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Anchor Line Partners Topps Off Cambridge Building: 100% Leased with Two Life Sciences Tenants – Boston Real Estate Times

Cambridge, Mass. Anchor Line Partners, LLC and partner Northwood Investors, LLC announced a construction milestone for 60 First Street in East Cambridge.

The team celebrated the topping off placing the last steel beam atop the two-story addition and overall retrofit of their Life Sciences project located at the former Sears building within the Cambridgeside 2.0 redevelopment. Anchor Line is also pleased to announce that ahead of completion, 60 First Street is now 100% leased.

Located at the intersection of First and Thorndike, 60 First Street is currently undergoing abuild outof the existing three stories, as well as a two-storyexpansion.Upon completion, the building willoffer cutting edge class-A lab/office, ground-floor retail, and a newwalkway connecting to the Cambridgeside 2.0 ecosystem in the East Cambridge / Kendall Square neighborhood.

Before placing the final steel beam last week, Anchor Line was pleased to welcome two tenants to the 60 First Street community.

Prime Medicine,a biotech startup focused on gene editing, announced earlier this year that they will occupy three floors and approximately 148,000-SFof the redevelopment.

Korro Bio, a leading RNA editing company focused on the discovery and development of novel genetic medicines, recently announced they will occupy 50,000-SF at 60 First Street.

East Cambridge continues to prove to be the nexus for finding cures to disease and improving the quality of life for people. It is our mission to provide these companies that are on the frontier of change the environments they need to succeed, said Andrew Maher, Managing Director at Anchor Line Partners. We are thrilled to welcome Prime Medicine and Korro Bio to 60 First Street.

Were excited to move forward with plans to relocate Korros corporate headquarters to the 60 First Street development in mid-2023. The company continues to grow and we anticipate having over 100 employees collaborating in this dynamic, cutting-edge space, in the heart of the reimagined Cambridgeside area, said Anna Barry, Chief Operating Office of Korro Bio

As an innovative headquarters integrated into the Cambridgeside 2.0 redevelopment, this is where solutions to the complex challenges of tomorrow are solved.Conveniently situated on the newly revitalized Lechmere MBTA station, 60 First and CambridgeSide are setting the bar for the future of mixed-use ecosystems.

Construction management firmGilbaneBuilding Company is the GC on this redevelopment.

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CAR T without the toxicity: Kelonia gets $50M for a new take on cell therapy – MedCity News

Cell therapy started as highly personalized, with treatments made by taking a patients own immune cells and engineering them in a lab. Multiple efforts are underway to develop off-the-shelf cell therapies but these treatments made from donor cells are not personalized and could prompt immune responses. Kelonia Therapeutics is proposing another alternative: an off-the-shelf cell therapy that is also personalized to the patient. The biotech company aims to offer both features with technology that enables the cell engineering to happen inside of the patient.

Were solving for something that no one else is solving for right nowthat in vivo gene delivery, said Kevin Friedman, Kelonias president and chief scientific officer.

The Cambridge, Massachusetts-based startup recently emerged from stealth with $50 million in financing closer to bring its research closer to clinical testing. The Series A round includes participation from Alta Partners, Horizon Ventures, and Venrock.

The cells used in cell therapy are engineered with lentiviruses that deliver a genetic payload. In a CAR T therapy, that genetic payload gets the cell to express a receptor that targets a protein on cancer cells. The multi-step process for making these therapies is expensive, laborious, and time consuming. It can take a month or more to turn a patients immune cells into a CAR T treatment.

Kelonia builds on work done with lentiviruses. Friedman said the problem with current lentiviral technology is that the virus binds to a receptor expressed on a broad number of tissues. That means some of it goes to unintended targets, leading to toxic effects. Kelonias technology enables targeted delivery. The technology modifies the envelope of the lentivirus, which detargets it, Friedman said. The virus is then decorated with antibodies that redirect the virus. Infused into the body, those viruses go to the desired cells taking with them their genetic cargos. The cells then express a therapeutic protein, such as a cancer-targeting receptor. Friedman said Kelonias approach avoids the multi-step manufacturing process required of currently available cell therapies.

Were eliminating all that, Friedman said. Were eliminating that and ending up with essentially a personalized medicine.

