Immunocore announces treatment of first patient in the Phase 1/2 trial of IMC-R117C targeting PIWIL1 in advanced gastrointestinal cancers

Rhea-AI Summary

Immunocore (IMCR) has initiated patient treatment in a Phase 1/2 trial for IMC-R117C, their fifth ImmTAC candidate, targeting PIWIL1 in colorectal and other gastrointestinal cancers. The trial will evaluate both monotherapy and combination treatments with standard care in HLA-A*02:01-positive patients with advanced solid tumors.

IMC-R117C represents the first immunotherapy program targeting PIWIL1, a cancer-testis antigen overexpressed in multiple malignancies, including colorectal cancer (CRC). The company estimates up to 20,000 colorectal cancer patients globally are positive for both PIWIL1 and HLA-A*02:01. This development addresses a significant unmet medical need, particularly in advanced colorectal cancer cases resistant to standard treatments.

Positive

• First-ever PIWIL1-targeted immunotherapy entering clinical trials
• Potential market of 20,000 colorectal cancer patients globally
• Addresses unmet medical need in advanced colorectal cancer

Negative

• Early-stage Phase 1/2 trial with uncertain outcomes
• to HLA-A*02:01-positive patients only

Insights

Medical Research Analyst

The initiation of a Phase 1/2 trial for IMC-R117C marks a significant milestone in gastrointestinal cancer treatment. This novel ImmTAC candidate targeting PIWIL1 is particularly noteworthy as it's the first immunotherapy of its kind. The focus on PIWIL1, a cancer-testis antigen linked to aggressive tumor growth, could potentially address a critical gap in treating microsatellite-stable colorectal cancer (CRC), which has historically shown resistance to immunotherapy. With an estimated 20,000 patients globally meeting the dual PIWIL1 and HLA-A*02:01 positive criteria, this represents a substantial market opportunity. The trial's dual approach - testing both monotherapy and combination with standard treatments - provides multiple pathways for potential success.

Financial Analyst

For Immunocore, this development strengthens their clinical pipeline as their fifth ImmTAC candidate to enter clinical trials, demonstrating consistent R&D execution. The targeting of colorectal cancer, particularly the microsatellite-stable subtype, represents a significant commercial opportunity given the large patient population and current treatment limitations. While early-stage trials carry inherent risks, successful development could position Immunocore to address an underserved market segment. The company's focus on both monotherapy and combination approaches maximizes potential commercialization pathways and partnership opportunities.

The Phase 1/2 trial will assess the safety and clinical activity of IMC-R117C, as a monotherapy and in combination with standards of care, in patients with advanced cancers expressing PIWIL1

First immunotherapy program to target PIWIL1, a cancer-testis antigen overexpressed in a range of cancers, including colorectal cancer

(OXFORDSHIRE, England & CONSHOHOCKEN, Penn. & ROCKVILLE, Md., US, 17 December 2024) Immunocore Holdings plc (Nasdaq: IMCR) (“Immunocore” or the “Company”), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, today announces that the first patient has been treated in the Phase 1/2 trial of its novel ImmTAC candidate, IMC-R117C, targeting PIWIL1 in colorectal and other gastrointestinal cancers.

IMC-R117C is Immunocore’s fifth ImmTAC candidate to enter the clinic. PIWIL1 is overexpressed in multiple malignancies, including colorectal cancer (CRC), and is associated with aggressive tumor growth and poor patient survival.ⁱ Despite the development and approval of novel therapeutics, there remains a significant unmet medical need in patients with these cancers, especially in advanced colorectal cancer that is refractory to or has relapsed following standard chemotherapies and targeted therapies.

The Company believes IMC-R117C is the first PIWIL1-targeted immunotherapy and estimates that there are up to 20,000 colorectal cancer patients globally that are positive for both PIWIL1 and HLA-A*02:01.

“We are proud to bring forward the first immunotherapy program to target PIWIL1, through our novel ImmTAC candidate, IMC-R117C,” said Mohammed Dar, Senior Vice President, Clinical Development and Chief Medical Officer of Immunocore. "PIWIL1 is expressed across all major subsets of colorectal cancer – including microsatellite-stable CRC, which has historically been insensitive to immunotherapy.”

The trial will evaluate the safety and clinical activity of IMC-R117C in HLA-A*02:01-positive patients with select advanced solid tumors. In addition to evaluating IMC-R117C as a single agent, the trial will also test combinations with standards of care.

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About ImmTAC^® molecules for cancer
Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune “cold” low mutation rate tumors.

About the Phase 1/2 trial of IMC-R117C

IMC-R117C-1004 is a Phase 1/2, multicenter, open-label, first-in-human trial of IMC-R117C in HLA-A*02:01-positive patients with advanced cancers that express PIWIL1. This trial is designed to assess the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics, and clinical activity of IMC-R117C as monotherapy and in combination with other therapies.

About colorectal cancer

Colorectal cancer (CRC) is one of the most prevalent forms of cancer affecting the colon and rectum. Most patients with CRC are diagnosed at an early stage, but survival rates remain low for those with advanced or metastatic disease. Despite advancements in CRC treatment, there is a significant need for new therapies that enhance first-line response rates and extend the duration of response, particularly for patients who do not respond to initial treatments. Early detection through regular screening is crucial for improving outcomes associated with CRC.

