On August 16, 2023 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported that the first patient has been dosed in the Phase 1 clinical trial evaluating EO-3021 in patients with advanced unresectable or metastatic solid tumors likely to express Claudin 18.2 including gastric, gastroesophageal junction, pancreatic or esophageal cancers (Press release, Elevation Oncology, AUG 16, 2023, View Source;utm_medium=rss&utm_campaign=elevation-oncology-announces-first-patient-dosed-in-the-phase-1-clinical-trial-evaluating-eo-3021 [SID1234634448]).

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"The dosing of the first patient is a major milestone in evaluating EO-3021’s potential benefit for these patients," said Valerie Malyvanh Jansen, M.D., Ph.D., Chief Medical Officer of Elevation Oncology. "Claudin 18.2 has emerged as a promising therapeutic target in gastric cancer and other solid tumors. Based on preclinical and early clinical data, EO-3021 represents a potentially safer and more effective therapeutic option for patients with advanced solid tumors that likely express Claudin 18.2, including gastric and gastroesophageal junction cancers. We look forward to evaluating the potential of EO-3021 and expect to report preliminary data on safety and anti-tumor activity from our Phase 1 study during the first half of 2025."

Meredith Pelster, M.D., MSCI, Assistant Director of Gastrointestinal Research for Sarah Cannon Research Institute and a principal investigator in the Phase 1 study of EO-3021, added, "Targeting Claudin 18.2 with an antibody-drug conjugate represents a promising therapeutic option for patients. The initial clinical data presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2023 Annual Meeting point to a safe and tolerable therapy that can induce deep responses in patients with gastric cancer. EO-3021 has the potential to provide a much-needed treatment option for patients with advanced solid tumors likely to express Claudin 18.2."

EO-3021 is a potential best-in-class antibody-drug conjugate (ADC) that has been designed to selectively deliver a cytotoxic payload directly to Claudin 18.2-expressing cancer cells to minimize payload-associated toxicities and maximize anti-tumor activity. EO-3021 is a fully human monoclonal antibody that targets Claudin 18.2 and is site-specifically conjugated to the cytotoxic agent monomethyl auristatin E via a cleavable linker, with a drug-to-antibody ratio of 2.

Elevation Oncology’s Phase 1 clinical trial (NCT05980416) is an open-label, multi-center dose escalation and expansion study that is expected to enroll up to approximately 120 patients to evaluate the safety, tolerability, and preliminary anti-tumor activity of EO-3021 in advanced solid tumors likely to express Claudin 18.2. The dose escalation portion of the study will enroll patients with advanced unresectable or metastatic solid tumors likely to express Claudin 18.2, including gastric, gastroesophageal junction, pancreatic or esophageal cancers. The expansion portion of the study is expected to further evaluate EO-3021 in patients with advanced unresectable or metastatic gastric or gastroesophageal junction cancers. An additional objective of the study will be to assess the association of Claudin 18.2 expression and objective response. Elevation Oncology expects to report preliminary safety and anti-tumor data from its Phase 1 study during the first half of 2025.

CSPC Pharmaceutical Group Limited (HKEX: 01093), is also evaluating SYSA1801 (EO-3021) in an ongoing Phase 1 clinical trial in China (NCT05009966). Preliminary data from CSPC’s Phase 1 study were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2023 Annual Meeting. The findings showed promising early signs of EO-3021 activity, including an objective response rate of 47.1% in patients with gastric cancer (8 PRs, including 4 confirmed PRs) and a disease control rate of 64.7%, along with a well-tolerated safety profile in patients with resistant/refractory tumors expressing Claudin 18.2. Elevation Oncology has licensed the exclusive rights to develop and commercialize EO-3021 in all global territories outside Greater China from CSPC.

About EO-3021

EO-3021 (also known as SYSA1801) is a differentiated, clinical-stage antibody drug conjugate (ADC) comprised of an immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets Claudin 18.2 and is site-specifically conjugated to the monomethyl auristatin E (MMAE) payload via a cleavable linker with a drug-to-antibody ratio (DAR) of 2. Claudin 18.2 is a specific isoform of Claudin 18 that is normally expressed in gastric epithelial cells. During malignant transformations, the tight junctions may become disrupted, exposing Claudin 18.2 and allowing them to be accessible by Claudin 18.2 targeting agents. Elevation Oncology is evaluating EO-3021 in a Phase 1 study in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2 including gastric, gastroesophageal junction, pancreatic or esophageal cancers.

