NVLT is on Track to Advance I-131-CLR1404 (HOT)
By Grant Zeng, CFA
On September 11, 2012,
Novelos Therapeutics, Inc. (
successfully completed the second cohort in a U.S. multi-center
dose-escalation trial of its cancer-targeted molecular
radiotherapeutic compound I-131-CLR1404 (HOT) in cancer patients
advanced solid tumors
As a reminder, Novelos initiated the above
dose-escalation / MTD trial in November 2011. First patient was
enrolled in Jan 2012. For each subject, the study will be conducted
in two phases, dosimetric and therapy. In the
, subjects will receive one 5 mCi dose of the study drug and
undergo whole body imaging on the day of infusion and on
post-infusion days 1, 2, 3, and 6 for assessment of biodistribution
of I-131-CLR1404. If normal and expected biodistribution are
demonstrated, the subject will begin the therapy phase. In the
, the first cohort of subjects will receive a dose of 12.5 mCi/m2.
Dose escalation in subsequent cohorts will initially be in
increments of 12.5 mCi/m2. Subjects will be followed and observed
for unacceptable toxicity through 56 days after the therapy dose
infusion with follow-up for up to one year.
The primary objective of this Phase Ib dose-escalation trial in
patients with a range of advanced solid tumors is to define the
Maximum Tolerated Dose (MTD) of HOT. In addition to determining the
MTD, the Phase Ib trial is intended to evaluate overall tumor
response (using standard RESIST I criteria) and safety.
Novelos completed the first cohort in the
dose-escalation trial of HOT in May,
2012. The first two-patient cohort was successfully dosed
with approximately 20 mCi of HOT. Data from the first cohort
indicates HOT was well-tolerated, without any grade 3 or 4
toxicities. HOT uptake in cancerous tumors persisted for at
least 21 days.
The second two-patient cohort was successfully dosed with
approximately 40 mCi of HOT, triggering enrollment into the third
cohort at approximately 60 mCi. Glenn Liu, M.D., Associate
Professor of Medicine and Director of the Cancer Therapy Discovery
and Development (Phase I) Program at the University of Wisconsin
Carbone Cancer Center, is the trial's principal investigator.
Detailed trial results are expected to be presented at a scientific
venue at a later date.
Data from the first two cohorts indicate that HOT was
well-tolerated, without any dose-limiting or sub-dose-limiting
toxicities, enabling enrollment of the third cohort as planned.
Selective uptake of HOT in cancerous tumors continues to be
observed where it persists for at least 21 days.
Data so far from the first two cohorts suggest that HOT has a
favorable safety profile and is selective in cancerous tumor uptake
Novelos expects to begin HOT Phase II proof-of-concept trials in
the third quarter of 2013
as soon as a minimal efficacious dose is established, if additional
funding can be secured. We believe the data generated from the
ongoing HOT Phase 1b trial combined with cancerous tumor imaging
data from the ongoing I-124-CLR1404 (LIGHT) clinical trials will
enable selection of indications for HOT Phase II trials and guide
trial designs. The target cancer will be NSCLC, triple-negative
breast cancer, brain cancer, soft tissue sarcoma, etc.
Since HOT has demonstrated synergistic efficacy when used in
combination with chemotherapeutics in animal models, the Company
plans to explore
HOT combination with chemotherapeutic agents
for the treatment of cancers if funds are available. A number of
chemotherapeutic agents are known to be radiosensitizers and could
have the potential to enhance the efficacy of HOT. Combination
therapy could greatly expand HOT usage in a variety of cancers and
could enhance its commercial potential as a cancer therapeutic.
Novelos' Diapeutic Platform is Presented at the Imaging in
On October 3, 2012, Novelos Therapeutics announced that an oral
presentation on research conducted by Jamey Weichert, Ph.D., Lance
Hall, M.D., Anne M. Traynor, M.D., Glenn Liu, M.D. and their
colleagues is being made by Dr. Weichert at the Imaging in 2020
Conference taking place September 30 to October 4, 2012 in Jackson
This presentation describes the mechanistic foundation for
(diagnostic + therapeutic) technology platform together with animal
data and initial findings in advanced cancer patients that
demonstrate selective and prolonged uptake of Novelos' PET imaging
and optical imaging CLR1502 (
) compounds in a range of tumor types. Dr. Weichert is Associate
Professor of Radiology, Dr. Hall is Assistant Professor of
Radiology, Dr. Traynor is Associate Professor of Medicine and Dr.
Liu is Associate Professor of Medicine, all in the School of
Medicine and Public Health at the University of Wisconsin, Madison
and all are members of the UW Carbone Cancer Center. Dr. Weichert
is also the Chief Scientific Officer of Novelos and the founder of
"LIGHT, HOT and GLOW2 were designed to exploit a common feature
of most, if not all cancer cells including cancer stem cells that
results in their selective uptake and retention in a wide range of
malignant tumors compared with normal tissues," said Dr. Weichert.
"By incorporating a unique functional property in each, we have
generated an array of potential products that could, singly and in
combinations, significantly improve the detection and treatment of
cancer in multiple ways."
The presentation is titled
Molecular Diapeutics: Phospholipid Ether Analogs as
Broad-Spectrum Cancer and Cancer Stem Cell Detection and
. Dr. Weichert presented data showing that LIGHT, HOT and GLOW2 all
share a common cancer-targeted core chemical structure. Each
attaches a unique moiety to this delivery vehicle - LIGHT a PET
imaging agent (iodine-124), HOT a radiotherapeutic agent
(iodine-131) and GLOW2 an optical imaging agent (near-infrared
tracer). Results described with LIGHT demonstrate broad-spectrum
tumor PET imaging in dozens of animal tumor models, and recent
human findings in ongoing Phase I-II clinical trials show selective
uptake and retention by primary tumors and metastases in advanced
non-small cell lung and brain cancer patients. HOT results shown
include single-dose efficacy in a wide range of animal tumor models
as well as selective uptake and retention in cancerous tumors in
clinical trials to date. The presentation highlights the potential
diapeutic application of LIGHT and HOT, based on their chemical
identity, to provide individualized treatment to cancer patients.
For example, LIGHT serves as an ideal biomarker to potentially
identify patients most likely to benefit from therapy with HOT. Dr.
Weichert's talk also describes how selective uptake of GLOW2 could
provide better definition of tumor margins in real time during
cancer surgery, enabling more complete and selective removal of
malignant tissue and potentially improving patients' prognosis.
Data illustrating the potential use of GLOW2 for non-invasive
detection of tumors is also being shown.
Novelos' diapeutic platform, which includes cancer-targeted PET
Imaging, therapeutic and optical Imaging Compounds, offer
broad-spectrum diagnosis and treatment for solid tumors.
We believe Novelos' platform technology has great potential for
cancer imaging and therapy, which can be used in various cancer
types. With all these progresses made in the past few months, we
believe Novelos' share price deserves further appreciation.
Please visit Grant Zeng's coverage page at
to access a free copy of the full research report.
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