T cell receptor (TCR) therapies equip T cells with receptors that target faulty and malignant cells. This offers patients a more personalized approach to treating cancers.
Over the years, TCR therapies have gained momentum, with Immunocore’s eye cancer drug earning the first-ever TCR therapy approval. As more biotechs step up in the TCR space, here are seven companies with promising candidates in the clinic.
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Adaptimmune
Headquartered in the U.K., Adaptimmune is a company focused on bringing its TCR therapies to the market. Dubbed SPEAR T-cells, which is short for Specific Peptide Enhanced Affinity Receptor T cells, the company’s therapies are designed to treat a wide range of cancer types.
TCRs scan the body for disease targets, and those T cells that identify healthy cells are removed during thymic selection, to specifically target only diseased cells. Adaptimmune’s SPEAR T cells use the patient’s own T cells, which are then modified to create enhanced TCRs that can recognize cancer cells without disturbing normal, healthy cells.
Most advanced in its pipeline is afamitresgene autoleucel, for which the U.S. Food and Drug Administration (FDA) has granted priority review to a biologics license application (BLA). If approved, the candidate will be used to treat synovial sarcoma, a rare type of cancer that develops from soft tissues like fat, muscles, and nerves. Its BLA clearance was based on data from a phase 2 trial where it had a 39% overall response rate (ORR), and it was estimated that patients who responded to the drug have a 70% chance of being alive at two years post-treatment.
The biotech also has Lete-cel, which targets the solid tumor antigen NY-ESO-1, in phase 2/3 trials for synovial sarcoma and myxoid/round cell liposarcoma – a rare cancer that grows in the cells that store fat in the body. And, uza-cel, which targets MAGE-A4, is in phase 1 trials to treat head and neck, and bladder cancer.
Last year, the biotech merged with Massachusetts-based TCR² Therapeutics, in a deal where Adaptimmune’s shareholders would own 75% of the combined company.
Affini-T
Specializing in TCR therapies, Affini-T’s therapies are autologous, meaning that T cells are collected from patients, which are then programmed to be target-specific. Once the cells are engineered, the company’s THRIVE platform scales up development, after which the cells are infused back into the patient.
With the help of its TETHER platform, it identifies highly specific and potent TCRs against endogenously presented oncogenic driver peptides to generate bispecific T cell engagers with balanced CD3 binders, aimed at improving T cell responses.
The American biotech has two candidates in the clinic, namely AFNT-111 and AFNT-211, both of which target KRAS G12V, one of several KRAS mutations that exist. The phase 1 trial of AFNT-111 aims to study the side effects and best dose of autologous CD8+ and CD4+ transgenic T cells expressing high affinity KRAS G12V mutation-specific T cell receptors and determine how well patients with pancreatic, colorectal, and non-small cell lung cancers respond to the treatment.
Last year, Affini-T collaborated with Memorial Sloan Kettering Cancer Center in New York to expand the company’s pipeline of oncogenic driver programs.
Immatics
Immersed in the field of TCR therapeutics, German biotech company Immatics is developing Adoptive Cell Therapies (ACT) consisting of autologous and allogeneic candidates as well as antibody-like TCR bispecifics, called T cell Engaging Receptors (TCER).
TCERs are biologics that are designed to bind T cells to target and destroy cancer cells. It contains a portion of the TCR which directly recognizes cancer cells and a T cell recruiter domain which recruits and activates the patient’s T cells.
Most advanced in its pipeline is its autologous TCR therapy, IMA203, which targets the preferentially expressed antigen in melanoma (PRAME) in patients with recurrent and refractory solid tumors. According to interim phase 1a data, the drug candidate had a 50% confirmed objective response rate (cORR) in patients with melanoma and the durability with some ongoing responses crossed 15 months, although the median duration of response was not reached at a median follow-up of 14.4 months.
Last year, Immatics embarked on a partnership with Moderna, where it received $120 million upfront, and stands to secure more than $1.7 billion in milestone payments. More recently, Immatics received a $175 million public offering.
Immunocore
British company Immunocore has a variety of TCR therapies in its roster. Most advanced in the clinic is Kimmtrak, a bispecific protein made up of a TCR fused to an anti-CD3 immune-effector function. The drug targets gp100, an antigen that is expressed in skin cancers like melanoma.
