Summary of Eledon Pharmaceuticals (ELDN) Conference Call Company Overview - **Company**: Eledon Pharmaceuticals - **Focus**: Development of tegoprubart for kidney transplant rejection prevention Industry Context - **Industry**: Biotech, specifically in transplant medicine - **Current Standard of Care**: Calcineurin inhibitors, primarily tacrolimus, which has been in use since 1994 Key Points and Arguments Unmet Need in Kidney Transplantation - Tacrolimus has significant limitations including nephrotoxicity, hypertension, and beta cell toxicity leading to hyperglycemia and insulin-dependent diabetes [4][5] - The average survival of transplanted kidneys is between 10 to 15 years, with patients often requiring multiple transplants due to organ scarcity [5][6] Tegoprubart Development - Tegoprubart is being evaluated in Phase 1B and Phase 2 trials as an alternative to tacrolimus [3] - The goal is to improve patient quality of life and organ survival by reducing adverse effects associated with tacrolimus [5] Clinical Trial Design and Endpoints - **Phase 1B Study**: Focused on safety and tolerability, with endpoints including rejection rates and kidney function measured by eGFR [14][15] - **Phase 2 Study (BESTOW)**: Designed to demonstrate superiority over tacrolimus, with a primary endpoint of kidney function at 12 months, aiming for an eight-point difference in eGFR [15][34] iBOX Score as a New Endpoint - iBOX is a composite endpoint that includes eGFR, DSA, proteinuria, and time since transplant, which is a better predictor of long-term graft survival than traditional biopsy-proven rejection [7][19] - Eledon reported an iBOX score of negative 4.1 in the on-treatment group, significantly better than the average CNI iBOX score of negative 2.9 [18][22] Rejection Rates and Safety Profile - The rejection rate in the Phase 1B study was reported at 18%, comparable to BALADA sub-studies in the low 20s, while standard care is in the high single digits [23][24] - The safety profile showed no significant adverse events typically associated with tacrolimus, such as graft loss or sepsis [45] Market Opportunity - Approximately 48,000 transplants occur annually in the U.S., with nearly 30,000 being kidney transplants [48] - The U.S. transplant immunosuppressant market is substantial, with tacrolimus generating nearly $1.5 billion in annual revenues [48] Future Expectations - Eledon anticipates presenting data from the Phase 2 study in Q4 and expects to launch Phase 3 trials in the second half of the following year [54][58] - The company is also exploring islet cell transplantation and xenotransplantation, with ongoing studies expected to yield more data [58] Additional Important Insights - The FDA is considering new approval endpoints that may allow for superiority claims based on iBOX scores [11][12] - The concentrated nature of the transplant market, with only 40 centers performing half of the transplants, presents a unique opportunity for Eledon to leverage existing relationships [48][51] This summary encapsulates the critical insights from the conference call, highlighting Eledon's strategic focus on addressing unmet needs in kidney transplantation through innovative therapies and the potential market impact.

Core Insights - Biogen has initiated dosing in a global, late-stage study of felzartamab for treating adult patients with primary membranous nephropathy (PMN), with top-line data expected in 2029 [1][4] - Felzartamab is an anti-CD38 antibody with a unique mechanism of action, and currently, there are no approved therapies for PMN, which typically relies on immunosuppressants or chemotherapy [1][6] - The PROMINENT study will evaluate the efficacy and safety of felzartamab compared to tacrolimus in moderate-to-high-risk PMN patients [3][5] Company Developments - Felzartamab was added to Biogen's pipeline through the acquisition of Human Immunology Biosciences last year, originally developed by MorphoSys AG [2] - The PROMINENT study will enroll approximately 180 PMN patients, with the primary endpoint being the percentage of patients achieving complete remissions at week 104 [5] - Biogen has also initiated dosing patients with felzartamab in two other phase III studies for late antibody-mediated rejection in kidney transplant recipients and IgA nephropathy [7] Clinical Study Details - The PROMINENT study will compare felzartamab to tacrolimus in 180 moderate-to-high-risk PMN patients, including newly diagnosed and relapsed cases [4][5] - Secondary endpoints will evaluate the effect of felzartamab on serum aPLA2R antibodies and patient-reported outcomes [5] - Previous phase II studies showed that felzartamab led to significant reductions in aPLA2R antibody levels and improvements in kidney markers [10] Market Context - PMN affects about 36,000 people in the United States and represents a serious unmet medical need, as current treatment options fail in about one-third of patients [6] - Year to date, Biogen's shares have declined by 17.9%, compared to the industry's decline of 3.6% [3]

Core Viewpoint - Biogen has initiated a Phase 3 clinical study, PROMINENT, to evaluate the efficacy and safety of felzartamab in treating primary membranous nephropathy (PMN), a severe kidney disease with no approved treatments [1][4]. Company Overview - Biogen is a leading biotechnology company founded in 1978, focused on innovative science to develop new medicines and create value for shareholders and communities [10]. - The company has a commitment to advancing treatment options for patients with kidney diseases, as evidenced by the launch of multiple Phase 3 trials for felzartamab in 2025 [3][5]. Drug Information - Felzartamab is an investigational anti-CD38 monoclonal antibody that selectively depletes CD38+ plasma cells, which are implicated in various immune-mediated diseases [2][6]. - The drug targets patients with PMN, where up to 80% have autoantibodies against PLA2R, and aims to provide a novel treatment option in a field lacking approved therapies [2][9]. Clinical Study Details - The PROMINENT study will enroll approximately 180 adults with PMN and is expected to read out in 2029 [1]. - The trial is designed as a 104-week, randomized, open-label study comparing felzartamab to tacrolimus, with the primary endpoint being the percentage of participants achieving complete remission of proteinuria at week 104 [3][4]. - Key secondary endpoints include the impact on serum anti-PLA2R antibodies and patient-reported outcomes [3]. Previous Research - Felzartamab has shown promising results in earlier Phase 2 studies, with significant reductions in aPLA2R titers and improvements in proteinuria and serum albumin levels observed [4][6]. - The majority of treatment-emergent adverse events reported were mild to moderate, primarily infusion-related reactions [4]. Market Context - PMN is a rare immune-mediated kidney disease with an estimated prevalence of approximately 36,000 patients in the U.S., highlighting the unmet medical need in this area [6][9].