4
BioTech Navigator, January 2000
demonstrated a statistically significant
clearance or almost complete clear-
ance of psoriasis, two weeks after dis-
continuation of therapy. These posi-
tive results from the Phase II study are
no guarantee that the Phase III clini-
cal trials will be a success, but they
are nonetheless encouraging. BSR is
enthusiastic about AMEVIVE as a
potent therapy for psoriasis.
XOMA is also pursuing a similar
approach. XOMA is evaluating
hu1124 (anti-CD11a), a humanized
monoclonal antibody being developed
in collaboration with Genentech, Inc.,
who originally discovered the anti-
body and characterized it as anti-
CD11a. The antibody is designed to
prevent the activation of T-cells and
their migration to sites of inflamma-
tion. XOMA just recently announced
favorable results of a Phase II clinical
trial and also announced the initiation
of a Phase III clinical trial for people
with moderate-to-severe plaque pso-
riasis. Although we do not know the
specific details of the Phase II trial,
the fact that they are initiating a
Phase III trial is significant and sug-
gests the results are more than favor-
able. The collaboration with Genen-
tech should also be viewed favorably,
as Genentech has been successful of
late bringing two monoclonal antibod-
ies to market. Success with hu1124
could bring XOMA up from their cur-
rent lows.
Protein Design Labs (PDL) is de-
veloping Zenapax a humanized anti-
body, created by PDL and licensed
exclusively to Roche, which binds to
the IL-2 receptor on T cells. IL-2 is a
cytokine, which stimulates T cells to
divide and participate in an immune
response. By blocking the binding of
IL-2 to its receptor, Zenapax inhibits
the proliferation of activated T cells
and can suppress the immune re-
sponse. Zenapax is more specific and
less toxic than other immunosuppres-
sive drugs such as cyclosporine, be-
cause Zenapax suppresses only acti-
vated T cells involved in an immune
response rather than all T cells and
possibly other cells. Zenapax has
been approved for kidney transplanta-
tion and is in Phase I/II clinical trials
for psoriasis. Look for Zenapax to
gain approval for psoriasis in future
years.
Medimmune is developing
MEDI-507 an anti-CD2 humanized
monoclonal antibody. MEDI-507 was
derived from a rat monoclonal anti-
body called BTI-322. BTI-322 is a
registered trademark of BioTrans-
plant. Both MEDI-507 and BTI-322
bind specifically to the CD2 antigen
receptor found on T cells and natural
killer cells. Laboratory studies have
suggested that BTI-322 and MEDI-
507 primarily inhibit the response of
T cells directed at transplant antigens
while subsequently allowing immune
cells to respond normally to other an-
tigens. The selectivity and long last-
ing effects of this inhibition suggest
that these molecules may have poten-
tial utility in applications in the trans-
plantation field including treatment or
prevention of graft-versus-host disease
or in patients with certain autoim-
mune diseases, such as psoriasis
where it is currently in Phase I clini-
cal trials. Its too early for BSR to rec-
ommend this compound, but given the
ability for Medimmune to bring prod-
ucts to market, expect approval of
MEDI-507 in future years unless piv-
otal Phase II and III clinical trials
prove insignificant.
BioCryst is also developing a
compound to inhibit T cell prolifera-
tion. BioCryst has completed a Phase
I/II clinical trial with an oral formula-
tion of BCX-34 for the treatment of
psoriasis. BCX-34 is a small com-
pound that inhibits an enzyme called
purine nucleoside phosphorylase
(PNP) that is thought to be involved
in T cell proliferation. Further devel-
opment will be dependent upon the
results of the Phase I/II clinical trial
with an oral formulation of BCX-34
that BioCryst is developing for cuta-
neous T cell lymphoma. Presently,
BSR is hesitant to endorse BCX-34 as
an effective treatment for psoriasis.
ISIS Pharmaceuticals is begin-
ning a Phase IIa study of a topical for-
mulation of ISIS 2302 in psoriasis
patients. ISIS 2302 is an antisense
inhibitor of Intercellular Adhesion
Molecule-1 (ICAM-1), which plays a
pivotal role in the inflammation that
psoriatic patients suffer. In preclinical
studies, the proprietary cream formu-
lation of ISIS 2302, when adminis-
tered topically, reduced ICAM-1 lev-
els in models of skin inflammation.
This formulation of the drug was also
very well tolerated in these studies. In
clinical trials, ISIS 2302 delivered
intravenously showed modest evi-
dence of activity in psoriasis with only
small amounts of the drug concentrat-
ing in the skin. Based on these results,
Isis created a more convenient topical
cream formulation of ISIS 2302 that
delivers much higher concentrations
of drug to the skin. In preclinical
studies of the topical formulation, a
thousand times greater concentration
of drug was observed in the epidermal
layer and a thirty times greater con-
centration of drug in the dermal layers
of the skin as compared to intrave-
nous administration. Topical delivery
should be viewed as a significant im-
provement for ISIS 2302 and a smart
move, as the Food and Drug Admini-
stration recently rejected the com-
pound as a treatment for Crohn's dis-
ease. BSR will anxiously await the
results from the clinical trial to see if
ISIS can recover from this recent set
back.
Other biotechs are also develop-
ing compounds for psoriasis. ICOS is
in early stage clinical trials for ICM3,
