Poster Abstracts

Deep dives into the science are at the heart of what we do at BioCentury, and posters take the BioCentury Grand Rounds discussions further by putting data, methods and mechanism front and center. Posters will be displayed in the conference foyer, and featured during the interactive Poster Spotlight Networking Session on Tuesday, Sept. 10 at 5:30 PM Central Time.

Get the conversation started by requesting 1x1 meetings with poster presenters via the BioCentury Grand Rounds 2024 digital platform, beginning August 19.

ENABLING PLATFORMS

• Investigating the ATN (Amyloid, Tau, Neurodegeneration) framework in Alzheimer’s Disease and its causal genetic-drivers using Digital Twins (DT)
  
• Discovery of small-molecule antagonists targeting cytokines for allergic diseases
  
• Self-Driving, Massively Parallel, Multi-Omic Bioreactors for Drug Development
  
• Developing New Drugs in Precision Ways Like No Others
  
• Genetic modification to producer cells enhances viral vector and antibody yields
  
• The InVitroProfiler - A cell culture platform to model dynamic drug concentrations in vitro
  
• AI-MPRO miniprotein drug discovery platform
  
• Molecular glue degrader development platform: Drugging the undruggable
  
• Increasing the Efficiency of Clinical Trials Using Ordinal Longitudinal Data
  
  

HUMAN BIOLOGY DISCOVERY

• Practicing Inclusive Precision Medicine
  
• Plasma cfDNA-based epigenetic liquid biopsy for demyelinating disease biomarkers
  
• Dysregulated metal biodynamics in amyotrophic lateral sclerosis (ALS) patients
  
• A New Diagnostic Test for Inflammatory Bowel Disease
  
• Therasid Bioscience is dedicated to MASH therapeutics
  
• Regulatory macrophages contribute to tumor cell plasticity in colorectal cancer metastases
  
• Molecular glue degrader development platform: Drugging the undruggable
  
• Development of a Multi-biomarker Risk Score Based on Serum Proteins by the Prognostic Lung Fibrosis Consortium (PROLIFIC)
  
• Restoring neutrophil function after burn via trained innate immunity
  
  

MODALITY INNOVATION

• Pioneering Oncology with 'Beyond ADC' Innovations in Precision Medicine
  
• Novel controllable CAR-T cells improve efficacy and durability of anti-cancer immunotherapy
  
• Curing epilepsies with precision gene therapies
  
• Base Editors and Prime Editors to Correct Genetic Disease
  
• Novel splicing driven gene regulation platform for precise dose responsive control of gene and cell therapies
  
• Exploring Nanobodies and Nanoparticles for Targeted Radionuclide Therapy
  
• Cell-type specific delivery using in vivo RNA sensors
  
• Development of MTOR-targeting ASOs for Treating mTORopathies with Intractable Focal Epilepsy
  
• In Vivo Gene Therapy using Lineage Reprogramming enables Walking Again after Complete Spinal Cord Injury
  
• GBA1-linked Parkinson’s Disease AAV gene therapy
  
• Pioneering first-in-human anti-inflammatory therapeutic modality: Nanozyme
  
• Injectable Hydrogel for Enhanced Arteriogenesis in Peripheral Artery Disease Treatment
  
• Revolutionizing ADC’s to Overcome Universal Resistance in Solid Tumors
  
• V-212, a novel peptide-based, serotype-independent vaccine candidate against Streptococcus pneumoniae
  
  

THERAPEUTIC CANDIDATES

• Tat Fusion Proteins Restore Cytokine Receptor Signaling In Anergic Cells, Allowing Immune-Mediated Tumor Reduction
  
• A first-in-class multimodal immunotherapy for induction of tertiary lymphoid structures as a novel therapeutic strategy for solid tumors
  
• A Safer Approach to Pain Management
  
• Innovative Antibody-based Therapeutics for Oncology and Autoimmune Disease
  
• ICT-1402, a potent, selective, and orally bioavailable MET degrader for treating NSCLC with MET alterations
  
• WARS1- Neutralizing Antibody for Rheumatoid Arthritis
  
• Translating NLRP3 Inflammasome Inhibition into Clinical Therapeutics: Rationale and Design for Two Clinical Trials of Dapansutrile (OLT1177®) in the Settings of Acute and Chronic IL-1β Mediated Inflammation
  
• Cell-free regeneration by miRNA-targeting technology
  
• Dual senolytic antibody that activates apoptosis and immune system to eliminate senescent cells
  
• Developing 20-alpha-hydroxycholesterol to reverse neonatal white matter injury
  
• TT125-802: a CBP/p300 BRD inhibitor against transcriptional resistance in cancer
  
• A first-in-class multimodal immunotherapy for induction of tertiary lymphoid structures as a novel therapeutic strategy for solid tumors
  
• Dual senolytic antibody that activates apoptosis and immune system to eliminate senescent cells
  
• High Throughput Screening of Immunomodulators for Vaccine Adjuvants and Beyond
  
• Decreased LPS-induced lung injury in pigs treated with a lung surfactant protein A-derived nonapeptide that inhibits peroxiredoxin 6 activity and subsequent NOX1,2 activation
  
• PNUT1, Dentin Regenerating Therapeutics as the Next Generation Treatment for Tooth Decay
  
  

BIOPHARMA INTELLIGENCE

• BioCentury's Innovation Distillery: Preclinical literature distilled down to targets and compounds with potential for translation
  
• Accelerating Translational Research
  
  

• Self-Driving, Massively Parallel, Multi-Omic Bioreactors for Drug Development
  Associated Company/University: Regemus Technologies, LLC. | Vanderbilt University
  Author: John Wikswo
  

Abstract:
Given the role of biologics in Pharma and the need to increase the efficiency of cell line development and media optimization, we address the technology gap between the identification of single-cell clones in nanoliter microfluidic pens as candidates for production of biopharmaceuticals, and the selection of a final clone and media formulation that can function effectively in a thousand-liter production bioreactor. To close this gap, the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE) has developed a new class of automated, massively parallel, stand-alone Continuous Automated Perfusion Culture Analysis Systems (CAPCAS) that are ideal for maintaining multiple miniature bioreactors. Each CAPCAS platform will function as a fully automated microfluidic system containing 1,000 or more biodevices, such as chemostats, bioreactors, or organ chips, for parallel, independent, long-duration, machine-guided experiments to optimize biological function or infer the dynamics of signaling and metabolism of living systems. CAPCAS could drive online mass spectrometers for quantitative metabolomic and proteomic analysis of both the cells and the cellular secretome. Computer-controlled fluidic coupling of multiple bioreactors may enable prediction of reduced cellular production due to zonation in larger bioreactors. The entire system is being designed to operate as a self-driving laboratory or robot scientist to autonomously refine metabolic and signaling models.

