Research and development at Merck
Merck conducts research and development worldwide in order to develop new products and services designed to improve the quality of life of patients and customers. In 2014, Merck focused on further optimizing the relevance and efficiency of its research and development activities. For this purpose, Merck increased the number of new collaborations with external research and development partners.
Around 4,700 employees work for Merck researching innovations to serve long-term health and technology trends in established and emerging markets as well as in developing countries.
Merck spent around € 1.7 billion on research and development in 2014. In our research and development activities, we focus on both in-house research and external collaborations, which enable us to increase the productivity of our research while simultaneously reducing financial outlay.
The organizational set-up of our research and development activities reflects the structure of Merck. Within the Executive Board, Stefan Oschmann, who became Vice Chairman of the Executive Board at the beginning of 2015, was responsible for Merck Serono and Consumer Health until December 31, 2014. Effective January 1, Belén Garijo assumed this responsibility as a Member of the Executive Board. Bernd Reckmann is responsible for Performance Materials and Merck Millipore.
Merck Serono R&D continues to evolve with a focus on both strategic and operational improvements. In the course of 2014, with new leadership in place after the appointment of Luciano Rossetti, MD, as Executive Vice President and Head of Global R&D in July, the R&D organization further enhanced the structure of R&D to strengthen collaboration across the spectrum of Research, Development and Commercial, prioritized key development programs, and created a governance model founded on collaboration, agility and objectivity in science.
Along with a sustained effort to foster an environment of end-to-end development – from early research through to late-stage development and product registration – there is also a resolute commitment to ensuring the patient’s needs are the primary driver in all decision-making. A patient-centric approach to R&D is becoming increasingly inherent across Merck Serono, from research of the highest quality through to quick and efficient clinical development. Across the continuum of R&D, there is a renewed energy to build a solution-oriented, collaborative and accountable culture that delivers value to the business and to patients. With an unwavering focus on world-class science and the development of strategic external opportunities, Merck Serono R&D aims to accelerate its pipeline.
Research and development strategy
In 2014, Merck Serono R&D continued its change strategy to better position the organization for success in the years to come. Today, founded on a solution-oriented and collaborative mindset, almost 2,300 R&D professionals are working to advance innovation across the Merck Serono R&D pipeline.
In Research, the early phases of discovery remain structured across three distinct yet closely aligned Translational Innovation Platforms (TIPs): Oncology, Immuno-Oncology, and Immunology, as well as a specific department focused on Global Health, which targets critical health needs in vulnerable populations.
With early development now part of Global Development, R&D teams share the common goal of advancing programs in a seamless fashion, collaborating to identify the right strategies for key programs as they progress along the pipeline, and aligning with Commercial from the earliest stages in the process, in order to build the right target product profile in the most effective way possible.
Program prioritization became a critical priority in 2014, streamlining the R&D portfolio based on key data milestones, among other things. With a core set of compounds now targeted as high-priority, the R&D organization can better distribute resources across its programs to optimize their potential for success.
With hubs in Darmstadt, Germany; Boston, Massachusetts, USA; Tokyo, Japan; and Beijing, China, the broad footprint of Merck Serono gives it access to innovation in its key markets. Across the entire biopharma spectrum – from academia and hospitals to research institutions and other companies in the biopharmaceutical industry – Merck Serono complements its internal expertise by leveraging the experience and knowledge of others through partnerships. In 2014, Merck Serono delivered clear examples of this strategic priority, announcing agreements with several companies and academic institutions around the world, as well as awarding external grants for research innovation in several disease areas, as detailed in the next section.
With a forward-looking view, the global Merck Serono R&D organization is positioning itself for future success. Strong collaboration, an unwavering commitment to exceptional science and a focus on objective decision-making are the key principles that will guide the R&D teams in 2015. As a recent example, the Global Medical Affairs (GMA) organization underwent a complete redesign and strategic refocusing in 2014. Patient centricity was at the core of this effort which has several cornerstones: enhancement of therapeutic area expertise in key areas, a global best-practice sharing working style and the establishment of a novel function known as medical excellence. The new GMA organization was launched in August and implementation at headquarters, in regions and in countries worldwide is progressing rapidly, and is on track for completion in early 2015. The new organization is already delivering enhanced value to life cycle management of Merck Serono’s registered products, as well as contributing significantly to the late-stage development process.
