Kosan's Lead Hsp90 Inhibitor, Tanespimycin, Shows High Level of Activity in Trastuzumab Resistant/Refractory HER2-Positive Breast Cancer in a Phase 2 TrialData Presented at ASCO Show 26% Partial Response, 63% Clinical Benefit Incidence
HAYWARD, Calif., June 03, 2008 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated today announced that its lead Hsp90 inhibitor, tanespimycin, demonstrated a high level of antitumor activity in a Phase 2 trial when administered in combination with trastuzumab (Herceptin(R)) to patients with HER2-positive metastatic breast cancer whose disease had either progressed after, or did not respond to, treatment with trastuzumab immediately prior to entering the trial. Of 27 evaluable patients, 17 patients showed clinical benefit including 7 patients with partial response (PR), 5 patients with tumor regression (minor response or MR) and 5 patients with extended stable disease (SD, greater than 4 cycles), yielding an overall clinical benefit incidence of 63%. Common toxicities were mainly mild to moderate and included fatigue and gastrointestinal symptoms.
Updated data from the Phase 2 trial were presented in a poster titled, "Phase 2 trial of the Hsp90 inhibitor tanespimycin (Tan) + trastuzumab (T) in patients (pts) with HER2-positive metastatic breast cancer (MBC)," by Shanu Modi, M.D., of Memorial Sloan-Kettering Cancer Center, at the 44th American Society of Clinical Oncology (ASCO) Annual Meeting being held in Chicago, IL.
"The response data from this Phase 2 trial of tanespimycin plus trastuzumab have grown stronger as more patients have been treated, underscoring our observation that tanespimycin is a highly active and tolerable agent in patients whose disease is refractory to trastuzumab," said Clifford A. Hudis, M.D., Chief, Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, and senior author on the poster. "We look forward to seeing tanespimycin advance into its next set of clinical trials with the goal of elucidating its potential role in the metastatic breast cancer treatment paradigm."
"Tanespimycin is the most advanced Hsp90 inhibitor in development for HER2-positive breast cancer and has generated what we believe is highly promising data in this indication," said Pamela Cohen, M.D., Kosan's Chief Medical Officer. "We believe that Hsp90 inhibition is among the most novel and broadly applicable anticancer targets being explored today, and that it may have broad applicability in breast cancer and other cancer indications."
Phase 2 Tanespimycin Data
Tanespimycin is an Hsp90 inhibitor that has demonstrated the potential to disrupt the activity of multiple oncogenes and cell signaling pathways implicated in tumor growth, including HER2, a key pathway in breast cancer.
The objective of the Phase 2 trial is to determine the objective response rate by RECIST in patients with HER2-positive metastatic breast cancer. To be eligible for the trial, patients must have had either progressive disease within 3 months following last dose of adjuvant treatment with trastuzumab or have progressive disease following initial therapy for metastatic disease with trastuzumab (trastuzumab may have been administered with cytotoxic chemotherapy or as a single agent). Tanespimycin was administered at a dose of 450 mg/m2 following administration of the standard dose of trastuzumab.
Of 31 patients enrolled in the trial, 27 were evaluable for efficacy (as of May 15, 2008).
-- Of the 27 patients evaluable for efficacy, 17 (63%) showed evidence of clinical benefit, including: -- 7 patients or 26% had PR (including 1 patient with an unconfirmed PR who remains on study) -- 5 patients or 19% had tumor regressions (20-29% decrease) -- 5 patients or 19% had SD of 4 or more cycles (4 week cycle)
Antitumor activity and toxicity were similar between the Injection and Injectable Suspension products.
-- Of the 31 patients enrolled, 21 were treated with Kosan's Injection product (Cremophor(R)-containing formulation and 10 were treated with Kosan's Injectable Suspension product (contains no Cremophor). In addition, 4 of the patients treated initially with the Injection formulation crossed over to receive the Injectable Suspension formulation. -- For the Injection product: 18 were evaluable and 11 responded (4 PR, 4 tumor regressions, 3 SD), yielding a PR response rate of 22% and a clinical benefit incidence of 61%. -- For the Injectable Suspension product: 9 were evaluable and 6 responded (3 PR, 1 tumor regression, 2 SD), yielding a PR response rate of 33% and a clinical benefit incidence of 67%. -- Patients with an objective response on the Injection product maintained their objective response after crossover to the Injectable Suspension product.
