On November 9, 2018 NewLink Genetics Corporation (NASDAQ:NLNK) reported that data from three separate trials are being presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Washington D.C (Press release, NewLink Genetics, NOV 9, 2018, View Source [SID1234531173]). Data from a Phase 1a clinical trial of NLG802, a prodrug of indoximod, as well as biomarker data from two Phase 2 studies of indoximod in combination therapy are being presented in poster sessions today and tomorrow, November 9th and 10th, from 8:00AM to 8:00PM ET. These posters with full data sets are provided on the company’s website in the "Posters & Presentations" section under the "Investors & Media" tab.

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"We are delighted to be able to present these data supporting both activity of indoximod within the tumor microenvironment and the higher exposure levels obtained by indoximod prodrug, NLG802, supporting the potential for these drugs to elicit therapeutic responses and improve the lives of patients with cancer," said Charles J. Link, Jr, MD, Chairman and Chief Executive Officer.

Phase 1 Clinical Trial of NLG802, Indoximod Prodrug with Enhanced Pharmacokinetic Properties
Preliminary data from a Phase 1a study of NLG802, a prodrug of indoximod, are being presented today by Olivier Rixe, MD, PhD, Professor of Medicine, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM in a poster session (P331). Co-author, Eugene Kennedy, MD, Chief Medical Officer, NewLink Genetics, will be present Friday, November 9th, 12:45-2:15PM and 6:30-8:00PM, to discuss these data.

NLG802 is being evaluated in an ongoing standard 3+3 dose escalation Phase 1a study in patients with recurrent advanced solid malignancies. The purpose of this trial is to assess the safety, maximum tolerated dose, and pharmacokinetic properties of this drug candidate. As of October 3rd, the cutoff date for these data, 11 patients were enrolled in this study in three separate dose cohorts, 180 mg BID, 363 mg BID, and 726 mg BID.
Key findings from these preliminary data:

NLG802, was well tolerated, with no unexpected safety signals.

At the time of analysis, neither maximum tolerated dose (MTD), nor maximum biologically achievable dose (MBAD) had been reached.

NLG802 produced 4-fold increase in CMAX and AUC after a single dose, and a 4-5.5 fold increases in CMAX and AUC after continuous BID dosing compared with the molar equivalent of indoximod dosing.

The Immunogenic Impact of Indoximod on the Tumor Microenvironment of Patients with Advanced Melanoma
Biopsy data from a Phase 2 study of indoximod plus checkpoint inhibition from patients with advanced melanoma are being presented today by Jiayi Yu, PhD, Senior Scientist, NewLink Genetics, in a poster session (P142). The author will be present Saturday, November 10th, 12:20-1:50PM and 7:00-8:30PM to discuss these data.
In this study, patients with unresectable advanced melanoma underwent pretreatment tumor biopsy followed by a repeat biopsy after cycle 3 of indoximod plus pembrolizumab. Fourteen pairs of tumor specimens (6 patients with objective response and 8 non-responders) underwent RNA sequencing analysis and immunofluorescence staining to
assess immune activity in the tumor microenvironment (TME), to define changes in the tumor genomic profile and gene expression. Baseline samples from the trial were used for predictive biomarker assessment (N = 38).
Key findings from these biopsy data:

Compared to published studies, these biopsy data suggested indoximod exclusively contributed to immunologic and metabolic changes in the TME.

Indoximod in combination therapy may contribute to immunologic and metabolic changes in a different manner than anti-PD-1 alone.

Decreased IDO1 in Ki67- cells supports indoximod’s mechanism of action (MOA).

Patients with high IDO expression showed a trend towards both higher rate of response to treatment and longer progression-free survival (PFS), results which were independent of PD-L1 expression.