At the Merck Serono Investor & Analyst Day in September, Merck gave an update on its plans for its Biosimilars activities. In addition to the already disclosed investment plan of € 100 million for 2014, the unit plans to continue to invest in 2015, depending on the outcome of ongoing Phase I studies. Existing partnerships with India’s Dr. Reddy’s and Brazil’s Bionovis will be expanded by another, as yet undisclosed in-licensing agreement for a late-stage biosimilar, initially for smaller emerging markets. Between 2015 and 2016, Merck plans to initiate between two and five Phase III clinical trials.
The Merck Serono pipeline in 2014
Merck Serono’s core R&D fields include oncology, immuno-oncology, immunology and neurology. The development pipeline continues to be weighted towards oncology; however, 2014 saw important scientific and business development advances in several disease areas. In line with its open collaborative model in R&D, Merck Serono entered into a number of collaborations during 2014, some of which are highlighted below.
In addition, the company announced the launch of Merck Global Grants with a total annual investment of over € 20 million, thereby underscoring Merck’s commitment to funding scientific innovation and independent medical education around the world. The Grants for Innovation in Research identify and fund what are considered to be the most promising research projects in specific fields worldwide, originating from across the biopharma spectrum, including: academia, research centers, and smaller biotech companies. During the third quarter, Grants for Innovation were awarded in the areas of Multiple Sclerosis, Oncology, Growth Disorders and Fertility.
There were several important changes in the oncology pipeline during 2014. Evofosfamide (also known as TH-302), an investigational hypoxia-activated prodrug which is being developed in collaboration with Threshold Pharmaceuticals, is currently being evaluated in two Phase III trials, respectively in locally advanced, unresectable or metastatic soft tissue sarcoma (STS) and in advanced pancreatic cancer. A pre-planned interim efficacy and safety analysis of the STS study was performed in the third quarter of 2014. The Independent Data Monitoring Committee (IDMC), which conducted the analysis, recommended that the study should continue as planned to its natural conclusion. The analysis of the primary endpoint, overall survival (OS), is expected to be conducted in 2016. This date is only an approximation since the final analyses will be triggered only when a certain number of events have occurred. The second Phase III study (known as MAESTRO), which is being performed in advanced pancreatic cancer, reached planned enrollment of 660 patients in October. It is estimated that the final analysis of the primary endpoint of this trial, which is OS, will be performed in 2016. A Phase II trial of evofosfamide in combination with pemetrexed as a potential second-line treatment for patients with advanced non-squamous non-small cell lung cancer (NSCLC) was initiated in the second quarter of 2014. The primary endpoint in this 440-patient trial is OS.
As regards Erbitux® (cetuximab), new biomarker findings from a retrospective analysis of the completed Phase III CRYSTAL study were presented at the American Society of Clinical Oncology (ASCO) 50th Annual Meeting in Chicago. This study compared Erbitux® plus FOLFIRI with FOLFIRI alone in the first-line treatment of metastatic colorectal cancer (mCRC). A significant clinical improvement in terms of response rate, progression-free survival and overall survival was observed in patients with RAS wild-type tumors when Erbitux® was added to FOLFIRI compared with patients receiving FOLFIRI alone. Additionally, the results of the FIRE-3 study, a randomized, controlled, open-label, Phase III trial to compare the efficacy of Erbitux® plus FOLFIRI with bevacizumab plus FOLFIRI in first-line KRAS wild-type mCRC (mCRC), were published in Lancet Oncology in August 2014. Updated results in the RAS wild-type population were presented at the 2014 ESMO Congress in Madrid in September. While the primary endpoint of increased overall response rate with Erbitux® plus FOLFIRI compared with bevacizumab plus FOLFIRI was not met, a pre-planned exploratory analysis in the patient sub-group selected based on RAS status showed a statistically significant difference in overall survival in favor of Erbitux®. Given this clinically meaningful difference in overall survival, the authors state that “the data suggest that FOLFIRI plus cetuximab should be chosen as the first-line treatment regimen for patients with RAS wild-type mCRC.” (Lancet Oncology 2014; 15: 1065-1075).
