Our Science

At Immatics, we are relentless in our pursuit of scientific advancement to create more effective cancer treatments. We're pioneering PRAME-directed immunotherapies that harness the power of T cells to fight cancer and create new therapeutic options for people living with it.

T-Cell

Understanding PRAME

PRAME is a protein found inside tumor cells but is not present in most healthy cells. Small fragments of this protein, known as peptides, are presented on the surface of tumor cells. This unique feature makes PRAME accessible to novel immunotherapies being developed by Immatics.

PRAME is expressed in >50 cancers

Despite major advances in cancer therapy, the majority of patients still do not benefit from existing treatments, highlighting the urgent need for innovative and more effective therapeutic options.

At Immatics, we are developing immunotherapies that target PRAME as a novel approach to making a meaningful impact on the lives of patients with cancer. PRAME is expressed in more than 50 cancers, emphasizing the potential of PRAME-directed immunotherapies to reach a broad patient population.

View PRAME prevalence in selected cancer types¹

Cutaneous melanoma

95%

Uterine carcinoma

95%

Uterine carcinosarcoma

95%

Synovial sarcoma

95%

Uveal melanoma

90%

Mucosal melanoma

90%

Ovarian carcinoma subtypes

85%

Squamous cell NSCLC

70%

Triple-negative breast carcinoma

65%

Small cell lung cancer

45%

Esophageal carcinoma subtype

45%

Kidney carcinoma subtype

40%

Cholangiocarcinoma

35%

HER2-enriched breast carcinoma

30%

Adenocarcinoma NSCLC

25%

Head & neck squamous cell carcinoma

25%

More than 50 other types of cancer express PRAME as well.

1. Data on file: PRAME target prevalence is based on a proprietary mass spec-guided expression threshold applied to RNAseq and/or IHC data (approximate values, values between 95-100% shown as 95%). 2. NSCLC: Non-small cell lung cancer; anzu-cel (IMA203), IM203CD8, IMA402 are being evaluated in separate clinical trials.

PRAME prevalence by cancer type (%)

95%

Cutaneous melanoma
Uterine carcinoma
Uterine carcinosarcoma
Synovial sarcoma

90%

Uveal melanoma
Mucosal melanoma

85%

Ovarian carcinoma subtypes

70%

Squamous cell NSCLC

How PRAME therapies treat cancer

T cells, a type of immune cell, typically detect and destroy abnormal cells before disease develops. However, cancer cells can sometimes go undetected. Our immunotherapies are novel treatments that help the body’s own immune system fight cancer by recognizing and destroying cancer cells that present the PRAME peptide.

We have developed two distinct therapeutic modalities to leverage the power of targeting PRAME: T cell-receptor (TCR)-based T-Cell Therapies and Bispecifics.

Why PRAME works

PRAME is considered one of the most promising targets for TCR-based immunotherapies. It combines several key characteristics that are important when seeking to deliver innovative treatment options that have the potential to make a meaningful impact on the lives of patients with cancer.

Widespread occurrence in more than 50 cancers

Limited or no presence in healthy tissues

Is homogeneously distributed throughout tumor tissue

Presented at high levels on the surface of tumor cells

Multiple functions in tumor biology, including enhancing tumor cell survival, tumor growth (proliferation) and resistance to tumor cell self-destruction (apoptosis)

Found to be associated with poor prognosis and shorter survival

Clinically validated

The Immatics PRAME franchise

Immatics has the broadest PRAME franchise with the most PRAME indications and modalities.

Anzu-cel PRAME cell therapy

Anzu-cel (anzutresgene autoleucel), previously called IMA203, is our lead PRAME cell therapy, and will be our first PRAME therapy to enter the market in advanced melanoma. The current addressable patient population for anzu-cel’s first target indications, 2L cutaneous melanoma as well as metastatic uveal melanoma, includes ~9,000 patients.¹

1. Clarivate Disease Landscape and Forecast; EU5: France, Germany, Italy, Spain, United Kingdom; ICI: Immune checkpoint inhibitor.

IMA203CD8 PRAME Cell Therapy (GEN2)

IMA203CD8 is Immatics’ second-generation PRAME cell therapy product candidate being developed with the goal of expanding into all advanced PRAME cancers. Given its enhanced pharmacology profile, once the target dose is reached, Immatics intends to pursue the clinical development of this product with a tumor-agnostic approach, starting with gynecologic cancers.

