Cystic Fibrosis Foundation Therapeutics Inc.

Bethesda, MD, United States

Cystic Fibrosis Foundation Therapeutics Inc.

Bethesda, MD, United States

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Q1 2017 marked by positive data from Phase 2 study of anabasum for the treatment of cystic fibrosis Company ended the quarter with $49 million of cash which is sufficient to fund operations through the end of 2018 NORWOOD, MA--(Marketwired - May 09, 2017) - Corbus Pharmaceuticals Holdings, Inc. ( : CRBP) ("Corbus" or the "Company"), a clinical stage drug development company targeting rare, chronic, serious inflammatory and fibrotic diseases, announced today its financial results for the first quarter ended March 31, 2017. The Company also provided an update to its corporate progress, clinical status and anticipated milestones for anabasum, its novel synthetic oral endocannabinoid-mimetic drug that is designed to resolve chronic inflammation and halt fibrosis. "We have made significant progress in both the corporate and clinical areas in the first quarter of 2017 and are in a strong financial position, which is expected to take us through key milestones for the Company over the next 20 months," stated Yuval Cohen, Ph.D., Chief Executive Officer of the Company. Corbus reported positive topline data results from a Phase 2 study in diffuse cutaneous systemic sclerosis ("systemic sclerosis") in November 2016, showing a clear signal of clinical benefit with anabasum. The 12-month open-label extension of this Phase 2 study is ongoing and is designed to capture long-term safety and efficacy data in subjects dosed with anabasum 20 mg twice per day. To date, subjects have been safely dosed with anabasum for up to 10 months and Corbus intends to present data at the 2017 American College of Rheumatology ("ACR") Annual Meeting. Following an end-of-Phase 2 meeting with the U.S. Food and Drug Administration ("FDA"), Corbus submitted a protocol to the FDA for its Phase 3 study in systemic sclerosis on March 31, 2017, and is moving forward as planned. The Company expects to commence this study in the fourth quarter of 2017. Protocol assistance from the European Medicines Agency ("EMA") on the Phase 3 study design is expected in the second quarter of 2017. The planned Phase 3 study is a double-blind, randomized, placebo-controlled, parallel dose, multi-center study to be conducted in approximately 270 adults with diffuse cutaneous systemic sclerosis. Subjects will be randomized to receive anabasum 20 mg twice per day, anabasum 5 mg twice per day, or placebo twice per day for 52 weeks. The primary efficacy outcome of the planned Phase 3 study will be change from baseline at Week 52 in modified Rodnan Skin Score ("mRSS"), a measure of skin thickening and a validated clinical outcome measure in systemic sclerosis. Topline results of the Phase 2 study showed that the mean improvement from baseline in mRSS for anabasum-treated subjects was greater than for the placebo-treated subjects, and considered medically meaningful. The improvement in mRSS was accompanied by statistically significant improvement in the anabasum arm in patient-reported skin symptoms and reduced expression of genes associated with inflammation and fibrosis in skin biopsies. Corbus expects to complete enrollment of the 52-week study in 2018. The Company also expects results by the end of 2019 and a New Drug Application ("NDA") application to be filed in 2020. Anabasum was granted Orphan Drug Designation and Fast Track status for the treatment of systemic sclerosis from the FDA in 2015 and Orphan Designation from the European Medicines Agency ("EMA") in January 2017. The Company was not granted Breakthrough Designation for systemic sclerosis, however Corbus' existing Fast Track status already