Sarepta Therapeutics Opens its Research and Manufacturing Center at Andover

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Sarepta Therapeutics, a U.S. commercial-stage biopharmaceutical company focused on the discovery and development of unique RNA-targeted therapeutics for the treatment of rare neuromuscular diseases, has announced the grand opening of its Research and Manufacturing Center in Andover, Massachusetts.

The 60,000 square foot state-of-the-art facility significantly enhances Sarepta’s research and manufacturing capabilities as it expands its global commercial footprint and rapidly advances its Duchenne muscular dystrophy (DMD) pipeline, which comprises a robust exon skipping platform, and next generation approaches such as gene therapy and utrophin upregulation programs. The current focus of the manufacturing facility will be to advance Sarepta’s development pipeline and research programs. By the end of the year, Sarepta could have up to seven investigational DMD treatments in the clinic.

Ultimately, Sarepta’s goal is to help as many individuals with DMD as possible. To support this objective, Sarepta plans to expand its headcount in Andover by 100 percent over the next 12 to 18 months, adding to the approximately 50 employees currently based in Andover.

“Since first moving to Massachusetts in 2013, Sarepta has benefited enormously from the Commonwealth’s talented and highly-educated workforce,” said Edward Kaye of Sarepta. “This expansion underscores our ongoing commitment to patients with Duchenne and investment in the vibrant Massachusetts economy. We are grateful to Governor Baker, the Massachusetts Life Sciences Center, MassBio, the Town of Andover, and other state and local officials who support our mission to serve the greater DMD community.”

System pharmacology modelers throw light on drug discovery in Alzheimer’s

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InSysBio scientific group led by Tatiana Karelina developed a quantitative system pharmacology model of Alzheimer’s disease. First part published in CPT PSP shows how to design initial phases of clinical trials of new drugs and to interpret the data obtained.

Alzheimer’s is a chronic neurodegenerative disease which leads to the senile cognitive impairment and memory loss. Every third person older than 70 years suffers from it. Such changes are caused by functional disorders and subsequent death of neurons. However triggers of processes resulting in brain cell death are still remain unknown. That’s why there is no effective therapy for Alzheimer’s disease.

At the moment, the most common hypothesis is a theory of the toxic effect of the beta-amyloid protein, which accumulates in the brain with age, aggregating into insoluble amyloid plaques. The presence of these plaques in the brain is the main marker of Alzheimer’s disease (unfortunately, often found postmortem). Soluble (not aggregated into plaques) forms of the protein are considered to be toxic too.

All modern therapies act in one of the three ways: they can block production of soluble beta-amyloid, destruct protein before transformation into insoluble form, or to stimulate the plaque degradation. “Clinical trials for Alzheimer’s therapies have got one significant feature – their short duration. They last for no more than 5 years, whereas the disease can progress for decades. And early Phase I-II tests last for only few weeks. With such experiment design one can affect only on the processes of distribution and degradation of the soluble beta-amyloid forms. Therefore we developed this part of our model to analyze and predict the dynamics of the new generation of drugs, for instance the inhibitors of amyloid production”, says Tatiana Karelina, the head of the neurodegenerative disease modeling group, InSysBio LLC.

The first difficulty encountered by drug developers is the interpretation of the results obtained in animal tests. In general, most studies of the distribution of amyloid are carried out on mice: scientists inject a labeled protein into the mouse brain and observe the distribution of the radioactive label. Alternatively, the dynamics of amyloid in the presence of drugs is studied. Based on the data obtained, researchers can calculate the “therapeutic window” for the medication – a range of doses from the minimum effective to the maximum non-toxic. Then doses for human or monkey are calculated by using mass or volume scaling (for the body, the parameters change as many times as its mass or volume is greater than the mass or volume of the mouse).

The project team collected the data from the literature and derived a system of equations that fully described the existing results. Firstly the model was calibrated (i.e. the missing parameters were estimated) for the mouse, and then for the human and monkey. It turned out that one cannot use the scaling method to transfer results from rodents to primates (as it’s often done). The deduced mathematical equations have shown that not only the rate of production of beta amyloid (as activity of corresponding genes) differs, but moreover the blood-brain barrier is different in rodents and higher primates. At the same time, there was no significant difference between the human and the monkey, and the standard scaling can be used to translate predictions between them.

