2016 INDUSTRY PARTNERING SUMMIT

SCHEDULE OF EVENTS
May 10, 2016 | Linder Reading Room, Michael F. Sorrell Center, UNMC | Omaha, Nebraska

9 a.m.

Opening Remarks

Overview: UNMC Pharmaceutical Research

9:10 a.m. Dept. of Pharmacology & Experimental Neuroscience Howard Gendelman, M.D.
9:25 a.m. Dept. of Cellular & Integrative Physiology Irving Zucker, Ph.D.
9:40 a.m. Dept. of Pathology & Microbiology Steven Hinrichs, M.D.
9:55 a.m. Center for Drug Delivery and Nanomedicine Joe Vetro, Ph.D.
10:10 a.m. Fred & Pamela Buffet Cancer Center TBA
10:25 a.m. Break

Technology & Start-up Presentations

10:35 a.m.

Vaccine Strategy for Parkinsons Disease:

Howard Gendelman, M.D.

Potent small molecule antibacterial

10:50 a.m. compounds:
Rongshi Li, Ph.D.
Glyoxalase-1 gene therapy for the treatment of
11:05 a.m. diabetes-related complications:
Keshore Bidasee, Ph.D.
Inhibiting MDSCs for the
11:20 a.m. treatment of biofilm infections:
Tammy Kielian, Ph.D.
11:35 a.m.

Welcome to
UNeMeds
2016 Industry
Partnering
Summit

CCL21 nanoparticles for cancer immunotherapy:

Joyce Solheim, Ph.D.

Lunch & Networking

1:10 p.m.

IKK-beta inhibitors:
Amar Natarajan, Ph.D.

Glucocorticoid prodrug for the improved

1:25 p.m. treatment of lupus:
Dong Wang, Ph.D.
1:40 p.m.

Immune stimulating peptides:

Prommune, Inc.

1:55 p.m.

Targeted radiopharmaceuticals:
Calidum, Inc.

Nanoformulations for the treatment of acute

2:10 p.m. spinal cord injury:
ProTransit Nanotherapy, LLC
2:30 p.m.

Poster Session & Networking

UNeMed.com | 402.559.2468

2016 INDUSTRY PARTNERING SUMMIT

UNMC Technology

Vaccine Strategy for

Parkinsons Disease

Prevents
future
disease,
treats
existing
disease

A group led by Howard Gendelman, M.D., at

UNMC has developed a novel vaccine strategy
capable of both preventing Parkinsons Disease
onset as well as preventing disease progression.
The vaccine combines the immunogen, N-Syn, with a molecular adjuvant that is capable
of promoting a regulatory adaptive immune response (regulatory T cell response) such as vasoactive intestinal peptide or GM-CSF.
Testing of the Parkinsons vaccine strategy
was carried out in a mouse model of Parkinsons
disease. Treatment using the novel vaccination strategy resulted in a
decrease in activated
microglia by 61 percent
and a 64 percent decrease
in
neuronal
injury.
Furthermore, this vaccine
strategy prevented loss of
dopaminergic
neurons
allowing for an astonishing
91 percent survival rate for
dopaminergic neurons.
Dr. Gendelmans group
has recently completed
a human study looking
at the effect of a potential adjuvant (GM-CSF)
to modulate the immune
profile in Parkinsons patients. Administration of
GM-CSF successfully upregulated the regulatory
T cell response providing
additional support for this
vaccine strategy.
Back

UNeMed.com | 402.559.2468

2016 INDUSTRY PARTNERING SUMMIT

UNMC Technology

Potent small molecule

antibacterial compounds

27 times more
potent than
vancomycin
against staph

Researchers at the University of Nebraska are

developing a new class of small molecules for the
treatment of bacterial infections.
They have currently developed lead compounds with nano-molar MICs against staph and
anthrax. One of these compounds had a potency
similar to ciprofloxacin against anthrax and was
27-fold more potent than vancomycin against
staph.
Some of these compounds also displayed
broad spectrum activity demonstrating low micromolar MICs against some gram negative bacteria such as A. baumannii, Enterobacter, and K.
pneumonia.
Work is currently being done to further evaluate some of the lead compounds in vivo against
staph and anthrax.
New analogs are also being designed to improve activity against gram negative bacteria.
Back
UNeMed.com | 402.559.2468

