BOLD-100 / Bold Therap, Hana Pharm - LARVOL DELTA

Unraveling BOLD-100 synergistic potential in pleural mesothelioma treatment: an in vitro study. (PubMed, Invest New Drugs) - "Our aim is to investigate cellular responses of several PM cell lines to a regimen that includes BOLD-100 in addition to other commonly used treatments. BOLD-100 is a ruthenium-based anticancer therapeutic."

Journal • Preclinical • Gastrointestinal Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor • HSPA5

Bold Therapeutics Presents Late-Breaking Poster on BOLD-100's Unique Ability to Mitigate Oxaliplatin-Induced Peripheral Neuropathy (OIPN) at AACR Annual Meeting 2025 (PRNewswire) - P1b/2a | N=220 | NCT04421820 | Sponsor: Bold Therapeutics, Inc. | "A surprising finding from this trial was a profound reduction in both the frequency and severity of oxaliplatin-induced peripheral neuropathy (OIPN), a relatively common and debilitating side effect of chemotherapy. In each patient cohort, rates of neuropathy were dramatically lower than those typically seen in historical benchmarks for FOLFOX alone: These results were supported by feedback from trial investigators, many of whom noted the unexpectedly low incidence of neuropathy in their patients treated with BOLD-100 — particularly those who were heavily pretreated and/or receiving FOLFOX again where one would expect both a high incidence and severity of neuropathy."

P1/2 data • Biliary Tract Cancer • Colorectal Cancer • Gastric Cancer • Pancreatic Ductal Adenocarcinoma

Bold Therapeutics Announces Presentation of Late-Breaking Data on BOLD-100's Unique Ability to Mitigate Oxaliplatin-Induced Peripheral Neuropathy (OIPN) (PRNewswire) - "Bold Therapeutics Inc...announced that its Sr. Director of Preclinical Development, Mark Bazett, PhD, will be presenting a late-breaking poster on BOLD-100's potent neuroprotective properties at the American Association for Cancer Research (AACR) Annual Meeting 2025, taking place April 25–30, 2025, in Chicago, Illinois. Mark Bazett will be joined by Jim Pankovich, EVP Clinical Development, and Ashish Kumar, PhD, Sr. Scientist....Bold Therapeutics is currently enrolling FOLFOX-naïve second-line mCRC patients in a multinational randomized clinical study comparing FOLFOX vs. FOLFOX + BOLD-100 in various efficacy, safety, and quality-of-life endpoints. Bold Therapeutics anticipates this trial will further demonstrate BOLD-100's potential as a transformative therapy in early-line colorectal cancer, biliary tract cancer and other solid tumor indications."

Late-breaking abstract • Preclinical • Trial status • Biliary Tract Cancer • Colorectal Cancer • Solid Tumor

Mechanical cues rewire lipid metabolism and support chemoresistance in epithelial ovarian cancer cell lines OVCAR3 and SKOV3. (PubMed, Cell Commun Signal) - "This was associated with increased cholesterol uptake/biosynthesis and decreased sensitivity to the ruthenium-based anticancer drug BOLD-100. Overall, the present study contributes to shedding light on the molecular pathways connecting mechanical cues, tumor metabolism and drug responsiveness."

Journal • Preclinical • Epithelial Ovarian Cancer • Metabolic Disorders • Oncology • Ovarian Cancer • Solid Tumor • YAP1

Clinical-stage anticancer agent BOLD-100 demonstrates protective effects against oxaliplatin-induced peripheral neuropathy in an in-vivo rat model (AACR 2025) - P1/2 | "Collectively, these findings provide strong evidence that BOLD-100 not only enhances oxaliplatin-based therapy in GI malignancies but also improves its clinical utility by markedly reducing OIPN. Ongoing clinical studies are evaluating BOLD-100's neuroprotective benefits and its potential to enhance the therapeutic index of standard-of-care regimens for advanced GI cancers."

Late-breaking abstract • Preclinical • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

PERK as a biomarker to optimize therapy of GRP78 inhibitor, BOLD-100, in gastric cancer (AACR 2025) - "BOLD-100 (GRP78 inhibitor), TUDCA (Tauroursodeoxycholic acid; ER stress inhibitor), and AZD6738 (ATR inhibitor) were used. The expression of PERK determines sensitivity to GRP78 inhibition by BOLD-100 in GC. PERK-high GC cells are sensitive to BOLD-100 and show efficacy as monotherapy. In PERK-low GC cells, the combination of BOLD-100 and ATR inhibitor is an optimal therapeutic option for GC treatment."

