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 Networking Session "Discover hidden gems, the Old Fashioned Way: Poster Spotlight and Networking Reception" on Thursday, June 5 at 6:15 PM Central Time.

Get the conversation started by requesting 1x1 meetings with poster presenters via the BioCentury Grand Rounds 2025 digital platform.

PLATFORMS

• “Inside-Out” Proteins: Novel Biomarkers for Targeted Immunotherapy
  
• From synapse to solution: A scalable platform for longitudinal and high-throughput neuroplasticity profiling
  
• MSR-seq™: Comprehensive profiling of non-coding RNA
  
• Illuminating the Structural Surfaceome: Discovering a Novel Class of Tumor-specific Targets for First-in-Class Therapeutic Opportunities
  
• Lipid-protein interaction inhibitors as a new drug discovery platform
  
• Developing a High-Throughput Technique for Protein Stability Measurements: cDNA Display Pulse Proteolysis
  
• Mass spectrometry-enabled protein and lipid biomarkers of Niemann-Pick Type C
  
• Genetic Biomarker Discovery in a Complex Human In Vitro Model Enables Precision Medicine and Drug Rescue
  
• Machine learning maps intracellular pocket conformations to multidimensional signaling efficacy
  
• Ubuntu Research: Transforming Biotech Clinical Development
  
• Translational Microbiome Innovation at the Duchossois Family Institute: From Strain Bank to Clinical Impact
  
• High Throughput Screening of Immunomodulators for Vaccine Adjuvants and Beyond
  
• From Genome to Compound: An AI Platform for Predicting Metabolic Potential and Accelerating Biotech Innovation
  
• New Companies and New Opportunities from Notre Dame Drug Discovery
  
  BIOMARKERS & DIAGNOSTICS
  
• Skye™: A Privacy-Preserving Digital Biomarker Collector for Cognitive Clarity
  
• Saliva-based Tumor Genomics Test Coupled with a Digital Health Patient Navigator for Oral Cancer Support
  
• Evaluation of Novel MUC1-C Targeted Near-Infrared Imaging Agent for Fluorescence-Guided Surgery of Cancer
  
  CANCER THERAPIES
  
• The Discovery of Novel Degrader Technology for KRAS-Dependent Cancer
  
• A Novel Tri-Specific T Cell Engager Improves In Vivo Outcomes by Addressing Glioblastoma Heterogeneity
  
• Advancing Precision Oncology Through Alpha Radiation
  
• PAN Biologics: Redefining Cancer Treatment with Precision Tools
  
• Programming cells to disrupt the root drivers of cancer
  
• Riptide Therapeutics: Targeting Telomerase Reverse Transcriptase (TERT) to Overcome Cancer Therapy Resistance
  
• Next-Generation Asparaginase for ASNS(low) Cancers - Expanding the Therapeutic Reach Beyond ALL
  
• Aplexis Advances APX-052: A First-in-Class PLEK2 Inhibitor Targeting Disease Progression in Myeloproliferative Neoplasms
  
  

NEUROLOGY THERAPIES

• Development of a Targeted Analgesic for Neuropathic Pain
  
• Safer Opioid with Reduced Respiratory Depression
  
• Targeting unwanted adverse effects of opioid analgesics without blocking analgesia: 6beta-naltrexol potently reduces opioid dependence and hyperalgesia
  
• Unlocking the Promise of Regenerative Medicine for Neurological Injuries and Disorders
  
• ENCUE INC: Developing Drugs to Treat Neurological and Neuropsychiatric Disorders: A Novel Approach for the Treatment of Rett Syndrome
  
  

THERAPIES FOR OTHER INDICATIONS

• Discovery and development of first-in-class TDO2 inhibitors for uterine fibroid treatment
  
• (R)-ND-336 for Treatment of Diabetic Foot Ulcers
  
• Targeted Macrophage Delivery of a Dexamethasone Prodrug (101-PGC-005) Enables Potent Anti-Inflammatory Activity with Reduced Systemic Toxicity: Preclinical, Phase 1 & Phase 2 Clinical Results
  
• Development of 3D Printed PLG-Based Liver Tissue Therapeutic for the Treatment of Alcoholic Liver Disease and Liver Failure
  
• A Benzothiophene-based Antimicrobial Agent Active Against MRSA
  
• Allosteric sirtuin-2 modulators are pathogen-agnostic anti-infectives that inhibit both viruses and bacteria, and have applications beyond infectious disease
  
• Imidazole-Linked Quinone Methide Precursors Lead to Broad-Scope Efficacy via a Proposed Role of Imidazole in Reactivation and Resurrection of OP-inhibited/aged Acetylcholinesterase
  
• A Novel Therapeutic for Cardiac Arrest
  
• A cell-permeable peptide therapeutic for the treatment of reperfusion injury
  
• Next-Generation Oral Small Molecule Therapeutics for Obesity and Metabolic Disease Synergistic in Combination with Incretin Therapies
  
• Enzyme Replacement Therapy for GM1 Gangliosidosis: Following a Proven Path to Clinical Success
  
• Development of DT678 and Clinical Studies to Evaluate the Antiplatelet Properties of DT-678 in Acute Coronary Syndrome Patients and Healthy Volunteers
  
• PiggyBac Transposon-Based Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB)
  

• Lipid-protein interaction inhibitors as a new drug discovery platform
  Associated Company/University: University of Illinois Chicago
  Author: Wonhwa Cho
  Abstract:
  Lipids control numerous cellular processes via lipid-protein interaction (LPI) and dysregulated LPI caused by the reprogrammed lipid metabolism leads to diverse human diseases, including cancer. Taking advantage of the highly specific and variable nature of LPI sites, we recently pioneered the LPI inhibitor-based drug discovery platform (1,2). In a proof-of-principle study, we developed a first-in-class LPI inhibitor (WC36) for acute myeloid leukemia (AML), which potently and specifically blocked LPI of Syk kinase (1). Because WC36 only blocked aberrant LPI of Syk in AML cells, which is crucial for cancer cell survival and resistance to conventional Syk inhibitors, WC36 potently suppresses viability and drug resistance of AML cells without causing detectable site effects to normal cells. Further, AML cells could not develop resistance to WC36, demonstrating the potential of LPI inhibitors as potent and resistance-proof anti-cancer agents. In colorectal cancer (CRC) cells with commonly observed APC mutation, locally elevated cholesterol constitutively activated WNT-β-catenin signaling via a scaffold protein Dvl(2). Our LPI inhibitor for Dvl (WC522) potently and specifically blocked WNT-β-catenin signaling in CRC cells. Since WC522 blocked LPI of Dvl in CRC cells, which is essential for CRC cells but dispensable in normal cells, it suppressed CRC tumors in vivo without causing cytotoxic effects on somatic stem cells (2), unprecedented for a WNT-targeting inhibitor. Additional examples of LPI inhibitors showcasing their high potency, specificity, and safety as anti-cancer agents against various human cancers, including breast cancer, will be presented.
  
  References:
  

• 1. I. Singaram et al., Targeting lipid-protein interaction to treat Syk-mediated acute myeloid leukemia. Nat. Chem. Biol. 19, 239-250 (2023).
     
• 2. A. Sharma et al., Cholesterol-targeting Wnt/b-catenin signaling inhibitors for colorectal cancer Nature Chem Biol DOI: 10.1038/s41589-025-01870-y (2025).
     

