Historic Milestone: Global TIL Pipeline Overview and Key Players

On February 16, good news came from the eastern shore of the Pacific: Lifileucel, the world's first TIL therapy, was approved for marketing by the FDA, adding a touch of warmth to this cold winter.

This is not only the world's first approved TIL therapy, but also the first T-cell therapy approved for the treatment of solid tumors, marking a milestone.

Tumor-Infiltrating Lymphocyte (TIL) therapy is a type of cellular drug based on the patient's own tumor-infiltrating lymphocytes. It boasts advantages such as a rich variety of tumor-specific targets, excellent tumor tropism, strong infiltration capability, and minimal side effects.

A large amount of clinical evidence has confirmed that TIL therapy has unique advantages for solid tumors such as melanoma, head and neck cancer, cervical cancer, and non-small cell lung cancer.

Apart from Lovance, there are alsoAchilles Therapeutics, Instil Bio, Obsidian, and TurnstoneSuch companies are laying out their strategies in China.DISCOVERY TO CURE, Grail Bio, Junse Biotech, Cellular Biomedicine Group, CartiHeal Medical, Lanma Medical, BioGencyDISCOVERY TO CURE is also actively exploring its potential and value in the treatment of other solid tumors.

The following are the main TIL pipelines in the global clinical stage:

Overall, due to the high difficulty of production technology, compared with CAR-T therapy,Global TIL Therapy Still in Early Stages of Development，Most pipelines are in clinical Phase I., and the approved clinical time is relatively short.It is precisely because of this that, in terms of preparation technology, clinical pathways, etc.,AlsoProviding broad exploration space for innovative enterprises。

Among the companies, Lovance is in an absolute leading position. In addition to the already marketed Lifileucel, its LN-145 has entered the Pivotal trial. The two most advanced pipelines, LN-145-S1 (PD-1 selective TIL therapy) and LN-145-Gen 3 (third-generation TIL therapy), have both entered Phase II clinical trials.

LN-145 has been granted Breakthrough Therapy Designation by the U.S. FDA for the treatment of patients with recurrent, metastatic, or persistent cervical cancer after receiving chemotherapy.

In addition, to expand the market coverage of Lifileucel, Lovance has been testing the product in combination with anti-cancer therapies and exploring its use in other types of cancer.

The fastest progressing company in China is DISCOVERY TO CURE.Its independently developed GT101 injection received the clinical trial implied permission from the National Medical Products Administration (NMPA) in April 2022, which isChina's First Approved Clinical TIL Therapy。

Grail Bio was founded in 2019. Since its establishment, the company has built TIL drug preparation processes, a cell drug development system, and multiple technical platforms applied to the development of next-generation TIL drugs.

The most low-key company should be DISCOVERY TO CURE, which was founded in 2020 by Dr. Fu Li Yu, who has rich experience in pharmaceutical technology product development and enterprise management. The company focuses on rapidly advancing the research and development and clinical application of tumor cell therapy products.

Silent but powerful,DISCOVERY TO CURE, founded less than two years ago, has advanced its TIL immunotherapy into Phase I clinical trials.

Equally noteworthy is CBMG, which was first established in 2010 and officially listed on NASDAQ in 2014, becomingThe First Chinese Cell Therapy Biopharmaceutical Technology Company Listed on NASDAQ。

In October 2022, CBT Biopharma announced that the FDA had approved the IND application for the company's novel TIL therapy, C-TIL051, for the treatment of advanced non-small cell lung cancer that is refractory or relapsed after PD-1 antibody therapy.

C-TIL051 utilizes CBMG's proprietary process, achieving clinical doses in the human body faster and more efficiently than TIL produced by traditional manufacturing methods.

From the perspective of indication layout, multiple pipelines correspond to various indications,Covering a wide range of solid tumor types including melanoma, non-small cell lung cancer, cervical cancer, lung cancer, and squamous cell carcinoma of the head and neck.。

Among them, BST02 under DISCOVERY TO CURE isThe World's First Liver Cancer TIL Therapy to Enter Clinical DevelopmentIt is a T-cell therapeutic product amplified from the patient's own tumor-infiltrating lymphocytes (TIL) and belongs to adoptive immunotherapy technology.

GC101, developed by JunSai Bio, is the world's first non-genetically modified TIL cell therapy product that requires neither lymphocyte depletion nor IL-2 infusion.

From a temporal perspective, 2023 marks the first year of TIL therapy development. Numerous TIL cell products in China have been successively approved for clinical trials, continuously achieving new R&D progress and setting multiple "first-ever" records.

In May, the world's firstTreatmentTumor-Infiltrating Lymphocytes (TIL) in Patients with Advanced Melanomatil）Therapy--Lifileucel (LN-144 Lifileucel) Receives FDA Priority Review, This is the First...FDASubmission of Biologics License ApplicationTIL Therapy。

January,Zhilin BioDISCOVERY TO CURE's second-generation TIL cell drug ZLT-001 injection has been approved for clinical trials, with indications for advanced recurrent or metastatic cervical cancer. This is the first TIL drug approved for clinical trials in South China.

This candidate product, purified by Zhi Ling Bio using unique technology, enhances TIL activity and the ability to kill solid tumors, expanding the cell count to billions or even tens of billions, with the aim of achieving rapid tumor cell killing after infusion.

January,Thick Without Biology / Tianke EleganceDISCOVERY TO CURE's HV-101 injection receives clinical trial approval in China for treating advanced recurrent or metastatic solid tumors.

July,Blue Horse MedicalDISCOVERY TO CURE's LM103 injection has been approved for clinical trials, marking the first clinical approval in China's TIL field to use the Feeder cell process.

September,Huasai BermanThe IND application for the first TIL therapy, HS-IT101, has been accepted by the CDE for the treatment of advanced solid tumors, and a Phase I clinical trial was initiated in January this year.

HS-IT101 is an enhanced TIL product that primarily achieves the required clinical infusion dose from a small amount of tumor tissue through optimized processes, while reducing the amount of IL-2 used, decreasing side effects, and shortening production time.

October,Baiji BioBST02's I/II Phase Clinical Trial Application Approved by U.S. FDA for the Treatment of All Types of Liver Cancer, Becoming the World’s First TIL Cell Therapy Drug for Liver Cancer to Enter Clinical Trials.

Overall, the trend of TIL therapy in China entering a phase of rapid development is a positive signal, which is expected to bring more treatment options and hope for cancer patients. However, it is also necessary to pay attention to issues related to product quality, safety, cost-effectiveness, and to strengthen the supervision and management of clinical applications and market regulation.