On September 7, 2016 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, reported that clinical data for its lead drug candidate CB-839, the company’s novel, orally bioavailable glutaminase inhibitor, will be presented at the 28th Annual EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics, which is being held from November 29 to December 2, 2016 in Munich, Germany (Press release, Calithera Biosciences, SEP 7, 2016, View Source;p=RssLanding&cat=news&id=2200049 [SID:1234514965]). Clinical results to be presented in a plenary session will be focused on data from Calithera’s CB-839 Phase I combination trial with everolimus in renal cell carcinoma.

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Phase 1 Study of CB-839, a small molecule inhibitor of glutaminase, in combination with everolimus in patients with clear cell and papillary renal cell carcinoma
Presenter: Funda Meric-Bernstam, M.D. Anderson Cancer Center
Plenary Session 2, Proffered Paper Session, Room 14
Wednesday, November 30, 2016, 4:30 p.m. CET
Two additional posters will be presented with preclinical results from CB-839 and the company’s novel metabolic immune checkpoint inhibitor CB-1158, respectively.

CB-839, a selective glutaminase inhibitor, has anti-tumor activity in renal cell carcinoma and synergizes with everolimus and receptor tyrosine kinase inhibitors
Presenter: Ethan Emberley, Calithera Biosciences
Poster Session: Molecular Targeted Agents II, Board P055
Thursday, December 1, 2016, 10:15 a.m.-5:00 p.m. CET
Arginase inhibitor CB-1158 elicits immune-mediated anti-tumor responses as a single agent and enhances the efficacy of other immunotherapies
Presenter: Suzanne Steggerda, Calithera Biosciences
Poster Session: Immunotherapy, Board P121
Wednesday, November 30, 2016, 10:15 a.m.-5:00 CET

On September 7, 2016 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors express PD-L1, with a PDUFA, or target action, date of Dec. 24, 2016 (Press release, Merck & Co, SEP 7, 2016, View Source [SID:1234514983]). Additionally, the FDA granted Breakthrough Therapy Designation for this indication. Merck has also submitted a Marketing Authorization Application to the European Medicines Agency for this indication.

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The submissions were based on data from the pivotal phase 3 KEYNOTE-024 study, which showed that KEYTRUDA monotherapy resulted in superior progression-free survival (PFS) as well as overall survival (OS) compared with standard chemotherapy in patients with advanced NSCLC whose tumors expressed high levels of PD-L1 (tumor proportion score of 50 percent or more). Based on the results, the trial was stopped early to give patients still on chemotherapy the opportunity to receive KEYTRUDA. Merck filed for approval of KEYTRUDA in the first-line setting at a dose of 200 mg every three weeks, the dose studied in KEYNOTE-024.

"Chemotherapy has been the foundation of first-line treatment for non-small cell lung cancer for decades, so the significant improvement in survival in patients with high PD-L1 expression seen with KEYTRUDA compared to chemotherapy is welcome news," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. "We appreciate the opportunity to work with regulatory authorities to make KEYTRUDA a first-line treatment option in non-small cell lung cancer."

The FDA’s Breakthrough Therapy Designation is intended to expedite the availability of promising new therapies that are planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates substantial improvement over existing therapies on one or more clinically significant endpoints. Merck previously announced that KEYTRUDA (pembrolizumab) was granted breakthrough status for specific patients with advanced melanoma, metastatic NSCLC in previously treated patients, microsatellite instability high metastatic colorectal cancer, and relapsed or refractory classical Hodgkin Lymphoma.

About KEYTRUDA (pembrolizumab)

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.

KEYTRUDA Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks.

Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test with disease progression on or after platinum-containing chemotherapy, at a dose of 2 mg/kg every three weeks. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA (pembrolizumab). This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. An sBLA is currently under review with the FDA for full approval of the existing second-line NSCLC indication. The application is based on data from KEYNOTE-010, a pivotal phase 2/3 confirmatory trial which demonstrated improved survival with KEYTRUDA compared to standard chemotherapy in previously treated patients with advanced NSCLC who had PD-L1 expression on one percent or more of the cancer cells. The FDA target action date is Oct. 24, 2016.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy at a fixed dose of 200 mg every three weeks. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

Immune-mediated pneumonitis occurred in 19 (3.5%) of 550 patients, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis and occurred more frequently in patients with a history of asthma/chronic obstructive pulmonary disease (5.4%) or prior thoracic radiation (6.0%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-mediated colitis occurred in 4 (0.7%) of 550 patients, including Grade 2 (0.2%) or 3 (0.4%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-mediated hepatitis occurred in patients receiving KEYTRUDA. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hypophysitis occurred in 1 (0.2%) of 550 patients, which was Grade 3 in severity. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA (pembrolizumab) for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

Hyperthyroidism occurred in 10 (1.8%) of 550 patients, including Grade 2 (0.7%) or 3 (0.3%) hyperthyroidism. Hypothyroidism occurred in 38 (6.9%) of 550 patients, including Grade 2 (5.5%) or 3 (0.2%) hypothyroidism. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 3 (0.1%) of 2117 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer anti-hyperglycemics in patients with severe hyperglycemia.

Immune-mediated nephritis occurred in patients receiving KEYTRUDA. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

Other clinically important immune-mediated adverse reactions can occur. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of 550 patients: rash, vasculitis, hemolytic anemia, serum sickness, and myasthenia gravis.

Severe and life-threatening infusion-related reactions have been reported in 3 (0.1%) of 2117 patients. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA (pembrolizumab).

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 14% of 550 patients. Serious adverse reactions occurred in 38% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pleural effusion, pneumonia, dyspnea, pulmonary embolism and pneumonitis. The most common adverse reactions (reported in at least 20% of patients) were fatigue (44%), cough (29%), decreased appetite (25%), and dyspnea (23%).

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck Oncology, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes more than 330 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

On September 7, 2016 Laboratory Corporation of America Holdings (LabCorp) (NYSE: LH) reported the successful completion of the offering period for the cash tender offer by its direct wholly owned subsidiary, Savoy Acquisition Corp. (Purchaser), for all outstanding shares of common stock of Sequenom, Inc. (NASDAQ: SQNM) (Sequenom), including the associated preferred stock purchase rights (together with the common stock, the Shares) (Press release, LabCorp, SEP 7, 2016, View Source;p=RssLanding&cat=news&id=2200115 [SID:1234514984]). The depositary for the tender offer has advised LabCorp that, as of 12:01 a.m., Eastern time, on September 7, 2016, the expiration of the offering period, stockholders of Sequenom had validly tendered 82,901,857 Shares (including Shares tendered through notices of guaranteed delivery) during the offering period, representing an aggregate of approximately 69% of Sequenom’s outstanding shares of common stock as of such time (or approximately 67% of outstanding shares excluding notices of guaranteed delivery), which Shares are sufficient to have met the minimum condition of the offer and to enable the Merger (as defined below) to occur under Delaware law without a vote of Sequenom’s stockholders. Purchaser has accepted for payment all Shares validly tendered and not properly withdrawn during the offering period, and the consideration for all such Shares either has been paid or will be paid promptly. The acceptance of the Shares effective as of September 7, 2016 constitutes a "Fundamental Change" and a "Make-Whole Fundamental Change" under the indentures related to Sequenom’s 5.00% convertible senior notes due 2017 and the Sequenom’s 5.00% convertible exchange senior notes due 2018.

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"With the addition of Sequenom, LabCorp is a market leader for non-invasive prenatal testing, women’s health and reproductive genetics," said David P. King, chairman and chief executive officer of LabCorp. "This strategic acquisition also expands our reach both domestically and internationally and furthers our mission to improve health and improve lives around the globe."

LabCorp also announced that, following the completion of the offering period, Purchaser was merged with and into Sequenom (the Merger) without a vote of the stockholders of Sequenom, as permitted by the Delaware General Corporation Law. In the Merger, each Share not tendered and accepted for payment in the offer, other than those Shares with respect to which the holders properly exercise appraisal rights and Shares held by LabCorp or Purchaser, has been converted into the right to receive $2.40 net to the seller in cash, without interest thereon and subject to applicable withholding taxes. As a result of the Merger, Sequenom became a direct wholly owned subsidiary of LabCorp and Sequenom’s shares will cease to be traded on the NASDAQ Global Select Market.

