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Merck Announces Orphan Drug Designation for Investigational Therapy Tepotinib in Patients with NSCLC Harboring MET Gene Alterations

On November 20, 2019 Merck, a leading science and technology company, reported that the Japanese Ministry of Health, Labour and Welfare (MHLW) has granted orphan drug designation (ODD) for its investigational therapy tepotinib* for patients with non-small cell lung cancer (NSCLC) harboring MET gene alterations (Press release, Merck & Co, NOV 20, 2019, View Source [SID1234551538]).

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"Advanced NSCLC harboring MET gene alterations is associated with aggressive tumor behavior and poor clinical prognosis," said Luciano Rossetti, Global Head of Research & Development for the Biopharma business of Merck. "This orphan drug designation helps to advance this program within Japan and, coupled with the SAKIGAKE ‘fast-track’ designation received last year, provides important mechanisms, such as priority review, to quickly deliver this medicine to Japanese patients with this difficult-to-treat disease."

The Japan MHLW ODD program is designed to promote research and development of orphan drugs for diseases that affect fewer than 50,000 patients in Japan, and for which significant unmet medical need exists. An investigational drug can qualify for ODD if there is no approved alternative treatment option or if there is an expectation of high efficacy or safety compared to existing treatment options. Drugs receiving ODD qualify for several benefits intended to support development, such as guidance and subsidies for research and development activities from the MHLW, preferential tax treatment, priority consultation for clinical development, and priority review of applications.

Discovered in-house at Merck, tepotinib is an investigational oral MET inhibitor that is designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations, including both MET exon 14 skipping alterations and MET amplifications, or MET protein overexpression. It has been designed to have a highly selective mechanism of action,1 with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations.

Alterations of the MET signaling pathway are found in various cancer types, including 3-5% of NSCLC cases, and correlate with aggressive tumor behavior and poor clinical prognosis.2-4 Lung cancer is the most common type of cancer worldwide, with two million cases diagnosed annually.5

Tepotinib is being investigated in the ongoing VISION study (NCT02864992), which showed preliminary efficacy in patients harboring METex14 skipping alterations detected by liquid biopsy (LBx) or tissue biopsy (TBx) across different lines of treatment.

Results from the interim analysis of the VISION study were presented in an oral presentation at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting6 and the 2019 Japan Society of Medical Oncology (JSMO) Annual Meeting.7 The use of both LBx and TBx to identify patients for the VISION study is intended to support improved patient selection and is consistent with the company’s focus on patient-centric drug development.

Tepotinib is also being investigated in the INSIGHT 2 study (NCT03940703) in combination with the tyrosine kinase inhibitor (TKI) osimertinib in epidermal growth factor receptor (EGFR) mutated, MET amplified, locally advanced or metastatic NSCLC having acquired resistance to prior EGFR TKI.

In March 2018, the Japan MHLW granted SAKIGAKE ‘fast-track’ designation for tepotinib in advanced (stage IIIB/IV) NSCLC harboring METex14 skipping alterations and, in September 2019, the US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) for tepotinib in patients with metastatic NSCLC harboring METex14 skipping alterations who progressed following platinum-based cancer therapy.

*Tepotinib is currently under clinical investigation and not approved for any use anywhere in the world.

About Non-Small Cell Lung Cancer

With two million cases diagnosed annually, lung cancer (including trachea, bronchus and lung) is the most common type of cancer worldwide, and the leading cause of cancer-related death, with 1.7 million mortality cases worldwide.5 Alterations of the MET signaling pathway, including MET exon 14 skipping alterations and MET amplifications, occur in 3-5% of NSCLC cases.2-4

About Tepotinib

Tepotinib, discovered in-house at Merck, is an investigational oral MET inhibitor that is designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations, including both MET exon 14 skipping alterations and MET amplifications, or MET protein overexpression. It has been designed to have a highly selective mechanism of action,1 with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations.

Tepotinib is currently being investigated in NSCLC and Merck, is actively assessing the potential of investigating tepotinib in combination with novel therapies and in other tumor indications.

