On October 13, 2024 Dizal (SSE:688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, reported that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for sunvozertinib for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins) who have not received prior systemic therapies (Press release, Dizal Pharma, OCT 13, 2024, View Source [SID1234647171]).

This designation is the fourth BTD that Dizal has received for sunvozertinib in EGFR exon20ins NSCLC. It follows the grant by the U.S. Food and Drug Administration (FDA) for the first-line setting in April this year. Sunvozertinib was previously granted BTDs by both the U.S. FDA and the China CDE for relapsed or refractory patients.

BTD procedures in the US and China are designed to expedite the development and regulatory review of new medicines that are intended to treat serious or life-threatening conditions with preliminary clinical evidence indicating substantial improvement over available therapies. Drug candidates with BTD can be considered for priority review when submitting a New Drug Application (NDA).

"The total of four Breakthrough Therapy Designations by both the U.S. and China’s regulatory agencies, reflects not only sunvozertinib’s transformative potential in EGFR exon20ins NSCLC, but also Dizal’s commitment to developing groundbreaking new medicines to address unmet medical needs globally." said Xiaolin Zhang, PhD, CEO of Dizal, "Sunvozertinib is the world first and only oral drug approved for the treatment of lung cancer patients with EGFR exon20ins. We are accelerating ongoing clinical studies and regulatory submissions, hoping to bring this new treatment option to more patients as quickly as possible."

The CDE granted the BTD based on results from the pooled analysis of the global multi-center phase I/II study (WU-KONG1) and the phase II study (WU-KONG15) focused on patients from China. Results from these studies showed that sunvozertinib, as a single oral agent, produced a confirmed objective response rate (cORR) of 78.6% and a median progression-free survival (mPFS) of 12.4 months in treatment-naïve patients with advanced or metastatic NSCLC with EGFR exon20ins. Additionally, sunvozertinib is well tolerated with overall safety profile similar to classic EGFR-TKIs.

Currently, sunvozertinib is being evaluated in the WU-KONG28 study, a phase III, multinational, randomized study to compare sunvozertinib vs. platinum doublet chemotherapies in treatment naive patients globally.

NSCLC with EGFR exon20ins are difficult to treat due to their unique spatial conformation, diverse mutation subtypes, and high heterogeneity. In some parts of the world, an antibody with platinum containing chemotherapies is the only treatment option in the first line setting.

Sunvozertinib was approved in China for the treatment of relapsed or refractory NSCLC with EGFR exon20ins in 2023 based on WU-KONG6 study results. In an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, Dizal revealed its WU-KONG1 Part B study results, a multinational study with patients from Asia, Europe, North America, and South America. The study met its primary endpoint. Regulatory submissions for market approvals are ongoing.

About sunvozertinib (DZD9008)

Sunvozertinib is an irreversible EGFR inhibitor discovered by Dizal scientists targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. In August 2023, sunvozertinib received approval from NMPA to treat advanced NSCLC with EGFR exon20ins after platinum-based chemotherapies. The approval is based on the results of WU-KONG6 study, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins. The primary endpoint of the study was the confirmed overall response rate (cORR) as assessed by the Independent Review Committee (IRC) reached 60.8%. 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.

Sunvozertinib showed a well-tolerated and manageable safety profile in the clinic. The most common drug-related TEAEs (treatment-emergent adverse event) were Grade 1/2 in nature and clinically manageable.

Two global pivotal studies are ongoing in ≥ 2nd line (WU-KONG1 Part B) and 1st line setting (WU-KONG28), respectively, in NSCLC patients with EGFR exon20ins.

Pre-clinical and clinical results of sunvozertinib were published in peer-reviewed journals Cancer Discovery (IF:39.397) and The Lancet Respiratory Medicine (IF: 76.2).

On October 13, 2024 Dizal (SSE:688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, reported that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for sunvozertinib for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins) who have not received prior systemic therapies (Press release, Dizal Pharma, OCT 13, 2024, View Source [SID1234647171]).

