Five T cell engager companies you should know about

T cell engagers are antibodies engineered to redirect the immune system’s T cells to recognize and kill cancer cells. They are designed to bind to a target antigen expressed on a cancer cell and trigger a molecule on T cells. These therapeutic molecules then engage T cells that are present in tumors but that are not capable of recognizing cancer cells, redirecting their activity toward the tumor.

Despite being primarily investigated to treat cancer, T cell engagers could also have the potential to treat autoimmune diseases, particularly B-cell driven ones, such as systemic lupus erythematosus and lupus nephritis, as these therapies can lead to deep B cell depletion in the bloodstream and tissues.

In this article, we take a look at five T cell engager companies that are leading the way in this emerging field.

Adaptin Bio 

Having emerged from stealth at the beginning of September 2024, Adaptin Bio is developing precision cancer therapies with improved delivery to the brain and other tissues. At the same time as it emerged from stealth, the company announced that it had received U.S. Food and Drug Administration (FDA) clearance of its Investigational New Drug (IND) application for its lead program, APTN-101, in glioblastoma – the most common and aggressive type of primary brain tumor. 

APTN-101 is a brain bispecific T cell Engager (BRiTE) created with Adaptin’s proprietary platform technology, which utilizes a combination of specifically manipulated T cells with bispecific antibodies to enhance the transport of bispecific antibodies to tissues of interest, including the brain. APTN-101 works by simultaneously targeting the EGFRvIII mutation, a variant commonly found in gliomas, and the CD3 receptor on T cells, in turn ensuring that the treatment is localized and effective, as well as harnessing the body’s own defense mechanisms by activating the T cells and directing them to attack the tumor cells. 

According to the company, in preclinical studies, APTN-101 has shown impressive efficacy in eliminating malignant glioma tumors across various aggressive orthotopic models. The recent FDA clearance will now enable the initiation of a first-in-human phase 1 trial to evaluate the drug candidate in patients who have been diagnosed with WHO Grade 4 malignant glioma (based on the World Health Organization (WHO)’s own grading system). Adaptin is also in the process of evaluating additional BRiTE targets.

Candid Therapeutics 

Another company that emerged in September is Candid Therapeutics, launching with one of the biggest private investments of the month after it managed to raise $370 million in capital. The company is developing T cell engager antibodies that can deplete specific B lymphocyte cell populations for the treatment of autoimmune diseases and is aiming to be the first to bring these novel therapies to the market.

In an unusual move, the T cell engager company’s launch also involved the acquisition of two biotech companies, Vignette Bio and TRC 2004, and their lead assets, CND106 and CND261, respectively. CND106 targets B-cell maturation antigen, while CND261 binds to CD20. Both then also bind to CD3 on the surface of T cells. 

Both candidates have completed phase 1 dose escalation studies with combined data from over 130 oncology patients. Candid is now focused on filing IND applications for them so that the company can study them in autoimmune diseases. Ken Song, chairman, president, and chief executive officer (CEO) of Candid, told Fierce Biotech that he hopes they will have clinical data on at least the drugs’ safety by 2025.

Clasp Therapeutics 

Clasp Therapeutics launched in March 2024 with $150 million to develop precision T cell engagers that are matched to patients with specific immune system and tumor signatures in order to tackle tough-to-treat tumors. 

The T cell engager company targets mutated protein fragments, or peptides, that are displayed by specialized human leukocyte antigen (HLA) molecules on the surfaces of cancer cells. This approach opens up the possibility of targeting the vast majority of cancer-driving proteins that are expressed exclusively inside the cell, and thus invisible to traditional antibody-like drugs. 

Clasp targets these protein fragments with pHLAre molecules, Clasp’s proprietary precision T cell engagers, which are designed to draw T cells into close contact with tumor cells. Clasp says that the resulting immune synapse is highly similar to a natural HLA molecule-T cell receptor interface, triggering T cells to destroy tumor cells, while sparing non-malignant cells.

At the time of its launch, the company said that its funding is large enough to simply work on pushing its programs forward, but would not disclose what its current lead asset is. 

Janux Therapeutics

Janux Therapeutics’ aim is to overcome the safety and efficacy limitations of traditional T cell engagers, which the company says has presented limitations in treating solid tumors, such as overactivation of the immune system leading to cytokine release syndrome (CRS), on-target, off-target effects, and poor pharmacokinetics leading to short half-life. Therefore, Janux is using its platform masking technology to engineer novel drug candidates called tumor activated T cell engagers (TRACTrs) and tumor activated immunomodulators (TRACIrs), which are purposefully designed to enhance tumor-specific activation with crossover pharmacokinetics to provide medicines with improved safety, dosing and efficacy.

The company’s lead asset is a T cell engager called JANX007, is being tested in patients with advanced or metastatic prostate cancer and targets targets prostate-specific membrane antigen (PSMA) and CD3. PSMA a protein expressed in prostate cancer tumors and the vasculature of tumors and is in the clinic for the treatment of metastatic castration-resistant prostate cancer.

In February 2024, Janux announced encouraging data for JANX007 from its ongoing phase 1a trial. Out of the 18 patients who received a starting dose of 0.1 mg, 14 (78%) achieved a prostate-specific antigen (PSA) decline of at least 30%, with 10 of those patients (56%) achieving a decline of 50%. At the time, according to Fierce Biotech, analysts at William Blair also said that this readout had raised their estimation of JANX007’s success from 40% up to 60%.

Lava Therapeutics

Lava Therapeutics N.V. is focused on advancing its proprietary Gammabody platform to develop a portfolio of bispecific gamma-delta T cell engagers for the potential treatment of solid tumors and hematologic malignancies. 

These drugs activate a unique and relatively abundant effector gamma delta T cell subset called Vγ9Vδ2 (Vgamma9 Vdelta2) T cells, which are the largest T cell subpopulation in healthy adults and are naturally occurring in the human immune system. They essentially have a tumor recognition mechanism, allowing them to specifically recognize and kill cells under stress, such as cancerous cells, while leaving healthy cells unharmed. The company’s approach is designed to make the most of this natural tumor recognition to direct Vγ9Vδ2 T cells to the tumor, selectively kill cancer cells, and trigger an immune response cascade.

Lava’s lead program is called LAVA-1207 and is being developed for patients with metastatic castration-resistant prostate cancer. It is currently being tested in a phase 1/2a trial. The T cell engager company also recently signed a partnership deal with Merck to evaluate LAVA-1207 with Keytruda. Consequently, Lava plans to expand its phase 1/2a study to include a combination arm with Keytruda.

T cell engager field set to take off

Some big names within the biotech and pharmaceutical industries have taken to developing or investing in T cell engagers, including Regeneron, which recently received the green light from the European Commission (EC) for its T cell engager treatment for two types of blood cancer, and Amgen, which presented positive data last year for its T cell engager tarlatamab in patients with small-cell lung cancer. Plus, as can be seen from this list, several biotech companies have recently launched specifically to develop these types of medicines.

This sudden spike in interest in T cell engagers suggests that the field is set to take off, and it probably won’t be long before we see multiple drugs of this type hit the market.