Kelonias detargeting technology comes from the MIT lab of Michael Birnbaum, a professor of biological engineering and a co-founder of the startup. He is among the authors of a research paper published last month in Nature Methods describing the detargeting and redirecting of lentivirus-like particles.

Kelonia is pushing forward with two partners that are helping the biotech develop its new therapies. Antibody specialist Adimab will discover the antibodies used to decorate the lentiviral envelope, directing it to the desired cells. The lentiviral particles will be manufactured by ElevateBio in its facility. Kelonia will codevelop the manufacturing process with ElevateBio. Friedman said that working with ElevateBio will reduce what are typically long lead times for transferring technology from process discovery labs to GMP facilities.

The first CAR T-therapies to reach the market were treatments for blood cancers. Kelonia is also going after blood cancers as its first indication, aiming to use its technology to offer an off-the-shelf CAR that avoids the adverse effects associated with the current treatments. Those risks include brain toxicities and a dangerous immune response called cytokine release syndrome. Friedman contends that Kelonias approach of producing the anticancer therapy inside the patient should be safer, but the company will need to prove it in clinical trials, of course.

Friedman declined to offer a timeline for beginning human testing, but he said that by getting this technology into the clinic quickly, Kelonia would leapfrog ex-vivo cell therapy approaches while also generating the clinical data to further understand the platform and lay the groundwork for additional therapies. Pursuing a new indication can be accomplished simply by switching out the cargo and engineering the lentivirus for delivery to different tissue. In addition to CARs, Friedman said the Kelonia technology can be applied to T cell receptors or a range of genetic cargos. Beyond cancer, the biotech aims to develop its technology for delivery to neurological, muscular, and renal tissues.

In addition to manufacturing advantages, Friedman said Kelonias technology offers the potential to improve the accessibility of these medicines. Without the need for a complex manufacturing process, Kelonia wont need to be administered only at major medical centers. It could also be offered at community hospitals, making the incredible clinical benefit democratized to the patient no matter where they are, Friedman said.

Kelonia already has big pharma competition. Last year, Sanofi spent $160 million up front to acquire Tidal Therapeutics, a preclinical startup with technology for in vivo delivery of messenger RNA to immune cells in order to reprogram them to address disease targets. Sanofi said Tidals technology could improve the safety profile of cell therapies while also enabling repeat dosing. The pharma giant added that this technology brings the potential for an off-the-shelf approach that could broaden the reach of these therapies to more patients. In addition to cancer, Sanofi said the technology also has applications in autoimmune diseases.

Photo: royaltystockphoto, Getty Images

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CAR T without the toxicity: Kelonia gets $50M for a new take on cell therapy - MedCity News

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New Dimension Added to Our Understanding of Genetic Mutations and Biological Evolution – Technology Networks

In biological evolution, we know that its all about the survival of the fittest: organisms that develop genetic traits that allow them to better adapt to their physical environment are more likely to thrive, and thus pass down their winning genes to their offspring.

From the longer-beaked Galapagos Island finches studied by biologist Charles Darwin that enabled them to more effectively snatch insects, to the ability of some humans over others to digest milk, the process of natural selection results in genetic differences that give some organisms an edge over others.

New research by University of Toronto Mississauga biology assistant professorAlex N. Nguyen Baadds an important dimension to our understanding of how genes interact in the evolutionary process.

Nguyen Ba is the co-principal investigator behinda study published this month in the journalScience.The first-of-its-kind study shows that different combinations of genetic mutations can have an impact on the evolutionary process a finding that could benefit areas such as personalized medicine and vaccine design.

Evolution is a force that drives all of life on this planet,"Nguyen Ba says.

"Understanding how much we can predict about adaptation has been of strong interest to many people in the field.

Adaptation can be compared to climbing a mountain. The paths taken to the various possible peaks are thought todue to successive mutations, and irregularitiesin the terrain can be attributed to the specific combinations of mutations acquired along the way.But how can scientists predict the route to the mountain top?

There are huge implications if we can figure out whats going to happen in the future for living organisms.