The next big question in Alzheimer’s clinical trials is how to understand if the drug affects specific target on the short term. It is impossible to observe the processes that occur in the human brain directly. Usually a cerebrospinal fluid probe is taken for analysis of the change in the concentration of beta-amyloid. Actually, these data strongly differ from the values of amyloid concentration in the brain, since the cerebrospinal fluid is strongly influenced by the processes taking place in the blood plasma, and amyloid demonstrates another dynamicsy.

“If there is such a big structural model calibrated on the big amount of data one can easily match the results of cerebrospinal fluid sample analysis with the real processes in the patient brain. This will greatly accelerate the development of new drugs and improve the accuracy of the therapy selection”, explains Tatiana Karelina.

Scientists report that their model allows to predict how these new drugs must be administered. Total daily dose can be diminished but should be split for several parts during the day, providing optimal brain efficacy. InSysBio team is confident that the systems-pharmacological modeling can greatly improve the development of drugs from Alzheimer’s disease and are already negotiating the introduction of technology with their partners in the pharmaceutical industry.

Novartis Access and government of Pakistan sign memorandum of understanding

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Ministry of National Health Services, Regulations and Coordination has signed a Memorandum of Understanding with a multinational healthcare company Novartis to help the poor gain access to treatment of chronic diseases.

Under the MoU, Ministry and Novartis will partner in the delivery of a program called Novartis Access. This program will provide access to a basket of high-quality medicines in the public sector targeting four key non communicable diseases (NCDs)–cardiovascular diseases, diabetes, respiratory illnesses, and breast cancer. These diseases kill one-fifth of Pakistanis between the ages of 30 and 70 years every year.

Products within the Novartis Access portfolio are among the world’s most frequently prescribed medicines for the targeted chronic diseases.

In pilot phase, Novartis Access medicines will be available through selected empanelled hospitals of district Islamabad under the Prime Minister’s National Health Program. The government is committed to making these NOT for SALE drugs available free of charge to patients within the program. The aim is to extend the program to all districts of Prime Minister’s National Health Program over time and work has already started in this regard.

Speaking after witnessing the signing, Saira Afzal Tarar Minister for National Health Services Regulations and Coordination, said: “I am very pleased over the signing of this Memorandum of Understanding with Novartis. Pakistan is grievously affected by the growth of non communicable diseases, and having access to high-quality treatment at low cost is a critical part of our work to lessen the impact of chronic disease in Pakistan. It is part of the Prime Minister’s ambitious plans to make Pakistan a true welfare state.”

The MoU was signed on behalf of Ministry of National Health Services, Regulations and Coordination by Director Prime Minister’s National Health Program Dr. Faisal Rifaq and CEO Novartis Mr. Shahab Rizvi.

This is the beginning of the Novartis Access partnership, and the first treatment against chronic diseases are expected to reach Pakistan soon.

Boehringer Ingelheim Inaugurates World-Class Biopharmaceutical Manufacturing Facility in China

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Boehringer Ingelheim inaugurated its commercial production site for biopharmaceuticals in Zhang Jiang Hi-tech Park of Shanghai (China). The site, with the first-phase investment of more than €70 million, is the first and only biopharmaceutical facility established by a leading multinational active biopharmaceutical manufacturer in China utilizing mammalian cell culture technology. With its global network of biopharmaceutical production sites in Biberach ( Germany), Vienna (Austria), Fremont (USA) and now Shanghai, the contract manufacturing business Boehringer Ingelheim BioXcellence™ is well positioned to fulfil strongly increasing demands of the biopharmaceutical industry for innovative products – both in China and worldwide.

“Our Shanghai facility plays an important role in our globally leading biopharmaceutical contract manufacturing business and embodies our continuous and long-term commitment to China,” said Hubertus von Baumbach, Chairman of the Board of Managing Directors at Boehringer Ingelheim. “With this investment, we expect to have a significant impact on the development of China’s biopharmaceutical industry to ultimately supply innovative medicines to patients following high quality standards.”

Boehringer Ingelheim has made this strategic move with the long-term goal to become a leader for contract development and manufacturing of monoclonal antibodies and recombinant proteins in China. Since 2014, Boehringer Ingelheim China Biopharmaceuticals has been operating its Good Manufacturing Practice (GMP) clinical material supply at 100L and 500L scales. After its inauguration, the facility will operate for clinical and commercial supply on a 2000L single-use bioreactor scale. It is designed to flexibly add additional 2000L single-use bioreactors and fill/finish capabilities to meet increasing market demand.

