ABSTRACTS

(ALPHABETICAL BY LAST NAME)

Aaron Almeida Senior Scientist II, Arrowhead Pharmaceuticals

ABSTRACT A primary challenge in the development of RNAi therapeutics is delivering the RNAi trigger molecules

into the cytoplasm of the cell where RNAi activity occurs. Dynamic PolyConjugates (DPC’s) are

Arrowhead’s innovative delivery system engineered specifically to induce efficient endosomal

escape. The endosomal release is facilitated by a peptide that is reversibly-masked for reduced non-

specific interactions during in vivo circulation, and is actively targeted to the desired cell type through

efficient receptor binding. Here we present an example of the DPC platform composed of a hepatocyte-

targeted endosome-releasing agent and a cholesterol-conjugated siRNA. This delivery platform forms

the basis of ARC-520, an siRNA-based therapeutic for the treatment of chronic hepatitis B virus (HBV)

infection. DPC’s have demonstrated rapid, deep and durable knockdown of target genes expressed

in the liver and has been well tolerated in clinical trials.

Yvonne Angell Scientific Consultant, Cogentis Therapeutics

ABSTRACT Cogentis is a pre-clinical stage biotechnology company dedicated to developing therapies that target the

dysregulated cyclin-dependent kinase 5 (CDK5) molecular pathway. Because clinical trials for

Alzheimer’s disease (AD) are costly and slow, Cogentis will focus initially on frontotemporal dementia

(FTD), a rare disorder that is an early-onset, rapidly-progressive neurodegenerative condition leading to

death within five years. FTD and AD are thought to be tauopathies, diseases characterized by toxic

accumulations of a normal protein called ‘tau’ in the brain. There are currently no approved drugs

to treat any of the tauopathies. In brains from FTD patients CDK5 over-phosphorylates tau, leading to

the toxic accumulation of tau. Post-mortem brains from AD and FTD patients were shown to have

elevated CDK5 activity. Previous efforts to inhibit CDK5 have proven too toxic due to lack of specificity.

Cogentis has exclusive rights to CT-526, a novel peptide which was invented at the NIH and is an

allosteric CDK5 inhibitor. CT-526 penetrates the blood-brain barrier and engages CDK5 away from the

active site, preventing aberrant activity while preserving normal function, showing zero signs of toxicity

at > 100x the effective dose. Preclinical success in multiple mouse models of AD, Parkinson’s disease

(PD), and amyotrophic lateral sclerosis (ALS) supports expansion/development to multiple diseases. In

advanced AD mice, it reversed tau phosphorylation, amyloid beta plaques (Ab), motor instability and

cognitive deficits to normal.

BIO For the past 20 years my career has focused on the discovery and development of new peptide

therapeutics in a wide range of disease areas, including oncology, endocrinology, hematology and

neurology. I have built a strong reputation in the peptide therapeutics field by leading successful

chemistry teams and research programs in small biotech companies, mid-size and large pharmaceutical

companies. My main expertise is in the design, synthesis and lead optimization of novel, challenging

peptides and peptidomimetics, peptide-conjugate linker design and synthesis, unnatural amino acid and

building block synthesis, peptide PEGylation and lipidation, formulation and CMC activities. I have

influenced the strategic direction to advance many drug discovery programs including three drug

candidates in preclinical development, one in the market, and one in phase I clinical trials.

Dana Ault-Riche CEO, Reflexion Pharmaceuticals

ABSTRACT Small proteins composed entirely of D-amino acids enhance the advantages of small proteins, such as

high tissue and tumor penetration rates, smaller dose volumes, and multi-specific formats, by enabling

greater stability, longer half lives and reduced immunogenicity. Chemical protein synthesis combined

with mirror image phage display has been used to produce potent inhibitors of VEGF-A and other

therapeutic targets. The role of stereochemistry in immune responses and recent progress in the

development of D-amino acid proteins as therapeutics will be presented.

Craig Beattie CSO, CDG Therapeutics Inc

ABSTRACT p28 is a cell-penetrating peptide that crosses the blood brain barrier, preferentially enters cancer cells

and binds to both wild-type and mutant p53 protein, inhibiting COP1-mediated ubiquitination. The

decrease in ubiquitination results in increased levels of p53 and induction of cell cycle arrest at G2/M.

Patients aged 3–19 years with recurrent or progressive central nervous system tumors received p28 at

the adult recommended phase 2 dose. Seven of 12 evaluable participants received ≥ 2 cycles (12

weeks) of p28 with the most common adverse event attributed to the drug a transient grade 1 infusion-

related reaction. PK analysis revealed a profile similar to adults. Three (of 12; 25%) participants

remained stable disease (SD) on the study; two for > 5 cycles (30 weeks) demonstrating that p28 is well-

tolerated in children with recurrent CNS malignancies at the adult recommended phase 2 dose.

