BX002 / BiomX - LARVOL DELTA

[VIRTUAL] A PHASE 1, RANDOMIZED, SINGLE-BLIND, PLACEBO- CONTROLLED PHARMACOKINETIC STUDY EVALUATING ORAL BX002-A BACTERIOPHAGE THERAPY FOR INFLAMMATORY BOWEL DISEASE / PRIMARY SCLEROSING CHOLANGITIS (AASLD 2021) - "All subjects received oral esomeprazole 40 mg daily from Day (D) -3 to D3 to increase gastric pH for phage survival during gastric passage . BX002-A was safe and well- tolerated in healthy adults . High levels of viable phages were detected in stool, with minimal loss after passage through the GIT . Oral phage therapy should be further explored to assess its ability to reduce pathogenic KP in the gut and serve as a potential therapeutic in IBD and PSC patients."

Clinical • P1 data • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Pneumonia • IL10

"18 healthy adults randomized 14:4 to BX002 or placebo for 3 days; also had esomeprazole to increase gastric pH; endpoints were safety/tolerability and phage viability in stool #UEGWeek" (@LancetGastroHep)

Clinical

[VIRTUAL] A PHASE 1, RANDOMIZED, SINGLE-BLIND, PLACEBO-CONTROLLED PHARMACOKINETIC STUDY EVALUATING ORAL BX002-A BACTERIOPHAGE THERAPY FOR INFLAMMATORY BOWEL DISEASE: Discussion (UEGW 2021) - No abstract available

Clinical • P1 data • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

[VIRTUAL] A PHASE 1, RANDOMIZED, SINGLE-BLIND, PLACEBO-CONTROLLED PHARMACOKINETIC STUDY EVALUATING ORAL BX002-A BACTERIOPHAGE THERAPY FOR INFLAMMATORY BOWEL DISEASE (UEGW 2021) - "All subjects also received oral esomeprazole 40 mg daily from Day -3 to Day 3 to increase gastric pH and optimize conditions for survival of phage during passage through the stomach. Orally administered BX002-A was safe and well-tolerated in healthy adults. Pharmacokinetic analysis showed high levels of viable phages in the stool with minimal loss after passage through the gastrointestinal tract. Oral phage therapy should be further explored to assess its ability to reduce pathogenic Klebsiella pneumoniae bacteria in the gut and serve as a potential therapeutic in IBD patients."

Clinical • P1 data • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Pneumonia • IL10

A Study to Evaluate the Safety, Tolerability, and Fecal Pharmacokinetics of BX002-A in Healthy Adults (clinicaltrials.gov) - P1; N=18; Completed; Sponsor: BiomX, Inc.

Clinical • New P1 trial

BiomX Announces Positive Results of a Phase 1a Pharmacokinetic Study for Inflammatory Bowel Disease/Primary Sclerosing Cholangitis (IBD/PSC) Evaluating Delivery of Oral BX002 Phage Therapy (Businesswire) - P1a, N=18; "BiomX Inc...announced positive results of a first-in-human Phase 1a pharmacokinetic study of BX002...BX002 was demonstrated to be safe and well-tolerated...the study met its objective of delivering high concentrations of viable phage to the gastrointestinal tract of approximately 1010 PFU (plaque forming units)...BiomX plans to advance to a Phase 1b/2a study evaluating the efficacy of BX003...Results from the Phase 1b/2a study are expected by mid-2022."

New P1/2 trial • P1 data • P1/2 data • Immunology • Inflammatory Bowel Disease

BiomX Announces Dosing of First Subject in Phase 1a Study of BX002 Phage Therapy for Inflammatory Bowel Disease (Businesswire) - "BiomX Inc...today announced that the first subject has been dosed in a Phase 1a study of BX002, a phage therapy candidate for the treatment of inflammatory bowel disease (IBD)....'Our goal is to demonstrate successful delivery of viable phage before proceeding to a study designed to measure the reduction of target bacteria. We look forward to announcing the results of this study in the first quarter of 2021.'"

P1 data • Trial status • Inflammatory Bowel Disease

BiomX Presents Preclinical Data on Phage Targeting Multidrug Resistant Klebsiella pneumoniae Bacteria at the Infectious Disease Society of America (IDSA) IDWeek Conference 2020 (Businesswire) - "BiomX Inc....today presented preclinical data from its phage panel for the treatment of inflammatory bowel disease at the Infectious Disease Society of America (IDSA) Infectious Disease Week (IDWeek) 2020 conference. The poster presentation details a phage therapy panel, comprised of phage directed against Klebsiella pneumoniae, showing a broad target host range and the potential to address carbapenem-resistant and extended spectrum beta-lactamase (ESBL)-producing bacteria."

