Yifang Biopharma recently shared updates on its innovative drug development pipeline, including positive Phase II clinical trial results for its TYK2 inhibitor, D-2570, in treating moderate to severe plaque psoriasis. The company also provided updates on its KRAS G12C inhibitor, Gesolexab (D-1553), and its oral selective estrogen receptor degrader (SERD), D-0502.
D-2570 for Psoriasis: Phase II Trial Results
The Phase II clinical trial of D-2570, initiated in December 2023, was a multicenter, randomized, double-blind, placebo-controlled study (NCT06278350) designed to evaluate the efficacy and safety of D-2570 in patients with moderate to severe plaque psoriasis. The trial enrolled 161 patients who were randomly assigned to low, medium, and high dose groups or a placebo control group. Patients received D-2570 tablets orally once daily for 12 weeks.
The results of the trial demonstrated that all efficacy measures in the three D-2570 dose groups showed statistically significant differences compared to the placebo group (P<0.001). At 12 weeks, PASI 75 response rates were between 85.0% and 90.0% in the D-2570 groups, compared to 12.5% in the placebo group, thus meeting the primary endpoint. Furthermore, PASI 90 response rates ranged from 70.7% to 77.5% in the D-2570 groups versus 5.0% in the placebo group, and PASI 100 response rates were 39.0% to 50.0% versus 2.5% in the placebo group. The sPGA 0/1 response rate ranged from 80.5% to 87.5% versus 20.0% in the placebo group.
D-2570 was reported to be well-tolerated and safe across all dose groups. The majority of adverse events and adverse reactions were mild to moderate, with an overall incidence slightly higher than the placebo group. Importantly, no serious adverse events (SAEs) were observed, aligning with the safety profile of similar TYK2 inhibitors.
Gesolexab (D-1553) for Non-Small Cell Lung Cancer
Gesolexab tablets (trade name: Anfanin®) received approval from the National Medical Products Administration (NMPA) in November 2024 for treating adult patients with advanced non-small cell lung cancer (NSCLC) harboring KRAS G12C mutations who have previously undergone at least one systemic therapy.
The first subject enrollment has been completed in a Phase III clinical study evaluating D-1553 versus docetaxel in KRAS G12C-mutation-positive locally advanced or metastatic NSCLC that has failed prior standard therapy. This randomized, controlled, double-blind, double-dummy, multicenter study is currently underway.
Additionally, D-1553 has been granted Breakthrough Therapy Designation (BTD) by the CDE for two indications: pancreatic ductal adenocarcinoma and colorectal cancer. A Phase II single-arm registrational clinical study of D-1553 for second-line and above advanced pancreatic ductal adenocarcinoma with KRAS G12C mutations is also underway. In September 2024, data from the Phase II study in NSCLC with KRAS G12C mutation was presented at the World Conference on Lung Cancer (WCLC), demonstrating an objective response rate (ORR) of 52%, a disease control rate (DCR) of 88.6%, a median duration of response (DOR) of 12.5 months, and a median progression-free survival (PFS) of 9.1 months. The median overall survival (OS) was 14.1 months.
D-0502 for Breast Cancer
D-0502, an oral selective estrogen receptor degrader (SERD), is currently in a Phase III clinical trial for second-line treatment in China, with ongoing international multi-center clinical trials in both China and the United States. Phase Ib safety and efficacy data (NCT03471663) of D-0502 monotherapy in estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer were presented at the 46th San Antonio Breast Cancer Symposium. The results indicated a good safety profile and initial anti-tumor effects, with a clinical benefit rate of 47.1% and an ORR of 15.7%. In subjects similar to the fulvestrant CONFIRM study, the median PFS was 7.4 months.
Other Pipeline Developments
D-0120, a Urate transporter 1 (URT1) inhibitor, is undergoing a Phase IIb clinical trial in China and a Phase II clinical trial in combination with allopurinol in the U.S.
