Human Behavior

Bess Marcus to head Brown University’s School of Public Health – The Providence Journal

Marcus, a leading scholar in health behavior changes and the first senior associate dean for public health at University of California San Diego School of Medicine, will succeed the schools inaugural dean, Terrie Fox Wetle, who steps down Sept. 1.

PROVIDENCE A top public health official at the University of California San Diego School of Medicine has been named the next dean of the Brown University School of Public Health.

Bess Marcus, a leading scholar in health behavior changes and the first senior associate dean for public health at UCSD, will succeed the schools inaugural dean, Terrie Fox Wetle, who is stepping down Sept. 1.

Marcus will assume the post Nov. 1.

A clinical health psychologist and expert in health promotion, Marcus served as a professor of community health and psychiatry and human behavior at Brown before leaving for UCSD in 2011, the university said in a news release.

Marcus was chair of the Department of Family Medicine and Public Health at the UCSD School of Medicine for six years and the schools senior associate dean for public health where she founded and directed the UCSD Institute for Public Health for three years.

Brown University President Christina Paxson announced her appointment in a June 14 email to the Brown community.

Marcus first arrived at Brown as a postdoctoral scholar in 1988 after earning her masters degree and Ph.D. in clinical psychology at Auburn University. After five years as an assistant professor, she became an associate professor of psychiatry and human behavior in 1995 and then a full professor in 2000. In 2004, she became director of the Centers for Behavioral and Preventive Medicine at Miriam Hospital, an affiliated hospital partner for Brown.

In 2007, Marcus joined the faculty of Browns Department of Community Health and remained on the faculty when the department became the School of Public Health in 2013.

larditi@providencejournal.com

(401) 277-7335

On Twitter: @LynnArditi

Link:
Bess Marcus to head Brown University's School of Public Health - The Providence Journal

Human Behavior

Noah’s Ark – The Potrero View

One of the most famous stories in the Bible occurs in Genesis, in a passage commonly known as Noahs Ark. In it, God, enraged over human behavior, decides to wipe out everything, in an extinction-by-flood event. Somehow, in the midst of the deitys hairy-eyed examination of all things wicked, Noah gets the Lords attention, and is requisitioned to build a vessel capable of safeguarding his family and propagating samples of each species. And, so on and so forth, until a rainbow appears to signal that this is one-time cleansing.

The story has deep layers, profoundly embedded in the psyches of most of the worlds population, if not as conveyed by Judaism, Christianity, or Islam, by other spiritual traditions that tell a similar tale. The accounts hold on the collective consciousness is no less powerful whether its factually true or an ancient version of fake news. The essential elements are whats important: humans willfully engage in destructive behavior, are thus destroyed, except a handful of righteous and morally untethered creatures, who plant the seeds for a new day. The rainbow is a kind of cherry on top, a sentimental teardrop from a God who isnt that bad after all.

Noahs Ark, the story and/or historical incident, is in the air these days. Weve created the conditions for catastrophic floods and mass species die-offs. Parts of the earth Niger; Sudan are becoming uninhabitable as a result of increasingly severe climate conditions, triggering mass migrates searching for a safe harbor. Meanwhile, Elon a name referring to oak trees in Hebrew; the Ark was made of wood! and other meritorious individuals are building space vessels to evacuate the planet when the time comes.

A thought stroll through the story further illuminates our current condition. While theres no indication that God issued a broad warning about the impending disaster, or that Noah conveyed the message to his neighbors, the Lords actions suggest that people were generally aware that their wicked ways could trigger harsh consequences, or at least a substantial time out. That is, the Deity was angry that creation was willfully doing things they knew to be wrong. These werent just folks ignorantly playing the fool, which might merit a sharp warning, like a localized flash flood, not the total destruction of the world. Past chronicles Adam and Eve and the like forewarned of paradise lost when God gets irritated.

What, exactly, constituted bad behavior was probably fiercely contested. One faction no doubt voraciously argued that it was the fault of the Gays, the abortionists, those creeping across boundaries without permission. Another group pointed to enslaving people, imposition of the death penalty, and bearing false witness. A third denounced those who worshiped the wrong, or too many, gods. And so on and so forth, until everyone stuck their fingers in their ears to block out the noise of those with whom they disagreed, and got back to whatever they were doing, evil or good.

Lets say an authority figure beyond reproach the council of elders; the chief water engineer intervened and stated, unequivocally, that the evil over which God was angry was something pretty much everybody did, like cooking food on open-flamed wood-fueled pits, and unless everyone stopped doing that it was curtains for sure. The announcement would unleash a flurry of fire-putting-out, a scramble for substitutes, and angry muttering that, first they take away our pointy sticks, now this? When the smoke settled, wealthy people would be sitting pretty with their souped-up, new, cookers, fueled by renewable whale blubber; the working class would be forced by decree to construct enclosed fireplaces with specialized exhaust screens, forgoing school fees to pay for the expense; and the poor would be left to eat raw millet, clandestinely cooking the same way they ever did, having no alternative, and, when caught, being ruinously fined for their troubles.

