foslinanib immediate release (CVM-1118) / TaiRx - LARVOL DELTA

CVM-005: A multicentre, single-arm, phase IIa study of CVM-1118, a novel oral anti-vasculogenic mimicry (VM) agent, in patients with treatment-refractory advanced neuroendocrine tumours (NET) (ENETS 2025) - "and 8.4 mos (95% CI 5.6–13.9 mos) for all 43 pts., exceeding the historical 4–6 mos of placebo groups in sunitinib (sun) and everolimus (eve) phase 3 trials...with ≥1 prior eve, sun, or Lu-177 dotatate (N=22) had an mPFS of 8.3 mos (95% CI 3.8–11.2 mos)...discontinued due to TRAEs. CONCLUSION CVM-1118 presents a promising therapy for advanced NETs with superior tolerability and safety profile to current target therapies, warranting further development."

Clinical • Metastases • P2a data • Anemia • Endocrine Cancer • Gastrointestinal Disorder • Hematological Disorders • Neuroendocrine Tumor • Oncology • Solid Tumor

Orphan Designation: treatment of pancreatic neuroendocrine tumor (FDA) - Date Designated: 01/30/2025

Orphan drug • Neuroendocrine Tumor • Pancreatic Adenocarcinoma

Taiwan Rui CVM-1118 will start clinical phase IIb trials and strive to be launched on the market by the end of this year [Google translation] (money.udn.com) - "The company will also plan the next stage of development. The company will seek to cooperate with other biotech companies to initiate clinical phase IIb trials in mainland China or the United States....We will apply for a science and technology enterprise approval letter in the first half of this year, and strive to complete the listing application before the end of this year....plan to target the indications of neuroendocrine tumors in pancreatic cancer and gastric cancer. Clinical phase IIb trial; clinical phase IIb trial of CVM-1118 in liver cancer will also be carried out. Both clinical trials will look for different biotech companies to accept cases in mainland China."

Commercial • New P2b trial • Liver Cancer • Neuroendocrine Tumor

CVM-005: Study of CVM-1118 for Patients With Advanced Neuroendocrine Tumors (clinicaltrials.gov) - P2 | N=34 | Active, not recruiting | Sponsor: TaiRx, Inc. | Trial completion date: Dec 2024 ➔ Dec 2025

Metastases • Trial completion date • Endocrine Cancer • Hepatology • Neuroendocrine Tumor • Oncology • Solid Tumor

Taiwan Rui's ADC anti-cancer drug high-dose injection was approved by the Ministry of Health and Welfare [Google translation] (stock.yahoo) - "Tai Rui Biotechnology...announced today (21st) that it will enter the ADC anti-cancer drug market and conduct clinical trials of CVM-1118 small molecule drug in the treatment of liver cancer and neuroendocrine tumors. It is expected to announce the final data in the second half of the year....The clinical 2a trial of CVM-1118 small molecule drug in the treatment of liver cancer is expected to be released in July. In terms of neuroendocrine tumors, the current progress is Phase 2. Clinical trial, efficacy results data are expected to be announced in August."

P2a data • Gastrointestinal Cancer • Liver Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor

CVM-005: Phase IIa study of CVM-1118, a novel oral anti-vasculogenic mimicry (VM) agent, in advanced neuroendocrine tumors (NET) after progression on prior therapy (ESMO 2024) - P2 | "With a median follow up of 12.8 mos (95% CI 8.2–20.1 mos) and 3 prior therapies, the mPFS has reached 10.3 mos (95% CI 5.9–23.8 mos), exceeding the historical 4–6 mos of placebo groups reported in sunitinib and everolimus Phase 3 trials. CVM-1118 presents a promising therapy for advanced NETs with superior tolerability and safety profile to the current targeted therapies and warrants further development."

Metastases • P2a data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor

Taiwan Rui: The company's second phase clinical trial of CVM-1118, the company's new oral anti-cancer drug, for the treatment of advanced neuroendocrine tumors has published the trial results in the form of a Mini Oral Presentation at the 2024 European Society for Medical Oncology (ESMO) Annual Meeting. [Google translation] (Anue Juheng) - P2 | N=34 | NCT03600233 | Sponsor: TaiRx, Inc. | "The second phase of the company’s new anti-cancer oral small molecule drug CVM-1118 for the treatment of advanced, unresectable neuroendocrine tumors...Clinical trial, selected for European Society for Medical Oncology 2024...Data on March 6, 2024, among the 34 patients actually admitted for efficacy evaluation, the main evaluation index median disease...Progression Free Survival (PFS) was 10.3 months, exceeding the historical control group median....Disease progression-free survival (4 to 6 months). In terms of safety, CVM-1118 was confirmed to be well tolerated, with no observed."

