On March 26, 2019 Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs that address cancer, liver and inflammatory diseases, reported that the Phase II advanced liver cancer study did not achieve its primary end point of overall survival in the whole population (n=78) (Press release, Can-Fite BioPharma, MAR 26, 2019, View Source [SID1234534634]). At the same time, superiority in overall survival was found in the largest study subpopulation of CPB7 (n=56) and in secondary end points in the whole population, including objective response measured by CT or MRI. These data strongly support the progression into Phase III.

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Advanced liver cancer in patients with underlying cirrhosis is categorized into three subclasses based on the severity of cirrhosis, starting with Child Pugh A (CPA), mostly treated with Nexavar and progressing to Child Pugh B (CPB) and Child Pugh C (CPC), for which there are no drugs on market with proven efficacy.

In the study, the Company enrolled only patients with CPB stage liver cancer with CBP stage patients being further divided into three categories of increasing severity, namely CPB7, CPB8, and CPB9. These patients already failed first line Nexavar and were treated with Namodenoson (25mg), or placebo, as a second line treatment, twice daily, using a 2:1 randomization. The primary endpoint of the study was defined as the length of time the patients lived after receiving treatment or median overall survival (OS). Secondary endpoints included safety, the length of time tumors did not grow after treatment, or progression free survival (PFS), the percent of patients whose tumors partially shrank after treatment, or partial response (PR), and the percent of patients who were PR or stable, or disease control rate (DCR).

Findings from the study include the following:

1.For the whole population (n=78), median OS was 4.1 months for Namodenoson vs. 4.3 months for placebo (HR: 0.82).

2Pre-planned subpopulation analysis of the CPB7 patients (n=56), revealed that the Namodenoson treated group (n=34) showed median overall survival of 6.8 months vs 4.3 months in placebo (n=22) [HR: 0.77 (95% CI 0.49-1.40)]. Similarly, for this subgroup of patients, PFS was 3.5 months for the Namodenoson treated group vs 1.9 (HR: 0.87) in the placebo group.

3.Objective response in the whole patient population measured by CT or MRI, demonstrated that 9% treated by Namodenoson achieved PR vs 0% in the placebo group.
4.Consistent with safety results from previously completed clinical trials, Namodenoson was generally well-tolerated, with no treated patients being withdrawn for toxicity and no cases of treatment-related deaths.
5.DCR was 18.0% in the Namodenoson group vs 7.1% in the placebo group (p=0.013) after four months of treatment.
6.32.0% of patients treated with Namodenoson completed at least 12 months of treatment vs 14.3% who were treated with placebo (p=0.058).
7.As of today, two patients in the Namodenoson group are ongoing after 19 and 28 months of treatment, respectively. These patients will continue to receive Namodenoson.
8.All nine patients with CBP9 cirrhosis, the most severe grade allowed into the trial, were randomly assigned to the Namodenoson treatment group (OS=3.5 months), a fact which has distorted the results in the whole population.

Dr. Llovet, a Founder and Director of the Liver Cancer Program and Full Professor of Medicine at the Mount Sinai School of Medicine, New York University, and Professor of Research-ICREA in the BCLC Group, Liver Unit, IDIBAPS-Hospital Clínic, University of Barcelona, stated, "The global incidence of liver cancer continues to increase and has more than tripled in the United States over the last three decades, and currently there are no recommended systemic treatment options for patients with advanced HCC and severe liver dysfunction (Child Pugh B)." Dr. Llovet added, "Considering that patients with advanced HCC and severe liver dysfunction do not have any accepted standard of care, the current data from this Phase II trial suggest a signal of efficacy that supports continuing the development of Namodenoson with a Phase III study in this population. I will be happy to help with the design of the Phase III and serve as the principal investigator of the trial."

Dr. Salomon M Stemmer, Institute of Oncology, Davidoff Center, Rabin Medical Center, Petah Tikva/Sackler Faculty of Medicine, Tel Aviv University, Israel and the study principal investigator, added, "Given the evidence of Namodenoson’s clinical benefit, I plan on offering it to selected HCC CPB patients in the compassionate use setting."