On September 7, 2016 Sutro Biopharma reported that it has received two milestone payments from drug discovery and development partner Celgene Corporation (Celgene) for achievements in preclinical development and manufacturing under the company’s 2014 immuno-oncology collaboration with Celgene (Press release, Sutro Biopharma, SEP 7, 2016, View Source [SID1234516952]). Financial terms of the milestones are not being disclosed.

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These payments support acceleration of Sutro’s pipeline from the late-stage preclinical phase into clinical development, as well as expansion of the company’s cell-free manufacturing capability. The payments fall under a September 2014 collaboration agreement in which Celgene paid Sutro $95 million, including an equity investment, and agreed to pay up to an additional $75 million for research and manufacturing milestones during an initial research phase.

"These milestone payments recognize the significant advances we have made toward developing and manufacturing best-in-class, multispecific antibodies and antibody drug conjugates (ADCs) using our proprietary platform," said Sutro’s CEO, Bill Newell.

Expanded Manufacturing capabilities have the potential to accelerate clinical development
Unlike conventional cell-based expression systems, Sutro’s technology isolates a cell’s protein production machinery into a cell-free extract, Xtract CF, that includes all the necessary biochemical components for energy production, transcription and translation. Xtract CF and Xtract CF+ are used in the Xpress CF and Xpress CF+ platforms to support cell-free biochemical protein synthesis by the addition of the specific DNA sequence for the desired protein. This process is capable of producing single proteins at gram per liter yields in eight to ten hours at large scale, unconstrained by cellular structures and their limitations.

Sutro’s GMP-compliant manufacturing facility in San Carlos, California, is built to maximize the speed and efficiency of cell-free extract and protein production. The Xtract CF and Xtract CF+ processes enable manufacture of cell-free extract through a continuous multi-day process, which in turn can drive the Xpress CF and Xpress CF+ reactions at scale. At full production capacity, the San Carlos manufacturing facility will be able to produce sufficient quantities of protein to support the early clinical development pipeline for Sutro and its collaboration partners.

The Sutro-Celgene three-year collaboration focuses on the discovery and development of multispecific antibodies and ADCs aimed at immuno-oncology therapeutics. Celgene has an option to extend the collaboration beyond the initial research term in exchange for an additional payment. Sutro is also eligible to receive additional clinical development and regulatory approval milestones for each compound selected by Celgene under the collaboration, as well as tiered royalties based on annual net sales of licensed products. Beginning in September 2016 through the end of the collaboration (as extended), Celgene will have the exclusive option to acquire Sutro based on a pre-specified valuation procedure, including rights to all Sutro-owned programs at that time.

On September 7, 2016 Exosome Diagnostics, Inc. reported the launch of its ExoDxProstate(IntelliScore) test (EPI) through the company’s CLIA certified laboratory in Cambridge, Massachusetts. EPI is a laboratory-developed test designed to provide clinicians and patients with information that will improve the prostate biopsy decision-making process. EPI is the first test using specific genetic information captured from a simple urine sample to provide physicians with a score to help evaluate their patient’s risk for high grade, potentially more aggressive prostate cancer.

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In the United States each year, approximately one million prostate biopsies are performed with up to 80 percent of the results indicating no cancer, or a low-grade cancer that could instead be monitored under a watchful waiting or active surveillance program. The EPI test was designed to reduce the number of unnecessary prostate biopsies and the associated overtreatment of low-grade disease. Complications associated with unnecessary prostate tissue biopsies range from discomfort and temporary incontinence or impotence, to hospitalization for serious infections in three to four percent of patients.