• From Genome to Compound: An AI Platform for Predicting Metabolic Potential and Accelerating Biotech Innovation
  Associated Company/University: MetabolicAI
  Author: Mariko Matsuura
  

Abstract:
MetabolicAI is a software platform designed to help biotech and pharmaceutical companies accelerate discovery and manufacturing by addressing critical R&D bottlenecks. Today, organizations invest significant resources into identifying promising bioactive compounds and optimizing their production—often relying on fragmented, custom-built software pipelines that require specialized expertise to operate and maintain. This complexity slows innovation at a time when speed and adaptability are increasingly essential. MetabolicAI replaces these bespoke workflows with a unified, AI-powered SaaS solution that streamlines the interpretation of genomic data into actionable metabolic insights. This poster introduces the concept and prototype of the platform, illustrating how MetaboliAI streamlines pathway exploration and supports more efficient decision-making in discovery and strain optimization.

• New Companies and New Opportunities from Notre Dame Drug Discovery
  Associated Company/University: University of Notre Dame
  Author: Brian Blagg
  

Abstract:
The Warren Center for Drug Discovery was established in 2017 and includes faculty from various departments on the Notre Dame campus who have an interest in developing drugs, delivery vehicles, and/or medical devices. In fact, these efforts have led to fourteen spinoffs as noted below. Moreover, 4 molecules are quickly approaching IND status, and two of those have completed pre-IND studies and are seeking investments to initiate clinical trials. Examples of three companies and their progress are succinctly provided.

• Skye™: A Privacy-Preserving Digital Biomarker Collector for Cognitive Clarity
  Associated Company/University: University of Illinois Chicago
  Author: Chioma Nnyamah
  

Abstract:
Skye™ by KeyWise AI is a first-in-class, passive digital biomarker platform that continuously assesses cognitive performance through keystroke dynamics without capturing typed content. Skye transforms everyday smartphone use into a privacy-preserving tool for monitoring attention, processing speed, and executive function in real time. Backed by over a decade of NIH- and NIA-funded research and neuropsychiatric expertise from multiple R1 universities, Skye is a novel tool for the patient, the clinician, and the pharmaceutical developer. Unlike conventional methods that require structured tasks or clinic-based assessments, Skye integrates seamlessly into daily life, analyzing typing behavior to generate a real-time Clarity Score™: an objective measure of cognitive clarity. This score enables users, clinicians, and researchers to track cognitive fluctuations over time and correlate them with life events, behavioral changes, mental health status, or treatment effects. Skye has been validated across multiple clinical populations, including individuals with depression, multiple sclerosis, and brain fog, and its output correlates with gold-standard cognitive assessments such as the NIH Toolbox, Symbol Digit Modalities Test (SDMT), and digital Trail Making Test (dTMT). The platform has been featured in Brain & Behavior and other peer-reviewed journals, and was the winner of the Apple ResearchKit Challenge. Skye is easily scalable and optimized for deployment in decentralized and hybrid clinical trials, enabling low-burden, real-time cognitive monitoring. For pharmaceutical partners, it offers a frictionless, easy-to-implement solution for passive cognitive endpoint tracking, reducing patient burden while enhancing data resolution. This poster presents key validation data and real-world applications for clinical trial enrichment, digital phenotyping, and longitudinal monitoring in neuropsychiatric research.

• Saliva-based Tumor Genomics Test Coupled with a Digital Health Patient Navigator for Oral Cancer Support
  Associated Company/University: University of Illinois Chicago
  Author: Chioma Nnyamah
  

Abstract:
Skye™ by KeyWise AI is a first-in-class, passive digital biomarker platform that continuously assesses cognitive performance through keystroke dynamics without capturing typed content. Skye transforms everyday smartphone use into a privacy-preserving tool for monitoring attention, processing speed, and executive function in real time. Backed by over a decade of NIH- and NIA-funded research and neuropsychiatric expertise from multiple R1 universities, Skye is a novel tool for the patient, the clinician, and the pharmaceutical developer. Unlike conventional methods that require structured tasks or clinic-based assessments, Skye integrates seamlessly into daily life, analyzing typing behavior to generate a real-time Clarity Score™: an objective measure of cognitive clarity. This score enables users, clinicians, and researchers to track cognitive fluctuations over time and correlate them with life events, behavioral changes, mental health status, or treatment effects. Skye has been validated across multiple clinical populations, including individuals with depression, multiple sclerosis, and brain fog, and its output correlates with gold-standard cognitive assessments such as the NIH Toolbox, Symbol Digit Modalities Test (SDMT), and digital Trail Making Test (dTMT). The platform has been featured in Brain & Behavior and other peer-reviewed journals, and was the winner of the Apple ResearchKit Challenge. Skye is easily scalable and optimized for deployment in decentralized and hybrid clinical trials, enabling low-burden, real-time cognitive monitoring. For pharmaceutical partners, it offers a frictionless, easy-to-implement solution for passive cognitive endpoint tracking, reducing patient burden while enhancing data resolution. This poster presents key validation data and real-world applications for clinical trial enrichment, digital phenotyping, and longitudinal monitoring in neuropsychiatric research.

• Evaluation of Novel MUC1-C Targeted Near-Infrared Imaging Agent for Fluorescence-Guided Surgery of Cancer
  Associated Company/University: Xentria
  Author: Qi Mao
  

Abstract:
Background: Tumor-targeted, near-infrared (NIR) fluorescent is an emerging field of real-time intraoperative imaging. Targeted NIR dyes contain NIR fluorophores and specific binding ligands such as antibodies, peptides and small molecules. Smaller ligands contribute to quicker imaging and clearance which both wanted to improve tumor background ratio (TBR). Therefore, peptide conjugates and small-molecule conjugates are more suitable for intraoperatively optical imaging even though individual difference in pharmacokinetics. However, it is difficult or impossible to generate small molecule ligands for many protein targets, such as those with flat, featureless surfaces or important protein-protein interactions (PPIs). Macrocyclic peptides are a molecular class with the potential to bridge the gap between small molecules and antibodies. Mucin 1 (MUC1) is an attractive target for the development of targeted therapeutics, but previous anti-MUC1 agents targeting the shed MUC1 N-terminal have shown limited clinical efficacy. Herein, We report the generation of a MUC1-C (cleaved MUC1) targeted peptidomimetic-NIR conjugate (SAG602) that concentrates specifically in cancer tissues and clears rapidly from healthy tissues.

Methods: Fifteen combinatorial single or double cyclic peptide libraries, which produce on phage and cyclized with different chemical linkers, were used for preliminary identification of high-affinity MUC1-C binders. To expand the chemical space around preliminary compounds, bespoke phage libraries were built further screening. After several rounds structure activity relationship studies, the substitution of individual amino acids in parent compounds to unnatural ones further improved the affinity, thermal and proteolytic stabilities. Binding affinities, high thermal and plasma stabilities, optical properties, transvascular extravasation, intratumoral penetration, in vitro and in vivo specificity, tumor-tobackground ratio (TBR), and pharmacokinetics (PKs) properties were evaluated in requisite models.

Results: SAG602 binds to MUC1-C-expressing cells with ∼10 nM affinity, high thermal stability (90 ℃, 20 min), concentrates selectively to MUC1-C-positive cancer tissues, and clears rapidly from healthy tissues with a half-time of < 1 hour. It also exhibits an excellent TBR (5:1) as well as safety profile in animals.

Conclusion: SAG602 has shown promising affinity, specificity, stability, and tumor-targeted imaging capabilities in all in vitro and in vivo studies. Based on the excellent tumor contrast in murine tumor models, we conclude that SAG602 holds great potential for fluorescence-guided surgery of MUC1-C positive malignant lesions, and is a candidate for translation into human use.

