eRapa (encapsulated rapamycin) / Emtora Biosci, Biodexa Pharma - LARVOL DELTA

Biodexa Activates First European Site for Registrational Phase 3 Serenta Trial in FAP (GlobeNewswire) - "...University of Bonn, Germany is now actively screening patients...The randomized, double-blind, placebo-controlled Serenta trial (NCT06950385) is designed to evaluate whether eRapa can prevent disease progression in patients with FAP....Nine additional European sites will activate during the next 2-3 months across the Netherlands, Spain, Denmark, and Italy."

Trial status • Genetic Disorders • Rare Diseases

Nanoencapsulated Sirolimus Plus Pegadricase (NASP) Reduces Gout Clinical Manifestations in Patients with Uncontrolled Gout (UG) and Stage 3 CKD (KIDNEY WEEK 2025) - P3 | "NASP (formerly SEL-212) is an investigational, novel, every 4-wk (Q4W), sequential 2-component infusion therapy consisting of targeted nanoencapsulated sirolimus (NAS) and pegadricase (P) that reduces serum uric acid (sUA). Safety was similar to the ITT population ( Table ), with only one case of proteinuria in each NASP arm (not considered drug related). Conclusion NASP was well tolerated and reduced disease burden in pts with UG and CKD."

Clinical • Chronic Kidney Disease • Gout • Inflammatory Arthritis • Nephrology • Renal Disease • Rheumatology

Effect of Nanoencapsulated Sirolimus Plus Pegadricase (NASP) on Kidney Outcomes: Results from the Phase 3 DISSOLVE Studies (KIDNEY WEEK 2025) - P3 | "Conclusion These data show stable renal function over the study period in NASP-treated patients with more patients having an improvement in CKD stage compared to PBO. Findings here suggest NASP may be a uricase treatment option for patients with UG and CKD-3."

P3 data • Chronic Kidney Disease • Gout • Inflammatory Arthritis • Nephrology • Renal Disease • Rheumatology

Biodexa Announces Approval of CTA in Europe for Phase 3 Serenta Trial in FAP First European patient expected to be enrolled in 4Q 2025 Addressable US - European Market Put at $7 Billion (GlobeNewswire) - "The CTA permits the Serenta trial to proceed in Europe, initially covering clinical sites in Denmark, Germany, Netherlands and Spain with Italy expected to be added in due course...The Serenta trial (NCT06950385) is a randomized, double-blind, placebo-controlled Phase 3 registrational study designed to evaluate the safety and efficacy of eRapa in patients diagnosed with FAP. Multiple sites in the US are actively screening eligible participants. It is expected that 168 patients will be recruited into the trial randomized 2:1 drug: placebo."

Trial status • Rare Diseases

Nanoencapsulated Sirolimus Plus Pegadricase Reduced Disease Burden in Patients With Uncontrolled Gout: Results From the Phase 3 DISSOLVE Trials (ACR Convergence 2025) - P3 | "NASP (formerly SEL-212) is an investigational, novel, every 4-wk (Q4W), sequential 2-component infusion therapy consisting of targeted nanoencapsulated sirolimus (NAS, formerly SEL-110), which mitigates the formation of antipegadricase antibodies, and a uricase (pegadricase [P]; formerly SEL-037), which reduces sUA. NASP-treated pts had meaningful reductions in disease burden and key clinical manifestations, as reflected by improvements in sUA levels and PROs. This therapy has a noteworthy impact on resolving acute gout symptoms over 6 treatments and shows promise for improving HRQOL."

Clinical • P3 data • Gout • Immunology • Inflammatory Arthritis • Rheumatology

Reduction in Tophi Observed in Patients with Uncontrolled Gout Treated with NASP: Results from Phase 3 DISSOLVE Studies (ACR Convergence 2025) - P3 | "NASP (formerly SEL-212) is a novel, every 4-week, sequential infusion therapy consisting of targeted immunomodulating, nanoencapsulated sirolimus (NAS; formerly SEL-110) co-administered with a pegylated uricase (formerly SEL-037) designed to reduce serum uric acid (sUA) levels in pts with UG. Treatment with NASP resulted in a greater tophus response compared to PBO. In addition, a robust sUA reduction, a key factor in tophus resolution, was observed in NASP-treated pts. These results highlight the effectiveness of NASP in lowering sUA and promoting tophus resolution."

