17
AREVA Med 212 Pb for Targeted Alpha Therapy
AREVA Med
212Pb for Targeted Alpha Therapy
Based on an R&D program started in 2005, AREVA Med has been able to develop new processes for producing high-purity lead-212 (212Pb), a rare radioactive isotope. 212Pb is currently at the heart of promising research projects in nuclear medicine to develop new treatments against cancer. The innovative approach, known as targeted alpha therapy (TAT), recognizes and destroys cancer cells without damaging nearby healthy cells.
AREVA Med is an AREVA Subsidiary Created in 2009 to Develop Innovative Therapies to Fight Cancer
What is AREVA Med?A Brief Introduction to our Activities
Targeted alpha therapy shows great potential in the fight against many types of cancer. In this innovative domain, we see AREVA Med as a key player in the development of new treatments to combat the disease.”
Patrick BourdetPresident and CEO of AREVA Med
• First clinical trial with lead-212 (212Pb) launched in 2012; patient enrollment complete in 2014
• First manufacturing facility to produce high-purity 212Pb operational since 2013
• Strategic acquisition of Macrocyclics, world leader in chelating agent production
• Strategic collaborations in cancer research:
- Roche
- National Cancer Institute (NCI)
- University of Alabama at Birmingham (UAB) Cancer Center
- University of Cincinnati (UC)
- French National Institute of Health and Medical Research (Inserm)
- University of California, San Diego (UCSD) Moores Cancer Center
Recognition and awards:
• The Clinton Global Initiative (CGI)
• The Marie Curie Medal from the French Society of Nuclear Energy (SFEN)
The data and information contained herein are provided solely for illustration and informational purposes and create no legal obligations by AREVA. None of the information or data is intended by AREVA to be a representation or a warranty of any kind, expressed or implied, and AREVA assumes no liability for the use of or reliance on any information or data disclosed in this document. © 2015 AREVA Med. All rights reserved.
follow @AREVAmed on twitter
For more information, contactAlison TiseTel: (301) [email protected]
Major Achievements of AREVA Med
Since its creation in 2009, AREVA Med has reached several important milestones, contributing to significant breakthroughs in nuclear medicine.
Nuclear MedicineNuclear medicine is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of some of the most aggressive types of cancer. The combination of nuclear technology and nuclear medicine provide an innovative approach, known as targeted alpha therapy.
Targeted Alpha Therapy with 212PbTargeted alpha therapy (TAT) works by combining the targeting capabilities of cancer cell-specific biological carriers (e.g., antibodies) with the short-range destroying capabilities of the radioactive isotope 212Pb. This approach targets and destroys cancer cells without damaging nearby healthy cells.
AREVA Med’s Innovative Approach in the Fight Against Cancer
AREVA Med and Nuclear MedicineTargeted Alpha Therapy (TAT) with 212Pb
How 212Pb Works An example of TAT: Radioimmunotherapy using 212Pb compounded with an antibody to attack and destroy cancer cells
Cancer cells express a specific
antigen
The chelatingagent links the antibody to the 212Pb
The antibody recognizes and
targets the cancer cell’s antigen
212Pb destroys the cancer cell
Cancer Cells Antibody 212Pb Radioisotope Radiolabeled antibody(212Pb Radioisotope, chelating agent, and antibody)
AntigensHealthy Cells
Antigen: A substance which provokes an immune response.Antibody: Recognizes and targets cell-specific antigens on cancer cells.Chelating Agent: A “molecular cage” used to attach isotopes to monoclonal antibodies.
A high potential for TAT was established long ago, but scarcity of isotopes was an obstacle to progress. Early preclinical studies and clinical trials from the 1980s with targeted alpha therapy showed potential for treating different types of cancer that do not respond to other conventional methods despite the significant efforts made by the global scientific and medical communities.
Though the effectiveness of 212Pb had been demonstrated, the development of TAT treatments using this isotope encountered setbacks early on due to its scarcity and the technical difficulties of producing high-purity 212Pb.
Technical and scientific breakthroughs make high-purity 212Pb more widely available to explore further TAT potential. AREVA Med’s research and development work has made it possible to produce high-purity 212Pb to develop new cancer treatments and increase production capacity. The AREVA Med team, in collaboration with leading scientists, chemists, and radiochemists, has developed innovative methods for radiolabeling a monoclonal antibody with a radioactive isotope. As a result, targeted alpha therapy using 212Pb has recently come back to the forefront of medical research.
