Five T-cell engager companies you need to know about

T cell engagers are antibodies designed 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 activate a molecule on T cells. These therapeutic molecules then engage T cells that are present in tumors but are unable to recognize cancer cells, redirecting their activity to the tumor.

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

In this article, we look at five T-cell engager companies that are leading in this emerging field.

Adaptin Bio

To have emerged from stealth Beginning in September 2024, Adaptin Bio will develop precision cancer therapies with enhanced delivery to the brain and other tissues. At the same time it emerged from stealth, the company announced that it had received approval from the U.S. Food and Drug Administration (FDA) for 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 uses a combination of specifically engineered T cells with bispecific antibodies to facilitate 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, ensuring that the treatment is localized and effective, and the body’s own defense mechanisms are utilized by activating the T. cells and orders them to attack the tumor cells.

According to the company, APTN-101 has shown impressive efficacy in eliminating malignant glioma tumors in several aggressive orthotopic models in preclinical studies. The recent FDA approval will now enable the initiation of a first-in-human Phase 1 study to evaluate the drug candidate in patients diagnosed with WHO Grade 4 malignant glioma (based on the World Health Organization’s own classification (WHO). Adaptin is also evaluating additional BRiTE targets.

Candid therapies

Another company that emerged in September is Candid Therapeutics, launch with one of the largest 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 aims to be the first to commercialize these new therapies.

In an unusual move, the launch of the T-cell engager company also included the acquisition of two biotech companies, Vignette Bio and TRC 2004, and their leading 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 more than 130 oncology patients. Candid is now focused on filing IND applications for them so the company can screen them for autoimmune diseases. Ken Song, chairman, president and CEO of Candid, told Fierce Biotech that he hopes they will have clinical data on the safety of the drugs at least by 2025.

Closure therapy

Closure therapy launched in March 2024 with $150 million to develop precision T-cell engagers tailored to patients with specific immune systems and tumor signatures to tackle difficult-to-treat tumors.

The T-cell engager company focuses on 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-causing proteins that are expressed exclusively within 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 bring T cells into close contact with tumor cells. Clasp says the resulting immune synapse closely resembles a natural HLA molecule-T cell receptor interface, prompting T cells to destroy tumor cells while sparing non-malignant cells.

At the launch, the company said the funding is large enough to simply work on advancing its programs, but wouldn’t reveal what its current key asset is.

Janux Therapeutics

Janux Therapeutics’ goal is to overcome the safety and efficacy limitations of traditional T cell engagers, which the company believes have presented limitations in the treatment of 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 a short half-life. Therefore, Janux is using its platform masking technology to develop new 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 target drugs with improved safety. , dosage and efficacy.

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

In February 2024 Janux announced encouraging data for JANX007 from the ongoing Phase 1a study. Of the 18 patients given a starting dose of 0.1 mg, 14 (78%) achieved a prostate specific antigen (PSA) reduction of at least 30%, with 10 of these patients (56%) achieving a 50% reduction achieved. . At that time, according to Fierce BiotechAnalysts at William Blair also said this reading increased their estimate of JANX007’s success from 40% to 60%.

Lava therapy

Lava Therapeutics NV 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 hematological malignancies.

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

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 agreement with Merck to evaluate LAVA-1207 with Keytruda. Therefore, Lava plans to expand its Phase 1/2a study to include a combination arm with Keytruda.

T cell engager field ready to go

Some big names in the biotech and pharmaceutical industries have begun 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. Furthermore, as this list shows, several biotech companies have recently been launched that specifically aim to develop these types of drugs.

This sudden spike in interest in T-cell engagers suggests that this field is about to take off, and it likely won’t be long before we see several of these types of drugs hit the market.