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

Evaluation of BOLD-100 as a Strategy to Overcome Drug Resistance in Multiple Myeloma (IMS 2026) - "A Phase 2 trial with FOLFOX reported reduced oxaliplatin-associated neuropathy, suggesting a potential neuroprotective effect worthy of exploration in MM... Isogenic MM cell lines including PI-sensitive (S), bortezomib-resistant (BR), and carfilzomib-resistant (CR) derivatives of AMO-1, RPMI-8226, U266 and OPM2 were used... Taken together, these findings position BOLD-100 as a clinically relevant strategy in PI-resistant myeloma. GRP78 suppression and UPR collapse provide a mechanistically coherent basis for PI synergy, and persistence in resistant models is important given the unmet need in relapsed/refractory disease. The neuronal findings, while early, are encouraging."

Hematological Malignancies • Multiple Myeloma • ATF4 • ATF6 • BDNF • CASP3 • HSPA5

BOLD-100 treatment induces systemic lipid crosstalk in metastatic colorectal carcinoma patients in a combination treatment with FOLFOX. (PubMed, iScience) - P1/2 | "BOLD-100 treatment was found to exhibit systemic, dose-dependent effects that were more pronounced on the lipid level compared with the protein level. This study indicates that BOLD-100 affects lipid profiles and influences systemic lipid crosstalk, which, in combination with oxaliplatin, leucovorin, and fluorouracil (FOLFOX) chemotherapy may, at least partially, account for the superior clinical outcomes over established therapies in mCRC patients."

Journal • Colorectal Cancer • Oncology • Solid Tumor • HSPA5

BOLD-100 in Combination with FOLFOX Is a Broadly Effective Therapeutic Strategy for Gastric Cancer. (PubMed, Int J Mol Sci) - "This study evaluated the therapeutic effects of BOLD-100 alone and in combination with 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX) and 5-fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT) in patient-derived organoid (PDO) models of gastric adenocarcinoma. These results support the potential of BOLD-100, particularly in combination with FOLFOX, as a broadly effective therapeutic strategy for gastric cancer. PDO models provide a clinically relevant platform to investigate treatment heterogeneity and identify regimens with high therapeutic indices in molecularly diverse tumours."

Journal • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • HSPA5

Leveraging Morphological Profiling for Mechanistic Elucidation of Metal-Based Anticancer Compounds. (PubMed, JACS Au) - "The validity of this strategy was established using a subset of clinically approved anticancer therapeutics, where morphological profiling discerned the mechanistic differences among oxaliplatin, cisplatin, carboplatin, and the clinical-stage ruthenium-based compound BOLD-100. This association was investigated further, revealing an accompanying increase in levels of mitochondrial reactive oxygen species and a corresponding depolarization of the mitochondrial membrane. This application of morphological profiling will enable the rapid identification of promising metal-containing therapeutics, aiding in rational development strategies and mitigating persistent challenges in metallotherapeutic development."

Journal • Developmental Disorders • Oncology

Novel ruthenium(II) complexes bearing polypyridyl and 1,2,4-oxadiazole ligands: from synthesis to in vitro and in vivo anticancer evaluation. (PubMed, Dalton Trans) - "The antiproliferative activity of the metal complexes in human colorectal (HCT116 and oxaliplatin- and BOLD-100-resistant derivatives) and ovarian (A2780 and A2780cis) cancer cell lines was evaluated. Finally, in vivo tests were conducted in BALB/c mice using the most promising compound, to evaluate its toxicity profile and its ability to inhibit CT-26 tumor growth. Interestingly, both duplex and G-quadruplex DNA can be excluded as potential molecular targets, as assessed by FRET-melting assays, UV-Vis spectroscopy, and circular dichroism."

Journal • Preclinical • Oncology

A Barcoding Strategy for Pooled Single-Cell LA-ICP-TOFMS Analysis of Metal-Containing Therapeutics. (PubMed, Anal Chem) - "Barcoding-enabled single-cell analysis confirmed a substantial reduction in oxaliplatin uptake in oxaliplatin-resistant HCT116 cells compared with the WT cell line, whereas BOLD-100 uptake was affected to a much lesser extent. These results demonstrate the utility of this strategy for the efficient and scalable assessment of metal-based therapeutics."