The data and information contained herein are provided solely for illustration and informational purposes and create no legal obligations by AREVA. None of the information or data is intended by AREVA to be a representation or a warranty of any kind, expressed or implied, and AREVA assumes no liability for the use of or reliance on any information or data disclosed in this document. © 2015 AREVA Med. All rights reserved.
follow @AREVAmed on twitter
For more information, contactAlison TiseTel: (301) [email protected]
AREVA Med Creates New Research Opportunities for
Targeted Alpha Therapy (TAT)
Our Ambition: Develop Powerful Therapies to Treat Cancer
AREVA Med’s StrategyThree Strategic Actions to Support One Ambition
Laboratoire Maurice Tubiana (LMT)
Produce High-Purity 212Pb to Meet Clinical Development NeedsConfronted with the scarcity of radioisotopes suitable for targeted alpha therapy, AREVA Med has developed a process for extracting and purifying 212Pb from an abundant supply of thorium derived from AREVA’s former mining activities. Thanks to several patented innovations implemented in the cutting-edge Laboratoire Maurice Tubiana, AREVA Med can produce high-purity 212Pb to conduct preclinical studies and clinical trials to develop new cancer treatments.
Three Strategic Actions:
The data and information contained herein are provided solely for illustration and informational purposes and create no legal obligations by AREVA. None of the information or data is intended by AREVA to be a representation or a warranty of any kind, expressed or implied, and AREVA assumes no liability for the use of or reliance on any information or data disclosed in this document. © 2015 AREVA Med. All rights reserved.
follow @AREVAmed on twitter
For more information, contactAlison TiseTel: (301) [email protected]
Extend the Reach of Innovative 212Pb Treatments Through Clinical DevelopmentBefore new drugs become available to doctors and patients, researchers must demonstrate the drug’s therapeutic safety and efficacy. AREVA Med and its scientific research partners are making great strides toward this end through extensive research and clinical trials.
In 2012, AREVA Med launched the first Phase 1 clinical trial with 212Pb in combination with Trastuzumab (preliminary results of this study were published in October 2014 in the Journal of Nuclear Medicine).
At the same time, AREVA Med is continuing preclinical studies that may target different pathologies using different antibodies and is looking forward to establish new partnerships to accelerate this research. Interested in partnering with AREVA Med?Please contact [email protected].
Provide 212Pb to the Scientific CommunityThanks to patented innovations and increased 212Pb production capacity achieved in the Laboratoire Maurice Tubiana, AREVA Med is now able to sell its Radium-224/Lead-212 generators to facilitate the research of other experts within the academic, scientific, biomedical, and pharmaceutical industries.
Interested in purchasing AREVA Med’s 212Pb generators?Please contact [email protected].
In 2012, AREVA Med launched the first Phase 1 clinical trial of 212Pb-TCMC-trastuzumab, aimed at combating intra-abdominal HER-2 expressing cancers. The preliminary results of this study were published in The Journal of Nuclear Medicine, October 2014.
AREVA Med’s Phase 1 Clinical Trial with 212PbPreliminary Results Are Now Available
PurposeStudy the safety, distribution, pharmacokinetics, immunogenicity, and tumor response of intraperitoneal 212Pb-TCMC-trastuzumab in patients with human epidermal growth factor receptor type 2 (HER-2)–expressing malignancy. Results & ConclusionsFive dosage levels (from 7.4 to 21.1 MBq/m2) showed minimal toxicity at more than one year for the first group and more than four months for others. The lack of substantial toxicity was consistent with the dosimetry assessments.
Dose Escalation and Dosimetry of First-in-Human α Radioimmunotherapy with 212Pb-TCMC-Trastuzumab
This first clinical trial was a significant milestone for AREVA Med. Building on these scientific results, we are actively working with our partners toward the next steps in clinical development.”
Julien TorgueScientific Director
AREVA Med
For the full article, please visit the Journal of Nuclear Medicinehttp://jnm.snmjournals.org/content/early/2014/08/25/jnumed.114.143842
The data and information contained herein are provided solely for illustration and informational purposes and create no legal obligations by AREVA. None of the information or data is intended by AREVA to be a representation or a warranty of any kind, expressed or implied, and AREVA assumes no liability for the use of or reliance on any information or data disclosed in this document. © 2015 AREVA Med. All rights reserved.
follow @AREVAmed on twitter
For more information, contactAlison TiseTel: (301) [email protected]
Valuable Insights from Oncology Experts
Ruby F. Meredith, M.D., Ph.D.Principal Investigator and Professor of Radiation Oncology at the University of Alabama at Birmingham
“Data from our first-in-human clinical trial with this promising novel technology shows encouraging results.”
