Though patients whose tumors harbor EGFR T790M mutation appear to benefit from rociletinib, there is a need to understand the molecular mechanisms that lead to primary and acquired resistance to rociletinib. The investigators propose to conduct a clinical trial of rociletinib of patients with EGFR-mutant NSCLC with activating EGFR mutations (including exon 19 deletion or L858R mutation), with or without EGFR T790M mutation. In these patients, pre-treatment and post-progression biopsy specimens will be subjected to genomic analysis to fully understand the clonal evolution and the molecular mechanisms underpinning treatment resistance.

Start Date01 May 2016

Sponsor / Collaborator

Washington University School of Medicine

[+1]

NCT02630186

/ TerminatedPhase 1/2

A Phase 1b/2 Study of the Safety and Efficacy of Rociletinib (CO-1686) Administered in Combination With MPDL3280A in Patients With Activating EGFR Mutation-positive (EGFRm) Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)

This clinical research study is being carried out in two parts, Phase 1 and Phase 2. The primary purpose of the Phase 1 portion of the study is to observe the safety of the combination of rociletinib and MPDL3280A in EGFR-mutant NSCLC patients.
The primary purpose of the Phase 2 portion of the study is to evaluate the safety and anti-tumor effects of the combination of rociletinib and MPDL3280A, at the best doses for the combination determined in Phase 1, in patients with EGFR-mutant NSCLC.

Start Date24 Feb 2016

Sponsor / Collaborator

Clovis Oncology, Inc.

[+1]

NCT02580708

/ TerminatedPhase 1/2

A Phase 1/2 Study of the Safety and Efficacy of Rociletinib When Administered in Combination With Trametinib in Patients With Activating EGFR Mutation-positive Advanced or Metastatic Non-small Lung Cancer (NSCLC)

The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib when administered in combination with trametinib.

Start Date30 Sep 2015

Sponsor / Collaborator

Clovis Oncology, Inc.

[+1]

100 Clinical Results associated with Rociletinib Hydrobromide

100 Translational Medicine associated with Rociletinib Hydrobromide

100 Patents (Medical) associated with Rociletinib Hydrobromide

219

Literatures (Medical) associated with Rociletinib Hydrobromide

14 Apr 2025·Journal of Chemical Information and Modeling

Probing the Effect of Protein and Inhibitor Conformational Flexibility on the Reaction of Rocelitinib-Like Covalent Inhibitors of Epidermal Growth Factor Receptor. A Quantum Mechanics/Molecular Mechanics Study

Article

Author: Kaewkham, Orathai ; Gleeson, M. Paul ; Fukasem, Poowadon ; Santatiwongchai, Jirapat ; Britton, Robert G. ; Gleeson, Duangkamol ; Jones, Donald J. L.

Epidermal growth factor receptor (EGFR) is a tyrosine kinase and a validated target for non-small cell lung cancer (NSCLC). Drug discovery efforts on this target initially focused on traditional competitive, reversible ATP-binding site inhibitors; however, irreversible covalent binding EGFR inhibitors have become increasingly more popular. Covalent EGFR inhibitors have been developed using a range of different scaffolds, and unsurprisingly, the incorporation of an electrophilic acrylamide group can result in sizable orientation differences relative to the Cys797 nucleophile and the Asp800 general base. In this work, we report a QM/MM study aiming to better understand the aspects of covalent adduct formation, including the role of protein flexibility on chemical reactivity, the impact of electrophile location within the ATP binding site, and the impact of the acrylamide conformation (s-cis vs s-trans). We focus here on the diaminopyrimidine scaffold, as exemplified by Rocelitinib, where the electrophile is attached to its back pocket binding group. Our goal is to elucidate how electrophilic groups can be incorporated onto different inhibitor scaffolds targeting reactive active site residues. We find that irrespective of the EGFR MD conformation chosen, acrylamide, in both the s-cis or s-trans, can undergo reaction with rate-determining barriers of ∼20 kcal/mol. Interestingly, the nature of the rate-determining step for Rocelitinib-like inhibitors was found to be either direct nucleophilic attack or keto-enol tautomerization, depending on the precise protein and inhibitor conformation.