• The Discovery of Novel Degrader Technology for KRAS-Dependent Cancer
  Associated Company/University: Chicago Biomedical Consortium
  Author: Sateja Paradkar
  

Abstract:
KRAS mutations are frequently observed in lung, colorectal and pancreatic cancers, with 25% of all solid tumors harboring a KRAS mutation as an oncogenic driver. There are over 20 different unique cancer-causing mutations identified in the KRAS protein. Given the prevalence of KRAS mutations, targeting oncogenic KRAS has been a focus for more than 20 years. KRAS has proven itself to be a difficult target to inhibit chemically, and only two KRAS inhibitors are currently approved drugs, and both target the G12C mutation. While the KRAS G12C inhibitors have shown encouraging results in the clinic, their efficacy is limited to KRAS-dependent cancers with the G12C mutation, and these drugs have run into pathway resistance and poor durability in the clinical setting. Allele-specific and pan-RAS inhibitors have emerged to address the larger KRAS mutational spectrum, but early clinical signals would suggest that the concerns of pathway resistance and mechanistic escape from direct inhibition remain. The extensive mutational spectrum seen in KRAS-dependent cancers beyond G12D/V/C, along with the lack of true pan-KRAS molecules that can address all KRAS mutations and block pathway resistance mechanisms, represent a high unmet need for patients and a challenge for drug hunters. Here we describe a novel and orthogonal mechanism for selectively degrading oncogenic KRAS in a mutationally agnostic way. This strategy lowers the amount of mutant KRAS in cancer cells and provides a novel target for selective clearance of the oncogenic protein. Selective mutant KRAS modulators (SMKM) were identified through genome-wide CRISPR/Cas9 mediated knockout (KO) screens in wild type (WT) and mutant KRAS cell lines using an immunomagnetic cell sorting approach amenable to comparative parallel screening. These findings uncover a previously unrecognized vulnerability in mutant KRAS-driven cancers and identify a novel druggable target for selective KRAS clearance.

• A Novel Tri-Specific T Cell Engager Improves In Vivo Outcomes by Addressing Glioblastoma Heterogeneity
  Associated Company/University: Northwestern University
  Author: Irina Balyasnikova
  

Abstract:
Glioblastoma (GBM) remains an incurable and aggressive brain tumor, with poor survival outcomes despite intensive multimodal therapies. A significant barrier to effective treatment is tumor heterogeneity, which allows cancer cells to evade therapies targeting a single antigen. To address this challenge, we have engineered a tri-specific T cell engager (TriTE) that simultaneously targets three tumor-associated antigens commonly overexpressed in GBM, such as IL13Rα2, EGFR, and the mutant variant EGFRvIII. TriTE effectively activated T cells and induced targeted killing of GBM cells in patient-derived xenograft (PDX) models. TriTE-mediated cytotoxicity was specific to target-expressing GBM, but spared normal EGFR-expressing cells, including primary human keratinocytes and lung fibroblasts, highlighting its potential safety profile. Compared to a bi-specific T cell engager (BTE) targeting IL13Rα2 alone, intravascular administration of TriTE demonstrated significantly enhanced tumor cell killing in heterogeneous GBM models. To improve pharmacokinetics, we engineered TriTE with a humanized Fc domain, which extended its half-life to approximately 41 hours and enabled its accumulation within intracranial tumors. In survival studies using humanized mice bearing intracranial PDX GBM tumors, TriTE—but not BTE—led to a significant extension of survival, with 45% of mice achieving long-term survival. These results were further validated in a genetically engineered mouse model (GEMM) of de novo GBM, again showing the superior efficacy of TriTE. Together, these findings establish TriTE as a potent, selective, and safe immunotherapeutic agent for GBM. Our results strongly support the advancement of this technology toward clinical development.

• Advancing Precision Oncology Through Alpha Radiation
  Associated Company/University: Oak Ridge National Lab
  Author: Debjani Pal
  

Abstract:
Cancer continues to be a leading cause of death worldwide, despite advances in treatment. Standard approaches like chemotherapy and external beam radiotherapy remain foundational but are often limited by systemic toxicity, off-target effects, and limited efficacy in resistant tumors. One promising, valuable therapeutic alternative could be using short-lived alpha-emitting radioisotopes due to their unique properties, including high linear energy transfer (LET) and highly cytotoxic nature. However, despite its advantages, the therapeutic utility of alpha-emitters (e.g. 225Ac) is limited by challenges such as the nonspecific release of its radioactive daughter products, which can lead to off-target toxicity. Here we present for the first time to our knowledge, biochemical subcellular fractionation studies that shows HER2-specific nanobody ²²⁵Ac conjugate that delivers cytotoxic alpha radiation selectively to HER2-positive breast cancer cells, with minimal signal in HER2-negative cells, underscoring the construct’s selectivity. Additionally, high-grade serous ovarian carcinoma (HGSOC) cells displayed an increased sensitivity to ²²⁵Ac, including in models resistant to small-molecule inhibitors such as prexasertib. The resulting alpha-induced DNA damage led to sustained tumor cell killing, highlighting the potential of this targeted approach. Compared to small-molecule inhibitors, targeted alpha therapies offer higher specificity and prolonged effects, supporting the broad therapeutic potential of ²²⁵Ac based radioligands for treating aggressive and treatment-resistant cancers.

• PAN Biologics: Redefining Cancer Treatment with Precision Tools
  Associated Company/University: PAN Biologics
  Author: Kuntal De
  

Abstract:
PAN Biologics is a biotechnology company developing first-in-class biologics and radiotherapeutics to treat aggressive and treatment-resistant cancers. Our innovation lies in two complementary approaches: a newly developed peptide therapeutic that blocks key oncogenic signaling at the receptor level, and a targeted alpha radioligand therapy delivering highly potent payloads directly to tumor sites. The engineered peptide currently developed by PAN Biologics is designed to engage specific cell-surface receptors that drive cancer progression but without triggering downstream pro-survival or proliferative pathways. This selective binding allows it to act as a functional antagonist, effectively outcompeting endogenous ligands and shutting down tumor-promoting signals. The peptide also serves as a powerful research tool to screen drug candidates in functional systems, addressing a key gap in current precision oncology pipelines that often rely on oversimplified models and nonspecific controls. In parallel, PAN Biologics is advancing a novel radioligand platform built around targeted delivery of Actinium-225, an alpha-emitting isotope with high energy and short path length, ideal for killing individual cancer cells with minimal collateral damage. Our radioligand constructs are based on compact biologics that exhibit strong tumor penetration, rapid clearance from healthy tissue, and precise delivery of radiation payloads, enabling effective treatment of both solid tumors and micrometastases. Together, these platforms offer a powerful synergy: the peptide blocks the upstream signaling that drives tumor growth, while the radioligand delivers cytotoxicity to cells already transformed. Early preclinical studies invitro and in 3D models have shown reduced viability, reduced invasiveness, and minimal off-target effects. PAN Biologics is currently advancing its lead programs toward IND-enabling studies, with issued patents. Our goal is to translate these technologies into life-saving therapies for patients with limited treatment options.

