On February 20, 2018 LabCorp (NYSE: LH), a leading global life sciences company, reported that it will host an Investor and Analyst Day for institutional investors and financial analysts in New York City on Tuesday, February 27, 2018 (Press release, LabCorp, FEB 20, 2018, View Source [SID1234524073]). The event, which will feature presentations by members of the management team, begins at 8:30 a.m. ET and will conclude by approximately 1:30 p.m. Prior registration is required to attend the event.

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All are invited to listen to the live event and view the presentation slides via webcast on the LabCorp Investor Relations website at www.labcorp.com. The audio portion of the presentation is also available by dialing 844-634-1444 (615-247-0253 for international callers). The access code is 4099115.

A replay of the webcast will be available following the conclusion of the live event. To access the webcast recording, visit www.labcorp.com. This webcast will be archived and accessible through February 22, 2019.

On February 20, 2018 Kancera AB (publ) hereby reports results from a Phase I study in healthy subjects with the immunoregulating drug candidate KAND567 (Press release, Kancera, FEB 20, 2018, View Source;releaseID=1434356 [SID1234524054]). The study shows that KAND567 is safe and well-tolerated up to 500 mg twice daily for 7 days. The plasma levels achieved with KAND567 at that dose are five to ten times higher than the calculated effective level for therapeutic effect in humans. Upon further increase of the dose, a reversible increase in markers for liver effects was noted. The results also showed that KAND567 blocks the Fractalkine system by reducing the number of Fractalkine receptors on the surface of immune cells. Furthermore, results are reported from three preclinical disease models showing cardiovascular protection properties of KAND567. The company is now evaluating the conditions for continued clinical development of KAND567 against cancer and inflammatory cardiovascular injuries, e.g. in connection with infarction.

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Design
The study was a randomized, double-blind, placebo-controlled Phase I study in healthy subjects aimed at studying safety, tolerability and pharmacokinetic properties (uptake, plasma concentrations and excretion) of KAND567. In a first part of the study, KAND567 was given in increasing single doses (8 – 2500 mg) to groups of healthy subjects where a group received KAND567 with and without food on different occasions. In the second part of the study, KAND567 was given in increasing doses up to 7 days (300 – 800 mg twice a day). In total, 82 subjects have been included in the study, 62 of which received active substance and 20 placebo.

Results
Results from the single dose part of the study showed that KAND567 was safe and tolerable in single doses up to 2500 mg as no clinically relevant side effects were noted. The results also show that KAND567 is absorbed efficiently from the intestine to the blood independent of food, and that KAND567 stays in the blood long enough in humans to allow dosage one to two times a day.

In the multiple dose part of the study, KAND567 proved safe and well-tolerated at doses up to 500 mg twice a day (total 1000 mg) for 7 days. This dose is five to ten times higher than the calculated effective dose in humans. Dose-limiting side effects at 800 mg twice a day (total 1600 mg) included gastric side effects in the form of diarrhea and a clinically relevant increase in markers for hepatic impairment, which returned to normal level after the end of treatment. No other clinically relevant side effects of KAND567 were noted.

In the multiple dose part of the study, the effect of KAND567 on the Fractalkine system in the immune cells of the blood was also studied. After 7 days of treatment with KAND567 (300 mg, twice daily), the number of Fractalkine receptors on the cell surface significantly decreased in specific immune cells such as NK cells, T cells and monocytes. These findings, along with in vitro findings showing that KAND567 in whole blood blocks the Fractalkine signal in human immune cells at low concentrations, show that KAND567 blocks the Fractalkine system through two co-operating mechanisms.

"It is encouraging that the results of the Phase I study show that KAND567 blocks the Fractalkine system as hoped and the drug candidate is well tolerated in doses up to levels that are five to ten times above the calculated effective dose," says Thomas Olin, CEO Kancera.

"We will now continue to deepen our understanding of how KAND567 affects the liver in relation to the desired pharmacological effects to develop a clinical development plan for both chronic and acute treatment of inflammatory diseases and cancer, eg lymphoma. There is support for the benefits of short-term treatment with KAND567 against, for example, myocardial infarction, giving the project additional opportunities because of the good safety margin we have seen in short term treatment, "says Thomas Olin.

