Mesoblast Receives FDA Clearance for Phase 2 Clinical Trial of Mesenchymal Precursor Cells in Patients With Active Rheumatoid

Mesoblast Receives FDA Clearance for Phase 2 Clinical Trial of Mesenchymal
Precursor Cells in Patients With Active Rheumatoid Arthritis

Key Points:

  *Mesoblast receives clearance from United States Food and Drug
    Administration (FDA) to begin Phase 2 trial of proprietary allogeneic, or
    "off-the-shelf", Mesenchymal Precursor Cells (MPCs) in patients with
    active Rheumatoid Arthritis (RA)
  *Trial will be randomized, double-blind placebo-controlled dose escalation
    study to evaluate the safety, tolerability and effectiveness of a single
    intravenous infusion of two MPC dose levels over an initial period of 3
    months in patients who have had poor or incomplete responses to biologic
    inhibitors of the TNF-alpha pathway
  *Mesoblast's MPCs have been shown in preclinical studies to have a broad
    immunomodulatory mechanism of action (MOA), simultaneously inhibiting T
    cells and monocytes involved in inflammation and autoimmunity
  *In an animal model of RA, MPC treatment significantly decreased the T cell
    and monocyte derived inflammatory cytokines TNF-alpha, IL-6 and IL-17 in
    the diseased joint and reduced tissue pathology
  *MOA provides the rationale for strategic development of MPCs in RA both in
    patients with incomplete responses to biologic inhibitors of the TNF-alpha
    pathway alone and as a first-line biologic treatment in those not
    responding to conventional anti-rheumatic agents
  *In addition, a second Phase 2 trial of MPCs as a first-line biologic
    treatment for active RA is planned to commence in Europe in 1H 2013.

MELBOURNE, Australia, Jan. 29, 2013 (GLOBE NEWSWIRE) -- Regenerative medicine
company Mesoblast Limited (ASX:MSB) (USOTC:MBLTY), today announced that it has
received clearance from the United States Food and Drug Administration (FDA)
to commence a Phase 2 clinical trial evaluating a single intravenous infusion
of allogeneic, or "off-the-shelf", Mesenchymal Precursor Cells (MPCs) for the
treatment of active rheumatoid arthritis.

The randomized, double-blind placebo-controlled trial is expected to commence
during the second quarter 2013, and will recruit across multiple sites in the
United States and Australia. The trial will compare the effects of a single
intravenous infusion of allogeneic MPCs dosed at 1 or 2 million cells/kg
compared with placebo in 48 patients who have had an incomplete or inadequate
response to a biologic inhibitor of the TNF-alpha pathway for active
rheumatoid arthritis. Safety and effectiveness of the MPC therapy will be
assessed at multiple time points with the primary endpoints defined as 3
months.

RA is an autoimmune disease caused by aberrant activation of multiple immune
pathways involving both monocytes and T cells, ultimately resulting in joint
destruction. Existing biologic treatments target only single immune pathways,
resulting in incomplete responses, need for chronic administration, and
potentially unacceptable infectious adverse events.

In contrast, Mesoblast's MPCs have been shown in preclinical studies to have a
broad immunomodulatory mechanism of action (MOA), simultaneously inhibiting T
cells and monocytes involved in inflammation and autoimmunity. The broader
effects of Mesoblast's MPCs on multiple immune pathways suggest that they may
be particularly useful agents for reducing the inflammation and permanent
joint damage associated with progression of RA.

In a randomized, placebo-controlled study in 30 sheep with collagen-induced
arthritis, a model that manifests joint damage characteristic of human RA,
treatment with Mesoblast's MPCs resulted in reduced TNF-alpha, IL-6, and IL-17
in the diseased joint. In comparison with saline treated controls, synovial
tissue from arthritic sheep 30 days after receiving a single intravenous
injection of 2 million MPCs/kg showed 88% reduction in IL-6 levels (p=0.029),
83% reduction in TNF-alpha levels (p=0.049), 53% reduction in IL-17 levels
(p=0.005), and 43% reduction in infiltrating monocytes/macrophages (p=0.018).
MPC-treated animals had a 31% reduction in histopathology severity scores
compared with controls (pless than 0.025).

These findings show that MPCs can concomitantly inhibit both Th17 T cells and
pro-inflammatory monocytes, and improve synovial tissue pathology. This
provides a rationale for their potential use as both a first-line biologic
treatment in those not responding to conventional anti-rheumatic agents and in
patients with incomplete responses to biologic inhibitors of the TNF-alpha
pathway alone.

Mesoblast Chief Executive Professor Silviu Itescu said: "We believe that the
broad immunomodulatory effects of our MPCs could provide a tangible benefit to
patients with debilitating autoimmune diseases, including rheumatoid
arthritis. This is the first in a series of programs designed to establish the
credentials of our intravenous product formulation for a broad-based spectrum
of inflammatory and immunologic conditions."

About Rheumatoid Arthritis

RA is a chronic systemic disease characterized by progressive joint deformity
and joint destruction driven by synovial inflammation and hyperplasia in which
cytokines play central pathogenic roles. The prevalence of RA is estimated to
be 0.8% worldwide, with women twice as likely to develop the disease as men.
In the United States, RA afflicts 1.3 million people. It is responsible for
250,000 hospitalizations and 9 million physician visits each year. According
to Global Data, the RA therapeutics market was valued at $10.3 billion
globally in 2010, and has doubled over a four-year period after growing at a
Compound Annual Growth Rate (CAGR) of 12.3%.

Mesoblast Limited

Mesoblast Limited is a world leader in the development of biologic products
for the broad field of regenerative medicine. Mesoblast's patented Mesenchymal
Precursor Cell technology is being developed for a broad range of major
clinical diseases, including inflammatory and immunologic conditions, diabetes
and its complications, orthopedic spine conditions, and cardiovascular
disorders. www.mesoblast.com

CONTACT: Julie Meldrum
         Global Head of Corporate Communications
         Mesoblast Limited
         T: + 61  3 9639 6036 E: julie.meldrum@mesoblast.com
 
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