On October 5, 2018 Generex Biotechnology Corporation (www.generex.com) (OTCQB:GNBT) (View Source) reported that the Company, in conjunction with its research collaborators Merck and the NSABP Foundation, will file an IND in October to initiate A Phase II Clinical Trial of Pembrolizumab (Keytruda) in Combination with the AE37 Peptide Vaccine in Patients with Metastatic Triple Negative Breast Cancer (Press release, Generex, OCT 5, 2018, View Source [SID1234529796]). It is anticipated that the trial will initiate sites in the fourth quarter and begin enrolling patients in the first quarter of 2019.

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Also, as previously announced, AE37 is being developed for the treatment of prostate cancer by the Company’s partner, Shenzhen Bioscien. The Company has nearly completed the non-clinical toxicology and pharmacology work required by the Chinese Food & Drug Administration (CFDA) and is preparing the necessary documentation for application to obtain authorization on the regulatory path for approval in China. Pending acceptance of that regulatory package, Shenzhen plans to initiate a Phase II clinical trial in Europe in 2019, with Generex maintaining Rest-of-World, ex-China rights to AE37 for the treatment of prostate cancer.

Further, in conjunction with the launch of the AE37/KEYTRUDA combination trial, and as part of the continuing restructuring of Generex, the Antigen Express name will be changed to NuGenerex Immuno-Oncology, remaining a wholly-owned subsidiary under the umbrella of the parent Company.

"We are excited to launch the clinical development of our HER2/neu immunotherapeutic vaccine AE37 in combination with Merck’s anti-PD-1 therapy, Keytruda, for the treatment of patients with triple-negative breast cancer," said Dr. Eric von Hofe, President of NuGenerex Immuno-Oncology. "With this trial and our partnership with Shenzhen Bioscien, NuGenerex Immuno-Oncology is positioned to realize the full potential of AE37 while advancing our proprietary Ii-Key technology platform for use in other cancers and diseases."

Generex Chief Medical and Scientific Officer, Dr. Jason Terrell, added: "NuGenerex Immuno-Oncology will be an important division within our restructured and diversified organization. This represents a successful advancement of our overall strategy to improve patient care through the development of innovative products and healthcare solutions."

Generex President & Chief Executive Officer Joe Moscato stated, "NuGenerex Immuno-Oncology is being established to not only to advance the Antigen Express core technology, but also to expand the Company’s portfolio in the field of immunotherapy and personalized medicine through partnerships and acquisitions. Generex has long demonstrated a belief and commitment to immune-therapy for the treatment of cancer through our extensive Ii-Key research & development program, and we are proud to be a leader in this emerging era of personalized, immuno-therapeutic cancer care."

On October 5, 2018 BerGenBio ASA (OSE: BGBIO) reported that the first patient has been dosed in the second stage of the phase II trial (BGBC008) evaluating the Company’s selective AXL inhibitor bemcentinib in combination with MSD’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in patients with previously treated advanced adenocarcinoma of the lung (non-small cell lung cancer, NSCLC) whose disease is progressing (Press release, BerGenBio, OCT 5, 2018, View Source [SID1234529834]).

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The trial was advanced into the second stage on the basis that the first stage met its clinical efficacy endpoint (as announced on 26 June 2018). Updated results from the first stage (n=24) were presented at the 19th Annual World Conference on Lung Cancer (WCLC: 25 September 2018)*. The Company reported an overall response rate (ORR) of 40% in patients who tested positive for AXL expression (4 out of 10 pts). Efficacy was also seen in PD-L1 negative patients (ORR of 27%, 3 out of 11 pts) for whom KEYTRUDA monotherapy is currently not indicated. Treatment with the bemcentinib/KEYTRUDA combination was well tolerated.

The second stage will enrol a further 24 patients at sites in Norway, Spain, UK and the US, and aims to confirm the safety and clinical efficacy of the combination. Comprehensive exploratory studies will continue to evaluate biomarkers in tumour and blood indicative of AXL expression and immune modulation. Preliminary results from the trial are expected during 2019.

The BGBC008 trial (ClinicalTrials.gov Identifier: NCT03184571) is being sponsored by BerGenBio. MSD, a tradename of Merck & Co., Inc., Kenilworth, New Jersey, USA, will continue to supply KEYTRUDA for use in the study under a collaboration agreement signed in March 2017.