On August 15, 2023 Day One Biopharmaceuticals (Nasdaq: DAWN), a clinical-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, reported it has entered into an exclusive, worldwide license agreement and research collaboration with Sprint Bioscience for its VRK1 program (Press release, Day One, AUG 16, 2023, View Source [SID1234634447]).

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Vaccinia-related kinase 1 (VRK1) is a novel target involved in the regulation of cell division and DNA damage repair. Over-expression of VRK1 is linked to poor prognosis in a variety of adult and pediatric cancers, and VRK1 has been identified as a synthetic lethal target in tumors where expression of its paralog, VRK2, is lost. Silencing of VRK2 expression via promoter methylation has been noted in the majority of high-grade gliomas and high-risk neuroblastomas, providing a concrete approach for selecting patients with tumors sensitive to VRK1 inhibition.

"This collaboration is an important continuation of measured portfolio development at Day One, which focuses on targeted therapies for children and adults with cancer in need of novel treatment approaches," said Dr. Samuel Blackman, co-founder and head of research and development, Day One. "We look forward to collaborating with Sprint Bioscience, who has strong discovery and research expertise, and working to advance the VRK1 program through lead optimization and into the clinic."

Under the terms of the agreement, Day One will make an upfront payment of $3 million to Sprint Bioscience and reimburse Sprint Bioscience for pre-clinical research and development expenses. Sprint Bioscience will be eligible to receive additional milestone payments of up to approximately $313 million plus single-digit royalties pending achievement of certain research, development, regulatory and commercial outcomes.

On August 16, 2023 Bristol Myers Squibb (NYSE: BMY) reported updated results from the registrational TRIDENT-1 study, demonstrating that repotrectinib, a next-generation ROS1/TRK tyrosine kinase inhibitor (TKI), continued to show high response rates and durable responses in patients with ROS1-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) (Press release, Bristol-Myers Squibb, AUG 16, 2023, View Source [SID1234634446]). Updated results will be featured in an oral presentation (Abstract #OA03.06) at the IASLC 2023 World Conference on Lung Cancer (#WCLC23) hosted by the International Association for the Study of Lung Cancer on September 10, 2023, from 1:02 a.m. to 1:12 a.m. EDT / 1:02 p.m. to 1:12 p.m. SGT.

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Based on results from the TRIDENT-1 trial, the U.S. Food and Drug Administration accepted the New Drug Application for repotrectinib for the treatment of patients with ROS1-positive locally advanced or metastatic NSCLC and granted Priority Review; a Prescription Drug User Fee Act goal date of November 27, 2023 was assigned.

In this updated analysis, repotrectinib continued to demonstrate durable efficacy in patients with ROS1-positive NSCLC, including intracranial activity, in patients who were TKI-naïve or previously treated with one TKI and no chemotherapy. Median duration of response (DOR) and median progression-free survival (PFS) will also be disclosed for the first time in the pooled Phase 1 and Phase 2 population of patients with ROS1-positive NSCLC:

In TKI-naïve patients (n=71) with median follow-up of 24.0 months, confirmed objective response rate (cORR) by Blinded Independent Central Review (BICR) was 79%, median DOR and PFS were 34.1 months and 35.7 months, respectively. In patients with measurable brain metastases at baseline (n=9), intracranial ORR per BICR was 89% and responses were prolonged.
In patients who had been previously treated with one TKI and no chemotherapy (n=56) with median follow-up of 21.5 months, cORR by BICR was 38%, and median DOR and PFS were 14.8 months and 9.0 months, respectively. In this subset of patients with measurable brain metastases at baseline (n=13), intracranial ORR per BICR was 38%.
At the recommended dose for Phase 2, the safety profile of repotrectinib was manageable and remained consistent with previous reports.
"The data from the TRIDENT-1 trial hold great significance in the field of non-small cell lung cancer research, as they add to the growing body of evidence pointing toward durable results with repotrectinib in patients who test positive for ROS1 gene fusions," said Byoung Chul Cho, M.D., Ph.D., Yonsei Cancer Center, Yonsei University College of Medicine, DAAN Cancer Laboratory. "With these results, we are seeing durable benefit, including in the brain, in patients with ROS1-positive NSCLC that differentiates repotrectinib from existing agents and is especially impressive in the context of historic data with current ROS1 TKIs. This targeted therapy has true potential to change the treatment landscape and become a new standard of care for patients with ROS1-positive NSCLC."

