Larry Gold named to 2017 National Academy of Inventors

The National Academy of Inventors (NAI) has named Larry Gold, the founder and chairman of the board of SomaLogic, as one of its 2017 fellows.

Election to NAI Fellow status is the highest professional distinction given to academic inventors. NAI Fellows are inventors on U.S. patents and were nominated by their peers for their spirit of innovation and creation of new technologies that have significantly impacted society.

Dr. Gold has been a professor in the department of Molecular, Cellular and Developmental Biology at the University of Colorado, Boulder since 1970 and is an elected fellow of the National Academy of Sciences and the American Academy of Arts and Sciences. A bioscience industry pioneer, Dr. Gold founded two other biotech companies prior to SomaLogic.

The NAI elected 155 fellows to the class of 2017. The induction ceremony will be in April as part of the Seventh Annual NAI conference in Washington, D.C.

 

Click here to read the story from the University of Colorado, Boulder.
Click here for more information on the National Academy of Inventors

An immune system timeline for tuberculosis progression

An international team of researchers has defined the series of immune system changes that occur when tuberculosis (TB) transitions from a non-infectious state to active disease. The results, published online in PLOS pathogens, highlight changes in inflammatory processes that can be detected in the blood long before clinical symptoms arise. These findings have important implications for developing diagnostics, vaccines and treatments to battle the TB epidemic.

An estimated 1.7 billion people—one quarter of the world’s population—are infected with the bacterium that causes TB, but only ~10% develop active pulmonary disease. In the article, scientists from the South African TB Vaccine Initiative, the University of Cape Town, the Center for Infectious Disease Research and SomaLogic looked for changes in various molecules in blood that together could predict the risk of TB progression. The time between the initial blood collection and TB diagnosis ranged from 1 to 894 days, so the investigators could construct a timeline of changes that occurred as the disease evolved.

The blood analyses revealed that TB progression associated with sequential modifications of immunological processes. Some of these processes, such as type I/II interferon signaling and complement cascade, were elevated as early as 18 months before TB diagnosis.

Understanding the biology of progression from infection to active pulmonary TB opens the door to blood-based tests that may determine those who are at risk of developing active disease and who need early treatment. These findings could also help development of better vaccines and host-directed therapies that accelerate eradication of TB infection.

Ref: Scriba, TJ et al. (2017) “Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease”PLOS Pathogens 13(11): e1006687.

Protein profiling reveals immune system dysfunction in Down syndrome

An article published online in Scientific Reports shows that Down syndrome may be a form of chronic immune disorder. In the largest and most comprehensive study of its kind to date, investigators at the Crnic Institute for Down Syndrome, the Sie Center for Down Syndrome, the University of Colorado, and Somalogic measured the levels of over 3500 proteins in the blood of Down syndrome patients and compared them to non-Down syndrome controls. Their results provide a new framework for understanding the physiological mechanisms that drive the altered disease susceptibilities seen in individuals with Down syndrome, and suggest that individuals with Down syndrome could benefit from therapies that decrease or modulate immune responses.

Down syndrome, or Trisomy 21, is caused by having three copies of chromosome 21 instead of two. Although the genetics of Down syndrome have been known for 60 years, it is still unclear how having the extra chromosome leads to various Down syndrome traits, including changes in common disease susceptibilities (e.g., Down syndrome individuals are more likely to develop Alzheimer’s, leukemia and autoimmune disorders, but less likely to develop solid tumors and cardiovascular disease). Understanding the biology that underlies these differences could inform a wide range of medical conditions that affect not only Down syndrome individuals, but the entire population.

The researchers used the SOMAscan assay to compare levels of blood proteins in 165 individuals with Down syndrome and 98 controls, and they identified 299 proteins that differed significantly between the two groups. Surprisingly, most of these proteins are not encoded by genes located on chromosome 21, but are associated with immune system control. Down syndrome individuals appear to have something that resembles an autoinflammatory condition, with elevated levels of proteins that promote inflammation but deficiencies in proteins that help eliminate foreign pathogens. The findings provide a new way to think about Down syndrome and possible targets of therapies to improve the health and lifespan of those with Down syndrome as well as the general population.

Sullivan, KD et al. (2017) “Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation” Scientific Reports 7(1): 14818.

