Cambridge Healthtech Institute’s Third Annual

Oligonucleotide Discovery and Delivery

Advances in the Development and Delivery of Aptamer, Antisense and RNA Therapeutics

March 26-28, 2018 | Boston Marriott Cambridge | Cambridge, MA

Oligonucleotide-based therapeutics have long been considered as forming the third major drug development platform specifically focused on modulating gene expression by targeting RNA transcripts or the genome itself. A key distinguishing attribute of utilizing nucleic acids as therapeutic agents is their ability to access the “undruggable” space left by small molecules and biologics, allowing drug developers to address disease areas currently with limited or no therapeutics options. However, first- and second-generation molecules exhibiting potency and safety issues have hindered the potential of oligonucleotide therapies dramatically impacting the drug development landscape. Recent advances in nucleic acid medicinal chemistry and delivery have led to the creation of a new generation of oligonucleotide therapies harnessing chemical modifications and conjugations to improve their stability, bioavailability, specificity and potency. These advances, along with a robust development landscape, and several late-stage clinical products poised for approval, have led to a sharp resurgence of interest in the discovery of oligonucleotide-based therapeutics.

Due to the remarkable success of the event, Cambridge Healthtech Institute is delighted to host the Third Annual Oligonucleotide Discovery and Delivery conference, March 26-28, in Cambridge, MA. Join leading oligonucleotide developers and discovery scientists to discuss technological and scientific advances in nucleic acid synthesis, medicinal chemistry and delivery, as well as preclinical and clinical findings.


Final Agenda

Sunday, March 25

4:30 pm Dinner Short Course and Pre-Conference Registration


5:00-8:00 SC1: Oligonucleotide Therapeutics: From Discovery to Manufacturing*

RNAi/antisense oligonucleotides can target virtually any disease-causing gene and promise to become a third major class of therapeutics (besides small molecules and biologics). For this to happen, however, several challenges have to be addressed. This course discusses considerations taken into account when selecting oligonucleotide therapeutic programs: from target and delivery selection to developmental and manufacturing particularities. Detailed discussion will focus on, but not be limited to, the tightly interconnected factors of therapeutic indication, delivery and targets, as well as chemistry manufacturing and controls (CMC), regulatory, cost, and intellectual property considerations. Developers who are seeking a comprehensive and up-to-date overview from recognized oligonucleotide development experts are highly encouraged to join.

Instructors:

Dmitry Samarsky, PhD, CSO, Silence Therapeutics

Muthiah (Mano) Manoharan, PhD, Senior Vice President, Drug Discovery, Alnylam Pharmaceuticals, Inc.

Thazha P. Prakash, Director, Medicinal Chemistry, Ionis Pharmaceuticals

Konstantin M. Linnik, PhD, Partner, Intellectual Property, Nutter, McClennen & Fish, LLP; former Lead Patent Counsel for Oligonucleotide Therapeutics, Pfizer, Inc.


* Separate registration required.

Monday, March 26

7:00 am Registration and Morning Coffee

ADVANCES IN OLIGONUCLEOTIDE THERAPEUTICS AND DELIVERY

8:00 Welcome Remarks from Conference Director

Kip Harry, Senior Director, Conferences, Cambridge Healthtech Institute

8:10 Chairperson’s Opening Remarks

Muthiah (Mano) Manoharan, PhD, Senior Vice President, Drug Discovery, Alnylam Pharmaceuticals, Inc.

8:15 GalNAc-Conjugated siRNAs as a New Paradigm in Oligonucleotide Therapeutics

Muthiah_ManoharanMuthiah (Mano) Manoharan, PhD, Senior Vice President, Drug Discovery, Alnylam Pharmaceuticals, Inc.

During this presentation, I will discuss the progress in the advancement of RNAi therapeutics and review delivery of RNAi and where the field is going. I will also discuss conjugated delivery of oligonucleotides to the liver and combining novel chemical modifications with conjugation strategies.