These results are in line with the Erbitux® label as updated by the European Medicines Agency (EMA) in December 2013, and were included in an update of the Summary of Product Characteristics in June 2014. They confirm that RAS biomarker testing is essential for patient-centric care and is thus a truly personalized approach to the treatment of mCRC. Results of a second randomized, controlled, open-label, Phase III trial (CALGB / SWOG 80405), comparing Erbitux® plus chemotherapy (either FOLFOX or FOLFIRI based on each investigator’s choice) as compared to bevacizumab plus chemotherapy, were presented at the ASCO 2014 Congress and the ESMO 2014 Congress. Although showing a slight but not significant trend towards improved overall survival for patients in the RAS wild-type population treated with Erbitux® plus chemotherapy, the results seemed to differ from those of the aforementioned study. However it should be noted that the data so far are immature and the final results have not yet been published in a peer-reviewed journal.
The Chinese Food and Drug Administration (SFDA) issued a negative opinion concerning the application of Erbitux® in squamous cell carcinoma of the head and neck (SCCHN) because it considered the bridging study in Chinese patients inadequate to justify approval in China. Merck Serono decided to perform a randomized, controlled study in China in SCCHN with a view to obtaining approval for this indication. Erbitux® is currently registered in over 90 countries in this indication.
In June, Merck announced it had signed an agreement to collaborate with Sysmex Inostics GmbH, Hamburg, Germany, for the development and commercialization of a blood-based RAS biomarker test for patients with mCRC. Blood-based biomarker testing is a faster and easier approach for determining the mutation status of tumors as it requires only a small blood sample rather than a tissue biopsy procedure. The test has the potential to provide mutation status results within days, which in turn can help guide treatment decisions. In addition, it may become the method of choice in situations where a tissue biopsy is difficult to obtain, for example in patients whose physical condition does not allow for a surgical procedure.
After a careful analysis, Merck Serono decided not to pursue its development program for Sym004, and to return the rights to the compound to Symphogen for further development. This decision was not related to any new safety or efficacy findings. It will allow the company to refocus its efforts on other pipeline candidates.
Subsequent to the promising results of pre-clinical work and the ongoing Phase I trial of its c-Met kinase inhibitor tepotinib (MSC 2156119J), Merck Serono decided to embark on Phase I / II studies in solid tumors, especially focusing on the indications of NSCLC and hepatocellular carcinoma. Studies in both indications were initiated in the first quarter of 2014.
For abituzumab, an investigational anti-integrin monoclonal antibody designed to target certain integrins expressed on tumor and endothelial cells, two Phase II trials were completed this year. The results of the POSEIDON study, a combination of abituzumab with Erbitux® and irinotecan in KRAS wild-type mCRC, were presented at the ESMO World Congress on Gastrointestinal Cancer. Although the primary endpoint of increased progression-free survival was not met, the addition of abituzumab to Erbitux® and irinotecan resulted in a trend toward improved overall survival; high αvβ6 integrin expression was identified as a potential predictive marker of increased response rate, as was prolonged overall survival in the abituzumab treatment arms. Further biomarker analyses are warranted to confirm and further validate the current findings. The results of the PERSEUS study in patients with metastatic castration-resistant prostate cancer were presented at the 2014 ASCO Meeting. No significant improvement in progression-free survival was observed and development therefore will not continue in this indication.
BGB-290 (an inhibitor of poly [ADP-ribose] polymerase, or PARP), currently being developed in collaboration with BeiGene, entered Phase I clinical testing in patients with solid tumors.
Enrollment was discontinued in a combination Phase II study of the MEK inhibitor pimasertib (a small-molecule inhibitor of MEK, an enzyme that is a part of a pathway that is frequently activated in many types of solid tumors) and the PI3K / mTOR inhibitor from Sanofi U.S. (SAR245409) in low-grade serous ovarian cancer. This decision was based on the results of a futility analysis, conducted by the IDMC, which indicated that the trial was no longer expected to achieve its objective of showing a meaningful difference between the efficacy of the combination compared with pimasertib alone. However, the safety profile was in line with previous clinical data for this combination, and no unusual toxicities outside of those associated with this class were observed. The further development of pimasertib in pancreatic cancer was also discontinued as a Phase II study in this indication did not reach its primary endpoint of prolongation of progression-free survival. Pimasertib will continue to be investigated in patients with NRAS mutant malignant melanoma in a Phase II trial which is fully recruited, and expected to report results on progression-free survival (primary endpoint) during 2015. Additionally, a Phase Ib trial in solid tumors, in collaboration with Sanofi U.S., investigating pimasertib in combination with Sanofi U.S.’s hDM2 antagonist (SAR405838) will also continue.
MSC 2490484A (DNA-PK inhibitor), a small-molecule inhibitor of the repair mechanisms of DNA damage in cancer cells, entered Phase I clinical testing in patients with solid tumors.
