5.22.2008 - 10 New Papers Published on Anti-Cancer Effects of Reata AIMs

IRVING, TX -- May 22, 2008-- Reata Pharmaceuticals, Inc. announced the publication of 10 separate peer-reviewed papers supporting the use of its Antioxidant Inflammation Modulators (AIMs) in cancer patients.  These papers reflect work conducted at leading academic institutions includingDartmouthMedicalSchool, The Burnham Institute, and the Dana-Farber Cancer Institute.  Collectively, they further elucidate the novel mechanism of action of the AIMs in cancer, demonstrate effects in a broad array of tumor types, and show consistent activity across multiple structural analogs.  RTA 402, the lead AIM, is currently in Phase 2 development for cancer and inflammation indications.  Data to be presented at the 2008 ASCO Annual Meeting will show that RTA 402 has better single agent activity than recently approved targeted therapies, with a markedly better safety profile.

"We at Reata are highly gratified that our academic collaborators continue to pursue and publish excellent work on our AIM compounds," commented Warren Huff, Reata's Chief Executive Officer.  "These papers bring the total number of peer-reviewed publications on the AIMs to 85, which reflects the high level of scientific interest in these compounds, their potent biological effects, and their novel mechanism of action."

Novel Mechanism of Action

RTA 402 is the clinical lead from a portfolio of AIMs being developed by Reata. These drugs suppress key inflammatory signaling pathways that promote tumor growth and progression.  RTA 402 inhibits the activity of NF-kappa B and STAT3, transcription factors that are chronically activated in many cancers and control the expression of many genes involved in inflammation and immune response.  Consequently RTA 402 inhibits the tumor's ability to grow, promote the formation of new blood vessels (known as "angiogenesis"), invade surrounding tissues, and spread to other parts of the body (known as "metastasis").  Additionally, STAT3 is believed to play a critical role in allowing tumors to evade detection and destruction by the immune system.  Preclinical studies with RTA 402 have shown that inhibiting STAT3 may allow the body to mount an anti-tumor immune response.  RTA 402 is the only anti-cancer agent with this mechanism currently in clinical development.

Among recently published papers, researchers at the Dana-Farber Cancer Institute further clarified the nature of the AIMs' interaction with the JAK1/STAT3 pathway, demonstrating that RTA 402 (also known as CDDO-Me) binds reversibly to specific sites on both JAK1 and STAT3.  Academics at the Henry Ford Health System confirmed the importance of NF-kappa B and its target genes including the well-established cancer target VEGF in preventing the development and progression of prostate cancer, while investigators at The Burnham Institute explored how AIMs induce programmed cell death in this tumor type.  Additionally, researchers at the Multimedica IRCCS inMilan,Italy, published new data demonstrating the highly potent antiangiogenic effects of RTA 402 both in cell culture and in animals, building on their earlier work in this area.

Applicability inBroadRangeof Tumor Types

The recent papers build on previously published data indicating that RTA 402 and related analogs have significant activity against a variety of cancer types.  Researchers atDartmouthMedicalSchooldemonstrated that one of Reata's AIMs, known as CDDO-Methyl Amide, was highly effective in preventing the development of lung cancer and was significantly more effective than a targeted therapy approved to treat lung cancer.  This work builds on a previous report by these authors showing similar activity with two other AIMs, including RTA 402.  These papers also include data showing activity of the AIMs in other solid tumors including prostate cancer, the B-cell malignancy Waldenstrom macroglobulinemia, chronic and acute leukemias, the brain tumor neuroblastoma, and various sarcomas including liposarcoma, Karposi's sarcoma, osteosarcoma, rhabdomyosarcoma, andEwing's sarcoma.

In clinical studies conducted to date, RTA 402 has produced a clinical benefit in patients with multiple tumor types, including pancreatic cancer, lymphoma, thyroid cancer, melanoma, and renal cancer. Further clinical studies in these and other types of cancer are planned.

List of Publications

The following papers have been published in recent months and include data on the anti-cancer effects of RTA 402 and other AIMs.

• Liby K,  et al., The rexinoid LG100268 and the synthetic triterpenoid CDDO-methyl amide are more potent than erlotinib for prevention of mouse lung carcinogenesis, Mol Cancer Ther. 2008 May;7(5):1251-7.
• Deeb D, et al., CDDO-Me inhibits proliferation, induces apoptosis, down-regulates Akt, mTOR, NF-kappaB and NF-kappaB-regulated antiapoptotic and proangiogenic proteins in TRAMP prostate cancer cells,  J Exp Ther Oncol. 2008;7(1):31-9.
• Elsawa SF, et al.,  CDDO-imidazolide mediated inhibition of malignant cell growth in Waldenstrom macroglobulinemia,  Leuk Res. 2008 May 9.
• Hyer ML, et al.,  Apoptotic activity and mechanism of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic-acid and related synthetic triterpenoids in prostate cancer, Cancer Res. 2008 Apr 15;68(8):2927-33.
• Ahmad R, et al.,  Triterpenoid CDDO-methyl ester inhibits the Janus-activated kinase-1 (JAK1)--> signal transducer and activator of transcription-3 (STAT3) pathway by direct inhibition of JAK1 and STAT3, Cancer Res. 2008 Apr 15;68(8):2920-6.
• Riccioni R, et al.,  Resistance of acute myeloid leukemic cells to the triterpenoid CDDO-Imidazolide is associated with low caspase-8 and FADD levels,  Leuk Res. 2008 Aug;32(8):1244-58. Epub 2008 Mar 4.
• To C, et al.,  The Synthetic Triterpenoid 2-Cyano-3,12-dioxooleana-1,9-dien-28-oic Acid-Imidazolide Alters Transforming Growth Factor {beta}-dependent Signaling and Cell Migration by Affecting the Cytoskeleton and the Polarity Complex, J Biol Chem. 2008 Apr 25;283(17):11700-13. Epub 2008 Feb 18.
• Alabran JL, et al., Human Neuroblastoma Cells Rapidly Enter Cell Cycle Arrest and Apoptosis Following Exposure to C-28 derivatives of the Synthetic Triterpenoid CDDO, Cancer Biol Ther. 2008 Feb 7;7(5).
• Hughes DT, et al., The synthetic triterpenoid CDDO-Im inhibits fatty acid synthase expression and has antiproliferative and proapoptotic effects in human liposarcoma cells, Cancer Invest. 2008 Mar;26(2):118-27.
• Vannini N, et al., The synthetic oleanane triterpenoid, CDDO-methyl ester, is a potent antiangiogenic agent, Mol Cancer Ther. 2007 Dec;6(12 Pt 1):3139-46.

About Reata

Reata Pharmaceuticals, Inc. is a biopharmaceutical company focused on translating innovative science into breakthrough medicines.  The company's two lead programs are in advanced clinical trials for deadly, late-stage cancers and proof of concept studies in inflammatory diseases.  In parallel with its clinical development, Reata is advancing a breakthrough drug discovery platform using protein misfolding, identified as a key factor in cancer and neurodegenerative disease, to feed its pipeline of small molecule therapeutic candidates. Reata takes a new and different approach to biotechnology, managing its pipeline as a portfolio of opportunities that can be advanced on a single management and physical infrastructure, streamlining the route to human trials and approval.   For more information, visit www.reatapharma.com.

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