“As a global leader in biopharmaceutical contract manufacturing, Boehringer Ingelheim has an extraordinarily long history in the field of biotechnology, having been in the industry for over 35 years,” said Dr Luo Jiali, General Manager of Boehringer Ingelheim Biopharmaceuticals (China) Co Ltd. “We offer tailor-made contract development and manufacturing services to the biopharmaceutical industry, providing the entire production technology chain from DNA to the finished product under one roof. With our strong know-how, global network, technology, and international quality standards we can support innovative Chinese and international companies to industrialize their research results.”

THE NCRI PARTNERSHIP LAUNCHES NEW FIVE-YEAR STRATEGY TO ACCELERATE PROGRESS IN CANCER RESEARCH

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The National Cancer Research Institute (NCRI) launches its new five-year strategy today (Tuesday) to accelerate progress in cancer research through collaboration. The strategy will help cancer research funders to maximise opportunities to improve the health and quality of life of people who have had, or may one day develop, cancer. It will also ensure research continues to drive improvements in prevention, treatment, and patient care and support.

Cancer survival rates have doubled in the last 40 years and research has been central to this success. However, many challenges lay ahead that are too vast for one organisation to tackle alone. The NCRI Partnership will work together to achieve four goals: to accelerate the translation of cancer research into clinical practice, to improve the quality and relevance of research related to cancer, to address major opportunities and challenges in cancer research and to ensure a coordinated portfolio of cancer research in the UK.

Around 2.5 million people are living with, or have experienced, cancer across the UK and this number is expected to rise to around 4 million by 2030 as the population ages and research develops better treatments to help more people live longer with and beyond cancer.

Karen Kennedy, Director of the NCRI, said: “There has never been a more urgent need for collaboration to fund research that addresses the complex needs of cancer patients at every stage of their journey through and beyond cancer. Research is making life-changing advances in cancer treatments, but the long-term effects of cancer can have a far-reaching impact, affecting people’s health and quality of life.”

The NCRI Partnership enables collaboration between 19 of the biggest funders of cancer research from the UK’s charity and government sectors. It facilitates more than 250 meetings per year, to bring together the right clinicians, scientists, research nurses, patient experts and other specialists to tackle the big issues facing cancer research.

Its activities include co-ordinating a Clinical Trials Unit Group, where trial specialists collaborate to identify needs common to all cancer clinical trials, and its Clinical Studies Groups – a series of advisory groups spanning all cancer types that bring together UK experts to accelerate research to improve cancer treatments, and help those affected by cancer to live well.

One of the NCRI’s strategic goals is to seize opportunities and address challenges in cancer-related research, and as part of this it will encourage research that meets the needs of people living with and beyond cancer. In partnership with the James Lind Alliance, its new initiative in ‘Living with and Beyond Cancer’ will mean people affected by cancer and clinical health care professionals can pose the questions they feel are unanswered about living with or beyond cancer, so they can be addressed through research. People affected by cancer and health care professionals will work together to prioritise the questions in to a top-ten. The NCRI will also be working with researchers to help ensure research proposals to address the top-ten questions are successfully funded.

It’s through this kind of collaboration that NCRI will help improve the health and quality of life of cancer patients and the wider public.

Baroness Delyth Morgan, chair of the NCRI, said: “Collaboration is at the centre of the NCRI’s new strategy, ensuring patients, health care professionals and researchers all have a voice. Working together will ensure the cancer research community overcomes the enormous challenges facing them in this uncertain political and economic environment.”

The NCRI partnership was set up to facilitate collaboration between cancer research funders and to address gaps and challenges in research that wouldn’t be possible for one organisation to tackle alone. It comprises 19 key funders in cancer research across the four UK nations which, collectively, have spent more than £6 billion pounds on cancer research since the partnership was established in 2001.

WHEN LIVER IMMUNE CELLS TURN BAD

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A high-fat diet and obesity turn “hero” virus-fighting liver immune cells “rogue,” leading to insulin resistance, a condition that often results in type 2 diabetes, according to research published today in Science Immunology.

Using cells from mice and human livers, Toronto General Hospital Research Institute researchers demonstrated for the first time how under specific conditions, such as obesity, liver CD8+ T cells, white blood cells which play an important role in the control of viral infections, become highly activated and inflammatory, reprogramming themselves into disease-driving cells.