grants it similar eligibility for more frequent meetings with the FDA to discuss the development plan for anabasum, as well as Priority Review and Rolling Reviews of completed sections of the NDA. In March 2017, Corbus reported positive topline data from the double-blind, randomized, placebo-controlled Phase 2 study of anabasum for the treatment of cystic fibrosis ("CF") showing that anabasum had an acceptable safety and tolerability profile, reduced pulmonary exacerbations treated with antibiotics, and reduced multiple inflammatory biomarkers in sputum collected from subjects in the study. The 16-week study was an international, multi-center study supported by a $5 million Development Award from Cystic Fibrosis Foundation Therapeutics, Inc. Anabasum successfully achieved the primary objective of the study by demonstrating an acceptable safety and tolerability profile with no serious or severe adverse events related to the study drug. Anabasum cohorts showed a reduction in a number (event rate per subject) of pulmonary exacerbations treated with intravenous antibiotics compared to placebo, which was a prespecified event of special interest in the protocol, as well as the number (event rate per subject) of pulmonary exacerbations treated with any new antibiotic. Patients in the highest dose cohort of anabasum (20 mg orally, twice per day) had a 75% reduction in the annualized rate of pulmonary exacerbations requiring IV antibiotics compared to placebo cohort. Forced expiratory volume in 1 second (FEV1) remained stable throughout the study in all treatment cohorts. Additionally, patients receiving anabasum showed a reduction in multiple inflammatory cell types in sputum, including total leukocytes, neutrophils, eosinophils, and macrophages. Also, a dose-dependent reduction in sputum inflammatory mediators, including interleukin-8, neutrophil elastase, and immunoglobulin G was observed. These data provide evidence of pharmacologic activity of anabasum at resolving ongoing innate immune responses in lungs of CF patients and support the potential of anabasum to reduce in pulmonary exacerbations in CF. Anabasum was granted Orphan Drug Designation and Fast Track status for the treatment of CF by the FDA in 2015 and Orphan Designation from the EMA in 2016. Corbus is currently evaluating anabasum in an on-going Phase 2 study for the treatment of skin-predominant dermatomyositis. In November 2016, the Company commenced a one-year, open-label extension to provide all enrolled subjects in the Phase 2 study with the option of receiving anabasum for one year after they complete the four-month, double-blind placebo controlled portion of the study. The Phase 2 study in skin-predominant dermatomyositis is being funded by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health to the University of Pennsylvania School of Medicine. For more information on the Phase 2 study with anabasum for the treatment of skin-predominant dermatomyositis, please visit ClinicalTrials.gov and reference Identifier NCT02466243. Corbus expects the National Institutes of Health ("NIH")-funded and operationally-executed Phase 2 clinical study evaluating anabasum for the treatment of systemic lupus erythematosus ("SLE") to begin in the second half of 2017. The Phase 2 SLE study will evaluate anabasum at doses of 5 mg, 20 mg, and 20 mg twice daily, administered orally for 12 weeks, with 1 month follow-up, at approximately 12 U.S. sites. "We are very pleased with our progress in the clinical development of anabasum over the past two years, advancing this experimental drug into multiple first-in-patient studies in serious chronic indications with high unmet medical needs, two of which have delivered positive clinical data and are moving ahead to their next stages of clinical development by year end," concluded Dr. Cohen. Summary of Financial Results for First Quarter 2017 For the quarter ended March 31, 2017, the Company reported a net loss of approximately $7,465,000, or a net loss per diluted share of $0.16, compared to a net loss of approximately $2,892,000, or a net loss per diluted share of $0.08 for the quarter ended March 31, 2016. Collaboration revenue for the quarter increased by approximately $0.9 million to $1.3 million due to revenue recognized from the $5 million development award received from the Cystic Fibrosis Foundation Therapeutics, Inc. Operating expenses increased by approximately $5.4 million to $8.7 million due to increased spending for clinical studies, manufacturing costs to produce anabasum for clinical studies and staffing costs. The Company ended the first quarter with $48.9 million of cash and cash equivalents, an increase of $33.9 million from the start of the quarter. The Company raised $41 million of capital during the first quarter including the following: The Company expects the cash on hand to fund operations through the fourth quarter of 2018, based on current planned expenditures. Anabasum is a novel synthetic oral endocannabinoid-mimetic drug that preferentially binds to the CB2 receptor expressed on activated immune cells and fibroblasts. CB2 activation triggers endogenous pathways that resolve inflammation and halt fibrosis. Preclinical and human clinical studies have shown anabasum to have a favorable safety, tolerability and pharmacokinetic profile. It has also demonstrated promising potency in preclinical models of inflammation and fibrosis. Anabasum is designed to trigger the production of "Specialized Pro-resolving Lipid Mediators" that activate an endogenous cascade responsible for the resolution of inflammation and fibrosis, while reducing production of multiple inflammatory mediators. Anabasum also is designed to have direct effects on fibroblasts to halt tissue scarring. In effect, anabasum triggers endogenous pathways to turn "off" chronic inflammation and fibrotic processes, without causing immunosuppression. Corbus Pharmaceuticals Holdings, Inc. is a clinical stage pharmaceutical company focused on the development and commercialization of novel therapeutics to treat rare, chronic, and serious inflammatory and fibrotic diseases. Our lead product candidate, anabasum, is a novel synthetic oral endocannabinoid-mimetic drug designed to resolve chronic inflammation, and fibrotic processes. Anabasum is currently in development for the treatment of cystic fibrosis, diffuse cutaneous systemic sclerosis, skin-predominant dermatomyositis, and systemic lupus erythematosus. For more information, please visit www.CorbusPharma.com and connect with the Company on Twitter, LinkedIn, Google+ and Facebook. This press release contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to the Company's product development, clinical and regulatory timelines, market opportunity, competitive position, possible or assumed future results of operations, business strategies, potential growth opportunities and other statement that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management's current beliefs and assumptions. These statements may be identified by the use of forward-looking expressions, including, but not limited to, "expect," "anticipate," "intend," "plan," "believe," "estimate," "potential," "predict," "project," "should," "would" and similar expressions and the negatives of those terms. These statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Such factors include those set forth in the Company's filings with the Securities and Exchange Commission. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this press release. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.


BEDMINSTER, N.J., Dec. 08, 2016 (GLOBE NEWSWIRE) -- Matinas BioPharma Holdings, Inc. (OTCQB:MTNB), a clinical-stage biopharmaceutical company focused on identifying and developing safe and effective broad spectrum therapeutics for the treatment of serious and life-threatening infections, announced today that it has received a research contract award from Cystic Fibrosis Foundation Therapeutics Inc. (CFFT), the non-profit drug discovery and development affiliate of the Cystic Fibrosis Foundation, to study its lead antibiotic product candidate MAT2501, for the treatment of pre-clinical nontuberculous mycobacterium infection (NTM) in models of cystic fibrosis (CF). The award provided by CFFT will support a collaborative research program between Matinas BioPharma and Colorado State University (CSU) to study the efficacy of MAT2501 in the treatment of NTM infection by a range of mycobacterium species, including mycobacterium abscessus, in a CF lung infection model developed by CSU. NTM infections have emerged in recent years as an increasing problem to individuals with cystic fibrosis and other lung diseases. NTM infections are or have become increasingly resistant to most available antibiotics, making them extremely difficult to treat. Currently available treatments have limited efficacy for treating these life-threatening infections in people with CF and have also been shown to be highly toxic to patients. MAT2501 is Matinas BioPharma’s orally-administered, encochleated formulation of the broad spectrum IV-only aminoglycoside antibiotic agent amikacin, which utilizes the Company’s proprietary lipid-crystal nano-particle delivery technology. Amikacin is currently used to treat different types of chronic and acute bacterial infections, including NTM infections and various multidrug-resistant gram negative bacterial infections. IV-administered amikacin is associated with major side effects including nephrotoxicity and ototoxicity (permanent loss of hearing) with long-term use. “We are honored to receive the support of Cystic Fibrosis Foundation Therapeutics for this important research program, and our hope is that this is the beginning of what promises to be a long-term relationship as we advance the clinical development of MAT2501. Mycobacterium infections in people with cystic fibrosis are very difficult to treat, to a significant degree, because of the unique complications associated with CF. In earlier pre-clinical work, we demonstrated the efficacy of MAT2501 against several mycobacterium species. Anti-infectives formulated in our cochleate technology are uniquely targeted toward the site of infection while significantly reducing toxicities. We are looking forward to working with CFFT and CSU with the goal to expand the treatment options for CF patients battling these multi-drug resistant mycobacterium infections,” said Raphael Mannino, Ph.D., Chief Scientific Officer of Matinas BioPharma and Principal Investigator of the CF research program. MAT2501 is specifically designed to provide targeted delivery of the potent antibiotic amikacin while providing a significantly improved safety and tolerability profile, in order to allow for chronic dosing of this potent antibiotic agent. In preclinical studies MAT2501 demonstrated oral bioavailability and targeted delivery of amikacin directly to the site of infection in both pulmonary (lung) and disseminated NTM infections. American Thoracic Society (ATS)/Infectious Disease Society of America (IDSA) guidance for the treatment of patients with NTM infections refractory to guideline therapy includes a treatment duration of 12 months or longer. The profile of MAT2501 was designed to allow for safe and tolerable use of amikacin during such long-term treatment. MAT2501 is designated as a Qualified Infectious Disease Product (QIDP) and as an Orphan Drug for the treatment of NTM by the U.S. Food and Drug Administration (FDA). Orphan Drug designation of MAT2501 provides for a seven-year marketing exclusivity period against competition in the United States upon FDA approval, as well as other incentives and exemptions, including waiver of Prescription Drug User Fee Act (PDUFA) filing fees and tax credits for the cost of the clinical research. If MAT2501 is ultimately approved by the FDA, the seven-year period of marketing exclusivity from orphan designation combined with the additional five years of marketing exclusivity provided by the QIDP designation, provides for a potential total of 12 years of marketing exclusivity. The Company also intends to explore the development of MAT2501 for the treatment of a variety of multi-drug resistant, gram negative bacterial infections. Nontuberculous mycobacteria (NTM) are naturally occurring organisms found in water, soil, plants and animals. NTM causes many serious and life-threatening diseases, including pulmonary disease, skin and soft tissue disease, joint infections and, in immunocompromised individuals, disseminated infection. The most common clinical manifestation of NTM disease is pulmonary, or lung, disease. NTM lung infection occurs when a person inhales the organism from their environment. While most people do not become ill, some individuals develop a slow, progressive and destructive disease when NTM infects the airways and lung tissue leading to inflammation in the respiratory system. Individuals susceptible to the infection often have an unknown defect in their lung structure or immune system, lung damage from a pre-existing chronic obstructive pulmonary disease (COPD), such as emphysema and bronchiectasis, cystic fibrosis, or an immune deficiency disorder, such as HIV or AIDS. There are about 50,000 to 90,000 people with NTM pulmonary disease in the United States, with a much higher frequency in older adults, and these numbers appear to be increasing. However, NTM can affect any age group. Without treatment, the progressive lung infection caused by NTM results in severe cough, fatigue, and often weight loss. In some people NTM infections can become chronic and require ongoing treatment. Treatment may be difficult because NTM bacteria may be resistant to many common types of antibiotics. Severe NTM lung disease can have a significant impact on quality of life and can be life-threatening. MAT2501 is an orally-administered, encochleated formulation of the broad spectrum IV-only aminoglycoside antibiotic agent amikacin, which utilizes the Company’s proprietary, lipid-crystal, nanoparticle delivery technology. Amikacin is currently used to treat different types of chronic and acute bacterial infections, including NTM infections and various multidrug-resistant gram negative bacterial infections. IV-administered amikacin is associated with major side effects including nephrotoxicity and ototoxicity (permanent loss of hearing) with long-term use. MAT2501 is specifically designed to provide targeted delivery of the potent antibiotic amikacin while providing a significantly improved safety and tolerability profile. In preclinical studies MAT2501 demonstrated oral bioavailability and targeted delivery of amikacin directly to the site of infection in both pulmonary (lung) and disseminated NTM infections. Matinas recently received FDA clearance to initiate a Phase 1 clinical study of MAT2501 under the open IND for the treatment of non-tuberculous mycobacterium infections. The FDA has also designated MAT2501 as a QIDP and an Orphan Drug for the treatment of NTM infections. The Company intends to initially develop MAT2501 for the treatment of NTM infections and will also explore the development of MAT2501 for the treatment of a variety of multi-drug resistant, gram negative bacterial infections. If approved, we believe MAT2501 would become the first orally bioavailable aminoglycoside and represent a significant improvement over existing therapies from a treatment and health economic perspective. Matinas BioPharma is a clinical-stage biopharmaceutical company focused on identifying and developing safe and effective broad spectrum therapeutics for the treatment of serious and life-threatening infections. The Company's proprietary, disruptive technology utilizes lipid-crystal nano-particle cochleates to nano-encapsulate existing drugs, making them safer, more tolerable, less toxic and orally bioavailable. The Company's lead drug candidate is MAT2203, an orally-administered, encochleated formulation of amphotericin B (a broad spectrum fungicidal agent). The Company has an open Investigational New Drug (IND) application for MAT2501, which is an orally-administered, encochleated formulation of amikacin (a broad spectrum aminoglycoside antibiotic agent) for acute bacterial infections, including non-tuberculous mycobacterium (NTM) and multi-drug resistant gram negative bacterial infections. The Company's lead anti-infective product candidates, MAT2203 and MAT2501, position Matinas BioPharma to become a leader in the safe and effective delivery of anti-infective therapies utilizing its proprietary lipid-crystal nano-particle cochleate formulation technology. For more information, please visit www.matinasbiopharma.com and connect with the Company on Twitter, LinkedIn, Facebook, and Google+. Forward Looking Statements: This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including those relating to the Company's strategic focus and the future development of its product candidates, including MAT2203 and MAT2501, the anticipated timing of regulatory submissions, the anticipated timing of clinical studies, the Company’s ability to identify and pursue development and partnership opportunities for its products or platform delivery technology on favorable terms, if at all, and the ability to obtain required regulatory approval and other statements that are predictive in nature, that depend upon or refer to future events or conditions. All statements other than statements of historical fact are statements that could be forward-looking statements. Forward-looking statements include words such as "expects," "anticipates," "intends," "plans," "could," "believes," "estimates" and similar expressions. These statements involve known and unknown risks, uncertainties and other factors which may cause actual results to be materially different from any future results expressed or implied by the forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties, including, but not limited to, our ability to obtain additional capital to meet our liquidity needs on acceptable terms, or at all, including the additional capital which will be necessary to complete the clinical trials of our product candidates; our ability to successfully complete research and further development and commercialization of our product candidates; the uncertainties inherent in clinical testing; the timing, cost and uncertainty of obtaining regulatory approvals; our ability to maintain and derive benefit from the Qualified Infectious Disease Product (QIDP), Orphan and/or Fast Track designations for MAT2203 and MAT2501, which does not change the standards for regulatory approval or guarantee regulatory approval on an expedited basis, or at all; our ability to protect the Company's intellectual property; the loss of any executive officers or key personnel or consultants; competition; changes in the regulatory landscape or the imposition of regulations that affect the Company's products; and the other factors listed under "Risk Factors" in our filings with the SEC, including Forms 10-K, 10-Q and 8-K. Investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this release. Except as may be required by law, the Company does not undertake any obligation to release publicly any revisions to such forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. Matinas BioPharma's product candidates are all in a development stage and are not available for sale or use.


Conti B.J.,Oregon Health And Science University | Devaraneni P.K.,Oregon Health And Science University | Yang Z.,Oregon Health And Science University | David L.L.,Oregon Health And Science University | And 2 more authors.
Molecular Cell | Year: 2015

The ER Sec61 translocon is a large macromolecular machine responsible for partitioning secretory and membrane polypeptides into the lumen, cytosol, and lipid bilayer. Because the Sec61 protein-conducting channel has been isolated in multiple membrane-derived complexes, we determined how the nascent polypeptide modulates translocon component associations during defined cotranslational translocation events. The model substrate preprolactin (pPL) was isolated principally with Sec61αβγ upon membrane targeting, whereas higher-order complexes containing OST, TRAP, and TRAM were stabilized following substrate translocation. BlockingpPL translocation by passenger domain folding favored stabilization of an alternate complex that contained Sec61, Sec62, and Sec63. Moreover, Sec62/63 stabilization within the translocon occurred for native endogenous substrates, such as the prion protein, and correlated with a delay in translocationinitiation. These data show that cotranslational translocon contacts are ultimately controlled by the engaged nascent chain and the resultant substrate-driven translocation events. © 2015 Elsevier Inc.


Solomon G.M.,University of Alabama at Birmingham | Konstan M.W.,Case Western Reserve University | Wilschanski M.,Hadassah University Hospitals | Billings J.,University of Minnesota | And 12 more authors.
Chest | Year: 2010

Background: The transepithelial nasal potential difference (NPD) is used to assess cystic fibrosis transmembrane conductance regulator (CFTR) activity. Unreliability, excessive artifacts, and lack of standardization of current testing systems can compromise its use as a diagnostic test and outcome measure for clinical trials. Methods: To determine whether a nonperfusing (agar gel) nasal catheter for NPD measurement is more reliable and less susceptible to artifacts than a continuously perfusing nasal catheter, we performed a multicenter, randomized, crossover trial comparing a standardized NPD protocol using an agar nasal catheter with the same protocol using a continuously perfusing catheter. The data capture technique was identical in both protocols. A total of 26 normal adult subjects underwent NPD testing at six different centers. Results: Artifact frequency was reduced by 75% (P < .001), and duration was less pronounced using the agar catheter. The measurement of sodium conductance was similar between the two catheter methods, but the agar catheter demonstrated significantly greater CFTR-dependent hyperpolarization, because Δ zero Cl- + isoproterenol measurements were significantly more hyperpolarized with the agar catheter (-24.2 ± 12.9 mV with agar vs 18.2 ± 9.1 mV with perfusion, P < .05). Conclusions: The agar nasal catheter approach demonstrates superior reliability compared with the perfusion nasal catheter method for measurement of NPD. This nonperfusion catheter method should be considered for adoption as a standardized protocol to monitor CFTR activity in clinical trials. © 2010 American College of Chest Physicians.


Ashlock M.A.,Cystic Fibrosis Foundation Therapeutics Inc. | Olson E.R.,Vertex Pharmaceuticals
Annual Review of Medicine | Year: 2011

Cystic fibrosis (CF) is a progressive genetic disease primarily involving the respiratory and gastrointestinal tracts. Multiple therapies directed at CF symptoms and clinical management strategies have emerged from iterative cycles of therapeutics development, helping to change the face of CF from a fatal childhood affliction to a disease in which nearly 50 of U.S. patients are adults. However, as a consequence of therapeutic advances, the burden of CF care is high, and despite progress, most patients succumb to respiratory failure. Addressing the basic defect in CF with systemic small molecules is evolving as a promising approach. A successful collaboration between a voluntary health organization and a pharmaceutical company, complemented by academic investigators and patients, has led to the clinical development of investigational drugs that restore function to defective CFTR protein in various tissues in CF patients. Important activities, leverage points, and challenges in this exemplary collaboration are reviewed with hope that the CF and other genetic disease communities can benefit from the lessons learned in generating new therapeutic approaches in CF. © 2011 by Annual Reviews. All rights reserved.


Wetmore D.R.,Cystic Fibrosis Foundation Therapeutics Inc. | Joseloff E.,Cystic Fibrosis Foundation Therapeutics Inc. | Pilewski J.,University of Pittsburgh | Lee D.P.,Metabolon | And 5 more authors.
Journal of Biological Chemistry | Year: 2010

Cystic fibrosis (CF) is a life-shortening disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. To gain an understanding of the epithelial dysfunction associated with CF mutations and discover biomarkers for therapeutics development, untargeted metabolomic analysis was performed on primary human airway epithelial cell cultures from three separate cohorts of CF patients and non-CF subjects. Statistical analysis revealed a set of reproducible and significant metabolic differences between the CF and non-CF cells. Aside from changes that were consistent with known CF effects, such as diminished cellular regulation against oxidative stress and osmotic stress, new observations on the cellular metabolism in the disease were generated. In the CF cells, the levels of various purine nucleotides, which may function to regulate cellular responses via purinergic signaling, were significantly decreased. Furthermore, CF cells exhibited reduced glucose metabolism in glycolysis, pentose phosphate pathway, and sorbitol pathway, which may further exacerbate oxidative stress and limit the epithelial cell response to environmental pressure. Taken together, these findings reveal novel metabolic abnormalities associated with the CF pathological process and identify a panel of potential biomarkers for therapeutic development using this model system. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.


Patent
Cystic Fibrosis Foundation Therapeutics Inc. | Date: 2010-04-05

The present invention relates to compositions for the treatment of conditions, including pancreatic insufficiency. The compositions of the present invention comprise lipase, protease and amylase in a particular ratio that provides beneficial results in patients, such as those afflicted with pancreatic insufficiency. This invention also relates to methods using such compositions for the treatment of pancreatic insufficiency.


PubMed | Cystic Fibrosis Foundation Therapeutics Inc
Type: Journal Article | Journal: The Journal of biological chemistry | Year: 2010

Cystic fibrosis (CF) is a life-shortening disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. To gain an understanding of the epithelial dysfunction associated with CF mutations and discover biomarkers for therapeutics development, untargeted metabolomic analysis was performed on primary human airway epithelial cell cultures from three separate cohorts of CF patients and non-CF subjects. Statistical analysis revealed a set of reproducible and significant metabolic differences between the CF and non-CF cells. Aside from changes that were consistent with known CF effects, such as diminished cellular regulation against oxidative stress and osmotic stress, new observations on the cellular metabolism in the disease were generated. In the CF cells, the levels of various purine nucleotides, which may function to regulate cellular responses via purinergic signaling, were significantly decreased. Furthermore, CF cells exhibited reduced glucose metabolism in glycolysis, pentose phosphate pathway, and sorbitol pathway, which may further exacerbate oxidative stress and limit the epithelial cell response to environmental pressure. Taken together, these findings reveal novel metabolic abnormalities associated with the CF pathological process and identify a panel of potential biomarkers for therapeutic development using this model system.


PubMed | Cystic Fibrosis Foundation Therapeutics Inc.
Type: | Journal: Annual review of medicine | Year: 2011

Cystic fibrosis (CF) is a progressive genetic disease primarily involving the respiratory and gastrointestinal tracts. Multiple therapies directed at CF symptoms and clinical management strategies have emerged from iterative cycles of therapeutics development, helping to change the face of CF from a fatal childhood affliction to a disease in which nearly 50% of U.S. patients are adults. However, as a consequence of therapeutic advances, the burden of CF care is high, and despite progress, most patients succumb to respiratory failure. Addressing the basic defect in CF with systemic small molecules is evolving as a promising approach. A successful collaboration between a voluntary health organization and a pharmaceutical company, complemented by academic investigators and patients, has led to the clinical development of investigational drugs that restore function to defective CFTR protein in various tissues in CF patients. Important activities, leverage points, and challenges in this exemplary collaboration are reviewed with hope that the CF and other genetic disease communities can benefit from the lessons learned in generating new therapeutic approaches in CF.

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