Previously published results from this Phase 2 study of indoximod plus pembrolizumab for patients with advanced melanoma may be found on the company’s website under "Posters & Publications" in the "Investors & Media" section.
Effects of indoximod plus gemcitabine/nab-paclitaxel on tumor microenvironment of patients with metastatic pancreas cancer
Biopsy data from a Phase 2 study of indoximod plus chemotherapy for patients with metastatic pancreatic cancer are being presented today by Jiayi Yu, PhD, Senior Scientist, NewLink Genetics, in a poster session (P706). Co-author, Gabriela Rossi, PhD, Vice President, Biologics Development, NewLink Genetics, will be present Saturday, November 10th, 12:20-1:50PM and 7:00-8:30PM to discuss these data.
In this study, treatment-naïve patients with metastatic pancreatic cancer underwent pre-treatment tumor biopsy with a repeat biopsy on week 8. Sixteen pairs of tumor specimens (8 patients with objective response, and 8 non-responders) underwent RNA sequencing analysis and immunohistochemistry (IHC) staining to assess immune activity in the tumor microenvironment.
Key findings from these biopsy data indicate that indoximod plus standard-of-care (SOC) chemotherapy:

Tumor samples observed to have increased recruitment of intratumoral T cells.

Increased recruitment of innate immune cells (NK cells) in responding patients.

Downregulated Treg population and IDO expression in the TME.

Increased both innate and adaptive immune responses in TME of these patients, supporting indoximod’s MOA.

Previously published results from this Phase 2 study of indoximod plus gemcitabine/nab-paclitaxel for patients with metastatic pancreatic cancer may be found on the company’s website under "Posters & Publications" in the "Investors & Media" section.
About Indoximod
Indoximod is an investigational, orally available small molecule targeting the IDO pathway. The IDO pathway is a key immuno-oncology target, suppressing immune response and allowing for immune escape by degrading tryptophan with the resultant production of kynurenine. Indoximod reverses the immunosuppressive effects of low tryptophan and high kynurenine through mechanisms that include modulation of the AhR-driven transcription of genes that control immune function. This results in increased proliferation of effector T cells, increased differentiation into helper T cells rather than regulatory T cells, and downregulation of IDO expression in dendritic cells. Indoximod is being evaluated in combination with treatment regimens including chemotherapy, radiation, checkpoint blockade and cancer vaccines across multiple indications including recurrent pediatric brain tumors, DIPG, and AML.

About NLG802

NLG802 is a prodrug of indoximod. NLG802 has been shown in preclinical trials to increase bioavailability and exposure to indoximod above the levels achievable by direct administration of indoximod. NLG802 is currently being evaluated in clinical trials.

On November 9, 2018 OPKO Health, Inc. (NASDAQ: OPK) reports financial results and business highlights for the three months ended September 30, 2018 (Press release, Opko Health, NOV 9, 2018, View Source [SID1234531170]).

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Financial Highlights

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Net loss for the three months ended September 30, 2018 decreased by 23% to $27.7 million or $0.05 a share compared to net loss of $35.9 million or $0.06 per share for the comparable 2017 period. Total revenues improved to $249.8 million during the three months ended September 30, 2018 compared to $246.0 million for the comparable period of 2017.
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Revenues from products during the three months ended September 30, 2018 include $5.8 million from RAYALDEE and revenues from services were $202.8 million for the 2018 period compared with $200.9 million for the corresponding 2017 period.
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During the three months ended September 30, 2018, costs of revenue and selling, general and administrative expenses decreased by approximately 8%, or $19.5 million, compared to the 2017 period. Research and Development expenses were $30.2 million compared to $32.5 million for the corresponding 2017 period.
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On November 8, 2018, OPKO secured approximately $150 million of additional capital, consisting of a private placement of common stock resulting in proceeds of $92.5 million, and an unsecured credit line of $60 million.

Business Highlights

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RAYALDEE total prescriptions reported by IMS for Q3 2018 increased 222% compared with Q3 2017 and 18% compared with Q2 2018: As of November 1, 2018, approximatley 79% of patients have access to RAYALDEE under their insurance plans.
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Initiated the Phase 2 clinical trial to study the safety and efficacy of RAYALDEE as a new treatment for secondary hyperparathyroidism (SHPT) in adults with vitamin D insufficiency and stage 5 chronic kidney disease (CKD) requiring hemodialysis. The trial will be conducted at multiple dialysis centers in the U.S. in two sequential cohorts. The first cohort of approximately 44 patients will be treated for 26 weeks in a randomized, open-label fashion with