Clinical • P3 data • Gout • Immunology • Inflammatory Arthritis • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Rheumatology

Nanoencapsulated Sirolimus plus Pegadricase (NASP) Demonstrates Long Term Efficacy and Safety in Patients with Uncontrolled Gout: Results from the 24-week Double-blind Extension of the Phase 3 DISSOLVE I Study (ACR Convergence 2025) - P3 | "Nanoencapsulated sirolimus plus pegadricase (NASP, formerly SEL-212) is a novel investigational therapy delivered every 4 weeks as a sequential, two-component infusion consisting of targeted nanoencapsulated sirolimus and pegadricase, a pegylated uricase (Figure 1A). These data support the long-term durability of NASP as shown by sustained sUA reductions and decreased gout flares over time, with 100% on HD NASP and 92.3% on LD NASP being flare-free at the end of the extension phase. NASP was generally well tolerated with low discontinuation rates during the extension phase. Overall, NASP led to improvements in key clinical manifestations of UG."

Clinical • P3 data • Gout • Inflammatory Arthritis • Rheumatology

Nanoencapsulated Sirolimus plus Pegadricase (NASP) Demonstrates a Reduction in Gout Flares: Results from the Phase 3 DISSOLVE Studies (ACR Convergence 2025) - P3 | "NASP (formerly SEL-212) is an investigational, every 4-week, sequential infusion therapy designed to reduce sUA levels in patients (pts) with uncontrolled gout (UG), consisting of targeted immunomodulating, nanoencapsulated sirolimus (NAS; formerly SEL-110), sequentially administered with pegadricase (a pegylated uricase; formerly SEL-037). The proportion of pts with flares and number of flares decreased with NASP compared to PBO over the course of the study, with 95.2% and 94.3% of HD and LD-treated pts being flare-free during weeks 21–24. These results highlight the potential of NASP as an effective therapy for reducing disease burden and improving a key clinical outcome in pts with UG."

P3 data • Gout • Immunology • Inflammatory Arthritis • Rheumatology

Characterization of Infusion Reactions Within 1 Hour of Treatment With Nanoencapsulated Sirolimus Plus Pegadricase: Pooled Results From the Phase 3 DISSOLVE I and DISSOLVE II Trials (ACR Convergence 2025) - P3 | "NASP (formerly SEL-212) is an investigational, novel, every 4-wk (Q4W), sequential 2-component infusion therapy consisting of tolerogenic nanoencapsulated sirolimus (NAS, formerly SEL-110), which mitigates formation of antipegadricase antibodies, and a uricase (pegadricase [P]; formerly SEL-037), which reduces sUA...All pts fully recovered with appropriate medical intervention (mainly steroids and antihistamines) provided at the infusion center; 1 pt received epinephrine for anaphylaxis... The low incidence (4.0%) of pts experiencing IRs, including hypersensitivity reactions, within 1 h of NASP suggests that NAS mitigates ADA formation. No pts required in-patient hospitalization or intubation, and all IRs resolved with standard measures (mainly at the infusion center)."

P3 data • Gout • Immunology • Inflammatory Arthritis • Rheumatology

Updates in uricase therapy for gout. (PubMed, Curr Opin Rheumatol) - "Exogenous uricases available and those under development are discussed, focusing on immunomodulation and anti-inflammatory prophylaxis to reduce flares, prevent antidrug antibody formation and infusion reactions, and mitigate loss of efficacy in patients with uncontrolled gout needing uricase replacement therapy."

Journal • Developmental Disorders • Gout • Immunology • Inflammatory Arthritis • Oncology • Rheumatology

Biodexa Announces Filing of CTA in Europe for Phase 3 Serenta Trial in Familial Adenomatous Polyposis (FAP) (GlobeNewswire) - "Biodexa Pharmaceuticals...announced the filing of a Clinical Trial Application (CTA) with the European Medicines Agency (EMA) for its Serenta trial in patients with familial adenomatous polyposis (FAP), a mostly inherited disease that, if left untreated, almost always leads to colorectal cancer. The only current treatment option is sequential resection of much of the gastrointestinal tract...if approved, it would permit the Serenta trial to proceed in Europe, initially covering clinical sites in Denmark, Germany, Netherlands and Spain with Italy expected to be added in due course....The Serenta trial (NCT06950385) is a randomized, double-blind, placebo-controlled Phase 3 registrational study designed to evaluate the safety and efficacy of eRapa in patients diagnosed with FAP....Following the 106 day approval timeline for the CTA, it is expected the European sites will begin enrolling in the fourth quarter of this year."