At UTMsannb lab, Nguyen Ba and his team of researchers explore genetic mutations in cells and their impact on evolution using next-generation technologies. These include high-throughput synthetic biology designing new biological systems or changing existing ones for research purposes and a desk-sized robot that can process numerous biological samples.

He started the study five years ago when he was a postdoctoral fellow at Harvard Universitys Desai Lab. There, he collaborated withChristopher Bakerlee, who is the studys co-principal investigator.

Together, Nguyen Ba and Bakerlee used CRISPR gene-editing technology to alter genes in the cells of yeast, which iscommonly used in genetic engineering research because it shares some genes with humans.

They worked with 10 missense mutations, which are aberrations in DNA code that change the production of amino acids. Considered the building blocks of life, amino acids are molecules that combine to form proteins, which conduct everything from healing wounds to providing energy to making antibodies.

The experimentation process involved testing out all possible combinations of these mutations 1,024 in total. The scientists wanted to determine how interactions between genes affectthe expression of certain genetic traits.

Nguyen Bacompleted the final year of the study at UTM, where he analyzed and interpreted the data. The study revealed that evolution frequently samples combinations of gene mutations with negative synergy between them. This acts on the yeasts evolutionary potential in negative ways, for example, by slowing their rate of adaptation.

The findings run counter to the dogma that all biological adaptation unfolds in a predictable way due to some unknown biological law.

Instead, combinations of mutations that have accumulated through time dictate the future evolutionary potential of an organism.

Moreover, he says, it challenges the dominant view in genetic research that we should study one gene mutation at a time.

Examining mutations in combination could help us understand diseases and lead to more precise medicine.

We're showing that in order for us to have a full understanding of how genes actually behave, says Nguyen Ba, the combinations of mutations are likely to be very important.

Reference: Bakerlee Christopher W., Nguyen Ba Alex N., Shulgina Yekaterina, Rojas Echenique Jose I., Desai Michael M. Idiosyncratic epistasis leads to global fitnesscorrelated trends. Science. 2022;376(6593):630-635. doi: 10.1126/science.abm4774.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Mapping out the human genome – VA’s Office of Research and Development

In VAs Million Veteran Program, researchers are mapping the human genome by using genotypinga process that spells out several hundred thousand data points, one-by-one. (Photo for illustrative purposes only Getty Images/alanphillips)

May 19, 2022

By Mike Richman VA Research Communications

"The importance of this cannot be overstated. Using TOPMed's imputation panel vastly enriches MVP's genetic database."

Since 2011, more than 875,000 Veterans have donated their DNA to the VA Million Veteran Program (MVP). In the program, VA researchers are sequencing Veterans' genomesa complete set of genetic materialto better understand how genes, lifestyles, and military exposures can affect a persons health and risk for illness.

Centrifugation helps scientists extract DNA from a Veteran's blood sample and prepare the DNA for genetic analysis, either through genotyping or whole genome sequencing.

Centrifugation helps scientists extract DNA from a Veteran's blood sample and prepare the DNA for genetic analysis, either through genotyping or whole genome sequencing.

Researchers map the genomes using genotypinga process that spells out several hundred thousand data points, one-by-one. To fill in any missing data, scientists look to genomes where all data points have been fully sequenced. These genomes are used as a reference to determine the missing letters.

MVP has created whole genome sequences for over 140,000 Veterans. However, it takes time to process this large amount of data and make it available for research. It takes even more time to develop a calculation toolcalled an imputation panelto determine the missing data points that remain when genotyping is complete.

In efforts to find a more accurate and cost-effective method for predicting missing genomic data points, VA investigators found a potential interim solution just across town in Bethesda, Maryland: a genomic research program at the National Institutes of Health (NIH).

As part of that solution, MVP has been collaborating with NIH to use a reference panel for imputation.

The panel is run by TOPMedthe Trans-Omics for Precision Medicine Program. The program, funded by NIHs National Heart, Lung, and Blood Institute (NHLBI), aims to generate scientific resources that will improve the understanding of heart, lung, blood, and sleep disorders and advance precision medicine, an approach in health care that takes into account a persons gene variants and his or her environment and lifestyle to find the right treatment.

Since 2014, TOPMed has collected the entire genome sequence of more than 100,000 people. Scientists created a new reference genome and imputation panel based off these whole-genome sequences.