• Programming cells to disrupt the root drivers of cancer
  Associated Company/University: University of Cambridge
  Author: Alexander Evans
  

Abstract:
To overcome solid cancer resistance, multiple problems must be solved simultaneously. Cell and gene therapies remain the only modalities that can be engineered to target cancer and address multiple challenges simultaneously. However, current approaches are fundamentally constrained by poor durability and exclusively targeting surface antigens that are dispensable to tumour survival, leading to inevitable tumour escape. We are bridging the fields of peptide therapy and cellular engineering to develop a novel platform enabling durable, cell-mediated and tumour-specific delivery of synthetic peptides targeting key oncogenes drivers of solid cancers. Our technology is versatile by design: it can be encoded in a single vector and implemented across multiple modalities – including in vivo gene editing – and across indications. Alceus Bio, the University of Cambridge spinout developing the therapeutic platform, will initially focus on creating autologous CAR T therapies modified to persist safely through memory reprogramming, and to deliver a best-in-class cell-penetrant peptide targeting a highly validated oncogene target. Pre-clinical in vivo data has shown transformative improvement over existing competing innovations, highlighting the strong translational potential for cell-based delivery of synthetic oncogene-targeted peptides.

• Riptide Therapeutics: Targeting Telomerase Reverse Transcriptase (TERT) to Overcome Cancer Therapy Resistance
  Associated Company/University: University of Chicago | Riptide Therapeutics
  Author: Stephen Kron
  

Abstract:
Riptide Therapeutics is a preclinical stage spin-out from the Scheidt lab at Northwestern University and the Kron lab at the University of Chicago, focused on targeting telomerase reverse transcriptase (TERT) as a critical driver of cancer therapy resistance. While TERT’s role in maintaining telomeres and enabling replicative immortality is well known—and exploited by ~85–90% of cancers—TERT also supports other cancer hallmarks through noncanonical functions, including deregulated transcription, enhanced oncogenic signaling, resistance to apoptosis, accelerated DNA repair, reduced oxidative stress, and immune evasion. Many tumors appear addicted to TERT, relying on its activity for survival and therapy resistance. Riptide is developing first-in-class small molecules that exploit this broader TERT dependency. Our platform has produced an irreversible covalent inhibitor of TERT's catalytic site, RTTX401, and a prototype TERT degrader, RTTX501. Both agents delay DNA double-strand break (DSB) repair after irradiation in vitro. In vivo, RTTX401 enhances radiation-induced, immune-dependent tumor clearance, supporting its promise as a radiosensitizer. By disrupting the survival mechanisms of TERT-addicted tumors and blocking TERT-dependent resistance, Riptide aims to open a new therapeutic window against some of the most treatment-resistant cancers. The company holds exclusive rights to an issued patent covering RTTX401 and related compounds, with additional filings pending on the use of TERT inhibitors to potentiate anti-tumor immunity and on our novel TERT degraders.

• Next-Generation Asparaginase for ASNS(low) Cancers - Expanding the Therapeutic Reach Beyond ALL
  Associated Company: University of Illinois Chicago | Enzyme by Design
  Author: Arnon Lavie
  

Abstract:
Introduction:
--Asparaginase has been a key component of pediatric acute lymphoblastic leukemia (ALL) treatment since the 1970s
--Mechanism - Depletes circulating asparagine, exploiting cancer cells deficient in asparagine synthetase (ASNS)

Problem:
Traditional asparaginases have:
--Off-target glutaminase activity → toxicity
--Bacterial origin → high immunogenicity
--This limits broader use of asparaginase (e.g., in ASNS(low) AML and solid tumors such as liver, gastric, and colorectal cancers)
--There is an unmet need for a well tolerated asparaginase

Solution:
Novel mammalian asparaginase engineered for:
--No glutaminase activity
--Reduced immunogenicity

Key preclinical results:
Potent anti-tumor activity in:
--ALL (T-cell & B-cell)
--ASNS(low) AML
--ASNS(low) solid tumor models (melanoma, liver cancer)
--Durable suppression of tumor growth
--Well-tolerated in animal models allowing for prolonged asparagine depletion

Future Applications & Impact:
Expands asparaginase utility beyond ALL:
--ASNS(low) AML
--ASNS(low) solid tumors
--Biomarker-driven patient selection (ASNS(low) status) enables precision oncology approach

Represents a next-generation, humanized asparaginase platform with:
--Predictable mechanism of action
--Reduced toxicity
--Broad anti-tumor potential

• Aplexis Advances APX-052: A First-in-Class PLEK2 Inhibitor Targeting Disease Progression in Myeloproliferative Neoplasms
  Associated Company/University: Northwestern University | Aplexis
  Author: Peng Ji
  

Abstract:
Aplexis, Inc., a Northwestern University spinout small business company, is developing APX-052, a first-in-class small molecule inhibitor targeting Pleckstrin-2 (PLEK2)—a key downstream effector of the JAK2-STAT5 signaling axis—with the goal of halting disease progression in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) and preventing transformation to acute myeloid leukemia (AML). Current therapies for MPNs, including JAK inhibitors, provide symptomatic relief but are limited by hematologic toxicity, lack of molecular remission, and eventual drug resistance. Critically, these agents do not prevent leukemic transformation, particularly in patients harboring TP53 mutations, which drive aggressive disease progression and confer resistance to conventional therapies. Aplexis has partnered with the Ji laboratory at Northwestern University to investigate PLEK2, a JAK2-STAT5 effector that integrates proliferative and survival signals through AKT stabilization. Genetic deletion of Plek2 in JAK2V617F murine models reversed myeloproliferation and significantly extended survival without affecting normal hematopoiesis, suggesting a favorable therapeutic index. PLEK2 is markedly overexpressed in MPN patient samples, positioning it as a selective and disease-relevant target. Importantly, Plek2 knockout mice are viable and exhibit only mild, late-onset anemia, supporting the potential safety of targeting PLEK2 in patients. Through structure-based virtual screening and biochemical validation, Aplexis has developed APX-052, a selective PLEK2-binding small molecule that disrupts PLEK2-AKT interactions and abrogates downstream signaling. APX-052 also markedly extended the survival of JAK2V617F and p53 knockout mice by preventing their transformation to AML. Mechanistic studies show that APX-052 impairs the proliferation of MPN cells and destabilizes oncogenic signaling complexes that include AKT, as well as PPIL2, a p53-suppressing component newly identified as part of the PLEK2 signalosome. Aplexis is currently funded by an NIH Phase II SBIR grant and is seeking additional funding to expedite drug development. Supported by exclusive licensing through Northwestern University’s Innovation and New Ventures Office (INVO), Aplexis is building a pipeline around this new therapeutic axis. APX-052 offers a differentiated approach to MPN management by targeting critical disease drivers beyond JAK2, with the potential to delay or prevent leukemic transformation and overcome current therapeutic limitations.

• Development of a Targeted Analgesic for Neuropathic Pain
  Associated Company/University: Northwestern University
  Author: Euan Parnell and Peter Penzes
  

Abstract:
Chronic Neuropathic Pain (CNP) is a widespread and highly damaging disorder, with few therapies available. This paucity of existing therapies is also limited to just a few molecular targets, resulting in a high percentage of low- and non-responding patients who have few therapeutic avenues and continue to suffer from ongoing pain. There is therefore a clear and unmet need for novel targets and therapeutics to extend the available treatments for this devastating disorder. Kalirin has been isolated as a novel therapeutic target with broad and robust mechanistic involvement in CNP. Kalirin is required for aberrant synaptic plasticity, a major component of CNP initiation and maintenance, and therefore represents an exciting target for CNP drug discovery. To drive the development of CNP treatments, we have isolated small molecule inhibitors of kalirin catalytic activity that confirm its validity as a CNP therapeutic target and represent exciting medicinal chemistry starting points for drug development. These compounds have oral bioavailability and blood-brain barrier permeability, no observable toxicity in vitro or in vivo, and provide analgesic relief in preclinical CNP models. These discoveries have the potential to drive the development of a CNP therapy directed at a novel molecular target, facilitate pain relief to CNP sufferers and expand viable therapeutic avenues. Vitally, a novel molecular target would provide additional options to patients non-responsive to existing standards of care and the expansion of CNP therapies is the strongest route to limit the widespread prescription of opioids for CNP, and provide opportunities for opioid cessation. Successful development of a kalirin-targeted CNP treatment may have a transformative impact for patients, and on the CNP market.

