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Amgen Highlights Progress Of Innovative Early Oncology Pipeline With New Data At AACR 2019

on February 28, 2019 Amgen (NASDAQ:AMGN) reported that new data from its early-stage oncology pipeline will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta, March 29 – April 3, 2019 (Press release, Amgen, FEB 28, 2019, View Source;p=RssLanding&cat=news&id=2389545 [SID1234533864]).

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"At Amgen, we are searching for and finding answers to incredibly complex questions to advance care and improve lives for cancer patients," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "In a significant milestone in the oncology community, we will share the latest preclinical data from our KRASG12C inhibitor, AMG 510. KRAS has eluded targeting despite more than 30 years of industry and academic research. Our program is the first to reach the clinical stage, which will evaluate its potential against a target that is easily identifiable and present in a wide range of solid tumors."

For the first time, preclinical data will be presented on AMG 510, a first-in-class investigational KRASG12C inhibitor being evaluated for the treatment of solid tumors. Data at the meeting will also showcase Amgen’s novel bispecific T cell engager (BiTE) platform, including preclinical data evaluating the use of AMG 757, a DLL3-targeted BiTE molecule, in resistant subtypes of melanoma. Additional research to be presented will include preclinical data evaluating the use of Amgen’s intravenous investigational MCL-1 inhibitor, AMG 176, in combination with standard of care therapies in acute myeloid leukemia.

A complete listing of abstracts can be found on the AACR (Free AACR Whitepaper) website. Notable abstracts of interest include:

KRASG12C Inhibition:

Discovery of AMG 510: A Noval Covalent Inhibitor of KRASG12C, Now in a Phase 1 Clinical Trial for Patients with Solid Tumors Harboring the KRAS P.G12C Allele
Oral Presentation, Sunday, March 31 from 4:28-4:52 p.m. ET in Georgia World Congress Center, Building A, Level 3, Room A305
Discovery and In Vitro Characterization of AMG 510, a Potent and Selective Covalent Small Molecule Inhibitor of KRASG12C
Abstract #4484, Oral Presentation, Tuesday, April 2 from 3-5 p.m. ET in Georgia World Congress Center, Building C, Level 3, Georgia Ballroom 3
Discovery of AMG 510, a First-In-Human Covalent Inhibitor of KRASG12C for the Treatment of Solid Tumors
Abstract #4455, Oral Presentation, Tuesday, April 2 from 3-5 p.m. ET in Georgia World Congress Center, Building B, Level 2, Room B206
In Vivo Characterization of AMG 510, A Potent and Selective KRASG12C Covalent Small Molecule Inhibitor in Preclinical KRASG12C Cancer Models
Abstract #3090/24, Poster Presentation, Tuesday, April 2 from 8 a.m.-noon ET in Georgia World Congress Center, Exhibit Hall B, Section 14
BiTE Antibody Construct:

Melanoma Subtypes that Emerge During Adaptive Resistance to Therapy are Targets for Bispecific T Cell Engager (BiTE) Antibody Constructs Directed to CDH19 And DLL3
Abstract #553/17, Poster Presentation, Sunday, March 31 from 1-5 p.m. ET in Georgia World Congress Center, Exhibit Hall B, Section 23
Evaluation of Mesothelin BiTE Antibody Constructs in Models of Pancreatic Ductal Adenocarcinoma
Abstract #1561/30, Poster Presentation, Monday, April 1 from 8 a.m.-noon ET in Georgia World Congress Center, Exhibit Hall B, Section 25
Additional Preclinical Data:

AMG 176 Exhibits Robust Antitumor Activity in Combination with Standard of Care Agents in Models of Acute Myeloid Leukemia
Abstract #2180/2, Poster Presentation, Monday, April 1 from 1-5 p.m. ET in Georgia World Congress Center, Exhibit Hall B, Section 14
CSF-1 Receptor-Mediated Macrophage Depletion Can Induce Immunomodulatory Resistance Mechanisms in Murine Tumor Models
Abstract #2803/19, Poster Presentation, Tuesday, April 2 from 8 a.m.-noon ET in Georgia World Congress Center, Exhibit Hall B, Section 3
About KRAS
The subject of more than three decades of research, RAS proteins make up the most frequently mutated gene family in human cancers.1,2 Within this family, KRAS is the most prevalent variant and is particularly common in solid tumors.2 A specific mutation known as KRASG12C accounts for approximately 12 percent of all KRAS mutations across tumor types.3 Amgen is exploring the potential of KRASG12C inhibition across a broad variety of tumor types.