P2 data • Neuroendocrine Tumor • Oncology • Solid Tumor

CVM-1118: An oral anti-vasculogenic mimicry (VM) agent in combination with nivolumab in patients with unresectable advanced hepatocellular carcinoma (HCC)—A phase IIa study. (ASCOBT 2024) - P2 | " Eligible pts had unresectable advanced HCC and were refractory to prior systemic therapy (e.g., sorafenib, lenvatinib, regorafenib, and/or ramucirumab), with the exception of prior immunotherapy. CVM-1118 combined with nivolumab demonstrated clinical activity in advanced HCC pts with a safety profile that appears favorable compared to atezolizumab plus bevacizumab. These data support further development of the combination of CVM-1118 and nivolumab in pts with unresectable advanced HCC."

Clinical • Combination therapy • Metastases • P2a data • Anemia • Cardiovascular • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Hepatocellular Cancer • Hypertension • Oncology • Solid Tumor

Taiwan Rui CVM-1118 made its mark at the international exhibition and was selected as the only oral presentation by ESMO to Taiwanese manufacturers [Google translation] (stock.yahoo) - "Tai Rui Biotechnology (6580-TW)'s anti-cancer drug CVM-1118's clinical trial results have been released one after another, and it has emerged on the international stage. Today (15th) it was announced that the phase II clinical trial of CVM-1118 for neuroendocrine tumors has been completed. The case was accepted, and the preliminary results were selected as an oral report for publication by the European Society of Medical Oncology ESMO, becoming the only Taiwanese manufacturer selected."

P2 data • Neuroendocrine Tumor • Oncology • Solid Tumor

Tai Rui CVM-1118 combined with immunotherapy inhibitors for the treatment of liver cancer Phase II clinical trial results summary [Google translation] (MoneyDJ) - P2 | N=95 | NCT05257590 | Sponsor: TaiRx, Inc. | "The second phase clinical trial of the company's new anti-cancer oral drug CVM-1118 combined with the immunotherapy inhibitor 'Opdivo' in the treatment of advanced liver cancer has completed the first phase of the target number of patients, and the trial results were selected in The research results will be published in the form of posters at the American Society of Clinical Oncology Breakthrough Summit (ASCO Breakthrough)...and the Japanese Society of Medical Oncology (JSMO) to discuss breakthrough developments in the field of oncology....This trial adopted Simon's two-stage trial design. Among the 31 patients admitted in the first stage, 2 subjects had complete response (CR) and 4 subjects had partial response (PR). The objective response rate (Objective response rate, ORR) is 19.4%....The current trial results have reached the goal of having more than 5 ORR subjects in the first phase, and can enter the..."

P2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

CVM-1118: A potent oral anti-vasculogenic mimicry (VM) agent in combination with nivolumab in patients with unresectable advanced hepatocellular carcinoma (HCC)—A phase IIa study. (ASCO 2024) - P2 | " Eligible pts had unresectable advanced HCC and were refractory to prior systemic therapy (e. g. , sorafenib, lenvatinib, regorafenib, and/or ramucirumab), with the exception of prior immunotherapy. CVM-1118 combined with nivolumab demonstrated clinical activity in advanced HCC pts with a safety profile that appears favorable compared to atezolizumab plus bevacizumab. These data support further development of the combination of CVM-1118 and nivolumab in pts with unresectable advanced HCC. Clinical trial information: NCT05257590."

Clinical • Combination therapy • Metastases • P2a data • Anemia • Cardiovascular • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Hepatocellular Cancer • Hypertension • Oncology • Solid Tumor

Vascular mimicry in zebrafish fin regeneration: how macrophages build new blood vessels. (PubMed, Angiogenesis) - "Inhibiting the formation of tubular vascular-like structures by CVM-1118 prevents vascular mimicry and network formation resulting in a 70% shorter regeneration area with 60% reduced vessel growth and a complete absence of any signs of regeneration in half of the fin area. Additionally, this is associated with a significant reduction in macrophages. Furthermore, depleting macrophages using macrophage inhibitor PLX-3397, results in impaired tissue regeneration and blood vessel formation, namely a reduction in the regeneration area and vessel network by 75% in comparison to controls."

Journal • Oncology

Study of CVM-1118 for Patients With Advanced Neuroendocrine Tumors (clinicaltrials.gov) - P2 | N=34 | Active, not recruiting | Sponsor: TaiRx, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2023 ➔ Dec 2024 | Trial primary completion date: Nov 2022 ➔ Sep 2024

Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Endocrine Cancer • Hepatology • Neuroendocrine Tumor • Oncology • Solid Tumor

Phase II clinical trials of anti-cancer drugs will release data as soon as the first quarter of next year [Google translation] (stock.yahoo) - "The Phase II clinical trial of CVM-1118, the main small molecule anti-cancer drug of New Drug Research and Development Company...will progress next year. CVM-1118 treats advanced liver cancer and neuroendocrine tumors respectively. Among them, the treatment of advanced liver cancer has been The case collection has been completed and the data results are expected to be released in the first quarter of next year....In addition, for the treatment of neuroendocrine tumors with CVM-1118, it is expected that 32 patients will be admitted this (November) month, and the follow-up observation period will also be 6 months. General Manager Jian Duxian explained that since this clinical trial is an open trial, and the number of cases received in the middle of this year has reached the clinical evaluation standard, and the main efficacy indicator, deterioration-free survival (PFS), is in line with expectations, the overall clinical trial results are expected next year."

