Author Archives: Barry Sugarman

FDA Accepts New Drug Application Filing for Ridaforolimus, Investigational mTOR Inhibitor

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http://www.merck.com/newsroom/news-release-archive/research-and-development/2011_1005.html

FDA Accepts New Drug Application Filing for
Ridaforolimus, Investigational mTOR Inhibitor

WHITEHOUSE STATION, N.J. & CAMBRIDGE, Mass., Oct. 5, 2011 — Merck (NYSE:MRK),
known outside the United States and Canada as MSD, and ARIAD Pharmaceuticals,
Inc., (NASDAQ:ARIA), today announced that the U.S. Food and Drug Administration
(FDA) has accepted for filing and review the New Drug Application (NDA) for
ridaforolimus, an investigational oral mTOR inhibitor under development for the
treatment of metastatic soft-tissue or bone sarcomas in patients who had a
favorable response to chemotherapy. The FDA assigned a Standard review
classification to this application.

Merck and ARIAD previously announced that the European Medicines Agency had
accepted the marketing authorization application for ridaforolimus. As part of
an exclusive license agreement with ARIAD, Merck is responsible for the
development and worldwide commercialization of ridaforolimus in oncology. ARIAD
intends to co-promote ridaforolimus in the United States.

About Sarcoma
Sarcomas are a group of cancers of connective tissue of the body for which there
are currently limited treatment options. Sarcomas can arise anywhere in the body
and are divided into two main groups – bone tumors and soft-tissue sarcomas.

About Ridaforolimus
Ridaforolimus is an investigational targeted and potent small-molecule inhibitor
of the protein mTOR, a protein that acts as a central regulator of protein
synthesis, cell proliferation, cell cycle progression and cell survival,
integrating signals from proteins, such as PI3K, AKT and PTEN, known to be
important to malignancy.

Merck's Commitment to Oncology
Merck is committed to advancing all aspects of cancer care – prevention,
treatment and supportive care. Through strong internal research capabilities,
selective alliances and acquisitions, and enabling technologies, Merck is
looking to lead in the discovery, development and delivery of anticancer
therapies.

About Merck
Today's Merck is a global healthcare leader working to help the world be well.
Merck is known as MSD outside the United States and Canada. Through our
prescription medicines, vaccines, biologic therapies, and consumer care and
animal health products, we work with customers and operate in more than 140
countries to deliver innovative health solutions. We also demonstrate our
commitment to increasing access to healthcare through far-reaching policies,
programs and partnerships. For more information, visit
www.merck.com and connect
with us on Twitter, Facebook and YouTube.

About ARIAD
ARIAD Pharmaceuticals, Inc. is an emerging global oncology company focused on
the discovery, development and commercialization of medicines to transform the
lives of cancer patients. ARIAD's approach to structure-based drug design has
led to three internally discovered, molecularly targeted product candidates for
drug-resistant and difficult-to-treat cancers, including certain forms of
chronic myeloid leukemia, soft tissue and bone sarcomas and non-small cell lung
cancer. For additional information, visit
http://www.ariad.com.

Merck Forward-Looking Statement
This news release includes “forward-looking statements” within the meaning of
the safe harbor provisions of the United States Private Securities Litigation
Reform Act of 1995. Such statements may include, but are not limited to,
statements about the benefits of the merger between Merck and Schering-Plough,
including future financial and operating results, the combined company's plans,
objectives, expectations and intentions and other statements that are not
historical facts. Such statements are based upon the current beliefs and
expectations of Merck's management and are subject to significant risks and
uncertainties. Actual results may differ from those set forth in the
forward-looking statements.

The following factors, among others, could cause actual results to differ
from those set forth in the forward-looking statements: the possibility that the
expected synergies from the merger of Merck and Schering-Plough will not be
realized, or will not be realized within the expected time period; the impact of
pharmaceutical industry regulation and health care legislation; the risk that
the businesses will not be integrated successfully; disruption from the merger
making it more difficult to maintain business and operational relationships;
Merck's ability to accurately predict future market conditions; dependence on
the effectiveness of Merck's patents and other protections for innovative
products; the risk of new and changing regulation and health policies in the
United States and internationally and the exposure to litigation and/or
regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking
statement, whether as a result of new information, future events or otherwise.
Additional factors that could cause results to differ materially from those
described in the forward-looking statements can be found in Merck's 2010 Annual
Report on Form 10-K and the company's other filings with the Securities and
Exchange Commission (SEC) available at the SEC's Internet site (www.sec.gov).

ARIAD Forward-Looking Statement
This press release contains “forward-looking statements” including, but not
limited to, statements relating to clinical data for ridaforolimus in the
treatment of metastatic soft-tissue and bone sarcomas. Forward-looking
statements are based on management's expectations and are subject to certain
factors, risks and uncertainties that may cause actual results, outcome of
events, timing and performance to differ materially from those expressed or
implied by such statements. These risks and uncertainties include, but are not
limited to, results of clinical studies of the Company's product candidates,
timing and acceptance of regulatory filings for drug approval, and other factors
detailed in the Company's public filings with the U.S. Securities and Exchange
Commission. The information contained in this press release is believed to be
current as of the date of original issue. The Company does not intend to update
any of the forward-looking statements after the date of this document to conform
these statements to actual results or to changes in the Company's expectations,
except as required by law.

 

# # #

Arsenic trioxide inhibits human cancer cell growth and tumor development in mice by blocking Hedgehog/GLI pathway

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http://www.jci.org/articles/view/42874?search[article_text]=arsenic&search[authors_text]=

Arsenic
trioxide inhibits human cancer

cell growth and tumor development in

mice by
blocking Hedgehog/GLI

pathway

Elspeth M.
Beauchamp1,
Lymor Ringer1,
Gülay Bulut1,
Kamal P. Sajwan1,
Michael D. Hall1,
Yi-Chien Lee1,
Daniel Peaceman1,
Metin Özdemirli1,
Olga Rodriguez1,
Tobey J. Macdonald2,
Chris Albanese1,
Jeffrey A. Toretsky1
and Aykut Üren1

1Lombardi
Comprehensive Cancer Center, Georgetown University Medical Center, Washington,
DC, USA.
2Department
of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.