Preclinical • Inflammatory Bowel Disease

BiomX Enters Collaboration with Boehringer Ingelheim with the Goal of Discovering Microbiome-Based Biomarkers for Inflammatory Bowel Disease (Businesswire) - "BiomX Inc....today announced that it has entered into a collaboration with Boehringer Ingelheim...As part of the collaboration, BiomX will generate metagenomic data of gut microbiome samples obtained from IBD patients with the aim of identifying biomarkers using the XMarker platform....The terms of the collaboration also include an option for Boehringer Ingelheim to negotiate an exclusive right to biomarkers discovered utilizing the XMarker platform. Independently of the collaboration, BiomX continues to advance the wholly-owned phage therapy candidate BX002 for the treatment of IBD..."

Licensing / partnership • Inflammatory Bowel Disease

Isolation and identification of Leptospira in patients with fever of unknown origin in Guizhou province (PubMed, Zhonghua Liu Xing Bing Xue Za Zhi) - "MLST genotyping showed that strain 17BX002 was typed as ST106, most closely clustered with Leptospira grippotyphosa, while strain 17BX003 and 17AJX008 were typed as ST96, the same as serogroup badaviae. There are leptospirosis cases in epidemic area of Guizhou in high incidence season, grippotyphosa and bataviae are the newly discovered serogroups of Leptospira in Guizhou."

Clinical • Journal

BiomX Reports Second Quarter 2020 Financial Results and Provides Business Update (Businesswire) - "The first-in-human Phase 1a study of BX002 is expected to begin in the third quarter of 2020, with results expected by the end of 2020....A Phase 1b/2a study aimed at evaluating the efficacy of BX002 in reduction of the target bacteria Klebsiella pneumoniae is expected to begin in 2021....Research and development expenses were $4.1 million in the second quarter of 2020...primarily due to the manufacturing of BX001 and BX002, the Company’s product candidates for acne-prone skin and IBD/PSC, respectively."

Commercial • New P1 trial • New P1/2 trial • P1 data • Inflammatory Bowel Disease

Hemodynamic forces enhance decidualization via endothelial-derived prostaglandin E2 and prostacyclin in a microfluidic model of the human endometrium. (PubMed, Hum Reprod) - "This work was supported by the Veterans Affairs (I01 BX002853), the Bill and Melinda Gates Foundation Grand Challenges Exploration (OPP1159411), the Environmental Toxicology Training Grant (NIH T32 ES007028) and the Environmental Protection Agency STAR Center Grant (83573601). The authors report no conflicts of interest. N/A."

Journal • Endometriosis • Gynecology • Immunology • Sexual Disorders

[VIRTUAL] Drug repurposing approach for developing novel therapy for castration resistant prostate cancer (AUA 2020) - "13:2288-302, 2014) has demonstrated that synergistic combination of simvastatin (SIM), a drug for the treatment of hypercholesterolemia and metformin (MET), a glucose lowering drug inhibits CRPC growth, invasiveness and migration potential with minimal effect on normal prostate epithelial cells... Human CRPC cells C4-2B-ENZU (C4-2B enzalutamide resistant) were generated by growing C4-2B cells in progressive concentration of ENZU 5-20µM to develop resistance and maintained in 5µM ENZU in the culture medium for >20 generations... Combined action of SIM and MET may be an effective regimen for treatment of ENZU-resistant tumors. This opens new therapeutic modality for castration-resistant prostate cancer patients. Source of Funding: VA Merit Review 1I01BX002494; Department of Defense grant W81XWH-15-1-0558, W81XWH-18-1-0618 and W81XWH-19-1-0720 to SG."

Dyslipidemia • Genito-urinary Cancer • Metabolic Disorders • Oncology • Prostate Cancer • Solid Tumor • AR

[VIRTUAL] Molecular reprogramming and rewiring of prostate cancer cells after enzalutamide exposure (AUA 2020) - "Our findings emphasized the role of molecular reprogramming and gene rewiring leading to the development of enzalutamide resistance. Source of Funding: VA Merit Review 1I01BX002494; Department of Defense grant W81XWH-15-1-0558, W81XWH-18-1-0618 and W81XWH-19-1-0720 to SG."

Genito-urinary Cancer • Metabolic Disorders • Oncology • Prostate Cancer • Solid Tumor • Type 2 Diabetes Mellitus • AKT3 • FOLH1 • GSTP1 • SPON2 • TMEM25 • TSPAN8

[VIRTUAL] Loss of DHEA-Targeting SULT2b1b Sulfotransferase Exacerbates Aggressive Traits of Prostate Cancer (ENDO-I 2020) - "The reciprocal expression pattern for SULT2B and AKR1C3 in clinical CRPC suggests that AKR1C3 upregulation, ERK1/2 activation and increased aggressive traits of SULT2B-ablated cells, observed in vitro in cell models, may be clinically significant. Pathways regulating the inhibitory SULT2B-AKR1C3 axis may inform new avenue(s) for delaying disease progression in SULT2B-deficient prostate cancer.Funding Support: 1I01BX000280, VA (BC); W81XWH-14-1-0606, DOD (BC); IK6 BX004207, VA (BC); P50 CA97186, NIH & W81XWH-12-1-0208, DOD (EAM)"

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CA9 • FKBP5 • SULT2B1 • VIM

Universal size properties of a star-ring polymer structure in disordered environments. (PubMed, Phys Rev E) - "...In particular cases f_{1}=1 and f_{1}=2, such a system restores the synthesized tadpole-shaped polystyrenes [Doi et al., Macromolecules 46, 1075 (2013)MAMOBX0024-929710.1021/ma302511j]...Applying the direct polymer renormalization approach, we evaluate the universal size characteristics such as the ratio of the radii of gyration of star-ring and star topologies, and compare the effective sizes of single arms in complex structures and isolated polymers of the same total molecular weight. The nontrivial impact of disorder on these quantities is analyzed."