Albert Bowers Professor, University of North Carolina at Chapel Hill

ABSTRACT RiPPs are a rapidly growing class of peptide derived natural products. RiPP enzymes carry out

remarkable chemistry en route to transforming short peptides into bioactive molecules. We have

recently developed new technology for generating large and diverse libraries of RiPP natural products

based on the promiscuity of key biosynthetic enzymes from RiPP pathways. Two examples will be

presented. First, by employing members of the new pyridine synthase family of macrocyclases,

discovered in our lab, we create non-natural analogues of the potent anti-MRSA antibiotics known as

thiopeptides to explore their structure activity relationships. Second, we exploit the sactionine synthase

AlbA from Bacillus subtilis to design stapled alpha-helical mimics for the inhibition of key therapeutic

targets.

BIO Born and raised in New Jersey, Dr. Bowers obtained his BA from the University of Chicago and went on

to complete his Ph.D. in organic chemistry in 2007, at the University of Illinois at Chicago, under the

guidance of Prof. David Crich. He was an NIH postdoctoral fellow in the labs of Professor Robert M.

Williams at Colorado State University and Professor Christopher T. Walsh at Harvard Medical School.

Aî‚•er spending a year as Assistant Professor at Purdue University, he joined the faculty of Chemical

Biology and Medicinal Chemistry at the University of North Carolina at Chapel Hill in 2012. His lab

engineers biosynthetic pathways and develops chemoenzymatic strategies to generate next-generation

therapeutics.

Jean Chmielewski Distinguished Professor of Chemistry, Purdue University

ABSTRACT A significant challenge in the development of effective antibacterial agents arises from bacterial

pathogens that have evolved to inhabit mammalian cells, such as phagocytic macrophages. Within these

intracellular safe havens the bacteria reproduce and form a repository, and are able to evade the host

immune response as well as a number of antibiotic drugs. Therefore, there is a great need to develop

antibiotics with the ability to enter mammalian cells and target intracellular pathogens at their specific

sub-cellular site. We have developed a class of molecules, cationic amphiphilic polyproline helices

(CAPHs), that enter mammalian cells through both direct transport and endocytosis. We have

determined that CAPHs also have potent antibacterial activity in vitro with a non-lytic mechanism of

action. This dual mode of action, non-lytic antibacterial activity with the ability to localize within

mammalian cells, provided us with agents with a pronounced ability to target and kill pathogenic

intracellular bacteria, including Mycobacterium tuberculosis, within human macrophages.

Danny Chou Assistant Professor, University of Utah

ABSTRACT For people with diabetes, maintaining blood glucose levels within the nondiabetic range is effective in

delaying or even preventing long-term complications, but achieving near normoglycemia is still

challenging for these patients. The current fast-acting insulin still has relatively slow absorption after

subcutaneous injection which leads to delayed insulin response and sub-optimal control of glycemia.

Furthermore, the long duration of action (4-5 hours) may lead to post-meal hypoglycemia. Innovation in

insulin design has been hampered by the hexameric status of insulin; an ultrafast-acting insulin requires

a monomeric insulin molecule. Therefore, despite millions of dollars invested, a truly monomeric,

ultrafast-acting insulin remains to be invented. In this presentation, I will discuss our bio-inspired

approach to utilize a venom insulin as a potential candidate with ultrafast-acting properties.

BIO Danny Chou is an assistant professor in Department of Biochemistry at University of Utah. His lab

focuses on using synthetic organic chemistry to develop new peptide and protein therapeutics in the

area of metabolic diseases. Danny has received a number of honors including Vertex Scholar, JDRF

Postdoctoral Fellowship and most recently American Diabetes Association Junior Faculty Development

Award.

Greg Czyryca President, Allosterix Pharmaceuticals, LLC

ABSTRACT Non-natural cyclic peptides constitute an underutilized yet attractive segment of the chemical diversity

space. Such peptides are conformationally, chemically and proteolytically stable, the incorporation of

non-proteinogenic amino acids generally lowers their immunogenicity, their binding interfaces can be of

the size and complexity not achievable in small molecules, and all these desirable properties materialize

in relatively short sequences that can be readily synthesized using the routine solid phase methodology.

Such artificial peptides cannot be, by definition, derived from natural sequences. Combinatorial

chemistry faces substantial difficulties in this case due to the combinatorial complexity involved. De

novo design is thus the preferred enabling technology for this class of molecular entities. An original

variant of the Monte Carlo chain growth algorithm was applied to the design of short cyclic peptides -

CD4-mimicking ligands of HIV gp120. In the role of entry inhibitors, the engineered cyclic peptides

performed by 1 to 2 orders of magnitude better than the mechanistically similar small molecule positive

standard NBD-556. Conclusion: Structure-based de novo design is capable of delivering cyclic peptides

that fill the gap between small molecules and biologics. The case study indicates a satisfactory capability

of these synthetic compounds to mimic biologics, while offering much better drug-like properties.

