Celine Halioua

, for the excellent piece. This round brings Loyal’s total financing to over $125M.

I started Loyal four and a half years ago as a naive 24 year old with an idea that literally had people laugh in my face — FDA-approved dog lifespan extension drugs. Since then, Loyal has created the 

 for a lifespan extension drug, earned FDA acceptance of the 

 in our pivotal lifespan extension study. I am so proud of the precedent we have set and the scientific rigor we have brought to an extremely challenging and important problem. 

Our $45M Series B was led by Bain Capital Ventures, a new investor in the company who brings growth and consumer expertise. We welcomed Valor Equity Partners (Jon Shulkin) as a new investor. And Khosla Ventures (Vinod Khosla), First Round Capital (Josh Kopelman), Box Group (Greg Rosen), Quiet Capital (David Greenbaum + Daniel Gruneberg), Collaborative Fund (Craig Shapiro), and Todd & Rahul, doubled or tripled down on their previous investments in the company. The round was near 2X oversubscribed and at a significant markup to our 2021 Series A.1

This new capital fuels us to very hopefully2 bring the first FDA-approved lifespan extension drug to market. We have the data, the team, and the path forward — this capital was the last puzzle piece to ensure that, if our vision is possible, we will achieve it. 

Funding from this round will help us reach future milestones: 

Building dog longevity drugs does not have a large margin for error, and I rely on our investors to ensure we continuously level up. I appreciate so much the continued belief of incumbent investors including Greg Rosen (who convinced me to start Loyal back in 2019), Josh Kopelman (my growth rate barometer), and Vinod Khosla (whose plans are measured in centuries). I admire both the rigor and leap of faith required of new investors Kevin Zhang and Jon Shulkin — including brainstorming sessions over Adeni chai (Kevin) and cider (Jon).  

It is the honor of a lifetime to build Loyal with this team of scientists, veterinarians, creatives, operators, animal lovers, and investors. We are committed to delivering our dog longevity drugs to patients and veterinarians, and with it building a new pharmaceutical company focused on the biology of aging and healthy lifespan extension.  

1Even high interest rates can’t stop dog longevity drugs.

2While I am a trained scientist, I am also 

 superstitious and you will not catch me mentioning FDA approval without many caveats 🙂

$125M to extend dog lifespan

Today we are <a href="https://www.businesswire.com/news/home/20240321591608/en/Loyal-Announces-45-Million-Ser[…]DA-Approved-Dog-Lifespan-Extension-Drug-for-Veterinary-Use">announcing</a> Loyal’s $45M Series B. Thank you, <a href="https://www.wsj.com/articles/dog-longevity-startup-loyal-secures-45-million-in-funding-23d85cf1?st=jlgyle3tong0t4b&amp;reflink=desktopwebshare_permalink">Wall Street Journal</a>, for the excellent piece. This round brings Loyal’s total financing to over $125M.



I started Loyal four and a half years ago as a naive 24 year old with an idea that literally had people laugh in my face — FDA-approved dog lifespan extension drugs. Since then, Loyal has created the <a href="https://longevity.technology/news/first-longevity-clinical-study-design-fetches-fda-approval/">first regulatory path</a> for a lifespan extension drug, earned FDA acceptance of the <a href="https://www.nytimes.com/2023/11/28/science/longevity-drugs-dogs.html">effectiveness dossier</a> for LOY-001, been on the <a href="https://www.wired.com/story/the-search-for-a-pill-for-dog-and-human-longevity/">cover of WIRED</a>, and dosed the <a href="https://loyalfordogs.com/posts/meet-boo-first-stay-study-dog-dosed">first dog</a> in our pivotal lifespan extension study. I am so proud of the precedent we have set and the scientific rigor we have brought to an extremely challenging and important problem.&nbsp;



Our $45M Series B was led by Bain Capital Ventures, a new investor in the company who brings growth and consumer expertise. We welcomed Valor Equity Partners (Jon Shulkin) as a new investor. And Khosla Ventures (Vinod Khosla), First Round Capital (Josh Kopelman), Box Group (Greg Rosen), Quiet Capital (David Greenbaum + Daniel Gruneberg), Collaborative Fund (Craig Shapiro), and Todd &amp; Rahul, doubled or tripled down on their previous investments in the company. The round was near 2X oversubscribed and at a significant markup to our 2021 Series A.1



This new capital fuels us to very hopefully2 bring the first FDA-approved lifespan extension drug to market. We have the data, the team, and the path forward — this capital was the last puzzle piece to ensure that, if our vision is possible, we will achieve it.&nbsp;



Funding from this round will help us reach future milestones:&nbsp;



<ol class="wp-block-list">
<li>FDA manufacturing, safety, and reasonable expectation of efficacy (RXE) dossier approval for LOY-002, our product for senior dog lifespan extension</li>



<li>Market launch of our first product, and build out of our distribution and commercial functions for nationwide supply&nbsp;</li>



<li>Complete enrollment in and execution of our STAY pivotal lifespan extension study for LOY-002</li>



<li>Continued development of LOY-001 (injectable) and LOY-003 (daily pill) for large dog lifespan extension, including LOY-003 RXE submission and final commercial formulation</li>
</ol>



Building dog longevity drugs does not have a large margin for error, and I rely on our investors to ensure we continuously level up. I appreciate so much the continued belief of incumbent investors including Greg Rosen (who convinced me to start Loyal back in 2019), Josh Kopelman (my growth rate barometer), and Vinod Khosla (whose plans are measured in centuries). I admire both the rigor and leap of faith required of new investors Kevin Zhang and Jon Shulkin — including brainstorming sessions over Adeni chai (Kevin) and cider (Jon).&nbsp;&nbsp;



It is the honor of a lifetime to build Loyal with this team of scientists, veterinarians, creatives, operators, animal lovers, and investors. We are committed to delivering our dog longevity drugs to patients and veterinarians, and with it building a new pharmaceutical company focused on the biology of aging and healthy lifespan extension.&nbsp;&nbsp;



C



1Even high interest rates can&#8217;t stop dog longevity drugs. 2While I am a trained scientist, I am also deeply superstitious and you will not catch me mentioning FDA approval without many caveats 🙂

I’m excited to share that Linda Rhodes, VMD, PhD, has joined our Board of Directors. There are few people who have the breadth and depth of experience across science, veterinary medicine, and entrepreneurship that Linda does. We’re fortunate to have her as part of the Loyal team.

I have long looked up to Linda and consider her a mentor and a friend. Linda has seen it all — from living and working on a feminist dairy cow commune in California to developing three FDA-approved animal health drugs in five years and sitting on the Board of one of the world largest animal health companies. I am honored to learn from her. 

Linda’s expertise in the science and regulation of developing animal health drugs are invaluable to Loyal. We are at an exciting inflection point — aiming to launch our first product to market next year, LOY-002 for senior dogs. We also continue to develop LOY-001 and LOY-003, the large- and giant-breed therapies in our pipeline. Across our portfolio, we will benefit from tapping into Linda’s experience of bringing novel animal drug therapies to market. 

I’m encouraged by the progress we are making across all aspects of the business toward realizing our mission of helping dogs live longer, healthier lives. And I’m inspired by the trails that Linda has blazed ahead of us. 

Please join me in welcoming Linda to Loyal!

Linda Rhodes joins the Loyal Board of Directors

I’m excited to share that Linda Rhodes, VMD, PhD, has joined our Board of Directors. There are few people who have the breadth and depth of experience across science, veterinary medicine, and entrepreneurship that Linda does. We’re fortunate to have her as part of the Loyal team. I have long looked up to Linda and consider her a mentor and a friend. Linda has seen it all — from living and working on a feminist dairy cow commune in California to developing three FDA-approved animal health drugs in five years and sitting on the Board of one of the world largest animal health companies. I am honored to learn from her.&nbsp;



Linda’s expertise in the science and regulation of developing animal health drugs are invaluable to Loyal. We are at an exciting inflection point — aiming to launch our first product to market next year, LOY-002 for senior dogs. We also continue to develop LOY-001 and LOY-003, the large- and giant-breed therapies in our pipeline. Across our portfolio, we will benefit from tapping into Linda’s experience of bringing novel animal drug therapies to market.&nbsp;



I’m encouraged by the progress we are making across all aspects of the business toward realizing our mission of helping dogs live longer, healthier lives. And I’m inspired by the trails that Linda has blazed ahead of us.&nbsp;



Please join me in welcoming Linda to Loyal!

