Antiviral Drugs Offer Quick Defense Against Pandemics

Startup Exchange Video | Duration: 12:25
August 17, 2023
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    RICK PIERCE: Hi, Eric. Rick Pierce, CEO of Decoy Therapeutics located here in Cambridge, Massachusetts. And we are focused on developing a platform to rapidly develop antivirals for pandemic preparedness and for commercial use. So antivirals that can be used commercially today against viruses or viral threats such as RSV or COVID or pan paramyxovirus, as well as viruses of tomorrow that share similar machinery to the viruses we know about today. And therefore with one drug, we can solve for many different viruses in a viral family.

    So the company was founded by myself, Barbara Hibner, our chief scientific officer, Peter Marschel, who is our chief business officer. Peter and Barb worked at Takeda together and Jodi Cooper also worked at Takeda, as well as Brad Pentelute. And since then we've added on collaborators. We've got our Chief Medical Officer came out of Vertex, Shahin Gharakhanian.

    And we have really a phenomenal list of folks, which is some have weighted to MIT. We've got a disciple of Bob Langer's lab, Michael Lipp, helping us with chemistry manufacturing and controls. So we've really put together a star-studded list of folks to help us take this chemistry into the clinic to help patients.

    One of the things I think we learned from the pandemic of COVID-19 in the last few years is that vaccines alone are not an effective strategy. They're a very important foundational product to protect us all from potentially having mortality, death. But they really don't treat people where vaccines are contraindicated.

    And we've also seen with mutations breakthrough in vaccines. So the next step in that process was folks made antibody-based therapies. And because of resistance, antibodies really didn't have a very long life. We saw antibodies that would work for four to six months and then the virus would replicate and mutate around their mechanisms.

    And so antivirals are really what I would call the final line of defense, where we can develop antivirals which have not been conquered by the virus and where we have been able to, using artificial intelligence and machine learning, identify parts of the viral sequence which allow us to create an antiviral drug, that the virus so far has not been able to beat. And so these are very important tools, these antivirals, going forward for patients who can't take a vaccine because they're immunocompromised, or for patients who for various reasons just don't want to have a vaccine, or if they do have a vaccine, we've seen vaccine breakthrough.

    So if you're in a high-risk area, you're either going out and you're getting on a plane, you're going for chemotherapy, you're going to a hockey game, very crowded space, and you're a high-risk patient, you're going to want to have a second line of defense above and beyond the vaccine. And so antivirals are a very effective way of doing that. This is an intranasally delivered antiviral.

    It will be non-systemic, non-immunogenic. So it truly blocks. It's a physical blocking, using very eloquent peptide conjugate chemistry. It blocks the virus from fusing to healthy cells in your nose, in your lungs, and has been shown in animal studies to be 100% effective at protecting animals from long exposure to COVID-19, SARS and MERS.

    Peptide conjugates are quite simple to think about. They are effectively a combination of differentiated components. And in the case of Decoy 101, for instance, which is our drug for COVID-19, it's a combination of a viral sequence, a proprietary linker which creates stability and solubility for the drug, attached to a lipid. And the lipid or the fat, in this case cholesterol, actually anchors the drug in the same place in cells that COVID-19 viruses want to adhere to in your nose.

    So the conjugate concept is basically combining in a plug-and-play set of warheads, linkers, and targeting lipids. And different lipids can be used to target different tissues. So you really have a unique set. The lipids are sort of the ability to map and find your target.

    Linkers really confer different properties. They allow you to provide greater solubility, greater stability. So many chemistries use chemistry which is intentionally unstable, so that when it meets the target, the warhead breaks off. In this case, we actually want a very strong linker that continues to link the warhead and the lipid together until it's confronted by a virus, at which point it will block that virus from entering the healthy cell.

    So I think the advantages of conjugates are you can have a monomer, one warhead with one linker and one lipid. You can have trimers where you can have three warheads, and that would allow you to basically target multiple pieces of a viral sequence of interest, which would effectively be a great opportunity to get around viral resistance and mutations. So we plan to use multiple warheads one day in future generations of drugs.

    So we were very fortunate back at the beginning of the pandemic to get a call from MIT Professor Brad Pentelute, who is a professor of peptide chemistry here at MIT in Cambridge. And Brad had sequenced and made a drug, he was the first person to make a peptide sequence against COVID-19. And he was looking for expertise in how to best deliver that and potentially conjugate it to something that would allow it to target more effectively and have a longer half-life.

    And through that phone call, a company, Decoy Therapeutics, was born and grew from a team of folks that Brad had known, who were actually working with Brad on linkers to develop ADCs or antibody conjugates. And Brad was aware of their expertise. And so when he made this new drug against COVID-19, he was thinking about how do you conjugate this.