This designation is the fourth BTD that Dizal has received for sunvozertinib in EGFR exon20ins NSCLC. It follows the grant by the U.S. Food and Drug Administration (FDA) for the first-line setting in April this year. Sunvozertinib was previously granted BTDs by both the U.S. FDA and the China CDE for relapsed or refractory patients.

BTD procedures in the US and China are designed to expedite the development and regulatory review of new medicines that are intended to treat serious or life-threatening conditions with preliminary clinical evidence indicating substantial improvement over available therapies. Drug candidates with BTD can be considered for priority review when submitting a New Drug Application (NDA).

"The total of four Breakthrough Therapy Designations by both the U.S. and China’s regulatory agencies, reflects not only sunvozertinib’s transformative potential in EGFR exon20ins NSCLC, but also Dizal’s commitment to developing groundbreaking new medicines to address unmet medical needs globally." said Xiaolin Zhang, PhD, CEO of Dizal, "Sunvozertinib is the world first and only oral drug approved for the treatment of lung cancer patients with EGFR exon20ins. We are accelerating ongoing clinical studies and regulatory submissions, hoping to bring this new treatment option to more patients as quickly as possible."

The CDE granted the BTD based on results from the pooled analysis of the global multi-center phase I/II study (WU-KONG1) and the phase II study (WU-KONG15) focused on patients from China. Results from these studies showed that sunvozertinib, as a single oral agent, produced a confirmed objective response rate (cORR) of 78.6% and a median progression-free survival (mPFS) of 12.4 months in treatment-naïve patients with advanced or metastatic NSCLC with EGFR exon20ins. Additionally, sunvozertinib is well tolerated with overall safety profile similar to classic EGFR-TKIs.

Currently, sunvozertinib is being evaluated in the WU-KONG28 study, a phase III, multinational, randomized study to compare sunvozertinib vs. platinum doublet chemotherapies in treatment naive patients globally.

NSCLC with EGFR exon20ins are difficult to treat due to their unique spatial conformation, diverse mutation subtypes, and high heterogeneity. In some parts of the world, an antibody with platinum containing chemotherapies is the only treatment option in the first line setting.

Sunvozertinib was approved in China for the treatment of relapsed or refractory NSCLC with EGFR exon20ins in 2023 based on WU-KONG6 study results. In an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, Dizal revealed its WU-KONG1 Part B study results, a multinational study with patients from Asia, Europe, North America, and South America. The study met its primary endpoint. Regulatory submissions for market approvals are ongoing.

About sunvozertinib (DZD9008)

Sunvozertinib is an irreversible EGFR inhibitor discovered by Dizal scientists targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. In August 2023, sunvozertinib received approval from NMPA to treat advanced NSCLC with EGFR exon20ins after platinum-based chemotherapies. The approval is based on the results of WU-KONG6 study, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins. The primary endpoint of the study was the confirmed overall response rate (cORR) as assessed by the Independent Review Committee (IRC) reached 60.8%. 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.

Sunvozertinib showed a well-tolerated and manageable safety profile in the clinic. The most common drug-related TEAEs (treatment-emergent adverse event) were Grade 1/2 in nature and clinically manageable.

Two global pivotal studies are ongoing in ≥ 2nd line (WU-KONG1 Part B) and 1st line setting (WU-KONG28), respectively, in NSCLC patients with EGFR exon20ins.

Pre-clinical and clinical results of sunvozertinib were published in peer-reviewed journals Cancer Discovery (IF:39.397) and The Lancet Respiratory Medicine (IF: 76.2).

On October 13, 2024 Dizal (SSE:688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, reported that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for sunvozertinib for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins) who have not received prior systemic therapies (Press release, Dizal Pharma, OCT 13, 2024, View Source [SID1234647171]).

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This designation is the fourth BTD that Dizal has received for sunvozertinib in EGFR exon20ins NSCLC. It follows the grant by the U.S. Food and Drug Administration (FDA) for the first-line setting in April this year. Sunvozertinib was previously granted BTDs by both the U.S. FDA and the China CDE for relapsed or refractory patients.

