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Compugen Reports Fourth Quarter and Calendar Year 2016 Results

On February 15, 2017 Compugen Ltd. (NASDAQ: CGEN), a leading predictive drug discovery company, reported financial results for the fourth quarter and year ended December 31, 2016 (Press release, Compugen, FEB 15, 2017, View Source [SID1234517721]).

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Anat Cohen-Dayag, Ph.D., CEO and President of Compugen, stated, "During the past year the Company has made important achievements and tremendous progress. For the first time in the history of the Company, we now have an internal preclinical development stage immuno-oncology pipeline that is being aggressively advanced towards a clinical stage pipeline. In addition, we have programs in the target validation stage, which are queued for incorporation into our therapeutic development pipeline. With these assets in hand, we firmly believe that we are positioned to take a transformational step forward that will establish Compugen’s position in the industry as a leading product discovery and development company with a portfolio of potential first-in-class products for cancer immunotherapy, and a promising immune-tolerizing therapy for autoimmune diseases, all based on our unique predictive discovery infrastructure."

Martin Gerstel, Chairman of Compugen, stated, "The largest portion of my long-term chairmanship at Compugen has been devoted to establishing a world leading, broadly applicable predictive discovery capability, and then, based on the initial use of this unique capability, developing an extremely promising early stage immuno-oncology pipeline. I believe that based on our past achievements, and in particular, the progress made last year as mentioned by Anat, we have now clearly accomplished these very impressive objectives. Furthermore, in my opinion, following the entrance of a potential first-in-class product candidate from our Pipeline Program into human clinical testing, and the signing of an additional high-value collaboration agreement, these past achievements will be more broadly recognized, and I have no doubt that we will then be seen as, and in fact be, a very different company with both new opportunities and new challenges. Accordingly, I believe it would be appropriate for Compugen to have a new chairperson on board at that time to guide the next chapter of our corporate growth as the Company leverages its unique capabilities to expand and enhance our medical and commercial value."

Mr. Gerstel continued, "Therefore, I have requested the Board to initiate a process to identify and recruit an appropriate person with the required capabilities and experience to replace me as chairperson. A recruitment process for a chairperson of a publicly owned company typically takes six months or more from initiation until the new chairperson is in place. We are announcing this now so that we can begin a careful and open search without undo time pressure. Based on current estimates, a new chairperson may be selected before we have achieved both an IND filing on a Pipeline Product candidate and the signing of an additional industry collaboration. In any case, it is my intention to both continue with the Company, but of course in a different capacity in the event of a new chairperson, and to also maintain in total my equity ownership position until at least both of these key objectives are achieved."

Dr. Cohen-Dayag commented, "Martin’s leadership and vision have been a driving force for the Company for two decades, however, I fully understand his belief that we are rapidly nearing a time when a new chairperson would be appropriate to guide the next chapter of our corporate growth."

Financial Results
Revenues for the fourth quarter of 2016 were $0.1 million, compared with $8.3 million in the comparable period of 2015. The decrease in revenues is primarily attributable to achievement of the third preclinical Bayer collaboration milestone for CGEN-15001T in the amount of $7.8 million in the comparable quarter of 2015. Revenues for the year ended December 31, 2016 were $0.7 million, compared with $9.3 million for the year ended December 31, 2015. The decrease in revenues is attributed to the lower amount of Bayer milestones achieved in 2016 and the amortization of the $10 million upfront payment received in 2013 at the time the collaboration was signed.

R&D expenses for the fourth quarter and year ended December 31, 2016 were $6.3 million and $24.5 million, respectively, compared with $5.8 million and $21.2 million for the comparable periods in 2015. The increase reflects a substantial increase in our preclinical activities involving our Pipeline Program candidates, primarily COM701 and our anti-TIGIT antibody.

Net loss for the fourth quarter of 2016 was $8.5 million, or $0.17 per diluted share, compared with a net loss of $0.5 million, or $0.01 per diluted share, in the comparable period of 2015. Net loss for the year ended December 31, 2016 was $31.5 million, or $0.62 per diluted share, compared with a net loss of $20.2 million, or $0.40 per diluted share, for the year ended December 31, 2015.

