SER-287 / Nestle, Seres Therap - LARVOL DELTA

THE MOLECULAR BACKGROUND DETERMINES THE EXTENT BY WHICH LSD1 INHIBITORS SENSITIZE AML CELLS TO KINASE AND RAS INHIBITORS (EHA 2025) - "These cells present FLT3, NRAS and JAK2 activating mutations, respectively.Independently of FLT3 and RAS mutations, Iadademstat, sensitized 10, 8, 8 and 7 AML cell lines to gilteritinib, trametinib, pictilisib and RMC-7977, respectively...These included the phosphorylations of pNIBAN2(Ser692) and pNFIL3(Ser287)...Remarkably, gilteritinib reduced STAT5A/B phosphorylation, and iadademstat sensitised HEL cells to the JAK inhibitor ruxolitinib. In summary, the heterogeneity by which LSD1 inhibition sensitizes AML cells to FLT3, PI3K, RAS and MEK inhibitors can be rationalised by differences in how LSD1 regulates the wirings of kinase signalling networks irrespective of FLT3 and RAS mutations."

Acute Myelogenous Leukemia • FLT3 • NRAS • STAT5

CANDIDATE BIOMARKERS OF MICROBIOME DISRUPTION FOR PATIENT SELECTION OR STRATIFICATION IN CLINICAL TRIALS OF MICROBIOME THERAPEUTICS IN ULCERATIVE COLITIS (UC) (DDW 2025) - P2b | "A post-hoc analysis of data from the Phase 2b trial of SER-287 has identified candidate biomarkers of microbiome disruption and clinical response. These data are consistent with a growing appreciation that not all patients with UC exhibit features of microbiome disruption. Furthermore, our data suggests that clinical features alone may not adequately enrich for these particular subjects during study enrollment."

Biomarker • Clinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

CHARACTERIZATION OF IBD MICROBIOMES IN MODELS OF MICROBIOME DISRUPTION AND INFLAMMATION TO EVALUATE CANDIDATE BIOMARKERS FOR PATIENT SELECTION (DDW 2025) - "Background: Post-hoc analysis of Seres' clinical trial of SER-287 in patients with mild-to-moderate ulcerative colitis (UC) have defined candidate biomarkers of a disrupted microbiome which may identify patient subpopulations more amenable to intervention with microbiome therapeutics... A biorepository of IBD stool samples has been created which cover not only candidate biomarkers of microbiome disruption but a range of inflammatory markers, consistent with the variable levels of microbiome disruption and inflammation observed in IBD patients. These results highlight the importance of considering microbial heterogeneity in IBD patients, where disruptions in the microbiome taxonomy and function may contribute to variable host inflammatory responses and disease pathogenesis."

Biomarker • Clinical • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • CXCL8 • IL10 • LCN2

Assessment of the binding mechanism of ergothioneine to human serum albumin: Multi-spectroscopy, molecular docking and molecular dynamic simulation. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "In addition of obvious van der Wall forces, attractive charge and Pi-alkyl interactions, the chiral betaine group (N+(CH3+)3) in the side chain of EGT was inclined to form hydrogen bonds with Lys199, Ser287 and Arg257 in the hydrophobic cavity of albumin. Moreover, the dynamic simulation reinforced the equilibrium and stability of formed docking complex by four indicators (RMSD, RMSF, Rg, SASA) within 100 ns."

Journal

Identification of cholinesterases inhibitors from flavonoids derivatives for possible treatment of Alzheimer's disease: In silico and in vitro approaches. (PubMed, Curr Res Struct Biol) - "While in the BChE-Kolaflavanone complex, Asn83, Ser79, Gln 47, and Ser287 are involved...These findings underscore the potential of Ginkgetin and Kolaflavanone as candidate inhibitors for the treatment of AD through the inhibition of AChE and BChE enzymes. Nevertheless, additional in vitro and in vivo studies are imperative to validate the efficacy of these compounds."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Pain

HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PATIENTS WITH MUCOPOLYSACCHARIDOSIS-IVA: A PRELIMINARY REPORT (EBMT 2023) - " Case/GenderAge at Diagnosis>HSCT(months)GenotypeDonoraGvHDChimerismFollow-up(FU, months)Last Enzyme Level (nmol/mg)Height(pre>post-HSCT)ADL Score(pre>post-HSCT)1/M22>120UndefinedMSDNofull714398>103 cm16>202/F40>48c.421T>A(p.Trp141Arg)MUDNofull1Early FUEarly FUEarly FU3/M29>66c.1168delC(p.Leu390)MUDNofull1127482>87 cm16>204/F59>108c.860C>T(p.Ser287Leu)MUDGrade 2 Skinfull1238998>100 cm17>205/M18>36c.139G>A(p.Gly47Arg)c.898+1G>AMUDNomixed924186>91 cm20>206/M19>84c.1019G>A(p.Gly340Asp)MUDNofull1913986>97 cm16>207/M22>48c.230C>G(p.Pro77Arg)MUDNofull929096>97 cm18>208/F1>126c.1168delC(p.Leu390)MUDNomixed7Normal92>103 cm18>209/M27>48c1157G>A(p.Arg386His)MUDNofull1Early FUEarly FUEarly FUCharacteristics and follow-up of the patients were presented in Table-1.This study was planned for long-term follow-up of MPS IVA cases after HSCT... HSCT is a promising modality for the treatment..."

Clinical • Bone Marrow Transplantation • Gene Therapies • Graft versus Host Disease • Lysosomal Storage Diseases • Metabolic Disorders • Orthopedics • Pediatrics • Rare Diseases • Transplant Rejection • Transplantation

ENDOSCOPIC SCORE INTER-READER CONCORDANCE ANALYSIS FROM A PHASE 2B STUDY IN PATIENTS WITH MILD-TO-MODERATE UC (CCCongress 2023) - "We present concordance rates between central and local readings from a Phase 2b study of investigational microbiome therapeutic SER-287 in patients with mild-to-moderate UC...Despite low concordance rates, efficacy conclusions remain unchanged if only local ES scores were used for endpoint assessments. Objective, standardized, and consistent methods for evaluating ES are needed to better quantify disease severity and the impact of UC therapies."

Clinical • Discordant • P2b data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Phase 2b Study to Evaluate the Efficacy and Safety of Investigational Microbiome Therapeutic SER-287 in Mildly-to-Moderately Active UC (AIBD 2022) - "A previous Phase 1b study of patients with mildly-to-moderately active UC demonstrated that SER-287 following vancomycin pre-conditioning was well-tolerated and provided clinical benefit.This double-blind, placebo-controlled Phase 2b study screened 494 adults and randomized 203 (51.7% male; mean age 45.6 years; 83.7% White) 1:1:1 to SER-287 Induction Dose, SER-287 Step-Down Induction Dose, or placebo, and stratified subjects by baseline endoscopic score (ES 1-2 vs 3) and by concomitant use of UC medications at baseline (5-ASA alone vs immunomodulators +/- 5-ASA vs none). The study did not meet its primary endpoint of clinical remission (10.3% for the SER-287 Induction Dose vs 11.6% for placebo [adjusted difference of −1.3; P = 0.802; 95% confidence interval: −11.7, 9.0]). No meaningful differences were observed across the 3 groups for endoscopic improvement, endoscopic remission, or symptomatic remission. During induction, 76/133 (57.1%) subjects who received SER-287, vs..."

Clinical • P2b data • Immune Modulation • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

OXGR1 Is a Candidate Disease Gene for Human Calcium Oxalate Nephrolithiasis (KIDNEY WEEK 2022) - "Interrogation of the OXGR1 locus in 1107 NL/NC families identified five additional dominant alleles (p.Ser56Profs*7, p.Tyr93His, p.Cys217Arg, p.Ser233Arg, p.Ser287Phe) in five families with calcium oxalate NL/NC...Four of five NL/NC-associated missense variants revealed impaired AKG-dependent Ca 2+ uptake at pH 5 and/or 7.4, demonstrating loss-of-function. Conclusion Rare, dominant OXGR1 variants are a candidate etiology of NL/NC, suggesting a novel mechanism for human NL/NC disease."