Address correspondence to: Aykut Üren, 3970
Reservoir Rd. NW, NRB, Room E312, Washington, DC 20057, USA. Phone:
202.687.9504; Fax: 202.687.1434; E-mail:
au26@georgetown.edu.

First published December 22, 2010
Received for publication March 4, 2010, and accepted in revised form October 13,
2010.



The Hedgehog (Hh) pathway is
activated in some human cancers, including medulloblastoma. The glioma-associated
oncogene homolog (GLI) transcription factors are critical mediators of the
activated Hh pathway, and their expression may be elevated in some tumors
independent of upstream Hh signaling. Thus, therapies targeting GLI
transcription factors may benefit a wide spectrum of patients with mutations
at different nodal points of the Hh pathway. In this study, we present
evidence that arsenic trioxide (ATO)
suppresses human cancer cell growth and tumor development in mice by
inhibiting GLI1. Mechanistically, ATO directly bound to GLI1 protein,
inhibited its transcriptional activity, and decreased expression of
endogenous GLI target genes. Consistent with this, ATO inhibited the growth
of human cancer cell lines that depended on upregulated GLI expression in
vitro and in vivo in a xenograft model of Ewing sarcoma. Furthermore, ATO
improved survival of a clinically relevant spontaneous mouse model of
medulloblastoma with activated Hh pathway signaling. Our results establish
ATO as a Hh pathway inhibitor acting at the level of GLI1 both in vitro and
in vivo. These results warrant the clinical investigation of ATO for tumors
with activated Hh/GLI signaling, in particular patients who develop
resistance to current therapies targeting the Hh pathway upstream of GLI.

 

Yondelis(R) Receives Five New Approvals Outside the European Economic Area

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http://www.prnewswire.com/news-releases/yondelisr-receives-five-new-approvals-outside-the-european-economic-area-87697802.html

Centocor Ortho Biotech Products, L.P.:
http://www.centocororthobiotech.com/cobi/index.html

Taiho
Pharmaceutical Co., Ltd.:
http://www.taiho.co.jp/english/

PharmaMar
SA:
http://www.pharmamar.com/

Yondelis(R) Receives Five New Approvals Outside the European
Economic Area

Yondelis(R) has been approved for soft
tissue sarcoma (STS) in Israel, Panama and Ukraine. Additionally, the
authorities in Paraguay and Azerbaijan have approved the drug for
platinum-sensitive recurrent ovarian cancer (ROC).

Yondelis(R) is
currently approved in 56 countries.

MADRID, March 15
/PRNewswire/ — Centocor Ortho Biotech Products has informed PharmaMar
SA (Grupo Zeltia, ZEL.MC) that the regulatory authorities in Israel, Panama
and Ukraine have approved Yondelis(R)
for advanced soft tissue sarcoma (STS) in adults. Furthermore, the
authorities in Paraguay and Azerbaijan have approved the drug for
platinum-sensitive recurrent ovarian cancer (ROC). Yondelis is already
approved for STS in Paraguay and Azerbaijan.

The
European Commission approved Yondelis(R) for platinum-sensitive ROC in September 2009. Outside the European Economic
Area (EEA), Yondelis(R) has now been approved for platinum-sensitive ROC
in Azerbaijan and Paraguay; it had already been approved in Kazakhstan and the
Philippines.

In view of
the three new approvals for STS, Yondelis(R) now has authorization for
this indication in 25 countries outside the EEA: Argentina, Azerbaijan,
Bolivia, Chile,
Colombia, Curacao,
Hong Kong, India,
Israel, Kazakhstan,
Macao, Malaysia,
Mexico, Panama,
Paraguay, The
Philippines, Russia, Singapore, South
Korea, Switzerland, Thailand, Ukraine,
Uruguay, Venezuela
and Vietnam. PharmaMar has already
begun collecting royalties from sales in the aforementioned countries.

Clinical
trials are under way to expand the use of Yondelis(R) in sarcoma,
including a trial as first-line treatment in patients with
translocation-associated tumors, in children with Ewing sarcoma,
rhabdomyosarcoma and other forms of STS. Yondelis(R) is also undergoing
trials in solid tumors, such as prostate, breast and lung cancer.

Yondelis(R)
has orphan drug status for soft tissue sarcoma and ovarian cancer in
the European Union, the United States, Switzerland, and for soft tissue sarcoma in South Korea.

According
to the licensing agreement between PharmaMar (Zeltia, S.A. subsidiary)
and Centocor Ortho Biotech Products, L.P., PharmaMar has the rights to
sell Yondelis(R) in Europe (including Eastern Europe), while Centocor Ortho
Biotech Products, L.P. has the rights to sell the drug everywhere else,
except in Japan, where Taiho
Pharmaceutical Co., Ltd. has a licensing agreement for the development
and sale of Yondelis(R).

About
PharmaMar

PharmaMar
is Zeltia Group's biotechnology subsidiary; it is a world leader in
discovering, developing and selling marine-based drugs to treat cancer.
Yondelis(R) is Spain's first
anti-cancer drug. It is currently approved for STS in 25 countries
outside the EEA, and in five of those countries for platinum-sensitive
ROC as well. Yondelis(R) is approved for STS and platinum-sensitive ROC
in all 30 countries of the EEA; in Switzerland
it is approved for STS. Phase II clinical trials with Yondelis(R) are
also under way on prostate, breast, lung and pediatric cancers.
PharmaMar has four other compounds in clinical development: Aplidin(R),
Irvalec(R), Zalypsis(R) and PM01183. PharmaMar also has a rich pipeline
of pre-clinical candidates and a major R&D programs.

