“This past year Synta made substantial progress in developing ganetespib
– including demonstrating clinical activity in certain types of lung and
breast cancer; reinforcing the differentiated, favorable safety profile;
and initiating a comprehensive development plan that allows for multiple
paths to registration with important data readouts in 2012,” said
Over 500 patients have been treated to date in clinical trials with ganetespib. The most common adverse event seen with ganetespib has been mild to moderate diarrhea, which has been transient and manageable with standard supportive care. There has been no evidence of the common ocular toxicities and serious liver toxicities reported with some other Hsp90 inhibitors; or the neurotoxicity, bone marrow toxicities, or alopecia characteristic of many chemotherapies.
“We are particularly excited that ganetespib has the potential to be the first compound to realize the therapeutic potential of chaperone inhibition,” continued Dr. Bahcall. “This is an entirely distinct approach to interrupting cancer cell signaling than either directly inhibiting a kinase with a small molecule, or directly binding a growth factor with a monoclonal antibody. We are hopeful that ganetespib can provide a new approach to treating cancer, which is different than, and potentially complementary to kinase inhibitors, monoclonal antibodies, and chemotherapy.”
Synta is currently initiating a global clinical trial in patients with
advanced non-small cell lung cancer whose tumors show an ALK gene
rearrangement (ALK+ NSCLC), and a global clinical trial in patients with
breast cancer whose tumors show either a HER2+ or triple-negative
genetic profile. The GALAXY trial – a Phase 2b/3 trial evaluating
ganetespib in combination with docetaxel vs. docetaxel alone in patients
with advanced lung cancer who have progressed following one prior
treatment – was initiated in 2011 and is currently enrolling patients in
the U.S. and
Ganetespib is a potent inhibitor of heat shock protein 90 (Hsp90) that is structurally unrelated to first-generation, ansamycin-family Hsp90 inhibitors such as 17-AAG, 17-DMAG and IPI-504.
Ganetespib Clinical Update
Highlights of Recent Ganetespib Results and 2011 Achievements
Activity in ALK+ NSCLC
Results presented at
ASCOin 2011 showed a 50% (4/8) objective response rate and 88% (7/8) disease control rate following treatment with ganetespib monotherapy (single-agent) in patients with advanced ALK+ NSCLC. These patients had previously failed to respond to, or progressed following treatment with, multiple prior treatments for advanced NSCLC, including combination chemotherapy. Responses were durable, with patients remaining on treatment an average of approximately one year.
- Preclinical results demonstrated that ganetespib activity is complementary to direct ALK inhibition (e.g. crizotinib) – suggesting promising potential for combination treatment in ALK+ NSCLC patients.
- Results presented at
Activity in breast cancer
Ganetespib is the first Hsp90 inhibitor to show single-agent
activity in breast cancer. Results presented at the
San AntonioBreast Cancer Symposium in 2011 showed encouraging anti-tumor activity in both HER2+ and triple-negative breast cancer.
- Ganetespib is the first Hsp90 inhibitor to show single-agent activity in breast cancer. Results presented at the
- Over 500 patients have been treated to date in trials with ganetespib. Results from ongoing safety reviews are consistent with previously reported findings: absence of the common ocular toxicities and serious liver toxicities seen with other Hsp90 inhibitors; and an absence of the neurotoxicity, bone marrow toxicities, or alopecia characteristic of chemotherapy. The most common adverse event seen with ganetespib has been transient, mild to moderate diarrhea, which has been manageable with standard supportive care.
- Synta scientists published preclinical results of physicochemical properties of ganetespib believed to contribute to the improved safety and activity profile seen relative to other Hsp90 inhibitors. These include smaller molecular weight, greater potency, greater lipophilicity, ability of ganetespib to enter the ATP binding pocket of Hsp90 in either the open- or closed-pocket lid conformation, ability of ganetespib to penetrate deep into tumor tissues, absence of the benzoquinone moiety in ganetespib’s molecular structure, and reduced accumulation in the retina.
Synergy with other anti-cancer agents
- Hsp90 is believed to be critical for cancer cells’ abilities to recover or resist a range of stresses – including those induced by certain chemotherapeutic and targeted agents. Synta scientists and collaborators published preclinical results showing synergistic activity of ganetespib with paclitaxel, docetaxel, cisplatin, carboplatin, PI3K/mTOR inhibitors, MEK inhibitors, HER2 inhibitors, and other widely used agents.
Parallel paths to registration
- Designed and initiated a comprehensive clinical plan that can potentially lead to seven or more separate paths to registration, with meaningful data readouts expected in 2012.
- The GALAXY trial de-risks the path to registration in second-line lung cancer through a two-stage Phase 2b/3 design – using the biomarker and subpopulation results, as well as operational experience, gained in the first-stage, 240-patient Phase 2b portion, to de-risk the second-stage, Phase 3 portion.
- Identified targeted patient populations, such as ALK+ NSCLC, HER2+ breast cancer, and triple-negative breast cancer with encouraging single-agent activity.
- Designed and initiated a development plan in these targeted patient populations that offers complementary paths to registration to the populations being evaluated in the GALAXY trial.
- Built third-party support for additional proof-of-concept trials in lung cancer, breast cancer, colon cancer, prostate cancer, melanoma, AML, and multiple myeloma already initiated, or expected to initiate in 2012.
Scientific and medical community awareness
- Over 15 investigator-sponsored, foundation-sponsored, or cooperative-group sponsored trials already initiated or expected to initiate in 2012.
