Category Archives: Press Releases

Reata Enrolls First Patient with Pulmonary Hypertension Associated with Interstitial Lung Disease in LARIAT, a Phase 2 Study Examining Bardoxolone Methyl for the Treatment of Patients with Pulmonary Hypertension

IRVING, Texas – January 5, 2016 – Reata has enrolled its first patient with pulmonary hypertension associated with interstitial lung disease (PH-ILD) into LARIAT, a Phase 2 study examining the safety, tolerability, and efficacy of bardoxolone methyl in patients with pulmonary hypertension (PH). The expanded LARIAT trial is now enrolling patients with PH associated with certain types of interstitial lung disease that are classified in the following categories:

    • WHO Group 3 pulmonary hypertension patients with interstitial lung diseases:
    • Connective tissue disease-associated (CTD-ILD);
    • Idiopathic pulmonary fibrosis (IPF);
    • Nonspecific interstitial pneumonia (NSIP);
    • WHO Group 5 pulmonary hypertension patients with sarcoidosis

Data recently presented at the CHEST meeting demonstrated that bardoxolone methyl improves functional capacity as assessed by the 6 minute walk test in WHO Group 1 PH (pulmonary arterial hypertension) patients who are already receiving stable, approved background therapies. The largest magnitude changes were noted in patients with connective tissue disease-associated PAH (CTD-PAH), and these patients typically respond less well to available therapies and have poorer overall outcomes. On the basis of these clinical data, as well as preclinical data demonstrating activity of bardoxolone methyl and analogs in several types of connective tissue disease and fibrotic pulmonary conditions, Reata has expanded its PH program into these interstitial lung disease patients.

    “We are pleased to announce that we have quickly expanded our PH program into interstitial lung disease patients who have no approved therapies to treat their pulmonary hypertension,” said Colin Meyer, M.D., Reata’s Chief Medical Officer. “We hypothesize that bardoxolone methyl’s novel mechanism of action of improving mitochondrial function and suppressing inflammation can translate to improved functional capacity in PH patients with interstitial lung disease.”

About Bardoxolone Methyl

Bardoxolone methyl is an experimental, oral, once-daily antioxidant inflammation modulator (AIM) that has received orphan drug designation for the treatment of PAH by the US Food and Drug Administration. Bardoxolone methyl directly targets the bioenergetic and inflammatory components of PH. PH patients experience mitochondrial dysfunction, increased production of NF-κB and related inflammatory pathways involved in ROS signaling, cellular proliferation, and fibrosis. Bardoxolone methyl, through the combined effect of Nrf2 activation and NF-κB suppression, has the potential to inhibit inflammatory and proliferative signaling, suppress ROS production and signaling, reduce the production of enzymes related with fibrosis and tissue remodeling, and increase ATP production and cellular respiration.

About the LARIAT Study

LARIAT (A Dose-Ranging Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Pulmonary Hypertension) is a Phase 2 dose-ranging study examining the safety, tolerability, and efficacy of bardoxolone methyl in patients with PH on stable background therapy. To determine if bardoxolone methyl could complement approved PAH therapies, the Phase 2 study is designed to assess efficacy through exercise capacity.

Reata announced initial data from the LARIAT trial evaluating bardoxolone methyl in pulmonary arterial hypertension (PAH) patients at the annual meeting of the 2015 American College of Chest Physicians (CHEST) in Montreal, Canada.

All patients in the initial study cohorts were on stable doses of background PAH therapies at baseline and throughout the study. Efficacy analyses showed that bardoxolone methyl increased 6-minute walk distance (6MWD) in idiopathic PAH patients at doses of 2.5 to 10 mg through 16 weeks of treatment. PAH patients treated with bardoxolone methyl demonstrated a statistically significant mean increase in 6MWD compared to baseline of 22 m and a placebo-corrected difference of 21.4 m (p = 0.037). Notably, patients with connective tissue disease associated PAH (CTD-PAH), who typically experience less therapeutic benefit from approved PAH therapies, demonstrated a mean increase from baseline in 6MWD of 30 m and a placebo-corrected change of 44 m. This change may reflect the novel anti-inflammatory, metabolic, and mitochondrial effects of bardoxolone methyl.

Safety analyses from LARIAT demonstrated that bardoxolone methyl was well-tolerated with relatively fewer discontinuations in bardoxolone methyl-treated PAH patients compared to those who received placebo. No drug-related serious adverse events were reported, and the adverse event profile was manageable. Importantly, unlike previous observations in a subset of patients with advanced kidney disease, no fluid retention events or less severe manifestations of fluid retention were observed in the LARIAT PAH subjects. No meaningful or dose-related changes in blood pressure, heart rate, other measures of fluid status, and echocardiographic parameters were noted.

Reata completed an end of phase 2 interaction with the FDA in October, and the FDA concurred with Reata’s proposal for an initial Phase 3 study in CTD-PAH patients using 6MWD as the primary endpoint. The primary endpoint will be assessed after 24 weeks of treatment. Reata plans to initiate this first Phase 3 study in the second half of 2016.

For more details on the LARIAT study visit https://www.clinicaltrials.gov/ct2/show/NCT02036970.

About Pulmonary Arterial Hypertension

PH is a multi-organ condition characterized by an abnormally high pressure in the network of arteries and veins that lead to and from the lungs due, in part, to narrowing of the pulmonary vasculature as a result of inflammation, remodeling, proliferation, and endothelial dysfunction. Mitochondrial dysfunction has also been implicated in PH. PH patients experience increased pressure on the right side of the heart, ultimately leading to ventricular failure and death. Although PH does not involve metastasis or disruption of tissue boundaries, it shares some features with cancer, including hyperproliferation and resistance to apoptosis, or programmed cell death, of vascular smooth muscle and other cells. Further, impaired energetics of skeletal muscle is a common feature of PH.

