Summary of Biogen's Immunology Pipeline Discussion Company Overview - **Company**: Biogen - **Focus**: Immunology pipeline, particularly the development of felzartamab, a CD38-directed treatment Key Points and Arguments Immunology Pipeline and CD38 Target - Biogen's immunology pipeline is centered around felzartamab, which targets CD38, a molecule implicated in various autoimmune diseases driven by pathogenic antibodies [2][3] - The therapy aims to selectively target plasma cells and plasma blasts, which are responsible for producing these pathogenic antibodies, allowing for more effective treatment options [2] Clinical Focus on Renal Diseases - The primary clinical focus is on late antibody-mediated rejection (AMR) in renal transplantation patients, a significant unmet medical need affecting approximately 11,000 individuals out of 300,000 to 400,000 kidney transplant recipients [8][10] - Late AMR is the leading cause of graft loss, and current therapies are ineffective, highlighting the importance of developing new treatments [8][10] Phase 2 Study Results - A small Phase 2 study with 22 participants showed that two-thirds of patients in the felzartamab group achieved microvascular inflammation (MVI) scores of zero at six months, indicating a significant reduction in inflammation [11] - The study demonstrated an 80% reversal of microvascular inflammation at the six-month mark, which is unprecedented compared to other therapies [11] Phase 3 Study Design - The upcoming Phase 3 study will include a one-year duration with participants randomized to receive either felzartamab or placebo, with a crossover design for placebo participants after six months [12][15] - The primary endpoint will focus on the reversal of AMR by histology, with additional supportive data on graft injury biomarkers and kidney function [16] IgA Nephropathy and Competitive Landscape - In the IgA nephropathy space, felzartamab is positioned as a potential option for durable disease control without the need for ongoing treatment, unlike other therapies that require continuous dosing [21][25] - The market for IgA nephropathy is competitive, but felzartamab's unique mechanism targeting plasma cells may provide a distinct advantage [21][25] PMN Patient Subgroups - In the context of primary membranous nephropathy (PMN), felzartamab may benefit high-risk patients who do not respond to anti-CD20 therapies, as these patients often have plasma cells that do not express CD20 [27][30] - Approximately 30%-50% of PMN patients may not respond to CD20 therapies, indicating a significant opportunity for targeted treatment with felzartamab [30] Future Development Plans - Biogen plans to initiate a Phase 1b study for lupus nephritis and a Phase 2 study for DSA negative AMR, recognizing the importance of these populations in the broader context of autoimmune diseases [32][33] - The company is also exploring additional autoantibody-driven diseases for potential future studies [35] Lupus Development Focus - Biogen is prioritizing systemic lupus erythematosus (SLE) due to its heterogeneous nature and the limited number of approved therapies, with only two currently available [37] - The company is developing two therapies targeting different mechanisms, with promising Phase 2 data and ongoing Phase 3 trials [38][39] Regulatory Considerations - Biogen has established a strong partnership with the FDA to align on endpoints and study designs across its lupus programs, ensuring a robust approach to clinical development [41] Additional Important Insights - The discussion highlighted the evolving landscape of autoimmune disease therapies and the importance of targeted treatments that address the underlying mechanisms of disease [2][21] - The potential for felzartamab to provide durable treatment effects without the need for ongoing dosing is a significant differentiator in the competitive market [25][30]

Group 1 - Biogen (BIIB) has signed a research collaboration agreement with Dayra Therapeutics to discover and develop oral macrocyclic peptides targeting immunological conditions [1][6] - The collaboration aims to leverage the strategic potential of oral macrocyclic peptides, which can provide biologic-like efficacy and safety in a more convenient oral form, enhancing patient adherence [2][4] - Biogen will pay an upfront fee of $50 million to Dayra and may also make milestone payments as it develops its immunology pipeline [6][8] Group 2 - The partnership will utilize Dayra's advanced macrocycle discovery platform to identify, validate, and optimize oral macrocyclic candidates against key immunological targets, with Biogen responsible for late-stage development and commercialization [4][6] - Biogen's existing immunology pipeline includes three late-stage candidates: dapirolizumab pegol, litifilimab, and felzartamab, which are in various phases of development for different indications [10][11]

