Amphinex (fimaporfin) / PCI Biotech - LARVOL DELTA

Mesenchymal stem cell membrane-coated polymeric nanoparticles for TPCS2a delivery (EACR 2023) - "Both formulations had comparable cell cytotoxic effects after red-light irradiation, in either 2D or 3D cell models, while no toxicity was observed in absence of irradiation. Lower uptake by macrophages was observed for mMSC-TPCS2a-NPs as compared to TPCS2a-loaded PLGA NPs.ConclusionOur results demonstrate the efficient loading of TPCS2a in PLGA-NPs and the successful coating of the nanosystem with mMSCs, thus avoiding PS aggregation, limiting the clearance by macrophages, and ensuring the production of singlet oxygen upon light irradiation.The in vitro uptake and cancer cell killing efficiency of mMSC-TPCS2a-NPs was comparable to that of TPCS2a-loaded NPs."

Breast Cancer • Oncology • Solid Tumor

All-trans retinoic acid enhances the anti-tumour effects of fimaporfin-based photodynamic therapy. (PubMed, Biomed Pharmacother) - "During the first 20 days post-ATRA+PDT, we obtained significant anti-tumour responses in HT-29 xenografts, including complete responses in 2/5 mice. In conclusion, ATRA+PDT represent a novel combination therapy for solid tumours that should be further tested in immunocompetent preclinical models."

Journal • Breast Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ATF3 • CD133 • EGR1

RELEASE: PCI Treatment/Gemcitabine & Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Extrahepatic Bile Duct Cancer (clinicaltrials.gov) - P2 | N=41 | Terminated | Sponsor: PCI Biotech AS | Trial completion date: Apr 2026 ➔ May 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Feb 2025 ➔ Apr 2022; Recent results from a Phase 3 study are expected to change the standard of care for patients with inoperable CCA, rendering the RELEASE study challenging to complete and potentially inadequate for NDA approval.

Trial completion date • Trial primary completion date • Trial termination • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor

Photochemical Internalization of Gemcitabine Is Safe and Effective in Locally Advanced Inoperable Cholangiocarcinoma. (PubMed, Oncologist) - "Photochemical internalization with gemcitabine was found to be safe and resulted in encouraging response and survival rates in patients with unresectable perihilar CCA."

Journal • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

RELEASE: PCI Treatment/Gemcitabine & Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Extrahepatic Bile Duct Cancer (clinicaltrials.gov) - P2 | N=41 | Active, not recruiting | Sponsor: PCI Biotech AS | N=186 ➔ 41

Enrollment change • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor

PCI Biotech fourth quarter and preliminary full year 2021 results (GlobeNewswire) - "fimaChem; The RELEASE trial was closed to recruitment in January 2022 due to changes in the competitor situation that renders the trial challenging to complete and potentially inadequate for approval...fimaVacc: The programme is progressing towards initiation of a Phase II clinical proof-of-concept study, with product definition and overall study design clarified following comprehensive consultations with international experts...These results are positive news for patients but will unfortunately render the RELEASE study challenging to complete, and the study was therefore terminated late January 2022."

New P2 trial • Trial termination • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Photochemically-Mediated Inflammation and Cross-Presentation of Mycobacterium bovis BCG Proteins Stimulates Strong CD4 and CD8 T-Cell Responses in Mice. (PubMed, Front Immunol) - "For this purpose, Mycobacterium bovis BCG (BCG) was combined with the photosensitiser tetraphenyl chlorine disulfonate (TPCS2a) and injected intradermally into mice...This study is the first to demonstrate that a live microbial vaccine can be combined with a photochemical compound and light for cross presentation of antigens to CD8 T cells. Moreover, the results revealed that PCI treatment strongly improved the immunogenicity of M. bovis BCG."

Journal • Preclinical • Immune Modulation • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4 • CD8 • IFNG • IL17A • IL1B • IL2 • TNFA

RELEASE: PCI Treatment/Gemcitabine & Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Extrahepatic Bile Duct Cancer (clinicaltrials.gov) - P2 | N=186 | Active, not recruiting | Sponsor: PCI Biotech AS | Recruiting ➔ Active, not recruiting

Enrollment closed • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor

PCI Biotech: Update on regulatory interactions for the RELEASE trial (GlobeNewswire) - "PCI Biotech...announced that the company has concluded on the interactions with regulatory authorities in the US (US Food and Drug Administration, FDA) and Europe (European Medicines Agency, EMA) held during 2H 2021. The interactions with the FDA and EMA were initiated to explore the opportunity for a modified study design to address the retention risk in the control arm of the RELEASE study. PCI Biotech argued that enrichment of the control arm of RELEASE with external control data, using existing patient-level data from past clinical trials and real-world data from a patient registry for patients with extra-hepatic cholangiocarcinoma receiving gemcitabine-cisplatin, could address the potential retention issue and that this approach may also benefit recruitment...Both regulatory authorities recognised the retention and recruitment challenges for RELEASE in bile duct cancer, a rare disease with high unmet medical need."