• Safer Opioid with Reduced Respiratory Depression
  Associated Company/University: Bluegrass Pharmaeuticals
  Author: Ben Register
  

Abstract:
BG-859 is a μ-opioid selective g-protein ligand with similar pharmacokinetics to fentanyl, but with reduced respiratory depression, a 4-fold increase in peak analgesia duration, and no catalepsy or wooden chest syndrome. Our poster demonstrates these findings across in-vitro and in-vivo models, demonstrating the readiness of this candidate for IND-enabling studies. Recent attention on Fentanyl has highlighted its deadly nature, but it is presently the most is the most widely used opioid by Morphine Milligram Equivalent (MME) volume. In calendar year 2025, the Drug enforcement agency authorized the production and sale of >290 Billion MME units of fentanyl. Our results demonstrate that BG-859 is a promising candidate to replace fentanyl in clinical practice, greatly reducing harm to patients at risk for complications of Opioid Induced Ventilatory Impairment.

• Targeting unwanted adverse effects of opioid analgesics without blocking analgesia: 6beta-naltrexol potently reduces opioid dependence and hyperalgesia
  Associated Company/University: Aether Therapeutics
  Author: Wolfgang Sadee and Aaron Schuchart
  

Abstract:
Opioid pain therapy is highly effective but encumbered by adverse effects, limiting both short and long-term treatment. Unwanted effects include dependence, tolerance, and drug craving – drivers of opioid use disorder – and numerous ADRs such as hyperalgesia, constipation, ileus, cognitive decline, sleep disturbances, constipation, pruritic, and more. We have shown that 6beta-naltrexol potently reduces opioid dependence and hyperalgesia in mice, rats, and guinea pigs, and appears to reduce heroin self-administration in rhesus monkeys (ongoing study). 6beta-Naltrexol also potently prevented neonatal opioid withdrawal symptoms in pups born to guinea pigs when co-administered with methadone during pregnancy, promising effective therapy of neonatal opioid withdrawal syndrome (NOWS) – largely resistant to current treatments. Effective doses of 6beta-naltrexol were 10-100-fold below those blocking opioid analgesia. Since opioid dependence and hyperalgesia result from inflammatory processes triggered by opioid analgesics, and many other adverse effect also involve inflammation, 6beta-naltrexol has the potential to offer a novel approach to safer and more effective opioid pain therapy. Whereas 6beta-naltrexol is known as a relatively weak opioid antagonist, exceptional potency as a dependence modulator stems from a novel mechanism: dependence appears to be driven by elevated sustained ligand-free basal signaling of the -opioid receptor (MOR) (no bound agonist), which is gradually reversed with high potency by 6beta-naltrexol to the silent ground state, reversing dependence (Sadee, Molecules 2023, 28, 6375. molecules28176375). Aether plans to develop co-administration and co-formulations of 6beta-naltrexol with opioid analgesics to improve pain therapy, facilitate weaning strategies, and prevent NOWS. In part funded by NIH research grants.

• Unlocking the Promise of Regenerative Medicine for Neurological Injuries and Disorders
  Associated Company/University: Amphix Bio
  Author: Nick Sather
  

Abstract:
Amphix Bio is pioneering an innovative new modality in regenerative medicine to address neurological injuries and disorders. Current regenerative approaches often lack potency or scalability, but Amphix Bio's scalable platform combines potent bioactivity with programmable peptide technology to overcome these limitations. Our Supramolecular Therapeutic Peptide (STP) technology encodes a blueprint for tissue regeneration, combining receptor-activating drugs and tissue scaffolds in one therapeutic. This technology has shown promising results in rodent models of acute spinal cord injury (SCI) and other neurological conditions, demonstrating robust functional recovery and neural tissue regeneration. Amphix Bio's AMFX-200 therapeutic represents a paradigm shift in treating neurological diseases, regenerating damaged neural tissue and restoring lost function through multiplexed targets. The treatment activates both FGFR1 and ITGB1 receptors, promoting axon regrowth, new blood vessel formation, remyelination, neuron survival, and reduced inflammation and glial scarring. Safety assessments in uninjured animals have shown no neuropathic pain, immunotoxicity, or spasticity from AMFX-200 administration. The company's platform technology was developed over the past 20 years in the Stupp laboratory at Northwestern University and leverages over $100M in past R&D funding, 30+ issued patents, 150+ peer-reviewed publications, the know-how from over 1000 STP molecules. Amphix Bio's breakthrough STP technology and lead AMFX-200 asset offer unprecedented bioactivity and scalability, promising to transform the landscape of regenerative medicine for neurological injuries and disorders.

• ENCUE INC: Developing Drugs to Treat Neurological and Neuropsychiatric Disorders: A Novel Approach for the Treatment of Rett Syndrome
  Associated Company/University: Northwestern University
  Author: Alicia Loffler
  

Abstract:
ENCUE Inc. is a preclinical-stage biotech company advancing a pipeline of small molecule therapeutics targeting CNS disorders with high unmet need. Our pipeline targets both large and orphan indications, including Alzheimer’s, traumatic brain injury (TBI), and rare diseases such as Rett and Fragile X and 22q schizophrenia. Our lead asset, NQ-13, offers a novel approach for treating Rett Syndrome, a rare neurodevelopmental disorder affecting girls, caused by MECP2 gene mutations in 90-95% of cases. NQ-13 is an oral bioavailable, low molecular weight (<500 Da) peptide derived from a novel class of IGFBP2 mimetics. It is highly soluble, easy to synthesize, and exhibits excellent blood-brain barrier penetration with a therapeutic index >1000 in rodent models, offering a robust drug-like profile. Mechanistically, NQ-13 selectively binds and activates IGF2 receptors (EC50 = 0.1 nM) without interacting with IGF1 or insulin receptors, minimizing off-target effects. In vivo, NQ-13 promotes de novo synthesis of IGF2, NMDA, and AMPA receptors; key to enhancing synaptic plasticity and cognitive resilience. Preclinical data show significant cognitive gains across multiple learning paradigms in both healthy and cognitively impaired rodents. In Rett syndrome models, oral administration of NQ-13 (0.1–1.0 mg/kg) rapidly and robustly reversed behavioral and physiological deficits, including motor, breathing, and cognitive impairments, suggesting being 1000x more potent than Trofinetide (Daybue®), the current FDA-approved treatment. NQ-13 normalized elevated MeCP2 levels in Rett mice to baseline within one-hour post-dose, indicating potential disease-modifying activity. NQ-13’s pharmacodynamic response, along with its oral bioavailability and safety margins, positions NQ-13 as a leading candidate for Rett Syndrome. NQ-13 completed IND-enabling studies and is advancing towards IND submission. ENCUE is exploring strategic partnerships to accelerate clinical development and expand its adjacent indications.

