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Industrial scientists from 3M, AbbVie, AstraZeneca, Bristol Myers Squibb, Merck & Co., Novartis, and Pfizer are being recognized with the American Chemical Society’s 2021 Heroes of Chemistry Awards. These researchers’ contributions have led to advancements in treatments for bloodstream infections, cancer, diabetes, and heart failure.
The Heroes of Chemistry Awards are ACS’s highest honor for industrial chemical scientists, who make up a significant proportion of ACS’s membership. The program, started in 1996, is sponsored by the ACS Board Committee on Corporation Associates and celebrates industrial advances that have benefited humankind.
Here’s a look at the commercial products being honored this year:
Catheter-related bloodstream infections (CRBSIs) are fatal to more than a quarter of patients who contract one. Over 40,000 cases of CRBSIs are reported per year. Contact with the catheter insertion site—for example, when a clinician lifts the tape and gauze to look for signs of infection—can expose the site to bacteria and increase the risk.
3M’s Tegaderm CHG Chlorhexidine Gluconate I.V. Securement Dressing is a highly breathable, transparent dressing that contains a gel pad of the antimicrobial chlorhexidine gluconate (CHG). The dressing is placed over the insertion site for central venous catheters. Clinicians can see through the dressing, minimizing contact with the insertion site. The dressing is clinically proven to reduce CRBSIs.
“When we got the evidence that we could significantly reduce bloodstream infections, that was just the top of my career,” says Bob Asmus, a retired corporate scientist from 3M and one of the award winners. Asmus led the development of Tegaderm CHG, which launched in 2008.
CHG is clear, which made it the antimicrobial of choice for this dressing, Asmus explains. But CHG photodegrades, is thermally unstable, and is prone to forming insoluble salts with certain anions. The Tegaderm CHG team successfully protected the CHG from these factors while ensuring the antimicrobial could still diffuse from the gel pad to the insertion site.
In 2018, 3M introduced a new product, Tegaderm Antimicrobial I.V. Advanced Securement Dressing, a lower-cost dressing intended for use with peripherally inserted IV catheters. Incorporating the antimicrobial directly into the adhesive as opposed to in a gel pad simplified manufacturing, explains Ying Zhang, a senior product development specialist in 3M’s medical solutions division and one of the award winners.
3M is now exploring the next generation of transparent securement dressings.
Cancer cells are able to short-circuit a form of programmed cell death known as apoptosis, and this ability gives them a survival advantage. Understanding resistance to apoptosis is a critical area in cancer research. Several hematologic cancers depend on B-cell lymphoma-2 (BCL-2) proteins to inhibit apoptosis.
AbbVie’s venetoclax, marketed as Venclexta in the US and Venclyxto outside the US, selectively inhibits BCL-2 proteins. The drug gives patients a new option to treat certain blood cancers.
Venclexta “took an entirely new approach to treating cancer by inducing programmed cell death, specifically in cancer cells, whereas most other chemotherapies just kill fast-growing cells,” including normal blood cells, explains Steve Elmore, vice president for drug discovery, science, and technology at AbbVie and one of the award winners.
Elmore led the team that discovered venetoclax, which took more than a decade of lab work. Venetoclax was the first marketed drug specifically designed to inhibit a protein-protein interaction.
Elmore says it gives him a sense of purpose and satisfaction to know that “our science and the stuff we did in the lab is helping people reclaim their lives.” He believes there are other opportunities for new drugs to act on different pathways of programmed cell death. “I think [Venclexta] is just the tip of the iceberg,” he says.
Hyperglycemia, or high blood glucose, is a manifestation of type 2 diabetes and over time can lead to serious health problems. The drug Farxiga (dapagliflozin) can help treat type 2 diabetes by inhibiting excess glucose from being reabsorbed from the kidneys into the blood, instead causing the glucose to be excreted into the urine.
Along with glucose, Farxiga also causes some excretion of water and sodium. As a result, the drug promotes a modest lowering of body weight and blood pressure. While the exact mechanisms are still being worked out, the combination of these effects has shown benefits for cardiovascular disease and kidney disease, in addition to its original indication as a diabetes treatment.
The compound was discovered by a team at Bristol Myers Squibb led by award winner Bill Washburn and developed as part of a clinical-stage partnership between Bristol Myers Squibb and AstraZeneca.
Farxiga represented a new class of sodium-glucose linked transporter 2 (SGLT2) inhibitors. The shift from an O-linked glucoside to a C-linked glucoside gave the compound more stability in the body and enabled the successful clinical development of SGLT2 inhibitors for diabetes and protection against morbidity from heart failure and chronic kidney disease.
Bruce Ellsworth, executive director and head of fibrotic disease discovery chemistry at Bristol Myers Squibb and another award winner, says it’s a thrill “that this training in organic chemistry could really lead to something that actually benefits human health.”
“It’s very rewarding and very gratifying to see,” says award-winner Nayyar Iqbal, vice president for clinical metabolism at AstraZeneca. “Our baby is now mature and grown up.”
Cancer is the second leading cause of death in the US, according to the US Centers for Disease Control and Prevention. Keytruda, a humanized monoclonal antibody treatment, is a checkpoint inhibitor that binds to and blocks a protein called PD-1, thus helping the immune system recognize and attack cancer cells.
Keytruda represents new hope in the treatment of various cancers. “People are seeing a meaningful benefit in many cancer indications,” says Parimal Desai, vice president of engineering in Merck & Co.’s manufacturing division and one of the award winners.