This first-of-its kind imputation panel offers far more statistical accuracy than any previous imputation panels. In that way, it will help scientists develop better treatments specific to a persons genes and environment.

MVP wanted to find a way to use this tool to improve its genetic database, now one of the largest in the world. The database supports the work of more than 500 researchers across VA. With better genetic data, the researchers can uncover new genetic markers associated with disease in Veterans that could someday revolutionize their health care. As such, MVP leaders set out to strike up a partnership with their colleagues in Bethesda.

In 2018, TOPMed and VA began discussions with the goal of using this new imputation panel to re-do genetic analysis on DNA shared by hundreds of thousands of Veterans in MVP.

The importance of this cannot be overstated, says Dr. Phil Tsao, MVPs co-principal investigator in data generation and access. Using TOPMeds imputation panel vastly enriches MVPs genetic database. Over 500 researchers use MVP data to find new genetic markers related to health and illness in Veterans. With better data, they can make better findings. With better findings, we can offer Veterans better care with more laser-focused accuracy.

The TOPMed reference genome for this imputation panel was selected with racial and ethnic diversity in mind. This means VA can make much more accurate sequencing predictions for people who come from non-European ancestry. This is critical for MVP, since approximately 30% of the more than 875,000 Veterans in MVP are from non-European descent.

To be able to more accurately assemble their genome means the research we do on non-European Veteran populations will be much more thorough, says Dr. Sumitra Muralidhar, the director of MVP. That means we can discover new, never-before-known genetic markers connected with health and disease in Veteran populations of non-European descent.

In 2020, VA acquired the TOPMed imputation panel from NIH, and researchers began methodically re-analyzing and updating more than 650,000 genomes from Veterans who provided blood samples when they joined MVP. In December 2021, the update was complete and the new, upgraded data on hundreds of thousands of Veterans became available to research.

Due to our collaboration with TOPMed, we have better genetic data now, which will hopefully lead to findings of new genetic markers for diseases, specifically in diverse Veterans, Muralidhar says. The end result will hopefully be new discoveries and better treatments, as well as a better understanding of the biology of diseases. That way, we can offer more precise treatments for diseases and other health conditions.

Now that MVPs genetic data is updated with TOPMeds reference panel, any findings from MVP data can becompared and validated with findings from other research based on genomes that were also imputed using TOPMeds reference panel.

Use of the TOPMed reference panel in MVP, which is one of the worlds largest genomic biobanks, allows for more collaboration between NIH and VA scientists to cross-validate each others analysis results, says Dr. Saiju Pyarajan, director of the Center for Data and Computational Sciences at the VA Boston Healthcare System. The more people around the world who have been compared to the same reference sample, the more were able to drastically increase the confidence in the conclusions or results from these genomic analyses. This is wonderful for the future of precision medicine.

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Fly Researchers Find Another Layer to the Code of Life – Duke Today

DURHAM, N.C. -- A new examination of the way different tissues read information from genes has discovered that the brain and testes appear to be extraordinarily open to the use of many different kinds of code to produce a given protein.

In fact, the testes of both fruit flies and humans seem to be enriched in protein products of these rarely-used pieces of genetic code. The researchers say the use of rare pieces of code may be another layer of control in the genome that could be essential to fertility and evolutionary innovation.

A decade after solving the structure of DNA as a double helix of the bases A,C, T and G, Francis Crick went on to decode the intermediate step by which three of these letters are translated into a codon, the recipe for a single amino acid, the building block of protein.

What was striking at the time and still somewhat puzzling is that this layer of lifes code used 61 different three-letter codons to produce just 20 amino acids, meaning many codons were being used to describe the same thing.

Were taught in our biology classes that when you change from one version of the codon to the other, and it doesn't change the amino acid, that's called a silent mutation. And that implies that it doesn't matter, said Don Fox, an associate professor of pharmacology and cancer biology in the Duke School of Medicine.

Yet when researchers have sequenced all these different organisms, they found a hierarchy, Fox said. Some codons are really frequent and some are really rare. And that distribution of codons can vary from one kind of tissue in an organism to another.

Fox wondered if the rarities play a role in how, say, a liver cell does liver things and how a bone cell does bone things.