Important
note

PharmaMar,
which is headquartered in Madrid (Spain), is a subsidiary of the Zeltia Group
(Spanish stock exchange: ZEL), which has been listed on the Spanish
Stock Exchange since 1963 and on Spain's
Electronic Market since 1998. This document is a press release, not a
prospectus. This document does not constitute or form part of an
offering or invitation to sell or a solicitation to purchase, offer or
subscribe shares of the company. Moreover, no reliance should be placed
upon this document for any investment decision or contract and it does
not constitute a recommendation of any type with regard to the shares of
the company.

SOURCE Group Zeltia

Scientists Are “Reolysin” the Power of Live Biologics to Fight Cancer in Two Recent Studies

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Scientists Are “Reolysin” the Power of Live Biologics to Fight Cancer in Two
Recent Studies

December 15, 2009

A
novel class of cancer therapies called live biologics is offering new hope
for patients affected by hard-to-treat cancers.

For_Immediate_Release:

 

 

(Free-Press-Release.com)
December 15, 2009 —

A novel class of cancer therapies called live biologics is offering new
hope for patients affected by hard-to-treat cancers, according to two
different studies testing the therapies in patients with sarcomas and
head and neck cancers.

Traditional cancer treatments such as chemotherapy and radiotherapy come
with a serious disadvantage: they cannot distinguish cancer cells from
normal cells. Since normal cells can be stunted by chemotherapy and
destroyed by radiation along with abnormal cells, patients may
experience serious health issues during a course of extended treatment.

Calgary-based Oncolytics Biotech Inc. has developed an innovative
approach to cancer therapy that might help patients avoid such serious
side effects. Their strategy relies on one of the human body’s
traditional foes: viruses. Specifically, Oncolytics is testing a live
cancer biologic called REOLYSIN®, which is derived from the human
reovirus.

“One of the distinguishing characteristics of the reovirus is its
tendency to replicate within certain cancer cells, namely, those that
possess a feature known as an activated Ras pathway,” said Brad
Thompson, Chairman, President and Chief Executive Officer of Oncolytics
Biotech. “Approximately two-thirds of all cancers involve cells that are
Ras-activated. REOLYSIN® appears to kill off these cancer cells by
rupturing their walls, creating a chain reaction of ‘explosions’ that
rip through tumors.”

A team lead by Dr. Monica Mita at the Institute of Drug Development (IDD),
the Cancer Therapy and Research Center at the University of Texas Health
Science Center (UTHSC) in San Antonio, Texas, recently provided updated
results from a Phase II study using REOLYSIN® in patients with sarcomas
metastatic to the lung.

The investigators reported that the treatment has been well-tolerated to
date, and that 19 of 44 patients experienced stable disease ranging from
2 to 20 months, resulting in a total clinical benefit rate (complete
response + partial response + stable disease) of 43%. The response
objective for the study was three or more patients having prolonged
stabilization of disease (>6 months) or better, for the agent to be
considered. The trial exceeded its established objective with six
patients experiencing stable disease for more than six months. Two
patients have experienced stable disease for more than 19 months. One of
these patients has synovial cell sarcoma that relapsed following
surgery, while the other has Ewing’s Sarcoma and had previously
progressed following multiple treatments.

“We were very happy to participate in the study,” said Dr. Mita.
“REOLYSIN® is a promising option for patients with sarcoma, as shown by
the results of this study. As a single agent, the virus had a clinical
benefit rate of 43% and it was very well-tolerated. We are contemplating
further studies combining REOLYSIN® with chemotherapy in order to
integrate the virus in the panoply of agents used for sarcoma
treatment.”

New Progress on Head and Neck Cancer

While the new viral treatment will not completely dispose of the need
for chemotherapy, its ability to weaken and shrink tumors might restrict
the amount of chemo that is required or help agents such as paclitaxel
and carboplatin do their jobs.

The company recently provided updated results from a Phase I/II UK trial
(REO 011) of REOLYSIN® combined with paclitaxel/carboplatin for patients
with advanced cancers in a poster presentation at the 2009
AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics conference in
Boston. The investigators reported that REOLYSIN® was well-tolerated
when administered intravenously in combination with paclitaxel and
carboplatin. Of 19 evaluable patients with head and neck cancer, mostly
SCCHN refractory to prior platinum-based chemotherapy for
recurrent/metastatic disease, eight experienced partial responses and
six had stable disease. The total clinical benefit rate (complete
response + partial response + stable disease) observed in head and neck
cancer patients in the trial was 74%. Of four patients with malignant
melanoma on the trial, one experienced a partial response and one had
stable disease.

“A 42% response rate and a 74% clinical benefit rate in a platinum
refractory patient population that typically has a poor prognosis and
limited therapeutic options is very encouraging,” said Dr. Thompson.
“These results further validate our decision to advance REOLYSIN® in
combination with paclitaxel and carboplatin into a Phase III trial in
this patient population.”

For more information, log on to

www.oncolyticsbiotech.com

Figitumumab has anti-tumor activity in Ewing's sarcoma, a cancer which affects mainly teenage boys

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Public release date: 23-Dec-2009

Contact: Dr. Johann S. de Bono
jane.bunce@icr.ac.uk
44-207-153-5106
Lancet

 

Figitumumab has anti-tumor activity in Ewing's sarcoma, a cancer which
affects mainly teenage boys

A preliminary study of the anticancer drug figitumumab has found that it has
antitumour activity in Ewing's sarcoma—a cancer which affects mainly teenage
boys. The results have led to the drug's progression to a Phase 2 trial in
patients with Ewing's sarcoma, which has recently finished recruiting. These are
the conclusions of an Article published Online First in the Lancet Oncology.
The study is by Dr Johann S de Bono, The Institute for Cancer Research (ICR),
Sutton, UK, and The Royal Marsden NHS Foundation Trust, Sutton, UK, and
colleagues.