Strategy for continued evaluation and development of KAND567
In parallel with in-depth studies of efficacy and safety for KAND567, Kancera AB has started preparations for a possible clinical development program to study the effect of KAND567 in the treatment of lymphoma (blood cancer) and cardiovascular disease. This focus has the potential to result in two products; a tablet for oral longer-term treatment of lymphoma and a product for short term treatment following myocardial infarction.

The focus on lymphoma and inflammation of the heart vessels is based on the following results.

Lymphoma (a form of blood cancer)

In 2017, results were published that support the correlation of the Fractalkine system in immune cells with an aggressive disease in lymphoma and suggest that a blockade of the Fractalkine system could inhibit the disease (1). In view of these results, as well as Kancera AB’s results from the clinical Phase I study, which show that KAND567 affects the identified immune cells, Kancera AB has initiated a collaboration with Karolinska Institutet. The collaboration aims to prepare for a clinical study by evaluating biomarkers for the Fractalkine system in blood and cancer tissue and the effect of KAND567 on these biomarkers (in isolated blood from the patients), which may provide information on which patients could benefit clinically from treatment with KAND567.

Inflammation of the blood vessels, for example in myocardial infarction

In three preclinical animal models, KAND567 has shown cardiovascular protective anti-inflammatory properties by significantly reducing infarct size (internal report), stabilizing vascular plaque (internal report) that can cause infarction and reversing relapse (restenosis) after widening of the coronary artery with so-called vessel stents (2). These studies were carried out when the project was owned by AstraZeneca. Publications of independent research groups also support blocking of the Fractalkine system to protect the heart in the context of myocardial infarction (in animal models) (3) and that the Fractalkine system is an independent risk marker and driving factor behind the inflammation of the blood vessels and the heart muscle after a heart attack in humans (4). Together, these results provide support for KAND567 as a drug candidate for the treatment of vascular disease. The results also provide information on appropriate biomarkers for the identification of patients who could benefit from such treatment.

Oncotarget. 2017 Nov 3; 8(54): 92289–92299
Biomaterials. 2015 Nov;69:22-9
Exp Physiol. 100.7. 2015: 805–817
J Clin Invest. 2015 Aug 3; 125(8): 3063–3076
About the Fractalkine project
KAND567 is an orally available small molecule that blocks CX3CR1, the Fractalkine receptor. Fractalkine is an immunomodulating factor, known as a chemokine, which transmits signals via the CX3CR1 receptor, thereby controlling the function of immune cells and cancer cells. The amount of Fractalkine and its receptor CX3CR1 has been shown to be elevated in several cancers, inflammatory diseases and in heart disease.

Kancera AB’s drug candidate KAND567 is the most advanced small molecule drug candidate against CX3CR1 and has been shown to be effective against inflammation, pain and cardiovascular disease in several preclinical disease models.

On February 20, 2018 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported that the Company’s scientists, and collaborators from the Mount Sinai School of Medicine, will present two abstracts at the American Chemical Society National Meeting & Expo (Press release, Onconova, FEB 20, 2018, View Source [SID1234524076]). The meeting is being held in New Orleans, LA, on March 18-22, 2018.

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The first abstract relates to the analysis of stability of the clinical product during storage and describes the synthesis and characterization of a de-sulfonylated product of rigosertib, Onconova’s lead phase 3 stage clinical candidate. The second abstract describes a new chemical entity ON 150030, which is a type 1 novel pre-clinical stage inhibitor of FLT3 and Src pathways, believed to be important for targeted therapy of relapsed and refractory AML.

Details for the poster presentations are listed below.

Title: Synthesis and characterization of de-sulfonylated product of rigosertib, a late phase III clinical candidate

Date: 18th March, 2018

Presentation Time: 7.00-9.00 PM CDT

Presenter: Dr. M.V. Ramana Reddy & Dr. Muralidhar Mallireddigari

Location: Ernest N. Morial Convention Center, Hall E.

Title: Discovery of a novel kinase inhibitor ON 150030, a type 1 inhibitor for relapsed and refractory AML

Date: 18th March, 2018

Presentation Time: 7.00-9.00 PM CDT

Presenter: Dr. M.V. Ramana Reddy

Location: Ernest N. Morial Convention Center, Hall E.