Journal • Colorectal Cancer • Oncology • Solid Tumor

Neuroprotective potential of BOLD-100 when utilized in combination with FOLFOX for the treatment of advanced gastrointestinal cancers. (ASCO 2026) - P1/2 | "The median number of prior systemic therapies was 3 (range 0-8) with 95% treated with oxaliplatin (65%) or cisplatin (30%)... Analysis of safety and dosing data from BOLD-100-001 suggests a potential neuroprotective effect of BOLD-100 against FOLFOX-induced PN. Further investigations are ongoing to characterize this effect in a randomized arm of the BOLD-100-001 clinical trial which is exploring changes in health-related and neuropathy-related quality of life per EORTC-QLQ-30 and EORTC-QLQ-CIPN20 scores."

Combination therapy • Metastases • Biliary Cancer • Biliary Tract Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRAF

Bold Therapeutics' Clinical-Stage Anticancer Agent BOLD-100 Demonstrates Neuroprotective Potential when Utilized in Combination with FOLFOX for the Treatment of Advanced Gastrointestinal Cancers (PRNewswire) - "This data is presented in an abstract as part of the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting....109 participants with advanced gastrointestinal cancer were evaluated in the study....On study, 24 patients (22%) experienced at least one oxaliplatin-induced peripheral neuropathy (OIPN) adverse event. Lower OIPN incidence was observed across all cohorts relative to benchmarks: mCRC (14% vs. 53%), BTC (32% vs. 68%), GC (19% vs. 63%), and pancreatic cancer (29% vs. 38%). Only 9 patients (8.2%) discontinued oxaliplatin, with only 2 attributed to OIPN. Of 69 dose reductions, 16 (23%) were due to OIPN. Patients at the highest BOLD-100 dose level (625 mg/m2) had the lowest OIPN incidence."

P2 data • Biliary Tract Cancer • Colorectal Cancer • Gastric Cancer • Pancreatic Cancer

Combinational studies of BOLD-100/KP1339 with established chemotherapeutics in gastrointestinal multicellular tumor spheroids. (PubMed, Cancer Chemother Pharmacol) - "The purpose of this study was to assess in vitro the impact of BOLD-100 combinations with oxaliplatin, 5-FU, cisplatin or SN38 in multicellular tumor spheroids (MCTSs) compared to single-drug treatments...Apoptosis and necrosis were induced in the spheroid models by single-drug and combined treatment, with no hints at antagonism in the combination settings. In conclusion, these findings emphasize the potential of BOLD-100 for combination therapy of gastric and colorectal cancers."

Journal • Colon Cancer • Colorectal Cancer • Gastric Cancer • Oncology • Solid Tumor • HSPA5

Clinical-stage anticancer agent BOLD-100 demonstrates protective effects against chemotherapy-induced peripheral neuropathy (AACR 2026) - P1/2 | "To assess BOLD-100's neuroprotective effects in vivo, Sprague-Dawley rats received vehicle (10 mL/kg), oxaliplatin (1.5 mg/kg), paclitaxel (1.0 mg/kg), or BOLD-100 (40 mg/kg) alone, plus BOLD-100 in combination with oxaliplatin and paclitaxel...Chemotherapy-induced peripheral neuropathies have limited therapeutic options; these results demonstrate BOLD-100's potential for both neuroprotection and treatment via impacting important stress pathways. Ongoing clinical study BOLD-100-001 is assessing BOLD-100's neuroprotective effects and its ability to enhance patient outcomes and reduce neurotoxicity."

Clinical • Biliary Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ATF6 • HSPA5

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

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 • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

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-100-001: BOLD-100 in Combination with FOLFOX for the Treatment of Advanced Solid Tumours (clinicaltrialsregister.eu) - P1/2 | N=52 | Recruiting | Sponsor: Bold Therapeutics Inc.