Under pressure, thered be a political backlash. The council of elders would be replaced, with younger people who have fuller lips; the chief engineer dismissed. While many would avoid returning to their wicked ways, fearing the consequences, others would dive back in, glancing at their neighbors to make sure they were doing the same. Some would even embrace the evil, yearning for Gods touch, however violent it might be.

And then, ba-bam, everyone is drowned.

The rainbow is akin to an abuser handing out a lollypop, his extended hand soaked in the blood of all those just slaughtered, the survivors just happy to be alive, so sweat-stained with relief that theyre ready to forgive and forget whatever nastiness may have occurred. While God announces that theyll be no future holocausts, there actually are many, with more to come. Perhaps the Lord found a loophole in the purported statement that never again will all creatures be eliminated. Hey, upwards of eight million Jews isnt all, nor is a few hundred thousand Syrians, and, anyways those are not my doing. Nothing to see, move along.

Its hard not to think that we humans have pushed the repeat button on this story. The details are different, sure, but the theme seems eerily familiar, even comforting. In Noahs Ark, the original, few of us identify with the wicked; were Noah, or his family, or perhaps one of the innocent creatures taken on board the vessel to the future. We, as defined by me, are not the drowned. We are the saved. Looking forward to our colorful sucker.

Read the rest here:
Noah's Ark - The Potrero View

Genetics

Genetics, data affect direction of ag research – Iowa Farmer Today

AMES, Iowa Data is key when it comes to research. And the world is getting to be very good at collecting and analyzing data.

Thats a big bucket research area, says Joe Colletti, senior associate dean in the College of Agriculture at Iowa State University and associate director of the Iowa Agriculture and Home Economics Experiment Station.

Colletti says that while research is being done in a variety of areas, a couple of types stand out today. One of those is the collection, standardization and use of data by and for farmers.

Another area of great advance is predictive genomics, which has been a hot issue for some time. Phenomics is a big thing in the plant and animal sciences research fields, Colletti says. Scientists are looking at genomes and phenotypes as a way of better predicting what the offspring of any genetic cross will look like, not only one generation down the road but many generations down the road. That type of assessment could help speed and fine tune research for crops and for livestock.

That fits into the work of the commodity organizations. Rod Williamson, director of research and development for the Iowa Corn Growers Association, says that his organization is looking at research in several basic areas.

The ICGA emphasis is on non-food industrial products. One example is bioplastics which are already being made using other biological products but which could be made using corn. Right now, he says, plastic water bottles are often made using sugar cane from South America.

The process includes a number of steps. If researchers can reduce the number of steps involved and can do so using corn, it could open up new markets. If corn captured just 3 percent of that market it could mean use for 100 million bushels of corn.

Williamson says other research supported by the corn growers includes work on higher blends of ethanol in fuel. On the production side, he says nitrogen efficiency by plants through better genetics is a priority. And he says the genomic efforts cited by Colletti are also a priority.

Other commodity organizations are also emphasizing research. Scott Nelson, director of the on-farm network for the Iowa Soybean Association, cites several research priorities.

He says crop inoculants are one area of interest. Another is better weed control, especially of waterhemp and Palmer amaranth. Soybean cyst nematode remains a priority, as does corn rootworm. And variable rate technology and multiple-variety planting technology are also items he sees developing.

But one of the most exciting topics of discussion for many researchers is CRISPR/Cas9 technology. CRISPR/Cas9 is an RNA-guided genome editing tool that allows researchers to knock out genes or insert genes more easily into a cell line.

Colletti says the technology isnt aimed at adding genes from other plants or animals, but instead, works toward more exact advances in a crop or animals existing genes.

This is a technique that is being improved daily, hourly, he says. It is moving us in the right direction.

That more specific genetic work on the plant, combined with better data gathering and analysis due to improved computer technology, will lead plant genetic work forward at a faster pace than was possible in the past.

Nelson agrees, saying the technology will help companies to develop better plant varieties.

It could be revolutionary, he says.

Meanwhile, Colletti says soil is also getting more and more attention from researchers.

The work on cover crops and an increased emphasis on erosion control, water and soil quality will influence research. Scientists are starting to look at how cover crops and larger yields lead to changes in plant biomass. That in turn can influence planting and harvest conditions, as well as soil quality and weed and bug pressure.

It is now easier to gather mass amounts of data in the lab and in the field through unmanned aircraft systems imagery, aerial photography and analysis, as well as through other means. That massive increase in the volume, variety, velocity, voracity and value of data that can be gathered and the increased speed at which it can be analyzed will lead to more flexibility for farmers to make decisions quickly in the field.

This can lead to more just-in-time nutrient applications or weed and pest control, for example. It will lead to better crop genetics. And it will lead to more informed management decisions and achievement of private and public goals in the future, Colletti says.