    And so the rest is history. We all came together. I think what Brad brought to the table and still brings to the table in an amazing way is his knowledge of peptide chemistry, his knowledge of building proprietary linkers, but also he happens to be the inventor of the world's fastest peptide synthesizer. So not only can we make novel chemistry and conjugate it with lipids that can target and warheads that can be switched out, but we can make these drugs at incredibly fast speed.

    So if, for instance, you were to give us a viral sequence of interest, within a matter of hours we can begin to print out drugs to test against a viral threat. And really, the future of Decoy is to work to do exactly that, as we're building a platform based on machine learning, artificial intelligence, and conjugation chemistry and peptide chemistry to create libraries ahead of time of linkers, warheads, and lipids that can be used to target viral threats of interest in looking at the future. So you would have a library of known chemical attributes.

    And if you found a sequence that had those attributes, you're then going to dial in and pull down a linker, pull down a warhead, pull out a lipid, and you're then going to begin and within a few hours to print those out and begin to test them in assays. And nothing like this has ever been done before in the peptide world. But I think what's exciting for us is peptide conjugates are about to become one of the largest selling drugs of all time.

    Eli Lilly and Novo Nordisk's peptide conjugates for diabetes and obesity are targeted to do over $48 billion in revenue in the next five years. And that's annualized $48 billion. So it's an enormous-- they're just working on diabetes and weight loss. And we're taking that same chemistry, which has been shown to be very safe, that uses a warhead which is a peptide, a linker, which is proprietary, and a lipid to keep the profile of the drug in the bloodstream.

    So same and it's delivered by a device like our intranasal device, they deliver it in under the skin as a bolus, very similar methodology, just applying that chemistry to a different problem set, in this case developing antivirals for pandemic preparedness and commercial use against viruses like RSV or the flu in patients where vaccines aren't effective. So currently Decoy has eight full-time, two part-time employees and seven very busy consultants working on quality, chemistry, manufacturing.

    We have a lab in New York City that is supported by Johnson & Johnson and BARDA at JLABS. And we have a lab at UMass Lowell here in Massachusetts. And then, of course, our collaboration, we work with Brad Pentelute as a co-founder who has a very large lab here at MIT. We also have collaborations with the University of Toronto with Dr. Philip Kim, using artificial intelligence to design non-natural amino acid-based antiviral drugs.

    And we have another collaboration with the University of Waterloo using artificial intelligence and machine learning to study all the viruses that we're working on to study forced evolution to figure out where mutations could occur and plan for them in advance, so that we can mitigate against mutations.

    [MUSIC PLAYING]

  • Interactive transcript
    Share

    [MUSIC PLAYING]

    RICK PIERCE: Hi, Eric. Rick Pierce, CEO of Decoy Therapeutics located here in Cambridge, Massachusetts. And we are focused on developing a platform to rapidly develop antivirals for pandemic preparedness and for commercial use. So antivirals that can be used commercially today against viruses or viral threats such as RSV or COVID or pan paramyxovirus, as well as viruses of tomorrow that share similar machinery to the viruses we know about today. And therefore with one drug, we can solve for many different viruses in a viral family.

    So the company was founded by myself, Barbara Hibner, our chief scientific officer, Peter Marschel, who is our chief business officer. Peter and Barb worked at Takeda together and Jodi Cooper also worked at Takeda, as well as Brad Pentelute. And since then we've added on collaborators. We've got our Chief Medical Officer came out of Vertex, Shahin Gharakhanian.

    And we have really a phenomenal list of folks, which is some have weighted to MIT. We've got a disciple of Bob Langer's lab, Michael Lipp, helping us with chemistry manufacturing and controls. So we've really put together a star-studded list of folks to help us take this chemistry into the clinic to help patients.

    One of the things I think we learned from the pandemic of COVID-19 in the last few years is that vaccines alone are not an effective strategy. They're a very important foundational product to protect us all from potentially having mortality, death. But they really don't treat people where vaccines are contraindicated.

    And we've also seen with mutations breakthrough in vaccines. So the next step in that process was folks made antibody-based therapies. And because of resistance, antibodies really didn't have a very long life. We saw antibodies that would work for four to six months and then the virus would replicate and mutate around their mechanisms.

    And so antivirals are really what I would call the final line of defense, where we can develop antivirals which have not been conquered by the virus and where we have been able to, using artificial intelligence and machine learning, identify parts of the viral sequence which allow us to create an antiviral drug, that the virus so far has not been able to beat. And so these are very important tools, these antivirals, going forward for patients who can't take a vaccine because they're immunocompromised, or for patients who for various reasons just don't want to have a vaccine, or if they do have a vaccine, we've seen vaccine breakthrough.

    So if you're in a high-risk area, you're either going out and you're getting on a plane, you're going for chemotherapy, you're going to a hockey game, very crowded space, and you're a high-risk patient, you're going to want to have a second line of defense above and beyond the vaccine. And so antivirals are a very effective way of doing that. This is an intranasally delivered antiviral.

