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Panel Discussion: Peptides as Radiopharmaceuticals
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Aaron Enke
Sr. Director, Clinical Science, 3B Pharmaceuticals GmbH

Peptide Radiopharmaceutical Panel

Abstract

3B Pharmaceuticals GmbH (3BP) is a German biotechnology company developing targeted radiopharmaceutical drugs and diagnostics for oncology indications with a high unmet medical need. As a leader in peptide discovery and optimization, 3BP has built a technology platform extending from hit identification to early clinical development.
The company was founded in 2008 by a team of renowned experts in peptide drug discovery and nuclear medicine from Berlin, Bern and Basel.

Bio

For more than 20 years, Aaron has worked in the biotech and pharmaceutical industry in the clinical evaluation and development of cancer therapeutic and diagnostic agents. Since 2019, Aaron has been working to develop peptide-based radioligand cancer theranostic agents, including Ga-68 and F-18 labeled PET tracers paired with therapeutic agents chelated with ionizing radioligand payloads.

Past YI Award Update Lecture
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Danny Chou
Associate Professor, Stanford University

Insulin Receptor Antagonists For Treating Hyperinsulinism

Abstract

The area of insulin receptor (IR) antagonism represents a significant but largely untapped research field with a promising potential for advancing our understanding of insulin signaling, and consequently, driving the development of innovative therapeutic strategies for metabolic disorders. Despite the numerous studies on insulin analogs with agonistic properties—owing to their critical role in diabetes treatment—the investigations into IR antagonists are sparse. Our recent discovery of an antagonistic insulin derivative represents a promising starting point for developing new IR antagonists using structure-based designs. Using this strategy, we have been able to identify potent IR antagonists, which have been demonstrated to restore normoglycemia in disease models of hyperinsulinism.

Bio

Danny Chou is an Associate Professor of Pediatrics (Endocrinology and Diabetes) at Stanford University. He received his PhD from Harvard University, working in the lab of Prof. Stuart Schreiber. His Ph.D. research involved the identification of suppressors of cytokine-induced apoptosis in pancreatic beta cells. He then moved to MIT, where he was a JDRF Postdoctoral Fellow in Department of Chemical Engineering. He worked under the guidance of Profs. Robert Langer and Daniel Anderson, focusing on the development of glucose-responsive insulin derivatives. Danny started his independent career in Department of Biochemistry at University of Utah in August, 2014. At Utah, Danny's research focused on protein and peptide therapeutics for the treatment in Type 1 Diabetes and other human diseases. In 2020, Danny moved his research lab to Stanford University to continue their efforts in developing novel insulin therapeutics. His laboratory has received funding support from NIH, DoD, JDRF and American Diabetes Association. Danny has received recognitions including an American Peptide Society Early Career Lectureship, Boulder Peptide Society Young Investigator Award, JDRF Career Development Award, Vertex Scholar, JDRF Postdoctoral Fellow and ADA Junior Faculty Award.

Panel Discussion: Peptides as Radiopharmaceuticals
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Kaveh Matinkhoo
Associate Director, Chemistry, Alpha-9 Oncology

Peptide Radiopharmaceutical Panel

Abstract

Alpha-9 Oncology is a leading clinical-stage radiopharmaceutical company advancing a distinctive portfolio of targeted cancer therapies. Our bespoke molecules are designed to deliver precise, effective treatment by selectively targeting cancer cells with high tumor specificity and excellent stability.
Radiopharmaceuticals offer transformative outcomes, demonstrating impressive efficacy and safety in patients who have exhausted multiple lines of treatment. This modality enables rapid, cost-effective progression from bench to bedside. Early human studies validate target engagement and ensure robust payload delivery to tumors, significantly de-risking clinical development.
Our systematic development approach is supported by state-of-the-art infrastructure and deep discovery and production expertise, facilitating efficient clinical translation and scalable manufacturing. Each Alpha-9 molecule is built from four key components – binder, linker, chelator, and radioisotope – optimized through an iterative, precision-driven design process.
At Alpha-9, we’re not just advancing cancer care – we’re illuminating new possibilities in precision medicine.

