Dizal Leads China's Biotech Innovation by Showcasing Strength of its Oncology Pipeline at 2023 ASCO

• Two highly anticipated oral presentations captured attention: first pivotal study of sunvozertinib (WU-KONG6) and multinational pivotal study of golidocitinib (JACKPOT8)
• Sunvozertinib achieved an ORR of 60.8% in ≥ second-line treatment and 77.8% in the first-line treatment for EGFR Exon20ins NSCLC
• Sunvozertinib demonstrated durable benefit in advanced NSCLC patients with TKI-resistant EGFR sensitizing mutations with a mPFS of 5.8 months and mDoR of 6.5 months
• Golidocitinib achieved an ORR of 44.3% and CRR of 23.9% in the treatment of r/r PTCL

SHANGHAI, June 7, 2023 /PRNewswire/ -- Dizal (688192.SH ) presented compelling data of its robust oncology portfolio at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting taking place June 2-6, 2023, in Chicago. Highlights include new or updated findings from Dizal's leading assets sunvozertinib (a selective EGFR TKI targeting a wide spectrum of EGFR mutations) and golidocitinib (a JAK1 only inhibitor), which have demonstrated superior efficacy in treating advanced non-small cell lung cancer (NSCLC) and relapsed and refractory peripheral T-cell lymphoma (r/r PTCL), respectively.

Sunvozertinib cemented "Best-in-Class" position for NSCLC patients with EGFR Exon20ins mutations

NSCLC patients with EGFR Exon20 insertion (Exon20ins) mutations have worse clinical outcomes due to the absence of effective targeted therapies. Sunvozertinib is a rationally designed, orally available, best-in-class tyrosine kinase inhibitor (TKI) that specifically targets these mutations. Its new drug application (NDA) has been accepted by the China National Medical Products Administration (NMPA) and granted priority review for the treatment of advanced NSCLC with EGFR Exon20ins mutations following platinum-based chemotherapies.

With longer follow-up, sunvozertinib showed an unprecedented ORR of 60.8% in the second-line setting and beyond

Updated results of WU-KONG6, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR Exon20ins mutations, were presented in an oral session. With longer follow-up, patients treated with sunvozertinib achieved a confirmed objective response rate (cORR) of 60.8% assessed by independent review committee (IRC). Anti-tumor efficacy was observed across a broad range of EGFR Exon20ins subtypes, and tumor response was also observed in patients with pretreated and stable brain metastasis.

Commenting on the findings, Prof. Mengzhao Wang, MD, PhD at Peking Union Medical College Hospital, the leading principal investigator of WU-KONG6, said, "Currently, only two new drugs have been approved in the US for≥2L treatment of EGFR Exon20ins NSCLC. However, their efficacy, particularly in terms of ORR, is significantly inferior to that of EGFR TKIs for EGFR sensitizing mutations. Nevertheless, WU-KONG6 study revealed that sunvozertinib had an impressive increase in ORR, reaching 60.8% in the ≥ second-line treatment of EGFR Exon20ins NSCLC. Additionally, sunvozertinib also demonstrated a high ORR regardless of mutation subtypes and insertion locations, as well as in patients with pre-treated and stable brain metastasis. These findings provide promising evidence for the treatment of EGFR Exon20ins NSCLC, and we are optimistic about sunvozertinib's potential in a broader realm of NSCLC."

Sunvozertinib showed the "Best-in-Class" potential with an ORR of 77.8% in the first-line setting

According to the pooled analysis from WU-KONG1 part A and WU-KONG15, sunvozertinib monotherapy demonstrated significant efficacy in the treatment-naive EGFR Exon20ins NSCLC patients, achieving a best objective response rate (BOR) of 77.8% in the 300 mg cohort.