• Developing New Drugs in Precision Ways Like No Others
  Associated Company: Safenia Pharmaceuticals
  

Abstract:
Safenia Pharmaceuticals, is led by a group of seasoned professionals, who have a collective experience of over 100 years in biotechs and pharmaceuticals/biopharmaceuticals. Its executives have a track record in managing multinational companies. Safenia Pharmaceuticals developed RSQ Platform based on the Human Genome Project (HGP). Our Company has developed technologies rooted deeply from the HGP and novel drug development. Safenia integrates genomics, bioinformatics, artificial intelligence (AI), biomarker discovery/validation into its RSQ platform, that enables to stratify patient populations to achieve maximum results through identifying beneficial subpopulations in efficacy and/or adverse effects quantitatively. Currently, the Company mapped more than 25,000 genes and 3.5 million of mutations (including but not limited to SNPs, indels, microsatellites, rearrangements, and re-allocations) on the entire human genome and built much extensive mechanism of action (MOA+) based networks for clinical development of new drug. Combining research in genotypes and clinical phenotypes, Safenia is able to generate patient genetic profiles for targeted subpopulations, and through these stratifications, one is able to carry out studying clinical outcomes in each subtype. So Safenia can obtain a better and closeup drug performance profile that can help to improve clinical results in targeted subpopulation(s). Safenia RSQ approach is an effective approach to improve drug clinical outcomes.

• Genetic modification to producer cells enhances viral vector and antibody yields
  Associated University: Vanderbilt University Medical Center
  Author: Zachary Bacigalupa
  

Abstract:
The production of bioactive materials such as viral vectors and neutralizing antibodies for research and clinical applications has realized an exponential increase in demand. One of the more cost-effective solutions to bioproduction are stable cell lines, such as HEK-293T cells, that support virus-based packaging of genetic material and are readily modified to support protein and antibody production. Our group has identified a proprietary genetic modification that that significantly improves the titers of viral vectors, on average, 264-fold reaching a maximum of nearly 1,000-fold. These massive increases in titers improve transduction efficiency and lower the input requirement. Analysis of the transcriptome revealed that the modified cells enrich for genes in the unfolded protein response and protein secretion pathways. With this, we then tested the ability of these cells to produce the PD-1 neutralizing antibody pembrolizumab, where we observed, on average, a nearly 3-fold increase of pembrolizumab in the supernatant. Mechanistically, we find that this modification leads to metabolic adaptations that enable fuel flexibility and promotes secretory pathways. Considering the widespread use of these systems in basic research and FDA-approved therapies, an approach that can improve yields of viral vectors and neutralizing antibodies could save millions of dollars in R&D and production costs, making these tools and therapies more equitable and accessible.

• The InVitroProfiler - A cell culture platform to model dynamic drug concentrations in vitro
  Associated University: Vanderbilt University
  Author: Catherine Leasure
  

Abstract:
The likelihood of drug approval upon a compound entering clinical trials is dismal, with 90% of compounds failing in clinical trials despite years of prior testing, often due to unexpected toxicity or poor clinical efficacy. Consequently, pharmaceutical companies need data that accurately predicts a drug's performance in humans. Traditional in vitro studies lack translational accuracy, leading drug developers to rely on costly animal studies for pharmacokinetic and pharmacodynamic (PK/PD) research. To address this need, we are developing the InVitroProfiler, an instrument and methodology that enhances the translational accuracy of in vitro studies We plan to offer this as a service to drug developers for testing PK/PD relationships of oncological drugs earlier in development. Our team comprises Drs. Gregor Neuert and Catherine Leasure. Dr. Neuert, an Associate Professor at Vanderbilt University with a diverse background in engineering, physics, biology, and physiology, conceived the InVitroProfiler technology. He will serve as the Chief Scientific Officer of InViDy, the company we’re building around the InVitroProfiler. Dr. Leasure has received entrepreneurial training as the 2023 ASPIRE to Innovate fellow at Vanderbilt and will help launch InViDy as the Chief Executive Officer. Our goal is to transition the InVitroProfiler from a basic science tool to a contract research service for drug developers, with the long-term vision of offering it as a purchasable instrument.

• AI-MPRO miniprotein drug discovery platform
  Associated Company: VRG Therapeutics
  Author: Zalan Peterfi, MD, PhD
  

Abstract:
Miniproteins are an emerging, game-changing modality that can revolutionize the biologics field by combining the benefits of small molecules and large biologics. These special polypeptides exhibit superior pharmacological properties due to their small size and well-defined structure stabilized by disulfide bridges. They offer exceptional stability, excellent tissue penetration, high affinity and selectivity, comparable to monoclonal antibodies. As a result, miniproteins provide novel therapeutic solutions for previously undruggable targets and inaccessible mechanisms of action. Miniproteins are developed through the VRG Tx’s drug discovery platform, AI-MPRO, which combines AI-driven in-silico design with state-of-the-art wet lab capabilities. AI-MPRO is an iterative design, build, test, learn process to create miniprotein scaffolds for virtually any target with unmatched speed and quality. We can deliver and validate novel hit molecules with extreme selectivity, sub-nanomolar affinity within 6 months. AI-MPRO has been particularly beneficial in developing our lead asset, VRG-K1, a novel miniprotein for treating atopic dermatitis and other autoimmune disorders. VRG-K1 is a highly selective, safe and effective blocker of the Kv1.3 potassium channel (~10.000x selectivity over homologous Kv1.x ion channels with sub-nanomolar EC50), targeting exclusively pathogenic T cells while preserving the function of other immune cells, unlike current immunosuppressant therapies.

• Molecular glue degrader development platform: Drugging the undruggable
  Associated Company: AevisBio
  Author: Dong Seok Kim
  

Abstract:
AevisBio has developed a proprietary technology called CBM/PDL, specifically designed for the discovery and development of molecular glue degraders targeting these previously "undruggable" proteins. There are more than 5,000 proteins associated with diseases, yet only 13% of them are currently within the scope of conventional drug development technologies. Currently, 62% of these proteins remain untargeted, primarily due to the intricate functions of these proteins, issues related to drug specificity, or resistance caused by overexpression or mutations. Molecular glue degraders work by binding to and altering the function of E3 ligases, leading to the degradation of disease-related proteins. Unlike conventional drugs that directly target the proteins of interest, molecular glue degraders exclusively target E3 ligases. This innovative approach holds the potential to overcome the limitations of current drug development technologies.