Fox and his team, headed by PhD student Scott Allen, wanted to zoom in on the rare codons, using their preferred model Drosophila melanogaster, the laboratory fruit fly. A growing body of work has shown that dissimilar tissues have varying codon bias that is, different frequencies of synonymous codons occurring in different tissues. Rare codons are known to slow down and even stop protein production and genes with a lot of these rare codons make a lot less protein, Fox said.

Fox was collaborating with colleague Christopher Counter, the George Barth Geller Distinguished Professor of Pharmacology at Duke to understand a gene called KRAS, which is known to be a bad actor in pancreatic cancer especially, and which carries a lot of rare codons. Why, they wondered, would a cancer mutation have slowed down protein production, when normally a cancerous mutation makes more of something.

It turns out, the way KRAS is designed, it should be very hard to make any of it, Fox said.

Foxs team developed a new way of analyzing tissue-specific codon usage to look at where and how rare codons can be used in the fruit fly, which has perhaps the best-known genome in science. They ran a series of experiments to vary which codons were included in the KRAS gene and found that rare codons had a dramatic effect on how KRAS controls signaling between cells.

I realized from this cancer collaboration that we could take similar approaches and apply them to my primary research question, which is how tissues know what they are, Fox said.

In further experiments, they found that testes in flies -- and in humans -- are more tolerant of a high diversity of codons, but fly ovaries are not. The fly brain was also more tolerant of diverse codons. The work appeared May 6 in the open access journal eLife.

One particular gene with a high number of rare codons, RpL10Aa, is evolutionarily newer and helps to build the ribosome, the protein-assembly machinery in the cell. Fox said it appears that this genes rare codons serve to limit its activity to just the more tolerant testes, and that, in turn, may be something critical to fertility.

The way the testes seem to permit almost any gene being expressed, perhaps that makes it a breeding ground, if you will, for new genes, Fox said. The testes seems to be a place where younger genes tend to first be expressed. So we think it's sort of this more permissive tissue, and it lets new genes take hold.

What we think were seeing is that rare codons are a way to limit the activity of this evolutionarily young gene to the testes, Fox said. That would make rare codons yet another layer of control and fine-tuning in the genes.

The editors of eLife said the work breaks new ground in identifying codon usage as a basis for tissue-specific gene expression in animals.

This research was supported by the American Cancer Society, (RSG-128945) the National Science Foundation, and the National Institutes of Health (R01-CA94184, P01-CA203657, R35-GM140844, R01-HL111527)

CITATION: "Distinct Responses to Rare Codons in Select Drosophila Tissues," Scott R Allen, Rebeccah K Stewart, Michael Rogers, Ivan Jimenez Ruiz, Erez Cohen, Alain Laederach, Christopher M Counter, Jessica K Sawyer, Donald T Fox. eLife, May 6, 2022. DOI: 10.7554/eLife.76893 https://elifesciences.org/articles/76893

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CHMP Recommends Approval of Lilly and Incyte’s OLUMIANT (baricitinib) as the First and Only Centrally-Authorized Treatment for Adults with Severe…

INDIANAPOLIS, May 20, 2022 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) and Incyte (NASDAQ:INCY) announced today that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for OLUMIANT (baricitinib) for the treatment of adults with severe alopecia areata (AA).

This opinion marks the first step toward European regulatory approval of OLUMIANT for patients with severe AA, and it is now referred to the European Commission for final action. If approved, OLUMIANT would be the first centrally-authorized oral treatment and first JAK inhibitor for patients with severe AA in the European Union. The European Commission's decision is expected in the next one to two months.

"Alopecia areata is an often-misunderstood autoimmune disease that can lead to unpredictable hair loss, ranging from bald patches to complete loss of all hair. The disease carries significant psychosocial burden and can impact patients of any race, ethnicity, or age, with many experiencing alopecia in their early to mid-20s," said Bianca Maria Piraccini, M.D., Ph.D., professor and head of the Dermatology Unit at the University of Bologna. "As there has never been a centrally-authorized therapy for alopecia areata, I'm delighted about Lilly's potential to provide this oral medicine with statistically significant and clinically meaningful Phase 3 clinical trial results for adults with severe alopecia areata across Europe."