Visit link:
Genetics, data affect direction of ag research - Iowa Farmer Today

Genetics

Cummings grants Tufts $100K to bolster genetics program – Wicked Local Medford

Tufts University will continue to teach local students about the possibilities of genetics work thanks to a $100,000 grant from Cummings Foundation.

Tufts University's popular Bioinformatics Inquiry through Sequencing (BioSeq) program will continue to teach local students about the possibilities of genetics work thanks to a $100,000 grant from Cummings Foundation.

BioSeq uses an interactive curriculum that emphasizes the value of genetics in personally relevant contexts, preparing students for research careers and enhancing understanding of how genetics work can shape and save lives.

The BioSeq program is part of Tufts and Cummings Foundation's legacy of support for science, technology, engineering and mathematics (STEM) education opportunities for students in greater Boston.

Started with funding from the National Institutes of Health Science Education Partnership Award and now in its fifth year, BioSeq has reached over 1,000 students in Medford, Somerville and Malden schools.

Until recently, genetic sequencing was labor-intensive, slow and expensive. Thanks to next-generation sequencing, however, scientists are employing new tools to gather genetic data and to draw meaningful conclusions on how the data can push the boundaries of medical knowledge and bring the promise of personalized medicine closer to reality. Despite these tremendous advances, this technology is largely out of the reach of the high school audience.

Due to cost and curriculum restraints, students in low-income and diverse urban communities often have limited opportunities to interact with genetics science, though within their lifetimes, current high school students will have to understand how their genetics may influence the treatments they receive and the drugs they are prescribed. The BioSeq program works to expose students to the possibilities of genetic sequencing so they will be more comfortable and better informed as genomics plays an increasingly influential role in health and medicine.

BioSeq engages and challenges students in their high school classrooms by focusing on inquiry-based experiments that relate to them directly. This grant will enable the program to continue to support classroom experiments such as "The Microbiome Portrait Experiment" in which students analyze their own DNA as well as local students and classes with their genomic science fair projects and will provide scholarships for the BioSeq summer program, run by Tufts Summer Studies.

"We're very grateful for Cumming Foundation's generosity and its continued commitment to both Tufts University and the goal of enhancing STEM education for young students from our local communities. Because of Cummings Foundation's support, students will have opportunities to learn by asking and answering their own questions about genetics," said Matthew Fierman, Ph.D., BioSeq's program administrator.

Cummings Foundation, Inc., founded by Tufts alumnus and trustee emeritus Bill Cummings and his wife, Joyce Cummings, has awarded more than $170 million in grants to non-profit organizations serving a broad range of causes in greater Boston and around the world, including human services, education, health care, and social justice. Cummings Foundation is active internationally through aid to the post-genocide rebuilding of Rwanda and support of education to help prevent future genocides and other intercultural violence and injustice. The Cummings' philanthropy has had a significant impact on the Tufts community in particular, including a naming gift in support of Cummings School of Veterinary Medicine at Tufts University.

For more information about the BioSeq program, including sample classroom activities, please visit: http://ase.tufts.edu/chemistry/walt/sepa/index.html

View original post here:
Cummings grants Tufts $100K to bolster genetics program - Wicked Local Medford

Genetics

At-home genetic test reveals secrets about your health – FOX 5 Atlanta

ATLANTA - You could call 23andMe a test for the genetically-curious.

For $199, you can find out what your genes reveal about not just your ancestry and your traits, but your health.

Dr. Jeffrey Pollard, Director of Medical Affairs for 23andMe says 2 million people have already taken the test.

"I think it's exciting to learn something about yourself," Dr. Pollard says. "Everyone likes learning new things about themselves."

The process is pretty simple.

You order the kit, collect a sample of your saliva and send it off to 23andMe.

A few weeks later, through an online portal, you can read you genetic health risk test results, and find out if you might be at higher risk of developing certain diseases like late-onset Alzheimer's Disease and Parkinson's Disease.

But genetics testing in relatively new, says Pollard, and there are limits to what 23andMe can reveal.

"We are not a diagnostic test," Pollard cautions. "So, we aren't telling anyone the have a certain condition. We're really presenting them with an element of their genetic risk, if you will."

Kimberly King-Spohn, Director of the WellStar Center for Genetics, says at least a third of her patients have mentioned 23andMe since April, when the US Food and Drug Administration cleared the direct-to-consumer genetic testing company to offer health risk information to consumers for 10 disease and conditions.

King-Spohn has some concerns.

"It's confusing," she says. "They get a very long report with a lot of information, and patients have had a difficult time interpreting what that means for their health."

Dr. Pollard says 23andMe provides a lot of context, to help customers make sense of their findings.

But, King-Spohn argues patients may not want to know they're at higher genetic risk of developing diseases they can't really do anything about.