Jesse Z. Dong Vice President, Peptide Chemistry, Neon Therapeutics

ABSTRACT Neon Therapeutics is pursuing an exciting clinical development program of a personalized neoantigen

vaccine. Neoantigens arise as a result of somatic mutations during the development and progression of

tumors. They are inherently non-self and are seen as foreign by the immune system. Mounting evidence

suggests that immune rejection of tumors, for example which is seen with checkpoint modulators, may

be mediated by recognition of neoantigens. Neon’s peptide vaccine targets neoantigens unlocking

the immune system to attack tumors.

BIO Jesse Dong is Vice President, Peptide Chemistry at Neon Therapeutics. At Neon he is leading the peptide

chemistry activities of developing personalized cancer vaccine NEO-PV-01. Prior to joining Neon, he was

the founder of Amphitide. Jesse worked at Ipsen from 1993 to 2013 as Vice President of Compound

Discovery, heading global peptide chemistry division and leading peptide-based R&D programs. He is the

inventor of Abaloparatide, Relamorelin, Setmelanotide, Taspoglutide and Dopastatin (BIM-065). Jesse is

named inventor or co-inventor in 64 issued US patents and over 80 US patent applications. He has over

145 publications and abstracts.

James Gilligan Chief Scientific Officer, Tarsa Therapeutics

ABSTRACT The presentation will describe the challenges of developing recombinant salmon calcitonin (rsCT) from a

CMC and drug development perspective; ranging from early phase development through the results of

the phase 3 program and NDA submission. The strategy and CMC development issues associated with a

505(b)(2) NDA dealing with a change in the route of administration (nasal to oral) as well as API

manufacturing will be discussed. In particular, the strategy for bridging a peptide manufactured using

recombinant DNA technology to the reference listed drug (RLD) manufactured by chemical synthesis will

be presented.

An overview of the development and scale up issues encountered for the oral delivery technology of a

peptide in a high potency modified release tablet, as well as issues related to the unique properties of

peptide based therapeutics versus small molecules will be addressed. The topline results from the

clinical development program (Phase I-III) will be presented.

BIO Currently Dr. Gilligan is Chief Scientific Officer and Co-Founder of Tarsa Therapeutics Inc. located in

Philadelphia, PA. Tarsa was founded in late 2009 with the goal of developing innovative therapies for the

treatment and prevention of osteoporosis and related bone diseases. Tarsa is developing TBRIAâ„¢ an

oral formulation of salmon calcitonin, a peptide hormone that inhibits bone resorption, a key process

underlying the development of osteoporosis. Tarsa has submitted it’s 505(b)(2) NDA application for

TBRIA to the FDA which is currently under review.

Prior to joining Tarsa, Dr. Gilligan held positions of increasing responsibility for nearly 30 years at

Unigene Labs, where he led the development of the oral calcitonin product now licensed to Tarsa. He

served as vice president of product development at Unigene, where he was project leader for the oral

and nasal calcitonin programs, as well as the oral parathyroid hormone and site-directed bone growth

programs. Dr. Gilligan was responsible for leading the clinical programs and successful U.S. and

European regulatory registrations for the nasal calcitonin product Fortical® Nasal Spray and the

injectable calcitonin product Forcaltonin® Injection.

Dr. Gilligan holds a Ph.D. in pharmacology & toxicology from the University of Connecticut, performed

his post-doctoral research at the Roche Institute of Molecular Biology and received a master’s

degree in international business from the Stillman School of Business at Seton Hall University.

Jan Johansson CEO and Founder, ARTERY Therapeutics, Inc.

ABSTRACT The novel apoE4 therapeutic CS6253 penetrates the blood brain barrier, upregulates the ABCA1

transporter and prevents Alzheimer’s disease pathogenesis Anat Boehm-Cagan1, Jan O. Johansson2,

John K. Bielicki3 and Daniel M. Michaelson11The Sagol School of Neuroscience, Tel Aviv University,

Israel; 2Artery Therapeutics, Inc.; 3Lawrence Berkeley Laboratory, USBackground: The allele ε4 of

apolipoprotein E (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD). No apoE4

specific therapeutic is presently available. ApoE is the natural ligand to the ABCA1 transporter, both

proteins found predominantly in astrocytes. The apoE to ABCA1 interaction regulate lipidation of apoE

and lipid composition of astrocyte cell membranes with many potentially favorable down-stream effects

of relevance for brain pathophysiology. We hypothesized that manipulating the apoE4 to ABCA1

interaction would have AD therapeutic actions. To this purpose we applied a peptide that selectively

causes ABCA1 mediated lipid removal from macrophage cells in established apoE4 vs. E3 in vitro and in

vivo models. Methods and results: Astrocyte cholesterol efflux is highly responsive to stimulation by

exogenous CS6253 peptide. Humanized astrocytes from apoE3 (E3) or apoE4 (E4) targeted replacement

mice were labeled for 2 days with [3H]cholesterol (1 mCi/mlL), and treated overnight with 22-

hydroxycholesterol/cis retinoic acid (each 10 mM final concentration) to upregulate ABCA1 expression.