Bio

Dr. Kaveh Matinkhoo is a biotech professional with expertise in peptide and medicinal chemistry, as well as radiopharmaceutical development. He currently leads chemistry initiatives at Alpha-9 Oncology, where he directs the design and synthesis of targeted radiopharmaceuticals for cancer treatment.
Dr. Matinkhoo earned his Ph.D. in Chemistry from the University of British Columbia, where he achieved the first total synthesis of α-amanitin – a highly complex bicyclic peptide. This breakthrough laid the foundation for its application in targeted cancer therapeutics.
Throughout his career, he has led chemistry teams within cross-functional drug discovery programs, with a focus on peptide and small molecule synthesis, payload optimization, and linker development. Before joining Alpha-9, he held scientific roles at Enveric Biosciences and Sygnature Discovery (North America), contributing to the advancement of novel small molecules and peptide-based therapies for oncology and central nervous system disorders.
As a scientific leader, Dr. Matinkhoo has played a pivotal role in translating early discovery efforts into development-ready candidates. He is a co-inventor on multiple U.S. patents and has authored publications in top-tier journals, including cover articles in Journal of the American Chemical Society and Chemistry – A European Journal. His work integrates synthetic chemistry with translational oncology and precision medicine.

The identification of selective, high-affinity ligands for membrane receptors and other protein targets is a critical step in the development of novel therapeutics. For small-molecule drug discovery, high-throughput screening (HTS) enables the rapid evaluation of 10⁵–10⁶ compounds per day through automated platforms. In contrast, for biologics such as peptides, proteins, and nucleic acids, selection technologies like phage, mRNA, ribosome, and yeast display offer significantly higher diversity, routinely screening libraries ranging from 10⁹ to 10¹³ variants. By implementing smart selection and deselection strategies, ligands with affinities in the low nanomolar range can often be identified.
Previously, we developed a synthetic strategy for the generation of multicyclic peptides [2]. We have now integrated this platform with mRNA display to enable the discovery of bioactive multicyclic peptides. In this presentation, we share initial findings on potent and selective multicyclic peptide binders targeting Frizzled-5 (FZD-5) and an anti-CCR7 monoclonal antibody, with affinities in the double-digit nanomolar range. Control experiments highlight the critical role of each individual peptide loop in target engagement. Furthermore, the multicyclic peptides exhibit markedly enhanced proteolytic stability compared to their linear or monocyclic counterparts. Together, these results demonstrate the readiness of this multicyclic peptide platform for broader application in the discovery of next-generation peptide therapeutics.

AI/Machine Learning with Peptides Workshop
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Daniela Kalafatovic
Associate Professor, University of Rijeka

AI/Machine Learning Worshop

Abstract

The discovery of active peptides, such as antimicrobial, antiviral, catalytic, or self-assembling is challenging, due to the vast search space and limited understanding of how peptide sequences correlate with desired activities and/or functions. The exponential growth of the peptide permutation space with increasing sequence length makes it difficult to explore all possibilities efficiently. To avoid expensive and time-consuming guesswork and experimental failure, we combine machine learning (ML)-based
predictions with genetic algorithm-based optimizations to accelerate peptide discovery. ML can find patterns or regularities in data, build mathematical models based on the theory of statistics and make up for the lack of knowledge.

We curated a dataset of experimentally validated self-assembling peptides and combined aggregation propensity data from molecular dynamics (MD) simulations with a sequential properties representation scheme to train a neural network classifier able to identify peptides with self-assembly propensity. The ML classifier achieved 81.9% accuracy, outperforming the current state-of-the-art models. Furthermore, we developed a flexible and adaptive generative model based on the ML-driven genetic algorithm that allows for a directed search of the sequence space by promoting self-assembly propensity. This enabled the discovery of sequences in unexplored regions of the peptide space, with low similarity to the dataset, which were validated using MD simulations and experiments [1]. This approach not only improves the efficiency of the search but also contributes new knowledge to expand existing peptide datasets, driving future advancements in the field.

[1] Njirjak, M., Žužić, L., Babić, M., Janković, P., Otović, E., Kalafatovic, D., Mauša, G. (2024) Nat. Mach. Intell., 6, 1487–1500.

Bio

Daniela Kalafatovic is Associate Professor at the University of Rijeka, where she was Head of Medicinal Chemistry Division from 2021 to 2024. She received her Ph.D. degree in chemistry from the University of Strathclyde in 2015. After the PhD, she was a Research Associate at the Advanced Science Research Centre, City University New York,
Nanoscience initiative. In 2016, she joined the Institute of Research in Biomedicine in Barcelona as a Marie-Curie cofund postdoctoral fellow. She began her independent career as Assistant Professor in 2019 at the University of Rijeka. She is the holder of a major national project for young researchers, the Croatian Science Foundation starting grant entitled “Design of short catalytic peptides and peptide assemblies” (DeShPet, UIP-2019-04-7999) and since 2024 she is Action Chair of the COST Action
“Searching for nanostructured or pore forming peptides for therapy” (CA23111) that has more than 330 participants from over 35 countries. She is also leading several University founded projects. She published more than 25 articles with the recent Nature Machine Intelligence worth mentioning.