Ewing's sarcoma is a rare disease in which cancer cells are found in the bone
or soft tissue, most commonly the pelvis, femur, humerus, and ribs. It occurs
most commonly it male teenagers with a male to female ratio of 1.6 to 1.

Data from preclinical studies have suggested that Ewing's sarcoma, and some
other sarcoma subtypes, are dependent on the insulin-like growth factor
signalling pathway. Figitumumab is a drug which targets the insulin-like
growth-factor-1 receptor (IGF-1R). This phase I study was carried out to assess
the effects of figitumumab in these sarcoma subtypes.

Between January, 2006, and August, 2008, patients with refractory, advanced
sarcomas received figitumumab (20 mg/kg) in two groups within a phase 1 trial.
The first cohort (15 patients) included patients with multiple sarcoma subtypes,
age 18 years or older, and the second cohort (14 patients) consisted of patients
with refractory Ewing's sarcoma, age nine years or older. The primary endpoint
was to assess the safety and tolerability of figitumumab.

Of the 29 patients that were enrolled, 16 had Ewing's sarcoma, and the 29
received a total of 177 cycles of treatment (median 2, mean 6, range 1

Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing's sarcoma: a phase 1 expansion cohort study

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http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70354-7/abstract

The Lancet Oncology, Volume 11, Issue 2, Pages 129 –
135, February 2010

 
doi:10.1016/S1470-2045(09)70354-7

Published Online: 24 December 2009

Safety, pharmacokinetics, and

preliminary activity of the anti-IGF-1R

antibody figitumumab
(CP-751,871) in

patients with sarcoma and Ewing's

sarcoma: a
phase 1 expansion cohort

study

David Olmos MD a, Sophie
Postel-Vinay MD a, L Rhoda Molife MD a, Scott H Okuno MD
b, Scott M Schuetze MD c, M Luisa Paccagnella PhD d,
Gretchen N Batzel MD b, Donghua Yin PhD d, Prof Kathryn
Pritchard-Jones MD a, Prof Ian Judson MD a, Francis P
Worden MD c, Antonio Gualberto MD d, Michelle Scurr MD
a, Dr Johann S
de Bono MD a , Paul Haluska MD b

 

Summary

Background

Figitumumab is a fully human IgG2 monoclonal
antibody targeting the insulin-like
growth-factor-1 receptor (IGF-1R). Preclinical
data suggest a dependence on insulin-like
growth-factor signalling for sarcoma subtypes,
including Ewing's sarcoma, and early reports
show antitumour activity of IGF-1R-targeting
drugs in these diseases.

Methods

Between January, 2006, and August, 2008,
patients with refractory, advanced sarcomas
received figitumumab (20 mg/kg) in two
single-stage expansion cohorts within a solid-tumour
phase 1 trial. The first cohort (n=15) included
patients with multiple sarcoma subtypes, age 18
years or older, and the second cohort (n=14)
consisted of patients with refractory Ewing's
sarcoma, age 9 years or older. The primary
endpoint was to assess the safety and
tolerability of figitumumab. Secondary endpoints
included pharmacokinetic profiling and
preliminary antitumour activity (best response
by Response Evaluation Criteria in Solid Tumours
[RECIST]) in evaluable patients who received at
least one dose of medication. This study is
registered with

ClinicalTrials.gov, number

NCT00474760.

Findings

29 patients, 16 of whom had Ewing's sarcoma,
were enrolled and received a total of 177 cycles
of treatment (median 2, mean 6·1, range 1—24).
Grade 3 deep venous thrombosis, grade 3 back
pain, and grade 3 vomiting were each noted once
in individual patients; one patient had grade 3
increases in aspartate aminotransferase and
gammaglutamyltransferase concentrations. This
patient also had grade 4 increases in alanine
aminotransferase concentrations. The only other
grade 4 adverse event was raised concentrations
of uric acid, noted in one patient.
Pharmacokinetics were comparable between
patients with sarcoma and those with other solid
tumours. 28 patients were assessed for response;
two patients, both with Ewing's sarcoma, had
objective responses (one complete response and
one partial response) and eight patients had
disease stabilisation (six with Ewing's sarcoma,
one with synovial sarcoma, and one with
fibrosarcoma) lasting 4 months or longer.

Interpretation

Figitumumab is well tolerated and has antitumour
activity in Ewing's sarcoma, warranting further
investigation in this disease.

Funding

Pfizer Global Research and Development.

GUMC Discovery Highlights New Direction For Drug Discovery

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http://explore.georgetown.edu/news/?ID=42483&PageTemplateID=295

FOR
IMMEDIATE RELEASE: July 5, 2009

CONTACT:

Karen Mallet

215-514-9751

mallet.karen@gmail.com

GUMC Discovery Highlights New Direction For Drug Discovery

Researchers
did what others thought was not possible by finding a small molecule to
stop “slippery” protein from binding to another, causing Ewing’s Sarcoma

Washington, DC – In a discovery that rebuffs conventional scientific thinking, researchers at the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center (GUMC)
have discovered a novel way to block the activity of the fusion protein
responsible for Ewing’s sarcoma, a rare cancer found in children and
young adults.

In the paper published online July 5 in Nature
Medicine, they report discovering and successfully testing a small
molecule that keeps the fusion protein from sticking to another protein
that is critical for tumor formation. The researchers say this
interaction is unique – and is especially surprising since the Ewing’s
sarcoma fusion protein is extremely flexible, which allows it to change
shape constantly.

