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Nanoparticle-based drug delivery enables sophisticated tactics to fight disease. With their small size and their intricate engineering, nanoparticles can improve control over drug release profiles, both spatially as well as temporally, and can reduce harmful side effects. Furthermore, improved targeting and shielding capabilities allows for more favorable pharmacokinetic and pharmacodynamic profiles. Due to the inherent flexibility in particle size, shape, charge, ligand functionalization, and density, nanotechnology can help open avenues to patient-specific treatments of different diseases. However, since nanoparticle drug delivery systems are so intricately designed and sophisticated, this can cause problems when translating these technologies from in vivo models to the clinic. Cambridge Healthtech Institute’s Third Annual NanoDrugs: Design and Delivery conference is here to bring together innovators, drug discovery scientists, to discuss strategies to accelerate the translation of nanoparticle drug delivery vehicles.


Final Agenda

Tuesday, June 19

7:30 am Registration Open(America Foyer) and Morning Coffee (Foyer)

NANOPARTICLES FOR IMMUNO-ONCOLOGY AND SCREENING
St. George AB

8:15 Chairperson’s Opening Remarks

James Dahlman, PhD, Assistant Professor, Department of Biomedical Engineering, Georgia Institute of Technoloy/Emory Medical School


8:20 KEYNOTE PRESENTATION: Nanotherapeutics in Oral and Parenteral Drug Delivery

Rakesh Dixit, PhD, DABT; Vice President, Research & Development, Vice President, R & D, Global Head, Biologics Safety Assessment-Translational Sciences, MedImmune

We have followed the progress of nanotechnology in pharmaceutical applications with key insights from oral and parenteral drug delivery, and how to modify our thinking to better utilize nanoparticles for immuno-oncology. In contrast to conventional “local” tumor targeting by nanoparticles, we propose a new mechanism whereby nanoparticles trigger priming of the T cells towards tumor destruction. The heterogenous biodistribution of nanoparticles lends itself to stimulating immune cells systemically in a “global” manner and with the right therapeutic combinations will be able to trigger tumor antigens to continually activate, retain memory effects and destroy tumor cells

8:50 Quantitative Analysis of Nanoparticle Delivery to Solid Tumors

Stefan_WilhelmStefan Wilhelm, PhD, Assistant Professor, Stephenson School of Biomedical Engineering, University of Oklahoma

The concept of “targeting” nanoparticles into solid tumors for diagnosis and treatment of cancer is attractive but challenging. Efficient delivery of intravenously administered nanoparticles to malignant tissues is limited due to complex interactions with off-target biological systems. In this presentation, a quantitative analysis of nanoparticle delivery to tumors from a preclinical perspective will be provided, followed by a discussion of the impact of results on clinical translation of cancer nanomedicine..

9:20 High-Throughput in vivo Nanoparticle Analysis Using DNA Barcodes

James_DahlmanJames Dahlman, PhD, Assistant Professor, Department of Biomedical Engineering, Georgia Institute of Technology/Emory Medical School

Genetic drugs are limited by inefficient delivery to target cells, and unwanted delivery to off-target cells. Thousands of chemically distinct nanoparticles can be synthesized to deliver genetic drugs. However, it is difficult to study many nanoparticles in vivo. Here we report JORDAN, a DNA barcoding system to study over 150 nanoparticles at once in vivo. JORDAN can be used to ask fundamental questions about in vivo drug delivery.

9:50 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)

CANCER AND NANOTECHNOLOGY
St. George AB

10:35 FEATURED PRESENTATION: Stimuli-Sensitive Combination Nanopreparations for Multidrug Resistant Cancer

Vladimir_TorchilinVladimir Torchilin, PhD, Distinguished Professor and Director, Center for Pharmaceutical Biotechnology and Nanomedicine, Bouvé College of Health Sciences, Northeastern University

Therapy of MDR cancers could be enhanced by using siRNA down-regulating proteins involved in cancer resistance together with chemotherapeutics. We have developed several types of nanopreparations, which are biologically inert, demonstrate prolonged circulation in the blood, can firmly bind RNA, and be co-loaded with chemotherapeutic agents. In order to specifically unload such nanopreparations, we made them sensitive to local tumor-specific stimuli, such as lowered pH, hypoxia, or overexpressed certain enzymes.

