Galectin Therapeutics' Phase 1 Data Presented at AASLD Annual Meeting Advances GR-MD-02 Into Phase 2 Clinical Development

NORCROSS, Ga., Nov. 9, 2014 (GLOBE NEWSWIRE) -- Galectin Therapeutics Inc. (Nasdaq:GALT), the leading developer of therapeutics that target galectin proteins to treat fibrosis and cancer, presented data today from the Company's Phase 1 clinical trial of GR-MD-02 in NASH (fatty liver disease) patients with advanced fibrosis at The Liver Meeting in Boston, Massachusetts. Stephen A. Harrison, MD, Chief of Hepatology at Brooke Army Medical Center in Fort Sam Houston and a clinical trial investigator in Galectin Therapeutics' Phase 1 clinical trial, shared the data during an oral presentation at the 65^th Annual Meeting of the American Association for the Study of Liver Diseases.

The Phase 1 first-in-man study evaluated the safety, tolerability, and drug pharmacokinetics for single and multiple doses of galectin-inhibiting drug GR-MD-02 when administered to patients with NASH (fatty liver disease) with advanced fibrosis. Additionally, exploratory serum biomarkers were evaluated as potential tools that may be used to aid in future studies. Dr. Harrison reviewed previously-reported results from the ongoing Phase 1 clinical trial including completed cohorts 1 and 2 and also presented, for the first time, interim data from completed patients from cohort 3. In the three-cohort design, eight patients (6 active drug and 2 placebo) completed cohort 1 at the 2 mg/kg dosage; nine patients (7 active drug and 2 placebo) completed cohort 2 at the 4 mg/kg dosage; and nine patients (6 active drug and 3 placebo) have so far completed cohort 3 at the 8 mg/kg dosage. Therefore, there was a similar number of patients from each of the cohorts for comparison purposes.

Overall, data from the multi-center, partially blinded Phase 1 trial showed that administration of 2, 4 and 8 mg/kg lean body weight of GR-MD-02 intravenously for four doses over 6 weeks was safe and well tolerated. Thus, the primary endpoint of the study has been met. There were no serious adverse events reported in any of the three cohorts and mild (grade 1) adverse events possibly related to study drug were found in 3 placebo patients and only 2 patients receiving active drug.

In cohorts 1 and 2, pharmacokinetic data demonstrated a proportional increase in total drug exposure with doubling of the dose of GR-MD-02 with no accumulation after four doses. In newly released data from cohort 3, Dr. Harrison reported that pharmacokinetic analysis of GR-MD-02 plasma levels for the 8 mg/kg dose provides drug coverage in the upper portion of the targeted therapeutic range derived from NASH animal model studies.

An evaluation of exploratory serum biomarkers in all three cohorts revealed that the vast majority of biomarkers do not seem to be useful tools to aid in the design of short-term therapeutic trials. These exploratory biomarkers showed marked variability over time in placebo patients as well as active drug patients.

In contrast to other biomarkers, FibroTest^®, a composite score that has been correlated with the extent of liver fibrosis, was significantly reduced by GR-MD-02 treatment in cohort 3. The treatment effect on FibroTest score was due to a statistically significant reduction of alpha-2 macroglobulin, one of the components of the score. This reduction in FibroTest score and alpha-2 macroglobulin was only seen in the high dose cohort 3 and not in cohort 1 and 2.

According to Dr. Harrison, "Today's presentation to the scientific community at AASLD reveals key insight into the safe use of GR-MD-02 on fatty liver disease in advanced fibrosis. The objective of the Phase 1 trial is to evaluate safety and pharmacokinetics of GR-MD-02. What we have seen so far in the Phase 1 trial is that GR-MD-02 is safe and well tolerated at multiple doses. It was an added bonus that we found a reduction for serum biomarker alpha-2 macroglobulin."

"The company is planning to initiate a Phase 2 clinical trial in the second quarter of 2015 based on the robust pre-clinical effects of the drug and these successful Phase 1 results," said Peter G. Traber, M.D., Chief Executive Officer, President and Chief Medical Officer of Galectin Therapeutics. "Following a recent meeting with the U.S. Food and Drug Administration, the company has determined its Phase 2 trial will be in NASH patients with cirrhosis with evaluation of portal hypertension (hepatic venous pressure gradient) as the primary surrogate endpoint and the amount of collagen, as determined by digital morphometric analysis, as a key secondary endpoint. Additional non-invasive measures of liver function and structure will also be assessed. Further details of the Phase 2 clinical trial will be announced prior to initiation. Given the positive results reviewed at AASLD today, cohort 3 of the Phase 1 trial will be ended after the completion of an additional four patients that have been enrolled (13 patients total in cohort 3)."

Dr. Traber added, "I want to sincerely thank three groups for their involvement in this study. First, and most importantly, I thank the individual patients who donated their time and effort to help advance a promising therapy—their contribution was critical to the Company's progress in development of GR-MD-02. Second, I thank the world-class group of investigators and their support groups who worked on this trial. Finally, CTI as our CRO partner worked tirelessly to accomplish the results."

GR-MD-02 is Galectin Therapeutics' patented, proprietary molecule derived from apple pectin material that binds to and inhibits galectin proteins, predominantly galectin-3. 

About Fatty Liver Disease with Advanced Fibrosis

Non-alcoholic steatohepatitis (NASH), also known as fatty liver disease, has become a common disease of the liver with the rise in obesity rates, estimated to affect nine to 15 million people, including children, in the U.S. Fatty liver disease is characterized by the presence of fat in the liver along with inflammation and damage in people who drink little or no alcohol. Over time, patients with fatty liver disease can develop fibrosis, or scarring of the liver, and it is estimated that as many as three million individuals will develop cirrhosis, a severe liver disease where liver transplantation is the only current treatment available. Approximately 6,300 liver transplants are done on an annual basis in the U.S. There are no drug therapies approved for the treatment of liver fibrosis.

About Galectin Therapeutics

Galectin Therapeutics (Nasdaq:GALT) is developing promising carbohydrate-based therapies for the treatment of fibrotic liver disease and cancer based on the Company's unique understanding of galectin proteins, key mediators of biologic function. We are leveraging extensive scientific and development expertise as well as established relationships with external sources to achieve cost effective and efficient development. We are pursuing a clear development pathway to clinical enhancement and commercialization for our lead compounds in liver fibrosis and cancer. Additional information is available at www.galectintherapeutics.com.

Forward Looking Statements

This press release contains, in addition to historical information, forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements relate to future events or future financial performance, and use words such as "may," "estimate," "could," "expect" and others. They are based on our current expectations and are subject to factors and uncertainties which could cause actual results to differ materially from those described in the statements. These statements include those regarding our plans, expectations and goals regarding clinical trials, including our expectation that a final clinical data report from the third cohort should be available in January 2015, plans regarding design and composition and timing of a Phase 2 clinical trial, and plans regarding future funding alternatives and the sufficiency of cash on hand to fund future operations and planned research and development through mid-2016. Factors that could cause our actual performance to differ materially from those discussed in the forward-looking statements include, among others, that our plans, expectations and goals regarding any clinical trial or any future trials are subject to factors beyond our control and there is no guarantee that we will avoid delays in the development of our drug products or receive FDA approval for any of our drugs in development. Any current clinical trials and any future trials may not produce positive results in a timely fashion, if at all, and any necessary changes during the course of a trial could prove time consuming and costly. We may have difficulty in enrolling candidates for testing, which would impact our estimates regarding timing, and we may not be able to achieve the desired results. Upon receipt of FDA approval, we may face competition with other drugs and treatments that are currently approved or those that are currently in development, which could have an adverse impact on our ability to achieve revenues from any proposed indications. Plans regarding development, approval and marketing of any of our drugs, including GR-MD-02, are subject to change at any time based on the changing needs of our company as determined by management and regulatory agencies. To date, we have incurred operating losses since our inception, and our ability to successfully develop and market drugs may be impacted by our ability to manage costs and finance our continuing operations. For a discussion of additional factors impacting our business, see our Annual Report on Form 10-K for the year ended December 31, 2013, and our subsequent filings with the SEC.  You should not place undue reliance on forward-looking statements. Although subsequent events may cause our views to change, we disclaim any obligation to update forward-looking statements.

Galectin Therapeutics Inc.
Peter G. Traber, MD, 678-620-3186
President, CEO, & CMO

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New drug for common liver disease improves liver health

For Immediate Release: Friday, November 7, 2014

An experimental drug aimed at treating a common liver disease showed promising results and potential problems in a multicenter clinical trial funded by the National Institutes of Health. The FLINT study found that people with nonalcoholic steatohepatitis (NASH) who took obeticholic acid (OCA) had improved liver health during that period, including decreased inflammation and fat in the liver and decreased body weight versus people receiving a placebo. OCA was also associated with increases in itching and total cholesterol.

“NASH is a common and potentially serious disease that currently has no approved treatment.”

—Averell Sherker, M.D.
NIDDK program official for the NASH Clinical Research Network (NASH CRN)

The findings of FLINT, or the Farnesoid X Receptor Ligand Obeticholic Acid in NASH Treatment Trial, were published online Nov. 6 in The Lancet. FLINT was sponsored by the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases.

“NASH is a common and potentially serious disease that currently has no approved treatment. Management typically includes weight loss through diet and exercise,” said Averell Sherker, M.D., NIDDK program official for the NASH Clinical Research Network (NASH CRN), which performed the FLINT study.

Liver health improved in 45 percent of people on OCA versus 21 percent of the placebo group. “Although obeticholic acid did not eliminate liver disease in FLINT participants, it demonstrated a promising effect. Larger studies will be required to determine the drug’s safety and efficacy,” Sherker said.

FLINT enrolled 283 people at eight centers across the country. At the study’s start, participants were 18 and older and had been diagnosed with definite or borderline NASH. They were randomly assigned to one of two groups: one took 25 milligrams of OCA daily and one received a placebo that resembled the OCA pill. The study was double-blinded, so neither participants nor investigators knew which person was in which group.

Trial investigators intended for the groups to receive the drug or placebo for 72 weeks, with an additional 24 weeks of follow-up off treatment. However, planned interim analysis for safety and efficacy showed that OCA had significant beneficial effects on NASH-related liver health.

The analysis also found unanticipated increases in total cholesterol in the OCA group. They had increased LDL cholesterol (“bad” cholesterol) and decreased HDL cholesterol (“good” cholesterol) – notable because NASH patients are already at higher risk for cardiovascular diseases. As cholesterol treatment was not standardized as part of the study, further research is needed to fully understand the potential effect of OCA on cholesterol.

Because of both factors, and with the concurrence of the Data Safety and Monitoring Board, NIDDK decided to stop treatment but continue the study, move all patients into the follow-up phase, and perform no additional liver biopsies – which carry their own risks. Adverse cholesterol increases were not sustained after stopping OCA.

“The FLINT trial represents an important advance in the search for treatments of NASH. The causes of NASH are not fully understood, and causes and treatments may be different among patients,” said the study’s lead author, Brent Neuschwander-Tetri, M.D., a professor at St. Louis University. “We need to study the changes in cholesterol levels more to know if the increases caused by obeticholic acid increase the risk of hardening of the arteries. We found that the improvement in liver enzymes with obeticholic acid were not sustained after treatment was stopped, so we would expect that treatment would need to be indefinite, much like the medications for diabetes and hypertension.”

The major feature of NASH is fat in the liver, along with inflammation and damage.  Over time, these may lead to loss of liver function, the need for liver transplantation and death. NASH may have no symptoms and can only be diagnosed with a liver biopsy. Beyond maintaining a healthy weight, people with NASH are advised to avoid alcohol and unnecessary medications. New cases of NASH have grown alongside the obesity epidemic. NASH is the third leading diagnosis requiring U.S. liver transplantation.

The FLINT trial (Clinical Trials No. NCT01265498) was supported by the NIDDK, National Cancer Institute and National Center for Advancing Translational Sciences, all part of NIH. Intercept Pharmaceuticals, Inc. provided partial funding and supplies.

The NIDDK, a component of the NIH, conducts and supports research on diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition and obesity; and kidney, urologic and hematologic diseases. Spanning the full spectrum of medicine and afflicting people of all ages and ethnic groups, these diseases encompass some of the most common, severe and disabling conditions affecting Americans. For more information about the NIDDK and its programs, see http://www.niddk.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH...Turning Discovery Into Health^®

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Intercept CEO says new drug could treat ‘next tsunami’ in liver disease

January 15, 2014, 1:41 PM

By Russ Britt

Intercept Pharmaceuticals’ chief executive said Wednesday the company’s new drug could tap into a vast market to treat what he called “the next tsunami of liver disease.”

Image of liver afflicted with NASH

Intercept ICPT +8.03% CEO Mark Pruzanski told the J.P. Morgan Healthcare Conference in San Francisco the liver disease his company hopes to treat — nonalcoholic steatohepatitis, or NASH — could affect 6 million adults. NASH also is expected to become the leading cause of liver transplants, and the market for treatments of the disease could be bigger than hepatitis C, Pruzanski said.

The disease creates fatty deposits in the liver and can lead to cirrhosis in roughly 10% of patients with 10 years, regardless of whether they drink alcohol. NASH patients are 10 times more susceptible to liver-related mortality. One-third of all patients with non-alcoholic fatty liver disease develop NASH, he added.

“This is considered to be irreversible on its own,” he said.

The company’s obeticholic acid, or OCA, met goals early in Phase 2 testing for treatment of NASH and was discontinued last week. That set off massive buying of the company’s shares last week. Now the company hopes to begin Phase 3 tests next year and seek expedited approval for the treatment from the U.S. Food and Drug Administration.

On Wednesday, Intercept was trading around the break-even point — up marginally to $255.97 in recent action. That’s relative calm compared with what the stock experienced over the last week, with its value multiplying almost seven times, from the low $70s to nearly $500 a share Thursday and Friday, then falling 18% Monday and 30% on Tuesday.

“It’s been an interesting few days,” Pruzanski said.

Some analysts reportedly believe the potential for OCA is strong. Bank of America analyst Rachel McMinn reportedly put a price target of $872 on the company’s shares; B. of A. won’t make its research notes public.

There is at least one caveat, however, as the National Institutes of Health pointed out over the weekend that OCA users experienced larger-than-expected levels of bad cholesterol after taking the drug. Pruzanski said those levels were up about 20% in some cases.

Follow Russ Britt on Twitter @russbrittmktw

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Intercept liver drug meets main goal in study, shares quadruple

BY VRINDA MANOCHA
Thu Jan 9, 2014 9:43am EST

(Reuters) - Intercept Pharmaceuticals Inc's drug to treat liver disease caused by fat buildup was found effective in a trial, paving the way for it to become the first approved treatment for the chronic condition.

The company's shares nearly quadrupled to a life high of $305 on Thursday morning on theNasdaq, valuing the company at about $6 billion.

Intercept said it had stopped the trial after the drug showed statistically significant improvement in patients, compared with a placebo, in a review by an independent safety committee.

The trial tested the drug, obeticholic acid, in patients with non-alcoholic steatohepatitis (NASH), a form of liver inflammation.

Analysts said the news came as a surprise to investors, who had previously focused on the drug as a treatment for primary biliary cirrhosis, an autoimmune disease in which bile ducts in the liver are destroyed. The drug is being tested for the condition in a late-stage study.

"We didn't expect this data until the fourth quarter," Wedbush analyst Liana Moussatos said. "It's a huge opportunity for the company as there are over 10 million patients worldwide."

Moussatos said Intercept could tie up with Big Pharma companies to conduct a late-stage trial of the drug. Intercept could also conduct a late-stage trial with its partner Dainippon Sumitomo Pharma, which is testing the drug in Japan, she said.

Obeticholic acid, Intercept's lead drug, is also being tested in mid-stage studies to treat bile acid diarrhea and portal hypertension, which is high blood pressure in veins that transport blood from the gastrointestinal tract and spleen to the liver.

The drug's structure is similar to that of a naturally occurring human bile acid.

Intercept said the safety committee made the recommendation after reviewing liver biopsy data from about half of the 283 patients enrolled in the mid-stage trial.

There is currently no specific treatment for NASH, according to the U.S. National Institutes of Health.

To manage the disease, patients are recommended to maintain a healthy weight, follow a balanced diet, increase physical activity and avoid alcohol.

(Reporting by Vrinda Manocha in Bangalore; Editing by Kirti Pandey)

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Liver function breath tests for differentiation of steatohepatitis from simple Fatty liver in patients with nonalcoholic Fatty liver disease

J Clin Gastroenterol. 2014 Jan;48(1):59-65. doi: 10.1097/MCG.0000000000000036.

Tribonias G, Margariti E, Tiniakos D, Pectasides D, Papatheodoridis GV.

Abstract

GOALS: We investigated the utility of liver function breath tests [C-Aminopyrine Breath Test (C-ABT), C-Galactose Breath Test (C-GBT)], for the diagnosis of nonalcoholic steatohepatitis (NASH) among nonalcoholic fatty liver disease (NAFLD) patients.

BACKGROUND: Liver biopsy is currently the gold standard for the differentiation between simple fatty liver (NAFL) and NASH in NAFLD patients.

MATERIALS AND METHODS: Thirty-six patients with histologically proven NAFLD (NAFL:16, NASH:20) underwent C-ABT and C-GBT. The results were expressed as the percentage of administered C dose recovered per hour (%dose/h) and as cumulative percentage of administered C dose recovered over time (%cumulative dose). Histologic lesions were scored according to Brunt and Kleiner's classifications.

RESULTS: C-ABT results correlated inversely with activity grade (r=-0.650, P=0.001), NAFLD activity score (r=-0.473, P=0.026), and fibrosisstage (r=-0.719, P=0.001). Compared with NAFL, NASH patients had significantly lower %dose/h and %cumulative dose at 60, 90, and 120 minutes (always P<0.04) by C-ABT. C-ABT %dose/h and %cumulative dose at 120 minutes could predict the presence of NASH (area under the receiver operating characteristic curve: 0.762 and 0.741, respectively). In contrast, there was no significant association between C-GBT results and any patient characteristic.

CONCLUSIONS: In the NAFLD patients, decreased and delayed liver microsomal function, as assessed by C-ABT, is associated with more severe necroinflammation and fibrosis, whereas C-ABT results at 120 minutes may be helpful for the diagnosis of NASH.

PMID: 24335903 [PubMed - in process]

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Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S

Hepatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Original Article

Robert J. Wong M.D.^1,2, Ramsey Cheung M.D.^1,2, Aijaz Ahmed M.D.^1,*

DOI: 10.1002/hep.26986

Copyright © 2013 American Association for the Study of Liver Diseases

Publication History

Accepted manuscript online: 25 DEC 2013 09:13PM EST
Manuscript Accepted: 18 DEC 2013
Manuscript Revised: 13 NOV 2013
Manuscript Received: 8 OCT 2013

Keywords: fatty liver;  hepatitis C virus;  liver cancer;  UNOS;  alcoholic liver disease

Abstract

Nonalcoholic steatohepatitis (NASH) is currently the third leading indication for liver transplantation (LT) in the U.S. and is predicted to become the leading indication for LT in the near future. The trends in NASH-related hepatocellular carcinoma (HCC) among LT recipients in the U.S. remain undefined. We performed a retrospective cohort study to evaluate trends in the etiology of HCC among adult LT recipients in the U.S. from 2002 to 2012, utilizing national data from the United Network for Organ Sharing registry. From 2002-2012, there were 61,868 adults who underwent LT in the U.S., including 10,061 patients HCC. The total number and proportion of HCC LT recipients demonstrated a significant increase following the implementation of the model for end stage liver disease (MELD) scoring system in 2002 (3.3%, n=143 in 2000 vs. 12.2%, n=714 in 2005 vs. 23.3%, n=1336 in 2012). The proportion of HCV-related HCC increased steadily from 2002 to 2012, and HCV remained the leading etiology of HCC throughout the MELD era (43.4% in 2002 vs. 46.3% in 2007 vs. 49.9% in 2012). NASH-related HCC also increased significantly, and NASH is the second leading etiology of HCC-related LT (8.3% in 2002 vs. 10.3% in 2007 vs. 13.5% in 2012). From 2002 to 2012, the number of patients undergoing LT for HCC secondary to NASH increased by nearly 4-fold, and the number of LT patients with HCC secondary to HCV increased by 2-fold. Conclusion: NASH is the second leading etiology of HCC leading to LT in the U.S. More importantly, NASH is currently the most rapidly growing indication for LT in patients with HCC in the U.S. (Hepatology 2013;)

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FDA's Fast Track

Provided by WLS-TV/DT

Thursday, December 26, 2013

December 26, 2013 (WLS) -- Speeding the development and availability of drugs that treat serious diseases are in everyone's interest, especially when the drugs are the first available treatment. The FDA developed a distinct approach to make sure these drugs are available as soon as possible, called Fast Track.

Researchers are on the fast track to develop a drug that could reverse fibrosis and cirrhosis in the kidneys, lungs, and liver of patients who have NASH-non-alcoholic steatohepatitis-more commonly known as fatty liver disease. Researchers say that currently there is not a FDA approved drug for fibrosis, so the potential is huge.

NASH affects between 9 to 15 million Americans. Over time, patients can develop fibrosis and about three million will develop cirrhosis. The phase 1 clinical trial will enroll patients at six clinical sites in the U.S.

Another potential breakthrough receiving fast track status is a treatment to improve overall survival in patients with metastatic non-small cell lung adenocarcinoma, who have progressed following one chemotherapy regimen.

The drug would be administered in combination with docetaxel. Lung cancer is the leading cause of cancer-related deaths in the world. Non-small cell adenocarcinoma accounts for 40 percent of all lung cancers. It is being evaluated in over 20 clinical trials.

By the way, in 2012 the FDA granted fast track status to 22 drugs. To learn more about the program, go to fda.gov.

BACKGROUND: Fast track is a new process that is created to speed the course of drug review. This was designed so patients with serious illness can receive their drugs at a quicker rate. This process will help patients who are in need of their medications to survive or to function. Heart failure, AIDS, cancer and Alzheimer's are all diseases that Fast Track will work with because it is imperative that these patients receive their medication and treatment. Other illnesses and conditions are considered for the process as well, like diabetes, epilepsy and depression. This process must be requested by the drug company and approved by the FDA before medication is administered, but this will cut the wait time for prescription drugs and keep patients more comfortable and satisfied. (Source: http://www.fda.gov/forconsumers/byaudience/forpatientadvocates/speedingaccesstoimportantnewtherapies/ucm128291.htm)

NONALCOHOLIC STEATOHEPATITIS: Galectin Therapeutics was recently approved by the FDA to release GR-MD-02 to Fast Track. GR-MD-02 is a complex carbohydrate drug that focuses on the galectin-3 protein to reverse liver, kidney and lung cirrhosis. This drug is targeted towards patients who suffer from NASH, nonalcoholic steatohepatitis with advanced fibrosis. This "silent" liver disease affects two to five percent of Americans and is becoming more common due to the growth in obesity. Gelactin Therapeutics conducted a clinical trial on patients with NASH consisting of four weekly doses of GR-MD-02. Forty volunteers at six different clinical sites in the U.S. participated in the study to measure the tolerability and safety of the product. Below is a list of locations that hosted the study:

• The Mount Sinai Medical Center (Division of Liver Diseases)
• Emory University Hospital (Transplant Center Clinical Research)
• Indiana University School of Medicine
• Virginia Commonwealth University Medical Center
• Brooke Army Medical Center
• St. Louis University School of Medicine

(Source: http://digestive.niddk.nih.gov/ddiseases/pubs/nash/ and http://phx.corporate-ir.net/phoenix.zhtml?c=135403&p=irol-newsArticle&ID=1846800&highlight)

METASTATIC NON-SMALL CELL LUNG ADENOCARCINOMA: Lung cancer is the leading cause of cancer deaths in the U.S. in both men and women. However, it is one of the most preventable cancers if detected in early stages. Synta Pharmaceuticals released a drug to stop cancer cell processes. Synta held more than 20 clinical trials with over 700 patients for the product to evaluate the effects on patients. The clinical trial is still ongoing but is not recruiting volunteers. Here are the locations where the trial was studied:

U.S.
• Tucson, Arizona
• Boston, Massachusetts
• Santa Monica, California
• Winston-Salem, North Carolina
• Atlanta, Georgia
• Kettering, Ohio
• Chicago, Illinois
• Portland, Oregon

Other:
• Canada
• Russian Federation
• Croatia
• Serbia
• Czech Republic
• Spain
• Poland
• United Kingdom
• Romania
• Germany

(Source: mayoclinic.org/lung-cancer/ and syntapharma.com)

(Copyright ©2013 WLS-TV/DT. All Rights Reserved.)

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Published Preclinical Study Demonstrates Therapeutic Effect of Galectin Inhibitors in Fatty Liver Disease With Fibrosis

PRESS RELEASE

Dec. 19, 2013, 8:01 a.m. EST

NORCROSS, Ga., Dec 19, 2013 (GLOBE NEWSWIRE via COMTEX) -- Galectin Therapeutics Inc. GALT +4.65% , the leading developer of therapeutics that target galectin proteins to treat fibrosis and cancer, today announced that new preclinical data show its leading galectin-inhibiting drugs - GR-MD-02 and GM-CT-01 - demonstrate positive therapeutic effects on nonalcoholic steatohepatitis (NASH, or fatty liver disease) with fibrosis. Results were published in an article titled "Therapy of Experimental NASH and Fibrosis with Galectin Inhibitors" in the peer-reviewed, open-access journal PLOS ONE.

In the study, NASH-induced mice were treated with GM-CT-01 and GR-MD-02 at two different points - early fibrosis and later more severe fibrosis. The studies evaluated twice-weekly, dose escalation of once weekly by intravenous administration, as well as evaluated different routes of administration including intravenous, subcutaneous and oral.

Results revealed that treatment with GR-MD-02 significantly improved NASH activity and reduced fibrosis including prevention of accumulation of collagen and/or reduced accumulated collagen in the liver. Similar effects were seen with GM-CT-01 but with approximately four-fold lower potency than GR-MD-02. The data also show reduction in galectin-3 expression and other inflammatory biomarkers. The PLOS ONE article can be found online at http://dx.plos.org/10.1371/journal.pone.0083481

"There are currently no approved treatments for fatty liver disease with fibrosis, a major health problem in the United States. These preclinical findings add to our scientific understanding of the role galectin inhibitors play in the treatment of fatty liver disease," said Peter G. Traber, M.D., Chief Executive Officer, President and Chief Medical Officer, Galectin Therapeutics. "The results support our current Phase 1 clinical trial of GR-MD-02 and our long-term development programs for GM-CT-01 and GR-MD-02."

GM-CT-01 and GR-MD-02 are proprietary molecules that bind to and inhibit galectin proteins, predominantly galectin-3. Six of eight patients have been enrolled and infused in cohort 1 of a blinded Phase 1 clinical trial of GR-MD-02 for patients with NASH with advanced fibrosis. Enrollment continues and no serious adverse events have been reported. The Phase 1 first-in-man study is evaluating the safety, tolerability, pharmacokinetics and exploratory biomarkers for efficacy for single and multiple doses of GR-MD-02 when administered to patients with fatty liver disease with advanced fibrosis. Clinical data from the first cohort is expected early in 2014.

About Fatty Liver Disease with Advanced Fibrosis

Non-alcoholic steatohepatitis (NASH), also known as fatty liver disease, has become a common disease of the liver with the rise in obesity rates, estimated to affect nine to 15 million people, including children, in the U.S. Fatty liver disease is characterized by the presence of fat in the liver along with inflammation and damage in people who drink little or no alcohol. Over time, patients with fatty liver disease can develop fibrosis, or scarring of the liver, and it is estimated that as many as three million individuals will develop cirrhosis, a severe liver disease where liver transplantation is the only current treatment available. Approximately 6,300 liver transplants are done on an annual basis in the U.S. There are no drug therapies approved for the treatment of liver fibrosis.

About Galectin Therapeutics

Galectin Therapeutics GALT +4.65% is developing promising carbohydrate-based therapies for the treatment of fibrotic liver disease and cancer based on the Company's unique understanding of galectin proteins, key mediators of biologic function. We are leveraging extensive scientific and development expertise as well as established relationships with external sources to achieve cost effective and efficient development. We are pursuing a clear development pathway to clinical enhancement and commercialization for our lead compounds in liver fibrosis and cancer. Additional information is available at www.galectintherapeutics.com .

Forward Looking Statements

This press release contains, in addition to historical information, forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements relate to future events or future financial performance, and use words such as "may," "estimate," "could," "expect" and others. They are based on our current expectations and are subject to factors and uncertainties which could cause actual results to differ materially from those described in the statements. These statements include those regarding preclinical data and the potential role for GR-MD-02 and GM-CT-01 in the treatment of liver fibrosis and cirrhosis in humans. Factors that could cause our actual performance to differ materially from those discussed in the forward-looking statements include, among others, that our plans, expectations and goals regarding any preclinical data and potential therapeutic uses and benefits of our drugs and any future pre-clinical or clinical studies are subject to factors beyond our control. Future clinical studies may not begin or produce positive results in a timely fashion, if at all, and could prove time consuming and costly. Plans regarding development, approval and marketing of any of our drugs are subject to change at any time based on the changing needs of our company as determined by management and regulatory agencies. Regardless of the results of current or future studies, we may be unsuccessful in developing partnerships with other companies or obtaining capital that would allow us to further develop and/or fund any studies or trials. To date, we have incurred operating losses since our inception, and our ability to successfully develop and market drugs may be impacted by our ability to manage costs and finance our continuing operations. For a discussion of additional factors impacting our business, see our Annual Report on Form 10-K for the year ended December 31, 2012, and our subsequent filings with the SEC. You should not place undue reliance on forward-looking statements. Although subsequent events may cause our views to change, we disclaim any obligation to update forward-looking statements.

Source

Systematic review with meta-analysis: non-alcoholic steatohepatitis - a case for personalised treatment based on pathogenic targets

Aliment Pharmacol Ther. 2013 Nov 10. doi: 10.1111/apt.12543. [Epub ahead of print]

Younossi ZM, Reyes MJ, Mishra A, Mehta R, Henry L.

Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.

Abstract

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an umbrella term, which encompasses simple steatosis and non-alcoholic steatohepatitis (NASH). The entire spectrum of NAFLD has been associated with metabolic syndrome. NASH is associated with increased mortality compared with that of the general population. Many therapeutic options for NASH have been studied. However, there is very little evidence supporting the efficacy of most regimens for the treatment of NASH.

AIM: To provide a review focusing on the current therapeutic options available for patients with NASH as well as to briefly introduce possible future interventions.

METHODS: A MEDLINE, Pubmed and Cochrane Review database search using a combination of keywords, which included non-alcoholic fatty liver disease, non-alcoholic hepatic steatosis, NAFLD, NASH, treatment, therapeutics, vitamin E, orlistat and bariatric surgery. An overall summary of the articles was developed for each section of discussion in this review.

RESULTS: NASH associated with metabolic syndrome can progress advanced fibrosis and cirrhosis. Weight loss and lifestyle modification have been shown to improve NASH. Other medications used for weight loss and metabolic syndrome have been evaluated, such as orlistat, metformin and thiazolidinediones. Alternative regimens using ursodeoxycholic acid, statins and probiotics as well as bariatric surgery have been evaluated, but have not been recommended as first-line treatment for NASH. Vitamin E for NASH patients without diabetes seems to be promising. The lack of effective treatment for NASH suggests the heterogeneity of patients presenting with the NASH phenotype. The best treatment strategy for these patients may be to identify their pathogenic target and develop personalised treatment protocols.

CONCLUSIONS: Currently, there are few options available for the management of NASH. Future targeted treatment strategies based on the pathogenic pathways may be needed to develop effective treatment for patients with NASH.

© 2013 John Wiley & Sons Ltd.

PMID: 24206433 [PubMed - as supplied by publisher]

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Galectin Therapeutics Reports Update on Enrollment of First Cohort of Phase 1 Clinical Trial and Third Quarter 2013 Financial Results

NORCROSS, Ga., Nov. 12, 2013 (GLOBE NEWSWIRE) -- Galectin Therapeutics Inc.(Nasdaq:GALT), the leading developer of therapeutics that target galectin proteins to treat fibrosis and cancer, today reported that five of the eight patients have been enrolled and infused in cohort 1 of its blinded Phase 1 clinical trial of GR-MD-02 for patients with nonalcoholic steatohepatitis (NASH or fatty liver disease) with advanced fibrosis. The Company also reported its financial results for the third quarter and first nine months ended September 30, 2013. These results are included in the Company's Quarterly Report on Form 10-Q, which has been filed with theSecurities and Exchange Commission.

"We are pleased to announce completion of enrollment of the first five of eight patients in our Phase 1 clinical trial for patients with NASH (fatty liver disease) with advanced fibrosis. The patients enrolled have not incurred any serious adverse events. Completion of the enrollment of the first cohort will be an important milestone in the development of our proprietary, novel technology and, if all goes as expected, the clinical data from the first cohort should be available early in 2014," said Peter G. Traber, M.D., Chief Executive Officer, President and Chief Medical Officer, Galectin Therapeutics. "This Phase 1 first-in-man study will evaluate the safety, tolerability, pharmacokinetics and exploratory biomarkers for efficacy for single and multiple doses of GR-MD-02 when administered to patients with fatty liver disease with advanced fibrosis."

The Company also is working with Providence Portland Medical Center in planning for a Phase 1 clinical trial to evaluate the combination of Bristol-Myers Squibb's Yervoy® (ipilimumab) and the Company's GR-MD-02 in patients with metastatic melanoma. This trial is based on pre-clinical data obtained in collaboration with Dr. Will Redmond at the center which demonstrated that the combination of immune checkpoint inhibitors like ipilimumab with GR-MD-02 enhances the antitumor effect in syngeneic mouse cancer models.

At September 30, 2013, the Company had $9.7 million of non-restricted cash and cash equivalents available to fund future operations. Subsequent to quarter end, the Company received$1.6 million from the exercise of warrants and options, with $1.5 million coming from warrant exercises by 10X Fund L.P. Additionally since September 30, 2013, the Company received $0.5 million in net proceeds from the issuance of 50,643 shares through its At Market stock issuance program at an average price per share of $10.82. The Company believes that the cash on hand at quarter end and already received is sufficient to fund operations and planned research and development into the third quarter of 2014. The Company routinely evaluates financing alternatives to raise additional funding to support the next steps in its clinical development program, including, from time to time, potentially issuing shares through the At Market stock issuance program.   

For the third quarter of 2013, the Company reported a net loss applicable to common stock of$3.7 million, or ($0.22) per share, basic and diluted, compared with a net loss applicable to common stock of $3.0 million or ($0.19) per share for the same period in 2012. The increase in net loss applicable to common stock is primarily due to a $989,000 increase in the non-cash charge related to stock based compensation.  Research and development expense for the third quarter of 2013 was $1.2 million, compared with $1.4 million for the same period in 2012.  General and administrative expense for the third quarter of 2013 was $2.4 million, compared with$1.5 million for the same period in 2012. The primary reasons for the increase were non-cash stock-based compensation and legal expense offset somewhat by decreased rent expense.

For the nine months ended September 30, 2013, the Company reported a net loss applicable to common stock of $18.8 million, or ($1.15) per share, basic and diluted, compared with a net loss of $8.2 million, or ($0.55) per share for the same period in 2012. The increase in net loss applicable to common stock is primarily due to an $8.8 million or ($0.53) per share one-time, non-cash stock compensation charge recorded in the second quarter of 2013. Research and development expense for the nine months ended September 30, 2012 increased to $4.3 millioncompared with $3.5 million for the same period in 2012, due primarily to clinical program expenses related to the Phase 1 clinical trial. As we continue to enroll patients in the Phase 1 trial, we expect our clinical activities costs may increase and fluctuate from quarter to quarter as the trial progresses. General and administrative expense for the nine months ended September 30, 2013 increased to $5.0 million compared with $4 million for the same period in 2012, due primarily to increases in non-cash stock based compensation and legal expenses related to ongoing litigation with the Company's former CEO and investor relations expenses, offset by decreased rent expense due to our relocation to Georgia in October 2013.

About Galectin Therapeutics

Galectin Therapeutics (Nasdaq:GALT) is developing promising carbohydrate-based therapies for the treatment of fibrotic liver disease and cancer based on the Company's unique understanding of galectin proteins, key mediators of biologic function. We are leveraging extensive scientific and development expertise as well as established relationships with external sources to achieve cost effective and efficient development. We are pursuing a clear development pathway to clinical enhancement and commercialization for our lead compounds in liver fibrosis and cancer. Additional information is available at www.galectintherapeutics.com.

Forward Looking Statements

This press release contains, in addition to historical information, forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements relate to future events or future financial performance, and use words such as "may," "estimate," "could," "expect" and others. They are based on our current expectations and are subject to factors and uncertainties which could cause actual results to differ materially from those described in the statements. These statements include those regarding our plans, expectations and goals regarding the clinical trial, including our expectation that clinical data from the first cohort should be available early in 2014 , the Company's plans regarding a potential Phase 1 clinical trial to evaluate the combination of Bristol-Myers Squibb's Yervoy® (ipilimumab) and the Company's GR-MD-02 in patients with metastatic melanoma, and plans regarding future funding alternatives and the sufficiency of cash on hand to fund future operations and planned research and development into the third quarter of 2014. Factors that could cause our actual performance to differ materially from those discussed in the forward-looking statements include, among others, that our plans, expectations and goals regarding the clinical trial or any future trials are subject to factors beyond our control and there is no guarantee that we will avoid delays in the development of our drug products or receive FDA approval for any of our drugs in development. Our clinical trial and any future trials may not produce positive results in a timely fashion, if at all, and any necessary changes during the course of a trial could prove time consuming and costly. We may have difficulty in enrolling candidates for testing, which would impact our estimates regarding timing, and we may not be able to achieve the desired results. Upon receipt of FDA approval, we may face competition with other drugs and treatments that are currently approved or those that are currently in development, which could have an adverse impact on our ability to achieve revenues from any proposed indications. Plans regarding development, approval and marketing of any of our drugs, including GR-MD-02, are subject to change at any time based on the changing needs of our company as determined by management and regulatory agencies. To date, we have incurred operating losses since our inception, and our ability to successfully develop and market drugs may be impacted by our ability to manage costs and finance our continuing operations. For a discussion of additional factors impacting our business, see our Annual Report on Form 10-K for the year ended December 31, 2012, and our subsequent filings with the SEC.  You should not place undue reliance on forward-looking statements. Although subsequent events may cause our views to change, we disclaim any obligation to update forward-looking statements.

Continue reading here …..

Immuron receives U.S. FDA approval to trial new liver disease treatment

Friday, November 08, 2013 by Proactive Investors

Immuron Limited (ASX: IMC) is set to trade higher after receiving investigational new drug clearance from the US Food and Drug Administration to commence a clinical trial of its bovine colostrum-derived therapeutic for the treatment of a liver disease, alcoholic steatohepatitis, or ASH.

Immuron is also in preparation for Phase IIb clinical trials of non-alcoholic steatohepatitis, or NASH.
Notably, the principal investigator for its NASH trial has been awarded a National Institutes of Health grant to conduct a clinical trial for ASH.\

This trial will be conducted by the TREAT consortium, one of the world’s leading collaborations for clinical research into fatty liver diseases.

TREAT consortium's ASH trial is expected to provide Immuron with additional guidance for its NASH trials commencing next year.

NASH and ASH arise from different causes; both result in liver damage potentially leading to liver fibrosis, liver cirrhosis hepatic carcinoma.

Proactive Investors Australia is the market leader in producing news, articles and research reports on ASX “Small and Mid-cap” stocks with distribution in Australia, UK, North America and Hong Kong / China.

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CV work-up key before NASH liver transplant

YOUR DOSE OF MEDICINE By Charles C. Chante, MD (The Philippine Star) | Updated November 10, 2013 - 12:00am

Nonalcoholic steatohepatitis patients may need a more thorough cardiovascular work-up before liver transplantation, according to a study presented at the meeting.

Standard pretransplant cardiac screening results were similar for 115 nonalcoholic steatohepatitis (NASH) and 127 alcohol-induced cirrhosis patients. Most patients had received transthoracic echocardiograms, and many had had other tests, including dobutamine stress echocardiograms, cardiac catheterizations, and ECGs.

The Revised Cardiac Risk index, a common heart screen for noncardiac surgeries that focuses mostly on ischemia, predicted cardiac events in 6.6% of both groups.

The rate of cardiac events was higher in the NASH group; 26% had significant cardiac events within a year of surgery, two-thirds  of those within a month. Cardiac arrests and arrhythmias — some fatal — were the most common events in the NASH group. Meanwhile, about 8% of the alcoholic-cirrhosis patients had cardiac events during their first postop year.

The inaccuracy of the screening of NASH patients illustrates the need for better methods of identifying cardiac risks prior to liver transplants, investigator in gastroenterology and hepatology at Nothwestern University, Chicago said.

“Current algorithms are designed to predict MI and plaque rupture. We tend to overutilize dobutamine stress echoes and other noninvasive stress tests to look for ischemic heart disease.”

In addition to atherosclerosis, NASH patients may have low systemic resistance, chronotropic incompetence, and other problems that a too-narrow focus on ischemia might miss. The cardiac arrests and arrhythmia noted in the study may not have been “related to plaque rupture. We really need to better risk-stratify these patients,” he said, hoping to develop a liver-transplant specific cardiac risk index.

Tricuspid regurgitation might have predictive value, as well as pulmonary hypertension and prolonged Qc interval, although the latter two did not differ significantly between the two groups before transplant.

Indeed, there were just two statistical differences; left ventricular hypertrophy was slightly more common in alcoholic cirrhosis patients (20% vs. 15%), and that group was more likely than the NASH group to have clean coronary arteries on left heart catheterization (20% vs. 14%).

The mean age in the NASH group was 58 years, and 45% of NASH patients were women. The mean age in the alcoholic-cirrhosis group was 53 years, and 18% of patients were women. Mean MELD (Model for End-Stage Liver Disease) scores were about 25 for both groups.

NASH patients were more likely to be obese, dyslipidemic, and hypertensive. But even after controlling for those factors, as well as for smoking and prior history of coronary artery disease, NASH patients were still more likely to have an adverse cardiovascular event within a year of transplant.

Most patients in both groups were alive at 1 year, but only 4% were alive in the NASH group at 10 years, compared with 18% in the alcoholic-cirrhosis group.

Before surgery, about 50% of NASH patients were on a beta-blocker, and 10% on a statin, although more than half had statin indications.

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In nonalcoholic steatohepatitis, men more likely to have severe fibrosis

NOV 6, 2013  | Reuters Health News

NEW YORK (Reuters Health) – Men with nonalcoholic steatohepatitis (NASH) are more likely to have severe fibrosis than are premenopausal women with the disease, according to a new study.

“Our findings suggest a protective effect from estrogen against development of severe fibrosis,” Dr. Ayako Suzuki from Central Arkansas Veterans Healthcare System in Little Rock, Arkansas, said in a statement. “Further study of the impact of estrogen on fibrosis progression in NASH patients in needed.”

Dr. Suzuki and colleagues used data from the Duke University Health System NAFLD (non-alcoholic fatty liver disease) Clinical Database to assess whether gender and menopause are associated with the severity of liver fibrosis. Their study, online October 1 in Hepatology, included 541 adult patients with a histological diagnosis of NASH.

Just over a third of the patients were men, 28% were premenopausal women, and 37% were postmenopausal women. After adjusting for site, grade of portal inflammation, hepatocyte ballooning, black race, body mass index, diabetes and hypertension, the risk of having severe liver fibrosis (stage 3 or 4) was 60% higher in men than in premenopausal women (p=0.03) and 40% higher in postmenopausal women (p=0.17).

Age of 50 years or older, the average age of menopause in the U.S., was also associated with a significantly increased risk of having more advanced fibrosis among women, but not among men.

In an exploratory analysis, estrogen replacement (in 23 of the 199 postmenopausal women) was associated with a 50% reduction in the risk of severe fibrosis, although this fell short of statistical significance.

“Considering the findings from previous animal experiments, the observed association between premenopausal women and a decreased risk of hepatic fibrosis may be explained by protective effects of estrogens in fibrogenesis,” the researchers conclude.

“Further studies are warranted to investigate the impact of estrogen on fibrosis progression in patients with NASH and potential preventive and/or therapeutic effects of estrogen among postmenopausal women with NASH.”

Dr. Suzuki did not respond to a request for comments.

SOURCE: http://bit.ly/1cE1Qzy

Hepatology 2013.

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Nimbus Discovery Advances Broad Portfolio of ACC Inhibitors for Potential Treatment of Diabetes, NASH and Liver Cancer

Posted on: 01 Nov 13

Nimbus Discovery LLC a biotechnology company discovering novel medicines against exciting but previously inaccessible drug targets will present preclinical data at The Liver Meeting® the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) that show the company has optimized a unique series of Acetyl Co-A Carboxylase (ACC) allosteric inhibitors that bind to the BC domain of ACC and demonstrate excellent potency drug-like properties and preclinical efficacy. The novel internally-developed small molecules ND-654 and ND-630 demonstrated desirable in vitro and in vivo efficacy in experimental models of metabolic disease diabetes and hepatic steatosis. In an iterative design fashion over 16 months the potency of this family of compounds were improved >1000x utilizing the company’s proprietary small molecule computational drug discovery technology and drug-like properties were optimized to efficiently deliver development candidate quality molecules.

Simultaneous inhibition of both isoforms of ACC decreases fatty acid synthesis and stimulates fatty acid oxidation and has the potential to favorably affect the morbidity and mortality associated with obesity diabetes and fatty liver diseases including non-alcoholic steatohepatitis (NASH). Nimbus’ ACC inhibitors including ND-654 and ND-630 are believed to be the first drug-like allosteric inhibitors to bind the biotin carboxylase (BC) domain of ACC with high potency and selectivity.

Key findings of the Nimbus compounds presented at the conference include:

• ND-654
  • Liver specific ND-654 has favorable drug-like properties with a 2700:1 liver to muscle exposure
  • Proof-of-mechanism: ND-654 acutely inhibits ACC with virtually no effect on muscle resulting in focused pharmacological effects on the liver
  • Proof-of-concept: ND-654 demonstrated target engagement in the liver and dose dependently decreased fatty acid production in the liver
• NC-630
  • Liver selective ND-630 has favorable drug-like properties with a 100:1 liver to muscle exposure
  • Proof-of-mechanism: ND-630 acutely inhibits ACC demonstrating efficacy in both liver and muscle by preventing malonyl Co-A production
  • Proof-of-concept: ND-630 demonstrated target engagement in the liver and muscle
  • Dosing of ND-630 in high sucrose fed diet-induced obesity (DIO) rats showed improvement in insulin sensitivity improvement in hepatic cholesterol and normalization of hepatic triglycerides dose dependent decrease of plasma triglycerides and FFAs and decrease in plasma cholesterol

“Within 16 months Nimbus has become the first company to identify and optimize a broad portfolio of liver directed small molecule inhibitors of ACC -- a previously intractable disease target” said Rosana Kapeller M.D. Ph.D. Chief Scientific Officer of Nimbus. “We are now preparing for ND-630 to enter the clinic in 2015 for the treatment of NASH and diabetes while we continue to progress ND-654 in preclinical models of hepatocellular carcinoma.”

About Nimbus

Nimbus Discovery a biotechnology company harnesses cutting-edge computational technologies to uncover breakthroughs in small molecule pharmacology. We focus on medically important and highly sought-after disease targets that have proven inaccessible to traditional industry approaches. Our robust pre-clinical pipeline includes novel agents for the treatment of cancer metabolic disease and inflammation. Nimbus is organized as a constellation of small nimble teams of experienced drug-hunters deployed across program-focused subsidiary companies. Each team is freed from conventional barriers to scientific success chartered to create solutions and geared for program asset deals with leading pharmaceutical companies. Founded in 2009 Nimbus partnered with Schrödinger to invent and apply a physics-based approach that establishes a new standard for rational drug design. Nimbus is backed by world-class life science investors including Atlas Venture SR One Lilly Ventures and Bill Gates. The company has been named by FierceBiotech as one of 2013's Fierce 15 designating it as one of the most promising private biotechnology companies in the industry. For more information please visit www.nimbusdiscovery.com.

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Estrogen protects women with NASH from severe liver fibrosis

Provided by MedicalXpress

October 29, 2013

New research suggests that estrogen protects women with nonalcoholic steatohepatitis (NASH) from severe liver fibrosis. According to the study published online in Hepatology, a journal of the American Association for the Study of Liver Diseases, men are at higher risk of more severe fibrosis compared to women prior to menopause, but liver fibrosis severity is similar in men and post-menopausal women.

Non-alcoholic fatty liver disease (NAFLD) includes a range of liver disorders from simple fatty liver to inflammation, fibrosis, and cirrhosis. With the rapid rise in obesity, diabetes and metabolic syndrome, the prevalence of NAFLD—the result of insulin resistance—has also steadily increased. In fact, studies suggest that the NAFLD prevalence is 10% to 30%, making it the most common liver disease in the U.S.

"While most NAFLD patients have a mild disease known as fatty liver or hepatic steatosis, some patients present with NASH, which is more severe and increases overall mortality," explains Dr. Ayako Suzuki with the Central Arkansas Veterans Healthcare System and University of Arkansas for Medical Sciences in Little Rock, the lead author of the present study. "Our study aim was to investigate whether gender and menopause significantly impact fibrosis severity among adult patients with NAFLD."

The research team analyzed data from 541 adults with NASH who were seen at Duke University Liver Clinics and the Duke Metabolic and Weight Loss Surgery Program. The mean age of subjects was 48 years, with 35% of the group being men, 28% pre-menopausal women and 37% post-menopausal women.

Findings indicate that 22% of the cohort had advanced fibrosis. After adjusting for known predictors of fibrosis, the risk for greater fibrosis severity in post-menopausal women and men vs. pre-menopausal women was 1.4-fold and 1.6-fold, respectively. Furthermore, when dividing the cohort at age 50, which is the average age at menopause in the US, the risk for greater fibrosis severity in men vs. women before age 50 was 1.8-fold, while after the age 50 the risk was reduced to 1.2-fold.

"Our findings suggest a protective effect from estrogen against development of severe fibrosis," concludes Dr. Suzuki. "Further study of the impact of estrogen on fibrosis progression in NASH patients is needed." Explore further: Cardiovascular issues up mortality rates in patients with advanced fibrosis

More information: "Gender and Menopause Impact Severity of Fibrosis Among Patients with Nonalcoholic Steatohepatitis." Ju Dong Yang, Manal F Abdelmalek, Herbert Pang, Cynthia D Guy, Alastair D Smith, Anna Mae Diehl and Ayako Suzuki. Hepatology; (DOI: 10.1002/hep.26761) Published online: October 1, 2013.

Journal reference: Hepatology

Provided by Wiley

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Galectin Stands Out in 2013 with Liver Fibrosis Drug

Oct. 14, 2013, 12:06 p.m. EDT

Oct 14, 2013 (ACCESSWIRE via COMTEX) -- Biotechnology has been an outperforming sector in 2013 with IBB, iShares Nasdaq Biotechnology Index Fund, rising about 57 percent through September 27 highs. BIB, the ProShares Ultra Nasdaq Biotechnology Index has roared ahead about 135 percent through highs on the same day.

While those gains are certainly robust, the September high of Galectin Therapeutics Inc. at $13.21 made them seem paltry, producing gains of more than 550 percent in 2013 for GALT shareholders. The surge in Galectin's valuation seems simply a product of corporate advancements as the company establishes itself as a leader in pioneering treatments for fibrosis, especially liver fibrosis that results from fatty liver disease.

Liver fibrosis can be an asymptomatic death sentence with no available therapeutics to treat the scarring in the liver that leads to liver complications, co-morbidities and death. The genesis of fibrosis is fatty liver disease, with the combined conditions, called non-alcoholic steatohepatitis, or "NASH," affecting as many as 15 million Americans today. Some estimates put the number of Americans affected by nonalcoholic fatty liver disease (NAFLD) as high as 30 percent of the population, or approximately 94 million people.

With the high diagnosis rate, researchers have mostly focused on developing therapies to stop the accumulation of fat in the liver, but with limited success. Companies devoting their resources toward new treatments for advanced stages of the diseases are minimal, with Galectin and Gilead Sciences +0.03% running promising programs in that space. Meanwhile, the select few other companies targeting fibrosis are focused on the early stages of the disease, a time where it can be very difficult to identify which patients will advance to more serious stages of the disease. Gilead has received plenty of attention in 2013 for its leadership role in HIV drugs as well as fibrosis efforts with simtuzumab in mid-stage trials for NASH patients, helping send shares about 70 percent higher so far this year.

While Galectin has its GM-CT-01 drug candidate in Phase 2 clinical trials for melanoma, perhaps an even larger driver has been their research of their galectin protein-inhibiting drugs that shows the potential for GR-MD-02 to not only treat NASH patients, but also actually reverse the scarring in the liver. A drug to treat fatty liver disease and fibrosis has blockbuster potential written all over it, but one that can actually reverse scarring can revolutionize fibrosis research.

While this article is only referencing the liver, fibrosis is prominent in other vital organs as a result of inflammation or damage, such as the lungs, heart, intestines and more. Galectin has conducted pre-clinical research on GR-MD-02 to expand into additional indications, with information released in September disclosing the drug showing a "robust effect" in reducing lung fibrosis. Separate research has also demonstrated tumor shrinkage and enhanced survival in immune competent breast and prostate cancer mouse models treated with GR-MD-02 in combination with immune checkpoint blockage inhibitors anti-CTLA-4 or anti-PD-1.

Galectin is evaluating GR-MD-02 in the Phase 1 trial under a Fast Track designation from the Food and Drug Administration with the first patient dosed in July. The trial is planned to enroll about 32 patients with NASH and stage 3 fibrosis across six clinical sites in the U.S.

There is no doubt that the biotech sector has been one of the best market performers in 2013 and it doesn't look to be losing any steam. Even as some of the majors take a breather as the new year approaches, investors should be looking for developmental companies that are starting to grow a stronger valuation based upon two things: the data supporting their drug and the future market potential if successfully maneuvered down the regulatory pathway. In the case of companies engaged in fibrosis treatments, market capitalizations in the low hundreds of millions of dollars should only represent a portion of the things to come.

To receive email updates on Galectin Therapeutics' progress please click here:

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Disclosure:

Except for the historical information presented herein, matters discussed in this release contain forward-looking statements that are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Emerging Growth LLC is not registered with any financial or securities regulatory authority, and does not provide nor claims to provide investment advice or recommendations to readers of this release. For making specific investment decisions, readers should seek their own advice. For full disclosure please visit: http://secfilings.com/Disclaimer.aspx

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TGen-led study identifies genes associated with unhealthy liver function

Public release date: 1-Oct-2013

Contact: Steve Yozwiak
syozwiak@tgen.org
602-343-8704
The Translational Genomics Research Institute

Study with Geisinger Health System tests nearly 2,300 extremely obese diabetes patients

PHOENIX, Ariz. — Oct. 1, 2013 — A groundbreaking study of nearly 2,300 extremely obese diabetes patients, led by the Translational Genomics Research Institute (TGen), has identified genes associated with unhealthy liver function.

This is believed to be the nation's first large-scale genome-wide association study in overweight patients with diabetes.

Results of the study, done in conjunction with the Geisinger Health System, will be presented at the 64th annual meeting of the American Association for the Study of Liver Diseases Nov. 1-5 at the Walter E. Washington Convention Center in Washington, D.C.

The study — Genome-wide analysis identifies loci associated with total bilirubin levels, steatosis, and mild fibrosis in nonalcoholic fatty liver disease — looked at how genomic factors affect the development of non-alcoholic fatty liver disease. It was selected for presentation from among a record 3,139 submittals from around the world proposed for what also is known as The Liver Meeting 2013.

"These genetic factors could help us identify patients who are most at risk of developing non-alcoholic forms of fatty-liver disease (NAFLD), and which patients may be more likely to progress to severe forms of NAFLD, such as steatohepatitis (NASH)," said Dr. Johanna DiStefano, the study's principal investigator and lead author. Dr. DiStefano is Director of TGen's Diabetes, Cardiovascular and Metabolic Diseases Division.

NAFLD is the build up of extra fat in liver cells, not caused by alcohol. It is one of the most common causes of chronic liver disease. NASH is liver inflammation and damage caused by a buildup of fat in the liver, not caused by alcohol.

"Our results showed evidence for new genetic loci that may play a role in the biological mechanisms of NAFLD and NASH," said Dr. Glenn S. Gerhard, a faculty member of the Geisinger Obesity Institute and a co-investigator of the study.

"We discovered genes that may help identify those patients most at risk for the types of liver disease so severe that they could require transplants," said Dr. Gerhard, Administrative Director for the Institute for Personalized Medicine at Penn State University-Hershey.

Patients included in this study were those with extreme obesity enrolled in a bariatric surgery program.

The study identified evidence for association with markers in the neurocan gene (NCAN) on chromosome 19p12, and rs2501843 on chromosome 1.

###

The American Association for the Study of Liver Diseases (AASLD) is the leading organization of scientists and healthcare professionals committed to preventing and curing liver disease. AASLD was founded in 1950 by a small group of leading liver specialists to bring together those who had contributed to the field of hepatology.

AASLD has grown to an international society responsible for all aspects of hepatology. Its annual meeting, The Liver Meeting, has grown in attendance from 12 to more than 9,500 physicians, surgeons, researchers, and allied health professionals from around the world.

About Geisinger Health System

Geisinger Health System is an integrated health services organization widely recognized for its innovative use of the electronic health record, and the development of innovative care models such as ProvenHealth Navigator® and ProvenCare®. As the nation's largest rural health services organization, Geisinger serves more than 2.6 million residents throughout 44 counties in central and northeastern Pennsylvania. The physician-led system is comprised of more than 19,500 employees, including a 1,000-member multi-specialty group practice, six hospital campuses, two research centers and a 448,000-member health plan, all of which leverage an estimated $6.1 billion positive impact on the Pennsylvania economy. The health system and the health plan have repeatedly garnered national accolades for integration, quality and service. In addition to fulfilling its patient care mission, Geisinger has a long-standing commitment to medical education, research and community service. For more information, visit http://www.geisinger.org, or follow the latest Geisinger news and more on Twitter and Facebook.

Press Contact:

Wendy Wilson
Media Team Director
Geisinger Health System
570-969-7807
wkwilson@geisinger.edu

About TGen

Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results. TGen is focused on helping patients with cancer, neurological disorders and diabetes, through cutting edge translational research (the process of rapidly moving research towards patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and rare complex diseases in adults and children. Working with collaborators in the scientific and medical communities literally worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. For more information, visit: http://www.tgen.org.

Press Contact:

Steve Yozwiak
TGen Senior Science Writer
602-343-8704
syozwiak@tgen.org

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Fatty Liver Disease: More Prevalent in Children

Cleveland Clinic

The Cleveland Clinic's Pediatric Preventive Cardiology and Metabolic Clinic treats and studies nonalcoholic steatohepatitis (NASH).

IN THE LAB Updated September 9, 2013, 7:27 p.m. ET

A type of liver disease once thought to afflict primarily adult alcoholics appears to be rampant in children.

Some 1 in 10 children in the U.S., or more than 7 million, are thought to have the disease, according to recent studies.

The condition, in which the normally rust-colored organ becomes bloated and discolored by yellowish fat cells, has become so common in non-drinkers that it has been dubbed nonalcoholic fatty liver disease.

The disease's prevalence is alarming doctors who worry about its progression to nonalcoholic steatohepatitis, or NASH, when the fatty liver becomes inflamed and cells are damaged. That leads to the end stage of cirrhosis, when the liver forms scar tissue and ultimately stops working.

The condition's rise is tied to the obesity epidemic—about 40% of obese children have it—but isn't caused solely by being overweight. The disease appears to be growing among normal-weight children too, experts say.

And even though obesity rates are starting to level off, the prevalence of fatty liver disease continues to rise, they say.

It also has no symptoms, which means a person could have it for decades without knowing.

"The disease is very silent," said Naim Alkhouri, director of the Pediatric Preventive Cardiology and Metabolic Clinic at the Cleveland Clinic.

Because fatty liver disease has been recognized only fairly recently in children, it's unclear how the disease progresses into adulthood. Roughly 10% of people with fatty liver disease will develop NASH; another 15% to 20% of those will get cirrhosis. While the early stages of fatty liver disease and NASH are reversible, cirrhosis is not.

"This is just really worrisome to have this number of children who have a disease this severe," said Miriam Vos, a pediatrics professor at Emory University School of Medicine who studies and treats kids with fatty liver disease.

In a study published this year, Dr. Vos and her colleagues looked at data from a national health study for elevated liver enzymes, a sign of fatty liver disease. The percentage of children in the sample suspected of having the disease grew to 10.7% between 2007 and 2010, from about 4% between 1988 and 1994.

In the last decade, more scientists have started studying fatty liver disease and NASH, trying to figure out who gets them and why. Last week, the U.S. Food and Drug Administration held a two-day meeting to discuss with industry and other stakeholders the best way to study new treatments and speed up clinical trials.

NASH, the inflamed fatty liver condition, is currently the third-most-common reason for liver transplants, behind alcoholism and hepatitis C. Experts expect it will eclipse the other two by 2030. The liver helps digest food, absorb nutrients and expel toxins from the body.

It's likely there are multiple factors that worsen fatty liver disease. Early research shows that the disease is partly genetic but likely needs to be triggered by environmental conditions, like obesity or insulin resistance. Much of the current research has focused on genes and specific nutrients in the diet that might cause the disease. One culprit is fructose, a type of sugar found in corn syrup and fruit juice, which are widely consumed in western diets, according to Dr. Vos's research.

Some imaging studies of children born from obese women show that even the infants have more fat on their liver.

Also, certain ethnic groups, including Mexican-Americans, appear to be particularly susceptible, whereas African-Americans appear more protected against fatty liver disease, even though rates of obesity are high in the U.S. population. Scientists have discovered several genes linked to the disease. At least one, PNPLA3, appears more often in the Mexican-American population, according to Dr. Vos.

Usually fatty liver disease is detected when other health problems arise. Obesity, insulin resistance or diabetes may prompt a doctor to order blood work to determine how the liver is functioning.

Sherry Waskowski's son Gregory was 12 when he was diagnosed with fatty liver disease two years ago. He had gone to see a doctor for his long-standing acid reflux, but because he was overweight, the physician checked his cholesterol levels, blood sugar, and—unbeknown to Ms. Waskowski—his liver enzymes, his mother says. His liver enzymes came back elevated and the ultrasound that followed glowed bright, indicating an accumulation of fat.

"It was very frightening and I felt so totally responsible," Ms. Waskowski says.

The medical team educated the Waskowskis, who live in Cleveland, about the condition and what Gregory needed to do to reduce his weight, which is the primary recommendation for treatment. He now exercises five hours a week, mostly by walking on the treadmill, and eats more fruits and vegetables. The Cleveland Clinic's Dr. Alkhouri, one of his doctors, wrote a note to his school advising against excess snacking there for Gregory.

Gregory's weight is now in the normal range and his last ultrasound, in March, showed his liver had much less fat, according to Ms. Waskowski.

There's a debate in the field about whether kids should be routinely screened for the condition and, if so, the best way to do it, Dr. Alkhouri says.

While elevated liver enzymes can be a sign of the disease, hepatitis C and other metabolic liver diseases must be ruled out first. Ultrasound helps detect the presence of fat on the liver, but is expensive. The best way of diagnosing a fatty liver is to take a sample of the liver with a biopsy, but this procedure can be painful and has side effects.

Researchers are trying to identify biomarkers detectable through breath or blood samples instead. At a major conference in the field called Digestive Disease Week, Dr. Alkhouri and his colleagues presented the results of a pilot study. It showed that different concentrations of chemicals were found in the breath of obese kids with fatty liver disease compared with those without. If the test is validated upon further study, it may be useful clinically in several years, he says.

Treatments for fatty liver disease are limited. They include weight loss through diet and exercise. Another way to battle the condition is vitamin E, an antioxidant found in supplements and foods including eggs and some leafy vegetables like spinach, that helps to reduce inflammation in adults and children with NASH, according to Joel Lavine, chief of Gastroenterology, Hepatology and Nutrition at Columbia University.

Several trials are under way for treatments for pediatric NASH. The National Institute of Diabetes and Digestive and Kidney Diseases is sponsoring one study and co-sponsoring another.

Bariatric surgery is also being studied as a possible treatment, though it's controversial because no randomized studies exist looking at NASH. Preliminary data from the Cincinnati Children's Hospital Medical Center—not yet published—suggest the procedure is very effective in adolescents with NASH, according to Stavra Xanthakos, medical director of the Surgical Weight Loss Program for Teens there, who collected data.

"If you could mimic the effect of surgery without going through the surgery, that's where a lot of interest is," said Dr. Xanthakos.

Write to Shirley S. Wang at Shirley.Wang@wsj.com

Organ Damage

Some facts about nonalcoholic fatty liver disease:

About 10% of children in the U.S. are thought to have the condition.

Several factors likely contribute, including genetics, obesity, diet and insulin resistance.

It has no detectable symptoms.

Weight loss is the standard treatment for earlier stages of liver disease.

—Source: Miriam Vos, Emory University

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Galectin Therapeutics Receives FDA Fast Track Designation for GR-MD-02 for Fatty Liver Disease with Advanced Fibrosis

Norcross, GA -- (SBWIRE) -- 09/02/2013 -- Galectin Therapeutics, the leading developer of therapeutics that target galectin proteins to treat fibrosis and cancer, today announced that the U.S. Food and Drug Administration (FDA) has granted GR-MD-O2 (galactoarabino-rhamnogalacturonate) Fast Track designation for non-alcoholic steatohepatitis (NASH) with hepatic fibrosis, commonly known as fatty liver disease with advanced fibrosis.

Galectin Therapeutics is currently conducting a Phase 1 clinical trial to evaluate the safety, tolerability and exploratory biomarkers for efficacy for single and multiple doses of GR-MD-02 over four weekly doses of GR-MD-02 treatment in patients with fatty liver disease with advanced fibrosis. The study will enroll 8 patients in each dose escalation cohort and there will be at least three cohorts and potentially up to 5 cohorts, with a maximum of 40 patients at six clinical sites in the US, which each have extensive experience in clinical trials in liver disease. More information on the first-in-man Phase 1 clinical study of GR-MD-02 is available at http://clinicaltrials.gov/ct2/show/NCT01899859?term=gt-020&rank=1.

“Our preclinical data has shown that GR-MD-02 has robust treatment effects in reversing fibrosis and cirrhosis. Fast Track designation enables us to expedite the compound’s development and review process, with the ultimate goal of bringing a first-in-class treatment to the millions of Americans suffering from fatty liver disease with advanced fibrosis," said Dr. Peter G. Traber, President, Chief Executive Officer, and Chief Medical Officer of Galectin Therapeutics Inc. “We are very pleased that the FDA sees the clinical value of GR-MD-02 and seriousness of fatty liver disease, and we look forward to working closely with the FDA throughout this process."

The FDA's Fast Track program is designed to expedite the review of new drugs that are intended to treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs.

About GR-MD-02
GR-MD-02 is a complex carbohydrate drug that targets galectin-3, a critical protein in the pathogenesis of fatty liver disease and fibrosis. Galectin proteins play a major role in diseases that involve scaring of organs such as cancer, and inflammatory and fibrotic disorders. The drug binds to galectin proteins and disrupts their function. Preclinical data has shown that GR-MD-02 has robust treatment effects in reversing fibrosis and cirrhosis in kidney, lung, and liver.
About Fatty Liver Disease with Advanced Fibrosis

Non-alcoholic steatohepatitis (NASH), also known as fatty liver disease, has become a common disease of the liver with the rise in obesity rates, estimated to affect nine to 15 million people, including children, in the US. Fatty liver disease is characterized by the presence of fat in the liver along with inflammation and damage in people who drink little or no alcohol. Over time, patients with fatty liver disease can develop fibrosis, or scarring of the liver, and it is estimated that as many as three million individuals will develop cirrhosis, a severe liver disease where liver transplantation is the only current treatment available. Approximately 6,300 liver transplants are done on an annual basis in the US. There are no drug therapies approved for the treatment of liver fibrosis.

About Galectin Therapeutics
Galectin Therapeutics is developing promising carbohydrate-based therapies for the treatment of fibrotic liver disease and cancer based on the Company's unique understanding of galectin proteins, key mediators of biologic function. We are leveraging extensive scientific and development expertise as well as established relationships with external sources to achieve cost effective and efficient development. We are pursuing a clear development pathway to clinical enhancement and commercialization for our lead compounds in liver fibrosis and cancer. Additional information is available at www.galectintherapeutics.com.

Forward Looking Statements
This press release contains, in addition to historical information, forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements relate to future events or future financial performance, and use words such as “may,” “estimate,” “could,” “expect” and others. They are based on our current expectations and are subject to factors and uncertainties which could cause actual results to differ materially from those described in the statements. These statements include those regarding plans, expectations and goals, expectations and goals regarding the clinical trial, our FAST TRACK submission and the potential benefits of a FAST TRACK designation, potential therapeutic uses and benefits of our Galectin inhibitors and further related studies and potential partnerships.

Factors that could cause our actual performance to differ materially from those discussed in the forward-looking statements include, among others, that the receipt of a FAST TRACK designation from FDA is no guarantee that we avoid delays in the development of our drug product and provide no assurance of FDA approval of our drug development plans and of the grant of marketing approval for our drug product. Future clinical studies may not begin or produce positive results in a timely fashion, if at all, and could prove time consuming and costly. Plans regarding development, approval and marketing of any of our drugs are subject to change at any time based on the changing needs of our company as determined by management and regulatory agencies. Regardless of the results of current or future studies, we may be unsuccessful in developing partnerships with other companies that would allow us to further develop and/or fund any studies or trials.

To date, we have incurred operating losses since our inception, and our ability to successfully develop and market drugs may be impacted by our ability to manage costs and finance our continuing operations For a discussion of additional factors impacting our business, see our Annual Report on Form 10-K for the year ended December 31, 2012, and our subsequent filings with the SEC. You should not place undue reliance on forward-looking statements. Although subsequent events may cause our views to change, we disclaim any obligation to update forward-looking statements.

For more information on Galectin Therapeutics, please visit: http://galectintherapeutics.com/

Galectin Therapeutics is represented by Eclectic Media Productions National PR firm. Website: http://mediaproductions.tv

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