Merck Serono and Sutro Biopharma, a privately held biotechnology company, entered into a collaboration and license agreement to develop next-generation antibody drug conjugates (ADCs) for multiple targets in oncology. Merck Serono and Mersana Therapeutics, Inc. also announced a cooperation agreement to develop next-generation ADCs. ADCs are composed of an antibody linked to a cytotoxic drug, whereby the antibody part specifically targets and delivers the cytotoxic drug to cancer cells, which could lead to higher drug levels at the tumor site.
In October 2014, Merck Serono, the Institute of Cancer Research (ICR), London, and the Wellcome Trust, London, entered into a co-development and license agreement building on two independent research programs at both the ICR and Merck Serono to identify inhibitors of tankyrase, an enzyme of the poly (ADP-ribose) polymerase (PARP) family. In a joint effort, this collaboration will aim to progress chemical compounds that have emerged from both organizations’ tankyrase inhibitor programs towards clinical development. At the end of the collaboration period, Merck Serono will take over full responsibility for the selected clinical development candidate. The agreements mentioned above underline Merck Serono’s approach to employing a collaborative research and development model, creating strategic partnerships in order to drive innovation.
For avelumab (also known as MSB0010718C), an investigational anti-PD-L1 antibody currently in development, initial data from the Phase I dose escalation study in solid tumors were presented at ASCO 2014. The study is advancing rapidly and anti-tumor activity of avelumab has already been observed in a number of patients, notably in NSCLC and in ovarian cancer. Avelumab is also being tested in a Phase II study initiated in July 2014 in patients with metastatic Merkel cell carcinoma. This is an aggressive form of skin cancer, which is rare and currently has limited treatment options. The study is a multicenter, single-arm, open trial in patients who have previously been treated with one line of chemotherapy.
In November 2014, Merck announced that it had entered into a global strategic alliance with Pfizer Inc. to develop and commercialize avelumab in order to accelerate both companies’ presence in immuno-oncology. The antibody will be developed as a single agent as well as in various combinations with Pfizer’s and Merck Serono’s broad portfolio of approved and investigational pipeline candidates. The two companies will also combine resources and expertise to advance Pfizer’s anti-PD-1 antibody into Phase I trials. As part of the strategic alliance, Merck will co-promote Pfizer’s Xalkori®, a medicine to treat NSCLC, in the United States and several other key markets. Global collaboration with Pfizer is expected to accelerate the development of avelumab in multiple tumor types. Up to 20 high priority immuno-oncology clinical development programs are expected to commence in 2015, including up to six pivotal registration studies. The global alliance is expected to enable Merck’s entry into the U.S. oncology market and to strengthen its Oncology franchise in several other important global markets.
Concerning tecemotide, an investigational cancer immunotherapy (also known as L-BLP25), a Phase III study called START2 was initiated in April 2014, following the results of the START study of tecemotide in stage III NSCLC. Although START did not meet its primary endpoint of demonstrating an improved OS with tecemotide compared with placebo in the overall patient population, data from an exploratory analysis of a pre-defined subgroup of patients who received tecemotide after concurrent chemo-radiotherapy (CRT), showed that these patients survived longer. However in September, the results of study EMR 63325-009, a Phase I / II trial in Japanese patients with stage III, unresectable, locally advanced NSCLC, the majority of whom had received concurrent CRT, indicated that no effect had been observed for either the primary endpoint, OS, or for any of the secondary efficacy endpoints. Based on these results, Merck Serono decided to discontinue the clinical development program for tecemotide.
After a careful analysis of its pipeline assets Merck Serono decided to discontinue development of NHS-IL2 (MSB0010445), also known as Selectikine, which was in Phase II testing in advanced melanoma. This decision was not related to any new safety or efficacy findings. It will allow the company to refocus its efforts on other pipeline candidates.
Merck and MorphoSys entered into a strategic immuno-oncology collaboration to discover and develop therapeutic antibodies against immune checkpoints. Under the terms of the agreement, the two companies will join forces to develop therapies that modulate the immune system’s natural ability to fight tumors. MorphoSys will apply its proprietary Ylanthia® antibody phage library and technology platform to identify antibodies against targets of interest. With its strong portfolio and capabilities in the field of immuno-oncology and clinical development, Merck Serono will be fully responsible for execution of development from Phase I onwards.
