“We continue to make strong progress in advancing our ganetespib program
along two parallel paths to registration: as a monotherapy in certain
targeted cancer patient populations, and in combination with
chemotherapy in a broader patient population,” said
Ganetespib is currently being evaluated in over 20 clinical studies, including trials enrolling genetically-defined targeted patient populations – such as ALK+ lung cancer, HER2+ breast cancer, and triple-negative breast cancer – and trials in combination with other anti-cancer agents, such as the GALAXY trial, which evaluates ganetespib plus docetaxel vs. docetaxel alone for the second-line treatment of advanced non-small cell lung cancer.
The safety profile of ganetespib has been favorable in over 600 patients treated to date. The most common adverse event reported with ganetespib has been transient, mild or moderate diarrhea, which can be prevented or effectively managed with standard supportive care. There has been no evidence of the neurotoxicity, bone marrow toxicities, and alopecia characteristic of many chemotherapies.
Preclinical studies have shown monotherapy administration of ganetespib can potently inhibit some well-known cancer-promoting oncogenes, such as ALK or HER2. In clinical trials as a monotherapy, ganetespib has demonstrated objective responses or anti-tumor activity in patients with ALK+ lung cancer, mutant BRAF lung cancer, mutant KRAS lung cancer, mutant KRAS gastric cancer, HER2+ breast cancer, triple-negative breast cancer, renal cancer, colorectal cancer, and melanoma.
Ganetespib also potently inhibits certain well-known mechanisms that drive drug-resistance, such as HIF-1alpha and cell-cycle and DNA-repair genes. In preclinical models, ganetespib has been shown to enhance the activity of commonly used anti-cancer agents including chemotherapies (docetaxel, paclitaxel, vincristine, pemetrexed, gemcitabine, cytarabine, carboplatin, cisplatin), hormone therapies (tamoxifen, fulvestrant), kinase inhibitors (temsirolimus, lapatinib, crizotinib, vemurafenib, selumetinib), and others (bortezomib, bevacizumab).
A recently announced interim analysis of the GALAXY lung cancer trial, evaluating the combination of docetaxel and ganetespib vs. docetaxel alone, showed encouraging improvements in PFS, ORR, and OS in the combination arm vs. the control arm. Trials of ganetespib in combination with a number of other agents have recently been initiated or are planned for later this year.
“We are excited by the potential benefit ganetespib may bring to patients,” continued Dr. Bahcall. “Our recently announced financing creates a strong financial foundation for supporting our plans for ganetespib.”
Key accomplishments in the second quarter 2012:
1. Completion of an interim analysis for the Phase 2b portion of the company’s Phase 2b/3 GALAXY trial in NSCLC.
a. A 2.5-3x increase in PFS in patients with elevated baseline serum LDH and PFS in patients with mutant KRAS, the co-primary endpoints of the study.
b. An overall survival improvement in patients with adenocarcinoma, a key secondary endpoint.
c. A favorable safety profile, consistent with previous findings.
d. Differential activity in patients with adenocarcinoma and squamous cell histologies, as has also been seen with anti-angiogenic agents such as VEGF inhibitors. This pattern is consistent with preclinical results demonstrating anti-angiogenic properties of ganetespib, including inhibition of VEGF production in cancer cells and reduction in tumor vascularization. The trial has been amended to enroll adenocarcinoma patients only.
2. Initiation of the Phase 2 CHIARA trial evaluating ganetespib monotherapy for the treatment of ALK+ NSCLC patients not previously treated with a direct ALK inhibitor such as crizotinib.
Design of this study was based on results of a Phase 2 lung cancer
trial, initially reported at
3. Initiation of the Phase 2 ENCHANT trial evaluating ganetespib monotherapy for the first-line treatment of metastatic HER2+ and triple-negative breast cancer.
Design of this study was based on positive results seen in earlier studies with ganetespib monotherapy in both HER2+ and triple-negative breast cancer patients. Evidence of anti-cancer activity in HER2+ disease has also been seen in preclinical and clinical studies with the first-generation Hsp90 inhibitor, 17-AAG.