IMA402 PRAME Bispecific

To expand the PRAME opportunity to early-stage PRAME cancers, Immatics is developing its off-the-shelf, next-generation, half-life extended TCR Bispecific, IMA402. Upon delivering clinical proof-of-concept (“PoC”) in last-line melanoma, Immatics plans to explore its potential in gynecologic cancers, non-small cell lung cancer (NSCLC), breast cancer and other solid tumor indications as well as earlier treatment lines of solid cancers, such as first-line (1L) cutaneous melanoma.

Adaptable modalities

Immatics’ PRAME-directed therapies and TCR bispecifics allow for various therapeutic modalities.

Table Table

1. Target product profile (TPP) in monotherapy in 2L or later settings post SOC at recommended phase 2 dose (“RP2D”). Other factors such as mPFS (median progression free survival) and mOS (median overall survival) may also be considered.

Combining Immatics’ Target and TCR platforms with Moderna’s mRNA technology

Exploring innovative treatment strategies by combining Immatics’ anzu-cel PRAME cell therapy with Moderna’s PRAME adaptive immune modulating therapy to further enhance anzu-cel T cell responses with the potential to significantly reduce turnaround time and costs through the infusion of a much lower cell dose.

From Facility to Future PRAME Therapy

Our proprietary manufacturing process, timeline, capabilities and facility support late-stage global clinical and commercial cell therapy development and supply.

TCR T-cell therapies are manufactured specifically for each patient. These therapies are derived from a patient’s leukapheresis—a procedure in which the white blood cells, including T cells, of a patient are isolated from their blood. During the cell product manufacturing, T cells are then engineered to carry a novel T cell receptor (TCR) that is designed to specifically detect the PRAME peptide on the patient’s tumor.

The manufacturing process is completed within seven-eight days, followed by seven day quality control (QC) release testing period.

Our manufacturing process generates TCR T cells that have been shown to achieve a high rate of objective responses, infiltrate the patient’s tumor and function in a challenging solid tumor microenvironment, with a favorable side effect profile.

Our state-of-the-art ~100,000 sq. ft. R&D and GMP manufacturing facility in the Houston Metropolitan Area was built with a modular design for efficient and cost-effective scalability to serve early-stage and registration-directed clinical trials as well as planned commercial supply. Through in-house manufacturing and QC testing, we aim to better control the manufacturing process, shorten the turnaround time, ensure the manufacturing success rate and quality of the product and realize potential cost efficiencies, including manufacturing capacity optimization through scalability for a competitive and profitable commercial cell therapy product.

Technologies behind PRAME

Finding the right cancer target is only half the equation, like finding a lock. The other half is creating the key that fits. At Immatics, we bring both sides together:

Discovery of tumor-specific targets like PRAME, and
Designing either engineered T-cell receptors (TCRs) or bispecific molecules that recognize and bind to those targets.

Our platforms are built to fine-tune both sides of this interaction, and they go even further: not just identifying the lock and the key, but ensuring a precise and selective fit. While PRAME is a well-characterized target, we focus on creating optimized molecules to engage it with precision.

Learn more about XPRESIDENT, XCEPTOR, and XCUBE – our platforms designed to enable the discovery and development of innovative TCR-based immunotherapies.

Tech 1 Tech 1

Tech 2 Tech 2

Advancing TCR therapy beyond PRAME

Driven by our work on PRAME, we are expanding the boundaries of TCR-based immunotherapy. We are actively exploring additional targets and approaches to address a broader range of patients with cancer.

IMA401 (MAGEA 4/8 Bispecific)

Immatics is driving innovation beyond PRAME by evaluating its off-the-shelf, next-generation, half-life extended TCR Bispecific, IMA401, targeting MAGEA4/8 in patients with non-small cell lung cancer (NSCLC), head & neck cancer, bladder cancer and other solid tumor indications, with the primary goal of developing this product candidate in earlier treatment lines.

IMA204 (COL6A3)

A TCR-T cell therapy candidate targeting the tumor stroma target COL6A3. Designed to engage both CD8⁺ and CD4⁺ T cells through a CD8-independent next-generation TCR, IMA204 represents a novel approach for targeting tumor stroma.

ACTallo

An allogeneic, off-the-shelf TCR T-cell therapy platform. Based on gene-engineered γδ T cells from healthy donors, ACTallo^® is designed to eliminate the need for patient-derived cells and personalized manufacturing. This approach aims to standardize starting material, streamline logistics and enable the production of multiple doses from a single donor leukapheresis.