Tanespimycin plus trastuzumab was highly tolerable at the recommended Phase 2 dose of 450 mg/m2 weekly. Common toxicities were mainly mild-to-moderate diarrhea, fatigue, nausea, headache and vomiting (limited duration and amenable to supportive care). The few drug-related Grade 3 and 4 toxicities (including fatigue, increased AST and headache, two patients each) were manageable and only one patient discontinued treatment for an adverse event. Noticeably absent were toxicities common to cytotoxic chemotherapy including alopecia and myelosuppression. The Injectable Suspension product provided considerable advantages over the Injection product, including shorter time of infusion, no need for steroid or antihistamine premedications and ease of pharmacist preparation.
Kosan anticipates conducting additional studies with tanespimycin with the goal of further characterizing the drug candidate's safety and efficacy profile and potentially paving the way to a registration program. Patients currently enrolled in the ongoing Phase 2 trial of tanespimycin plus trastuzumab will continue on study per protocol. Kosan does not plan to enroll additional patients in this trial.
Kosan Biosciences is a biotechnology company advancing two new classes of anticancer agents through clinical development -- a Hsp90 (heat shock protein 90) inhibitor and an epothilone. 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 Velcade(R) (bortezomib) in patients with multiple myeloma in a clinical program called TIME. Tanespimycin is also being studied in HER2-positive metastatic breast cancer in combination with Herceptin(R) (trastuzumab). KOS-1584 epothilone product candidate is in a Phase 2 clinical trial in patients with non-small cell lung cancer. Kosan's epothilone program is licensed to Bristol-Myers Squibb. Kosan's motilin agonist compound, KOS-2187, licensed to Pfizer for development in gastroesophagel reflux disease, is in a Phase 1 trial. Kosan recently agreed to be acquired by Bristol-Meyers Squibb.
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, commercial potential and other characteristics of Kosan's product candidates; the continuation of current clinical trials; the initiation of additional clinical trials and the timing thereof and the use of Kosan's financial resources. Words such as "will," "expect," "believe," "may," "intend," "plan," "potential" and similar expressions are intended to identify forward-looking statements. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. These forward-looking statements are based upon Kosan's current expectations. Forward-looking statements involve risks and uncertainties. Kosan's actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, the risk that the acquisition of Kosan by Bristol-Myers Squibb may not be consummated as the transaction is subject to certain closing conditions, risks related to the uncertain progress and results of Kosan's preclinical and clinical testing, including the risks that studies and trials may not demonstrate safety and efficacy sufficient to initiate clinical trials on the timing currently anticipated, or at all, continue clinical development, obtain the requisite regulatory approvals or result in a marketable product; the conduct of clinical trials; manufacturing; regulatory approval requirements and process; the effort and expense necessary for further development of Kosan's product candidates, including the costs of bortezomib; intellectual property matters, including Kosan's ability to obtain valid and enforceable patents covering its product candidates; Kosan' dependence on it license with Bristol-Myers Squibb to develop its epothilone products in order for Kosan to receive milestones or royalties, Kosan's dependence on its collaboration with Pfizer for development of its motilin agonist product candidate; Kosan's need for additional financing and Kosan's strategy to enter into partnering or licensing arrangements. These and other risk factors are discussed under "Risk Factors" in Kosan's Annual Report on Form 10-K for the year ended December 31, 2007 and other periodic filings with the SEC. Kosan expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein.
Velcade(R) (bortezomib) is a registered trademark of Millennium Pharmaceuticals, Inc.
Herceptin(R) (trastuzumab) is a registered trademark of Genentech, Inc.
Cremophor(R) is a registered trademark of BASF Corporation
Posted: June 2008