Biogen Conference Call Summary Company Overview - **Company**: Biogen (NasdaqGS:BIIB) - **Date**: November 13, 2025 - **Event**: TD Cowen's 2025 I&I Summit Key Industry and Company Insights Immunology and Kidney Strategy - Biogen has reinvigorated its immunology and kidney efforts, leveraging its expertise in neuroimmunology from its historical focus on neuroscience [2][3] - The strategy aims to support a diverse product portfolio by targeting immunological pathways applicable to multiple disease indications [2][3] R&D Pipeline Structure - The ideal R&D pipeline in immunology is driven by scientific understanding, allowing for efficient early development trials and multi-indication strategies [4][5] - Biogen's approach includes starting with multiple indications simultaneously to build confidence for further expansion [5] Investor Perception - Investors currently undervalue Biogen's immunology and kidney pipeline, potentially missing the strategic rationale behind the development of drugs like felzartamab [6] - Felzartamab is positioned to address antibody-mediated rejection in kidney transplants, supported by robust clinical data [6][7] Lupus Pipeline Confidence - Biogen has two late-stage candidates for lupus: dapirolizumab pegol and litifilimab, with confidence stemming from data-driven insights and successful proof of concept studies [9][10] - The company emphasizes the importance of clinical trial execution and understanding disease management in lupus, which has historically been challenging [10][11] Ongoing Trials - The Topaz 1 and 2 trials for systemic lupus erythematosus (SLE) have completed enrollment, with data expected by the end of 2026 [14][15] - These trials are designed to test different dosing paradigms and measure various endpoints related to disease control [15][16] Key Risks and Considerations - Risks to trial success include the complexity of lupus management and the need for precise clinical trial execution [17][18] - Biogen aims to meet statistical significance and meaningful patient outcomes in its trials, focusing on reducing flares and steroid use [19][20] New Programs and Future Directions - Biogen recently introduced BIIB142, an IRAK4 degrader, which is an oral molecule with potential applications across various autoimmune diseases [32][33] - The company is exploring multi-indication strategies for this new asset and continues to build its early-stage pipeline through collaborations and acquisitions [36] Additional Insights - Biogen is committed to reducing steroid dependency in lupus patients, aligning with evolving treatment guidelines [20] - The company is optimistic about the potential of its lupus candidates to provide meaningful improvements in patient quality of life [10][11] This summary encapsulates the key points discussed during the conference call, highlighting Biogen's strategic focus on immunology and kidney disease, ongoing clinical trials, and future directions in research and development.

Core Insights - Biogen Inc. is set to present new data on felzartamab, an investigational anti-CD38 monoclonal antibody, at Kidney Week 2025, highlighting its potential in treating various kidney diseases [1][2] - The first data readout from the TRANSCEND study, focusing on adult kidney recipients with late antibody-mediated rejection, is expected in 2027 [1] Company Activities - Biogen will showcase first-of-its-kind gene expression data and evidence of preserved humoral immunity in patients with IgA nephropathy receiving felzartamab [2] - Presentations will include an oral presentation on RNAseq data from the Phase 2 IGNAZ study and a poster on the impact of felzartamab on vaccine immunity in IgAN patients [2][5] - The company will also host an Exhibitor Spotlight discussing the role of CD38+ cells in immune-mediated kidney diseases [2][5] Clinical Development - Felzartamab is currently being evaluated in three pivotal Phase 3 studies targeting late antibody-mediated rejection, IgA nephropathy, and primary membranous nephropathy [1][2] - The ongoing studies include TRANSCEND, PREVAIL, and PROMINENT, with specific presentations scheduled during the conference [6][7] Product Information - Felzartamab selectively depletes CD38+ plasma cells and is considered a potential first-in-class therapeutic candidate for various immune-mediated diseases [4][5] - The drug was originally developed by MorphoSys AG and is now exclusively licensed to Human Immunology Biosciences, which Biogen acquired in July 2024 [7] Company Overview - Biogen, founded in 1978, focuses on pioneering innovative science to deliver new medicines and create value for shareholders [8] - The company aims to leverage its understanding of human biology to advance first-in-class treatments [8]

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].

Core Insights - Biogen has initiated a phase III study for its candidate felzartamab in adult kidney transplant recipients with late antibody-mediated rejection (AMR), a major cause of transplant failure [1][2] - The study will enroll approximately 120 participants and aims to evaluate the efficacy and safety of felzartamab compared to a placebo, with a primary endpoint focused on AMR resolution by biopsy at 6 months [2] - Felzartamab has received Breakthrough Therapy designation from the FDA for the AMR indication [2] Pipeline Development - Biogen is exploring felzartamab for various immune-mediated diseases, indicating its potential as a "pipeline-in-a-product" [4] - Ongoing phase II studies for felzartamab include indications for primary membranous nephropathy (PMN) and Immunoglobulin A nephropathy (IgAN), with plans to start phase III studies in 2025 [5] - The candidate was acquired through Biogen's purchase of Human Immunology Biosciences in July last year, which included rights to felzartamab globally, excluding China [6] Financial Implications - Following the start of the phase III study, Biogen will make a milestone payment of $35 million to MorphoSys [7] - Biogen's stock has seen a decline of 36.6% over the past year, compared to an 8.5% decline in the industry [3]