Article Excerpt:
TWST: Please give us an overview of what you're covering in the biotech space.Mr. Reames: Predominately, I'm covering oncology and CNS-focused companies. Within CNS, it's predominantly in insomnia, but there are a few other areas. The largest focus is in oncology, and then there are several one-offs in metabolic disorders, for example, like Arena (ARNA).
TWST: Let's look at the oncology space first. What's going on?
Mr. Reames: I think there are a number of different things that are relatively
exciting. Right now, we've got a few new pathways that are starting to show
life. The mTOR pathway, which is upstream from VEGF, is a pathway that has been
validated with temsirolimus, which is Wyeth's (WYE) compound. It demonstrated an
overall survival of 10.9 months in a Phase II study of poor-risk patients with
renal cell carcinoma versus 7.3 months for patients receiving interferon and 8.4
months for the combination of interferon plus temsirolimus. This is a validation
of that pathway. The big question that remains is whether or not this will
broadly reinvigorate studies using generic rapamycin in the treatement of cancer
(temsirolimis is a prodrug of rapamycin). So folks are focused on that pathway
and that particular approach.
The immunomodulatory drugs (IMiDs) from Celgene (CELG) are generating a
substantial amount of interest, as they're showing influence on a number of
different pathways and indications. Certainly the approval of Thalomid back-to-
back with Revlimid was a big win for the company, and it started to open up a
regulatory pathway in myeloma. We have a meeting at the agency coming up to
discuss clinical end points within multiple myeloma, so I think that was
certainly an interesting outcome.
Within breast cancer, we've seen some additional data come out from a few
compounds. In particular, we've continued to see good data with Herceptin
(trastuzumab), Avastin and laptinib in different forms of breast cancer. We're
focused on tesmilifene from YM BioSciences (YMI), which has demonstrated a good
improvement in survival in one Phase III study (50% improvement), and if it
replicates that data in a second ongoing study, it may provide insight that
tesmilifene is actually hitting a diseased stem cell line that is responsible
for much of the relapse that occurs five to 10 years after somebody is deemed
clinically cured. Those are basically cells that have a substantial amount of
protein pumps on their surface, and they are usually mutagenic stem cells that
have lain dormant and are responsible for much of the relapse and the ultimate
demise of the patient. So that's a trial we are focused on and a mechanism that
we're looking at relatively closely.
Within the EGFR pathway, we're seeing more compounds targeting the pathway in
novel ways. Beyond the household names, Merck (MRK) has matuzumab and Genmab
recently started a Phase III with zalutumumab. In addition, YM is developing
TheraCIM (nimotuzumab) that lacks the class side effects. The Fc region may be
eliciting this effect in a novel way. We have seen data in indications where
other EGFR agents have been studied. For example, in nasopharyngeal carcinoma,
nimotuzumab plus radiation elicited a 90% complete response rate, versus 50% for
radiation alone.
Within the "me-too" or second generation compounds, there are improvements on
already available drugs, such as albumin-bound paclitaxel and nab-paclitaxel.
Obviously TOCOSOL paclitaxel in a vitamin E emulsion - is intriguing as well. In
any of these approaches, you are basically tying it to something that the body
will process in a more physiologically stable manner so that you reduce some of
the side-effect profiles associated with the chemotherapy. I think that is
certainly an area where we're going to see additional data and life over time.
Along the purine nucleoside analog front, you've got Bioenvision (BIVN) with
clofarabine. That's starting to show a lot of interesting data in multiple types
of leukemias. Traditionally, the purine nucleoside analogs have really only
shown efficacy with the lymphocytic cell lines, and here we're seeing efficacy
in not only those lymphocytic cell lines, but in the myelogenous-derived
cancers. So that is certainly exciting and has a lot of potential in a number of
different areas.
In the field of blood cancers, we would also mention that Hana Biosciences
(HNAB) has very intriguing data with a sphingosomal encapsulation of free
vincristine called Marquibo.
In addition to improved versions of standard line agents, we are seeing new and
novel uses for agents that are currently on the market. For example, GTx (GTXI)
is a name that we cover and like. They're using toremifene, which is approved
for metastatic breast cancer, in a novel way. As a treatment for breast cancer,
toremifene has not seen a lot of use in the US, because tamoxifen was launched
just prior to toremifene coming to market, and AstraZeneca (AZN) was really
focused on branding that compound. However, toremifene has been widely used in
Japan, allowing significant data to emerge and become documented. GTx is
exploring toremifene because of its unique properties, including lipid lowering
and bone mineral density increasing to ameliorate the side effects associated
with androgen deprivation therapy. They also are evaluating low dose (20mg)
toremifene to prevent prostate cancer, an indication where a large randomized
Phase II trial demonstrated that 20mg of toremifene daily for a year reduced the
incidence of prostate cancer by 48%.
On the immunotherapy side, we're starting to see some additional life in the
treatment of melanoma and within the treatment of prostate cancer. You're
starting to see some new and novel approaches along those lines. That seems to
be relatively interesting.
With the CTLA-4 pathway, we're starting to see more data. We know what the
toxicities are associated with that. Enterocolitis is the main issue, and we are
seeing this side-effect across the board with a high correlation to efficacy.
That is with Medarex's (MEDX) compound, ipilimumab. You're seeing that in
responders, so it's sort of a high correlation to response. That may limit the
ultimate use of that compound, but it's certainly interesting. Within melanoma,
we are also anxiously awaiting additional data on Nexavar from Onyx
Pharmaceuticals (ONXX). Along the lines of anxiously awaiting, we hope to see
the Phase III data on Telik's (TELK) Telcyta in ovarian cancer by year-end. This
is data that keeps getting pushed out.
In non-small cell lung cancer, Antisoma has presented very intriguing survival
data with the first vascular disrupting agent, AS1404. At ASCO, they presented a
12-month versus a 7.6-month median survival in lung cancer, so that was
something that caught the attention of folks.
You've got epothilones that are starting to show some interesting data as well
in lung cancer and breast cancer. That's an area that we're going to be focusing
on for the long run. Lastly, one area that's probably going to show some life -
and it's probably going to be from an underdog - is the toll-like receptors.
That might be from Idera (IDP), Coley (COLY) and Dynavax (DVAX). Idera seems to
have a nice intellectual property position established.
From a 20,000-foot view, those are the main pathways that we're taking a look
at, as well as the HDAC inhibitor from Kosan (KOSN). The N-cadherin pathway
targeted by ADH-1 from Adherex (ADH) is also very interesting, but the data is
early.
Tickers included in this excerpt: BIVN, CELG, GTXI, HNAB, ONXX, YMI
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