    It will be non-systemic, non-immunogenic. So it truly blocks. It's a physical blocking, using very eloquent peptide conjugate chemistry. It blocks the virus from fusing to healthy cells in your nose, in your lungs, and has been shown in animal studies to be 100% effective at protecting animals from long exposure to COVID-19, SARS and MERS.

    Peptide conjugates are quite simple to think about. They are effectively a combination of differentiated components. And in the case of Decoy 101, for instance, which is our drug for COVID-19, it's a combination of a viral sequence, a proprietary linker which creates stability and solubility for the drug, attached to a lipid. And the lipid or the fat, in this case cholesterol, actually anchors the drug in the same place in cells that COVID-19 viruses want to adhere to in your nose.

    So the conjugate concept is basically combining in a plug-and-play set of warheads, linkers, and targeting lipids. And different lipids can be used to target different tissues. So you really have a unique set. The lipids are sort of the ability to map and find your target.

    Linkers really confer different properties. They allow you to provide greater solubility, greater stability. So many chemistries use chemistry which is intentionally unstable, so that when it meets the target, the warhead breaks off. In this case, we actually want a very strong linker that continues to link the warhead and the lipid together until it's confronted by a virus, at which point it will block that virus from entering the healthy cell.

    So I think the advantages of conjugates are you can have a monomer, one warhead with one linker and one lipid. You can have trimers where you can have three warheads, and that would allow you to basically target multiple pieces of a viral sequence of interest, which would effectively be a great opportunity to get around viral resistance and mutations. So we plan to use multiple warheads one day in future generations of drugs.

    So we were very fortunate back at the beginning of the pandemic to get a call from MIT Professor Brad Pentelute, who is a professor of peptide chemistry here at MIT in Cambridge. And Brad had sequenced and made a drug, he was the first person to make a peptide sequence against COVID-19. And he was looking for expertise in how to best deliver that and potentially conjugate it to something that would allow it to target more effectively and have a longer half-life.

    And through that phone call, a company, Decoy Therapeutics, was born and grew from a team of folks that Brad had known, who were actually working with Brad on linkers to develop ADCs or antibody conjugates. And Brad was aware of their expertise. And so when he made this new drug against COVID-19, he was thinking about how do you conjugate this.

    And so the rest is history. We all came together. I think what Brad brought to the table and still brings to the table in an amazing way is his knowledge of peptide chemistry, his knowledge of building proprietary linkers, but also he happens to be the inventor of the world's fastest peptide synthesizer. So not only can we make novel chemistry and conjugate it with lipids that can target and warheads that can be switched out, but we can make these drugs at incredibly fast speed.

    So if, for instance, you were to give us a viral sequence of interest, within a matter of hours we can begin to print out drugs to test against a viral threat. And really, the future of Decoy is to work to do exactly that, as we're building a platform based on machine learning, artificial intelligence, and conjugation chemistry and peptide chemistry to create libraries ahead of time of linkers, warheads, and lipids that can be used to target viral threats of interest in looking at the future. So you would have a library of known chemical attributes.

    And if you found a sequence that had those attributes, you're then going to dial in and pull down a linker, pull down a warhead, pull out a lipid, and you're then going to begin and within a few hours to print those out and begin to test them in assays. And nothing like this has ever been done before in the peptide world. But I think what's exciting for us is peptide conjugates are about to become one of the largest selling drugs of all time.

    Eli Lilly and Novo Nordisk's peptide conjugates for diabetes and obesity are targeted to do over $48 billion in revenue in the next five years. And that's annualized $48 billion. So it's an enormous-- they're just working on diabetes and weight loss. And we're taking that same chemistry, which has been shown to be very safe, that uses a warhead which is a peptide, a linker, which is proprietary, and a lipid to keep the profile of the drug in the bloodstream.

    So same and it's delivered by a device like our intranasal device, they deliver it in under the skin as a bolus, very similar methodology, just applying that chemistry to a different problem set, in this case developing antivirals for pandemic preparedness and commercial use against viruses like RSV or the flu in patients where vaccines aren't effective. So currently Decoy has eight full-time, two part-time employees and seven very busy consultants working on quality, chemistry, manufacturing.

    We have a lab in New York City that is supported by Johnson & Johnson and BARDA at JLABS. And we have a lab at UMass Lowell here in Massachusetts. And then, of course, our collaboration, we work with Brad Pentelute as a co-founder who has a very large lab here at MIT. We also have collaborations with the University of Toronto with Dr. Philip Kim, using artificial intelligence to design non-natural amino acid-based antiviral drugs.

    And we have another collaboration with the University of Waterloo using artificial intelligence and machine learning to study all the viruses that we're working on to study forced evolution to figure out where mutations could occur and plan for them in advance, so that we can mitigate against mutations.

    [MUSIC PLAYING]

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