either RAYALDEE or placebo to identify the appropriate dosing to be studied in the second cohort. Data readout for this first cohort is expected in 2019. The second cohort of more than 200 patients will be treated for 26 weeks in a randomized, double-blind fashion with one of three different doses of RAYALDEE or placebo. The primary efficacy endpoint will be correction of vitamin D insufficiency and control of SHPT. Patients will then be treated with RAYALDEE for another 26 weeks in an open-label extension.
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4Kscore utilization in Q3 2018 was approximately 18,700 tests compared to 18,900 during Q3 2017. Utilization of the 4Kscore remains strong while we continue to work with our Medicare administrator, Novitas, on their proposed local coverage determination. During this process, Novitas has continued to provide coverage of the 4Kscore to Medicare beneficiaries.
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Completed the enrollment of a Global Phase 3 study of somatrogon (hGH-CTP) in Growth Hormone Deficient Children: The somatrogon Phase 3 trial is a randomized, open-label study comparing once-weekly somatrogon to once daily Genotropin. This study has enrolled 228 treatment naïve children with growth hormone deficiency (GHD) in 21 countries. The primary endpoint of the trial is height velocity at 52 weeks. Secondary endpoints are safety and pharmacodynamics.
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Enrollment in Japanese Phase 3 registration trial of somatrogon in growth hormone deficient children expected to complete by year end: The global and Japanese pediatric studies utilize the multiple dose pen device that will be launched commercially upon approval.
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Completed the enrollment of a Phase 2b clinical trial for our once-weekly oxyntomodulin dual GLP1-Glucagon agonist to treat type 2 diabetes and obesity: In a previous Phase 2 trial in 420 overweight patients with type 2 diabetes, the drug was shown to be safe and effective. The current trial is to study a new dosing schedule to achieve even greater weight loss and topline results are anticipated during 1Q 2019.
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Advanced the Phase 2b trial for our SARM (selective androgen receptor modulator) to treat benign prostatic hyperplasia (BPH): Enrollment of approximately 110-120 patients in this dose ranging study of our orally administered SARM is expected to be completed by the end of this year.
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Premarket Approval (PMA) application for Claros point-of-care PSA test under review by FDA; decision anticipated during 1H 2019: OPKO has completed a PMA submission to FDA for Sangia, our point of care PSA test utilizing the Claros 1 immunoassay analyzer. This is the first test on our proprietary diagnostic platform that can provide rapid, quantitative blood test results in the physician’s office with only a finger stick drop of whole blood. Several biomarkers and biological meaningful chemistry tests such as testosterone and Vitamin D utilizing the Claros platform are advancing toward a 510(k) submission to the FDA.

Conference Call & Webcast Information

OPKO’s senior management will provide a business update and discuss results in greater detail in a conference call and live audio webcast at 4:15 p.m. Eastern time today. The conference call dial-in and webcast information is as follows:

WHEN: Friday, November 9, 2018 at 4:15 p.m. Eastern time
DOMESTIC DIAL-IN: (866) 634-2258
INTERNATIONAL DIAL-IN: (330) 863-3454
PASSCODE: 3487296
WEBCAST: www.investor.opko.com/events

For those unable to participate in the live conference call or webcast, a replay will be available beginning November 9, 2018 two hours after the close of the conference call. To access the replay, dial (855) 859-2056 or (404) 537-3406. The replay passcode is: 3487296. The replay can be accessed for a period of time on OPKO’s website at www.investor.opko.com/events.

On November 9, 2018 Cytori Therapeutics, Inc. (NASDAQ: CYTX) reported that it will provide a live webcast of its third quarter financial results and business update on Wednesday, November 14, 2018 at 5:30 PM Eastern Time (Press release, Cytori Therapeutics, NOV 9, 2018, View Source [SID1234531153]).

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The dial-in information is as follows:
Dial-In Number: +1.877.402.3914
Conference ID: 9699923

Prior to the webcast at approximately 4:30 PM Eastern Time on November 14, Cytori will issue its third quarter earnings release which will review Cytori’s third quarter and year-to-date performance. The webcast will be available both live and by replay two hours after the call in the "Webcasts" section of the company’s investor relations website.