• Discovery and development of first-in-class TDO2 inhibitors for uterine fibroid treatment
  Associated Company/University: Northwestern University
  Author: Ping Yin and Serdar E. Bulun
  

Abstract:
Uterine leiomyoma (or fibroids) are benign tumors that affect 70-80% of reproductive-aged women and can cause recurrent pregnancy loss, excessive uterine bleeding, and severe pain. Current treatment options are limited and often invasive—a hysterectomy permanently removes the uterus, while other invasive procedures like myomectomy and embolization do not always prevent fibroids from returning. The only FDA-approved medications, GnRH modulators (Myfembree, Oriahnn, Lupron), provide temporary symptom relief but do not shrink the fibroids and cause hormone-related side effects, making them unsuitable for long-term use. As a result, millions of women are left without effective, long-lasting treatment options, highlighting the urgent need for a therapy that directly targets fibroid growth rather than just managing symptoms. Research has found that over 70% of fibroids have a genetic mutation in the MED12 gene, which helps fibroid cells survive and grow. The Bulun lab has identified tryptophan 2,3-dioxygenase (TDO2) as a key driver of this process. Studies show that blocking TDO2 can shrink fibroids and trigger cell death, making it a promising new drug target. Based on these findings, the Bulun lab is developing a first-in class, non-hormonal oral therapy that selectively blocks TDO2. The team is optimizing and refining TDO2 inhibitors, confirming their effectiveness in cell and mouse models and assessing their ability to block TDO2 without affecting other enzymes. Future steps include safety studies and drug formulation, which will position the most promising drug candidate for clinical testing and commercialization. Given the lack of non-hormonal treatments for fibroids, this drug development program has the potential to pioneer a groundbreaking therapy—a long-term, non-invasive solution for millions of women.

• (R)-ND-336 for Treatment of Diabetic Foot Ulcers
  Associated Company/University: University of Notre Dame
  Author: Mayland Chang
  

Abstract:
Diabetic foot ulcers (DFUs) are a complication of diabetes. A single drug (becaplermin containing platelet-derived growth factor) has been approved in the past three decades by the FDA for DFUs, however it is seldom used because of its modest efficacy. The standard-of-care for DFUs is debridement, off-loading, and infection control with antibiotics, with hyperbaric oxygen therapy being the treatment of last recourse. The paucity of understanding what prevents the diabetic wound from healing and the lack of suitable treatment options result in more than 150,000 lower-limb amputations in the United States alone every year. A new paradigm for treatment of DFUs based on the knowledge of what prevents DFUs from healing led to the discovery of (R)-ND-336. (R)-ND-336 is a potent inhibitor of active matrix metalloproteinase (MMP)-9. We documented the presence of two active forms of MMPs, MMP-8 and MMP-9, in human DFUs. Our studies revealed that MMP-8 promotes wound healing, whereas MMP-9 prevented it. Furthermore, as severity of DFUs increases, so does the level of MMP-9. A feature of (R)-ND-336 is that it is highly selective for MMP-9 and leaves MMP-8 unscathed, which favors the natural repair mechanisms to proceed in parallel to elimination of MMP-9 as the detrimental factor. (R)-ND-336 showed better efficacy than becaplermin in diabetic mice. (R)-ND-336 is a first-in-class topical treatment that has completed IND-enabling studies and is poised to enter clinical trials for treatment of DFUs.

• Targeted Macrophage Delivery of a Dexamethasone Prodrug (101-PGC-005) Enables Potent Anti-Inflammatory Activity with Reduced Systemic Toxicity: Preclinical, Phase 1 & Phase 2 Clinical Results
  Associated Company/University: 101 Therapeutics
  Author: Alec Goldberg
  

Abstract:
Systemic corticosteroids are potent anti-inflammatory agents, but their utility is limited by immunosuppression, metabolic toxicity, and hypothalamic-pituitary-adrenal (HPA) axis suppression. 101-PGC-005 (’005) is a first-in-class dexamethasone prodrug that targets CD206+ macrophages using a mannose-conjugated, pH-sensitive linker, enabling intracellular steroid release only at sites of inflammation. Targeting CD206 presents technical hurdles—low monovalent binding affinity (~3.5 mM KD), intracellular delivery, and linker stability—that have been overcome in the design of ’005. Cellular assays confirmed selective uptake, lysosomal release, and apoptosis in CD206+ macrophages. ’005 suppressed IL-6 and TNF-α while sparing CXCL10, suggesting preserved antiviral immunity and reduced HPA-disrupting signals. In murine models of viral pneumonitis, dengue, LPS-induced sepsis, and pulmonary fibrosis, ’005 improved survival, reduced cytokine load, and maintained viral clearance. Pharmacokinetics showed stable prodrug in plasma and CSF with no systemic dexamethasone release. A GLP toxicology program in rats demonstrated reduced lymphoid and hematologic toxicity compared to dexamethasone, with reversibility after cessation. Two Phase 1 studies confirmed safety, linker stability, and dose-proportional PK/PD. In a Phase 2 trial (n = 62) in hospitalized COVID-19 patients, ’005 met its primary endpoint of non-inferiority to dexamethasone and achieved faster clinical recovery, earlier discharge, and greater viral clearance by Day 3, with fewer steroid-associated side effects. By localizing corticosteroid action and sparing systemic cortisol signaling, ’005 may facilitate HPA axis recovery—a central unmet need in chronic corticosteroid therapy. This platform has broad potential across severe acute and chronic inflammatory conditions, including cytokine storm, autoimmunity, cancer, and rare macrophage-driven diseases.

• Development of 3D Printed PLG-Based Liver Tissue Therapeutic for the Treatment of Alcoholic Liver Disease and Liver Failure
  Associated Company: Dimension Bio
  Author: Rafal P. Witek
  

Abstract:
Introduction: Alcoholic liver disease (ALD) is a major cause of liver failure-related deaths globally. Severe forms of ALD, such as alcohol-associated hepatitis (AH) and severe alcohol-associated hepatitis (SAH), have high mortality rates up to 50% at 28 days for AH and up to 70% at six months for SAH. While existing treatment options offer limited benefit, liver transplantation remains the only curative solution. Alternatively, an ectopic implant containing hepatocytes (main liver cells), capable of providing both immediate and sustained liver function, could be developed and serve as a bridge to liver transplantation or recovery. In this study, we explore the potential of 3D printed poly lactide-co-glycolide (PLG) scaffolds as a more effective means of delivering high-density functional hepatocytes through minimally invasive subcutaneous implants, offering a novel solution for liver failure treatment. Methods: 3D printed PLG scaffolds were seeded with primary human hepatocytes. In vitro, cell-laden scaffolds were cultured for 2+ weeks and assessed for viability, albumin and urea synthesis, and CYP3A4 activity. In vivo, scaffolds were implanted subcutaneously in NOD SCID mice for one month, with circulating human albumin (hALB) measured over time. Explants were analyzed via histology/IHC for tissue integration and vascularization. Results: In vitro results showed that seeded scaffolds produced stable albumin and urea secretion for over two weeks while maintaining metabolic activity. In vivo, steady hALB levels persisted for up to four weeks post-implantation. Histological analysis at one month revealed dense vascular networks in PLG scaffolds. Conclusions: 3D-printed porous PLG scaffolds provide a promising approach for ectopic liver implants. Our data demonstrates efficient hepatocyte delivery and sustained functional phenotype (synthetic and metabolic), supported by robust vascularization. Future studies will evaluate the efficacy of using PLG scaffolds to deliver hepatocytes for the therapeutic treatment of liver conditions characterized by rapid loss of hepatic function, such as liver failure.

