ecubectedin (PM14) / PharmaMar - LARVOL DELTA

The novel transcriptional inhibitor ecubectedin demonstrates strong antitumor activity in patient-derived xenograft models of soft tissue sarcoma (AACR 2025) - "Doxorubicin (DOX)-based chemotherapy is standard of care for advanced/metastatic disease, despite low response rates and poor disease control...Mice were randomized to 5 experimental groups and treated by tail vein injection once weekly: 1) vehicle (VEH) (5% dextrose) 5 mL/kg; 2) DOX 5 mg/kg; 3) trabectedin (TRA) 0.15 mg/kg; 4) lurbinectedin (LUR) 0.18mg/kg; 5) ECU 1.2 mg/kg... ECU has antitumor effects in PDX models of STS, with the most prominent activity seen in STS134. Next step includes investigating the role of DNA repair mechanisms in response to ECU treatment."

Preclinical • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Ecubectedin as a promising therapeutic agent against gastric cancer through WNT/β-Catenin modulation (AACR 2025) - "In vivo, a single i.v. dose of Ecubectedin (0.6 mg/kg) inhibited tumor growth by 61% after 7 days in both RNA-seq and in vivo protein data (from tumors in ecubectedin-treated mice) support that ecubectedin represses WNT/β-catenin signaling. In conclusion, ecubectedin shows strong antitumor activity against gastric cancer, modulating the often-dysregulated WNT/β-catenin pathway, highlighting its potential as a promising therapeutic for further clinical exploration."

Gastric Cancer • Oncology • Solid Tumor • CTNNB1

Ecubectedin's role in targeting transcriptional regulators in neuroendocrine prostate cancer (AACR 2025) - "Ecubectedin may impact transcriptional networks driving the cell plasticity and NE transformation in NEPC tumors. More importantly, a significant in vitro and in vivo antitumor activity of ecubectedin was observed in NEPC models, suggesting a significant potential as a promising novel therapeutic for this indication associated to very poor outcomes."

Genito-urinary Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • ASCL1 • MYCN • NEUROD1 • SOX2

Ecteinascidin synthetic analogues: a new class of selective inhibitors of transcription, exerting immunogenic cell death in refractory malignant pleural mesothelioma. (PubMed, J Exp Clin Cancer Res) - "Collectively, these findings reveal a previously unknown mechanism of action of ecteinascidins that merits further investigation for potential clinical applications in the treatment of MPM, as new first line treatment in monotherapy or in association with immunotherapy."

Journal • Gene Therapies • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor • CD8

THE DNA MINOR GROOVE BINDING AGENTS ECUBECTEDIN AND PM54 DEMONSTRATE ANTITUMOR ACTIVITY IN PATIENT-DERIVED XENOGRAFT MODELS OF SOFT TISSUE SARCOMA (CTOS 2024) - "Objective: We explored the antitumor activity of two DNA minor groove binding derivatives of lurbinectedin (LUR), under development by PharmaMar (Spain): ecubectedin (ECU) and PM54, in four patient-derived xenograft (PDX) models of soft tissue sarcoma (STS)...Xenografted mice were randomized to six treatment groups: 1) vehicle (VEH) (5% dextrose) 5 mL/kg once weekly (QW) intravenously (IV); 2) doxorubicin (DOX) 5mg/kg QW IV; 3) trabectedin (TRA) 0.15 mg/kg QW IV; 4) LUR 0.18 mg/kg QW IV; 5) ECU 1.2mg/kg QW IV; 6) PM54 1.2 mg/kw QW IV... The novel compounds ECU and PM54 have antitumor activity in the PDX models tested here. We are now exploring the agents in additional PDX models of synovial sarcoma and DDLPS. We will also study the impact of the DNA repair capacity of the models on the antitumor effects observed with the drugs."

Preclinical • Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma

Phase I/II clinical and pharmacokinetic study of ecubectedin in combination with irinotecan in patients with selected advanced solid tumors (ESMO 2024) - P1/2 | "Legal entity responsible for the study: PharmaMar S.A. Background: Ecubectedin –PM14– (ECU) is a new chemical entity that forms DNA adducts that inhibit RNA synthesis and active transcription of protein-coding genes. At the RD, ECU + IRI + 1ry GCSF prophylaxis has a manageable safety profile. Hematological abnormalities, fatigue, transaminase increase and nausea were the main toxicities. No major PK drug-drug interactions between ECU and IRI were found."

