On January 12, 2020 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, reported the initiation of a Phase 2 trial evaluating ZW25 combination therapy and an agreement with Pfizer which advances the study (Press release, Zymeworks, JAN 12, 2020, View Source [SID1234553032]). Zymeworks’ HER2-targeted bispecific antibody ZW25 is being evaluated in combination with Pfizer’s Ibrance (palbociclib), an oral CDK4/6 inhibitor, and the hormone therapy fulvestrant in patients with previously-treated locally advanced and/or metastatic HER2-positive, HR-positive breast cancer. Zymeworks will sponsor the study, and Pfizer will provide palbociclib.

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"The initiation of this Phase 2 trial and collaboration with Pfizer mark significant milestones in our progress towards establishing ZW25 as the foundational HER2 therapy in multiple regimens across breast and other cancers," said Diana Hausman, M.D., Chief Medical Officer at Zymeworks. "Together, ZW25 and palbociclib have the potential to improve anti-tumor activity and minimize side effects for people living with advanced HER2‑positive, HR-positive breast cancer."

This Phase 2 clinical trial is a multicenter, open-label, two-part study (clinicaltrials.gov: NCT04224272). Part one of the study will evaluate the safety and tolerability of ZW25 in combination with palbociclib and fulvestrant and identify the recommended doses (RD) of ZW25 and palbociclib. Part two of the study will evaluate anti-tumor activity at the RD level. The trial will enroll up to 76 patients at sites in the United States and Canada, and expansion to Spain is planned.

ZW25 is being evaluated within a broad clinical development program in multiple HER2‑expressing cancers, including biliary tract, gastroesophageal adenocarcinoma (GEA), breast, colorectal, and gynecologic cancers. In an ongoing Phase 1 clinical trial, Zymeworks is evaluating ZW25 as a single agent and in combination with chemotherapy as potential treatments for patients with HER2-expressing cancers (clinicaltrials.gov: NCT02892123). For patients with HER2-positive GEA, ZW25 is being studied in a Phase 2 trial as a first-line treatment in combination with standard of care chemotherapy (clinicaltrials.gov: NCT03929666). Zymeworks plans to initiate a registration-enabling Phase 2 trial in previously-treated or recurrent HER2-positive biliary tract cancer in 2020.

About Breast Cancer

Breast cancer occurs when cells of the breast grow uncontrollably. According to the World Health Organization, each year, over 2 million new cases of breast cancer are diagnosed and over 600,000 deaths occur globally. Rates are increasing in nearly every region of the world. For locally advanced or metastatic breast cancer, the American Cancer Society estimates over 271,000 new US cases in men and women this year. About 15 to 20 percent of all breast cancers are positive for human epidermal growth factor receptor 2, or HER2. These cancers make too much HER2 protein, which may cause them to grow more quickly and spread to other parts of the body. Despite the advances with available HER2-targeted therapies, there is still an unmet medical need for people with all HER2-expressing cancers, particularly recurrent or metastatic disease that has progressed after standard of care therapy.

About ZW25

ZW25 is being evaluated in Phase 1 and Phase 2 clinical trials across North America and South Korea. It is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging anti-tumor activity in patients. Zymeworks is developing ZW25 as a HER2-targeted treatment option for patients with solid tumors that express HER2. The FDA has granted Fast Track designation to ZW25 for first-line gastroesophageal adenocarcinoma in combination with standard of care chemotherapy and Orphan Drug designation to ZW25 for the treatment of both gastric and ovarian cancers.

On January 12, 2020 Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, reported its strategic priorities and expected upcoming milestones (Press release, Syros Pharmaceuticals, JAN 12, 2020, View Source [SID1234553031]).

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"2019 was marked by significant progress across our pipeline, as Syros redefines the power of small molecules to control the expression of genes," said Nancy Simonian, M.D., Syros’ Chief Executive Officer. "We shared promising clinical data for SY-1425 in newly diagnosed unfit RARA-positive AML patients, as well as exciting preclinical data for SY-5609 that speak to its potential as a best-in-class oral CDK7 inhibitor. We ended the year on a strong note, entering into a collaboration with Global Blood Therapeutics that allows us to expand and accelerate our efforts to bring an oral medicine to market that may provide a functional cure for people living with sickle cell disease or beta thalassemia."

