BI-1206 is a high-affinity monoclonal antibody that selectivity binds to FcγRIIB (CD32B), the only inhibitory member of the FcγR family. FcγRIIB is overexpressed in several forms of NHL and overexpression has been associated with poor prognosis in difficult-to-treat forms of NHL, such as mantle cell lymphoma.
By blocking FcγRIIB, BI-1206 is expected to recover and enhance the activity of rituximab or other anti-CD20 monoclonal antibodies in the treatment of these diseases. The combination of the two drugs could provide a new and important option for patients suffering from NHL and represents a substantial commercial opportunity.
Clinical phase 1/2a study ongoing with BI-1206 in combination with rituximab and acalabrutinib for the treatment of non-Hodgkin’s lymphoma (NHL).
While anti-CD20 antibodies such as rituximab are a cornerstone of NHL care, approximately 15% of patients are refractory to treatment and 25% relapse within 3 years after treatment. The inhibitory Fc receptor CD32b (FcγRIIB) promotes resistance by triggering tumor cells to internalize and destroy rituximab. BI-1206 has been designed as an anti-FcγRIIB mAb to block rituximab internalization.
BioInvent is conducting a Phase 1/2a trial in several R/R B-cell NHL subtypes to evaluate safety and tolerability of BI-1206 in combination with rituximab and acalabrutinib. In September 2024, the company announced that the first patient has been enrolled in the triple combination arm of the Phase 1/2a study of BI-1206 in non-Hodgkin's lymphoma (NHL).
The Phase 2a study arm will combine the subcutaneous formulation of BI-1206 and rituximab with Calquence® (acalabrutinib), a selective inhibitor of Bruton's tyrosine kinase (BTK). Approximately 30 patients are expected to be enrolled in Spain, Germany, the US, and Brazil. Preliminary data are expected by the end of 2024. In February 2024 BioInvent signed a clinical supply agreement with AstraZeneca (LSE/STO/Nasdaq: AZN) to provide Calquence® for the combination arm.
Based on the presented strong data, the subcutaneous formulation of BI-1206 was selected for the ongoing triplet study.
As anti-CD20 based therapy will remain central for the treatment of NHL, BI-1206 has the potential to be uniquely positioned within NHL.
Safety and Efficacy Results of BI-1206 + rituximab (as of October 2024):
Additional positive data have been observed in the Phase 1 part of the study with BI-1206 as subcutaneous (SC) formulation for the treatment of relapsed/refractory (R/R) non-Hodgkin's lymphoma (NHL). As of October 2024, one additional complete response (CR), one more partial response (PR) and two more patients with stable disease (SD) are reported. This data adds to the positive data previously reported at the EHA 2024 (European Hematology Association) conference in June this year. For BI-1206 as a subcutaneous formulation, a total of two CR, three PR and three SD out of nine evaluable patients have now been observed.
At EHA 2024, first data for the subcutaneous (SC) study arm were presented and the results then showed one CR, two PR and one SD out of four evaluable patients.
All patients in BioInvent's study with BI-1206 have previously received at least one previous line of rituximab-containing treatments. For the subgroup of patients with follicular lymphoma (FL), IV and SC dosing have so far in total yielded response rates of 55% ORR (overall response rate), 35% CRR (complete response rate) and 85% DCR (disease control rate).
In the responding patients, the responses have been long-lasting, several of them have lasted several years after the end of treatment. The results show how BI-1206 can restore the efficacy of rituximab in the treatment of advanced NHL.
Study design
The Phase 1/2a study (NCT03571568) is divided into two parts:
Phase 1, dose escalation with the aim of selecting the dose of BI-1206 to be further studied in Phase 2a; and
Phase 2a, this part consists of a signal seeking with a safety run-in, , and a dose optimization to select the recommended dose of BI-1206 in combination with rituximab and acalabrutinib.
CASI Pharmaceuticals – our partner in China
Since October 2020, BioInvent has a licensing agreement in place with CASI Pharmaceuticals for China, Hong Kong, Macau and Taiwan. Under the terms of the agreement, BioInvent and CASI will develop BI-1206 in both hematological and solid cancers, with CASI responsible for commercialization in China and associated markets. BioInvent received USD 12 million upfront in combination of cash and equity investment and eligible to receive up to USD 83 million in milestone payments, plus tiered royalties.