tosposertib (NCE 401) / Tium Bio, Chiesi - LARVOL DELTA

Tiumbio announced on November 25 that the World Health Organization (WHO) has approved the International Nonproprietary Name (INN) for its anticancer drug candidate, TU2218 (development code), as 'Tosposertib.' (The Bio)

Commercial • Squamous Cell Carcinoma of Head and Neck

TiumBio’s TU2218 combination shows 82% disease control rate in phase 2 head and neck cancer trial (Korea Biomedical Review) - "According to TiumBio, as of July 31, 12 of 17 evaluable patients (70.6 percent) achieved a partial response (PR) to the combination therapy, leading to a disease control rate (DCR) of 82.4 percent. The updated DCR represents an improvement from the previously reported 66.7 percent announced in the SITC abstract from June 20, which was based on earlier patient data."

P2 data • Squamous Cell Carcinoma of Head and Neck

Phase 2 trial of TU2218, TGFβ-RI and VEGF-R2 dual inhibitor in combination with Pembrolizumab in patients with head and neck squamous cell carcinoma (SITC 2025) - P1/2 | "The most frequently observed ≥ Grade 3 TRAE in all dosed patients were mucositis (16.7%), rash (22.2%) and no Grade 5 AE was reported.The evaluable patients were aged 43 ~ 72 years (average age: 60.7) and 75% of patients were male. The most common primary tumor locations were oropharynx (25%), oral cavity (16.7%), hypopharynx (16.7%).Conclusions TU2218 in combination with Pembrolizumab in patients with HNSCC demonstrated high response rate and manageable toxicity supporting its potential as a first-line therapy for HNSCC warranting further investigation in larger trials.Acknowledgements TiumBio Co., Ltd., Republic of Korea Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USATrial Registration Clinicaltrials.gov: NCT05204862 (Phase 1a) NCT05784688 (Phase 1b&2a)"

Clinical • Combination therapy • IO biomarker • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • KDR • PD-L1 • TGFB1

Phase II trial of TU2218, TGFβ-RI and VEGF-R2 dual inhibitor in combination with pembrolizumab in patients with head and neck cancer (ESMO 2025) - P1/2 | "Legal entity responsible for the study TiumBio Co., Ltd. Funding TiumBio Co., Ltd."

Clinical • Combination therapy • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • KDR • PD-L1 • TGFB1

Phase 2 trial of TU2218, TGFβ-RI, and VEGF-R2 dual inhibitor in combination with pembrolizumab in patients with biliary tract cancer and head and neck cancer. (ASCO 2025) - P1/2 | "Up to 40 BTC patients and up to 36 HNSCC patients are planned to be enrolled and a dropout rate of up to 10% is expected. As of this abstract submission date, 14 BTC patients and 8 HNSCC patients have been enrolled."

Clinical • Combination therapy • P2 data • Biliary Cancer • Biliary Tract Cancer • Dermatology • Head and Neck Cancer • Oncology • Pruritus • Renal Disease • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • KDR • TGFB1

TiumBio Announces Phase 2 Clinical Trial Results of 'TU2218' at ASCO 2025 [Google translation] (HIT News) - "Tium Bio...announced on the 30th that it will participate in the 'American Society of Clinical Oncology (ASCO) 2025' to be held in Chicago, USA starting on the 30th of next month...TiumBio announced that its abstract submitted to ASCO 2025 was accepted and that it plans to disclose the interim results of the phase 2 clinical trial of oral immunotherapy drug TU2218 for biliary tract cancer and head and neck cancer."

P2 data • Biliary Tract Cancer • Head and Neck Cancer

KEYNOTE-E34: Study of TU2218 in Combination With KEYTRUDA®(Pembrolizumab) in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=140 | Recruiting | Sponsor: TiumBio Co., Ltd. | Phase classification: P1b/2a ➔ P1/2

Phase classification • Biliary Cancer • Cholangiocarcinoma • Colorectal Adenocarcinoma • Colorectal Cancer • Head and Neck Cancer • Hepatology • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BRAF • EGFR • KRAS • NRAS

TiumBio Announces First Patient Dosed in Phase 2 Clinical Trial of Oral Immuno-Oncology Drug TU2218 (PRNewswire) - "TiumBio Co., Ltd...announced today that the first patient has been dosed in its Phase 2 clinical trial of TU2218....The first dose was administered to an HNSCC patient."