About Immunocore

Immunocore is a commercial-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies called ImmTAX – Immune mobilizing monoclonal TCRs Against X disease – designed to treat a broad range of diseases, including cancer, autoimmune diseases, and infectious diseases. Leveraging its proprietary, flexible, off-the-shelf ImmTAX platform, Immunocore is developing a deep pipeline in multiple therapeutic areas, including nine active clinical and pre-clinical programs in oncology, infectious diseases and autoimmune diseases. The Company’s most advanced oncology TCR therapeutic, KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom.

Forward Looking Statements

This press release contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “believe,” “expect,” “plan,” “anticipate,” and similar expressions (as well as other words or expressions referencing future events or circumstances) are intended to identify forward-looking statements. All statements, other than statements of historical facts, included in this press release are forward-looking statements. These statements include, but are not limited to, statements regarding Immunocore’s expectations regarding the design, progress, timing, scope and results of Immunocore’s existing and planned clinical trials, including the Phase 1/2 trial of IMC-R117C in patients with advanced cancers expressing PIWIL1; the ability of IMC-R117C to target PIWIL in colorectal and other gastrointestinal cancers; and the value proposition of Immunocore’s product candidates, including IMC-R117C, including expectations regarding the significant unmet need for patients with colorectal cancer and the potential market opportunity of IMC-R117C. Any forward-looking statements are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual events or results to differ materially and adversely from those set forth in or implied by such forward-looking statements, many of which are beyond the Company’s control. These risks and uncertainties include, but are not limited to, the impact of worsening macroeconomic conditions on the Company’s business, financial position, strategy and anticipated milestones, including Immunocore’s ability to conduct ongoing and planned clinical trials; Immunocore’s ability to obtain a clinical supply of current or future product candidates or commercial supply of KIMMTRAK or any future approved products, including as a result of health epidemics or pandemics, war in Ukraine, the conflict in the Middle East or global geopolitical tension; Immunocore’s ability to obtain and maintain regulatory approval of its product candidates, including KIMMTRAK; Immunocore’s ability and plans in continuing to establish and expand a commercial infrastructure and to successfully launch, market and sell KIMMTRAK and any future approved products; Immunocore’s ability to successfully expand the approved indications for KIMMTRAK or obtain marketing approval for KIMMTRAK in additional geographies in the future; the delay of any current or planned clinical trials, whether due to patient enrollment delays or otherwise; Immunocore’s ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; competition with respect to market opportunities; unexpected safety or efficacy data observed during preclinical studies or clinical trials; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or future regulatory approval; Immunocore’s need for and ability to obtain additional funding, on favorable terms or at all, including as a result of inflation, interest rates and unfavorable general market conditions, and the impacts thereon of war in Ukraine, conflict in the Middle East and global geopolitical tension; Immunocore’s ability to obtain, maintain and enforce intellectual property protection for KIMMTRAK or any of its product candidates it or its collaborators are developing; and the success of Immunocore’s current and future collaborations, partnerships or licensing arrangements. These and other risks and uncertainties are described in greater detail in the section titled "Risk Factors" in Immunocore’s filings with the Securities and Exchange Commission, including Immunocore’s most recent Annual Report on Form 10-K for the year ended December 31, 2023 filed with the Securities and Exchange Commission on February 28, 2024, as well as discussions of potential risks, uncertainties, and other important factors in the Company’s subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and the Company undertakes no duty to update this information, except as required by law.

Contact Information

Immunocore

Sébastien Desprez, Head of Communications
T: +44 (0) 7458030732
E: sebastien.desprez@immunocore.com
Follow on Twitter: @Immunocore

Investor Relations

Clayton Robertson, Head of Investor Relations
T: +1 (215) 384-4781
E: ir@immunocore.com

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ⁱ Sun, Rui, Chun-li Gao, Dong-hai Li, Bo-jun Li, and Yan-hong Ding. 2017. “Expression Status of PIWIL1 as a Prognostic Marker of Colorectal Cancer.” Disease Markers 2017:1204937. https://doi.org/10.1155/2017/1204937

FAQ

What is the significance of IMCR's IMC-R117C Phase 1/2 trial in gastrointestinal cancers?

It's the first-ever immunotherapy targeting PIWIL1, addressing an unmet medical need in advanced colorectal cancer patients who are resistant to standard treatments.

How many patients could potentially benefit from IMCR's IMC-R117C treatment?

Immunocore estimates up to 20,000 colorectal cancer patients globally who are positive for both PIWIL1 and HLA-A*02:01 could potentially benefit from the treatment.

What is the current development stage of IMCR's IMC-R117C program?

IMC-R117C has just entered Phase 1/2 clinical trials, with the first patient being treated to evaluate safety and clinical activity in advanced solid tumors.

How will IMCR's IMC-R117C be administered in the Phase 1/2 trial?

The trial will evaluate IMC-R117C both as a monotherapy and in combination with standard care treatments for patients with advanced cancers expressing PIWIL1.