Trial status • Rare Diseases

Induction of Mixed Chimerism for Renal Allograft Tolerance Using Bcl-2 Inhibition and Nanoparticle Encapsulated Rapamycin without Genotoxic Treatments (WTC 2025) - "In the current study, we investigated the use of ImmTOR in a Bcl-2 inhibitor-based conditioning regimen to achieve mixed chimerism induction without genotoxic treatments (e.g. TBI and chemotherapy).* Without including any genotoxic treatment, all recipients were conditioned with ATG, Bcl-2 inhibitor (venetoclax 10mg/kg for 11 doses), 7Gy local thymic irradiation followed by combined kidney and bone marrow or peripheral blood stem cell (PBSC) transplantation. Mixed chimerism and renal allograft tolerance can be achieved without genotoxic treatments through the combination of Bcl-2 inhibition and ImmTOR. Although studies with PBSC are still ongoing, replacing BMT with PBSC transplantation may enhance peak chimerism levels, potentially improving renal allograft tolerance."

Bone Marrow Transplantation • CD40LG

Phase 3 Trial of eRapa in Patients With Familial Adenomatous Polyposis (clinicaltrials.gov) - P3 | N=168 | Recruiting | Sponsor: Rapamycin Holdings Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders

Biodexa Announces Activation of First Clinical Study Site for Phase 3 Serenta Trial in Familial Adenomatous Polyposis (FAP) (GlobeNewswire) - "Biodexa Pharmaceuticals PLC...is pleased to announce the activation of the first clinical study site for its Serenta trial in patients with familial adenomatous polyposis (FAP). The trial, which is now enrolling, represents a significant milestone in the development of a potential new treatment option for FAP."

Trial status • Genetic Disorders • Rare Diseases

Biodexa Receives Orphan Drug Designation in Europe for eRapa in FAP (GlobeNewswire) - "Biodexa Pharmaceuticals PLC...announced the European Commission (EC) has granted Orphan Drug Designation for eRapa in familial adenomatous polyposis (FAP), a largely inherited precancerous disease of the colon for which there is currently no pharmaceutical intervention....The Phase 3 study of eRapa in FAP is in the final stages of implementation. It will be a double-blind placebo-controlled trial in 168 patients, randomized 2:1 drug / placebo. It is expected the study will be conducted in approximately 30 clinical sites across the US and Europe."

Orphan drug • Trial status • Rare Diseases

Phase 3 Trial of eRapa in Patients With Familial Adenomatous Polyposis (clinicaltrials.gov) - P3 | N=168 | Not yet recruiting | Sponsor: Rapamycin Holdings Inc.

New P3 trial • Genetic Disorders

Exosomal delivery of rapamycin modulates blood-brain barrier penetration and VEGF axis in glioblastoma. (PubMed, J Control Release) - "In this study, we utilized an exosome-encapsulated rapamycin (Exo-Rapa) delivery strategy, which permits the use of smaller drug dosages to achieve effects typically seen with higher dosages, thus enhancing drug efficacy. Additionally, a series of in vivo experiments have further demonstrated the permeability of Exo-Rapa across the BBB, enabling it to accumulate at tumor sites; it also ameliorates inflammatory responses in Glioblastoma multiforme (GBM) mouse models and enhances anti-tumor activity through the regulation of angiogenesis via the VEGF/VEGFRs axis. Our results indicate that MSC-derived exosomes are a potent therapeutic carrier for GBM, offering an effective strategy for enhancing drug delivery across the BBB and providing a scientific foundation for the use of exosomes in the treatment of GBM and other diseases."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Biodexa Announces Successful Outcome of a Type C Meeting with FDA Regarding the Phase 3 Program for eRapa in FAP (GlobeNewswire) - "Biodexa Announces Successful Outcome of a Type C Meeting with FDA Regarding the Phase 3 Program for eRapa in FAP; Clears the way to finalize Phase 3 protocol and recruit sites for U.S; Phase 3 substantially funded by $17.0 million CPRIT grant and $8.5 million Company match."