The positive opinion was based on Lilly's Phase 3 BRAVE-AA1 and BRAVE-AA2 trials evaluating the efficacy and safety of OLUMIANT in 1,200 patients with severe AA, the largest Phase 3 clinical trial program with completed primary endpoints. Severe AA was defined as having a Severity of Alopecia Tool (SALT) score 50 (50% scalp hair loss). The primary endpoint was the proportion of patients achieving SALT 20 (i.e., 80% or more scalp hair coverage) at Week 36. Across both studies, 1 out of 3 patients treated with OLUMIANT 4-mg achieved 80% or more scalp hair coverage (BRAVE-AA1=35.2% [n=99]; BRAVE-AA2=32.5% [n=76]), compared to 1 out of 20 patients (5.3%, n=10) and 1 out of 50 patients (2.6%, n=4) taking placebo in BRAVE-AA1 and BRAVE-AA2, respectively (p0.001 for all comparisons to placebo).

Achievement of full regrowth or regrowth with minimal gaps in eyebrow and eyelash hair was also seen at 36 weeks with OLUMIANT 4-mg for 1 in 3 patients who at baseline had significant gaps or no notable eyebrows or eyelashes, as compared to patients taking placebo (BRAVE-AA1: 4-mg dose: eyebrow=31.4% [n=59]; eyelash=33.5% [n=56]; placebo: eyebrow=3.2% [n=4]; eyelash=3.1% [n=3]; BRAVE-AA2: 4-mg dose: eyebrow=34.8% [n=56]; eyelash=34.3% [n=48]; placebo: eyebrow=4.5% [n=5]; eyelash=5.6% [n=5]; p0.001 for all comparisons to placebo). Eyebrow and eyelash hair loss was evaluated using the Clinician-Reported Outcome (ClinRO) Measure for Eyebrow Hair Loss and ClinRO Measure for Eyelash Hair Loss novel, clinically-validated tools developed by Lilly.

The Phase 3 BRAVE-AA clinical program also evaluated the safety profile of OLUMIANT, and no new safety signals were observed. Few patients discontinued treatment due to adverse events (2.6% or less across both studies), and the majority of treatment-emergent adverse events were mild or moderate in severity.

"We're proud of today's CHMP opinion as it reflects our commitment to immunological diseases with high unmet need," said Patrik Jonsson, Lilly senior vice president, president of Lilly Immunology and Lilly USA, and chief customer officer. "This is a significant step for OLUMIANT on the path to becoming the first and only centrally-authorized medicine in Europe for adults with severe alopecia areata. We eagerly anticipate additional regulatory decisions around the world this year."

InFebruary 2022, theU.S. Food and Drug Administration(FDA) granted priority review for OLUMIANT in adults with severe AA.Lillyexpects additional regulatory decisions in theU.S. andJapanin 2022.

About OLUMIANT

OLUMIANT, a once-daily, oral JAK inhibitor, was discovered by Incyte and licensed to Lilly. It is approved in the U.S. and more than 75 countries as a treatment for adults with moderate to severe rheumatoid arthritis and is approved in more than 50 countries, including the European Union and Japan, for the treatment of adult patients with moderate to severe atopic dermatitis who are candidates for systemic therapy. FDA approval was granted for OLUMIANT for the treatment of certain hospitalized adult patients with COVD-19 in May 2022. Marketing authorization for OLUMIANT in COVID-19 has been granted in six other countries including Japan and Switzerland. Baricitinib is authorized for emergency use in eight countries. Over 400,000 patients have been treated with OLUMIANT for approved indications, in addition to nearly one million patients with COVID-19 worldwide. The U.S. FDA-approved labeling for OLUMIANT includes a Boxed Warning for Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events, and Thrombosis. See the full Prescribing Information here. OLUMIANT is being investigated in alopecia areata (AA), juvenile idiopathic arthritis (JIA) and in pediatric patients with atopic dermatitis (AD).

In December 2009, Lilly and Incyte announced an exclusive worldwide license and collaboration agreement for the development and commercialization of OLUMIANT and certain follow-on compounds for patients with inflammatory and autoimmune diseases.