Biomarker • Gastric Cancer • Oncology • Solid Tumor • ANXA5 • CHEK1 • EIF2A • EIF2S1 • HSPA5

From Concept to Cure: The Road Ahead for Ruthenium-Based Anticancer Drugs. (PubMed, ChemMedChem) - "Among these, Ru complexes, exemplified by BOLD-100 and TLD1433, have shown exceptional promise due to their selective activity, lower propensity for resistance, and the ability to target spescific cellular pathways. This paper explores the journey of such Ru candidates, focusing on the mechanisms, efficacy, and clinical potential of these Ru-based drugs, which stand at the forefront of current research, aiming to provide more targeted, less toxic, and highly effective cancer treatments."

Journal • Review • Oncology

Recent trends in the design and delivery strategies of ruthenium complexes for breast cancer therapy. (PubMed, Dalton Trans) - "The discovery of cisplatin marked the beginning of the development of anticancer metal-based medications, although the drug's severe side effects have limited its usage in clinical settings. The remarkable antimetastatic and anticancer activity of different ruthenium complexes such as NAMI-A, KP1019, KP1339, etc. reported in the 1980s has bolstered the discovery of ruthenium complexes with various types of ligands for anticancer applications...These findings underscore the promising therapeutic avenues offered by ruthenium-based compounds, particularly in addressing the challenges posed by conventional treatments in refractory or aggressive breast cancer subtypes. Moreover, the review comprehensively integrates a spectrum of ruthenium complexes, spanning traditional metal complexes to nano-based formulations and light-activated variants, underscoring the versatility and adaptability of ruthenium chemistry in breast cancer therapy."

Journal • Breast Cancer • Oncology • Solid Tumor

BOLD-100-001: BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours (clinicaltrials.gov) - P1/2 | N=220 | Recruiting | Sponsor: Bold Therapeutics, Inc. | Active, not recruiting ➔ Recruiting | Phase classification: P1b/2a ➔ P1/2 | N=117 ➔ 220 | Trial completion date: Sep 2024 ➔ Sep 2026 | Trial primary completion date: Dec 2023 ➔ Jun 2026

Combination therapy • Enrollment change • Enrollment open • Metastases • Phase classification • Trial completion date • Trial primary completion date • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gallbladder Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Targeting regulated cell death pathways in rhabdomyosarcoma using a trinuclear ruthenium(II) complex (ACS-Fall 2024) - "Platinum-Group Metal (PGM) complexes, particularly those containing ruthenium, present promising avenues for drug discovery, this is exemplified by complexes like BOLD-100, NAMI-A and NKP-1339. Notably, this ruthenium(II) complex also inhibited the migratory ability of metastatic RMS cells and maintained its enhanced cytotoxicity relative to cisplatin in 3D multicellular tumor spheroid models. Mechanistic investigations revealed that the lead ruthenium(II) complex proficiently induced double-stranded DNA damage and triggered various forms of programmed cell death, including both intrinsic and extrinsic apoptotic pathways as well as autophagy, in RMS cells."

Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Ruthenium drug BOLD-100 regulates BRAFMT colorectal cancer cell apoptosis through AhR/ROS/ATR signaling axis modulation. (PubMed, Mol Cancer Res) - "These results unveil possible novel therapeutic opportunity for BRAFMT CRC. Implications: BOLD-100 induces BRAFMT-dependent replication stress, and targeted strategies against replication stress (eg. by using ATR inhibitors) in combination with BOLD-100 may serve as a potential novel therapeutic strategy for clinically aggressive BRAFMT CRC."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CHEK1 • CYP1A1

Positive Phase 2 and Mechanism-of-Action Data for BOLD-100 Presented at 2024 'Metals in Medicine' Gordon Research Conference (PRNewswire) - "Dr. Bazett presented positive Phase 2 clinical results of BOLD-100 in colorectal, biliary tract, and gastric cancers, as well as sharing updates on Bold Therapeutics' unique novel metallotherapeutic screening program and development strategy....Yasmin Borutzki...a close collaborator of Bold Therapeutics, presented a poster on translational research into BOLD-100 entitled: Of Mice and Men: Reverse Translation Investigation of BOLD-100's Mechanism-of-Action."

P2 data • Preclinical • Biliary Tract Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Solid Tumor

BOLD-100-001: A phase II study of BOLD-100 in combination with FOLFOX in advanced mCRC patients that have failed at least two prior lines of therapy (ESMO-GI 2024) - P1b/2a | "Despite previous oxaliplatin treatment, fewer than 5% of pts reported peripheral neuropathy; those reported were G1/2. There remains an unmet need for improved treatment options for patients with mCRC... There remains an unmet need for improved treatment options for patients with mCRC. BOLD-100 + FOLFOX is an active and well-tolerated treatment despite a heavily pretreated population. The mPFS, mOS, ORR and DCR data demonstrate clinical benefit with minimal neuropathy or significant toxicities."