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "We recently reported positive data from this phase II clinical trial at WCLC. Patients that were AXL positive reported a clinical response rate of 40%. Most notably, this included PD-L1 negative patients who do not benefit from KEYTRUDA monotherapy. These data strengthen our confidence in bemcentinib’s mode of action, as well as the value of AXL inhibition to enhance patient outcomes to KEYTRUDA immunotherapy. Additional combination data in NSCLC, including bemcentinib with targeted and chemotherapy, also presented at WCLC provide further proof supporting the concept that AXL is a key player in mediating resistance to therapy and immune evasion, and that bemcentinib has the potential to become a
cornerstone therapy in this challenging indication. We look forward to reporting outcome and biomarker data at upcoming leading medical congresses."

* James Lorens et al. Ph II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with Pembrolizumab in Patients with Advanced NSCLC(abstract P2.04-27)

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

– END –

About NSCLC
It is estimated that more than 230,000 new cases of lung cancer will be diagnosed in the US in 2018 and it is the leading cause of cancer deaths. 65% of NSCLCs are of adenocarcinoma pathology. Although various treatments exist for NSCLC, they are often curtailed by acquired resistance to therapy and immune evasion. Novel treatments overcoming these mechanisms in NSCLC are urgently required.

About the BGBC008 trial
The BGBC008 trial is a phase II multi-centre open-label study of bemcentinib in combination with KEYTRUDA (pembrolizumab) in previously treated, immunotherapy naïve, patients with advanced adenocarcinoma of the lung, the most common form of non-small cell lung cancer (NSCLC). The objective of the trial is to determine the anti-tumour activity of this novel drug combination and responses will be correlated with biomarker status (including AXL kinase and PD-L1 expression).

On October 5, 2018 Quest Diagnostics Incorporated (NYSE: DGX), the world’s leading provider of diagnostic information services, reported that it will report third quarter 2018 results on Tuesday, October 23, 2018, before the market opens (Press release, Quest Diagnostics, OCT 5, 2018, View Source [SID1234529799]). It will hold its quarterly conference call to discuss the results beginning at 8:30 a.m. Eastern Time on that day.

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The conference call can be accessed by dialing 888-455-0391 within the U.S. and Canada, or 773-756-0467 internationally, using the passcode: "Investor." The earnings release and live webcast will be posted on www.QuestDiagnostics.com/investor. 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, no passcode is required. Telephone replays will be available from approximately 10:30 a.m. Eastern Time on October 23, 2018 until midnight Eastern Time on November 6, 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 October 5, 2018 The U.S. Food and Drug Administration reported a supplemental application for Gardasil 9 (Human Papillomavirus (HPV) 9-valent Vaccine, Recombinant) expanding the approved use of the vaccine to include women and men aged 27 through 45 years (Press release, US FDA, OCT 5, 2018, View Source,aged%2027%20through%2045%20years. [SID1234607430]). Gardasil 9 prevents certain cancers and diseases caused by the nine HPV types covered by the vaccine.

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"Today’s approval represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range," said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. "The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90 percent of these cancers, or 31,200 cases every year, from ever developing."

According to the CDC, every year about 14 million Americans become infected with HPV; about 12,000 women are diagnosed with and about 4,000 women die from cervical cancer caused by certain HPV viruses. Additionally, HPV viruses are associated with several other forms of cancer affecting men and women.

Gardasil, a vaccine approved by the FDA in 2006 to prevent certain cancers and diseases caused by four HPV types, is no longer distributed in the U.S. In 2014, the FDA approved Gardasil 9, which covers the same four HPV types as Gardasil, as well as an additional five HPV types. Gardasil 9 was approved for use in males and females aged 9 through 26 years.

The effectiveness of Gardasil is relevant to Gardasil 9 since the vaccines are manufactured similarly and cover four of the same HPV types. In a study in approximately 3,200 women 27 through 45 years of age, followed for an average of 3.5 years, Gardasil was 88 percent effective in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine. The FDA’s approval of Gardasil 9 in women 27 through 45 years of age is based on these results and new data on long term follow-up from this study.

Effectiveness of Gardasil 9 in men 27 through 45 years of age is inferred from the data described above in women 27 through 45 years of age, as well as efficacy data from Gardasil in younger men (16 through 26 years of age) and immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months.

The safety of Gardasil 9 was evaluated in about a total of 13,000 males and females. The most commonly reported adverse reactions were injection site pain, swelling, redness and headaches.

The FDA granted the Gardasil 9 application priority review status. This program facilitates and expedites the review of medical products that address a serious or life-threatening condition.