Time-course showed basal [3H]cholesterol efflux from cells to serum-free medium was compromised in

apoE4 astrocytes. Incubating with peptide CS6253 (10 µg/mL) showed 6-fold improvement in

[3H]cholesterol efflux to serum-free medium containing in both apoE4 and E3 astrocytes. CS6253 i.p.

injection (20 mg/kg/48h for 6 weeks) in apoE4 target replacement mice prevented AD phenotype

pathogenesis and cognition decline. CS6253 crossed the BBB providing brain levels higher than the in

vitro EC50-value for ABCA1 mediated cholesterol efflux, and was found to co-localize with astrocytes in

the brain in both apoE3 and E4 mice. Levels of hippocampus ABCA1 were significantly lower in apoE4

mice compared to apoE3 mice in PBS treated groups and significantly increased by CS6253 treatment in

apoE4 mice. Lipidation of apoE in the hippocampus was compromised in apoE4 compared to apoE3

mice. CS6253 treatment increased apoE4 lipidation. Further analysis showed that CS6253 treatment

counteracted the apoE4-driven phenotype in the hippocampus resulting in decreased Aβ42 and

phosphorylated tau and increased levels of VGluT1 and apoER2. Cognitive decline was fully prevented in

apoE4 mice by CS6253 treatment as assessed by novel object recognition and Morris water maze.

Conclusion: ABCA1 agonist treatment by CS653 resulted in improved apoE4 lipidation in cells and in

mice. Six weeks treatment consistently counteracted apoE4 driven AD with regard to both phenotype

and cognition. The data point to the potential therapeutic utility of CS6253 in apoE4 sporadic AD.

Jesper Lau vice president, Novo Nordisk A/S

ABSTRACT Following the successful development of the first once-daily GLP-1 analog liraglutide we aimed to

discover analogs suitable for once-weekly dosing through acylation with fatty acids, enabling binding to

serum albumin in vivo. This technology allows a drug molecule that is structurally near human GLP-1,

which is not possible with fusion protein strategies. To go from once-daily to once-weekly dosing, the

aim of our studies were to increase albumin affinity and obtain full stability against DPP-4 degradation,

without compromising a high GLP-1 receptor (GLP-1R) affinity. The human GLP-1R was used for testing

of receptor and albumin affinity. Pharmacokinetic properties were investigated in rats and pigs.

Alterations in the peptide sequence as well as the fatty acid “sidechain― were explored. The latter

was the key feature to secure the combination of high albumin affinity and high GLP-1R potency. Length

and type of fatty acid as well as the linking chemistry between the fatty acid and GLP-1 were the

parameters investigated. Semaglutide was selected as the optimal once weekly candidate. Semaglutide

has two amino acid substitutions compared to human GLP-1 (Aib(8), Arg(34)) and is derivatized at lysine

26. The GLP-1R affinity of semaglutide (0.38 ± 0.06 nM) was three-fold decreased compared to

liraglutide, whereas the albumin affinity was increased. The plasma half-life was 46.1 h in mini-pigs

following i.v. administration, and semaglutide has an MRT of 63.6 h after s.c. dosing to mini-pigs.

Semaglutide is currently in phase 3 clinical testing.

Fa Liu Director of Chemistry, Novo Nordisk

ABSTRACT The challenges involved in the chemical synthesis of insulin and its analogs hinder the exploration of the

structure-function relationships of this indispensable therapeutic. Problematic features such as the

hydrophobicity of the A-chain and the complexity of the disulfide architecture are unique to insulin and

have required implementation of specialized strategies. Our efforts have centered on two fundamental

approaches: the single chain biomimetic route and the two-chain directed disulfide method. An example

of the former is our use a novel single chain precursor “desDi― which enabled superior folding

efficiency and proved to be less sensitive to individual substitutions. The latter approach is exemplified

by the directed disulfide approach using orthogonally protected cysteine pairs to form insulin. We have

additionally expanded the scope of the two-chain directed disulfide method to other insulin like

peptides which contain oxidation-sensitive residues through the use of an iodine-free method

employing Phacm cysteine protection and enzymatic conversion to form the (A7-B7) disulfide bond. We

will also highlight application of the isoacyl concept to address the hydrophobicity of the A-chain and

preparative recovery of both chains. Application of the isoacyl route afforded human insulin in 24%

overall yield based on initial resin substitution representing the most efficient chemical synthesis of

human insulin to date.

Len Luyt Associate Professor, University of Western Ontario

ABSTRACT The interaction of the polysaccharide hyaluronan (HA) with RHAMM (receptor for hyaluronan mediated

motility) is implicated in the promotion of inflammatory responses. RHAMM is an intracellular tubulin-

binding protein that, in response to injury, is exported to the cell surface, associates with CD44 and,

upon binding to HA, results in activation of growth factor signalling pathways, including ERK1,2.

Interfering with RHAMM-HA interactions has therapeutic potential for inflammation-related diseases

including arthritis, chronic fibrosis and cancer. We have discovered peptides that interfere with

RHAMM-HA binding. In one approach, peptides that bind to RHAMM were developed based upon

sequences of the carboxy-terminal tail region of tubulins that bind to the RHAMM HA binding region.

