|
Archexin
First in Class Potent Anti-cancer Akt Inhibitor:
ArchexinTM is a first-in-class, potent inhibitor of the Akt-1
protein kinase in cancer cells. ArchexinTM is in Phase II trials for
treatment of renal cell carcinoma (RCC) and pancreatic cancer, and
has US FDA orphan drug designations for five cancers (RCC,
glioblastoma, and cancers of ovary, stomach and pancreas). Multiple
indications for other solid tumors can also be pursued. ArchexinTM
is an antisense oligonucleotide (ASO) compound that is complementary
to Akt mRNA, and highly selective for inhibiting mRNA expression and
production of Akt protein. Akt activation leads to cancer cell
survival, proliferation, and angiogenesis. Both native and activated
forms of Akt are involved in cancer cell signaling. Activated Akt
also play a role as a drug resistance mechanism, in particular, of
targeted therapies.
ArchexinTM is the first anticancer drug that inhibits both forms of
Akt, with the potential to inhibit cancer survival and
proliferation, angiogenesis and drug resistance. In the ArchexinTM
Phase I clinical study, grade 3 (G3) fatigue was the only dose
limiting toxicity observed. No significant hematological effects or
other adverse events were observed.
The ArchexinTM Phase II study goals are to assess efficacy and
safety in treating advanced RCC and pancreatic cancer. The primary
study endpoint is objective tumor response. Other endpoints include
survival (PFS, OS), biomarkers, and quality of life measures. We
will conduct clinical trials concurrently and globally to expand
indications.
RX-0047-Nano
Nanoliposomal anti-cancer HIF-1α inhibitor
RX-0047-Nano is a nanoliposomal cancer drug candidate that
selectively inhibits expression of the HIF-1α transcription factor.
HIF-1α is a key signaling molecule in angiogenesis, cancer cell
survival and invasion, and radiation resistance. RX-0047 is a
first-in-class anticancer candidate that directly inhibits
expression of mRNA and protein of HIF-1α.
HIF-1α is over-expressed in a broad range of human cancers, and
associated with increased cancer mortality and resistance.
In preclinical studies, RX-0047 significantly downregulated
expression of HIF-1α mRNA and protein. At nanomolar concentrations,
RX-0047 reversed resistance in radiation-resistant cancer cells.
RX-0047 inhibited growth of solid tumors in lung as well as prostate
cancer xenograft models, and significantly blocked metastasis in a
lung metastatic model. RX-0047-Nano is expected to provide
significant clinical benefits including targeted higher cellular
uptake, extended circulation time, reduced drug-related toxicity,
and improved efficacy.
Zoraxel
Sexual Dysfunction
ZoraxelTM is a CNS-based sexual dysfunction drug that is being
developed to treat Erectile Dysfunction (ED), and has extensive
safety in humans. ZoraxelTM is a dual serotonin and dopamine
enhancer in the brain, where these neurotransmitters play a key role
in three phases (sexual motivation-arousal, erection and release) of
sexual activity. ZoraxelTM may be the first ED drug to affect all
three phases of the sexual activity. In preclinical studies and
animal models, ZoraxelTM significantly improved sexual performance
and suggested positive behavioral effects on sexual motivation and
arousal.
Erectile dysfunction (ED) is defined as the consistent inability to
attain and maintain an erection sufficient for satisfactory sexual
intercourse. Erectile problems may be due to psychogenic causes
(e.g., depression or stress) or 'organic' causes. In many cases,
both organic and psychogenic factors are present. The launch of
Viagra in 1998 as the first orally available phosphodiesterase (PDE)-5
inhibitor established a new standard of care for ED, and pioneered
the ED market. Cialis and Levitra were subsequently launched in 2003
as second-generation PDE-5 inhibitor drugs. Beyond the leading PDE-5
inhibitors, there is currently no single class of ED drugs to
dominate the ED pipeline. An estimated 30% of US men are refractory
to the leading PDE-5 inhibitor drugs, which work peripherally and
mechanically. Certain segments of the ED patient population that
respond less to PDE-5 inhibitors include diabetics, obese or
post-surgical prostatectomy or coronary risk patients. PDE-5
inhibitors may have significant drawbacks of cardiovascular risks
and other side effects (e.g., priapism, severe hypotension,
myocardial infarction, ventricular arrhythmias, sudden death and
increased intraocular pressure).
Rexahn is developing ZoraxelTM as an orally available drug that has
extensive safety and addresses specific features of male ED. Unlike
the PDE-5 inhibitors working at the peripheral blood vessel and only
mechanically affecting erection, ZoraxelTM is centrally acting and
works in the brain and affects all three functions of sexual
activity, i.e. sexual arousal, erection, and release. ZoraxelTM is
well tolerated and appears to lack serious side effects associated
with PDE-5 inhibitors. ZoraxelTM may be superior to PDE-5
inhibitors, and offer clinical benefits over dopamine agonists.
Phase II trials are ongoing for 2009 for ZoraxelTM.
|
