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Development of fluorogenic substrates for the diagnosis of pancreatic cysts

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43DK115341-01A1
Agency Tracking Number: R43DK115341
Amount: $235,341.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 300
Solicitation Number: PA16-302
Timeline
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-09-20
Award End Date (Contract End Date): 2019-09-19
Small Business Information
27 CABRILLO ST, APT E
San Francisco, CA 94118-4081
United States
DUNS: 078643292
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 GISELLE KNUDSEN
 (415) 476-1196
 knudsen@cgl.ucsf.edu
Business Contact
 CHARLES CRAIK
Phone: (415) 476-8146
Email: charles.craik@ucsf.edu
Research Institution
N/A
Abstract

Abstract
The dramatic increase in the number of patients being diagnosed with incidental pancreatic cysts
through improved imaging represents a unique opportunity to detect and treat cystic precursor
lesions before the onset of malignancy However pancreatic cysts also represent a major clinical
challenge because current diagnostics do not adequately reflect the biology of cyst malignant
transformation Misregulated pericellular proteolysis is a hallmark of invasive cancer Therefore
we are exploiting the activities of proteases in cyst fluid to develop an enzyme based diagnostic
test for the sensitive and specific identification of pre malignant pancreatic lesions Our goals
are to develop a rapid and minimally invasive assay that improves patient stratification over
current standard diagnostic markers and guides clinical decision making to avoid unnecessary
surgical intervention The Alaunus Biosciences diagnostic pipeline takes advantage of a substrate
profiling technology developed in the Craik Laboratory at UCSF referred to as Multiplex Substrate
Profiling by Mass Spectrometry MSP MS The MSP MS assay uses a peptide library platform to
monitor global protease substrate specificity and kinetic efficiency in complex biological samples
in an unbiased manner Through applying this substrate profiling approach to small volumes of cyst
fluid andlt L obtained by endoscopic ultrasound we have identified proteases that have highly
increased activity in pre malignant cysts and developed a proof of principle fluorogenic substrate
assay that achieves improved sensitivity and specificity compared to the current clinical standard
CEA In Aim we propose to use our activity based profiling approach to identify additional
distinguishing protease markers in an expanded patient cohort and already evident in our existing
cyst fluid data In Aim substrate specificity profiles then will be used to rationally design
and optimize specific fluorogenic peptide substrates that are cleaved by the target proteases
discovered Lead candidate substrates will be benchmarked in a blinded validation cohort for their
performance compared to CEA in distinguishing pre malignant from benign cysts If successful this
proposal will lay the groundwork for an actionable diagnostic test that will enable early
identification of pre malignant cysts and transform the clinical management of these challenging
lesions Project Narrative
Early diagnosis is the single most important tool to delay or avoid cancer related mortality Many
people undergoing abdominal MRI or CT scans today are found to have cysts in their pancreas which
in some cases can evolve into pancreatic cancer however it is currently very difficult to predict
which cysts are true precursor lesions and which will remain asymptomatic We are developing a
minimally invasive and highly sensitive diagnostic assay to identify cysts with a high likelihood
of progressing into pancreatic cancer to facilitate early detection of malignancy as well as avoid
unnecessary and costly surgeries for cases with benign cystic lesions

* Information listed above is at the time of submission. *

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