BTD procedures in the US and China are designed to expedite the development and regulatory review of new medicines that are intended to treat serious or life-threatening conditions with preliminary clinical evidence indicating substantial improvement over available therapies. Drug candidates with BTD can be considered for priority review when submitting a New Drug Application (NDA).

"The total of four Breakthrough Therapy Designations by both the U.S. and China’s regulatory agencies, reflects not only sunvozertinib’s transformative potential in EGFR exon20ins NSCLC, but also Dizal’s commitment to developing groundbreaking new medicines to address unmet medical needs globally." said Xiaolin Zhang, PhD, CEO of Dizal, "Sunvozertinib is the world first and only oral drug approved for the treatment of lung cancer patients with EGFR exon20ins. We are accelerating ongoing clinical studies and regulatory submissions, hoping to bring this new treatment option to more patients as quickly as possible."

The CDE granted the BTD based on results from the pooled analysis of the global multi-center phase I/II study (WU-KONG1) and the phase II study (WU-KONG15) focused on patients from China. Results from these studies showed that sunvozertinib, as a single oral agent, produced a confirmed objective response rate (cORR) of 78.6% and a median progression-free survival (mPFS) of 12.4 months in treatment-naïve patients with advanced or metastatic NSCLC with EGFR exon20ins. Additionally, sunvozertinib is well tolerated with overall safety profile similar to classic EGFR-TKIs.

Currently, sunvozertinib is being evaluated in the WU-KONG28 study, a phase III, multinational, randomized study to compare sunvozertinib vs. platinum doublet chemotherapies in treatment naive patients globally.

NSCLC with EGFR exon20ins are difficult to treat due to their unique spatial conformation, diverse mutation subtypes, and high heterogeneity. In some parts of the world, an antibody with platinum containing chemotherapies is the only treatment option in the first line setting.

Sunvozertinib was approved in China for the treatment of relapsed or refractory NSCLC with EGFR exon20ins in 2023 based on WU-KONG6 study results. In an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, Dizal revealed its WU-KONG1 Part B study results, a multinational study with patients from Asia, Europe, North America, and South America. The study met its primary endpoint. Regulatory submissions for market approvals are ongoing.

About sunvozertinib (DZD9008)

Sunvozertinib is an irreversible EGFR inhibitor discovered by Dizal scientists targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. In August 2023, sunvozertinib received approval from NMPA to treat advanced NSCLC with EGFR exon20ins after platinum-based chemotherapies. The approval is based on the results of WU-KONG6 study, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins. The primary endpoint of the study was the confirmed overall response rate (cORR) as assessed by the Independent Review Committee (IRC) reached 60.8%. 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.

Sunvozertinib showed a well-tolerated and manageable safety profile in the clinic. The most common drug-related TEAEs (treatment-emergent adverse event) were Grade 1/2 in nature and clinically manageable.

Two global pivotal studies are ongoing in ≥ 2nd line (WU-KONG1 Part B) and 1st line setting (WU-KONG28), respectively, in NSCLC patients with EGFR exon20ins.

Pre-clinical and clinical results of sunvozertinib were published in peer-reviewed journals Cancer Discovery (IF:39.397) and The Lancet Respiratory Medicine (IF: 76.2).

On October 11, 2024 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with cancer and inflammatory diseases, reported financial results for the third quarter ended August 31, 2024, and provided a corporate update (Press release, Nurix Therapeutics, OCT 11, 2024, View Source [SID1234647156]).

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"We continue to make great progress and remain focused on execution as we advance our pipeline of wholly owned and partnered programs in oncology, inflammation and immunology," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "As we approach the end of the year, we are well capitalized and look forward to building further momentum as we head into clinical data readouts in the fourth quarter of 2024 and the initiation of pivotal studies of NX-5948 in 2025."

Recent Business Highlights

•Expanded clinical development of NX-5948: In the third quarter of 2024, Nurix initiated the Phase 1b portion of its ongoing Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. The Phase 1b expansion includes a randomization to a low dose (200mg QD) or a high dose (600mg QD) of NX-5948 in patients with chronic lymphocytic leukemia (CLL) who have been treated with at least two prior regimens including a Bruton’s tyrosine kinase (BTK) inhibitor and a BCL2 inhibitor. This is the patient population for which the FDA granted Nurix Fast Track designation in January 2024. Cohorts were also initiated to evaluate NX-5948 in patients with Waldenstrom’s macroglobulinemia (WM), marginal zone lymphoma and follicular lymphoma.