Commercial • FDA event • New P3 trial • Rare Diseases

Biodexa Announces Appointment of Precision for Medicine LLC as CRO for European Component of Phase 3 Study of eRapa in FAP (GlobeNewswire) - "Biodexa Pharmaceuticals PLC...today announced the appointment of Precision for Medicine, LLC ('Precision') as the clinical research organization ('CRO') to conduct the European component of the upcoming registrational Phase 3 study of eRapa in FAP. The U.S. component of the study will be conducted by LumaBridge, based in San Antonio, Texas....The planned registrational Phase 3 study of eRapa in FAP will be a double-blind placebo-controlled trial in 168 patients, randomized 2:1 drug / placebo. It is expected the study will be conducted in approximately 30 clinical sites across the US and Europe."

Commercial • New P3 trial • Rare Diseases

Biodexa Announces Allowance of U.S. Patent Covering Oral Rapamycin Nanoparticle Preparations ('eRapa') and Use (GlobeNewswire) - "Biodexa plans to initiate a Phase 3 registrational study of eRapa in Familial Adenomatous Polyposis (FAP) next quarter...Biodexa Pharmaceuticals PLC...today announced that the U.S. Patent and Trademark Office allowed has U.S. patent application No. 17/391.495 titled 'Oral Rapamycin Nanoparticle Preparations and Use' which was exclusively licensed to Biodexa by Rapamycin Holdings, Inc. d/b/a Emtora Biosciences, along with other patents, in a transaction which closed in April 2024. The patent is due to issue on March 4, 2025 and, in the absence of any patent term extensions, is expected to expire in March, 2034."

New P3 trial • Patent • Colonic Polyps • Rare Diseases

Rapamycin Reduces Noise-Induced Vestibular Loss and Improves Walking Speed in Noise Exposed Rats (ARO 2025) - "A commercially prepared pelleted chow diet containing encapsulated rapamycin or vehicle was given to rats at a dose of approximately 42 mg/kg body weight per day... These results demonstrate a protective effect on the vestibular periphery and a significant improvement in walking speed, both shortly after noise exposure and for months after discontinuation of the rapamycin diet. Taken together, these results demonstrate a measurable effect of rapamycin that may have long-term benefits for mobility and vestibular function that can be observed at the cellular level."

Preclinical • Otorhinolaryngology • mTOR

Biodexa Receives US FDA Fast Track Designation for eRapa in Familial Adenomatous Polyposis (GlobeNewswire) - "Biodexa Pharmaceuticals PLC...announced today that the US Food and Drug Administration ('FDA') has granted Fast Track designation for eRapa, a proprietary encapsulated form of rapamycin being developed for the treatment of familial adenomatous polyposis (FAP)...Today, the only treatment option is surgical resection of the colon and/or rectum. Data from the Phase 2 study of eRapa in FAP showed eRapa to be safe and well-tolerated with a median 17% reduction in total polyp burden at 12 months compared with baseline and an overall 75% non-progression rate."

Fast track • Rare Diseases

Trial of ERapa to Prevent Progression in Familial Adenomatous Polyposis Patients Under Active Surveillance (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Rapamycin Holdings Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • APC

Rapamycin Reduces Carcinogenesis and Enhances Survival in Mice when Administered after Nonlethal Total-Body Irradiation. (PubMed, Radiat Res) - "Immediately after TBI, along with untreated control groups, animals were placed on chow containing different concentrations of encapsulated rapamycin (14, 40, 140 mg/kg chow). Further, there was a survival advantage when delaying the rapamycin chow by 1 month after TBI. Rapamycin is FDA-approved for human use and could be considered for use in individuals exposed to nonlethal TBI from a nuclear accident or attack or after significant therapeutic doses for cancer treatment."

Journal • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Trial of eRapa to Prevent Progression in Familial Adenomatous Polyposis Patients Under Active Surveillance (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Rapamycin Holdings, Inc. dba Emtora Biosciences | Active, not recruiting ➔ Recruiting | Phase classification: P2a ➔ P2 | Trial completion date: Feb 2023 ➔ Mar 2025 | Trial primary completion date: Feb 2023 ➔ Mar 2025

Enrollment open • Phase classification • Trial completion date • Trial primary completion date • Genetic Disorders • APC