References

Bladt, F, et al. Clin Cancer Res 2013;19:2941-2951
Reungwetwattana T, et al. Lung Cancer 2017;103:27-37.
Mo HN, et al. Chronic Dis Transl Med 2017; 3(3):148-153.
Lutterbach B, et al. Cancer Res 2007;67:2081–8.
Bray F, et al. CA Cancer J Clin. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 2018;68(6):394–424. View Source View Source
Paik P, et al. J Clin Oncol 2019;37: (suppl; abstr 9005).
Sakai H, et al. Ann Oncol 2019;30(Suppl_6):Abstract MO2-15-5.
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Anixa Biosciences Announces Collaboration with Idaho Urologic Institute on Cchek™ Prostate Cancer Study

On November 20, 2019 Anixa Biosciences, Inc. (NASDAQ: ANIX), a biotechnology company focused on harnessing the body’s immune system in the fight against cancer, reported its collaboration with Idaho Urologic Institute, PA (IUI) in the Cchek early cancer detection study (Press release, Anixa Biosciences, NOV 20, 2019, View Source [SID1234551536]). IUI will provide patient samples for Anixa’s ongoing prostate cancer study, including support of clinical validation of Anixa’s Cchek Prostate Cancer Confirmation test.

IUI is one of several sites across the U.S. participating in this study. Dr. Lisa Parillo will serve as the Principal Investigator for the study at IUI.

Dr. Amit Kumar, Chief Executive Officer of Anixa, stated, "We are pleased to have IUI join our expanding group of Cchek collaboration partners. Our large and growing team of influential collaborators has been key to the development of our artificial intelligence driven liquid biopsy for early cancer detection. We look forward to IUI’s participation as we continue the clinical validation phase of the Cchek Prostate Cancer Confirmation test, in preparation for commercial launch later this year."

About Cchek
Cchek is an early cancer detection technology, which measures a patient’s immunological response to a malignancy by analyzing immune system cells in peripheral blood. The goal is to utilize the technology to determine a patient’s cancer status from a simple blood draw, eliminating the need for a biopsy, which can be an expensive, painful and invasive procedure. Further, conventional methods using current cancer screening tests often lack accuracy and reliability. Anixa’s orthogonal approach using flow cytometry coupled with artificial intelligence provides an alternative method with greater affordability, efficacy and efficiency. To date, Anixa has successfully used Cchek to detect the presence of 20 different cancers including lung, colon, breast and prostate. The robust cancer detection performance of Cchek makes it a platform from which multiple cancer diagnostic tests may be developed. The first such test, a prostate cancer confirmation test, is slated for commercial launch by the end of 2019.

Sierra Oncology Launches the MOMENTUM Phase 3 Clinical Trial for Patients with Myelofibrosis

On November 20, 2019 Sierra Oncology, Inc. (Nasdaq: SRRA), a late-stage drug development company focused on the development and commercialization of momelotinib, a JAK1, JAK2 & ACVR1 inhibitor with a potentially differentiated therapeutic profile for the treatment of myelofibrosis, reported that it has launched the MOMENTUM clinical trial for patients with myelofibrosis (Press release, Sierra Oncology, NOV 20, 2019, View Source [SID1234551535]). The randomized double-blind global Phase 3 trial is designed to confirm the efficacy of momelotinib on myelofibrosis symptoms, transfusion independence and splenomegaly, as compared to danazol. The trial is targeting enrollment of 180 myelofibrosis patients who are symptomatic, anemic and have been treated previously with a JAK inhibitor.

"I am pleased to act as Chief Investigator for this important global trial for the myelofibrosis patient community," said Dr. Srdan Verstovsek, MD, PhD, Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, Houston, Texas. "JAK inhibitors remain the cornerstone of myelofibrosis treatment but new options in this class are needed for the majority of patients who have difficulty tolerating the currently approved agents due to the cytopenias they can exacerbate or induce. Momelotinib could become a suitable alternative for many patients previously treated with a JAK inhibitor due to its ability to positively address all three hallmarks of myelofibrosis – symptoms, anemia and an enlarged spleen. Critically, momelotinib has consistently demonstrated positive anemia benefits in its prior clinical trials. This anemia benefit is biologically-driven, via potent inhibition of the ACVR1/hepcidin axis, a mechanism that is unique in the JAK inhibitor class."

"The launch of the MOMENTUM trial is a key milestone in our global registration strategy for momelotinib, aimed at bringing this important and differentiated therapy to patients with myelofibrosis," said Dr. Barbara Klencke, Chief Development Officer of Sierra Oncology. "MOMENTUM is designed to confirm the array of benefits observed in prior Phase 3 studies, where momelotinib demonstrated a unique ability to improve anemia and reduce transfusion dependency in patients with myelofibrosis, while also providing clinically comparable benefits on constitutional symptoms and enlarged spleens to other JAK inhibitors. To support our proposed study timeline, global clinical trial sites are anticipated to be activated over the coming months with top-line data from MOMENTUM anticipated in the fourth quarter of 2021."

