Glenmark's Novel Molecule 'GRC 27864' for Chronic Inflammatory Diseases Including Pain Entering Human Trials

   Glenmark's Novel Molecule 'GRC 27864' for Chronic Inflammatory Diseases
                     Including Pain Entering Human Trials

  PR Newswire

  MUMBAI, April 3, 2014

MUMBAI, April 3, 2014 /PRNewswire/ --

- GRC 27864 is a Potent, Selective, Orally Bioavailable Inhibitor of mPGES-1

- The Molecule has Successfully Completed Pre-clinical and Phase 1 Enabling
Studies. Regulatory Submission has Been Filed for Phase 1 Trial
(First-in-Human) With MHRA, UK

- mPGES-1 Inhibitors Selectively Block the Production of PGE [2] While Sparing
Other Prostanoids of Physiological Importance

- With This Announcement, Glenmark has Reaffirmed its Position Globally in the
Development of Novel Pain Therapies

Glenmark Pharmaceuticals today announced that its Novel Chemical Entity (NCE)
'GRC 27864' is entering human trials. This NCE program targets Microsomal
Prostaglandin E synthase-1 (mPGES-1) as a novel therapeutic target in pain
management. Selective mPGES-1 inhibitors are expected to inhibit increased
prostaglandinE2 (PGE2) production in the disease state without affecting
other prostanoid metabolites and, consequently, may be devoid of the GI
(gastrointestinal) and cardiovascular side effects seen with NSAIDs and COX‑2
inhibitors, respectively.

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Glenmark has completed preclinical studies and Phase 1 enabling GLP studies
for its selected lead molecule, GRC 27864 and has filed a Phase 1 application
for first-in-human trial with the MHRA, UK. The Phase 1 studies are to be
initiated soon and are likely to get completed by January 2015. Following
this, Glenmark will also be initiating a proof of concept study in patients
with acute pain. 

Dr. Michael Buschle, Chief Scientific Officer, Glenmark Pharmaceuticals Ltd.,
mentioned, "We are excited that our mPGES-1 discovery program is moving
forward to human trials. This is another potential first-in-class molecule and
there is a significant unmet medical need. This announcement also reaffirms
our position globally in the development of novel pain therapies."

GRC 27864 is a potent, selective, and orally bioavailable inhibitor of
mPGES-1, an enzyme which is up‑regulated under inflammatory conditions.
Blocking the mPGES‑1 enzyme is a novel strategy and expected to selectively
inhibit increased PGE [2] production during inflammation, without affecting
other prostanoids of physiological importance. PGE [2] is a potent
pro‑inflammatory prostanoid and mediator of inflammatory response, which has
been implicated in many pathological conditions including inflammation, pain,
atherosclerosis, and fever. Thus, GRC27864 has the potential to be beneficial
in the chronic treatment of inflammatory diseases and associated pain.

GRC 27864 is currently being developed as a drug for the potential treatment
of chronic inflammatory disorders such as osteoarthritis (OA) and rheumatoid
arthritis (RA).

Note on mPGES-1

PGE [2] is a lipid mediator produced by arachidonic acid, which serves pivotal
functions in disease conditions associated with fever, inflammation, and pain.
mPGES-1 is a terminal enzyme in the PGE [2] biosynthetic pathway and solely
responsible for PGE [2] synthesis during inflammation. Over expression of
mPGES-1 is observed in various nonclinical animal models, such as RA, OA,
atherosclerosis, experimental autoimmune encephalomyelitis, cancer,
inflammatory bowel disease, multiple sclerosis, periodontitis, fibrosis,
Parkinson's disease, and Alzheimer's disease. On the contrary, mPGES‑1 deleted
cells produced significantly lower levels of PGE [2] in response to
inflammatory stimuli and were less sensitive to inflammatory and neuropathic
pain, and refractory to the development of joint pathology in rodent arthritis
models. Selective mPGES-1 inhibitors are expected to inhibit increased PGE [2]
production in the disease state without affecting other prostanoid metabolites
and are, consequently, may be devoid of the GI and cardiovascular side effects
seen with NSAIDs and COX‑2 inhibitors, respectively, potentially making them
suitable for chronic treatment of inflammatory diseases that are accompanied
with pain.

Addressable market

Recent reports indicate that more than 1.5billion people worldwide suffer
from chronic pain in some form with a direct correlation between incidence
rates and increasing age. It is estimated that, at some point in their lives,
20% of the global adult population suffers from pain with 10% of newly
diagnosed cases of chronic pain being added each year. Despite incremental
advances in opioid-based or cyclooxygenase-based therapies, there has been
little success in identifying and developing treatments based upon new targets
that might overcome the limitations of currently available analgesic
treatments for the management of chronic pain.

About collaboration with Forest

Glenmark has entered into a Collaboration and Option Agreement with Forest
Laboratories ("Forest"), a leading, fully integrated, specialty pharmaceutical
company, for the development of novel mPGES-1 inhibitors to treat chronic
inflammatory conditions, including pain. Forest has an exclusive option to
obtain license rights to the program upon the completion of Phase 1 clinical
trials. Under the terms of the agreement signed in FY 2013, Forest made USD 6
million upfront payment and also provided an additional USD 3 million to
support the next phase of work. In September 2013 and March 2014, Glenmark
received additional amounts of USD 2 million and USD 4 million, respectively,
as research fee payments from Forest. Hence, the total amount received by
Glenmark from Forest towards its novel mPEGS-1 inhibitors program is USD15

About Glenmark Pharmaceuticals Ltd.

Glenmark Pharmaceuticals Ltd. (GPL) is a research-driven, global, integrated
pharmaceutical company and ranked among the top 80 Pharma & Biotech companies
of the world in terms of revenues. Glenmark is a leading player in the
discovery of new molecules both NCEs and NBEs. Glenmark has several molecules
in various stages of clinical development and primarily focused in the areas
of Inflammation, Pain and Oncology. The company has significant presence in
branded formulations across emerging economies including India. Its
subsidiary, Glenmark Generics Limited services the requirements of the US and
Western Europe markets.

Media Contact: Corporate Communications, , +91 22
40189999, Glenmark Pharmaceuticals Ltd
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