Yingli Pharma Announces presentations on the Phase 1 trials of linperlisib, a PI3Kδ selective inhibitor, and YL-13027, an oral TGFβR1 inhibitor, at the American Society for Clinical Oncology 2021 Annu

Shanghai Yingli Pharmaceuticals Ltd, a clinical stage pharmaceutical company providing new therapies for cancer and metabolic diseases, announced today that there will be three presentations on clinical trials sponsored by the company at the annual meeting of the American Society for Clinical Oncology (ASCO) June 4-7, 2021.

Linperlisib in Peripheral T cell lymphoma

The clinical trial report entitled "A phase Ib study of a PI3Kδ inhibitor Linperlisib in patients with relapsed or refractory peripheral T-cell lymphoma" was presented at the June 4, 2021 proceedings of the conference.

In this phase Ib study that enrolled 38 relapsed and refractory Peripheral T cell lymphoma patients, linperlisib, a novel oral PI3Kδ inhibitor, was evaluated as monotherapy for safety, tolerability and efficacy at recommended phase 2 dose of 80mg once daily. The clinical data from an interim data cutoff was presented at ASCO by Dr. Jie Jin, professor of First Hospital Affiliated with Zhe Jiang Medical University. Top line data from this study indicated that for the 38 r/r PTCL patients enrolled, 30 were evaluable. As of the data cutoff, an Overall Response Rate (ORR) of 70% was reported of which 33% were complete responses. A 100% disease control rate was also observed. Linperlisib was well-tolerated with Grade 1 and Grade 2 adverse events most frequently observed, and with limited Grade 3 adverse events of neutrophil decrease in 4 pts, (10.5%), and 1 (2.6%) case each of leukopenia, thrombocytopenia, blood lipase increase, pneumonia and stomatitis.

"Peripheral T cell lymphoma is a devastating and aggressive lymphoma where patients have very few treatment options in the relapsed and refractory setting," said Dr. Jie Jin. "The results of this Phase1b clinical trial suggest that linperlisib is a promising PI3Kδ selective inhibitor with important anti-tumor properties in this indication, and we hope it will be able to bring clinical benefits of linerlisib to patients suffering from this serious disease. Globally, there are no PI3K inhibitors that have been approved for the treatment of T cell lymphomas. In China, no PI3K inhibitors have been approved for any indications. By evaluating linperlisib for its safety, tolerability and efficacy, we are optimistic that this novel oral therapy will advance into registration clinical trials in PTCL for regulatory approval."

Linperlisib evaluated in advanced solid tumors

Another clinical study of linperlisib was also presented at ASCO entitled "A phase Ib study of the PI3Kδ inhibitor linperlisib in patients with advanced solid tumors". In this study that enrolled 78 advanced solid tumor patients, linperlisib monotherapy was evaluated for safety, tolerability, and durability at the recommended phase2 dose of 80 mg once daily, the dose previously established for the treatment of lymphomas. The clinical data from an interim analysis of this study was presented by Dr. Jin Li, Professor and Oncologist at Shanghai East Hospital.

Linperlisib is an immunomodulatory PI3Kδ inhibitor in solid tumors that has been demonstrated to alter the tumor immune microenvironment in preclinical research. "These properties of solid tumors are a challenge for therapeutic intervention because the regulatory immune cells will frequently repress an anti-tumor immune response. Our hypothesis is that linperlisib will unleash the anti-tumor suppression in a beneficial manner for patient treatments", said Zusheng Xu, General Manager of Yingli Pharma.

In the open-label Phase 1b study including 15 advanced solid tumor types, linperlisib was demonstrated to be safe and well-tolerated. The most common treatment related adverse events were Grade 1 and Grade 2, with the Grade 3 TRAE of neutropenia (3.8%), diarrhea (2.6%), elevated γ-glutaminase (1.3%) and leukopenia (1.3%) observed. The disease control rate with linperlisib monotherapy was reported to be 41.4%, with one complete response observed in a patient with thymic carcinoma.

Dr. Jin Li stated "Linperlisib is a PI3K inhibitor with a distinct chemical structure highly selective to the δ isoform, compared to other PI3K inhibitors. The preliminary clinical findings are supportive of Linperlisib demonstrating a favorable safety profile with very limited off-target effects that have been associated with other PI3K inhibitors in the clinic. We were pleased to see that Linperlisib can be administered to patients with advanced solid tumors in a manner that is safe and well-tolerated. Linperlisib has great potential for combination therapies and additional indications in the future. We committed to investigating how this new PI3K inhibitor can improve the health condition of patients suffering from advanced solid tumors."

YL-13027, a novel and selective TGFβR1 inhibitor in a Phase 1 dose escalation study

A first-in-human clinical trial of YL-13027, an oral, potent, and selective TGFβR1 inhibitor, is being presented at the ASCO meeting, entitled "A phase I study of a TGF-β receptor I kinase inhibitor YL-13027 in patients with advanced solid tumors".