Journal • Biosimilar

BiomX reports first quarter 2020 financial results and provides business update (PRNewswire) - "Results from the first-in-human Phase 1a study of BX002 in IBD expected in the fourth quarter of 2020. The Phase 1a study will be conducted in healthy volunteers to provide pharmacokinetic and safety data. The Phase 1b/Phase 2a study will evaluate the eradication of the target bacteria, Klebsiella pneumoniae, in subjects carrying the identified bacteria with results expected in the second half of 2021."

P1 data • P1/2 data • Immunology • Inflammation • Inflammatory Bowel Disease

TITLE: Bruton's Tyrosine Kinase Deficiency Alters Gut B Lymphocyte Populations and IgA Recognition of Commensal Bacteria in Autoimmune Disease (AAAAI 2020) - "B cell receptor signaling supports the interplay between B lymphocytes, IgA and commensal microbes. BTK-inhibitors in clinical trials for autoimmune and allergic diseases may may have unforeseen effects on the microbiome that influence disease outcome.Funding: NIH: R01 DK084246, K12 HD 043483 and Veteran’s Affairs I01 BX 002882."

Clinical

BiomX announces completion of enrollment for double-blind, placebo-controlled clinical study of BX001 in acne-prone skin (Businesswire) - "...we are advancing our pipeline of innovative, targeted phage therapies and expect to have our second product candidate, BX002, enter the clinic in 2020 for the treatment of inflammatory bowel disease."

Clinical

Targeted Drug Delivery Using a Novel Joint-homing Peptide for Arthritis Therapy (ACR-ARHP 2019) - " We developed a peptide-directed liposomal drug delivery system to deliver dexamethasone (DEX) to arthritic joints of rats with adjuvant-induced (AA) arthritis. Our results furnish a proof-of concept for the use of a novel joint-homing peptide for targeted delivery of drugs including biologics or small molecule compounds to arthritic joints with enhanced efficacy and reduced systemic exposure. This targeted therapy platform may be suitable for use in RA patients. (Supported by VA Merit Review I01 BX002424, NIH R01AT004321, and RRF.)"

Proteostasis by HSP70/STUB1 complex regulates androgen receptor variants expression and confers resistance to enzalutamide and abiraterone (AUA 2019) - "Introduction: Proteostasis is a complementary process by which cells control the protein biosynthesis, folding, trafficking and degradation. Enzalutamide and abiraterone treatment induces the imbalance of AR-V7 proteostasis through the ubiquitin-proteolysis alteration. HSP70/STUB1 complex controls AR and AR variants proteostasis. Targeting HSP70 could be a valuable strategy to overcome the next generation anti-androgen resistance and improve their therapy."

AKR1C3 promotes AR-V7 protein stabilization and confers anti-androgen resistance in advanced prostate cancer (AUA 2019) - "AKR1C3 induces AR-V7 overexpression and stabilizes AR-V7 protein in resistant cells through the ubiquitin proteasome system alteration. Apalutamide and darolutamide are cross resistant to enzalutamide and abiraterone via AKR1C3/AR-V7 complex regulation. Source of Funding: This work was supported in part by grants NIH/NCI CA168601, CA179970, DOD PC150229, and the U.S. Department of Veterans Affairs, Office of Research & Development BL&D grant number I01BX0002653 (A.C."

Dual targeting of EZH2 and Androgen Receptor synergistically inhibits castration-resistant prostate cancer (AUA 2019) - "Treatment with new generation androgen receptor (AR) antagonist Enzalutamide (ENZU) offers an initial response followed by drug resistance and the patient clinically progresses on this agent. Dual targeting of AR and EZH2 with ENZU and GSK126 exhibited synergistic inhibition of AR-dependent and gene-specific EZH2-mediated expression of CRPC potentiating cell death thus opening avenues simultaneously targeting EZH2 and AR in CRPC. Source of Funding: VA Merit Review 1I01BX002494; Department of Defense grant W81XWH-15-1-0558, and W81XWH-18-1-0618; USPHS grants RO1CA108512, to SG"

Helminth Exposure Alters Th17 Subpopulation Plasticity Promoting Regultory Behavior (DDW 2019) - "Unlike Th17 lineage cells from helminth naïve mice, Th17 lineage cells from helminth-infected mice function like T regulatory cells suppressing proliferation and inhibiting development of transfer colitis. This work was supported by the Department of Veterans Affairs, Veterans Health Administration, ORD-BLRD Grant 1BX002715."

Clinical