Scientists have been trying for many years to discover why the liver continues to pump out too much glucose in people with diabetes. This paper sheds light on the markers of activation and inflammation in CD8+ T cells and the Interferon-1 pathway which helps stimulate their function.

The research is entitled, “Type 1 Interferon Responses Drive Intrahepatic T cells to Promote Metabolic Syndrome,” by first authors Magar Ghazarian, a former graduate student, Dr. Xavier Revelo, a post-doctoral fellow in the lab of Dr. Daniel Winer, and senior authors Dr. Shawn Winer, Laboratory Medicine, St. Michael’s Hospital, Laboratory Medicine and Pathobiology, University of Toronto, and Dr. Daniel Winer, Diabetes Research Group and the Department of Pathology, Toronto General Hospital Research Institute and the Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto.

“We found that under conditions of obesity and a high-fat diet, the cells that typically strengthen our immune system by killing viruses and pathogens instead increase blood sugar. They become pathogenic and worsen insulin resistance,” explains Dr. Dan Winer. In fact, the normal function of the immune cells becomes misdirected. The pathways they would typically use to fight infection create inflammation, unleashing a chemical cascade which impacts insulin and glucose metabolism.     

“The immune system in the liver represents a key missing link in our understanding of how the liver malfunctions in obesity to dysregulate sugar levels,” adds Dr. Revelo.

In the study, researchers fed mice a high-fat diet, 60 per cent of which was saturated fat, for 16 weeks. Compared with normal chow diet-fed mice, the high-fat diet mice showed worsened blood sugar, increased triglycerides, a type of fat (lipid) in the blood, and a substantial increase in the numbers of CD8+ T cells in the liver.   

Instead of responding to viruses or other foreign invaders in the body, the activated CD8+ T cells launch an inflammatory response to fat, and to bacterial components that migrate to the liver from the gut through the blood.

The activated T-cells divide rapidly, pumping out increased numbers of cytokines, proteins that assist them in an active and excessive immune response.  This pro-inflammatory response in turn interferes with normal metabolism in the liver, specifically jamming up or blocking insulin signaling to the liver cells.

Since the liver stores and manufactures glucose or sugar depending upon the body’s need, the hormone insulin signals whether the liver should store or release glucose. This system keeps circulating blood sugar levels in check. If that signal is disrupted or blocked, the liver continues to make more sugar, pouring it into the bloodstream. If the liver is over-producing glucose, it becomes difficult to regulate blood sugar.

“This response never manifested itself until humans started to eat high-sugar, high-fat, high-calorie diets,” says Magar Ghazarian, now a medical student in Ireland.

Adds Dr. Shawn Winer: “We’re moving from studying diabetes as a metabolic syndrome – a combination of nutritional and hormonal imbalances – to include the role of the immune system and inflammation. That’s the developing link. Inflammation is emerging to be a major mediator of insulin resistance.”

Insulin resistance is a pathological condition linked to obesity, in which cells fail to respond normally to the hormone insulin which helps the body metabolize glucose. This results in poor absorption of glucose by cells, causing a buildup of sugar in the blood. Long-term insulin resistance eventually leads to diabetes.

The findings were confirmed in genetically-modified mice, as well as in human liver cells.

The researchers found that in genetically-modified mice lacking Interferon-1, who were also fed a high-fat diet, the CD8+ T cells did not produce an inflammatory response, and the mice had near normal blood sugar levels.

In further investigations of human liver cells from nearly 50 donor tissues of humans with varying degrees of body mass index (BMI) and liver fat, higher levels of CD8+ T cells were linked with higher levels of blood sugar or more advanced fatty liver disease. Donor tissues were obtained from Saint Louis University Hospital, Washington University School of Medicine and Mid-American Transplant Services from St. Louis and University Health Network.

The researchers note that CD8 + T cells could potentially be used as markers for the progression of fatty liver disease, which is expected to become the leading indication for liver transplantation within the next one or two decades. 

Type 2 diabetes is one of the fastest growing diseases in Canada with more than 60,000 new cases yearly. Nine out of 10 people with diabetes have type 2 diabetes. Being overweight or obese is an important risk factor for diabetes. It is estimated that 3.5 million, or about 9 per cent, of Canadians have diabetes.

The study was funded by the Canadian Institutes of Health Research, the Canadian Diabetes Association, the J.P. Bickell Foundation, and the Ontario Ministry of Research, Innovation & Science.