• Practicing Inclusive Precision Medicine
  Associated Company: Actio Biosciences
  Authors: Sunil Sahdeo
  

Abstract:
Actio Biosciences is leveraging advances in precision medicine to develop new therapeutics targeting shared biology between rare and common diseases. We aim to identify programs where both biological and technical risks can be minimized, thereby streamlining the drug development process and allowing rapid advancement of precisely targeted therapeutics. Monogenic rare diseases with a high unmet need are prioritized, where disease-modifying medicines can be developed to directly target the underlying genetic cause of the disease. We prioritized initial targets where activating mutations cause disease and pharmacological inhibition is predicted to be well tolerated. To ensure we can treat all patients, we test the activity of our compounds against all known disease-causing mutations. This work shows it is possible to develop treatments that are applicable to each and every patient that has disease because of a mutation in the targeted protein. This approach has led to ABS-0871 for the treatment of Charcot-Marie-Tooth Disease Type 2C and ABS-1230 for genetic epilepsies. We are committed to treating every patient with a disease-causing mutation in our targeted proteins and to establishing connections between these targets and biologically related indications to increase market size.

• Plasma cfDNA-based epigenetic liquid biopsy for demyelinating disease biomarkers
  Associated University: University of Cambridge
  Author: Hallie Gaitsch
  

Abstract:
Multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML) are neurological conditions characterized by demyelination with neuroinflammatory and neurodegenerative features. In both conditions, there is a clinical need for fluid biomarkers to monitor disease progression and assess treatment response, including for novel therapies targeting myelin repair. Circulating cell-free DNA (cfDNA) represents a promising biomarker released during cell turnover. An epigenetic liquid biopsy approach was used to identify cellular contributors to circulating cfDNA in human demyelinating disease. A 200+ sample repository was built at the NIH, containing plasma from healthy volunteers (HVs), MS patients, and PML patients. Plasma was collected in cfDNA-stabilizing tubes and cfDNA was extracted using the QIAsymphony platform. Then, cfDNA was bisulfite converted and whole-genome bisulfite sequenced. PML patients were found to have increased bulk cfDNA levels compared to HVs and MS patients (p = 0.0005), consistent with the increased disease severity, and increased plasma cfDNA source heterogeneity. Oligodendrocyte- and neuron-derived cfDNA was found to be elevated in MS patients with progressive disease compared to those with relapsing-remitting course (p = 0.0003; p = 0.0276). In combination with time-matched clinical and radiographic data, this cfDNA-based epigenetic liquid biopsy approach may be used to develop clinically relevant biomarkers for demyelinating disease.

• Dysregulated metal biodynamics in amyotrophic lateral sclerosis (ALS) patients
  Associated Company: LinusBio
  Author: Manish Arora
  

Abstract:
Amyotrophic lateral sclerosis (ALS) is a progressive degenerative motor-neuron disease. Approximately 5-10% of cases arise from genetic predispositions, but the vast majority are sporadic, reflecting an unknown etiology involving both environmental and genetic factors. Toxic environmental exposures have been implicated but reliable mechanistic information is lacking. We propose that the interaction between genes and the environment relies on the temporal dynamics of key molecular pathways, which can only be elucidated by biomarkers collected at hundreds of time points. To test this hypothesis, we applied a novel laser ablation-inductively coupled plasma-mass spectrometry approach to measure nutritional and toxic elements in single hair strands from a nationwide US sample of ALS cases, and a regional US hospital (n=391). This assay provides molecular profiles at over 500 time points, which were analyzed to characterize patterns of association in longitudinal elemental dynamics. We were able to identify a distinct molecular signature of elemental metabolism in non-ALS participants. Furthermore, we show that these signatures were dysregulated in ALS-positive cases. Overall, systemic perturbations of complex network dynamics in elemental metabolism are a key molecular feature of ALS.

• A New Diagnostic Test for Inflammatory Bowel Disease
  Associated Company: American African Health Team, LLC
  Associated University: Meharry Medical College
  Authors: Rabi Thangaiyan, MS, PhD and Amosy M'Koma, MD, MSc, PhD
  

Abstract:
Inflammatory bowel disease (IBD) is evolving worldwide & has become a global emergent disease. Improving the colonic diagnosis for IBD subtypes i.e., ulcerative colitis (UC) & Crohn’s disease (CD) & indeterminate colitis (IC). Here, the central medical challenge is the delineation of IC into UC/CD because it greatly affects the surgical care. Diagnostic accuracy is of utmost importance when determining a patient’s candidacy for pouch surgery. Further, incorrect diagnosis & treatment carry potential morbidity from inappropriate and unnecessary surgery and cost. There is 15 percent of IBD patients cannot be accurately diagnosed as UC or CD and another 15 percent CD diagnosed as UC. We discovered the aberrant expression of DEFA5 in IBD patient biopsy samples underlie the distinct pathogenesis of CD and may be exploited as a reliable diagnostic biomarker to differentiate CD/UC in otherwise IC cohort. The expansion of colonic ileal metaplasia in colonic crypt mucosa contribute to distinct pathology and accurate diagnosis of CD. The mission is to develop a diagnostic sandwich ELISA test using blood serum with high sensitivity and specificity. Commercially available anti-DEFA5 antibodies are either not specific for DEFA5 or less avid. We developed two tested functional anti-DEFA5 mouse mAbs Clone 1A8 and Clone 4F5 that have shown specificity for DEFA5 and amenable for use in Western blotting and 4F5 Immunohistochemistry and Sandwich ELISA to accurately delineate UC from CD or IC.

• Therasid Bioscience is dedicated to MASH therapeutics
  Associated Company/University: Therasid Bioscience | Seoul National University
  Author: Jay Kim
  

Abstract:
Fibrosis is the final, common pathological outcome of many chronic inflammatory diseases and is defined by the excessive accumulation of the extracellular matrix (ECM) such as collagen and fibronectin. The excessive myofibroblasts is a central feature of tissue fibrosis. These cells are master regulators of the fibrotic response and have been a major focus of anti-fibrotic therapies. The activated hepatic stellate cells (aHSCs) are recognized as resident liver myofibroblast and the major player of liver fibrosis with interplays between hepatocytes and immune cells. Although the first MASH drug approved in this March, the fibrosis still remains unresolved and highly unmet needed disease activity in MASH. Therasid Bioscience is trying to provide the solution for MASH-fibrosis in terms of the control of aHSCs.

• Regulatory macrophages contribute to tumor cell plasticity in colorectal cancer metastases
  Associated University: Vanderbilt University Medical Center
  Authors: Matthew Cottam
  

Abstract:
Metastatic disease is the common cause of death in colorectal cancer. To better understand the cellular landscape of colorectal metastasis, we profiled primary tumors and liver, lung, and peritoneal metastases using single-cell RNA sequencing. Our analysis revealed a subset of tumor epithelial cells with a highly plastic transcription profile and, inversely, low expression of stemness markers. Tumor cells with plasticity markers were spatially enriched at the tumor-stroma interface with exposure to tissue microenvironmental factors. Cell-free malignant ascites, which recapitulates the tumor microenvironment, impaired expression of proliferation and stem-like markers in favor of plasticity markers and enhanced migration of tumor cells. Furthermore, Co-culture of colorectal tumor cells with CD11b+ macrophages isolated from malignant ascites from patients was sufficient to recapitulate tumor cell plasticity. Profiling of tumor-associated macrophages identified enrichment for a lipid-handling features and high spatial correlation with plastic tumor cells. Taken together, we demonstrate that tumor-associated macrophages contribute to disease progression through development of pro-malignant features.