"The launch of MOMENTUM is a major step in advancing Sierra’s vision of becoming a commercial company. Momelotinib is a promising late stage asset that targets a sizable unaddressed global market with a clear path forward to registration. Importantly, momelotinib’s clinical potential has been previously demonstrated in two large, completed Phase 3 clinical trials, which informed the design of MOMENTUM," said Dr. Nick Glover, President and CEO of Sierra Oncology. "As recently announced, Sierra has secured capital that we expect to be sufficient to execute our development strategy into the second half of 2022, providing us with the financial runway to advance momelotinib towards its anticipated commercialization. Moreover, we also recently announced that we had amended our Asset Purchase Agreement (the "Amendment") with Gilead Sciences, Inc. ("Gilead"). Pursuant to the terms of the Amendment, and subject to certain conditions, Gilead will become a stockholder in Sierra in exchange for substantive reductions in the annual royalty rates payable by Sierra to Gilead upon commercialization of momelotinib. This Amendment will meaningfully benefit Sierra’s stockholders should momelotinib prove commercially successful."

About Momelotinib
Momelotinib is a potent, selective and orally-bioavailable JAK1, JAK2 & ACVR1 inhibitor with a differentiated therapeutic profile in myelofibrosis encompassing robust constitutional symptom improvements, a range of meaningful anemia benefits, including eliminating or reducing the need for frequent blood transfusions, and comparable spleen control to ruxolitinib. More than 1,200 subjects have received momelotinib since clinical studies began in 2009, including more than 800 patients treated for myelofibrosis.

Chronic, progressive anemia is a key hallmark of myelofibrosis and transfusion dependence is the most important negative prognostic indicator of reduced survival in this disease. Approximately 60% of patients are anemic and 45% are transfusion dependent within one year of diagnosis, with most patients ultimately progressing to transfusion dependency. Unfortunately, currently approved JAK inhibitor therapies can induce or worsen anemia, exacerbating this significant unmet medical need in anemic myelofibrosis patients.

The marked systemic inflammation seen in myelofibrosis leads to increased ACVR1 activity which in turn increases secretion of hepcidin, resulting in perturbed iron homeostasis and an iron-restricted anemia. Momelotinib’s inhibition of ACVR1 in addition to JAK1 and JAK2, unique amongst the JAK inhibitor class, results in notable reductions of both hepcidin and inflammation, restoring iron homeostasis and RBC production, thereby alleviating anemia and transfusion dependency.

The SIMPLIFY-1 trial was a double-blind, active-controlled Phase 3 study in which 432 patients received randomized treatment with momelotinib or ruxolitinib for 24 weeks (JCO. 2017;35:3844–50). In addition to a significant reduction in splenomegaly and improvements in constitutional symptoms, previously reported analyses of the SIMPLIFY-1 data demonstrated that patients in the momelotinib arm achieved nominal-statistical significance for all anemia endpoints tested, including a higher rate of transfusion independence (p < 0.001) and lower rates of transfusion dependence (p = 0.019) at Week 24, compared to patients on ruxolitinib.

Retrospective analyses of SIMPLIFY-1 transfusion data, to be presented in a poster at ASH (Free ASH Whitepaper) 2019, demonstrate that the odds of momelotinib patients remaining transfusion free are nearly 10-times higher than those for ruxolitinib treated patients.

Momelotinib is an investigational drug that is not approved for any use in any country. The U.S. Food and Drug Administration has granted Fast Track designation to momelotinib for the treatment of patients with intermediate/high-risk myelofibrosis who have previously received a JAK inhibitor.

Momelotinib is wholly owned by Sierra Oncology and is protected by patents anticipated to provide potential exclusivity to 2040 in the United States and Europe (including Patent Term Extension or Supplementary Protection Certificate).

About the MOMENTUM Phase 3 Clinical Trial for Patients with Myelofibrosis:
The MOMENTUM Phase 3 clinical trial is a randomized double-blind trial designed to enroll 180 myelofibrosis patients who are symptomatic and anemic, and who have been treated previously with a JAK inhibitor. Patients will be randomized 2:1 to receive either momelotinib or danazol. Danazol has been selected as an appropriate treatment comparator given its use to ameliorate anemia in myelofibrosis patients, as recommended by NCCN and ESMO (Free ESMO Whitepaper) guidelines. After 24 weeks of treatment, patients on danazol will be allowed to crossover to receive momelotinib.

