Kosan Initiates Phase 2 Trial of Alvespimycin, Second-Generation Hsp90 Inhibitor,...

Kosan Initiates Phase 2 Trial of Alvespimycin, Second-Generation Hsp90
Inhibitor, in HER2-Positive Metastatic Breast Cancer

HAYWARD, Calif., Jan. 15 /PRNewswire-FirstCall/ -- Kosan Biosciences
Incorporated (Nasdaq: KOSN) today announced the initiation of a Phase 2 trial
of alvespimycin, the company's second-generation Hsp90 inhibitor, in patients
with HER2-positive metastatic breast cancer. Alvespimycin has demonstrated the
potential to disrupt the activity of multiple oncogenes and cell signaling
pathways implicated in tumor growth, including HER2, a key signaling pathway
in breast cancer. The objective of the Phase 2 trial is to evaluate the safety
and anticancer activity of alvespimycin as a single agent in patients who have
not previously received Herceptin for metastatic disease except in an adjuvant
setting. Antitumor data in patients with advanced HER2-positive cancer
presented at the September 2007 American Society of Oncology (ASCO) Breast
Cancer Symposium demonstrated encouraging antitumor activity of alvespimycin
in combination with trastuzumab (Herceptin(R)).
"HER2-positive metastatic breast cancer represents a major market
opportunity for Kosan that we intend to pursue," said Robert G. Johnson, Jr.,
M.D., Ph.D., Kosan's President and Chief Executive Officer. "We believe that
emerging safety and efficacy data from our clinical trials in this indication
with both of our Hsp90 inhibitors and the demonstrated activity in refractory
disease represent a meaningful therapeutic opportunity. We believe that
characterization of the single-agent activity of an Hsp90 inhibitor in
HER2-positive metastatic breast cancer will provide valuable information to
support the design of later-stage trials."
Alvespimycin Phase 2 Development Plan
The single-agent trial of alvespimycin will be conducted in Eastern Europe
and will recruit up to 30 patients in a two-stage trial design. Patients with
HER2-positive metastatic disease and no prior trastuzumab treatment except as
adjuvant therapy (with the last dose more than 12 months prior to study entry)
are eligible to participate in the trial. Alvespimycin will be administered
intravenously on a one-hour weekly infusion schedule of 80 mg/m2 for three
weeks out of four weeks in repeated cycles.
Kosan is also testing alvespimycin delivered orally in a Phase 1 dose
escalation trial exploring different schedules.
Promising Antitumor Activity Shown in Phase 1
In September, at the 2007 ASCO Breast Cancer Symposium, Kosan reported
that alvespimycin demonstrated promising antitumor activity and tolerability
in combination with trastuzumab in a Phase 1 trial of patients with refractory
HER2-positive metastatic breast cancer, and in patients with refractory
ovarian cancer who were progressing on standard chemotherapy. Of the 27
heavily-pretreated patients enrolled in the Phase 1 trial, 24 patients had
HER2-positive metastatic breast cancer and 3 patients had ovarian cancer (HER2
status unknown). Clinical benefit was observed in 42% of patients (8 of 19
evaluable) with HER2-positive metastatic breast cancer. Of the 3 patients with
ovarian cancer, 1 patient (13 prior regimens) who was on study for more than
16 months had a near complete resolution of ascites and left pleural effusion,
and an 83% decrease in CA125. Toxicities in this Phase 1 trial were mainly
Grade 1 and 2 (diarrhea, fatigue, headache, arthralgia, nausea) with 80 mg/m2
established as the recommended Phase 2 dose for weekly intravenous
administration. Kosan is currently enrolling a Phase 1 trial to investigate
alvespimycin plus trastuzumab and paclitaxel to establish the initial safety
profile and pharmacokinetics of this triplet regimen and to lay the groundwork
for a potential larger Phase 2/3 trial.
About Kosan
Kosan Biosciences is a biotechnology company advancing two new classes of
anticancer agents through clinical development -- Hsp90 (heat shock protein
90) inhibitors and epothilones. Kosan is leveraging its proprietary discovery
platform to generate a pipeline of potentially significant product candidates,
primarily in the area of oncology.
Hsp90 inhibitors have a novel mechanism of action targeting multiple
pathways involved in cancer cell growth and survival. Tanespimycin (KOS-953)
is being tested in combination with bortezomib (Velcade(R)) in patients with
multiple myeloma in a registration program called TIME. Tanespimycin is also
being studied in a Phase 2 trial in HER2-positive metastatic breast cancer in
combination with trastuzumab (Herceptin(R)), and as monotherapy in metastatic
melanoma. Kosan's second-generation Hsp90 inhibitor, alvespimycin (KOS-1022),
is being evaluated in a Phase 1 trial in solid tumors in combination with
trastuzumab and paclitaxel (Taxol(R)) and in a Phase 2 trial as monotherapy in
HER2-positive metastatic breast cancer (intravenous) and in a Phase 1 trial in
solid tumors (oral).
Epothilones inhibit cell division with a mechanism of action similar to
taxanes, one of the most successful classes of anti-tumor agents. KOS-1584 is
in Phase 1 clinical trials in patients with solid tumors.
Kosan's motilin agonist compound, KOS-2187, licensed to Pfizer, is in a
Phase 1 safety trial, with plans to pursue development in gastroesophageal
reflux disease (GERD).
For additional information on Kosan Biosciences, please visit the
company's website at http://www.kosan.com.
This press release contains forward-looking statements within the meaning
of the "safe harbor" provisions of the Private Securities Litigation Reform
Act of 1995 (the "Act"). Such forward-looking statements include but are not
limited to statements regarding the further development and potential safety,
efficacy, regulatory status, commercialization and other characteristics of
Kosan's product candidates; and the opening or initiation of additional
clinical trials and the timing thereof. Any statements contained in this press
release that are not statements of historical fact may be deemed to be
forward-looking statements. There are a number of important factors that could
cause the results of Kosan to differ materially from those indicated by these
forward-looking statements, including, among others, risks related to the
development of Kosan's product candidates, including the risk that studies may
not accrue patients on a timely basis, demonstrate safety and efficacy
sufficient to design or initiate clinical trials, continue clinical
development, obtain the requisite regulatory approvals or to result in a
marketable product; the costs of conducting preclinical and clinical studies
for Kosan's product candidates; Kosan's ability to obtain valid and
enforceable patents covering its product candidates; Kosan's dependence on its
collaboration with Pfizer for development of its motilin agonist product
candidate; Kosan's dependence upon the formation and sustainability of
partnering arrangements and other risks detailed from time to time in the
Kosan's SEC reports, including its Quarterly Report on Form 10-Q for the
quarter ended September 30, 2007 and other periodic filings with the SEC.
Kosan does not undertake any obligation to update forward-looking statements.
Velcade(R) (bortezomib) is a registered trademark of Millennium
Pharmaceuticals, Inc.
Herceptin(R) (trastuzumab) is a registered trademark of Genentech, Inc.
Taxol(R) (paclitaxel) is a registered trademark of Bristol-Myers Squibb
Company
SOURCE Kosan Biosciences Incorporated

Jane Green, VP, Corporate Communications of Kosan Biosciences Incorporated,
+1-510-731-5335, mobile, +1-415-652-4819, green@kosan.com