“Most targeted small molecule cancer drugs
inhibit the intrinsic activity of a single protein, but our agent stops
two proteins from interacting. This has never been shown before with a
cancer-causing fusion protein and represents a potentially novel
medical therapy in the future,” says the study’s lead investigator, Jeffrey Toretsky, MD, a pediatric oncology physician and researcher at GUMC’s Lombardi Comprehensive Cancer Center.

The
study could provide a model upon which to design treatment for other
disorders caused by the interaction between two proteins, and may be
especially useful in cancers caused by translocations of genes, such as
sarcomas and leukemias, the researchers say. Agents in use now that
work against fusion proteins inhibit a single protein to stop intrinsic
enzymatic activity; one example is Gleevec, used for chronic
myelogenous leukemia (CML). The Ewing’s sarcoma fusion protein, known
as EWS-FLI1, lacks enzymatic activity, “and this difference is why our
work is significant,” Toretsky says.

In the United States,
about 500 patients annually are diagnosed with the cancer, and they are
treated with a combination of five different chemotherapy drugs.
Between 60-70 percent of patients survive over time, but with side
effects from the treatment. Few additional treatment options are
available for patients whose cancer progresses, Toretsky says.

Ewing’s
sarcoma is caused by the exchange of DNA between two chromosomes, a
process known as a translocation. The new EWS-FLI1 gene is created when
the EWS gene on chromosome 22 fuses to the FLI1 gene on chromosome 11,
and its product is the fusion protein responsible for cancer formation.
It is a so-called disordered protein, which means it does not have a
rigid structure. A number of cancer-causing proteins are disordered.

In
their 15-year search for a new treatment for Ewing’s sarcoma, Toretsky
and his colleagues were the first to make a recombinant EWS-FLI1 fusion
protein. They used it to discover that the fusion protein stuck to
another protein, RNA helicase A (RHA), a molecule that forms protein
complexes in order to control gene transcription. “We believe that when
RHA binds to EWS-FLI1, the combination becomes more powerful at turning
genes on and off,” says the study’s first author, Hayriye Verda
Erkizan, PhD, a postdoctoral researcher in Toretsky’s lab.

Then,
from a library of 3,000 small molecules loaned to Georgetown from the
National Cancer Institute, the researchers searched for a small
molecule that would bind on to EWS-FLI1. They found one, and further
discovered the same molecule, NSC635437, could stop EWS-FLI1’s fusion
protein from sticking to RHA.

This was a wonderful discovery,
Erkizan says, because the notion long accepted among scientists is that
it is not possible to block protein-protein interactions given that the
surface of many of these proteins are slippery – much too flexible for
a drug to bind to.
They tested the agent in laboratory cell
culture, and with the help of GUMC’s Drug Discovery Program, the
researchers designed a stronger derivative compound they called
YK-4-279. In this study, they tested YK-4-279 in two different animal
models of Ewing’s sarcoma and found that the agent significantly
inhibited the growth of tumors. There was an 80% reduction in the
growth of treated tumors compared to untreated tumors.

Toretsky
says that while the agent needs to be “optimized,” these results serve
as a proof of principle that inhibiting protein-protein interaction can
work as a novel therapeutic that will target only cancer cells.

“We may be able to use this strategy to attack proteins we thought to be impervious to manipulation,” he says.

The
study was funded by grants from the National Institutes of Health,
Children’s Cancer Foundation of Baltimore, MD, Go4theGoal Foundation,
Dani’s Foundation of Denver, the Liddy Shriver Sarcoma Initiative, the
Amschwand Sarcoma Cancer Foundation, the Burroughs-Wellcome Clinical
Scientist Award in Translational Research, and the GUMC Drug Discovery
Program.

Toretsky and co-authors Milton L. Brown, Aykut Üren
and Yali Kong are inventors on a patent application that has been filed
by Georgetown University related to the technology described in this
paper. The other authors report no related financial interests.

About Georgetown University Medical Center
Georgetown
University Medical Center is an internationally recognized academic
medical center with a three-part mission of research, teaching and
patient care (through Georgetown’s affiliation with MedStar Health).
GUMC’s mission is carried out with a strong emphasis on public service
and a dedication to the Catholic, Jesuit principle of cura personalis
— or “care of the whole person.” The Medical Center includes the
School of Medicine and the School of Nursing and Health Studies, both
nationally ranked, the world-renowned Lombardi Comprehensive Cancer
Center and the Biomedical Graduate Research Organization (BGRO), home
to 60 percent of the university’s sponsored research funding.

###

PharmaMar announced Yondelis has gained approval for price and reimbursement in Italy

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PharmaMar announced Yondelis® has gained approval for price and reimbursement in Italy

Madrid, 26th January 2009:
PharmaMar announced today that Yondelis® has gained approval for price
and reimbursement in Italy. With this approval, PharmaMar has
successfully finalised negotiations for the price and reimbursement of
Yondelis® with the Italian authorities. Yondelis® will have same price
it has in the rest of European countries.
 
Once
price and reimbursement approval for Yondelis® has been gained, the
next steps towards the commercialization of the drug in Italy will be
taken soon. This means Yondelis ® may be commercially available to
patients in Italy in the nest weeks.
 
YONDELIS®
is currently being marketed in the European Union for the treatment of
Soft tissue Sarcoma in adults after the failure of standard therapy.
PharmaMar has started a phase III multicenter study of Yondelis® as
first-line therapy in patients with tumor traslocation, Ewing's
sarcoma, or not rhabdomyosarcomatose soft tissue sarcomas and other
types of STS. Yondelis® is being studied in solid tumors with high
incidence and prevalence in the population, such as prostate, breast
and lung cancer.
 
Yondelis® has been designated
orphan drug for the treatment of soft tissue sarcomas and ovarian
cancer in the European Union, United States and Switzerland, and for
soft tissue sarcomas in Korea.
 