Trial status • Squamous Cell Carcinoma of Head and Neck

Phase Ib trial results of safety, pharmacokinetics and pharmacodynamics of TU2218, TGFβ-RI and VEGF-R2 dual inhibitor in combination with pembrolizumab in patients with advanced solid tumors (ESMO 2024) - P1/2, P1b/2a | "TU2218, a first-in-class dual inhibitor against TGFβ-RI and VEGF-R2 was safe and well-tolerated in combination with pembrolizumab. The Recommended Phase 2 Dose of the Combination (RP2DC) was established for subsequent trials in specific cancer types."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • PK/PD data • Oncology • Solid Tumor • CTGF • PD-L1 • TGFB1 • TGFBR1

TiumBio Announces Interim Results of Phase 1b Clinical Trial of TU2218 and Keytruda (Medipana) - P1b/2a | N=142 | KEYNOTE-E34 (NCT05784688) | Sponsor: TiumBio Co., Ltd. | "Among 16 patients with tumor evaluability, 3 had partial response (PR) and 7 had stable disease (SD), resulting in an ORR of 19% and a DCR of 63%. In the high dose (195 mg/day) group, ORR of 30% and DCR of 80% were achieved....Tium Bio, a company specializing in research and development of treatments for rare and intractable diseases, announced the interim results of the phase 1b clinical trial of the immunotherapy drug 'TU2218' at the 'European Society for Medical Oncology (ESMO)' on the 14th (local time)....In the phase 1b clinical trial results of TU2218 presented at the ESMO Congress, among the 16 patients whose tumors could be evaluated, three showed a partial response (PR) in which cancer cells were reduced by more than 30% compared to the baseline, and seven patients showed stable disease (SD) in which there was no significant change in tumor size."

P1 data • Solid Tumor

ALK5/VEGFR2 dual inhibitor TU2218 alone or in combination with immune checkpoint inhibitors enhances immune-mediated antitumor effects. (PubMed, Cancer Immunol Immunother) - "The inactivation of endothelial cells induced by VEGF stimulation was completely ameliorated by TU2218, an effect not observed with vactosertib, which inhibits only TGFβ signaling. As another strategy, combination of anti-CTLA4 therapy and TU2218 resulted in high complete regression (CR) rates in CT26 and WEHI-164 tumor models. In particular, immunological memory generated by the combination of anti-CTLA4 and TU2218 in the CT26 model prevented the development of tumors after additional tumor cell transplantation, suggesting that the TU2218-based combination has therapeutic potential in immunotherapy."

Checkpoint inhibition • Combination therapy • IO biomarker • Journal • Oncology • Transplantation • CD8 • TGFBR1 • VCAM1

American Oncology Network Announces the Research Studies Presented at the ASCO 2024 Annual Meeting (GlobeNewswire) - "American Oncology Network...is pleased to announce that several research studies, co-authored by AON physicians and leaders, were accepted at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting."

Clinical data • Breast Cancer • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Non Small Cell Lung Cancer • Oncology • Small Lymphocytic Lymphoma

Phase 1 trial of TU2218, TGFβ-RI and VEGF-R2 dual inhibitor in monotherapy and combination with pembrolizumab in patients with advanced solid tumors. (ASCO 2024) - P1/2, P1b/2a | "TU2218, a first-in-classoral dual inhibitor against TGFβRI and VEGFR2 was well-tolerated in the monotherapy and in the combination therapy with pembrolizumab. The RP2DC was established for subsequent trials in specific cancer types."

Clinical • IO biomarker • Metastases • Monotherapy • P1 data • Dermatology • Oncology • Pruritus • Solid Tumor • CTGF • KDR • PD-1 • TGFB1 • TGFBR1

TiumBio Presents Phase 1b Interim Results for TU2218 in Combination with Pembrolizumab at ASCO 2024 Annual Meeting (PRNewswire) - P1b/2a | N=142 | KEYNOTE-E34 (NCT05784688) | Sponsor: TiumBio Co., Ltd. | "TiumBio Co., Ltd...announced interim results from the Phase 1b clinical trial of TU2218 in combination with pembrolizumab at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting....Data from the full Phase 1b trial, which includes 18 patients, will be available in the second half of 2024. In the poster released at the 2024 ASCO Annual Meeting, five patients treated at the recommended phase 2 dose (RP2D) of 195mg/day TU2218 in combination with pembrolizumab demonstrated an ORR of 40% at PR (n=2) and 60% at SD (n=3) with a DCR of 100%. And across all dosage groups, patients (n=12) receiving the combination therapy showed PR at 16.7% (n=2), SD at 50.0% (n=6) and PD at 25.0% (n=3)."

