CJRB-102 / 4D Pharma, CJ Biosci - LARVOL DELTA

A safety and feasibility study of the oral live biotherapeutic MRx0518 with hypofractionated preoperative radiation for resectable pancreatic cancer (SITC 2023) - P1 | "Conclusions The administration of MRx0518 with hypofractionated neoadjuvant chemoradiation in resectable PDAC was well tolerated. Further analysis of immune cell infiltrates within recected tumors will help reveal further associations to changes in the local microbiome."

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

Immune modulation and the oral live biotherapeutic product, MRx0518, in treatment-naïve patients with cancer: Updated safety data. (ASCO 2023) - P1, P2 | "This study demonstrates the long-term safety profile of MRx0518 therapy in treatment-naïve cancer patients. Analysis of PBMCs reveals clear evidence of immune modulation, consistent with significant anti-cancer efficacy. This is concordant with prior findings from this study."

Clinical • Breast Cancer • Immune Modulation • Immunology • Melanoma • Oncology • Solid Tumor • CD4 • CD8 • NCAM1

A Study of Live Biotherapeutic Product MRx0518 With Hypofractionated Radiation Therapy in Resectable Pancreatic Cancer (clinicaltrials.gov) - P1 | N=13 | Terminated | Sponsor: 4D pharma plc | Trial completion date: Oct 2023 ➔ May 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2023 ➔ May 2023; Sponsor insolvency

Trial completion date • Trial primary completion date • Trial termination • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

KEYNOTE MK3475-823: Live Biotherapeutic Product MRx0518 and Pembrolizumab Combination Study in Solid Tumors (clinicaltrials.gov) - P1/2 | N=63 | Terminated | Sponsor: 4D pharma plc | N=132 ➔ 63 | Trial completion date: Mar 2024 ➔ May 2023 | Active, not recruiting ➔ Terminated; Sponsor insolvency

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial termination • Bladder Cancer • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

AVENU: Study of MRx0518 and Avelumab in Patients With Urothelial Carcinoma (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: 4D pharma plc | N=30 ➔ 0 | Trial completion date: Jan 2024 ➔ Apr 2023 | Active, not recruiting ➔ Withdrawn | Trial primary completion date: Oct 2023 ➔ Apr 2023

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial withdrawal • Oncology • Solid Tumor • Urothelial Cancer

[VIRTUAL] Safety and emerging evidence of immune modulation of the live biotherapeutic MRx0518 in the neoadjuvant setting for patients awaiting surgical removal of solid tumours (SITC 2020) - P1, P1/2 | "Exploratory analyses of post-treatment samples has echoed preclinical observations of increased infiltration of immune cells following treatment and will undergo further validation. Part B will focus on investigating efficacy in a further 100 treatment naïve patients with a placebo-controlled arm."

Clinical • IO Biomarker • Late-breaking abstract • Breast Cancer • Melanoma • Oncology • Solid Tumor • CD8

[VIRTUAL] A phase I/II study of live biotherapeutic MRx0518 in combination with pembrolizumab in patients refractory to immune checkpoint inhibitors (SITC 2020) - P1/2 | "Exploratory objectives are to evaluate biomarkers of treatment effect, impact on microbiota and OS and correlation of clinical outcome with PD-L1 CPS/TPS. Results N/A Conclusions N/A"

Checkpoint inhibition • Clinical • Combination therapy • IO biomarker • P1/2 data • Bladder Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer • CD8 • PD-L1

[VIRTUAL] Safety and efficacy signals in the complete phase I study of live biotherapeutic MRx0518 in combination with pembrolizumab in patients refractory to immune checkpoint inhibitors (ICIs) (SITC 2020) - P1/2 | "10 patients received nivolumab previously (83%), one received avelumab (8%) and one received pembrolizumab and nivolumab (8%). The combination was tolerable and there were preliminary signals of efficacy. Part B (phase II) in NSCLC, RCC and bladder cancer is ongoing."

