On July 24, 2018 BioXcel Therapeutics, Inc. ("BTI") (Nasdaq: BTAI), is a clinical stage biopharmaceutical development company utilizing proprietary artificial intelligence approaches to identify the next wave of medicines across neuroscience and immuno-oncology, reported that dipeptidyl peptidase (DPP) 8/9 inhibition, the primary mechanism of action of its lead immuno-oncology candidate, BXCL701, was highlighted in an article in the July 2018 edition of the peer-reviewed journal Nature Medicine (Press release, BioXcel Therapeutics, JUL 24, 2018, View Source [SID1234527859]).

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BXCL701 is a potential first-in-class, highly potent oral small molecule immuno-modulator that has demonstrated single agent activity in melanoma, with an established safety profile from 700 healthy subjects and cancer patients. It is designed to stimulate both the innate and acquired immune systems by inhibiting DPP8/9 and blocking immune evasion by inhibiting Fibroblast Activation Protein (FAP).

The paper titled "DPP8/DPP9 inhibitor-induced pyroptosis for treatment of acute myeloid leukemia" by Darren C. Johnson, et al., concluded that activation of caspase recruitment domain-containing protein 8 (CARD8) acts as an inflammasome sensor to activate caspase-1 and mediates DPP8/9 inhibitor-induced cell death in myeloid cells(1). This therapeutic strategy serves as a potential pathway for direct cytotoxicity of acute myeloid leukemia (AML) cells and indirect response to solid tumors. Multiple prior studies have established DPP8/9 as a novel immune checkpoint that controls the activation of the innate immune system(2),(3)

"BXCL701 is novel in its ability to stimulate both the innate and acquired immune systems by inhibiting DPP8/9 and blocking immune evasion by inhibiting FAP," said Vimal Mehta, PhD, Chief Executive Officer of BTI. "This publication highlights one component of BXCL701’s dual mechanism of action, providing valuable insights on the effects of DPP8/9 inhibition. BXCL701 differentiates itself by activating the innate immune system and stimulating neutrophils, natural killer cells and effector T cells. The paper provides further mechanistic understanding of DPP8/9 inhibition and validates its importance as a promising therapeutic approach, not only for solid tumors but for hematologic malignancies as well."

BTI expects to initiate Phase 2 proof of concept studies evaluating BXCL701 in pancreatic cancer and tNEPC later this year. BTI is also evaluating BXCL701’s potential in additional indications, both as a monotherapy and in combination with other immuno-oncology agents and partnering strategies.

Vincent J. O’Neill, MD, Chief Medical Officer of BTI added, "BXCL701 has generated compelling preclinical data in pancreatic cancer and a variety of other tumor models. Particularly exciting is its ability to block immune evasion and aid in the formation of memory T-cells, which may support long-term immunity in certain types of cancer as presented by BTI at ASCO (Free ASCO Whitepaper) 2018(4)."

This study in AML led by Dr. Bachovchin’s team at the Memorial Sloan Kettering Cancer Center and the Weil Cornell Graduate School of Medical Sciences, demonstrates that the therapeutic potential of a DPP8/9 inhibitor such as BXCL701 can extend beyond solid tumors into hematologic malignancies.

Dr O’Neill concluded, "We look forward to further evaluating BXCL701 in our lead indications, and potentially expanding its application to other cancer types."

(1) Johnson, DC, et al. DPP8/DPP9 inhibitor-induced pyroptosis for treatment of acute myeloid leukemia." Nat Med (2018), PMID: 29967349; DOI:10.1038/s41591-018-0082-y

(2) Okondo, Marian C., et al. "DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis." Nat Chem Biol 13.1 (2017): 46-53. PMID: 27820798; DOI:10.1038/nchembio.2229

(3) Okondo, Marian C., et al. "Inhibition of Dpp8/9 activates the Nlrp1b inflammasome." Cell Chem Biol 25.3 (2018): 262-267. PMID: 29396289; DOI:10.1016/j.chembiol.2017.12.013

(4) Rastelli et al., Presented at ASCO (Free ASCO Whitepaper) 2018, Illinois, Abstract #3085

On July 24, 2018 Quest Diagnostics Incorporated (NYSE: DGX), the world’s leading provider of diagnostic information services, reported that financial results for the second quarter ended June 30, 2018 (Press release, Quest Diagnostics, JUL 24, 2018, View Source [SID1234527834]).