•Re-initiated enrollment in NX-2127 Phase 1a/b trial: Nurix recently reinitiated enrollment with its new chirally controlled drug product in a standard dose escalation study within the current Phase 1a/1b trial. As previously announced, in March 2024, the U.S. Food and Drug Administration (FDA) lifted a manufacturing-related, partial clinical hold on the NX-2127 clinical trial. Patients enrolled prior to the partial clinical hold who are deriving clinical benefit continue to receive uninterrupted treatment with the original drug product.

•Presented early preclinical data from ongoing collaboration with Pfizer to develop Degrader-Antibody Conjugates, a new class of therapeutics: On September 10, 2024, at the ADC & Radiopharmaceuticals Pharma & Biotech Partnering Summit, Nurix’s chief scientific officer, Gwenn M. Hansen, Ph.D., presented an outline of the advantages of DACs, Nurix’s matrixed approach to the generation and optimization of DACs using its DELigase platform, and early preclinical data demonstrating cell-type selective degradation of targeted proteins by DACs. Nurix believes that DACs may represent a next generation of antibody drug conjugate (ADC) technology that could broaden its use in oncology and potentially other indications. DACs combine the catalytic activity of a targeted protein degrader with the tissue specificity of an antibody which has the potential to provide improved therapeutic index and broader applicability than standard ADCs and which can potentially be applied to any protein target in any tissue.

Upcoming Program Highlights*

NX-5948: NX-5948 is an investigational, orally bioavailable degrader of BTK that is currently being evaluated in the Phase 1b portion of a Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. By year-end 2024, Nurix plans to present additional clinical data from this study for patients with CLL. Later this month, at the 12th International Workshop on Waldenstrom’s Macroglobulinemia (IWWM 12), Nurix will present a clinical update from this study on patients with WM. Additional information on the Phase 1a/b clinical trial can be accessed at www.clinicaltrials.gov (NCT05131022).

Nurix is also conducting a Phase 1 healthy volunteer study to assess food effects and drug-drug interactions in anticipation of initiating pivotal development in 2025. Additional information on this Phase 1 clinical trial can be accessed at www.clinicaltrials.gov (NCT06593457).

Nurix continues to lay the groundwork for indication selection in autoimmune and inflammatory diseases and expects to complete ongoing preclinical studies in 2024 that can enable an investigational new drug (IND) application for NX-5948 in autoimmune indications. An abstract titled "NX-5948, a Clinical-Stage BTK Degrader, Achieves Deep Suppression of BCR, TLR, and FcR Signaling in Immune Cells and Demonstrates Efficacy in Preclinical Models of Arthritis and Other Inflammatory Diseases" was accepted for a poster presentation at the upcoming annual meeting of the American College of Rheumatology (ACR 2024), being held November 14–19, 2024, in Washington, D.C.

NX-2127: NX-2127 is an orally bioavailable BTK degrader that also degrades cereblon neosubstrates IKZF1 (Ikaros) and IKZF3 (Aiolos) for the treatment of relapsed or refractory B‑cell malignancies. Nurix is conducting a Phase 1a/b clinical trial of NX-2127, which includes Phase 1b expansion cohorts focused on patients with diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Nurix recently introduced a new chirally controlled drug product, which is being evaluated in a dose escalation within this Phase 1a/b trial. Future clinical updates are anticipated in 2025. Additional information on the clinical trial can be accessed at www.clinicaltrials.gov (NCT04830137).

NX-1607: NX-1607 is an orally bioavailable inhibitor of the E3 ligase Casitas B-lineage lymphoma proto-oncogene B (CBL-B) for immuno-oncology indications, including a range of solid tumor types and lymphoma. Nurix is evaluating NX-1607 in an ongoing Phase 1 trial in monotherapy and in a combination cohort utilizing paclitaxel in adults in a range of oncology indications. This study includes a thorough investigation of both dose and schedule in Phase 1a. Nurix anticipates providing a program update by year-end 2024. Additional information on the clinical trial can be accessed at www.clinicaltrials.gov (NCT05107674).

