On March 4, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Device Designation to the Elecsys GALAD score (Press release, Hoffmann-La Roche, MAR 4, 2020, View Source [SID1234555161]).* This algorithmic score combines gender and age with the biomarker results of the Elecsys AFP, AFP-L3 and PIVKA-II and is intended to aid diagnosis of early stage hepatocellular carcinoma (HCC).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Dr. Amit Singal, Medical Director of the Liver Tumor Program and Clinical Chief of Pathology at UT Southwestern Medical Center in Dallas, USA, stated, "HCC is the fourth leading cause of cancer-related death worldwide, with the highest burden of disease in East Asia and Africa. This high mortality is largely driven by most patients being detected at a late stage, when curative therapies are no longer possible. Therefore, improving early HCC detection is a critical area of need."

The Elecsys GALAD score will be the first GALAD score, with regulatory approval, for use in In Vitro Diagnostics and is an integral part of the Roche Diagnostics Liver Indication Program, which aims to improve diagnostic workflows throughout chronic liver disease management. Combined with ultrasound, the Elecsys GALAD score has the potential to support clinicians by giving them more accurate information at an earlier stage, thus improving patient outcomes while being minimally invasive for people and potentially also more affordable to healthcare systems.

Liver cancer is one of the few cancers that are on the rise.2 While recent developments in screening and new treatments are making advances in the prevention, diagnosis and treatment of HCC, clinicians still face challenges in diagnosing the disease early enough. Only 44% of liver cancer patients are diagnosed at an early stage.3 Of HCC patients, which are diagnosed with late-stage disease, less than 16% survive a period of 5 years. Of the patients diagnosed at an early stage, 70% percent are still alive after five years1. Therefore, diagnosing HCC, as early as possible, is essential to improving patient outcomes.

"We are excited about FDA’s recognition of the potential clinical benefit the Elecsys GALAD score could bring in diagnosing hepatocellular cancer at an early stage," said Thomas Schinecker, CEO of Roche Diagnostics. "The combination of blood-based biomarkers with clinical algorithms has the potential to significantly reduce mortality of HCC patients as they can receive a more timely diagnosis and treatment."

About GALAD Score
Pioneered by Professor Philip Johnson, Deputy Director of NWCR Centre and Professor in Translational Oncology at the University of Liverpool, and colleagues from the UK, the GALAD score is a serum biomarker-based model that predicts the probability of having hepatocellular carcinoma in patients with chronic liver disease. This combines gender and age with the results from assays AFP, AFP-L3 and PIVKA-II to give the clinician a clearer picture of HCC risk.

In chronic liver diseases, such as hepatitis and cirrhosis, Alpha1-fetoprotein (AFP) may be chronically elevated. Very high concentrations of AFP may be produced by certain tumors. This characteristic makes the AFP test useful as a tumor marker. AFP-L3 is a subtype of AFP and can be used to differentiate an increase in AFP due to HCC, or benign liver disease. PIVKA-II is a precursor and abnormal form of prothrombin that is found in patients with HCC. This can be used to differentiate HCC from non-HCC hepatic diseases.PIVKA-II is an alternate name for des-gamma-carboxy prothrombin (DCP).

About Hepatocellular Carcinoma
The American Association for the Study of Liver Diseases (AASLD) guidelines recommend surveillance of high risk populations for HCC, every 6 months using ultrasound, either with or without a blood test to check protein levels (AFP).4 Ultrasound examinations can be sensitive enough to detect small masses on the liver. While easily done in a doctor’s office, ultrasound examinations are less conclusive with inexperienced technicians and in patients with obesity and fatty liver disease. A recent meta-analysis suggested that ultrasound may miss more than half of early stage HCCs.5 Therefore, other methods of diagnosis, such as abdominal CT scan, abdominal MRI scan or liver biopsy are often needed.4 These are more accurate than ultrasound, though are more invasive and uncomfortable for patients, as well as being costly to the healthcare system.

Liver cancer is one of the few cancers that are on the rise, and hepatocellular carcinoma (HCC), the primary type of liver cancer, accounts for 90% of these cases.6 Worldwide, the most common risk factor for HCC is viral hepatitis – known to cause inflammation of the liver.6,7 Chronic hepatitis B accounts for approximately 50% of all cases of HCC, and the majority of cases of childhood HCC.8 Other risk factors include aflatoxin – a carcinogenic mould found in contaminated foods, especially rice, in hot and humid climates.6

Viral hepatitis B has a particularly high prevalence in most countries in Asia, and this prevalence directly contributes to higher incidences of HCC in the region.7,9 An increasingly important risk factor for the development of HCC is non-alcoholic fatty liver disease (NAFLD), linked with fatty foods and obesity.10 This is the fastest-growing rate of any cancer and is thought to be driven in part by this risk factor, along with increased alcohol use.11