Enrollment status • Regulatory • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology

Light-controlled elimination of PD-L1+ cells. (PubMed, J Photochem Photobiol B) - "Using fluorescence microscopy, we reveal that the anti-PD-L1 antibody binds to PD-L1 on the surface of the MDA-MD-231 cells and overnight accumulates in late endosomes and lysosomes where it co-localizes with the PCI photosensitizer fimaporfin (TPCS)...In conclusion, our work provides an in vitro proof-of-concept of PCI-enhanced targeting and eradication of PD-L1 positive immunosuppressive cells. This light-controlled combinatorial strategy has a potential to advance cancer immunotherapy and should be explored in preclinical studies."

IO biomarker • Journal • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • Triple Negative Breast Cancer • IFNG • PD-L1

Inhibiting autophagy increases the efficacy of low-dose photodynamic therapy. (PubMed, Biochem Pharmacol) - "Here, we show that photochemical treatment with the PCI-photosensitizer TPCS/fimaporfin results in both induction of autophagy and inhibition of the autophagic flux...An active autophagic response and the presence of p62, however, is important for cancer cells to survive low-dose TPCS-PDT. Thus, targeting both p62 and autophagy together and independently, in a light-controlled/PCI based delivery of cancer therapeutics could increase the effectiveness of the treatment regime."

Clinical • Journal • Oncology • Targeted Protein Degradation • LGALS3

RELEASE: PCI Treatment/Gemcitabine & Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Extrahepatic Bile Duct Cancer (clinicaltrials.gov) - P2; N=186; Recruiting; Sponsor: PCI Biotech AS; Trial completion date: Apr 2024 ➔ Apr 2026; Trial primary completion date: Jul 2023 ➔ Feb 2025

Clinical • Trial completion date • Trial primary completion date • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor

PhotoChemical Internalization of gemcitabine followed by gemcitabine/cisplatin in perihilar cholangiocarcinoma – results from a phase I dose escalation trial (ESMO 2018) - P1/2; "NCT01900158.;Background: Cholangiocarcinoma is a rare cancer with a poor survival and an approximate response rate of 26% and a median PFS/OS of 8.0 and 11.7months respectively with current standard treatment (gemcitabine/cisplatin). In this dose escalation trial of PCI of gemcitabine in perihilar CCA patients, a safe and tolerable dose of light and Amphinex® was established. The overall safety profile and promising results, including a proportion of patients with highly durable objective tumor response, are encouraging. A larger, controlled and randomized study is underway."

P1 data • Biliary Cancer • Cholangiocarcinoma

Phase I clinical study for validation of fimaporfin-based photochemical internalisation: A novel technology for enhancing cellular immune responses important for therapeutic effect of peptide-and protein-based vaccines (ESMO-IO 2019) - P1; "Both antigens were formulated with fimaporfin and the TLR3 agonist poly-ICLC (Hiltonol) and administered in up to three vaccinations. The photochemically based fimaVacc vaccination technology can be applied safely in humans, and enhances T-cell responses to an HPV peptide vaccine over what is achieved in a control group which received antigen + adjuvant without fimaVacc.Legal entity responsible for the study: PCI Biotech AS. Funding: PCI Biotech AS. Clinical trial identification: NCT02947854."

Clinical • P1 data • CD8

PCI Biotech receives Orphan Drug Designation in South Korea for fimaporfin in the treatment of bile duct cancer (GlobeNewswire) - "PCI Biotech...today announced that the Ministry of Food and Drug Safety (MFDS) in South Korea has granted Orphan Drug Designation to its lead product candidate, fimaporfin, for combination treatment with gemcitabine in patients with inoperable locally advanced or metastatic bile duct cancer (cholangiocarcinoma). No approved treatment alternatives exist today for the first-line treatment of patients with this disease and fimaChem (fimaporfin) has the potential to play a role in this area of high unmet medical need."

Non-US regulatory • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology

Photochemical Internalization Enhanced Vaccination Is Safe, and Gives Promising Cellular Immune Responses to an HPV Peptide-Based Vaccine in a Phase I Clinical Study in Healthy Volunteers. (PubMed, Front Immunol) - P1 | "An enhancement of the humoral immune response to KLH vaccination was also observed. Using PCI in combination with Hiltonol for intradermal vaccination is safe at fimaporfin doses below 17.5 µg, and gives encouraging immune responses to peptide and protein based vaccination."