23 Dec 2024·Journal of Chemical Information and Modeling

Kinase-Bench: Comprehensive Benchmarking Tools and Guidance for Achieving Selectivity in Kinase Drug Discovery

Article

Author: Li, Nian-Guang ; Cao, Peng ; Zhao, Zong-Hao ; Yang, Jin ; Yu, Yan-Cheng ; Ding, Ning ; Li, Qing-Qing ; Zhou, Shuang-Shuang ; Yin, Xiao-Ying ; Wei, Tian-Hua ; Sun, Meng ; Zhou, Yun ; Xue, Xin ; Ling, Cheng-Xiao ; Wang, Xue ; Shi, Zhi-Hao ; Liu, Jia-Chuan ; Jing, Xiao-Long ; Wang, Xiao-Long ; Wang, Zi-Xuan ; Sun, Shan-Liang

Developing selective kinase inhibitors remains a formidable challenge in drug discovery because of the highly conserved structural information on adenosine triphosphate (ATP) binding sites across the kinase family. Tailoring docking protocols to identify promising kinase inhibitor candidates for optimization has long been a substantial obstacle to drug discovery. Therefore, we introduced "Kinase-Bench," a pioneering benchmark suite designed for an advanced virtual screen, to improve the selectivity and efficacy of kinase inhibitors. Our comprehensive data set includes 6875 selective ligands and 422,799 decoys for 75 kinases, using extensive bioactivity and structural data from the ChEMBL database and decoys generated by the Directory of Useful Decoys-Enhanced version. Our benchmarking sets and retrospective case studies were designed to provide useful guidance in discovering selective kinase inhibitors. We employed a Glide High-Throughput Virtual Screen and Standard Precision complemented by three scoring functions and customized protein-ligand interaction filters that target specific kinase residue interactions. These innovations were successfully implemented in our virtual screen efforts targeting JAK1 inhibitors, achieving selectivity against its family member, TYK2. Consequently, we identified novel potential hits: Compound 2 (JAK1 IC₅₀: 980.5 nM, TYK2 IC₅₀: 4.5 μM) and the approved pan-AKT inhibitor Capivasertib (JAK1 IC₅₀: 275.9 nM, TYK2 IC₅₀: 10.9 μM). Using the Kinase-Bench protocol, both compounds demonstrated substantial JAK1 selectivity, making them strong candidates for further investigation. Our pharmaceutical results underscore the utility of tailored virtual screen protocols in identifying selective kinase inhibitors with substantial implications for rational drug design. Kinase-Bench offers a robust toolset for selective kinase drug discovery with the potential to effectively guide future therapeutic strategies effectively.

01 Nov 2024·BIOORGANIC & MEDICINAL CHEMISTRY

Design, preparation and biological evaluation of new Rociletinib-inspired analogs as irreversible EGFR inhibitors to treat non-small-cell-lung cancer

Article

Author: Lamtha, Thomanai ; Pickering, James D. ; Jones, Donald J L ; Paul Gleeson, M. ; Britton, Robert G ; Gleeson, M Paul ; Konsue, Adchata ; Choowongkomon, Kiattawee ; Pickering, James D ; Jones, Donald J.L. ; Britton, Robert G. ; Gleeson, Duangkamol

Epidermal growth factor receptor (EGFR) kinase has been implicated in the uncontrolled cell growth associated with non-small cell lung cancer (NSCLC). This has prompted the development of 3 generations of EGFR inhibitors over the last 2 decades due to the rapid development of drug resistance issues caused by clinical mutations, including T790M, L858R and the double mutant T790M & L858R. In this work we report the design, preparation and biological assessment of new irreversible 2,4-diaminopyrimidine-based inhibitors of EGFR kinase. Twenty new compounds have been prepared and evaluated which incorporate a range of electrophilic moieties. These include acrylamide, 2-chloroacetamide and (2E)-3-phenylprop-2-enamide, to allow reaction with residue Cys797. In addition, more polar groups have been incorporated to provide a better balance of physical properties than clinical candidate Rociletinib. Inhibitory activities against EGFR wildtype (WT) and EGFR T790M & L858R have been evaluated along with cytotoxicity against EGFR-overexpressing (A549, A431) and normal cell lines (HepG2). Selectivity against JAK3 kinase as well as physicochemical properties determination (logD_7.4 and phosphate buffer solubility) have been used to profile the compounds. We have identified 20, 21 and 23 as potent mutant EGFR inhibitors (≤20 nM), with comparable or better selectivity over WT EGFR, and lower activity at JAK3, than Osimertinib or Rociletinib. Compounds 21 displayed the best combination of EGFR mutant activity, JAK3 selectivity, cellular activity and physicochemical properties. Finally, kinetic studies on 21 were performed, confirming a covalent mechanism of action at EGFR.