These peptides act as mimics of HA and it has been shown that they have selectivity for RHAMM over

other HA receptors such as CD44. In another approach, stapled peptides consisting solely of the HA

binding domain of RHAMM were discovered to maintain the alpha-helical character of RHAMM and bind

to HA. The evaluation of these peptides for their effect on cell migration/invasion, inflammation and

fibrosis, will be discussed. The ability to discover peptides that interfere in RHAMM-HA interactions sets

a precedent for a new approach in the development of drugs that target protein-carbohydrate

interactions.

BIO Dr. Len Luyt received his Ph.D. from the University of Western Ontario in Chemistry and subsequently

undertook a post-doctoral fellowship with Prof. John Katzenellenbogen at the University of Illinois,

Urbana-Champaign. He then led a research team as a Senior Medicinal Chemist with the

pharmaceutical company Bayer-Schering. Dr. Luyt joined Western University in 2005 as a faculty

member with a joint appointment in the departments of Oncology, Chemistry and Medical Imaging. He

has published 36 journal articles, 5 book chapters, greater than 80 conference abstracts, and has 9

patents granted or applied for. He was awarded the Early Researcher Award (ERA) from the Ministry of

Research and Innovation and has held peer-reviewed grant funding from NSERC, CIHR, OICR, Prostate

Cancer Canada and the Canadian Breast Cancer Foundation. The research program of Dr. Luyt spans

from basic chemistry activities, looking at novel methods of incorporating metal complexes into peptide

structures, through to applied research, investigating new peptide therapeutics and molecular imaging

agents for novel cancer targets.

Adam Mezo Sr. Research Advisor, Group Leader, Eli Lilly and Company

ABSTRACT Peptides possess enormous potential to contribute to the current standard of care across many

therapeutic areas. By virtue of their inherently short plasma residence time, it is advantageous to

identify robust strategies to extend their time-of-action in circulation to lessen the burden of frequent

injections. GIP/GLP-1-based dual agonists represent a novel approach to treat diabetes, but such

peptides still require protraction in circulation to reduce the burden of frequent injections. In this study,

a GIP/GLP-1-based dual-agonist peptide was derivatized with iodoacetamide and conjugated to thiol-

bearing time-extension moieties. Four different time-extension technologies were evaluated and

compared: native human albumin, XTEN (3 sizes), heparosan (3 sizes), and hydroxyl ethyl starch (3 sizes).

The presentation will discuss the in vitro activity of the peptide analogs against the GLP1-R and GIP-R, as

well as their pharmacokinetic and pharmacodynamic characteristics in preclinical in vivo models.

BIO Adam Mezo, PhD. is currently a Sr. Research Advisor and leads a team of discovery peptide and protein

chemists at Eli Lilly and Company in search of next-generation therapeutics primarily in the fields of

endocrinology and neurology. Prior to this role, he spent 12 years at Biogen Idec and Syntonix

Pharmaceuticals in a variety of roles, most recently as a Director, Molecular Discovery, where he led a

diverse team of chemists, biochemists, and molecular biologists in the discovery and development of

peptide and protein therapeutics in the fields of hemophilia and immunology. He performed

postdoctoral work at the Massachusetts Institute of Technology in the field of peptide chemistry,

received a Ph.D. in organic chemistry from the University of British Columbia in 1999 and a B.S. from

Queen’s University (Kingston, Canada) in 1993.

Stephen O'Connor Senior Director, Chemistry Research and CMC, Cara Therapeutics, Inc.

ABSTRACT Peptides with high affinity and selectivity for the kappa opioid receptor have been known for more than

20 years, but peptides suitable for clinical development have not been forthcoming. CR845 is a potent

and selective synthetic peptide kappa opioid receptor (KOR) agonist being developed as both

intravenous (IV) and oral formulations (enteric-coated tablets). CR845 is currently in mid- to late stage

clinical development (Phase 2-3) to assess the safety and efficacy of this drug in patients with post-

operative pain, osteoarthritis or uremic pruritus using the IV or oral formulation depending upon the

particular indication. CR845 has full agonist activity at rodent and human kappa opioid receptors (EC50 =

0.16 nM) with no other detectable off-target activities. Non-clinical pharmacological studies indicate

that CR845 has combined analgesic, antipruritic, and anti-inflammatory properties which support the

therapeutic indications of pain and pruritus being pursued with this compound. CR845 is composed of 5

unnatural amino acids and does not readily cross the blood-brain barrier. Consequently, CR845

predominantly activates KORs expressed in peripheral neurons and on immune cells. CR845 is primarily

excreted unchanged into the urine and bile with no major metabolites identified. The safety data

available to-date and the potential benefit of CR845 treatment support continued study and

development of this compound.