On February 20, 2018 Myriad Genetics, Inc. (NASDAQ:MYGN) reported that the National Comprehensive Cancer Network (NCCN) has updated its medical guidelines for prostate cancer treatment to broadly include biomarker testing in prostate cancer (Press release, Myriad Genetics, FEB 20, 2018, View Source [SID1234524056]). The changes to the guidelines include new language supporting Prolaris as standard of care in treatment decision making for patients with low and favorable-intermediate risk prostate cancer. Additionally, the new guidelines support an expansion of hereditary cancer testing for prostate cancer to include all patients with a family history regardless of Gleason score along with all patients with metastatic disease, and new recommendations supporting testing for homologous recombination deficiency (HRD) in patients with metastatic prostate cancer.

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"We view this significant update in guidelines as a clear indication of the increasing importance of molecular biomarkers in guiding prostate cancer care and Myriad is uniquely positioned with its broad portfolio of tests to address these clinical needs," said Nicole Lambert, general manager, Urology. "These new guidelines are critical in our efforts to broaden insurance coverage and increase patient access to Myriad’s entire portfolio of prostate cancer molecular diagnostic tests."

Below are the key updates from the guidelines:

Prolaris: now standard of care for 110,000 patients per year identified as low or favorable-intermediate risk patients.
myRisk Hereditary Cancer: now recommended for approximately 70,000 prostate cancer patients per year including all patients with metastatic prostate cancer and those with a family history of cancer regardless of Gleason score.
myChoice HRD: now recommended for 20,000 patients per year with metastatic prostate cancer to identify tumors with homologous recombination deficiency (HRD) so that these patients can be considered for targeted therapies.
About Prolaris
Prolaris is a novel 46-gene RNA-expression test that directly measures tumor cell growth characteristics for stratifying the risk of disease progression in patients with prostate cancer. Prolaris provides a quantitative measure of the RNA expression levels of genes involved in the progression of tumor growth. Low gene expression is associated with a low risk of disease progression in men who may be candidates for active surveillance and high gene expression is associated with a higher risk of disease progression in patients who may benefit from additional therapy. For more information visit: www.prolaris.com.

About Myriad myRisk Hereditary Cancer
The Myriad myRisk Hereditary Cancer test uses an extensive number of sophisticated technologies and proprietary algorithms to evaluate 28 clinically significant genes associated with the development of eight hereditary cancers including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma. The myRisk Hereditary Cancer test offers physicians several distinct advantages over other commercial tests, including unsurpassed lab accuracy, industry leading variant classification, a medical management tool and exceptional customer service.

Men with prostate cancer can take the Hereditary Cancer Quiz to find out if they might be at risk for an inherited mutation and therefore eligible for myRisk Hereditary Cancer test.

About myChoice HRD
Myriad’s myChoice HRD is the most comprehensive homologous recombination deficiency test, enabling physicians to identify tumors that have lost the ability to repair double-stranded DNA breaks, resulting in increased susceptibility to DNA-damaging drugs such as platinum drugs or PARP inhibitors. The myChoice HRD test is a composite of three proprietary technologies (loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions).

Positive myChoice HRD scores, reflective of DNA repair deficiencies, are prevalent in all breast cancer subtypes, ovarian cancer and most other major cancers. It is estimated that 1.4 million people in the United States and Europe who are diagnosed with cancers annually may be candidates for treatment with DNA-damaging agents. Learn more: View Source

On February 20, 2018 Fate Therapeutics, Inc. (NASDAQ:FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, announced today that the first subject has been treated in the DIMENSION study of FATE-NK100 for the treatment of advanced solid tumors (Press release, Fate Therapeutics, FEB 20, 2018, View Source [SID1234524182]). The clinical trial is intended to evaluate the safety and determine the maximum dose of FATE-NK100, the Company’s first-in-class, allogeneic donor-derived adaptive memory natural killer (NK) cell cancer therapy, when administered as a monotherapy and in combination with trastuzumab or cetuximab, two FDA-approved targeted monoclonal antibody therapies that are widely used today to treat various cancers.