Tom Roseberry

Aging remains a challenging biological process to quantify. Designing effective aging therapeutics hinges on the ability to reliably measure it.

One promising strategy is assessing age-related changes to the 3D structure of DNA. 

quantify these structural changes, using them as inputs to predict the biological age of the tissue.

In addition to the nucleotide sequence, the 3D structure of a DNA strand holds valuable information, too. The most common structural change to DNA is 

 – the addition of a methyl group to a cytosine base at a cytosine/guanine nucleotide pair (

). Methylation changes the shape, and therefore the function, of certain areas of DNA; the methylation status of certain CpG sites change predictably with age.

These changes can be used to create epigenetic “clocks” to quantify the age of an animal or tissue. Just like DNA, methylation can be easily and cheaply sequenced. Different epigenetic clocks weight different combinations of CpG sites, often 1000s, to calculate the predicted age of an animal or tissue.

The use of epigenetics in aging drug development

Loyal is developing drugs intended to extend lifespan (years of life) and healthspan (quality of life). However, it inevitably takes years to determine whether a potential aging drug actually impacts the aging process. Epigenetic clocks may allow one to predict the efficacy (or lack thereof) of a novel aging drug potentially years before measurable changes in healthspan and lifespan.

Put simply, a reliable epigenetic clock may help us understand if an animal is aging quickly or slowly in relation to its peers, and whether a specific intervention has affected that rate of aging.

Loyal has licensed a novel clock and methodology from the Ideker Group at The University of California, San Diego.

This clock identified aging-relevant CpG sites that are conserved between mice, dogs and humans, laying the foundations for conserved aging quantification. In their Cell Systems publication[1], the Ideker Group showed that their epigenetic clock can determine, within one year, the chronological age of a dog. The paper also proposes a more accurate conversion of dog and human years, especially relevant given Loyal’s thesis that developing dog aging drugs will be a key step to developing human aging drugs.

In addition to determining the chronological age of a dog – especially important in the case of shelter dogs and others without birth records – this work out of the Ideker group may help:

In addition, Loyal has partnered with the Morris Animal Foundation to investigate the potential use of DNA methylation changes to predict cancer onset in Golden Retrievers [2].

B-cell lymphoma and hemangiosarcoma are the leading causes of death in Goldens; earlier detection and therefore intervention could result in longer, happier lives for this breed. Additionally, understanding conserved risk-factors for age-related cancers may help identify potential drug development targets for both Goldens and humans.

Most of the methodology for building epigenetic clocks has involved using basic linear regressions and simple representations of methylation as single numbers. Loyal is leveraging the latest machine and deep learning models – in addition to representations of genomic data gleaned from natural language processing algorithms – to access the full richness of information available within the epigenome. We believe this will yield insights beyond age measurement and provide a more holistic view of the aging organism.

Quantifying the Aging Process: Loyal in-licenses mouse-canine-human homogeneous epigenetic clock from UCSD

Aging remains a challenging biological process to quantify. Designing effective aging therapeutics hinges on the ability to reliably measure it.



One promising strategy is assessing age-related changes to the 3D structure of DNA. Epigenetic clocks quantify these structural changes, using them as inputs to predict the biological age of the tissue.



<h2 class="wp-block-heading">Epigenetics 101</h2>



In addition to the nucleotide sequence, the 3D structure of a DNA strand holds valuable information, too. The most common structural change to DNA is&nbsp;methylation&nbsp;&#8211; the addition of a methyl group to a cytosine base at a cytosine/guanine nucleotide pair (CpG site). Methylation changes the shape, and therefore the function, of certain areas of DNA; the methylation status of certain CpG sites change predictably with age.



