On November 5, 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 ended September 30, 2019 (Press release, CymaBay Therapeutics, NOV 5, 2019, View Source [SID1234550318]).

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"The third quarter marked one of our most productive periods, culminating in reaching target enrollment in ENHANCE, our global, Phase 3 registration study of seladelpar in PBC, earlier than originally projected," said Sujal Shah, President and CEO of CymaBay. "We expect to complete enrollment in ENHANCE by the end of November and remain on track to report topline data from this 52-week study in early 2021. We also made significant progress in our efforts to expand development of seladelpar into a second rare, cholestatic liver disease with the initiation of our Phase 2 dose-ranging study in PSC. As our development activities advance in the coming months, we look forward to topline data from our completed open-label Phase 2 study in PBC, and topline 52-week biopsy data from our Phase 2b study in NASH, in the first and second quarters of 2020, respectively."

Third Quarter and Recent Business Highlights

Reached target enrollment of 240 patients in ENHANCE, our global, Phase 3 registration study of seladelpar for the treatment of primary biliary cholangitis (PBC).
The study is expected to be fully enrolled by the end of November 2019 with topline data release anticipated in early 2021.
Initiated a Phase 2 clinical study of seladelpar in primary sclerosing cholangitis (PSC).
The Phase 2 study is a randomized, placebo-controlled, dose-ranging study that will enroll approximately 100 patients at 60 sites globally.
Patients will be randomized to placebo or seladelpar 5, 10 or 25 mg in a 1:1:1:1 randomization.
The study includes an interim assessment of safety and efficacy after approximately 10 patients in each dose group reach 12 weeks of treatment.
Confirmed additional pharmacodynamic effects in the 12-Week interim analysis of the Phase 2b dose-ranging study in NASH.
Dose-dependent decreases of plasma C4 of up to 55% at 50 mg, a key mechanistic marker of hepatocellular bile acid synthesis.
Dose-dependent increases in carnitine and short-chain acyl carnitines of over 35% considered to be plasma markers of increased lipid metabolism.
No significant effects were observed using the ELF panel, a plasma-based marker of fibrosis, or in corrected-T1, an exploratory magnetic resonance imaging method being developed to identify inflammation associated with NASH. These measures will be assessed at additional timepoints as the study continues.
The study remains blinded until the 52-week liver histology endpoint, expected in 2Q 2020.
Announced acceptance of two abstracts for presentation at The Liver Meeting hosted by the American Association for the Study of Liver Diseases (AASLD) in Boston, MA (November 8-12, 2019).
"Pharmacokinetics of Seladelpar in Patients with Primary Biliary Cholangitis, with or without Cirrhosis" (Publication #1328)
"Structural and Biophysical Characterization of the Origins of the Selectivity of Seladelpar and Elafibranor, Peroxisomal Proliferator Activated Receptor (PPAR) Agonists Targeting Inflammatory Liver Diseases" (Publication #2253)
Third Quarter Financial Highlights & Results

Held $218.6 million in cash, cash equivalents and marketable securities at September 30, 2019. Existing cash is expected to fund the current operating plan into 2021.
Research and development expenses were $23.2 million in the third quarter of 2019 as compared to $17.9 million in the same period of 2018. The increase was primarily driven by higher manufacturing costs incurred to support our ongoing clinical trials and registration batches as well as a severance expense incurred due to the departure of an executive.
General and administrative expenses were $4.5 million in the third quarter of 2019 as compared to $3.3 million in the same period of 2018. The increase was driven primarily by higher employee compensation and other administrative expenses as we hired additional personnel to support our expanding operations.
Net loss was $26.3 million, or ($0.38) per diluted share in the third quarter of 2019, as compared to $18.6 million, or ($0.34) per diluted share in the same period of 2018. Net loss was higher primarily due to increased research and development expenses.
Nine Months Ended September 30, 2019 Financial Highlights & Results

Raised $107.7 million in net proceeds through our March public offering of common stock.
Research and development expenses were $62.9 million in the nine months ended September 30, 2019 as compared to $41.7 million in the same period of 2018. The increase was primarily driven by increases in seladelpar-related clinical trial expenses including enrollment activities related to our ENHANCE PBC Phase 3 clinical study, start-up and enrollment activities related to our PSC Phase 2 clinical study, higher manufacturing costs incurred to support our ongoing clinical trials and registration batches, and execution of other NDA-enabling studies.
General and administrative expenses were $14.7 million in the nine months ended September 30, 2019 as compared to $10.2 million in the same period of 2018. The increase was driven primarily by higher employee compensation expense and other administrative expenses as we hired additional personnel to support our expanding operations.
Net loss was $73.4 million, or ($1.10) per diluted share in the nine months ended September 30, 2019 as compared to $53.1 million, or ($0.93) per diluted share in the same period of 2018. Net loss was higher primarily due to increased research and development expenses.
Conference Call Details
CymaBay management will host a conference call today at 4:30 p.m. ET to discuss third quarter 2019 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# 13694084. 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