8:45 Messenger RNA as a Novel Therapeutic Approach

Melissa_MooreMelissa J. Moore, PhD, CSO, mRNA Research Platform, Moderna

The contemplation of mRNA as a therapeutic platform has historically been shunned owing to challenges in oligonucleotide delivery and, maybe more importantly, the perceived shortcomings of mRNA with regard to stability and immunogenicity. Significant advances in oligonucleotide delivery have been realized over the past decade thereby enabling mRNA therapeutics. Recent discoveries in mRNA chemistry further enhance the attractiveness of this platform by eliminating innate immune activation and maximizing protein expression.

9:15 Talk Title to be Announced

Punit_SethPunit Seth, PhD, Vice President, Medicinal Chemistry, Ionis Pharmaceuticals




9:45 Sponsored Presentation (Opportunity Available)

10:15 Networking Coffee Break

ADVANCES IN OLIGONUCLEOTIDE THERAPEUTICS AND DELIVERY (CONT.)

10:30 Temporary Inhibition of p53 for Tissue Protection: from Therapeutic Concept to Prevention of Acute Kidney Injury Following Kidney Transplantation and Cardiac Surgery

Elena_FeinsteinElena Feinstein, MD, PhD, CSO, Quark Pharmaceuticals

Although therapeutic inhibition of the master tumor suppressor p53 is counterintuitive, its temporary inhibition for tissue protection under conditions of genotoxic and/or oxidative stress was proven not only safe but also efficient. Using an siRNA compound targeting p53, we have achieved efficacy proof-of-concept (POC) in the animal models of ischemia-reperfusion and toxic kidney injury as well as in the model of chemotherapy-induced hair loss. Clinical POC was achieved in two large multicenter double-blinded placebo-controlled Phase 2 trials studying efficacy of QPI-1002, a p53-targeting siRNA compound, in prevention of delayed graft function following kidney transplantation and of acute kidney injury following cardiac surgery.

11:00 Sarepta’s Exon Skipping PMO-ASOs

Marco Passini, PhD, Senior Director, Biology, Sarepta Therapeutics

11:30 Development of Stereopure Nucleic Acid Therapeutics

Chandra_VargeeseChandra Vargeese, PhD, Senior Vice President and Head, Drug Discovery, WAVE Life Sciences

WAVE Life Sciences is utilizing its innovative and proprietary synthetic chemistry drug development platform to design, develop and commercialize stereopure nucleic acid therapeutics that precisely target the underlying cause of rare genetic diseases, delivering exceptional treatment options for patients. Given the unique versatility of its chemistry platform, WAVE’s pipeline will span multiple oligonucleotide modalities including antisense, exon-skipping and single-stranded RNAi.

12:00 pm Session Break

12:10 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:40 Session Break

SYNTHESIS AND MEDICINAL CHEMISTRY

1:25 Chairperson’s Remarks

Gunnar J. Hanson, PhD, Senior Director, Research Chemistry, Sarepta Therapeutics, Inc.

1:30 Breakthrough Innovation in Phosphorodiamidate Morpholino Oligomer (PMO) Delivery Chemistry

Gunnar_HansonGunnar J. Hanson, PhD, Senior Director, Research Chemistry, Sarepta Therapeutics, Inc.

Phosphorodiamidate morpholino oligomers (PMOs) enable Watson-Crick binding to pre-mRNA in the nucleus and thereby enable the control of new definitions of intron-exon junctions within the spliceosome. Such splice alteration is limited by the efficiency of PMO delivery into the cytosol and nucleus. To solve this 40-year old delivery problem, new cell-penetrating peptides (CPPs) were designed, which by covalent attachment to PMOs, dramatically enhance the delivery of these macromolecules into the cytosol and nucleus.