New P1/2 trial • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRAF

BOLD-100-001: BOLD-100 in Combination with FOLFOX for the Treatment of Advanced Solid Tumours (clinicaltrialsregister.eu) - P1/2 | N=52 | Recruiting | Sponsor: Bold Therapeutics Inc. | N=38 ➔ 52

Enrollment change • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRAF

Bold-100-001: A randomized phase 2 study of bold-100 plus FOLFOX vs FOLFOX in patients with refractory metastatic colorectal cancer. (ASCO-GI 2026) - P1/2 | "Prior oxaliplatin is permitted if: 1) received in the adjuvant setting; 2) received in first line setting with no progression on treatment or within 3 months of oxaliplatin treatment cessation...120 patients are expected to be enrolled. Enrollment is ongoing at sites in Canada, South Korea and Europe."

Clinical • Metastases • P2 data • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • KRAS

Additional functionality for plecstatin-1-analogous anticancer Ru(η6-p-cymene)Cl complexes. (PubMed, J Inorg Biochem) - "Complexes 1a-3a showed no activity but 4a was moderately potent with an IC50 value of 35 μM in NCI-H460 cells. Organoruthenium compound 4a was also more active than its PCA ligand 4 and the clinically investigated Ru complex KP1339 in NCI-H460 cells."

Journal • Cervical Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BOLDSARC-01: BOLD-100 Plus Doxorubicin in Advanced Soft Tissue Sarcomas (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: University Health Network, Toronto | Initiation date: Jun 2025 ➔ Mar 2026

Trial initiation date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

The Role of Metallodrugs in Enhancing Neuroendocrine Neoplasm Therapies: The Promising Anticancer Potential of Ruthenium-Based Complexes. (PubMed, Molecules) - "Currently, medicinal inorganic chemistry is investigating new metal-based drugs to mitigate the side effects of existing agents, including cisplatin and its derivative compounds. This review focuses on the promising antitumor effects of certain Ru compounds in NEN therapy, emphasizing their potential in NEN treatment through interaction with new potential targets. Among these, IT-139 (also known as KP-1339 or NKP-1339), which has already entered clinical trials, and other new Ru compounds are highlighted."

Journal • Review • Endocrine Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Solid Tumor

Ultrasound-Targeted Nanobubbles Codelivering NKP-1339 and miR-142-5p for Synergistic Mitochondrial Immunogenic Cell Death and PD-L1 Inhibition in Cancer Therapy. (PubMed, Biomater Res) - "Moreover, the UTMD technique enhanced the tumoral accumulation and penetration of nanobubbles, improving delivery specificity and minimizing off-target effects. This combined treatment strategy, including UTMD, provides a promising translational potential for ESCC therapy."

IO biomarker • Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gene Therapies • Metabolic Disorders • Oncology • Solid Tumor • Squamous Cell Carcinoma • CALR • CD8 • MIR142 • PD-1 • PD-L1

Machine Learning-Enhanced Calculation of Quantum-Classical Binding Free Energies. (PubMed, J Chem Theory Comput) - "The ML potential approach takes electrostatic embedding and long-range electrostatics into account. We demonstrate the applicability of the workflow on the well-studied protein-ligand complex of myeloid cell leukemia 1 and the inhibitor 19G and on the anticancer drug NKP1339 acting on the glucose-regulated protein 78."

Journal • Hematological Malignancies • Leukemia • Oncology • MCL1

Therapeutic potential of BOLD-100, a GRP78 inhibitor, enhanced by ATR inhibition in pancreatic ductal adenocarcinoma. (PubMed, Cell Commun Signal) - "BOLD-100 synergizes with AZD6738, an ATR inhibitor, to enhance anti-tumor efficacy compared to either agent alone in both in vitro and in vivo models. These findings suggest that BOLD-100, especially in combination with an ATR inhibitor, represents a promising therapeutic option for patients with PDAC."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CHEK1 • HSPA5

BOLD-100 Plus Doxorubicin in Advanced Soft Tissue Sarcomas (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: University Health Network, Toronto

New P1 trial • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

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