Expected 2012 Ganetespib Milestones
GALAXY trial: Phase 2b/3 trial evaluating ganetespib in combination
with docetaxel vs. docetaxel alone in patients with advanced NSCLC who
have progressed following one prior treatment for metastatic disease
- Complete enrollment of 240-patient, first-stage Phase 2b portion in Q2
- Interim Phase 2b results in Q2
- Final PFS data and preliminary OS data from Phase 2b portion in 2H
- Initiate Phase 3 portion in 2H, based on results from Phase 2b
ALK+ trial: monotherapy ganetespib treatment in advanced NSCLC
patients previously untreated with ALK inhibitor
- Preliminary results by year-end
Breast cancer trial: HER2+ and triple-negative breast cancer patients
- Preliminary results by year-end
Investigator, foundation, or cooperative group trials initiating in
- Trial in combination with crizotinib in ALK+ NSCLC
- Trial in combination with paclitaxel and Herceptin® in HER2+ breast cancer, and in combination with paclitaxel in triple-negative breast cancer
- Trial in combination with Velcade® in multiple myeloma
- Trial in combination with radiotherapy in rectal cancer
- Randomized trial in elderly patients with acute myeloid leukemia in combination with the chemotherapy drug ara-C
“We have worked closely with investigators over the past year to develop
a diversified, risk-mitigated registration plan,” said Dr.
Additional Programs at Synta
In addition to progress with our ganetespib program in 2011, we also
made significant progress with our elesclomol and CRAC programs. For our
elesclomol program we published preclinical results demonstrating that
elesclomol triggers cancer cell apoptosis by disrupting mitochondrial
energy metabolism, potentially establishing elesclomol as a leading
compound in the emerging field of anti-cancer therapies targeting cancer
cell metabolism. We also continued development of elesclomol in patients
with advanced ovarian cancer, in a trial being conducted by the
Please go to www.syntapharma.com for additional details.
Fourth Quarter and Full Year 2011 Financial Results
In the fourth quarter of 2011, Synta recognized total revenue of
Research and development expenses were
General and administrative expenses were
The Company reported a net loss of
In January and
More detailed financial information and analysis may be found in the
Company's Annual Report on Form 10-K, which was filed with the
Based on our current operating levels, the Company expects its cash
resources, including the
Management will conduct a conference call at
The call also can be accessed by dialing (877) 407-8035 or (201)
689-8035 prior to the start of the call. For those unable to join the
live conference call, a replay will be available from
Ganetespib (formerly STA-9090) is a potent, synthetic, small-molecule inhibitor of heat shock protein 90 (Hsp90). Hsp90 is a molecular chaperone required for the proper folding and activation of many cancer-promoting proteins, and is recognized as a key facilitator of cancer cell growth and survival. In preclinical experiments, ganetespib has shown activity in multiple tumor models both as a single agent and in combination with certain widely used cancer agents. Ganetespib is currently being evaluated in a broad range of cancer clinical trials. In these trials, ganetespib has shown clinical activity in heavily pretreated patients and has been well tolerated to date with no evidence of severe liver or common ocular toxicities seen with other Hsp90 inhibitors. The most common adverse event seen to date has been transient, mild or moderate diarrhea, which has been manageable with standard supportive care. Information on clinical trials with ganetespib can be found at www.clinicaltrials.gov.
About the Phase 2b/3 GALAXY TrialTM in NSCLC
The Phase 2b/3 trial will evaluate treatment with ganetespib and docetaxel vs. docetaxel alone, with 1:1 randomization, in patients with Stage IIIB or IV NSCLC who have completed one prior systemic therapy for advanced disease. The first stage, Phase 2b portion, will assess efficacy as measured by progression-free survival in approximately 240 patients. Results from this stage will also be used to inform the choice of patient subpopulation, by histology or biomarker, or other disease characteristic for the second stage, Phase 3 portion. The second stage will enroll between 400 and 600 patients. Interim results from the first-stage portion of the trial are expected in Q2 2012. More information on the trial can be found at www.clinicaltrials.gov.
About Non-small Cell Lung Cancer
Lung cancer is the leading cause of cancer-related mortality in
Safe Harbor Statement
This media release may contain forward-looking statements about
Synta Pharmaceuticals Corp.
Three Months Ended
Twelve Months Ended
|License and milestone revenue||$||3,302||$||1,143||$||6,731||$||4,572|
|Cost sharing reimbursements, net||—||1,916||—||
|Total collaboration revenues||3,302||3,059||6,731||13,825|
|Research and development||10,859||9,347||41,464||40,252|
|General and administrative||
|Total operating expenses||13,662||12,402||53,016||51,701|
|Loss from operations||(10,239||)||(8,365||)||(45,432||)||(36,898||)|
|Interest expense, net||(504||)||(458||)||(1,948||)||(569||)|
|Basic and diluted net loss per common share||$||(0.22||)||$||(0.21||)||$||(1.00||)||$||(0.93||)|
|Basic and diluted weighted average number of|
|common shares outstanding||49,426,806||41,263,628||47,197,572||40,365,215|
Synta Pharmaceuticals Corp.
|December 31, 2011||December 31, 2010|
Cash, cash equivalents and
|Other current assets||561||547|
|Property and equipment, net||1,407||2,181|
|Other non-current assets||
Liabilities and Equity
Total liabilities and
Synta Pharmaceuticals Corp.
Rob Kloppenburg, 781-541-7125