2:00 Challenges in the Synthesis of Conjugated LNA Oligonucleotides

Nanna Albaek, PhD, Principal Scientist and Group Leader of New Chemistry, Roche Pharma Research and Early Development, Roche Innovation Center

Recently there has been considerable focus in the conjugation of oligonucleotides with non-nucleotide moieties which, for example, enable targeting of therapeutic oligonucleotides to specific organs and tissues in vivo. The conjugation of different chemical moieties to oligonucleotides is often achieved by post-synthetic amide bond formation. This approach requires the synthesis of LNA-oligonucleotides with a primary amine the 5’ end. During this work, we noticed a (to us) new impurity with M+28.

2:30 Approaches to Improve Potency of Antisense Oligonucleotides in Extrahepatic Tissues

Thazha_PrakashThazha P. Prakash, Director, Medicinal Chemistry, Ionis Pharmaceuticals

Antisense oligonucleotide (ASO)-based drug development is evolving as an effective therapeutic modality. In order to fully realize the potential of this technology, it is necessary to improve the potency of ASOs in extrahepatic tissues. We investigated the effect of conjugating hydrophobic ligand capable of interacting with plasma proteins on productive uptake of ASO into extrahepatic tissues. Our results suggest that conjugation of hydrophobic ligands improved potency of ASOs in extrahepatic tissues.

3:00 Refreshment Break in the Exhibit Hall with Poster Viewing

DELIVERY TO THE CNS

3:45 nOligos: A Cell Specific Oligonucleotide Delivery Platform: Application to MDD and PD Treatments

Andres_MontefeltroAndres Montefeltro, PhD, CEO, nLife Therapeutics, S.L.

nLife Therapeutics has developed different nucleic acid chemical modifications with the aim to optimize cell specific delivery capabilities to neurons. We have combined siRNAs and antisense oligonucleotides (ASOs) with some specific and potent small molecule ligands to neuronal receptors or transporters, named nOligos (neuronal specific oligonucleotides). These combinations proved to deliver the nucleic acid to the target neuron in an effective way. Also, the intranasal administration of the modified nucleic acids reached the targeted brain area and neurons in mice and monkeys.

4:15 Expanding the Chemical Diversity of Therapeutic Oligonucleotides

Maire_OsbornMaire Osborn, PhD, Research Scientist, Khvorova Lab, RNA Therapeutics Institute, University of Massachusetts Medical School

We have identified several novel chemical classes of conjugates that demonstrate markedly improved brain distribution and robust in vivo efficacy. Direct conjugation of a fully chemically modified siRNA to docosahexaenoic acid (DHA), the most abundant poly-unsaturated fatty acid in the brain, results in improved tissue retention with wide distribution and robust efficacy in the striatum and cortex after single injection. Most importantly, DHA-hsiRNA conjugates do not induce neural cell death or measurable innate immune activation following administration of concentrations 20-fold over the efficacious dose, establishing a new approach toward development of RNAi-based therapeutics for a wide range of neurodegenerative disorders.

4:45 Sponsored Presentation (Opportunity Available)

5:15 Welcome Reception in the Exhibit Hall with Poster Viewing



6:15 Dinner Short Course Registration


6:30-9:30 SC2: Overcoming Challenges with Peptide Delivery*

Peptides make attractive drug candidates due to their specificity, potency and low toxicity, but present particular challenges for their delivery to the site of action, due to their short half-life and susceptibility to proteolytic degradation. This short course reviews the latest challenges in peptide drug delivery and the various options available, including oral, transdermal and nanosystems. We also look at challenges around half-life, bioavailability, stability and formulation.

Instructor:

Joël Richard, PhD, Senior Vice President, Peptides Development, Ipsen


* Separate registration required.

Tuesday, March 27

7:30 am Breakfast Breakout Roundtable Discussions

Grab a cup of coffee and join a roundtable discussion. These are moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic.

ADVANCES IN RNA THERAPEUTICS AND DELIVERY

8:25 Chairperson’s Remarks

Balkrishen (Bal) Bhat, PhD, Vice President, Chemistry, RaNA Therapeutics, Inc.

8:30 Novel Strategies for Endogenous mRNA Upregulation

Balkrishen_BhatBalkrishen (Bal) Bhat, PhD, Vice President, Chemistry, RaNA Therapeutics, Inc.