Metabolic Disorders • Nephrology • Renal Calculi • SLC26A4

Seres Therapeutics announces initiation of SER-287 phase 2b ECO-RESET clinical study for ulcerative colitis (PipelineReview) - "Seres Therapeutics...announced that it has enrolled the first patient in its Phase 2B trial, ECO-RESET, evaluating microbiome development candidate SER-287 in patients with active mild-to-moderate ulcerative colitis. Seres has received $40 million in milestone payments associated with this study start from Nestlé Health Science."

Enrollment status • Inflammatory Bowel Disease • Ulcerative Colitis

Molecular characterization of a large cohort of Mucopolysaccharidosis patients: Iran Mucopolysaccharidosis RE-diagnosis Study (IMPRESsion). (PubMed, Hum Mutat) - "Geographical origin analysis unveiled a pattern of distribution for frequent variants in ARSB (c.430G>A, c.962T>C [p.Leu321Pro], c.281C>A [p.Ser94*]), GALNS (c.319G>A [p.Ala107Thr], c.860C>T [p.Ser287Leu], c.1042A>G [p.Thr348Ala]), and IDUA (c.1A>C [p.Met1Leu], c.1598C>G [p.Pro533Arg], c.1562_1563insC [p.Gly522Argfs*50])...Geographical origin analysis unveiled a pattern of distribution for frequent variants in ARSB (c.430G>A, c.962T>C [p.Leu321Pro], c.281C>A [p.Ser94*]), GALNS (c.319G>A [p.Ala107Thr], c.860C>T [p.Ser287Leu], c.1042A>G [p.Thr348Ala]), and IDUA (c.1A>C [p.Met1Leu], c.1598C>G [p.Pro533Arg], c.1562_1563insC [p.Gly522Argfs*50]). Our extensive patient cohort reveals the genetic and geographic landscape of MPS in Iran, which provides insight into genetic epidemiology of MPS and can facilitate a more cost-effective, time-efficient diagnostic approach based on the region-specific variants."

Clinical • Journal • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Seres Announces Preliminary SER-287 Phase 2b ECO-RESET Study Microbiome Data Analysis (Businesswire) - P2, N=203; ECO-RESET (NCT03759041); Sponsor: Seres Therapeutics, Inc; "Seres Therapeutics, Inc...today announced preliminary microbiome data analyses from the Phase 2b ECO-RESET study evaluating SER-287 in patients with mild-to-moderate ulcerative colitis (UC). Following the topline clinical data...did not achieve its primary endpoints....The Company continues to conduct analyses on its SER-287 and SER-301 UC clinical stage programs to inform next steps for further development. Based on the SER-287 Phase 2b microbiome data analyses, engraftment of SER-287 bacteria was statistically significant in patients receiving SER-287 versus placebo (p ≤ 0.001 at all timepoints). The magnitude and kinetics of engraftment were comparable to Seres’ Phase 1b study. However, unlike the Phase 1b study, anticipated changes in disease-relevant metabolites post-administration with SER-287 in the Phase 2b study were not observed."

P2b data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

ECO-RESET: A Study to Assess Efficacy and Safety of SER-287 in Adults With Active Mild-to-Moderate Ulcerative Colitis (clinicaltrials.gov) - P2b; N=203; Terminated; Sponsor: Seres Therapeutics, Inc.; Trial completion date: Jul 2022 ➔ Oct 2021; Active, not recruiting ➔ Terminated; Due to the lack of a clinical efficacy signal in the induction treatment phase, Seres closed the dosing phases of open label and maintenance portions of the study. Patients who had received prior doses were followed for safety data.

Clinical • Trial completion date • Trial termination • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Further SAR studies on natural template based neuroprotective molecules for the treatment of Alzheimer's disease. (PubMed, Bioorg Med Chem) - "Molecular docking and dynamics studies revealed that 13b fits well into the active sites of AChE and BChE, forming stable and strong interactions with key residues Trp86, Ser125, Glu202, Trp 286, Phe295, Tyr 337 in AChE, and with Trp 82, Gly115, Tyr128, and Ser287 in BChE. Finally, the in-vivo efficacy of 13b at dose of 10 mg/kg in scopolamine AD model has been demonstrated. The present study strongly suggests that the naturally inspired multifunctional molecule 13b may behave as a potential novel therapeutic agent for AD management."

