pegsiticase/SVP-rapamycin (SEL212) / SOBI, Cartesian Therap - LARVOL DELTA

Impact of Anti-drug Antibodies on the Efficacy of SEL-212 in Patients with Chronic Gout Refractory to Conventional Therapy (ACR Convergence 2024) - P3 | "Background/Purpose: SEL-212 is a once-monthly, investigational, two-component infusion therapy consisting of pegadricase (SEL-037, a pegylated uricase) and immune-tolerizing nanoparticles containing sirolimus (SEL-110), for the treatment of patients with chronic gout refractory to conventional therapy. In the DISSOLVE studies, SEL-110 mitigated ADA formation for up to 12 months of treatment, allowing for sUA control in patients with chronic gout refractory to conventional therapy treated with SEL-212. Anti-uricase ADAs were the most common, as expected. However, loss of sUA control was typically restricted to high-titer anti-uricase ADAs and IRs were few, making this combination therapy a promising option for patients with severe gout."

Clinical • Gout • Immunology • Inflammatory Arthritis • Rheumatology

Safety and Efficacy of SEL-212 in the US and ex-US Subgroups: Results from the Phase 3 DISSOLVE Studies (ACR Convergence 2024) - P3 | "Background/Purpose: The DISSOLVE Phase 3 study program investigated the efficacy and safety of SEL-212, a novel, once-monthly, two-component infusion therapy consisting of pegadricase (SEL-037, a pegylated uricase) and immune-tolerizing nanoparticles containing sirolimus (SEL-110), in United States (US) and Eastern European patients with chronic gout refractory to conventional therapy. This post hoc analysis of the DISSOLVE studies suggests that SEL-212 is safe and effective at lowering sUA in patients in both regions, including in those patients with a higher disease burden at baseline, as demonstrated by the number of swollen and tender joints, HAQ-DI and SF-36 PCS scores. The findings support SEL-212 as a potential novel once-monthly treatment option that can alleviate the disease burden of chronic gout refractory to conventional therapy."

Clinical • P3 data • Gout • Inflammatory Arthritis • Rheumatology

Improvements in Patient-Reported Outcomes After Treatment with SEL-212 in Adults with Refractory Gout: Results from Two Randomized Phase 3 Trials (ACR Convergence 2024) - "SEL-212 is a novel, once-monthly, two-component infusion therapy of nanoparticles containing sirolimus (SEL-110) followed by pegadricase (SEL‑037, a pegylated uricase) designed to reduce sUA. Clinically meaningful changes in PROs were reported after 3 doses of SEL-212, which further improved after 3 additional doses, indicating patients reported an incremental HRQoL benefit with prolonged treatment duration. SEL-212 improved clinical and HRQoL outcomes, including functional ability, mental health and pain, in adults with refractory gout, which is likely reflective of improved urate lowering with this novel agent."

Clinical • P3 data • Patient reported outcomes • Gout • Immunology • Inflammation • Inflammatory Arthritis • Pain • Rheumatology

Efficacy and Safety of SEL-212 in Patients with Refractory Gout and CKD: A Post Hoc Analysis from the Two Phase 3 DISSOLVE Studies (KIDNEY WEEK 2024) - P3 | "Here, we present Phase 3 efficacy and safety data on the investigational uricase-based therapy SEL-212 in patients with CRG and CKD. DISSOLVE I (NCT04513366) and DISSOLVE II (NCT04596540) investigated the efficacy and safety of SEL-212, a two-component infusion therapy of pegadricase (a pegylated uricase) and immune-tolerizing nanoparticles containing sirolimus in the treatment of CRG. Data from DISSOLVE I and II endorsed the efficacy and safety of SEL-212 in patients with gout refractory to conventional therapy with CKD stage 3. Further studies are needed to establish the use of this novel combination product in refractory gout with end-stage kidney damage."