On March 4, 2019 Embleema, the patient-driven healthcare blockchain network for secure sharing of personal health records, reported a strategic partnership with Gustave Roussy Institut, Europe’s leading cancer center, to develop blockchain-based health data sharing applications for oncology clinical research and development (Press release, Institut Gustave Roussy, MAR 4, 2019, View Source [SID1234553810]). Embleema will deploy its technology and develop new standards for real-world oncology studies at the cancer center.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Embleema brings its expertise and technological solutions to enable the secure exchange of health data, allowing patients to consolidate all their data on a single repository. Blockchain technology guarantees that each patient can exercise full data sovereignty, while providing researchers and pharmaceutical companies with an authenticated supply chain of regulatory-grade data to evaluate the safety and efficacy of new investigational drugs.

Embleema launched PatientTruth, the industry’s healthcare blockchain platform that stores and distributes electronic medical records and allows patients to assemble their own medical history, with full control and access to personal data. Individuals can also receive digital tokens in exchange for participation in clinical studies. Building on its proprietary blockchain technology, Embleema is also developing a decentralized platform for data sharing in clinical research. Blockchain offers patient consent and smart contracts, that allow individuals to tailor how they opt-in and share anonymous data. At any time, a patient can cancel, modify access, or control the destination and use of their data.

This strategic partnership will enable the integration of health data, and consolidation onto a real world evidence data exchange, that will enable patients of the Gustave Roussy Institut to access and control their data. For the first time, healthcare data will become reusable for life sciences research, an important step forward in breaking data silos that typically slow down the development of new drugs.

"Our partnership with Embleema will define a new ethical model in drug development, so individual healthcare data may be used to further clinical research, in a transparent manner that fully respects patient rights," said Professor Alexander Eggermont, General Director of the Gustave Roussy Institut. "Blockchain technology allows real world data to finally be able to evaluate the effectiveness and safety of treatments, and deliver new treatments to patients faster."

Robert Chu, CEO of Embleema added: "We are honored to take part in this strategic partnership with Gustave Roussy, which is internationally recognized for the quality of care they provide to cancer patients and their advanced research in immunotherapy and molecular medicine. By streamlining the collection and sharing of clinical information, while ensuring patient consent, Embleema aims to accelerate the development of new drugs and improve the real-world data collection of existing marketed drugs."

Embleema has formed a Consortium that brings together patient advocacy groups, medical providers like Gustave Roussy, life sciences companies, technology companies, standardization bodies and regulators to define and provide solutions that standardize the secure collection and exchange of digital health data. This will serve to define regulatory-grade "Real World Data" (RWD). Gustave Roussy will be one of the first centers to allow its patients to take part in this new exchange that allows regulators to assess the efficacy and safety of health products on an ongoing basis.

On March 3, 2020 Cytokinetics, Incorporated (Nasdaq:CYTK) reported financial results for the fourth quarter and full year 2019. Net loss for the fourth quarter was $30.6 million or $0.52 per share and net loss for the year 2019 was $121.7 million, or $2.11 per share. Net loss for the fourth quarter of 2018 was $26.5 million, or $0.48 per share and net loss for the year 2018 was $106.3 million, or $1.95 per share. Cash, cash equivalents and investments totaled $267.7 million at December 31, 2019.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We had a productive fourth quarter of 2019 which positions us well to deliver against our Vision 2025 that we recently announced pointing towards commercialization of our novel drug candidates, doubling our development pipeline and expanding the breadth of our muscle biology focused research," said Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. "In 2020, we look forward to reaching several key milestones, including sharing top-line results of GALACTIC-HF and completing enrollment in METEORIC-HF, both alongside continued preparations for the potential commercialization of omecamtiv mecarbil and the development of a co-promotion plan in collaboration with Amgen. We are also advancing our pipeline of cardiac myosin inhibitors, including CK-274 in REDWOOD-HCM and CK-271 which we expect to enter Phase 1 soon. We began 2020 with a strong balance sheet enabling our continued execution on key objectives that we believe will empower us to deliver on the promise of our science for patients."

Recent Highlights

Cardiac Muscle Programs

omecamtiv mecarbil (cardiac myosin activator)

Continued conduct of GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), the Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil, following the recently completed second and final planned interim analysis, which considered pre-specified criteria for futility and superiority. We expect top-line results in Q4 2020.

Announced the publication of a manuscript relating to the design of GALACTIC-HF in the Journal of American College of Cardiology: Heart Failure (JACC: HF).