News (Medical) associated with Rociletinib Hydrobromide

20 Jul 2023

·www.biospace.com

Agenus Expands Executive Leadership Team

Robin Taylor, MBA, Ph.D., Appointed Chief Commercial Officer Homa Yeganegi Appointed Chief Product Strategy and Global Medical Affairs Officer Stephanie Fagan Appointed Chief Communications Officer LEXINGTON, Mass.--(BUSINESS WIRE)-- Immuno-oncology leader, Agenus Inc. (“Agenus”) (Nasdaq: AGEN), today announced the appointment of Robin Taylor, Ph.D., Homa Yeganegi and Stephanie Fagan to its executive team. The newly appointed leaders bring a wealth of industry experience to drive the company’s next phase of growth in the development and planned commercialization of botensilimab and a deep pipeline of immuno-oncology programs, which offer potential breakthroughs in cancer therapeutics. Chief Commercial Officer, Robin Taylor, Ph.D., is an accomplished leader with demonstrated success in global commercial development in oncology. His expertise in commercialization strategies, market access, and product launches will accelerate Agenus’ growth and ultimately enable the delivery of the company’s therapies to patients as the company evolves to a multi-product organization. Chief Product Strategy and Global Medical Affairs Officer, Homa Yeganegi, brings expertise in medical affairs and a passion for advancing patient care. Her success in building and leading global medical affairs teams will play a pivotal role in deepening physicians’ understanding of the transformational potential of botensilimab. By fostering strong relationships with the medical community, she will contribute to the development and future commercialization of the company’s immuno-oncology programs. Chief Communications Officer, Stephanie Fagan, brings extensive experience working with leading healthcare companies and executing successful communication, investor relations and advocacy strategies. Her proven record in building strong brands and engaging stakeholders will shape Agenus’ communication efforts and drive patient-centered initiatives to enhance the potential role of botensilimab in the treatment of cancer. "We are at an incredibly exciting juncture in our company's history, with a portfolio of promising therapies showing significant clinical activity across a range of hard-to-treat cancers in patients who have not responded to previous therapies," said Chairman and Chief Executive Officer Garo Armen, Ph.D. "With the addition of Robin, Homa, and Stephanie to our team, Agenus is poised to accelerate our growth and, most importantly, deliver novel therapies that we believe will enhance and extend the lives of patients in need." Agenus has a growing body of robust clinical data from trials studying botensilimab in approximately 600 patients. Botensilimab alone, or the botensilimab/balstilimab combination has shown clinical responses across nine metastatic solid tumor cancers. The company is in late-stage development in highly prevalent cancers of the colon, lung, and skin with an estimated market opportunity of 150,000 patients across the United States (U.S.), United Kingdom, France, Spain, Italy, Germany, and Japan1. Agenus plans to submit its first Biologics License Application to the U.S. Food and Drug Administration (FDA) for the approval of the combination in patients with refractory non-MSI-H metastatic colorectal cancer in 2024. The ongoing global randomized phase 2 trial for patients with non-active liver metastases has been granted Fast Track designation from the FDA. About Robin Taylor Robin Taylor, Ph.D. has extensive experience across oncology global development and commercialization, with a proven track record in building the commercial foundation to execute successful launches. Most recently, Taylor was an independent consultant providing strategic commercial advice to biotechnology companies. Taylor was previously the chief commercial officer at Seagen, where he led the organization through a period of significant growth in preparation for the launches of PADCEV® (enfortumab vedotin), and TUKYSA® (tucatinib). Prior to this role Taylor served as vice president and immuno-oncology franchise head in the oncology business unit at AstraZeneca, where he led the global medicine and product teams responsible for IMFINZI® (durvalumab), and IMJUDO® (tremelimumab). Before joining AstraZeneca, Taylor served in commercial roles of increasing responsibility at Genentech, a member of the Roche Group, contributing to the launch and commercialization of HERCEPTIN® (trastuzumab) and AVASTIN® (bevacizumab), and ultimately serving as vice president, lung and cancer immunotherapy franchise head, global product strategy, responsible for the development and commercialization of ALECENSA® (alectinib) and TECENTRIQ® (atezolizumab) across multiple indications. He received a Doctor of Philosophy in molecular and medical genetics from the University of Toronto; a Master of Business Administration from the University of California, Berkeley; and a Bachelor of Science from the University of British Columbia. About Homa Yeganegi Homa Yeganegi is an expert leader in building and leading oncology-focused global product strategy and medical affairs, with a strong commitment to medical excellence and patient care. Yeganegi joins Agenus from her position as senior vice president and global program leader at Bristol Myers Squibb (BMS) where she led the global regulatory submission for repotrectinib in non-small cell lung cancer (NSCLC). Prior to BMS, she was senior vice president and head of medical affairs for Turning Point Therapeutics, directing development and commercialization strategies for the U.S. approval of repotrectinib in NSCLC. Prior to that role, Yeganegi was senior vice president and head of global medical and scientific affairs at Halozyme responsible for medical commercialization strategy and operational planning for the company’s investigational oncology drug candidate. Yeganegi previously served as vice president of global medical affairs at Clovis Oncology where she directed pre-launch activities for rociletinib in NSCLC in the U.S. and Europe. She also built and led oncology-focused global medical affairs teams at Exelixis, and at Onyx Pharmaceuticals where she led launch planning for carfilzomib in multiple myeloma. She received her Bachelor of Science in biology from the University of Tehran, Iran; her Master of Science in neuroanatomy from the University of Western Australia; and is completing a doctorate in health sciences. About Stephanie Fagan Stephanie Fagan brings a breadth of expertise across corporate affairs and communications, leading the development and execution of multi-stakeholder communication strategies. She joins Agenus from Pillar Communication, LLC, a consulting firm providing fractional chief communications officer leadership. Prior to that, she was senior vice president and chief communications officer at Acadia Pharmaceuticals, overseeing all internal and external communications. Fagan joined Acadia from bluebird bio, Inc., where she was senior vice president, corporate communications, and built the first communications function as the company transitioned from a clinical-stage to commercial-stage company. Prior to bluebird, Fagan led the corporate affairs functions at Alexion, Shire and West Health and has experience overseeing corporate, financial, product and internal communications as well as corporate social responsibility, patient advocacy, and government affairs. Over the course of her career, Fagan has served in positions of increasing influence and impact in the healthcare industry, including roles at Johnson & Johnson, Allergan, Pharmacia, Inc. (now Pfizer), and Boston Scientific Corporation. Fagan earned a Master of Science in communications from Boston University and a Bachelor of Arts in English from Wheaton College. About Botensilimab Botensilimab, an investigational multifunctional CTLA-4 antibody, is designed to extend immunotherapy benefits to "cold" tumors, which have not historically responded to standard of care or other investigational therapies. Besides binding to the CTLA-4 receptor, its Fc-enhanced structure induces a memory immune response, downregulates regulatory T cells, and activates T cells, thereby enhancing immune responses. Approximately 600 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit with the identifiers NCT05608044, NCT05630183, and NCT05529316. About Agenus Agenus is a leading immuno-oncology company targeting cancer and infectious diseases with a comprehensive pipeline of immunological agents. The company’s mission is to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants (through SaponiQx). Agenus is headquartered in Lexington, MA. For more information, visit or follow us on LinkedIn and Twitter @agenus_bio. Forward-Looking Statements This press release contains forward-looking statements under the safe harbor provisions of federal securities laws. These include statements related to botensilimab’s and balstilimab’s regulatory strategy and use, such as anticipated therapeutic benefit, efficacy, mechanism of action, potency, durability, and safety pro the company's therapeutic candidates. Any statements containing "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions signify forward-looking statements. Actual results could differ materially due to risks and uncertainties, including those described under the Risk Factors section in our most recent Quarterly Report on Form 10-Q or Annual Report on Form 10-K filed with the Securities and Exchange Commission. Agenus urges investors not to place significant reliance on the forward-looking statements in this release. These statements only reflect the views as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. 1 Data/information supplied by Kantar Health, LLC.

