AACR 2022: LAG-3, one of the most trending Next-generation Immunotherapy

Updates on F-star Therapeutics’ and Akeso’s Bi-specific Antibody targeting LAG-3 and PD-L1

F-star Therapeutics presented the preclinical mechanistic data on the Novel LAG-3 Reduction and Shedding Mechanism with FS118 at AACR 2022. The data demonstrated that the tetravalent and unique structure of FS118 played a critical role in driving LAG-3 shedding and cell surface reduction by Tumor Infiltrating Lymphocytes (TILs), which enables FS118 to overcome compensatory up regulation of LAG-3 induced by PD-(L) 1 blockade in patients with cancer.  This bi-specific antibody demonstrated simultaneous binding to LAG-3 and PD-L1 with high affinity that resulted in enhancing T-cell activity. We expect the drug’s potential to overcome immunotherapy resistance once it enters the pivotal studies.

As per recent updates, the company intends to provide preliminary data from a Phase II proof-of-concept trial in PD-(L) 1 acquired resistance patients with PD-1 Resistant Head and Neck Cancer in mid-2022, with the possibility for a fast registration route. In addition, the company is exploring a wider potential for FS118 with a CPI naive study in NSCLC and DLBCL. The company anticipates the first data read-out for NSCLC and DLBCL in the first and second halves of 2023, respectively.

In addition to F-star Theraputics, Akeso, a china based company also announced positive preclinical results of its bi-specific antibody AK129, which showed good antigen binding to PD-1 and LAG-3. AK129 demonstrated a similar PD-1 blocking activity compared to penpulimab, and similar LAG-3 blocking activity compared to relatlimab.

Recently, Lag-3 space has witnessed the approval of BMS’ Opdualag (Opdivo + Relatlimab), which is BMS’ third cancer checkpoint inhibitor class in immune-oncology and the first approval in LAG-3 space ever. As per Delveinsight’s analysis, we project Opdualag’s revenue to exceed USD 1.5 billion in the United States considering that the company is conducting multiple trials for this drug in liver cancer, NSCLC, head & neck, colorectal, gastric, renal, STS, Chordoma, Basal Cell Carcinoma, and many others — demonstrating the asset’s wide potential.

Taking into consideration, the expected strong uptake of Relatlimab, we expect Immutep’s Eftilagimod alpha to follow behind. Immutep’s Eftilagimod alpha is the only soluble LAG-3 fusion protein among developing LAG-3 therapies.

Apart from F-star’s bispecific , companies such as Merck (favezelimab [MK-4280]), Immutep (eftilagimod alpha [IMP321]), Incyte Corporation (INCAGN02385), EpimAb Biotherapeutics (EMB-02), Roche (RG6139 [RO7247669]), Xencor (XmAb22841 [XmAb841]), AnaptysBio/GlaxoSmithKline (Encelimab [TSR-033]), Macrogenics (Tebotelimab [MGD013]), Regeneron Pharmaceuticals/Sanofi (Fianlimab [(REGN3767]),Symphogen (Sym022)andothersare involved in the development of LAG-3 therapies.

As per our analysis, the LAG-3 next-generation therapies market is expected to grow in the upcoming years owing to the potential entry of these major LAG-3 candidates and their readily uptake, increase in incident cases of various solid tumors, increase in PD-1/PD-L1 relapsed/refractory cases in various cancers, label–expansion in multiple cancer types, robust and unique pipeline (anti-LAG-3 monoclonal, bispecific antibodies and, soluble LAG-3 molecule), and improvement in the outcome of patients.

Looking at the current scenario, LAG-3 space will have several intended and unintended rivals in the market in near future. Due to high competitiveness in future with expected entry of other novel therapies, the fight will be based on the first-to-market race, market positioning (target patient pool, and line of therapy) and differentiated efficacy, as well as a better safety profile along with convenient dosage schedule

For more information, refer to Delveinsight’s- “LAG-3 Immunotherapy Next-generation Immunotherapies- Competitive Landscape & Market Forecast- 2035” Report.