Ascenta Therapeutics Announces Presentation of Promising Results From Clinical Trials...

Ascenta Therapeutics Announces Presentation of Promising Results From Clinical
Trials of AT-101 in Prostate, Brain, and Lung Cancers at 2009 ASCO Annual
Meeting

MALVERN, Pa., June 1 /PRNewswire/ -- Ascenta Therapeutics announced today that
promising results from ongoing clinical studies in prostate, brain and lung
cancers were among the data presented on AT-101, an oral, pan-Bcl-2 inhibitor,
at the 2009 American Society of Clinical Oncology (ASCO) Annual Meeting, May
29-June 2, in Orlando, Florida.

(Logo: http://www.newscom.com/cgi-bin/prnh/20090227/PH75873LOGO )

"We are delighted with the depth and breadth of the data available on our lead
compound, AT-101, at this important scientific conference" said Mel Sorensen,
MD, CEO of Ascenta Therapeutics. "The clinical utility of AT-101 is being
explored in several major tumor types and treatment regimens, with prostate
cancer at the most advanced stage of development."

AT-101 in Prostate Cancer
Researchers presented updated data from an open-label, multicenter, Phase I/II
study of AT-101 in combination with docetaxel and prednisone in men with
castrate-resistant prostate cancer (CRPC)(1). This study enrolled 36
patients, who were treated with a standard docetaxel/prednisone regimen with
the addition of AT-101 given twice a day on days 1-3 of each docetaxel
treatment cycle. Thirty-six percent of patients completed at least ten 21-day
cycles of treatment.

Responses to therapy were evaluated according to both PSA and RECIST (tumor
shrinkage) criteria. As of last follow-up, 67 percent of patients had
achieved a PSA partial response (a decrease in PSA level of at least 50
percent) and 45 percent of those with measurable disease achieved partial
responses per RECIST. A reduction in circulating tumor cells was also
reported after the first cycle of treatment and tended to be predictive of
RECIST response. AT-101 was well tolerated in this combination as the
majority of adverse events were Grade 1 or 2. Serious adverse events occurred
in only 16 patients but there were no notable differences in the rates or
severities of fatigue, gastrointestinal toxicities, or cytopenia compared to
those generally associated with docetaxel/prednisone alone.

"The initial response rates we are seeing in this trial demonstrate strong
evidence of antitumor activity in patients with metastatic CRPC," said Gary R.
MacVicar, MD, Northwestern University's Feinberg School of Medicine. "Our
data suggest that adding AT-101 to docetaxel/prednisone may improve clinical
outcomes, without incremental toxicity, and we look forward to confirming this
in larger studies."

Complementing these findings from the chemotherapy-naive setting, another
presentation reported data from a cohort of men with docetaxel-refractory
prostate cancer who were treated with the same docectaxel/prednisone/AT-101
regimen(2). A rigorous definition of refractory was used in this trial, as
the 38 patients had to have had documented disease progression during prior
therapy with a docetaxel-containing regimen to qualify for enrollment. In
this analysis, 41 percent of patients had a 30 percent reduction in PSA and 22
percent achieved a PSA partial response. In the group with measurable
disease, 24 percent of patients achieved a partial response per RECIST. The
regimen was also well tolerated, with rates and severity of toxicity
comparable to those associated with the standard docetaxel/prednisone therapy.
Only one reported serious adverse event, a case of small bowel obstruction
(Grade 2), was considered potentially treatment-related.

AT-101 in Brain Cancer
Preliminary results from a National Cancer Institute (NCI) sponsored Phase II
study of AT-101 as monotherapy for recurrent glioblastoma multiforme (GBM),
the most aggressive form of brain cancer, were also presented(3) . Fifty-six
patients were enrolled with daily oral doses of AT-101 given for 21 of 28 days
in repeated cycles. The treatment was well tolerated, with a low incidence of
serious adverse events and no unique central nervous system toxicities.
Responses were evaluated in 43 patients and included one confirmed partial
response and 8 patients with stable disease, representing half of the patients
still alive at the time of analysis. Progression-free survival (PFS) in these
patients ranged from 8 to 13 months. Determination of the impact of AT-101 on
overall survival (OS), the primary endpoint, is ongoing.