As of December 31, 2016, cash, cash related accounts, short-term and long-term bank deposits totaled $61.5 million, compared with $81.4 million at December 31, 2015. The Company has no debt.

Genomic Health Announces 2016 Fourth Quarter and Year-End Financial Results, Provides 2017 Financial Outlook

On February 14, 2017 Genomic Health, Inc. (Nasdaq: GHDX) reported financial results and business progress for the quarter and year ended December 31, 2016 (Press release, Genomic Health, FEB 14, 2017, View Source [SID1234517742]).

Total revenue was $327.9 million in the full year 2016, compared with $287.5 million in 2015, an increase of 14 percent.

U.S. product revenue was $280.1 million in the full year 2016, compared with $246.0 million in 2015, an increase of 14 percent. Prostate test revenue in the U.S. was $10.8 million and contributed to approximately 3 percent of total product revenue growth in the year.

International revenue for the full year 2016 was $46.8 million compared with $41.5 million in 2015, an increase of 13 percent, and an increase of 15 percent on a constant currency basis.i

"In 2016, we delivered double-digit revenue and test growth for the year, and achieved profitability in the fourth quarter," said Kim Popovits, chairman of the board, chief executive officer and president of Genomic Health. "With substantial opportunity for growth in our global breast and U.S. prostate business and leverage of our unique commercial channel with the planned launch this year of Oncotype DX AR-V7 Nucleus Detect, we expect to continue to deliver long-term revenue growth with improved profitability."

Operating loss was $15.4 million for the year ended December 31, 2016, compared with an operating loss of $34.0 million for the year ended December 31, 2015. Net loss was $13.9 million for the year ended December 31, 2016, compared with a net loss of $33.3 million for the year ended December 31, 2015.

Basic and diluted net loss per share was $0.42 for the year ended December 31, 2016, compared with a basic and diluted net loss per share of $1.03 for the year ended December 31, 2015.

More than 118,570 Oncotype test results were delivered for the year ended December 31, 2016, an increase of 11 percent, compared with more than 107,030 test results delivered in 2015. Oncotype DX breast cancer tests delivered in the U.S. grew 7 percent in the full year, compared to the prior year. Oncotype DX Genomic Prostate Score tests delivered in the U.S. grew 16 percent in the full year, including 29 percent in the fourth quarter, and represented approximately 8 percent of total test volume in 2016. International tests delivered grew 23 percent in the full year compared to the prior year and represented approximately 24 percent of total test volume in 2016.

Additional Fourth Quarter 2016 Financial Results

Total revenue was $82.7 million in the fourth quarter of 2016, compared with $75.1 million in the fourth quarter of 2015, an increase of 10 percent.

U.S. product revenue was $70.0 million in the fourth quarter of 2016, an increase of 9 percent, compared with $64.5 million in the same period in the prior year. Prostate test revenue in the U.S. of $3.6 million contributed to approximately 4 percent of the year-over-year growth.

International product revenue was $12.0 million in the fourth quarter of 2016, compared with $10.6 million a year ago, an increase of 13 percent, and an increase of 16 percent on a constant currency basis.i

In the fourth quarter of 2016, more than 30,020 Oncotype test results were delivered, an increase of 8 percent, compared with more than 27,730 test results delivered in the same period in 2015.

Operating income for the fourth quarter of 2016 was $1.5 million, compared with an operating loss of $3.1 million for the fourth quarter of 2015. Net income was $1.4 million for the fourth quarter of 2016 compared with a net loss of $2.7 million for the fourth quarter of 2015.

Basic and diluted net income per share was $0.04 for the fourth quarter of 2016 compared with basic and diluted net loss per share of $0.08 for the same period in 2015.

Cash and cash equivalents and short-term marketable securities at December 31, 2016 were $87.7 million excluding the fair value of the company’s investment in a marketable security of $9.3 million, compared with $76.8 million at December 31, 2015 excluding the fair value of the company’s investment in a marketable security of $18.1 million.

2017 Financial Guidance

"In 2017 at the mid-point of revenue guidance, we expect to deliver 11 percent revenue growth and positive net income for the full year, which requires operating leverage of more than 40 percent," said Brad Cole, chief operating officer and chief financial officer of Genomic Health. "We anticipate that expected reimbursement progress in the second half of the year will contribute to accelerated revenue growth."

The company is providing the following financial guidance for the full year ending December 31, 2017:

· Total product revenue of between $355 to $370 million, representing growth of between 9 and 13 percent compared to 2016; and

· Positive net income at mid-point of revenue guidance.

Recent Business Highlights

Oncotype DX Commercial Progress

· The American Joint Committee on Cancer (AJCC) incorporated the Oncotype DX Breast Recurrence Score in its recently published Eighth Edition AJCC Cancer Staging Manual. Representing a rigorous, multi-disciplinary assessment, the updated criteria identify Oncotype DX as the only multi-gene test with Level I evidence to be used by pathologists and clinicians for formal staging of breast cancer patients.

· Established additional coverage for the Oncotype DX Genomic Prostate Score, bringing the total number of U.S. covered lives to more than 65 million.

· Knappschaft, one of Germany’s largest public health insurance funds, began offering Oncotype DX to early-stage breast cancer patients through an exclusive agreement, bringing the total number of German private covered lives to nearly 9 million.

Presentations and Publications

· Received acceptance to present results from a large Oncotype DX Genomic Prostate Score validation study, conducted in collaboration with Kaiser Permanente Northern California, at the Genitourinary (GU) Cancers Symposium, the European Association of Urology (EAU) Congress and the American Urological Association (AUA) Annual Meeting. With these new data, Oncotype DX is the first and only genomic prostate test validated in all major short- and long-term endpoints, including adverse pathology, biochemical recurrence, metastasis and prostate cancer specific death.

· Investigators from Memorial Sloan Kettering Cancer Center (MSK) and Epic Sciences Inc. published findings in European Urology demonstrating that only nuclear localization of the AR-V7 protein in circulating tumor cells (CTCs) from metastatic castration-resistant prostate cancer (mCRPC) patient blood samples is predictive of therapeutic benefit. Genomic Health expects to begin offering the Oncotype DX AR-V7 Nucleus Detect test this year.

· Presented results from multiple studies demonstrating the unparalleled value of the Oncotype DX test in individualizing breast cancer treatment decisions for patients with various stages of the disease at the 2016 CTRC-AACR San Antonio Breast Cancer Symposium. Presentations included two overviews of prospective outcomes data and clinical evidence supporting use of the test in both node-positive and node-negative disease.

· The Journal of the National Cancer Institute published results of an NSABP-led study demonstrating the Oncotype DX Breast Recurrence Score is an independent predictor of locoregional recurrence risk in node-positive breast cancer patients treated with chemo-endocrine therapy.

· The Journal of the National Cancer Institute published results of an additional analysis from the second clinical validation study of the Oncotype DX DCIS Score demonstrating its ability to identify women with low risk of recurrence following surgery who can avoid radiation therapy.

· The European Journal of Surgical Oncology published a UK decision impact study of node-negative and node-positive breast cancer patients demonstrating the Oncotype DX Breast Recurrence Score significantly reduced the use of chemotherapy and can lead to significant cost savings for the National Health Service (NHS).

· Received acceptance to present four Oncotype DX studies at the upcoming Miami Breast Cancer Conference and 15 Oncotype DX studies at the upcoming St. Gallen Breast Cancer Conference in March.

Incyte and Agenus Amend Collaboration Agreement

On February 14, 2017 Incyte Corporation (Nasdaq:INCY) and Agenus Inc. (Nasdaq:AGEN) reported that the companies have amended the License, Development and Commercialization Agreement that was originally entered into January 9, 2015 (Press release, Incyte, FEB 14, 2017, View Source [SID1234517737]). The amended agreement converts the ongoing GITR and OX40 antibody programs from co-funded development and profit-sharing arrangements to royalty-bearing programs, with Incyte now responsible for funding and conducting global development and commercialization. Should candidates from either of these two programs be approved, Agenus would now become eligible to receive 15 percent royalties on global net sales of each approved product.

The ongoing TIM-3 and LAG-3 antibody programs remain royalty-bearing programs, at tiered rates of 6 to 12 percent, with Incyte retaining exclusive world-wide clinical development and commercial responsibilities.

Pursuant to the amended agreement, Agenus will receive today accelerated milestone payments of $20 million from Incyte related to the clinical development of INCAGN1876 (anti-GITR agonist) and INCAGN1949 (anti-OX40 agonist). Across all programs in the collaboration, Agenus will now be eligible to receive up to a total of $510 million in future potential development, regulatory and commercial milestones.

The parties have also entered into a separate Stock Purchase agreement whereby Incyte will purchase 10 million shares of Agenus common stock today at $6 per share.

"The antibody discovery collaboration between Incyte and Agenus has progressed well and has already resulted in two programs in clinical trials. We look forward to further developing our GITR and OX40 antibody programs, and exploring immunotherapy combinations with these compounds and other agents in the near future," said Hervé Hoppenot, CEO of Incyte.

"We believe the amended agreement will help streamline the development of our collaboration portfolio, provide the opportunity to prioritize our other internal programs towards rapid commercialization and help foster the development of our portfolio of novel I-O programs," said Garo Armen, Ph.D., Chairman and CEO of Agenus. "The revised agreement will also strengthen Agenus’ balance sheet and reduce cash burn."

Chi-Med Initiates First-In-Human Clinical Trial of Novel FGFR Inhibitor HMPL-453 in Australia

On February 14, 2017 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) reported that it has initiated the first-in-human ("FIH") Phase I clinical trial of HMPL-453 in Australia (Press release, Hutchison China MediTech, FEB 14, 2017, http://www.chi-med.com/initiates-fih-trial-of-fgfr-inhibitor-hmpl-453/ [SID1234517720]). HMPL-453 is a novel, highly selective and potent small molecule inhibitor targeting fibroblast growth factor receptor ("FGFR"). The first drug dose was administered on February 14, 2017.

FGFRs are a sub-family of receptor tyrosine kinases. Activation of FGFR signaling pathways is central to several biological processes, including angiogenesis, tissue growth and repair. Given its complexity and critical role in a number of important physiological processes, aberrant FGFR signaling has been found to be a driving force in tumor growth, promotion of angiogenesis, as well as, conferring resistance to anti-tumor therapies. To date, there are no approved therapies specifically targeting the FGFR signaling pathway.

The FIH dose-escalation trial aims to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of HMPL-453 in patients with advanced or metastatic solid malignancies, who have failed or are unable to tolerate standard therapies or for whom no standard therapies exist. This open-label study consists of two preliminary phases, a dose-escalation (stage 1) and a dose-expansion stage (stage 2).

In pre-clinical studies, HMPL-453 demonstrated superior potency and better kinase selectivity as compared to other drugs in the same class, as well as a favorable safety profile. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02966171.

Chi-Med and AstraZeneca Present Savolitinib Papillary Renal Cell Carcinoma Phase II Results at 2017 Genitourinary Cancers Symposium

On February 14, 2017 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) and AstraZeneca PLC ("AstraZeneca") reported that they will present data from the ongoing Phase II clinical trial of savolitinib in patients with papillary renal cell carcinoma ("PRCC") at the 2017 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO-GU"), to be held in Orlando, Florida from February 16 to 18, 2017 (Press release, Hutchison China MediTech, FEB 14, 2017, http://www.chi-med.com/savolitinib-prcc-at-2017-asco-gu/ [SID1234517719]). Savolitinib, a highly selective inhibitor of c-Met receptor tyrosine kinase, has shown early clinical benefit in multiple Phase I and II studies in a number of cancers. It was developed as a potent and highly selective oral inhibitor specifically designed to address issues observed in the clinic with first-generation c-Met inhibitors, including renal toxicity.