Biogaran takes over Swipha’s activities in Nigeria to produce generic drugs for the local market

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In order to develop new markets to meet its commitment to provide all patients with quality medication, Biogaran, a pioneer in generics and a subsidiary of Servier, has just taken over Swipha, a Nigerian pharmaceutical company that produces generics to meet local health needs. Its portfolio is mainly focused on three families of products which treat Nigeria’s most widespread infections and health issues: antimalarial drugs and antibiotics, anti-anxiety and tranquillizers.

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Nigeria is the largest economy in Africa and its most populated country (184 million inhabitants in 2016 according to the IMF).

Swipha was the first Nigerian pharmaceutical company to obtain ISO 9001 certification in 2007. Approved by the World Health Organization (WHO) in 2014, Swipha employs 300 people locally and generated record sales of NGN 4bn (approximately € 20 million) in 2012. Beyond its production unit, the company also has a wide distribution network covering most parts of Nigeria.

Health issues are particularly important in Africa. Beyond significant needs for good quality, inexpensive and effective medicines, the problem of counterfeits is also becoming of concern. The WHO estimates that 100,000 deaths are due to fake medicines in Africa every year[1]. In this context, supplying Nigeria’s population with reliable medicines that are produced locally is a strong commitment made by Biogaran.

“Biogaran’s international expansion strategy is to create synergies by bringing its expertise and investment capacity in production to existing structures”, commented Pascal Brière, President of Biogaran. “Nigeria quickly came out as the best entry point on the African continent with its strong population and solid economic fundamentals, including a very dynamic market economy; Swipha’s know-how, reputation and network have immediately convinced us that it was the right partner for us.”

Lilly Announces $850 Million Investment in U.S.

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Lilly has announced this month plans to invest $850 million in its U.S. operations in 2017. The company’s investments span facilities across its U.S. enterprise, including research laboratories, manufacturing sites, and general and administrative areas. The investments are being driven by demand for Lilly products, as well as its robust pipeline of potential medicines in development targeting cancer, pain,
diabetes and other unmet medical needs.

Company leaders were joined by federal, state and local government officials at Lilly Technology Center, where the details of the investments were unveiled, including plans for a new $85 million expansion of its Trulicity® (dulaglutide) device assembly operations in the U.S. This expansion is part of a massive five-year investment by the company to expand its diabetes products manufacturing operations in the U.S., which also includes a $140 million insulin cartridge production
facility that was officially dedicated at today’s announcement.

David A. Ricks, Lilly’s president and chief executive officer, said that Lilly’s potential for growth and its long-standing commitment to the U.S. market led to its decision to invest in its U.S. operations and expand its manufacturing footprint in Indianapolis.

“Our future at Lilly is bright, as we’re on a path to launch 20 new products in a 10-year time frame,” Ricks said. “As we have for our entire 140-year history, we continue to see Indiana and the United States as attractive places to research and make the medicines that we sell around the world.”

Ricks explained that Lilly’s $850 million investment will fund both projects that are already underway as well as new projects that will be initiated throughout the course of the year, including additional projects in Indianapolis.

Diabetes products manufacturing investment

Company officials focused much of today’s announcement around its massive investment in diabetes products manufacturing. Over the course of the last five years (2012-2016), Lilly has invested approximately $1.1 billion to boost its diabetes products manufacturing operations in the U.S. These investments include upgrades to existing facilities, as well as the addition of new capacity and capabilities based on the evolution of the company’s diabetes pipeline and portfolio and
the increased prevalence of the disease.

During this period, Lilly has increased its U.S manufacturing workforce by more than 1,000 employees—from 5,000 to 6,000 roles—with approximately 400 added in Indianapolis.

“More than 400 million people around the world have diabetes—and that includes approximately 30 million people in the U.S. alone,” said Enrique Conterno, president, Lilly Diabetes and Lilly USA. “Lilly has spent more than 90 years providing solutions to people with diabetes, and today’s announcement extends the deep commitment of our heritage. This manufacturing expansion, along with the introduction of several other new treatments over the last two and a half years, will allow Lilly to continue to be a leader in diabetes care.”

Conterno added that the new investments underscore Lilly’s diabetes manufacturing presence in Indianapolis. Lilly’s stateof-the-art manufacturing facility in Indianapolis is part of the company’s nine-decade legacy of producing insulin.

