Synta Announces Launch of Proprietary Small Molecule Hsp90-inhibitor Drug Conjugate Platform

  Synta Announces Launch of Proprietary Small Molecule Hsp90-inhibitor Drug
  Conjugate Platform

  – Novel drug conjugates that exploit Hsp90 biology to selectively deliver
                potent anti-cancer payloads to cancer cells –

– Over 350 HD-Conjugates developed, including HD-Conjugated Alimta®, Nexavar®,
       Paraplatin®, Revlimid®, Sutent®, Taxotere®, Velcade®, Zytiga® –

– Broad intellectual property platform; first IND expected in next 18 months –

     – Company to host conference call and webcast today at 5:00 PM EDT –

Business Wire

LEXINGTON, Mass. -- September 10, 2013

Synta Pharmaceuticals Corp. (NASDAQ: SNTA) today announced the launch of its
Hsp90-inhibitor Drug Conjugate (HDC) platform, which leverages the Company’s
expertise in chaperone biology and medicinal chemistry to create a new class
of anti-cancer therapies.

The need: delivering potent anti-cancer drugs directly to tumors

Current oncology therapeutics generally fall into two categories: cytotoxic
agents and molecularly targeted therapies. Cytotoxic agents are often broadly
active, but have the disadvantage of high toxicity caused by damage to normal
cells, which limits their utility. Drugs that target specific protein drivers
of cancer cell growth are generally more tumor selective, yet often lead to
tumor resistance via point mutations in their target (e.g. ALK, BRAF, EGFR
inhibitors) or activation of alternative signaling pathways (e.g., MEK, ERK,
or AKT upregulation).

Targeted delivery strategies, such as Antibody Drug Conjugates (ADCs), offer a
solution to these limitations by delivering potent anti-cancer payloads more
directly to tumors. HDCs offer many of the advantages of antibody-driven
targeted delivery with potentially broader applicability. Because of its
unique properties, Hsp90 (heat shock protein 90) may represent one of the most
compelling targets for delivering drug payloads to tumors.

HDCs exploit the preferential accumulation of Hsp90-inhibitors in tumors to
increase the selective delivery of anti-cancer payloads

Hsp90 is a chaperone protein required by many cancer cells to maintain the
stability and function of numerous proteins that drive cancer cell growth,
survival, and metastasis. Small molecule inhibitors of Hsp90, including
Synta’s drug candidate ganetespib as well as first-generation inhibitors such
as 17-AAG and its derivatives, are retained in tumors for as much as 20 times
longer than in blood or normal tissue [1, 2]. These properties are believed to
be due to overexpression of an active form of Hsp90 in cancer cells as
compared to normal tissues, and have been recently applied for tumor imaging
[3, 4].

HDCs are drugs consisting of an Hsp90 inhibitor (targeting moiety) joined to
an anti-cancer agent (payload) via a cleavable chemical linker optimized for
controlled release of payload drug inside cancer cells. Because HDCs are small
molecules, they diffuse into the cell passively, avoiding reliance on cell
surface antigens or transporters.

Essentially, the active Hsp90 in tumors acts as a magnet to attract the
Hsp90-inhibitor moieties in HDCs, bringing the entire HDC molecule
preferentially to tumors. This results in higher concentration and longer
duration of active payload drug inside cancer cells than occurs with standard
administration of unconjugated chemotherapy or other payloads. The enhanced
delivery creates the potential for greater cancer cell killing and reduced
side effects.

The Synta HDC platform and intellectual property: Over 350 HD-Conjugates
developed to date

Synta has developed over 350 HD-Conjugated chemotherapeutics, kinase
inhibitors, hormone therapies, immunomodulators, and epigenetic modifiers,
creating the potential for next-generation compounds in each of these
categories.

Proof-of-concept has been demonstrated in preclinical models of cancer,
showing both improved delivery, including greatly increased concentration and
duration of payload in tumors as compared to plasma and normal tissues, as
well as significantly improved anti-tumor activity compared to administration
of unconjugated payload.