"We are excited to build on this progress in 2020, with multiple milestones expected across our clinical and discovery-stage pipeline," Dr. Simonian continued. "We look forward to advancing SY-5609 into clinical development in the first quarter, and to reporting clinical data for both SY-1425 and SY-5609, including potential proof-of-concept data for SY-1425 in RARA-positive relapsed or refractory AML patients, in the fourth quarter. In parallel, we continue to advance our discovery pipeline in cancer and monogenic disease areas where we believe we have the potential to deliver transformative gene control medicines for diseases that have eluded other genomics-based approaches."

Expected Clinical Milestones

SY-1425

Report potential proof-of-concept data in fourth quarter of 2020 from ongoing Phase 2 trial cohort evaluating SY-1425 in combination with azacitidine in RARA-positive relapsed or refractory acute myeloid leukemia (AML) patients.
Report mature data in fourth quarter of 2020 from fully enrolled Phase 2 trial cohorts evaluating SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.
SY-5609

Initiate Phase 1 trial of SY-5609 in first quarter of 2020 in patients with breast, colorectal, lung and ovarian cancers, as well as in patients with solid tumors of any histology harboring Rb pathway alterations.
Report initial safety, tolerability, pharmacokinetic and pharmacodynamic data in fourth quarter of 2020 from dose escalation portion of Phase 1 trial.
Report additional dose escalation data, including clinical activity data, in mid-2021.
Preclinical Pipeline

Syros expects to nominate its next development candidate by the end of 2021.
Syros also announced today that the Company’s second monogenic disease program is in myotonic dystrophy type 1.

Financial Guidance
Based on its current operating plans, Syros expects that its existing cash, cash equivalents and marketable securities are sufficient to fund its anticipated operating expenses and capital expenditure requirements into the fourth quarter of 2021 through key clinical milestones for both SY-1425 and SY-5609.

On January 12, 2020 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, reported that the company has obtained a license from Novartis to develop and commercialize an antibody cytokine engrafted protein, referred to as IOV-3001 (Press release, Iovance Biotherapeutics, JAN 12, 2020, View Source [SID1234553030]). Under the agreement, Iovance will pay an upfront payment to Novartis as well as low single digit milestones involved in initiation of patient dosing in various phases of clinical development for IOV-3001 and approval of the product in the U.S., EU and Japan. Novartis is also entitled to low-to-mid single digit royalties from commercial sales of the product.

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"As we progress our development efforts to commercialize TIL, we continue exploring ways to optimize the TIL treatment regimen which includes administration of IL-2," said Maria Fardis, Ph.D., MBA, Iovance’s President and Chief Executive Officer. "We therefore see a great strategic and long-term fit for Iovance to pursue development of a targeted and selective IL-2 analog with better pharmacokinetic properties. This product further adds to our research efforts in making safe and more potent TIL products with the potential opportunity for chronic administration."

IOV-3001 is an engineered IL-2 CDR graft which targets IL2R beta-gamma-expressing cells and limits IL2R alpha-beta-gamma-dependent Treg activation. The protein has an improved half-life leading to a better exposure while minimizing Cmax possibly reducing the side effects associated with IL-2 protein. Iovance will focus on GMP manufacturing of IOV-3001 during 2020 and may initiate IND-enabling activities as early as 2021.

On January 12, 2020 Exelixis, Inc. (Nasdaq: EXEL) reported its key priorities and anticipated milestones for 2020-21, including generating top-line data from key clinical trials, completing enrollment of ongoing studies, initiating new pivotal trials, and progressing its mid-stage and early pipeline (Press release, Exelixis, JAN 12, 2020, View Source [SID1234553029]). The company intends to make appropriate investments to maximize the clinical development opportunities for CABOMETYX (cabozantinib), which Exelixis believes could lead to as many as four additional approved indications by year-end 2021, while concurrently working to advance a pipeline of potential new Exelixis medicines through internal drug discovery and business development.