Spotlight on Discovery
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Stephanie Seminara
Chief, Reproductive Endocrine Unit, Mass General Brigham

A Kiss to Remember

Abstract

KISS1 encodes a 145 amino acid peptide that is processed into various C-terminal fragments, all of which bind and activate its G protein coupled receptor KISS1R (formerly known as GPR54). KISS1R signaling has a fundamental role in the physiology of the reproductive axis and is required for pulsatile secretion of gonadotropin hormone releasing hormone (GnRH) as well as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) at puberty. The kisspeptin system is also present in organs outside the reproductive tract including the liver and bone. This presentation will review the discovery of the kisspeptin signaling system, its C terminal fragments, as well as diagnostic and therapeutic applications.

Bio

Stephanie Seminara, MD is a reproductive endocrinologist and translational investigator at Mass General Brigham, Director of the MGH Harvard Center for Reproductive Medicine and Professor of Medicine at Harvard Medical School.

Dr. Seminara received her BA from Harvard College in 1987 and her MD from Harvard Medical School in 1991. She completed her internship and residency in Internal Medicine as well as fellowship in Endocrinology, all at Massachusetts General Hospital (MGH). During her fellowship, Dr. Seminara received training in genetics and clinical investigation in the Reproductive Endocrine Unit (REU). In 1997, Dr. Seminara joined the faculty of the REU and in 2017, became its Chief.

With expertise in endocrine physiology, human genetics and clinical investigation, Dr. Seminara has built a broad, multi-disciplinary research program utilizes to elucidate the neuroendocrine control of human puberty and fertility throughout reproductive life. Her career goal is to advance genetic discoveries to novel diagnostic tools and targeted therapeutics to reduce the suffering caused by reproductive disease. Of her many contributions, Dr. Seminara is best known for discovering brain hormones (i.e. kisspeptin) that act as “gas pedals” and “brakes” for puberty and fertility.

Dr. Seminara has published over 145 articles and has mentored >50 pre/post-doctoral fellows (majority women). Her research program has been independently funded for 25 years with a portfolio notable for its diversity and longitudinal nature. She received the Presidential Early Career Award for Scientists and Engineers, the highest honor bestowed by the U.S. government on outstanding scientists and engineers at the beginning of their careers. In 2023, Dr. Seminara co-founded SeNa Therapeutics.

Peptides in the Clinic
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Corey Adams
Chief Business Officer, NoNO Inc.

Clinical Development of a PSD-95 Inhibitor for Acute Ischemic Stroke

Abstract

NoNO Inc. is developing emergency stroke treatments and has demonstrated clinical proof of concept for the in-hospital use of the eicosapeptide nerinetide to improve outcomes for acute ischemic stroke (AIS) patients. Even with the best currently available treatments, at 3 months post-stroke approximately 15% of acute ischemic stroke patients still die, half lose functional independence and more than 80% have residual functional deficits. The global burden of disease for stroke is 2-4 times that of all dementias combined (for mortality and disability adjusted life years, respectively, including Alzheimer’s) and is the second leading cause of death globally. NoNO has conducted three large, randomized, placebo-controlled trials (FRONTIER, ESCAPE-NA1 and ESCAPE-NEXT) demonstrating clinical proof of concept that nerinetide, a first-in-class PSD-95 inhibitor, can ‘help the brain hold its breath’ long enough for blood flow to be restored and improve outcomes. The results underscore the critical importance of rapid treatment – as soon as possible and at least within 3 hours of stroke onset – to improve outcomes for the 12.2 million annual cases and 101.5 million people living in the aftermath of stroke globally.

Bio

Dr. Adams joined NoNO Inc. in 2017 bringing 20 years of operational experience in drug discovery and development, strategic partnering and global pharmaceutical transactions with a particular focus on the Central Nervous System (CNS). Dr. Adams leads the company’s financial, intellectual property and partnering functions. He began his career in the Department of Neurology at Boston Medical Center supporting a broad portfolio of CNS disease research focused primarily on neurodegeneration. He completed his PhD in Pharmacogenomics at the University of California San Francisco where he also served as Executive Director of the UCSF Innovation Accelerator spinning out technologies and companies from the University. Dr. Adams spent the next decade in business development roles incubating new ventures and leading transactions for both small biotech and specialty pharma.

