Race Oncology (ASX:RAC) Announces Expansion of RC220 Clinical Pipeline into $10B Cancer Markets

Race Oncology (ASX:RAC) has issued an investor update detailing a significant expansion of its clinical pipeline, with the Race Oncology RC220 clinical programs now targeting Acute Myeloid Leukaemia (AML) and Non-Small Cell Lung Cancer (NSCLC). This move positions the company’s lead compound, RC220, to address cancer markets valued at over $10 billion annually, leveraging the recent discovery of its unique G4-DNA binding mechanism of action.

This expansion builds upon Race’s established cardioprotection programme, opening pathways to larger patient populations and commercial opportunities. With 18% of piggyback options already converted and detailed trial planning underway, Race is advancing its position in cancer treatment innovation. As of 30 September 2025, the company maintains a cash position of $11.3 million and is progressing three clinical trials.

CEO Dr Daniel Tillett commented: “The opportunity to use RC220 to delay, or even prevent, TKI resistance across a range of cancers is a compelling opportunity. The scale of the opportunity is enormous, with more than US$10 billion of EGFRm TKIs sold every year for lung cancer alone.”

Race Oncology is a Phase 3 clinical biopharmaceutical company. Its lead asset, RC220 ((E,E)-bisantrene), is a small molecule anticancer agent that functions primarily via G4-DNA and RNA binding, leading to potent inhibition of the important cancer growth regulator MYC.

What Are the Race Oncology RC220 Clinical Programs?

The Race Oncology RC220 clinical programs represent a multi-faceted development strategy targeting several cancer indications with significant unmet medical needs. Following the discovery of RC220’s unique mechanism of action, the company has positioned its lead compound to address three distinct clinical opportunities.

The HARNESS-1 trial is the most commercially significant programme, targeting the $10+ billion EGFRm TKI market in non-small cell lung cancer. This Phase 1a/b study will evaluate RC220’s ability to delay resistance to market-leading drugs like Tagrisso (osimertinib), which generated $6.6 billion in sales during 2024.

Furthermore, Race has identified a rapid and cost-effective clinical pathway to potential regulatory approval of RC220 in relapsed/refractory AML. This Phase 3 programme includes a bridging and dose optimisation stage to establish the pharmacokinetic and pharmacodynamic equivalence of RC220 with the original RC110 formulation.

Key Trial Parameters for HARNESS-1:

• Patient Population: Approximately 100 patients screened, 52-80 treated
• Study Design: Phase 1a dose escalation followed by a randomised Phase 1b expansion
• Clinical Sites: Five major Australian centres (Sydney, Melbourne, Brisbane)
• Timeline: First patient expected Q1 2026
• Investment: Approximately A$11.5 million before R&D tax rebate

The trial will use circulating tumour DNA (ctDNA) monitoring to measure treatment efficacy, with conversion from ctDNA-positive to ctDNA-negative serving as a key endpoint alongside traditional progression-free survival measures.

How Does the G4-Binding Mechanism Work in Cancer Treatment?

The discovery that RC220 binds to G-quadruplex (G4) DNA/RNA structures represents a different approach from many traditional cancer therapeutics. These structures act as molecular switches controlling gene expression, particularly the MYC oncogene, which is reported to be found in up to 70% of cancers.

RC220 binds to and stabilises these G4 structures, which in turn regulates cancer-related genes. The regulation of MYC, a primary driver of growth in many cancers, is particularly important. MYC has remained a difficult target for drug development due to its unstructured protein nature. RC220’s indirect approach through G4-binding presents a potential new method for addressing this critical cancer driver.

Cancer Types with Elevated MYC Activity:

• Pancreatic: 97%
• Esophagus: 90%
• Lung: 82%
• Melanoma: 82%
• Bladder: 80%
• Stomach: 81%
• Breast: 68%
• Brain: 64%
• Liver: 62%

The mechanism also reportedly blocks the activity of other enzymes that help cancer cells grow and divide, such as telomerase and topoisomerase II. Additionally, it is understood to increase m6A levels in RNA, which may make cancer cells less aggressive and less resistant to treatment.

What Is the Commercial Opportunity for EGFRm Non-Small Cell Lung Cancer?

The EGFRm NSCLC treatment market presents a large commercial opportunity, with current annual sales exceeding $10 billion globally. The Race Oncology RC220 clinical programs targeting this indication address a fundamental challenge in cancer treatment: the development of resistance to tyrosine kinase inhibitors (TKIs).

EGFR-mutated non-small cell lung cancer is a subtype of lung cancer with specific gene mutations in the epidermal growth factor receptor (EGFR) that drive uncontrolled cell growth. The most common mutations are deletions in exon 19 (E19del) and a point mutation in exon 21 (L858R).

Market Leaders in EGFRm TKI Treatment:

Despite 14 approved EGFRm TKIs and 8 in Phase 3, nearly all patients develop resistance to EGFRm TKI therapy, with a median progression-free survival of approximately 18 months. A therapy that could slow resistance development could significantly extend treatment duration.

Why Do Patients Develop Resistance to TKI Therapy?

Understanding the mechanisms behind TKI resistance is central to appreciating the potential value of the Race Oncology RC220 clinical programs. EGFR TKI resistance can arise through the activation of alternative cell growth signalling pathways, creating a complex challenge known as the subclone problem.

Primary Resistance Mechanisms:

1. Bypass Signalling Activation: Multiple bypass pathways can be activated in a single patient, including MET amplification, HER2 amplification, IGFR1 activation, and FGFR amplification.
2. Downstream Pathway Activation: Even when EGFR is blocked, cancer cells can activate downstream signalling through PI3K/AKT, MAPK, and JAK/STAT pathways.
3. Subclone Selection: Treatment with any single new target drug selects for the growth of subclones driven by other resistance pathways.

Preclinical evidence suggests that the majority of EGFRm NSCLC patients on TKI therapy have two or more independent pathway resistance subclones present upon disease progression. This creates a need for new treatments that can target multiple resistance pathways simultaneously. RC220’s G4-binding mechanism aims to address this challenge by targeting multiple pathways through MYC silencing, Topoisomerase II inhibition, and increased m6A RNA modification.

What Are the Advantages of RC220 Over Existing Treatments?

The Race Oncology RC220 clinical programs are designed to offer several distinct advantages over current treatment approaches for both EGFRm NSCLC and AML. These advantages stem from RC220’s unique mechanism of action.

Firstly, by indirectly targeting the MYC oncogene via G4-binding, RC220 offers a potential solution to a long-standing challenge in oncology, as MYC has been historically difficult to target with drugs. Secondly, its ability to act on multiple cancer pathways at once—including Topoisomerase II inhibition and m6A RNA modification—may overcome the problem of subclone resistance that limits the effectiveness of many single-target therapies.

Finally, Race Oncology’s previous work suggests RC220 has cardioprotective qualities, a notable point of differentiation from many chemotherapies that carry risks of heart-related side effects. This combination of a novel mechanism, multi-pathway targeting, and a potential safety advantage underpins the company’s clinical development strategy for RC220.

Want more ASX news?

Looking to stay ahead of major developments in ASX biotechnology companies like Race Oncology? Subscribe to StockWire X’s free Big News Blasts and join over 20,000 investors receiving instant email alerts on significant biotechnology announcements, each accompanied by detailed analysis. With a quality filter ensuring only major news events are distributed, subscribers gain access to the most important market-moving information without the noise. Join today to receive comprehensive insights delivered directly to your inbox.