Indications and Usage for OLUMIANT (baricitinib) tablets (in the United States)

OLUMIANT is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. Limitations of Use: Not recommended for use in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine.

OLUMIANT is indicated for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

IMPORTANT SAFETY INFORMATION FOR OLUMIANT (baricitinib) tablets

WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS

SERIOUS INFECTIONS

Patientstreated with Olumiant are at risk for developing serious infections that may lead to hospitalization or death. Most patients with rheumatoid arthritis (RA) who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt Olumiant until the infection is controlled. Reported infections include:

Carefully consider the risks and benefits of Olumiant prior to initiating therapy in patients with chronic or recurrent infection.

Closely monitor patients for the development of signs and symptoms of infection during and after treatment with Olumiant including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

The most common serious infections reported with Olumiant included pneumonia, herpes zoster, and urinary tract infection. Among opportunistic infections, tuberculosis, multidermatomal herpes zoster, esophageal candidiasis, pneumocystosis, acute histoplasmosis, cryptococcosis, cytomegalovirus, and BK virus were reported with Olumiant. Some patients have presented with disseminated rather than localized disease, and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Avoid use of Olumiant in patients with an active, serious infection, including localized infections. Consider the risks and benefits of treatment prior to initiating Olumiant in patients: with chronic or recurrent infection; who have been exposed to TB; with a history of a serious or an opportunistic infection; who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or with underlying conditions that may predispose them to infection.

The risks and benefits of treatment with Olumiant in COVID-19 patients with other concurrent infections should be considered.

Consider anti-TB therapy prior to initiation of Olumiant in patients with a history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection.

Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical studies with Olumiant. If a patient develops herpes zoster, interrupt Olumiant treatment until the episode resolves. The impact of Olumiant on chronic viral hepatitis reactivation is unknown. Screen for viral hepatitis in accordance with clinical guidelines before initiating Olumiant.

MORTALITY

In a large, randomized, postmarketing safety study in RA patients 50 years of age and older with at least one cardiovascular risk factor comparing another Janus kinase (JAK) inhibitor to tumor necrosis factor (TNF) blockers, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Olumiant.

MALIGNANCIES

Lymphoma and other malignancies have been observed in patients treated with Olumiant. In RA patients treated with another JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer [NMSC]) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers and an additional increased risk of overall malignancies were observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Olumiant, particularly in patients with a known malignancy (other than successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers.

NMSCs have been reported in patients treated with Olumiant. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

MAJOR ADVERSE CARDIOVASCULAR EVENTS

In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction [MI], and stroke) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue Olumiant in patients that have experienced a myocardial infarction or stroke.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Olumiant, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Inform patients about the symptoms of serious cardiovascular events and the steps to take if they occur.

THROMBOSIS

Thrombosis, including deep venous thrombosis (DVT) and pulmonary embolism (PE), has been observed at an increased incidence in patients treated with Olumiant compared to placebo. In addition, there were cases of arterial thrombosis. Many of these adverse events were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid Olumiant in patients at risk. Discontinue Olumiant and promptly evaluate patients with symptoms of thrombosis.

GASTROINTESTINAL PERFORATIONS

Gastrointestinal perforations have been reported in Olumiant clinical studies, although the role of JAK inhibition in these events is not known. Monitor Olumiant-treated patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis). Promptly evaluate patients who present with new onset abdominal symptoms for early identification of gastrointestinal perforation.

LABORATORY ABNORMALITIES

Neutropenia Olumiant treatment was associated with an increased incidence of neutropenia (absolute neutrophil count [ANC] <1000 cells/mm3) compared to placebo. Evaluate at baseline and thereafter according to routine patient management.

In patients with RA, avoid initiation or interrupt Olumiant treatment in patients with an ANC <1000 cells/mm3. In patients with COVID-19, avoid initiation or interrupt Olumiant treatment in patients with an ANC <500 cells/mm3.

Lymphopenia Absolute lymphocyte count (ALC) <500 cells/mm3 were reported in Olumiant clinical trials. Lymphocyte counts less than the lower limit of normal were associated with infection in patients treated with Olumiant, but not placebo. Evaluate at baseline and thereafter according to routine patient management.