According to the
agreement between PharmaMar – a subsidiary of Zeltia, S.A- and Ortho
Biotech Products, L.P. –a subsidiary of Johnson & Johnson- , under
which Yondelis® is developed, PharmaMar will market Yondelis® in Europe
(including Eastern Europe) and Japan, and Ortho Biotech Products, L.P.
will market Yondelis® in the rest of the world. Both companies filed a
registration dossier to the EMEA and the FDA for Yondelis for the
treatment of refractory ovarian cancer at the end of 2008. At the end
of 2008 both companies submitted a Registration Dossier of Yondelis® in
relapsed ovarian cancer (ROC) to the EMEA and the FDA. A decision on
the approval for this indication is expected to take place during 2009.
 
Soft tissue sarcomas
STS
are a diverse group of more than 50 types of tumours that appear in
fatty tissue, muscle, nerve tissue, tendons and blood and lymph
vessels. Nearly half of them affect the extremities.
According to
data from GEIS (Spanish research group in sarcomas) soft tissue
sarcomas (STS) have an incidence of around 3/100,000 new cases per
year, which represents 2% of the overall mortality from cancer. The
highest incidence is situated in patients around 50 years of age.
The
five-year survival rate of patients with STS is around 90% when
detected early (stage I), that is, when the tumour is small and with no
metastasis. However, the five-year survival rate in patients with
metastatic disease is 10-20% . The estimated life expectancy in
metastatic patients is 8-12 months after receiving the first line of
cytotoxic therapy.
 
PharmaMar
PharmaMar
is the world-leading biopharmaceutical company of the Zeltia Group,
committed to advancing the treatment of cancer through the discovery
and development of new marine-derived medicines. Yondelis® is the first
Spanish antitumoral compound, currently marketed in the European
Union
for the treatment of soft tissue sarcomas in adults after the failure
of standard therapy. Last December 4th, 2008 PharmaMar submitted a
Registration Dossier of Yondelis® in relapsed ovarian cancer (ROC) to
the EMEA. A decision on the approval for this indication is expected to
take place by
mid-2009. PharmaMar has four novel compounds in
clinical development: Yondelis® is also in Phase II studies in
prostate, breast and pediatric cancers. Aplidin ®, Zalypsis ®, and
Irvalec ® are new marine-derived agents in clinical development.
PharmaMar also has an extensive portfolio of products in preclinical
research and a sound R&D program.
 
Important note
PharmaMar,
based in Madrid, Spain, is a company of the Zeltia Group (Spanish Stock
Exchange, ZEL) that has been listed on the Spanish Stock Exchange since
1963. This document is a press release, not a brochure. This document
does not constitute nor is it part of any offer or invitation to sell
or issue any application of purchase, offer, or shares subscription of
the Group. Likewise, this document nor its
distribution is part or
can be of base for any contract or investment decision and does not
constitute any kind of recommendation in relation with the shares of
the Company.
 
For further information:
Media Relations (Ph: +34 91 846 60 00)
Fernando Mugarza
Carlos Martínez de la Serna
Carolina Lanzas Otazu
 
Capital Markets ( Ph: +34 91 444 45 00)
Alfonso Hurtado de Mendoza
Florencia Radizza
 
This press release is also available in the News Area of www.pharmamar.com

PharmaMar presents new data of Zalypsis® and Irvalec® in pediatric, solid tumours and lymphoma at the 20th AACR-NCI-EORTC Symposium

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NEWS RELEASE



http://www.pharmamar.com/en/press/news_release.cfm?newsReleaseID=194&year=2008

PharmaMar presents new data of Zalypsis® and Irvalec® in pediatric,
solid tumours and lymphoma at the 20th AACR-NCI-EORTC Symposium

23 October 2008
 

– Irvalec® and Zalypsis® are two compounds of marine origin, with a novel
mechanism of action, in phase I clinical development for the treatment of
various tumors
– A clinical study of 37 patients with solid tumors or lymphoma shows
Zalypsis has a good safety profile and is highly active. These findings
enable the continuation of Zalypsis clinical development
– Irvalec® shows significant antiproliferative activity in trials against
different tumor cell lines, at doses equivalent to the clinical
administration and higher to those obtained with five other antitumoral
compounds of ErbB pathway
– Two new preclinical studies made in collaboration with the European
Consortium for Innovative Therapies for Children with Cancer (ITCC) show
significant activity of the two compounds in pediatric tumors
– PharmaMar, a company of the Zeltia Group, is presenting data on four
trials during the 20th EORTC-NCI-AACR symposium, held in Geneva from 21- 24
October

Geneva, 23 October, 2008: PharmaMar, a biotechnology company of Zeltia
Group, has presented new data on two antitumoral compounds of marine origin,
Zalypsis® and Irvalec®, in Phase I trials in clinical development and in
vitro studies and with animal models.

Zalypsis® is a novel chemical entity related to the marine natural compounds
Jorumycin and the family of Renieramycins, obtained from molluscs and
sponges, respectively. Irvalec®, a new synthetic depsipeptide derived from
PharmaMar Development Program of marine origin compounds, is a new drug with
antiproliferative activity against a wide range of tumors, including breast,
colon, pancreas, lung and prostate.

PharmaMar has presented the results of 4 studies at the 20th annual
symposium of the European Organization for Research and Treatment of Cancer
(EORTC), the U.S. National Cancer Institute (NCI) and the American
Association for Cancer Research (AACR), taking place in Geneva (Switzerland)
from 21 to October 24.

In the first study, the safety of Zalypsis ® in 37 patients with solid
tumors or lymphoma was evaluated. The trial shows a good safety profile of
the drug, which enables the

continuation of its clinical development. The study was made in
collaboration with the Institut Gustave Roussy (Villejuif, France) and the
Northern Centre for Cancer Treatment (Newcastle, United Kingdom).