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"Once again, we grew revenues and delivered strong earnings growth in the second quarter," said Steve Rusckowski, Chairman, President and CEO. "We continue to strengthen our strategic relationship with UnitedHealth Group and are excited to serve as a national in-network lab provider for UnitedHealthcare members beginning January 1, 2019. Overall, we remain focused on delivering on our two-point strategy and have updated our outlook for the full-year 2018 to reflect our confidence in achieving our commitments for the year."

Net revenues and selling, general and administrative expenses for the three and six months ended June 30, 2017 have been restated to reflect the impact of new revenue recognition rules that became effective January 1, 2018 and were adopted on a retrospective basis. Under the new rules, the Company reports uncollectible balances associated with patient responsibility as a reduction in net revenues; historically these amounts were classified as bad debt expense within selling, general and administrative expenses.

For further details impacting the year-over-year comparisons related to operating income, operating income as a percentage of net revenues, net income attributable to Quest Diagnostics, and diluted EPS, see note 2 of the financial tables attached below.

The updated outlook for 4% to 4.5% revenue growth in 2018 represents management’s estimates for 2018 versus 2017 reported revenues adjusted to reflect the impact of new revenue recognition rules that became effective January 1, 2018. Full year 2017 revenues adjusted to reflect the new rules were $7,402 million. See note 5 of the financial tables attached below.

Note on Non-GAAP Financial Measures

As used in this press release the term "reported" refers to measures under the accounting principles generally accepted in the United States ("GAAP"). The term "adjusted" refers to non-GAAP measures as follows: (i) for the purpose of income measures the term "adjusted" refers to operating performance measures that exclude special items such as restructuring and integration charges, excess tax benefit ("ETB") associated with stock based compensation and other items; and (ii) the term "adjusted diluted EPS excluding amortization" represents the company’s diluted EPS before the impact of special items (described above) and amortization expense.

Non-GAAP adjusted measures are presented because management believes those measures are useful adjuncts to GAAP results. Non-GAAP adjusted measures should not be considered as an alternative to the corresponding measures determined under GAAP. Management may use these non-GAAP measures to evaluate our performance period over period and relative to competitors, to analyze the underlying trends in our business, to establish operational budgets and forecasts and for incentive compensation purposes. We believe that these non-GAAP measures are useful to investors and analysts to evaluate our performance period over period and relative to competitors, as well as to analyze the underlying trends in our business and to assess our performance. The additional tables attached below include reconciliations of adjusted measures to GAAP measures.

Conference Call Information

Quest Diagnostics will hold its quarterly conference call to discuss financial results beginning at 8:30 a.m. Eastern Time today. The conference call can be accessed in listen-only mode by dialing 773-756-0467, passcode 3214469. The company suggests participants dial in approximately 10 minutes before the call.

A replay of the call may be accessed online at www.QuestDiagnostics.com/investor or by phone at 866-483-9044 for domestic callers or 203-369-1586 for international callers. Telephone replays will be available from approximately 10:30 a.m. Eastern Time on July 24, 2018 until midnight Eastern Time on August 7, 2018. Anyone listening to the call is encouraged to read the company’s periodic reports, on file with the Securities and Exchange Commission, including the discussion of risk factors and historical results of operations and financial condition in those reports.

On July 24, 2018 Amgen (NASDAQ:AMGN) reported that it will report its second quarter 2018 financial results on Thursday, July 26, 2018, after the close of the U.S. financial markets (Press release, Amgen, JUL 24, 2018, View Source;p=RssLanding&cat=news&id=2359722 [SID1234527838]). The announcement will be followed by a conference call with the investment community at 2:00 p.m. PT. Participating in the call from Amgen will be Robert A. Bradway, chairman and chief executive officer, and other members of Amgen’s senior management team.