Journal • Alzheimer's Disease • CNS Disorders • Pain

Seres Therapeutics Reports Second Quarter 2021 Financial Results and Provides Business Updates (Businesswire) - "SER-287 Phase 2b ECO-RESET study in ulcerative colitis:...The Company expects to obtain SER-287 Phase 2b study microbiome data in H2 2021....Seres is enrolling its Phase 1b study for SER-301, an investigational oral, rationally-designed, cultivated microbiome therapeutic...The study is being conducted in Australia and New Zealand and is designed to enroll approximately 65 subjects...Research and development expenses for the second quarter of 2021 were $36.0 million, compared with $20.1 million for the same period in 2020. The research and development expenses were primarily related to Seres’ late-stage SER-109 and SER-287 clinical development programs, as well as personnel expenses."

Commercial • Enrollment status • P2b data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Seres Therapeutics Announces Topline Results for SER-287 Phase 2b Study in Mild-to-Moderate Ulcerative Colitis (Businesswire) - P2b, N=201; ECO-RESET (NCT03759041); Sponsor: Seres Therapeutics, Inc.; "Seres Therapeutics, Inc...announced topline results from the Phase 2b ECO-RESET study evaluating SER-287 in patients with mild-to-moderate ulcerative colitis (UC). The study did not meet its primary endpoint of improving clinical remission rates compared to placebo. Both dosing regimens of SER-287 were generally well tolerated. Given the lack of a clinical efficacy signal identified in ECO-RESET, the Company has decided to close the open label and maintenance portions of the study...we believe this data-rich study, including microbiome analyses expected in the second half of 2021...The Company continues to advance its SER-301 program currently in a Phase 1b study...The Phase 1b is currently enrolling in Australia and New Zealand...Results from the SER-287 ECO-RESET study...will be submitted for presentation at a future scientific meeting."

Enrollment status • P2b data • Trial termination • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Seres Therapeutics to Host Conference Call and Webcast to Discuss Topline Results from Phase 2b Study of SER-287 to Treat Mild-to-Moderate Ulcerative Colitis (Businesswire) - "Seres Therapeutics, Inc...announced that management will host a conference call and live audio webcast today at 8:30 a.m. ET to discuss topline results from the Phase 2b ECO-RESET study evaluating SER-287 in patients with mild-to-moderate ulcerative colitis (UC)."

P2b data • Inflammatory Bowel Disease • Ulcerative Colitis

Seres Therapeutics to Host Virtual Investor Event on June 21, 2021 (Businesswire) - "Seres Therapeutics, Inc...announced that it will host a virtual investor event focused on SER-287 and SER-301, potential new therapeutic options for ulcerative colitis (UC) on Monday, June 21, 2021 from 8:30 a.m. to 10:00 a.m. ET...During the event, Seres’ management and Stephen Hanauer, M.D....will discuss the UC patient burden, the need for new therapeutic approaches, and SER-287 and SER-301, Seres’ microbiome therapeutic candidates in clinical development for UC....Topline clinical data from the SER-287 Phase 2b induction study are expected in mid-2021 and additional microbiome pharmacology data are expected in H2 2021."

Live event • P2b data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

[VIRTUAL] SER-301, AN INVESTIGATIONAL, RATIONALLY-DESIGNED BACTERIAL CONSORTIUM FOR MILD-TO-MODERATE ULCERATIVE COLITIS, RECAPITULATES THE EFFECTS OF SER-287, A CONSORTIUM OF FIRMICUTE SPORES, ON REMISSION ASSOCIATED MICROBIAL METABOLITES AND HOST GENE EXPRESSION (DDW 2021) - "SER-301, a rationally-designed consortium of bacteria, recapitulates several hypothesized mechanisms of action of SER-287. SER-301 is currently being evaluated in a Phase 1b study in adults with active mild-to-moderate UC (ACTRN12620000963921) to test the hypothesis that engraftment of drug product species results in a reduction of intestinal inflammation and repair of epithelial barrier damage."

Clinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • CXCL8 • IFNG • TNFA

Seres Therapeutics to Present Key Data on Investigational Microbiome Therapeutics for Recurrent C. difficile Infection and Ulcerative Colitis at the Digestive Disease Week (DDW) Annual Meeting (Businesswire) - "Seres Therapeutics, Inc...announced that it will present recent research findings from its microbiome drug development portfolio at Digestive Disease Week® (DDW), which is taking place virtually from May 21-23, 2021. With two oral presentations and two posters of distinction, Seres will demonstrate the potential of microbiome-based therapies for patients with serious diseases like recurrent Clostridioides difficile infection (CDI) and ulcerative colitis (UC)."

Clinical data • Preclinical • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Seres Therapeutics Reports First Quarter 2021 Financial Results and Provides Business Updates (Businesswire) - "Topline clinical data from SER-287 Phase 2b study in patients with mild-to-moderate ulcerative colitis expected in mid-2021, microbiome biomarker data anticipated in H2 2021...Virtual ulcerative colitis microbiome therapeutic investor event to be held June 21, 2021."

Biomarker • P2b data • Inflammatory Bowel Disease • Ulcerative Colitis

ECO-RESET: A Study to Assess Efficacy and Safety of SER-287 in Adults With Active Mild-to-Moderate Ulcerative Colitis (clinicaltrials.gov) - P2b; N=201; Active, not recruiting; Sponsor: Seres Therapeutics, Inc.; Recruiting ➔ Active, not recruiting; Trial completion date: Aug 2021 ➔ Jul 2022; Trial primary completion date: Jul 2020 ➔ Jun 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Seres Therapeutics Announces Achievement of Target Enrollment in SER-287 Phase 2b ECO-RESET Study for Ulcerative Colitis (Businesswire) - "Seres Therapeutics, Inc...announced today that the Company has achieved target enrollment of the Phase 2b ECO-RESET clinical study of SER-287 in patients with mild-to-moderate ulcerative colitis (UC) in both the U.S. and Canada...Seres believes the study could serve as one of two required pivotal trials supporting a Biologics License Application (BLA). The Company expects to share topline clinical data from ECO-RESET in mid-2021."

Enrollment closed • P2b data • Inflammatory Bowel Disease • Ulcerative Colitis

[VIRTUAL] SER-287, AN INVESTIGATIONAL MICROBIOME THERAPEUTIC FOR PATIENTS WITH ACTIVE MILD-TO-MODERATE ULCERATIVE COLITIS, PRODUCES REMISSION ASSOCIATED METABOLITES, REDUCES INTESTINAL EPITHELIAL IL-8 SECRETION AND PROTECTS EPITHELIAL BARRIER FUNCTION IN VITRO (CCCongress 2021) - "SER-287 supernatants significantly decreased IFN-γ-mediated barrier disruption, while the pro-inflammatory consortium was not protective(Figure 2). Conclusions Production of remission-associated metabolites, reduction of epithelial inflammation, and protection from epithelial barrier damage are shown to be pharmacological properties of SER-287 which may underlie the mechanism of action of this microbiome therapeutic for mild-to-moderate UC."

Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • CXCL8 • IFNG • TNFA

Seres Therapeutics Publishes Positive SER-287 Phase 1b Ulcerative Colitis Study Results in Journal Gastroenterology (Businesswire) - P1, N=58; NCT02618187; Sponsor: Seres Therapeutics, Inc.; "Seres Therapeutics, Inc...announced the publication of data analyses from the Company’s Phase 1b trial of SER-287 in patients with active mild-to-moderate ulcerative colitis (UC)...The study results demonstrated that SER-287 administration was associated with positive impacts on clinical remission, endoscopic improvement, modulation of the gastrointestinal microbiome, and a favorable tolerability profile...'The Phase 2b study continues to recruit patients...The study is nearly 90% enrolled, and we expect to obtain topline results in the second half of 2021.'"

P1 data • P2 data • Inflammatory Bowel Disease • Ulcerative Colitis