• Pioneering Oncology with 'Beyond ADC' Innovations in Precision Medicine
  Associated Company: Abion Inc.
  Author: Claire Kim
  

Abstract:
ABION, INC., founded in 2007, is a biopharmaceutical company specializing in innovative companion diagnostic-based drugs for first-in-class and best-in-class markets. Abion excels in developing and validating new drug entities through rigorous protocols, focusing on precision medicine to enhance public healthcare. Key oncology pipelines include ABN401 (Vabametkib), ABN202, and ABN501. ABN202 is a cutting-edge antibody cytokine fusion protein, positioned as "beyond ADC" technology. This platform combines interferon-beta mutein (ABN102) with cancer-targeting antibodies, delivering both direct and indirect cancer treatment mechanisms. It offers tumor growth inhibition and stimulates anti-tumor immunity. ABN202 shows promise in overcoming ADC resistance and is advantageous for combination therapy with immune checkpoint inhibitors, positioning it for novel applications and collaborations.

ABN501 is a first-in-class antibody therapeutic targeting CLDN3, a tight junction protein and pan-carcinoma marker. With strong affinity and specificity for CLDN3, which is present only in cancers, ABN501 exhibits low toxicity and impressive pre-clinical results. By diligently developing these pipelines, Abion aims to significantly contribute to oncology and public health, advancing treatment options and improving patient outcomes. Abion is also actively seeking partnerships to in-license its assets and accelerate the development and commercialization of its therapies

• Novel controllable CAR-T cells improve efficacy and durability of anti-cancer immunotherapy
  Associated Company/University: Dynamic Cell Therapies | Harvard University, Dana-Farber Cancer Institute
  Author: John Newcomb
  

Abstract:
Dynamic Cell Therapies (DCT) is developing two platform technologies that address major limitations of current CAR-T cell therapies. The first is a redirectable chimeric antigen receptor T cell, called BAT-CAR, which is short for binary activated T cells expressing a chimeric antigen receptor. BAT-CAR allows for control over CAR-T cells that can mitigate toxicity and can be re-directed to different targets on the surface of tumors as they evolve in response to therapies. Controlled stimulation of BAT-CAR T cells appears to result in less exhaustion compared to direct CAR-T. As a result, BAT-CAR T cells eliminate tumors more efficiently at lower cell doses relative to direct CAR-T therapy. Thus BAT-CAR will enable both greater efficacy and improved safety. DCT’s second technology is a chimeric cytokine receptor or CCR. Activating cytokine responses can help T cells overcome a repressive tumor microenvironment, can increase T cell persistence promoting durable responses, and when activated during CAR-T cell production, likely will improve the time and cost of manufacturing. We have shown that CCR-expressing CAR-T cells display more robust expansion and maintenance of memory phenotypes relative to direct CAR-T cells alone. This leads to improved durability of CAR-T cells expressing CCR. These results have been shown using mouse models of human myeloma and AML. We are expanding use of these platforms to enable better outcomes for patients with solid tumors.

• Curing epilepsies with precision gene therapies
  Associated Company/University: EpiCure Therapeutics, Inc. | Allen Institute for Brain Science | Seattle Children’s Research Institute
  Authors: John K. Mich1,2, Bryan B. Gore1,2, Rong Guo2, Refugio A. Martinez2, Yemeserach M. Bishaw2, August Liu2, Robert J. Christian2, Emily M. Luber2, Jonathan T. Ting2, Ed S. Lein1,2, Franck Kalume1,3, Boaz P. Levi1,2
  

Abstract:
Despite decades of research and development, epilepsies remain a major unmet medical need. These life-threatening brain diseases affect over 1% of the US population and lead to economic costs of over $100B annually, and current anti-epileptic therapies fail one-third of patients and often show debilitating side effects. We developed a new strategy to target epilepsies using cell type-specific gene delivery, leveraging precise modern Enhancer-AAV technology developed at the Allen Institute for Brain Science. Applying this scalable approach, our therapeutic promoted complete symptom reversal in a mouse model of Dravet syndrome (DS), a severe genetic epilepsy caused by loss of the voltage-gated sodium channel SCN1A. 100% of treated DS mice survived beyond one year, versus 50% of untreated DS mice died from seizures. This strong survival benefit coincided with reductions in seizures and abnormal brain patterns. We also restored normal behavior in tests of motor function and anxiety, demonstrating that our disease-modifying, precise, and durable treatment can ameliorate the comorbid symptoms of this devastating brain disease. Building on this success, we are leveraging this platform technology to target other epilepsies, having generated equally strong proof-of-concept data, as well as extending the Enhancer-AAV platform to other disease-relevant cell populations with fine control of expression levels. Ultimately the confluence of these technologies will unleash a revolution in brain treatments for epilepsy and neurological diseases.

• Base Editors and Prime Editors to Correct Genetic Disease
  Associated University: Johns Hopkins University
  Author: Gregory Newby
  

Abstract:
Base editors can efficiently install or correct transition mutations. Prime editors are more versatile and can rewrite sequences as desired, but require more effort and screening to optimize. Either tool is amenable to in vivo delivery by AAVs or by nanoparticles that require only RNA components. Together with several teams of collaborators, we are adapting these technologies to serve as a new generation of genome editing medicines to treat genetic disease in the blood, lung, heart, retina, liver, and brain.

• Novel splicing driven gene regulation platform for precise dose responsive control of gene and cell therapies
  Associated Company: MeiraGTx
  Author: Xuecui Guo
  

Abstract:
Precise control of delivered transgenes allows in vivo delivery of therapeutic biologics. However, gene regulation systems that have clinical applicability have been lacking. Here, by linking aptamers to an alternative splicing-based gene expression platform, we have created a robust riboswitch-based gene regulation system that controls gene expression via bespoke small molecule inducers. Using these novel riboswitches and inducers, we have regulated multiple therapeutic genes including hormones, incretins, antibodies and chimeric antigen receptors (CARs). We observed the robustness of our riboswitch system in controlling Epo expression in anemic animals and in regulating AAV-vectorized, anti-HER2 antibody. In Diet-Induced Obesity (DIO) animals, riboswitch-controlled expression of incretins resulted in significant body weight loss and improved glucose tolerance. CAR-T cells containing riboswitch were remotely controlled in vivo by orally administered inducers, showing superior anti-tumor activities when compared with CAR-T cells expressing constitutive CAR. Attributable to the uniquely high dynamic range of our riboswitch and the safety and oral bioavailability of the small molecule inducer, our riboswitch-based gene regulation platform enables precise control of therapeutic genes to advance the development of gene and cell therapies for a broad range of human diseases, including large indications with unmet needs such as metabolic disease, oncology and autoimmune disease.