Drug Delivery
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Shubhangini Verma
PhD student, Indian Institute of Technology Guwahati

Injectable and biocompatible hydrogel from amyloidogenic peptide stretch of human tau306–311

Abstract

A vast majority of peptide hydrogelators harbor a bulky, non-native aromatic moiety. Such foreign moieties raise safety concerns as far as biomedical applications of hydrogels are concerned. The hydrogel research, therefore, has branched to another dimension– to identify native or native-like short peptide stretches that could cause the gelation of biological fluids. Using well-defined criteria to identify native peptide stretches that could form a viscous solution in water but cause gelation of phosphate-buffered saline (PBS), we identified the hexapeptide stretch from human tau, viz. tau306–311, as a promising injectable hydrogelator. The peptide causes instant gelation of PBS and the cell culture media. Such hydrogels find applications as drug delivery vehicles, scaffolds for mammalian cell culture, wound-dressing material, etc.

Bio

Shubhangini Singh Verma is a PhD student in IIT Guwahati, India. She has her expertise in both experimental and computational approaches. Her PhD work focuses on the development of peptide-based biocompatible hydrogels for biomedical applications. She is currently exploring short native peptides to design injectable hydrogels with promising potential in drug delivery and cell culture systems. Recently she has published a research article. In future, by integrating molecular design, characterization techniques, and in vitro evaluations, she aims to contribute to the development of next-generation biomaterials that are tunable, safe, and efficient.

Drug Delivery
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Marvin Albers
PhD Student, VU Amsterdam

grabRNA: Smart RNA delivery enables novel therapeutic strategies

Abstract

Many diseases including various forms of cancer are not curable today since current therapeutics and modalities are not suitable to address the relevant biomolecular targets. Alongside the urgent need for new treatments in medicine, there is a growing demand for environmentally friendly innovations in agriculture, particularly for sustainable crop protection. In principle, RNA interference (RNAi) can enable the specific targeting of relevant biomolecules.This technology can be adopted and offers a highly specific and efficient tool to virtually suppress any desired target gene.

Despite RNAi’s vast potential, its broader application is hindered by significant challenges. Double-stranded RNA (dsRNA), the central component of RNAi, suffers from poor stability and limited cellular uptake. In relevant conditions, dsRNA is quickly degraded, reducing its effectiveness. Existing technologies have yet to provide a universal method to protect and stabilize dsRNA, limiting RNAi’s use in real-world applications.

Our innovative approach introduces a breakthrough solution based on synthetic peptides inspired by the tomato aspermy virus 2b (TAV2b) protein. These custom-designed peptides bind dsRNA, shielding it from degradation and preserving functionality. Once inside the cell, the peptides release the dsRNA in the reducing intracellular environment, allowing it to activate the RNAi machinery. Designed as a platform technology, our peptide stabilizers can bind any dsRNA sequence or length, making them broadly applicable across diverse fields. Their unique structure-specific interaction also allows seamless integration with existing RNA delivery systems, enhancing overall effectiveness.

RNAi is entering a new era and the field is advancing rapidly. However, delivery and stability remain the final barriers to widespread adoption. Our peptide-based stabilizers aim to overcome these hurdles. We are now demonstrating our technology in collaboration with global start-ups, unlocking RNAi’s full potential in medicine, biotechnology, and agriculture.

Bio

Marvin Albers holds a bachelor's degree in chemistry from Technische Universität Darmstadt (Germany) and a master's degree in chemistry from Universität Münster (Germany). During his master's studies, he participated multiple times in iGEM, the prestigious international synthetic biology competition that promotes interdisciplinary research and innovation. He also completed a one-year research stay at the Karolinska Institute in Sweden, where he gained advanced experience in molecular biology and translational research.

Since 2023, Marvin has been pursuing his PhD in the Grossmann Lab, where his research focuses on the structure-based design of RNA-targeting peptides. He also serves as the project leader of grabRNA, an initiative dedicated to developing next-generation RNA stabilizers to advance RNA delivery technologies.

The Orbit Peptide Discovery platform allows for the identification of highly efficacious peptide binders. There is renewed interest in the use of peptides as targeting agents for therapeutic delivery, particularly nucleic acid (eg siRNA) or radiopharmaceuticals. These peptides bind to specific disease or tissue specific biomarkers to allow for targeted action of a conjugated payload. Transferrin Receptor 1 (TfR1) has been a hotly pursued target, due to its ability to transcytose payloads across the Blood-Brain Barrier (BBB) for therapeutic delivery within the central nervous system. Its additional expression on the surface of muscle cells has also been exploited to deliver corrective nucleic acid in the treatment of Duchenne Muscular Dystrophy (DMD). Orbit has sought to leverage its unique affinity screening technology to identify novel peptide binders to TfR1. Subsequent validation in cells demonstrates that these peptides specifically bind TfR1 and bind in a manner non-competitive to the binding of transferrin. These hit peptides represent an ideal starting point for further development towards novel TfR1 specific treatments. ​