Nektar's Technology Enables First-Ever PEGylation of a Small Molecule with Demonstrated Therapeutic Activity SAN CARLOS, Calif., May 16
SAN CARLOS, Calif., May 16 /PRNewswire-FirstCall/ -- Nektar Therapeutics
(Nasdaq: NKTR) announced initial results today from a Phase 1 study of NKTR-
102, PEGylated irinotecan. The data shows significant anti-tumor activity in
patients with refractory solid tumors. The study also demonstrates that
Nektar's small molecule PEGylation technology produced an increase in SN38
exposure that was up to six-fold higher than the exposure previously reported
with irinotecan at equivalent doses. SN38, a topoisomerase I inhibitor, is
the active metabolite of irinotecan.
The ASCO abstract reports interim data on 27 of 32 patients in the first
of three dose schedules from the Phase 1 trial.(1) Results for the first
schedule (weekly x3 q4 weeks) found anti-tumor activity in 7 out of the total
32 patients evaluable for efficacy. Partial responses were confirmed in three
patients, or 10% (greater than 30% tumor regression per RECIST), and other
evidence of anti-tumor activity was confirmed in four patients, or 12% (tumor
regression by more than 15% but less than 30% per RECIST, or significant
biomarker evidence).
"This significant anti-tumor activity in a number of patients whose tumors
have progressed on prior therapies makes NKTR-102 one of the most promising
cancer drugs I have ever studied," said Daniel D. Von Hoff, M.D., lead Phase 1
investigator for NKTR-102, Physician-in-Chief at the Translational Genomics
Research Institute and Chief Medical Officer for the Scottsdale Clinical
Research Institute at Scottsdale Healthcare.
Nektar's proprietary PEGylation technology can enhance the properties of
therapeutic agents by increasing drug circulation time, improving
pharmacokinetics, decreasing immunogenicity and dosing frequency, increasing
bioavailability and improving drug solubility and stability.
"The impressive Phase 1 results with NKTR-102 represent a major
advancement for our small molecule PEGylation platform," said Howard W. Robin,
President and CEO of Nektar. "Using our proprietary technology, Nektar is the
first company to create a PEGylated small molecule with a unique
pharmacokinetic profile that has demonstrated therapeutic activity in
patients. This pioneering success with NKTR-102 validates our platform and
opens the door to a wide range of potential small molecule opportunities. "
Clinical Trial Summary
In the Phase 1 dose-escalation trial, the safety, pharmacokinetics and
anti-tumor activity of NKTR-102 monotherapy was evaluated in patients with
refractory solid tumors. Patients received 90-minute infusions of NKTR-102
(PEGylated irinotecan) repeated as follows: weekly for three weeks with the
fourth week off; every two weeks; or every three weeks. Tumor responses are
being evaluated according to RECIST (Response Evaluation Criteria in Solid
Tumors) criteria.
In the first dose schedule (weekly x3 q4 weeks), NKTR-102 was administered
to a total of 32 patients with advanced solid tumors who had failed prior
treatments or had no standard treatment available to them. Doses ranged from
58 mg/m2 to 230 mg/m2. Tumor regression, anti-tumor activity or prolonged
disease stabilization was observed in a number of cancer types, including non-
small cell lung cancer, ovarian, small cell lung cancer, cervical,
adrenocortical, esophageal, and Hodgkin's lymphoma.
Results from the second and third dose schedules of this Phase 1 trial
will be presented by featured speaker, Dr. Daniel D. Von Hoff, at an investor
event on June 2, 2008. The Webcast event will begin at 6 pm Central time and
will occur during the American Society of Clinical Oncology (ASCO) 2008 Annual
Meeting in Chicago, Illinois. Nektar will also present its Phase 2 clinical
development plan for NKTR-102.
Side effects in the first dose schedule were diarrhea and neutropenia and
were identified as manageable toxicities, with diarrhea being the dose-
limiting toxicity associated with administration of NKTR-102. The recommended
Phase 2 dose (RP2D) was 115 mg/m2. No Grade 4 or Grade 5 toxicities were
observed with administration of NKTR-102.