PH can be caused by a number of different underlying defects, which have been classified into five groups by the World Health Organization, or WHO1.

PAH, like PH more generally, results in a progressive increase in pulmonary vascular resistance, which ultimately leads to right ventricular heart failure and death. PAH has a number of different etiologies, with approximately 72% of PAH cases being associated with either connective tissue disease, or CTD, or being idiopathic2. Patients with CTD-PAH are generally less responsive to existing therapies and have a worse prognosis than patients with other forms of PAH3. In comparison to patients with idiopathic PAH, or I-PAH, patients with CTD-PAH have a higher occurrence of small vessel fibrosis and greater incidence of pulmonary veno-obstructive diseases4. CTD-PAH represents a subset of the PAH population with a significant unmet medical need.

Interstitial lung disease, or ILD, patients experience extensive pulmonary vascular remodeling, which ultimately leads to PH-ILD in approximately 30% to 40% of ILD patients5. PH-ILD falls under both WHO Groups III and V1. PH-ILD patients have a one-year survival rate of approximately 63%, as compared to approximately 92% for ILD patients without PH6. Recent studies have demonstrated that mitochondrial abnormalities are key contributors to PH-ILD7. Currently, there are no therapies that are specifically approved to treat PH in interstitial lung disease patients.

About Reata Pharmaceuticals, Inc.

Reata Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on identifying, developing, and commercializing product candidates that modulate the activity of key regulatory proteins involved in the biology of oxidative stress, mitochondrial function, and inflammation to address the unmet medical needs of patients with a variety of serious or life-threatening diseases. We focus on drugs with novel mechanisms of action that modulate important regulatory proteins, called transcription factors, that coordinate the cellular response to stressors by activating or suppressing the activity of many target proteins. The effects of AIM pharmacology have been documented in more than 200 scientific papers and are potentially relevant to a wide range of diseases.

CONTACT:
Reata Pharmaceuticals, Inc.
(972) 865-2219
info@reatapharma.com
http://reatapharma.wpengine.com/investors-news/news-room/

Investor Relations:
The Trout Group
Lee M. Stern, CFA
(646) 378-2992
lstern@troutgroup.com

References

  1. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, Gomez Sanchez MA, Krishna Kumar R, Landzberg M, Machado RF, Olschewski H, Robbins IM, and Souza R. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013;6:D34-41.
  2. Badesch DB, Raskob GE, Elliot G, Krichman AM, Farber HW, Frost AE, Barst RJ, Benza RL, Liou TG, Tunrer M, Giles S, Feldkircher K, Miller DP, McGoon MD. Pulmonary arterial hypertension: baseline characteristics from the REVEAL registry. CHEST 2010;137(2):376-387.
  3. Rhee RL, Gabler NB, Sangani S, Praestgaard A, Merkel PA, Kawut SM. Comparison of treatment response in idiopathic and connective tissue disease-associated pulmonary arterial hypertension. Am J Respir Crit Care Med 2015.
  4. Overbeek MG, Vonk MC, Boonstra A, Vosukyl AE, Vonk-Noordegraaf A, Smit EF, Dijkmans BAC, Postmus PE, Mooi WJ, Heijdra Y, Grunberg K. Pulmonary arterial hypertension in limited cutaneous systemic sclerosis: a distinctive vasculopathy. Eur Respir J 2009;34:371-379.
  5. Behr J and Ryu JH. Pulmonary hypertension in interstitial lung disease. Eur Respir J 2008;31:1357-1367.
  6. Lettieri CJ, Nathan SD, Barnett SD, Ahmad SA and Shorr AF. Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis. Chest 2006; 126: 746-752.
  7. Cottrill KA and Chan SY. Metabolic dysfunction in pulmonary hypertension: the expanding relevance of the Warburg effect. European Journal of Clinical Investigation 2013; 43: 855-865.

Reata Announces Initial Phase 2 Pulmonary Arterial Hypertension Data for Bardoxolone Methyl and Planned Initiation of Phase 3 Study

Montreal, Quebec – October 27, 2015 – Reata Pharmaceuticals announced initial data from the LARIAT trial evaluating bardoxolone methyl in pulmonary arterial hypertension (PAH) patients at the annual meeting of the 2015 American College of Chest Physicians (CHEST) in Montreal, Canada. The presentation, “Initial Data Report from ‘LARIAT’: a Phase 2 Study of Bardoxolone Methyl in PAH Patients on Stable Background Therapy,” was presented by Ronald Oudiz, M.D., Professor of Medicine, David Geffen School of Medicine at UCLA. Dr. Oudiz is Director of the Pulmonary Hypertension Center and a Faculty Cardiologist at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center in Southern California.

All patients in the study were on stable doses of background PAH therapies at baseline and throughout the study. Efficacy analyses showed that bardoxolone methyl increased 6-minute walk distance (6MWD) at doses of 2.5 to 10 mg through 16 weeks of treatment. Patients treated with bardoxolone methyl demonstrated a statistically significant mean increase in 6MWD compared to baseline of 22 m and a placebo-corrected difference of 21.4 m (p = 0.037). Many current therapies have shown a limited ability to improve 6MWD in patients who have baseline 6MWD values greater than 450 m. However, 6MWD changes in patients with baseline values greater than 450 m were similar to those with baseline values less than 450 m. Changes in 6MWD were associated with improvements in metabolic parameters, including mean weight loss of 3 kg relative to placebo and reductions in creatine kinase, a marker of muscle inflammation.

Notably, patients with connective tissue disease associated PAH (CTD-PAH), who typically experience less therapeutic benefit from approved PAH therapies, demonstrated a mean increase from baseline in 6MWD of 30 m and a placebo-corrected change of 44 m. This change may reflect the novel anti-inflammatory, metabolic, and mitochondrial effects of bardoxolone methyl.