Clinical • P3 data • Retrospective data • Chronic Kidney Disease • Gout • Inflammatory Arthritis • Nephrology • Rheumatology

ONCE-MONTHLY SEL-212 DEMONSTRATES EFFICACY AND SAFETY FOR UP TO 6-MONTHS IN GOUT REFRACTORY TO CONVENTIONAL THERAPY: COMBINED DATA FROM THE DISSOLVE I & II PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED CLINICAL TRIALS (EULAR 2024) - "SEL-212 is a novel, once-monthly therapeutic platform that consists of sequential infusions of immune-tolerising nanoparticles containing sirolimus (SEL-110), followed by a pegylated uricase (pegadricase, SEL-037). Combined DISSOLVE I & II data confirm the results from the individual studies. Both SEL-212 doses demonstrated clinical efficacy and safety. The lower proportion of patients meeting the stopping rule with HD vs LD SEL-212 suggests that HD SEL-212 may be more efficacious."

Clinical • P3 data • Dental Disorders • Gout • Infectious Disease • Inflammatory Arthritis • Novel Coronavirus Disease • Pain • Rheumatology • Stomatitis

LONG-TERM IMPROVEMENTS IN SERUM URIC ACID LEVELS, GOUT SYMPTOMS, AND SAFETY UP TO 12-MONTHS WITH SEL-212 IN GOUT REFRACTORY TO CONVENTIONAL THERAPY: RESULTS FROM THE DISSOLVE I PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED CLINICAL TRIAL (EULAR 2024) - "SEL-212 is a novel, once-monthly treatment of sequential infusions of immune-tolerising, sirolimus-containing nanoparticles (SEL-110) followed by a pegylated uricase (pegadricase, SEL-037). SEL-212 efficacy was maintained over the 12-month follow-up period and no new safety signals were observed, suggesting that investigational SEL-212 has the potential to be an effective therapy for patients with refractory gout. Once-monthly dosing, and the novel use of sirolimus-containing nanoparticles to mitigate against the development of anti-uricase immunity, differentiates SEL-212 from the currently-approved uricase therapy."

Clinical • P3 data • Dental Disorders • Gout • Inflammatory Arthritis • Rheumatology • Stomatitis

HEALTH-RELATED QUALITY OF LIFE (HRQOL) AND OTHER SECONDARY CLINICAL OUTCOMES IN ADULTS WITH GOUT REFRACTORY TO CONVENTIONAL THERAPY TREATED WITH SEL-212: POOLED 6-MONTH DATA FROM THE PHASE 3 DISSOLVE I & II CLINICAL TRIALS (EULAR 2024) - "SEL-212 is a novel, once-monthly uricase-based therapy comprising sequential infusions of tolerogenic nanoparticles containing sirolimus (SEL-110) followed by a pegylated uricase (pegadricase; SEL-037). Aggregated data from DISSOLVE I & II demonstrate improvements in HRQoL and tender joint count in patients with gout refractory to standard therapy treated with both doses of SEL-212. Similar gout flare incidence during the first three months and subsequent reductions in flare frequency by the end of the study indicate a decline in the body's burden of urate over time."

Clinical • Clinical data • HEOR • P3 data • Gout • Inflammatory Arthritis • Pain • Rheumatology

Gout symptom improvements and patient outcomes with SEL-212 in gout refractory to conventional therapy: DISSOLVE I & II phase 3, double-blind, placebo-controlled clinical trials (BSR 2024) - "SEL-212 is a novel, once-monthly treatment of sequential infusions of tolerogenic nanoparticles containing sirolimus (SEL-110) followed by a pegylated uricase (pegadricase, SEL-037). SEL-212 was well tolerated and provided significant reductions in mean sUA over time, improvement in SF-36 physical and HAQ-DI measures and reduced the number of tender/swollen joints."

