Gene Therapy as Immunotherapy

Technology Snapshot

Overview

Indication: Broad oncology applicability – works in tandem with T cell engagers (TCEs).

Unmet need: Many patients relapse after TCE therapy largely due to T cell dysfunction

Encelta’s Approach: “AED T cells” – allogeneic T cells designed to augment TCE therapy.

Real-World Impact: Provides a scalable and therapeutically robust way to achieve broader, more durable responses to TCEs

Encelta’s Team: Led by Dr. Edo Kapetanovic (MD, PhD), synthetic immunology expert from ETH Zürich

Clinical Development

Lead Program: AED T cells in combination with TCEs

Delivery Route: Intravenous, allogeneic “off-the-shelf” administration

Stage: Preclinical

Planned Study: Poised for early-stage trials supporting proof-of-concept in combination with established TCEs

Current Status: Platform optimization, early manufacturing scale-up, and partnership positioning underway

Impact & Market Opportunity

Incidence: TCEs already treat thousands of patients annually; more than 100 TCEs are in development

Market Growth: The global TCE market is projected to grow from $0.81B in 2023 to $18.7B by 2032 (41.8% CAGR). Sources below.

Expansion Potential: AED T cells are compatible with any CD3-targeting TCE, opening a universal, platform-level opportunity

Competitive Landscape

Incidence: TCEs already treat thousands of patients annually; more than 100 TCEs are in development

Market Growth: The global TCE market is projected to grow from $0.81B in 2023 to $18.7B by 2032 (41.8% CAGR). Sources below.

Expansion Potential: AED T cells are compatible with any CD3-targeting TCE, opening a universal, platform-level opportunity

Technology Breakdown: T Cell Engagers for Solid Tumors

Encelta AG is a Swiss-based biotech startup developing a first-in-class allogeneic T cell therapy platform designed to augment the clinical activity of T cell engagers (TCEs) – a rapidly growing class of cancer immunotherapies. Spun out of ETH Zürich’s Systems and Synthetic Immunology department in 2023, Encelta’s core technology, Allogeneic-Engineered-Decoupled (AED) T cells, addresses a major limitation of TCEs: their reliance on healthy T cells in the patient’s body, which are often highly compromised in late-stage disease.

AED T cells provide a safe, off-the-shelf source of healthy T cells that can be co-administered with any TCE to boost efficacy – without the risk of graft-versus-host disease. This approach is shaping up to offer a scalable and cost-effective strategy to enhance TCE performance across a broad range of indications.

The company is led by Dr. Edo Kapetanovic, MD, PhD, a physician-scientist and award-winning expert in synthetic immunology and cancer biology, who is driving a focused and clinically feasible strategy to deliver the next generation of immunotherapies to cancer patients.

Encelta AG - Major Sections

The Medical Need

The Challenge: T Cell Engagers Fail Due To Poor T Cell Health

T cell engagers (TCEs) are one of the most promising classes of cancer immunotherapies, but their clinical success is often limited by a fundamental biological constraint: TCEs rely entirely on the patient’s own T cells to mediate tumor cell killing.

This is a serious liability because, by the time patients receive TCEs, they have often undergone prior rounds of chemotherapy, radiation, or other treatments that significantly damage their T cells – not to mention the cancer itself can induce direct immunosuppression on the T cells.

As a result, many patients relapse after receiving TCEs, not because the target antigen is absent, but likely because their immune systems lack the functional T cells needed to mount an effective response.

It’s really bad, actually.

In one study of patients treated with the CD19-targeted TCE blinatumomab, 92% of those who relapsed did so with antigen-positive disease (Jabbour E, et al., Am J Hematol. 2018), strongly suggesting that relapse was not due to antigen escape, but rather to insufficient T cell activity.

Without enough healthy or functional T cells, even a perfectly targeted TCE can fail.

This creates a clear and addressable clinical need: how can we safely and effectively get a large population of healthy T cells into the patient to ensure TCEs can perform as intended?

This is the precise challenge Encelta’s AED T cells were built to solve.

Encelta's Solution

Encelta's Solution: Allogeneic Engineered "Decoupled" (AED) T Cells

Encelta’s answer to this problem combines a proper amount of innovation with a tried a tested approach: a novel class of engineered T cells that can be safely co-administered with any T cell engager to restore and amplify its anti-tumor activity.

These cells, called Allogeneic-Engineered-Decoupled (AED) T cells, are an off-the-shelf “TCR-T cell therapy” that have been carefully engineered to simultaneously: i) retain full expression of the CD3/TCR complex, allowing them to respond to TCEs, while ii) not inducing TCR-mediated graft-versus-host…but how?

Encelta’s AED T cells incorporate two precise genetic edits:

Disruption of the endogenous TCR – preventing graft-versus-host disease
Re-expression of a mutated TCR-α chain that is expressed normally – allowing for proper surface expression of the entire TCR/CD3 complex – but is incapable of actually inducing signaling.

So, the mutant TCRα is basically a decoy – its there, but its not going to do anything.

Here’s the thing though, since the full complex is still expressed on the surface of the cell, CD3 remains fully functional and capable of responding to T cell engagers. This enables AED T cells to augment the therapeutic activity of basically any TCE without risking GvHD.

So, Encelta has solved the paradox and developed a way to combine allogeneic T cells with TCEs, positioning themselves as a potential universal partner in the TCE field.

Impact & Market Opportunity

Real-World Impact: Enhancing TCE Therapy

Since AED T cells can be safely paired with any TCE, regardless of the tumor target, and can be feasibly manufactured at scale, Encelta could be a highly valuable partner to the entire TCE space – and it’s a big one!

Right now, there are nine FDA-approved T cell engagers already being used to treat thousands of cancer patients across both blood cancers and solid tumors.

On top of that, there are over 100 more in clinical development, and many of them could benefit from a simple, off-the-shelf source of healthy T cells to boost their effectiveness.

That puts Encelta in a great position – not just to make a real difference for patients, but also to become a valuable partner to dozens of biotech and pharma companies working in the TCE space.

Market Opportunity: T Cell Engagers in Oncology and Autoimmunity

T cell engagers are absolutely exploding in oncology right now, and represent one of the hottest markets in healthcare. Due to AED T cells’ ability to interact with any TCE, Encelta would theoretically have access to the entire market.

According to Wise Guy Reports, the global bispecific T cell engager therapeutics market was valued at $0.81 billion in 2023 and is projected to grow to $18.7 billion by 2032, representing a remarkable compound annual growth rate (CAGR) of 41.78% from 2024 to 2032.

Overall, the TCE field is rapidly expanding, driven by things like advances in T cell engineering, combination therapy strategies, and strategies to enhance TCE efficacy. As TCEs become more sophisticated and broadly applied, Encelta’s AED T cells may become a highly sought after bolt-on addition to improve clinical activity.

Major Players

Real-World Impact: Enhancing TCE Therapy

Right now, there are nine FDA-approved T cell engagers already being used to treat thousands of cancer patients across both blood cancers and solid tumors.

On top of that, there are over 100 more in clinical development, and many of them could benefit from a simple, off-the-shelf source of healthy T cells to boost their effectiveness.

That puts Encelta in a great position – not just to make a real difference for patients, but also to become a valuable partner to dozens of biotech and pharma companies working in the TCE space.

Market Opportunity: T Cell Engagers in Oncology and Autoimmunity

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Encelta AG

Encelta AG is a swiss-based biotech developing a universal TCR-T cell platform designed to augment CD3-targeting T cell engagers.

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