggering a graft-versus-leukemia (GvL) effect. This immune-mediated mechanism, in which donor immune cells recognize and eliminate residual host leukemia cells post-transplant, is the most effective path to long-term remission. Yet despite its potential, the GvL response has remained under-leveraged in post-transplant relapse treatment. LEUMUNA aims to change that, and it brings a head start and distinct advantages that made its acquisition a strategic fit for Helix.

LEUMUNA exemplifies our strategy of innovating from strength, in that it builds on a strong foundation of prior clinical research while introducing a novel formulation that unlocks new therapeutic potential. The active compound in LEUMUNA is ulodesine hemiglutarate, a patented, novel salt form of ulodesine that retains the pharmacodynamic properties of its predecessor while offering distinct advantages in safety, manufacturing, and intellectual property protection.

Ulodesine (BCX-4208) was originally developed by BioCryst Pharmaceuticals in collaboration with Roche as an immunosuppressant for autoimmune conditions, such as psoriasis. However, its mechanism of action was not fully understood at the time; whereas the goal of ulodesine’s initial development was to suppress immune activity, subsequent research revealed that PNP inhibition selectively depletes immunosuppressive regulatory T cells (Tregs), effectively enhancing anti-tumor immune responses by unmasking effector T cell activity. After failing to meet efficacy endpoints in a Phase IIa psoriasis trial, Roche discontinued the program in 2008. BioCryst then pursued ulodesine as a treatment for gout, completing Phase IIb trials that confirmed a strong safety profile in over 500 volunteers, but the program was ultimately shelved for strategic reasons.

Further validating LEUMUNA’s mechanism as an immune checkpoint modulator is the case of forodesine hydrochloride, an analogous PNP inhibitor also out-licensed by BioCryst to Mundipharma International in 2006. Forodesine showed early clinical efficacy in various hematological malignancies, with two patients achieving complete remission after relapsing with T-cell acute lymphoblastic leukemia after allo-SCT. One of these patients was a three-year-old little girl, whose patient case titled “When a Drug Becomes a Child’s Last Hope for T-Cell Leukaemia” is available on YouTube. Forodesine was eventually approved in Japan for peripheral T-cell lymphoma (PTCL) under the trade name Mundesine™, but its broader clinical development was hampered by a complex manufacturing process, followed by patent expiry.

LEUMUNA not only mirrors forodesine’s therapeutic potential—it improves upon it. With a simplified five-step synthesis, a clean clinical safety record via ulodesine, and a long intellectual property runway to 2041, LEUMUNA offers a scalable, efficient, and biologically targeted treatment approach for a devastating and underserved cancer relapse scenario.

Its re-development as ulodesine hemiglutarate was initiated by Laevoroc Immunology AG, the company from which Helix acquired the asset, in a research collaboration with UCLA. Laevoroc Immunology was co-founded by hemato-oncologist Thomas Mehrling, MD, PhD, now CEO of Helix BioPharma, who previously oversaw the development of forodesine during his tenure at Mundipharma, and Shanta Bantia, PhD, a recognized expert in PNP biology who was instrumental in advancing both forodesine and ulodesine at BioCryst Pharmaceuticals. This continuity of insight—from compound to clinical strategy—positions Helix to unlock LEUMUNA’s full therapeutic potential with a rare combination of scientific, developmental, and operational strength. LEUMUNA has additionally been granted Orphan Drug Designation (ODD) by the US FDA in December 2022, further reinforcing Helix’s strategy of innovating from strength by enabling a more capital-efficient path to market, regulatory incentives, and validating the therapeutic potential of the compound in a critically underserved population.

ii) GEMCEDA™

GEMCEDA (LR 06B, an oral gemcitabine prodrug combined with cedazuridine) is a first-in-class, oral chemotherapy agent designed to transform the administration of gemcitabine—a cornerstone of cancer treatment and a World Health Organization (WHO) Essential Medicine.