In patients with RA, avoid initiation or interrupt Olumiant treatment in patients with an ALC <500 cells/mm3. In patients with COVID-19, avoid initiation or interrupt Olumiant treatment in patients with an ALC <200 cells/mm3.

Anemia Decreases in hemoglobin levels to <8 g/dL were reported in Olumiant clinical trials. Evaluate at baseline and thereafter according to routine patient management.

In patients with RA, avoid initiation or interrupt Olumiant treatment in patients with hemoglobin <8 g/dL. In patients with COVID-19, there is limited information regarding use of Olumiant in patients with hemoglobin less than 8 g/dL.

Liver Enzyme Elevations Olumiant treatment was associated with increased incidence of liver enzyme elevation compared to placebo. Increases of alanine transaminase (ALT) 5x upper limit of normal (ULN) and increases of aspartate transaminase (AST) 10x ULN were observed in patients in Olumiant clinical trials.

Evaluate at baseline and thereafter according to routine patient management.Promptly investigate the cause of liver enzyme elevation to identify potential cases of drug-induced liver injury. If increases in ALT or AST are observed and drug-induced liver injury is suspected, interrupt Olumiant until this diagnosis is excluded.

Lipid Elevations Treatment with Olumiant was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Assess lipid parameters approximately 12 weeks following Olumiant initiation in patients with RA. Manage patients according to clinical guidelines for the management of hyperlipidemia.

VACCINATIONS

Avoid use of live vaccines with Olumiant. Update immunizations in patients with RA prior to initiating Olumiant therapy in agreement with current immunization guidelines.

HYPERSENSITIVITY

Reactions such as angioedema, urticaria, and rash that may reflect drug hypersensitivity have been observed in patients receiving Olumiant, including serious reactions. If a serious hypersensitivity reaction occurs, promptly discontinue Olumiant while evaluating the potential causes of the reaction.

ADVERSE REACTIONS

In RA trials, the most common adverse reactions (1%) reported with Olumiant were: upper respiratory tract infections, nausea, herpes simplex, and herpes zoster.

In COVID-19 trials, the most common adverse reactions (1%) reported with Olumiant were: ALT 3x ULN, AST 3x ULN, thrombocytosis (platelets >600,000 cells/mm3), creatine phosphokinase >5x ULN, neutropenia (ANC <1000 cells/mm3), DVT, PE, and urinary tract infection.

PREGNANCY AND LACTATION

Limited data on Olumiant use in pregnant women are not sufficient to inform a drug-associated risk for major birth defects or miscarriage. Advise women with RA not to breastfeed during treatment with Olumiant.

HEPATIC AND RENAL IMPAIRMENT

Olumiant is not recommended in patients with RA and severe hepatic impairment or severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73m2).

Olumiant should only be used in patients with COVID-19 and severe hepatic impairment if the potential benefit outweighs the potential risk. Olumiant is not recommended in patients with COVID-19 who are on dialysis, have end-stage renal disease, or with eGFR <15 mL/min/1.73m2.

Please click to access full Prescribing Information, including Boxed Warning about Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events, and Thrombosis, and Medication Guide.

BA HCP ISI ALL 17MAY2022

About LillyLilly unites caring with discovery to create medicines that make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 47 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges, redefining diabetes care, treating obesity and curtailing its most devastating long-term effects, advancing the fight against Alzheimer's disease, providing solutions to some of the most debilitating immune system disorders, and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/newsroom or follow us on Facebook, Instagram, Twitter and LinkedIn.

About IncyteIncyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development and commercialization of proprietary therapeutics. For additional information on Incyte, please visit Incyte.com and follow @Incyte.

OLUMIANT is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.

P-LLY

LillyCautionary Statement Regarding Forward-Looking Statements

This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about OLUMIANT (baricitinib) as a treatment for patients with rheumatoid arthritis and as a possible treatment for other conditions and reflects Lilly's and Incyte's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there can be no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with the results to date, and that OLUMIANT will receive additional regulatory approvals, or be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's and Incyte's most recent respective Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly and Incyte undertake no duty to update forward-looking statements to reflect events after the date of this release.

SOURCE Eli Lilly and Company; Incyte

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