ANNUAL REPORT 2012 - TiGenix

Different routes of administration of eASCs
Products
The choice of injecting the eASCs through
different routes relies on a combination of the
type of disease and targeting the immune
system in the most optimal way. For local
diseases or tissue damage, depositing the
cells as close as possible to the affected
tissue or organ is expected to optimize
the effect of the cells. Indeed, locally
administered cells will not be diluted, and
thus achieve the highest concentration of
cells at the site of action. Moreover, the cells
will encounter immediately the inflamed
environment leading to direct activation
of the eASCs and their immunomodulatory
actions. Therefore, diseases like fistulas and
IBD are targeted by local administration of
the cells.
For systemic diseases like rheumatoid arthritis
(“RA”), where the cells need to act at several
places in the body, systemic administration
of the cells is the method of choice. Indeed,
systemic administration, either through the
blood or lymphatic circulation, will allow the
cells to be distributed throughout the body
to reach the affected tissues. The capacity of
eASCs to sense inflammation and to migrate
to the site of inflammation is expected to
result in an efficient mechanism of action at
the site of inflammation.
6.5.1.1. Cx601
Cx601 is a suspension of allogeneic eASCs
delivered locally in the fistula through intralesional
injection. Cx601 is being developed
for the treatment of perianal fistulizing
Crohn’s disease.
As set out in more detail in section 6.5.2.1,
Crohn’s disease is a chronic inflammatory
disease of the intestine. It is characterized by
focal or segmental transmural inflammation,
which may occur in any part of the digestive
tract. Crohn’s patients can suffer from
complex perianal fistulas for which today no
efficient treatment exists.
Cx601 received Orphan Drug designation by
the EMA in Q4 2009.
Clinical development
TiGenix is developing Cx601 for the treatment
of complex perianal fistula in Crohn’s disease
patients. Cx601 utilizes expanded adult
allogeneic stem cells derived from adipose
tissue, which the Company understands to
have anti-inflammatory properties and be
an effective mechanism for the treatment of
fistulas.
Finally, the intralymphatic route appears to
be very attractive, since it is expected that
the systemic effect of the cells will ultimately
be executed at the secondary lymphoid
organs : draining lymph nodes and spleen.
Recent preclinical and clinical experience
with vaccines 16 and antitumor 17 agents has
demonstrated the feasibility and practical
use of this administration route.
In a Phase II clinical trial, Cx601 showed
efficacy at 24 weeks of 56 % in treated
fistula tracts, which is more than 2 times
higher than the current standard of care
(anti TNF). Efficacy was measured as the
complete closure and re-epithelization of
the fistula being treated with absence of
drainage. Additionally, 69.2 % of patients
had a reduction in the number of initially
draining tracts. The trial also confirmed the
16
Curr Opin Allergy Clin Immunol. 2009 Dec;9(6) :537-43. “Intralymphatic immunotherapy.”Senti G, Johansen P, Kündig TM.
17
Cytotherapy. 2007;9(8) :755-70. Epub 2007 Oct 4.”Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment
of pediatric cancer.” Dohnal AM, Witt V, Hügel H, Holter W, Gadner H, Felzmann T.
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