The second study presented at the Geneva meeting evaluated the activity of
Irvalec® in of colon cancer, breast, ovarian, lung, prostate, head and neck
and pancreas cell lines. Cytotoxicity data obtained with Irvalec® were
compared with five other compounds that inhibit the Erb-B/HER Pathway.

According to the results, Irvalec® shows a significant antiproliferative
activity at doses that may be achieved in the clinic, being a more potent
inhibitor of cell proliferation than other ErB inhibitors used in the
trials, and showing a differential activity profile. The study was made in
collaboration with the Beaujon University Hospital (Clichy, France).

In two other new studies presented at the meeting in Geneva, PharmaMar
evaluated the therapeutic potential of Irvalec® and Zalypsis® in pediatric
tumors.

The preclinical evaluation of the first compound for the treatment of
pediatric cancer was made against six types of pediatric tumors cell lines
that represent 50% of treatment failures in this population: neuroblastoma,
Ewing's sarcoma, rhabdomyosarcoma, acute lymphoblastic leukemia,
medulloblastoma and osteosarcoma. Osteosarcoma and rhabdomyosarcoma cell
lines were the most sensitive to the drug.

The same methodology was followed for the evaluation of Zalypsis®. The most
significant results in in vitro tests were obtained in neuroblastoma and
rhabdomyosarcoma cell lines. The evaluation of the compound in animal models
also showed significant results, especially in the activity in
rhabdomyosarcoma.

The trials were conducted by the R&D Department of PharmaMar in partnership
with the Emma Children's Hospital (Amsterdam, Netherlands), the University
Children's Hospital (Munster, Germany) and the Institut Gustave Roussy
(Villejuif, France), and members of the Innovative Therapies for Children
with Cancer (ITCC) which brings together 35 centres specializing in
pediatric oncology of six European countries.

The aim of the studies carried out in collaboration with ITCC is to
facilitate the identification of new compounds with significant potential in
the treatment of pediatric tumors.

Within PharmaMar Cancer Research Program and as part of the company’s
commitment with cancer patients, this biotech company of the Zeltia Group is
also evaluating the therapeutic potential of its marine origin compounds in
pediatric tumors.

About Zalypsis® (PM00104)
Zalypsis® (PM00104/50) is a new marine derived compound in Phase II
clinical trials for the treatment of solid tumours. Zalypsis® is a novel
chemical entity related to the marine natural compounds Jorumycin and the
family of Renieramycins, obtained from molluscs and sponges, respectively.
Zalypsis binds to DNA and is cytotoxic; however, it does not activate the
“DNA damage checkpoint” response. Thus, Zalypsis has cytotoxic effects
dependent on DNA binding that are not associated with DNA damage. In
pre-clinical trials, Zalypsis demonstrated strong in vitro and in vivo
antitumoural activity in a wide variety of solid and haematological tumour
cell lines and human transplantable breast, gastric, prostate and renal
xenografted tumours. Zalypsis also demonstrated a manageable and reversible
preclinical toxicology profile.

About Irvalec® (PM02734)
Irvalec® is a new depsipeptide from PharmaMar’s internal research
program for derivatives of the marine natural compounds. PM02734 is
manufactured synthetically by PharmaMar. Preliminary in vitro in-house
studies identified PM02734 as a new antiproliferative drug demonstrating
activity against a broad spectrum of tumor types: breast, colon, pancreas,
lung and prostate, among others. PM02734 has been selected for clinical
development based on its in vivo activity in xenografted human tumors, as
well as an acceptable non-clinical toxicology profile. PM02734 is in Phase I
clinical trials in patients with advanced malignant solid tumors.

PharmaMar
PharmaMar is the world-leading biopharmaceutical company of the Zeltia
Group, and is committed to advancing the treatment of cancer through the
discovery and development of new marine-derived medicines. PharmaMar has
four novel compounds in clinical development. Yondelis® has received
Authorization for Commercialization from the European Commission for
treating advanced soft tissue sarcoma. Yondelis® is currently being marketed
in the European Union for the treatment of soft tissue sarcomas in adults
after failure of standard therapy. Aplidin®, Zalypsis®, and Irvalec® are
other marine-derived new agents in clinical development by PharmaMar, which
also has a rich pipeline of preclinical candidates, and a strong R&D
program.

For further information:

Media Relations (Ph: +34 91 846 60 00)
Fernando Mugarza
Carlos Martínez de la Serna
Carolina Lanzas Otazu

Capital Markets (Ph: +34 91 444 45 00)
Alfonso Hurtado de Mendoza
Florencia Radizza

This press release is also available in the News area at www.pharmamar.com


More news releases

Neotropix® Announces Presentation of Relevant Preclinical Results of NTX-010 in Pediatric Oncology Models

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http://www.neotropix.com/news_20081022.htm
 

Neotropix® Announces
Presentation of Relevant Preclinical Results of NTX-010 in Pediatric Oncology
Models


Malvern, PA, October 22, 2008 – Neotropix®,
Inc., a clinical-stage development company focused on neuroendocrine cancer
treatments, announced today exciting data from an extensive pediatric
preclinical study performed by the National Cancer Institute (NCI) funded
Pediatric Preclinical Testing Program on the use of NTX-010 (Seneca Valley
Virus-001), a tumor-selective naturally-occurring oncolytic virus.  The results
support the initiation of clinical development of Neotropix’s lead candidate,
NTX-010 for the treatment of pediatric cancers.  NTX-010 has been developed as a
cancer therapeutic to treat some of the most aggressive cancers known which
occur in adults including small cell lung cancer, large cell non-small cell lung
cancer, as well as other adult cancers such as carcinoid and various
neuroendocrine cancers.      
 