HDCs are a promising new therapeutic class with the potential to enhance the
safety and efficacy of a wide range of small molecule anti-cancer drugs. The
portfolio of HDCs developed by Synta to date, using a broad range of
Hsp90-inhibitor moieties, cleavable linkers, and anti-cancer payloads,
includes:

                                  
Category                           Example synthesized HDCs
                                           HD-Conjugated bendamustine
Alkylating agents                  (Treanda®)
                                           HD-Conjugated temozolomide
                                           (Temodar®)
Anthracyclines                     HD-Conjugated doxorubicin
                                           (Adriamycin®)
Antimetabolites                    HD-Conjugated 5-FU (Xeloda®)
                                           HD-Conjugated pemetrexed (Alimta®)
Camptothecins                      HD-Conjugated SN-38 (Camptosar®)
                                           HD-Conjugated topotecan (Hycamtin®)
                                           HD-Conjugated vorinostat / SAHA
Epigenetic modifiers               (Zolinza®)
                                           HD-Conjugated panobinostat
                                           (Faridak®)
                                           HD-Conjugated fulvestrant
Hormonal therapy                   (Faslodex®)
                                           HD-Conjugated abiraterone (Zytiga®)
                                           HD-Conjugated lenalidomide
IMIDs                              (Revlimid®)
                                           HD-Conjugated pomalidomide
                                           (Pomalyst®)
Microtubule stabilizers            HD-Conjugated docetaxel (Taxotere®)
Platinums                          HD-Conjugated carboplatin
                                           (Paraplatin®)
Proteasome inhibitors              HD-Conjugated bortezomib (Velcade®)
Tyrosine Kinase Inhibitors         HD-Conjugated sunitinib (Sutent®)
                                           HD-Conjugated sorafenib (Nexavar®)
                                  

Broad intellectual property

Synta has filed worldwide patent applications that include comprehensive
claims covering the HDC platform, compositions of matter for the over 350
compounds noted above, methods for identifying therapeutically effective
compounds and methods of use of such compounds against a wide range of
diseases and conditions. Publication of the first patent filings is expected
within the next several weeks.

HDCs compared to other targeted delivery strategies

HDCs rely on the presence of active Hsp90 in tumors – which may lead to
broader application than ADCs, whose development has focused on cancers
uniquely expressing a surface antigen that can be targeted with an antibody
(e.g., HER2+ breast cancer) [5]. Another advantage of HDCs is that they can
achieve substantially higher payload concentrations inside cancer cells than
may be achieved with ADCs, due to differences in uptake mechanism (passive
diffusion vs. active uptake). HDCs can therefore deliver a much broader range
of payloads as compared to ADCs.

Partnering

The Synta HDC platform offers multiple partnering opportunities centered on
improved delivery of both approved and investigational anti-cancer agents,
across a broad range of oncology indications. Synta intends to realize the
breadth of application of this platform through a series of focused
pharmaceutical company partnerships.

HDC platform upcoming milestones

Synta expects the first patent filings covering the HDC platform to be
published in the next several weeks. The company anticipates a number of
scientific presentations and publications highlighting the potential of HDCs
in 2014, and expects one or more IND filings within the next 18 months.

“From the idea, to proof-of-concept and the creation of a broad platform with
strong intellectual property protection, our scientists have made tremendous
progress in creating an exciting, new class of anti-cancer therapies,” said
Safi R. Bahcall, Ph.D., President and CEO. “We are hopeful this platform can
lead to meaningful improvements over existing therapies, and ultimately to
better outcomes for patients.”

For further information on the Synta HDC platform, please click here.

Company to host conference call and webcast today, September 10, at 5:00 PM
EDT

Management will conduct a conference call at 5:00 p.m. (EDT) today to discuss
the launch of the new HDC drug technology platform. The conference call will
be webcast live and can be accessed by logging on to the Investors section of
the Synta Pharmaceuticals website, www.syntapharma.com.