• TA Benzothiophene-based Antimicrobial Agent Active Against MRSA
  Associated Company/University: University of Notre Dame
  Author: Christian Melander
  

Abstract:
Methicillin-resistant Staphylococcus aureus (MRSA) represents an ongoing health challenge. Despite new therapeutic advances, such as fifth generation cephalosporins and lipoglycopeptides, resistance to these agents is emerging. We have discovered a novel benzothiophene that has broad acting antimicrobial activity against diverse MRSA isolates, including those from Cystic Fibrosis patients, activity is retained in the presence of fetal bovine serum, the compound has a low frequency of resistance, and low mammalian cell toxicity. Mechanism of action studies have indicated these compounds target penicillin binding proteins, including the alternative penicillin binding protein 2a (PBP2a). Evolved mutants that are resistant to antimicrobial activity of this compound are still susceptible to its PBP2a activity, and the compound acts as an adjuvant for other beta-lactams, such as oxacillin. Preliminary in vivo studies have shown efficacy in a wound model of infection.

• Allosteric sirtuin-2 modulators are pathogen-agnostic anti-infectives that inhibit both viruses and bacteria, and have applications beyond infectious disease
  Associated Company/University: Evrys Bio
  Author: Lillian Chiang
  

Abstract:
Sirtuin-2 (SIRT2) is an NAD+-dependent lysine de-acylase that regulates cellular metabolic reprogramming by post-translationally removing marks from histones and many other nuclear and cellular protein targets. A metabolic switch occurs during many physiological processes, including somatic reprogramming, tumorigenesis, and immune cell differentiation, activation, and tolerance. Indeed, intracellular infection by viruses or bacteria, often invokes metabolic reprogramming that the pathogen needs to coordinate nuclear and cellular events with the changing host-cell metabolic status to achieve optimal productive infection. Evrys Bio has developed a portfolio of >1000 SIRT2-selective small molecules that do not compete with NAD+ or the (peptide) target of SIRT2 post-translational modification. Instead, these are allosteric modulators that change the relative rate of de-acylation mediated by SIRT2 for targets differing in acyl-chain modification and/or peptide sequence. Additionally, even at saturating concentrations, these allosteric modulators never completely shut down SIRT2 enzyme function. As a result, Evrys is developing multiple anti-infective drugs that provide “fit-to-purpose” SIRT2 modulation and therapeutic window (compared to uninfected cells) for (1) opportunistic viruses that threaten immunocompromised patients including actively immunosuppressed transplant recipients, (2) chronic hepatitis B, (3) pan-biothreat RNA viruses, and (4) diverse gram +/- intracellular bacteria. Preclinical data from cell-based and animal models of tolerability and pathogen challenge will be presented including for Evrys’ first IND-ready candidate, EV 100, to prophylactically treat immunosuppressed transplant recipients. Interestingly, exploratory research indicates that Evrys’ SIRT2 portfolio provides bioavailable and well-tolerated SIRT2 modulators as proof-of-concept for application to non-infectious disease conditions.

• Imidazole-Linked Quinone Methide Precursors Lead to Broad-Scope Efficacy via a Proposed Role of Imidazole in Reactivation and Resurrection of OP-inhibited/aged Acetylcholinesterase
  Associated Company/University: Ohio State University
  Author: Christopher Hadad
  

Abstract:
Acetylcholinesterase (AChE) is a serine hydrolase enzyme responsible for the hydrolysis of acetylcholine (ACh) and is found primarily in the central and peripheral nervous systems. Organophosphorus (OP) compounds are neurotoxicants that target AChE by covalent inhibition of the serine residue, which prevents the hydrolysis of ACh, leading to respiratory failure. FDA-approved therapeutics can return the OP-inhibited form of the enzyme back to the native form but are ineffective against the OP-aged form of the enzyme, which is formed by an O-dealkylation. Our team has observed that quinone methide precursors (QMPs), a category of compounds that contain a Mannich phenol moiety, can recover (resurrect) the activity of OP-aged AChE as well as perform reactivation of OP-inhibited AChE. 23 unique frameworks with imidazole linked to the QMP framework were synthesized. These QMPs were tested against 8 OP-inhibited forms and 4 OP-aged forms of AChE. Efficacies of the QMPs were confirmed by in vitro biochemical studies using Ellman’s assay to determine the relative activity of the enzymes being returned to the native state. First, we found that these QMPs were highly effective at the reactivation of methylphosphonate-inhibited (i.e., OEt-, OiPr-, OiBu-), phosphoramidate-inhibited (i.e., (OEt)(NMe2)-) and organophosphate-inhibited (i.e., from methyl paraoxon and ethyl paraoxon) AChE, being able to recover over 50% of the native enzyme from each of these inhibited forms. One framework also does well against the OCyclohexyl methylphosphonate-inhibited form and (diisopropyl fluorophosphate)-inhibited AChE, recovering nearly 20% of the native enzyme from each. Many frameworks also do well in resurrection, with some providing up to 65% recovery of the native enzyme from ethoprophos-aged AChE, further cementing their superiority against FDA-approved oximes. We will also present kinetic results for the imidazole-based QMP compounds.

• A Novel Therapeutic for Cardiac Arrest
  Associated Company/University: University of Illinois Chicago
  Author: Jing Li
  

Abstract:
Cardiac arrest is a leading cause of death in the USA, affecting 650,000 people annually with an overall survival rate of less than 10% for patients outside the hospital. Cardiac arrest has a greater public health impact than lung and breast cancer, HIV or stroke combined. Despite this public health challenge, no drugs exist that improve cardiac arrest outcomes. The standard of care for cardiac arrest includes defibrillation, cardiopulmonary resuscitation CPR, and temperature management for optimal recovery. For those patients who achieve return of spontaneous circulation (ROSC), targeted temperature management (32-37.5°C) immediately after ROSC can improve neurological function and survival. Pre-clinical studies show that earlier cooling a few degrees during CPR prior to ROCS is highly protective but is almost impossible to implement in the clinical setting. A therapeutic agent that exerts comparable or more profound protection without the need for physical cooling could transform cardiac arrest care. We have developed an injectable rapidly acting peptide, UIC-101. It is a 20 amino acid synthetic peptide that inhibits the binding of phosphatase PHLPP1 to its membrane adaptor NHERF1, preventing deactivation of Akt, a pivotal kinase that regulates multiple cellular events related to metabolism and survival. UIC-101 reaches the heart and brain within minutes of intravenous injection and rapidly activates Akt and enhances metabolic recovery in these vital organs. When administered intravenously during CPR, UIC-101 markedly improves neurologically intact survival in mouse and swine models of cardiac arrest. These preclinical studies suggest that UIC-101 could be a first-in-class drug for cardiac arrest that addresses a substantial unmet emergency medical need. We have developed a robust intellectual property estate with coverage in the US, Europe, Canada, Australia, and Japan. UIC-101 has potential to expand its treatment landscape into a platform biotechnology for ischemic tissue rescue.

