New Data Presented at AACR Meeting Support the Clinical Potential of Semafore`s Novel PI3K Prodrug
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Posted on: 04/19/2005
New Data Presented at AACR Meeting Support the Clinical Potential of Semafore's Novel PI3K Prodrug
- Prominent Cancer Advisors Are Encouraged by SF 1126's Unique Mechanism and
Promising Initial Results in a Variety of Pre-Clinical Cancer Models -
INDIANAPOLIS and ANAHEIM, Calif., April 19 /PRNewswire/ -- Semafore
Pharmaceuticals, Inc., an emerging leader in small molecule cancer therapies
addressing critical cell signaling pathways, today presented new in vivo data
further demonstrating the potential utility of SF1126, the company's PI3K
inhibitor delivered as a tumor-targeting prodrug. Despite the growing
attention given to the importance of the PI3 kinase (PI3K) pathway in treating
cancer, there currently are no PI3K inhibitors in clinical trials for
oncology. The data presented today are the latest from a series of preclinical
studies that demonstrate the potential safety, efficacy, and biological target
activity of SF1126 and support its progress to clinical trials by early 2006.
The data are being presented by Semafore researchers at the 96th Annual
Meeting of the American Association for Cancer Research (AACR).
The PI3K pathway is a critical intercept point in cell signaling that
controls multiple cellular functions including angiogenesis, apoptosis,
migration, invasion and metastasis. Inhibiting PI3K is expected to minimize
the possibility that alternative pathways will stimulate malignant cell
growth. The high degree of interest in this pathway also reflects the fact
that activation of PI3K is associated with resistance to Herceptin and a
number of other cancer drugs, as well as to radiation treatment.
"SF1126 is a highly specific inhibitor of this well-characterized
cell-signaling pathway that plays a crucial role in the life and death of
cancer cells," said Gordon Mills, M.D., Ph.D., scientific advisor to Semafore
and chairman, Department of Molecular Therapeutics at MD Anderson Cancer
Center. "SF1126 achieves prolonged knockdown of PI3K in vivo with significant
anti-tumor activity at multiple dose levels, and is well-tolerated. We are
especially interested too in the fact that the Semafore prodrug shows activity
against all three distinct isoforms of the PI-3 kinase pathway, which is
important because each isoform may play a different role in cancer
development. We look forward to helping to test whether this promising
profile is confirmed in human studies."
Preclinical studies with SF1126 have demonstrated promise in a variety of
cancers, including glioma, prostate, non-small cell lung, ovarian, and breast
cancer. Researchers at Semafore, the National Cancer Institute, MD Anderson,
Duke University, Johns Hopkins University, Emory University, Indiana
University, the University of Pennsylvania, and others are also in the process
of assessing SF1126 in colon cancer, melanoma, multiple myeloma, leukemia and
other cancer types.
"SF1126 may be the first representative of a promising new class of drugs.
In addition to sensitizing cancers to standard therapies, it affects both the
tumor neovasculature and the tumor itself -- it's a dual effect," said
Jonathan Simons, M.D., director of the Winship Cancer Center at Emory
University and pro-bono science advisor to Semafore. "SF1126 may achieve
these multiple effects at least in part by controlling levels of HIF-1a, which
our studies at Emory have shown is a key transcription factor controlling
angiogenesis and the production of VEGF. The data presented today are very
promising in their demonstration that SF1126 reduces levels of HIF-1a in a
dose dependent manner."
The importance of the Pl3K pathway in promoting tumor angiogenesis was
discovered by Donald Durden, M.D., Ph.D., now senior scientific advisor to
"Semafore's SF1126 builds upon our work to harness the power of a
well-characterized PI3K inhibitor compound originally used as a research
tool," said Dr. Durden, now at Emory University School of Medicine and a
scientific director of the AFLAC Cancer Center at Emory. By targeting SF1126
to tumor neovascularization and delivering it as a prodrug, this compound has
been transformed into an anticancer agent that appears to be safe and
biologically active with an attractive pharmacokinetic profile -- everything
one would want to see in a clinical candidate. These new data expand and
confirm the promising data in the IND package for SF1126 which is currently
The data presented at the AACR meeting show for the first time that high
doses of SF1126 demonstrate significant efficacy, with up to 91% tumor growth
inhibition, and were well tolerated in a multi-dose two week treatment study
of mouse models of human prostate cancer. The doses were 50 and 100 mg/kg
administered 7 times over two weeks of the six and one half week study period.
The safety data presented are the first comprehensive analyses of such high
dosages of this potent PI3K inhibitor, and they show that the treated mice
exhibited no significant body or organ weight loss relative to controls.
Also, their blood glucose and insulin levels were normal after 24 hours, and
all blood cell count levels (white and red blood cells, hemoglobin,
hematocrit, and platelet) were within normal ranges and statistically no
different than controls.
Semafore researchers are also presenting data on key drug-like qualities
of SF1126, including in vivo evidence of PI3K targeting and prolonged
knockdown of the PI3K signal, complete shutdown of angiogenesis, and evidence
that SF1126 controls tumor cell migration and the transcriptional activity of
Poster Title: Targeting critical signaling pathways with a Pan-PI-3 kinase
inhibitor: Focus on Safety and Efficacy of SF1126, HIF1a and the angiogenic
process. Session Title: Late-Breaking Abstracts: Poster Session 1; 4/19/2005
8:00am-12:00pm; Exhibit Hall B-D, Anaheim Convention Center.
Authors: Jing Dong Su, Joseph R. Garlich, Xiaodong Peng, Toni Miller, Mary
Patterson, Veranika Pazharskaya, Donald L. Durden. Semafore Pharmaceuticals,
Inc., AFLAC Center for Cancer Research, Winship Cancer Center, Emory
University School of Medicine.
Semafore is an Indianapolis-based drug discovery and development company
focused on small molecule modulators of the PI3 Kinase (PI3K) and PTEN cell
signaling pathway, one of the most promising target pathways for multiple
disorders, including the company's focus -- cancer. Semafore is one of the
first biopharmaceutical companies to focus on PI3K and PTEN and has
successfully discovered and is developing a portfolio of drug candidates.
These programs have the potential to be the first of a new class of targeted
cancer agents. The company's lead clinical candidate, SF1126, is a pan-PI3K
inhibitor, and the company expects to file an IND in early 2006, with
subsequent studies in brain, breast, prostate, and ovarian cancers. Semafore
has also discovered the first drug-like PTEN inhibitors for cell protection,
therapeutic angiogenesis and cancer sensitization. These compounds have
exciting potential to completely change the way cancer and other disorders are
treated. For more information, see the company's Website
Semafore Pharmaceuticals, Inc. Media:
Derek A. Small Stephen Gendel
Director of Corporate Development GendeLLindheim BioCom Partners
(317) 876-3075 (212) 918-4650
SOURCE Semafore Pharmaceuticals, Inc.
Web Site: http://www.semaforepharma.com
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