In the field of Immunology, a Phase IIb study of atacicept, an anti-Blys and anti-APRIL fusion protein, in patients with systemic lupus erythematosus (SLE) was initiated. This study is known as ADDRESS II and follows the promising results of the completed APRIL SLE study which were presented at the Annual Meeting of the European League against Rheumatism (EULAR) in 2013. ADDRESS II is a double-blind, placebo-controlled study of atacicept given at two doses in 279 patients with active SLE to assess its efficacy and safety in reducing SLE-disease activity in patients receiving standard-of-care therapy. The outcome of this study is expected in 2016. A two-year long-term extension study (ADDRESS II LTE) has also been initiated in order to develop atacicept’s safety database.
Also aiming at the treatment of SLE, an agreement was entered into by Merck KGaA, Pfizer Inc. and the Broad Institute in Cambridge, Massachusetts, in April. The collaboration is focused on the genomic profiling of patients with SLE and lupus nephritis. The goal of this research project, which will be jointly funded by Merck Serono and Pfizer, is to identify biomarkers to better define target patient populations for future therapies as well as to discover potential novel drug targets for innovative therapies.
The FORWARD study, a Phase II trial of sprifermin, an investigational fibroblast growth factor given at four doses vs placebo in patients with primary osteoarthritis of the knee, is being conducted in collaboration with Merck’s strategic alliance partner, Nordic Bioscience Clinical Development. The study completed enrollment in mid-2014, following the inclusion of 549 patients, and the outcome of the study is expected to become available in 2016. Following the completion of a Phase I study in healthy volunteers of the anti-IL-17-A/F nanobody, MSB 0010841 (also known as ALX-0761), a Phase Ib study in patients with psoriasis has been initiated.
A small-molecule BTK inhibitor (MSC 2364447) entered Phase I clinical testing in healthy volunteers in the third quarter of 2014. This investigational agent is a highly selective inhibitor of the Bruton’s tyrosine kinase (BTK), which is important in the development and functioning of various immune cells including B-lymphocytes and macrophages. Preclinical research suggests it may be therapeutically useful in certain autoimmune diseases.
Merck Serono and the Institute of Experimental Neurology at San Raffaele University and Research Hospital in Milan announced the continuation of a strategic alliance to develop pre-clinical and clinical research projects in the field of neurodegenerative diseases. The translational research will focus on developing innovative therapies against serious and disabling neurological diseases affecting young adults in particular, such as multiple sclerosis (MS). Established in 2004, the renewal of this partnership extends the agreement between the parties for two additional years.
Following completion of a Phase I clinical study that demonstrated encouraging MRI results following intradermal treatment of patients with relapsing multiple sclerosis (RMS) with ATX-MS-1467, an investigational immune-tolerizing agent, a Phase II study has been initiated in RMS.
Following a thorough portfolio review, Merck Serono decided not to pursue further development of plovamer acetate, an investigational second-generation copolymer for relapsing-remitting MS. As a consequence, the Phase II study was terminated early. Merck and Ono Pharmaceutical reached a mutual agreement to terminate the license agreement on ceralifimod (ONO-4641) since the project did not meet Merck’s threshold for continued investment.
Merck Serono remains committed to driving innovation in the field of MS and improving the lives of people living with the disease. In refocusing the pipeline, additional resources will be available to strengthen our pipeline in this area and bring additional, meaningful products and devices to people with MS.
In the field of Fertility, a Phase III trial of Pergoveris® was initiated in the first quarter of 2014 and enrollment was already completed, following the inclusion of 946 patients, in the third quarter. The trial, which is known as ESPART® (Evaluating the Efficacy and Safety of Pergoveris® in ART), is a multicenter, randomized, controlled, single-blind trial with the primary endpoint being the total number of retrieved oocytes. The study is designed to assess the efficacy and safety of Pergoveris® (follitropin alfa and lutropin alfa) versus Gonal-f® (follitropin alfa) for multifollicular development as part of an Assisted Reproductive Technology (ART) treatment cycle in women who are classified as poor ovarian responders (POR) to previous ART. Data are expected in 2015.