It was cleared by the FDA to treat uveal melanoma, a rare cancer that affects the eye. Its approval two years ago was following a successful phase 2 study where the drug had a median overall survival rate of 21.7 months versus 16 months for patients in the control group, with an almost 50% lower risk of death.
Now, the biotech is studying Kimmtrak as an adjuvant therapy for uveal melanoma in a phase 3 trial and in cutaneous melanoma in a phase 2 trial. Apart from Kimmtrak, it is developing IMC-F106C, for a number of indications. The candidate, which targets PRAME, is in phase 2 and 3 trials to treat cutaneous melanoma, a type of skin cancer. It is also evaluating the drug against ovarian, endometrial, non-small cell lung cancers, and solid tumors.
Immunocore has partnered with pharma giant Bristol Myers Squibb to test IMC-F106C in combination with the latter’s immune checkpoint inhibitor, nivolumab, in first-line advanced cutaneous melanoma.
Lion TCR
With operations in Singapore and China, Lion TCR aims to tackle viral infections by advancing its TCR therapies in the clinic. Its autologous TCR therapy targets the hepatitis B virus in hepatocellular carcinoma (HCC), a type of liver cancer, and is in preclinical development in chronic hepatitis B. HBV infections increase the risk of HCC, accounting for at least 50% of HCC cases worldwide and at least 80% of cases in Asia.
In advanced HCC, the candidate is undergoing a multi-center phase 2 trial. Besides, it has allogeneic TCRs in the preclinical stages for viral diseases as well as TCR bispecific antibodies aimed at targeting chronic hepatitis B.
The biotech has formed a partnership with MaxCyte, an American, cell-engineering company, to boost MaxCyte’s presence in Asia, as well as potentially expand its U.S. and European markets. As a result, Lion TCR will be granted clinical and commercial rights to use MaxCyte’s Flow Electroporation technology for cell engineering.
Last year, the company bagged $40 million in a series B fundraise to support its HBV-targeting clinical trials.
Neogene Therapeutics
AstraZeneca-owned Neogene Therapeutics is building a portfolio of TCR therapy candidates to address solid tumors.
Its autologous, fully-individualized TCR therapy, NT-125, is designed to contain up to five distinct neoantigen-specific TCRs per patient in a single cell product. The candidate is in phase 2 in the clinic to treat a variety of solid tumors. NT-125 aims to reduce the probability of antigen escape and looks to maximize the depth and durability of clinical responses in a patient population with difficult-to-treat tumors and high unmet need.
The biotech also has NT-175 and NT-112 in clinical trials.
AstraZeneca’s acquisition of the company was completed in January last year. Neogene received $200 million upfront, and according to the terms, was expected to receive $120 million in milestone payments. Previously, the company collaborated with the National Cancer Institute in the U.S., to strengthen its portfolio of TCRs targeting KRAS and TP53 mutations.
TScan Therapeutics
TScan Therapeutics’ TCR discovery process involves an immunobank where targets and receptors are screened against one another to ensure the safety of the drugs moving forward. This allows for TCR therapies to potentially address an array of solid tumors.
The American biopharma has multiple candidates in early-stages in the clinic. Its TCR, TSC-100, which is being investigated in patients with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia, is in a phase 1 study. Its other lead candidate is TSC-101, for the same indications as TSC-100.
Last month, the company announced encouraging trials results for both the lead candidates. All the eight patients in the treatment arm were relapse-free and achieved complete donor chimerism. Chimerism is the state in which donor cells have been properly engrafted in the recipient. Patients with high-risk MDS were found to be relapse-free for more than a year after being treated with TSC-101.
Last year, multinational pharmaceutical Amgen joined forces with TScan Therapeutics to discover new targets for Crohn’s disease.
TCR therapy market set to grow
The TCR therapy market was estimated to be worth $0.03 billion last year, and the market is expected to witness an annualized growth rate of 51% in the next decade, according to the market research firm Roots Analysis.
Lately, investors have been betting on TCR therapies as well. University of Cambridge spin-out T-Therapeutics, which develops TCRs, raised £48 million ($59 million) in a venture round last November. Moreover, TCR developers Adaptimmune and TCR2 Therapeutics came together to form a company focused on bringing TCRs for solid tumors to the market. Plus, AstraZeneca’s acquisition of Neogene and Lion’s stronghold in Asia, indicate that the global TCR market seems to be looking up.
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