We are developing two gene upregulation platforms. The first approach targets lncRNAs (long non-coding RNA) with chemically modified oligonucleotides to block recruitment of PRC2 to the target gene of interest which results in significant upregulation of mRNA and protein. In the second approach, we selectively upregulate target mRNA and the corresponding protein by stabilizing identified regions of mRNA with chemically modified oligonucleotides.

9:00 microRNA Targeted Therapies for Hematological Malignancies and Pathological Fibrosis: Translation from Basic Sciences to the Clinic

William_MarshallWilliam S. Marshall, PhD, President and CEO, miRagen Therapeutics


9:30 Development of Novel Breakthrough Cancer Therapies Based on the Unique Functions of miRNAs

Roel_SchaapveldRoel Q.J. Schaapveld, PhD, MBA, CEO, InteRNA Technologies BV

To explore miRNAs as therapeutic agents for the treatment of cancer, InteRNA Technologies has performed functional screens in cell lines covering different types of cancer. Lead candidates are now advancing in preclinical development programs with a focus on hepatocellular cancer. This presentation will provide insights into the latest progress in the preclinical development of InteRNA’s lead miRNA compounds.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

EMERGING NUCLEIC ACID DEVELOPMENT PLATFORMS

10:30 Chairperson’s Remarks

Balkrishen (Bal) Bhat, PhD, Vice President, Chemistry, RaNA Therapeutics, Inc.

10:35 An RNA Aptamer Platform

Christopher_Arico-MuendelChristopher Arico-Muendel, PhD, Manager, Platform Capabilities, Encoded Library Technologies, NCE Molecular Discovery, R&D Platform Technology & Science, GlaxoSmithKline


11:05 ZATA’s Novel Oligonucleotides (ZONs) with Self-Neutralizing Backbones

David_TabatadzeDavid Tabatadze, PhD, President and CEO, R&D, ZATA

We developed a nucleic acid platform enabling the new generation oligonucleotides (ZONs) comprising target number of branched charge-neutralizing groups (CNGs) on the internucleoside phosphates of ON by phosphotriester bonds. The CNGs are terminated with positively charged amino groups, and are optimized to form ion pairs with the neighboring phosphate groups. ZONs can be synthesized by standard automated phosphoramidite chemistry in good yield and purity.

11:35 Sponsored Presentation (Opportunity Available)

11:50 Session Break

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:30 Dessert Break in the Exhibit Hall with Poster Viewing

ADVANCES IN OLIGONUCLEOTIDE DELIVERY

1:15 Chairperson’s Remarks

Dmitry Samarsky, PhD, CSO, Silence Therapeutics

1:20 Development of Novel Therapies Using Advanced GalNAc-siRNA Technology

Dmitry_SamarskyDmitry Samarsky, PhD, CSO, Silence Therapeutics

Silence Therapeutics utilizes RNA interference (RNAi) technology to develop a new generation of drugs to treat serious human diseases with unmet needs. Attachment of the N-acetylgalactosamine (GalNAc) moieties to the RNAi triggers (siRNA) allows the resulting conjugates to travel to the liver and to downregulate genes specifically in hepatocytes. We will present our advances with the GalNAc-siRNA technology, as well progress with company’s therapeutic programs.

1:50 A Novel Nano-Medicine Platform for Oligonucleotide Discovery and Delivery

Art_LevinArt Levin, Ph.D., Executive Vice President, Research and Development, Avidity NanoMedicines

Despite the considerable promise, delivery has proven to be one of the central challenges of oligonucleotide-based therapeutics. Oligonucleotides are large, hydrophilic and highly negatively charged, so they don’t cross cell membranes. We have pioneered the development of Precision NanoMedicines, which are targeted, polymeric nanoparticles encapsulating siRNA drug payloads for delivery to specific tumor types. These self-assembling nanoparticles can be decorated with antibodies, proteins, peptides and small molecules to bind to extracellular receptors and facilitate cellular uptake.

