Paloma Pharmaceuticals Presents at the AACR-NCI-EORTC International Conference Molecular Targets and Cancer Therapeutics

Presentation highlights Palomid 529 as a first-in-class dual TORC1/TORC2 inhibitor in Brain Cancer -

JAMAICA PLAIN, Massachusetts, November 16 - Paloma Pharmaceuticals, Inc. announced it will give a presentation today
at the AACR-NCI-EORTC International Conference Molecular Targets and Cancer
Therapeutics, "Palomid 529, a dual mTor1/2 inhibitor, efficiently penetrates
the blood brain barrier and may be an attractive agent for treatment of
glioblastoma" by Dr. Olaf van Tellingen, Ph.D. of The Netherlands Cancer
Institute, Amsterdam, The Netherlands.

(Logo: www.newscom.com/cgi-bin/prnh/20081117/NEM057LOGO )

Palomid 529 (P529) is a non-steroidal, synthetic, small molecule
anti-tumor agent created through computational design, synthetic and
medicinal chemistry, the result of three generations of Palomid design work.
Palomid's broad activity as an anti-tumor agent is shown to reside in its
ability to target and inhibit the PI3K/Akt/mTOR signal transduction pathway
as a dual TORC1/TORC2 inhibitor.

"Glioblastoma Multiforme is the most frequent primary brain tumor for
which very few active drugs are available. The blood brain barrier is a major
obstacle in the efficient delivery of drugs to the brain. In particular, the
activities of ABC transporters such as P-glycoprotein and breast
cancer-resistance protein (BCRP) are important. We were, therefore, pleased
to see that Palomid 529 is only a very weak substrate of P-glycoprotein and
BCRP and that high brain-to-plasma ratios were achieved following drug
administration. This property makes Palomid 529 an attractive candidate for
targeting this potentially important PI3K-Akt-mTOR signal transduction route
in brain cancer," said Dr. Van Tellingen.

"Work form the laboratory of Dr. van Tellingen is significant in that it
shows administration of P529 penetrates the brain-blood-barrier, enters the
brain and is not affected by the ABC transporters — a common problem in
cancer therapy where cancer drugs are actively pumped out of cancer cells,"
said David Sherris, Ph.D., President and CEO of Paloma Pharmaceuticals. "This
work adds to our mounting compendium of data showing P529 as a potent oral
anti-tumor agent in variety of tumor animal models including breast, prostate
and glioblastoma," said Dr. Sherris.

About the PI3K/Akt/mTOR Pathway

The PI3K/Akt/mTOR pathway has been implicated in a wide variety of
biological responses and is considered a major therapeutic target in cancer.
Activation of this signaling pathway, via direct or indirect mutagenic
events, is common in many types of human cancer resulting in deregulation of
PI3K/Akt/mTOR pathway in cancer. Thus, agents capable of inhibiting the
PI3K/Akt/mTOR pathway are attractive targets for therapeutic intervention in
cancer. Central within the signalling pathway are two distinct protein
complexes, one of which regulates growth through the signal transduction
protein S6K, TORC1, and the other that regulates cell survival through Akt,
TORC2. These complexes define both rapamycin-sensitive and insensitive
branches of the PI3K/Akt/mTOR pathway. Inhibition of the TORC2 pathway
suppresses the formation of tumors driven by the loss of the PTEN tumor
suppressor, a gene which when lost contributes to carcinogenicity. Inhibitors
of TORC2 may then have beneficial effects as anti-cancer agents without
toxicity to normal tissues since loss of TORC2 through genetic alteration
does not appear to affect normal tissue. TORC1 antagonists as rapamycin and
other such rapalogs have shown activity in both animal models of cancer and
in human clinical trials. As inhibition of both TORC1 and TORC2 should result
in more complete inhibition of PI3K/Akt/mTOR signaling up-regulated in
cancer, dual inhibitors are of active interest for pharmaceutical
development.

About Paloma Pharmaceuticals

Paloma Pharmaceuticals, Inc. is an early stage drug development company
utilizing its PI3K/Akt/mTOR inhibitors focusing on cancer, ocular diseases
(macular degeneration and diabetic retinopathy), CNS (epilepsy, Parkinson's
disease, Alzheimer's disease), fibrotic diseases (pulmonary and renal
fibrosis), antiviral (HIV, HCV) and skin diseases (psoriasis and atopic
dermatitis). Paloma owns the intellectual property relating to a library of
novel, proprietary, small molecule drugs created through an integrated design
platform incorporating proprietary, customized and industry standard
computational tools that has therapeutic potential for the treatment of the
foregoing diseases.

www.palomapharma.com

    David Sherris
    +1-617-407-6314
    dsherris@palomapharma.com

David Sherris of Paloma Pharmaceuticals, Inc., +1-617-407-6314, dsherris at palomapharma.com