"We don't have a treatment or intervention for Alzheimer's disease," she says. "So, what would you do with that information?"

Pollard says the information 23andMe offers is just a piece of a much larger puzzle.

"We like to highlight the fact that your genetic risk is just one element in play," he says.

Because, Pollard says, there are a lot of factors you can control, when it comes to your health.

"You might be able to change certain other things that you do in your life, whether it's exercise, or your activity level, your diet, whether or not you smoke," he says.

Both Pollard and King-Spohn agree it's important to read the fine print, before you get screened, to make sure you understand what 23andMe can and cannot tell you.

It's a lot to absorb, they both say.

"But it's also empowering" Dr. Pollard says. "And, we hear that our customers are taking this information and doing something with it in their lives. So, that, I think, is a very powerful beginning."

See the rest here:
At-home genetic test reveals secrets about your health - FOX 5 Atlanta

Genetics

Select Sires to acquire Accelerated Genetics – Farm and Dairy

(Story being updated)

SALEM, Ohio Two of the nations largest genetic companies for dairy and beef breeders have announced plans to merge.

The board of directors for Select Sires, based in Plain City, Ohio, and Accelerated Genetics, based in Baraboo Wisconsin, have both reached a unanimous decision to unite the two cooperatives.

According to the agreement, Select Sires will acquire the assets of Accelerated Genetics, joining employees and independent sales representatives.

The two entities have been working closely together since 2001, when a collaborative agreement made them both owners of World Wide Sires the international marketing arm for both companies in Europe, Africa, Asia, the Middle East and Oceania.

Shirley Kaltenbach, director of communications for Select Sires, said both organizations have the same goals and both have the same cooperative business structure and business principals.

She said both entities will continue to operate under the same names until a long-term strategy is reached. Accelerated Genetics still needs the approval at its June 22 delegate meeting, but she said the outcome is looking positive.

Accelerated Genetics has about 250 employees and works with an additional 180 independent sales representatives, said Angie Lindloff, vice president of marketing and communications.

She said the merger provides more opportunity for both customers and employees.

Joining forces gives us huge opportunity for our genetic lineup, Lindloff said. It helps everybody and it will allow us to serve our customers better.

Lindloff expects the current Accelerated Genetics facilities will remain operational, including the bull facility and main office.

Kaltenbach said Select Sires will continue to be located in Plain City. She said the goal will be to retain as many employees from both organizations as possible, but positions will be evaluated.

This impending endeavor will create a well-rounded genetics program and solutions-based animal health care product line that will fit the needs of dairy and beef producers worldwide, according to the release.

Select Sires bills itself as North Americas largest artificial insemination organization and is comprised of nine farmer-owned and controlled cooperatives.

Accelerated Genetics is a producer-owned cooperative, with solutions focussed on genetics and value-added products, programs and services for dairy and beef customers worldwide.

Up-to-date agriculture news in your inbox!

See the article here:
Select Sires to acquire Accelerated Genetics - Farm and Dairy

Genetics

Second annual Jewish Genetics/DNA Conference – KOAT Albuquerque

ALBUQUERQUE, N.M.

A special conference is being held this Sunday at the Jewish Community Center of Greater Albuquerque to help the public learn more about their health care options.

The conference is being held from 9:30 a.m. to 4 p.m. Tickets will cost $25 and include lunch.

Speakers will talk about BRCA-related cancers, genetic conditions and DNA testing.

The JCC is located at 5520 Wyoming Blvd. NE.

Click here for more details.

Here is the original post:
Second annual Jewish Genetics/DNA Conference - KOAT Albuquerque

Genetics

NewLink Genetics Is Still Undervalued, Despite The Disappointment From Navoximod – Seeking Alpha

NewLink Genetics (NASDAQ:NLNK) lost 40% of its value in a single day, as it surprisingly announced that Roche ([[OTCQX:RHHBY]], [[OTCQX:RHHBF]])/Genentech would return the rights on Navoximod, an IDO inhibitor, to the company. In this article, I will discuss what the reasons for this decision were and importantly why I believe that NewLink Genetics is highly undervalued at the current, all-time low, share price of $6.46 (Figure 1).

Figure 1. Common stock chart for NLNK. Source: Yahoo Finance

NewLink Genetics pipeline concentrates on the development of IDO (indoleamine-2, 3-dioxygenase) pathway inhibitors. IDO inhibitors, in general, are expected to boost the body's immune system to fight against cancer, similar to PD-1 and CTLA-4 pathway inhibitors.

NewLink was focused on two distinct IDO pathway inhibitors:

One is the already mentioned Navoximod, a direct inhibitor of IDO, which works very similar to Incyte's (NASDAQ: INCY) Epacadostat and Bristol-Myers Squibb's (NYSE: BMY) BMS-986205. Their most advanced drug is Indoximod, which is no direct blocker of IDO but rather mimics the effect of IDO inhibition.