These changes can be used to create epigenetic “clocks” to quantify the age of an animal or tissue. Just like DNA, methylation can be easily and cheaply sequenced. Different epigenetic clocks weight different combinations of CpG sites, often 1000s, to calculate the predicted age of an animal or tissue.







<h2 class="wp-block-heading">The use of epigenetics in aging drug development</h2>



Loyal is developing drugs intended to extend lifespan (years of life) and healthspan (quality of life). However, it inevitably takes years to determine whether a potential aging drug actually impacts the aging process. Epigenetic clocks may allow one to predict the efficacy (or lack thereof) of a novel aging drug potentially years before measurable changes in healthspan and lifespan.



Put simply, a reliable epigenetic clock may help us understand if an animal is aging quickly or slowly in relation to its peers, and whether a specific intervention has affected that rate of aging.







<h2 class="wp-block-heading">Loyal has licensed a novel clock and methodology from the Ideker Group at The University of California, San Diego.</h2>



This clock identified aging-relevant CpG sites that are conserved between mice, dogs and humans, laying the foundations for conserved aging quantification. In their Cell Systems publication[1], the Ideker Group showed that their epigenetic clock can determine, within one year, the chronological age of a dog. The paper also proposes a more accurate conversion of dog and human years, especially relevant given Loyal’s thesis that developing dog aging drugs will be a key step to developing human aging drugs.



In addition to determining the chronological age of a dog &#8211; especially important in the case of shelter dogs and others without birth records &#8211; this work out of the Ideker group may help:



<ul class="wp-block-list">
<li>Provide early evidence for potential future customers that an aging treatment is indeed slowing or reversing the aging process in their dog.</li>



<li>Speed up drug development iteration by use as a surrogate endpoint/aging biomarker in clinical trials.</li>



<li>Point to new aging targets by studying the specific structural changes to DNA and their downstream consequences.</li>
</ul>



<figure class="wp-block-image size-large"><img loading="lazy" decoding="async" width="1024" height="757" src="https://blog-admin.loyalfordogs.com/wp-content/uploads/2024/01/wang-et-al-1024x757.webp" alt="" class="wp-image-972" srcset="https://blog-admin.loyalfordogs.com/wp-content/uploads/2024/01/wang-et-al-1024x757.webp 1024w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2024/01/wang-et-al-300x222.webp 300w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2024/01/wang-et-al-768x568.webp 768w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2024/01/wang-et-al.webp 1402w" sizes="(max-width: 1024px) 100vw, 1024px" /></figure>



<h2 class="wp-block-heading">In addition, Loyal has partnered with the Morris Animal Foundation to investigate the potential use of DNA methylation changes to predict cancer onset in Golden Retrievers [2].</h2>



B-cell lymphoma and hemangiosarcoma are the leading causes of death in Goldens; earlier detection and therefore intervention could result in longer, happier lives for this breed. Additionally, understanding conserved risk-factors for age-related cancers may help identify potential drug development targets for both Goldens and humans.



Most of the methodology for building epigenetic clocks has involved using basic linear regressions and simple representations of methylation as single numbers. Loyal is leveraging the latest machine and deep learning models &#8211; in addition to representations of genomic data gleaned from natural language processing algorithms &#8211; to access the full richness of information available within the epigenome. We believe this will yield insights beyond age measurement and provide a more holistic view of the aging organism.



<ol class="wp-block-list">
<li>Wang T et al. Quantitative Translation of Dog-to-Human Aging by Conserved Remodeling of the DNA Methylome. Cell Syst. 2020 Aug 26;11(2):176-185.e6. doi: 10.1016/j.cels.2020.06.006.</li>



<li>Morris Animal Foundation Partners with Loyal to Study Dogs’ Genetic Changes that Occur as They Age. June 7, 2021.&nbsp;<a href="https://www.morrisanimalfoundation.org/article/loyal-dog-aging-study-golden-retriever" rel="noreferrer noopener" target="_blank">https://www.morrisanimalfoundation.org/article/loyal-dog-aging-study-golden-retriever</a>.</li>
</ol>