About BiTE Technology
Bispecific T cell engager (BiTE) antibody construct is an innovative technology that can be engineered to target any tumor antigen expressed by any type of cancer. The protein molecules are designed to kill malignant cells using the patient’s own immune system by bridging T cells to tumor cells. BiTE antibody construct helps connect the T cells to the targeted cell, with the intent of causing T cells to inject toxins which trigger cancer cell death (apoptosis). Amgen is developing BiTE antibody constructs to uniquely (or specifically) target numerous hematologic malignancies and solid tumors.

About Amgen’s Commitment to Oncology
Amgen is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen’s supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.

Halozyme Announces FDA Approval Of Herceptin Hylecta™

On February 28, 2019 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported that Genentech, a member of the Roche Group, has received approval from the U.S. Food and Drug Administration (FDA) for Herceptin Hylecta, a subcutaneous fixed-dose combination of trastuzumab and hyaluronidase-oysk (Press release, Halozyme, FEB 28, 2019, View Source [SID1234533861]). Herceptin Hylecta is approved for the treatment of certain people with HER2-positive early breast cancer (node-positive, or node-negative and ER/PR-negative or with one high-risk feature) in combination with chemotherapy and HER2-positive metastatic breast cancer in combination with paclitaxel or alone in people who have received one or more chemotherapy regimens for metastatic disease. Herceptin Hylecta is a co-formulation of trastuzumab with Halozyme’s proprietary recombinant human hyaluronidase enzyme (ENHANZE technology). Herceptin Hylecta is a ready-to-use formulation that can be administered in two to five minutes, compared to 30 to 90 minutes for intravenous trastuzumab.

"We are delighted that Herceptin Hylecta has been approved in the U.S. and that the potential for two- to five-minute administration time will now be available to patients in most of the major developed markets," said Dr. Helen Torley, president and chief executive officer. "Herceptin Hylecta is the third product co-formulated with ENHANZE to receive FDA approval, which represents an important achievement."

About ENHANZE Technology
Halozyme’s proprietary ENHANZE drug-delivery technology is based on its patented recombinant human hyaluronidase enzyme (rHuPH20). rHuPH20 has been shown to remove traditional limitations on the volume of biologics that can be delivered subcutaneously (just under the skin). By using rHuPH20, some biologics and compounds that are administered intravenously may instead be delivered subcutaneously. ENHANZE may also benefit subcutaneous biologics by reducing the need for multiple injections. This delivery has been shown in studies to reduce health care practitioner time required for administration and shorten time for drug administration.

TG Therapeutics Announces Proposed Public Offering of Common Stock and Closing of $60.0 Million Venture Debt Financing

on February 28, 2019 TG Therapeutics, Inc. (NASDAQ: TGTX), a biopharmaceutical company dedicated to developing medicines for patients with B-cell mediated diseases, reported that it intends to offer and sell shares of its common stock in an underwritten public offering (Press release, TG Therapeutics, FEB 28, 2019, View Source [SID1234533858]). The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering. TG Therapeutics intends to grant the underwriter a 30-day option to purchase up to an additional 15% of the shares of its common stock offered in the public offering. Cantor Fitzgerald & Co. is acting as sole book-running manager for the offering.

In addition, the Company announced that it has entered into a debt financing agreement for up to $60.0 million with Hercules Capital, Inc. (NYSE: HTGC), a leader in customizing debt financing for companies in the life sciences and technology-related markets. The first advance of $30.0 million was funded at closing. Two additional advances of $10.0 million may be drawn at the Company’s option, subject to certain clinical trial milestones, and the fourth advance of $10.0 million, is available through December 15, 2020 subject to the approval of Hercules.

The loan will mature on March 1, 2022. Payments under the loan are interest-only for a period of 18 months, followed by equal monthly installments of principal and interest thereafter. The interest-only period may be extended to 24 months contingent upon the Company achieving certain clinical development or fundraising milestones. In connection with the debt financing, the Company issued Hercules a warrant to purchase up to 147,058 of its common shares at an exercise price of $4.08 per share.

Further information with respect to the debt financing agreement with Hercules will be contained in a Current Report to be filed on Form 8-K by the Company with the Securities and Exchange Commission (the "SEC").

TG Therapeutics intends to use the net proceeds of the public offering and the debt facility to fund the ongoing development of ublituximab and umbralisib, for research and development activities and for general corporate purposes.