"Prostate cancer is really a spectrum of disease. Not all patients have the same type of tumor or the same grade of disease," stated Peter Carroll M.D., chair of urology at the University of California, San Francisco and an investigator in the EPI clinical validation trial. "Very few men need immediate treatment. Repeat PSA testing, PSA/protein based diagnostic tests, MRI scans and now molecular genetic testing with EPI will provide important data to help clinicians, patients and their families make better informed decisions about whether to proceed with an initial prostate biopsy. This test launch marks an important step forward in efforts to develop more sensitive markers for assessing the risk of aggressive prostate cancer and the ability to monitor disease progression in a completely non-invasive approach."

The scientists and clinicians at Exosome Diagnostics developed this innovative test with input from the Prostate Cancer Foundation, urologists, patients and insurance providers. The EPI test uses a simple urine catch without a digital rectal exam, making it completely non-invasive for the patient and easy to integrate into patient care. The EPI test utilizes a three-gene signature, in combination with a proprietary algorithm. The score generated is simple for physicians to understand and discuss with their patients. The EPI test is unique from other tests in this space because it is a stand-alone diagnostic, as it does not take into account other standard of care parameters in the score thus making it a powerful complement to the existing PSA test.

A final clinical evaluation study enrolled over 1,500 patients through collaborations with 26 leading urology centers across the United States. Results from the study demonstrated that the EPI test was highly accurate for ruling out the presence of high-grade cancer (Gleason score seven or higher) prior to an initial prostate biopsy. The data from this blinded, prospective U.S. clinical validation study were published in JAMA Oncology in March 2016.

"Molecular and genetic testing are improving the quality of cancer care and patient outcomes. We are excited to provide this first-of-its-kind test to men at risk for prostate cancer," said Tom McLain, Chief Operating Officer of Exosome Diagnostics. "Using our patented technology to analyze the RNA released by prostate cancer cells, we provide a simple score to help evaluate the patient’s risk for high-grade prostate cancer. This will better inform clinicians and patients and help to clarify the decision process surrounding prostate biopsy."

EPI is one test in a portfolio of diagnostic and companion diagnostic tests being developed and launched by the company. "Today’s announcement provides another demonstration of the value of Exosome Diagnostics’ platform combining patented, leading isolation methodologies, ancillary technologies to increase the signal over the noise, tissue specific exosome identification methodologies, and proprietary algorithms to develop sensitive diagnostic assays and accelerate the development of companion diagnostics," said John Boyce, President and CEO of Exosome Diagnostics. "Our tests are unique in the liquid biopsy space. By combining the information about disease from exosomes and cell-free DNA captured from any biofluid sample, we are able to achieve the clinical and analytical performance needed for liquid biopsy tests to provide clinicians with real-time, patient specific information that can be used to improve care, select the right therapy, avoid unnecessary procedures and lower overall healthcare costs."

About the EPI Test
The EPI test is a completely non-invasive, urine-based test designed to be used along with clinical assessment and other standard of care factors (including age, race and family history) to enable physicians to assess whether an individual patient presenting for an initial biopsy is at greater risk for high-grade prostate cancer. As a "rule out" test, it is designed to more accurately predict whether a patient presenting for an initial biopsy does not have high-grade prostate cancer and, thus, could potentially avoid the discomfort, complications and cost of an initial biopsy and, instead, continue to be monitored. EPI, which is intended for use in men 50 years or older with a prostate-specific antigen (PSA) result of 2-10ng/mL presenting for an initial biopsy, involves patients submitting a simple urine sample, without having to first undergo a digital rectal exam (DRE).

The EPI test analyzes the urine for three biomarkers on exosomal RNA (exoRNA) that are expressed in men with high-grade prostate cancer. Using a proprietary algorithm that combines the relative weighted expression of the three-gene signature, the test assigns an individual risk score for patients ranging from zero to 100. Scores above a pre-defined cut point are associated with an increased likelihood of high-grade prostate cancer on a subsequent biopsy.

This test was evaluated and its performance characteristics determined by Exosome Diagnostics Inc. It has not been cleared or approved by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. Exosome Diagnostics is certified under the Clinical Laboratory Improvement Amendments (CLIA) act of 1988 as qualified to perform high complexity clinical testing.