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"Exelixis is moving decisively to pursue important new indications for our lead product, CABOMETYX, and potentially bring new medicines to cancer patients in need of better treatment options," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "Cabozantinib is now an oncology franchise with global net revenue of more than $1 billion on an annual basis. Over the course of the next two years, we intend to expand the depth and breadth of the cabozantinib development program by obtaining top-line results from as many as six ongoing trials with label-enabling potential and initiating at least three new pivotal trials. If the data from these trials are market differentiating and result in regulatory approvals, we believe we could dramatically expand the number of patients that might benefit from cabozantinib, addressing a potential patient population more than four times greater in magnitude than our current opportunities in advanced renal cell and previously treated hepatocellular cancer. This result could have a significant impact on our business as we continue to invest in a multi-product oncology portfolio with the potential to lead to annual U.S. net product revenues approaching $4 billion by 2025."

Dr. Morrissey continued: "We continue to make strong progress in building our pipeline. Between our internal discovery activities and the four business development deals we’ve signed over the past two years, there are approximately 20 ongoing discovery programs focused on potentially adding novel and differentiated assets to the Exelixis development portfolio. In 2020, we believe these efforts could yield as many as three Investigational New Drug filings, and we also expect to advance multiple additional programs into preclinical development. As cabozantinib advances, we believe this earlier stage work, which we intend to complement with external strategic assets by leveraging our strong balance sheet, could bring forth a new generation of Exelixis medicines with the potential to strengthen our business and help cancer patients recover stronger and live longer."

Anticipated Cabozantinib Data Readouts in 2020

CheckMate 9ER: Bristol-Myers Squibb (BMS) and Exelixis anticipate results from CheckMate 9ER, the phase 3 pivotal trial evaluating cabozantinib in combination with nivolumab in previously untreated advanced or metastatic renal cell carcinoma (RCC), in the first half of 2020. BMS is sponsoring this trial, which completed enrollment in early 2019. If the data are positive, Exelixis, BMS and their respective partners plan to expeditiously pursue regulatory filings.
COSMIC-311: In the first half of 2020, Exelixis anticipates completing enrollment of the first 100 patients in this phase 3 pivotal trial evaluating cabozantinib versus placebo in patients with radioactive iodine-refractory differentiated thyroid cancer who have progressed after up to two VEGF receptor-targeted therapies. As planned, Exelixis expects to conduct an interim analysis in these first 100 patients for the co-primary endpoints of objective response rate and progression-free survival (PFS) and reach total enrollment of 300 patients in the second half of 2020.
COSMIC-312: Exelixis expects to complete enrollment in the first half of 2020 and conduct the analysis for the co-primary endpoint of PFS and an interim analysis for overall survival (OS) for this phase 3 pivotal trial evaluating cabozantinib in combination with atezolizumab (TECENTRIQ), Genentech’s anti-PD-L1 immune checkpoint inhibitor (ICI), versus sorafenib in previously untreated advanced hepatocellular carcinoma (HCC). The analyses are event-driven and may occur as early as in the second half of 2020.
COSMIC-021: COSMIC-021, the phase 1b trial evaluating cabozantinib in combination with atezolizumab in patients with locally advanced or metastatic tumors, enrolled more than 550 patients across the 24 expansion cohorts by the end of 2019. Exelixis expects to present data from the metastatic castration-resistant prostate cancer (mCRPC) cohort of the trial at the ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium in February 2020, and from the non-small cell lung cancer (NSCLC) cohort when data have matured and at the appropriate time in 2020. Based on regulatory feedback from the U.S. Food & Drug Administration (FDA) and if supported by the data from the mCRPC expansion cohorts, Exelixis intends to file with the FDA for accelerated approval in an mCRPC indication as early as 2021.
CheckMate 040, EXAMINER, and CANTATA: BMS and Exelixis expect that results of a cohort from the phase 1/2 CheckMate 040 trial investigating the safety and efficacy of nivolumab plus cabozantinib with or without ipilimumab in patients with advanced HCC will be presented at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium in January 2020. In addition, the PFS results for the medullary thyroid cancer EXAMINER trial, which compares the 140 mg capsule formulation with the 60 mg tablet formulation of cabozantinib, are expected in 2020. Finally, Calithera expects the analysis of CANTATA, a randomized phase 2 pivotal study of cabozantinib plus glutaminase inhibitor telaglenastat (CB-839) versus cabozantinib in previously treated RCC patients, to take place in the second half of 2020. CANTATA completed enrollment in October 2019 and is sponsored by Calithera; Exelixis provides cabozantinib for the trial.
Based on the milestones for trial enrollment and data readout, and if supported by the results, the current pivotal trials could support regulatory filings for cabozantinib in various additional tumor types and settings beginning in 2020.

