>>PALO ALTO, Calif., April 9 /PRNewswire-FirstCall/ --
Telik, Inc. (Nasdaq: TELK) announced a series of preclinical studies of its
TLK286 product candidate, currently in a Phase 3 registration trial for
ovarian cancer, and in clinical trials in non-small cell lung, breast and
colorectal cancer. The studies were published in the March 2003 Proceedings of
the Annual Meeting of the American Association for Cancer Research.
TLK286 is a prodrug which is administered in an inactive form. It is
activated in cancer cells by GST P1-1, an enzyme present in higher levels in
important cancers including ovarian, lung, breast, colorectal, pancreas and
lymphoma, than in normal tissue. In previous studies, Telik scientists have
reported that TLK286 induces cancer cell death via the stress response
signaling pathway. New preclinical data published on TLK286 include:
-- TLK286-induced activation of the stress response apoptotic signaling
pathway: confirmation of novel antitumor mechanism of action
(Abstract # 2643). TLK286 toxicity to cancer cells increases in a
time- and dose-dependent manner after it is cleaved by GST P1-1.
Using an analog of TLK286 that could not be cleaved by GST P1-1,
Telik scientists demonstrated that the non-cleavable analog was
inactive, and therefore that cleavage is required for TLK286
activation and subsequent cancer cell killing. This result supports
the premise that the selective activation of TLK286 within cancer
cells contributes to the generally mild side effect profile and
antitumor activity of TLK286 seen in clinical trials.
-- Enhanced antitumor activity of TLK286 in combination with
oxaliplatin, carboplatin, doxorubicin, paclitaxel and docetaxel in
human colorectal, ovarian, non-small cell lung and breast cancer
cell lines (Abstract # 1722). Human cancer cell lines were treated
with TLK286 in combinations with several important chemotherapeutic
drugs. The studies consistently demonstrated enhanced or synergistic
cancer cell growth inhibition. For example, treatment of a
colorectal cancer cell line with TLK286 and oxaliplatin resulted in
a fifteen-fold increase in growth inhibition compared to the sum of
either agent alone. These data, and the mild, non-overlapping
toxicities seen in clinical trials of TLK286, suggest that
combinations may be appropriate and provide scientific support for
ongoing clinical trials using TLK286 in regimens with docetaxel,
carboplatin and doxorubicin (Doxil(R)).
-- Sensitization of a human cancer cell line to paclitaxel following
prolonged treatment with TLK286 (Abstract # LB123). Following up on
the combination studies, Telik scientists examined the effects of
prolonged exposure of human ovarian cancer cells to TLK286. TLK286
exposure was associated with enhanced sensitivity of the cancer
cells to taxanes, an important class of chemotherapeutic drugs.<<
>>PALO ALTO, Calif., April 9 /PRNewswire-FirstCall/ --
Telik, Inc. (Nasdaq: TELK) announced positive interim results from the ongoing
Phase 1-2a clinical trial of its TLK199 product candidate in patients with
myelodysplastic syndrome (MDS), a form of pre-leukemia. The abstract for the
study was published in the March 2003 Proceedings of the Annual Meeting of the
American Association for Cancer Research (AACR).
The open label, multicenter dose escalation trial is designed to evaluate
safety, pharmacokinetics, pharmacodynamics and efficacy. Twelve MDS patients
had been enrolled in the dose-escalation stage of the trial at the time of
interim analysis. TLK199 has been well-tolerated, and the maximum tolerated
dose has not been reached.
Evidence of clinical activity has been observed in 50% of evaluable
patients. All responders showed clinically significant increases in at least
two of the three major blood elements (white cells, red cells and platelets),
with one patient showing increases in all three elements. This patient also
had a significant decrease in red cell transfusion requirements, an important
clinical benefit. In addition, one patient with a particularly advanced type
of MDS had a decrease in levels of pre-leukemic cells, consistent with a
direct anti-proliferative effect of TLK199.
"These interim results suggest that TLK199 may act at a point in the bone
marrow differentiation cycle that affects the subsequent development of all
three major blood elements," said Gail L. Brown, M.D., senior vice president
and chief medical officer. "Clinical activity has been seen even at the lowest
dose levels, and these exciting preliminary findings are being further
explored as the dose escalation continues."<<
snipped the about & forward looking stuff
Chers, Tuck |
