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Tony barber

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05/12/23

20:47

Post #: 71289067
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Originally posted by Agent-86 ↑

Worth a read .....

Note: "4. Did you also discover NNZ-2591? Yes we discovered NNZ-2591 and synthesized many similar compounds to this, but NNZ2591 was the best compound in a Parkinson’s Disease model."

https://trailtoatexastrial.wordpress.com/2019/03/26/in-the-spotlight-dame-margaret-brimble/

Posted on by
Soon the Phase III Pivotal trial for Trofinetide will begin. I have a personal goal of full recruitment within three months. That doesn’t mean everyone has started, but that all the spots are ready to be filled. WE CAN MAKE THIS HAPPEN!! I’ve decided to do a series of blog posts, called “In the Spotlight”, to introduce parents to some of the people who have made this whole process possible.

When I thought about how I would like to start it off, the words of Julie Andrews… “Lets start at the very beginning, A very good place to start… seemed appropriate; the first name that came to mind was the Mother of Trofinetide, herself- Dame Margaret Brimble. I hope that all of you can feel the power and excitement behind her words and those of all the people who have agreed to take part.

photo credit to: World Class New Zealand Awards
“Dame Margaret Brimble is a Distinguished Professor at the , New Zealand where her research program focuses on the synthesis of bioactive natural products and peptides as potential new medicines. She has published more than 475 papers, 75 reviews and is an inventor on >35 patents.
Margaret was awarded the 2018 Royal Society of Chemistry for Cancer Therapy, 2016 , (NZ’s top science prize), and , 2011 , , , 2015 and conferred the Queen’s Honour .
Margaret is an Associate Editor for Organic Letters, Past-President of IUPAC Organic and Biomolecular Division III, the International Society for Heterocyclic Chemistry and the Rutherford Foundation RSNZ. She discovered the first drug “trofinetide” to treat Rett Syndrome that is in phase III clinical trials with Neuren Pharmaceuticals. She also co-founded the “spin-out” company that is using her innovative peptide lipidation chemistry to generate self-adjuvanting cancer vaccines.”
1. What or who inspired you to go into chemistry?
I really enjoyed my undergrad organic chemistry classes at the . The logic and organization behind organic chemistry really inspired me as I love logic and having explanations for everything. I am not good at arty, wordy subjects so maths and chemistry appealed to me, although I did well at languages like French and German.
2. How did the discovery of Trofinetide come about? Did you have a “Eureka” moment? And did you realize it’s potential right away?
We were working on trying to make mimetics of GPE () as potential neuroprotective agents but we were getting frustrated because simple substitutions destroyed the biological activity of the parent tripeptide. We always wanted to position an additional methyl group at the C-2 position on the proline but we had trouble with the synthetic chemistry to do this. In a pharmaceutical company environment we would have given up and just made more compounds that were easy to make. In the end we persisted with the synthesis over several months because we had a hunch that this molecule would be a good one! When we got the in vitro biological data back we knew straight away that we had our drug candidate called NNZ2566 (now named!).
3. How many people were on your team? And how does a discovery in your lab make its way to a pharmaceutical company?
Our team was very small – we did the work as a contractual arrangement with (initially called Neuronz). We did all the chemistry in our small team – one main research fellow and me. The biology was carried out by biologists employed by Neuren. We were frustrated that there were more biologists than chemists as making compounds takes longer than doing the assays so we felt the pressure.
4. Did you also discover NNZ-2591?
Yes we discovered and synthesized many similar compounds to this, but NNZ2591 was the best compound in a Parkinson’s Disease model.
5. What’s up next for you and your team?
We have co-founded a cancer immunotherapy company called . In this work We developed a novel chemistry platform for coupling immunogenic peptides to TLR2-agonist adjuvants to generate fully-synthetic, self-adjuvanting cancer vaccines. The Sapvax team is now developing a pipeline of products for the treatment of different cancers.
We are currently making new toxins for antibody-drug conjugates to treat cancer and using some of our proprietary self-adjuvanting chemistry platform to make new generation antibiotics .

6. On a personal note, what has been the highlight of your career for you?
Being elected a Fellow of the(FRS). To be elected FRS based on work carried out in Auckland, New Zealand is a considerable feat. I was the first NZ-based female kiwi to be elected. It is hard to get funds for fundamental research in New Zealand and I have had to carry out applied work in the Agritech area to fund my academic work so gaining international recognition for my organic synthesis work on natural products was a real honour for me. It is hard to justify why we want to make challenging natural product molecules but at least I can point to making some useful molecules like trofinetide and the Sapvax vaccines as application of molecule-making. In order to make compounds for the pharmaceutical industry we have to be able to advance the field of organic synthesis and this is the work that I do in academia that led to my election as a Fellow of the Royal Society. Being elected FRS made me appreciate that perseverance and hard work do pay off eventually and makes up for the >90% of experiments that fail. I have also tried to do science at an international level which has been hard as the emphasis in NZ is on application and translation. Science is not about instant gratification and you can’t back winners. Applications for science stem from carrying out innovative fundamental science.
***************************************************************************************
I want to thank Dame Margaret for taking the time to participate in this blog series. I hope that those reading this realize the immense knowledge of only two people is responsible for our children being on the cusp of having a real treatment.

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