WASHINGTON, March 29, 2017 /PRNewswire/ -- Vanda
Pharmaceuticals Inc. (Vanda) (NASDAQ: VNDA) announced today that it
has entered into a license agreement with UC San Francisco (UCSF), under which Vanda will
acquire an exclusive worldwide license from UCSF to develop and
commercialize a portfolio of Cystic Fibrosis Transmembrane
Conductance Regulator (CFTR) activators and inhibitors.
CFTR activators and inhibitors may have broad applicability in
addressing a number of high unmet medical needs, including chronic
dry eye, constipation, polycystic kidney disease, cholestasis and
secretory diarrheas. This portfolio of CFTR activators and
inhibitors was developed in the UCSF laboratory of Alan S. Verkman, M.D., Ph.D. The portfolio of
compounds are at a pre-investigational new drug (IND) stage where
in addition to ongoing chemistry optimization work, several lead
compounds have been identified which are ready for further
IND-enabling work.
"The licensing of the CFTR portfolio of activators and
inhibitors is an important milestone for Vanda, as we continue to
realize our vision of developing treatments to address unmet
medical needs. The recently published animal model data from Dr.
Verkman's team related to dry eye, constipation, polycystic kidney
disease and diarrhea indications demonstrates the broad potential
applicability of these compounds," said Mihael H. Polymeropoulos, M.D., President and
CEO of Vanda.
"I am excited to be working with Vanda to advance the CFTR
activators and inhibitors into the clinic. While CFTR
modulators have been recently approved for the treatment of certain
mutations in cystic fibrosis, the work we have done suggests these
unique activators and inhibitors of wild-type, non-mutated CFTR
could have utility in a number of prevalent conditions, including
some where there is currently no available therapy," said Verkman,
professor of medicine and of physiology, and director of the Cystic
Fibrosis Research Development Program at UCSF.
This licensing agreement was negotiated with UCSF's Office of
Technology Management (OTM). The OTM leads UCSF's licensing and
business development efforts that translate cutting-edge science
into therapies and products that directly benefit patients
worldwide.
Under the terms of the agreement, Vanda will pay UCSF an initial
license fee of $1 million and will be
responsible for all development costs. UCSF is eligible to receive
up to $46 million in potential
development, regulatory and sales milestones as well as
single-digit tiered royalties on net sales should a product be
successfully commercialized.
In 2017, Vanda intends to complete the technology transfer
activities from UCSF and initiate IND enabling studies for several
CFTR indications.
About CFTR
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
protein functions as a channel for the movement of chloride ions in
and out of cells, which is important for salt and water balance on
epithelial surfaces, such as in the lungs, intestines and the
surface of the eye.
The only currently FDA-approved therapies to target CFTR in
humans are KALYDECO® (ivacaftor) and its combination with
lumacaftor (ORKAMBI®), both made by Vertex. The CFTR potentiator
therapy ivacaftor was developed to treat cystic fibrosis (CF)
patients who have one of the following mutations in their CFTR
gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N,
or S549R. The combination of ivacaftor and lumacaftor was developed
to treat CF patients who have two copies of the F508del mutation in
their CFTR gene.
CFTR modulators that do not target specific rare mutations are
expected to have utility in a variety of conditions in patients who
have a disorder related to either impairment of or excessive fluid
secretion across epithelial surfaces. In these disorders, CFTR
activators have the ability to enhance fluid flow while CFTR
inhibitors restrict fluid flow, in both cases helping restoring
balance of fluids across membranes.
As CFTR activators increase water excretion into the
extracellular space they may be beneficial in treating a number of
conditions such as dry eye(1,2), cholestasis,
constipation(3), and some lung conditions such as COPD,
among others. Work in Verkman's lab demonstrated preliminary in
vivo efficacy for certain compounds in both dry eye and
constipation models, and work is ongoing in identifying and
validating additional CFTR activator indications.
As CFTR inhibitors decrease water excretion across epithelia,
such as where aberrant CFTR activation occurs, they may be useful
in the treatment of cholera, traveler's diarrhea(4),
polycystic kidney disease(5), and other conditions of
water hyper-excretion. To date, Verkman's work has shown evidence
of blocking cholera and E. coli-toxin-induced water
excretion as well as activity in models of polycystic kidney
disease.
About the UCSF CFTR Modulator Portfolio
The CFTR portfolio consists of patents and recently filed
application families describing CFTR activators and inhibitors,
some of which have proof-of-principle efficacy data in relevant
in vivo disease models and which possess high affinities for
CFTR.
About Vanda:
Vanda is a global biopharmaceutical company focused on the
development and commercialization of innovative therapies to
address high unmet medical needs and improve the lives of
patients.
For more on Vanda Pharmaceuticals, please visit
http://www.vandapharma.com.
About UCSF
UCSF is the nation's leading university exclusively focused on
health. UCSF is dedicated to transforming health worldwide through
advanced biomedical research, graduate-level education in the life
sciences and health professions, and excellence in patient care. It
includes top-ranked graduate schools of dentistry, medicine,
nursing and pharmacy; a graduate division with world-renowned
programs in the biological sciences, a preeminent biomedical
research enterprise and top-tier hospitals, UCSF Medical Center and
UCSF Benioff Children's Hospitals. For more on UCSF, please visit
www.ucsf.edu.
References
- Lee, S., P.W. Phuan, C.M. Felix,
J.A. Tan, M.H. Levin and A.S.
Verkman (2017). Nanomolar-potency aminophenyl-1,3,5-triazine
activators of the cystic fibrosis transmembrane conductance
regulator (CFTR) chloride channel for prosecretory therapy of dry
eye diseases. J. Med. Chem. 60:1210-1218.
- Flores, A.M., S.D. Casey,
C.M. Felix, P.W. Phuan, A.S. Verkman and M.H.
Levin (2016). Small-molecule CFTR activators increase tear
secretion and prevent experimental dry eye disease. Faseb J.
30:1789-1797.
- Cil, O., P.W. Phuan, J.H. Son,
J.S. Zhu, C.K. Ku, N.A.
Tabib, A.P. Teuthorn, L.
Ferrera, N.C. Zachos, R. Lin,
L.J. Galietta, M. Donowitz,
M.J. Kurth and A.S. Verkman (2017). Phenylquinoxalone CFTR
activator as potential pro-secretory therapy for
constipation. Transl. Res. 182:14-26.
- Cil, O., P.W. Phuan, A.M.
Gillespie, S. Lee, L. Tradtrantip, J. Yin, M. Tse,
N.C. Zachos, R. Yin, M. Donowitz and
A.S. Verkman (2017).
Benzopyrimido-pyrrolo-oxazine-dione CFTR inhibitor (R)-BPO-27 for
antisecretory therapy of diarrheas caused by bacterial
enterotoxins. Faseb J. 31:743-750.
- Snyder, D., L. Tradtrantip, C. Yao, M.J. Kurth and A.S.
Verkman (2011). Potent, metabolically stable
pyrimido-pyrrolo-quinoxolindione CFTR inhibitor for polycystic
kidney disease. J. Med. Chem. 54:5468-5477.
COMPANY CONTACT:
Jim Kelly
Executive Vice President & Chief Financial Officer
Vanda Pharmaceuticals Inc.
(202) 734-3428
jim.kelly@vandapharma.com
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SOURCE Vanda Pharmaceuticals Inc.