Navoximod

In 2016 Roche/Genentech licensed all worldwide commercialization rights for Navoximod and paid NewLink Genetics $150 million upfront, with eligibility to $1 billion more if certain milestones are met.

Navoximod is currently tested in phase 1 trials in several solid cancers including non-small-cell lung cancer ("NSCLC"), renal cell cancer ("RCC"), urothelial bladder cancer ("UBC"), triple-negative breast cancer ("TNBC") in combination with Atezolizumab (the PD-L1 inhibitor from Genentech/Roche). In all these cohorts combined (separated data is not available yet) Navoximod + Atezolizumab showed a partial response in only 9% (4/45) of patients [1].

Epacadostat is tested in many different solid cancers in partnership with Merck's (NYSE: MRK) Keytruda. If the same patient cohorts of Epacadostat and Keytruda are pooled they achieve 27% (40/146 pooled; stratified in cancer types: 14/40 NSLC, 13/37 UBC, 9/30 RCC, 4/39 TNBC) [2][3]. Based on this data Roche/Genentech decided to return the rights for Navoximod to NewLink Genetics.

I think one of the reasons why Navoximod doesn't perform as well as Epacadostat could be rooted in their differential efficacies to inhibit IDO. This is read out by measuring the kynurenine levels in the blood (kynurenine is the product of an active IDO enzyme, so the greater the drop in kynurenine levels the better inhibited is IDO). Navoximod brings down blood kynurenine to 70% of the pre-treatment level. In comparison to that, Epacadostat achieves a 50% reduction and even better is BMS-986205, which manages to drop the kynurenine level to about 40% of pre-treatment levels [4][5]. This indicates that Navoximod is not such a potent IDO inhibitor than the ones of the competitors and thus might explain why Navoximod has less efficacy than Epacadostat.

Based on the disappointing preliminary results and especially with a competitor that is, first, much further in the development (multiple clinical phase 3 trials of Epacadostat + Keytruda will be started in 2017) and second, shows better efficacy, it is understandable that Roche/Genentech decided to not further develop Navoximod. I personally think it is unlikely that NewLink will continue to develop Navoximod unless they see potential in any of the single cancer types. My feeling is that in neither of the single cancer types Navoximod performed comparable to Epacadostat, otherwise Roche/Genentech wouldn't have returned the rights to the drug.

Indoximod

Indoximod is tested in combination with several different agents in phase 2 studies in melanoma, pancreatic cancer, breast cancer, metastatic castration-resistant prostate cancer (mCRPC) and glioblastoma.

Melanoma

Beginning of April 2017, NLNK released preliminary results of Indoximod in combination with Keytruda in advanced melanoma. The combination achieved a 59% objective response rate and 80% disease control rate (Table 1) [6]. Including patients with ocular melanoma, a very hard to treat patient population, the ORR is 52% and the DCR is 73%.

Treatment

Objective response rate

Disease control rate

Grade 3 adverse events

Epacadostat / Keytruda

n = 19

58%

74%

19%

Indoximod / Keytruda

n = 51

59%

80%

Nivolumab / Ipilimumab

n = 314

58%

71%

55%

Table 1. Objective response rates and adverse events in melanoma. For Indoximod/Keytruda only data from non-ocular patients are included. *Only incomplete data available

This news was followed by a 33% drop in NLNK's stock price, due to disappointment that the Indoximod/Keytruda combination was not much better than the 58% ORR and 74% DCR achieved with Epacadostat/Keytruda in treatment-naive advanced melanoma [7]. Another reason for the disappointment is the complete response rate of 26% for Epacadostat/Keytruda, compared to only 12% for Indoximod/Keytruda. Here it should be taken into account, however, that the presented data for Epacadostat consist of only 19 patients, whereas the data for Indoximod include 51 patients. So it is possible that the complete response rates of Epacadostat will drop once more patients are added.

I was positively surprised by how similar the two drugs performed, given that the mechanism of action differ quite significantly between Indoximod and Epacadostat and would rate it as a good sign that in melanoma Indoximod is able to perform similarly than Epacadostat.

The current, best-in-class, treatment option for metastatic melanoma is the combination of Nivolumab with Ipilimumab (PD-1 and CTLA-4 inhibitors from BMY), which achieves 58% ORR and 71% DCR (Table 1) [8].

The phase 3 trials of Indoximod and Epacadostat in melanoma will likely be benchmarked against this combination. The IDO inhibitor combinations seem to be unable to surpass anti-PD-1/CTLA-4 inhibition in terms of ORR or DCR. But then the rate of serious adverse events will come into play. Epacadostat/Keytruda has 19% of Grade 3 adverse events and although no concrete numbers are available for Indoximod/Keytruda, they are not higher than with Keytruda alone.

This means that both IDO inhibitors are exceptionally well tolerated and well below the 55% of Grade 3 adverse events observed with the anti-PD-1/CTLA-4 treatment. Therefore, there is a good chance that the IDO inhibitors will be approved based on the more manageable safety profile.