• A cell-permeable peptide therapeutic for the treatment of reperfusion injury
  Associated Company/University: Laborecom Therapeutics
  Author: Lucas Shores
  

Abstract:
The most deadly type of heart attack, ST-segment elevation myocardial infarction (STEMI) involves blockage of the coronary artery and affects approximately 750,000 people annually in the US. While percutaneous coronary intervention (PCI) saves lives by restoring blood flow to the ischemic heart, as much as half of the long-term damage to the heart is due to the reperfusion injury, for which there is no approved therapeutic shown to significantly reduce resulting cardiac infarct size. Larger infarcts are strongly associated with reinfarction, hospitalization with heart failure, and all-cause mortality. Laborecom Therapeutics Inc. is developing a novel therapeutic peptide, TAT-KLC1c, to reduce myocardial reperfusion injury and infarct size. While other therapeutics have attempted to reduce reperfusion injury by direct immune suppression or reduction in mitochondrial stress, this approach targets a motor protein expressed in endothelial cells to prevent transendothelial migration. This allows our therapeutic to work in the post-reperfusion period, as opposed to being required to be delivered prior to reperfusion—a major limitation of previous attempts at treating reperfusion injury. Importantly, TAT-KLC1c does not impair wound healing in rodent models, despite robust inhibition of inflammatory cell infiltration. Testing of TAT-KLC1c in swine models of myocardial infarction and reperfusion injury shows a 50% reduction in infarct size 72 hours post-reperfusion compared to scrambled peptide controls. With a recent favorable Phase I SBIR review, we anticipate advancing TAT-KLC1c through the next stage of lead optimization for myocardial reperfusion injury, with the goal of addressing this critical unmet need.

• Next-Generation Oral Small Molecule Therapeutics for Obesity and Metabolic Disease Synergistic in Combination with Incretin Therapies
  Associated Company/University: State 4 Therapeutics
  Author: Robert Williams
  

Abstract:
Obesity and its related comorbidities, including type 2 diabetes, heart failure, and nonalcoholic fatty liver disease, represent one of the most unmet needs globally. While incretin-based therapies such as GLP-1 receptor agonists have transformed obesity care, limitations remain in terms of tolerability, lean mass preservation, and breadth of efficacy. State 4 Therapeutics is developing novel, orally available small molecules designed to synergize with incretin and other nutrient-stimulated hormone therapies. Our approach enhances metabolic signaling pathways implicated in central and peripheral energy balance, driving durable weight loss while preserving lean muscle mass. Our lead compound demonstrates single-agent efficacy in preclinical models of both obesity and type 2 diabetes, with synergistic effects when used in combination with incretin therapies. These effects include improved glycemic control and muscle augmentation. The compound is well tolerated and has favorable drug-like properties supportive of once-daily oral dosing. Supported by non-dilutive funding from the Blavatnik Fund for Innovation at Yale, we are advancing toward development candidate (DC) nomination. We are now raising a seed round to enable IND-enabling studies and first-in-human clinical development. By unlocking novel, complementary mechanisms, State 4 aims to expand the therapeutic potential of next-generation metabolic therapies and improve outcomes for patients with obesity and related disorders.

• Enzyme Replacement Therapy for GM1 Gangliosidosis: Following a Proven Path to Clinical Success
  Associated Company/University: Cure GM1 Foundation
  Author: Dawn Blessing
  

Abstract:
Enzyme Replacement Therapy (ERT) is a proven modality for the treatment of Lysosomal Storage Disorders (LSDs); seventeen ERTs have been approved for twelve LSDs to date. GM1 gangliosidosis is a fatal neurodegenerative disease that primarily affects children. It is caused by mutations in the GLB1 gene, which encodes lysosomal beta-galactosidase, an enzyme that catalyzes the stepwise degradation of multiple galactose-containing substrates in the lysosome. The accumulated damage to the nerve cells in the brain and spinal cord cause clinical deterioration over time; children eventually lose the ability to walk, to talk, and to eat. Proof of concept for ERT for GM1 was demonstrated in the GLB1 KO mouse model of disease [Source: Chen 2020]. In this study, 100 micrograms of human beta-galactosidase enzyme were delivered via intra-cerebroventricular (ICV) injection once weekly for eight weeks. Beta-gal protein was evidenced by Western blotting in brain, liver, and bone marrow of treated mice. Broad bilateral biodistribution throughout the brain was confirmed by MS and substrate was reduced to near normal levels. To build upon these efforts, the Cure GM1 Foundation funded a dose ranging study in the GLB1-deficient mouse model at Tega Therapeutics. In this study, doses of 10 micrograms, 30 micrograms, and 100 micrograms were dosed via ICV injection and evaluated over a period of 24 weeks. Both biochemical and behavioral outcomes were captured, including beta-gal enzyme levels, reduction of GM1 ganglioside, and the rotarod performance test. Data analysis is ongoing. More recently, the Cure GM1 Foundation has funded cell line development for manufacture of enzyme for IND-enabling toxicity studies and future clinical studies. The Foundation intends to hold a pre-IND meeting with FDA in early 2026 to confirm our proposed clinical development path forward.

• Development of DT678 and Clinical Studies to Evaluate the Antiplatelet Properties of DT-678 in Acute Coronary Syndrome Patients and Healthy Volunteers
  Associated Company/University: Diapin Therapeutics
  Author: Jessica Reed
  

Abstract:
DT-678 is a novel prodrug being developed for the treatment of acute coronary syndrome (ACS), stroke and myocardial infarction (MI). When metabolized DT678 generates the active metabolite (AM) of clopidogrel. DT678 has completed nonclinical IND enabling studies, 6 and 9m chronic toxicology studies and IND’s have been filed in China and the US. In nonclinical studies DT678 has been shown to reduce bleeding and show neuro and cardioprotective benefits compared with clopidogrel. DT678 is being developed via the accelerated 505b2 pathway in the US. DT678 was designed to overcome clopidogrel high on-treatment platelet reactivity (HTPR). DT678 was studied in Chinese ACS patients and healthy volunteers. A total of 300 ACS patients naive to P2Y12 inhibitors were recruited and genotyped for CYP2C19 alleles. Blood samples were drawn before and after administration of 600 mg clopidogrel. DT678 was applied ex vivo to whole blood samples to examine its antiplatelet effects. Platelet reactivity index (PRI) and plasma AM concentrations were determined. Patient effects were analyzed based on their CYP2C19 genotypes. To further examine the effectiveness of DT678 in vivo, 20 healthy volunteers in a Phase I clinical trial were treated with a single dose of 3 mg DT678 or 75 mg clopidogrel. The pharmacokinetics and pharmacodynamics in different CYP2C19 genotype groups were compared. In ACS patients the CYP2C19 genotype, body mass index (BMI), hyperuricemia, and baseline PRI were significantly associated with HTPR. Addition of DT-678 ex vivo decreased baseline PRI regardless of CYP2C19 genotypes, overcoming clopidogrel HTPR. This finding was also confirmed in healthy volunteers receiving 3 mg of DT-678 or clopidogrel 75 mg. These results suggest that DT-678 effectively overcomes clopidogrel HTPR resulting from genetic and/or clinical factors in Chinese ACS patients and healthy volunteers, demonstrating its potential as an improved antiplatelet therapy suitable for all patients.

• PiggyBac Transposon-Based Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB)
  Associated Company/University: University of Chicago
  Author: Xiaoyang Wu
  

Abstract:
Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating genetic skin disorder caused by mutations in the COL7A1 gene, leading to deficient type VII collagen and fragile, blistering skin. We have developed a novel non-viral gene therapy approach using the PiggyBac transposon system to stably reintroduce COL7A1 into patient-derived keratinocytes. Patient skin biopsies were used to isolate keratinocytes, which were genetically corrected ex vivo and expanded for autologous skin grafting. In vitro analysis confirmed robust and stable re-expression of type VII collagen. Our first-in-human application (investigator initiated clinical trial) demonstrated successful engraftment of the corrected skin graft, marking a promising step toward durable, gene-based therapy for RDEB.