4. Initiation of enrollment in several investigator-sponsored trials including:
a. A Phase 1/ 2 trial of ganetespib in combination with crizotinib for
treatment of ALK+ NSCLC being conducted at
b. A randomized Phase 2 trial of ganetespib in combination with
fulvestrant for treatment of hormone positive breast cancer being
conducted at the
c. A Phase 1 trial of ganetespib in combination with radiotherapy and
capecitabine for treatment of rectal cancer being conducted at the
d. A Phase 1/2 trial of ganetespib both as a single agent and in
combination with bortezomib for the treatment of multiple myeloma. This
is a multi-center trial being conducted in collaboration with the
5. Presentation of company sponsored studies at the 2012 meeting of the
a. Preclinical activity of ganetespib in ALK, ROS, and RET driven cancers: results showed potent single-agent activity against cancer lines resistant to direct ALK inhibitors, as well as synergistic activity of ganetespib and crizotinib in ALK+ tumor models
b. Ocular toxicity profiles of Hsp90 inhibitors: certain Hsp90 inhibitors have shown a high incidence of ocular toxicity in clinical trials; ganetespib and 17-AAG have not. Results showed that these other Hsp90 inhibitors accumulated in the retina and led to pronounced retinal damage in in vivo models, whereas ganetespib and 17-AAG did not.
c. Final results from the Phase 1b trial evaluating the ganetespib plus docetaxel combination, as used in the GALAXY trial, which demonstrated favorable safety.
As previously announced, Synta intends to complete a second interim
analysis of the Phase 2b portion of the GALAXY trial in Q3 2012. Results
are planned for presentation at the
Based on current estimates, Synta expects to complete enrollment of the 240-patient Phase 2b portion of the GALAXY trial in Q4 2012 and have final data from this portion of the study in the first half of 2013. Also based on current estimates, Synta expects preliminary results from the CHIARA and ENCHANT trials by the end of this year.
There were no revenues in the second quarter in 2012 compared to total
Research and development expenses were
More detailed financial information and analysis may be found in the
Company's Quarterly Report on Form 10-Q, which was filed with the
Based on our current operating levels, the Company expects its cash
resources of approximately
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 is a potent inhibitor of heat shock protein 90 (Hsp90) that is structurally unrelated to first-generation, ansamycin-related Hsp90 inhibitors. 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. Company-sponsored clinical trials with ganetespib include the Phase 2b/3 GALAXY Trial(TM) evaluating ganetespib in combination with docetaxel for second-line treatment of non-small cell lung cancer (NSCLC); the CHIARA(TM) trial, evaluating ganetespib monotherapy in ALK+ NSCLC; and the ENCHANT(TM) trial evaluating ganetespib monotherapy as first-line treatment for HER2+ and triple-negative metastatic breast cancer. In addition, ganetespib is being evaluated in investigator-sponsored trials including lung, breast, prostate, gastric, pancreatic, and colorectal cancers as well as melanoma, ocular melanoma, acute myeloid leukemia and multiple myeloma. 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 GALAXY Trial
The GALAXY (Ganetespib Assessment in Lung cAncer with docetaXel) trial is a randomized Phase 2b/3 trial comparing the combination of ganetespib and docetaxel versus docetaxel alone in patients with Stage IIIB/IV NSCLC who have received one prior systemic therapy. More information about the GALAXY trial can be found at www.clinicaltrials.gov (NCT01348126).
About the CHIARA Trial
The CHIARA (CHaperone Inhibition in Alk Rearranged lung cAncer) trial is a single arm, Phase 2 study evaluating ganetespib monotherapy in patients with Stage IIIB/IV non-small-cell lung cancer harboring an ALK gene rearrangement and who have not been previously treated with a direct ALK inhibitor. The primary endpoint of the study is objective response rate. A total of 110 patients are planned for accrual. More information about the CHIARA trial can be found at www.clinicaltrials.gov (NCT01562015).
Safe Harbor Statement
This media release may contain forward-looking statements about
|Synta Pharmaceuticals Corp.|
|Condensed Consolidated Statements of Operations|
|(in thousands, except share and per share amounts)|
Three Months Ended
Six Months Ended
|License and milestone revenue||$||—||$||1,143||$||—||$||2,286|
|Total collaboration revenues||—||1,143||—||2,286|
|Research and development||11,252||10,417||23,318||19,854|
|General and administrative||2,882||2,946||5,528||5,618|
|Total operating expenses||14,134||13,363||28,846||25,472|
|Loss from operations||(14,134||)||(12,009||)||(28,699||)||(22,975||)|
|Interest expense, net||(486||)||(493||)||(972||)||(928||)|
|Basic and diluted net loss per common share||$||(0.25||)||$||(0.26||)||$||(0.52||)||$||(0.53||)|
Basic and diluted weighted average number of
|Synta Pharmaceuticals Corp.|
|Condensed Consolidated Balance Sheets Data|
|June 30, 2012||December 31, 2011|
|Cash, cash equivalents and marketable securities||$ 44,656||$ 39,725|
|Other current assets||839||561|
|Property, plant and equipment, net||1,166||1,407|
|Other non-current assets||503||631|
|Liabilities and Equity|
|Current liabilities||$ 18,254||$ 15,148|
Total liabilities and
Synta Pharmaceuticals Corp.
George Farmer, 781-541-7125