2016 INDUSTRY PARTNERING SUMMIT

UNMC Technology

Improve
brain & heart
function in
diabetic
patients

Gene therapy for the treatment

of diabetes-related complications
Reactive carbonyl species are
often over-produced in diseases like
diabetes, resulting in increases in
oxidative stress, inflammation and
DNA damage.
Methylglyoxal, or MGO, is
the most potent of these reactive
carbonyl species. It increases as early
as three days after hyperglycemia and
could be responsible for vascular/
cardiovascular dysfunction.
UNMC research Keshore Bidasee,
Ph.D., and his group have developed
a gene therapy to strategically
reduce MGO by overexpressesing
glyoxalase-1, an enzyme that degrades
MGO. The gene therapy contains a
key promoter region that expresses
glyoxalase-1 only in damaged cells
that are producing excess MGO.

When injected intravenously in

diabetic animals, the viral construct
improved the functions of the heart
and brain, two key end-organs
negatively impacted in diabetes. The
therapy also improved cognition and
reduced stroke damage (cerebral
ischemia-reperfusion injury), and
also modestly lowered blood glucose.
Glyoxalase-1 overexpression is
a novel therapeutic approach for
blunting cerebral vascular dysfunction
and cognitive impairment in diabetes.
Since microvascular dysfunction is an
established cause for other diabetic
complicationsblindness,
kidney
failure, diabetic cardiomyopathy,
erectile dysfunction and stroke
lowering MGO levels will also
diminish these complications.
Back

UNeMed.com | 402.559.2468

2016 INDUSTRY PARTNERING SUMMIT

UNMC Technology

Inhibiting MDSCs for the

treatment of biofilm infections
Prevent,
treat and
destroy
biofilms by
targeting
the immune
system

Tammy Kielian, Ph.D., has generated a

method to enhance the ability of a patients
immune system to eliminate bacterial biofilms.
This method focuses on the inhibition of specific cell populations knows as myeloid-derived
suppressor cells, or MDSCs.
In the presence of MDSCs, inflammation
persists but does not facilitate bacterial clearance. In addition, monocyte/macrophage infiltrates are reduced and T cell proliferation and
cytokine production are inhibited. Depletion of
MDSCs enhances the proinflammatory properties of infiltrating monocytes and macrophages
allowing for improved bacterial clearance.
Dr. Kielians group is currently testing various approaches to inhibit MDSC function
(such as STAT3 inhibitors) to identify potential
therapeutic strategies for the treatment of biofilm infections.
Back

UNeMed.com | 402.559.2468

2016 INDUSTRY PARTNERING SUMMIT

UNMC Technology

Significant
inhibition
of tumor
growth in
animal
studies

CCL21 nanoparticles for

cancer immunotherapy
Tatiana Bronich, Ph.D., and Joyce
Solheim, Ph.D., are developing the
chemokine CCL21 as an immunotherapy. Intratumoral administration
of CCL21 elicits a potent anti-tumor
response through the recruitment of
immune cells into the tumor, such
as dendritic cells, T cells and natural
killer T cells.
However, one problem with this
approach is that CCL21 doesnt last
long inside the body, and its effects
are short-lived.
To get around this, Drs. Bronich
and Solheim created a nanoformulation that protects CCL21 from degradation and will allow for extended
release of CCL21 within the tumor
site, prolonging the chemotactic effect

and increasing the overall therapeutic

impact.
Release kinetics of the nanoparticles have been analyzed and optimized. The researchers have also
performed small scale animal studies
using subcutaneous Pan02 tumors
where the nanoformulated CCL21
showed significant inhibition of tumor growth over nine days.
In addition to use as a standalone
immunotherapy, the CCL21 nanoparticles can also enhance other immunotherapies.
By enhancing immune infiltration
into tumors, the CCL21 nanoparticles
can greatly enhance the efficacy of tumor vaccines, cell therapies, oncolytic
viruses and antibody therapies.
Back