Participants can also connect by phone by dialing (877) 407-8035 or (201)
689-8035 prior to the start of the call. A replay will be available from 8:00
p.m. (EDT) this evening through midnight (EDT) on September 17. To access the
replay, dial (877) 660-6853 or (201) 612-7415 and refer to conference ID
420728.

References

1. J.L. Eiseman et al. Cancer Chemother Pharmacol. 2005 Jan;55(1):21-32
2. K.P. Foley et al. AACR-NCI-EORTC Conference 2009 (abstr #C91)
3. G. Chiosis, L. Neckers, ACS chemical biology. 2006;1(5):279-284
4. J. F. Gerecitano et al., J Clin Oncol 31, 2013 (suppl; abstr 11076)
5. B. A. Teicher and R. V. J. Chari, Clin Canc Res 2011; 17: 6389-6397

About Ganetespib

Ganetespib, an investigational drug candidate, is a selective inhibitor of
heat shock protein 90 (Hsp90), a molecular chaperone which controls the
folding and activation of a number of client proteins that drive tumor
development and progression. Many solid and hematologic tumors are dependent
on Hsp90 client proteins including proteins involved in “oncogene addiction”
(ALK, HER2, mutant BRAF and EGFR, androgen receptor, estrogen receptor, JAK2);
proteins involved in resistance to chemotherapy and radiation therapy (ATR,
BCL2, BRCA1/2, CDK1/4, CHK1, survivin, and WEE1); proteins involved in
angiogenesis (HIF-1alpha, VEGFR, PDFGR, and VEGF); and proteins involved in
metastasis (MET, RAF, AKT, MMPs, HIF-1alpha, and IGF-1R). In preclinical
models, inhibition of Hsp90 by ganetespib results in the inactivation,
destabilization, and eventual degradation of these cancer-promoting proteins.
Ganetespib is being evaluated in trials in lung cancer, breast cancer, and
other tumor types. 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 these trials can be found at
www.clinicaltrials.gov.

About Synta Pharmaceuticals

Synta Pharmaceuticals Corp. is a biopharmaceutical company focused on
discovering, developing, and commercializing small molecule drugs to extend
and enhance the lives of patients with severe medical conditions, including
cancer and chronic inflammatory diseases. Synta has a unique chemical compound
library, an integrated discovery engine, and a diverse pipeline of clinical-
and preclinical-stage drug candidates with distinct mechanisms of action and
novel chemical structures. All Synta drug candidates were invented by Synta
scientists using our compound library and discovery capabilities. For more
information, please visit www.syntapharma.com.

Safe Harbor Statement

This media release may contain forward-looking statements about Synta
Pharmaceuticals Corp. Such forward-looking statements can be identified by the
use of forward-looking terminology such as "will", "would", "should",
"expects", "anticipates", "intends", "plans", "believes", "may", "estimates",
"predicts", "projects", or similar expressions intended to identify
forward-looking statements. Such statements, including statements relating to
the timing of patent publications, scientific publications and presentations
covering the HDC platform, the plans relating to HDC partnerships, and the
timing of IND filings for HDC drug candidates, reflect our current views with
respect to future events and are based on assumptions and subject to risks and
uncertainties that could cause actual results to differ materially from those
expressed or implied by such forward-looking statements, including those
described in "Risk Factors" of our Form 10-K for the year ended December 31,
2012 as filed with the Securities and Exchange Commission. Synta undertakes no
obligation to publicly update forward-looking statements, whether because of
new information, future events or otherwise, except as required by law.

Contact:

Synta Pharmaceuticals Corp.
George Farmer, 781-541-7213
gfarmer@syntapharma.com
or
Argot Partners
Andrea Rabney, 212-600-1494
andrea@argotpartners.com
 
Press spacebar to pause and continue. Press esc to stop.