In the field of Endocrinology, Merck Serono announced in April that the Phase IIIb study of Kuvan® (sapropterin dihydrochloride) had met its primary endpoint. At the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium in Innsbruck in early September, detailed 26-week data from the study known as SPARK (Safety Pediatric EfficAcy PhaRmacokinetic with Kuvan®) were presented. Results from the study showed that the addition of Kuvan® at a dose of 10 or 20 mg / kg / day to a phenylalanine-restricted diet significantly increased phenylalanine tolerance in children with phenylketonuria (PKU) who are below four years of age and responsive to Kuvan®, compared with patients on diet alone. The SPARK study was requested by the EMA as a post-authorization measure. Given the positive outcome of the study, Merck Serono has submitted an application to the EMA for a label extension.
Merck Serono pipeline, as of December 31, 2014Show table
|Oncology||Evofosfamide (TH-302; hypoxia-activated prodrug)||Soft tissue sarcoma||Phase III|
|Evofosfamide (TH-302; hypoxia-activated prodrug)||Pancreatic cancer||Phase III|
|Evofosfamide (TH-302; hypoxia-activated prodrug)||Non-small cell lung cancer||Phase II|
|Evofosfamide (TH-302; hypoxia-activated prodrug)||Melanoma||Phase II|
|Evofosfamide (TH-302; hypoxia-activated prodrug)||Hematological malignancies & solid tumors||Phase I|
(DI17E6; anti-integrin mAb)
|Colorectal cancer||Phase II|
|Pimasertib (MEK inhibitor)||Melanoma||Phase II|
|Pimasertib / hDM2 inhibitor combination||Solid tumors||Phase I1|
(MSC 2156119J; c-Met kinase inhibitor)
|Solid tumors||Phase I|
(P70S6K and Akt inhibitor)
|Solid tumors||Phase I|
|BGB-283 (BRAF inhibitor)||Solid tumors||Phase I|
|BGB-290 (PARP inhibitor)||Solid tumors||Phase I|
|MSC 2490484A (DNA-PK inhibitor)||Solid tumors||Phase I|
(NHS-IL12; cancer immunotherapy)
|Solid tumors||Phase I2|
(MSB 0010718C; anti-PD-L1 mAb)
|Merkel cell skin carcinoma||Phase II|
(MSB 0010718C; anti-PD-L1 mAb)
|Solid tumors||Phase I|
|Immunology||Atacicept (anti-Blys / anti-APRIL fusion protein)||Systemic lupus erythematosus||Phase II|
(fibroblast growth factor 18)
|MSB 0010841 (ALX-0761; anti-IL-17 A / F nanobody)||Psoriasis||Phase I|
|MSC 2364447 (BTK inhibitor)||Healthy volunteers||Phase I|
|Multiple sclerosis||Phase II|
|Fertility||Pergoveris® (follitropin alfa and lutropin alpha)||Assisted Reproductive Technology, poor ovarian responders||Phase III|
|Endocrinology||Kuvan® (sapropterin dihydrochloride)||PKU in pediatric patients < 4 years||Submitted for approval3|
In its Consumer Health business, Merck markets over-the-counter medicines and food supplements in Europe – primarily for France, Germany, and the United Kingdom – as well as in Latin America and Southeast Asia, where sales volumes are rising. The focus of research and development activities in Consumer Health is on constantly improving tried and proven formulations consistent with the needs of consumers. Innovations by Consumer Health center on consumers and their needs. On the one hand, established products are being adapted to changing consumer needs while on the other hand, new technological innovations are being developed to satisfy entirely new needs. A good example of this is the new product Apaisyl® Nits Detect, which colors nits on the scalp with a fluorescent dye, thus making it much easier to comb them out. Since 2014 Merck has been increasingly entering into cooperation agreements with independent research institutions in order to tap into their expertise in developing new and existing products in a targeted manner. At the same time, Consumer Health is further developing its established brand-name products by making them simpler to use and by offering accompanying services.
Merck is the undisputed market and technology leader in liquid crystals, which are primarily used in televisions and mobile communication applications. We are also one of the leading suppliers of decorative and functional effect pigments. Our high-tech materials and solutions are used by customers in the consumer electronics, lighting, coatings, printing technology, plastics applications, and cosmetics industries. In Performance Materials, Merck is also focusing on the growth dynamics of emerging markets. As a new part of Performance Materials, AZ Electronic Materials (AZ) brings additional fields of business to the Merck portfolio. AZ serves two main markets, the sector of IC Materials for integrated circuit manufacture, and materials for display applications (Optronics).
