Preclinical Data Show Can-Fite's Namodenoson (CF102) Prevents Progression of Liver Fibrosis

New Preclinical Data Show Can-Fite's Namodenoson (CF102) Prevents Progression of Liver Fibrosis

- Phase II trial to treat NAFLD/NASH expected to commence in 2017

- Lowering liver fat content and fibrosis are the main unmet needs in NASH, according to KOL Dr. Rifaat Safadi

Feb 28, 2017, 07:00 ET
PETACH TIKVA, Israel, Feb. 28, 2017 /PRNewswire/ -- Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address cancer, liver and inflammatory diseases, today announced new data that show its liver disease drug candidate Namodenoson (CF102) prevented liver (hepatic) fibrosis progression in preclinical studies.

"These latest study results add to the growing body of data that demonstrate Namodenoson's potential efficacy in combating non-alcoholic fatty liver disease (NAFLD), the precursor to non-alcoholic steatohepatitis (NASH), indications for which there is currently no FDA approved drug. We are advancing Namodenoson into a Phase II trial in NAFLD and expect to commence patient enrollment in the coming months through leading medical institutions in Israel," stated Can-Fite CEO Dr. Pnina Fishman. 

Liver fibrosis is the excessive accumulation of scar tissue resulting from ongoing inflammation. It can result in diminished blood flow throughout the liver and is associated with NAFLD.

Recent preclinical studies in a mouse model of liver fibrosis demonstrated the anti-fibrotic effects of Namodenoson. The Namodenoson treated group exhibited normal liver under macroscopic view, no accumulation of fluid (ascites), a low fibrosis profile, and lower serum levels of transaminases as compared to the control group. In addition, liver protein extracts and mRNA for the alpha smooth muscle actin showed a significant anti-fibrotic effect in the Namodenoson treated group as compared to the control group.

These studies were conducted by a third party under the supervision of Prof. Rifaat Safadi M.D., a Key Opinion Leader in the field of liver diseases, and Director of Liver Unit, Institute of Gastroenterology and Liver Diseases, Hadassah University Hospital, Ein Kerem.

Prof. Safadi commented, "Lowering liver fat content and fibrosis are the main unmet needs in NASH. Today there is a huge market need for drugs that fight the worldwide NASH epidemic."

"Namodenoson is uniquely compelling for its potential to treat NAFLD and NASH because its safety profile has already been de-risked, increasing the likelihood it can advance through late stage trials and into clinical use for this large and unmet need," Dr. Safadi added. "In general, there is significant development risk for new potential drugs in development due to safety risks including drug induced liver injury (DILI), drug-to-drug interactions (DDI), and metabolites in safety testing (MIST). Namodenoson, however, has demonstrated a good safety profile and is low or negative for DILI, DDI and MIST."

"In addition, Namodenoson recognizes the difference between diseased and normal cells, and targets only the diseased cells through the specific A3 adenosine receptor. This precision targeting is designed to lead to higher efficacy and safety by leaving healthy cells unaffected. We are all looking for drugs with this profile to treat NASH," concluded Dr. Safadi.

About Namodenoson (CF102) 
Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug. In Can-Fite's pre-clinical and clinical studies, Namodenoson has demonstrated a robust anti-tumor effect via deregulation of the Wnt signaling pathway, resulting in apoptosis of liver cancer cells. Based on preclinical data showing Namodenoson has strong liver protective properties, Can-Fite intends to initiate a Phase II study in NASH. Can-Fite has received Orphan Drug Designation for Namodenoson in Europe and the U.S., as well as Fast Track Status in the U.S. as a second line treatment for hepatocellular carcinoma.

http://ir.canfite.com/press-releases/detail/781/new-preclinical-data-show-can-fites-namodenoson-cf102-prevents-progression-of-liver-fibrosis       

FDA Grants Fast Track Designation to Can-Fite's CF102 in the Treatment of Liver Cancer

U.S. Food and Drug Administration Grants Fast Track Designation to Can-Fite's CF102 in the Treatment of Liver Cancer

PETACH TIKVA, Israel, Sept. 17, 2015 /PRNewswire/ -- Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs that address inflammatory and cancer diseases, today announced the U.S. Food and Drug Administration (FDA) has granted the Company's drug candidate CF102 Fast Track designation as a second line treatment for hepatocellular carcinoma (HCC), the most common form of liver cancer. CF102 had already received the FDA's Orphan Drug designation.

