BioNTech (Germany)

Efficient poultry production depends on the optimal supplementation of energy and standardized ileal digestible (SID) amino acids to realize the genetic potential for whole-body protein deposition. While the requirements for energy and SID amino acids-such as the SID lysine-to-energy ratio-are well-documented, industry adoption of these findings remains slow. Consequently, many commercial formulations still rely on crude protein (CP) as a primary constraint. This reliance on high levels of protein meal inclusion leads to increased indigestible protein and excess absorbed amino acids, which in turn trigger various metabolic, health, welfare, and environmental challenges. This symposium paper explores how the poultry industry can effectively manage nitrogen emissions while maintaining optimal growth performance by leveraging the latest advancements in precision nitrogen (N) nutrition.

Triple-negative breast cancer (TNBC) is frequently associated with metastatic relapse, even at an early stage1. Here we assessed an individualized neoantigen mRNA vaccine in 14 patients with TNBC following surgery and after neoadjuvant oradjuvant therapy. In peripheral blood of nearly all patients, high-magnitude, vaccine-induced, mostly de novo T cell responses to multiple neoantigens were detected that remained functional for several years. Characterization of individual patients revealed that a large proportion of these T cells developed into two subsets: a late-differentiated phenotype with markers indicative of 'ready-to-act' cytotoxic effector T cells, and T cells with a stem cell-like memory phenotype. Eleven patients remained relapse-free for up to six years post-vaccination. Recurrence occurred in three patients: the individual with the weakest vaccine-induced T cell response relapsed, but achieved complete remission on subsequent anti-PD-1 therapy; another patient had a tumour with low major histocompatibility complex (MHC) class I expression with MHC class I-deficient cells growing out under vaccination; and the third patient was BRCA-positive and had a recurrence from a genetically distinct primary tumour. These findings demonstrate the feasibility of individualized RNA vaccines in TNBC, document persistence of vaccine-induced, functional neoantigen-specific T cells and provide insights into possible immune escape mechanisms that will guide future approaches.

175 Background: Lutetium-177 vipivotide tetraxetan (Lu 177) significantly improves progression-free survival (PFS) and overall survival (OS) in patients (pts) with pre-treated mCRPC. Combination strategies are being explored to enhance therapeutic outcomes. Preclinical models have demonstrated that radiotherapy selectively expands and activates regulatory T cells (Tregs) in the tumor microenvironment (TME). Gotistobart, an investigational pH-sensitive anti-CTLA-4 antibody, enhances Treg depletion in the TME and, combined with Lu 177, has demonstrated manageable safety and promising preliminary PSA50 rates in pts with mCRPC (#5067, ASCO 2025). Here, we report updated efficacy analyses from this Phase 1 trial. Methods: PRESERVE-006 (NCT05682443) is an open-label, randomized, phase 1/2 trial evaluating gotistobart with Lu 177 in pts with mCRPC post-androgen receptor pathway inhibition. Pts received gotistobart (3 mg/kg Q4W, 6 mg/kg Q6W, or 10 mg/kg Q6W, up to 13 doses) plus Lu 177 or Lu 177 alone (up to 6 doses). Efficacy endpoints were assessed per PCWG3 guideline. Results: As of August 8, 2025, this Phase 1 enrolled 25 pts who had a median age of 69 years (range: 52–86), 64.0% of the pts were White, 24.0% were Black and 4.0% were Asian. All pts had prior taxane and androgen receptor pathway inhibitors. Safety data for all 25 pts were reported at ASCO 2025, and no new safety signals were observed. With a median follow-up time of 11.9 m, median radiographic PFS (rPFS) was 4.8 m, 12.2 m, 8.3 m and not reached in the Lu 177 only, 3 mg/kg combo, 6 mg/kg combo, and 10 mg/kg combo group, respectively (Table). Among the 7 pts with measurable disease at baseline who received combination therapy, 5 (71.4%) achieved a partial response, and 2 pts achieved stable disease. Median PSA PFS was not reached for the cohorts dosed at 3 mg/kg and 6 mg/kg. Conclusions: Preliminary efficacy with a manageable safety profile was observed for gotistobart in combination with Lu 177 in pts with mCRPC during the Phase 1 study. The three arm randomized Phase 2 dose optimization stage (n=122) has completed enrollment at the 3 mg/kg combo, 6 mg/kg combo and Lu 177 only groups. Clinical trial information: NCT05682443 . Gotistobart 3 mg/kg + Lu 177(N = 6) Gotistobart 6 mg/kg + Lu 177(N = 6) Gotistobart 10 mg/kg + Lu 177(N = 6) Lu 177(N=7) Median follow-up time, m 17.8 9.2 11.9 12.3 Confirmed PSA50, n (%) (95% CI) 4 (66.7) (22.3, 95.7) 3 (50.0)(11.8, 88.2) 3 (50.0) (11.8, 88.2) 2 (28.6) (3.7, 71.0) PSA90, n (%) (95% CI) 3 (50)(11.8, 88.2) 0 (0.0, 45.9) 2 (33.3)(4.3, 77.7) 1 (14.3)(0.4, 57.9) Median rPFS, m(95% CI) 12.2(2.0, NE) 8.3(5.8, NE) Not reached (11.0, NE) 4.8(3.8, NE) 6m rPFS rate, (%) (95% CI) 66.7(28.9, 100) 75.0(32.6, 100) 83.3(53.5, 100) 28.6(0, 62.0) Median PSA-PFS, m (95% CI) Not reached(9.72, NE) Not reached (5.39, NE) 10.4(4.8, NE) 4.9(4.4, 6.0)