BIO I have been with Cara Therapeutics for 9 years primarily focused on the GMP manufacturing of CR845

drug substance and drug product for the clinical development program. Prior to Cara, I was at Bayer (in

West Haven, CT) for 8 years working in both the research (Medicinal Chemistry) and Development

(Project Management). I began my professional career with Abbott Laboratories as a Medicinal Chemist

in 1993.

Deborah O'Neil CEO/CSO, NovaBiotics Ltd

ABSTRACT Impaired immunity as a consequence of chemotherapy, infection or malignancy leads to a reduced

antimicrobial peptide (AMP) host immune response. This is because of the depletion (in number &

functionality) of the sources of these key immune effector molecules; neutrophils & epithelial cells.

Patients in this immunocompromised state are consequently susceptible & often succumb to fungal

infections from organisms such as Aspergillus Spp, Candida Spp & Cryptococcus Spp which a functioning

AMP system would normally keep in check. Increasing infection & mortality rates from fungal infections

drive an urgent need for new antifungal solutions to these poorly served clinical challenges. NovaBiotics

has engineered Novamycin, a novel, arginine-based AMP to target these infections as a more potent

"replacement" of naturally occurring AMP. As a membrane-acting, rapidly fungicidal agent, Novamycin

has multiple benefits & USPs over the existing, limited armoury of ineffective &/or toxic hydrophobic

small molecule antifungals; not least its lack of toxicity, resistance development, more rapid time of kill

& broader spectrum of antifungal activity. NovaBiotics has demonstrated that as a hydrophilic peptide,

Novamycin has the physicochemical benefit over existing therapeutic options of being able to be

successfully formulated & delivered by inhalation, parenterally & mucocutaneously to effectively target

at least Aspergillus Spp & Candida Spp in the respiratory tract, blood stream/deep tissues & in the oral &

vaginal cavities. Novamycin is highly differentiated as a much needed antifungal therapeutic candidate

& on the basis of the in positive in vitro and in vivo efficacy & toxicology data sets obtained thus far, will

progress quickly into clinical development as an inhaled therapy in pulmonary Aspergillosis in the first

instance.

Parth Patwari CSO, ProteoThera, Inc.

ABSTRACT Therapeutic peptides and proteins are not effective when they are not able to reach their targeted

tissues and remain there long enough for activity. In particular, therapies for diseases of the joint cannot

penetrate into avascular tissues such as the articular cartilage and meniscus. ProteoThera solves this

probem with a proprietary matrix-binding peptide that allows for optimal transport into tissues and

extended residence in those tissues while maintaining activity of the therapeutic cargo.

Scott Peterson Executive Director, Business Development, Intarcia Therapeutics

ABSTRACT The technology behind ITCA 650, an investigational therapy for T2DM and currently in Phase 3 of

development, is an osmotic mini-pump that can deliver exenatide, a GLP-1 receptor agonist,

subcutaneously for extended periods of time. This presentation will highlight the technology behind the

Intarcia Osmotic Mini-Pump combined with in-vitro, in-vivo and human data generated with ITCA-650.

BIO Scott is currently a member of Intarcia Therapeutics’ Corporate Development Team and focused on

identifying and evaluating opportunities for collaborations involving new molecules and Intarcia’s

proprietary, subcutaneous drug delivery system. The Intarcia osmotic mini-pump, combined with the

company’s unique formulations for stabilizing peptides and proteins at human body temperatures

for extended periods of time, enables the continuous delivery of therapy for up to twelve months.

Previously, Scott was a member of Merck’s Business Development and Licensing Innovation Hub in

Boston, MA where he evaluated new opportunities for collaborations and partnerships, including those

involving novel formulations and drug delivery platforms. Scott received his Ph.D. in Synthetic Organic

Chemistry from Harvard University under the mentorship of Prof. David A. Evans before joining Merck

Research Laboratories in Boston, MA, initially as a Medicinal Chemist where he contributed to the

discovery and development of small molecule therapies for the treatment of human cancers, auto-

immune and neurological diseases.

Robin Polt Professor of Chemistry & Biochemistry, BIO5, The University of Arizona

ABSTRACT The incorporation of O-linked glycosides into endogenous neuropeptides provides glycopeptides of

enhanced stability that penetrate the Blood-Brain Barrier (BBB), and retain affinity for their G-Protein

Coupled Receptors (GPCRs). Several examples have been explored to produce analgesic and

neuroprotective CNS drugs with masses ranging from 700—3,500 M.W., including enkephalins,

endorphinsdynorphins, secretins and other potent peptide hormones. We may regard this class of

drugs as one that bridges the gap between "small molecules" and "biologics."

BIO Polt has embraced several relatively diverse scientific disciplines in his career, often running counter to

the prevailing wisdom and advice. He studied chemistry at IUPUI under the direction of Prof. Martin J.