Phase 2Executive ChangeImmunotherapyFast TrackPhase 1

01 Jun 2022

·www.globenewswire.com

Black Diamond Therapeutics Appoints Sergey Yurasov, M.D., Ph.D., as Chief Medical Officer

- Dr. Yurasov brings over 25 years of experience in oncology drug development and regulatory expertise - CAMBRIDGE, Mass. and NEW YORK, June 01, 2022 (GLOBE NEWSWIRE) -- Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a precision oncology medicine company pioneering the discovery and development of MasterKey therapies, today announced the appointment of Sergey Yurasov, M.D., Ph.D., as Chief Medical Officer. In conjunction with the appointment of Dr. Yurasov, Karsten Witt, M.D., is transitioning from his current role as the Company’s Interim Chief Medical Officer to a clinical advisory role. “We are delighted to welcome Sergey to Black Diamond as Chief Medical Officer. His considerable expertise in precision oncology medicine, specifically with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) and glioblastoma multiforme (GBM), positions Sergey as an invaluable leader for our drug development team,” said David Epstein, Ph.D., President and Chief Executive Officer of Black Diamond Therapeutics. “We remain focused on advancing our MasterKey therapies, including our lead clinical program, BDTX-1535, and BDTX-4933, currently in IND-enabling studies, and Sergey’s diverse clinical and regulatory experience in the development of targeted oncology therapies for the treatment of solid tumors will be essential as we further advance our pipeline and utilize our innovative MAP drug discovery engine to develop novel MasterKey therapies.” Dr. Yurasov joins Black Diamond Therapeutics from Nuvation Bio, an oncology therapeutics company. As Chief Medical Officer at Nuvation Bio, Dr. Yurasov was instrumental in the company’s successful public offering in February 2021, and spearheaded the company’s clinical development strategy in multiple oncology indications for a number of small molecule programs. Prior to Nuvation Bio, Dr. Yurasov was the Chief Medical Officer and Senior Vice President of Clinical Development at Immune Design Corp., an immune-oncology company, which was acquired by Merck in March 2019. He was previously Senior Vice President of Clinical Development at Clovis Oncology, where he oversaw clinical development and led clinical teams through regulatory filings for multiple oncology development programs, including rociletinib for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) and RUBRACA® (rucaparib) for homologous-recombination deficient ovarian cancer. Earlier in Dr. Yurasov’s career, he was a senior physician at ImClone Systems, a subsidiary of Eli Lilly and Company, leading the approval of CYRAMZA® (ramucirumab) in NSCLC and a clinical lead on multiple oncology early development programs at Roche. Dr. Yurasov holds an M.D. from the Russian State Medical University and a Ph.D. from the Research Institute for Pediatric Hematology, in Moscow, Russia. “Black Diamond’s MAP drug discovery engine represents a novel approach to addressing major unmet medical needs for patients within the precision oncology treatment landscape by targeting overlooked mutation families, and I was particularly drawn to this differentiated way of tackling the gaps in genetically defined cancer treatment. I am excited to be joining this team to further execute on the development of Black Diamond’s pipeline programs as the Company prepares for key milestones across its programs in 2023,” said Dr. Yurasov. “This is a crucial time for Black Diamond with a newly refined pipeline strategy and clear prioritization of programs in development and I look forward to joining this fantastic group of leaders and scientists as we work together to expand the reach of precision medicines in oncology.” Dr. Yurasov succeeds Dr. Witt, who was Black Diamond’s founding Chief Medical Officer and will continue to support the Company in an advisory capacity. “On behalf of everyone at Black Diamond, the management team and Board of Directors, we thank Karsten for his significant contributions to our progress and mission of expanding the reach of precision cancer medicines. Karsten has been instrumental in the building of Black Diamond, and we are grateful for the integral role he has played in our growth. I want to thank him for his leadership and continued commitment to the value proposition of MasterKey therapies,” said Dr. Epstein. About Black Diamond Therapeutics, Inc. Black Diamond Therapeutics is a precision oncology medicine company pioneering the development of novel MasterKey therapies. Black Diamond is addressing the significant unmet need for novel precision oncology therapies for patients with genetically defined cancers who have limited treatment options. Black Diamond is built upon a deep understanding of cancer genetics, onco-protein function, and drug discovery. The Company’s proprietary Mutation-Allostery-Pharmacology, or MAP, drug discovery engine, is designed to allow Black Diamond to analyze population-level genetic sequencing tumor data to predict and validate oncogenic mutations that promote cancer across tumor types as MasterKey mutations. Black Diamond discovers and develops selective MasterKey therapies against these families of oncogenic mutations. Black Diamond was founded by David M. Epstein, Ph.D., and Elizabeth Buck, Ph.D. For more information, please visit www.blackdiamondtherapeutics.com. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: the continued discovery and development of MasterKey therapies, the continued development and advancement of BDTX-1535 in clinical studies and BDTX-4933 in Investigational New Drug (IND)-enabling studies, including the timing and potential achievement of upcoming clinical and preclinical milestones for each program, and the continued development of the MAP drug discovery engine. Any forward-looking statements in this statement are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include those risks and uncertainties set forth in the Company’s Annual Report on Form 10-K for the year ended December 31, 2021, filed with the United States Securities and Exchange Commission and in its other filings filed with the United States Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Contacts: For Investors:Julie Seidel(212) 362-1200investors@bdtx.com For Media:Kathy Vincent(310) 403-8951media@bdtx.com

Small molecular drug

07 Dec 2016

·www.biospace.com

BioPharm Executive: So Long 2016 (and Good Riddance?)