Abstract Background: Current therapeutic approaches for patients with HR+/HER2-low metastatic breast cancer (mBC) do not differ from patients with HR+/HER2- mBC, with systemic chemotherapy remaining the standard of care (SOC) following progression on multiple lines of endocrine therapy (ET)-based treatment or in cases of primary endocrine resistance. Given the scarcity of real-world data on treatment patterns and real-world overall survival (rwOS) in this population, further research is essential to inform decision making and better understand the effectiveness of SOC treatments. Methods: A cohort of adults (≥18 years old) treated with chemotherapy following ET for HR+/HER2- mBC in the United States (US) was identified retrospectively in the Komodo Research Database (1/1/2016-4/30/2024). A 12-month washout period was used to identify patients with newly diagnosed mBC based on the presence of ≥2 medical claims with diagnosis codes for the primary BC followed by ≥2 claims with diagnosis codes for secondary neoplasms, excluding breast, skin, or lymph nodes. HR+/HER2- statuses were inferred from treatments received based on expert’s input. As such, HER2 expression profile below the threshold for positivity was not further stratified. Patients were included if they initiated chemotherapy after ≥2 prior lines of ET-based treatment (with or without targeted agents) or within 6 months of starting first-line ET + CDK4/6i (primary endocrine resistance) in the mBC setting. Treatment sequences in the mBC setting were described. rwOS was assessed from chemotherapy initiation to follow-up end among patients who initiated chemotherapy between 1/1/2017-10/31/2022 (i.e., had ≥18 months of potential observation, based on expert clinical input) using the Kaplan-Meier method. Results: The study identified 1,371 patients receiving chemotherapy for HR+/HER2- mBC. Median age at chemotherapy initiation was 59 years, 98.0% were female, 71.3% were White, 12.6% were Black or African American, 9.2% were Hispanic or Latino, and 3.8% were Asian or Pacific Islander. Most patients were commercially insured (67.8%), followed by Medicare (24.4%) and Medicaid (7.8%). The most common comorbidities were liver disease (30.3%), diabetes (21.4%), cardiovascular disease (20.6%) and chronic obstructive pulmonary disease (15.8%). Median time from initiation of mBC treatment to follow-up end was 31.6 months. Among the 1,371 patients, 25.1% initiated chemotherapy after one line, 49.1% after two lines, and 25.8% after ≥3 lines of mBC treatment. Most common regimens at chemotherapy initiation were capecitabine-based (60.2%), paclitaxel-based (17.3%) and albumin-bound paclitaxel-based (10.4%). Most patients (53.6%) received a next line of therapy, 37.7% remained on initial chemotherapy, and 8.7% discontinued all treatments after chemotherapy initiation. The most common next regimens included additional chemotherapy (49.1%), ET + other targeted therapy (excluding CDK4/6i; 10.9%), and ET + CDK4/6i (4.1%). Among 996 patients with sufficient potential observation to assess rwOS (≥18 months), median rwOS was 18.9 months (95% confidence interval [CI]: 17.4, 20.0 months), and rwOS rates at 12, 24, and 36 months were 65.0% (95% CI: 61.9%, 67.8%), 40.5% (95% CI: 37.4%, 43.6%) and 24.1% (95% CI: 21.2%, 27.1%), respectively. Conclusions: Real-world outcomes for patients with HR+/HER2- mBC treated with chemotherapy following progression on multiple lines of ET-based treatment or with primary endocrine resistance are poor, with median rwOS of approximately 1.5 years. These results highlight a need for more effective therapies with tolerable safety profiles to improve outcomes among patients with HR+ and HER2- or HER2-low mBC expression profiles who progress on ET-based treatments. Citation Format: T. A. Traina, C. Rossi, M. Levesque-Leroux, A. Tardif-Samson, P. Gagnon-Sanschagrin, A. Guérin, S. Vlassak, V. Guan, J. Salcedo. Real-world treatment patterns and overall survival in patients with HR+/HER2- metastatic breast cancer treated with chemotherapy following endocrine therapy in the US [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-11-03.

Abstract Background: Patients with PD-L1-negative locally recurrent inoperable or metastatic triple-negative breast cancer (lr/m TNBC) have limited treatment options and typically receive first-line (1L) chemotherapy in clinical practice. Real-world evidence on patient outcomes, particularly real-world progression-free survival (rwPFS) from 1L treatment initiation in PD-L1-negative lr/m TNBC, remains scarce. Additional data are needed to better understand clinical outcomes in this population and support evidence-based treatment decision-making. Methods: A retrospective cohort of adults (≥18 years old) receiving 1L treatment for PD-L1-negative lr/m TNBC was identified in Komodo Research Data (01/2016-12/2023), a large claims database that covers approximately 30% of the United States (US) population. Patients with lr/m TNBC were identified using an algorithm developed with medical expert guidance that required systemic treatment initiation within 3 months of a biopsy and no observed surgery in the 12 months following the biopsy. Triple-negative and PD-L1 statuses were inferred from treatments received in the lr/m setting. Demographics were described on the date of 1L treatment initiation, and comorbidities were assessed during the preceding 12 months. Real-world proxies of progression were also defined with medical expert guidance and included death, hospice admission, initiation of a second line of systemic treatment, or initiation of radiotherapy. Among patients who initiated 1L treatment ≥6 months before the end of data availability, the Kaplan-Meier method assessed rwPFS from 1L treatment initiation until the first real-world proxy of progression or end of follow-up, defined as the earliest of end of continuous health plan enrollment or end of data availability. Results: A total of 929 patients with lr/m TNBC were identified in this study. The median (interquartile range [IQR]) age at 1L initiation was 59 (51-66) years. Most patients were female (98.6%). Among those with a recorded race (69.3%), 60.1% were White, 26.4% were Black or African American, and 9.2% were Hispanic or Latino. Most patients had commercial insurance (64.9%), followed by Medicare (26.7%) and Medicaid (8.4%). The most frequent comorbidities prior to 1L treatment initiation were liver disease (26.8%), chronic obstructive pulmonary disease (22.7%), diabetes (22.0%), and peripheral vascular disease (13.6%). Median (IQR) follow-up from 1L initiation was 10.3 (5.7-20.1) months. The most common 1L treatments in the lr/m TNBC setting included cyclophosphamide+doxorubicin-based regimens (28.1%), followed by capecitabine (12.7%), paclitaxel (10.4%), carboplatin+paclitaxel (9.4%), and carboplatin+gemcitabine (8.6%), with frequent use of non-NCCN-guideline-preferred regimens. Among the 910 patients with sufficient follow-up to assess rwPFS, 703 (77.3%) had an indicator of progression following 1L initiation. Median (95% confidence interval [CI]) rwPFS was 4.7 (4.5-5.2) months. rwPFS rates (95% CI) were 69.0% (65.9%-71.9%) at 3 months, 41.7% (38.4%-45.0%) at 6 months, 22.6% (19.7%-25.6%) at 12 months, and 18.3% (15.5%-21.2%) at 18 months. The observed indicators of progression were, in order of frequency, initiation of a second line of systemic treatment (43.8%), death (25.5%), initiation of radiotherapy (18.1%), and hospice admission (12.7%). Conclusions: In US clinical practice, patients with PD-L1-negative lr/m TNBC experience rapid disease progression following initiation of 1L treatment, with a median time to progression of less than 5 months. These findings underscore a critical unmet need for effective 1L treatment options with tolerable safety profiles to improve outcomes in this patient population. Citation Format: T. A. Traina, E. Serra, J. Bedard, M. Levesque-Leroux, P. Gagnon-Sanschagrin, A. Guérin, S. Guenther, G. Joseph, V. Guan, J. Salcedo. Real-world progression-free survival from first-line treatment initiation in patients with PD-L1-negative locally recurrent inoperable or metastatic triple-negative breast cancer in the United States [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-03-06.

Chronic low-grade inflammation is increasingly recognized as a key driver of heart failure (HF) progression; however, the direct contribution of systemic inflammatory disorders such as osteoarthritis (OA) remains unclear. Here, we establish a murine model of OA-induced HF using destabilization of the medial meniscus (DMM) to induce systemic inflammation and sex-specific cardiac remodeling. Longitudinal echocardiography revealed that females develop diastolic dysfunction with preserved ejection fraction, resembling HFpEF, whereas males exhibit progressive systolic impairment, consistent with a transitional HFmrEF-to-HFrEF phenotype. Morphometric and histological analyses confirmed concentric hypertrophy in females and eccentric remodeling in males. Transcriptomic profiling identified distinct molecular programs: females upregulated extracellular matrix, cytoskeletal, and calcium-handling genes, while males showed enrichment of inflammatory and immune signaling pathways. Immunoblot analyses further validated these sex-specific molecular signatures: females displayed increased ANP, BNP, Sirt1, and AMPK expression, consistent with metabolic resilience and fibrotic remodeling, whereas males exhibited elevated p38 MAPK, NF-κB, LC3B, and cleaved caspase-3, reflecting heightened inflammation, autophagy, and apoptosis. Both sexes demonstrated downregulation of mitochondrial and lipid metabolic proteins, indicating convergent energetic stress. Collectively, these findings identify OA as a systemic inflammatory driver of heart failure, delineate the molecular and proteomic basis of sex-dependent cardiac remodeling, and introduce a translational preclinical model that recapitulates the clinical heterogeneity of HFpEF and HFmrEF/HFrEF, providing a foundation for mechanistic and therapeutic exploration.