The Primary Endpoint of the trial is the Total Symptom Score (TSS) response rate of momelotinib compared to danazol at Week 24 (99% power; p-value < 0.05).

Secondary and exploratory endpoints include:

Transfusion Independence (TI) rate at Week 24 (key secondary: >90% powered; p-value < 0.05),
Splenic response rate (SRR) at Week 24 (>90% powered; p-value < 0.05),
Duration of TSS response to Week 48,
Other measures of anemia benefit, including Transfusion Dependence response rate and various measures of cumulative transfusion burden,
Patient Reported Outcome measures of fatigue and physical function.

Quest Diagnostics Declares Quarterly Cash Dividend

On November 20, 2019 Quest Diagnostics (NYSE: DGX), the world’s leading provider of diagnostic information services, reported that its Board of Directors declared a quarterly cash dividend of $0.53 per share, payable on January 29, 2020 to shareholders of record of Quest Diagnostics common stock on January 14, 2020 (Press release, Quest Diagnostics, NOV 20, 2019, View Source [SID1234551534]).

Kronos Bio Appoints Biopharma Industry Veteran Jorge F. DiMartino, M.D., Ph.D., as Chief Medical Officer

On November 20, 2019 Kronos Bio, Inc., dedicated to the development of first-in-class therapies that modulate historically undruggable targets, reported that it has appointed Jorge F. DiMartino, M.D., Ph.D., as Chief Medical Officer and Executive Vice President, Clinical Development. In this newly created position, Dr. DiMartino will lead Kronos Bio’s clinical function and oversee the advancement of its oncology pipeline, which includes two preclinical programs discovered via the company’s Small Molecule Microarray (SMM) screening platform (Press release, Kronos Bio, NOV 20, 2019, View Source [SID1234551533]). Dr. DiMartino will be based in Kronos’ San Mateo office.

"As a physician-scientist focused on translational development, Jorge is ideally suited to join Kronos at this stage of our growth, as we are focused on discovering bioactive molecules against oncology targets that have historically been considered undruggable," said Norbert Bischofberger, Ph.D., President and Chief Executive Officer of Kronos. "Jorge’s deep expertise in epigenetics and protein homeostasis will be uniquely valuable in our effort to develop drugs which interfere with transcription factors, pursue targeted protein degradation, and advance highly-differentiated products into human testing."

Dr. DiMartino joins Kronos from Celgene Corp., where he served as Vice President, Translational Development, Protein Homeostasis and Epigenetics Thematic Center of Excellence. At Celgene, Dr. DiMartino built a discovery team with industry leading epigenetic profiling capabilities in pursuit of chromatin modifier targets. His translational team has driven BET and LSD1 inhibitor programs through Phase 1, delivering robust data packages to support proof of concept trial designs. Prior to Celgene, he was Group Medical Director, BioOncology/ Exploratory Clinical Development at Genentech Inc., where he was the Development Team Leader for the BCL2 (venetoclax, navitoclax) collaboration with Abbvie, Inc. and managed a team advancing a broad portfolio of early-stage oncology compounds.

"I look forward to leveraging my oncology drug development expertise, which spans drug discovery to Phase 3 trial design, to help Kronos build its clinical organization and progress its two lead preclinical programs toward Investigational New Drug applications," said Dr. DiMartino. "Kronos’ mission to discover and develop novel therapies against historically undruggable cancer targets dovetails perfectly with my passion for understanding cancer biology and translating this knowledge into clinical development strategies to benefit cancer patients."

In addition to his work in industry, since 2007 Dr. DiMartino has been an Adjunct Clinical Assistant Professor of Pediatrics in the Division of Hematology/Oncology at Stanford University School of Medicine, participating in the care of pediatric oncology patients. Earlier in his academic career, he was Assistant Professor of Pediatrics, Division of Experimental Hematology, at Cincinnati Children’s Hospital Medical Center. Prior to that, he was an Instructor in the Departments of Pathology and Pediatrics at Stanford University School of Medicine, where he studied how chimeric transcription factors mediate leukemogenesis.

Dr. DiMartino received a B.A. in genetics from the University of California, Berkeley, a Ph.D. in immunology from Cornell University Graduate School of Medical Sciences, and an M.D. from the University of California, San Diego, School of Medicine. He completed a residency in pediatrics and a fellowship in pediatric hematology/oncology at the Lucile Salter Packard Children’s Hospital at Stanford, and a post-doctoral fellowship in the Department of Pathology at Stanford.