Clinical • P3 data • Gout • Inflammatory Arthritis • Rheumatology

Safety & Efficacy of SEL-212 in Patients with Gout Refractory to Conventional Treatment: Primary Outcomes from Two Randomized, Double Blind, Placebo-Controlled, Multicenter Phase 3 Studies (ACR Convergence 2023) - "SEL-212 consists of an infusion of tolerogenic nanoparticles containing rapamycin (SEL-110) followed by pegadricase (SEL-037). In the DISSOLVE trials, once-monthly treatment with SEL-212 demonstrated statistically significant response rates and reductions in sUA versus placebo. The safety profile of SEL-212 was consistent with that of uricase therapies. Targeted immunomodulation with SEL-212 has the potential to provide a new uricase-based treatment option for patients with gout refractory to conventional therapies."

Clinical • P3 data • Gout • Immunology • Inflammatory Arthritis • Novel Coronavirus Disease • Rheumatology

The COMPARE head-to-head, randomised-controlled trial of SEL-212 (pegadricase plus rapamycin-containing nanoparticle, ImmTOR™) versus pegloticase for refractory gout. (PubMed, Rheumatology (Oxford)) - P2 | "SEL-212 efficacy and tolerability were comparable to pegloticase in refractory gout. This was associated with substantial reduction in treatment burden with SEL-212, due to decreased infusion frequency vs pegloticase."

Head-to-Head • Journal • Dental Disorders • Gout • Infectious Disease • Inflammatory Arthritis • Rheumatology • Stomatitis

SAFETY & EFFICACY OF SEL-212 IN PATIENTS WITH GOUT REFRACTORY TO COVENTIONAL TREATMENT: OUTCOMES FROM TWO RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED, MULTICENTER PHASE III STUDIES (EULAR 2023) - "SEL-212 consists of an infusion of tolerogenic nanoparticles containing rapamycin (SEL-110) followed by pegadricase (SEL-037). In the DISSOLVE trials, once-monthly treatment with SEL-212 demonstrated statistically significant response rates and reductions in sUA versus placebo. The safety profile of SEL-212 was consistent with that of uricase therapies. Targeted immunomodulation with SEL-212 has the potential to provide a new uricase-based treatment option for patients with gout refractory to conventional therapies without the need for traditional immunosuppressants."

Clinical • Late-breaking abstract • P3 data • Gout • Immune Modulation • Inflammatory Arthritis • Rheumatology

DISSOLVE II: A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy II (clinicaltrials.gov) - P3 | N=153 | Completed | Sponsor: Selecta Biosciences, Inc. | Recruiting ➔ Completed | Trial completion date: Sep 2022 ➔ Jan 2023 | Trial primary completion date: Sep 2022 ➔ Jan 2023

Trial completion • Trial completion date • Trial primary completion date • Gout • Inflammatory Arthritis • Rheumatology

DISSOLVE I: A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy (clinicaltrials.gov) - P3 | N=112 | Completed | Sponsor: Selecta Biosciences, Inc. | Active, not recruiting ➔ Completed

Trial completion • Gout • Inflammatory Arthritis • Rheumatology

Phase 2 Dose-Finding Study in Patients with Gout Using SEL-212, a Novel PEGylated Uricase (SEL-037) Combined with Tolerogenic Nanoparticles (SEL-110). (PubMed, Rheumatol Ther) - P2 | "Results provide continued support for the use of multiple monthly administrations of SEL-037 0.2 mg/kg + SEL-110 0.1-0.15 mg/kg in clinical trials for SEL-212."

Journal • P2 data • Gout • Inflammatory Arthritis • Rheumatology

"$SELB Phase 3 DISSOLVE Program of SEL-212 in Chronic Refractory Gout Meets Primary Endpoint https://t.co/u8c7PmbUim" (@stock_titan)

Gout • Inflammatory Arthritis • Rheumatology

"$SELB topline data for Phase 3 DISSOLVE I & II trials of SEL-212 in chronic refractory gout on track for Q1" (@BioStocks)

P3 data • P3 data: top line • Gout • Inflammatory Arthritis • Rheumatology

DISSOLVE I: A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy (clinicaltrials.gov) - P3 | N=120 | Active, not recruiting | Sponsor: Selecta Biosciences, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gout • Inflammatory Arthritis • Rheumatology