On November 5, 2019 CANbridge Pharmaceuticals Inc., a biopharmaceutical company developing innovative drug candidates to treat underserved medical conditions in China and other markets, reported that it received market approval from the Department of Health in Hong Kong for NERLYNX (neratinib) for the extended adjuvant treatment of adult patients with early‑stage hormone receptor positive HER2-overexpressed/amplified breast cancer, and who completed adjuvant trastuzumab-based therapy less than one year ago (Press release, CANbridge Life Sciences, NOV 5, 2019, View Source [SID1234550317]). This is the first targeted therapy approved in the CANbridge oncology platform and the first NERLYNX approval in greater China. CANbridge acquired the exclusive NERLYNX development and commercial rights for China, Taiwan, Hong Kong and Macao in 2018, and submitted the NDA for NERLYNX to the National Medical Products Administration (NMPA) in China for the extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy, last year.

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"The rapid and smooth advancement of NERLYNX through the Hong Kong regulatory process to market approval is a testament to the quality of our regulatory expertise, and the CANbridge commitment to bring new treatments to underserved patient populations in greater China," said James Xue, PhD, Founder, Chairman and CEO, CANbridge Pharmaceuticals. "With this first targeted therapy approved in our oncology platform, CANbridge is able to provide women in Hong Kong, with HER2-positive breast cancer at risk of recurrence, a new and vital treatment option shortly after it was approved in the West."

About HER2-Positive Breast Cancer

Approximately 20 to 25 percent of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Research has shown that trastuzumab treatment can reduce the risk of early-stage HER2-positive breast cancer returning after surgery. However, up to 25% of patients treated with trastuzumab experience recurrence. There were 4,391 reported new cases of all types of breast cancer in Hong Kong in 2017, according to a report released by the Hong Kong Registry, Hospital Authority. Of these, it is reasonable to assume that 20-25% could be HER2-positive.

About Neratinib

Neratinib is a potent irreversible tyrosine kinase inhibitor that inhibits tumor growth and metastasis through the blocking of the pan-HER family (HER1, HER2 and HER4) and downstream signal transduction. Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX (neratinib) tablets. Neratinib was also approved by the European Medical Agency (EMA) in September, 2018.

On November 5, 2019 Conatus Pharmaceuticals Inc. (Nasdaq:CNAT) reported financial results for the quarter and nine months ended September 30, 2019 (Press release, Conatus Pharmaceuticals, NOV 5, 2019, View Source [SID1234550316]).

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Recent Developments

In June 2019, Conatus announced that top-line results from its ENCORE-LF clinical trial of emricasan did not meet its primary endpoint, and, Conatus and its partner, Novartis, had no further development plans for emricasan. In September 2019, Conatus and Novartis mutually agreed to terminate the collaboration agreement between the parties for the global development and commercialization of emricasan.

As previously announced, Conatus has engaged Oppenheimer & Co., Inc., as its financial advisor to assist in the exploration and evaluation of strategic alternatives to enhance shareholder value. There can be no assurance of a successful outcome from these efforts, or of the form or timing of any such outcome.

In connection with the discontinuation of emricasan and Conatus’ efforts to explore and evaluate strategic alternatives, Conatus announced in June 2019 that it was implementing a restructuring plan in order to extend its resources, which included reducing staff and suspending development of its inflammasome disease candidate, CTS-2090, and in September 2019 it implemented another restructuring plan in order to extend its resources, which included further reducing staff.

Financial Results
The net loss for the third quarter of 2019 was $3.3 million compared with $4.6 million for the third quarter of 2018. The net loss for the first nine months of 2019 was $8.7 million compared with $14.1 million for the first nine months of 2018.

All revenues were related to the company’s collaboration with Novartis. Total revenues were $3.4 million for the third quarter of 2019 compared with $7.7 million for the third quarter of 2018. Total revenues were $21.2 million for the first nine months of 2019 compared with $26.2 million for the first nine months of 2018. The decreases in revenues for both periods were primarily due to lower emricasan-related research and development expenses resulting in corresponding lower revenues from Novartis.

Research and development expenses were $4.7 million for the third quarter of 2019 compared with $9.7 million for the third quarter of 2018. The decrease in research and development expenses was primarily due to lower spending related to emricasan-related activities. Research and development expenses were $22.7 million for the first nine months of 2019 compared with $32.5 million for the first nine months of 2018. These decreases were primarily due to lower emricasan-related research and development expenses.

General and administrative expenses were $2.0 million for the third quarter of 2019 compared with $2.7 million for the third quarter of 2018. General and administrative expenses were $7.7 million for the first nine months of 2019 compared with $8.0 million for the first nine months of 2018. These decreases were primarily due to lower personnel costs resulting from the restructuring plan announced in June 2019.