Intravenous (IV) gemcitabine remains a mainstay of cancer treatment, indicated as first-line therapy alone or in combination with other cytotoxic drugs for advanced or metastatic pancreatic cancer, advanced or metastatic non-small cell lung cancer (NSCLC), and metastatic breast cancer after failure of adjuvant chemotherapy, among other indications. These are among the most challenging cancers to treat—aggressive, often diagnosed late, and associated with poor prognosis and limited durable treatment options. In addition to its cytotoxic effects, gemcitabine has immune modulating effects on tumor cells within the tumor microenvironment (TME) and enhances innate anti-tumor responses, making it a promising candidate for combinations with immunotherapies like checkpoint inhibitors. Low-dose, metronomic therapy with IV gemcitabine combined with a PD-1 inhibitor in 61 patients with advanced lung, pancreatic, breast and other cancers has been shown to be well tolerated and to significantly improve treatment outcomes, particularly in post-operative patients. However, the full potential of gemcitabine as a combination therapy and metronomically dosed agent is limited by its IV administration, due to its rapid degradation, short half-life, and spiking peak-trough levels, which together reduce treatment flexibility, and require frequent hospital visits that add to the burden of people fighting advanced cancers.

Oral chemotherapy is increasingly used in the treatment of cancer; a total of 88 oral chemotherapy agents have been approved by the FDA over the past 20 years, with over 30% of the 900 chemotherapy agents currently in development being oral formulations. However, there are currently no oral forms of gemcitabine, largely due to its poor bioavailability (less than 10%), which has made it nearly impossible to achieve the necessary drug concentrations in the body for an effective therapeutic effect. Numerous efforts to develop oral gemcitabine have been discontinued due to challenges in achieving sufficient systemic exposure.

In 2022, Laevoroc Chemotherapy AG announced the development of a novel active pharmaceutical ingredient (API), LR 06B (GEMCEDA): a rationally-designed, novel chemical entity to enable new uses of gemcitabine as a single agent in oral metronomic/maintenance therapy and/or combinations with oral targeted therapies. The compound was developed under a joint venture between Laevoroc Chemotherapy and Lipomed AG, succeeding a collaboration agreement between the two companies. When combined with cedazuridine, a cytidine deaminase inhibitor, GEMCEDA achieved a staggering 90% bioavailability in a pharmacokinetic study in large animal models—near-matching the bioavailability of IV gemcitabine.

Gemcitabine’s long-standing use across multiple tumor types, combined with its well-established safety and efficacy profile, significantly de-risks the clinical development of GEMCEDA. As a novel, rationally-designed prodrug of a chemotherapy agent with a validated mechanism of action and improved oral bioavailability, GEMCEDA may qualify for development via the FDA’s 505(b)(2) regulatory pathway, which allows for abridged timelines and reduced development costs by referencing existing data with gemcitabine. The compound benefits from an established synthetic route and scalable manufacturing process, designed to enable cost-effective production from the outset. Importantly, GEMCEDA is a patented new chemical entity with composition-of-matter protection extending to 2042, offering Helix and a potential future partner a long IP runway and commercial defensibility. An added strength for Helix is that Dr. Davide Guggi, Chief Technology Officer (CTO) of Helix and an expert in Chemistry, Manufacturing, and Controls (CMC), is one of the inventors of LR 06B, bringing deep knowledge of the compound’s formulation and production.

GEMCEDA may be used as a single agent for oral maintenance therapy or in combination with oral targeted or immunotherapies—including PARP inhibitors, ATR inhibitors, and PD-1/PD-L1 checkpoint inhibitors—presenting new ways to fight and better ways to live for people with advanced cancers. The program has already attracted early interest from leading generics companies seeking strategic partnerships around next-generation oral chemotherapies.

iii) Broadening the Horizon with Our New Acquisitions

The strategic addition of LEUMUNA and GEMCEDA to our asset portfolio expands the reach of our pipeline to deliver urgently needed therapies for hard-to-treat cancers. These assets complement our CEACAM6-targeting platform (consisting of our lead candidate, Tumor Defence Breaker™, L-DOS47, and CEACAM6-targeting antibody-drug conjugates, currently in discovery) in that they, too, transform hard-won learnings into faster, smarter and more accessible solutions for some of cancer’s biggest, most urgent challenges.