2:20 Translation of Messenger RNA Therapeutics from Preclinical Research into Clinical Studies

Pad_ChivukulaPad Chivukula, PhD, CSO & COO, Arcturus Therapeutics

Arcturus has developed a novel, potent and safe RNA therapeutics platform called LUNAR™, a proprietary lipid-enabled delivery system for RNA medicines including small interfering RNA, messenger RNA, antisense and microRNA oligotherapeutics. In addition, we incorporate Unlocked Nucleic Acid (UNA) chemistry into the oligonucleotide drug candidate enabling the targeting of any gene in the human genome. This presentation will provide an update on our lead asset, a UNA-modified, LUNAR-formulated siRNA targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis.

2:50 Sponsored Presentation (Opportunity Available)

3:05 Refreshment Break in the Exhibit Hall with Poster Viewing

NOVEL AND EMERGING APPROACHES FOR IN VIVO DELIVERY

3:35 DsiRNA Applications for Oncology and Chronic Liver Diseases

Marc_AbramsMarc Abrams, PhD, Senior Director, Preclinical Development, Dicerna Pharmaceuticals, Inc.

Dicerna is advancing two platforms for delivery of Dicer-substrate siRNAs (DsiRNA): EnCore lipid nanoparticles for oncology, and GalNAc-DsiRNA-EX conjugates for liver indications. Lipid Nanoparticle (LNP) technology is an elegant solution for delivery of RNAi triggers, since it enables both bioavailability to target organs as well as the ability to transfect target cells.

4:05 Therapeutic Protein Expression in vivo Using Messenger RNA-Lipid Nanoparticles

Thomas_MaddenThomas D. Madden, PhD, President and CEO, Acuitas Therapeutics

Therapeutic applications of messenger RNA (mRNA) are currently being advanced into clinical development. However, mRNA is relatively labile and requires a delivery system to efficiently access the cytoplasmic compartment where the mRNA is translated. Acuitas is developing lipid nanoparticle systems (LNP) that allow the efficient delivery and expression of mRNA via different routes of administration. Biophysical characteristics that facilitate efficient mRNA delivery and provide a favorable safety profile will be discussed.

4:35 Development of Anti-Fibrosis siRNA Therapeutics Using HKP Polypeptide Nanoparticle Technology

Patrick_LuPatrick Y. Lu, PhD, President & CSO, Sirnaomics, Inc.

Using a proprietary and optimized polypeptide-based delivery technology, we have developed the novel anti-fibrotic therapeutics with siRNAs targeting both TGFß1 and Cox-2 simultaneously, for initial indication of skin hypertrophic scar followed with liver fibrosis and other fibrotic conditions. I will discuss the unique advantage of HKP polypeptide nanoparticle technology for efficient siRNA delivery, its pharmaceutical properties for manufacturing and its preclinical safety profile.

5:05 Dinner Short Course Registration


5:30-8:30 SC3: CRISPR-Based Gene Editing for Targeted Therapies*

While the challenges and risks associated with oligonucleotide therapies still remain, there is a new and better understanding of how genes can be effectively manipulated and delivered. With the rise of gene editing tools and enhanced knowledge of targeted delivery, these therapeutic modalities are once again being embraced with renewed hope and enthusiasm. This course helps you understand how gene editing – particularly the one enabled by the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 system – works, and how it can be used to help develop targeted therapies with good efficacy and delivery.

Instructors:

Clifford Steer, MD, Professor of Medicine and Genetics, Cell Biology, and Development; Director, Molecular Gastroenterology Program, University of Minnesota Medical School

Ciro Bonetti, PhD, Scientist, Regeneron Pharmaceuticals

Eric B. Kmiec, PhD, Director, Gene Editing Institute; Senior Research Scientist, Center for Translational Cancer Research, Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System


* Separate registration required.