December 14, 2016 By Karl Thiel for BioSpace.com Many of us will be glad to see the end of 2016, a year that was marked by terrorism both domestic and international, a string of celebrity deaths, a new disease scourge (Zika became the new Ebola), and a whole lot of political turmoil that made for some tense Thanksgiving table conversations. Here in our little corner of the world, there was plenty of volatility too. So without further delay, let’s count down this year’s wholly subjective list of the year’s top 10 biotech trends and events. #10: Brexit. The U.K.'s decision to exit the European Union will likely have some broad-reaching and long-lasting effects, most of which are yet to be felt. In the short term, the move has been on balance positive for U.K.'s pharma sector—for a simple reason. A historically weak pound sterling is helping companies like GlaxoSmithKline and AstraZeneca boost dollar-denominated profits. Rumors initially swirled that both these pharma giants would pull up roots and leave the U.K., but that doesn’t appear to be the case, at least for now. Longer term, it remains to be seen if some of the bigger fears—failure to attract or retain top talent, securing investment, and keeping favorable trade deals—come to fruition. #9: Sharply declining approvals. Both 2014 and 2015 were tough acts to follow. There were 45 novel drugs approved last year; 41 the year before. As I write, there have only been 19 novel drugs approved in 2016—putting this on track to be the worst year since 2007. This isn’t necessarily the FDA’s fault—they can only approve the applications these receive…and some would argue that the agency has, if anything, been overly lenient in granting approvals this year. #8: Lots of big clinical failures. While 2016 has certainly had its bright spots, the year has been more notable for high-pro failures than for its successes. There’s BioMarin’s drisapersen, Celldex Therapeutics’ Rintega, Eli Lilly’s solenuzumab, Alnylam’s Revusiran, Clovis Oncology’s rociletinib, and Bristol Myers-Squibb’s Opdivo in lung cancer. Juno Therapeutics has run into some serious, perhaps program-ending difficulties with JCAR-015. Gilead has had a bad run of luck with almost everything it touched this year, from GS-5745 (in ulcerative colitis) to simtuzumab to eleclazine to Zydelig (in first-line cancer applications). Bluebird Bio went from hot to not after turning out disappointing early results in its sickle cell programs. There have been some great achievements (see below)—but it’s hard to counter-balance this depressing list. #7: The drug price debate continues, then stops, then starts up again. Drug companies always make juicy political targets, so it’s no surprise that the heat stayed high all during this election year. It’s been a debate long on rhetoric and short on substance, with the main result being that companies grew more eager to get in price increases before the music stopped. Some, of course, were a little more ham-fisted about than others (cough, Mylan ). Pharma investors breathed a sigh of relief after the election of Donald Trump (see point #1 below), but that sense of resolution may have come too early. Also, don’t forget about some of the most visible faces of price-gouging— Valeant subsidiary Philidor and its CEO have had criminal charges filed against them, and there may be more to come. Martin Shkreli is guaranteed to be back in the news in 2017, since that’s when his criminal fraud trial is likely to take place. #6: M&A slowed to a comparative crawl. 2015 was a record-breaking year for biopharma M&A, with some $330 billion in deals, even after you factor out the $183 billion Pfizer - Allergan link-up that never happened. Few expected this year to match that sum, but fewer still expected the totals to drop so sharply. The final tallies won’t be in until the New Year, but 2016 was recently running under $100 billion in pharma and biotech M&A. Will a flood of repatriated cash, courtesy of a new Trump tax policy, change the calculus in 2017? I have my doubts (and not only because it will take a while to change the tax code, even with a willing Congress). But it wouldn’t be surprising to see the pace pick up at least a little next year. #5: Market meltdown. The “Trump bump” to the stock market—and the biotech market in particular—was nice for investors while it lasted. Even at its best, it did little to erase what happened in the opening weeks of 2016. As we stand now, the Nasdaq Biotech Index, up less than 2 percent since the election. It is down over 20 percent year-to-date. A number of other points in this list help explain why. #4: The (controversial) rise of antisense. Antisense has been kicking around since the 1980s without much commercial success. While that technically continued to be true this year, it’s about to change. Spinraza, the antisense drug for spinal muscular atrophy developed by Ionis Pharma and Biogen , produced strong enough results in a study of infantile onset spinal muscular atrophy that the trial was stopped early. Since