Anticipated New Pivotal Trials in 2020

In 2020, based on emerging data from the COSMIC-021 trial, Exelixis and its collaboration partner Roche expect to initiate three new pivotal trials of cabozantinib in combination with atezolizumab under the companies’ expanded clinical development collaboration announced on December 19, 2019. The clinical program, which Roche and Exelixis will co-fund, is expected to include three phase 3 pivotal trials in advanced NSCLC, mCRPC and RCC. Additional details will be provided when the individual trials are initiated.

Additional Clinical Updates

COSMIC-021: In late 2020, Exelixis anticipates completing enrollment in COSMIC-021, which currently includes a total of 24 expansion cohorts and a projected target enrollment of up to 1,700 patients, pending the initiation of additional cohorts or expansion of selected existing cohorts. Since its initiation in 2017, data from COSMIC-021 have been instrumental in guiding Exelixis’ clinical development strategy for cabozantinib plus ICIs, including supporting the initiation of COSMIC-312 and the additional future trials described above.
COSMIC-313: Exelixis expects to complete enrollment for COSMIC-313, the phase 3 pivotal trial evaluating the triplet combination of cabozantinib, nivolumab and ipilimumab versus the combination of nivolumab and ipilimumab in patients with previously untreated advanced intermediate- or poor-risk RCC, in early 2021 and to report top-line results of the event-driven analyses from the study in the 2022 timeframe.
XL092: The dose escalation phase 1 trial for this next generation MET, AXL and VEGFR targeting tyrosine kinase inhibitor is ongoing, and Exelixis anticipates that dose expansion cohorts and potential combination cohorts with ICIs will begin to enroll in 2020.
Anticipated Discovery Milestones in 2020

Exelixis and its partners are currently advancing three compounds through preclinical development. If the data are supportive, Exelixis believes there is the potential for these compounds to reach Investigational New Drug (IND) filing status before the end of 2020. The programs are anticipated to include both small molecules (a CDK7 inhibitor and a TAM kinase inhibitor) and a next generation antibody-drug conjugate targeting tissue factor. In addition, multiple development candidates from internal and collaborative efforts are expected to reach preclinical development in 2020, and Exelixis believes these candidates have the potential to move into clinical trials starting in 2021.

Preliminary Fourth Quarter and Full Year 2019 Financial Results

Exelixis is providing the following unaudited preliminary 2019 financial results:

Total revenues for 2019 are approximately $972 million for the full year and approximately $245 million for the fourth quarter 2019.
Net product revenues for 2019 are approximately $765 million for the full year and approximately $200 million for the fourth quarter 2019.
Research and development expenses for 2019 are approximately $340 million for the full year and approximately $98 million for the fourth quarter 2019.
Selling, general and administrative expenses for 2019 are approximately $230 million for the full year and approximately $60 million for the fourth quarter 2019.
Cash and investments at year-end 2019 were approximately $1.4 billion.
The preliminary 2019 financial information presented in this press release has not been audited and is subject to change. The complete Exelixis Fourth Quarter and Full Year 2019 Financial Results are planned for release after market on Wednesday, February 26, 2020.