• Exploring Nanobodies and Nanoparticles for Targeted Radionuclide Therapy
  Associated Company/University: Oak Ridge National Laboratory
  Author: Debjani Pal
  

Abstract:
Nanoparticles offer a promising strategy for delivering α-emitting radionuclides like 225Ac and 223Ra to tumor sites, potentially reducing off-target effects and maximizing tumor impact. This study explores two targeted approaches for breast cancer cells: directly conjugating 225Ac with an anti-HER2 nanobody and encapsulating the radionuclides in surface-functionalized nanoparticles to improve biocompatibility and stability. Confocal microscopy and live cell imaging confirmed effective nuclear localization of the nanoparticles, following the endolysosomal pathway, which enhanced their therapeutic efficacy. The study demonstrated dose-dependent killing of breast cancer spheroids using 225Ac-doped nanoparticles, measured by apoptosis and DNA damage assays. The combination of HER2-targeting nanobodies with surface-activated nanoparticles is being developed to encapsulate all α-emitters in the decay chain, potentially improving treatment specificity and effectiveness. These findings are key to advancing radiolabeled nanoparticle-based delivery systems for more precise and individualized cancer therapies.

• Cell-type specific delivery using in vivo RNA sensors
  Associated Company/University: Radar Therapeutics | Stanford University
  Author: Natalie Kolber
  

Abstract:
Off-tissue expression is a major challenge for in vivo gene therapies. Off-tissue transgene expression can disrupt the functioning of nontarget tissues, exacerbate immune responses, and increase the chance of off-targets in the context of gene editing. While significant progress has been made towards limiting off-target expression using tissue-specific microRNAs and promoters, engineered delivery vehicles, and other strategies, a truly modular and programmable strategy for limiting off-target expression is lacking. We therefore sought to take advantage of the abundance of single-cell transcriptomics data to target specific cell types based on RNA expression. We developed molecular (RNA-based) sensors for RNA transcripts that function in living mammalian cells using adenosine deaminases acting on RNA (ADARs). These sensors generate an arbitrary protein output specifically in the presence of an arbitrary RNA. We develop design rules for optimal RNA sensors and demonstrate their utility in clinically relevant contexts, including delivery specifically to virus-infected and cancerous cells. Overall, this strategy could better enable cell-type specific in vivo delivery for a wide variety of applications, including the treatment of genetic disorders, the ablation of cancer cells, and in vivo immune cell engineering.

• Development of MTOR-targeting ASOs for Treating mTORopathies with Intractable Focal Epilepsy
  Associated Company/University: Sovargen | KAIST
  Author: Eric Maeng
  

Abstract:
Focal malformations of cortical development (FMCD), including focal cortical dysplasia (FCD), hemimegalencephaly (HME), and tuberous sclerosis (TSC), are significant contributors to medically intractable epilepsy. Brain-only mutations (so-called ‘brain somatic mosaicism') causing the aberrant activation of mTOR signaling have been identified as a major genetic cause of FCD and HME, classifying them as mTORopathies. Epilepsy surgery is the only treatment option for FCD and HME with intractable seizures. In TSC, everolimus, the approved mTOR inhibitor drug, shows limited efficacy for controlling seizures with notable adverse events such as immunosuppression and increased risk of infections. Thus, there is a need for more efficient and safer therapeutic options targeting MTOR in the brain. This study explores the use of antisense oligonucleotide (ASO) technology to target and modulate mTOR signaling in the brain as a potential therapeutic strategy for mTORopathies with potentially fewer adverse events.

• In Vivo Gene Therapy using Lineage Reprogramming enables Walking Again after Complete Spinal Cord Injury
  Associated Company: StandUp Therapeutics
  Author: Junsang Yoo
  

Abstract:
Spinal cord injury (SCI) remains a critical unmet medical need, with limited treatment options available that effectively restore lost motor and sensory functions. STUP-001 is a groundbreaking AAV-based gene therapy developed by Stand Up Therapeutics, targeting the restoration of neuronal function in SCI patients. Unlike traditional approaches, STUP-001 leverages proprietary cell resetting technology to promote direct lineage reprogramming and regeneration of spinal cord neurons, offering a revolutionary therapeutic strategy for SCI. Pre-clinical studies demonstrate that STUP-001 efficiently converted the glial cells / astrocytes to neuron showing robust axonal regrowth in the injured spinal cord. Behavioral assessments in SCI models reveal marked improvements in motor function, with treated animals exhibiting substantial recovery in locomotion and sensory perception. Additionally, molecular analyses confirm the successful reprogramming of glial cells / astrocutes into neurons, accompanied by increased expression of neurotrophic factors and synaptic markers. STUP-001 represents the world’s first AAV gene therapy for spinal cord injuries, pioneering a novel approach in regenerative medicine. Our findings suggest that STUP-001 holds significant potential for transforming the treatment landscape of SCI. Ongoing studies are focused on further validating these results in human clinical trials (I/IIa), with the aim of bringing this innovative therapy to the clinic.

• GBA1-linked Parkinson’s Disease AAV gene therapy
  Associated Company: Spur Therapeutics
  Author: Henning Stennicke
  

Abstract:
Parkinson’s disease (PD) is a neurodegenerative disorder characterised by α-synuclein accumulation, Lewy Body formation and loss of dopaminergic neurones within the substantia nigra. Associated with more severe disease, 5-15% of people with PD carry GBA1 mutations, resulting in dysfunctional glucocerebrosidase (GCase). AAV gene therapy delivering functional GCase may reduce the accelerated disease progression in GBA1 PD. GCase85, with two amino acid substitutions to wildtype GCase (GCaseWT), has been established as a more stable enzyme with potential for effective delivery to and improved distribution across the brain. In vitro transduction of brain-derived cell lines demonstrated up to 10-fold more GCase activity with AAV9-GCase85 compared to AAV9-GCaseWT. Expression and distribution were evaluated in mice injected unilaterally into the right-hand caudate putamen with vehicle or AAV9-GFP, AAV9-GCaseWT or AAV9-GCase85 and analysed four weeks post dose. Whole brains were coronally cryosectioned at the striatal site of injection and the substantia nigra and sections were immunofluorescently labeled for GCase or GFP. The AAV9-GFP reporter showed effective retrograde transport from the caudate putamen, with wide distribution in axons of the substantia nigra. Qualitative immunofluorescent staining for GCase gave a more intense signal in numerous somata and neuropil of the injected right hemisphere and signal in the left hemisphere for AAV9-GCase85 compared to AAV9-GCaseWT.