PRCC, the second most common histologic subtype of renal cell carcinoma ("RCC"), is associated with alterations in the c-Met gene (e.g. mutations, amplifications, and/or chromosomal changes). Therapies that are currently available for RCC patients have demonstrated only modest benefit in PRCC and there are no therapies specifically approved for the treatment of c-Met-driven PRCC. National Comprehensive Cancer Network guidelines recommend enrolling patients in clinical trials for first-line systemic therapy.

"There is a clear unmet medical need in PRCC," said Toni Choueiri, Director of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute. "The dataset from this Phase II study is compelling, with a very clear efficacy signal in MET-driven patients and an encouraging long duration of response, while remaining very well tolerated." He added, "These results support the initiation of the pivotal Phase III trial in a selected population of MET-driven PRCC. This innovative patient selection approach would be the first ever molecularly selected trial in renal cell carcinoma."

"We are delighted to report this highly encouraging progression-free survival data in Met-driven papillary renal cell carcinoma, a disease with no approved treatment options," said Christian Hogg, Chief Executive Officer of Chi-Med. "With development of the companion diagnostic assay to screen Met-driven disease now also complete we are preparing for the initiation of our global Phase III study, the first global registration trial for savolitinib."

The current Phase II trial is the largest prospective clinical study ever conducted in PRCC patients. It is a global single arm study of savolitinib in 109 patients with locally advanced or metastatic PRCC and was initiated in May 2014. It is being conducted in 22 clinical centers in the US, Canada, UK, and Spain, and completed enrollment in October 2015. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02127710. The most recent results of the study will be presented in detail as follows:

Presentation Title: A Single-Arm Biomarker-Based Phase II Trial of Savolitinib in Patients with Advanced Papillary Renal Cell Cancer
Authors: Toni K. Choueiri, Elizabeth Plimack, Hendrik-Tobias Arkenau, Eric Jonasch, Daniel Y. C. Heng, Thomas Powles, Melanie M. Frigault, Edwin Clark, Amir Handzel, Humphrey Gardner, Shethah Morgan, Laurence Albiges, Sumanta Kumar Pal
Abstract No: 436
Session: Session C: Penile, Urethral, and Testicular Cancers; Renal Cell Cancer
Date & Time: Saturday, February 18, 2017, 7:00 AM-7:55 AM and 11:30 AM-1:00 PM (EST)

Once presented, the presentation will be available at www.chi-med.com/news. Further information about ASCO (Free ASCO Whitepaper)-GU is available at gucasym.org.

Chi-Med and AstraZeneca are currently initiating a global pivotal Phase III trial, the first pivotal study ever conducted in c-Met-driven PRCC and the first molecularly selected trial in RCC.

Over the course of 2017, Chi-Med and AstraZeneca are also conducting a comprehensive molecular epidemiology study of approximately 300 PRCC patient samples to further understand the correlations between c-Met alterations and patient outcomes, including any predictive biomarkers.

ABSTRACT
A single-arm biomarker-based phase II trial of savolitinib in patients with advanced papillary renal cell cancer (PRCC)

Toni K. Choueiri1, Elizabeth Plimack2, Hendrik-Tobias Arkenau3, Eric Jonasch4, Daniel Y. C. Heng5, Thomas Powles6, Melanie M. Frigault7, Edwin Clark7, Amir Handzel7, Humphrey Gardner7, Shethah Morgan8, Laurence Albiges9, Sumanta Kumar Pal10

1Dana-Farber Cancer Institute, Boston, US 2Fox Chase Cancer Center, Philadelphia, US 3Sarah Cannon Research Institute, London, UK 4MD Anderson Cancer Centre, Houston, US 5Tom Baker Cancer Center, Calgary, Canada 6Barts Cancer Institute, London, UK 7AstraZeneca, Waltham, US, 8AstraZeneca, Cambridge, UK 9Institute Gustave Roussy, Paris, France 10City of Hope, Duarte, US