Cash, cash equivalents and marketable securities were $22.7 million at September 30, 2019, compared with $40.7 million at December 31, 2018. The company is projecting a year-end 2019 net balance of cash, cash equivalents and marketable securities of between $10 million and $15 million.

On November 5, 2019 Genecast (Beijing) Technology reported that it closed a $43 million Series D financing to expand its non-invasive cancer diagnostic business (Press release, ChinaBio, NOV 5, 2019, View Source [SID1234550315]). Founded in 2014, Genecast has developed a circulating tumor DNA detection technology that provides individualized cancer diagnoses. The company offers oncology diagnostic products and services to China biopharmas, collaborating with more than 20 biopharmas and providing comprehensive pre-clinical and clinical testing services. The D round, which brings Genecast’s total VC backing to $93.5 million, was led by CICC Capital.

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On November 5, 2019 The University of Texas MD Anderson Cancer Center and Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported an exclusive license agreement and research agreement to develop cord blood-derived chimeric antigen receptor-directed natural killer (CAR NK)-cell therapies, ‘armored’ with IL-15, for the treatment of B-cell malignancies and other cancers (Press release, Takeda, NOV 5, 2019, View Source [SID1234550313]).

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Under the agreement, Takeda will receive access to MD Anderson’s CAR NK platform and the exclusive rights to develop and commercialize up to four programs, including a CD19-targeted CAR NK-cell therapy and a B-cell maturation antigen (BCMA)-targeted CAR NK-cell therapy. Takeda and MD Anderson will also conduct a research collaboration to further develop these CAR NK programs.

"Our vision is to improve upon existing treatments by developing armored CAR NKs that could be administered off-the-shelf in an outpatient setting—enabling more patients to be treated effectively, quickly and with minimal toxicities," said Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson. "With their expertise in hematologic malignancies and commitment to developing next-generation cell therapies, Takeda is the ideal collaborator to help our team advance CAR NK-cell therapies to patients in need of treatments."

A Novel Approach to Delivering Off-the-Shelf CARs in an Outpatient Setting
MD Anderson’s allogeneic CAR NK platform isolates NK cells from umbilical cord blood and engineers them to express CARs against specified cancer targets. CAR NK cells are modified with a retroviral vector to deliver genes and enhance their effectiveness to attack specific tumors. A CD19 CAR increases the cells’ specificity for B-cell malignancies while the immunocytokine IL-15 enhances the proliferation and survival of the CAR NK cells in the body.

In contrast to current CAR T-cell therapies that utilize a patient’s own genetically modified T-cells and require a multi-week manufacturing process, CAR NK cells are intended to be manufactured from a non-related donor source and stored for off-the-shelf use, allowing treatment to be delivered more rapidly.

It is anticipated that the CD19 CAR NK-cell therapy could be administered in an outpatient setting. In an ongoing phase 1/2a clinical study treating patients with relapsed and refractory B-cell malignances, the CD19 CAR NK-cell therapy has not been associated with the severe cytokine release syndrome (CRS) or neurotoxicity observed with existing CAR-T therapies.

The development of MD Anderson’s CAR NK platform is led by Dr. Rezvani and is further supported by the adoptive cell therapy platform, Chronic Lymphocytic Leukemia Moon Shot and B-Cell Lymphoma Moon Shot, all part of the institution’s Moon Shots Program, a collaborative effort to rapidly develop scientific discoveries into meaningful clinical advances that save patients’ lives.

Takeda: Accelerating the Development of Multiple Next-Generation CAR Platforms
"MD Anderson’s CAR NK platform represents the curative potential of cell therapies, which is why we are establishing the CD19 CAR NK as our lead cell therapy candidate in oncology," said Andy Plump, M.D., Ph.D., President of Research and Development at Takeda. "We need to work swiftly and with purpose, and as such, we intend to initiate a pivotal study of the CD19 CAR NK in 2021."

In addition to CAR NK-cell therapies, Takeda and its partners are investigating multiple approaches to improving the safety, efficacy and accessibility of first-generation CAR T-cell therapies including gamma delta CAR Ts, induced pluripotent stem cell-derived CAR Ts, CAR Ts targeting solid tumors, and other next-generation approaches. Takeda plans to advance five oncology cell therapies to the clinic by the end of FY20.1 These platforms are being developed both with partners and by applying the expertise of Takeda’s translational cell therapy engine which provides bioengineering, chemistry, manufacturing and control (CMC), clinical and translational capabilities in a single footprint to overcome many of the manufacturing challenges experienced in cell therapy development.

Takeda is responsible for the development, manufacturing and commercialization of CAR NK products resulting under the agreement. MD Anderson will receive an upfront payment and is eligible to receive development and commercial milestones for each target as well as tiered royalties on net sales of any such CAR NK product.

MD Anderson and Takeda will continue research for the additional targets and CAR NK platform under the direction of a joint research committee. MD Anderson will implement an Institutional Conflict of Interest Management and Monitoring Plan for this research.