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"Patients with cancer often have deficient or dysfunctional natural killer cells. The co-administration of FATE-NK100 alongside a targeted monoclonal antibody therapy is a novel approach to restore a patient’s immune cell function and to selectively recognize and kill antibody-coated tumor cells," said Manish R. Patel, D.O., Assistant Professor of Medicine, Division of Hematology, Oncology and Transplantation at the University of Minnesota and the lead investigator of the clinical trial at the Masonic Cancer Center. "We are excited to have initiated what we believe to be the first clinical investigation of healthy allogeneic donor NK cell therapy in combination with FDA-approved monoclonal antibody therapy for solid tumor malignancies. This new treatment paradigm holds great promise for cancer patients who have progressed on or failed monoclonal antibody therapy and have no other therapeutic options."

Monoclonal antibodies are a well-established class of cancer immunotherapy agents designed to selectively target and bind to proteins on the surface of tumor cells. Compelling clinical data indicate that NK cells mediate the therapeutic effect of monoclonal antibody therapy by recognizing and efficiently killing antibody-coated tumor cells via a potent immune response mechanism known as antibody-dependent cellular cytotoxicity (ADCC). The combination of FATE-NK100 and monoclonal antibody therapy is designed to enhance ADCC by administering an activated population of healthy allogeneic donor NK cells to augment the killing of antibody-coated tumor cells. It is estimated that the worldwide market for cancer monoclonal antibodies is over $30 billion, and is poised to reach $45 billion by the end of 2020.

DIMENSION is the third clinical trial of FATE-NK100 currently being conducted. FATE-NK100 is also being clinically investigated in the VOYAGE study for the treatment of refractory or relapsed acute myelogenous leukemia and in the APOLLO study for the treatment of ovarian cancer resistant to, or recurrent on, platinum-based treatment.

About DIMENSION
DIMENSION is a multi-center, open-label, accelerated dose-escalation Phase 1 clinical trial of FATE-NK100 in subjects with advanced solid tumors who have progressed on or failed available approved therapies. The clinical trial is designed to evaluate the safety and determine the maximum dose of a single intravenous infusion of FATE-NK100 when administered as a monotherapy and in combination with monoclonal antibody therapy after outpatient lymphoconditioning therapy followed by sub-cutaneous IL-2 administration. Other endpoints to be assessed include objective response rates and progression-free and overall survival.

The clinical trial is being conducted across three independent treatment arms: (i) as a monotherapy for advanced solid tumor malignancies, including small cell lung cancer and hepatocellular carcinoma; (ii) in combination with trastuzumab for advanced human epidermal growth factor receptor 2 positive (HER2+) cancers, including breast and gastric cancers; and (iii) in combination with cetuximab for advanced epidermal growth factor receptor 1 positive (EGFR1+) cancers, including colorectal and head and neck cancers. In the combination arms, subjects will receive the monoclonal antibody therapy two days prior to and seven days following administration of FATE-NK100. Subjects with evidence of tumor shrinkage at Day 29 following administration of FATE-NK100 may be considered for retreatment.

Up to three dose levels in the monotherapy arm, and up to four dose levels in the monoclonal antibody therapy arms, of FATE-NK100 are intended to be assessed. In the event a dose limiting toxicity is observed in an arm, the arm will convert to a 3+3 design. Following dose escalation, expansion cohorts of 20 subjects per arm may be enrolled.

About FATE-NK100
FATE-NK100 is a first-in-class, allogeneic donor-derived natural killer (NK) cell cancer immunotherapy comprised of adaptive memory NK cells, a highly specialized and functionally distinct subset of activated NK cells expressing the maturation marker CD57. Higher frequencies of CD57+ NK cells in the peripheral blood or tumor microenvironment in cancer patients have been linked to better clinical outcomes. In preclinical studies, FATE-NK100 has demonstrated enhanced anti-tumor activity across a broad range of hematologic and solid tumors, with augmented cytokine production, improved persistence, enhanced antibody-dependent cellular cytotoxicity and increased resistance to immune checkpoint pathways compared to other NK cell therapies that are being clinically administered today. FATE-NK100 is produced through a feeder-free, seven-day manufacturing process during which NK cells sourced from a healthy allogeneic donor are activated ex vivo with pharmacologic modulators. In August 2017, non-clinical data describing the unique properties and anti-tumor activity of FATE-NK100 were published by Cancer Research (doi:10.1158/0008-5472.CAN-17-0799), a peer-reviewed journal of the American Association of Cancer Research.