PS101 / Exact Therap - LARVOL DELTA

First-in-human study of acoustic cluster therapy consisting of PS101 combined with chemotherapy and insonation in patients with liver metastases of colorectal cancer origin (ESMO 2025) - P1 | "Methods We describe a first-in-human study to evaluate the safety, pharmacokinetics, and preliminary anti-cancer activity of ACT treatment and the chemotherapy regimens FOLFOX or FOLFIRI in patients with liver metastases of colorectal origin...Legal entity responsible for the study Exact Therapeutics AS. Funding Exact Therapeutics AS."

Clinical • First-in-human • P1 data • Colorectal Cancer • Oncology • Solid Tumor

A phase 2 study to investigate the efficacy and safety of acoustic cluster therapy with modified FOLFIRINOX in patients with locally advanced pancreatic cancer Free (AACRPanCa 2025) - P2 | "Acoustic cluster therapy (ACT) is an investigational ultrasound-mediated drug delivery platform that combines a proprietary intravenous formulation (PS101) with focused ultrasound to enhance chemotherapeutic delivery...Key eligibility include 1) histologically or cytologically proven diagnosis of PDAC not deemed suitable for primary curative surgery and have radiographic and pathological disease consistent with inoperable LAPC or borderline resectable pancreatic cancer 2) no previous anti-cancer treatment for pancreatic cancer, 3) tumor localizable with ultrasound without contrast with a maximum distance of 14 cm between the furthest tumor margin and the probe as measured by ultrasound and 4) suitable to receive treatment with mFOLFIRINOX. Enrollment began in June 2025."

Clinical • Metastases • P2 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Evaluation of the immunostimulatory potential of Acoustic Cluster Therapy (ACT®) in melanoma and breast cancer models in mice (CICON 2025) - "Acoustic Cluster Therapy (ACT®) involves intravenous injection of PS101, clusters of microbubbles (MB) and microdroplets...The number of CD8+ T cells correlated with the area under DCE-US curves (p=0.0048). The findings suggest that ACT may improve the therapeutic effectiveness of checkpoint inhibitors, cause tumours to generate a heightened immunogenic response, and provide opportunities for imaging biomarkers that are predictive of these effects."

IO biomarker • Preclinical • Breast Cancer • Colorectal Cancer • Melanoma • Oncology • Solid Tumor • CD4 • CD8 • IL33 • STC1

Acoustic Cluster Therapy (ACT®) increases Anti-PD1 checkpoint inhibitor uptake in prostate cancer in mice (CICON 2025) - "ACT is based on PS101, which is microclusters of negatively charged perfluorobutane (PFB) microbubbles and positively charged microdroplets of perfluoromethylcyclopentane (PFMCP) that are injected intravenously...5 min post-treatment, ACT tumors showed 1.8x higher fluorescence than controls; at 4 hours (ex vivo), the ratio was 1.6x, indicating a sustained effect despite enhanced-permeability and retention-driven uptake in controls. In conclusion, ACT improved uptake and distribution of anti-PD1 in a mouse model of prostate cancer, suggesting that ACT may be used as a complementary therapy to immunotherapy to improve therapeutic efficacy."

Checkpoint inhibition • Preclinical • Colorectal Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

EXACT Therapeutics announces first patient dosed in Phase 2 trial in patients with locally advanced pancreatic cancer (GlobeNewswire) - "EXACT Therapeutics...is pleased to announce first patient dosed in its ENACT trial. The trial is a multi-centre, open-label Phase 2 clinical trial testing the safety and efficacy of Acoustic Cluster Therapy (ACT) in combination with standard of care (modified FOLFIRINOX chemotherapy) in first line patients with borderline resectable or unresectable locally advanced pancreatic cancer...'We are on track with the opening of sites for patient recruitment and initial safety data are expected in 2025'...The Phase 2 trial will enroll up to 25 patients in the U.S., U.K. and Europe..."

P2 data • Trial status • Pancreatic Cancer

Acoustic Cluster Therapy (ACT®) mediated Enhancement of [68Ga]Ga-PSMA-617 in a Murine Glioblastoma Multiforme (GBM) Model verified with simultaneous PET/MRI (SNMMI 2025) - "ACT, an ultrasound (US) mediated microbubble (PS101) platform for targeted therapeutic enhancement has been shown to increase the accumulation of drugs by safely and transiently modifying the permeability of the vasculature [3]... Accumulation of [68Ga]Ga-PSMA-617 in the tumors was significantly higher following ACT (n=6) compared to sham (n=5)(0.35 ± 0.04 vs 0.15 ± 0.04 SUV ± SD; p<0.001) 40-60 min post injection. The tumor-to-brain ratio of [68Ga]Ga-PSMA-617 was higher in the ACT group (2.6 ± 0.9) compared to the sham (2.0 ± 0.3), 45 min post injection. Logan analysis revealed a significantly higher volume of distribution (Vt) following ACT vs sham (0.39 ± 0.16 vs 0.27 ± 0.13 mL/cm3; p<0.05)."

Preclinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Acoustic Cluster Therapy (ACT®) mediated Enhancement of [68Ga]Ga-PSMA-617 in a Murine Glioblastoma Multiforme (GBM) Model verified with simultaneous PET/MRI (SNMMI 2025) - "ACT, an ultrasound (US) mediated microbubble (PS101) platform for targeted therapeutic enhancement has been shown to increase the accumulation of drugs by safely and transiently modifying the permeability of the vasculature [3]... The study showed the potential of ACT to enhance accumulation of [68Ga]Ga-PSMA-617 in a mouse model of GBM, which was validated by PK. Cordance Medical’s device and ACT as well as [68Ga]Ga-PSMA-617 are currently in individual preclinical and clinical development stages respectively, supporting their potential for a combined translational application to humans. Applying ACT as a complementary therapy to TRT might not only improve treatment efficacy in GBM but is potentially also applicable for a variety of other solid tumors."

Preclinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

EXACT Therapeutics announces positive final results in Phase 1 ACTIVATE trial in liver metastases from colorectal cancer (The Manila Times) - P1 | N=11 | ACTIVATE (NCT04021277) | Sponsor: EXACT Therapeutics AS | "EXACT Therapeutics...is pleased to announce the final and positive data set from its Phase 1 ACTIVATE trial.... Among patients who responded to chemotherapy, tumor shrinkage was significantly greater with ACT and chemotherapy compared to chemotherapy alone in the same individuals (−29% vs. −7%, p<0.05). ACT treatment with EXACT's proprietary agent PS101 had a clear dose-response relationship. Shrinkage of tumour lesions was significantly greater in patients who received 40 µl/kg PS101 compared with 20 µl/kg PS101. In the group of patients who showed a response to chemotherapy in the control lesions, 3 out of 4 patients who received 40 µl/kg PS101 showed tumour shrinkage of more than 30% in diameter. Tumour shrinkage was seen in 6 out of 9 patients who received ACT with chemotherapy."

P1 data • Colorectal Cancer

PS101-mediated ACT With Chemotherapy in Liver Metastases From Cancer of Gastrointestinal Origin (clinicaltrials.gov) - P1 | N=11 | Terminated | Sponsor: EXACT Therapeutics AS | Active, not recruiting ➔ Terminated; Business reason

Trial termination • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

PS101-mediated ACT With Chemotherapy in Liver Metastases From Cancer of Gastrointestinal Origin (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: EXACT Therapeutics AS | Recruiting ➔ Active, not recruiting | N=32 ➔ 11 | Trial completion date: Jun 2024 ➔ Sep 2024 | Trial primary completion date: Jun 2024 ➔ Sep 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

First-in-human study of acoustic cluster therapy consisting of PS101 combined with chemotherapy and insonation in patients with liver metastases of colorectal cancer origin (AACR 2024) - P1 | "Following preclinical activity in xenograft models, the ongoing first in human study of ACT in patients with colorectal cancer has shown clinical translation of differential activity in insonated metastasis. Reference:Reference: 1.Bush N et al Front Pharmacol 2019, 10:1299"

Clinical • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

PS101-mediated ACT With Chemotherapy in Liver Metastases From Cancer of Gastrointestinal Origin (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: EXACT Therapeutics AS | Unknown status ➔ Recruiting | Trial completion date: Jul 2022 ➔ Jun 2024 | Trial primary completion date: Jul 2022 ➔ Jun 2024

Enrollment open • Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

EXACT Therapeutics completed the dose escalation part of ACTIVATE study (Exact Sciences Press Release) - "EXACT THERAPEUTICS AS today announces that the dose escalation part of the ACTIVATE study is completed...This part of the study enrolled 8 patients, with 6 patients eligible for evaluation. The study is conducted at the Institute of Cancer Research (ICR), Royal Marsden Hospital, London with Professor Udai Banerji as the principal investigator. A presentation of the safety and efficacy findings will be released when the full results are available....The study Trial Monitoring Committee reviewed the safety data from the dose escalation and approved initiation of the dose expansion part of the ACTIVATE study. The dose expansion is designed to determine the dose level for further development of ACT and expand the safety and efficacy data with 12 to 20 patients with metastatic colorectal cancer."

Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A genetic toolkit for co-expression of multiple proteins of diverse physiological implication. (PubMed, Biotechnol Rep (Amst)) - "The three plasmids contain ColE1, p15A and pSC101 origin of replication for high, medium and low copy plasmids, respectively, and same promoter (T5) and RBS...Each of these reporter proteins exhibited diverse impact on growth, plasmid copy number and stability, and expression of other reporter proteins. Our results indicate that GFP and RFP were the most and the least favorable proteins for the cells, respectively, in terms of these parameters, especially on impacting expression of other co-expressed proteins."

Journal

[VIRTUAL] Phase I trial of acoustic cluster therapy (ACT) with chemotherapy in patients with liver metastases of gastrointestinal origin (ACTIVATE study). (ASCO 2021) - P1 | "ACT is an innovative platform technology using sonopermeation to induce ultrasound (US) mediated targeting of therapeutic agent of choice by co-administration of an emulsion of microbubble-microdroplet clusters (PS101) for intravenous injection...Patients with advanced solid tumors with liver metastases for whom FOLFOX/FOLFIRI is considered an appropriate treatment option are eligible for Part 1 (n=6-12); two separate cohorts of patients with liver metastases, one with metastatic colorectal cancer eligible for 1L or 2L standard of care (SOC) FOLFOX/FOLFIRI (n=25) and one with metastatic pancreatic ductal adenocarcinoma (n= 6) eligible for SOC gemcitabine-nab-paclitaxel will be treated in Part 2...Assessment is made of the target lesion and the pre-defined control lesions outside of the US field . Part 1 has enrolled 5 patients without DLT, with part 2 expected to start in mid-2021."

Clinical • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • MRI

Differential Chromosome- and Plasmid-Borne Resistance of Escherichia coli hfq Mutants to High Concentrations of Various Antibiotics. (PubMed, Int J Mol Sci) - "We found that the presence of Hfq was required for survival of plasmid-containing Escherichia coli cells against high concentrations of chloramphenicol (plasmid p27cmr), tetracycline (pSC101, pBR322) and ampicillin (pBR322), as hfq strains were more resistant to these antibiotics than the hfq-null mutant. Studies with pBR322Δrom may also suggest an interplay between Hfq and Rom in the regulation of ColE1-like plasmid replication. Results of experiments with a mutant devoid of the part of the hfq gene coding for the C-terminal region of Hfq suggested that this region, as well as the N-terminal region, may be involved in the regulation of expression of antibiotic resistance in E. coli independently."

Journal

Psychrosphaera ytuae sp. nov., isolated from the deep-sea cold seep sediment of South China Sea. (PubMed, Int J Syst Evol Microbiol) - "Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain MTZ26 belonged to the genus Psychrosphaera and was closely related to Psychrosphaera aestuarii PSC101 (97.5 % sequence similarity) and Psychrosphaera haliotis KDW4 (97.5 %)...nov. is proposed with the type strain MTZ26 (=MCCC 1K05568=JCM 34321)."

Journal

Plasmid replication-associated single-strand-specific methyltransferases. (PubMed, Nucleic Acids Res) - "Genetic and biochemical studies suggest that enzyme action depends on replication mode: DNA Polymerase I (PolI)-dependent ColE1 and p15A origins support asymmetric modification, while the PolI-independent pSC101 origin does not...M.EcoGIX helps to establish pESBL in new hosts by blocking the action of restriction enzymes, in an orientation-dependent fashion. Expression and action appear to occur on the entering single strand in the recipient, early in conjugal transfer, until lagging-strand replication creates the double-stranded form."

Journal

Acoustic Cluster Therapy (ACT) With Chemotherapy in Metastatic Liver Metastases of Gastrointestinal Origin (clinicaltrials.gov) - P1; N=37; Recruiting; Sponsor: Phoenix Solutions; Trial completion date: Jan 2021 ➔ Jul 2022; Trial primary completion date: Jan 2021 ➔ Jul 2022

Clinical • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Liver Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Oral vaccination with live attenuated Yersinia pseudotuberculosis strains delivering a FliC180-LcrV fusion antigen confers protection against pulmonary Y. Pestis infection. (PubMed, Vaccine) - "Levels of FliC180-LcrV synthesis were same in Yptb5 either harboring pSMV4, a p15A ori plasmid or pSMV8, a pSC101 ori plasmid containing the fliC180-lcrV fusion gene driven by P promoter...Immunization with each mutant strain conferred complete protection against pulmonary challenge with 5.5 × 10 CFU (55 LD) of Y. pestis, but partial protection (50% survival) against 100 LD of Y. pestis. Our results demonstrate that arabinose-dependent regulated delayed fur shut-off is an effective strategy to develop live attenuated bacterial vaccines while retaining strong immunogenicity."

Journal • Immunology • Infectious Disease • Tuberculosis • IL17A