The public offering of common stock is being made pursuant to a shelf registration statement previously filed with the SEC on May 26, 2017 and declared effective by the SEC on June 13, 2017. The offering will be made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement and the accompanying prospectus related to the offering has been filed with the SEC and is available on the website of the SEC at www.sec.gov. Copies of the preliminary prospectus supplement and accompanying prospectus, when available, may also be obtained from Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Ave., 6th Floor, New York, New York 10022, or by e-mail at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of, these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

CymaBay Reports Fourth Quarter and Fiscal Year End 2018 Financial Results and Provides Corporate Update

On February 28, 2019 CymaBay Therapeutics, Inc. (NASDAQ: CBAY) a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet need, reported financial results and a corporate update for the quarter and year ended December 31, 2018 (Press release, CymaBay Therapeutics, FEB 28, 2019, View Source [SID1234533857]).

"The initiation of ENHANCE, our global, Phase 3 registration study of seladelpar in primary biliary cholangitis (PBC) at the end of 2018 was a major milestone for CymaBay," said Sujal Shah, President and CEO of CymaBay. "ENHANCE was initiated on the strength of what we believe to be a very compelling and differentiated profile in Phase 2, which highlighted the potential for seladelpar to offer patients with PBC improved efficacy and better tolerability than existing second line treatment. Seladelpar has now been granted Breakthrough Therapy Designation for PBC by the FDA and PRIority MEdicine status by the EMA. In parallel, we are advancing clinical development of seladelpar in nonalcoholic steatohepatitis (NASH) and were excited earlier this month to announce the completion of enrollment in our Phase 2b study, one quarter ahead of schedule. Seladelpar is the only highly selective and potent PPARδ agonist in development for liver disease, and we believe it may be particularly well suited to treat NASH. The ability of seladelpar to lower bile acids, cholesterol and lipotoxic lipids, coupled with anti-inflammatory and anti-fibrotic actions may position it as a foundational therapy for NASH."

Recent Business Highlights

In February 2019, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for seladelpar for the treatment of early stage PBC in combination with ursodeoxycholic acid (UDCA) in adult patients with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA.
In February 2019, enrollment was completed in a Phase 2b dose-ranging, paired liver biopsy study of seladelpar for the treatment of nonalcoholic steatohepatitis (NASH).
A total of 181 patients enrolled with elevated liver fat and biopsy-confirmed NASH.
Topline data on the primary efficacy outcome, the change from baseline in liver fat content at 12 weeks as measured by magnetic resonance imaging using the proton density fat fraction method (MRI-PDFF), are expected 2Q 2019.
Fourth Quarter 2018 Highlights

Initiated ENHANCE, a global, Phase 3 registration study of seladelpar for the treatment of primary biliary cholangitis (PBC).
ENHANCE is being conducted in more than 150 centers in over 20 countries. The study is intended to establish the efficacy and safety of seladelpar for the treatment of PBC to support the submission of a global registration dossier with health authorities to obtain approval.
The study is expected to be fully enrolled by the end of 2019 with the 52-week treatment period targeted to be completed by the end of 2020.
Positive data from an ongoing Phase 2 study of seladelpar in PBC were featured at late-breaking presentations during The Liver Meeting 2018 hosted by the American Association for the Study of Liver Diseases.
Sustained anti-cholestatic and anti-inflammatory effects observed with no worsening of pruritus through 52 weeks.
Results highlight the potential for seladelpar to offer patients an efficacious and safe second line treatment option.
Results suggest that seladelpar is not associated with drug-induced pruritus and may support the hypothesis that seladelpar decreases pruritus in PBC patients.
Held $178.7 million in cash, cash equivalents and marketable securities at December 31, 2018. Existing cash is expected to fund the current operating plan into 2021.
Fourth Quarter Ended December 31, 2018 Financial Results

There was no collaboration revenue in the fourth quarter of 2018 as compared to $5.2 million of revenue in the same period of 2017. Fourth quarter 2017 revenue earned was primarily due to the achievement of a $5.0 million milestone under a collaboration agreement with Kowa Pharmaceuticals America, Inc.
Research and development expenses were $16.4 million in the fourth quarter of 2018 as compared to $6.7 million in the same period of 2017. The increase was primarily driven by increases in seladelpar-related clinical trial expenses from the expansion and extension of our PBC Phase 2 clinical study, start-up activities related to our ENHANCE PBC Phase 3 clinical study, the ongoing enrollment of our NASH Phase 2b clinical study, and the execution of other NDA-enabling studies.
General and administrative expenses were $4.2 million in the fourth quarter of 2018 as compared to $2.9 million in the same period of 2017. The increase was driven primarily by employee compensation expense as we hired additional personnel to support our expanding operations.
Net loss was $19.4 million, or ($0.32) per diluted share in the fourth quarter of 2018, as compared to $5.0 million, or ($0.11) per diluted share in the same period of 2017. Net loss was higher primarily due to increased research and development expenses and decreased revenues.
Year Ended December 31, 2018 Financial Results