TGFβ signaling is known to be a driver contributing to the immunosuppressive properties of many solid tumors. In principle, agents that interfere with TGFβ signaling may be beneficial towards interrupting tumor progression and supplying additional targets for anti-cancer therapies. YL-13027 was developed as a potent small molecule inhibitor of TGFβR1, a tyrosine kinase, and has demonstrated anti-tumor efficacy in preclinical models. In this open-label phase1 dose escalation study, the initial safety evaluation of YL-13027 was presented. The most frequent treatment related adverse events in twelve patients who had completed Cycle 1 safety evaluation period as of the data cut, were the following (all Grades/≥Grade 3): γ-glutamyl transferase elevation (38.5%/7.7%), hemoglobin decrease (38.5%/0%), blood alkaline phosphatase elevation (23.1%/7.7%), AST (23.1%/0%), and blood phosphorus decrease (23.1%/0%). Of the 6 evaluable patients with advanced solid tumors treated as of the data cutoff date, 1 triple negative breast cancer patient had a confirmed Partial Response.

"In recent years, immunotherapy has gradually replaced chemotherapy and radiotherapy, and has shown good clinical results for different types of advanced solid tumors, but we still encounter bottlenecks in terms of safety, tolerability and tumor indication selection'' said Dr. Jin Li, professor of Shanghai East Hospital, and a lead investigator on the study. "YL-13027 has demonstrated to be a safe and tolerable oral agent that is highly selective for TGFβR1 over TGFβR2. These results are giving us confidence for the dose escalation of YL-13027, and its performance on other tumor types and combination therapies. We are very optimistic about the further development of YL-13027 as an anti-cancer agent."

Schedule for Linperlisib and YL-13027 presentations at ASCO

Abstract # 7531; 'A phase Ib study of a PI3Kδ inhibitor Linperlisib in patients with relapsed or refractory peripheral T-cell lymphoma' is being presented in the Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia Session. Citation: J Clin Oncol 39, 2021 (suppl 15; abstr 7531)

Abstract # 3099; 'A phase Ib study of the PI3Kδ inhibitor linperlisib in patients with advanced solid tumors' is being presented in the Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology Session. Citation: J Clin Oncol 39, 2021 (suppl 15; abstr 3099)

Abstract # 3098; 'A phase I study of a TGF-β receptor I kinase inhibitor YL-13027 in patients with advanced solid tumors' is being presented in the Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology Session. Citation: J Clin Oncol 39, 2021 (suppl 15; abstr 3098)

About Linperlisib

Linperlisib (YY-20394) is a highly selective and potent PI3Kδ inhibitor that has shown favorable safety profile, exciting anti-tumor activities, and good PK and pharmaceutical properties as an oral once-a-day agent in late-stage clinical development. A phase 1 clinical trial was completed in 2020 demonstrating linperlisib to be a safe and tolerable agent, and a recommended phase 2 dose of 80 mg QD was established. Linperlisib received FDA Orphan Drug Designations for FL, CLL/SLL, and T cell lymphoma. Linperlisib was awarded NMPA Breakthrough Therapy status in China.  A clinical trial in r/r FL for 93 patients having 2 or more prior systemic therapies has been completed and submitted for marketing approval in China. Additional linperlisib clinical trials are ongoing in other lymphomas, solid tumors, and in combination with gemcitabine/oxaliplatin in r/r DLBCL.

About YL-13027

YL-13027 is a potent small molecule antagonist of TGFβR1 kinase activity in early-stage clinical development. The compound was optimized with selectivity against TGFβR2 and other tyrosine kinases, differentiating YL-13027 from other inhibitors blocking TGFβ signaling. In preclinical studies, YL-13027 demonstrated anti-tumor efficacy and combination benefit with immunotherapy. In IND-enabling studies, YL-13027 showed reliable dose-proportionality and pharmacokinetic properties, and the agent proved to be safe and tolerable in toxicity studies. A phase 1 dose escalation of YL-13027 is continuing to establish a recommended phase2 dose of YL-13027.

About Yingli Pharma

Yingli Pharma, headquartered in Shanghai with a subsidiary in San Francisco, is an innovative clinical stage biopharmaceutical company. Yingli Pharma is developing best-in-class and first-in-class oral investigational agents for the treatment of cancer, metabolic and autoimmune diseases. Yingli Pharma currently has three investigational agents in clinical development, linperlisib (YY-20394) and YL-13027 in advanced cancers, as well as YL-90148, an investigational oral URAT-1 inhibitor for the treatment of in hyperuricemia/gout. Several additional oncology programs are in IND-enabling or candidate development stages.