In the area of LC displays for mobile devices, Merck has developed a new LC switching mode, UB-FFS technology (ultra-brightness fringe field switching). The new LC switching mode has the potential to increase display light transmittance by 15 %. The new technology offers many advantages: Firstly, it reduces energy consumption and increases the battery life of the mobile devices. Secondly, it improves mobile display quality and supports the trend towards higher resolutions. The market launch is proceeding faster than expected. The new switching mode is already used in many smartphones and tablet PCs.
The Merck “LC 2021” strategic initiative combines the company’s future LC activities, with a special focus on applications beyond displays. For example, liquid crystals can regulate the light and heat transmittance of windows in building facades. Since the acquisition in July 2014 of the remaining interest in Peer+, a Dutch specialist for smart window technology, the company has now been fully integrated. Merck is investing further in LC windows, the new name for the material development of these applications. The pilot production of the windows is in full swing. Several examples were installed in Merck’s own Innovation Center at the Darmstadt site in early 2015. Collaborations with partners in the glass and facade technology sector are planned for broad-based marketing of the windows.
In November, a Merck team won the 2014 Meyer-Galow Prize for business chemistry. Four LC researchers and managers were recognized for their work on the project “Energy-efficient liquid crystals for smartphones and tablet PCs”.
Organic light-emitting diodes (OLEDs) are used in innovative lighting applications and display technologies. They provide brilliant colors and sharp images from any viewing angle; they have a long lifespan and are highly energy-efficient. In addition, OLEDs enable round or flexible displays, making them perfect for use in the latest technical applications. One such example is the smartwatch, a wristwatch that provides Internet access along with additional computer functionality.
The name of the Merck product line for these types of applications is livilux®. Merck has developed a strong portfolio of worldwide patents, based on more than ten years of experience. Development partnerships with customers are a way of testing new technologies and making them market-ready. For instance, Performance Materials has co-developed a technology that can be used to print OLED displays in collaboration with printer manufacturer Seiko Epson. While Merck contributed its expertise in OLED material and ink development to the collaboration, Seiko Epson contributed its expertise in print heads featuring Micro Piezo inkjet technology as well as process expertise. The jointly developed technology offers the advantage of lower costs and higher material efficiency. In contrast to evaporated OLED displays, the materials are applied at room temperature and under normal pressure in the case of printed OLED displays. In addition, this technique only deposits material in the areas where diodes are actually located, thereby helping to conserve resources.
High-quality pigments and functional materials
Besides high-quality decorative effect pigments, Merck also offers functional materials used, for example, in laser marking of plastics, conductive coatings, and heat-reflective glazing for greenhouses. The Meoxal® brand is the latest development in effect pigments. These pigments captivate with their brilliant color saturation and exceptional performance, as a result of their innovative layer technology and the use of aluminum flakes as substrate. They are highly suitable for a multitude of high-performance applications, especially for automotive and plastic coatings. The third pigment in the new brand family – Meoxal® Atacama Red – was launched in the second quarter of 2014.
With Xirallic® NXT, Merck is launching a new patented product generation of the well-known high-tech effect pigments. These offer customers an exceptional “living-sparkle-effect”, high styling potential and consistent quality. The first product of the new generation – Xirallic® NXT Panthera Silver – is a dark-gray, metallic effect pigment, which Merck has been offering since April 2014.
AZ Electronic Materials
In the IC (Integrated Circuit) Materials business, which supplies products for integrated circuit manufacture, AZ has developed a range of products for “Extreme UV Lithography” (EUV) applications which has already been qualified by several customers from the semiconductor industry for their processes. AZ’s “shrink” technology makes it possible to reduce lithographically generated structures after patterning, thus circumventing resolution limitations of existing exposure equipment in a cost-effective manner. New products are on the verge of production implementation. AZ is a leader in Directed Self Assembly (DSA), a revolutionary technology which is crucial to all advanced semiconductor manufacturers. In DSA, the information for the smallest structures is already contained in the chemical make-up of the coating material. Additionally, AZ is intensively engaged in developing thick perhydropolysilazane (PHPS) products for 3D-chip-technology as well as novel insulator materials.
The continuous development of flat-panel display technology towards larger formats and higher operating frequencies requires the use of transistors with feature sizes that are at the limit of the resolution capability of the exposure tools. In the Optronics business, AZ has successfully transferred from its IC sector so-called tandem resin technology with a specific molecular weight distribution, thus achieving a photoresist resolution near the theoretical resolution limit. In silicon technology, new siloxane materials are in an advanced stage of qualification as planarization materials for high-resolution displays and as a thin film barrier for OLED lighting.