DISSOLVE II: A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy II (clinicaltrials.gov) - P3 | N=120 | Recruiting | Sponsor: Selecta Biosciences, Inc. | Trial completion date: May 2022 ➔ Sep 2022 | Trial primary completion date: May 2022 ➔ Sep 2022

Trial completion date • Trial primary completion date • Gout • Inflammatory Arthritis • Rheumatology

[VIRTUAL] IMMTOR NANOPARTICLES ENHANCE THE TOLEROGENIC ENVIRONMENT OF THE LIVER IN MICE (EULAR 2021) - "Background: Tolerogenic ImmTOR biodegradable nanoparticles encapsulating rapamycin have been shown to mitigate the formation of anti-drug antibodies against pegadricase, a pegylated uricase enzyme, which enabled monthly dosing and sustained reduction of serum uric acid levels in a Phase 2 clinical trial of SEL-212, a combination of pegadricase + ImmTOR, in patients with symptomatic gout with hyperuricemia. These results suggest that the liver may contribute to the tolerogenic properties of ImmTOR in mitigating anti-drug antibody responses to biologic therapies, such as pegadricase."

Preclinical • Gout • Immune Modulation • Inflammation • Inflammatory Arthritis • Rheumatology • CD4 • CD8 • CTLA4 • PD-1

DISSOLVE II: A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy II (clinicaltrials.gov) - P3; N=105; Recruiting; Sponsor: Selecta Biosciences, Inc.

Clinical • New P3 trial • Gout • Inflammatory Arthritis • Rheumatology

"ah my favorite topic The Company's lead product candidate, SEL-212, is a combination of a therapeutic enzyme and its SVP technology designed to be the biologic treatment for gout." (@thumbs_five)

Gout • Inflammatory Arthritis • Rheumatology

A Study to Compare the Efficacy of SEL-212 to KRYSTEXXA® in Gout Patients Refractory to Conventional Therapy (clinicaltrials.gov) - P2; N=170; Completed; Sponsor: Selecta Biosciences, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Gout • Inflammatory Arthritis • Rheumatology

DISSOLVE I: A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy (clinicaltrials.gov) - P3; N=105; Recruiting; Sponsor: Selecta Biosciences, Inc.; Not yet recruiting ➔ Recruiting; Trial completion date: May 2022 ➔ Sep 2022; Trial primary completion date: Dec 2021 ➔ Mar 2022

Clinical • Enrollment open • Trial completion date • Trial primary completion date • Gout • Inflammatory Arthritis • Rheumatology

DISSOLVE I: A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy (clinicaltrials.gov) - P3; N=105; Not yet recruiting; Sponsor: Selecta Biosciences, Inc.

Clinical • New P3 trial • Gout • Rheumatology

Development of ImmTOR Tolerogenic Nanoparticles for the Mitigation of Anti-drug Antibodies. (PubMed, Front Immunol) - "The focus of this review is the development of ImmTOR, a platform technology designed to prevent the formation of ADAs that can be applied broadly across a wide variety of biologics by inducing immunological tolerance with ImmTOR nanoparticles encapsulating rapamycin...The ability of ImmTOR to mitigate the formation of ADAs has been demonstrated for coagulation factor VIII in a mouse model of hemophilia A, an anti-TNFα monoclonal antibody in a mouse model of inflammatory arthritis, pegylated uricase in hyperuricemic mice and in non-human primates, acid alpha-glucosidase in a mouse model of Pompe disease, recombinant immunotoxin in a mouse model of mesothelioma, and adeno-associated vectors in a model of repeat dosing of gene therapy vectors in mice and in non-human primates. Human proof-of concept for the mitigation of ADAs has been demonstrated with SEL-212, a combination product consisting of ImmTOR + pegadricase, a highly immunogenic enzyme therapy for the treatment..."

Journal • Review • Gene Therapies • Gout • Hematological Disorders • Hemophilia • Immunology • Inflammatory Arthritis • Lung Cancer • Mesothelioma • Oncology • Rare Diseases • Rheumatology • Thoracic Cancer