George Sgouros, Ph.D.AREVA Med Scientific Committee Member & Professor and Director at Johns Hopkins University
“Targeted alpha-particle emitter therapy is a novel approach to treating patients with disseminated metastatic cancer. Its effectiveness depends on mechanisms that are fundamentally different from those required for chemotherapy. It is, therefore, far less
susceptible to resistance and has tremendous potential to have a substantial positive impact in patients with aggressive metastatic abdominal cancers.”
Christine White, Ph.D.AREVA Med Scientific Committee Member, Medical Oncologist, and Former Senior Vice President Medical Affairs at Biogen IDEC
“Alpha emitting radioimmunotherapy utilizes monoclonal antibodies to carry packets of short range radiation to kill cancer cells. New developments have resolved logistic barriers to this approach. Preclinical and Phase 1 studies have yielded encouraging mechanism
and safety data. Clinical studies are planned to explore different administration routes and to evaluate safety and efficacy. The development of this type of novel anti-cancer therapy aims to give oncologists additional tools to treat patients with cancer.”
Laboratoire Maurice Tubiana (LMT)
AREVA Med’s 212Pb Production FacilitiesScaling Up Production in France and the U.S.
Laboratoire Maurice Tubiana (LMT)
AREVA Med has built a unique facility to produce high-purity 212Pb needed for clinical development. This facility is located in Bessines-sur-Gartempe in the Limousin region of France. In 2013, this one-of-a-kind facility, named after world-renowned oncologist Professor Maurice Tubiana, became fully operational and began producing 212Pb generators.
Increase the production capacity of high-purity 212Pb following cGMP (current Good Manufacturing Practices) Supply 212Pb for development of new cancer treatments
The LMT has two main objectives:
The data and information contained herein are provided solely for illustration and informational purposes and create no legal obligations by AREVA. None of the information or data is intended by AREVA to be a representation or a warranty of any kind, expressed or implied, and AREVA assumes no liability for the use of or reliance on any information or data disclosed in this document. © 2015 AREVA Med. All rights reserved.
follow @AREVAmed on twitter
For more information, contactAlison TiseTel: (301) [email protected]
Following the completion of the LMT in France in 2013, this new facility, to be located in Plano, Texas, will supplement AREVA Med’s 212Pb production capacity.
With production facilities operational in both the U.S. and France, AREVA Med will be positioned to serve the needs of the medical community even better, both domestically and abroad. At the same time, the DDPU will support the development of AREVA Med’s pipeline focused on innovative, targeted, and powerful 212Pb treatments to fight cancer.
Conceptual rendering of the DDPU © MJMc Architects
Conceptual rendering of the Caen Facility
Developing Plans For New 212Pb Production
New Production Facility in Caen (France)
In 2014, the city of Caen, in the Normandy region of France, was selected as the location for AREVA Med’s future 212Pb production facility.
This facility will supplement the production capacity of the Laboratoire Maurice Tubiana in France and DDPU in the U.S. to serve future commercial medical needs. Construction of this facility will be confirmed following important scientific programs underway.
Domestic Distribution and Purification Unit (DDPU)
The complementary expertise of Roche and AREVA Med is simply remarkable. With this new common research laboratory, along with the
expertise of our American subsidiary Macrocyclics, and Maurice Tubiana Facility, AREVA Med has unrivalled competencies and means through which we hope for major advances in the fight against cancer.”
As part of this new alliance, Roche and AREVA Med have completed the construction of a common research laboratory located in France (Limousin Region). Operational since 2013, ARCoLab (AREVA Med Roche Common Laboratory) is dedicated to the co-development of targeted alpha therapy (TAT), an innovative and promising approach in the fight against cancer.
ARCoLab is one the world’s leading nuclear medicine laboratories. Supported by experts from both organizations, a joint team of researchers and engineers from the Roche Institute of Research and Translational Medicine (IRRMT, part of Roche Pharma Research and Early Development) and AREVA Med currently evaluate the anti-tumor efficiency of the targeted alpha therapy (TAT) in different preclinical models. The ARCoLab team is actively working on scientific experiments to prove the mechanism of action.
In 2012, Roche and AREVA Med Launched a Strategic Alliance to create a novel, advanced alpha radioimmunotherapy platform to target and kill cancer cells. The agreement is focused on malignant disease with a high unmet medical need.