Background: Savolitinib (HMPL-504/Volitinib, AZD6094) is a potent, selective mesenchymal epithelial transition ("MET") inhibitor (IC50 of 4 nM). MET and its ligand, hepatocyte growth factor ("HGF"), are known to play an important role in the molecular events underlying oncogenesis in PRCC, a disease without a clear standard of care and marked by alterations of chromosome 7 (containing both MET and HGF genes) in a majority of patients as well as gene amplification or MET kinase domain mutations (Albiges et al 2014, Linehan et al, 2015).

Methods: This study evaluates savolitinib in PRCC patients dosed at 600 mg daily until disease progression. Objective Response Rate ("ORR") is the primary endpoint. Progression-Free Survival ("PFS") & Duration of Response are secondary endpoints. Patient Reported Outcome ("PRO") and Health-Related Quality of Life ("HRQoL") questionnaires are exploratory endpoints. Eligibility includes naïve and previously treated metastatic PRCC, ECOG PS 0 or 1. Archival tumor was used to centrally confirm PRCC pathology post hoc and to determine MET status using Next Generation Sequencing (Foundation Medicine, Inc., US).

Results: As of 27 June 2016, 109 patients were dosed. Best response was PR n=8, SD n=43, PD n=48 & 10 patients were not evaluable for response. 44 patients are MET-driven (MET/HGF gene copy number gain or kinase domain mutations), 46 patients were MET-negative, 19 patients are status unknown. MET-driven pts included Papillary Type I & II histologies. All 8 responders were in the MET-driven group, 18% ORR in this subset. Median PFS in the MET-driven group was 6.2 months (95% CI: 4.1–7.0) vs. 1.4 months (95% CI: 1.4–2.7) in the MET-negative group (p=0.002). Overall 10/109 patients had adverse events ("AEs") leading to discontinuation. 23/109 patients had ≥ Grade 3 toxicity related to savolitinib. The most common AEs (all grades) includes: nausea (39%), fatigue (27%), edema (18%) and abnormal liver function tests ("LFTs") (17%). One death from hepatic encephalopathy was considered related to savolitinib. PRO & HRQoL data was not statistically analyzed, descriptive data support main efficacy findings.

Conclusions: In the largest biomarker-profiled trial dedicated to PRCC, savolitinib was generally well tolerated with anti-tumor activity in MET-driven patients. These findings warrant further clinical investigation of savolitinib in MET-driven PRCC.

About the Unmet Medical Need in c-Met-Driven PRCC Patients
Worldwide, about 366,000 new patients are diagnosed with kidney cancer annually, and the total market for kidney cancer treatments is expected to reach US$4.5 billion in 2020, according to Frost & Sullivan. RCC accounts for approximately 80-85% of kidney cancer and has several histological sub-types with different genetic and biochemical characteristics. Among these histologic variants of RCC, clear cell RCC ("ccRCC") is the most common, accounting for 75-80% of RCC.

PRCC is the most common of the non-clear cell renal carcinomas accounting for 10-15% of RCC. The proportion of PRCC patients whose tumors are c-Met-driven has historically been estimated at 40-70%. In the largest study to date, presented at the annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2014, analysis of 220 frozen tumor samples catalogued in the French RCC Network indicated that 55-60% of PRCC patients showed gains in Chromosome 7 (i.e. c-Met amplification).

The biology and molecular characteristics of PRCC are different from those of ccRCC. This results in significantly worse prognosis and treatment outcomes for patients with PRCC when compared to patients with ccRCC. Highlighting the unmet need is the fact that, although there are several drugs approved for use in RCC (the latest being approved in April 2016), these approvals were generally on the basis of studies conducted with a preponderance of ccRCC patients. The need for different agents and more specific data tailored to the PRCC disease setting has been identified as a critical gap in the care of these patients.