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Live audio of the conference call will be simultaneously broadcast over the internet and will be available to members of the news media, investors and the general public.

The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

On July 24, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that the first patient was dosed in a Phase 3 clinical trial of tislelizumab, an investigational anti-PD-1 antibody, combined with chemotherapy, as a potential first-line treatment in Chinese patients with Stage IIIB or IV non-squamous non-small cell lung cancer (NSCLC) (Press release, BeiGene, JUL 24, 2018, View Source;p=RssLanding&cat=news&id=2359778 [SID1234527839]). Tislelizumab is also being studied in global Phase 3 trials in solid tumors, including second-line non-small cell lung cancer, first-line hepatocellular carcinoma, and second-line esophageal squamous cell carcinoma; two global Phase 2 trials in previously treated advanced hepatocellular carcinoma and relapsed/refractory mature T- and natural killer-cell lymphomas; and two pivotal Phase 2 trials in China in relapsed/refractory classical Hodgkin’s lymphoma and second-line urothelial cancer.

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"We are pleased to be enrolling patients in this important trial evaluating the potential impact of adding tislelizumab, an investigational immuno-oncology therapy, to platinum plus pemetrexed chemotherapy, the current global standard of care in first-line treatment of patients with advanced stage non-squamous NSCLC," commented Amy Peterson, M.D., Chief Medical Officer for Immuno-Oncology at BeiGene.

"As shown by the most recent data from other checkpoint inhibitors, combining immunotherapy and chemotherapy can improve anti-tumor activity and significantly improve outcomes for patients. Our Phase 3 study will assess whether the addition of tislelizumab to standard-of-care chemotherapy will improve outcomes in Chinese patients with advanced lung cancer, a disease known for its poor prognoses even with chemotherapy treatment," commented Lai Wang, Ph.D., Senior Vice President and Head of China Development at BeiGene.

The Phase 3, open-label, multi-center trial is expected to enroll approximately 320 chemotherapy naïve patients who have Stage IIIB or IV non-squamous NSCLC in mainland China. The trial is designed to compare progression-free survival (PFS) as assessed by the Independent Review Committee (IRC) per RECIST v1.1. Key secondary endpoints include overall survival, overall response rate, PFS by investigator, and safety and tolerability.

"We look forward to building upon our clinical experience with tislelizumab to date by testing the efficacy and safety of this investigational agent in an area of great unmet need, where patients currently have poor outcomes. We are hopeful that patients with Stage IIIB/IV NSCLC will see benefit through enrollment in this trial," said Prof. Shun Lu, M.D, Director of Shanghai Lung Cancer Center, Shanghai Chest Hospital of Shanghai Jiao Tong University, and the Principal Investigator of this pivotal study.

For more information about the trial, patients and physicians should email BeiGene at [email protected].

About Non-Small Cell Lung Cancer
In China, there were an estimated 733,300 new cases of lung cancer in 2015.1 Lung cancer is the leading cause of cancer-related death in both men and women, with an estimated 610,200 deaths in China in 2015.1 According to the
American Cancer Society, about 80 to 85 percent of lung cancers are non-small cell lung cancer (NSCLC) and there are three main subtypes: adenocarcinoma, squamous cell (epidermoid) carcinoma and large cell (undifferentiated). For patients with advanced NSCLC, five-year survival rates are approximately 26 percent for Stage IIIB, 10 percent for Stage IVA, and 1 percent for Stage IVB.2

About Tislelizumab
Tislelizumab (BGB-A317) is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. Discovered by BeiGene scientists in Beijing, tislelizumab is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. Tislelizumab has demonstrated high affinity and specificity for PD-1. It is potentially differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells, based on preclinical data. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumor cancers outside of Asia (except Japan).

On July 23, 2018 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) has initiated a Phase Ib/II proof-of-concept study of sulfatinib in pancreatic neuroendocrine tumors ("NET") patients and in biliary tract cancer ("BTC") patients in the U.S.. Sulfatinib is an oral small molecule angio-immuno kinase inhibitor that can simultaneously block tumor angiogenesis and immune evasion (Press release, Hutchison China MediTech, JUL 23, 2018, https://www.chi-med.com/sulfatinib-poc-pnet-btc-us/ [SID1234528657]). This study follows several trials that are underway in China, including two Phase III studies in pancreatic and non-pancreatic NET that commenced after positive results from a Phase II study, and a Phase II study in BTC patients. In addition, a Phase I dose escalation part of this study in the U.S. was recently completed.