Safety analyses from LARIAT demonstrated that bardoxolone methyl was well-tolerated with relatively fewer discontinuations in bardoxolone methyl-treated patients compared to those who received placebo. No drug-related serious adverse events were reported, and the adverse event profile was manageable. Importantly, unlike previous observations in a subset of patients with advanced kidney disease, no fluid retention events or less severe manifestations of fluid retention were observed in the LARIAT PAH subjects. No meaningful or dose-related changes in blood pressure, heart rate, other measures of fluid status, and echocardiographic parameters were noted.

Reata completed an end of phase 2 interaction with the FDA in October, and the FDA concurred with Reata’s proposal for an initial phase 3 study in CTD-PAH patients using 6MWD as the primary endpoint. The primary endpoint will be assessed after 24 weeks of treatment. Reata plans to initiate this first phase 3 study in 2016 and is considering additional studies in other subtypes of PAH.

“The initial data from LARIAT are very encouraging and indicate that bardoxolone methyl’s novel mechanism of action may provide a new approach to PAH therapy. Clinically, these effects may acutely translate to increased muscular function, and as we have observed in preclinical models, may reduce pathological cardiovascular remodeling in the long-term,” said Colin Meyer, M.D., Reata’s Chief Medical Officer. “This pharmacology is particularly meaningful to PAH patients with connective tissue disease. These patients have autoimmune disease that causes their PAH, and their inflammatory disease processes often involve more remodeling than other subtypes. This explains why these patients often do not respond well to approved vasodilator therapy relative to idiopathic PAH patients and represent a subset of the PAH population with significant unmet need. On the basis of these data and recent interactions with the FDA, we are excited to announce that we are planning to initiate a phase 3 study of bardoxolone methyl in patients with CTD-PAH in 2016.”

About Bardoxolone Methyl

Bardoxolone methyl is an experimental, oral once daily antioxidant inflammation modulator (AIM) that has received orphan drug designation for the treatment of PAH by the US Food and Drug Administration. Bardoxolone methyl directly targets the bioenergetic and inflammatory components of PH. PH patients experience mitochondrial dysfunction, increased production of NF-κB and related inflammatory pathways involved in ROS signaling, cellular proliferation, and fibrosis. Bardoxolone methyl, through the combined effect of Nrf2 activation and NF-κB suppression, has the potential to inhibit inflammatory and proliferative signaling, suppress ROS production and signaling, reduce the production of enzymes related with fibrosis and tissue remodeling, and increase ATP production and cellular respiration.

About the LARIAT Study

LARIAT (A Dose-Ranging Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Pulmonary Hypertension) is a Phase 2 dose ranging study examining the safety, tolerability, and efficacy of bardoxolone methyl in patients with PAH on stable background therapy. To determine if bardoxolone methyl could complement approved PAH therapies, the Phase 2 study was designed to assess efficacy through exercise capacity.

This initial data report is from analysis performed on the initial 3 cohorts (24 patients). World Health Organization (WHO) Group 1 PAH patients (n = 24) were randomized in cohorts of 8 patients in a 1:3 ratio to receive once-daily placebo or bardoxolone methyl at doses of 2.5, 5, or 10 mg for 16 weeks. Each dosing cohort completed week 4 assessments before the next dosing cohort opened. Patients were WHO functional class II or III and using stable doses of at least one approved PAH therapy were included in the study. The primary efficacy variable, 6-minute walk distance (6MWD), was collected at baseline and every 4 weeks post-randomization. A Safety Review Committee monitored the study, and all eligible participants were offered open-label extension therapy after the initial 16 weeks. For more details on the LARIAT study visit https://www.clinicaltrials.gov/ct2/show/NCT02036970.

About Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a multi-organ condition characterized by an abnormally high pressure in the network of arteries and veins that lead to and from the lungs due, in part, to narrowing of the pulmonary vasculature as a result of inflammation, remodeling, proliferation, and endothelial dysfunction. Mitochondrial dysfunction has also been implicated in PAH. PAH patients experience increased pressure on the right side of the heart, ultimately leading to ventricular failure and death. Although PAH does not involve metastasis or disruption of tissue boundaries, it shares some features with cancer, including hyperproliferation and resistance to apoptosis, or programmed cell death, of vascular smooth muscle and other cells. Further, impaired energetics of skeletal muscle is a common feature of PAH.

About Reata Pharmaceuticals, Inc.

Reata Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company located in Irving, Texas, focused on the development of drugs that target proteins involved in the cellular biology of oxidative stress, inflammation, and mitochondrial function to address the unmet medical needs of patients with serious or life threatening diseases. We focus on drugs with novel mechanisms of action that modulate important regulatory proteins, called transcription factors, that coordinate the cellular response to stressors by activating or suppressing the activity of many target proteins. The effects of AIM pharmacology have been documented in more than 200 scientific papers and are potentially relevant to a wide range of diseases.

CONTACT:
Reata Pharmaceuticals, Inc.
(972) 865-2219
info@reatapharma.com
http://reatapharma.wpengine.com/investors-news/news-room/

Investor Relations:
The Trout Group
Lee M. Stern, CFA
(646) 378-2992
lstern@troutgroup.com

Reata to Present Initial Phase 2 Data on Bardoxolone Methyl, a Novel Experimental Therapy for Pulmonary Hypertension Used in Patients on Stable Background PAH Therapy

IRVING, Texas – September 16, 2015 – Reata Pharmaceuticals announced today that initial data evaluating bardoxolone methyl in pulmonary arterial hypertension (PAH) patients on stable background therapy will be presented at the 2015 American College of Chest Physicians (CHEST) annual meeting in Montreal, Canada.

The presentation is scheduled on October 27, 2015 as part of the Late-Breaking Abstracts session from 8:45 to 10:00 am, in the Palais des Congrès de Montréal Convention Center (Room 513ef). The presentation, “Initial Data Report from ‘LARIAT’: a Phase 2 Study of Bardoxolone Methyl in PAH Patients on Stable Background Therapy,” will be presented by Ronald Oudiz, M.D., Professor of Medicine, David Geffen School of Medicine at UCLA. Dr. Oudiz is Director of the Pulmonary Hypertension Center and a Faculty Cardiologist at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center in Southern California.

“We are excited to present top-line data from our Phase 2 LARIAT study. Bardoxolone methyl has the potential to be a first-in-class treatment for PAH that impacts aspects of the disease that are unaddressed by current therapies, including inflammation and mitochondrial dysfunction. Clinically, these manifest as markedly reduced exercise capacity and fatigue, despite optimal treatment with available therapies. In preclinical models, we have demonstrated that bardoxolone methyl directly improves mitochondrial function and energy production in the skeletal muscle while not affecting systemic hemodynamics,” said Colin Meyer, M.D., Reata’s Chief Medical Officer. “This profile is unique and should complement available therapies, all of which have primary vasodilatory effects. On the basis of the emerging preclinical and clinical data, we are further expanding our development program and plan to study bardoxolone methyl in other forms of pulmonary hypertension, including pulmonary hypertension caused by interstitial lung disease.”

About Bardoxolone Methyl

Bardoxolone methyl is an experimental, oral once daily antioxidant inflammation modulator (AIM) that has received orphan drug designation for the treatment of PAH by the US Food and Drug Administration. Bardoxolone methyl targets the Nrf2 pathway, which controls the transcription of genes that increase cellular antioxidant content and anti-inflammatory mediators. Preclinical data suggest that activation of the Nrf2 pathway also regulates multiple genes that promote the production of cellular energy within the mitochondria and facilitates mitochondrial homeostasis and efficiency. Unlike therapies that primarily promote vasodilation, preclinical data suggest that bardoxolone methyl may directly target inflammation as well as mitochondrial dysfunction in PAH. Bardoxolone methyl and analogs have demonstrated activity in preclinical models of lupus and scleroderma, and these autoimmune conditions contribute to the second most common subtype of PAH, known as connective tissue disease-associated PAH. The available preclinical data suggest that bardoxolone methyl has the potential to impact multiple aspects of PAH pathology not significantly attenuated by current therapies.

About the LARIAT Study

LARIAT (A Dose-Ranging Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Pulmonary Hypertension) is a Phase 2 dose ranging study examining the safety, tolerability, and efficacy of bardoxolone methyl in patients with PAH on stable background therapy. To determine if bardoxolone methyl could complement approved PAH therapies, the Phase 2 study was designed to assess efficacy through exercise capacity.

This initial data report is from analysis performed on the initial 3 cohorts (24 patients). Patients were randomized 1:3 to receive once-daily placebo or bardoxolone methyl for 16 weeks. Patients were required to be stable on at least one approved PAH therapy. The primary efficacy variable, 6MWD, was collected at baseline and at every 4 weeks. For more details on the LARIAT study visit https://www.clinicaltrials.gov/ct2/show/NCT02036970.

About Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a life-threatening disease involving chronic fatigue, endothelial dysfunction, vasoconstriction in small pulmonary arteries, dysregulated proliferation of certain vascular cells, and dysregulated pro-inflammatory signaling leading to vascular remodeling, pulmonary fibrosis, and right ventricular hypertrophy. PAH affects an estimated 15,000-20,000 people in the United States, predominantly middle-aged women. Available treatments for PAH can provide symptomatic improvement, primarily by relieving vasoconstriction. However, even with existing treatments the disease continues to progress, and PAH has a high mortality rate with 60 to 80 percent of patients dying within five years of diagnosis. Consequently, there is a very high unmet clinical need for new therapies.

About Reata Pharmaceuticals, Inc.

Reata Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company located in Irving, Texas, focused on the development of drugs that target proteins involved in the cellular biology of oxidative stress, inflammation, and mitochondrial function to address the unmet medical needs of patients with serious or life threatening diseases. We focus on drugs with novel mechanisms of action that modulate important regulatory proteins, called transcription factors, that coordinate the cellular response to stressors by activating or suppressing the activity of many target proteins. The effects of AIM pharmacology have been documented in more than 250 scientific papers and are potentially relevant to a wide range of diseases.

CONTACT:
Reata Pharmaceuticals, Inc.
(972) 865-2219
info@reatapharma.com
http://reatapharma.com/investors-news/news-room/

Investor Relations:
The Trout Group
Lee M. Stern, CFA
(646) 378-2992
lstern@troutgroup.com

Reata Enrolls First Patient in the MOTOR Study, a Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Mitochondrial Myopathies

IRVING, Texas, July 8, 2015 – Reata announces the enrollment of the first patient in MOTOR, a Phase 2 dose-ranging study examining the safety, tolerability, and efficacy of RTA 408 Oral Capsules for the treatment of patients with mitochondrial myopathies (MM).

MOTOR is a multi-center study planned for approximately 52 patients with MM. MM is a collective term for a group of individual rare diseases associated with mitochondrial DNA mutations. These defects cause respiratory chain deficits and impaired energy production. Most patients with MM share a similar phenotype with skeletal muscle weakness and fatigue. They also may have additional symptoms due to impaired energy production in other organ systems and often have reduced lifespans. Approximately 20,000 people in the United States are believed to have a form of MM. There are currently no approved therapies for MM.

The primary efficacy endpoint is the change in peak workload (Watts/kg) during exercise testing. The secondary endpoint includes a patient’s 6-minute walk distance. The study is also exploring the change in peak oxygen utilization during maximal exercise testing and changes in the Fatigue Severity Scale.

“Emerging translational research demonstrates that activation of Nrf2 (the target of RTA 408) can improve mitochondrial function and cellular energy production. These observations underlie our hypothesis that RTA 408 may improve exercise capacity and quality of life in patients with mitochondrial myopathies,” noted Dr. Colin Meyer, Reata’s Chief Medical Officer. “We are hopeful that RTA 408 will benefit mitochondrial myopathy patients, and we appreciate the guidance and support that Reata has received from the UMDF and the MM patient community.”

“We are very excited this trial will be underway with its first patient,” said Charles A. Mohan, Jr., Executive Director and CEO of the United Mitochondrial Disease Foundation. “Coordination, communication and collaboration between our industry partners and our patients to promote and support clinical trials is the only way we will accelerate the development of diagnostic tools, therapies, and potential cures for mitochondrial disease. We are pleased with the role Reata has taken in this endeavor and honored to call them a partner. We must all remember; no patients no trials, no trials no treatments nor cures.”

For more information on this study, visit: https://clinicaltrial.gov/ct2/show/NCT02255422.

About RTA 408 and Bioenergetics Effect

RTA 408 activates the body’s anti-oxidative pathways through transcription factor Nrf2 and is able to improve mitochondrial function. In mouse models of bioenergetic disease, RTA 408 demonstrated the ability to increase glucose uptake, fatty acid oxidation and oxygen consumption, direct signs of healthier cellular metabolism (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003357). RTA 408 analogs have also demonstrated in mouse models of oxidative stress the ability to induce genes related to mitochondrial biogenesis through the activation of Nrf2, which showed signs of potentially improving muscle function (http://www.ncbi.nlm.nih.gov/pubmed/21457778).

About Reata Pharmaceuticals, Inc.

Reata Pharmaceuticals, Inc. is a privately held company aiming to translate innovative research into breakthrough medicines for difficult diseases that have significant unmet needs. Reata is the leader in developing a novel class of drugs with potent transcription-regulating activity, called antioxidant inflammation modulators (AIMs). AIMs activate Nrf2, promoting the production of numerous antioxidant, detoxification, and anti-inflammatory genes, and inhibit NF-κB, a gene that regulates many pro-inflammatory proteins. The pharmacology of the AIMs mimics that of endogenous prostaglandin metabolites that are responsible for the orchestrated resolution of inflammation. The anti-inflammatory, cytoprotective and energy metabolism effects of AIM pharmacology have been documented in more than 250 scientific papers and are potentially relevant to a wide range of diseases.

CONTACT:
Reata Pharmaceuticals, Inc.
(972) 865-2219
info@reatapharma.com

Investor Relations:
The Trout Group
Lee M. Stern, CFA
lstern@troutgroup.com
(646) 378-2992

Reata Pharmaceuticals’ bardoxolone methyl receives FDA Orphan Drug Designation in Pulmonary Arterial Hypertension

IRVING, TX – April 10, 2015– Reata Pharmaceuticals, Inc., a biopharmaceutical company dedicated to the development of breakthrough medicines for difficult-to-treat diseases, today announced that the FDA Office of Orphan Products Development (OOPD) has granted orphan drug designation for bardoxolone methyl for the treatment of pulmonary arterial hypertension. Pulmonary arterial hypertension (PAH) is a life-threatening disease involving endothelial dysfunction, pulmonary vasoconstriction, vascular remodeling, pulmonary fibrosis, and right ventricular hypertrophy. Additionally, PAH involves skeletal muscle dysfunction that contributes to the exercise intolerance observed in PAH patients. In preclinical studies, bardoxolone methyl has demonstrated potent antioxidant, anti-inflammatory, and bioenergetic properties, which may lead to improved exercise tolerance in patients.

“Pulmonary arterial hypertension is a devastating disease for patients and significantly decreases their quality of life and lifespan. The FDA’s decision to grant orphan designation is an important step in the development of bardoxolone methyl to potentially treat this population with high unmet need,” said Colin Meyer, MD, Chief Medical Officer of Reata. “We believe the novel mechanism of activating Nrf2 has profound bioenergetic effects which have the potential to meaningfully impact the course of disease.”

Bardoxolone methyl is currently being evaluated in the LARIAT study, a Phase 2 dose-ranging study examining the safety, tolerability and efficacy of bardoxolone methyl in patients with PAH. LARIAT is a multi-center, double-blind, randomized, dose-ranging, placebo-controlled study. The primary efficacy endpoint is a six minute walk test. For more information on this study, visit: http://clinicaltrials.gov/show/NCT02036970.

The Orphan Drug Designation program provides orphan status to novel drugs or biologics that are intended to treat a rare disease or condition affecting fewer than 200,000 patients in the US. There are several benefits of the orphan designation, including seven years of market exclusivity, tax credits for clinical research costs, and waiver or partial payment of application fees. Orphan Drug Designation does not alter the standard regulatory requirements for obtaining marketing approval.

About Reata Pharmaceuticals

Reata Pharmaceuticals, Inc. translates innovative research into breakthrough medicines to create options for patients with rare and difficult to treat diseases. Reata’s lead drugs are called antioxidant inflammation modulators (AIMs). AIMs are potent activators of the transcription factor Nrf2 and potent inhibitors of the transcription factor NF‑κB. Through this pharmacology, AIMs have cytoprotective and anti-inflammatory effects, and they promote increased cellular energy production by restoring mitochondrial function.

CONTACT:
Reata Pharmaceuticals, Inc.
(972) 865-2219
info@reatapharma.com

Investor Relations:
The Trout Group
Lee M. Stern, CFA
lstern@troutgroup.com
(646) 378-2992

Reata Enrolls First Patient in the MOXIe Study, a Phase 2/3 Study Examining RTA 408 in Friedreich’s Ataxia Patients

IRVING, Texas, January 29, 2015 – Reata announces enrollment of the first patient in a Phase 2 dose-ranging study examining the safety, tolerability, and efficacy of RTA 408 Oral Capsules versus placebo for the treatment of patients with Friedreich’s ataxia.

MOXIe (A two-part, randomized, placebo-controlled Phase 2/3 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Friedreich’s Ataxia) is a multi-center study in approximately 52 patients and is designed to support a potential NDA submission. Part 1 of the study is a randomized, placebo-controlled, double-blind, dose-escalation study to evaluate the safety of RTA 408 at 2.5 mg, 5 mg, and 10 mg in patients with Friedreich’s ataxia. Part 2 of the study is a randomized, placebo-controlled, double-blind, parallel-group study to evaluate the safety, efficacy, and pharmacodynamics of up to 2 dose levels of RTA 408. The study is designed to evaluate a variety of clinical, and biochemical endpoints, including exercise capacity and quality of life measures.

Friedreich’s ataxia (FA) is an inherited disorder caused by defects in the gene for frataxin, a protein that regulates iron levels in the mitochondria. Defects in frataxin result in mitochondrial iron overload, causing impaired metabolism, oxidative stress, and damage to mitochondrial DNA. Patients with FA suffer progressive degeneration of the central and peripheral nervous systems, impaired motion and gait, and eventually may develop cardiomyopathy and diabetes. FA patients have substantially lowered quality of life, with most becoming wheelchair bound by their mid-20s and surviving only into their 30s. Approximately 20,000 people in the US and Europe have FA. There are currently no approved therapies for FA.

“Our large body of preclinical and clinical data with RTA 408 and related molecules provides strong support for the hypothesis being tested in MOXIe that RTA 408 may be beneficial in patients suffering from Friedreich’s ataxia”, noted Dr. Colin Meyer, Reata’s Chief Medical Officer. “We have been productively collaborating with key FA clinicians and patient advocacy, and we look forward to evaluating the results of MOXIe as they become available”.

For more information on this study, visit: https://clinicaltrial.gov/ct2/show/NCT02255435.

About RTA 408 and Bioenergetic Effects

In preclinical studies, RTA 408 and analogs have been shown to improve cellular bioenergetics. Mouse models have demonstrated that frataxin deficiency is correlated to lower expressions of the transcription factor Nrf2 and lower mitochondrial function (http://www.ncbi.nlm.nih.gov/pubmed/23350650). RTA 408 directly activates the body’s anti-oxidative pathways through Nrf2 and may be able to improve mitochondrial function. In mouse models, RTA 408 and analogs demonstrated the ability to increase glucose uptake, fatty oxidation, and oxygen consumption – direct signs of healthier cellular metabolism (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003357).

About Reata Pharmaceuticals, Inc.

Reata Pharmaceuticals, Inc. is a privately held company aiming to translate innovative research into breakthrough medicines for difficult diseases that have significant unmet needs. Reata is the leader in developing a novel class of drugs with potent transcription-regulating activity, called antioxidant inflammation modulators (AIMs). AIMs activate Nrf2, promoting the production of numerous antioxidant, detoxification, and anti-inflammatory genes, and inhibit NF-κB, a gene that regulates many pro-inflammatory proteins. The pharmacology of the AIMs mimics that of endogenous prostaglandin metabolites that are responsible for the orchestrated resolution of inflammation. The anti-inflammatory, cytoprotective and energy metabolism effects of AIM pharmacology have been documented in more than 250 scientific papers and are potentially relevant to a wide range of diseases.

CONTACT:
Reata Pharmaceuticals, Inc.
(972) 865-2219
info@reatapharma.com

Investor Relations:
The Trout Group
Lee M. Stern, CFA
lstern@troutgroup.com
(646) 378-2992

Reata Announces the Initiation of Phase 2 Studies Examining RTA 408 for the Treatment of Friedreich’s Ataxia and Mitochondrial Myopathies

IRVING, Texas, September 30, 2014 – Reata has received clearance from the Division of Neurology Products of the FDA to begin two new Phase 2 clinical programs in patients with Friedreich’s Ataxia and Mitochondrial Myopathies. Both of these orphan diseases are associated with reduced energy production, fatigue, and impaired exercise capacity. There are no existing therapies specifically approved to treat patients with these diseases.

Friedreich’s ataxia (FA) is an inherited disorder caused by defects in the gene for frataxin, a protein that regulates iron levels in the mitochondria. Defects in frataxin result in mitochondrial iron overload, causing impaired metabolism, oxidative stress, and damage to mitochondrial DNA. Patients with FA suffer progressive degeneration of the central and peripheral nervous systems, impaired coordination and gait, and fatigue from energy deprivation and muscle loss.

Mitochondrial Myopathies are a collection of individual orphan diseases that are associated with mitochondrial DNA mutations. These defects cause respiratory chain deficits and impaired energy production. Most of these patients share a similar phenotype characterized by skeletal muscle weakness and fatigue. These patients also may have other symptoms due to impaired energy production in other organ systems.

RTA 408 works by inducing Nrf2, which regulates multiple genes that play both direct and indirect roles in the production of cellular energy (i.e., adenosine triphosphate or ATP) within the mitochondria. Directly, activation of the Nrf2 pathway increases the efficient use of fuel (fatty acids and glucose) by mitochondria and increases mitochondrial biogenesis and basal oxygen consumption. Indirectly, activation of Nrf2, through its antioxidative effects, balances reducing equivalents and maintains mitochondrial homeostasis and efficiency. In addition to its positive effects on metabolic efficiency, Nrf2 activation has been shown in preclinical studies to promote muscle repair and recovery and reduce markers of oxidative stress and muscle injury.

“Our collaborators and we have shown in preclinical studies that genetic or pharmacologic Nrf2 activation positively regulates mitochondrial function and energy production. We hope to translate this effect into improved physical functioning and reduced fatigue in patients with Friedreich’s ataxia and mitochondrial myopathies. These rare, debilitating diseases currently have no approved therapies,” noted Dr. Colin Meyer, Reata’s Chief Medical Officer.

The two initial Phase 2 trials will both be multi-center, double-blind, randomized, dose-ranging, placebo-controlled studies. The primary efficacy endpoint in both studies will be peak work as assessed during exercise testing. The studies will also explore changes in other measures of physical activity, fatigue, and biomarkers associated with mitochondrial functioning.

About Reata Pharmaceuticals, Inc.

Reata Pharmaceuticals, Inc. is a privately held company aiming to translate innovative research into breakthrough medicines for difficult diseases that have significant unmet needs. Reata is the leader in developing a novel class of drugs with potent transcription-regulating activity called antioxidant inflammation modulators (AIMs). AIMs activate Nrf2, promoting the production of numerous antioxidant, detoxification, and anti-inflammatory genes, and inhibit NF-κB, a transcription factor that regulates many pro-inflammatory proteins. The pharmacology of the AIMs mimics that of endogenous prostaglandin metabolites that are responsible for the orchestrated resolution of inflammation. The anti-inflammatory, cytoprotective and energy metabolism effects of AIM pharmacology have been documented in more than 250 scientific papers and are potentially relevant to a wide range of diseases.

Due to the broad applicability of AIM biology, Reata is actively conducting or initiating phase 2 programs with AIMs in multiple therapeutic areas, including pulmonary arterial hypertension, oncology, Friedreich’s ataxia, mitochondrial myopathies, dermatology, and ophthalmology.

CONTACT:
Reata Pharmaceuticals, Inc.
(972) 865-2219
info@reatapharma.com

Investor Relations:
The Trout Group
Lee M. Stern, CFA
lstern@troutgroup.com
(646) 378-2992

Reata Enrolls First Patient in the PRIMROSE Study, a Phase 2 Study Examining RTA 408 in Breast Cancer Patients at Risk for Radiation Dermatitis

IRVING, Texas, July 25, 2014 – Reata today announced the enrollment of the first patient in a Phase 2 dose-ranging study examining the safety, tolerability, and efficacy of RTA 408 Lotion (3% and 0.5%) versus vehicle for the prevention and treatment of radiation dermatitis in breast cancer patients for whom radiation therapy (RT) is recommended.

PRIMROSE (A Randomized Double-Blind, Vehicle-Controlled, Parallel-Group Phase 2 Study of the Efficacy Safety, Pharmacokinetics, and Pharmacodynamics of RTA 408 Lotion in the Treatment of Patients at Risk for Radiation Dermatitis) is a multi-center study in approximately 180 patients. The primary efficacy endpoint is the time-averaged effect on radiation dermatitis severity.

Radiation dermatitis is a complication experienced by a majority of patients receiving radiation therapy for cancer. RT can damage the cellular structures in the skin and cause pain, ulceration, necrosis, and fibrosis of exposed skin tissues. Radiation dermatitis usually manifests within one to four weeks after initiation of RT and can result in delays in or failure to complete RT, limiting the dose effect of RT, which can negatively affect treatment outcomes. There are currently no approved agents for the prevention of radiation-induced dermatitis.

“Based on the preclinical and Phase 1 human data, we believe that RTA 408 Lotion may have the potential to become the first treatment to prevent and mitigate radiation dermatitis in breast cancer patients undergoing radiation therapy,” noted Dr. Colin Meyer, Reata’s Chief Medical Officer. “We are enthusiastic about investigating a therapy in an area where there is a lack of approved agents and high unmet medical need.”

For more information on this study, visit: http://clinicaltrials.gov/show/NCT02142959.

About RTA 408 Lotion

RTA 408 Lotion has been assessed in a Phase 1 study which evaluated the safety, pharmacokinetics, and local pharmacodynamics of RTA 408 Lotion in 32 healthy volunteers (http://clinicaltrials.gov/show/NCT02029716). Twice daily application for up to 28 days of 0.5% and 3% RTA 408 Lotion was safe and well-tolerated on skin areas up to 500 cm2. No drug-related systemic adverse events were observed in any subject and systemic exposure was negligible.

RTA 408 Lotion also has shown efficacy in mouse models of radiation dermatitis with both fractionated and acute radiation regimens. In the fractionated radiation dermatitis model, RTA 408 Lotion demonstrated a decrease in the severity of dermatitis in mice that received a cumulative radiation dose of 60 Gray (http://www.ncbi.nlm.nih.gov/pubmed/24720753). In this study, RTA 408 Lotion treatment was associated with a 55% reduction in the percentage of days with grade ≥2 radiation dermatitis compared with vehicle controls. Further, RTA 408 Lotion is not anticipated to interfere with radiation therapy, as RTA 408 has demonstrated enhanced therapeutic efficacy when orally administered concomitantly with radiation therapy in mouse cancer models.

About Reata Pharmaceuticals, Inc.

Reata Pharmaceuticals, Inc. is a privately held company aiming to translate innovative research into breakthrough medicines for difficult diseases that have significant unmet needs. Reata is the leader in developing a novel class of drugs with potent transcription-regulating activity, called antioxidant inflammation modulators (AIMs). AIMs activate Nrf2, promoting the production of numerous antioxidant, detoxification, and anti-inflammatory genes, and inhibit NF-κB, a gene that regulates many pro-inflammatory proteins. The pharmacology of the AIMs mimics that of endogenous prostaglandin metabolites that are responsible for the orchestrated resolution of inflammation. The anti-inflammatory, cytoprotective and energy metabolism effects of AIM pharmacology have been documented in more than 250 scientific papers and are potentially relevant to a wide range of diseases.

CONTACT:
Reata Pharmaceuticals, Inc.
(972) 865-2219
info@reatapharma.com

Investor Relations:
The Trout Group
Lee M. Stern, CFA
lstern@troutgroup.com
(646) 378-2992

Reata Begins Enrolling the LARIAT study, a Phase 2 Study Examining Bardoxolone Methyl for the Treatment of Patients with Pulmonary Arterial Hypertension

IRVING, Texas, May 12, 2014 – Reata has enrolled the first patient in a Phase 2 dose ranging study examining the safety, tolerability and efficacy of bardoxolone methyl in patients with pulmonary arterial hypertension (PAH).

PAH is a life-threatening disease involving endothelial dysfunction, vasoconstriction in small pulmonary arteries, aberrant proliferation of certain vascular cells, and dysregulated inflammatory signaling leading to vascular remodeling, pulmonary fibrosis, and right ventricular hypertrophy. PAH has been estimated to affect 15 to 20 thousand people in the United States, predominantly middle-aged women. Available treatments for PAH can provide symptomatic improvement, primarily by relieving vasoconstriction (e.g., by inhibiting signaling in the endothelin-1 pathway), but they do not directly suppress inflammation or proliferation pathways and the disease continues to progress. Consequently, there is a very high unmet clinical need for new therapy; PAH has a high mortality rate with 60 to 80 percent of patients dying within five years of diagnosis.

An extensive body of research by leading academic and Reata scientists has demonstrated that bardoxolone methyl and related compounds have highly potent antioxidant and anti-inflammatory properties, including beneficial effects on endothelial dysfunction, as well as anti-proliferative and anti-fibrotic effects.

“Internal Reata research has demonstrated that AIMs promote normal vasodilatory tone by restoring endothelial function and suppressing vasoconstrictive endothelin signaling. While this activity should complement available PAH therapies, through inhibition of pro-inflammatory NF-κB signaling bardoxolone methyl also directly suppresses inappropriate proliferation, which is not directly affected by currently approved products,” noted Dr. Colin Meyer, Reata’s Chief Medical Officer. “Additionally, our collaborators and we have shown in preclinical studies that Nrf2 activation positively regulated mitochondrial function, promoting increased cellular energy production. This is reduced in many PAH patients and results in significant fatigue and functional impairment.”

This trial is a multi-center, double-masked, randomized, dose-ranging, placebo-controlled study. The primary efficacy endpoint is a six minute walk test. The study will also explore changes from baseline in cardiopulmonary exercise testing, cardiac magnetic resonance imaging, parameters collected during Doppler echocardiography and other measures. For more information on this study, visit: http://clinicaltrials.gov/show/NCT02036970.

About Reata Pharmaceuticals, Inc.

Reata Pharmaceuticals, Inc. is a privately held company aiming to translate innovative research into breakthrough medicines for difficult diseases that have significant unmet needs. Reata is the leader in developing a novel class of drugs with potent transcription-regulating activity, called antioxidant inflammation modulators (AIMs). AIMs activate Nrf2, promoting the production of numerous antioxidant, detoxification, and anti-inflammatory genes, and inhibit NF-κB, a gene that regulates many pro-inflammatory proteins. The pharmacology of the AIMs mimics that of endogenous prostaglandin metabolites that are responsible for the orchestrated resolution of inflammation. The anti-inflammatory, cytoprotective and energy metabolism effects of AIM pharmacology have been documented in more than 250 scientific papers and are potentially relevant to a wide range of diseases.

CONTACT:
Reata Pharmaceuticals, Inc.
(972) 865-2219
info@reatapharma.com

Reata Pharmaceuticals Announces Completion of Enrollment in First Cohort of Phase 1 Trial of RTA 408 in Non-Small Cell Lung Cancer and Melanoma

IRVING, Texas, May 2, 2014 – Reata Pharmaceuticals, Inc., announced that patient enrollment and safety evaluation in the first cohort of a Phase 1 trial of RTA 408 is now complete. The first-in-human study is evaluating the safety, tolerability, pharmacodynamic activity, and efficacy of RTA 408 when administered to patients with metastatic NSCLC and melanoma who have failed available treatment options.

Dr. Colin Meyer, Chief Medical Officer, noted that “Initial data from this study are encouraging and consistent with RTA 408’s preclinical safety profile. Based on the favorable pharmacokinetic data from this first cohort, we are preparing to initiate a Phase 2 study of RTA 408 in combination with ipilimumab in patients with advanced or unresectable melanoma to exploit the immune unmasking effect of RTA 408.”

RTA 408 is a novel oleanane triterpenoid that (through activation of Nrf2 and inhibition of NF-κB) suppresses tumor-driven inflammation that is believed to mask cancers from the immune system. Myeloid-derived suppressor cells (MDSCs) produce large amounts of reactive oxygen (ROS) and nitrogen species (RNS) in the tumor micro-environment. ROS and RNS act as a molecular “cloak” that prevents killer T-cells from recognizing tumor antigen. Recent clinical studies have reported that high levels of MDSCs predict lack of response to ipilimumab and are associated with poor survival in melanoma patients. Preclinical data show that RTA 408 and analogs reduce tumor ROS and RNS levels, inhibit the activity of MDSCs, augment T-cell anticancer activity, and restore immune recognition of tumor-specific antigens, thereby enhancing the capacity of the immune system to mount an antitumor response.

For more information on this study, visit: http://clinicaltrials.gov/show/NCT02029729.

About Reata Pharmaceuticals, Inc.

Reata Pharmaceuticals, Inc. is a privately held company aiming to translate innovative research into breakthrough medicines for difficult diseases that have significant unmet needs. Reata is the leader in developing a novel class of drugs with potent transcription-regulating activity called antioxidant inflammation modulators (AIMs). AIMs activate Nrf2, promoting the production of numerous antioxidant, detoxification, and anti-inflammatory genes, and inhibit NF-κB, a transcription factor that regulates many pro-inflammatory proteins. The pharmacology of the AIMs mimics that of endogenous prostaglandin metabolites that are responsible for the orchestrated resolution of inflammation. The anti-inflammatory, cytoprotective and energy metabolism effects of AIM pharmacology have been documented in more than 250 scientific papers and are potentially relevant to a wide range of diseases.

CONTACT:
Reata Pharmaceuticals, Inc.
(972) 865-2219
info@reatapharma.com