11:05 MM-310: A New Generation Antibody-Directed Nanotherapeutic

Andrew_SawyerAndrew Sawyer, PhD, Research Team Lead, Discovery, Merrimack

Antibody-directed nanotherapeutics (ADN) represent a new generation of antibody targeted cytotoxic drugs. In contrast with antibody-drug conjugates, an ADN indirectly links several copies of an antibody with tens of thousands of cytotoxic molecules via encapsulation in a nanoliposome. ADNs enhance the specificity of cytotoxic molecules by increasing exposure to cancer cells, while simultaneously limiting exposure to normal tissues. In this talk we will discuss ADN development at Merrimack using the example of MM-310, an EphA2 targeted nanoliposome containing a docetaxel prodrug.

11:35  Q & A with Speakers Nanoparticle Fabrication

Ghazal Hariri, PhD, Senior Scientist, Pfizer Global Research and Development

12:05 Enjoy Lunch on Your Own

CLINICAL TRANSLATION OF NANOTECHNOLOGY
St. George AB

1:15 Chairperson’s Remarks

Christopher Hartshorn, PhD, Program Director, Division of Cancer Treatment and Diagnosis, National Cancer Institute

1:20 NCI Funding of Nanotechnology Strategies to Advance Outcomes for Clinical Cancer Care

Christopher_HartshornChristopher Hartshorn, PhD, Program Director, Division of Cancer Treatment and Diagnosis, National Cancer Institute

The National Cancer Institute launched the Alliance for Nanotechnology in Cancer (Alliance) in 2004 to advance a number of promising nanotechnologies for the diagnosis, treatment and prevention of cancer. The progress since this time has been substantial and has led NCI to begin several more initiatives in this space with continued program support. This talk will focus on many of the platforms, outcomes, and future relative to the vision of the NCI.

1:50 Nanobiointerfaces: Implications of Biomolecular Corona

Morteza_MahmoudiMorteza Mahmoudi, PhD, Instructor, Center for Nanomedicine and Department of Anesthesiology, BWH, Harvard Medical School

Nanoparticles (NPs) are becoming increasingly promising tools for medical diagnostics and therapeutics. Despite the advances in their biomedical applications and numerous publications, fewer than expected NPs have made it to clinical trials and even fewer have reached clinical practice. This wide gap between bench discoveries and clinical applications is mainly because of our limited understanding of the nanobiointerfaces. Although extensive studies have been conducted to enhance our understanding of the nanobiointerfaces, the literature remains unclear and contains conflicting information, even for seemingly identical NPs. The main goal of this talk is to introduce some of the existing “hidden” factors at the nanobiointerfaces to determine – unambiguously and reproducibly – the biological fate of NPs both in vitro and in vivo. Deeper understanding of the nanobiointerfaces, using the hidden factors, may accelerate clinical translation of nanobiotechnologies

2:50 Refreshment Break in the Exhibit Hall with Poster Viewing (America Ballroom)

3:30 Hafnium Oxide Nanoparticles Activated by Radiotherapy for Treatment of Solid Tumors

Stéphanie Decollogne, PhD, Senior Manager, Preclinical & Toxicology, Clinical Development, Nanobiotix

A new class of material with high electron density, hafnium oxide, was designed at the nanoscale (HfO2-NP) to efficiently absorb ionizing radiation from within the tumor cells and augment the dose deposited to a tumor (“hot spot” of energy deposit), to more focus and efficient cell killing. HfO2-NPs are taken up by cancer cells and, when exposed to radiotherapy, locally increase the radiation dose deposit, triggering more cancer cell death when compared to radiotherapy alone.