The Phase 1 trial, sponsored by Nektar Therapeutics, includes clinical
sites at Translational Generational Clinical Research Services at Scottsdale
Healthcare and the Louisville Oncology Clinical Research Program. The company
also expects to present results from this trial at additional scientific
forums later this year.
The NKTR-102 abstract entitled "Phase 1 dose finding and pharmacokinetic
study of NKTR-102 (PEGylated irinotecan): early evidence of anti-tumor
activity" (Abstract No. 13518, published in the ASCO proceedings) can also be
found on Nektar's website at http://www.nektar.com/wt/page/nktr102media.
About NKTR-102
Nektar is developing NKTR-102, a PEGylated form of irinotecan, which was
invented by Nektar using its world-leading small molecule PEGylation
technology platform. The product is currently in Phase 2 clinical development
to evaluate its efficacy and safety in combination with cetuximab. Irinotecan
is an important chemotherapeutic agent used for the treatment of solid tumors,
including colorectal and lung cancers. By applying Nektar's small molecule
PEGylation technology to irinotecan, NKTR-102 may prove to be a more powerful
and tolerable anti-tumor agent.
Nektar PEGylation technology is used in eight additional approved
partnered products in the U.S. or Europe today, including UCB's Cimzia(R),
Roche's PEGASYS(R) for hepatitis C and Amgen's Neulasta(R) for neutropenia.
About Nektar
Nektar Therapeutics is a biopharmaceutical company that develops and
enables differentiated therapeutics with its industry-leading PEGylation and
pulmonary drug development technology platforms. Nektar PEGylation and
pulmonary technology, expertise, manufacturing capabilities have enabled eight
approved products for partners, which include the world's leading
pharmaceutical and biotechnology companies. Nektar also develops its own
products by applying its PEGylation and pulmonary technology platforms to
existing medicines with the objective to enhance performance, such as
improving efficacy, safety and compliance.
This press release contains forward-looking statements regarding the
potential of NKTR-102 and Nektar's PEGylation technology platform. These
forward-looking statements involve important risks and uncertainties,
including but not limited to: (i) clinical trials for NKTR-102 are long,
expensive and uncertain processes; (ii) because NKTR-102 is in the early
phases of clinical development, the risk of failure is high and can occur at
any stage of development regardless of promising data from one or more prior
preclinical or clinical studies, (iii) the timing or success of the
commencement or end of clinical trials may be delayed or unsuccessful due to
slower than anticipated patient enrollment, drug manufacturing challenges,
changing standards of care, clinical trial design, and/or clinical outcomes;
(iv) Nektar may fail to obtain regulatory approval of NKTR-102; (v) potential
competition from existing approved products (branded or generic) or product
candidates under development by other companies could negatively impact the
commercial potential of NKTR-102 due to such common industry competitive
factors as efficacy and safety profiles, pricing, and reimbursement by third
party payers; and (vi) Nektar's patent applications for NKTR-102 may fail to
issue; patents that have issued may not be enforceable; or unanticipated
intellectual property licenses from third parties may be required in the
future. Other important risks and uncertainties are detailed in Nektar's
reports and other filings with the SEC including its most recent Quarterly
Report on Form 10-Q filed with the SEC on May 9, 2008. Actual results could
differ materially from the forward-looking statements contained in this press
release. Nektar undertakes no obligation to update forward-looking
statements, whether as a result of new information, future events, or
otherwise. No information regarding or presented at the scientific meetings
referred to above (or contained at the Internet links provided) is intended to
be incorporated by reference in this press release.
Contacts:
Tim Warner (650) 283-4915 or twarner@nektar.com
Stephan Herrera (415) 488-7699 or sherrera@nektar.com
Jennifer Ruddock (650) 631-4954 or jruddock@nektar.com
References and Glossary
(1) Borad, M.J., Hamm, J.T., Rosen, L.S., Jameson, G., Utz, J., Mulay, M.,
Eldon, M., Dhar, S., Acosta, L., Von Hoff, D.D., "Phase 1 Dose-finding
and pharmacokinetic study of NKTR-102 (Pegylated irinotecan): early
evidence of anti-tumor activity"; ASCO 2008 Annual Meeting
Proceedings, May 15, 2008.
SOURCE Nektar Therapeutics