then, robust signals have been seen in patients with later-onset disease. And the drug reportedly has a reasonably clean safety pro since side effects and safety concerns have dogged some other antisense drugs. Then there’s Sarepta’s eteplirsen, trade-named Exondys 51, approved to treat Duchenne muscular dystrophy is a specific subset of patients. The decision to approve was controversial and, according to some, undermined the credibility of the FDA. Certainly it remains unclear whether the drug’s miniscule effect on dystrophin production will create a meaningful change in the course of the disease. But that probably won’t stop it from racking up hundreds of millions of dollars in sales. #3: CAR-T meltdown? Cancer immunotherapy has been so hot over the past few years that some pundits have bemoaned a lack of research dollars going elsewhere. CAR-T seems like an obvious next step—a way to program T-cells to attack specific cancers. And early clinical results have shown astounding success, producing apparent cures in leukemia. But the therapy has turned out to be quite dangerous in some situations, dousing another fire that burned so bright for biotech in 2015. That’s been particularly true for Juno Therapeutics , which has put its pivotal trial of JCAR-015 on clinical hold twice. Novartis , once arguably the leader in the area, seemingly stepped back from CAR-T this past summer, dissolving its dedicated unit, bringing programs back into the larger organization and perhaps putting less emphasis on the technology (though they continue to push forward). Kite Pharma is the beneficiary of these developments, yet investors are regarding the company warily. The stock is down sharply for the year and well off its 52-week high even as it files for its first approval. Call it another case of hype waking up to reality: CAR-T remains a very promising technology, but it’s still unclear how effective it will be outside of blood cancers, and how it will be used even in leukemias, where oncologists will have to weigh up robust results against serious potential risks. #2: CRISPR goes public. At the start of the year, there were zero pure-play companies in the CRISPR space. Now there are three— Editas Medicine , Intellia Therapeutics , and CRISPR Therapeutics —not to mention a bunch more companies dabbling in the space. But these companies—which have had a mixed-at-best reception with investors—are only the tip of the iceberg, held back in part by complex and acrimonious intellectual property disputes. CRISPR has exploded around the world, with the University of Pennsylvania planning a seeming Hail Mary pass into clinical trials thanks to funding from the Parker Institute, only to be beaten to the punch by Sichuan University in China. Even without clinical trials, the technology is making all sorts of experiments possible—even if some raise safety or ethical issues. By this time next year, perhaps we’ll all have access to giant CRISPR beagles . #1: Trump elected president. This election upset takes the number one spot. But what it means for the biotech sector (or anything else) remains unclear. Trump has certainly been known to spout anti-science rhetoric and anti-vaxxer drivel. He’s said he wants to cut drug prices, using mechanisms like reimportation and direct Medicare negotiation. But then he went mum on those topics. And then he started up again, so who knows? He has said he wants to streamline FDA and get medicines to people more quickly, pushing a popular political hot button. But does that mean a bigger FDA budget, laxer standards, or something else? It seems likely, based on both his rhetoric and his choice of Rep. Tom Price (R-Ga.) as Secretary of Health and Human Services , that he plans to make good on his promise to repeal and replace Obamacare. Yet how will that play out? The Affordable Care Act has generally been popular with drug companies, because it has given them millions of new customers. But it has also come with new regulatory burdens, like requirements to compile and submit data to Patient Centered Outcomes Research Institutes. What is simply repealed and what is replaced will have a big impact on companies. Here’s another irony: One interesting impact of Obamacare is that it gives the president fairly broad authority to enact price controls when Medicare grows at a certain level beyond inflation—as it is expected to do in 2017 for the first time since the law was passed. So biopharma companies who’ve thus far seen the most favorable side of the law may be saved from its restrictions just before the hammer comes down—if Trump and Congress do indeed repeal. But maybe Trump will decide he likes the authority in the current law. However it goes down, it’s going to be an interesting 2017. - Karl Thiel Read the BioPharm Executive online newsletter December 14, 2016. Sign-up for the free monthly subscription to the BioPharm Executive Related Jobs VP, Clinical Development Director, Genomics VP, Clinical Development Director of Operations VP, Sales Director, Biostatistics View More Jobs