Wednesday, March 28

8:00 am Morning Coffee

TOLL-LIKE RECEPTOR (TLR) AGONISTS AND CHECKPOINT COMBINATIONS

8:25 Chairperson’s Remarks

Art Krieg, MD, Founder and CEO, Checkmate Pharmaceuticals

8:30 Making “Cold” Tumors “Hot” with Intratumoral Injection of CpG-A Oligonucleotide

Art_KriegArt Krieg, MD, Founder and CEO, Checkmate Pharmaceuticals

CMP-001 is a formulation of a CpG-A oligonucleotide, G10, within a virus-like particle, Qb. We are performing a Phase Ib dose escalation study of intratumoral CMP-001 given in combination with systemic pembrolizumab in advanced melanoma patients whose cancer has previously progressed on an anti-PD-1 Ab, or who have failed to respond to at least 12 weeks of such therapy.

9:00 Creating a Beneficial Tumor Microenvironment for Effective Cancer Immunotherapy

Sudhir_AgrawalSudhir Agrawal, DPhil, FRSC, President, Research, Idera Pharmaceuticals

We are evaluating the role of endosomal Toll-like receptors 3, 7, 8, and 9, in the TME by administering intratumorally an agonist of these receptors. IMO-2125, a TLR9 agonist, has shown potent anti-tumor activity following i.t. administration and has led to an abscopal effect. These anti-tumor activities are associated with beneficial changes in the TME, which potentiated the anti-tumor activity of anti-CTLA4, anti-PD1, and IDO-1 inhibitor. A Phase I/II trial of intratumoral IMO-2125 in combination with ipilimumab in PD-1 refractory melanoma patients is in progress.

9:30 TLR9-Targeted Spherical Nucleic Acids for Cancer Immunotherapy

Ekambar_KandimallaEkambar Kandimalla, PhD, CSO, R&D, Exicure

Spherical nucleic acids (SNAs) are dense and radially arranged synthetic oligonucleotides on a central nanoparticle core. The 3D structure of SNA provides enhanced cellular uptake, and nuclease stability, compared with linear oligonucleotides with advantages for local delivery. A novel TLR9-targeted SNA has shown greater antitumor activity as a monotherapy and in combination with an anti-PD-1 antibody compared with a linear oligo in syngeneic tumor models with the induction of innate immune responses and long-term tumor-specific memory responses to subsequent challenge with the same tumor cell line.

10:00 Networking Coffee Break

10:30 Development of Pluripotent Stem Cell-Based Therapies for Neurologic and Oncologic Disorders

Kevin_NishimotoKevin Nishimoto, PhD, Scientist, Asterias Biotherapeutics

Our group has established protocols to produce oligodendrocyte progenitors that upon transplantation into animals with spinal cord injuries can remyelinate denuded axons, induce axonal sprouting, and improve locomotor activity. Extensive preclinical studies have been completed to examine the activity, biodistribution, dosing, delivery, and potential toxicity and tumorigenicity of the oligodendrocyte progenitors. In collaboration with Cancer Research UK, Asterias is preparing for a clinical trial using these hESC derived dendritic cells as a cancer immunotherapy in non-small cell lung carcinoma in the neoadjuvant setting.

11:00 Bi-Functional Oligonucleotides to Unleash TLR9-Driven Antitumor Immune Responses

Marcin_KortylewskiMarcin Kortylewski, PhD, Associate Professor, Department of Immuno-Oncology, City of Hope

Here we demonstrate a strategy based on type A CpG ODN (D19) can be employed for the delivery of functional miR146a mimics as well as anti-miR146a oligonucleotides (146AMO). Both CpG-miR146a mimic and CpG- 146AMO conjugates were quickly internalized by target human and mouse non-malignant myeloid cells, as well as by AML cells. Unexpectedly, the CpG/TLR9 activation to accelerate endosomal escape, was not indispensable for the inhibitory effect of the CpG-146AMO.