 

Modified DNA aptamer inhibits IL-1α signaling

Modified DNA aptamer inhibits IL-1α signaling

In an article published online in Nature Communications, scientists from SomaLogic and Yale University report that they have successfully generated a novel Slow Off-rate Modified Aptamer (SOMAmer) molecule that binds tightly to interleukin 1 alpha (IL-1α), an essential inflammatory protein implicated in cancer and other diseases. The SOMAmer (called SL1067) shows high specificity for IL-1α and can block its activity. SL1067 could therefore be a useful tool for elucidating IL-1α’s role in producing inflammation and regulating the immune system.

IL-1α/SL1067 structure with IL-1α in green. SL1067 is in cyan with naphthyl-modified residues in orange.

The researchers determined the three-dimensional structure of SL1067 bound to IL-1α, providing the first high-resolution structure of this essential protein. This is also the first crystal structure of a SOMAmer that contains bases modified with naphthyl groups, five of which are involved in IL-1α binding. The naphthyl modifications allow SL1067 to adopt a very compact structure with unusual three-dimensional shapes that have never been seen before. Since SL1067 is small (only 22 nucleotides in length), stable and easily synthesized, it serves as an excellent starting point for development of novel therapeutic molecules that target IL-1α.

 

Ren, X et al. (2017) “Structural basis for IL-1α recognition by a modified DNA aptamer that specifically inhibits IL-1α signaling” Nat Commun, epub ahead of print.
https://www.nature.com/articles/s41467-017-00864-2

Protein changes may signal side effects in drug trials

Protein changes in blood can provide early warning of potential harmful side effects from experimental drug candidates

In an article published “early online” in the American Heart Association journal Circulation, researchers at Pfizer, the Karolinska Institute, the University of California, San Francisco and SomaLogic describe how the measurement of blood-based protein changes in response to treatment with an experimental drug candidate may improve the efficiency and safety of clinical drug development. The published study used a nine-protein-based risk score to detect potential cardiovascular problems with a drug candidate (torcetrapib) well before significant adverse symptoms manifested themselves in patients in the drug’s clinical trial. Their analysis also identified changes in approximately 200 additional proteins that help describe the biology behind those adverse symptoms, which is applicable more broadly in cardiovascular disease management.

Pfizer’s phase three clinical trial (named “ILLUMINATE”) of torcetrapib, a drug candidate that had been shown to raise levels of “good” cholesterol and lower levels of “bad” cholesterol, was expected to confirm its blockbuster potential in reducing the risk of serious cardiovascular events such as heart failure and stroke. Instead, ILLUMINATE was halted abruptly in 2006 due to an unexpected increase in deaths and cardiovascular problems in trial subjects receiving the new drug candidate. At the time the trial was halted, Pfizer had invested 15 years and nearly a billion dollars in developing torcetrapib.

The Circulation study describes an attempt to determine if the problems from torcetrapib treatment could have been detected earlier, and thus at a lower cost. In this study, the researchers used the SOMAscan® assay to measure changes in the levels of over 1,000 proteins in blood samples from ILLUMINATE trial participants. Using a previously validated, nine-protein cardiovascular risk score, they found that they could successfully predict the harmful effects of torcetrapib in specific patients after only three months of treatment—much earlier than the point at which the ILLUMINATE trial was terminated (18 months).

In addition, a wider analysis of approximately 200 blood proteins that significantly changed in torcetrapib-treated patients revealed that the drug candidate had widespread, unexpected effects on normal immune and inflammatory processes. In addition, changes in only eight of the proteins measured were sufficient to explain the biology underlying the hypertension side effect seen in clinical trials. Beyond torcetrapib, these insights can also provide additional guidance for more personalized and targeted prescribing of currently marketed cardiovascular drugs, such as statins and ACE inhibitors.

Torcetrapib is just one member of a promising class of cardiovascular disease-prevention drugs, cholesteryl ester transferase (CETP) inhibitors, that have garnered considerable interest from the pharmaceutical industry. In addition to Pfizer, both Eli Lilly and Roche had candidate CETP inhibitors that were dropped late in development due to lack of efficacy. However, Merck recently announced that their drug candidate anacetrapib successfully completed the longest CETP clinical trial to date.