With nearly 800 employees focused on R&D, Merck Millipore is working with customers to develop innovative solutions for the research, development and production of pharmaceutical and biotech processes worldwide. Through dedicated collaboration on new scientific and engineering insights, Merck Millipore serves as a strategic partner to customers and helps advance the promise of life science.
In 2014, Merck Millipore launched over 20 new products, proving the innovative power of its Research & Development organization, and once again received R&D Magazine 100 Awards for innovative products. The 52nd annual R&D Awards recognize the 100 most technologically significant products introduced onto the market over the past year. The Merck Millipore products that were recognized are the SmartFlare™ detection reagent and Clarisolve® depth filters.
The SmartFlare™ detection reagent is a novel probe capable of detecting specific mRNAs and miRNAs in live, intact cells. This technology allows for carrier-free cellular endocytosis of the reagent, followed by detection and relative quantitative analysis of RNA levels. Because the reagent leaves the cell after the detection event, the same sample can be used for any downstream analysis, meaning it is possible to assess multiple biomarkers or downstream functionalities in the same cells.
Clarisolve® depth filters are specifically tuned to the particle size distribution of various pretreatment methodologies, enabling the fastest and most efficient way to clarify high-density streams and easily transfer processes from upstream to downstream without the use of centrifugation. Clarisolve® depth filters were designed for high cell density / titer mammalian cell culture feed streams for mAb production. Early success has also been achieved in microbial and vaccine applications.
In March 2014, Merck Millipore announced a clinical research, licensing and joint development agreement with Sysmex Corporation of Japan. This collaboration will use Merck Millipore’s flow cytometry technology as a platform to accelerate the creation of new, more powerful diagnostic tools for research in blood disorders. If successful, Sysmex and Merck Millipore will collaborate on developing the imaging flow technology platform for future commercialization in hematology.
In the second quarter of 2014, Merck Millipore launched a € 12 million investment in its Molsheim, France facility. This investment will expand Merck Millipore’s ready-to-use (RTU) media manufacturing capabilities, better provide security of supplies for customers in the region, and sustain the heipha Hycon product lines. The increased manufacturing capacity will serve global market demand, and will ensure sufficient capacity to support the market growth.
The Bioscience business area launched Simplicon™ RNA Reprogramming Technology, which uses synthetic self-replicating RNA to create large numbers of human induced pluripotent stem cells (iPSCs) using a single transfection step. This efficient reprogramming of somatic cells offers a more defined and safer system for iPSC generation.
The Process Solutions business area expanded Provantage® upstream bioproduction services to the North American market. The expansion provides North American customers with media and feed screening, small-scale material production, and optimization of conditions for scale-up and technology transfer. Process Solutions also announced a new Formulation Lab in India, its first outside of Europe. The Lab is strategically located at Nerul, Navi Mumbai, with easy accessibility from the major pharmaceutical manufacturing centers at Ahmedabad, Goa and Hyderabad. The facilities at the lab are built to provide services and application assistance to the pharmaceutical industry for classical pharmaceutical clients working on solid-dose formulations.
2014 also marked the 40th anniversary of the Steritest™ system, the first closed filtration device for sterility testing. Since introducing the Steritest™ system in 1974, Merck Millipore has improved standards in sterility testing, reducing the risk of false positive and false negative results, increasing reliability and streamlining workflows for microbiologists around the world. As part of the celebration of 40 years of sterility testing, Merck Millipore will be launching three new pumps in 2014.
In August 2014, Merck Millipore and Samsung BioLogics signed a Memorandum of Understanding for a strategic alliance in the biopharmaceutical business. The proposed alliance is intended to encompass a long-term supply agreement in which Merck Millipore will provide raw materials for biopharmaceutical manufacturing.
In the third quarter of 2014, Merck Millipore also announced the opening of a new Biomanufacturing Sciences Training Center (BSTC) facility in Tokyo, Japan. The state-of-the-art facility is designed to help biopharmaceutical companies develop manufacturing processes and find solutions to processing challenges in collaboration with engineers from Merck Millipore. The goal for this facility, now the ninth of its kind for Merck Millipore, is to enhance the customer experience by delivering innovation, quality products, and comprehensive technological support – all major components of our product and service portfolio offering.
In December, Merck Millipore launched its first round of new large lab water purification systems (AFS) expanding the ability to feed high-throughput analyzers.