GS-6791 (previously NX-0479): GS-6791 is a potent, selective, oral IRAK4 degrader. Degradation of IRAK4 by GS-6791 has potential applications in the treatment of rheumatoid arthritis and other inflammatory diseases. Nurix’s partner, Gilead, is responsible for conducting IND-enabling studies and advancing this program to clinical development. An abstract titled "IRAK4 Degrader GS-6791 Inhibits TLR and IL-1R-Driven Inflammatory Signaling, and Ameliorates Disease in a Preclinical Arthritis Model" was accepted for a poster presentation at ACR 2024.
STAT6 degrader: In April 2024, Nurix announced an extension of the ongoing research program with Sanofi for STAT6 (signal transducer and activator of transcription 6), a key drug target in type 2 inflammation, with the goal of nominating a development candidate in the first year of the extended term. Nurix remains on track for this goal.
Continued pipeline advancement of strategic collaborations with Gilead, Sanofi and Pfizer: Nurix expects to continue to achieve substantial research collaboration milestones throughout the terms of its collaborations with Gilead, Sanofi and Pfizer.

*Expected timing of events throughout this press release is based on calendar year quarters.

Fiscal Third Quarter 2024 Financial Results

Collaboration revenue for the three months ended August 31, 2024, was $12.6 million compared with $18.5 million for the three months ended August 31, 2023. Revenue from the collaboration with Gilead decreased as the initial research term for certain drug targets ended. The decrease was offset by an increase in revenue from the collaboration agreement with Pfizer that was entered into in the fourth quarter of fiscal year 2023.
Research and development expenses for the three months ended August 31, 2024, were $55.5 million compared with $47.9 million for the three months ended August 31, 2023. The increase was primarily due to clinical and contract manufacturing costs as Nurix continued to accelerate the enrollment of NX-5948 and progress its other clinical trial programs for NX-2127 and NX-1607.

General and administrative expenses for the three months ended August 31, 2024, were $11.7 million compared with $10.6 million for the three months ended August 31, 2023. The increase was primarily due to an increase in professional service and consulting costs.

Net loss for the three months ended August 31, 2024, was $49.0 million, or ($0.67) per share, compared with $37.0 million, or ($0.68) per share, for the three months ended August 31, 2023.
Cash, cash equivalents and marketable securities was $457.5 million as of August 31, 2024, compared to $452.5 million as of May 31, 2024.

On October 11, 2024 Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, reported the selection of three abstracts for presentation, including a late-breaking oral presentation, at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics (ENA 2024), taking place October 23-25, 2024, in Barcelona, Spain (Press release, Tyra Biosciences, OCT 11, 2024, View Source [SID1234647157]).

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Details of the presentations are below:

Title: "Preliminary safety and anti-tumor activity of TYRA-300, a highly selective FGFR3 inhibitor, in participants with advanced solid tumors with activating FGFR3 mutations/fusions (SURF301)"

Session: Late Breaking Abstracts and Proffered Papers: Novel discoveries in drug development
Date: Friday, October 25, 2024
Time: 15:36 – 15:48 hrs CEST
Abstract #: LBA500

Title: "TYRA-300, an oral, FGFR3-selective inhibitor: Preliminary pharmacokinetic and pharmacodynamic analysis from SURF301, the multicenter open-label phase 1/2 study of TYRA-300 in advanced urothelial carcinoma and other solid tumors with activating FGFR3 alterations"

Abstract #: 72
Poster #: PB060

Title: "A Multicenter, Open-label Phase 1/2 Study of TYRA 300 in Advanced Urothelial Carcinoma and Other Solid Tumors with Activating FGFR3 Gene Alterations (SURF301)"

Abstract #: 35
Poster #: PB023

The abstracts related to the presentations are under embargo until 00.01 hrs CEST on Friday, October 25, 2024.