Keytruda was initially approved to treat metastatic melanoma, but today is approved for more than 30 indications across 16 different tumor types. Tumors that express PD-1 can generally be classified for Keytruda treatment.
When it saw the promise of Keytruda, “Merck moved heaven and earth,” Desai says. “The whole company got aligned.” Desai led a team of more than 1,000 scientists and engineers to expedite chemistry, manufacturing, and control (CMC) development. The company compressed CMC development timelines and expanded production volumes to keep pace with positive data from clinical trials. The US Food and Drug Administration granted the drug accelerated approval in 2014.
Desai expects that anti-PD-1 inhibitors, either alone or in combination with other drugs, will change the practice of cancer treatment. “Doctors are feeling for the first time that we have control over a terminal disease,” he says.
People over 40 years old have a 20% lifetime risk of developing heart failure, which occurs when the heart is unable to pump enough blood around the body.
Novartis’s Entresto (sacubitril/valsartan) has been approved to reduce the risk of death and hospitalization in patients with chronic heart failure with reduced ejection fraction, meaning the heart’s left ventricle does not pump sufficiently. It has also been approved in certain countries to treat chronic heart failure with preserved ejection fraction.
Entresto is a combination angiotensin receptor-neprilysin inhibitor. Valsartan blocks angiotensin II receptor type 1, which causes blood vessels to dilate and reduces extracellular fluid (ECF) volume. Sacubitril is a prodrug that is activated to sacubitrilat; this metabolite inhibits the enzyme neprilysin, thereby increasing the levels of certain peptides that cause blood vessels to dilate and ECF volume to lower as a result of sodium excretion.
The American College of Cardiology now recommends Entresto as the frontline therapy ahead of the previous standard of care, which was based on ACE inhibitors and angiotensin receptor blockers.
For patients with ALK-positive non-small-cell lung cancer, treatments can fail as a result of resistance mutations or brain metastases. Drugs that cross the blood-brain barrier to treat such metastases can be risky because of the potential for side effects.
Lorbrena is an ALK inhibitor that was developed to treat all known drug-resistance mutations, plus brain metastases. It was designed to cross the blood-brain barrier and enter the central nervous system. “It was risky, but it was a risk we wanted to take,” says Ted W. Johnson, a research fellow with Pfizer and one of the award winners.
The Pfizer team used structure-based drug design, which allows researchers to target a specific mutation that’s driving a tumor. This approach meant the compound was safer and gave a higher likelihood it would be efficacious in the clinic.
“As someone in research, most of the programs I work on never make it to Phase 1 clinical trials,” Johnson says. He was the co–project lead for the Lorbrena program and is the coinventor of Lorbrena.
Lorbrena is an oral therapy and has less severe side effects than traditional chemotherapy. It was approved as a frontline therapy earlier this year. Johnson believes Lorbrena has opened the door to more such targeted therapies.
Nominations are being accepted for the 2022 Heroes of Chemistry Awards until Feb. 1 and can come from any area of industrial chemistry. For more information, visit www.acs.org/heroes or email chemhero@acs.org.
3M
Bob Asmus
Dan Duan
Jim DiZio
Don Peterson
Dan Popko
Maria Ruiz
Deb Schwab
Terry Smorch
George Zhicheng Tian
Kheng Vang
Ying Zhang
AbbVie
Milan Bruncko
Vincent Chan
Alan Christesen
Hong Ding
Steve Elmore
Timothy Grieme
Lisa Hasvold
Yi-Yin Ku
Aaron Kunzer
Mathew Mulhern
Chang Park
Cheol-Min Park
Yu-Ming Pu
Saul Rosenberg
Xiaohong Song
Andrew Souers
Gerald Sullivan
Zhi-Fu Tao
Le Wang
Xilu Wang
Michael Wendt
AstraZeneca/Bristol Myers Squibb
Elisabeth Björk
David Boulton
Prashant Deshpande
Bruce Ellsworth
Karen From
Nayyar Iqbal
Anna Maria Langkilde
Per Lindblom
Peggy McCann
Wei Meng
Daniele Paone
Phil Sher
Bill Washburn
Gang Wu
Merck & Co.
Marc Bastiaansen
Parimal Desai
Stephen Farrand
Kevin Gurney
Brad Holstine
Beth Junker
Sunitha Kandula
Thomas Linden
Nguyen Ly
Gargi Maheshwari
Athena Nagi
Chakravarthy Narasimhan
Dennis Rendeiro
Daisy Richardson
David Roush
Patricia Rowicki
Mohammed Shameem
Manoj Sharma
Markus Tanner
Scott Tobler
Nihal Tugcu
Novartis
Thomas Blacklock
Reynalda deJesus
Clive Diefenbacher
Lili Feng
Michael Girgis
Sven Godtfredsen
Bin Hu
Piotr Karpinski
Gary Ksander
Yugang Liu
Mahavir Prashad
Paul Sutton
Andrew Yuan
Pfizer
Simon Bailey
Benjamin Burke
Michael Collins
J. Jean Cui
Judith Deal
Bob Dugger
Mingying He
Jacqui Hoffman
Robert Hoffman
Peter Qinhua Huang
Ted Johnson
Robert Kania
John Kath
Phuong Le
Bryan Li
Michele McTigue
Sebastien Monfette
Cindy Palmer
Paul Richardson
Peter Rose
Neal Sach
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