Clinical • Combination therapy • Metastases • P2 data • Colorectal Cancer • Dermatology • Fatigue • Hematological Disorders • Neutropenia • Pain • Pruritus • HSPA5

Coumarin-modified ruthenium complexes: Synthesis, characterization, and antiproliferative activity against human cancer cells. (PubMed, Arch Pharm (Weinheim)) - "Among ruthenium complexes studied as anticancer metallodrugs, NKP-1339, NAMI-A, RM175, and RAPTA-C have already entered clinical trials due to their potent antitumor activity demonstrated in preclinical studies and reduced toxicity in comparison with platinum drugs...Coumarin derivative 2a positively regulated the expression and activity of c-Myc and NPM1 in RKO colon carcinoma cells, while the Ru(II) half-sandwich complex 2cRu induced downregulation of AKT and ERK signaling in PANC-1 cells concomitant with reduced intracellular levels of reactive oxygen species. Altogether, our findings indicated that coumarin-modified half-sandwich Ru(II) complexes held potential as anticancer agents against gastrointestinal malignancies."

Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatocellular Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • MYC • NPM1

A phase 2 study of BOLD-100 in combination with FOLFOX chemotherapy in patients with pretreated advanced biliary tract cancer: Efficacy and safety analysis (BOLD-100-001). (ASCO 2024) - P1b/2a | "BOLD-100 combined with FOLFOX is an active and well-tolerated treatment regimen in Stage IV BTC. There were no new safety signals detected. The mPFS, mOS, ORR and DCR data in this advanced BTC cancer population indicate a treatment combination worthy of further study for this difficult to treat cancer."

Clinical • Combination therapy • Metastases • P2 data • Biliary Cancer • Biliary Tract Cancer • Fatigue • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pain • Solid Tumor

A phase 2 study of BOLD-100 in combination with FOLFOX chemotherapy in patients with advanced gastric cancer: Efficacy and safety analysis (BOLD-100-001). (ASCO 2024) - P1b/2a | "BOLD-100 plus FOLFOX is an active, well-tolerated treatment regimen in the heavily pre-treated advanced GC. The reported mPFS, mOS, ORR and DCR data in this analysis shows promising clinical activity. The combination of BOLD-100 with FOLFOX is worthy of further study."

Clinical • Combination therapy • Metastases • P2 data • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pain • Solid Tumor

Bold Therapeutics Announces Positive Phase 2 Safety and Efficacy Results for BOLD-100 in Advanced Metastatic Biliary Tract and Gastric Cancers at ASCO 2024 (PRNewswire) - P2 | N=117 | NCT04421820 | Sponsor: Bold Therapeutics, Inc. | "Bold Therapeutics...announced positive Phase 2 safety and efficacy results for...BOLD-100 in the treatment of advanced metastatic biliary tract cancer (BTC) and gastric cancer (GC) at the American Society of Clinical Oncology...BTC Efficacy and Safety...Median progression-free survival (PFS) of 6.0 months [95% CI: 3.8 – 10.0] and median OS of 7.3 months [95% CI: 4.5 – 13.0], which compares extremely favorably with standard-of-care outcomes...GC Efficacy and Safety...Median progression-free survival (PFS) of 4.2 months [95% CI: 2.8 – 7.1] and median OS of 7.9 months [95% CI: 4.8 – 15.0], which compares extremely favorably with standard-of-care outcomes...'Bold Therapeutics expects to announce intriguing nonclinical data later this year, specifically biomarker data'....Later this month, Bold Therapeutics expects to begin enrolling patients into a multinational Phase 2...with second-line FOLFOX-naïve colorectal cancer."

Enrollment status • P2 data • Preclinical • Biliary Tract Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology

Combination Of Novel Ruthenium-based Small Molecule Bold-100 And Capecitabine Is Effective In Inhibiting Growth Of Estrogen Receptor Positive Metastatic Breast Cancer (ENDO 2024) - P1b/2a | "ER+ tumors that progress on antiestrogens are subsequently treated with a combination of antiestrogens and CDK4/6 inhibitors (palbociclib, ribociclib or abemaciclib)...BOLD-100 has recently been investigated in a multicenter global Phase 1B/2A trial (NCT04421820) of gastrointestinal cancer patients in combination with chemotherapy FOLFOX, which includes fluorouracil, the active form of capecitabine...Cells treated with combination of capecitabine and BOLD-100 shows increase in apoptosis and DNA damage compared with cells treated with monotherapies or control. Therefore, capecitabine and BOLD-100 is a potential novel combination therapy for breast cancer that has progressed on standard of care treatment."