On November 9, 2018 Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, reported that new preclinical data on SY-1365, its first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor, will be featured in a Spotlight poster discussion session at the San Antonio Breast Cancer Symposium taking place December 4-8 in San Antonio (Press release, Syros Pharmaceuticals, NOV 9, 2018, View Source [SID1234531109]). The data show that SY-1365 has dose-dependent inhibitory activity in hormone receptor-positive breast cancer cell lines that are resistant to treatment with CDK4/6 inhibitors.

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The abstract for this presentation is now available online on the SABCS website at View Source

Details on the presentation are as follows:

Presentation Title: Inhibition of CDK7 overcomes resistance to CDK4/6 inhibitors in hormone receptor-positive breast cancer cells
Session Date & Time: Friday, December 7, 7:00-9:00 a.m. CT (8:00-10:00 a.m. ET)
Session Title: Spotlight Session 7: Lobular Breast Cancer
Presenter: Dr. Cristina Guarducci, Dana Farber Cancer Institute
Abstract Number: 1008
Program Number: PD7-12
Location: Stars at Night Ballroom, Henry B. Gonzalez Convention Center

On November 9, 2018 Harpoon Therapeutics, Inc. ("Harpoon"), a clinical-stage immunotherapy company developing a novel class of T cell engagers that harness the power of the body’s immune system to treat patients suffering from cancer and other diseases, reported preclinical data supporting the development of a new Protease-activated Tri-specific T cell Activating Construct ("ProTriTAC") platform (Press release, Harpoon Therapeutics, NOV 9, 2018, View Source [SID1234531108]). The new ProTriTAC platform is based on Harpoon’s Tri-specific T cell Activating Construct ("TriTAC") technology, which is designed to bind a patient’s immune cells to cancer cells. This binding leads to activation of the immune cell, which then attacks and kills the cancer cell. Data were presented at the 2018 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Washington, D.C., held November 9-11, 2018.

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Therapeutics derived from the new ProTriTAC platform are intended to be administered as T cell inactive prodrugs and are optimized for serum exposure to ensure delivery to solid tumor tissues. At the site of the tumor, these prodrugs can be locally activated by tumor-associated proteases. This induces T cells to kill tumor cells expressing target antigen without affecting other tissues.

"We are very pleased to launch our ProTriTAC platform, which retains the advantages of our TriTAC platform, including activity at low levels of target expression, extended serum half-life and conventional manufacturing. Our ProTriTAC platform allows us to access tumor-associated antigens that have been historically challenging because they are expressed in both tumors and non-tumor tissues. ProTriTAC therapeutics are designed to be serum half-life extended, but do not engage T cells until they are clipped by tumor-associated proteases. Once clipped, a T cell activator is released at the site of the tumor. However, this T cell activator now has a short half-life and is quickly removed from circulation before it can impact non-tumor tissues," said Holger Wesche, PhD, Chief Scientific Officer of Harpoon. "Harpoon plans to bring its first ProTriTAC product candidate into IND-enabling studies in 2019."

"ProTriTAC is an important extension of Harpoon’s proprietary TriTAC platform, a T cell engager platform designed to harness the natural power of the patient’s own immune system to fight cancer and other diseases," said Jerry McMahon, PhD, President and CEO of Harpoon. "ProTriTAC product candidates have the potential to increase the number of possible tumor antigen targets for Harpoon’s emerging pipeline."

The poster entitled "ProTriTAC: A Protease-Activatable T Cell Engager Platform That Links Half-Life Extension to Functional Masking" can be found on the Publications page of Harpoon’s website. Key proof-of-concept data include:

Biological Activity Dependent on Protease Activation

Intact ProTriTAC proteins can block binding to T cells by more than 500-fold, but they can become fully active after a single proteolytic cleavage event, enabling T cell binding and activity in the tumor microenvironment.

Potent Anti-Tumor Activity In Vivo Is Protease-Dependent

When administered to tumor-bearing mice, ProTriTAC molecules can completely inhibit tumor growth with doses as low as 0.03 mg/kg. These data imply that this activity depends on proteolytic activation of the ProTriTAC in the tumor.

Reduced T Cell Binding and Rapid Clearance of the Active Drug in Non-Human Primates

Pharmacokinetic data derived from non-human primates confirm that ProTriTACs exhibit long serum half-life and support that T cells are not being engaged by the prodrug form.