UNeMed.com | 402.559.2468

2016 INDUSTRY PARTNERING SUMMIT

UNMC Technology

IKK-beta inhibitors

Researchers at UNMC have identified a set of compounds that act as inhibitors of the NF-B pathway and specifically inhibit IKK. Initial work has
focused on the lead compound called 13-197.
13-197 has been evaluated using a wide variety of in vitro assays and
demonstrated antiproliferative activity against a
panel of cancer cell lines. It also inhibited NF-B
mediated gene transcription, enhanced caspase
3/7 activity, induced apoptosis, and sensitized
pancreatic cancer cells to gemcitabine.
13-197 has been tested in two different
in vivo cancer models. In an orthotopic mouse
model of pancreatic cancer, 13-197 significantly decreased tumor size and tumor metastasis. 13-197 also decreased inflammation and
microvessel density within the pancreatic tumors while increasing tumor necrosis.
13-197has also been tested in a mouse model of mantle cell lymphoma where it reduced tumor burden in the kidney, liver and lungs, and
significantly increased the overall survival of the
mice.
Researchers are now working on developing
additional analogs of 13-197, and hope to advance into the clinic soon.

Potent
inhibitor
of cancer cell
proliferation

Back
UNeMed.com | 402.559.2468

2016 INDUSTRY PARTNERING SUMMIT

UNMC Technology

Longer-lasting
and more
effective than
traditional
daily
treatments

Glucocorticoid prodrug for the

improved treatment of lupus
A UNMC team led by Dong Wang,
Ph.D., has developed a promising
drug candidate for the therapy of Lupus Nephritis, a kidney disease that
affects 30 percent to 60 percent of Systemic Lupus Erythematosus patients.
The drug candidate is a prodrug of
a commonly prescribed treatment for
Lupus, a cortiocosteroid called glucocorticoid. Cortiocosteroids are limited in their ability to effectively treat
Lupus because they cause severe systemic side effects, including adrenal
gland suppression, osteoporosis and
impaired liver function.
When modified with polyethylene glycol (PEG), the glucocorticoid
prodrug created by Dr. Wangs team
specifically targets inflamed kidney

tissue. The modification essentially made it possible to eliminate the

harmful side effects, and create a far
more effective long-term treatment
option for lupus nephritis.
Animal studies showed the new
prodrug compound, PEG-glucocorticoid, has a long-lasting effect, and
that monthly dosing had a better
overall effect on established nephritis
than daily traditional treatments. The
tests also showed that the monthly
PEG-glucocorticoid treatment increased lifespan and reduced incidence of severe kidney disease. The
new treatment also did not affect
bone quality, the peripheral white
blood cell count or suppress the adrenal gland.

UNeMed.com | 402.559.2468

Back

2016 INDUSTRY PARTNERING SUMMIT

UNMC Startup

Immune stimulating peptides

Prommunes lead immune simulatory peptide, EP67, selectively engages and activates antigen presenting cells (monocytes, macrophages,
dendritic cells) to induce the cellular
and molecular elements associated
with innate immunitythe bodys
first line of immune defense against
infection.
Once activated by EP67, these antigen presenting cells are primed to take
up infective pathogens (bacteria, viruses, fungi) and destroy them via natural cellular mechanisms.
Thus, EP67 can be used
to awaken and direct the
bodys own innate immune responses against
infective
pathogens

Host-Directed Immune Therapy

(HDIT).
Importantly, the EP67-activated
cellular processes for HDIT make
no distinction between normal or
antibiotic-resistant pathogens. Thus,
EP67-mediated HDIT can be used
to fight normal as well as antibiotic-resistant infections, and could be
used as a complement to traditional
antibiotics to deliver a powerful dual
therapeutic assault on troublesome
infections.
Back

Prommune Inc.
is a research and
development company
that has created a
unique and patented
means to safely and
effectively awaken the
bodys own natural
immune defenses
without inflammatory
side-effects
UNeMed.com | 402.559.2468