“In addition to providing the capacity necessary for the safe and reliable supply of medicines to patients, these investments have allowed us to add U.S. manufacturing jobs,” said Maria Crowe, president of Lilly Manufacturing. “These include highlyskilled technicians, scientists and engineers, which are an economic catalyst for local communities.”

Further, Crowe noted that during the past five years, construction-trade staffing has averaged nearly 500 jobs, and had a peak level of nearly 1,000 workers. The ongoing operations together with the investment programs will continue to require a significant level of construction-trade workers at the Lilly Technology Center.

“Lilly’s announcement today is a clear example of what a fiscally sound state with a strong business climate—coupled with a world-class company—can achieve,” said Indiana Gov. Eric J. Holcomb. “I am grateful for Lilly’s continued investment in Hoosiers and in our home state, and will work to maintain the strength of the life-sciences industry and advanced manufacturing in Indiana.”

“Despite a global presence and diverse interests, Lilly’s continued investment in Indianapolis is a testament to their exceptional level of faith in our workforce and a decades-long commitment to this community,” said Indianapolis Mayor Joe Hogsett. “As the biotech industry continues to grow in Indianapolis, Lilly remains a clear leader, bringing advancements to the field and high paying jobs to the city. I’m excited for what today’s announcement means for the company’s future and
look forward to Lily’s continued advancements as their footprint in our city grows.”

Ricks concluded by saying that Lilly has invested approximately $5 billion in its U.S. facilities during the last decade and that more investments can be expected, particularly if the U.S. adopts a more favorable tax environment.

“The equitable treatment of foreign earnings, a lower U.S. corporate tax rate, and U.S. innovation incentives—similar to the rest of the world—will encourage significant investment in the U.S., creating economic growth and good jobs for Americans,” said Ricks. “The House Republican Blueprint with border adjustability is designed to achieve these priorities, puts America’s global companies on a level playing field with competitors around the world, and creates economic growth and employment
within the U.S.”

Sanofi and Lonza Enter into a Strategic Partnership to Establish a Large-Scale Biologics Production Facility

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Sanofi and Lonza have announced that they have entered into a strategic partnership to build and operate a large-scale mammalian cell culture facility for monoclonal antibody production in Visp, Switzerland. The strategic partnership in the form of a joint venture combines the strong biologics development pipeline of Sanofi with the expertise of Lonza to design, construct, start-up and operate a state-of-the-art large-scale mammalian cell culture facility. The initial investment will be around CHF 290 million (€ 270 million), to be split equally between each company.

The initial phase of the facility will commence construction in 2017, pending necessary regulatory approvals, and is expected to be fully operational by 2020. Lonza has previously built and licensed three similar facilities in the U.S. and Singapore.

“In addition to the investments we are making in building our own internal production capabilities, the joint venture between Sanofi and Lonza emphasizes our commitment to provide access for patients to high quality therapeutic monoclonal antibodies,” said Philippe Luscan, Executive Vice President, Global Industrial Affairs, Sanofi. “Approximately sixty percent of our pipeline is made up of biologics, including monoclonal antibodies, dedicated to key disease areas such as cardiovascular, immunology and inflammation, neurology and oncology. Lonza is a highly experienced partner in this field and the capabilities which this joint venture will create are critical to meeting our patients’ needs for these important therapies.”

“By entering into this long-term strategic relationship we have developed a tailor-made business model that best fits both Sanofi’s and Lonza’s requirements. It provides to Sanofi dedicated capacity, which allows for a clear win-win situation for all participants,” said Marc Funk, COO Pharma & Biotech, Lonza. “As part of our strategic roadmap, we will develop further innovative business models based on the requirements of our customers. We intend to address these long-term market needs by establishing a state-of-the-art strategic biologics manufacturing platform. The strategic partnership with Sanofi represents the first module in this undertaking; and we are convinced that with this future-oriented approach, we can serve additional customers.”

The partnership provides both Sanofi and Lonza with substantial flexibility in an innovative setup:

  • Each party will share the available capacity in line with their equity shareholding in the joint venture
  • Sanofi will have additional access to bio-manufacturing capacity to support increasing demands for their portfolio of biologic therapeutic products, should they require it
  • Lonza will be free to market their share of capacity, if not required by Sanofi, and will also market unused Sanofi capacity, where available.
  • Lonza will construct the facility and will support the joint venture in its operation of the facility.