• Tat Fusion Proteins Restore Cytokine Receptor Signaling In Anergic Cells, Allowing Immune-Mediated Tumor Reduction
  Associated Company: Ascensus Therapeutics, Inc.
  Author: Yosef Refaeli
  

Abstract:
T cells communicate with each other using cytokines to orchestrate a response against pathogens or malignant cells. Tumor cells can cause a breakdown in this communication by altering the cell signaling process and preventing cytokine receptors from properly transmitting their signals. Ascensus Therapeutics’ technology is a collection of fusion proteins engineered from naturally occurring proteins and cell penetrating peptides. These “Rescue Proteins” passively enter immune cells, restore the cytokine signaling pathway and liberate them to kill cancer. We have clinical proof of concept with a Tat-MYC fusion protein in patients with solid tumors. In multiple cancer patients Tat-MYC was able to reawaken T cells and restore their tumor fighting activity. Given these promising results, Ascensus is developing a next generation Rescue Protein. Because this New Rescue Protein has inherent enzymatic activity, it is more potent on a per molecule basis. It also operates through a well-known mechanism of action and can be shut down by approved drugs. Our approach is unique because it’s a protein-based method for correcting defective signaling pathways. This new technology does not rely on modifying the cytokine, modifying the cell surface receptor, or expanding a particular immune cell population ex vivo. Ultimately, these Rescue Proteins will enable patients’ immune systems to overpower the tumor and will give clinicians a pioneering new treatment option.

• A first-in-class multimodal immunotherapy for induction of tertiary lymphoid structures as a novel therapeutic strategy for solid tumors
  Associated Company: Candel Therapeutics
  Author: Francesca Barone
  

Abstract:
Immune checkpoint inhibitors (ICI) have transformed cancer treatment. Formation of organized intratumoral aggregates of lymphocytes (tertiary lymphoid structures, TLS) has been associated with response to ICI. The enLIGHTEN™ Discovery Platform aims to create multimodal therapeutics by leveraging human biology and advanced analytics to select multigene payloads delivered by herpes simplex virus vectors to the tumor microenvironment. Alpha-201 was selected from a suite of modified HSV vectors as the biological chassis due to its ability to release tumor antigens and activate pathways associated with response to ICI. A library of single gene encoding Alpha-201 vectors was constructed, each expressing one in silico predicted payload component. The top two scoring combinations of these viral gene constructs (Multiplex A and Multiplex B) were next tested for their effects on TLS induction and anti-tumor efficacy in complementary in vivo models. As predicted, delivery of both multiplexes increased the number, size, organization and maturity of virally induced TLS. Second, anti-tumor efficacy was tested in mice. Both multiplexes induced tumor growth inhibition compared to vehicle control mice. In conclusion, we have demonstrated the ability of enLIGHTEN™ to design multimodal specific therapeutics, resulting in the development of a first-in-class immunotherapeutic for TLS induction in solid tumors.

• A Safer Approach to Pain Management
  Associated Company: Epiodyne
  Author: Douglas Crawford
  

Abstract:
Epiodyne is advancing a novel partial mu opioid agonist that matches the pain-relieving effects of oxycodone, yet eliminates respiratory depression and minimizes abuse risk. This compound could play a crucial role in reducing opioid-induced respiratory complications in the perioperative environment.

• Innovative Antibody-based Therapeutics for Oncology and Autoimmune Disease
  Associated Company: Fatiabgen
  Author: JayJay Lee
  

Abstract:
Fatiabgen is a leading antibody-based platform company with a broad clinical pipeline for Oncology and Allergy disease treatment using our best-in-class therapeutic antibodies. The two most advanced assets are: - Collaboration with Duality Biologics to co-develop MSLN ADC with unique properties and strong data in mouse xenograft models of various solid tumor cancer - Collaborate with Lonza to develop a Novel IgE backbone for allergy/asthma indications, with favorable properties compared to Xolair.

• ICT-1402, a potent, selective, and orally bioavailable MET degrader for treating NSCLC with MET alterations
  Associated Company: Innocure therapeutics
  Author: Jong Seok Kang
  

Abstract:
MET alterations, including MET exon 14 skipping mutation, overexpression, and amplification are oncogenic drivers for non-small cell lung cancer (NSCLC). More importantly, MET amplification is one of most common acquired resistance mechanisms to EGFR tyrosine kinase inhibitors (TKIs) with EGFR mutated NSCLC. There are no effective treatments for NSCLC patients with MET amplification and overexpression. We discovered ICT-1402, a first-in-class MET degrader, for targeting MET altered NSCLC and compared its efficacy to the MET TKI, Tepotinib. Results: ICT-1402 induced highly selective MET degradation through ubiquitin-proteasome system. ICT-1402 showed strong anti-proliferative activity in solid cancer cell lines with MET alterations compared to normal cells. ICT-1402 potently suppressed MET downstream signal, which is superior to MET TKI and showed durable MET degradation effects. In addition, ICT-1402 had favorable PK profile for oral administration in mouse, rat, and dog. ICT-1402 exhibited rapid, robust and sustained tumor growth inhibition in MET amplified NSCLC CDX and PDX models, which were superior in vivo efficacy to MET TKI, Tepotinib. Conclusion: These results demonstrate that ICT-1402 is a potent, selective, and orally available first-in-class MET degrader for treating NSCLC with MET alterations.

• WARS1- Neutralizing Antibody for Rheumatoid Arthritis
  Associated Company: MirimGENE Co., Ltd.
  Author: Byoung Cheol Kang
  

Abstract:
MirimGENE focuses on the development of innovative biologics to treat autoimmune diseases and infectious disorders. According to Nature Microbiology, Novel target WARS1 secreted by monocytes is a primary defense mechanism against infection. Autoimmune diseases can be treated by blocking the hyperactive Novel target WARS1, according to POC data on RA, AD, IBD, sepsis and MAS in animal models. Also, immunosuppressive tuberculosis patients' innate immunity can be boosted to fight a variety of infectious diseases by activating the reduced Novel target WARS1. MirimGENE's antibody biologics were were upstream- and downstream- processed in association with Samsung Biologics. GLP toxicological studies are expected to be produced in 2025, and an IND application for the clinical phase 1 trial is anticipated in 2026. We seek to treat autoimmune and infectious diseases by targeting Novel target WARS1 using the exclusive discovery platform of MirimGENE. There are Unmet needs for doctors to have much stronger biologics and measure biomarkers and suppress pannus formation fundamentally and block several cytokines at the same time. WARS1 neutralizing antibodies can be effective in Humira- non-responders and suppress synoviocyte hyperplasia & pannus formation fundamentally and WARS1 can be measured as biomarkers because WARS1 are secreted hundreds of time higher than TNF in the synovium of RA patients.