"We are encouraged by the advantage shown by Namodenoson in the CPB7 HCC population, a group for which there are no drugs with proven effectiveness," stated Pnina Fishman, Chief Executive Officer of Can-Fite. "Since Namodenoson has a favorable safety profile and shows no evidence of hepatotoxicity, it may possess a unique therapeutic index in this high-need population. Given that Namodenoson has been granted Fast Track status by the FDA, we look forward to engaging regulatory authorities in a dialog at the earliest opportunity."

An abstract for the late-breaking session has been submitted to The American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, to take place May, 2019 in Chicago, IL, USA.

Conference Call

The Company’s management will host a conference call today at 8:30 a.m. Eastern time to discuss the results of the Phase II advanced liver cancer trial. To participate in the conference call, please dial 877-705-6003 (domestic) or 201-493-6725 (international) or 1 809 406 247 in Israel, five minutes prior to the start of the call and provide the Conference ID: 13689112. Investors may also listen via webcast at: View Source A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 90 days following the call.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson is being evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). 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.

on March 26, 2019 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has obtained regulatory approval for the humanized anti-human IL-6 receptor monoclonal antibody, "Actemra Intravenous Infusion 80 mg, 200 mg, and 400 mg" [generic name: tocilizumab (genetical recombination)] from the Ministry of Health, Labour and Welfare (MHLW) for an additional indication of "cytokine release syndrome induced by tumor-specific T cell infusion therapy" and an additional dosing regimen for cytokine release syndrome (CRS) (Press release, Chugai, MAR 26, 2019, View Source [SID1234534619]). CRS is an adverse reaction associated with chimeric antigen receptor (CAR)-T cell therapy. It is caused by overactive immune response, leading to death if aggravated. CAR-T cell therapy is a type of tumor-specific T cell infusion therapies.

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"We are very pleased to gain additional approval which enables us to provide Actemra as the first approved treatment in Japan for the treatment of CRS induced by CAR-T cell therapy," said Dr. Yasushi Ito, Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit. "We will continue our efforts for safety information collection and prompt information provision to healthcare providers so that they can use the drug for their patients with confidence."

The approval is based on the results of two global phase II studies conducted by Novartis, to investigate efficacy and safety of tisagenlecleucel as CAR-T cell therapy in patients with blood cancers (B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma). Actemra was administered as monotherapy or combination therapy with corticosteroids or other treatments to patients with severe CRS.

Prescribing Information *The underlined parts were newly added.
[Indications]

The following diseases that have not responded sufficiently to existing therapies:
rheumatoid arthritis (including inhibition of structural joint damage), polyarticular-course juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis
Improvement of symptoms and laboratory findings associated with Castleman’s disease (high C-reactive protein, high fibrinogen, elevated erythrocyte sedimentation rate, low hemoglobin, low albumin, and general malaise), excluding those for whom lymphadenectomy is indicated.
Cytokine release syndrome induced by tumor-specific T cell infusion therapy
[Dosage and Administration]

Rheumatoid arthritis and polyarticular-course juvenile idiopathic arthritis
The recommended dose of tocilizumab (genetical recombination) is 8 mg/kg as a single intravenous injection administered at 4-week intervals.
Systemic juvenile idiopathic arthritis and Castleman’s disease
The recommended dose of tocilizumab (genetical recombination) is 8 mg/kg as a single intravenous injection administered at 2-week intervals. The dosing interval can be shortened to a minimum of 1 week depending on patients’ disease symptoms.
Cytokine release syndrome
The recommended dose of tocilizumab (genetical recombination) is 8 mg/kg in patients weighing at least 30 kg and 12 mg/kg in patients weighing less than 30 kg, as a single intravenous injection.
About Tumor-Specific T Cell Infusion Therapy
Tumor-specific T cell infusion therapy is an immunotherapy to enhance immune response to target tumor cells and to inject extracorporeally amplified T-cells expressing a specific receptor to recognize cancer cells. Tumor-specific T cell infusion therapies currently in development are chimeric antigen receptor (CAR)-T cell therapy and T cell receptor (TCR)-T cell therapy.

About Cytokine Release Syndrome
CRS is induced by the release of a large amount of cytokines in association with excessive immune response, and results in an extreme elevation of cytokine concentration in the blood.* CRS is an adverse reaction relatively common in CAR-T cell therapy, and many patients show mild to moderate influenza-like symptoms (pyrexia, nausea and chills, myalgia, etc.). However, severe hypotension, tachycardia, dyspnea, and others may be induced in some patients, and the symptoms may progress rapidly and may lead to death.

* Lee DW, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014 Jul 10; 124(2): 188-95.

On March 26, 2019 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a Phase 3 stage biopharmaceutical company focused on discovering and developing novel small molecule drug candidates to treat cancer, with a primary focus on Myelodysplastic Syndromes (MDS), reported financial results for the fourth quarter and fiscal year ended December 31, 2018 (Press release, Onconova, MAR 26, 2019, View Source [SID1234534635]).

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"This year was a period of important progress for Onconova, as we advanced our clinical pipeline, strengthened our balance sheet and senior leadership team, advanced our business development activities and expanded our intellectual property estate," said Steven M. Fruchtman, M.D., President and Chief Executive Officer. "As we move through 2019, we anticipate continued progress across the Company, including recruiting for our Phase 3 IV rigosertib trial in second-line higher-risk MDS (HR-MDS) patients and advancing oral rigosertib in combination with azacitidine toward a pivotal phase 3 trial in first-line HR-MDS patients. In addition, we have surpassed the 75% accrual figure and anticipate completion of recruitment to the pivotal Phase 3 INSPIRE trial in the second half of 2019. We anticipate reporting top-line data following full enrollment and reaching 288 death events."

2018 and Recent Highlights

Executed succession plan by promoting Steven M. Fruchtman, M.D., who previously served as Chief Medical Officer, to President and Chief Executive Officer upon the transition of Ramesh Kumar, Ph.D., to an advisory role
Strengthened the senior leadership team with the appointment of Richard Woodman, M.D., as Chief Medical Officer and Senior Vice President of Research and Development; and Avi Oler, J.D., M.B.A., as Vice President, Corporate Development and General Counsel
Achieved greater than 75% enrollment in the INSPIRE study, and enrollment is expected to be completed in 2019
Opening of new geographical areas to expedite completion of enrollment in the INSPIRE study
A new patent was issued covering oral and IV formulations of rigosertib by the U.S. Patent and Trademark Office extending the Company’s patent for rigosertib to 2037
Hosted a well-attended Key Opinion Leader Breakfast on February 7, 2019, focused on rigosertib development and earlier-stage programs
Oral Rigosertib in Combination with Azacitidine for First-Line HR MDS Trial Progress and Near-Term Milestones

Reported promising efficacy and acceptable safety profile from the Phase 2 study of a higher dose of oral rigosertib in combination with azacitidine (Vidaza) in patients with HR-MDS at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2018
Overall response rate of 90% reported in Onconova’s multi-institutional Phase 2 study in hypomethylating agent (HMA) naïve patients demonstrating a complete remission rate of 34%
Submitted a Special Protocol Assessment (SPA) to the FDA for a Phase 3 Trial of oral rigosertib in combination with azacitidine (Vidaza) for treatment of first-line HR-MDS, and are in discussions with the FDA to finalize the protocol
Business Development Progress for Rigosertib and Pipeline Products

Entered into a license agreement with Pint Pharma to commercialize rigosertib in Latin America including an up to $2.5 million investment by Pint Pharma and up to $42.75 million in regulatory and sales milestones
ON 123300, a first-in-class dual inhibitor of CDK4/6 + ARK5 with the potential to treat a variety of cancers, is advancing toward clinical development in partnership with HanX Biopharmaceuticals, Onconova’s greater China collaborator. HanX has begun manufacturing the compound and initiated toxicology studies to support an IND filing in the U.S., anticipated in the first half of 2019
Collaboration ongoing with preclinical studies of rigosertib for pediatric cancer associated RASopathies
Scheduled scientific presentations on rigosertib development and clinical trials at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, MDS Symposium in Copenhagen, European Hematology Association (EHA) (Free EHA Whitepaper) Congress, and American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting
Discussions with potential partners are ongoing
Year End 2018 Financial Results

Cash and cash equivalents as of December 31, 2018, totaled $17.0 million, compared to $4.0 million as of December 31, 2017. Based on current projections, the Company expects that cash and cash equivalents will be sufficient to fund ongoing trials and operations into the fourth quarter of 2019.

Net loss was $20.4 million for the year ended December 31, 2018, compared to $24.1 million for the year ended December 31, 2017, primarily due to cost controls resulting in lower operating expenses and improved revenue in 2018 from collaboration agreements executed during the first half of 2018. Research and development expenses were $16.9 million for the year ended December 31, 2018, and $19.1 million for the comparable period in 2017. General and administrative expenses were $7.6 million for the year ended December 31, 2018, and $7.4 million for the comparable period in 2017.

Conference Call and Webcast Information

The Company will host a conference call today, March 26, at 9 a.m. Eastern Time, to provide a corporate update and discuss year-end 2018 financial results. Interested parties may access the call by dialing toll-free (855) 428-5741 from the U.S., or internationally (210) 229-8823 and using conference ID: 1878978. The call will also be webcast live. Please click here to access the webcast. A replay will be available following the live webcast.

About Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are conditions that can occur when the blood-forming cells in the bone marrow become dysfunctional and thus produce an inadequate number of circulating blood cells. It is frequently associated with the presence of blasts or leukemic cells in the marrow. This leads to low numbers of one or more types of circulating blood cells, and to the need for blood transfusions. In MDS, some of the cells in the bone marrow are abnormal (dysplastic) and may have genetic abnormalities associated with them. Different cell types can be affected, although the most common finding in MDS is a shortage of red blood cells (anemia). Patients with higher-risk MDS may progress to the development of acute leukemia.

On March 26, 2019 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors, reported positive interim safety and efficacy data from two ongoing open label, single arm Phase 1/2 studies of Annamycin. In the first study, being conducted in the US, four patients have completed treatment at 100 mg/m2 with no significant adverse events related to Annamycin, and the study will now proceed to the next higher dose of 120 mg/m2 (Press release, Moleculin, MAR 26, 2019, https://www.prnewswire.com/news-releases/moleculin-announces-positive-interim-results-in-first-cohort-of-phase-12-clinical-studies-of-annamycin-in-acute-myeloid-leukemia-in-the-us-and-in-poland-300818195.html [SID1234534636]). The second trial, taking place in Poland, started at a 120 mg/m2 dose of Annamycin and has treated three patients. The first patient treated in that trial received a single course of Annamycin and his bone marrow blasts have reduced from 60% to 11%. Our principal investigator considers this response sufficient for the patient to proceed to consolidation therapy, with the goal of receiving a potentially curative bone marrow transplant. To date in Poland, one patient experienced grade 2 mucositis (which resolved to grade 1 within 2 days) and no other adverse events related to Annamycin have been reported. Trial results for the other two patients treated in Poland will not be known until the second quarter of this year.

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"We are very pleased to have completed the treatment of patients in cohort 1 of the US trial and move to the next higher dose," commented Walter Klemp, Moleculin’s Chairman and CEO. "In Poland, we are pleased to have such a positive response at the starting dose level in this trial. Of course the response of a single patient doesn’t necessarily predict the outcome of the trial, but this is a great way to begin and it’s consistent with our expectations for Annamycin."

Mr. Klemp continued: "One of the advantages we believe Annamycin will offer is a lack of cardiotoxicity. We have seen no evidence of cardiotoxicity in any of the patients treated thus far. We intend to advance the clinical study of Annamycin with the goal of ultimately demonstrating the drug’s safety and effectiveness to support regulatory approval in the US and European Union."

Dr. Robert Shepard, Moleculin’s Chief Medical Officer for Annamycin added: "A prior clinical trial for Annamycin in acute leukemia demonstrated activity at its Maximum Tolerable Dose of 150 mg/m2, so we are pleased for the US trial to move to the next higher dose in cohort 2 of 120 mg/m2. In Poland, we consider reducing bone marrow blasts for Patient 1 down to 11% with a single course of Annamycin to be very encouraging. Of course, significant additional study is necessary to definitively demonstrate causality."

"We have begun a second course of Annamycin as a consolidation phase for Patient 1," commented Dr. Lidia Gil, Principal Investigator in the Polish Annamycin clinical trial. "Considering that this patient was refractory to standard of care induction therapy, I am very pleased to see that Annamycin appears to be showing activity. While this is considered a ‘Partial Response,’ I believe it’s enough of a reduction to serve as a ‘bridge to transplant’ for this patient. Importantly, with the first course of Annamycin, no toxicities have been observed that would limit continued dosing with Annamycin."

Study Design

The Company is studying Annamycin in both the US and Poland in open label, single arm clinical trials to assess the safety and efficacy of Annamycin for the treatment of adults with relapsed or refractory acute myeloid leukemia. Both the US and Polish trials have the same study design, providing for a Phase 1 intended to establish a "Recommended Phase 2 Dose," ("RP2D") with cohorts of 3 patients each where the first cohort starts at a low beginning dose and each successive cohort receives the next higher dose level until "dose limiting toxicities" prevent further increases. In the case of cohort 1 in the US, one patient did not complete the evaluation protocol, so a fourth patient was added to complete that cohort.

A key difference in the US is that the starting dose was 100 mg/m2, whereas, in Poland, the starting dose was 120 mg/m2. Having completed the first cohort in the US, the Company is seeking patients for the second cohort at a dose level of 120 mg/m2. Once 3 patients have completed the safety evaluation period of the first cohort in Poland, the second cohort will begin there at a dose level of 150 mg/m2. Once the Company establishes an RP2D, the intent is for each trial to advance to a Phase 2 arm planned to assess the safety and efficacy of Annamycin in 21 additional patients.

The US trial also differs from the Polish trial in that the FDA would like to review safety data relating to cardiotoxicity from patients treated prior to advancing beyond 120 mg/m2. The Company believes that the additional patient safety data gained from the Polish trial may also assist in the FDA’s review of cardiac safety.

On March 26, 2019 OSE Immunotherapeutics (ISIN: FR0012127173; Mnémo: OSE), reported a new research collaboration agreement with premier cancer research hospital, Léon Bérard Cancer Center in Lyon, France, to use artificial intelligence (AI)-based bioanalysis and bioinformatics to identify novel targets in immuno-oncology (Press release, OSE Immunotherapeutics, MAR 26, 2019, View Source [SID1234553881]).

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Léon Bérard Cancer Center (CLB) has both a cancer immunotherapy laboratory and translational research laboratory and is recognized as a scientific expert in oncology, particularly in tumor targeting and in the immune environment. Additional resources at CLB include its state-of-the-art bioinformatics platform and biological resource center. Their experience in analyzing and integrating data from The Cancer Genome Atlas (TCGA) allows detailed analysis of clinically relevant targets in populations that could potentially benefit from an innovative therapeutic approach.

This new collaborative immuno-oncology research program will use different patient cohorts and tumor biopsies to identify novel molecular targets associated with the primary and secondary resistance to
PD-1/PD-L1 immune checkpoint inhibitors and to validate a strategy of combining drugs based on target expression profile.

The research is based on an artificial intelligence approach jointly developed which will be applied to analyze gene expression in the human tumor microenvironment and the composition of tumor infiltrates. The findings from this collaboration will be used for the selection and validation of innovative targets for early development of new drug candidates from the platform of bispecific fusion proteins targeting PD-1 and innovative targets (BiCKI).

"We are very excited to begin a new collaboration with an expert team and the CLB, a premier cancer research center. The goal of this partnership is to identify and validate new targets that will help streamline the development of new treatment approaches for cancer, especially in difficult to treat tumors," said Alexis Peyroles, chief executive officer of OSE Immunotherapeutics.

Professor Jean-Yves Blay, M.D., Ph.D., director of the Léon Bérard Cancer Center commented, "Our AI approach combined with our translational and immunological research platforms will enable us to analyse tumor immune parameters and to identify potential new pathways to address unmet needs for cancer patients. This partnership brings together top experts in oncology research and translational science with the hopes of rapidly advancing the discovery of first-class treatment options for cancer patients. We are very pleased to work in collaboration on this cutting-edge research with OSE Immunotherapeutics."