AT-101 in Lung Cancer
Reports from two studies in lung cancer also showed promising signals of
antitumor effect. The first presentation described results from a randomized,
double-blind, placebo-controlled Phase II trial in 105 patients who had
received one prior chemotherapy regimen for non-small cell lung cancer
(NSCLC)(4). While the primary endpoint, a statistically significant
improvement in PFS, was not met, the docetaxel plus AT-101 arm demonstrated a
positive trend in OS, as reflected in the Kaplan-Meier curves (hazard ratio
0.82). This group also demonstrated a 33 percent increase in median survival
and a 34 percent increase in 6-month survival compared to the docetaxel plus
placebo arm. Common adverse events included fatigue (18 percent), anemia (18
percent) and dyspnea (18 percent). Using NSCLC cell lines, a genomic profile
predicting response to AT-101 was developed in collaboration with Duke
University. Opportunities to validate this biomarker will be pursued in
future trials.

The second presentation reported on an open-label, Phase I/II study of AT-101
in combination with topotecan in patients with relapsed or refractory small
cell lung cancer (SCLC) who had received prior platinum-based first line
chemotherapy(5). The Phase II portion of the trial included 25 patients
divided into chemo-sensitive (A) and chemo refractory (B) cohorts. Median
time to progression was 17.4 weeks (range 5.3 - 36.1 weeks) in A and 11.7
weeks (range 1.9 - 19.4 weeks) in B, considered by the investigators to be
favorable compared to historical controls. Observed toxicities with the
combination were consistent with those associated with topotecan.

Abstracts of all eleven presentations or publications on AT-101 made in
conjunction with the 2009 ASCO Annual Meeting are available at www.asco.org.

About AT-101
AT-101 is an orally-active, pan-Bcl-2 inhibitor (including Bcl-2, Bcl-xL,
Bcl-w, and Mcl-1 inhibition) that has been shown to induce apoptosis directly
by operating as a BH3 mimetic and indirectly as an independent upregulator of
Noxa and Puma. By blocking the binding of Bcl-2 family members with
proapoptotic proteins and upregulating specific proapoptotic factors, AT-101
lowers the threshold for cancer cells to undergo apoptosis in various tumor
types.

About Ascenta Therapeutics
Ascenta Therapeutics, Inc. is a privately-held, clinical-stage
biopharmaceutical company that discovers and develops new medicines for the
treatment of cancer. The company is headquartered in Malvern, Pennsylvania,
and has a preclinical research facility in Shanghai, China. Its technology is
focused on discovering molecules that restore the natural potential for cancer
cells to undergo cell death (apoptosis). Ascenta's lead agent, AT-101, is an
orally-active small molecule pan Bcl-2 inhibitor (Bcl-2, Bcl-xL, and Mcl-1)
currently in Phase 2 clinical trials. The Company's preclinical pipeline
includes the oral multi-IAP antagonist AT-406, and an HDM2-p53 inhibitor
program.

For additional information on Ascenta Therapeutics, please visit the company's
website at www.ascenta.com

1. MacVicar G, et al. An open-label, multicenter, phase I/II study of
AT-101 in combination with docetaxel (D) and prednisone (P) in men with
castrate resistant prostate cancer (CRPC). Abstract #5062; Poster
Board
#17; Poster Discussion, May 31, 8:00 a.m.-12:00 p.m.
2. Poiesz B, et al. Preliminary report of an open-label, multicenter,
phase
I/II study of AT-101 in combination with docetaxel (D) and prednisone
(P)
in men with docetaxel refractory prostate cancer. Abstract #5145;
Poster
Board #J13; GU General Poster Session, May 31, 2:00 p.m.-6:00 p.m.
3. Fiveash J, et al. NABT-0702: A phase II study of AT-101 in recurrent
glioblastoma multiforme (GBM). Abstract #2010; Poster Board #2; Poster
Discussion, May 30, 8:00 a.m.-12:00 p.m.
4. Ready N, et al. AT-101 or placebo (P) with docetaxel (D) in second
line
NSCLC with gene signature biomarker development. Abstract #3577;
Poster
Board #J19; Developmental Therapeutics, May 30, 8:00 a.m.-12:00 p.m.

5. Heist R, et al. A phase I/II study of AT-101 in combination with
topotecan (T) in patients with relapsed or refractory small cell lung
cancer (SCLC) after prior platinum containing first line chemotherapy.
Abstract #8106; Poster Board #R14; Lung Cancer - Metastatic, May 30,
2:00
p.m.-6:00 p.m.

SOURCE Ascenta Therapeutics

Mike Beyer, Sam Brown Inc., +1-773-463-4211, beyer@sambrown.com