3
BioTech Stock Report, January 2004
Besides Biogen-Idec, another
company that had encouraging news
at ASH was Celgene (NASDAQ:
CELG). Celgene's lead product, Thalo-
mid, was featured in over 50 abstracts
at ASH that highlighted its use as
monotherapy or in combination with
other agents for newly diagnosed and
relapsed/refractory MM patients. One
of the studies presented data with
Thalomid plus dexamethasone as first
line therapy for MM, which is now
considered the treatment of choice for
initial therapy in my eloma. According
to investigators, 43% would use Tha-
lomid plus dexamethasone for front-
line treatment, which is an increase
from data presented at ASH last year,
where 21% of the clinicians indicated
they would use Thalomid plus dexa-
methasone. This demonstrates grow-
ing acceptance of this relatively low
toxicity, all oral regimen for front-line
use. The relative ease of drug admini-
stration, coupled with Thalomid effi-
cacy has greatly increased acceptance
for MM in combination with other che-
motherapeutic agents, including Ve l-
cade.
We believe that increased applica-
tion of Thalomid in MM, along with
favorable patient responses will drive
the FDA to approve Thalomid for MM.
Off-label prescriptions are the current
avenue for Celgene to generate reve-
nue and we anticipate revenue to in-
crease after Thalomid receives FDA
approval.
Equally if not more encouraging
for Celgene was the clinical response
patients with AML have a mutation in
their FLT-3 gene, specifically an inter-
nal tandem duplication (ITD), which
may be implicated in the growth and
survival of the leukemia. In preclinical
studies, MLN518 selectively killed hu-
man FLT-3/ITD-positive AML cancer
cells. It is also possible that the activa-
tion of the FLT-3 receptor may play a
role in patients without a mutation, as
leukemia cells express both the FLT-3
receptor and its ligand in a majority of
AML patients. Additionally, because
MLN518 targets the tyrosine kinases
associated with the platelet-derived
growth factor receptor (PDGFR) and c-
KIT, as well as FLT-3, it may have
broader potential utility for other he-
matologic malignancies or solid tu-
mors.
Millennium had little data from a
Phase I clinical trial of MLN 518 to pre-
sent at ASH. However, questions are
beginning to rise about the effective-
ness of a FLT-3 receptor inhibitor. No-
vartis is also developing a FLT-3 in-
hibitor and their data continues to
show limited efficacy. Novartis plans
to develop it only in combination with
other therapies. This doesn't bode well
for Millennium's MLN 518 and Cepha-
lon (NASDAQ: CEPH) who is also
developing a FLT-3 inhibitor, as inves-
tigators believe that the efficacy of
MLN 518 and Cephalon's FLT-3 inhibi-
tor are similar to Novartis's. The com-
panies had hoped that the FLT-3 in-
hibitors would have a rapid route to
the market in AML, but increasing evi-
dence suggests that a lot of work re-
mains for this class of molecule.
ment of 42 patients. We await further
data from this study. If these clinical
studies continue to look promising for
first line therapy, Millennium will be
able to expand Velcade's usage.
Expanding usage of a compound
is the goal of most biotechs and Big
Pharma and Millennium is no excep-
tion. Millennium is trying to expand
usage for Velcade in NHL and prelimi-
nary studies show that Velcade has
promise in NHL. Investigators remain
positive on the potential for Velcade in
certain subtypes of low-grade NHL,
especially follicular (one of the most
prevalent) and mantle cell (relatively
less common). Data were less impres-
sive in aggressive subtypes of NHL (a
large market), and small lymphocytic
lymphoma (a small market). Investiga-
tors are evaluating whether Velcade
has the potential to supplant radioim-
munotherapies, such as Biogen-Idec's
Zevalin and Corixa's (NASDAQ:
CRXA) Bexxar as a treatment of choice
for Rituxan failures. This would be
good for Millennium, as the company
needs to expand Velcade's market if
they want to generate any significant
revenue from this product.
Also on the horizon for Millen-
nium is a new small molecule, MLN
518, which is being evaluated for acute
myeloid leukemia (AML). MLN518 is a
novel small molecule drug candidate
specifically designed to inhibit the
FLT-3 receptor tyrosine kinase (RTK).
It is the first compound from the RTK
program at Millennium to enter human
clinical trials. Approximately 30 % of