Acute myeloid leukemia

In acute myeloid leukemia, Indoximod is tested in combination with 7+3 chemotherapy. This combination leads to a complete remission in 83% of tumors (5 of 6 patients) with no evidence of minimal residual disease [9]. With 7+3 chemotherapy alone in young adults, complete remission can also be achieved in up to 75% of patients [10]. The big problem rather is that the relapse rate is very high and thus it will be critical for Indoximod to show prolonged relapse-free survival and overall survival.

Pancreatic cancer

In pancreatic cancer, the combination of Indoximod with chemotherapy achieved an ORR of 45% (14/31) vs. 23% for chemotherapy alone [11]. Pancreatic cancer is a notoriously hard to treat cancer type and many drugs failed to get approved. NewLink, for instance, also tried to get a drug approved for pancreatic cancer, called Algenpantucel-L. After promising objective response rates in a phase 2 study, the drug failed to enhance overall survival in a phase 3 trial. So I think that also for Indoximod it is important to remain patient and to wait whether the convincing ORR in pancreatic cancer can be transformed into a survival benefit.

Metastatic castration-resistant prostate cancer

Indoximod is combined with PROVENGE (a vaccine already approved for prostate cancer) for patients with mCRPC. The combination was able to enhance radiographic progression-free survival (rPFS) from 4.1 months in the placebo arm to 10.3 months in the treatment arm [12]. This compares to the rPFS of Enzalutamide, an androgen receptor inhibitor, which is 8.3 months [13]. In general, rPFS is highly associated with overall survival in mCRPC and so it is likely that Indoximod/PROVENGE will also enhance overall survival [14].

Glioblastoma

In addition to these trials, Indoximod is also tested in glioblastoma also in combination with chemotherapy and a 6-month progression free survival in 25% of patients compared to a historical rate of 15% [15].

Breast cancer

Recently a statement was released, that Indoximod plus chemotherapy failed to meet the primary end points of statistically different progression-free survival and overall survival in metastatic breast cancer [16].

The use of IDO inhibitors in breast cancer thus continues to disappoint, as also the combination of Epacadostat and Keytruda only achieved a 10% objective response rate in triple negative breast cancer [17].

Valuation and Conclusion

NewLink Genetics has a current market capitalization of $ 189 million. If cash of $ 75 million, expected at the end of 2017 and debt plus royalty obligations of $ 6.5 million are taking into account, the whole company is currently valued at $ 120.5 million.

Their most promising and also furthest developed indication for Indoximod is in melanoma. I think it was very important for NewLink to show comparable objective response rates, which, since they have a different mechanism of action, was far from certain. As estimated by Bhavneesh Sharma in his article, the current, risk-adjusted, peak revenue of Indoximod in melanoma alone is $ 106 million in 2024. This means the company is currently valued at little above the peak revenue of a single indication. They furthermore have promising first results in other indications as well, importantly in cancer types that Incyte is currently not pursuing or lagging behind.

Given the general high valuation of companies developing novel immunotherapies, NewLink Genetics market capitalization is extremely low. This was majorly caused by disappointment that Indoximod didn't surpass Epacadostat's objective response and complete response rates in melanoma and of course by Roche/Genentech returning their rights on Navoximod to the company.

At this price, NewLink Genetics to me seems to be an attractive takeover candidate for companies who want to quickly spice up their immune-oncology portfolio but are not willing to pay a high premium for it. Bristol-Myers Squibb, for instance, paid $ 800 million upfront (total deal volume is $ 1.25 billion) for Flexus Therapeutics, which developed a preclinical IDO inhibitor of in 2015 [18].

If NewLink Genetics is not bought up or they continue to develop Indoximod unpartnered, they will need to raise additional capital at some point until the end of 2018. Other risks include the failure of clinical trials or that their drugs do not get approved by the regulatory agencies.

Summing this up, I believe the current valuation of NewLink Genetics is very cheap and I fully expect their stock price to rise again, once investors have digested the disappointments of the last months and regain their faith in the company again.

Disclosure: I am/we are long NLNK.

I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

See more here:
NewLink Genetics Is Still Undervalued, Despite The Disappointment From Navoximod - Seeking Alpha

Cell Biology

Watch This 3D Cell Culture Space – Genetic Engineering & Biotechnology News (press release)

GEN: Are 3D cell culture models as strongly focused as ever on drug safety testing, or are they finding new applications?

Dr. Aho: The focus of 3D cell culture models has definitely expanded beyond drug safety testing. It is becoming increasingly clear that these models mimic cells in vivo at a greater capacity than traditional cell culture.

In addition to drug toxicity, 3D models are progressively being developed and used in developmental biology research, disease modeling, and regenerative medicine. 3D models also provide an enhanced system for drug discovery. Because they better recapitulate disease in vitro, 3D models have the potential to accelerate the testing timeline for drug efficacy studies.