There was no collaboration revenue for the year ended December 31, 2018 as compared to revenue of $10.0 million in the prior year. Collaboration revenue was recognized in 2017 upon the delivery of our performance obligation under a collaboration agreement with Kowa Pharmaceuticals America, Inc.
Research and development expenses were $58.1 million in the year ended December 31, 2018 as compared to $18.9 million in the same period of 2017. The increase was primarily due to increased R&D project costs related to the expansion and extension of our PBC Phase 2 clinical study, start-up activities related to our ENHANCE PBC Phase 3 clinical study, enrollment in our NASH Phase 2b clinical study, and the execution of other NDA-enabling studies. R&D project costs also increased due to manufacturing of seladelpar to support ongoing and planned clinical trials and other development activities. Internal R&D costs also increased, primarily due to higher employee compensation related expenses as additional clinical, scientific and regulatory personnel were hired to support expanding clinical development activities.
General and administrative expenses were $14.4 million in the year ended December 31, 2018, as compared to $12.4 million in the same period of 2017. The increase was primarily due to higher compensation and consulting expenses, partially offset by a decrease in severance.
Net loss was $72.5 million, or ($1.26) per diluted share in the year ended December 31, 2018, as compared to $27.6 million, or ($0.79) per diluted share in the same period of 2017.
Conference Call Details
CymaBay management will host a conference call today at 4:30 p.m. ET to discuss fourth quarter 2018 financial results and provide a business update. To access the live conference call, please dial 877-407-0784 from the U.S. and Canada, or 201-689-8560 internationally, Conference ID# 13687140. To access the live and subsequently archived webcast of the conference call, go to the Investors section of the company’s website at View Source

Sierra Oncology Reports 2018 Year End Results

On February 28, 2019 Sierra Oncology, Inc. (Nasdaq: SRRA), a clinical stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, reported its financial and operational results for the year ended December 31, 2018 (Press release, Sierra Oncology, FEB 28, 2019, View Source [SID1234533856]).

"In 2018, with our opportunistic acquisition of the Phase 3 asset, momelotinib, we transformed Sierra into a late-stage company developing a diverse portfolio of promising drug candidates. We are currently advancing discussions with regulators to determine the registration path for momelotinib and expect to report next steps in the first half of 2019. Our registration strategy envisions conducting one additional Phase 3 trial in second line myelofibrosis patients, a population with significant unmet medical needs, in order to recapitulate the meaningful clinical benefits observed in two previously completed Phase 3 trials," said Dr. Nick Glover, President and CEO of Sierra Oncology. "We have also enrolled a substantial number of patients into the two ongoing trials for our oral Chk1 inhibitor, SRA737, and remain on track to report clinical data from these studies in the first half of 2019. In addition, our Cdc7 inhibitor, SRA141, recently delivered compelling preclinical efficacy data and has been cleared by the FDA to begin clinical trials."

2018 Highlights:

Momelotinib:

In August 2018, we acquired momelotinib, a potent, selective and orally-bioavailable JAK1, JAK2 and ACVR1 inhibitor. Momelotinib has been investigated in two completed Phase 3 trials for the treatment of myelofibrosis and has demonstrated a potentially differentiated therapeutic profile encompassing anemia-related clinical benefits, as well as achieving substantive splenic volume reduction and constitutional symptom control.

In October 2018, we hosted a Key Opinion Leader call featuring a presentation by distinguished medical oncologist Dr. Srdan Verstovsek, MD, PhD, Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, Houston, Texas, who discussed momelotinib and its potential to address unmet medical needs in myelofibrosis.

In December 2018, we reported aggregated transfusion independence responses from more than 150 transfusion dependent myelofibrosis patients demonstrating robust and consistent response rates within and across the two completed SIMPLIFY Phase 3 clinical trials and a translational biology study in transfusion dependent patients with myelofibrosis. More than 44% of these patients became transfusion free for at least 12 weeks and nearly 50% were transfusion independent for at least 8 weeks. Data from the latter study were also presented in a poster at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in San Diego, California.