• Translating NLRP3 Inflammasome Inhibition into Clinical Therapeutics: Rationale and Design for Two Clinical Trials of Dapansutrile (OLT1177®) in the Settings of Acute and Chronic IL-1β Mediated Inflammation
  Associated Company/University: Olatec Therapeutics, Inc. | University of Colorado - Denver | University Hospital Basel
  Author: Mustafa Noor
  

Abstract:
Dapansutrile (OLT1177®) is an NLRP3 inhibitor in clinical development that to date has preliminary clinical efficacy and safety. It is currently undergoing 2 large trials. PODAGRA-II is a multicenter, placebo-controlled, prospective, randomized, double-blind trial. A total of 300 patients with acute symptomatic gout flare are being randomized to receive either dapansutrile or matching placebo tablets for 7 days. The primary endpoint is the subject-reported pain intensity score in the target joint (evaluated on a 100-mm visual analogue scale) at 72 hours. Secondary endpoints include biomarkers associated with acute gout inflammation (IL-1 β, IL-6 and CRP). DAPAN-DIA is a multicenter, placebo-controlled, prospective, randomized, double-blind trial. A total of 300 patients with type 2 diabetes, HbA1c >7.5% and hsCRP>1.5 mg/L are being randomized to receive either dapansutrile or matching placebo tablets for 6 months. The primary endpoint is change from baseline HbA1c after 6 months. Secondary endpoints include biomarkers associated with diabetic complications, as well as chronic inflammation (IL-1 β, IL-6 and hsCRP). PODAGRA II and DAPAN-DIA are two large studies with dapansutrile to investigate its effects in high-grade acute as well as low-grade chronic inflammation and will provide important new data on translating NLRP3 inhibition into clinical therapeutics.

• Cell-free regeneration by miRNA-targeting technology
  Associated Company/University: Regen Innopharm | The Catholic University of Korea
  Author: Il-Hoan Oh
  

Abstract:
RegenInnopharm is a company in Korea developing cell-free, molecular therapeutics for tissue regeneration. Our key platforms technologies are “wake-up stem cell” technologies that can stimulate the regenerative/repair potential of tissue by using miRNA-targeting peptide- or miRNA-targeting antagomir. RengenInnopharm is being supported by KDDF in the development of drugs for myocardial infarction and diabetic foot ulcers. The main features of pipelines are as follows: 1) RH001, an RNA-based antagomir drug for acute myocardial infarction. This exerts a multi-modal action, including anti-inflammation, anti-fibrosis, and pro-angiogenesis in infarcted hearts. RH001 shows safety and efficacy in swine model, leading to the recovery of heart function up to 90% of the healthy state (non-clinical stage). 2) PN001, a peptide drug for cerebral infarction. This drug decreases infarct size as much as 80% of SOC control, accompanied by functional recovery without neurological sequalae. It works in IV and ICA injection, suitable for stroke in broad clinical spectrums (non-clinical stage). 3) PU001, a peptide drug for diabetic foot ulcer. This peptide can regenerate healthy, non-leaky vasculatures and accelerate the regeneration of mature epithelium structure, enabling its application for ischemia-complicated or therapy-resistant diabetic foot ulcer. This asset is now ready for clinical development (IND approved). Our company is open for funding, licensing, or development partnerships.

• Dual senolytic antibody that activates apoptosis and immune system to eliminate senescent cells
  Associated Company/University: Senelix | College of Pharmacy, Chungbuk National University
  Author: Brian Bongcheol Kim
  

Abstract:
CHI3L1 (Chitinase 3-like protein 1) is a 40 KDa secreted protein whose plasma levels rise with age. It is a marker of low-grade chronic inflammation and has been linked to a number of age-related illnesses. The Senelix team discovered that CHI3L1 is a senescence factor that promotes both cellular and immuno-senescence. The key findings include: 1. CHI3L1 inhibits apoptosis by binding to p53 and inducing degradation. Anti-CHI3L1 mAb enhanced p53 and downstream apoptotic signaling proteins in vivo. In in vitro fibroblast culture under oxidative stress, anti-CHI3L1 mAb decreased SA-β-galactosidase staining, showing that CHI3L1 is a cellular senescence factor. 2. CHI3L1 is an immunosenescence factor that causes M2-polarization of macrophages, increases PD-1/PD-L1 expression, and lowers cytotoxic granules in NK/CD8+ T cells, leading to insufficient immune clearance. 3. Hallmark of fibrosis is persistent myofibroblasts that resist apoptosis. Anti-CHI3L1 mAb shows potential as a dual senolytic therapy for fibrosis since it induces myofibroblasts apoptosis while also enhancing immune clearance of myofibroblasts and apoptotic bodies. 4. In a bleomycin-induced lung fibrosis model, SL300, an anti-CHI3L1 mAb, showed significant anti-fibrotic activity. In conclusion, CHI3L1-neuralizing antibodies such as SL300 may be a viable treatment for fibrotic diseases, notably idiopathic pulmonary fibrosis (IPF). The CMC development for SL300 is presently underway.

• Developing 20-alpha-hydroxycholesterol to reverse neonatal white matter injury
  Associated Company: Tellus Therapeutics
  Author: Khadar Abdi
  

Abstract:
White matter injury (WMI) is the leading cause of neurological impairment among infants born prematurely, yet there are currently no effective treatment options. Outcomes include cerebral palsy and cognitive deficits. The most common forms of WMIs in infants occur prior to the onset of normal myelination, when a transient pool of neural progenitor cells located within the germinal matrix retains robust oligodendrogenic potential. 20-alpha-hydroxycholesterol (20HC), an oxysterol found in human breast milk, enhances the production of oligodendrocyte progenitors during this critical time in brain development. Following WMI in neonatal mice, 20HC treatment induced subventricular zone oligodendrogenesis improved periventricular white matter myelination and motor outcomes. A major challenge in developing an effective therapy for infants with WMI is the need for early diagnosis. Prior clinical trials in this population have had mixed success due to the heterogeneity of brain injuries and the inability to diagnose them early. To overcome this hurdle, physician-scientists working with Tellus have developed an imaging approach to diagnose this type of brain injury within 48-hours. With this approach, Tellus can reduce the heterogeneity of this patient pool and treat infants most likely to benefit from 20HC, thus increasing the probability of achieving a clinically successful outcome. Finally, Tellus is committed to developing safe and effective therapeutics for unmet needs in the NICU.

