Navigate the Synta Pharma SNTA Research Notes Pages
- Introduction (valuation, financials, outlooks, catalysts)
- Ganetespib - Background (HSP90, basic drug info, regulatory strategies and business development)
- Ganetespib - HSP90 inhibitor safety and toxicity (info on liver and ocular toxicities associated with this class of drugs)
- Ganetespib - NSCLC (lead programs in lung cancer including ALK+ group and combo w/ docetaxel)
- Ganetespib - Clinical Trials (complete list of trials in other indications and links to data presentations)
- Elesclomol & Pipeline (information about other drug candidates in the SNTA pipeline)
- HSP90 Inhibitors - learn more about targeting heat shock protein 90 and all inhibitors in development
- This cancer drug was previously SNTA's lead compound with promising randomized Phase 2b results in metastatic melanoma, a graveyard of drug development. However, the Phase 3 trial was discontinued because pts receiving elescomol had higher mortality. This was later found to be based on extremely poor outcomes in patients with high LDH due to the mechanism of action of the drug related to induction of oxidative stress. This drug was partnered with GSK for $50m upfront but they backed out after trial failure (no restrictions on future development but would owe GSK a low single digit royalty).
- This drug is unique in that it is not chemotherapy agent and does not target signal transduction. Instead it is part of the emerging cancer metabolism field and targets energy production, with LDH as a biomarker that has been validated in 3 randomized clinical trials
- When tumors are in hypoxic (low oxygen) conditions, mitochondria are inactive, and LDH is detected in bloodstream. These high LDH patients do not respond to elescomol
- 2010 10k: "With respect to elesclomol, we have 2 issued U.S. patents that claim the chemical structure of elesclomol that expire no earlier than 2022. Both of these issued U.S. patents also claim related chemical structures, pharmaceutical compositions, and methods for treating a subject with cancer. In addition, we have an issued U.S. patent claiming the salt form of elesclomol that expires no earlier than 2025."
- Data regarding the mechanism of action were presented at AACR in April 2011 (click for link) - press release mentions LDH and TRX-1 as biomarkers that will be used to select pts in future trials
- New trials are beginning to be initiated in other cancers in low-LDH patients
- Phase 2 open label combination with paclitaxel in persistent or recurrent ovarian cancer sponsored by NCI ($0.3m support) and initiated February 2011 (NCT00888615, 4/2011 active and recruiting pts, targets up to 50 patients w/ LDH <0.8x ULN)
- Phase 1 monotherapy in AML initiated 1/2011- up to 36 pts with low LDH (<0.8x ULN) treated once weekly starting at 200 mg/m2 (NCT01280786, 4/2011 active and recruiting pts)
- 2/2011: First-line multinational randomized phase 2b trial in NSCLC pts w/ low to normal LDH will begin 2q2011. 4q2010 conference call: start first with a dose ranging portion, and then the randomized portion will start in 4q2011 (so relatively little expense in 2011)
CRACM ion channel inhibitors program
- Preclinical program for autoimmune diseases, transplant, and respiratory conditions (2010 10k)
- 2010 10k: "The CRACM ion channel is the primary route for calcium entry into T cells and other immune cells, regulating multiple immune cell processes important for initiating and maintaining an inflammatory immune response. CRACM channels regulate the calcium signaling pathway driving immune cell activation and secretion of TNFalpha, IL-2, and other inflammatory factors. The therapeutic importance of inhibiting this calcium signaling pathway has been demonstrated through clinical experience with calcineurin inhibitors, such as cyclosporine, which are potent immunomodulators but have significant toxicities due to the broad role calcineurin plays in nonimmune cells. In contrast to calcineurin, CRACM channels are believed to be critical exclusively to immune cell function. CRACM inhibitors therefore have the potential to achieve potent anti-inflammatory activity with an improved safety profile, creating the potential for a new category of disease-modifying agents comparable to biologic agents, such as TNF-alpha inhibitors, but orally available."
- This preclinical program was partnered with Roche for $16m upfront, but Roche let research program expire year-end 2010, they had been funding all costs at ~$10m per year ($21m received total by 12/31/10) and continue to hold rights to certain compounds
- 2/2011: agreement extended til 6/30/11 for Roche to continue research on 3 specific compounds, all other rights returned to SNTA and no further research funding paid to SNTA. 7/2011: term of Roche research period for the 3 compounds extended thru royalty obligation term of original agreement (Click here for details)
- "Development milestones across multiple indications of up to $245 million could be earned for the first product, and up to half of this amount could be earned for each of the second and third products. Commercialization milestones of up to $170 million could be earned for each of three products." (2010 10k) No milestones achieved as of 3/31/2011
- 4q2010 10k results and cc, March 2011 investor presenatations: several compounds exclusively licensed to Roche for further preclinical and clinical development (remain eligible for milestones and royalties), and discovered other CRACM inhibitors that SNTA fully owns. SNTA has stated that this program/candidates is one of 3 programs that are in active partnering discussions about. If no partnership materializes, SNTA would "re-evaluate" this program
Oral IL-12/IL-23 inhibitors for autoimmune and inflammatory diseases
- 2010 10k: "The IL-12 cytokine is an important "master switch" that triggers the immune response of the T cell known as T helper type 1, or Th1. T cells play a critical role in the coordination of the body's immune response, and while Th1 cells are normally involved in the body's defense against intracellular attack by bacteria and other micro organisms, an overactive Th1 response can lead to various autoimmune or inflammatory diseases including Crohn's disease, psoriasis, RA, multiple sclerosis, and common variable immunodeficiency. The IL-23 cytokine is critical to the generation of a class of T cells known as Th17, which produce other pro-inflammatory proteins such as IL-17, which are critical in driving chronic inflammation. We believe that the clinical trial results observed with anti-IL-12/23 antibody therapies validate the inhibition of IL-12/23 activity as a promising approach for the treatment of inflammatory and autoimmune diseases."
- Apilimod was a drug in this program that completed a Phase 2 trial in RA but was abandoned
- Considering topical apilimod for psoriasis as well as other preclinical compounds
- 2010 10k: program described as in "lead optimization stage" for autoimmune diseases
STA-9584 Vascular Disrupting Agent
- No timeline for IND of this preclinical cancer candidate, which disrupts new and existing tumor vasculature, has ever been given- low priority
- 2010 10k: rec'd $1m grant from Dept of Defense to support this program in advanced prostate cancer, listed as in preclinical development, studies supported by this grant will start 2q2011
- Competitors in this space include: CA4P, being developed by Oxigene; AVE8062 being developed by Sanofi-Aventis, BNC105, being developed by Bionomics, MPC-6827 (Azixa), being developed by Myrexis, EPC-2407 (crolibulin), being developed by EpiCept, NPI-2358 (plinabulin) being developed by Nereus Pharmaceuticals, and CYT997, being developed by YM BioSciences.