On October 5, 2019 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported two new clinical trial collaborations to evaluate Pfizer’s palbociclib, also known as IBRANCE, and the investigational dual-mechanism poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib, each in combination with Calithera’s glutaminase inhibitor CB-839 (Press release, Calithera Biosciences, OCT 5, 2018, View Source [SID1234535235]). As part of the collaboration, Pfizer will provide palbociclib and talazoparib, as well as financial support.

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"Tumor metabolism is a unique therapeutic approach that exploits the way in which cancer cells utilize nutrients to grow and survive," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. "CB-839, a novel glutaminase inhibitor, has the potential to be developed in combination with palbociclib or talazoparib to improve patient outcomes. We look forward to collaborating with Pfizer on the combination clinical trials planned in the first quarter of 2019.

" Preclinical data suggest that CB-839, which is designed to starve tumor cells of the key nutrient glutamine, synergizes with CDK4/6 inhibitors by enhancing cell cycle arrest and blocking cancer cell proliferation. The combination of CB-839 with CDK4/6 inhibitors has demonstrated synergistic activity in a number of preclinical cancer models, including colorectal cancer (CRC), non-small cell lung carcinoma (NSCLC), triple negative breast cancer (TNBC) and ER+ breast cancer. Based on these data, Calithera will initiate a Phase 1/2 clinical trial of the combination of CB-839 plus palbociclib in patients with KRAS mutated CRC and patients with KRAS mutated NSCLC in the first quarter of 2019.

CB-839 also synergizes with PARP inhibitors to impair DNA synthesis, enhance DNA damage, and block cancer cell proliferation. The combination of CB-839 with PARP inhibitors has demonstrated synergistic activity in a number of preclinical cancer models, including renal cell carcinoma (RCC), TNBC, CRC, NSCLC, ovarian cancer and prostate cancer. Based on these data, Calithera will initiate a Phase 1/2 clinical trial of the combination of CB-839 plus talazoparib in patients with RCC, and TNBC in the first quarter of 2019

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 4, 2018 Heat Biologics, Inc. ("Heat") (NASDAQ: HTBX), a biopharmaceutical company developing drugs designed to activate a patient’s immune system against cancer, and its Pelican Therapeutics subsidiary ("Pelican") reported on its novel PTX-35 co-stimulatory antibody. PTX-35 is designed to harness the body’s natural antigen-specific immune activation mechanisms (Press release, Heat Biologics, OCT 4, 2018, View Source [SID1234529871]). When combined with immunotherapies, including checkpoint inhibitors as well as Heat’s ImPACT and ComPACT technologies, PTX-35 has been shown to enhance antigen-specific T-cell activation to eliminate tumor cells in pre-clinical models.

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Recent PTX-35 highlights:

Completed cell line development and creation of validated master cell bank for cGMP manufacturing
Established CMC path for the production of GMP clinical material and non-clinical preliminary pharmacology / non-GLP toxicology studies
Preliminary non-GLP pharmacology demonstrates positive results, including efficient binding and activation on cells expressing the TNFRSF25 receptor, as well as increased expansion of T-cells in-vivo
2-week IND enabling dose range finding toxicology studies in primates receiving two doses show no signs or signals of clinical toxicity across wide dose range
Ongoing pre-IND discussions with FDA; expect to submit IND in Q1 2019
Rahul Jasuja, Ph.D., CEO of Pelican, commented, "We are progressing rapidly with our pre-clinical activities and expect to submit an IND for PTX-35 in the first quarter of 2019. We are strongly encouraged by the preliminary pre-clinical efficacy and safety data which shows no signs of toxicity across a wide range of doses."

Dr. Jasuja continued, "We have been efficient in our use of funds, which has allowed us to come in under budget, further extending our runway for this program. Given our operating efficiency thus far, we expect to receive the next tranche of grant funding once we fully utilize the funds that the Cancer Prevention Research Institute of Texas ("CPRIT") has previously provided. As we progress, our plan is to advance a broad clinical development program that could include combination therapy with Heat’s ImPACT and ComPACT therapies, as well as other costimulatory agonists, checkpoint inhibitors and immune modifiers to address the unmet need for patients who do not respond well to current cancer therapies."

The Company further reported that PTX-35 was featured in Nature’s Biopharma Dealmakers September 2018 edition, which is available at: View Source

To-date, Pelican has received $8.3 million in grants from CPRIT. The CPRIT award supports pre-clinical development, manufacturing and clinical development through a comprehensive 70-patient Phase 1 clinical trial for PTX-35. The Company expects to meet the qualifications to receive the third tranche of its $15.2 million CPRIT grant award, totaling $6.9 million, later this year.