Can-Fite is currently conducting a Phase II study for this indication in the U.S., Europe and Israel. The randomized, double blind, placebo controlled study is expected to complete enrollment by the end of the first half of 2016 in 78 patients with Child-Pugh Class B cirrhosis who failed the only FDA approved drug on the market, Nexavar® (sorafenib). Patients are treated twice daily with 25 mg of oral CF102, which has been found to be the most efficacious dose in Can-Fite's earlier Phase I/II study resulting in the longest overall survival time, with excellent safety results.

Fast Track, aimed at getting important new drugs that meet an unmet need to patients earlier, is expected to expedite the development of CF102. Drugs that receive Fast Track designation benefit from more frequent meetings and communications with the FDA to review the drug's development plan to support approval. It also allows the Company to submit parts of the New Drug Application (NDA) on a rolling basis for review as data becomes available. Since the Fast Track Program started, from March 1998through June 30, 2015 a total of 318 Fast Track applications have been received by the FDA. The FDA has granted 202 of them, and denied 110, with 6 more pending.

"We are very pleased that the FDA recognizes the potential for CF102 to treat HCC patients who have tried, and not been responsive to Nexavar, the only FDA approved drug currently on the market for this indication," stated Can-Fite CEO Dr. Pnina Fishman. "We consider Fast Track designation to be a major catalyst for our CF102 development program and we believe it could shorten our time to market for CF102, thereby making a considerable difference for patients."

According to Global Industry Analysts, the global market for liver cancer drugs is projected to exceed $2 billion in 2015. Nexavar® annual sales, as reported by Bayer, were €773 million in 2014.

About CF102
CF102 is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). A3AR is highly expressed in tumor cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug. In Can-Fite's pre-clinical and clinical studies, CF102 has demonstrated a robust anti-tumor effect via deregulation of the Wnt signaling pathway, resulting in apoptosis of liver cancer cells.

Can-Fite Submits Protocol to U.S. FDA for Phase II Liver Cancer Study

Can-Fite Submits Protocol to U.S. FDA for Phase II Liver Cancer Study

Tufts University will be a clinical site for international trial of CF102 with Orphan Drug Designation

PETACH TIKVA, Israel, April 29, 2014 /PRNewswire/ -- Can-Fite BioPharma Ltd. (NYSE MKT:CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs that address inflammatory and cancer diseases, announced today that it has submitted a study protocol to the U.S. Food and Drug Administration for its Phase II clinical trial of CF102 for the treatment of advanced liver cancer. The FDA has granted Orphan Drug designation to CF102 in this indication. The protocol, which has already been approved by the Institutional Review Board (IRB) in Israel, will also be filed in Europe.

The planned Phase II study will be conducted in Israel, Europe and the U.S. with 78 subjects who will be dosed with CF102 as a second-line treatment of advanced hepatocellular carcinoma (HCC) with Child-Pugh Class B cirrhosis. The study will investigate the efficacy and safety of CF102 as compared to placebo.

Dr. Keith Stuart, MD, assisted in developing the study protocol. He is Chairman, Department of Hematology at Lahey Clinic and Oncology Professor of Medicine, Tufts University School of Medicine. Tufts University will participate as the study's U.S. clinical site.

The protocol submission is supported by strong, positive data from Can-Fite's Phase I/II HCC study published in The Oncologist, and presented at the 18th World Congress on Advances in Oncology. The Phase I/II study data demonstrated that the trial objectives were successfully achieved. CF102 had a very favorable safety profile with very encouraging median overall survival and one patient who has been treated for 4 years with CF102. The A3 adenosine receptor (A3AR), which is the target of CF102, was also found to potentially serve as a biomarker to predict patients' reaction to treatment with CF102.

"We are planning to initiate our Phase II trial for advanced liver cancer during the current quarter. Having already received IRB approval in Israel, we look forward to the FDA's response to the protocol. Advanced liver cancer is an indication that is a clear, unmet medical need and we believe the FDA's Orphan Drug Designation for CF102 will support our clinical development path," stated Can-Fite CEO Dr. Pnina Fishman.

According to Global Industry Analysts, the global liver cancer drug market is expected to exceed $2 billion by 2015.

About CF102

CF102 is a small orally bioavailable drug which binds with high affinity and selectivity to the A3 adenosine receptor. The latter is highly expressed in tumor cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug. In our pre-clinical and clinical studies, CF102 induces a robust anti-tumor effect via de-regulation of the Wnt signaling pathway, resulting in apoptosis of liver cancer cells.

About Can-Fite BioPharma Ltd.

Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (TASE: CFBI) is an advanced clinical stage drug development company with a platform technology that is designed to address multi-billion dollar markets in the treatment of cancer and inflammatory diseases. The Company's CF101 is in Phase II/III trials for the treatment of psoriasis and the Company is preparing for a Phase III CF101 trial for rheumatoid arthritis. Can-Fite's liver cancer drug CF102 is in Phase II trials and has been granted Orphan Drug Designation by the U.S. Food and Drug Administration. CF102 has also shown proof of concept to potentially treat other cancers including colon, prostate, and melanoma. These drugs have an excellent safety profile with experience in over 1,200 patients in clinical studies to date. For more information please visit: www.can-fite.com

Results:CF102 in the treatment of hepatocellular carcinoma (HCC).

Can-Fite BioPharma Announces Successful Results of its Phase I/II Liver Cancer Study with its CF102 Drug; the Study Achieved the Primary and Secondary Endpoints

Can-Fite BioPharma Ltd (TASE:CFBI), a biotechnology company developing small molecule drugs for the treatment of inflammatory, and liver diseases, traded on the Tel Aviv Stock Exchange announced today the successful results of the Phase 1/2 study of its drug candidate CF102 in the treatment of hepatocellular carcinoma (HCC).

The company also announced today that a separate phase 1/2 study in patients with Hepatitis C (HCV) reached the study's main objectives of safety and pharmacokinetic behavior.
The HCC study which was conducted under the supervision of Dr. Salomon M. Stemmer, Institute of Oncology, Davidoff Center, Rabin Medical Center, included 18 patients with HCC, most of them had failed prior treatment with Sorafenib (Nexavar), the only currently approved drug for this indication.

The primary study objectives were to evaluate the safety profile of long-term administration of CF102 at 3 different dose levels in patients with HCC, and to determine the pharmacokinetic behavior of CF102 in this patient population. The secondary objective of the trial was to document evidence of clinical efficacy and to look at the correlation between A3 adenosine receptor expression levels at base line and patients' response to CF102.

The study data demonstrate that the trial objectives were successfully achieved, showing a very favorable safety profile for CF102 in a patient population with hepatocellular carcinoma and Child-Pugh cirrhosis classes A and B. In addition, the median overall survival time was 7.8 months, which is very encouraging data given that most patients were treated in the second-line setting and some were Child-Pugh class B. Remarkably, the median overall survival time of the Child-Pugh B patients was 9.4 months, the longest overall survival time that has been reported in the literature for this patient population.

Out of the 18 patients, 9 were infected with Hepatitis C. In 7 patients treated with the high CF102 dosages, a reduction in HCV load was observed.

According to Dr. Keith Stuart, MD, Chairman, Department of Hematology and Oncology, Lahey Clinic Medical Center, Professor of Medicine, Tufts University School of Medicine: "The safety and efficacy data of the CF102 Liver Cancer study are impressive and encouraging in the context of other investigational drugs. Therefore, I would recommend further clinical development of this drug for the treatment of patients with hepatocellular carcinoma. I hope that the present data will be reproducible and that patients could benefit from this drug."
In parallel, the company also announced today that a separate phase 1/2 study in patients with Hepatitis C (HCV) reached the study's primary objectives of safety and pharmacokinetic behavior. However, a reduction in the HCV viral load was not observed. It should be noted that patients on this study were treated for several months only with the low dose of CF102.
According to Dr. Pnina Fishman, the company CEO, "We are very pleased that the study achieved all of its objectives in patients with HCC, most of whom had failed prior treatment with Nexavar. The impressive results in the HCC study encourage us to continue development of CF102 in patients with Liver Cancer. We will focus on this disease and will continue to observe the viral load of HCC patients who also suffer from HCV."

CF102 is a small orally bioavailable drug which binds with high affinity and selectivity to the A3 adenosine receptor. The latter is highly expressed in tumor cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug. The drug induces a robust anti-tumor effect via de-regulation of the Wnt signaling pathway, resulting in apoptosis of liver cancer cells agonist at the A3 adenosine receptor.
About Can-Fite Biopharma Ltd.

Can-Fite Biopharma Ltd is a public company, trading on the Tel Aviv Stock Exchange. The company, which commenced business activity on 2000, was founded by Prof Pnina Fishman, researcher in the Rabin Medical Center, and Dr Ilan Cohen, patent attorney and senior partner at Reinhold Cohen Patent Attorneys. Prof Fishman serves as CEO of the company. The company was founded on the basis of Prof Fishman's scientific findings, and is focused on the development of small molecule drugs, ligands to the A3 adenosine receptor. The latter mediates anti-inflammatory and anti-cancer effects and is suggested as a biological predictive marker. The company's lead drug, CF101, is in advanced clinical development for the treatment of autoimmune inflammatory diseases. The CF102 drug candidate is being developed for the treatment of liver diseases. Can-Fite has a wealth of clinical experience: to date, more than 700 patients have participated in clinical trials conducted by the company. Can-Fite recently licensed its activity in the ophthalmic field to OphthaliX Inc.

About OphthaliX Inc (formerly Denali Concrete Management Inc).
OphthaliX Inc. (OTCBB:DCMG) is an advanced clinical-stage biopharmaceutical company focused on developing therapeutic products for the treatment of ophthalmic disorders. Denali's product candidate, CF101, is being developed to treat three ophthalmic indications: dry eye syndrome; glaucoma and uveitis. Can-Fite holds 82.3% in OphthaliX Inc.
Can-Fite BioPharmaPnina Fishman, Ph.D., Chief Executive OfficerTel: +972-3-9241114Fax: +972-3-9249378

pnina@canfite.co.ilhttp://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.canfite.com%2F&esheet=50118903&lan=en-US&anchor=http%3A%2F%2Fwww.canfite.com&index=1&md5=af5a23fca4c73f2d3252e21ea76b556e
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CF102 Drug; Interim Analysis Data Phase I/II Liver Cancer Study

Can-Fite BioPharma Ltd (TASE:CFBI), a biotechnology company developing small molecule drugs for the treatment of inflammatory, ophthalmic, and liver diseases, traded on the Tel Aviv Stock Exchange, announced today promising Phase 1/2 interim analysis data regarding its drug candidate CF102 in the treatment of hepatocellular carcinoma (HCC). This trial included 18 patients with HCC, most of whom had failed prior treatment with Sorafenib (Nexavar), the only currently approved drug for this indication. The primary study objectives were to evaluate the safety profile of long-term administration of CF102 at 3 different dose levels in patients with HCC, and to determine the pharmacokinetic behavior of CF102 in this population. The secondary objective of the trial was to document evidence of clinical efficacy in this patient population.

The interim analysis data demonstrate the trial successfully achieved its objectives, showing a very favorable safety profile for CF102 in a patient population with primary liver cancer and Child-Pugh cirrhosis classes A and B. In addition, the median overall survival time was 8.1 months, which is very encouraging data given that most patients were treated in the second-line setting and some were Child-Pugh class B. The company continues to follow those patients who remain on CF102 treatment and will release further data after the final analyses are completed.

According to Dr. Pnina Fishman, the company CEO, "We are quite pleased with these interim data and the fact that the study achieved all of its objectives. Not only was CF102 shown to be safe at all dose levels, with well-behaved pharmacokinetic profile; the fact that patients achieved such an impressive median survival despite their advanced underlying disease encourages us to continue development in patients with hepatic disorders."

CF102 is a small molecule drug, agonist at the A3 adenosine receptor that has a favorable safety profile, which emerges from its selective activity on diseased cells. The latter over-express the receptor while normal cells express very low levels of the A3 receptor.

Source:
Can-Fite BioPharma Ltd

View drug information on Nexavar.