SRA737:

During 2018, we continued to enroll patients into the two ongoing trials for SRA737, our potent, highly selective, orally bioavailable small molecule inhibitor of Chk1. Supported by emerging clinical validation for Chk1 inhibition in high grade serous ovarian cancer (HGSOC), we prioritized enrollment of genetically defined HGSOC patients into the SRA737 monotherapy trial, while continuing to enroll patients into the trial’s other indications. The SRA737+LDG (low dose gemcitabine) trial which has been enrolling across four indications, was also modified to prioritize for the enrollment of genetically defined HGSOC patients. In April 2018, we presented preclinical data in a late-breaking poster at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) 2018 Annual Meeting in Chicago demonstrating that SRA737 is active in both poly ADP-ribose (PARP) inhibitor resistant and CCNE1 amplified HGSOC. In November 2018, we reported preclinical data in a poster presented at the 30th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium in Dublin, Ireland demonstrating that SRA737 has impressive efficacy in highly aggressive models of ovarian cancer (CCNE1-amplified and MYCN-overexpressing HGSOC patient-derived xenograft models).

During 2018, we prepared for a potential Phase 1b/2 combination trial of SRA737 with the PARP inhibitor niraparib, in subjects with metastatic castration-resistant prostate cancer. In February 2018, we signed a supply agreement with Janssen Research & Development, LLC where they will supply niraparib for the study. We are currently evaluating the optimal timing to commence this trial within the context of our recently expanded portfolio. In April 2018, we presented supportive preclinical data at the AACR (Free AACR Whitepaper) 2018 Annual Meeting in Chicago demonstrating that SRA737 synergizes with niraparib to kill carcinoma cells via multiple cell death pathways.

In November 2018, we reported preclinical data for SRA737 combined with Immunotherapy in a poster presented at the AACR (Free AACR Whitepaper) Conference on Tumor Immunology and Immunotherapy in Miami Beach, Florida. SRA737 activated the innate immune signaling STING pathway and demonstrated significant anti-tumor activity in an immunocompetent preclinical model of small cell lung cancer (SCLC).

SRA141:

During 2018, we successfully completed the Investigational New Drug Application (IND) filing process with the U.S. Food and Drug Administration (FDA) for our novel oral Cdc7 inhibitor, SRA141, and have prepared for a potential Phase 1/2 trial of the drug candidate in patients with advanced colorectal cancer. We are currently evaluating the optimal timing to commence this trial within the context of our recently expanded portfolio.

In November 2018, we reported preclinical data for SRA141 in a poster presented at the 30th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium held in Dublin, Ireland, demonstrating that SRA141 potently and selectively inhibits Cdc7, thereby interfering with DNA replication and cell cycle dynamics within tumor cells while sparing normal cells. This unique mechanism results in significant in vitro anti-proliferative activity in a broad spectrum of tumor cell lines derived from both solid and hematologic cancers and translates into robust efficacy and tumor regressions in rodent xenograft cancer models.

Year End 2018 Financial Results (all amounts reported in U.S. currency)

Research and development expenses were $41.1 million for the year ended December 31, 2018, compared to $30.2 million for the year ended December 31, 2017. The increase was primarily due to an increase of $7.2 million in clinical trial costs mainly related to SRA737, a $3.0 million upfront fee paid to Gilead for the acquisition of our lead product candidate momelotinib and a $3.0 million increase in personnel-related and allocated overhead costs, partially offset by decreases of $1.9 million in third-party manufacturing costs related to SRA737 and SRA141 and $0.4 million in research, preclinical and other support costs. Research and development expenses included non-cash stock-based compensation of $4.5 million and $4.0 million for the year ended December 31, 2018 and 2017, respectively.

General and administrative expenses were $14.3 million for the year ended December 31, 2018, compared to $12.5 million for the year ended December 31, 2017. This increase was primarily due to a $1.7 million increase in personnel-related costs, professional fees and allocated overhead and a $0.2 million increase in business development costs. General and administrative expenses included non-cash stock-based compensation of $2.3 million and $1.9 million for the years ended December 31, 2018 and 2017, respectively.

For the year ended December 31, 2018, Sierra incurred a net loss of $53.3 million, compared to a net loss of $42.0 million for the year ended December 31, 2017.

Cash and cash equivalents totaled $106.0 million as of December 31, 2018, compared to $100.3 million as of December 31, 2017. At December 31, 2018, there were 74,365,965 shares of common stock issued and outstanding, with another 10,577,941 issuable upon exercise of stock options and warrants, and a term loan of $4.9 million.