Drug ApprovalImmunotherapy

100 Deals associated with Rociletinib Hydrobromide

External Link

KEGG	Wiki	ATC	Drug Bank
-	Rociletinib Hydrobromide	L01XE37	DB11907

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	NDA/BLA	United States	Clovis Oncology, Inc.	-
Non-Small Cell Lung Cancer	NDA/BLA	European Union	Clovis Oncology, Inc.	-
EGFR-mutated non-small Cell Lung Cancer	Phase 3	United States	Clovis Oncology, Inc.	01 Feb 2015
EGFR-mutated non-small Cell Lung Cancer	Phase 3	Australia	Clovis Oncology, Inc.	01 Feb 2015
EGFR-mutated non-small Cell Lung Cancer	Phase 3	France	Clovis Oncology, Inc.	01 Feb 2015
EGFR-mutated non-small Cell Lung Cancer	Phase 3	Germany	Clovis Oncology, Inc.	01 Feb 2015
EGFR-mutated non-small Cell Lung Cancer	Phase 3	Italy	Clovis Oncology, Inc.	01 Feb 2015
EGFR-mutated non-small Cell Lung Cancer	Phase 3	Netherlands	Clovis Oncology, Inc.	01 Feb 2015
EGFR-mutated non-small Cell Lung Cancer	Phase 3	Spain	Clovis Oncology, Inc.	01 Feb 2015
EGFR-mutated non-small Cell Lung Cancer	Phase 3	Taiwan Province	Clovis Oncology, Inc.	01 Feb 2015