Enrollment status • P2 data • Gastrointestinal Cancer • Liver Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor

CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative, promotes apoptosis and inhibits vasculogenic mimicry via targeting TRAP1. (PubMed, Pathol Oncol Res) - "Most importantly, the loss-of-function mutations of STK11 and NF2 are potential biomarkers of CVM-1118 which can be applied in the selection of cancer patients for CVM-1118 treatment. CVM-1118 is currently in its Phase 2a clinical development."

Biomarker • Journal • Oncology • HIF1A • STK11

CVM-1118: A potent oral anti-vasculogenic mimicry (VM) agent in patients with advanced neuroendocrine tumors (NETs)—A phase IIa study. (ASCO 2023) - P2 | "CVM-1118 has demonstrated a durable DCR with acceptable safety and tolerability. PK results showed good drug exposure with T1/2 of CVM-1125 ~2.2 hr. These data support future studies in patients with advanced NETs."

Clinical • Metastases • P2a data • Anemia • Endocrine Cancer • Gastrointestinal Disorder • Hematological Disorders • Neuroendocrine Tumor • Oncology • Solid Tumor

CVM-1118 and Sorafenib Combination in Subjects With Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=12 | Terminated | Sponsor: TaiRx, Inc. | N=40 ➔ 12 | Trial completion date: Mar 2022 ➔ Dec 2022 | Active, not recruiting ➔ Terminated; The study has been terminated due to slow enrollment

Enrollment change • Metastases • Trial completion date • Trial termination • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Tairui liver cancer drug phase II clinical case acceptance progress is lower than expected and the trial is terminated early [Google Translation] (Anue Juheng) - "Tairui...conducted a phase II open clinical trial of oral cancer drug CVM-1118 and Nexavar in the treatment of advanced unresectable liver cancer. Due to the slower than expected progress of the case acceptance, it was decided to terminate the clinical trial early. Tairui explained that due to the new first-line drugs being launched during the clinical trial period, the number of patients taking Nexavar has dropped sharply, resulting in lower-than-expected progress in accepting cases. In view of the clinical trial schedule and funding Therefore, it was decided to terminate the phase II clinical trial of oral CVM-1118 and Lesava in patients with advanced liver cancer in advance."

Trial termination • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology

CVM-1118 in Combination With Nivolumab for Unresectable Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=95 | Recruiting | Sponsor: TaiRx, Inc. | Not yet recruiting ➔ Recruiting | Initiation date: Mar 2022 ➔ May 2022

Enrollment open • Trial initiation date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

CVM-1118 in Combination With Nivolumab for Unresectable Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=95 | Not yet recruiting | Sponsor: TaiRx, Inc.

Combination therapy • New P2 trial • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

CVM-1118 and Sorafenib Combination in Subjects With Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P2; N=40; Active, not recruiting; Sponsor: TaiRx, Inc.; Recruiting ➔ Active, not recruiting; Trial completion date: Aug 2022 ➔ Mar 2022; Trial primary completion date: May 2022 ➔ Dec 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Study of CVM-1118 for Patients With Advanced Neuroendocrine Tumors (clinicaltrials.gov) - P2; N=30; Recruiting; Sponsor: TaiRx, Inc.; Trial completion date: Nov 2022 ➔ Nov 2023; Trial primary completion date: Nov 2021 ➔ Nov 2022

Clinical • Trial completion date • Trial primary completion date • Endocrine Cancer • Hepatology • Neuroendocrine Tumor • Oncology • Solid Tumor

The safety assessment of Tairui’s oral anticancer drugs was approved by the Food and Drug Administration [Google translation] (money.udn.com) - "Tai Rui...announced today...that the rapid release dosage form of the new oral anticancer drug CVM-1118 under development, and its new dosing frequency design clinical trial plan (code CVM-006) has been approved by the Food and Drug Administration (TFDA) has passed the review. The safety assessment of CVM-1118 administered three times a day and human pharmacokinetic studies will be conducted in Taiwan. It is expected to provide future clinical trial design and implementation options for new drug delivery methods....The first phase of the clinical trial is expected to accept 13 people in Taiwan."

Enrollment status • Non-US regulatory • Oncology

CVM-1118 and Sorafenib Combination in Subjects With Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P2; N=40; Recruiting; Sponsor: TaiRx, Inc.; Trial completion date: Jun 2021 ➔ Aug 2022; Trial primary completion date: Dec 2020 ➔ May 2022

Clinical • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor

A Safety and Pharmacokinetic Study of TRX-818 Administered Orally to Patients With Advanced Cancer (clinicaltrials.gov) - P1; N=36; Completed; Sponsor: TaiRx, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion