Welcome to the official Program & Abstracts of the Seno-Therapeutics Summit 2025. Here you will find the complete scientific program, including detailed session descriptions and speaker abstracts. This resource is designed to help you dive deeper into the content of the summit and engage fully with the cutting-edge research, discussions and perspectives shaping the field.
The Seno-Therapeutics Summit 2025 strives to lead the way in addressing crucial challenges in cellular senescence and therapeutics. Our program showcases the latest breakthroughs in cellular senescence and therapeutic development, bringing together world-leading researchers, industry pioneers, and visionaries. Through sessions and discussions, we highlight the collective effort to unlock new strategies, accelerate translation, and shape the future of senescence-targeted medicine.
For the latest updates on all summit-related information and guidelines, we invite you to regularly visit our website and stay tuned to our official communications. Your active engagement is crucial, and we are thrilled to have you as part of our community!
Consiglio Nazionale delle Ricerche (CNR)
Piazzale Aldo Moro, 7, 00185 Roma RM, Italy
Professor
UCLA
James L. Kirkland, M.D., Ph.D., F.R.C.P. (C)
Professor
Mayo Clinic
Senescent cells accumulate in the aging body and brain and influence systemic and local microenvironments through the senescence associated secretory phenotype. Our lab leverages translational biomarker discovery and high-dimensional approaches, including single-cell spatial mapping, to define systemic and brain-resident senescent cell fates, biomarkers, and mechanisms. Using Olink proteomics, we identified interleukin-23 receptor (IL-23R) as a novel senescence-linked plasma biomarker that increases with age in mice and humans, is produced by senescent cells in aged tissues, and is reduced by senolytic interventions, implicating IL-23R as an important aging- and senescence-linked biomarker. Through NIH Cellular Senescence Network Consortium research, we apply single-cell CosMx spatial molecular imaging and orthogonal approaches to map senescent and aged cell identities. We discovered white matter-localized microglia, as well as other glial subtypes, with high senescence biomarker scores across multiple molecular domains, and we are leveraging proximity-integrated ligand-receptor inference to predict senescent and aged cell signaling interactomes in distinct brain niches. Collectively, these studies reveal therapeutically responsive senescence biomarkers and spatially defined brain cell states with senescent features, which provide a framework for mechanistic insight and advancement of targeted interventions to mitigate senescence-driven decline in aging.
Professor
IOR, ETH Zurich
Recent research underscores the dual and context-dependent role of cellular senescence in cancer, where it can either suppress or promote tumor progression. Notably, senescent tumor cells have been implicated in enhancing metastasis across multiple cancer types, including prostate cancer.
Mechanistically, I will present evidence that the tumor-promoting effects of senescent tumor cells are driven by the senescence-associated secretory phenotype (SASP) and the release of mitochondrial DNA (mtDNA) into the tumor microenvironment.
Importantly, senescence is not confined to tumor cells. Recent findings reveal that immune cells within the tumor microenvironment, particularly polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), can also acquire a senescent-like state. These cells exhibit markedly increased immunosuppressive and tumor-supportive properties compared to their non-senescent counterparts. This senescence-driven intercellular communication represents a critical axis of immune evasion and tumor progression.
Finally, I will highlight emerging therapeutic strategies aimed at eliminating senescent cells both tumor and immune cells using senolytic agents, as well as approaches to reprogram or suppress the SASP. Both strategies show significant promise in limiting metastasis and improving anti-tumor immunity.
Affiliations
Presenting Author: Andrea Alimonti 1,2,3,4,5
Professor
Johannes Kepler University
As the audience of this meeting is well aware of, senescent cells that accumulate during aging, persist upon oncogenic activation in preneoplastic lesions, or remain in a dormancy-like state as therapy-surviving cancer cells may underlie detrimental outcomes via their pro-inflammatory and matrix-remodeling secretome as well as through their stem-like reprogramming which becomes evident upon occasional cell-cycle re-entry. Collectively, these harmful features provide a strong rationale for the selective therapeutic elimination of senescent cells.
We present here a novel class of a redox-activatable agent, dubbed SenLyt, which preferentially kills senescent cells by exploiting senescence-characteristic redox features as its activating principle. Reduced SenLyt generates H2O2 in the presence of high NADH and low glutathione levels, and kills the labile iron-enriched senescent cells by ferroptotic and apoptotic death mechanisms. When equal pro-senescent triggers were applied to senescence-incapable model systems, the cytotoxic potential of SenLyt was largely neutralized, as a molecular SenLyt derivative that cannot utilize NADH for H2O2 generation no longer killed senescent cells. Likewise, engineered catalase overexpression or iron chelation blunted senolytic activity.
SenLyt consistently removed cells in replicative, oncogene-, oncogene-inhibition-, therapy- and virus-induced senescence in preclinical cell culture and animal models with remarkable senescence selectivity (‘senolytic index’), also when compared to established senolytics. SenLyt, which was well-tolerated in all in vivo settings tested, reduced the content of senescent cells in organs of aged animals, alleviated age-related pulmonary fibrosis, partly restored physical strength of old mice when compared to a cohort of young animals, and significantly prolonged lifespan compared to mock treatment. SenLyt eliminated therapy-surviving senescent persisters and improved long-term outcome to anticancer therapy in vivo.
Moreover, tumor cells in which we restored oncogene-induced senescence by reverting the underlying escape mechanism became susceptible to SenLyt as well. Most strikingly, SenLyt delayed and reduced full-blown tumor formation in Ras- or Braf-driven mouse models by eliminating early senescent lesions, thereby establishing a novel system-wide cancer prevention strategy. In essence, SenLyt operates as a broadly active, well-tolerated and highly specific pan-senolytic based on its dual senescence-related mode of activation and killing.
Authors: Clemens A. Schmitt1–3 and colleagues
1 Charité – Universitätsmedizin Berlin, Molekulares Krebsforschungszentrum (MKFZ), Campus Virchow Klinikum, 13353 Berlin, Germany
2 Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße, 13125 Berlin, Germany
3 Kepler University Hospital, Department of Hematology and Oncology, Johannes Kepler University, Krankenhausstraße 9, 4020 Linz, Austria
Professor
UT Health San Antonio
Recent research underscores the dual and context-dependent role of cellular senescence in cancer, where it can either suppress or promote tumor progression. Notably, senescent tumor cells have been implicated in enhancing metastasis across multiple cancer types, including prostate cancer.
Mechanistically, I will present evidence that the tumor-promoting effects of senescent tumor cells are driven by the senescence-associated secretory phenotype (SASP) and the release of mitochondrial DNA (mtDNA) into the tumor microenvironment.
Importantly, senescence is not confined to tumor cells. Recent findings reveal that immune cells within the tumor microenvironment, particularly polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), can also acquire a senescent-like state. These cells exhibit markedly increased immunosuppressive and tumor-supportive properties compared to their non-senescent counterparts. This senescence-driven intercellular communication represents a critical axis of immune evasion and tumor progression.
Finally, I will highlight emerging therapeutic strategies aimed at eliminating senescent cells both tumor and immune cells using senolytic agents, as well as approaches to reprogram or suppress the SASP. Both strategies show significant promise in limiting metastasis and improving anti-tumor immunity.
CEO
Rubedo Life Sciences
CEO
Rubedo Life Sciences
Professor
UCLA
Professor
Mayo Clinic
Professor
IOR, ETH Zurich
Professor
UT Health San Antonio
Chief Scientist
Unity Biotechnology
Diabetic macular edema (DME), a leading cause of diabetes-related vision loss, is characterized by breakdown of the blood-retina barrier resulting in extravasation of fluid and proteins into the retina. Current standard of care for DME, anti-vascular endothelial growth factor (VEGF) agents, effectively improve visual acuity and reduce macular edema, but the majority of effect is observed in the first 6 months of treatment and suboptimal in a significant proportion of patients. Based on preclinical rationale demonstrating elevated burden of senescent cells in diabetic retinas and their role in driving disease, we tested the effects of intravitreal (IVT) delivery of foselutoclax (hereafter UBX1325), a senolyticsmall molecule inhibitor of anti-apoptotic protein BCL-xL, in participants with DME. In a phase 1 and the BEHOLD phase 2 trial, UBX1325 led to clinically meaningful gains in visual acuity lasting up to 48 weeks in a patient population who had visual acuity deficit despite prior anti-VEGF treatment. In the ASPIRE Phase 2b trial, we enrolled 52 patients with prior anti-VEGF treatment who received 10μg UBX1325 or 2mg aflibercept IVT every 8 wks. UBX1325 achieved vision gains comparable to standard of care aflibercept and showed non-inferiority to aflibercept at wks 24 and 36. It was superior in 7 out of 9 time points in patients with lesser edema (baseline CST<400 μm representing 60% of patients enrolled in the trial). UBX1325 however did not achieve noninferiority by averaging week 20 and 24 (a prespecified primary endpoint). The overall benefits of UBX1325 in promoting long lasting improvements in retinal function compared to standard of care warrant for further investigation with a likely focus on a patient population with earlier DME.
Head, Emerging Sciences
Chiesi Pharmaceuticals
Chiesi Group is an international biopharmaceutical company founded in Parma (Italy) in 1935 by Giacomo Chiesi. From its beginnings as a small laboratory, the company has expanded globally and established itself as a reference in the treatment of chronic respiratory diseases such as asthma, COPD, neonatal pathologies and, more recently, rare diseases.
Today, Chiesi operates directly in 31 countries and exports to more than 100 nations. With over 7,000 employees and seven research and development (R&D) centers across Europe, the Americas and Asia, the Group achieved more than €3 billion in sales in 2024, reinvesting around 24% of revenues into R&D.
Its business is structured into three main areas: AIR (respiratory diseases), RARE (rare and ultra-rare diseases) and CARE (neonatology and special care). Chiesi employs more than 1,300 people in R&D, including 757 researchers, and ranks as the leading Italian pharmaceutical company in R&D investment, as well as among the top ten in Europe.
Its R&D centers in Parma, France, the UK, Sweden, the US, Canada and China ensure a global approach to innovation. Chiesi is expanding its interest beyond traditional small molecules into biological products (antibodies, proteins) and advanced therapies (gene/cell therapies) with the goal of building an innovative pipeline enriched with cutting-edge solutions. In recent years the company strengthened its preclinical pipeline through strategic collaborations with global partners such as Moderna, Affibody and, more recently, Serna Bio; these agreements for the discovery and development of next-generation therapeutics are based on innovative technologies that enable Chiesi to explore more effective therapeutic options in alignment with its mission.
At the core of the company’s mission is the development and delivery of innovative solutions to improve people’s quality of life, combining scientific research with social and environmental responsibility. As a certified B Corp and Benefit Corporation, Chiesi redefined its values in 2020 to embed sustainability, inclusiveness and fairness at the center of its corporate culture.
The company not only develops life-saving medicines but also serves as a model for how business can care for people, the environment and the future of society.
VP, External Innovation
Eli Lilly and Company
Head, Emerging Sciences
Chiesi Pharmaceuticals
Managing Director
Otsuka Pharmaceutical Italy
Head of Research & Innovation
OneSkin
Hair loss is a prevalent condition associated with aging, stress, and other intrinsic and extrinsic factors, with growing evidence implicating cellular senescence as a critical driver of follicular miniaturization and progressive hair thinning. Current clinically approved treatments, such as minoxidil and finasteride, are constrained by variable efficacy and adverse effects and were not designed to specifically target senescent cells. To address these limitations, we evaluated OS-01 HAIR, a novel topical formulation developed to target senescent cells within hair follicles and promote hair growth.
Preclinical studies demonstrated that OS-01 peptide significantly reduced CDKN1A expression in outer root sheath cells (ORSCs) treated with corticotropin-releasing hormone (CRH), a stress-associated factor. Additional actives, including a ginseng and biotin mix, decreased IL-6 and MMP1 expression in vitro. The complete OS-01 HAIR formulation also reduced senescence markers in ORSCs. Building on this rationale, an independent, double-blind, third-party clinical trial was conducted in which 32 participants received OS-01 HAIR and 25 participants received minoxidil, applied twice daily with dermarolling for six months. A comprehensive panel of hair growth and density metrics was assessed at baseline, 3 months, and 6 months using HairMetrix®, trichoscopy, and phototrichogram.
OS-01 HAIR demonstrated superior efficacy to minoxidil across multiple parameters. Hair count/cm2, follicular units/cm2, cumulative hair width/cm2, and anagen hairs/cm2 significantly increased, while interfollicular distance decreased. In a separate microbiome study of 30 participants, six months of OS-01 HAIR use improved bacterial taxa associated with follicle formation, reduced fungal species enriched in hairless patches, and decreased the Malassezia restricta/M. globosa ratio, consistent with a healthier scalp environment and reduced dandruff.
By targeting cellular senescence, OS-01 HAIR improved hair density, follicular health, and anagen hair numbers while supporting a balanced scalp microbiome. These findings highlight senescence-targeting formulations as a promising strategy for promoting scalp health.
Authors: Lear Brace1, Nathaniel Harder1, Ana Lopez2,3, Caroline Jensen3,4, Belen Campos2,3, Fiona Li1, Carolina Reis de Oliveira1, Jia Xie1, Alessandra Zonari1
1 OneSkin Technologies, California, USA
2 University of Copenhagen, Denmark
3 Innovation Centre Denmark, California, USA
4 Aarhus University, Denmark
CSO & Co-Founder
Oisin Biotechnologies
Approaches to eliminate senescent cells in vivo have demonstrated significant improvements in lifespan and healthspan. At Oisin Biotechnologies, we have developed a clinically viable senolytic gene therapy using inducible caspase 9 (iCasp9) under the control of the p53 or p16Ink4a promoters, enabling selective clearance of different populations of senescent cells. Systemic delivery via the FAST-PLV platform in aged mice significantly reduced senescent cell burden, extended post-treatment survival by 123%, decreased frailty and improved physical and cardiac function. Furthermore, we observed a threefold reduction in tumor incidence. RNA-seq analysis revealed broad transcriptional changes in the treated animals consistent with reduced senescence and inflammation. Across 12 tissues, key stress-related genes (Jun, Fos, EGR1, GDF15) were downregulated, indicating FAST-PLV treatment resulted in dampened p53 signaling and systemic anti-inflammatory effects. These results demonstrate a clinically viable, transcriptionally targeted senolytic gene therapy with systemic impact on aging and age-related disease.
Affiliations:
Oisin Biotechnologies, 701 Fifth Ave, Suite 4200, Seattle, Washington, US, 98104
Department of Oncology, University of Alberta, Edmonton, Alberta, Canada, T6G 2E1
Founder & CEO
Phoenix SENOLYTIX
Authors: Keshav Karki, Ph.D., Daniel Jasinski, Ph.D., Meena Balakrishnan, Kyra Courtney, Kevin Slawin, MD. and David Spencer, Ph.D.
In a series of landmark studies, Baker et al. in 2011 initially, and then again in 2016, demonstrated proof-of-concept that in a genetic mouse model built using technology related to Bellicum’s CaspaCIDeTM iCasp9 “suicide” switch, periodic and regular removal of senescent cells (“SnCs”) by apoptosis leads to a reversal of the aging phenotype. The genetic mouse model, named p16Ink4a-ATTAC, was designed to induce apoptosis in p16Ink4a-expressing SnCs of these genetically modified mice by injection of a dimerizer drug “trigger,” AP20187, which induced crosslinking and subsequent activation of a caspase genetically fused to the drug-binding domain, FKBP12-V36.
They showed that compared to vehicle alone, AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. The clearance of p16Ink4a-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs, including kidney, heart and fat, without apparent side effects. They demonstrated that p16Ink4a-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in several organs and suggested that their therapeutic removal may be an attractive approach to extend healthy lifespan. Other investigators soon followed with similar studies using the p16Ink4a-ATTAC Mouse Model to show reduction in age-related bone loss (Farr et al.), reduction in obesity-related metabolic dysfunction (Palmer et al.), and reduction in age-related brain inflammation and cognitive impairment (Ogrodnik et al.) with dimerizer-induced elimination of SnCs.
We have developed a novel, proprietary gene therapy vector, ApoptiCIDe-CE-GERO-002TM, carrying the iCasp9 “suicide” switch, that targets SnCs via a proprietary p16Ink4a-specific promoter, leading to their elimination following administration of the ApoptiCIDe enhanced proprietary dimerizer “trigger” molecule, PTC-1202. Over ~60% to 70% of splenic SnCs are eliminated compared to negative controls in naturally aged 75-week-old mice. Accordingly, Lamin B1 expression increases significantly in a dimer-dependent fashion.
Phoenix SENOLYTIX is developing gene therapy technologies to more specifically and efficiently target senescent cells for elimination utilizing an improved, proprietary version of CaspaCIDeTM, named ApoptiCIDeTM, an improved version of the technology originally used in the p16Ink4a-ATTAC Mouse Model. Pre-clinical PoC validation of this approach provides a solid rationale for future clinical trials in patients.
References / Links:
Founder & CEO
Eos SENOLYTIX
Authors: Daniel Jasinski, Ph.D., Meena Balakrishnan, Kyra Courtney, Samantha Moreno, Stephen Shaw, Stacey Allen, PhD, Danielle Grabert, Ashley Perry and Kevin Slawin, MD.
MitoXcelTM Technology – powered geropeptides have the remarkable ability to rejuvenate naturally aged mice via two separate mechanisms, both via targeting the lower Mitochondrial Membrane Potential (MMP, ΔΨm) that develops in aging cells, to dramatically eliminate senescent cells throughout the body, and to enhance the efficiency of mitochondrial function in aging cells. In naturally aged 75-week-old mice, senescent cell burden was reduced by treatment with MitoXcelTM geropeptide PTC-2105 in iWAT by 67.8% (P<0.0001), 53.8% (P<0.0001), and 52.5% (P = 0.0993) as analyzed by uPAR, p16, and SA-β-gal histological staining, respectively, relative to saline-treated control mice. This resulted in body composition reshaping towards a higher lean muscle to fat ratio, as indicated by a DEXA-measured increase in muscle mass and reduction in body fat percentage, and led to improved endurance, balance, strength, and overall exercise capability as measured by Rotarod, motorized treadmill, and grip strength testing. After 20 weeks of treatment with MitoXcelTM geropeptide PTC-2107, we demonstrated an overall 11% weight loss, remarkably comprised of a 34% fat mass loss and a 23% lean mass GAIN, without directly targeting either fat or muscle, compared to saline-treated controls in naturally aged 75-week-old mice.
Furthermore, MitoXcelTM Technology-powered oncopeptide PTC-2110 significantly improved overall survival in an aggressive B cell Acute Lymphoblastic Leukemia (“B-ALL”) in vivo TOM-1 tumor model, harboring both a wild type ABL1 and JAK2 V617F mutation, that, similarly to SnCs, exhibit a lower Mitochondrial Membrane Potential (MMP, ΔΨm) compared to normal cells (log rank – saline vs PTC-2110 = 0.0034). In animals alive on Day 31, at End of Study, animals treated with PTC-2110 exhibited almost complete control of tumor cells, equivalent to ponatinib-treated mice, as evidenced by flow cytometry of lung and spleen, despite the significantly lower exposure to drug treatment (24 vs 5 total doses per animal per group or almost 5X greater in the ponatinib-treated group) and the absence of any ABL1-targeted TKI therapy in PTC-2110-treated animals. These results open the door for a potential safe and effective new class of cancer therapeutics and highlight the potential of MitoXcelTM Technology in mitigating age-related decline and improving overall healthspan, the hallmark features of a gerotherapeutic. Eos SENOLYTIX is performing IND-enabling studies of this technology with the goal of beginning human clinical trials in 2026.
References / Links:
Vitalist
VitaDAO
CBO
Minicircle
CEO & Co-Founder
Deciduous Therapeutics