Expanding the work described in the Circulation paper to include comparative analyses from all of these drug candidate trials from different companies could provide, not only enhanced understanding of critical protein changes related to side effects, but could also reveal early signs of “positive” protein changes that would help accelerate the successful development of more promising candidates from not only this drug, but across many different classes and even disease types.

Reference: Williams, SA et al. (2017) “Improving Assessment of Drug Safety Through Proteomics: Early Detection and Mechanistic Characterization of the Unforeseen Harmful Effects of Torcetrapib” Circulation (published early online October 3, 2017).

Contact:
Fintan R. Steele, Ph.D.
Chief Communications Officer
T: 720-214-3080
C: 617-816-9834
fsteele@somalogic.com

About SomaLogic
SomaLogic is committed to helping people worldwide receive timely, accurate, trustworthy and actionable information that helps them manage their personal health and wellness. To realize this vision, we are creating and delivering the ”SOMAscan Platform,” a clinically useful and affordable health information system based on comprehensive and personalized protein measurement, delivered broadly through a global ecosystem of partners and users.

 

 

Reynolds appointed CEO of SomaLogic

Reynolds appointed CEO of SomaLogic

Former CEO Byron Hewett steps down after successfully building the foundation for SomaLogic’s future growth

Boulder CO – April 5, 2017 – SomaLogic announced today that Board of Directors member Alister W. (Al) Reynolds has agreed to become the next company Chief Executive Officer.  He is replacing Byron Hewett, who elected to step down from the role following several years of successfully leading the company through its initial growth into a successful commercial entity.

Alister (Al) Reynolds

Alister (Al) Reynolds (Photo by Glenn J. Asakawa)

The announcement was made by SomaLogic Founder and Board Chairman Larry Gold, who praised both Hewett’s leadership over the past several years, as well as the uniquely relevant experience that Reynolds now brings to the role. “As we now enter a new phase in our development we are absolutely delighted that Al, with his deep knowledge of SomaLogic and his broad experience in healthcare, is available and willing to step into top-level leadership at this critical time,” said Gold.

Reynolds, who has served on the SomaLogic Board since 2003, said that he is both excited about taking on this new role and eager to get started. “I don’t think the potential impact of SomaLogic on the quality of life of so many people around the world can be overstated,” said Reynolds. “I have been fortunate to be a contributor to the company’s progress to date, and I look forward to serving this ground-breaking company in new ways going forward.”

In addition to his Board position at SomaLogic, Reynolds currently serves on the Board of Prodigo Solutions Inc. Previously, he served in a variety of senior executive positions for Quest Diagnostics Inc. and its predecessor company Corning Inc. for over 20 years, culminating in responsibility for the nationwide operations of Quest Diagnostics. For the past 14 years Reynolds has served on the Boards and been a private investor in several successful early-phase companies, primarily in healthcare. Reynolds holds a bachelor’s degree in economics from Colgate University and an MBA in finance from Cornell University.

“I am very proud of what the SomaLogic team has accomplished these past several years,” said Hewett, “particularly the initiation and growth of an outstanding commercial program that matches the unequalled research program already here when I arrived, and the intensive strategic planning we have done to successfully build the foundation for the company’s future growth.” Hewett cites the strategic plan as the main reason for his decision: “The different kind of leadership expertise it requires to fully achieve this strategy led me to the decision that now is the right time to hand off the baton to a new CEO.”

Hewett will stay on as an advisor to SomaLogic, and will work with the Board and Reynolds through the transition and beyond. “Byron has been a valued colleague and leader in helping SomaLogic develop a needed commercial focus,” said Gold. “We are grateful to Byron not only for his contributions to date, but also for his willingness to help and support SomaLogic in the future.”

Contact:
Fintan R. Steele, Ph.D.
Chief Communications Officer
T: 720-214-3080
C: 617-816-9834
fsteele@somalogic.com

About SomaLogic
SomaLogic is committed to helping people worldwide receive timely, accurate, trustworthy and actionable information that helps them manage their personal health and wellness. To realize this vision, we are creating and delivering the ”SOMAscan Platform,” a clinically useful and affordable health information system based on comprehensive and personalized protein measurement, delivered broadly through a global ecosystem of partners and users.