Dr. Banks: Another major application area of 3D cell culture models is in oncology. Spheroids in both media and Matrigel can be used as surrogate models of tumor proliferation and tumor invasion. Automated brightfield or fluorescence microscopy is typically used for spheroid or invadipodia area measurements. In addition to spheroids, collagen-based scaffolds that encourage cell aggregation into tumoroids have been used for immunotherapy applications such as natural killer cell cytotoxicity assays. Finally, magnetic particles have been used to bioprint cells for cell migration and invasion experiments.

Dr. Eglen: We would argue that 3D cell culture models have been used for many years in basic research and disease modeling, notably in cancer researchthis was, after all, one of the original applications of Corning Matrigel, a naturally occurring extracellular matrix for us in 3D cell culture. That said, it is true that 3D cell culture models are increasingly being used in preclinical lead optimization, particularly in evaluating potential compound toxicity and metabolic liability.

Furthermore, disease research areas are expanding to include neurology, stem cell research, cell therapy, and (potentially) tissue engineering. Perhaps the most exciting work is the development of 3D technologies for the optimal production of patient-specific cells, either for compound testing or possibly cell therapy.

Interestingly, spheroids derived from stem cells grown in 3D models show improved stemness, that is, characteristics that may lead to increased efficacy in regenerative medicine. Researchers have seen that spheroids display enhanced anti-inflammatory, tissue regenerative, and reparative responses, as well as better post-transplant survival of mesenchymal stem cells.

Autologous tissue for transplantation may also come from organoids produced via 3D cell culture. For example, renal organoids derived from pluripotent stem cells have been successfully transplanted under the renal capsules of adult mice. Clearly, research in this area is advancing rapidly, probably due to a convergence of several multidisciplinary fields, ranging from bioengineering, materials science, phenotypic screening, and cell biology.

Dr. Trezise: Drug safety continues to be a significant application area for 3D models. This application area has become only more interesting as more data has become available indicating that 3D models offer translational benefits. In addition, there is a growing trend to develop 3D models that can advance developmental biology, target validation, and drug efficacy studies. This trend is particularly evident in the field of oncology, where researchers are combining patient-specific tumor cells and 3D cell culture methods to create tumor organoids. These mini-tumors are being used to determine sensitivity to combinations of different chemical, biological, and cellular therapeutics in the context of personalized medicine.

Dr. Klette: 3D cell culture models are widely used for drug safety testing, such as studying hepatic injury from compound screens, and for examining drug metabolism using 3D hepatocyte models. In personalized medicine, however, patient-derived primary 3D models are being used for cancer screening in biotherapeutics. Here, 3D models provide enhanced physiological relevance to determine drug efficacy and potential impacts on carcinogenesis, metastasis, and tumor reoccurrence. If we look outside drug discovery and biologics, we notice that areas such as regenerative medicine and cell therapies can take advantage of 3D models as a predictor of disease and (when scaled to therapeutic levels) as a disease treatment.

Dr. Guye: 3D cell models are applied throughout the biomedical and life sciences. 3D technologies that are compatible with high-throughput screening are used not only for screening purposes, but also for target and hit validation, lead optimization, and investigational toxicology.

Basically, given their ability to extend cell lifetimes and incorporate multiple cell types, 3D models are increasingly finding their way into basic research, where they are helping to recapitulate disease progression and assess the impact of certain genes and pathways on disease progression/preventionactivities that help scientists define adverse outcome pathways. Importantly, we expect human 3D cell culture models to significantly reduce the percentage of drugs that progress to clinical trials and fail due to lack of efficacy.

Dr. Kugelmeier: The focus on drug safety testing is still valid, and sophisticated organoid models might contribute to even more accurate drug safety testing because of increased physiological fidelity of these models. But there are also significant new research areas. Combining organoid technology with stem cell biology could lead to therapeutic applications. Also, cancer researchespecially cancer research that focuses on cancer stem cellsneeds 3D models. Of these models, cell spheroids are among the most important. Sophisticated cell-spheroid platforms not only allow research but also provide drug-testing possibilities using patient cells for personalized medicine. Finally, these platforms may enable therapeutic applications with stem cell spheroids in regenerative medicine.

Mrs. Hussain: The focus for 3D cell culture methods is still the drug safety testing that occurs before in vivo testing. Recently, there has been a renewed interest in phenotypic drug screening to discover new drug targets. With this shift, there is growing emphasis on bridging the gap between phenotypic screens and 3D methods. Phenotypic screens, in vitro, were traditionally carried out using 2D methods that do not take into account the complexity of the in vivo environment. 3D methods are now sought to build biologically relevant models that are more predictive of phenotypic response to new drug targets.

