Combination of Lenalidomide and SNS01-T Effective in Cancer Model
01 May 2012 - 10:30PM
Business Wire
Senesco Technologies, Inc. (“Senesco” or the “Company”) (NYSE
AMEX: SNT) announced today that a high level of tumor eradication
in a mouse model of human multiple myeloma was achieved with a
combination of SNS01-T and lenalidomide.
“SNS01-T has once again demonstrated excellent efficacy alone
and even more when combined with lenalidomide,” said Leslie J.
Browne, Ph.D., President and CEO of Senesco. “Lenalidomide is the
active ingredient of REVLIMID®, which is marketed by Celgene and is
widely used to treat multiple myeloma. While SNS01-T alone
performed well by completely eliminating tumors in 40% of the
animals, complete tumor eradication was achieved in five out of six
or 83%of the treated animals that received SNS01-T combined with
the optimal study dose of lenalidomide. This effect has lasted
throughout 3 weeks of observation after the end of treatment.
Neither dose of lenalidomide used alone eliminated tumors in any of
the treated mice.”
The Company recently reported that SNS01-T significantly
inhibits the growth of both human mantle cell and diffuse large
B-cell lymphomas in mouse xenograft models and that the combination
of lenalidomide and SNS01-T, performs better than either treatment
alone in a mouse xenograft model of human mantle cell lymphoma.
Summary of Multiple Myeloma Model Results
The purpose of the study was to determine whether SNS01-T
treatment increases the effectiveness of lenalidomide in a murine
xenograft model of multiple myeloma. SNS01-T (0.375 mg/kg i.v.) was
combined with either a sub-optimal dose (15 mg/kg i.p.) or an
optimal dose of lenalidomide (50 mg/kg i.p.). Mice received SNS01-T
twice weekly and 5 doses/week of lenalidomide for 6 weeks.
Tumors were initiated by implanting human myeloma RPMI 8226
cells into the flank of SCID mice. The mice were randomized into 6
groups of 5 or 6 animals when the subcutaneous tumors were
approximately 40 mm3 in size.
At the end of 6 weeks of dosing, tumor growth was inhibited
compared to control nanoparticles by 96 % (p = 0.0001), 94 % (p =
0.0002), and 99 % (p = 0.00003) in animals treated with SNS01-T,
SNS01-T plus 15 mg/kg lenalidomide and SNS01-T plus 50 mg/kg of
lenalidomide, respectively. By comparison, tumor inhibition in mice
treated with 5 doses/week of lenalidomide for 6 weeks at 15 mg/kg
i.p. or 50 mg/kg i.p. was 51 % (p = 0.03) and 78 % (p = 0.0008),
respectively.
No surviving animals treated with control nanoparticles or
lenalidomide alone had undetectable tumors at the end of 6 weeks.
In the SNS01-T and SNS01-T plus 15 mg/kg of lenalidomide groups, 2
of 5 animals in each group had no detectable tumor. In the SNS01-T
plus 50 mg/kg treatment group, 5 of 6 animals (83 %) had no
detectable tumor, and remained undetectable even after 3 weeks
without further treatment.
The median survival of mice treated with control nanoparticles
or 15 mg/kg lenalidomide was 48 days and 53 days, respectively.
Mice treated with SNS01-T or SNS01-T in combination with
lenalidomide had 100 % survival following 6 weeks of dosing and 11
days of observation after cessation of treatment.
In conclusion, SNS01-T alone and in combination with sub-optimal
and optimal (15 and 50 mg/kg respectively) doses of lenalidomide
demonstrated significantly improved efficacy compared to
lenalidomide alone. However the most significant finding was that
SNS01-T plus 50 mg/kg of lenalidomide completely eliminated tumor
burden in 83% of treated animals compared to 40% in animals treated
with SNS01-T alone or SNS01-T plus 15 mg/kg lenalidomide. The
eradication of tumor has lasted for at least 3 weeks.
About Multiple Myeloma
Multiple myeloma is an incurable cancer of plasma cells, a type
of white blood cell derived from B-lymphocytes, normally
responsible for the production of antibodies, in which abnormal
cells accumulate in the bone marrow leading to bone lesions and
interfering with the production of normal blood cells. Senesco was
previously granted orphan drug status for SNS01-T, the Company’s
lead drug candidate for treatment of multiple myeloma.
REVLIMID® is a registered trademark of Celgene Corporation.
About Senesco Technologies, Inc.
Senesco, a leader in eIF5A technology, is running a clinical
study in multiple myeloma with its lead therapeutic candidate
SNS01-T, which targets B-cell cancers by selectively inducing
apoptosis by modulating eukaryotic, translation, initiation Factor
5A (eIF5A), which is believed to be an important regulator of cell
growth and cell death. Accelerating apoptosis may have applications
in treating cancer, while delaying apoptosis may have applications
in treating certain inflammatory and ischemic diseases. Senesco has
already partnered with leading-edge companies engaged in
agricultural biotechnology and is entitled to earn research and
development milestones and royalties if its gene-regulating
platform technology is incorporated into its partners’
products.
Forward-Looking Statements
Certain statements included in this press release are
forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995. Actual results could
differ materially from such statements expressed or implied herein
as a result of a variety of factors, including, but not limited to:
the ability of the Company to consummate additional financings; the
development of the Company’s gene technology; the approval of the
Company’s patent applications; the successful implementation of the
Company’s research and development programs and collaborations; the
success of the Company's license agreements; the acceptance by the
market of the Company’s products; the timing and success of the
Company’s preliminary studies, preclinical research and clinical
trials; competition and the timing of projects and trends in future
operating performance, the Company’s ability to comply with the
continued listing standards of the NYSE Amex, as well as other
factors expressed from time to time in the Company’s periodic
filings with the Securities and Exchange Commission (the "SEC"). As
a result, this press release should be read in conjunction with the
Company’s periodic filings with the SEC. The forward-looking
statements contained herein are made only as of the date of this
press release, and the Company undertakes no obligation to publicly
update such forward-looking statements to reflect subsequent events
or circumstances.
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