Expect presentation of baseline characteristics from GALACTIC-HF at the American College of Cardiology meeting in March 2020.

Continued conduct of METEORIC-HF (Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure), the second Phase 3 trial of omecamtiv mecarbil. We expect to complete enrollment in METEORIC-HF in 2020.

Presented results from COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure) at the American Heart Association’s Scientific Sessions in Philadelphia. In this post-hoc analysis, patients with heart failure with reduced ejection fraction (HFrEF) treated with omecamtiv mecarbil, in addition to previously reported improvements in cardiac contractility measures (including systolic function, or pumping action of the heart), measures of diastolic function were not different from placebo and, for some measures, trended toward improvement.
AMG 594 (cardiac troponin activator)

Continued conduct of the Phase 1 study of AMG 594 to assess its safety, tolerability, pharmacokinetics and potential to increase cardiac function in healthy volunteers. AMG 594 is a novel, selective, oral, small molecule cardiac troponin activator, discovered under our joint research program with Amgen. This Phase 1 study is being conducted by Amgen in collaboration with Cytokinetics. We expect to complete the SAD/MAD cohorts of the study in 2H 2020.
CK-3773274 (CK-274, cardiac myosin inhibitor)

Prepared for and started REDWOOD-HCM (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM), the Phase 2 clinical trial designed to determine the safety and tolerability of CK-274 in patients with obstructive hypertrophic cardiomyopathy (HCM). REDWOOD-HCM started in Q1 2020 and will continue through 2020. We expect data from the first cohort of patients enrolled in REDWOOD-HCM to be available in 2H 2020.
CK-271 (CK-271, second cardiac myosin inhibitor)

We expect to file an IND and begin a Phase 1 study of CK-271 in 1H 2020.
Skeletal Muscle Program

reldesemtiv (next-generation fast skeletal muscle troponin activator (FSTA))

Presented subgroup analyses of FORTITUDE-ALS (Functional Outcomes in a Randomized Trial of Investigational Treatment with CK-2127107 to Understand Decline in Endpoints – in ALS), the Phase 2 clinical trial of reldesemtiv in patients with amyotrophic lateral sclerosis (ALS) at the 30th International Symposium on ALS/MND in Perth, Australia, showing that the effect of reldesemtiv on patients with ALS was similar whether or not patients were also receiving edaravone and/or riluzole.

Received Orphan Designation for reldesemtiv for the potential treatment of ALS by the U.S. Food and Drug Administration (FDA).

Held regulatory interactions and conducted feasibility and other planning activities in preparation for the potential advancement of reldesemtiv to a Phase 3 trial in patients with ALS. We expect to continue to engage with regulatory and reimbursement authorities in 2020 in preparation for the potential trial.
Pre-Clinical Development and Ongoing Research

Continued pre-clinical development of CK-3762601 (CK-601), a next-generation FSTA, under our collaboration with Astellas. We expect to continue the conduct of IND-enabling studies of CK-601 in 2020.

Continued research in collaboration with Astellas directed to the discovery of next-generation skeletal muscle activators.

Continued independent research activities directed to our other muscle biology research programs.
Corporate

We raised $120.5 million capital through a convertible note offering in November 2019. The convertible note carries a 4% coupon rate, a 27.5% convert premium, and matures in November 2026.
Financials

Revenues for the three and twelve months ended December 31, 2019 were $5.2 million and $26.9 million, respectively, compared to $9.4 million and $31.5 million for the corresponding periods in 2018. The decrease in revenues for the three and twelve months ended December 31, 2019 was due primarily to the winding down of FORTITUDE-ALS in addition to a lack of license revenue in 2019. License revenues in the fourth quarter and twelve months of 2018 were related to the Phase 2 trial of reldesemtiv in spinal muscular atrophy completed in 2018.

Research and development expenses for the three and twelve months ended December 31, 2019 were $18.3 million and $86.1 million, respectively compared to $23.3 million and $89.1 million for the same periods in 2018, respectively. The changes were primarily due to reduced spending for reldesemtiv as well as tirasemtiv following suspension of development of tirasemtiv in late 2017 offset by increased spending related to METEORIC-HF and the development of CK-274.

General and administrative expenses for the three and twelve months ended December 31, 2019 increased to $10.6 million and $39.6 million, respectively, from $7.6 million and $31.3 million for the same periods in 2018, respectively, due primarily to an increase in outside legal counsel and personnel related costs including stock-based compensation.

2020 Financial Guidance

The company also announced financial guidance for 2020. The company anticipates cash revenue will be in the range of $18 to $22 million, operating expenses will be in the range of $120 to $130 million, and net cash utilization will be approximately $105 to $115 million.