O’Donnell, where he was involved in the enantioselective alkylation of masked glycine anion and

cation equivalents to produce the first of the “O’Donnell Schiff Bases.― (Ph2C=O +

H2NCH2CO2CH2CH3 → Ph2C=NCH2CO2CH2CH3) A NSF Fellowship that took him to Columbia

University where he studied with Prof. Gilbert J. Stork, and then on to Prof. Dieter Seebach’s group in

Zürich where he studied the alkylation of peptides in addition to glycine equivalents. Robin shifted his

interests toward the synthesis and evaluation of glycopeptide drugs at the University of Arizona.

Glycosylated neuropeptides show excellent biological activity, extended stability in vitro and in vivo, and

also cross the blood-brain barrier to produce centrally-mediated effects. Presently, Robin is involved in

the study of glycolipid surfactants in collaboration with Prof. Jeanne Pemberton, as well as Prof. Michael

Heien, who uses MS2 and MS3 techniques coupled with microdialysis to quantify our drugs and their

metabolites in vivo.

Jonathan Ryves Chief Executive Officer, Cupid Peptides

ABSTRACT Cell penetrating peptides (“CPPs―) have a huge role to play in both research and drug delivery.

However, the majority of bio-medical researchers rarely use the most sophisticated CPPs available. We

present our novel CPP “Cupid― capable of carrying large proteins into the cytosols of living cells

where they refold into biologically active forms. With Cupid technology we offer the researcher Speed

– Cargoes are bioactive in 30-60 mins; Control – GFP fluorescence allows monitoring Cupid-Cargo

entry and Versatility – Mutant proteins or parts of proteins up to 80kD can now be delivered.

BIO Dr W Jonathan Ryves founded Cupid Peptides in 2012. He has over 25 years’ experience in Protein

Biochemistry and Molecular Biology working in UCL and Cardiff University and has co-authored over 40

peer-reviewed scientific publications. With over 10 years experience in Cell Penetrating Peptide (CPP)

research, he is pioneering the practical use of “Cupid―, the most powerful form of CPP, as a

technology platform for Biomolecular Researchers to understand protein-protein interactions.

Weijun Shen Principal Investigator, California Institute for Biomedical Research

ABSTRACT As a drug class, peptides offer exquisite specificity and potency, but also present challenges associated

with poor stability and short half-life, manifesting in the need for frequent injections, poor patient

compliance, and overall compromised efficacy. Exendin-4, a glucagon-like peptide-1 receptor agonist

administered twice daily via subcutaneous injection, improves glycemic control, often with associated

weight reduction. To further improve the therapeutic efficacy of exendin-4, we have developed a novel

peptide engineering strategy that incorporates a serum protein binding motif onto a covalent side-chain

staple and applied to the peptide to enhance its helicity and as a consequence, its potency and serum

half-life. We demonstrated that one of the resulting peptides, E6, has significantly improved half-life and

glucose tolerance in an oral glucose tolerance test (OGTT) in rodents. Chronic treatment of E6

significantly decreased body weight and fasting blood glucose, improved lipid metabolism and also

reduced hepatic steatosis in DIO mice. Moreover, the high potency of E6 allowed us to administer this

peptide using a novel microstructure-based transdermal delivery system. Pharmacokinetic and

pharmacodynamic studies in guinea pigs showed that a single 5 min application of a microstructure

system containing E6 significantly improved glucose tolerance for 96 hours. This delivery strategy may

offer an effective and patient-friendly alternative to currently marketed GLP-1 injectables. Current

progress in applying this half-life extension strategy to other peptide hormones will also be discussed.

References: Peng-Yu Yang, Huafei Zou, Elizabeth Chao, Lance Sherwood, Vanessa Nunez, Michael

Keeney, Esi Ghartey-Tagoe, Zhongli Ding, Herlinda Quirino, Xiaozhou Luo, Gus Welzel, Guohua Chen,

Parminder Singh, Ashley K. Woods*, Peter G. Schultza* and Weijun Shen* Engineering a long-acting,

potent GLP-1 analog for microstructure-based transdermal delivery, Proc Natl Acad Sci USA 2016, Early

EditionAvinash Muppidi, Huafei Zou, Elizabeth Chao, Pengyu Yang, Lance Sherwood, Vanessa Nunez,

Ashley Woods, Peter G Schultz*, Qing Lin* , Weijun Shen* “Design of potent, proteolytically stable

oxyntomodulin analogs― ACS Chem Biol 2016,11(2):324-8

Vinay Singh Founder & CEO, SYNG Pharmaceuticals Inc

ABSTRACT Endometriosis is estimated to affect 5-10% of women of reproductive age and causes infertility in about

50% of cases; affecting over 200 million women and girls globally. Currently, there are over 15 million

surgically confirmed patients of Endometriosis in North America with an overall impact of approximately

$22 Billion dollar on economy. Endometriosis, for which there is no absolute cure, is a painful female

reproductive disease in which tissue from the uterine lining (endometrium) migrates outside the womb

and implants in other areas of the body. Endometrium in ectopic sites must establish its own blood

supply to supports its growth and development into an endometriosis lesion. SYNG Pharma’s novel

target is an intrinsically disordered protein that functions in its physiologically unfolded form, has

elevated expression in endothelial cells of endometriosis lesions compared to eutopic endometrium.