Clinical • Combination therapy • Metastases • P1/2 data • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

PM14 Administered Intravenously to Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=150 | Recruiting | Sponsor: PharmaMar | Trial completion date: Feb 2023 ➔ Aug 2025 | Trial primary completion date: Feb 2023 ➔ Aug 2025

Metastases • Trial completion date • Trial primary completion date • Adrenal Cortex Carcinoma • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • BRCA

Ecubectedin and PM54 demonstrate antitumor activity in patient-derived xenograft models of soft tissue sarcoma (AACR 2024) - "Doxorubicin (DOX)-based chemotherapy is the standard for advanced or metastatic STS, despite low response rates and poor disease control. We explored the antitumor activity of two novel compounds, ecubectedin (ECU; PM14) and PM54 (PharmaMar), in two patient-derived xenograft (PDX) models of STS, leiomyosarcoma (LMS) and CIC-rearranged sarcoma (CRS). Mode of action of ECU and PM54 is similar to lurbinectedin (LUR), inhibiting oncogenic transcription by eviction of oncogenic transcription factors from gene promotors' recognition sequences, while inducing the generation of double strand breaks through DNA adduct formation. Female NMRI nu/nu mice (n=104) were transplanted bilaterally with STS PDX: UZLX-STS134 (CRS) and UZLX-STS22_2 (LMS). Xenografted mice were randomized to six treatment groups: 1) vehicle (VEH) (5% dextrose) 5 mL/kg once weekly (QW) intravenously (IV); 2) DOX 5 mg/kg QW IV; 3) trabectedin (TRA) 0.15 mg/kg QW IV; 4) LUR 0.18 mg/kg QW IV; 5) ECU 1.2 mg/kg..."

Preclinical • Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma

A phase III study of lurbinectedin alone or in combination with irinotecan vs investigator's choice (topotecan or irinotecan) in patients with relapsed small cell lung cancer (SCLC; LAGOON trial). (ASCO 2023) - P1/2, P2, P3 | "Main exclusion criteria include platinum-naïve patients, patients pretreated with more than one prior chemotherapy regimen (including platinum re-challenge), and prior treatment with lurbinectedin, trabectedin, PM14, or topoisomerase I inhibitors. An Independent Review Committee will provide the patient’s response at each tumor assessment endpoint to determine the best patient’s response and the date of objective response or progression/censoring according to RECIST v.1.1. Clinical trial information: NCT05153239."

Clinical • Combination therapy • P3 data • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

Ecubectedin is a novel transcriptional inhibitor that displays potent antitumor effects in vitro and in vivo (AACR 2023) - "Background - Ecubectedin (PM14) is a novel transcriptional inhibitor related to ecteinascidins family...In mice bearing MDA-MB-231, H526 and 22Rv1 tumors, complete tumor remissions were seen in 1/10 (lasting 103 days), 9/10 (lasting 220 days) and 7/10 (lasting 13 days) ecubectedin-treated animals, respectively.Conclusions - Ecubectedin is a novel transcriptional inhibitor that displays potent antiproliferative activity in different human solid cancer models in vitro and in vivo. The drug is currently in clinical development in Phase II trials."

Preclinical • Lung Cancer • Neuroendocrine Tumor • Oncology • Sarcoma • Small Cell Lung Cancer • Soft Tissue Sarcoma • Solid Tumor • ANXA5 • NF-κβ • TNFA

"https://t.co/RGxYOvRDej #pharmamar #AACR23 #lurbinectedina #zepzelca #sclc #ecubectedina @PhrmMar" (@pistoto2017)

Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

"Good examples, #lurbinectedin & #trabectedin from @PhrmMar , and I suppose #ecubectedin, but of the latter we have a little information." (@pistoto2017)

PM14 Administered Intravenously to Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=150 | Recruiting | Sponsor: PharmaMar | Active, not recruiting ➔ Recruiting

Enrollment open • Adrenal Cortex Carcinoma • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA

PRIME: Multicohort Trial of Different Schemes of PM14 in Monotherapy and in Combination With Radiotherapy in Soft Tissue Sarcomas and Other Solid Tumor (clinicaltrials.gov) - P1/2; N=195; Recruiting; Sponsor: Grupo Espanol de Investigacion en Sarcomas

Combination therapy • Monotherapy • New P1/2 trial • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • MRI

PM14 Administered Intravenously to Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=150; Active, not recruiting; Sponsor: PharmaMar; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Adrenal Cortex Carcinoma • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA

PM14 Administered Intravenously to Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=150; Recruiting; Sponsor: PharmaMar

Clinical • New P1 trial • Adrenal Cortex Carcinoma • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA

[VIRTUAL] First-in-human study of PM14 in patients with advanced solid tumors. (ASCO 2021) - "RDs were determined for two PM14 schedules in pts with advanced solid tumors . At the RDs, PM14 is well tolerated and has a manageable safety profile . An expansion phase in specific tumor types, with an optional Bayesian continual reassessment method for RD fine-tuning, is ongoing with both schedules."