Conference Call and Webcast Information

Members of Cytokinetics’ senior management team will review the company’s fourth quarter 2019 results via a webcast and conference call today at 4:30 PM Eastern Time. The webcast can be accessed through the Investors & Media section of the Cytokinetics website at www.cytokinetics.com. The live audio of the conference call can also be accessed by telephone by dialing either (866) 999-CYTK (2985) (United States and Canada) or (706) 679-3078 (international) and typing in the passcode 8698309.

An archived replay of the webcast will be available via Cytokinetics’ website until March 17, 2020. The replay will also be available via telephone by dialing (855) 859-2056 (United States and Canada) or (404) 537-3406 (international) and typing in the passcode 8698309 from March 3, 2020 at 7:30 PM Eastern Time until March 17, 2020.

On March 3, 2020 Exact Sciences Corp. reported the completion of its acquisitions of Paradigm Diagnostics, Inc. and Viomics, Inc., two privately held companies based in Phoenix (Press release, Exact Sciences, MAR 3, 2020, View Source [SID1234555160]). Together, Paradigm and Viomics provide a differentiated late-stage therapy selection test and deep competencies in sequencing and biomarker discovery, extending Exact Sciences’ lab testing and research and development capabilities.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The addition of these companies and their talented team members to Exact Sciences is another step forward in extending our leadership in advanced cancer diagnostics," said Kevin Conroy, chairman and CEO of Exact Sciences. "Viomics’ research capabilities and the Paradigm therapy selection test and scalable clinical lab, combined with the powerful Exact Sciences commercial platform, allow us to provide patients with smarter, faster answers throughout the cancer continuum."

Paradigm currently offers a comprehensive genomic profiling test for patients with advanced, refractory, or recurrent cancer, allowing physicians to better understand a patient’s tumor profile and more effectively recommend targeted therapies or clinical trials. Palmetto GBA, a Medicare Administrative Contractor that assesses molecular diagnostic technologies under its MolDx program, recently covered the test under its existing local coverage determination for Next-Generation Sequencing for Solid Tumors. Differentiated from other tests by a design that requires smaller sample requirements and delivers faster results, the test is critical in supporting treatment decisions and builds upon the successful foundation of the Exact Sciences’ Precision Oncology team.

Viomics provides extensive sequencing capabilities and expertise in identifying unique biomarkers that indicate the presence of cancer in solid tissue and blood. The expertise of their team brings additional resources to Exact Sciences’ world-class research and development team, and any future biomarker discoveries may be used in Exact Sciences’ pipeline cancer tests. Sequencing will play a pivotal role in bringing tissue and blood-based advanced cancer diagnostics to patients and physicians.

Paradigm and Viomics will remain based in Phoenix. Financial terms of the transactions are not being disclosed. XMS Capital Partners served as advisor to Exact Sciences on these transactions.

On March 3, 2020 Targovax ASA (OSE: TRVX), a clinical stage biotechnology company developing immune activators to target hard-to-treat solid tumors, reported that it has completed patient enrollment in the phase I trial with ONCOS-102 in combination with Keytruda (pembrolizumab) in patients with advanced anti-PD1 checkpoint inhibitor (CPI) refractory melanoma (Press release, Targovax, MAR 3, 2020, View Source [SID1234555157]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In this trial, ONCOS-102 immune activation is being tested in patients with advanced, unresectable melanoma who have had disease progression on treatment with anti-PD1 CPI. This is a particularly challenging patient population, with few treatment alternatives available. In July 2019, Targovax reported encouraging results from part 1 of the trial – see link to press release here.

Part 2 of this trial is testing an extended ONCOS-102 dosing regimen with up to twelve injections compared to three injections in part 1. The enrollment of 12 patients into part 2 of the trial has now been completed. The last patients will complete their six months treatment and data on a total of 21 patients are expected in the second half of 2020.

The primary and secondary endpoints of the trial are to assess safety, immune activation and clinical responses of ONCOS-102 and Keytruda combination treatment. The main scientific aim is to test the hypothesis that ONCOS-102 can immune activate anti-PD1 refractory patients to respond to re-challenge with an anti-PD1 CPI.

Magnus Jäderberg, CMO of Targovax, said: "We are very pleased to have completed enrollment of our melanoma trial. ONCOS-102 is currently one of the most clinically advanced oncolytic viruses in this difficult to treat cancer, and therefore a high priority for us. With this trial also being a proof of concept trial, clinical and immune data from this study will not just indicate whether ONCOS-102 in combination with CPIs can help patients with hard to treat melanoma but potentially also other tumor indications. Supportive data could open the path for a registrational trial."