SYNG Pharma has developed a specific peptide inhibitor, SP011, a potential first non-hormonal therapy

of endometriosis. In vitro binding studies demonstrate that SP011 specifically binds to the target.

Localization of SP011-FITC was shown using intra-vital fluorescence microscopy, which also confirmed

inhibition of neovascularization in presence of peptide inhibitor using an animal model of endometriosis.

Data from pre-clinical efficacy studies using animal model shows inhibition of human endometrial lesion

growth and reduction of neovascularization. Treated group also had reduced blood vessel growth when

given daily intraperitoneal injections of SP011 compared to phosphate buffered saline control.

BIO Vinay is a dynamic and innovative educator and an entrepreneur in the Biotechnology field who

combines an accomplished academic career with strong success in business and management. He has

proven achievements in Biotechnology Research and Development, specifically Molecular Diagnostics,

Cancer Therapeutics and Biomarkers. He has 18 years of business experience in product development,

marketing and sales and successfully started and exited 3 companies He was an Adjunct Professor at

Queen's University School of Medicine till 2015 where he taught biotechnology and studied Natively

Unfolded Proteins as Therapeutic Targets. In a short span of his academic career, he has an exemplary

record as a researcher and a Professor with 35 high impact International papers with over few thousand

total citations and 4 independent discoveries with granted patents and multiple pending patent

applications worldwide. Vinay has given invited talks around the world and presented research in over

70 conferences. He is an active volunteer with multiple organizations and recently received 15 Year

Volunteer Services Award by the Ministry of Immigration, Government of Canada. Vinay received his

Ph.D. in Biotechnology with specialization in Bioinformatics and Molecular Diagnostics in 2001 and an

MBA from Smith School of Business, Queen's University in 2012.

Michael Stowell CTO, AmideBio

ABSTRACT The maintenance of glycemic control is most conveniently achieved using insulin pumps which require

an insulin formulation that is stable for extended periods of time at body temperature. Current insulin

formulations are only stable for days before chemical degradation and/or fibrillation results in loss of

activity and the potential for clogging of insulin pumps. We have demonstrated the use of Cap-ClipTM

technology for the rapid SAR discovery of conformation locked ultra-stable and ultra-concentrated

insulins. Novel insulin analogues with both long acting and short acting profiles were discovered that are

stable at 40â•°C for more than 3 months and can be concentrated to U1000 and greater. I will provide a

summary of the discovery program and a preliminary SAR tree relating design principles to activity and

stability.

Lex Van der Ploeg CSO, Rhythm Pharmaceuticals

ABSTRACT None provided.

BIO Dr. Van der Ploeg has been our Chief Scientific Officer since October 2011. He has more than 25 years of

drug development experience focused on obesity, metabolic disorders, oncology, and

neurodegenerative diseases. Before joining Rhythm, he was Senior Vice President of Integrative

Medicine and Translational Science at Abraxis Bioscience and Head of R&D at Abraxis Health; both

companies were acquired by Celgene Corporation. Prior to that, he held R&D leadership roles at MRL

directing drug development programs in metabolism, oncology, and neurodegenerative diseases as Vice

President, Basic Research and Site Head, MRL Boston; Site Head, MRL San Diego; and Head, Obesity

Research for Merck Rahway and Banyu, Japan. Previously, Dr. Van der Ploeg was an associate professor

in the Department of Genetics and Development at Columbia University. He has received numerous

awards and grants for his research and has published more than 200 peer-reviewed research papers. Dr.

Van der Ploeg is a named inventor on more than 50 patents and patent applications. He received an

M.S. in Biochemistry from the University of Amsterdam and a Ph.D. in

Biochemistry/Enzymology/Genetics from the University of Amsterdam/Netherlands Cancer Institute.

Carolina Vega Director of Pharmaceutical Development, Apellis Pharmaceuticals

ABSTRACT The complement system is part of the body’s immune system. It can be activated by three principal

activation pathways: the classical pathway, the lectin pathway and the alternative pathway. All three

activation pathways converge on C3, leading to three principal effects of complement activation:

opsonization, inflammation and the membrane attack complex formation. Under conditions of excessive

or uncontrolled activation, the complement system plays a key role in a wide range of autoimmune and

inflammatory diseases. Apellis lead product candidate, APL-2, targets the complement system at the C3

level, inhibiting all effects of the complement cascade. By inhibiting C3, we believe that APL-2 may effect

disease control and disease modification.

APL-2 is the conjugate of APL-1, a synthetic cyclic peptide, with a long half-life. It is currently in the clinic

for the treatment of PNH and AMD. Recent data from healthy volunteer studies confirmed that

pharmacological doses of APL-2 were safe and well tolerated and that APL-2’s PK/PD profile supports

daily SC administration. In addition, daily APL-2 doses of 180 mg and 270 mg significantly reduced

hemolytic activity as early as eight days after the start of dosing, and this inhibition was maintained

through the dosing period.