The FDA granted approval of this supplement to the Gardasil 9 Biologics License Application to Merck, Sharp & Dohme Corp. a subsidiary of Merck & Co., Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

On October 5, 2019 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage pharmaceutical company focused on discovering and developing small molecule drugs that target novel and critical metabolic pathways in tumor and cancer-fighting immune cells, reported that it will provide an update on the company’s growing research pipeline of novel therapies in oncology and cystic fibrosis during an R&D day hosted today in New York City (Press release, Calithera Biosciences, OCT 5, 2018, View Source [SID1234535234]).

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Calithera management, including Susan Molineaux, PhD, President and Chief Executive Officer and Keith Orford, MD, PhD, Senior Vice President of Clinical Development will discuss progress on Calithera’s clinical and emerging programs. Nizar Tannir, MD, Deputy Department Chair, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center will discuss the advanced renal cell carcinoma treatment landscape.

"R&D Day is an opportunity to provide additional insight into our clinical development programs, delineate key milestones, and highlight our innovative pipeline," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. "In 2019, we plan to report data from our Phase 2 ENTRATA study in renal cell carcinoma. In addition, we and our partner Incyte expect data on INCB001158 to be presented at a medical meeting in the first half of 2019.

Pipeline Highlights

During R&D Day, Calithera will discuss its clinical development pipeline of innovative therapies including:

Two Randomized Phase 2 Combination Trials of CB-839 for the Treatment of Patients with Renal Cell Carcinoma. The ENTRATA trial, a randomized double-blind placebo-controlled study of late line patients, will enroll approximately 66 patients to receive either everolimus and CB-839 or everolimus alone. Topline results are expected in 2019. CANTATA is a randomized, global, double-blind, placebo-controlled trial comparing patients treated with cabozantinib and CB-839 to patients treated with cabozantinib alone. This trial will enroll approximately 300 clear cell renal cell carcinoma patients who have previously received one or two prior lines of therapy. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for CB-839 in combination with cabozantinib for the treatment of this patient population.

CB-839 Phase 1b Cabozantinib Combination Data in Patients with Advanced Renal Cell Carcinoma. Updated results of CB-839 in combination with cabozantinib will be presented. In the Phase 1b trial, 12 advanced renal cell carcinoma patients, including 10 clear cell and two papillary patients, were treated with CB-839 plus cabozantinib and were evaluable for response. Patients enrolled in the trial have advanced or metastatic disease and had received a median of three prior treatments, which included tyrosine kinase inhibitors, mTOR inhibitors, and checkpoint inhibitors. One hundred percent of evaluable patients experienced tumor shrinkage and disease control, including five patients who had a partial response and seven patients who had stable disease. In the clear cell patient population, the disease control rate was 100% and the response rate was 50%.

Pfizer collaboration to develop CB-839 in combination with PARP inhibitors and CDK4/6 inhibitors. As part of a clinical collaboration with Pfizer announced today, Calithera will initiate Phase 1/2 clinical studies in the first quarter of 2019. Preclinical data suggest that CB-839 synergizes with CDK4/6 inhibitors by enhancing cell cycle arrest and blocking cancer cell proliferation. CB-839 also synergizes with PARP inhibitors to impair DNA synthesis, enhance DNA damage, and block cancer cell proliferation.

INCB001158 Arginase Inhibitor Immuno-oncology Program. INCB001158 is being evaluated in multiple clinical trials for the treatment of patients with solid tumors both as a monotherapy, and in combination with immunotherapies and chemotherapy. INCB001158 is being developed as part of a collaboration and license agreement with Incyte. Data from INCB001158 is expected to be presented at a medical meeting in the first half of 2019.

CB-280 Arginase Inhibitor for the Treatment of Cystic Fibrosis. Arginase is believed to be critical in the pathology of cystic fibrosis. It impairs production of nitric oxide and generates metabolites of arginine that may impair lung function. CB-280 is an orally administered small molecule inhibitor of arginase. An investigational new drug (IND) application for CB-280 with the U.S. FDA is planned for the first half of 2019.

CB-708 Oral Small Molecule CD73 Inhibitor. The immuno-oncology target CD73 is an enzyme that plays a critical role in the process of ATP conversion to adenosine. An IND application for CB-708, an orally administered small molecule inhibitor of CD73, is planned for 2019. Webcast Information Calithera will host R&D Day today from 8:00 a.m.-10:15 a.m. ET in New York, NY. For those not able to attend, a live webcast that will include audio and slides of the presentation can be accessed through the Investors section of the Company’s website at www.calithera.com. Following the live presentations, a replay of the webcast will be available on the company’s website for at least 90 days