2016 INDUSTRY PARTNERING SUMMIT

10

UNMC Startup

Targeted cancer therapy

Calidum Inc.
is developing
products based on
a novel concept of
receptor-targeted
& DNA co-targeted
delivery of radiation
directly to the DNA
of a cancer cell

Calidum Inc. is developing compounds that

are tagged with a radioactive isotope that will
help clinicians better diagnose, track and treat
various cancers that include prostate, ovarian,
and triple negative breast cancers, neuroblastoma and glioblastoma.
Calidum is developing radiopharmaceuticals
that target the androgen receptor, butyrylcholinesterase and a third target.
Due to the strong safety and activity data of
Calidums lead compound, CDM-P123I, the U.S.
Food and Drug Administration has approved a
Phase-1 clinical trial in prostate cancer patients.
CDM-P123I specifically targets the androgen receptor on prostate cancer cells, thus it can
both identify and effectively destroy those cells
with dramatically reduced side-effects and with higher specificity than current
techniques.
Calidum will begin its Phase 1 trial for prostate cancer within the next 12
months, while completing the necessary preclinical studies to initiate human
trials for the additional targets in the next three years.
Back

UNeMed.com | 402.559.2468

2016 INDUSTRY PARTNERING SUMMIT

UNMC Startup

11

Nanoformulations for
treating acute spinal cord injury

ProTransit
Nanotherapy LLC is
developing therapies
based on potent
biomacromolecular
therapuetics
using patented
nanoparticle
technology

Nearly 1.3 million Americans, most of

them young people, are living with paralysis due to spinal cord injury, costing
$40.5 billion for their annual care.
The pathophysiology of traumatic spinal cord injury involves the initial physical impact, which leads to secondary injury cascades of degenerative cellular and
molecular events. The secondary injury
spreads along the spinal cord over time,
which adds new levels of disability and
has devastating effects.
ProTransit Nanotherapy is developing
nanoformulated biotherapeutics to prevent the degenerative events that follows
the injury.
Called Pro-NP, the technology proved
effective in regaining locomotive functions when used three hours after injury.
Pro-NP could potentially be administered in the field at the accident site of or
en route to a health care facility.
Back

UNeMed.com | 402.559.2468

2016 INDUSTRY PARTNERING SUMMIT

12

Poster Titles
CD74-based gene therapy for
Alzheimers disease (Tomomi Kiyota, Ph.D.)
Development of subtype selective
NMDA modulators (Dan Monaghan, Ph.D.)
New approaches for the diagnosis & treatment
of pancreatic cancer (Surinder Batra, Ph.D.)
Role of miR-133a in pathophysiology of
diabetic hearts (Paras Kumar Mishra, Ph.D.)
Screen to identify genes that are essential
and selective for tumor cells (Rob Lewis, Ph.D.)
Antimicrobial peptides and UNMCs
antimicrobial peptide database (Gus Wang, Ph.D.)
Pancreatic Differentiation Factor 2 a target for
the treatment of cancer (Surinder Batra, Ph.D.)

Department Overviews
Dept. of Pharmacology and
Experimental Neuroscience
Chair: Howard Gendelman, M.D.

siRNA Delivery System (Joe Vetro, Ph.D.)

Dept. Cellular and

Integrative Physiology
Chair: Irving Zucker, Ph.D.

The role of the thromboxane receptor in

obesity and diabetes
(Saraswathi Viswanathan, Ph.D.)

Dept. of Pathology and

Microbiology
Chair: Steven Hinrichs, M.D.

Efficient insertion of sequences using longer

single stranded repair DNAs
with CRISPR/Cas9 genome editing
(Channabasavaiah Gurumurthy, Ph.D.)

Center for Drug Delivery

and Nanomedicine
Joe Vetro, Ph.D.

Cyclophilin D: A target for the

treatment of renal diseases and obesity
(Babu Padanilam, Ph.D.)

Fred & Pamela

Buffet Cancer Center
TBA
Back

UNeMed.com | 402.559.2468

25TH ANNIVERSARY

Transferring technology for UNMC since 1991