P1 data • Oncology • Solid Tumor

TU2218 (TGFβRI/VEGFR2 dual inhibitor) maximizes the benefit of cancer immunotherapies (AACR 2024) - "In the 4T1 of TNBC type, a level of tumor reduction was significant to p<0.001 on TU2218 and anti-PD-1 antibody combination group compared to vehicle, whereas anti-PD-1 antibody alone or anti-PD-1 antibody and paclitaxel combination group was not significant...In CT26, the efficacy of Lenvatinib and anti-PD-1 antibody combination therapy was compared with the combination of Lenvatinib, anti-PD-1 antibody, and TU2218...Moreover, a statistical difference in anti-tumor activity between the two groups was significant at p<0.001. Collectively, the combination therapies using TU2218 not only improved efficacy but also showed high safety profiles without weight loss or any toxicity signs, supporting the feasibility of the combination strategy of TU2218."

Oncology • Triple Negative Breast Cancer • TGFB1

Tium Bio receives approval for domestic clinical trial change for cancer immunotherapy candidate [Attention e-Notice] [Google translation] (Hankyung) - "Tium Bio announced...that it received approval from the Ministry of Food and Drug Safety of Korea on the 16th to change the domestic clinical trial plan for TU2218, an oral immunotherapy candidate. Tium Bio, which was conducting a phase 1/2 clinical trial using TU2218 in combination with Keytruda (pembrolizumab) for patients with advanced solid cancer, selected three carcinomas, including amdo cancer, head and neck squamous cell cancer, and colorectal cancer, as indications for phase 2a clinical trials....This clinical trial is scheduled to run until the end of 2026."

Clinical protocol • Trial completion date • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

TiumBio to Initiate Phase 2 Trial of TU2218 for Cancer (PRNewswire) - P1/2 | N=240 | NCT05204862 | Sponsor: TiumBio Co., Ltd. | "TiumBio Co., Ltd...announced that it has submitted Investigational New Drug (IND) application to the Korean Ministry of Food and Drug Safe (MFDS) for a Phase 2a study of TU2218, an oral immuno-oncology drug, in late February, 2024 and that preclinical results of TU2218 will be presented at the upcoming 2024 American Association for Cancer Research (AACR) Annual Meeting....The poster abstract highlights the improved efficacy and safety profile of TU2218 in combination with various immuno-oncology drugs. Specifically, the combination of lenvatinib, anti-PD-1 antibody, and TU2218 demonstrated a significant tumor growth inhibition (TGI) of 99% and a complete response (CR) rate of 67% in the CT 26 model, compared to a TGI of 76% and CR of 17% in the control group receiving only lenvatinib and anti-PD-1 antibody."

New P2a trial • P1/2 data • Preclinical • Oncology • Solid Tumor

TiumBio Secures KRW 38.5 Billion in Anticipation of Upcoming Clinical Data (PRNewswire) - "TiumBio Co., Ltd...today announced the completion of a stock financing of 2,320,185 shares of its convertible preferred shares at a price of KRW 8,620 per share in a private placement. TiumBio sold the stock to SK Chemicals Co., Ltd. securing 20 billion won to fund its development of lead pipeline assets...The funds will be primarily allocated to support its clinical programs that include a Phase 2 trial of merigolix, a once-daily, oral gonadotropin-releasing hormone (GnRH) receptor antagonist, in endometriosis, and a Phase 1b trial of TU2218, a first-in-class oral immune-oncology therapy targeting TGF-β and VEGF, in combination with pembrolizumab, and a Phase 1 trial of TU7710, a recombinant protein designed to treat people with hemophilia who have inhibitors...'we look forward to sharing results with all stakeholders from the ongoing Phase 2 trial in endometriosis....expected in the first half of 2024.'"

Financing • P2 data • Endometriosis • Hemophilia • Oncology • Solid Tumor • Women's Health

“Tium Bio pays attention to clinical results of combination use of TGF-β/VEGFR inhibitor ‘TU2218’” [Google translation] (Insight Korea) - "SK Securities reported on the 4th that the reevaluation of major R&D pipelines based on the development performance of Tium Bio is expected to begin in earnest in 2024....'First of all, it is necessary to pay attention to the clinical results of the combination of the TGF-β/VEGFR inhibitor 'TU2218'....'Currently, clinical trials 1b/2a are being conducted in the U.S. and Korea as a combination therapy with the immunotherapy drug Keytruda. The award is in progress, and we expect to announce the results of phase 1b clinical trials at AACR and ASCO in the first half of 2024'."

