Results of RTA 402 Phase I Cancer Trial Presented at AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference
First-in-Class AIM Shows Exceptional Tolerability, Significant Anti-cancer Activity-Additional Studies in Progress
IRVING, TX -- October 24, 2007 -- Reata Pharmaceuticals, Inc. announced today the presentation of results from a Phase I cancer trial of its lead Antioxidant Inflammation Modulator (AIM), RTA 402, in a poster session at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference in San Francisco, CA. A first-in-class targeted therapy, RTA 402 inhibits the activity of two transcription factors, NF-kappa B and STAT3, that play a central role in cancer progression, metastasis, and resistance to therapy.
This Phase I dose escalation study, which is now largely complete, demonstrated that RTA 402 given orally once a day was exceptionally well tolerated and provided a high degree of disease control (stable disease or objective response) in patients with a variety of advanced cancers. Extended periods of stable disease (6 to 12 months) have been achieved in a number of patients with metastatic melanoma, renal cell carcinoma, and thyroid cancer. Furthermore, treatment with RTA 402 inhibited the formation of new metastases in a high percentage of patients.
Tumor biopsy data from several patients confirmed inhibition of NF-kappa B activity and STAT3 activation. Additionally, several NF-kappa B and STAT3 target gene products including inducible nitric oxide synthase (iNOS), COX-2, arginase, and cyclin D1 were consistently reduced in patient biopsies. Elevated levels of these proteins are strongly correlated with poor clinical outcomes. Of note, these reductions occurred at doses as low as 4% of the maximum tolerated dose.
The tolerability profile of RTA 402 was also outstanding. Doses from 5 to 900 mg per day given orally were well tolerated, with only grade 1 or 2 adverse events observed. Importantly, no neutropenia, thrombocytopenia, mucositis or hypertension was observed. The overall tolerability of RTA 402 is highly favorable in comparison with standard cytotoxic agents and approved targeted therapies.
"We are very encouraged by the results of this Phase I trial," said Warren Huff, CEO of Reata. "RTA 402 shows significant single-agent activity in patients with advanced, treatment-refractory cancers and has been exceptionally well tolerated. Since preclinical studies have shown that RTA 402 can potentiate the anti-cancer effects of many other drugs and protect against major toxicities associated with radiation and standard chemotherapy agents, Reata believes these Phase I results confirm its potential to become an important new treatment for multiple forms of cancer. Combination therapy is the standard of care in most forms of cancer, but many targeted therapies have significant toxicities that limit their use in combination with other agents. The outstanding tolerability of RTA 402 and its ability to inhibit the activity of transcription factors that drive tumor progression and resistance to therapy, put this drug in a unique position for use in combination therapy."
Based on early results from the Phase I trial and preclinical studies, Reata is currently conducting a Phase II study of RTA 402 in patients with metastatic melanoma and a Phase I/II study of RTA 402, in combination with gemcitabine, in patients with advanced pancreatic cancer. Additional studies are planned.
About the Presentation
The poster, entitled "Phase I Trial with a Novel Orally Administered Synthetic Triterpenoid RTA 402 (CDDO-Me) in Patients with Solid Tumors and Lymphoid Malignancies," was presented by investigators at the University of Texas M. D. Anderson Cancer Center, the Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Massachusetts General Hospital Cancer Center, and Case Western Reserve University.
About RTA 402
RTA 402 is a first-in-class Antioxidant Inflammation Modulator (AIM) that has demonstrated significant anti-cancer activity in preclinical and clinical studies. This agent operates by a unique mechanism of action that directly inhibits the activation of important redox-sensitive transcription factors, notably NF-kappa B and STAT3. Chronically activated NF-kappa B and STAT3 are found in many forms of cancer and are associated with tumor progression, invasion, metastasis, and resistance to therapy. RTA 402 has also shown outstanding potential for use in combination with standard cancer therapies, including radiation. In view of the exceptional tolerability profile shown by RTA 402 in clinical studies, this property creates broad opportunities for the agent to be combined with existing standard of care regimens. Because NF-kappa B and STATs are important targets for the treatment of inflammation, RTA 402 and related analogues have shown outstanding activity in many different preclinical models of autoimmune and inflammatory disease. Accordingly, RTA 402 is also under development as an oral, once-daily therapy for inflammatory and autoimmune conditions including rheumatoid arthritis.
About Reata
Reata Pharmaceuticals, Inc. is a biopharmaceutical company focused on selecting and discovering promising early drug development opportunities and translating them into successful marketed drugs that target major unmet clinical needs in cancer, inflammation and neurodegenerative disease. The company's two lead programs are entering 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.
Media Contact:
Kathryn Morris
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