Strategic Alliance with RocheAREVA Med Roche Common Laboratory
Patrick BourdetPresident and CEO of AREVA Med
The data and information contained herein are provided solely for illustration and informational purposes and create no legal obligations by AREVA. None of the information or data is intended by AREVA to be a representation or a warranty of any kind, expressed or implied, and AREVA assumes no liability for the use of or reliance on any information or data disclosed in this document. © 2015 AREVA Med. All rights reserved.
follow @AREVAmed on twitter
For more information, contactAlison TiseTel: (301) [email protected]
AREVA Med’s Scientific Research Partners
In 2011, AREVA Med signed a cooperative research agreement with the French National Institute of Health and Medical Research (Inserm).
In 2008, AREVA Med and the United States National Cancer Institute (NCI) signed a Cooperative Research and Development Agreement for the design of a new radiopharmaceutical drug using 212Pb.
In 2010, AREVA Med and the University of Cincinnati Ohio collaborated on a preclinical study to develop a new treatment to combat prostate cancer.
In 2012, AREVA Med and the University of Alabama at Birmingham (UAB) Cancer Center launched the first clinical trial using 212Pb.
Macrocyclics is dedicated to providing clients with both established and innovative chelating agents and services to meet the challenges of molecular imaging and nuclear medicine.
AREVA Med and Macrocyclics have created a long-term strategic alliance with Roche to create a novel alpha radioimmunotherapy platform. Macrocyclics is developing new chelating agents currently used in
preclinical studies to support Roche’s antibody engineering technologies for use in future clinical trials.
Macrocyclics Services & Products:
• Process chemistry and ligand design
• Feasibility studies for process optimization
• Bioconjugation development and cGMP manufacturing
• Custom design, manufacture, and cGMP production of chelates
• Identification and selection of appropriate chelating agent for specific applications
Key Figures:
• Over 300 clients in 30 countries
• More than 70 catalog products available
• Products shipped within one business day
• Commercial offices in the U.S., China, Japan, India, South Korea, and France
In 2011, AREVA Med acquired Macrocyclics, Inc., the global leader in high performance chelating agent technologies.
Macrocyclics: Molecular Innovation for MedicineA Strategic Alliance to Develop Innovative Treatments
Find out more at www.macrocylics.com
The data and information contained herein are provided solely for illustration and informational purposes and create no legal obligations by AREVA. None of the information or data is intended by AREVA to be a representation or a warranty of any kind, expressed or implied, and AREVA assumes no liability for the use of or reliance on any information or data disclosed in this document. © 2015 AREVA Med. All rights reserved.
follow @AREVAmed on twitter
For more information, contactAlison TiseTel: (301) [email protected]
Other Partners Within the AREVA Group Supporting AREVA Med’s Development
AREVA Med benefits from the AREVA Group’s core competencies to increase services and add value to our research partners.
AREVA TNwith its logistical capabilities and its global reach, has opened new routes for the safe and rapid delivery of 212Pb to AREVA Med’s various partners. To date, more than 80 generators have been shipped to France and the U.S.
AREVA CANBERRA provides AREVA Med with its expertise in the design and manufacture of high-precision nuclear measurement equipment.
AREVA E&Psupports AREVA Med in the process implementation and scale-up, and ensures that the highest safety standards are met.
AREVA TA is responsible for the conception, design, and construction of the high-purity 212Pb production laboratory, Laboratoire Maurice Tubiana (LMT).
As a world leader in nuclear power, AREVA in North America (AREVA Inc.) combines U.S. and Canadian leadership to provide utilities with proven expertise and uncompromising dedication to safety in every stage of the nuclear fuel cycle, reactor design and construction, and operating services. AREVA also invests in renewable energies to develop, via partnerships, high technology solutions. Through the complementary nature of nuclear and renewables, AREVAs nearly 5,000 U.S. and Canadian employees contribute to building tomorrow’s energy model: Supplying the greatest number of people with energy that is safer and with less CO2.
www.areva.com
For more information, contact Alison Tise, Tel: (301) 841-1673 – [email protected]
www.arevamed.com
The
data
and
info
rmat
ion
cont
aine
d he
rein
are
pro
vide
d so
lely
for i
llust
ratio
n an
d in
form
atio
nal p
urpo
ses
and
crea
te n
o le
gal o
blig
atio
ns b
y A
RE
VA. N
one
of th
e in
form
atio
n or
dat
a is
inte
nded
by
AR
EVA
to b
e a
repr
esen
tatio
n or
a w
arra
nty
of a
ny k
ind,
exp
ress
ed o
r im
plie
d, a
nd A
RE
VA a
ssum
es n
o lia
bilit
y fo
r the
use
of o
r rel
ianc
e on
any
info
rmat
ion
or d
ata
disc
lose
d in
this
doc
umen
t.
© 2
015
AR
EVA
Med
, All
righ
ts r
eser
ved.
AREVA Med
follow @AREVAmed on twitter