3:50 Ex vivo Perfusion of Isolated Human Organs: A New Setting for Clinical Translation of Vascular-Targeted Nanomedicines

Greg_TietjenGregory Tietjen, PhD, Assistant Professor, Department of Surgery, Section of Transplantation and Immunology, Yale School of Medicine

Ex vivo normothermic machine perfusion, a new tool in clinical transplant used to revive marginal organs, provides a unique opportunity to deliver therapeutics directly to an isolated organ. Working in collaboration with leading transplant clinicians at the University of Cambridge, we have taken advantage of this setting to perform preclinical quantitative studies to assess retention of vascular-targeted nanoparticles in a series of isolated human kidneys.

4:10 Bioinspired Antioxidative Nanomaterials for Ischemic Stroke

Jinjun_ShiJinjun Shi, PhD, Assistant Professor, Harvard Medical School; Director, Laboratory for Nanoengineering & Drug Delivery, Brigham and Women’s Hospital

Antioxidative nanomaterials are emerging as a novel strategy for treating a myriad of important diseases through scavenging excessive reactive oxygen and nitrogen species (RONS). Herein, we develop bioinspired melanin nanoparticles (MeNPs) for more potent and safer antioxidative therapy. We provide exhaustive characterization of the activities of MeNPs against multiple RONS and RONS-mediated inflammatory responses. In vivo results demonstrate that the MeNPs can effectively protect ischemic brains with negligible side effects.

4:40 Application of Wet Media Milling in Preclinical and Early Phase Studies

Sonali Bose, PhD, Associate Technical Project Leader, TRD (Technical Research and Development), Novartis

5:00 Find Your Table and Meet Your Moderator

5:05 Interactive Breakout Discussion Groups

This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas and active networking.

Using Big Data to Help Nanotechnology

Cory Sago, PhD Student, James Dahlman Lab, Georgia Institute of Technology / Emory Medical School

  • DNA barcodes can be used to track more than 100 nanoparticles in a single mouse.
  • Big data analytics can be applied to understand how nanoparticle traits affect delivery in vivo.
  • The biology of drug delivery can be studied using DNA barcodes.

Nanoparticle Fabrication

 Sonali Bose, PhD, Associate Technical Project Leader, TRD (Technical Research and Development), Novartis

  • Challenges in nanoparticle fabrication and scale up for pharmaceutical production
  • Opportunities and applications for nanoparticle technology in the pharmaceutical industry
  • Impact of nanoparticle fabrication on drug development

5:45 Reception in the Exhibit Hall with Poster Viewing (America Ballroom)

7:00 Close of Day

Wednesday, June 20

7:45 am Registration Open (America Foyer) and Morning Coffee (Foyer)

NANOPARTICLE DELIVERY ACROSS THE BBB
Essex North West

8:25 Chairperson’s Remarks

Jiangbing Zhou, Assistant Professor of Neurosurgery and of Biomedical Engineering, Department of Neurosurgery, Yale University

8:30 FEATURED PRESENTATION: Nanoparticle-Loaded Cells and Exosomes for Treatment of Brain Diseases

Alexander_KabanovAlexander (Sasha) Kabanov, PhD, DrSci, MAE, Director, Center for Nanotechnology in Drug Delivery; Co-Director, Carolina Institute for Nanomedicine; Mescal S. Ferguso Distinguished Professor, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill

Macrophages traverse the BBB and deliver therapeutic “nanozymes” and genes (such as GDNF) to inflammatory sites in the brains of Parkinson’s disease (PD) mouse models. This produces anti-inflammatory and neuroprotective effects and improves behavior in PD models. The enzymes and neurotrophins are also packaged into exosomes secreted by macrophages to improve delivery of these proteins to the brain. The uptake of exosomes is increased in the presence of inflammation.

9:00 Engineering Nanoparticles for Drug Delivery to the Brain

Jianbing_ZhouJiangbing Zhou, Assistant Professor of Neurosurgery and of Biomedical Engineering, Department of Neurosurgery, Yale University

Due to the existence of the BBB, drug delivery to the brain has been a major challenge. In this talk, I will first introduce a serial of techniques established in our laboratory for locoregional drug delivery to the brain, systemic drug delivery to the brain, and more recently, oral drug delivery to the brain. Next, I will give a few examples to show how these techniques can be utilized for treatment of neurological disorders.