Clinical • Journal • P1 data • Dermatology • Immunology • Pain • CD8

PCI Biotech: Publication of case report series from the Phase I study in bile duct cancer (GlobeNewswire) - "PCI Biotech...today announced that a case report series from the Phase I study with PCI Biotech's proprietary drug fimaporfin (AmphinexTM), for the treatment of inoperable extrahepatic bile duct cancer (eCCA), is accepted for publishing in Endoscopy International Open. The article has the title 'Photochemical Internalisation and gemcitabine combined with first-line chemotherapy in perihilar cholangiocarcinoma – observations in three patients' and will soon be available online...look forward to work...in the RELEASE study..."

Observational data • P1 data • Cholangiocarcinoma • Oncology

Photochemical internalisation as a novel delivery strategy to enhance efficacy of antibiotic treatment of staphylococcal intracellular infection (ECCMID 2019) - "Confocal microscopy RAW264.7 cells were incubated overnight with 10 μg/ml Alexa Fluor 405-labeled gentamicin alone or combined with 1 μg/ml TPCS2a, then illuminated for 2 minutes and prepared for confocal microscopy. PCI can significantly enhance efficacy of antibiotics with limited activity (e.g. gentamicin) against intracellular staphylococcal infection, likely owing to PCI-induced cytosolic release of antibiotics."

Clinical

High aldehyde dehydrogenase activity does not protect colon cancer cells against TPCS-sensitized photokilling. (PubMed, Photochem Photobiol Sci) - "Likewise, both 5-FU and oxaliplatin chemotherapy efficacy was not reduced in ALDHbright as compared to ALDHdim cancer cells. This study demonstrates that the cytotoxic response to PDT (using TPCS2a as photosensitizer) is independent of ALDH activity in HT-29 cancer cells. Our results further strengthen the use of TPCS2a to target CSCs."

Journal • CD133

Recurrent chondroblastic osteosarcoma of the right mandible subjected to photochemical internalization. (PubMed, Photodiagnosis Photodyn Ther) - No abstract available

Clinical • Journal

PCI Biotech to present phase I fimaVacc results at ESMO Immuno-Oncology 2019 (GlobeNewswire, PCI Biotech Holding ASA) - "The poster named '109P - Phase I clinical study for validation of fimaporfin-based photochemical internalisation: A novel technology for enhancing cellular immune responses important for therapeutic effect of peptide-and protein-based vaccines' will be made available on PCI Biotech’s website (www.pcibiotech.com ) under 'Other presentations'."

P1 data

A Phase I/II Safety and Efficacy Study of PCI of Gemcitabine and Chemotherapy in Patients With Cholangiocarcinomas (clinicaltrials.gov) - P1/2; N=24; Completed; Sponsor: PCI Biotech AS; Recruiting ➔ Completed; N=55 ➔ 24; Trial primary completion date: Aug 2019 ➔ Feb 2019

Clinical • Enrollment change • Trial completion • Trial primary completion date

RELEASE: PCI Treatment/Gemcitabine & Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Extrahepatic Bile Duct Cancer (clinicaltrials.gov) - P2; N=186; Recruiting; Sponsor: PCI Biotech AS

Clinical • New P2 trial

Study to Assess Safety, Tolerability and Immune Response of Fimaporfin-induced Photochemical Internalisation of Antigen/Adjuvant (clinicaltrials.gov) - P1; N=96; Completed; Sponsor: PCI Biotech AS; Recruiting ➔ Completed

Clinical • Trial completion

Co-delivery of docetaxel and disulphonate tetraphenyl chlorin in one nanoparticle produces strong synergism between chemo- and photodynamic therapy in drug-sensitive and -resistant cancer cells. (PubMed, Mol Pharm) - "Cancer therapies based on the combinations of different drugs and/or treatment modalities are emerging as important strategies for increasing efficacy and cure, decreasing unwanted toxicity, and overcoming drug resistance, provided that optimized drug concentration ratios are delivered into the target tissue. Importantly, drug co-delivery in NPs was very efficient in inducing cell mortality also in DTX resistant HeLa-R cells over-expressing P-glycoprotein 1, in which the dose of the chemotherapeutic can be reduced by more than 100-times using DTX/TPCS2a-NPs. Overall, our data demonstrate that the protocol for the preparation of our HA-targeted double layer polymeric NPs allows to control the concentration ratio of co-loaded drugs and the delivery of the transported drugs for obtaining a highly synergistic interaction combining DTX-chemotherapy and TPCS2a-PDT."

Journal