Dr. Bulpin: Applications continue to expand for 3D models, including the development of specific disease models and complex tissue models that can be used for basic research as well as drug discovery. Another promising area for 3D models is personalized medicine. Several types of cells can be used in these models including immortalized cells, genetically engineered cells, induced pluripotent stem cellderived cells, primary human cells, and patient-derived cells (including patient-derived xenografts). Another potential research avenue is engineering 3D tissues for organ transplants.

Dr. Joore: Over the last year, we observed a growing interest in 3D tissue models that could be used in studies of disease processes, whether the studies emphasized screening or efficacy analysis. These are, I think, two sides of the same coin. Once researchers realize they need better predictive models for safety testing, they start to see that improved models would also have potential for discovery and development. Molecule-to-molecule screens have generated lots of very specific inhibitors, but not so many therapies. Researchers are now starting to appreciate the richness of 3D model data, especially in combination with the throughput of our organ-on-a-chip platforms.

Ms. Floyd: Cancer researchers and developmental biologists have certainly benefitted from 3D cell culture models, which are more physiologically relevant than are 2D systems to the study of cellular differentiation. Further, 3D in vitro systems are well positioned to obtain approvals from authorities such as the Organization for Economic Co-operation and Development Organization (OECD). The OECD and other bodies are considering alternatives to whole-animal testing, including alternatives that can accomplish skin-sensitization studies for the safety assessment of chemicals.

Prof. Przyborski: What has changed more recently is the ease of access to innovative technologies on the market that enable researchers to more readily practice 3D cell culture routinely. 3D cell culture has had impact in multiple areas in basic research, drug screening, and safety assessment. Researchers are now looking to 3D technologies to create more sophisticated models that are representative of real human tissues. Investment in more advanced in vitro assays at an early stage will improve predictions of drug action and inform the decision-making process as to whether to further invest in a particular drug candidate.

Dr. Kennedy: 3D cell cultures continue to be extensively explored for drug safety screening; however, there is a growing interest in expanding the use of more complex 3D models into areas such as disease modeling and precision medicine. For example, preclinical hepatic research is now looking to exploit the benefits of spheroid cultures by building 3D co-culture models that consist of multiple primary liver cell types to create new models of hepatic and biliary disease. Likewise, stem cellderived organoids are opening the possibility of tailoring therapeutic regimens to patients genetic makeups and to identify the best treatment options.

Read the original here:
Watch This 3D Cell Culture Space - Genetic Engineering & Biotechnology News (press release)

Cell Biology

RNA errors linked to ALS and dementia – Harvard Gazette

Fixing glitches in the assembly of RNA may hold the key to treating ALS and frontal lobe dementia, according to a Harvard Medical School(HMS) study published this week in Cell Reports.

Researchers found that a genetic mutation often linked to those diseases creates a toxic protein that disrupts the editing, or splicing, of RNA, the molecular messengers that turn genes into functional proteins.

What we are finding is that disruptions in RNA splicing appear to be a common thread linking these motor neuron disorders, said senior study author Robin Reed, professor of cell biology at HMS.Much more research is needed, but if we could correct splicing errors with so-called splicing modulator compounds, we could prevent disruptions which may have efficacy for the treatment of ALS and FTD.

In the HMS study, toxic peptides produced by mutation of gene C9ORF72dislocated part of the spliceosome, the molecular machine responsible for RNA assembly, driving it to the cytoplasm of the cell instead of the nucleus, where it should be located. Exactly how these peptides cause toxicity was previously unclear but studies have shown that they significantly increase splicing failures.

Since splicing is upstream of so many critical cellular functions, Reed said, a better understanding of this mechanism could illuminate new approaches to help patients with these diseases, which currently have no effective treatments.

The C9ORF72 mutation accounts for around 25 percent of cases of frontotemporal dementia and 30-40 percent of inherited forms of amyotrophic lateral sclerosis. Roughly one in five patients with ALS also develops FTD.

The mutation causes the abnormal duplication of a segment of DNA that is processed by cells into messenger RNA. These extraneous copies of RNA messengers code for proteins, two of which GR and PR have been found to be toxic in human, yeast, and fruit fly cells.

Reed and her colleagues found that these toxic peptides associate with a component of the spliceosome known as U2 snRNP.

It was striking how these peptides are so specific to U2 snRNP. No other cellular processes appeared to be affected, whereas splicing was completely blocked, Reed said. When these peptides are expressed at high levels, they are completely toxic to the cell, but if they are produced at a low enough level, they can inhibit the splicing of genes that are U2-dependent, which may have some role in the development of disease.

Co-authors on the study include Shanye Yin, Rodrigo Lopez-Gonzalez, Ryan C. Kunz, Jaya Gangopadhyay, Carl Borufka, Steven P. Gygi and Fen-Biao Gao.

This work was supported by the National Institutes of Health (grants GM043375, NS057553 and NS079725), an ALS Therapy Alliance Grant and the ALS Association.

Continued here:
RNA errors linked to ALS and dementia - Harvard Gazette