04.10-11.24-HST-Startups-Externa-Biosciences

HELENA DE PUIG GUIXE: Hi, everyone. Thanks for having me my name is Helena. My background is a PhD from MIT as well as postdoctoral research here between MIT and Harvard. And most importantly, I'm one of the co-founders of Externa.

Now, did you know that most proteins in nature as well as most proteins in therapies are made up of 20 building blocks? These are the 20 canonical amino acids. At Externa, we are exploring the huge chemical space of synthetic amino acids to produce proteins with new-to-nature functionalities.

And this is the team that's making this happen. We come from the labs of George Church and Jim Collins, both of them pioneers in the field of synthetic biology. The three additional co-founders are Erkin Kuru, who is a chemical and synthetic biology scientist, Michael Moret, who is a computational scientist, and myself, with experience in antibody development. The three of us have together 23 patents, 73 papers, and over 6,000 citations.

Now, synthetic amino acids are already used in the clinic, and one example is Ozempic. Ozempic comes from the GLP-1 peptide, which by itself there is no point in getting FDA approval because it's cleared by the kidneys in minutes. So what Novo Nordisk did is that they added synthetic amino acids to the GLP-1 peptide to increase the half life, and then they were able to produce a billion dollar product.

Now, Novo Nordisk is able to do this because they produce a peptide which can be synthesized chemically. However, the big problem comes when we want to produce proteins with synthetic amino acids. And that is really difficult to do because we need to produce them with a ribosome, and the ribosome is going to require the tRNA conjugated with the synthetic amino acid of interest.

Now, there are two methods nowadays to produce this tRNA. They are-- sorry. There are these two methods to produce the tRNA. They are enzymatic and chemical, and both of them fall short.

The founders of Externa, we discovered and patented a new chemistry to produce proteins with synthetic amino acids, and we are able to access this tRNA in a way that's much faster and efficient than previous methods. Our method takes two hours, we can purify in the benchtop, and we have a 30% yield. And most importantly, the method can be done by a lab assistant.

Now, with this technology we have already integrated 47 amino acids in a year in the lab, and we plan to expand to 100 amino acids per month by December this year.

Now, if we look into the competitive landscape, there have been many efforts to incorporate synthetic amino acids into proteins. Most efforts in the field have relied on synthetics evolution, which means that it will take around one year to incorporate one new synthetic amino acid into a protein.

In our case, we can very rapidly prototype and incorporate new synthetic amino acids in a way that's super fast and low cost. And what this means at the end of the day is that by the time a competitor is able to evolve the cellular machinery for one synthetic amino acid that they think is going to work, we have time to explore hundreds of candidates and take a protein all the way to animal studies.

Now, obviously with this technology we can explore many different applications. Options are covalent proteins, so these are proteins that can bind to their targets covalently and irreversibly at the specific amino acid locations. We are exploring proteins that can sense their surroundings and then change shape depending on the pH of the surroundings or ATP concentrations.

Other applications we are looking into include expanded half life similar to Ozempic as well as post-translational modification, cell penetration, and antibody drug conjugates.

Out of all these applications, the first contract that we are doing at Externa is for a covalent protein, and this one is for Oddity, which is a global cosmetics company. So as you know, cosmetics products have two main issues-- they are either not effective or they have very short half lives. In this case, what we are doing is that we are producing a protein that combines irreversibly in a way that allows us to have a much longer efficacy.

So we are currently expanding, and we are looking for partnerships. We think that the applications of covalent proteins as well as pH-sensitive or ATP-sensitive proteins can lead to partnerships with pharmaceutical companies for therapies. And we are also looking for partnerships in the fields of cosmetics, consumer health, research tools, or diagnostics. And thank you so much.

[APPLAUSE]