The detailed study results are being presented at the 20th
Annual Molecular Targets and Cancer Therapeutics International Meeting
in Geneva, Switzerland from October 21-24, 2008.  The meeting is hosted jointly
by the European Organization for Research and Treatment of Cancer (EORTC), the
National Cancer Institute (NCI), and the American Association for Cancer
Research (AACR).
 

The Pediatric Preclinical Testing Program (PPTP) presentation
described encouraging results from an extensive evaluation of NTX-010 in over 30
different tumor models representing the most common types of childhood solid
tumors.  Extensive analysis has previously determined that these carefully
selected models, many derived directly from patients’ tumors, are predictive of
clinical activity and an important tool for screening promising new drug
candidates for their relevance for specific childhood cancers.  The PPTP results
indicated that NTX-010 was active against a wide range of pediatric solid
cancers, including neuroblastoma, rhabdomyosarcoma, Wilms tumors, rhabdoid,
Ewing sarcoma and glioblastoma.  Complete responses were observed following a
single intravenous treatment in the majority of neuroblastoma models and in all
alveolar rhabdomyosarcoma tumor models, demonstrating both activity and potency.


Paul Hallenbeck, Ph.D., President and Chief Scientific Officer
of Neotropix®, Inc., commented, “We are very encouraged by the results of this
extensive analysis of NTX-010 in pediatric oncology models, particularly because
these in vivo cancer models that the NCI has developed can
prospectively identify novel agents subsequently shown to have clinical activity
against specific cancers of children and adolescents.”

Dr. Hallenbeck continued, “We are excited that the
NCI-supported Children’s Oncology Group Phase I Consortium has expressed the
interest to lead an effort to test NTX-010 in pediatric patients with cancer in
the near future.”
 
Neotropix® has been working closely with many collaborators around the world,
including the NCI to create a treatment paradigm shift for hard to treat
cancers.  The Company has developed an innovative approach to harness the power
of natural products screening using viruses to kill or slow down the spread of
cancer.  The result has been that many viruses have been identified that may
provide simple, safe and effective ways to treat patients who would otherwise
fail conventional treatments using traditional small molecule and antibody
approaches.


About NTX-010 and the Current Clinical Trial


NTX-010 is a natural occurring oncolytic virus, which is highly selective for
certain tumor cell types expressing a biomarker that indicates the cancer has
neuroendocrine properties such as synaptophysin, chromogranin A, or CD56.  At
least one of them is required to be positive before treatment.  Unlike many
previous oncolytic virus product candidates developed by others, NTX-010 is a
stable, naturally occurring virus, is systemically deliverable, and has not been
observed to be pathogenic to humans, and therefore, has not had to be
genetically modified.


NTX-010 is systemically delivered in a single one-hour
infusion on an outpatient basis at each of the treatment centers, which
simplifies the treatment process for patients.  The product is anticipated to
have enhanced efficacy and less toxicity than currently approved therapies for
permissive cancers.

The clinical trial is being conducted at multiple institutions
around the country, including John Hopkins (MD), Mary Crowley (TX), Lahey Clinic
(MA) and many U.S. Oncology Cooperative Group treatment sites (FL, IN, NY, OH,
SC, TX, VA, and WA).  In addition, other treatment centers are joining the trial
in the New England area of the U.S.


The current Phase I / II clinical trial is enrolling adults
(18 and over) that meet the criteria for the following cancers: carcinoid
cancers (all types), large cell lung cancer-neuroendocrine, alveolar  rhabdomyosarcoma,
neuroblastoma, glioblastoma, Ewing’s family of tumors, Wilms tumors,
retinoblastoma, rhabdoid, and medulloblastoma.  For more about the clinical
trials:

www.clinicialtrials.gov


Also of note, CEO Peter Lanciano of Neotropix®
will be available for one-on-one meetings with potential investors at
the 7th Annual BIO Investor Forum that is taking place from October 29-31, 2008,
in San Francisco, CA.  At the conference, Mr. Lanciano will present a corporate
overview on the Company. For more information, please visit:

www.investorforum.bio.org


About Neotropix®


Neotropix® Inc., is focused on the development of anti-cancer
products that have a high degree of selectivity for cancer cells resulting in an
excellent safety and therapeutic efficacy profile. Neotropix® develops and
commercializes systemically deliverable oncolytic viruses for the treatment of
solid tumors.  Capitalizing on its unique sources of naturally occurring viruses
that selectively target tumors discovered using the company’s proprietary
technology platform Viruscreen™, the Company has the knowledge and skills to
translate these discoveries into commercial products.  Neotropix® is committed
to making a difference in the lives of cancer patients.

Neotropix® commenced operations in 2005 in Malvern,
Pennsylvania.  Neotropix ® is funded by venture-capital investors including
Aurora Funds, Quaker BioVentures and VIMAC Ventures.  For more information,
please visit
http://www.neotropix.com
 

About the Pediatric Preclinical Testing Program


The NCI-supported Pediatric Preclinical Testing Program (PPTP) is a
comprehensive program to systematically evaluate new agents against childhood
solid tumor and leukemia preclinical models. The PPTP is supported through an
NCI research contract to St. Jude Children’s Research Hospital (SJCRH) with Dr.
Peter Houghton as the Principal Investigator.  Testing occurs both at SJCRH and
also at subcontract sites that have expertise in specific childhood cancers,
including: Children’s Hospital of Philadelphia (John Maris), Albert Einstein
Medical Center (E. Anders Kolb & Richard Gorlick), Duke University (Stephen Keir),
Texas Tech University Health Sciences Center (Patrick Reynolds), and Children’s
Cancer Institute Australia (Richard Lock).  Detailed information about the PPTP
and its testing procedures is available at
http://www.pptp.stjude.org.