11:30 Sponsored Presentation (Opportunity Available)

11:45 Session Break

11:55 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:25 pm Session Break

NOVEL IMMUNOMODULATORY NUCLEIC ACIDS

1:15 Chairperson’s Remarks

R.P. (Kris) Iyer, PhD, Co-Founder & CSO, Spring Bank Pharmaceuticals

1:20 Selective Stimulation of RIG-1 with Novel Synthetic RNA Induces Strong Anti-Tumor Immunity in Mouse Tumor Models

Jim_BarsoumJim Barsoum, PhD, Chair, Scientific Advisory Board, Rigontec GmbH

We describe a novel immunotherapy approach in which a natural viral defense system is harnessed to stimulate anti-tumor immunity. The cytosolic RNA receptor RIG-I recognizes double-stranded RNA bearing a 5’-triphosphate. RIG-I activation induces apoptosis preferentially in tumor cells and activates the immune system via type I interferon signaling. We developed an optimized, synthetic oligonucleotide, RGT100, as a RIG-I selective ligand. RGT100 activates RIG-I leading to the induction of cytokines, including interferons.

1:50 CureVac’s Sequence-Optimized mRNA – En Route to the Next Generation Biologicals

Mariola_Fotin-MleczekMariola Fotin-Mleczek, PhD, CSO, CureVac

Recent advances strongly suggest that mRNA is the basis for a new class of vaccines and drugs. RNActive®, one of CureVac’s technologies has been developed on this basis and provides potent prophylactic vaccines and novel immunotherapies against cancer. These successes could be extended preclinically to mRNA protein and gene replacement therapy.

2:20 RNAi-Mediated β-Catenin Inhibition Promotes T Cell Infiltration and Potentiates Immune Checkpoint Blockade

Shanthi Ganesh, PhD, Associate Director, Preclinical Oncology, Dicerna Pharmaceuticals, Inc.

Recent research implicates Wnt/β-catenin signaling as a mechanism of resistance to cancer immunotherapy. DCR-BCAT is an RNAi-based experimental drug targeting β-catenin, formulated in a tumor-selective nanoparticle. In preclinical models, systemic administration of DCR-BCAT induced rapid increases in tumor T cells and dramatically improved responses to immunotherapy agents. In this presentation, we explore the mechanism of synergistic efficacy and suggest clinical evaluation of this first-in-class RNAi agent.

2:50 SB 11285, a Novel STING Agonist for Immunotherapy of Cancer

Kris_IyerR.P. (Kris) Iyer, PhD, Co-Founder & CSO, Spring Bank Pharmaceuticals

Immunotherapy has emerged as a transformative approach for the treatment of cancer. Evidence suggests that the activation of Stimulator of Interferon Genes (STING) pathway in tumor cells and/or immune cells induce type I Interferon production leading to apoptosis of tumor cells, as well as induction of adaptive immune response, thereby providing a powerful anti-cancer strategy. Herein, we describe the discovery and preclinical studies of SB 11285, a novel STING agonist for application in immuno-oncology.

3:20 Networking Refreshment Break

3:35 Targeting hIDO1, CD39 and CD73 with 3rd Generation Antisense Oligonucleotides

Frank_JaschinskiFrank Jaschinski, PhD, CSO, Secarna Pharmaceuticals


4:05 Identification of LAG3 High Affinity Aptamers by HT-SELEX and Conserved Motif Accumulation (CMA)

Fernando_Pastor_RodríguezFernando Pastor Rodríguez, PhD, Principal Investigator, Aptamers, Molecular Therapy, CIMA


4:35 Cancer Immunotherapy: Charting a Course in the Rough Seas of Intellectual Property

Konstantin_LinnikKonstantin M. Linnik, PhD, Partner, Intellectual Property, Nutter, McClennen & Fish, LLP; former Lead Patent Counsel for Oligonucleotide Therapeutics at Pfizer, Inc.

Both immuno-oncology and oligonucleotide IP spaces are crowded – the number of drugs in R&D far exceeds the number of targets. Navigating the IP around major targets is critical but, more importantly, every drug developer faces challenges in protecting its own intellectual property. What are the patenting strategies that allow entry into this crowded IP space, while preserving the broadest scope of protection and commercialization opportunities?

5:05 Close of Conference