Checkpoint inhibition • Clinical • Combination therapy • P1 data • Bladder Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer • CD8 • IFNG • PD-L1

Oral administration of MRx0518 in treatment-naïve cancer patients is associated with compositional taxonomic and metabolomic changes indicative of anti-tumorigenic efficacy (SITC 2022) - P1 | "Further investigation is required to link post-treatment metabolomic changes to taxonomic changes in the gut microbiome. Trial Registration NCT03934827"

Clinical • Oncology

[VIRTUAL] Baseline biomarkers associated with clinical benefit in patients with solid tumors refractory to immune checkpoint inhibitors (ICIs) treated with live biotherapeutic MRx0518 in combination with pembrolizumab (ESMO 2021) - P1/2 | "Understanding mechanisms of resistance to ICIs is key in identifying patients who may respond to subsequent therapies. This limited analysis, together with the observations of increased CD8+ T-cell activation and reduced induction of Treg cells in the presence of tolerogenic cytokines in vitro and in preclinical models, provides insight for further investigation into the potential for MRx0518 + pembrolizumab to overcome Treg-mediated acquired resistance to ICIs."

Biomarker • Checkpoint inhibition • Clinical • Combination therapy • IO biomarker • Oncology • Solid Tumor • CD68 • CD8 • FOXP3 • PD-1

Combination MRx0518 and anti-PD-1 overcomes checkpoint inhibitor resistance via myeloid modulation (SITC 2022) - "We hypothesized that a PD-1 checkpoint inhibitor in combination with MRx0518 would decrease suppressive myeloid cells and increase T-cell activation Study design: Patients who had developed resistance to checkpoint inhibitors received MRx0518 (1 x 10 10 to 1 x 10 11 CFU) PO BID and 200mg pembrolizumab IV Q3W for up to 2 years or disease progression. Conclusions Immune activation was recovered in R patients with MRx0518 and anti-PD-1 combination therapy. Immune changes associated with improved outcome include: 1) increased expression of HLA-DR and decreased PD-L1 expression on myeloid cells and 2) increased CD8+ T-cell frequencies in circulation."

Checkpoint inhibition • IO biomarker • Oncology • CD4 • CD8 • CTLA4 • HAVCR2 • IL6 • PD-L2

Trial in progress: A phase II switch maintenance study of live biotherapeutic MRx0518 and avelumab in patients with unresectable locally advanced or metastatic urothelial carcinoma (UC) who did not progress on first-line platinum-containing chemotherapy. (ASCO 2022) - P2, P3 | "Stool and urine samples collected before, during and after treatment will allow investigation of changes to the microbiome and metabolome. Recruitment is open, awaiting accrual."

Clinical • IO biomarker • P2 data • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • Urothelial Cancer • CD4 • CD8

4D pharma Announces Two Presentations at The Society for Immunotherapy of Cancer Annual Meeting (SITC 2022) (4D pharma Press Release) - "4D pharma plc...announces two poster presentations at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting (SITC 2022), held from November 8-12, 2022....'With these two presentations at SITC 2022, 4D pharma continues to generate clinical data deepening our understanding of the mechanisms driving the activity of MRx0518 to both overcome resistance to checkpoint inhibitors, and act as a monotherapy in the treatment of solid tumors,' commented Alex Stevenson, Chief Scientific Officer, 4D pharma. 'These data are further evidence of the positive effects of a single strain Live Biotherapeutic on both the human immune system and the microbiome, leading to better treatment outcomes for patients'."

Clinical data • Oncology • Solid Tumor

MICROBIOME: MRx0518 in Patients With Solid Tumours Waiting Surgical Removal of the Tumour (clinicaltrials.gov) - P1 | N=120 | Active, not recruiting | Sponsor: Imperial College London | Unknown status ➔ Active, not recruiting | Trial completion date: Feb 2022 ➔ Dec 2022 | Trial primary completion date: Aug 2021 ➔ Dec 2022

Enrollment closed • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Genito-urinary Cancer • Head and Neck Cancer • Immune Modulation • Inflammation • Kidney Cancer • Lung Cancer • Melanoma • Oncology • Ovarian Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Urethral Cancer • Urothelial Cancer • Uterine Cancer

KEYNOTE MK3475-823: Live Biotherapeutic Product MRx0518 and Pembrolizumab Combination Study in Solid Tumors (clinicaltrials.gov) - P1/2 | N=132 | Active, not recruiting | Sponsor: 4D pharma plc | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Bladder Cancer • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

A Study of Live Biotherapeutic Product MRx0518 With Hypofractionated Radiation Therapy in Resectable Pancreatic Cancer (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: 4D pharma plc | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2021 ➔ Oct 2023 | Trial primary completion date: Jul 2021 ➔ Jan 2023