For us, next-generation cancer therapies are exactly that: advancements standing on the shoulders of what came before. Innovation is a continuum, and innovating from strength is simply being honest about that and intentional in how we move forward.

Reference:

1 https://www.cancerresearch.org/blog/december-2023/exploring-the-different-types-of-cancer-and-treatment-options
2 https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21834
3 https://www.thenewswire.com/press-releases/1BOxF12pw-helix-biopharma-tsx-hbp-otc-pink-hbpcd-frankfurt-hbp0-secures-pre-ind-candidates-leumuna-tm-and-gemceda-tm-in-strategic-acquisition-from-the-laevoroc-group.html
4 https://pubmed.ncbi.nlm.nih.gov/18026156/; https://haematologica.org/article/view/8281
5 https://pmc.ncbi.nlm.nih.gov/articles/PMC9850970/; https://www.sciencedirect.com/science/article/pii/S0006497119620185
6 https://link.springer.com/article/10.1007/s12185-024-03793-1
7 See unpublished data on p. 17 of our non-confidential deck: https://www.helixbiopharma.com/wp-content/uploads/2025/06/Helix-Public-Deck_June-2025.pdf
8 https://pmc.ncbi.nlm.nih.gov/articles/PMC10978651/
9 https://ir.biocryst.com/static-files/f139814f-6bdc-4843-a901-312f08d139f7
10 https://www.jci.org/articles/view/160852
11 https://ir.biocryst.com/news-releases/news-release-details/biocryst-reports-results-bcx-4208-phase-iia-trial-subjects
12 https://ir.biocryst.com/news-releases/news-release-details/biocryst-announces-positive-results-two-ulodesine-phase-2-trials; https://www.sec.gov/Archives/edgar/data/882796/000117184315004473/gfpf10q_080715.htm
13 https://ir.biocryst.com/news-releases/news-release-details/biocryst-announces-presentation-and-update-results-intravenous; https://www.sciencedirect.com/science/article/abs/pii/S0093775407002242?via%3Dihub
14 https://newdrugapprovals.org/2018/03/06/forodesine-hydrochloride/
15 https://www.nature.com/articles/d43747-023-00010-6
16 https://laevoroc.com/28-02-2023-laevoroc-immunology-announces-fda-orphan-drug-designation-granted-to-lr-09-a-novel-metabolic-immune-checkpoint-inhibitor-for-the-treatment-of-leukemia-relapse-after-allogeneic-st/
17 https://list.essentialmeds.org/recommendations/409
18 https://www.medicines.org.uk/emc/product/7298/smpc#gref
19 https://www.scientificarchives.com/article/gemcitabine-in-the-era-of-cancer-immunotherapy
20 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.882172/ful
21 https://www.hoparx.org/documents/288/Oral_Chemotherapy_Issue_Brief_-_Updated_02.22.24.pdf
22 https://pubs.acs.org/doi/10.1021/acsnano.3c04793
23 https://pubmed.ncbi.nlm.nih.gov/32603666/ ; https://aacrjournals.org/clincancerres/article/14/11/3477/72692/Oral-Administration-of-Gemcitabine-in-Patients; https://aacrjournals.org/clincancerres/article/17/18/6071/76510/Phase-I-Study-of-Oral-Gemcitabine-Prodrug; https://pmc.ncbi.nlm.nih.gov/articles/PMC7606647/
24 https://laevoroc.com/18-03-2022-laevoroc-oncology-announces-evolution-of-former-subsidiary-into-joint-venture-with-lipomed-ag/

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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