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02147990 (NSCLC, CTgov)	Phase 2	Non-Small Cell Lung Cancer	318	Rociletinib (Rociletinib 625 mg BID T790M+)	ntgqzsovzb = pdcamkiozp jvfqsjnnue (xvwakbrlgj, klcfktcohl - ynnfqhnvti) View more	-	12 Aug 2020
				Rociletinib (Rociletinib 500 mg BID T790M+)	ntgqzsovzb = iftqvtkwin jvfqsjnnue (xvwakbrlgj, usfxecpwfd - uvskxwiyje) View more
NCT02322281 (CTgov)	Phase 3	EGFR-mutated non-small Cell Lung Cancer	149	Rociletinib (Rociletinib 500 mg BID)	jrhgenmpdy(tfzrcaqvmp) = wsqwvauadd vqkheklvms (oqiwvwoczy, jnxetzfpsi - drdqsazzyp) View more	-	23 Jul 2019
				Rociletinib (Rociletinib 625 mg BID)	jrhgenmpdy(tfzrcaqvmp) = uerqswivuy vqkheklvms (oqiwvwoczy, dcmfxcuslq - zfzrjfmvjn) View more
NCT02630186 (CTgov)	Phase 1/2	metastatic non-small cell lung cancer	3	Rociletinib+MPDL3280A	pjrqvalgxm = yshbhabkkf sargcaoxec (efzwlmjpdg, nndbdelhid - xtrrpklelj) View more	-	05 Jul 2019
NCT02186301 (EGFR, CTgov)	Phase 2/3	Non-Small Cell Lung Cancer \| EGFR-mutated non-small Cell Lung Cancer	100	Rociletinib (Rociletinib 500mg Tablets)	nqjslgjfeh(vrxklffxim) = qqmofchhyy fijxdtdgey (wmpxfkqxbd, jolkocbdbk - adumeuhdzk) View more	-	30 Apr 2019
				Rociletinib (Rociletinib 625mg Tablets)	nqjslgjfeh(vrxklffxim) = kqydqviaxx fijxdtdgey (wmpxfkqxbd, pmbzqkkfvd - qvlkhudsjh) View more
NCT01526928 (TIGER-X, ASCO 12016 \| ASCO 22016) Manual	Phase 1/2	EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma EGFR T790M-positive	417	rociletinib 500 mg	aachyecdgi(ufejludwvj) = 500 mg,Hyperglycemia（26.9%），Diarrhea（1.7%），Nausea（1.7%），Fatigue（2.9%），QTc prolongation（5.1%），Decreased appetite（0.6%）;625 mg ,Hyperglycemia（35.5%），Diarrhea（5.0%），Nausea（2.5%），Fatigue（6.2%），QTc prolongation（9.5%），Decreased appetite（1.7%） cwoqqzfdtv (xesxxyyupr )	Positive	04 Jun 2016
				rociletinib 625 mg
NCT01526928 (TIGER-X, WCLC2015)	Phase 1/2	EGFR-mutated non-small Cell Lung Cancer	231	Rociletinib 500 mg BID	knxiraecve(pjosfrzalt) = zjjwhxwhvy dpekoactep (squobyfzwq ) View more	-	08 Sep 2015
				Rociletinib 625 mg BID	knxiraecve(pjosfrzalt) = jjdmgmucig dpekoactep (squobyfzwq ) View more
NCT01526928 (TIGER-X, WCLC2015)	Phase 1/2	EGFR-mutated non-small Cell Lung Cancer	401	Rociletinib	eeqdsgzgrz(eqkumkfmxl) = xmkncfpsol ptlkbqvzuf (hmyxntwobb )	-	08 Sep 2015
NCT01526928 (TIGER-X, WCLC2015)	Phase 1/2	EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	36	Rociletinib	acxkymceut(iejjtlpktj) = qeentlrbpg hjfyetnedb (zjvyxujska )	-	07 Sep 2015
NCT01526928 (TIGER-X, AACR2015)	Phase 1/2	Non-Small Cell Lung Cancer	139	Rociletinib (CO-1686)	mcntuenjbm(tiuaewwsyb) = ibhhkfekez rikasxpxua (qqsfboyjuy ) View more	-	01 Aug 2015
NCT01526928 (TIGER-X, ASCO2015) Manual	Phase 1/2	EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma EGFR T790M Mutation	345	Rociletinib Hydrobromide	bfgiqezyfi(kidaruqmct) = eklpurrnxl yytexkuibq (pjpgseezhd ) View more	Positive	20 May 2015

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