"These updated results reflect the potential of repotrectinib as a best-in-class ROS1 inhibitor. Furthermore, the data offer hope for the patients with ROS1-positive non-small cell lung cancer who still face high remaining unmet needs," said Joseph Fiore, executive director, global program lead, repotrectinib, Bristol Myers Squibb. "Building on our heritage of transformational science with immunotherapy in the treatment of NSCLC, we are excited to advance this next-generation precision medicine, which has shown an unprecedented level of durability of responses and robust intracranial responses in patients with ROS1-positive NSCLC, so that it can hopefully help patients in their fight against cancer."

The study remains ongoing to assess long-term outcomes and additional endpoints across patient populations with ROS1-positive locally advanced or metastatic NSCLC and NTRK-positive advanced solid tumors. Bristol Myers Squibb thanks the patients and investigators involved with the TRIDENT-1 clinical trial.

Turning Point Therapeutics is a wholly owned subsidiary of the Bristol-Myers Squibb Company. As of August 2022, Bristol Myers Squibb acquired the leading clinical stage precision oncology company and its pipeline of investigational drugs across precision oncology and advanced solid tumors, including repotrectinib.

About TRIDENT-1

TRIDENT-1 is a Phase 1/2 open-label, global, multi-center, first-in-human clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of repotrectinib (TPX-0005, BMS-986472) in patients with advanced solid tumors, including non-small cell lung cancer (NSCLC). Phase 1 of the trial includes several primary and secondary safety and pharmacokinetics endpoints. Phase 2 of the trial has a primary endpoint of overall response rate (ORR) as assessed by Blinded Independent Central Review (BICR) using RECIST v1.1 and key secondary endpoints including duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR) in six distinct expansion cohorts, including tyrosine kinase inhibitor (TKI)-naïve and TKI-pretreated patients with ROS1-positive locally advanced or metastatic NSCLC and NTRK-positive advanced solid tumors.

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer, representing up to 84% of diagnoses. Survival rates vary depending on the stage and type of the cancer when diagnosed. ROS1 fusions are rare and occur in about 1-2% of patients with NSCLC. Patients with tumors that are ROS1-positive tend to be younger than the average patient with lung cancer, more often female and may have little to no smoking history. Per international treatment guidelines, ROS1 targeted agents are preferred in patients with a tumor harboring this alteration.

On August 15, 2023 CStone Pharmaceuticals ("CStone", HKEX: 2616), a leading biopharmaceutical company focused on research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, reported 2023 interim results and recent business updates (Press release, CStone Pharmaceauticals, AUG 15, 2023, View Source [SID1234634974]).

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"In the first half of 2023, CStone delivered robust growth and positive results. Our three precision medicines achieved a 53% year-on-year increase in sales revenue with significant improvement of gross profit margin. Our cash reserves amount to RMB 1,005.4 million, and we significantly reduced our net losses." said Dr. Jason Yang, CEO of CStone.

"We made remarkable progress in our global product pipeline. We expanded the First-in-Human (FIH) global study of CS5001, a key product of our CStone Pipeline 2.0 Strategy, to China from the United States and Australia, accelerating its development. The phase I clinical trial completed safety evaluation of several dose levels. CS5001, one of the most advanced ROR1 ADCs in global clinical development, showed promising safety, stability, and preliminary anti-tumor activity in hematological and solid malignancies.

We are awaiting the approval of sugemalimab (PD-L1) as first-line treatment of Stage IV NSCLC in the UK and the EU, with the GCP inspection notification from the EMA received recently. We expect the approval in the first half of 2024. We are also actively looking for partners to develop and commercialize sugemalimab and nofazinlimab (PD-1) outside of the Greater China, to advance the global commercialization of these assets.

Going forward, we will continue to strengthen our research and development capabilities for innovative products, optimize the commercial potential of existing products, and improve our global strategic positioning, to create more growth opportunities for the company and more value for investors, partners, and stakeholders."

On August 15, 2023 Stada reported its Interim Report on the First Six Months of 2023 (Presentation, Stada, AUG 15, 2023, View Source [SID1234634827]).

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