Clinical • P1 data • Breast Cancer • Genito-urinary Cancer • Hematological Disorders • Kidney Cancer • Lung Cancer • Neuroendocrine Tumor • Neutropenia • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Sarcoma • Small Cell Lung Cancer • Soft Tissue Sarcoma • Solid Tumor

Moloney murine leukemia virus p12 is required for histone loading onto retroviral DNAs. (PubMed, J Virol) - "Infection by virions containing a mutant p12 (PM14) defective in chromatin tethering results in the formation of viral DNAs that do not accumulate in the nucleus...p12 mutants lacking tethering activity fail to acquire histones, retain capsid and nucleocapsid proteins, and are poorly transcribed. The work defines a new requirement for a viral protein to allow chromatinization of viral DNA."

Journal • Preclinical • Hematological Malignancies • Infectious Disease • Leukemia • Oncology

First report of peach leaf pitting-associated virus (PLPaV), plum bark necrosis stem pitting-associated virus (PBNSPaV), and mume virus A (MuVA) from Mei (Prunus mume) in China. (PubMed, Plant Dis) - "2020) with 92.30% of sequence identity; the scalffold of MuVA (MW217572) covered 14.50% of the genome of the isolate pm14 from Japan (NC 040568.1) (Marais et al.2018) with 98.47% sequence identity; the scaffold of PLPaV (MW217573) covered 15.26% of the genome of the isolate XJ-6 from peach (KY867750.1) (He et al...Although it is difficult to link a particular virus with the observed symptoms due to mixed infections, the symptoms were significantly associated with viral infection because almost all symptomatic leaf samples were virus(es)-positive. Further studies would be required to determine the distribution and impact of these viruses on mei trees and other stone fruits species and to understand the possibility that mei trees may play a role in PLPaV epidemiology."

Journal • Infectious Disease

Multi-stress tolerant PGPR Bacillus xiamenensis PM14 activating sugarcane (Saccharum officinarum L.) red rot disease resistance. (PubMed, Plant Physiol Biochem) - "Augmented production of antioxidative enzymes and proline content may lead to the induced systemic resistance against red rot disease of sugarcane. Thus, the future application of native multi-stress tolerant bacteria as bio-control agents in combination with current heat, drought, salinity, and heavy metal tolerance strategy could contribute towards the global food security."

Journal

Deciphering metal toxicity responses of flax (Linum usitatissimum L.) with exopolysaccharide and ACC-deaminase producing bacteria in industrially contaminated soils. (PubMed, Plant Physiol Biochem) - "gibsonii PM11 and B. xiamenensis PM14 in metal phytoremediation of metals, their survival and plant growth promotion potential in metal polluted environment as well as alterations in physio-biochemical responses of inoculated L. usitatissimum plants towards heavy metal toxicity...In current study, inoculation of IAA, EPS and ACC-deaminase producing bacteria enhances plant growth and nutrient availability by minimizing metal-induced stressed conditions. Moreover, elevated phytoextraction of multi-metals from industrial contaminated soils by PGPR inoculated L. usitatissimum plants reveal that these strains could be used as sweepers in heavy metals polluted environment."

Journal

Assisted phytoremediation of chromium spiked soils by Sesbania Sesban in association with Bacillus xiamenensis PM14: A biochemical analysis. (PubMed, Plant Physiol Biochem) - "Our findings revealed first report of B. xiamenensis as phytoremediator and its inoculation on Sesbania plant. It also exposed dual effects of B. xiamenensis to ameliorate Cr stress along with improved plant growth and induced heavy metal stress tolerance in spiked soils."

Journal

A multimodal virtual keyboard using eye-tracking and hand gesture detection. (PubMed, Conf Proc IEEE Eng Med Biol Soc) - "04 pm 14 .55$ bits per minute. The results highlight that the hand gesture assigned for the selection of an item is inter-subject dependent."

Journal

PharmaMar presents at MaNaPro & ECMNP its latest advances in the development of compounds of marine origin (Pharmamar Press Release) - "PharmaMar (MSE:PHM) presents its latest advances in the development of its marine-derived compounds with antitumor activity at the XVI International Symposium on Marine Natural Products (MaNaPro) and the XI European Conference on Marine Natural Products (ECMNP)...PharmaMar will present two posters with two new ADCs: MI180021 and MI130110....Finally, a poster on its latest compound in clinical development, PM14, will also be presented. This poster shows the chemical synthesis and activity of the compound in breast, sarcoma and gastric tumors in pre-clinical studies."

Preclinical

Management Strategies And Outcomes Of Signature Long QT Syndrome Arrhythmia Presenting In The Perinatal Period: A Multicenter Registry Study (RHYTHM 2019) - "...Pre-discharge management was antiarrhythmic drugs in 36, sympathectomy in 7 (6 L, 0 R, 1 bilateral), and cardiac device implantation in 22 (PM 14, ICD 8)... Signature LQTS presentation portends high risk for neurologic and cardiac events, especially with SCN5A/CACNA1C genotypes. Such data should be useful to inform future therapeutic strategies."

Clinical