2020 Financial Guidance

Exelixis is providing the following financial guidance for 2020:

Total revenues are expected to be between $850 million and $900 million.
Net product revenues from the cabozantinib franchise (COMETRIQ and CABOMETYX) are anticipated to be between $725 million and $775 million, reflecting the continued evolution of the metastatic RCC and HCC treatment landscapes.
Cost of goods sold are expected to be between 4 percent and 5 percent of net product revenues.
Research and development expenses are expected to be between $460 million and $500 million corresponding with the expected initiation and completion of numerous late-stage cabozantinib trials as outlined previously and are expected to include non-cash expenses related to stock-based compensation expense of $25 million.
Selling, general and administrative expenses are expected to be between $230 million and $250 million with the continued commercial investment in CABOMETYX and the broader organization and are expected to include non-cash stock-based compensation expense of $30 million.
Guidance for the effective tax rate in 2020 is between 20 percent and 22 percent.
Cash and investments at year end 2020 are expected to be in the $1.5 billion to $1.6 billion range, reflecting our continued focus on balancing the appropriate level of investment in the business with a continued emphasis on generating free cash flow. Importantly, this cash guidance does not include any potential new business development activity, which remains a key priority for Exelixis as we continue to build toward becoming a multi-product oncology company.
Presentation and Webcast

Exelixis President and Chief Executive Officer Michael M. Morrissey, Ph.D., will provide a corporate overview and discuss the company’s preliminary fourth quarter and full year 2019 financial results, 2020 financial guidance, and key priorities and milestones for 2020-21 during the company’s presentation at the J.P. Morgan Healthcare Conference beginning at 4:30 p.m. PT on Tuesday, January 14, 2020.

To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company’s website at least 15 minutes prior to the presentation to ensure adequate time for any software download that may be required to listen to the webcast. A replay will also be available at the same location for 14 days

On January 12, 2020 Kitov Pharma Ltd. ("Kitov") (NASDAQ/TASE: KTOV), a clinical-stage company advancing first-in-class therapies to overcome tumor immune evasion and drug resistance, reported that it has appointed Bertrand Liang, M.D., Ph.D., as its Chief Medical Officer (Press release, Kitov Pharmaceuticals , JAN 12, 2020, View Source [SID1234553028]). Dr. Liang brings to Kitov extensive experience leading clinical development programs in oncology, and he will lead the medical affairs of Kitov in the development of its oncology pipeline including, CM-24, a novel checkpoint inhibitor, and NT-219, a novel small molecule targeting cancer drug resistance pathways. Kitov intends to initiate clinical trials for both programs in 2020.

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"Dr. Liang’s deep oncology expertise and demonstrated track record of successful drug development from concept through approval will be vital resources for Kitov as we begin progressing our novel assets into the clinic this year," said Isaac Israel, chief executive officer of Kitov. "Dr. Liang is an innovative leader who has founded multiple successful biopharmaceutical companies based on cutting-edge technologies across oncology, and we are thrilled to have him join our team. Furthermore, Dr. Liang’s prior leadership experience across all phases of clinical development at leading large biopharmaceutical companies, including Biogen, IDEC and Amgen, will be invaluable to Kitov’s clinical development plans."

Dr. Liang previously founded several leading biotechnology companies, including Tracon Pharmaceuticals, Coronado Biosciences (subsequently merged with Fortress Biotech) and Pfenex Inc. Earlier in his career, Dr. Liang was Site Head at Biogen IDEC (now Biogen), leading pre-clinical and clinical development, and Vice President, New Ventures; managing member, Forward Medical Sciences (a venture capital firm). He also served as Vice President and Head of Hematology and Oncology at IDEC; and Global Development Leader at Amgen, where he led the development of various cytokines that received U.S. Food and Drug Administration approval, including Neulasta. Dr. Liang has also held academic positions at the National Cancer Institute, University of Colorado and University of Vermont, where he headed Human Medical Genetics. He is an alumnus of the Feinberg School of Medicine at Northwestern University, the Institute of Materials Research and Innovation, University of Bolton, the Law School at University of London, Boston University, Regis University, and the MIT Sloan School of Management. Dr. Liang has authored over 75 peer-reviewed publications, chapters and books, and edited a number of volumes in the fields of Neurology and Oncology.

"Kitov’s focused approach in oncology to specifically target the challenges associated with current standards of care, namely the pathways leading to cancer drug resistance and tumor immune evasion, is a compelling strategy and I am incredibly excited to join the clinical development and leadership team," said Dr. Liang. "As a clinician and entrepreneur committed to advancing promising and innovative oncology treatments, I was encouraged by the differentiated mechanisms of action and early preclinical data for both CM-24 and NT-219 and I look forward to bringing both programs into the clinic and to strengthen Kitov as a leader in the Oncology arena."