The strategic partnership enables Sanofi to react quickly to fluctuations in demand in a short timeframe, reinforcing their capability to launch high-quality, next generation biologic medicines and ensure consistent access for patients. It also provides Lonza with needed capacities to respond to growing manufacturing demands for large-scale mammalian cell culture based therapeutic proteins, therefore allowing Lonza to better serve its customers. By adding flexibility in this way, this model will help to optimize biologics production capacity across the whole industry.

Spider web of cancer proteins reveals new drug possibilities

Senior author Haian Fu, PhD

Scientists at Winship Cancer Institute of Emory University have mapped a vast spider web of interactions between proteins in lung cancer cells, as part of an effort to reach what was considered “undruggable.”

This approach revealed new ways to target cells carrying mutations in cancer-causing genes. As an example, researchers showed sensitivity to an FDA-approved drug, palbociclib, for a gene that is commonly mutated in lung cancer cells, which is now being tested in a clinical study.

 

Senior author Haian Fu, PhD

Many genes that drive the growth of cancer cells don’t have any drugs available against them. For “tumor suppressor” genes, researchers are often not sure how to go after them. When the tumor suppressors are gone, cells often become more deranged, but there’s no bullseye left to target. Exploiting the cancer cells’ derangement remains a daunting challenge, says senior author Haian Fu, PhD.

“Our approach is to place tumor suppressors in the context of a network of cancer-associated proteins and link tumor suppressors to drugs through a known drug target protein” Fu says. “In this way, changes in a tumor suppressor may be linked with the response of the target to the connected drug.”

The study is part of a push by the National Cancer Institute’s Cancer Target Discovery and Development (CTD2) network to translate genomics data into therapeutic strategies, he says. Emory is a member of the NCI CTD2 network.

Fu holds the Winship Partner in Research endowed chair and is leader of Winship’s Discovery and Developmental Therapeutics Program, director of the Emory Chemical Biology Discovery Center and professor of pharmacology and hematology and medical oncology. Co-corresponding author Fadlo Khuri, MD, maintains his professor appointment at Winship Cancer Institute and is now president of the American University of Beirut in Lebanon.

Cancer researchers have been searching for ways to target mutations in the gene STK11/LKB1, found in 15 to 25 percent of non-small cell lung cancers. The tumor suppressor STK11/LKB11 encodes an enzyme that is thought to regulate cell migration and metabolism.

One of the Winship team’s newly identified interactions — a “thread” in the spider web — suggested that palbociclib, recently approved against metastatic breast cancer, may work against cells carrying mutations in LKB1, through LKB1’s connection to CDK4, the target of palbociclib.

That prediction was supported by genomic data analysis and cell culture experiments: lung cancer cells with LKB1 defects showed a tendency of increased sensitivity to palbociclib. Now a study led by Taofeek Owonikoko, MD, at Winship is using LKB1 status as a biomarker for interpreting the effect of palbociclib.

How OncoPPI works

If cells are complex machines, then a number of ways exist for figuring out how the machines’ parts, dominated by proteins, fit together. Some of them involve multiple washing steps to remove nonspecific partners after breaking cells apart, but FRET (Förster resonance energy transfer) does not. If two fluorescent molecules with colors that are near on the spectrum are close enough (less than 10 nanometers), that proximity can be detected by FRET.

Fu and his colleagues established a large-scale platform for tagging proteins with two different fluorescent molecules, introducing them into cancer cells, and then detecting interactions between the proteins. They call this network of cancer-associated proteins “OncoPPI.”

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Starting witha set of 83 lung cancer-related proteins, the team detected more than 260 interactions that were not known previously. They tested the interactions several times, in different orientations, and in other lung cancer cell lines with selected interactions to establish reliability. More than 80 percent of the interactions the researchers detected could be confirmed by another method (GST pulldown).

As an additional example to illustrate the utility of a protein interaction web, the team focused on the prominent oncoprotein Myc, which was also considered “undruggable.” But the researchers could connect Myc indirectly through NSD3 to another protein called Brd4, against which inhibitors have been developed. Brd4 inhibitors are being currently tested in clinical trials. This finding revealed a new pathway Brd4-NSD3-Myc as potential targets for therapeutic intervention, Fu says.

The OncoPPI research was supported by the National Cancer Institute Cancer Target Discovery and Development network, lung cancer program project and Winship Cancer Institute and the Georgia Research Alliance, and the Emory University Research Committee. The clinical study of palbociclib is sponsored by Pfizer.