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This proof-of-concept study is a multi-center, single-arm, open-label study to evaluate the efficacy and safety of sulfatinib as a monotherapy in (a) patients with advanced BTC that have progressed on standard first-line chemotherapy, and (b) in patients with advanced pancreatic NET. The primary and secondary endpoints include progression-free survival ("PFS") rate, objective response rate ("ORR"), disease control rate ("DCR"), duration of response ("DoR"), time to response, overall survival ("OS"), safety and tolerability. Additional details of the study may be found at clinicaltrials.gov, using identifier NCT02549937.

About Sulfatinib
Sulfatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptor ("VEGFR"), fibroblast growth factor receptor ("FGFR") and colony stimulating factor-1 receptor ("CSF-1R"), three key tyrosine kinase receptors involved in tumor angiogenesis and immune evasion. Inhibition of the VEGFR signaling pathway can act to stop angiogenesis, the growth of the vasculature around the tumor, and thereby starve the tumor of the nutrients and oxygen it needs to grow rapidly. Aberrant activation of the FGFR signaling pathway, which can be increased by anti-VEGFR therapy treatment, is shown to be associated with cancer progression by promoting tumor growth, angiogenesis and formation of the myeloid derived suppressor cells. Inhibition of the CSF-1R signaling pathway blocks the activation of tumor-associated macrophages, which are involved in suppressing immune responses against tumors. Its unique angio-immuno kinase profile supports sulfatinib as a potentially attractive candidate for exploration of possible combinations with checkpoint inhibitors against various cancers.

Sulfatinib is the first oncology candidate that we have taken through proof-of-concept in China and subsequently started clinical development in the U.S. We are currently conducting studies in six target patient populations on sulfatinib and retain all rights to sulfatinib worldwide.

About Sulfatinib Development in China
Sulfatinib is currently in development as a single agent for patients with NET, thyroid cancer and BTC in China.

Pancreatic NET: In March 2016, we initiated the SANET-p study, which is a randomized, double-blind, placebo-controlled, multi-center, Phase III pivotal registration trial to treat about 190 patients with low- or intermediate-grade, advanced pancreatic NET in China. The primary endpoint is PFS, with secondary endpoints including ORR, DCR, DoR, time to response, OS, safety and tolerability. Additional details of the SANET-p study may be found at clinicaltrials.gov, using identifier NCT02589821. We expect to complete enrollment in 2019 and present top-line results thereafter.

Extra-pancreatic NET: The SANET-ep study, which was initiated in December 2015, is similar to the SANET-p study and is targeted at treating about 270 patients with advanced extra-pancreatic NET in China. Additional details of the SANET-ep study may be found at clinicaltrials.gov, using identifier NCT02588170. We expect to complete enrollment in 2019 and present top-line results thereafter.

Thyroid cancer: In March 2016, we initiated Phase II in two target patient populations in China to evaluate the efficacy and safety of sulfatinib in patients with advanced medullary thyroid cancer and iodine-refractory differentiated thyroid cancer. Additional details of this study may be found at clinicaltrials.gov, using identifier NCT02614495.

BTC: In January 2017, we began a Phase II study in patients with BTC (also known as cholangiocarcinoma), a heterogeneous group of rare malignancies arising from the biliary tract epithelia. Gemzar is the currently approved first-line therapy for biliary tract cancer patients, with a total of approximately 18,000 new patients per year in the U.S. according to the National Cancer Institute, but median survival is less than 12 months for patients with unresectable or metastatic disease at diagnosis. As a result, we see a major unmet medical need for patients who have progressed when being treated with Gemzar, and sulfatinib may offer a new targeted treatment option in this tumor type. Additional details of this study may be found at clinicaltrials.gov, using identifier NCT02966821.