9:30 V-Smart® Nanomedicines: Non-Invasive Targeted Therapeutics for Brain Diseases

Susan_RosenbaumSusan Rosenbaum, J.D., Founder, Chairman & CEO, Lauren Sciences LLC

V-Smart® breakthrough innovation solves greatest medical challenge in brain disease treatment -- non-invasive targeted delivery of therapeutics to brain. V-Smart® novel nanotechnology platform enables non-brain penetrant therapeutic agents to both cross BBB into brain by non-invasive administration, and target to, and selectively release at, CNS disease-specific brain sites. V-Smart® Nanomedicines pipeline of transformative therapeutics to meet medical needs of patients with brain diseases, such as Parkinson’s, ALS, GBM and Alzheimer’s.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)

10:45 MR Image-Guided Nanoparticle Delivery across the Blood-Brain Barrier with Focused Ultrasound

Richard_PriceRichard J. Price, PhD, Professor, Biomedical Engineering, University of Virginia

MR image-guided focused ultrasound can safely open the blood-brain barrier, facilitating highly localized delivery of systemically-administered brain-penetrating nanoparticles to the CNS. Our group is developing this approach as a means to treat (i) Parkinson’s disease via neurotrophic gene therapy and (ii) brain tumors via controlled-release chemotherapy, tumor suppressive miRNAs, and immunotherapies.

11:15 Delivery of Transferrin Receptor-Targeted Nanoparticles and Biologics to the Brain Via Transport Through the Blood-Brain Barrier

Torben_MoosTorben Moos, PhD, Professor, Section for Neurobiology, Aalborg University

Directed delivery to the brain using targeted therapeutics represents a feasible method for drug delivery to the CNS. Our research group is developing targeting constructs to enable delivery of nanoparticles and biologics to the CNS in conditions without perturbation of the blood-brain barrier. In my presentation I will give an update on our attempts to transport transferrin receptor targeted nanoparticles and biologics through this blood-brain barrier.

11:45 Enjoy Lunch on Your Own

12:20 pm Dessert and Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)


1:00 PLENARY KEYNOTE SESSION
Essex South

Partnering for Sustainable Funding

The panel is designed to discuss partnering between various stake holders such as drug discovery startups, VC firms, large pharmaceutical companies and academic labs in order to advance new target discovery and preclinical research. VC companies, and pharma search & evaluation departments will be represented on the panel.

Jens Eckstein, PhD, President, SR One

Barbara K. Sosnowski, PhD, Vice President and Global Head, External R&D Innovation, Pharmatherapeutics and WRD External Partnerships, Pfizer, Inc.

Kevin Bitterman, PhD, Partner, Atlas Venture

Vivian Berlin, PhD, Director of Business Development, Life Sciences, Office of Technology Development, Harvard University

Ben Thorner, Senior Vice President and Head, MRL Business Development & Licensing, Merck

Plenary Technology Panel

Advancing Innovation in Drug Discovery and Translational Research

This year’s Plenary Technology Panel features a group of technical experts from life science technology and service companies, who share their perspectives on various trends and tools that will likely change the way in which we traditionally approach preclinical drug discovery and development. Attendees will have an opportunity to ask questions and understand the impact of recent technical advances.

Moderator: Leigh Zawel, PhD, Managing Director, MPM Capital

Ashley Rae Kark, MBS, Director, Corporate Relations, Scientist.com

Stefan Braam, PhD, Technical Director, Ncardia

Mark Paris, PhD, Director, Translational Applications, Mitra Biotech

Edgard Wood, PhD, Senior Research Director, Discovery, Charles River

2:30 Refreshment Break in the Exhibit Hall with Poster Viewing (America Ballroom)

3:10 Close of Conference


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