Enrollment closed • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

AVENU: Study of MRx0518 and Avelumab in Patients With Urothelial Carcinoma (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: 4D pharma plc | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor • Urothelial Cancer

4D pharma Presents Trial in Progress Poster on Study of MRx0518 in Combination with BAVENCIO in Patients with Unresectable Locally Advanced or Metastatic Urothelial Carcinoma at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Businesswire) - "4D pharma plc...announced the presentation of a trial in progress poster from the Phase II clinical trial of MRx0518 in combination with BAVENCIO (avelumab), a PD-L1 blocking antibody, as a first-line maintenance therapy for patients with unresectable locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy, at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting....The multi-center study (NCT05107427) will enroll 30 patients with unresectable locally advanced or metastatic urothelial carcinoma. Patients must have measurable disease after a partial response (PR) or stable disease (SD) on 4-6 cycles of platinum-containing induction chemotherapy."

Clinical protocol • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

A Study of Live Biotherapeutic Product MRx0518 With Hypofractionated Radiation Therapy in Resectable Pancreatic Cancer (clinicaltrials.gov) - P1; N=15; Not yet recruiting; Sponsor: 4D pharma plc

Clinical • New P1 trial

4D pharma Announces Positive Interim Results from the Phase I/II Study of the Combination of MRx0518 and KEYTRUDA (pembrolizumab) for the Treatment of Renal Cell Carcinoma (Businesswire) - P1/2 | N= 139 | NCT03637803 | Sponsor: 4D pharma plc | "4D pharma plc...announces that in Part B of its signal finding study of MRx0518 in combination with MSD’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in patients with solid tumors that have progressed on a prior immune checkpoint inhibitor (ICI), the renal cell carcinoma (RCC) group has met its primary efficacy endpoint ahead of enrollment completion...4D pharma management will be joined by key opinion leaders (KOLs)Dr. Petros Grivas...and Dr. Scott T. Tagawa..."

P1/2 data • Bladder Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

4D pharma Reports Full Year 2021 Financial Results, Operational Highlights, and Guidance for Key Milestones in 2022 (Businesswire) - "Anticipated Development Milestones and Key Objectives for 2022: First patient dosing in our Phase II study of MRx0518 & Bavencio® as a first-line maintenance therapy for urothelial carcinoma expected in Q2 2022; Complete enrollment of Phase I study of MRx0518 in pancreatic cancer expected to be Q2 2022; Provide update on next steps in Phase I/II study of MRx0518 and Keytruda® in the Renal Cell Carcinoma (RCC) group."

Trial status • Bladder Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Kidney Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Urothelial Cancer

4D pharma Announces Positive Interim Results from the Phase I/II Study of the Combination of MRx0518 and KEYTRUDA (pembrolizumab) for the Treatment of Renal Cell Carcinoma (Businesswire) - P1/2 | N= 132 | NCT03637803 | Sponsor: 4D pharma plc | "4D pharma plc...announces that in Part B of its signal finding study of MRx0518 in combination with MSD’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) in patients with solid tumors that have progressed on a prior immune checkpoint inhibitor (ICI), the renal cell carcinoma (RCC) group has met its primary efficacy endpoint ahead of enrollment completion...The primary efficacy endpoint for Part B of the study is more than three out of 30 patients per tumor group achieving clinical benefit...20 patients with RCC, of which four out of the first 16 evaluable patients have achieved clinical benefit, each having achieved at least 6 months of stable disease...Part B of the study has enrolled 47 patients of up to a total of 120 patients with RCC, non-small cell lung cancer, bladder cancer, and head and neck squamous cell carcinoma. MRx0518 continues to be safe and well tolerated."

P1/2 data • Bladder Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

AVENU: Study of MRx0518 and Avelumab in Patients With Urothelial Carcinoma (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: 4D pharma plc | Trial completion date: Jul 2025 ➔ Jan 2024

Trial completion date • Oncology • Solid Tumor • Urothelial Cancer

"$LBPS took patients who had relapsed after responding to Keytruda, gave them Keytruda + MRx0518, and got an ORR = 0%. Stock +30% in the premarket. OK!" (@JacobPlieth)

Clinical

AVENU: Study of MRx0518 and Avelumab in Patients With Urothelial Carcinoma (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: 4D pharma plc | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor • Urothelial Cancer