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Medicinal Chemistry Group

How We’re Developing the Next Generation of mRNA Delivery Liquid Nano Particles (LNPs)

By Kerry Benenato, VP of Platform Chemistry, Moderna

Organized by the Medicinal Chemistry Section
of the Northeastern Section, American Chemical Society (NESACS)
Thursday – June 17th, 2021
4:00 pm
Register for the June Webinar meeting here:
Ed Ha
Kerry Benenato
VP of Platform Chemistry, Moderna

Abstract: A major challenge of developing mRNA as a therapeutic is the necessity of a delivery vehicle. The delivery vehicle must protect the mRNA from degradation, shield the mRNA from the immune system and release its cargo in a tissue and cell specific manner. At Moderna we are invested in the development of new modalities for the delivery of mRNA, with a major focus on new classes of lipid nanoparticles (LNPs). These efforts have resulted in the development of multiple new classes of LNPs with demonstrated clinical translation. The ability of a LNP to deliver mRNA is a function of the components of the particle and the particle architecture. Over the course of our work we have identified critical design criteria for the LNP components, specifically for mRNA cargoes. This talk will highlight these criteria, our medicinal chemistry approaches, and how we apply Molecular Dynamic simulations, live cell imaging and other biophysical characterization techniques to develop our mechanistic understanding.

Bio: Kerry received her B.S. in Chemistry from Providence College after which she moved to Boston College, where she obtained her Ph.D., working in the labs of Amir Hoveyda, focusing on Cu-catalyzed enantioselective allylic substitution reactions. Following that she worked in the labs of Matt Shair at Harvard University as a NIH postdoctoral fellow. After her post-doc she joined Astra Zeneca Pharmaceuticals, where she worked in the Infectious Diseases group, focusing on the identification of new therapies for Gram-negative infections. After seven years at AZ, she moved to Moderna, where she is Vice President of Platform Chemistry, which focuses on the development of mRNA-based therapies. Since joining Moderna she has led the discovery of multiple novel delivery vehicles and have progressed them into human clinical trials for a range of indications. Kerry is an inventor on over 20 US Patents including sole inventor on two of the patents covering mRNA-2173, Moderna’s COVID vaccine.
Symposium Organizing Committee: Brian Aquila, Mark Ashwell, Scott Edmondson, Dan Elbaum, Jeremy Green, Paul Greenspan, Adrian Hobson, Blaise Lippa, Lisa Marcaurelle, Min Lu, Kap-Sun Yeung, Andrew Scholte, Mala Gopalsamy, Raj (SB) Rajur (Chair)

Our Mission
The mission of the medicinal chemistry group is to advance knowledge and understanding of drug discovery research by organizing world class quality symposia.
Our meetings provide our attendees with access to top quality science presenters and offer unique networking connectivity with thought leaders in the scientific community.
Our members work at the forefront of the life science sector and are constantly striving to bring new medicines and therapies forward to the clinic to meet unmet need.

Volunteer Opportunities
The Medicinal chemistry group will be interested in volunteers to assist with annual symposium specifically for contacting potential vendors and fund-raising efforts. Please contact the med chem chair, Raj Rajur at, if interested.

Who are we?
  Dr. Raj (SB) Rajur, Chair
  CreaGen Inc.
  Andrew Scholte
  Daniel Elbaum
  Mala Gopalsamy
  Jeremy Green
  Blaise Lippa
  Morphic Therapeutic
  Adrian Hobson
  Brian Aquila
  Scott Edmondson
  Nimbus Therapeutics
  Paul Greenspan
  Min Lu
  Lisa Marcaurelle
  Kap-Sun Yeung
  Bristol-Meyers Squibb
Mark Ashwell    
  Mark Ashwell
  Nimbus Therapeutics

Medicinal Chemistry Webinar Series for the Year 2020
By Paul Greenspan, Takeda Oncology Cambridge, Cambridge, MA 02139
Last winter (which seems like a lifetime ago), the NESACS medicinal chemistry seminar committee was putting the final touches on preparations for our annual “Advances in Chemical Sciences” symposium, which was scheduled for May 2020. When March rolled around, however, everything changed. It became apparent that the COVID-19 pandemic would make it impossible to hold a large indoor event in the intended time frame. We initially considered delaying until later in the year, but it soon became clear that there was just too much uncertainty to give us a high level of confidence in our ability to stage the symposium even in late 2020. (Subsequent events, as we all know, have validated our concerns!)
Despite our disappointment, the committee was determined to find a way to bring high-quality presentations to the local medicinal and organic chemistry community. We quickly settled on a monthly webinar series, with one seminar for each session. Rather than charging for attendance, we’d do it for free! We chose to hold each seminar on the 2nd Thursday of the month, at 4 pm.
We were thrilled when Derek Lowe (Novartis) agreed to be our very first speaker. Derek’s long-running “In the Pipeline” blog has become required reading for anyone looking for in-depth yet highly accessible analysis of the latest scientific COVID news. Derek’s presentation on September 10th, entitled “Coronavirus Therapies: What’s Probably Coming, and What Probably Isn’t”, did not disappoint. He provided an outstanding high-level overview of the current state of the COVID-19 treatment and vaccine landscape, which concluded with a robust Q+A which lasted for over 30 minutes! And perhaps best of all, we had no technical issues!! (Special thanks go to Casi Leal from Sanofi, for her support and guidance on the optimal use of the Zoom webinar platform.)
Our second seminar speaker, on October 8th, was Rebecca Ruck (Merck), who presented “Enabling Technologies for the Development of Best Process.” She highlighted how her teams were able to generate efficient and green process chemistry synthesis routes for 3 key compounds in Merck’s development pipeline. She incorporated scientific successes in hot areas like biocatalysis, traditional catalysis, and flow chemistry and showed how Merck thinks about both cost-of-goods as well as environmental sustainability.
For our 3rd webinar, Atwood Cheung (Novartis) presented the medicinal chemistry story behind the identification of Icenticaftor, a novel potentiator of the cystic fibrosis CFTR Channel, with a focus on its use as a treatment for COPD.
Most recently, Nathan Fuller from Alkermes described his team’s success in identification of selective dual HDAC 1/2 inhibitors. A fascinating aspect of the presentation was the ability of the highlighted compounds to inhibit the HDAC’s only in the context of the CoREST complex, which distinguishes these compounds from other known HDAC inhibitors.
The series has now hit its stride, and we have an exciting series of diverse webinars planned through next spring. Planned speakers are Brian Lanman from Amgen (January 21st), Ed Ha from Angiex (February 11th), Sara Buhrlage from Dana-Farber Cancer Institute (March 11th), and Matthew Clark from X-Chem (May 13th).
As rewarding and successful as thiswebinar series has been, the committee has its attention focused on a return to an in-person symposium in the coming year. We have now targeted Nov. 5th, 2021 for our 10th annual “Advances in Chemical Sciences” symposium, (hopefully sufficient time for vaccination and herd immunity to take hold), and we’re in the process of building an outstanding lineup of speakers, to make up for our lost opportunity in 2020. We are looking forward to seeing everyone in person next year for what will be a truly momentous event! Until then, keep checking this page for more details about the ongoing webinar series?