• TT125-802: a CBP/p300 BRD inhibitor against transcriptional resistance in cancer
  Associated Company: TOLREMO Therapeutics AG
  Author: Stefanie Flückiger-Mangual
  

Abstract:
Drug resistance is a major challenge in oncology. While intrinsic resistance to cancer therapies limits the rate and depth of response, acquired resistance limits the duration. The reactivation of oncogenic signaling is a well-studied source of resistance. In parallel to this, plastic cell states associated with EMT, stemness, and immune escape also contribute to poor and short-lived disease control. A high-throughput, phenotypic screen identified the epigenetic regulator CBP/p300 as a novel master regulator of transcriptional resistance cell states that govern resistance independent of oncogenic signaling. TT125-802 is a highly selective CBP/p300 bromodomain (BRD) inhibitor and serves as a powerful combination partner for multiple targeted cancer therapies. In preclinical models of EGFR- and KRAS-mutated non-small cell lung cancer (NSCLC) and colorectal cancer (CRC), and in AR-driven prostate cancer, TT125-802 boosted response rates and progression free survival in the combination setting. By addressing non-oncogene dependencies, TT125-802 also showed some single agent activity in these models. In a phase I monotherapy dose-escalation study in solid tumor all-comers, TT125-802 has shown good safety and tolerability, with confirmed target engagement in surrogate tissues. Several patients have experienced disease stabilization and one NSCLC patient a confirmed partial response. Combination studies with KRAS and EGFR inhibitors in NSCLC patients are planned for 2025.

• A first-in-class multimodal immunotherapy for induction of tertiary lymphoid structures as a novel therapeutic strategy for solid tumors
  Associated Company: Candel Therapeutics
  Author: Francesca Barone
  

Abstract:
Immune checkpoint inhibitors (ICI) have transformed cancer treatment. Formation of organized intratumoral aggregates of lymphocytes (tertiary lymphoid structures, TLS) has been associated with response to ICI. The enLIGHTEN™ Discovery Platform aims to create multimodal therapeutics by leveraging human biology and advanced analytics to select multigene payloads delivered by herpes simplex virus vectors to the tumor microenvironment. Alpha-201 was selected from a suite of modified HSV vectors as the biological chassis due to its ability to release tumor antigens and activate pathways associated with response to ICI. A library of single gene encoding Alpha-201 vectors was constructed, each expressing one in silico predicted payload component. The top two scoring combinations of these viral gene constructs (Multiplex A and Multiplex B) were next tested for their effects on TLS induction and anti-tumor efficacy in complementary in vivo models. As predicted, delivery of both multiplexes increased the number, size, organization and maturity of virally induced TLS. Second, anti-tumor efficacy was tested in mice. Both multiplexes induced tumor growth inhibition compared to vehicle control mice. In conclusion, we have demonstrated the ability of enLIGHTEN™ to design multimodal specific therapeutics, resulting in the development of a first-in-class immunotherapeutic for TLS induction in solid tumors.

• Dual senolytic antibody that activates apoptosis and immune system to eliminate senescent cells
  Associated Company/University: Senelix | College of Pharmacy, Chungbuk National University
  Author: Brian Bongcheol Kim
  

Abstract:
CHI3L1 (Chitinase 3-like protein 1) is a 40 KDa secreted protein whose plasma levels rise with age. It is a marker of low-grade chronic inflammation and has been linked to a number of age-related illnesses. The Senelix team discovered that CHI3L1 is a senescence factor that promotes both cellular and immuno-senescence. The key findings include: 1. CHI3L1 inhibits apoptosis by binding to p53 and inducing degradation. Anti-CHI3L1 mAb enhanced p53 and downstream apoptotic signaling proteins in vivo. In in vitro fibroblast culture under oxidative stress, anti-CHI3L1 mAb decreased SA-β-galactosidase staining, showing that CHI3L1 is a cellular senescence factor. 2. CHI3L1 is an immunosenescence factor that causes M2-polarization of macrophages, increases PD-1/PD-L1 expression, and lowers cytotoxic granules in NK/CD8+ T cells, leading to insufficient immune clearance. 3. Hallmark of fibrosis is persistent myofibroblasts that resist apoptosis. Anti-CHI3L1 mAb shows potential as a dual senolytic therapy for fibrosis since it induces myofibroblasts apoptosis while also enhancing immune clearance of myofibroblasts and apoptotic bodies. 4. In a bleomycin-induced lung fibrosis model, SL300, an anti-CHI3L1 mAb, showed significant anti-fibrotic activity. In conclusion, CHI3L1-neuralizing antibodies such as SL300 may be a viable treatment for fibrotic diseases, notably idiopathic pulmonary fibrosis (IPF). The CMC development for SL300 is presently underway.

• Accelerating Translational Research
  Associated Company: Chicago Biomedical Consortium
  Author: Eric Schiffhauer
  

Abstract:
The Chicago Biomedical Consortium (CBC) is a translational platform that accelerates biomedical discovery and is working to expand the Illinois biotech ecosystem. With an experienced in-house team and a unique evaluation process, the CBC provides industry-level expertise, guidance, and early-stage funding to researchers with the goal of transforming research into biomedical applications. The consortium offers early, non-dilutive funding of up to $250,000 to catalyze high-potential projects, implementing milestone driven development plans to inform the path to Investigational New Drug (IND) applications.
Entrepreneurial fellows — junior scientists who apprentice full-time with industry experts — perform advanced scientific evaluation and commercial and transactional due diligence on potential CBC projects. This process serves as both a grant application and a deep analysis of professors' potential biomedical applications. This approach saves time for researchers, while providing valuable insights.
Through its expert commercial guidance including sophisticated market analytics, in-depth product development education, industry connections, and project management, the CBC is helping build early-stage biotech ecosystem in Illinois.

• BioCentury's Innovation Distillery: Preclinical literature distilled down to targets and compounds with potential for translation
  Associated Company: BioCentury Inc.
  Author: Karen Tkach Tuzman
  Abstract:
  BioCentury's Innovation Distillery is a data and analytics solution built specifically for Innovation Hunters—whether driven by investment or competitive needs. It identifies primary biomedical research articles containing preclinical innovations with potential for translation into medicine. What sets The Innovation Distillery apart is its ability to highlight transformative innovations, and innovation trends, without requiring users to spend countless hours reading through biomedical literature.

Triple Distillation: The Innovation Distillery provides users with three levels of literature distillation: 1) Curation of the biomedical literature for innovations with near-term therapeutic potential 2) Indexing of each innovation by 16 parameters, including molecular target, disease, principal investigators, country and institution of origin, experimental systems and patent status, if disclosed 3) Capturing of key experiments and molecular mechanisms via succinct, standardized summaries.

Now part of BioCentury's BCIQ database, the Innovation Distillery enables cross-sectional analyses of trends in the biomedical literature, and helps power BioCentury's Discovery & Translation Analysis.