P1 data • Oncology • Solid Tumor

Pharmacokinetics and pharmacodynamics study of TU2218, TGFβRI and VEGFR2 dual inhibitor in patients with advanced solid tumors (SITC 2023) - P1/2 | "The starting dose of TU2218 in combination with pembrolizumab was 105mg/day, with subsequent incremental doses of 150mg/day and 195mg/day. Conclusions TU2218, a first-in-class oral dual inhibitor against TGFβRI and VEGFR2, was well-tolerated in the monotherapy and will be subsequently investigated for the combination therapy with PD-L1."

Clinical • IO biomarker • Metastases • PK/PD data • Oncology • Solid Tumor • CTGF • KDR • TGFB1 • TGFBR1

First-in-human study of TU2218, TGFβRI and VEGFR2 dual inhibitor in patients with advanced solid tumors (ESMO 2023) - P1/2 | "This is a first-in-human study to investigate the safety and tolerability of TU2218 mono- and combination therapy with pembrolizumab. To date, clinical studies of TU2218 are ongoing. Conclusions TU2218, a first-in-class oral dual inhibitor against TGFβRI and VEGFR2, was well-tolerated in the monotherapy."

Clinical • Metastases • P1 data • Oncology • Solid Tumor • KDR • TGFB1 • TGFBR1

Tium Bio announces first clinical data on cancer immunotherapy drug TU2218 at ESMO [Google translation] (Medifonews) - P1/2 | N=240 | NCT05204862 | Sponsor: TiumBio Co., Ltd. | "Tium Bio announced the data of Phase 1a clinical trial, a single-administration clinical trial, of the immunotherapy drug 'TU2218' at the European Society for Medical Oncology (ESMO) on the 23rd (local time)....'In the first patient clinical trial of TU2218, the dosage was increased starting from 30 mg per day to 270 mg, but no dose limiting toxicity (DLT) occurred, and there were no drug-related side effects of grade 3 or higher, so this clinical trial was approved. We were able to confirm the safety and tolerability of TU2218, which was the main objective'...Meanwhile, Tium Bio is currently conducting a phase 1b clinical trial (NCT05784688) on the combination of TU2218 and Keytruda at three clinical institutions in the United States and is expected to produce clinical results early next year. In addition, it is scheduled to enter phase 2a clinical trials in the first half of next year for solid cancer patients."

P1 data • Trial status • Oncology • Solid Tumor

Tium Bio secures 18.5 billion won in funding… Continue stable clinical development [Google translation] (Medifonews) - "Tium Bio announced on the 13th that it decided to issue convertible bonds (CB) worth 18.5 billion won to raise major pipeline clinical development and operating funds....Tium Bio will use the funds raised through this CB issuance to conduct Phase 2 clinical trials in the U.S. and Korea for the immunotherapy drug 'TU2218', which is currently undergoing clinical trials for combination administration with Keytruda, and NovoSeven of Novo Nordisk."

Financing • Oncology • Solid Tumor

Korean pharma firms gear up for ESMO 2023, Europe's premier cancer conference (Korea Biomedical Review) - "As the opening of the European Society for Medical Oncology Annual Meeting (ESMO 2023), Europe's largest cancer conference, draws near, attention here is focused on Korean participants....TiUm Bio will present top-line results from its phase 1a clinical trial of TU2218, an oral immuno-oncology candidate. TU2218 is a dual inhibitor of transforming growth factor (TGF)-ß and vascular endothelial growth factor (VEGF). The company conducted a phase 1 study of TU2218 alone in patients with advanced solid tumors in the U.S. and Korea. The presentation will be made by Professor Oh Do-youn of the Department of Medical Oncology at Seoul National University Hospital, who is the principal investigator of the clinical trial."

P1 data • Solid Tumor

KEYNOTE-E34: Study of TU2218 in Combination With Pembrolizumab in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1b/2a | N=142 | Recruiting | Sponsor: TiumBio Co., Ltd. | Trial completion date: May 2024 ➔ Dec 2028 | Trial primary completion date: Dec 2023 ➔ Dec 2026

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Cholangiocarcinoma • Colorectal Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • EGFR • KRAS • NRAS