"EGFR Exon20ins is a primary resistant mutation, and there are currently no effective targeted therapies available for the first-line treatment. However, sunvozertinib demonstrated impressive efficacy in the ≥ second-line treatment of EGFR Exon20ins NSCLC, indicating its potential to become a superior therapeutic option in this area. Additional research is warranted to further explore its potential in the frontline." said Prof. Yan Xu, MD, PhD at Peking Union Medical College Hospital, the principal investigator of WU-KONG15, "The ASCO data revealed that sunvozertinib had an ORR of 77.8% in treatment-naive patients at the recommended Phase 2 dose (RP2D) of 300mg QD, exceeding the ORR of 71.2% observed with gefitinib in the IPASS study for treatment-naive patients with EGFR sensitizing mutations. A global multicenter, randomized phase III study (WU-KONG28) is ongoing to evaluate the efficacy and safety of sunvozertinib as a first-line treatment for NSCLC with EGFR Exon20ins mutations as compared to platinum-based doublet chemotherapy. We look forward to additional data readouts to strengthen the position of sunvozertinib in the EGFR Exon20ins domain."

In addition to expressive antitumor efficacies, sunvozertinib continues showing favorable overall safety profile, similar to other EGFR-TKIs. With its superior efficacy and manageable safety profile, sunvozertinib is poised to become a robust player in the realm of EGFR Exon20ins mutations.

Sunvozertinib showed encouraging anti-tumor efficacy in advanced NSCLC patients after failure of EGFR TKI treatment

While EGFR-targeted therapy can provide a durable survival benefit to NSCLC patients with EGFR mutations, resistance invariably emerges to current generation EGFR inhibitors.

Findings of the pooled analysis from WU-KONG1 Part A, WU-KONG2 and WU-KONG15 revealed that sunvozertinib exhibited encouraging anti-tumor efficacy in NSCLC patients with common EGFR mutations who failed standard EGFR TKI treatment.

A total of 37 heavily pretreated (median 5 lines of prior treatment) patients were treated with sunvozertinib, among whom 70.3% had previously received third-generation EGFR TKI, 91.9% received chemotherapy and 40.5% had baseline brain metastasis. At the data cut-off date of April 3, 2023, the median progression-free survival (mPFS) was 5.8 months, and the median duration of response (mDoR) was 6.5 months. And the safety profile was consistent with previous reports.

"Preclinical studies revealed that sunvozertinib showed potent antitumor activity against EGFR Exon20ins as well as EGFR sensitizing, T790M and uncommon mutations. It is worth noting that in patients with EGFR sensitizing mutations who had failed multiple lines of treatment, sunvozertinib monotherapy achieved a mPFS of 5.8 months, which is comparable to the efficacy of second-line chemotherapy." said Prof. James Chih-Hsin Yang, MD, PhD at National Taiwan University Hospital and National Taiwan University Cancer Center, the leading principal investigator of WU-KONG1, "According to the retrospective studies, re-challenge with EGFR TKIs may be a viable approach. In other words, re-administering EGFR TKIs after chemotherapy may help to overcome resistance that developed during previous EGFR TKI treatment. As chemotherapy and EGFR TKI may target different cell populations, switching to a different EGFR TKI could expand the treatment options for patients who are resistant to existing therapies. Further investigation is warranted to explore the potential of sunvozertinib in this area."

WU-KONG studies refer to clinical trials with sunvozertinib being conducted both as monotherapy and as combination therapy in NSCLC including WU-KONG1, WU-KONG2, WU-KONG6, WU-KONG15, WU-KONG21, and WU-KONG28 etc.

Golidocitinib yielded promising tumor responses in r/r PTCL

Relapsed or refractory peripheral T-cell lymphoma (r/r PTCL) is an aggressive non-Hodgkin lymphoma with a five-year survival rate of less than 30%. Currently there is no consensus on the standard treatment for r/r PTCL. New innovative treatment strategies are needed to improve survival in this patient population.

Dizal identified that JAK/STAT may mediate the pathogenesis of PTCL and launched clinical studies of golidocitinib to test the hypothesis. Golidocitinib is the First-in-Class Janus kinase 1 (JAK1) only inhibitor currently being evaluated in a multinational, pivotal study in r/r PTCL (JACKPOT8 Part B). Consistent with earlier data, golidocitinib demonstrated potent and durable anti-tumor efficacy in the pivotal study, with the presentation of clinical data delivered orally at 2023 ASCO.

A total of 112 r/r PTCL patients were included in the analysis. IRC assessed ORR was 44.3% in 88 patients with PTCL including 21 complete responses (CRR, 23.9%). Anti-tumor efficacy was observed across different PTCL subtypes. The mDoR has not been reached. The longest DoR was 16.8 months, and the patient is still responding.

The safety profile of golidocitinib was benign. The majority of treatment-related adverse events (TRAEs) were hematological in nature and amenable to monitoring and management in the clinical setting. The median relative dose intensity was 100%, and the longest treatment duration was 18 months.

"Patients with r/r PTCL have limited treatment options and a poor prognosis. Golidocitinib has demonstrated superior efficacy compared to current treatment options for r/r PTCL, with an ORR of 44.3% and a complete response rate of 23.9%. These findings validate earlier research results and suggest golidocitinib as a potential therapeutic option to improve patients' survival outcomes." said Qingqing Cai, MD, PhD at Sun Yat-sen University Cancer Center, the principal investigator of JACKPOT8, "Moreover, the favorable safety profile of golidocitinib suggests that highly selective JAK1 inhibitors may address the limitations of non-selective inhibition of JAK/STAT signaling pathway, thus offering a novel and effective targeted approach for treating PTCL."

Golidocitinib was granted Fast Track Designation by the US FDA in 2022. With promising efficacy and favorable safety profile, golidocitinib could be an innovative approach for this difficult-to-treat disease.

"The data presented at 2023 ASCO demonstrated the differentiation of our pipeline." said Xiaolin Zhang, PhD, Chairman and CEO of Dizal, "At Dizal, our focus is on advancing scientific research and development to deliver innovative drugs that can effectively address unmet medical needs and improve patient outcomes worldwide."

About sunvozertinib (DZD9008)

Sunvozertinib was designed with the goal to address the limitations of existing NSCLC therapies. It is a rationally designed, irreversible EGFR inhibitor targeting various EGFR mutations with wild-type EGFR selectivity. The first pivotal study WU-KONG6 of sunvozertinib has achieved its primary objective, demonstrating superior anti-tumor efficacy in pretreated NSCLC patients with EGFR Exon20ins. In January 2023, the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) granted priority review status to sunvozertinib and accepted the New Drug Application (NDA) for sunvozertinib for the treatment of advanced NSCLC with EGFR Exon20ins mutations after platinum-based chemotherapies. The confirmed objective response rate (cORR) at 300 mg was 60.8% assessed by IRC (Data cut-off date: October 17, 2022). Anti-tumor efficacy was observed across a broad range of EGFR Exon20ins subtypes, and in patients with pretreated and stable brain metastasis. In addition, sunvozertinib also demonstrated encouraging anti-tumor activity in NSCLC patients with EGFR sensitizing, T790M and uncommon mutations (such as G719X, L861Q, etc.), as well as HER2 Exon20ins mutations.

Sunvozertinib showed a well-tolerated and manageable safety profile in the clinic. Two multinational pivotal studies are ongoing in ≥ 2nd line (WU-KONG1) and 1st line setting (WU-KONG28), respectively, in NSCLC patients with EGFR Exon20ins mutations.

Pre-clinical and Phase 1 clinical results of sunvozertinib were published in peer-reviewed journal Cancer Discovery (IF:39.397) in April 2022. The China NMPA has accepted NDA filing and granted priority review for sunvozertinib for the treatment of advanced NSCLC with EGFR Exon20ins mutations after platinum-based chemotherapy.

About Golidocitinib (DZD4205)

Golidocitinib is the first-in-class Janus kinase 1 (JAK1) only inhibitor currently being evaluated in a global, multicenter pivotal study in r/r PTCL. At the data cut-off date of February 16, 2023, Golidocitinib has demonstrated strong and durable anti-tumor activity, with an ORR of 44.3%. Over 50% of the patients with tumor remission achieved complete response. The longest duration of response (DoR) exceeded 16 months. Golidocitinib was granted Fast Track Designation for the treatment of r/r PTCL by US FDA in February 2022.

About Dizal

Dizal is a clinical-stage, biopharmaceutical company, dedicated to the discovery and development of differentiated therapeutics for the treatment of cancer and immunological diseases. Deep-rooted in translational science and molecular design, it has established an internationally competitive portfolio of five clinical-stage assets with two leading assets in global pivotal studies.

To learn more about Dizal, please visit www.dizalpharma.com, or follow us at  Linkedin or Twitter.

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