100 Great Investigational Drugs

Gap is slowly filled

By Lyle Fitzsimmons

Pfizer leads the way with five of 100 great investigationals, but lesser-sized companies also make
an impact.

New product development at small and mid-tier pharmaceutical companies, as well as

biotechnology organizations, is doing more to fill the productivity gap that large pharmaceutical
companies have been experiencing, according to a study done by the Tufts Center for the Study
of Drug Development (csdd.tufts.edu). Although large pharmaceutical companies were
responsible for more than two-thirds of the new molecular entity approvals in the United States in
2001, that rate dropped to fewer than one-third by 2004 and remained less than 50% in 2005.

According to Tufts experts, the enhanced use of new technologies to reduce late-stage
development failures and contain rising costs have begun to prompt companies toward optimism
despite recurring challenges that include increased regulatory stringency and mounting public
hostility over safety.

"While drug developers have understood that their long-term viability depends on improving R&D
productivity — and have taken steps to address that issue, they’re about to see their efforts pay
off in terms of improved success rates and greater numbers of new medicinal products reaching
the marketplace," says Kenneth Kaitin, director, Tufts.

Pfizer (pfizer.com) continues to feel the effects of the late-stage failure of torcetrapib — which had
been an $800 million development investment — but the company is attempting to right the
industry’s largest R&D ship with several other potentially promising pipeline compounds, derived
in-house and from license agreements.

The company, which increased its industry-leading research and development expense budget
from $7.26 billion in 2005 to $7.60 billion in 2006, is ahead of its peers with five compounds on
R&D Directions’ sixth-annual list of 100 great investigational drugs in development.

Ninety-seven companies have a complete or partial development stake in the 100 drugs listed,
including Pfizer’s five compounds, four drugs from Sanofi-Aventis (sanofi-aventis.com), and three
drugs each from Novartis (novartis.com) and Vertex Pharmaceuticals (vrtx.com).

Many of the compounds on the list address unmet medical needs and were selected for inclusion
from the thousands being developed at large and small companies throughout the world.

To be included, the substances had to show potential in a major or growing therapeutic area and
be active in development.

Seven of the 100 drugs on the 2005 R&D Directions list have since received regulatory approval
from FDA.

Pfizer’s five drugs include axitinib for lung and genitourinary cancer amd thyroid neoplasm; CP-
675206 for melanoma and lung, gastrointestinal, and genitourinary cancer; CP-945598 for
obesity; fesoterodine for overactive bladder; and maraviroc for HIV/AIDS.

Bear Stearns analyst John Boris forecast CP-945598 for annual sales of $400 million in 2012 and
Axitinib for annual sales $200 million in the same year.
"Drug companies are improving their management of risk, especially by actively lowering late-
stage attrition rates through greater use of information technology and other development
practices," Dr. Kaitin says.

1D09C3 — B-cell lymphoma

1D09C3 is an anti-MHC class II monoclonal antibody. The antibody was isolated by GPC
Biotech Inc. (gpcbiotech.com) in collaboration with MorphoSys from MorphoSys’ HuCAL library
of human antibodies. 1D09C3 binds to MHC class II molecules on the cell surface and selectively
kills activated, proliferating tumor cells, which include B-cell and T-cell lymphomas. In 2005, more
than 56,000 people in the United States and about 70,000 people in the European Union were
diagnosed with non-Hodgkin’s lymphoma, the most common form of lymphoma.

In preclinical studies 1D09C3 has been shown to induce programmed cell death and does not
require a functioning immune system for its cell-killing effect. A Phase 1 clinical program is under
way at major cancer centers in Europe. This program is evaluating 1D09C3 in patients with
relapsed or refractory B-cell lymphomas, such as Hodgkin’s and non-Hodgkin’s lymphomas and
chronic lymphocytic leukemia, who have failed prior standard therapy. 1D09C3 has been granted
orphan medicinal product designation in the European Union for the treatment of Hodgkin’s
lymphoma, chronic lymphocytic leukemia, and multiple myeloma.

5-HMF — Sickle-cell disease

Research led by Dr. Donald Abraham of Virginia Commonwealth University has shown 5-HMF to
be the best potential anti-sickling agent in 30 years of sickle-cell research performed by his group.
5-HMF not only is a natural product with very little, if any, toxicity, but it has a high affinity for
sickle cell hemoglobin. The compound is also active in genetically modified mice as shown by Dr.
Toshio Asakura, director, and his colleagues at the NIH-NHLBI Sickle Cell Disease Reference
Laboratory at the Children’s Hospital of Philadelphia, University of Pennsylvania.

According to Xechem’s (xechem.com) chairman and CEO, Dr. Ramesh Pandey, "We are pleased
with the FDA’s decision granting orphan-drug designation to 5-HMF. 5-HMF is a new type of drug
that interacts specifically with intracellular hemoglobin without interacting with other proteins in
the body. Today there are no non-toxic drugs available on the market to treat SCD."

Acapodene — Prostate cancer

GTx Inc. is conducting a pivotal Phase III clinical trial evaluating Acapodene 80 milligrams for the
treatment of multiple side effects of androgen deprivation therapy for prostate cancer. About
1,400 patients have been enrolled in the trial, which is being conducted under a special protocol
assessment with FDA. The primary endpoint of the trial is a reduction in fractures. Other
endpoints include improvements in bone mineral density, hot flashes, lipid profiles, and
gynecomastia. In December 2005, GTx (gtxinc.com) conducted a planned interim analysis of
bone mineral density in the first 197 patients to complete a full year of treatment with Acapodene,
comprising toremifene. In each of three measurements — lumbar spine, hip, and femoral neck —
highly statistically significant positive changes were observed in patients on Acapodene, when
compared with patients on placebo, who on average lost bone.

In June 2006, GTx conducted a lipid interim analysis of the same cohort of patients. Patients
treated with Acapodene had statistically significantly lower levels of total cholesterol, LDL, and
triglycerides, as well as a reduction in the ratio of total cholesterol to HDL, when compared to
patients on placebo. GTx expects to receive final data from the trial in the fourth quarter of 2007.
GTx is conducting a separate pivotal Phase III clinical trial evaluating Acapodene 20 milligrams
for the prevention of prostate cancer in men with high grade prostatic intraepithelial neoplasia.
The endpoint of the trial is a reduction in prostate cancer incidence. GTx expects to conduct an
interim efficacy analysis between the fourth quarter of 2007 and the first quarter of 2008.

Actilon — Hepatitis C

Actilon is an investigational Toll-like receptor 9 agonist designed to induce both rapid and
sustained immune responses that can have durable anti-viral effects. Positive data from a 12-
week Phase Ib clinical study of Actilon in combination with pegylated interferon and ribavirin
among treatment-refractory patients, who had initially responded but then relapsed after
treatment with pegylated interferon and ribavirin, were presented in April 2006. The drug is being
developed by Coley Pharmaceutical Group (coleypharma.com).

A 48-week Phase II clinical study evaluating safety and activity of Actilon in combination with
pegylated interferon and ribavirin is enrolling treatment-refractory HCV patients who never
responded after a minimum of 12 weeks of pegylated interferon and ribavirin treatment.

Albuferon — Hepatitis C

Albuferon is a novel, long-acting form of interferon alpha, which was created by Human Genome
Sciences Inc. (hgsi.com) using the company’s proprietary albumin fusion technology. Albuferon
results from the genetic fusion of human albumin and interferon alpha. Human albumin is the
most prevalent naturally occurring blood protein in the human circulatory system, persisting in
circulation in the body for more than 20 days. Research has shown that genetic fusion of
therapeutic proteins to human albumin decreases clearance and prolongs the half-life of the
proteins. Recombinant interferon alpha is approved for the treatment of hepatitis C, hepatitis B,
and a broad range of cancers.

Albuferon is being developed by Human Genome Sciences and Novartis (novartis.com) under
an exclusive worldwide development and commercialization agreement entered into in June
2006. Under the agreement, Human Genome Sciences and Novartis will jointly commercialize
Albuferon in the United States, and will share clinical development costs, U.S. commercialization
costs, and U.S. profits equally. Novartis will be responsible for commercialization in the rest of the
world and will pay Human Genome Sciences a royalty on those sales. Human Genome Sciences
received an upfront fee of $45 million. Clinical development, commercial milestone and other
payments to Human Genome Sciences could total as much as $507.5 million, including a $45
million upfront payment and $47.5 million payable upon dosing of the first patient in a Phase III
trial.

Altabax — Skin-lesion infection, impetigo

Altabax, comprising retapamulin, is the first in a new class of antibiotics called pleuromutilins
being developed by GlaxoSmithKline (gsk.com). Retapamulin demonstrates a unique
mechanism of action. By binding to a distinct site on the 50s sub-unit of the bacterial ribosome,
retapamulin inhibits protein synthesis. The drug has shown no target-specific cross-resistance to
other established classes of antibiotics. Laboratory studies have demonstrated that the antibiotic
shows a high degree of in vitro potency against key pathogens commonly associated with skin
and skin-structure infections, consistently showing potent activity when compared with other
commonly prescribed topical and oral antimicrobial agents. Furthermore, retapamulin
demonstrated a low propensity for development of resistance in target pathogens.

Continued widespread use of antibiotics has promoted the spread of antibiotic resistance and has
created an urgent need for antibacterial agents with no known cross resistance.
Ambrisentan — Pulmonary arterial hypertension

Ambrisentan is a non-sulfonamide, propanoic acid-class, endothelin receptor antagonist that is

selective for the endothelin type-A receptor. Endothelin is a small peptide hormone that plays a
critical role in the control of blood flow and cell growth. Elevated endothelin blood levels are
associated with pulmonary arterial hypertension. Ambrisentan has been granted orphan drug
designation for the treatment of pulmonary arterial hypertension in the United States and
European Union.

Gilead Sciences Inc. (gilead.com) acquired the U.S. rights to ambrisentan after completing the
acquisition of Myogen Inc. in November 2006. GlaxoSmithKline (gsk.com) holds rights to
commercialize ambrisentan outside the United States.

Amigal — Fabry disease

Amigal acts as a pharmacological chaperone that restores natural function to the misfolded target
protein — in this case the defective enzyme — in the treatment of Fabry disease. The drug is in
Phase II clinical trials. According to developer Amicus Therapeutics (amicustherapeutics.com),
initial data from the first four Fabry disease patients enrolled in one of the Phase II studies
showed that the level of activity of the enzyme known to be deficient in Fabry disease after six
weeks of treatment was, on average, more than five-fold higher than before treatment. The Phase
I studies in healthy volunteers demonstrated that Amigal was well-tolerated, even at the highest
doses, without any drug-related adverse events. In addition, Amigal was shown to have high oral
bioavailability and good pharmacokinetics. Finally, studies showed a statistically significant and
dose-related increase in the level of activity of the target enzyme in healthy volunteers.

Amigal received orphan-drug designation in April 2006 from the Committee for Orphan Medicinal
Products of the European Medicines Agency. The drug received U.S. orphan-drug designation in
2004.

Amphotericin B inhalation powder — Pulmonary fungal infections

Amphotericin B inhalation powder is being developed by Nektar Therapeutics Inc. for the
prevention of pulmonary fungal infections such as aspergillosis in high-risk immunosuppressed
patients. Amphotericin B inhalation powder recently completed a multi-dose, dose-escalation
clinical study in preparation for pivotal trials to begin in 2007.

The product is designed to target the site of infection directly with a novel formulation of
amphotericin B, a broad spectrum, fungicidal drug. Nektar’s (nektar.com) innovative formulation
and pulmonary delivery method could potentially eliminate systemic, dose-limiting toxicities found
with available formulations of amphotericin B that are delivered intravenously.

Immunosuppressed patients are vulnerable to opportunistic fungal infections, such as

aspergillosis, which start in the lungs and spread throughout the body. Aspergillosis has a
mortality rate of more than 50%, and in some immunosuppressed patient groups the mortality
rate may be almost 100%. Using amphotericin B inhalation powder for patients at risk of
developing the infection may potentially reduce the incidence of these infections, as well as
associated high morbidity and mortality and significant treatment costs.

Anthim — Anthrax infection

Anthim is a high-affinity monoclonal antibody that targets the protective antigen component of
anthrax, blocking the bacteria’s ability to form deadly toxins. The drug is being developed by
Elusys Therapeutics Inc. for prophylaxis and post-exposure treatment of inhalation anthrax.
Anthim has been granted fast-track status and orphan-drug designation by FDA and is being
developed under the FDA Animal Rule, a regulatory process specifically designed for the
development of medical countermeasures to bioterror threats.

In 2005, Elusys (elusys.com) was awarded more than $5 million from the National Institute of
Allergy and Infectious Diseases and the Department of Defense for advanced formulation
development. To date, the company has been awarded more than $20 million from the U.S.
government for the development of novel therapeutics to combat bioterror agents.

AS1411 — Pancreatic cancer, renal cancer, nonsmall cell lung cancer, acute myelogenous
leukemia

Aptamers are short pieces of DNA or RNA that can fold into stable, three-dimensional structures
capable of interacting with particular target proteins. AS1411 is the first aptamer to be tested as a
treatment for cancer. Antisoma Plc. (antisoma.co.uk) added AS1411 to its pipeline after
acquiring Aptamera Inc. in February 2005.

AS1411 works by binding to the protein nucleolin, which is found on the surface of cancer cells.
The drug is then internalized and has been shown to kill cells from a variety of cancer cell lines as
well as cancer cells from acute myelogenous leukemia patients patients. The drug has also
shown anti-cancer effects in animal models and promising signs of anti-cancer activity in the clinic
in renal cance.

AS1411 was originally developed by Dr. Paula Bates, Dr. John Trent and Prof. Donald Miller at
the University of Alabama and then at the University of Louisville.

Atiprimod — Multiple myeloma, cancer, carcinoid tumors

Atiprimod is an orally bioavailable small molecule drug that displays multiple mechanisms of
action. The drug has been shown to be antiangiogenic, inhibit secretion of VEGF and IL-6, elicit
an apoptotic response — programmed cellular death — and inhibit phosphorylation of key
kinases involved in tumor progression and survival including Akt and STAT3.

The drug is being developed by Callisto Pharmaceuticals Inc. and is in two clinical trials: a Phase
II trial in advanced carcinoid cancer patients, and a Phase I/IIa human clinical trial in relapsed or
refractory multiple myeloma patients. Callisto (callistopharma.com) announced in June 2006
interim data from a Phase I trial of Atiprimod in advanced cancer patients. The patients who were
entered into this trial had growing tumors and symptoms that were no longer controlled by
standard therapies. During treatment, three of the five advanced carcinoid patients had
measurable tumor regressions and loss of many of the debilitating symptoms of this disease.

AVE0010 — Type 2 diabetes

AVE0010 is a glucagon-like peptide 1 receptor agonist developed for subcutaneous injection

treatment of type 2 diabetes and licensed to Sanofi-Aventis (sanofi-aventis.com) in 2003.

Endogenous GLP-1 is released from the small intestine in response to food intake and stimulates
insulin liberation from the pancreas when blood sugar levels are elevated. In addition, GLP-1
suppresses the production of glucagon as well as reduces appetite and delays food absorption.
GLP-1 only stimulates the release of insulin in case of elevated blood sugar levels but not during
periods of normal or low blood sugar. This unique mechanism is associated with a lower risk of
hypoglycemia than conventional antidiabetic drugs.
In previous Phase I/II and Phase II safety and tolerability trials, a glucose-lowering activity, similar
to that of competing GLP-1 compounds, was observed. In both trials, AVE0010 was safe and
well-tolerated. Although nausea is a common side effect of GLP-1 compounds, four weeks of
treatment with AVE0010 was not associated with increased nausea relative to placebo.

AVE1642 — Solid tumors

Sanofi-Aventis has initiated clinical testing of AVE1642, a therapeutic antibody that binds to the
Insulin-like growth factor 1 receptor. This event triggered a $2 million milestone payment to
ImmunoGen (immunogen.com). AVE1642 is an anticancer compound that was developed by
ImmunoGen and licensed to Sanofi-Aventis (sanofi-aventis.com) as part of a broader
collaboration between the companies. AVE1642 is an unconjugated antibody that targets IGF-1R,
a receptor that is overexpressed on many different cancers.

For each compound in the collaboration with Sanofi-Aventis, ImmunoGen is entitled to receive
milestone payments that could potentially total $21.5 million to $30 million, plus royalties on sales.
ImmunoGen also has certain joint-promotion rights and receives manufacturing payments for
preclinical and initial clinical materials made on behalf of Sanofi-Aventis.

Additionally, the agreement provides ImmunoGen with committed funding for the course of the
research collaboration between the two companies.

Axitinib — Lung cancer, genitourinary cancer, thyroid neoplasm

Axitinib is an oral inhibitor of VEGFR-1 and VEGFR-2 being developd by Pfizer Inc. (pfizer.com).
In a Phase II study, 52 patients with metastatic renal cell carcinoma who previously failed
cytokine therapy were treated with Axitinib 5 milligrams. None of the patients achieved a
complete response, but 21 patients achieved a partial response and 15 had stable disease, for an
overall clinical benefit of 69%.

Axitinib has demonstrated significant activity on advanced cytokine-refractory renal cell

carcinoma and is being evaluated in a Phase II trial in patients who failed previous therapy with
sorafenib. Sorafenib is marketed as Nexavar by Bayer Healthcare (bayerhealthcare.com).

Azedra — Neuroendocrine tumors

Molecular Insight Pharmaceuticals (molecularinsight.com) initiated a Phase I clinical trial for its
lead oncology candidate, Azedra, for the treatment of neuroendocrine tumors such as carcinoid,
pheochromocytoma, and neuroblastoma.

The Phase I dosimetry trial is designed to evaluate the safety, tolerability, and distribution of
Azedra in adult patients with one of two forms of neuroendocrine cancer — either carcinoid or
pheochromocytoma. Azedra recognizes unique molecular targets expressed by certain
neuroendocrine cancers that enable the drug to be accumulated in the tumor. Azedra is designed
to maximize the delivery of radiolabeled MIBG molecules to targeted neuroendocrine tumors to
effectively enable safe and effective diagnosis and treatment while minimizing the amount of non-
radioactive MIBG molecules that are delivered to the patient.

A trial for the treatment of neuroblastoma, a cancer that primarily affects children, is planned
pending preliminary assessment of the safety and distribution of Azedra in adults and input from
FDA.

BAL8557 (Isavuconazole) — Fungal infections

Isavuconazole has a potent and broad spectrum of activity against yeasts and molds. This new
triazole is being developed by Basilea Pharmaceutica AG as a water-soluble pro-drug to allow
safe and simple intravenous administration without contraindication in renally impaired patients.
In addition, taken as convenient once-daily or once-weekly capsules, the prodrug results in rapid
and almost complete absorption and distribution to infected tissues.

Basilea (basilea.com) successfully completed a Phase II trial with high clinical cures rates and a
safety profile comparable to gold standard therapy, but with potentially a more flexible dosing
schedule. Clinical drug interaction studies showed attractive pharmacokinetic features and the
potential for less drug-drug interactions than a number of broad-spectrum antifungal drugs in use.

Bevirimat — HIV infection

Bevirimat is the first in a new class of oral HIV therapeutics under development called maturation
inhibitors, discovered by Panacos Pharmaceuticals and academic collaborators. Based on its
novel mechanism of action, bevirimat is designed to have potent activity against a broad range of
HIV, including strains that are resistant to existing classes of drugs.

Panacos (panacos.com) has completed seven clinical studies of bevirimat in more than 300
subjects, showing significant reductions in viral load in HIV-infected subjects and a promising
safety profile, and is now in Phase IIb clinical trials. In Phase IIb, bevirimat is being tested in
combination with approved drugs, with the goal of selecting a dose or doses to take into pivotal
clinical trials.

BG-12 — Multiple sclerosis

Data suggest that BG-12, an oral fumarate derivative, is an immunomodulator with a novel
mechanism of action with a combination of cytoprotective and anti-inflammatory properties.
Based on available clinical and scientific information with BG-12 and fumarates, there is strong
technical rationale for development of BG-12 in a number of T-cell mediated autoimmune and/or
inflammatory diseases.

In January, Biogen Idec (biogenidec.com) initiated a Phase III clinical program. The DEFINE
(determination of the efficacy and safety of oral fumarate in relapsing-remitting multiple sclerosis)
and CONFIRM (comparator and an oral fumarate in relapsing-remitting multiple sclerosis) studies
will include more than 2,000 total patients in North America, Europe, and the rest of the world.
These studies have been initiated internationally, and Biogen Idec plans to initiate these studies
in the United States later in 2007.

DEFINE and CONFIRM are two-year, randomized, multi-center, double-blind, placebo-controlled,

dose-comparison studies to determine the safety and efficacy of BG-12 in subjects with relapsing-
remitting multiple sclerosis. CONFIRM will also include a reference comparator arm with
glatiramer acetate, which is marketed as Copaxone.

Endpoints of both studies include evaluating the effect of BG-12 on measurements of clinical
relapse, the progression of disability, and various MRI measures.

BiovaxID — Non-Hodgkin’s lymphoma

Accentia Biopharmaceuticals (accentia.net) has reported a study that the administration of a

BiovaxID formulation given to patients with relapsed follicular non-Hodgkin’s lymphoma following
chemotherapy, with or without concomitant Rituxan, can induce complete long-lasting remissions.
These second remissions are uniquely characterized by a duration that exceeds the duration of
the first remission. In the study, 80% of patients achieved an immune response to the BiovaxID
formulation, and among these responders, the median time of complete tumor remission has not
been reached after 33 months of mean follow-up.

Dr. Dan Longo, National Institutes of Health, characterized the results as remarkable. "Among the
20 immunologic responders, the median duration of the second complete response has not been
reached after nearly three years of follow-up and in every case, the second remissions have been
longer than the initial remissions," Dr. Longo says. "By contrast, all five immunologic non-
responders have relapsed, and in every case their second remission was shorter than their first.
Long second remissions do not occur at this rate, even after high-dose therapy and autologous
hematopoietic stem cell transplant."

Bronchitol — Bronchiectasis, cystic fibrosis

Bronchitol is a patented, inhalable dry powder formulation of mannitol administered by a hand-

held, pocket-sized device. Pharmaxis Ltd. (pharmaxis.com.au) is developing Bronchitol as a
twice-daily treatment for improving mucus clearance in the lungs of patients with cystic fibrosis,
bronchiectasis, and chronic obstructive pulmonary diseases.

Bronchiectasis is an incurable, degenerative, and chronic lung condition affecting more than
500,000 people worldwide. In the United States, at least 110,000 people are receiving treatment
for bronchiectasis. Patients spend between $6,000 and $13,000 on treatment. Widespread
availability of high-resolution scanners is leading to increases in diagnosis rates and the
understanding that bronchiectasis is more common than previously thought.

Ceflatonin — Chronic myeloid leukemia, myelodysplastic syndrome

Ceflatonin is a potent inducer of apoptosis in myeloid cells and inhibits angiogenesis. In Phase II
studies, the drug has demonstrated clinical activity in patients with chronic myeloid leukemia as a
single agent and in combination with other chemotherapeutic drugs. ChemGenex
Pharmaceuticals Ltd. (chemgenex.com) is developing Ceflatonin for the treatment of chronic
myeloid leukemia, and pilot studies are under way in myelodysplastic syndrome and in acute
myeloid leukemia.

Ceflatonin has a different mechanism of action than tyrosine kinase inhibitors, and ongoing and
proposed clinical studies seek to determine efficacy in treatment of chronic myeloid leukemia
patients who have developed resistance to tyrosine kinase inhibitor therapy due to development
of the T315I Bcr-Abl kinase domain point mutation; efficacy in chronic myeloid leukemia patients
who have failed therapy with two tyrosine kinase inhibitors; and efficacy as combination therapy
with Gleevec, for the treatment of residual disease and to prolong Gleevec sensitivity in chronic
myeloid leukemia patients who have developed resistance to Gleevec.

Ceftaroline — Complicated skin and skin-structure infection

Ceftaroline acetate is a member of the cephalosporin class of antibiotics, the most frequently
prescribed class of antibiotics in the world. In preclinical studies and clinical trials to date,
ceftaroline demonstrated a favorable safety profile, similar to that of existing cephalosporins.
Unlike marketed cephalosporins, ceftaroline exhibits bactericidal activity against the most
resistant strains of gram-positive bacteria, including methicillin-resistant Staphylococcus aureus.

Ceftaroline has also demonstrated bactericidal activity against penicillin-resistant Streptococcus

pneumoniae and common gram-negative bacteria. Cerexa Inc. (cerexa.com) licensed from
Takeda Pharmaceutical Co. the exclusive right to develop and commercialize ceftaroline in all
countries worldwide except Japan.
Cladribine — Multiple sclerosis

Merck Serono’s (merckserono.net) proprietary oral formulation of cladribine is being evaluated in

Phase III as a treatment for patients with relapsing forms of multiple sclerosis. Cladribine is a
small molecule that interferes with the behavior and the proliferation of certain white blood cells,
particularly lymphocytes, which are involved in the pathological process of multiple sclerosis.

Through its differentiated mechanism of action, oral cladribine may offer a safe and effective new
option to patients with multiple sclerosis.

CNTO 1275 — Psoriasis

CNTO 1275 is a fully human monoclonal antibody in Phase III development by Centocor Inc.
(centocor.com) for the treatment of moderate-to-severe plaque psoriasis. CNTO 1275 targets
interleukin-12 (IL-12) and interleukin-23 (IL-23), naturally occurring proteins that are important in
regulating the immune system but are also believed to play a role in inflammatory diseases.

Phase II data published in the New England Journal of Medicine showed that patients with
moderate-to-severe plaque psoriasis receiving subcutaneous injections of CNTO 1275
experienced significant clearance of skin disease and significant improvements in quality of life.
At week 12 of the study, 81% of patients receiving four weekly 90-milligram doses of CNTO 1275
achieved at least 75% improvement in their psoriasis, as measured by the Psoriasis Area
Severity Index, compared with 2% of patients receiving placebo. In addition, significantly more
patients in each of the three additional CNTO 1275 dosing groups achieved at least a PASI 75
improvement in their psoriasis versus patients receiving placebo.

CP-675206 — Melanoma, lung cancer, gastrointestinal cancer, genitourinary cancer

Of 39 patients given a single injection of CP-675,206, tumors disappeared in three patients,

shrunk in a fourth patient, and cancer stopped growing in five other patients. These responses
have remained since the patients’ initial treatment, which ranged from 13 to 28 months previous,
according to researchers at the University of Texas M.D. Anderson Cancer Center. The drug is
being developed by Pfizer Inc. (pfizer.com).

Biological therapies such as CP-675,206 work in different ways to stimulate the immune system
and stop tumor cells from growing. Vaccines may make the body build an immune response to kill
tumor cells. Combining CP-675,206 with vaccine therapy may cause a stronger immune
response and kill more tumor cells.

A Phase I trial is studying the side effects and best dose of CP-675,206 when given with vaccine
therapy in treating patients with stage III or stage IV melanoma that can not be removed with
surgery began in October 2006.

CP-945598 — Obesity

CP-945,598 is a compound that inhibits appetite and could be a useful medicine to combat
obesity. The drug works at the cannabinoid-1 receptor, which is also a biological target for
therapies against alcohol and nicotine addiction. The compound was well-tolerated in Phase I
trials and is one of four CB-1 candidate medicines in development at Pfizer (pfizer.com).

A study is to determine if CP-945,598 is effective in the treatment of obesity in type 2 diabetic

patients began in February.
CX-3543 — Cancer

CX-3543 is being developed by Cylene Pharmaceuticals Inc. (cylenepharma.com). The product

is in late-stage Phase I clinical studies in patients with advanced solid tumors. CX-3543 directly
inhibits rRNA biogenesis by targeting a protein, DNA interaction, that is amplified during Pol I
transcription of the rRNA genes of cancer cells. This protein, DNA interaction, is selectively
disrupted by CX-3543 and induces apoptotic cell death in cancer cells.

CX-3543 demonstrates in vivo efficacy with a broad therapeutic window in xenograft models
using multiple types of cancers, and biomarker analyses supported the in vivo anti-tumor effect
on rRNA biogenesis leading to apoptosis of tumor cells. Thus, inhibition of rRNA biogenesis is an
important new approach in oncology drug discovery and development.

Dapagliflozin — Type 2 diabetes

Dapagliflozin is a sodium glucose cotransporter-2 inhibitor in development from Bristol-Myers

Squibb Co. (bms.com). The SGLT2 transporter protein is located only in the kidney, where it
normally reabsorbs glucose from urine while waste products are filtered out. Patients with type 2
diabetes continue to reabsorb glucose from the urine, even though this process contributes to
high blood glucose levels, or hyperglycemia.

Dapagliflozin has a novel mechanism of action that blocks re-absorption of glucose from urine in
patients with type 2 diabetes. Inhibiting SGLT2 activity decreases re-absorption of glucose by the
kidney, helping to improve glucose control in patients with type 2 diabetes.

Defibrotide — Severe hepatic venous occlusive disease, veno-occlusive disease

FDA has granted orphan-drug designation to defibrotide for the prevention of hepatic veno-
occlusive disease in the United States. Developer Gentium SpA is in a Phase III trial of
defibrotide to treat severe veno-occlusive disease. Defibrotide had previously had been granted
orphan-drug status to treat severe veno-occlusive disease and fast-track designation for the
treatment of severe veno-occlusive disease in recipients of stem cell transplants.

"Previous studies have demonstrated compelling clinical results using defibrotide to prevent
VOD," says Laura Ferro, M.D., president and CEO, Gentium (gentium.com). "We are currently
conducting a Phase II/III trial of defibrotide to prevent VOD in pediatric patients in Europe, and
are looking forward to initiating a U.S. and European Phase II/III study of defibrotide to prevent
VOD in adults in the coming months."

Denufosol tetrasodium — Cystic fibrosis

Inspire Pharmaceuticals Inc. (inspirepharm.com) updated its development program for denufosol
tetrasodium in January. The company’s TIGER-1 Phase III clinical trial is a randomized, double-
blind comparison of 60 milligrams of denufosol to placebo in about 350 cystic fibrosis patients.
The trial is designed to include a 24-week efficacy treatment period, followed by a 24-week safety
extension period.

In cystic fibrosis, chloride builds up in cells lining the airways because the cystic fibrosis gene
makes a faulty ion channel that does not allow chloride to exit. The result is thick, sticky mucus
that leads to chronic lung infections. Denufosol tetrasodium is a selective P2Y2 agonist designed
to enhance the lung’s innate mucosal hydration and mucociliary clearance mechanisms by
activating an alternative ion channel that acts in the same way as the defective ion channel
normally would in moving salt and water to the surface of the airways.
DG031 — Heart attack

DeCode Genetics Inc. is evaluating formulation and process combinations to develop new
tablets of DG031, the Phase III compound targeting the leukotriene pathway for the prevention of
heart attack. DeCode suspended its Phase III trial of DG031 last fall due to tablet manufacturing
issues, and the company’s manufacturing schedule is to have sufficient clinical supplies to restart
Phase III testing by the end of 2007. DeCode is also examining the feasibility of resuming testing
of DG031 with a once-a-day dosing regimen.

"Faced with this problem, we felt that our only option was to put the trial on hold and improve the
formulation of the tablets," says Kari Stefansson, CEO, DeCode (decode.com). "This is the right
thing to do both for patients and for the company, who have a common interest in successfully
developing drugs to prevent heart attack. We are leading the way in targeting the leukotriene
pathway to this end, and will continue our other therapeutic and diagnostic programs in heart
attack as we work to develop new clinical supplies of DG031."

DG041 — Peripheral arterial occlusion

In late December DeCode Genetics Inc. completed its Phase IIa trial for DG041, the novel, oral,
first-in-class anti-platelet compound being developed as a lesion-specific means of preventing
arterial thrombosis without increasing bleeding time. The dose-ranging Phase IIa trial is
examining safety and efficacy in platelet inhibition using biomarkers related to atherosclerosis.
The company expects to present data from the trial in the second quarter 2007.

DG041 has shown to be a selective and potent antagonist of the EP3 receptor for PGE2. DeCode
(decode.com) identified EP3 as a target through the company’s population genetics research,
which led to the discovery of variants in the gene encoding EP3 that confer risk of peripheral
arterial disease. In the Phase I clinical program, DG041 was found to be well-tolerated at all dose
levels tested; to provide a dose-dependent reduction in platelet aggregation after stimulation with
collagen and sulprostone, and to do so without any significant changes in bleeding time.

Doripenem — Urinary tract infection, nosocomial pneumonia, complicated intra-abdominal

infections

Doripenem is an investigational carbapenem antibiotic being developed by Johnson & Johnson

Pharmaceutical Research LLC (jnj.com), which submitted a new drug application in December
2006. In Phase III clinical trials, doripenem achieved a high clinical cure rate of 83% in patients
with intra-abdominal infections. Doripenem also was active against a wide range of gram-positive
and gram-negative bacteria that cause serious hospital infections, including Pseudomonas.

Pseudomonas aeruginosa, a gram-negative bacterium with increasing multi-drug resistance, is

one of the leading causes of nosocomial infections for which treatment options are limited.
Johnson & Johnson licensed doripenem from Shionogi & Co. (shionogi.co.jp).

Droxidopa — Neurogenic orthostatic hypotension

Droxidopa is being developed by Chelsea Therapeutics Inc. An orally active synthetic precursor
of norepinephrine, the drug increases the supply of norepinephrine available for delivery to its
receptors to improve orthostatic blood pressure and alleviate symptoms of orthostatic
hypotension.

Midodrine, the only FDA-approved treatment for orthostatic hypotension, fails to treat the
underlying cause of symptomatic neurogenic orthostatic hypotension and is limited in its use by a
pronounced side-effect profile and black box warning for supine hypertension. Given the chronic
nature of symptomatic neurogenic orthostatic hypotension and the proven safety and tolerability
of droxidopa, Chelsea (chelsearx.com) expects that daily oral treatment with droxidopa should
provide a significant improvement in the long-term treatment of symptomatic neurogenic
orthostatic hypotension.

EPI-A0001 — Inherited mitochondrial respiratory chain diseases

FDA granted orphan-drug designation to EPI-A0001 based on review of the application submitted
by Edison Pharmaceuticals (edisonpharma.com), which included preclinical data demonstrating
a favorable efficacy and safety profile. Data is consistent with EPI-A0001 targeting electron
shuttling and energy production — two processes that are impaired by genetic defects in the
respiratory chain.

The respiratory chain is located within the inner mitochondrial membrane and is comprised of
numerous proteins encoded for by both the nuclear and mitochondrial genome. Genetic errors in
the synthesis of these proteins result in a variety of clinical conditions that have disruptions in
energy production as a common biochemical feature. These diseases frequently affect skeletal
and cardiac muscle, as well as the nervous system, and thus are often classified as mitochondrial
encephalomyopathies. These diseases are highly debilitating and life-shortening.

Fesoterodine — Overactive bladder

Efficacy results of Phase III trials with fesoterodine for the treatment of overactive bladder
demonstrated statistically significant improvements compared to placebo in all primary variables
requested by FDA and the European regulatory authorities. More than 90% of patients chose to
enter the open-label trials that followed.

Developer Pfizer Inc. (pfizer.com) completed the acquisition of worldwide rights to the new drug
candidate from Schwarz Pharma in June 2006, following the expiration of the waiting period
under the Hart-Scott-Rodino Antitrust Improvements Act of 1976.

GAP-486 — Arrhythmia

GAP-486 is a peptide that acts specifically on protein channels called gap junctions. In the heart,
these channels are responsible for conducting electrical impulses between cells to maintain the
heart’s normal rhythm. The drug is being developed by Wyeth Pharmaceuticals (wyeth.com).

In preclinical studies, GAP-486 has been shown to prevent ventricular arrhythmia in acute
myocardial infarction. In studies to date, the drug has demonstrated to be devoid of any pro-
arrythmic or hemodynamic effects. As such, GAP-486 offers a new therapeutic option to also
safely prevent life-threatening arrhythmias associated with ischemic disease.

Gestiva — Premature labor

The new drug application submission from Adeza Biomedical Corp. (adeza.com) for Gestiva
includes data from a clinical study conducted by the NIH’s National Institute of Child Health and
Human Development. The NIH studied a long-acting form of a naturally occurring progesterone,
17 alpha-hydroxyprogesterone caproate, in a multi-center, double-blind, placebo-controlled trial
that enrolled 463 women with a prior history of preterm birth.

Patients were enrolled at 16 to 21 weeks of gestation and randomly assigned to receive weekly
injections of 17P or placebo. Treatment continued until delivery or 37 weeks of gestation,
resulting in a reduction in the preterm birth rate of 34% among women treated with 17P. In
addition, infants born to women treated with 17P had significantly lower rates of necrotizing
enterocolitis, intraventricular hemorrhage, use of supplemental oxygen, and mean number of
days of respiratory therapy.

Glufosfamide — Solid tumors, pancreatic cancer, ovarian cancer, small cell lung cancer

Glufosfamide combines the active part of an approved alkylator, a member of a widely used class
of chemotherapy drugs, with a glucose molecule. Because of its glucose component and a tumor
cell’s increased need for glucose, glufosfamide may be preferentially transported into tumors
compared to most normal tissues.

Metabolic targeting offers the potential to provide increased selectivity for tumor cells and thereby
improve the treatment of many solid tumors. Inside cells, the linkage between glucose and the
alkylator is cleaved to release the active drug. With glucose as the side product, glufosfamide has
fewer side effects than other drugs in its class, which are known to cause hemorrhagic cystitis, a
serious condition characterized by severe bladder bleeding. Glufosfamide is being developed by
Threshold Pharmaceuticals Inc. (thresholdpharm.com).

GVAX Pancreatic Cancer Vaccine — Pancreatic cancer

Cell Genesys Inc. (cellgenesys.com) released follow-up data from a Phase II clinical trial of
GVAX immunotherapy for pancreatic cancer in 60 patients with operable pancreatic cancer who
received the immunotherapy after surgical resection of their tumor and adjuvant radiation and
chemotherapy. The updated results showed a median survival of 26.8 months.

This compares favorably with published, historical data from multiple single-arm and randomized
studies in patients undergoing pancreatic cancer surgery and adjuvant therapy for whom the
median survival has been reported to be in the range of 17 to 22 months, including the most
recently reported results for gemcitabine chemotherapy. Of note, 52 of the 60 patients in the
study were considered high risk, based on the unfavorable finding that their cancer had spread to
regional lymph nodes. Treatment was well tolerated.

HD-02 — Huntington’s disease

Avicena Group has initiated a chronic toxicology study of HD-02, the company’s lead candidate
for Huntington’s disease. The study is expected to conclude during the second half of 2007. Upon
successful completion, Avicena (avicenagroup.com) intends to start a Phase III clinical trial.

Results from a previous Phase I/II clinical study of HD-02 demonstrated that the drug was safe
and well- tolerated at a dose of 8 g/day in HD patients. HD-02 patients also showed reduced
levels of an oxidative marker, serum 8-hydroxy-2-deoxyguanosine, which some researchers have
linked to reduced oxidative injury in patients with Huntington’s disease. Earlier preclinical trials
examining the effects of HD-02 in a model of Huntington’s disease showed significantly improved
survival and slowed the rate of brain atrophy.

Icatibant — Osteoarthritis, hereditary angiodema, ascites in liver cirrhosis

Icatibant, a synthetic peptidomimetic, works by blocking the B2 receptor as an antagonist to the

peptide-hormone bradykinin. Bradykinin has been shown to be elevated in hereditary
angioedema patients and responsible for edema formation during hereditary angioedema attacks.
Icatibant has been granted orphan-drug status for the treatment of angioedema by FDA and the
European Medicines Agency.
FDA has granted fast-track designation to icatibant for hereditary angioedema. Icatibant’s
subcutaneous administration, along with its excellent safety profile demonstrated in clinical
studies to date and one-year-stability at room temperature, all offer key benefits to hereditary
angioedema patients. The drug is being developed by Jerini AG (jerini.com).

IL-1 trap — CIAS1-associated periodic syndrome, juvenile idiopathic arthritis

IL-1 trap is a potent blocker of interleukin-1 activity, has a long half-life in the blood, penetrates
into the inflamed joint, and blocks cartilage erosion in animal models. The arthritis caused by
tumor necrosis factor in some animals can be prevented by blocking the action of Interleukin-1 —
indicating that the arthritogenic action of tumor necrosis factor may be mediated in part through
Interleukin-1.

Developer Regeneron Pharmaceuticals Inc. (regeneron.com) announced positive data from a

Phase III clinical program designed to provide two demonstrations of efficacy for IL-1 trap within a
single group of patients suffering from CIAS1-related autoinflammatory periodic syndromes. The
Phase III program of the IL-1 trap included two studies. Both studies met their primary endpoints.
The primary endpoint of the studies was the change in disease activity, which was measured
using a composite symptom score composed of a daily evaluation of fever/chills, rash, fatigue,
joint pain, and eye redness/pain.

Increlex — Growth failure

Increlex is an rhIGF-1 replacement therapy indicated for the long-term treatment of growth failure
in children with severe primary insulin-like growth factor-1 deficiency. The product is being
developed by Tercica Inc. The active ingredient of Increlex is identical to the natural hormone
IGF-1, which the body normally produces in response to stimulation by growth hormone. IGF-1 is
the direct mediator of growth hormone’s effect on statural growth and must be present in order for
children’s bones, cartilage and organs to grow normally.

Without adequate IGF-1, children can not achieve a height within the normal range. Tercica
(tercica.com) submitted for marketing approval of Increlex in the European Union and has been
granted an orphan product designation.

Indiplon — Insomnia

Neurocrine Biosciences Inc. plans to resubmit its new drug application for indiplon capsules by
the end of second-quarter 2007. The decision to accelerate the resubmission is based on the
results of interactions with FDA regarding further analyses of data previously submitted on
indiplon capsules, as well as reviewing this data with independent statistical, regulatory and
clinical consultants.

Neurocrine (neurocrine.com) expects FDA will characterize the resubmission as Class 2, which
has a targeted review timeline of six months. "We believe that indiplon will offer an important new
alternative for the treatment of insomnia by providing flexibility to treat insomnia as needed, to
help patients quickly fall asleep or return to sleep after a nighttime awakening," says Gary Lyons,
president & CEO, Neurocrine.

INNO-406 — Chronic myelogenous leukemia

INNO-406 is an orally bioavailable, rationally designed, dual Bcr-Abl and Lyn-kinase inhibitor in
Phase I clinical studies. The drug is being developed by Innovive Pharmaceuticals Inc.
(innovivepharma.com). According to a study published in the journal Blood, INNO-406 is 25 to 55
times more potent than imatinib in vitro, and at least 10 times as effective as imatinib mesylate in
suppressing the growth of Bcr-Abl bearing tumors.

INNO-406 has demonstrated activity in 12 of 13 imatinib-resistant cell lines. In addition to its Bcr-
Abl inhibitory properties, INNO- 406 inhibits Lyn kinase. Upregulation of Lyn kinase activity is a
well-recognized cause of imatinib resistance. Lyn kinase activation has also been documented in
a variety of solid tumors, including prostate cancer.

IPH 2101 — Acute myeloid leukemia

The therapeutic principle of IPH 2101 is based on the activation of NK cells by a monoclonal
antibody that blocks the latter’s KIR inhibitory receptors thereby potentiating NK cells anti-cancer
action.

Previous observations in a human clinical situation — HLA-mismatched allogenic bone marrow

transplantation — provide a model in which the NK inhibitory receptors are not functional. A
therapeutic benefit has been observed in this setting for acute myelogenous leukemia patients
having received alloreactive NK cells from unrelated donors, supporting the therapeutic concept.
According to developer Innate Pharma SA (innate-pharma.com), IPH 2101 aims at reproducing
this effect with a pharmacological agent.

KPBA101 — nosocomial pneumonia, ventilator-associated pneumonia

KBPA101 is a promising new treatment option for Pseudomonas aeruginosa pneumonia because
of its unique mode of action, in which it binds to Pseudomonas aeruginosa bacteria and,
independent from the microbiological sensitivity of antibiotics, kills the bacteria. Developer Kenta
Biotech Ltd. (kentabiotech.com) expects that KBPA101 will represent a significant progress in the
treatment of life-threatening Pseudomonas aeruginosa pneumonia.

KBPA101 is the first fully human monoclonal antibody in development against serotype O11
Pseudomonas aeruginosa pneumonia. In animal models, a single dose of KBPA 101
demonstrated rapid clearance of the pseudomonas lung-infection after a lethal challenge with
pseudomonas bacteria.

The compound has already successfully completed Phase I in healthy volunteers. There were no
serious adverse events and the drug was well-tolerated, showing a favorable risk/benefit profile.
The efficacy and safety of KPBA101 is being investigated in patients with ventilator-associated
pneumonia caused by Pseudomonas serotype O11.

Lestaurtinib (CEP-701) — Acute myeloid leukemia, multiple myeloma

Laboratory findings demonstrate lestaurtinib inhibits a specific genetic mutation targeted by the
compound in patients’ blood samples and were predictive of a positive clinical response,
according to preliminary data from a Phase II study of patients with acute myeloid leukemia who
bear a FLT3 activating mutation at first relapse from standard induction chemotherapy.

The early data suggest that chemotherapy followed by lestaurtinib may offer a clinical benefit
compared to chemotherapy alone. Preliminary results of an ongoing, randomized multi-center trial
sponsored by developer Cephalon Inc. (cephalon.com) were announced in a platform
presentation at the 47th Annual Meeting of the American Society of Hematology.

Linaclotide — Irritable bowel syndrome, chronic idiopathic constipation

Linaclotide is a first-in-class compound being developed by Microbia Inc. (microbia.com) for
treating irritable bowel syndrome, chronic constipation, and other gastrointestinal disorders.
Linaclotide is an agonist of guanylate cyclase type-c, a receptor found on the lining of the
intestine.

In preclinical testing, linaclotide was shown to increase fluid secretion into the intestine,
accelerate intestinal transit, and decrease visceral pain. Linaclotide was designed to exert its
effect on the intestine with minimal systemic exposure. In Phase 1 testing, linaclotide was safe
and well-tolerated and was not detected in the systemic circulation of healthy subjects.

Locteron — Hepatitis C

Locteron combines BLX-883, a recombinant interferon alfa produced in Biolex’s (biolex.com)

proprietary LEX System, with PolyActive, an advanced controlled-release drug-delivery
technology developed by the company’s joint-development partner OctoPlus. The
pharmacokinetic and pharmacodynamic results demonstrated in the Phase 1 study of Locteron
support dosing of hepatitis C patients once every two weeks, a substantial improvement over
marketed pegylated interferons that require dosing every week.

In addition, Locteron is designed to reduce the severity and duration of certain side effects, such
as flu-like symptoms, by eliminating the undesirable early high peak plasma levels that are
typically observed with marketed pegylated interferons and newer interferon product candidates
under development.

Lorcaserin — Obesity

Lorcaserin is an orally administered drug candidate for the treatment of obesity that was internally
discovered at Arena Pharmaceuticals Inc. (arenapharm.com). The drug, which is in an ongoing
Phase III program, stimulates the 5-HT2C serotonin receptor. This receptor is located in the
hypothalamus, an area of the brain that helps regulate satiety and influences metabolic rate.
Results from a Phase II study demonstrated that treatment with lorcaserin produced highly
statistically significant, progressive, and dose-dependent weight loss over a 12-week period.

In the study, which excluded diet and exercise, patients taking a daily 20-milligram dose of
lorcaserin realized a mean weight loss of 7.9 pounds, while patients on placebo lost less than one
pound. Lorcaserin was generally well-tolerated at all doses and had no apparent effects on heart
valves or pulmonary artery pressure.

Maraviroc — HIV/AIDS

If approved by the regulatory agencies, maraviroc will be the first in a new class of HIV/AIDS
treatments called CCR5 antagonists that work by blocking viral entry. Rather than fighting HIV
inside white blood cells, CCR5 antagonists prevent the virus produced by infected cells from
entering uninfected cells by blocking its predominant entry route, the CCR5 co-receptor.

"There is a profound global need for new medicines to help HIV/AIDS patients," says John
LaMattina, president, Pfizer Global Research and Development (pfizer.com). "We expect that
CCR5 antagonists like maraviroc will become critically important new treatment options for
patients who are resistant or intolerant to their current HIV/AIDS therapies."

Marqibo — Relapsed lymphoma, non-Hodgkin’s lymphoma, lymphoblastic leukemia

Marqibo uses vincristine encapsulated in a rigid, lipid bilayer of sphingomyelin. The sphingosome-
encapsulated technology employed by Marqibo results in a more rigid liposome that is designed
to allow the active vincristine to leak out of the liposome slowly, maintaining drug levels for
prolonged periods of time. This improved pharmacokinetic profile of Marqibo, which mimics a
continuous vincristine infusion, potentially results in greater activity in rapidly dividing cancers.
The drug is being developed by Hana Biosciences Inc. (hanabio.com).

The anticipated activity associated with vincristine has traditionally been limited by its short half-
life, and its inability to be dose escalated beyond 2 milligrams due to neurotoxicity. In Phase I and
II clinical trials, Marqibo has shown to have a significantly longer half-life, and patients have been
able to tolerate doses which are approximately 100% greater than conventional vincristine. These
trials provide the rationale for using this technology in lymphoproliferative diseases, such as acute
lymphocytic leukemia, and Hodgkin’s and non-Hodgkin’s lymphoma.

MCT-125 — Multiple sclerosis fatigue

MCT-125 completed a Phase II clinical trial and demonstrated significant efficacy in reducing
chronic fatigue in multiple sclerosis patients. There is no drug specifically approved for the
treatment of chronic fatigue in multiple sclerosis patients anywhere in the world. MCT-125 is
being developed by MultiCell Technologies Inc. (multicelltech.com).

In an earlier 138-patient, multi-center, double-blind placebo controlled Phase II clinical trial

conducted in the United Kingdom, MCT-125 demonstrated efficacy in reducing the levels of
fatigue in multiple sclerosis patients enrolled in the study. MCT-125 proved to be effective within
four weeks of the first daily oral dosing, and showed efficacy in multiple sclerosis patients who
were moderately as well as severely affected..

MCT-275 — Type 1 diabetes

Multicell Technologies Inc. is developing MCT-275, a immunoglobulin-peptide that specifically

targets autoaggressive T-Cells which attack pancreatic islet cells resulting in the loss of insulin
production. MCT-275 has demonstrated efficacy in animals of type 1 diabetes. Humans and
animals naturally have a blood glucose level of 100 milligrams per deciliter. The symptoms of
diabetes, such as frequent urination and lethargy, historically start when an individual’s glucose
level rises to 150-200mg/dl.

In animal models, MultiCell (multicelltech.com) treated animals following clinical onset of the
disease. After slightly increasing, the animals injected with MCT-275 showed a reversal in blood
glucose levels. The animals not treated continued to have a rise in glucose until the disease
progressed and resulted in death.

Methylnaltrexone — Postoperative ileus, opioid-induced constipation

Methylnaltrexone is a mu-opioid receptor antagonist designed to reverse the peripheral side

effects caused by opioids, particularly in the gastrointestinal tract. The drug does not interfere
with brain-centered pain relief. In a pilot Phase II clinical trial previously conducted by developer
Progenics Pharmaceuticals Inc. (progenics.com), patients who received methylnaltrexone
following segmental colectomy exhibited improvements in clinically important measures of
gastrointestinal recovery, including time to first bowel movement and discharge eligibility from the
hospital.

MK-0457 — Hematologic cancer, colorectal cancer, lung cancer, chronic myelogenous

leukemia, acute lymphocytic leukemia
MK-0457 was discovered by scientists at Vertex Pharmaceuticals Inc.’s Oxford, U.K., research
site as part of a broad research effort targeting the kinase gene family. Researchers at Vertex
(vrtx.com) published the three-dimensional atomic crystal structure of Aurora-A kinase in 2002, a
key scientific advance that enabled the design and optimization of multiple classes of small
molecule Aurora kinase inhibitors.

Vertex has presented data that shows that MK-0457 prolonged survival and induced sustained
remission in an oncogene driven model of human acute myelocytic leukemia.

In June 2004, Vertex entered into a global collaboration with Merck & Co. (merck.com) to
develop and commercialize MK-0457 and other follow-on Aurora kinase inhibitors. As part of the
collaboration, Vertex and Merck conducted a joint-research program to characterize MK-0457’s
activity across a broad range of cancer types and identified additional drug candidates targeting
the Aurora kinases.

MLN0415 — Inflammatory disorders

MLN0415 is a novel, small molecule IKK2 inhibitor, discovered by Millennium Pharmaceuticals

Inc. In preclinical studies, MLN0415 was shown to decrease NF-kB activation and down-regulate
the expression of a number of inflammatory proteins. Because inflammatory proteins play a
critical role in inflammation and drive the inflammatory response to disease, controlling these
proteins may prevent or slow disease progression.

"[MLN0415] selectively targets a key pathway involved in inflammatory response, which makes it
an attractive product candidate for preventing or delaying disease progression," says Nancy
Simonian, M.D., senior VP, clinical, medical, and regulatory affairs, Millennium (millennium.com).
"We continue to advance novel molecules into the clinic and this study is part of a larger
inflammatory development program that includes five product candidates."

MORAb-003 — Ovarian cancer

Morphotek Inc.’s lead antibody specifically targets the folate receptor alpha, a cell-surface
receptor over-expressed on ovarian, breast, colorectal, lung, and renal tumors. Preclinical studies
have demonstrated that the folate receptor alpha pathway is critical for initiating and sustaining
malignant characteristics of cancer cells over-expressing this protein.

The antibody is being evaluated by Morphotek (morphotek.com) in a multi-institutional Phase II

clinical trial in patients with relapsed platinum-sensitive ovarian cancer.

To date, clinical results have shown that the antibody is well-tolerated with no significant drug-
related adverse events reported when administered either in mono or combination therapy.

MORAb-009 — Pancreatic cancer, ovarian cancer, lung cancer, mesothelioma

Preclinical data for Morphotek Inc.’s MORAb-009, a monoclonal antibody targeting mesothelin,
show that mesothelin is highly over-expressed in tumors of patients with pancreatic
adenocarcinoma and other prevalent cancers including non-small lung carcinoma and ovarian
carcinoma, and that mesothelioma and may be associated with disease activity.

Research has shown MORAb-009 to inhibit tumor growth by inhibiting mesothelin binding to
extracellular substrate and also through antibody dependent cellular cytotoxicity. Morphotek
(morphotek.com) obtained exclusive rights to develop and commercialize the antibody worldwide
from the National Cancer Institute where the mesothelin protein and its expression association
with various cancer types were discovered.

Myodur (C101) — Muscular dystrophy, Becker’s muscular dystrophy

Myodur includes carnitine, a membrane transport carrier molecule that targets skeletal muscle,
and its passenger molecule, leupeptin, a known calpain inhibitor.

Calpain is the primary protease that degrades skeletal muscle. Because calpain is upregulated in
muscular dystrophy, developer CepTor Corp. (ceptorcorp.com) believesthat the inhibiting effect
of leupeptin along with the efficient targeting effect of carnitine makes Myodur an ideal candidate
for this orphan disease.

MyVax — Chronic lymphocytic leukemia

MyVax personalized immunotherapy is a patient-specific active immunotherapy based on the

unique genetic makeup of a patient’s tumor and is designed to activate the patient’s immune
system to identify and attack cancer cells.

Developer Genitope Corp. (genitope.com) initiated a Phase III pivotal trial evaluating MyVax in
Stage III/IV fNHL patients. The pivotal trial was based upon results from three Phase II trials,
evaluating the long-term efficacy of this treatment.

Results from the Genitope Phase II trial, which were released in 2005, showed nine of the 21
patients in this trial remained progression-free as of their last clinical follow-up at 56 to 78 months
post-chemotherapy.

NOV-002 — Nonsmall cell lung cancer, radiation contamination, ovarian cancer

NOV-002 is a small-molecule drug based on oxidized glutathione that acts as a chemoprotectant

and immunomodulator. The drg is being developed by Novelos Therapeutics Inc. (novelos.com).
In a controlled randomized U.S. Phase I/II clinical trial, advanced nonsmall cell lung cancer
patients treated with NOV-002 in combination with paclitaxel and carboplatin demonstrated
improved objective tumor response and higher tolerance of chemotherapy versus the control
group.

In a controlled randomized Russian trial, when used in combination with cisplatin-based

chemotherapy, NOV-002 increased the one-year survival of advanced nonsmall cell lung cancer
patients from 17% to 63%. NOV-002 has an extensive safety database. FDA granted fast-track
designation to NOV-002 for use in combination with first-line chemotherapy.

Ostabolin-C — Osteoporosis, psoriasis

Ostabolin-C, a cyclic 31 amino acid parathryoid hormone analogue, is a bone formation agent
designed to improve upon the safety and efficacy of marketed osteoporosis therapies.

Preclinical and Phase I studies have shown that Ostabolin-C stimulates significant bone formation
with little to no stimulation of bone resorption. This means Ostabolin-C has the potential for
enhanced efficacy but with reduced potential to cause hypercalcemia, a common side effect of
marketed parathyroid hormone therapies. Ostabolin-C is being developed by Zelos Therapeutics
Inc. (zelostherapeutics.com).

Ostarine — Male testosterone deficiency, muscle wasting, bone loss

Ostarine, a first-in-class selective androgen receptor modulator, met its primary endpoint in a
Phase II proof-of-concept double-blind, randomized, placebo-controlled clinical trial in 120
subjects, comprising 60 elderly men and 60 postmenopausal women. Without a prescribed diet or
exercise regimen, all subjects treated with ostarine had a dose-dependent increase in total lean
body mass, with the 3 milligram cohort achieving an increase of 1.3 kg compared to baseline and
1.4 kg compared to placebo after three months of treatment.

Treatment with ostarine also resulted in a dose-dependent improvement in functional

performance measured by a stair climb test, with the 3 milligram cohort achieving a clinically
significant improvement in both speed and power. Ostarine demonstrated a favorable safety
profile, with no serious adverse events reported. The drug is being developed by GTx Inc.
(gtxinc.com).

Provecta — Metastatic melanoma

Provectus Pharmaceuticals Inc. (pvct.com) is nearing completion of a 20-subject Phase I study

of the safety and efficacy of Provecta, also known as PV-10, for the ablation of metastatic
melanoma, an aggressive and often fatal form of skin cancer. Provectus expects to commence a
pivotal Phase II/III study of the efficacy of Provecta in the treatment of metastatic melanoma
shortly thereafter.

The clinical trial of Provecta is being conducted at two of the world’s leading melanoma treatment
and research centers, the Sydney Melanoma Unit and the Newcastle Melanoma Unit of New
South Wales, Australia. Each subject enrolled in the study has one or more tumors treated with a
single injection of Provecta and the local response to the treatment is then observed for a period
of 12 to 24 weeks.

Preclinical animal studies have shown broad-spectrum applicability of the agent for selective
ablation of a number of cancers, including melanoma, breast carcinoma, and hepatocellular
carcinoma.

Recombinant human c1 inhibitor (Rhucin) — Hereditary angioedema

Rhucin is being developed by Pharming Group NV (pharming.com) for the treatment of patients
with acute attacks of hereditary angioedema. The condition is a human genetic disorder caused
by a shortage of C1 inhibitor activity.

Hereditary angioedema is characterized by acute attacks of painful and in some cases fatal
swelling of several soft tissues, which usually last up to five days when untreated. In the Western
world, about one in 30,000 individuals suffers from hereditary angioedema, having an average of
seven acute attacks per year. ?

Removab — Gastric cancer

Removab, comprising catumaxomab, showed a clear advantage over a therapy with puncture
alone in a Phase II/III pivotal study on malignant ascites in patients with ovarian cancer. The drug
is being developed by Fresenius AG (fresenius-ag.de). The median puncture-free survival period
in the group of patients treated with Removab was significantly longer compared to the control
group and clinically relevant. The median puncture-free survival was 52 days in the Removab
group versus 11 days in the control group. ??

Positive results were also achieved with regard to key secondary endpoints. The median time to
the first therapeutic puncture was 71 days. In contrast to the primary endpoint, patients who died
before the next puncture were not included in this metric. Also, the EpCAM-positive tumor cell
concentration in the ascites fluid decreased significantly in patients treated with Removab. At the
same time, an increase in CD45-positive leukocytes was seen. Both results indicate a direct anti-
tumor effect of the trifunctional antibody.

Renvela — End-stage renal disease, chronic kidney disease

The development of sevelamer carbonate, a next-generation version of Renagel, took a major

step forward in fourth-quarter 2006 when Genzyme Corp. submitted a new drug application to
FDA seeking approval of sevelamer carbonate for the control of serum phosphorus in patients
with chronic kidney disease on dialysis.

Genzyme (genzyme.com) expects to launch the product commercially in 2008 under the trade
name Renvela. Following the anticipated approval of Renvela, Genzyme plans to submit a
supplemental new drug application seeking marketing approval for the product’s use in treating
hyperphosphatemic patients with chronic kidney disease who are not on dialysis. The company
also intends to seek approval for a powder form of Renvela taken once per day, which would
provide patients with a more convenient formulation and dosing schedule.

RX-0201 — Cancer

RX-0201 is a first-in-class signal inhibitor that directly blocks the production of Akt, a protein
kinase that plays a key role in cancer progression. Akt is overactivated in cancers such as breast,
colorectal, gastric, head and neck, ovarian, pancreatic, prostate, and thyroid cancers. Akt’s
transformation ability, as well as its role in cancer progression, makes it a highly attractive and
unique target in the treatment of cancer.

The clinical trial of RX-0201 was an open-label, dose-escalation study intended primarily to
determine the safety and tolerability of the drug in patients with advanced cancer. The trial has
demonstrated that the dose limiting toxicity of RX-0201 occurs at 315 mg/m2 dose in the form of
fatigue. No other serious adverse reactions such as hematological toxicities were observed in this
study. The drug is being developed by Rexahn Pharmaceuticals (rexahn.com).

SCH 530348 — Arterial thrombosis

Schering-Plough Corp. is developing SCH 530348 for the prevention of arterial thrombosis in
patients with acute coronary syndrome and those with prior myocardial infarction or stroke, as
well as in patients with existing peripheral arterial disease.

Schering-Plough (sgp.com) is investigating SCH 530348 to determine whether the drug has the
potential to provide clinical benefit through inhibition of thrombin-mediated platelet activation
without the liability of increased bleeding, a tendency associated with drugs that block
thromboxane or ADP pathways. SCH 530348 is being investigated as an oral antiplatelet agent
for patients with established vascular disease.

SGN-33 — Acute myeloid leukemia, myelodysplastic syndrome

SGN-33, or lintuzumab, is a humanized monoclonal antibody that targets the CD33 antigen and is
in a Phase I clinical trial for the treatment of acute myeloid leukemia and myelodysplastic
syndromes. The compound is being developed by Seattle Genetics Inc. (seattlegenetics.com).

Preliminary data from the ongoing Phase I study have shown that SGN-33 is well-tolerated and
has antitumor activity, including improved blood counts, decreased transfusion requirements, and
decreased myeloblasts in multiple patients with acute myeloid leukemia or myelodysplastic
syndrome.

SGN-35 — Hematologic cancer, Hodgkin’s disease

SGN-35 is an antibody-drug conjugate that links an anti-CD30 monoclonal antibody to a potent,

synthetic drug payload, monomethyl auristatin E. SGN-35 is being evaluated in a Phase I clinical
trial by developer Seattle Genetics Inc. (seattlegenetics.com) for Hodgkin’s disease and other
CD30-positive hematologic malignancies.

In preclinical studies, SGN-35 demonstrated potent antitumor activity at well-tolerated doses. Of

the more than 500,000 people in the United States with lymphoma, approximately 134,000 have
Hodgkin’s disease. The National Cancer Institute estimates that there will be more than 8,000
new cases of Hodgkin’s disease diagnosed in the United States during 2007.

Shigamabs — Shigatoxin-producing bacterial infections

Shigamabs is a single, intravenously administered product that consists of two monoclonal

antibodies: caStx1 and caStx2. Shigamabs is being developed for the treatment of shigatoxin-
producing bacterial infections. The most common of these infections is caused by shigatoxin-
producing E. coli, which is transmitted by contaminated food or water and is responsible for such
outbreaks as the one in Walkerton, Ontario, in May 2000. Shigatoxin-producing E. coli affects
about 250,000 people annually in industrialized countries. In 50% of people that experience
shigatoxin-mediated events, clinical outcomes include hemolytic anemia, thrombocytopenia,
kidney failure, brain damage, and for 2% to 3% of such patients, death. There is currently no
approved treatment for shigatoxin-producing E. coli infections.

Preclinical animal models have demonstrated the efficacy of Shigamabs and Phase I trials have
shown the antibodies to be independently safe and well-tolerated in healthy volunteers.
Developer Caprion Pharmaceuticals Inc. (caprion.com) expected to initiate a pivotal Phase II/III
trial by the close of first-quarter 2007.

SIGA-246 — Smallpox

SIGA-246 represents a new approach to achieve a novel, orally active, antiviral therapeutic. Thr
drug has already demonstrated significant antiviral activity in various animal trials, including the
complete protection against human smallpox virus in primates as well as complete protection in
two primate trials against high doses of monkeypox.

In February, Siga Technologies Inc. launched a 21-day, escalating, multiple-dose, Phase I

safety, tolerability, and pharmacokinetics human trial of SIGA-246. The study will examine the
safety and pharmacokinetics of SIGA-246 at three dosages in healthy volunteers when taken
once a day for 21 days.

"This is one more milestone in the path to FDA approval," says Dr. Dennis E. Hruby, chief
scientific officer, Siga (siga.com). "This important study we believe will confirm the safety findings
of an earlier human study and establish the likely human dose of SIGA-246."

SinuNase — Sinusitis

Accentia Biopharmaceuticals (accentia.net) has begun a Phase III clinical trial for SinuNase in
patients with severe chronic sinusitis that are refractory to sinus surgery. SinuNase is the first and
only product in a Phase III clinical trial for chronic sinusitis. There is no approved pharmaceutical
available for chronic sinusitis, a condition that affects 31 million patients, and represents a market
almost twice the size of the asthma market, which is the next largest among respiratory diseases.
To date, 43 clinical trial sites have been initiated and 29 have been cleared to enroll patients.

The trial will be a 16-week, double-blinded comparison with 300 patients randomized between
SinuNase and placebo, with the primary endpoint being the resolution of the key cardinal
symptoms of chronic sinusitis. Secondary endpoints include endoscopy scores and sinus
mucosal thickening on CT scan.

SLX-4090 — Dyslipidemia

SLX-4090 is a novel microsomal triglyceride transfer protein inhibitor being developed Surface
Logix Inc. for the treatment of dyslipidemia. Surface Logix designed SLx-4090 using its
proprietary small molecule Pharmacomer technology to act specifically in the gastrointestinal tract
to prevent the transport of fats through the intestinal wall. This unique feature of intestinal
selectivity allows activity against fat uptake while avoiding toxicity at other sites of MTP
expression including the liver, heart, testis, ovary, and eye.

"The SLx-4090 development program continues to validate our Pharmacomer platform and our
ability to take novel approaches to overcome difficult challenges in drug development," says Paul
Sweetnam, chief scientific officer, Surface Logix (surfacelogix.com). "We are very pleased to see
that the preclinical development of SLx-4090 has been very robust in predicting the drug
candidate’s performance in the clinic."

SPI-1005 — Hearing loss

SPI-1005 is an oral capsule and contains as its active ingredient a selenium-based small
molecule mimic of the enzyme glutathione peroxidase. In multiple preclinical studies, low oral
doses of SPI-1005 have been shown to be effective in preventing and treating noise-induced
hearing loss.

"These animal studies have been replicated by three independent labs, all demonstrating that the
active ingredient in SPI-1005 is effective in reducing both the temporary and permanent hearing
loss associated with exposure to loud noise," says Eric Lynch, Ph.D., VP and director of
research, Sound Pharmaceuticals Inc. (soundpharmaceuticals.com).

SQ109 — Tuberculosis

SQ109 is an orally active small-molecule antibiotic that inhibits cell wall synthesis and acts on
multiple cellular pathways in a select group of microorganisms, including Mycobacterium
tuberculosis. SQ109 enhances, in vitro and in vivo, the activity of the anti-tubercular drugs
isoniazid and rifampin, thereby shortening by 25% the time required to cure mice of experimental
tuberculosis.

SQ109 is in Phase I clinical trials and could replace one or more of the current first-line anti-TB
drugs, simplify therapy, and shorten the treatment regimen. SQ109 was developed by Sequella
Inc. (sequella.com) in partnership with the NIH, with several grants from the National Institute of
Allergy and Infectious Diseases and the assistance of the NIAID and the National Cancer Institute
Inter-Institute Program for IND-enabling studies.

STA-4783 — Metastatic melanoma

STA-4783 is an investigational, novel, small-molecule drug candidate from Synta
Pharmaceuticals Corp. that induces a stress response in a wide variety of cancer cell types. This
stress response results in two changes that may be important to the role of STA-4783 in tumor
cell killing in combination with taxanes. These changes are a dramatic increase in the production
of Hsp70 and other heat shock and stress-related proteins, which can enhance immune-mediated
killing of tumor cells; and the alteration of certain signal transduction pathways in tumor cells,
which can affect cell proliferation and induce programmed cell death, or apoptosis.

In preclinical studies, STA-4783 combined with taxanes has shown activity against a broad range
of cancers, including breast, lung, colon, lymphomas, and melanoma. To date, STA-4783 has
been studied by Synta (syntapharma.com) in about 300 patients across multiple studies.

Talabostat — Neutropenia, non-Hodgkin’s lymphoma, chronic lymphocytic leukemia,

nonsmall cell lung cancer, melanoma, pancreatic cancer, solid tumors

Point Therapeutics Inc. is studying talabostat in two Phase III double-blind, placebo-controlled
trials in non-small cell lung cancer and in a Phase II trial in combination with gemcitabine in
metastatic pancreatic cancer. Point (pther.com) has also studied talabostat in several Phase II
trials, including as a single-agent in metastatic melanoma, in combination with cisplatin in
metastatic melanoma, in combination with rituximab in advanced chronic lymphocytic leukemia,
and in combination with docetaxel in NSCLC.

Of the 21 evaluable patients who entered the metastatic pancreatic cancer study at least six
months ago, 10 (48%) have survived more than six months. In addition, 31 patients are currently
evaluable for tumor response. To date, three patients (9.7%) have demonstrated a clinical
response to treatment, including one complete response and two partial responses. One patient
with metastatic disease to the liver experienced a complete response to treatment — defined as
the complete disappearance of tumor. Thus far, no unexpected toxicities have been seen in the
trial that would prevent the company from continuing to study talabostat in combination with
gemcitabine.

Talactoferrin — Renal cell cancer, nonsmall cell lung cancer, diabetic ulcers

Talactoferrin alfa is a unique recombinant form of human lactoferrin, an immunomodulatory

protein, that is being developed by Agennix Inc. (agennix.com). Talactoferrin acts by binding to
specific receptors found on target cells and inducing the production of key immunomodulatory
cytokines and chemokines. Orally administered talactoferrin binds to enterocytes lining the upper
gastrointestinal tract, initiating an immunostimulatory cascade in the gut associated lymphoid
tissue. This results in the activation of both innate and adaptive immunity including recruitment
and activation of dendritic cells, NK-T cells and CD8+ lymphocytes.

This is followed by systemic immunostimulation, the activation of tumor-draining lymph nodes,

and infiltration of distant tumors by immune cells, which results in killing of the cancer cells.
Topically administered talactoferrin binds to keratinocytes and fibroblasts and increases the local
production of cytokines and chemokines critical to wound healing.

Tapentadol — Acute pain, chronic pain

Tapentadol is a novel, investigational, centrally acting analgesic with a dual mode of action for the
treatment of moderate-to-severe pain. Phase III studies of tapentadol have recently been initiated
in the United States and in Europe by Johnson & Johnson Pharmaceutical Research &
Development (jnjpharmarnd.com). If successfully developed, tapentadol would be the first new
molecular entity to enter medical practice in the oral opioid category in more than 25 years.
The drug was effective in a series of pain models in the rat, which included a sciatic nerve ligature
model for neuropathic pain. Its potency was between that of morphine and tramadol. The drug
achieved satisfactory serum levels after intravenous and oral administration, and was generally
well-tolerated.

Tesmilifene — Prostate cancer, breast cancer

Tesmilifene is a novel, small molecule that selectively targets multiple-drug resistant tumor cells,
sensitizing them to chemotherapy. Tesmilifene, which is being developed by YM Biosciences
Inc., may offer clinical benefit in a number of tumor types and is being tested with a variety of
chemotherapeutic regimens. In addition to the current pivotal trial, a Phase III trial of tesmilifene
with doxorubicin in metastatic or recurrent breast cancer has been completed and a Phase II
study to evaluate tesmilifene plus docetaxel in patients with metastatic breast cancer is being
conducted by YM Biosciences (ymbiosciences.com) in collaboration with Sanofi-Aventis (sanofi-
aventis.com).

In hormone-refractory prostate cancer, two single-arm Phase II trials of tesmilifene in combination

with chemotherapy and a randomized Phase II trial comparing cyclophosphamide alone to
cyclophosphamide plus tesmilifene have been conducted. Based on the clinical data generated
from these three studies, the company is currently evaluating additional clinical work in patients
with hormone-refractory prostate cancer. In addition, the company and its partners are evaluating
clinical studies in patients with gastric cancer as well as patients with hepatic cancer.

TG-C — Cartilage repair

TissueGene (tissuegene.com) has developed TG-C to regenerate cartilage in patients suffering

from degenerative arthritis and more specifically for indications such as osteoarthritis of the knee.
As an alternative to other methods of cartilage repair, TG-C will involve minimally invasive
injections versus a surgical approach. Other techniques currently involve multiple and often
invasive surgical procedures and have mixed results.

"We are pleased with the approval to start our Phase I program with TG-C and feel that our drug
candidate has the potential to be not first-in-class, but also best-in-class," says Dr. K.H. Lee,
president, founder, and CEO, TissueGene.

TG100-115 — Acute myocardial infarction

TG100-115 is a selective PI3 kinase inhibitor that has demonstrated the ability to suppress
vascular leakage, inflammation and thus significantly reduce infarct size and reperfusion injury in
pre-clinical models of acute myocardial infarction. A Phase I/II multi-center clinical trial involving
TG100-115 is in progress in the United States and Canada with completion expected before the
end of first-quarter 2007. The drug was internally discovered by TargeGen Inc. (targegen.com).

Following a heart attack, the condition of hypoxia activates kinase-signaling cascades which
cause biochemical changes to blood vessels which permit leakage. The leakage out of the
vasculature contributes to microcirculatory collapse, inflammation, reperfusion injury, heart tissue
damage, and ultimate infarct size. TG100-115 has been designed to selectively block vascular
leakage and inflammation for up to six hours after an ischemic event.

TMC125 — HIV infection

TMC125 is a next-generation NNRTI active against NNRTI-resistant strains of HIV. The Phase III
clinical trials in treatment-experienced HIV-1 infected patients are ongoing and have recently
completed enrollment. The safety and efficacy of TMC125 in combination with other antiretroviral
agents have not been established.

"We know that many people living with HIV/AIDS have limited treatment options because of the
increasingly significant issue of viral resistance, and we are working to provide eligible individuals
with access to TMC125 as soon as possible through this program," says Roger Pomerantz, M.D.,
president, Tibotec Research and Development (tibotectherapeutics.com).

Tolvaptan — Congestive heart failure, hypoantremia, polycystic kidney disease

Tolvaptan is being evaluated as a preventive product for a serious manifestation of autosomal

dominant polycystic kidney disease, increased renal size, and the secondary complications such
as hypertension, proteinuria, and renal pain. Otsuka Pharmaceutical Co. (otsuka.com) plans to
conduct efficacy studies in patients with autosomal dominant polycystic kidney disease. The
company believes that tolvaptan might be effective in the treatment of autosomal dominant
polycystic kidney disease based on what is known regarding the pathophysiology of the disease,
the known mode of action of tolvaptan, and the results from nonclinical animal model studies.

In Phase II studies with polycystic kidney disease subjects, tolvaptan has been associated with
side effects that include increased thirst and urination. Otsuka has completed several Phase II
clinical trials with tolvaptan in patients with autosomal dominant polycystic kidney disease, and is
beginning global Phase III clinical trials.

Treanda — Non-Hodgkin’s lymphoma

Treanda, an investigational therapeutic under development by Cephalon (cephalon.com), is a

novel hybrid cytotoxic alkylating agent that differs from conventional compounds in its apparent
multi-functional mechanism of action. In addition to killing cells by damaging their DNA and
triggering a self-destruct signal known as apoptosis, researchers demonstrated that Treanda also
causes mitotic catastrophe, or the disruption of cell division. Preclinical data suggest that
Treanda’s multi-functional mechanism of action may derive from its chemical structure in which
one molecular ring common to traditional alkylators is altered.

TRO19622 — Amyotrophic lateral sclerosis, spinal muscular atrophy, neuropathic pain

TRO19622 is representative of a class of novel compounds identified using the proprietary

neuronal cell-screening platform developed at Trophos SA (trophos.com). In preclinical studies
these "first-in-class" compounds have been demonstrated to promote the survival of a wide range
of neurons in vitro, as well as in several in vivo models of neurodegenerative diseases.

"We are excited that TRO19622, the lead molecule discovered using our innovative phenotypic
screening platform has successfully completed these Phase Ib trials and continues to
demonstrate an excellent clinical safety profile," says Dr. Jean-Louis Abitbol, chief medical officer,
Trophos.

TZP-101 — Post-operative ileus, gastroparesis

Tranzyme Pharma (tranzyme.com) has been developing TZP-101 as a potent prokinetic agent
for the treatment of postoperative ileus. Under an amended investigational new drug application,
Tranzyme has initiated a single-dose study in diabetic patients suffering from gastroparesis. This
new study will provide a lead-in to more detailed Phase II evaluation of TZP-101 in postoperative
ileus and gastroparesis.
In a previous Phase I single-dose study, Tranzyme reported TZP-101 demonstrated excellent
tolerability and safety, and a desirable pharmacokinetic profile in healthy subjects. The Company
plans to initiate full Phase II development of TZP-101 in early 2007.

Urocidin — Bladder cancer, colorectal cancer

Urocidin is a formulation of mycobacterial cell wall-DNA complex for the treatment of high-grade
non-invasive bladder cancer. This is a composition prepared from from Mycobacterium phlei, a
saprophytic mycobacteria. Mycobacterial cell wall-DNA complex has immune stimulatory as well
as apoptosis inducing activity against cancer cells.

The study under way by developer Bioniche Life Sciences (bioniche.com) uses Urocidin for the
treatment of non-muscle invasive bladder cancer in patients who are refractory to Bacillus
Calmette-Guerin, a live, attenuated strain of Mycobacterium bovis and the current standard
therapy. Bacillus Calmette-Guerin therapy can result in treatment-limiting side effects in some
patients.

Valopicitabine — Hepatitis C

Interim analysis of a Phase IIb Hepatitis C study of 200 milligrams per day of valopicitabine,
combined with pegylated interferon, resulted in favorable viral suppression with a low rate of side
effects in treatment naive patients with genotype-1 HCV infection after 24 weeks of treatment.
The drug is being developed by Idenix Pharmaceuticals Inc. (idenix.com).

At 24 weeks, the 200 mg/day dose of valopicitabine in combination with pegylated interferon
achieved marked HCV RNA reductions in treatment-naive patients with genotype-1 infection. A
mean 4.24 log10 reduction in viral load was achieved among patients being treated with 200
mg/day of valopicitabine, in combination with pegylated interferon. About 68% of patients
receiving this combination regimen achieved viral clearance at week 24, using the TaqMan
assay’s lower limit of quantification of 20 IU/mL.

VP025 — Neuroinflammatory disorders

In a preclinical model designed to develop diabetes, VP025 was shown to have a significant
effect on reducing the expression, in the retina, of several pro-inflammatory cytokines including
IL-1, IL-6, and MCP-1, which are associated with the initiation stages of diabetic retinopathy.
Concurrently, the intramuscular administration of VP025 resulted in the increased expression of
both IL-10 and TGF-beta, two potent anti-inflammatory cytokines.

Developer Vasogen Inc. (vasogen.com) believes this effect is mediated via the regulation of
microglial cell activation. Microglial cells are inflammatory cells found within the central nervous
system and in the retina. VP025 has been previously shown to down-regulate microglial cell
activation in a number of other preclinical models of neuroinflammatory disease.

VQD-001 — Cancer

VQD-001 is a clinical-stage drug with a novel anti-tumor action that has potential as a treatment
for cancer, either alone or in combination with other therapeutics. The drug has shown compelling
preclinical activity,in multiple myeloma, malignant melanoma, bladder, and colon cancer cell lines.
VQD-001 is being developed by VioQuest Pharmaceuticals Inc.
(vioquestpharm.com).
VQD-001 seems to inhibit specific protein tyrosine phosphatases, which are overexpressed in
certain cancers. This overexpression plays an integral role in tumor growth in certain cancers.

VX-770 — Cystic fibrosis

VX-770 may act to restore the function of the cystic fibrosis transmembrane conductance
regulator protein, the defective cell membrane protein responsible for the progression of cystic
fibrosis. Defects in this protein affect the transport of chloride and other ions across cells, and
lead to the accumulation of thick, sticky mucus in the lungs of patients with cystic
fibrosis.Potentiator compounds such as VX-770 are designed to increase the probability that the
CFTR channel is open, which could result in an increase in chloride transport across the cell
surface in some patients. The drug is being developed by Vertex Pharmaceuticals Inc.
(vrtx.com).

VX-950 — Hepatitis C

VX-950 is an investigational oral inhibitor of HCV protease, an enzyme essential for viral
replication, and is one of the most advanced investigational agents in development that
specifically targets hepatitis C virus. Developer Vertex Pharmaceuticals Inc. (vrtx.com) is
conducting a global Phase IIb clinical development program for VX-950 consisting of three large
clinical trials that are expected to enroll about 1,000 patients with hepatitis C at clinical centers in
the United States and Europe.

The U.S.-based PROVE 1 trial is fully enrolled and ongoing. The PROVE 2 study is under way in
Europe and is expected to complete enrollment with about 320 patients. Also, Vertex expects to
initiate PROVE 3, a clinical trial that will enroll more than 400 treatment-experienced patients..

YSPSL — Delayed graft function

YSPSL is a clinical-stage recombinant molecule resulting from fusion of P-selectin glycoprotein

ligand-1 to human IgG1. The drug is under evaluation for the prophylaxis of delayed graft function
following kidney transplantation. YSPSL blocks a class of adhesion molecules known as selectins
and prevents the accumulation of both leukocytes and platelets at sites of inflammation.

Administration of YSPSL in animal models of transplantation suggests the drug may also
upregulate anti-apoptotic genes such as hemoxygenase-1 that protect organs from ischemia-
reperfusion injury. The drug is being developed by Y’s Therapeutics Inc. (ysthera.com).

Trials and errors

Pfizer perennially leads the pharmaceutical industry in research and development spending,
having topped $7.5 billion in 2006 alone. That prodigious investment has paid off the in the past
with blockbusters like Lipitor — an acquisition the company developed into the world’s best-
selling prescription drug. On the other hand, when one of the company’s big drugs fails, it quickly
becomes headline news.

Five of Pfizer’s pipeline projects were selected for inclusion on the 2007 list of 100 great
investigational drugs, compiled by R&D Directions’ editorial staff.

Dr. John LaMattina, Pfizer’s president of global research and development, recently discussed
those issues and others with the magazine’s managing editor, Lyle D. Fitzsimmons.
R&D Directions: What are the specific challenges associated with being the biggest R&D
spender in the industry? Is it always an advantage?

The size of Pfizer’s R&D budget directly reflects our past success in delivering medicines to
patients in need. The scale of investments also shows our firm confidence that we will continue
making a significant difference in many areas of strong unmet medical need.

Scale delivers significant advantages — it limits our risk exposure and it allows us to share
resources and knowledge across our broad portfolio. Scientists come to Pfizer because they have
access to the latest and best technologies and because there are more opportunities here to
learn, to grow, and to collaborate.

We all know that size is a handicap if you allow complexities and bureaucracies to flourish, but at
Pfizer we fully understand that downside. That’s why we’ve taken firm, decisive action to create
smaller, more focused, and entrepreneurial business units that can still draw on the advantages
of scale and resources.

R&D Directions: With that standing, I’d imagine that both failures and successes are
magnified by media observers. Do you find that the case?

Pfizer is an A-list celebrity in its field and we’ve learned to thrive under intense scrutiny. In fact,
we are committed to even greater transparency.

We want patients, doctors, investors and others to see the real Pfizer. That means realism in the
way we’re looking at our challenges and opportunities, transparency in the way we communicate,
and accountability in the way we manage our business. One example is on our Website, where
we publish a very detailed pipeline.

R&D Directions: Could you speak briefly about torcetrapib and what led to the decision to
halt its development? How difficult a decision was it to make, factoring in the major
investments that had been made in its development program? Was there consensus?

The ILLUMINATE study was run under the auspices of an independent data safety monitoring
board — made up of some of the world’s leading experts in cardiovascular medicine. Their
responsibility was to protect patient safety and to alert us if they saw a problem.

Until that weekend, they were satisfied with what they saw, but the moment they spotted an
issue, they told us. There was never any discussion about what to do. The leadership of Pfizer
had a conference call within two hours of hearing the news. We never questioned stopping the
program — stopping the program was the right thing to do. We then immediately focused on
contacting patients and physicians.

R&D Directions: How important is it for the company to achieve development successes in
the wake of that setback?

This was very disappointing, particularly for patients waiting for new treatments for heart disease
— still the most common cause of death.

In Pfizer, we felt that blow but we know all about risk. We manage disappointment and we quickly
shift attention and resources to lots of other important work across 10 therapeutic areas. We have
18 compounds in advanced development or registration and about 170 more in early and mid-
stage development. Pfizer’s scale is a significant advantage. It allows us to make major plays, like
torcetrapib, to manage disappointment, to apply lessons learned, and to quickly move on to other
promising programs.

In fact, the opportunities have never been greater. The world’s population is growing older so
there is increasing demand for affordable, quality health care. We have the people, the skills, the
resources and the experience to deliver better health care. Already, we’re seeing newer products,
like Lyrica, Chantix, and Sutent doing well in their markets but we are well-placed to do far
more.

Pfizer Global Research & Development aims to deliver four new products each year, starting in
2011, and Business Development will generate another two per year from external sources,
starting in 2010. We are establishing a smaller and more flexible cost base and we are constantly
improving the way we work. So, the torcetrapib setback has probably caused us to accelerate the
transformation of Pfizer into an even more productive organization.

R&D Directions: Our magazine is citing five particular compounds — axitinib, CP-675206,
CP-945598, fesoterodine, and maraviroc — for inclusion on this year’s 100 great
investigational drugs list. Could you touch on each of the five and give their respective
statuses and prospects for the future?

These are five out of the very many promising development compounds in a pipeline that has
never been larger and that continues to grow. We are appropriately cautious about predicting
success or promising timelines, but I’m happy to provide some detail.

Axitinib is in Phase II development and follows on the heels of Sutent — one of the most exciting
new compounds in cancer treatment. Like Sutent, it is an anti-angiogenesis therapy but
preclinical data indicate that it is an even more potent inhibitor of vascular endothelial growth
factor receptor (VEGFR) and we have promising data in thyroid and pancreatic cancer. This
mechanism is the key to the growth and spread of tumors so we hope to demonstrate clinical
benefit across other types of cancer.

CP-675206 is our first fully human monoclonal antibody for the treatment of cancer. If it’s
approved, it will represent a real advance for patients with metastatic melanoma and, possibly in
combination with other agents, with other conditions. The antibody binds to the CTLA-4 receptor
on the cell surface of T cells and releases an "immune system brake" — allowing the body to
tackle cancer cells. Recently, we showed clinical photographs of a primary skin melanoma that
had progressed despite prior treatments. After one monthly dose of CP-675206, there was
significant regression of the tumor. This was one patient but it certainly greatly encouraged us.
We are now progressing our Phase II trials.

CP-945598 is a cannabinoid receptor-1 antagonist that offers the potential to reduce appetite and
favorably impact metabolic risk factors, such as cholesterol and blood glucose. Again, we recently
showed six-month, Phase II data indicating statistically different weight loss over placebo. We
think the safety and toleration profile is also favorable, and we started Phase III trials late last
year.

Fesoterodine has shown promising results in treating symptoms of overactive bladder and it’s
currently under FDA review. We expect to receive approval early this year. It’s one of the four
medicines we have in registration.

Another is maraviroc, a drug also invented at Pfizer, that tackles HIV in an entirely new way. This
is an oral medicine that blocks viral entry to human cells. Rather than fighting HIV inside white
blood cells, it prevents the virus from entering uninfected cells by blocking its predominant entry
route, the CCR-5 co-receptor. Last month (February), we presented pivotal data from a 24-week
analysis showing significant decreases in viral load and increase in CD4 cells when maraviroc is
added to the standard optimized treatment regimen. Regulatory authorities in the U.S. and
Europe have granted accelerated review and the FDA’s Antiviral Drugs Advisory Committee will
discuss maraviroc in April.

R&D Directions: At what point in development have past successes at Pfizer distinguished
themselves? Can you generally tell immediately when a specific compound will be a major
success, or is it farther down the line that they exhibit that potential?

Torcetrapib taught others what this industry already knows — our business is about taking
careful, calculated risks to prove or disprove a hypothesis. In this case, the hypothesis was
founded on excellent science and we conducted a cautious, appropriate clinical program to test a
theory that HDL elevation was beneficial. The results were a huge surprise and we’re now
working with outside experts to understand more.

That careful, step-by-step approach with considerable regulatory oversight and review by leading
experts is how we progress scientific understanding. As that understanding grows and
technologies develop, we are getting much better at making early decisions — spotting potential
problems long before we start large-scale clinical trials. The fact of the matter is, however, we can
never express total confidence until the data read out.

R&D Directions: How have the recent changes at Pfizer affected the R&D focus? Has there
been a philosophy change, or has that area of the company been affected less? How
would you characterize the philosophy as it stands now? What are the priorities? Are
changes forthcoming?

There is no philosophy change because we remain in the business of delivering significant

advances in areas of unmet medical need. We did, however, recently announce changes that
allow us to deliver more products of more value, more rapidly, while maintaining the same level of
investment. We hope to triple our Phase III pipeline between now and 2009 and we will generate
four internally generated products, starting in 2011. With a flat budget, we have a financial
challenge because the most expensive component of R&D is late-stage development.

Our response is to get smart and find the right way to fund an increasing number of clinical trial
programs without busting our budget. Once again, our scale is a distinct advantage because we
can find considerable savings and efficiencies in this very large organization. Through various
acquisitions, Pfizer had inherited an overly-complex R&D site network so we acted to simplify that
structure, close some sites, and transfer spending from infrastructure to science. We’re proud of
our people at all our sites so those decisions were very difficult and very carefully thought
through.

The result is we can reallocate hundreds of millions of dollars from bricks and mortar and reduce
the budget for support staff and facilities by 20%. Those savings will fund our burgeoning late-
stage portfolio plus investments in biotherapeutics and third-party collaborations. We are already
a major player In biotherapeutics, and we plan to increase the output of candidates in this area to
20% of our internal portfolio. Within the next 10 years, we could have one biotherapeutic launch a
year. We’ll see new vaccines, antibodies, and other large molecules.

Third-party collaborations have always been important to Pfizer because we recognize that
excellent science lies inside and outside our walls. We have a lot to learn from our partners and a
lot to offer. We’ve identified many areas that will help us succeed including computational biology,
systems biology, translational pharmacology, and investigational toxicology.
A smaller global network means we can implement a one-site-per-therapeutic-area strategy and
single leaders with more authority, control and accountability. One site per TA means better
interactions with our commercial colleagues, faster decision-making and less time wasted on
bureaucracy, travel, and meetings.