Late-breaking abstract • Metastases • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CCND1 • ER

Co-downregulation of GRP78 and ATR enhances apoptosis in pancreatic ductal adenocarcinoma (AACR 2024) - "GRP78 could serve as one of the potential therapeutic targets in PDAC. The combination of BOLD-100 and AZD6738 demonstrates a synergistic effect suggesting GRP78/ATR dual targeting as a promising therapeutic option for patients with PDAC."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • ANXA5 • CHEK1 • EIF2A • EIF2S1 • HSPA5

BOLD-100 and ATR Inhibitors as a New Avenue for PDAC Targeting at AACR 2024 (PRNewswire) - "BOLD-100 elevates ER stress and ROS, leading to activation of the UPR pathway and CHOP-dependent apoptosis, which inhibits PDAC growth; ROS accumulation activates the ATR-CHK1 DNA damage repair pathway, which NAC can abrogate; and The combination of BOLD-100 with the ATR inhibitor AZD6738 exhibits a synergistic effect, suggesting GRP78/ATR dual targeting as a promising therapeutic approach for PDAC."

Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Synthesis and preclinical evaluation of BOLD-100 radiolabeled with ruthenium-97 and ruthenium-103. (PubMed, Dalton Trans) - "Our results indicate that the higher injected dose (30 mg kg-1) leads to more unspecific accumulation of the compound in non-targeted tissue, which is likely due to an overload of the albumin transport system. It was also shown that lower amounts of injected c.a. [103Ru]BOLD-100 resulted in a relatively higher tumor uptake and, therefore, a better tumor-to-background ratio, which are encouraging results for future imaging studies using c.a. [97Ru]BOLD-100."

Journal • Preclinical • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor

Onco-metabolically active ruthenium complex KP1339 displays immunomodulatory properties in cancer and cells of the tumor microenvironment (EACR-AACR 2024) - "BOLD-100-induced lactate reduction bares potential to induce an immunosupportive environment, differentially regulating the cancer-CAF-crosstalk. Further investigations are currently underway."

Biomarker • Immunomodulating • Tumor microenvironment • Metabolic Disorders • Oncology • BSG • CAFs • HSPA5 • MCT1

BOLD-100-001 (TRIO039): A phase 2 study of BOLD-100 in combination with FOLFOX in patients with advanced mCRC previously treated with FOLFOX/CAPOX—Efficacy and safety analysis. (ASCO-GI 2024) - P1b/2a | "Despite previous oxaliplatin treatment, fewer than 6% of pts reported peripheral neuropathy or peripheral sensory neuropathy and all were G1/2... BOLD-100 + FOLFOX is an active and well-tolerated treatment in this heavily pre-treated Stage IV mCRC study population. There were no new safety signals. The mPFS, mOS, ORR and DCR data demonstrate significant clinical benefit and improvement over the currently available therapies, with minimal treatment emergent neuropathy or significant toxicities."

Clinical • Combination therapy • Metastases • P2 data • Colorectal Cancer • Gastrointestinal Cancer

Bold Therapeutics Announces Positive Phase 2 Safety and Efficacy Results for BOLD-100 in Advanced Metastatic Colorectal Cancer at ASCO GI 2024 (PRNewswire) - P2 | N=117 | NCT04421820 | Sponsor: Bold Therapeutics, Inc. | "Bold Therapeutics...presented positive Phase 2 safety and efficacy data in advanced metastatic colorectal cancer (mCRC) patients treated with BOLD-100 in combination with FOLFOX previously treated with FOLFOX/CAPOX at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium on January 18-20, 2024...Key findings...67% of patients had progressive disease on prior FOLFOX/CAPOX...the objective response rate (ORR) was 7.0%, with 2 partial responses (PR) and 20 stable diseases (SD) resulting in a disease control rate (DCR) of 76%...Phase 2 safety and efficacy results in biliary tract and gastric cancer are currently available under confidentiality and will be presented publicly at a major cancer conference later this year....'We look forward to advancing BOLD-100 into late-stage studies in the near-future, initially targeting a 2027 FDA approval in advanced metastatic colorectal cancer.'"

NDA • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Complexes of Ruthenium(II) as Promising Dual-Active Agents against Cancer and Viral Infections. (PubMed, Pharmaceuticals (Basel)) - "In this context, numerous metal-based substances, including cisplatin, auranofin, various gold metallodrugs, and ruthenium complexes, are under study as possible anticancer and antiviral agents. The two Ru(III) and Ru(II) complexes, namely, BOLD-100 and RAPTA-C, are presently being studied in a clinical trial and preclinical studies evaluation, respectively, as anticancer agents...Ru-based complexes could be very suitable in this respect. Thus, this review focuses on the most recent studies regarding newly synthesized Ru(II) complexes for use as anticancer and/or antiviral agents."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases