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 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported its financial results for the fourth quarter and year ended December 31, 2018 (Press release, Curis, MAR 26, 2019, View Source [SID1234534631]).

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"2018 was a pivotal year for Curis as we transitioned from a company broadly engaged in discovery research and pipeline expansion into a company singularly focused on clinical execution," said James Dentzer, President and Chief Executive Officer of Curis. "We now have three novel programs in the clinic, all potential blockbusters and all with significant data catalysts expected in 2019."

Dentzer continued, "With our recently announced agreement with Oberland Capital, we secured the financial flexibility needed to ensure we can continue to move forward aggressively in our clinical execution on all three programs and produce the data readouts everyone is so excited to see.

"As we move through 2019, we are focused on the development of first-in-class and best-in-class precision medicines that we hope will transform the lives of patients," he concluded.

Full Year and Fourth Quarter 2018 Financial Results

For the year ended December 31, 2018, Curis reported a net loss of $32.6 million, or $0.98 per share on both a basic and diluted basis, as compared to a net loss of $53.3 million, or $1.79 per share on both a basic and diluted basis in 2017. For the fourth quarter of 2018, Curis reported a net loss of $5.9 million or $0.18 per share on both a basic and diluted basis, as compared to a net loss of $8.0 million, or $0.24 per share on both a basic and diluted basis for the same period in 2017.

Revenues for the year ended December 31, 2018, were $10.4 million as compared to $9.9 million for the same period in 2017. Revenues for both periods comprise primarily royalty revenues recorded on Genentech and Roche’s net sales of Erivedge. Revenues for the fourth quarters of 2018 and 2017 were $2.8 million and $3.3 million, respectively.

Operating expenses for the year ended December 31, 2018 were $39.8 million as compared to $59.7 million for the same period in 2017. Operating expenses for the fourth quarter of 2018 were $7.9 million, as compared to $10.4 million for the same period in 2017, and comprised the following:

Costs of Royalty Revenues. Costs of royalty revenues, primarily amounts due to third-party university patent licensors in connection with Genentech and Roche’s Erivedge net sales, were $0.6 million for the year ended December 31, 2018 as compared to $0.5 million for the same period in 2017. Cost of royalty revenues were $0.1 million for the fourth quarter of 2018, as compared to $0.2 million for the same period in 2017.

Research and Development Expenses. Research and development expenses were $24.4 million for the year ended December 31, 2018, as compared to $45.1 million for the same period in 2017. The decrease was primarily due to aggregate payments to Aurigene of $7.5 million, for an exclusivity option that was paid in 2017 as well as decreased costs related to ongoing clinical activities for CA-170. These costs included decreased clinical site, patient, clinical research organization, formulation and manufacturing and consulting costs for our ongoing Phase 1 clinical trial. Employee-related expenses decreased over the prior year period primarily due to a reduction in headcount that occurred in the fourth quarter of 2018. Research and development expenses were $4.7 million for the fourth quarter of 2018 as compared to $6.9 million for the same period in 2017.

General and Administrative Expenses. General and administrative expenses were $14.8 million for the year ended December 31, 2018 as compared to $14.1 million for the same period in 2017. The increase in general and administrative expenses was driven primarily by higher legal, professional and consulting services and other administrative expenses, partially offset by lower stock-based compensation for the period. General and administrative expenses were $3.0 million for the fourth quarter of 2018, as compared to $3.3 million for the same period in prior 2017.

Other expense, net, was $3.2 million for the year ended December 31, 2018, as compared to $3.6 million for the same period in 2017. Other expense, net primarily consisted of interest expense related to the debt obligations of Curis Royalty (a wholly owned subsidiary of Curis). The decrease in interest expense in the current year was related to a lower principal balance on Curis Royalty’s outstanding debt with HealthCare Royalty, which was refinanced in the first quarter of 2017. Other expense, net was $0.8 million and $0.9 million for the fourth quarter of 2018 and 2017, respectively.

As of December 31, 2018, Curis’ cash, cash equivalents, marketable securities and investments totaled $24.3 million and there were approximately 33.2 million shares of common stock outstanding. The previously announced sale of a portion of Erivedge royalties to Oberland Capital Management will provide net proceeds of approximately $30 million before closing costs and transaction fees.

Full Year 2018 and Recent Operational Highlights

Precision oncology, fimepinostat (HDAC/PI3K inhibitor):

Curis initiated its study of fimepinostat (a MYC inhibitor) with venetoclax (a BCL-2 inhibitor) combination regimen in diffuse large B-cell lymphoma (DLBCL), including patients with Double-Hit/Double-Expressor Lymphoma. In preclinical models, fimepinostat administered in combination with venetoclax resulted in an enhanced benefit relative to each agent alone.
In December 2018 at the American Society of Hematology (ASH) (Free ASH Whitepaper)’s (ASH) (Free ASH Whitepaper) annual meeting, Curis presented a pooled analysis of patients with relapsed/refractory DLBCL treated with fimepinostat, including individuals with MYC-alterations that demonstrated the treatment’s safety and durable benefit in this patient population.
Precision oncology, CA-4948 (IRAK4 Inhibitor; Aurigene collaboration):

In 2018, Curis initiated and continued to enroll patients with relapsed or refractory non-Hodgkin lymphoma in a Phase 1 dose escalation study. CA-4948 is designed to target cancers with MYD88 mutations present in various tumor cell lines including DLBCL, Waldenström’s macroglobulinemia (WM), and acute myeloid leukemia.
In December 2018, at the ASH (Free ASH Whitepaper) annual meeting, Curis presented preclinical results showing potent anti-tumor in vivo activity for CA-4948 as a single agent as well as an enhanced effect when combined with other agents supporting the potential for IRAK4-based combination regimens.
Immuno-oncology, CA-170 (VISTA / PDL1 antagonist; Aurigene collaboration):

In November 2018, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s Annual Meeting, Curis presented three posters providing an update to the ongoing CA-170 Phase 1 trial and preclinical support of VISTA’s role as an oncology target of interest. At the same conference, collaborator Aurigene presented a poster detailing key findings from its ongoing Phase 2 trial of CA-170 in patients with advanced solid tumors and Hodgkin lymphoma who are immunotherapy treatment-naïve.
In January 2019, Curis announced the first mesothelioma patient dosed in its ongoing Phase 1 CA-170 trial, which recently started to enroll patients with mesothelioma, following evidence supporting high levels of VISTA expression in mesothelioma tumor samples. Recent publications have identified VISTA as a possible resistance mechanism to treatment with anti-PD1 antibodies in several cancer indications.
Full Year 2018 and Recent Corporate Highlights

Curis announced a 1-for-5 reverse stock split that came into effect on May 29, 2018.
In May 2018, Curis appointed Robert Martell, M.D., Ph.D., a practicing oncologist, experienced drug developer and former CMO of Tesaro, as Head of Research and Development.
In September 2018, Curis announced the appointment of James Dentzer to the position of President and Chief Executive Officer.
In October 2018, Curis implemented a 27% reduction in headcount and a re-allocation of pre-clinical resources to strengthen focus on clinical development. The result of these changes reduced the forecasted cash burn from approximately $11 million to $8 million per quarter going forward.
In March 2019, Curis announced that it sold a portion of its Erivedge royalties to Oberland Capital for up to $135.7 million, including $65 million upfront and $70.7 million in future milestones.
2019 Data Catalysts

Curis expects to report initial data on the combination of fimepinostat and venetoclax regimen in patients with R/R DLBCL, including patients with DH/DE Lymphoma, in the second half of 2019.
Curis expects to report initial efficacy data from its CA-4948 dose escalation study in patients with D/DE DLBCL in mid-year 2019.
Curis expects to report initial efficacy data from its CA-170 Phase 1 trial in patients with mesothelioma (high VISTA expressors) in the second half of 2019.
Conference Call Information

Curis management will host a conference call today, March 26, 2019, at 4:30 p.m. ET, to discuss these financial results, as well as provide a corporate update.

To access the live conference call, please dial 1-888-346-6389 (from the United States) or 1-412-317-5252 from other locations, shortly before 4:30 p.m. ET. The conference call can also be accessed in the Investors section on the Curis website at www.curis.com.

On March 26, 2019 NANOBIOTIX (Euronext: NANO – ISIN: FR0011341205 – the ‘‘Company’’), a clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported that the Company has clarity on its regulatory pathway in the treatment of Head and Neck cancers for first-in-class radioenhancer NBTXR3 (Press release, Nanobiotix, MAR 26, 2019, View Source [SID1234534630]).
The announcement follows pre-IND feedback from the US FDA received on March 18, 2019.

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Stage III and IV Head and Neck cancers include large primary tumors which may invade underlying structures and/or spread to regional nodes. Treatment of these locally advanced forms of the disease—which makes up more than 50% of all Head and Neck cancers—requires aggressive, concerted measures that often remain a clinical challenge with an estimated 5-year survival rate of 50% with the current standard of care.

Within the Stage III and IV Head and Neck cancers patient population, the Company targets a subpopulation of patients, who have a higher risk of recurrence, or a poorer prognosis as they have an inability to receive cisplatin, the frontline chemotherapy drug for advanced Head and Neck cancers. Additionally, the localization of the tumor focuses on oropharynx, hypopharynx, and oral cavity – representing the majority of Head and Neck cancers.

Based on US FDA feedback, the Company plans to design an Overall Survival (OS)-based, randomized, event-driven Phase II/III clinical trial. 50% of patients will receive standard of care radiotherapy combined with NBTXR3 while the other 50% will receive radiotherapy in combination with cetuximab. The expected total number of patients to participate in this global clinical trial is approximately 600, and an efficacy interim analysis is planned.

Notably, the US FDA has not objected to the use of the data from the dose-escalation phase of the Company’s European Phase I clinical trial in elderly and frail patients with locally advanced Head and Neck cancers as well as the Company’s current CMC (chemical, manufacturing and control) development plan.

The Company plans to initiate its global clinical trial authorization process with US FDA in 2H2019.-Ends

About NBTXR3

NBTXR3 is a first-in-class product candidate designed to destroy tumors and metastasis when activated by radiotherapy. NBTXR3 has a high degree of biocompatibility and requires one single administration before the whole radiotherapy treatment. Nanobiotix believes NBTXR3 has the ability to fit into current worldwide standards of radiation care. Nanobiotix’s broad clinical program includes 7 clinical trials. In June 2018, Nanobiotix established human proof of concept for this first-in-class product candidate in its Soft Tissue Sarcoma (STS) Phase III clinical trial. 2 NBTXR3 is actively being studied in head and neck cancer with locally advanced squamous cell carcinoma of the oral cavity or oropharynx in elderly and frail patients who are unable to receive chemotherapy or cetuximab and have very limited therapeutic options. Promising results from these clinical studies have been observed from the ongoing Phase I/II trial regarding the local control of tumors. Nanobiotix is also running an Immuno-Oncology development program. In the United States, Nanobiotix has received approval from the US FDA to launch a clinical study of NBTXR3 activated by radiotherapy in combination with anti-PD1 antibodies in lung, and head and neck cancer patients (head and neck squamous cell carcinoma and non-small cell lung cancer). The other ongoing NBTXR3 trials are treating patients with liver cancers (hepatocellular carcinoma and liver metastasis), locally advanced or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with concurrent chemotherapy, and prostate adenocarcinoma. The first market authorization process (CE Marking) is ongoing in Europe in the STS indication.

On March 26, 2019 BioInvent International AB (OMXS: BINV), a biotech company focused on the discovery and development of novel immuno-regulatory antibodies to treat cancer and Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of solid tumors, reported the extension of their collaboration to co-develop multi-functional oncolytic viruses (OV) encoding for undisclosed antibodies sequences capable of treating a broad range of solid tumors (Press release, Transgene, MAR 26, 2019, View Source [SID1234534629]).

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Under the terms of the extension agreement, Transgene will contribute its industry-leading OV design and engineering expertise, some non-antibody transgenes, as well as its proprietary engineered vaccinia virus (TK-, RR-) backbone, which forms the basis of its Invir.IO platform. BioInvent will provide its cancer biology and antibody expertise to the collaboration as well as one or more antibodies sequences, generated through its proprietary n-CoDeR/F.I.R.S.T. platforms. Certain sequences for an undisclosed target will be selected for encoding within Transgene’s Invir.IO backbone to create a multi-functional OV.

In November 2018, Transgene and BioInvent presented positive data from their initial collaboration at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). These initial data covered the collaboration’s work on an anti-CTLA-4 antibody-armed oncolytic vaccinia virus, based on Transgene’s proprietary vaccinia virus (TK-, RR-) backbone. This enhanced oncolytic vaccinia virus demonstrated its ability to ensure the expression of BioInvent’s anti-CTLA-4 antibody in the tumor with low systemic exposure. It also showed improved efficacy and a better safety profile when compared to the combination of the antibody and the non-armed corresponding oncolytic virus given individually in pre-clinical models.

Consistent with the initial collaboration, research and development costs as well as revenues and royalties from the multifunctional OVs generated as a result of the new collaboration will be shared 50:50.

Encoding BioInvent’s antibodies sequences in Transgene’s proprietary Invir.IO platform, for a direct expression into the tumor, promises to optimize the efficacy and tolerability of these antibodies. Both Transgene and BioInvent believe that these novel multifunctional OVs could be significantly more effective than co-administering an OV and an antibody together.

Commenting on the agreement, Martin Welschof, CEO of BioInvent, said: "The extension of our collaboration with Transgene opens up further opportunities for both companies to combine their expertise and knowledge to develop antibody oncolytic virus combinations capable of treating a broad range of solid tumors. By leveraging BioInvent’s unique and proprietary n-CoDeR/F.I.R.S.T. platforms, we will be able to develop a number of novel first-in-class antibodies that could be delivered directly into the tumor via Transgene’s vaccinia viral backbone, potentially enhancing their efficacy and improving their side effect profile."

Philippe Archinard, PhD, Chairman and CEO of Transgene, said: "We are pleased to extend the scope of our highly productive collaboration with BioInvent. We believe that the next generation of multi-functional oncolytic viruses expressing BioInvent’s highly targeted immune modulators directly in the tumor micro-environment will deliver much improved overall survival outcomes in patients with solid tumors. This agreement further expands Transgene’s broad portfolio of oncolytic viruses in development, the first of which is expected to enter the clinic in 2020."

On March 26, 2019 Integral Molecular, the industry leader in discovering antibodies against multipass membrane proteins, reported that it will showcase updated data on its discovery of highly specific Claudin 6 MAbs at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) conference in Atlanta on Monday, April 1 (Press release, Integral Molecular, MAR 26, 2019, View Source [SID1234534628]). Claudin 6 is an established membrane protein target expressed in multiple cancers, including ovarian and gastric tumors, and absent from healthy adult tissues. Until now, the structural complexity of Claudin 6 and its similarity to proteins expressed on healthy tissue have limited its exploitation for targeted oncology therapies.

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"There is a strong need for therapeutic monoclonal antibodies that can provide more specific and less toxic treatments for ovarian cancer," said Ross Chambers, VP of Antibody Discovery. "Our lead antibody, isolated using our MPS Antibody Discovery platform, shows best-in-class Claudin 6 specificity. We are currently looking for partners to further develop these exciting assets."

Integral Molecular’s MPS Antibody Discovery platform encompasses a comprehensive technology suite that overcomes the obstacles of working with highly conserved and structurally complex membrane protein targets, like Claudin 6. This suite includes antigen engineering and presentation on Lipoparticles, immunization of divergent species, and the use of B-cell cloning to recover rare antibodies. Integral Molecular is currently isolating MAbs against dozens of membrane protein targets and welcomes antibody licensing opportunities and discovery partnerships.