Obesity Tx End-Around With Skye Bioscience's Punit Dhillon

On one side of the continuum , there's the billions of dollars being spent by the vanity crowd people looking for a quick weight loss bump in advance of a wedding or a vacation and on the other end of the continuum are patients whose lives quite literally depend on obesity drugs , those for whom losing weight , improving the vasculature , increasing insulin production ,

improving cardiac function isn't just a convenience . It's a necessity to address metabolic conditions that come with a very long list of comorbidities , conditions that come with a very long list of comorbidities .

This broad spectrum has all sorts of consequences on the space and how its players are approaching it , from the foundations of protein selection and design to indication selection and regulatory considerations , to trial design and commercial strategy and more . It's a space that's fraught with a lot more big make or break decisions than most niche drug markets .

I'm Matt Pillar . This is the Business of Biotech , and on today's show we're talking metabolic health and GLP-1 alternatives with a guy who's charting a different course into metabolic health Sky Bioscience Chairman and CEO , Punit Dhillon .

We're going to get to know Punit and learn about Sky's CB1 inhibition play in the space , a play that's garnered a significant amount of backing from the likes of 5AM Ventures and Versant Punit . Welcome to the show .

But one of the things that jumped out at me right off the bat when I was looking into your background was the fact that you founded Oncosec . Now you and I talked I don't know a week and a half two weeks ago , briefly , and I think at the time I hadn't realized it .

But it kind of excited me a little bit because when I read about that I saw that you transitioned the role after you founded the company . You transitioned that CEO role to a really good friend of the business of biotech , in Dan O'Connor , who's been on the show a couple of times .

He was my guest here when he was a CEO at Oncosec after you had departed , I believe , and he came on the show again in the same capacity at Ambrex , believe , and he came on the show again in the same capacity at Ambrex , which was just an advance of his $2 billion exit with J&J .

So I like to say that we you know the business biotech platform played a role in that exit for him . You know , I'll give myself a little . Yeah , absolutely , but that was your first founding . I believe you worked in biotech prior to that , but that was the first time you founded a company , wasn't it ? That's right .

I had previous exposure in solid tumor treatments . What can we do to really address significant unmet needs in cancer treatment ?

I had previous exposure in solid tumor treatments and I really wanted to take the next step of an immunotherapy approach based on really interesting data that was generated by Dr Adil Daud and it was using IL-12 , where he saw a very strong efficacy signal in a phase one melanoma trial .

So the idea was to leverage this cutting edge delivery technology to really enhance the delivery , such as DNA L12 , and minimize the toxicity , which was because previously the approach was it was a systemic delivery of L12 , which had its own challenges in terms of side effects . So the technology held an interesting promise .

Patient outcomes really showed a targeted approach was effective , it reduced the side effects and it offered a great opportunity . We generated some really compelling data and , yeah , dan is a fantastic CEO and I'm really good friends with him .

I have had the pleasure of following his success over the years and was very lucky to be connected to him I think in the summer of 2017 , which led me to kind of have this opportunity to pass the baton over to him as CEO .

You know those are two kind of foundational building blocks . I'm sure that gave you some confidence to say you know what I think I'm going to , I'm going to go out and I'm going to start my own company . What other , I guess , foundational building blocks did you feel like armed you to do that at that time for the first time ?

So two part question what are their kind of building blocks like ? Gave you the confidence to do that ? And then the other side of the question would be when you did it , did you realize , like in retrospect , where you're like , yeah , I probably could use the little , little stronger chops in this area or that area before I went off and launched the company ?

So I had an opportunity to take kind of the technologies that we had put on the shelf and see how we can monetize them . And Oncosec was born out of that unique kind of circumstance .

I think the interesting thing for me as an entrepreneur was yeah , I mean , at that time when I started that company , I was 29 years old , so there was a hugely different risk profile . I started that company , I was 29 years old , so there was this hugely different risk profile .

And I think I , having been in a startup environment , kind of really recognized the opportunity for agility with biotech leadership . If you have the right people around you , then you can really pivot .

And in that business plan , what was interesting was we were initially focused on solid tumors and then more broadly focused on skin cancers and then we narrowed in on melanoma and actually narrowed in further on the combination of pd1 and then um .

So so , like you know , going from from from a wide to a very narrow and a few years gave us a lot of credibility . We were able to scale an organization from nothing like zero clinical programs to three phase two programs in a year and then scale into a pretty large R&D pipeline and then getting into registration trials as well .

It was in a rapidly changing environment . So if you rewind the clock in 2011 , immunotherapy in cancer immunotherapy was just taking off because you had Opdivo got approved not Opdivo , sorry . Irvo got approved from Bristol . It was the CTLA-4 , anti-ctla-4 therapy and then , subsequent to that , was the anti-PD-1 therapy .

So this was an opportunity to really evolve a business plan , to look at the non-responders to the checkpoint inhibitors , and it really underscored kind of the need to build a strong , adaptable team . You know the value of a clear plan .

Being a public company , having you know ability to have decisive leadership , like those are the things I learned in that company because I was a first time CEO and I got a chance to leverage some really good experience around me me because we had recruited a pretty large amount of large pharma executives in that organization .

So my CMO , chief legal officer , chief business officer they were all ex-MIRC and so I was still probably the youngest person in the boardroom and the youngest person in the management team . But it was a great experience and really highlighted kind of the importance of working together as a team and transition leadership roles where it was needed .

Eventually , with that registration program that we launched with Merck , it gave us an opportunity to move forward and it ensured some sort of continuity and growth and Dan took it from there . Unfortunately , that company didn't reach its data point and that's what happens in biotech . It was the primary endpoint in the registration trial wasn't met .

In retrospect the data was pretty compelling . But yes , subsequently the company has now moved on .

So , yeah , it's been a really good learning experience in terms of that , but collectively with that pharma experience , the Anovio experience and then just being in on on the other side , being back in , I got back into bio , into buy side , and that's where I came across Sky .

So tell us a little bit about that , like your experiences with guys who , by the way , you just told me , was also named Puneet , so we'll call him Puneet 2 .

So I tell my team this we should always hire A people and if we can afford to hire the best people that we can in the industry and at the same time always hire better than we can for better than ourselves in terms of teams , so that's the only way you can really surround yourself with the high performers and continue to scale at the pace we need to .

Of course , you know there's always a dynamic that comes along with that , so you have to take the time to make sure that we don't compromise the culture that's required to kind of operate at that scale .

But that's always worked out for the way that my hiring policy is that you know A people , hire A people and better and don't make any compromise on that hiring . We have been really successful of also leveraging kind of this broader network right .

So I'm lucky that I have a fantastic board of directors and a fantastic group of shareholders and a cap table that really enables that success in that whole pharma ecosystem that we have . So the network that we've been able to build over the last in my career , over 20 years , can really , you know , bounce ideas off of people , do back channel checks .

A lot of the things that you know weren't probably as accessible when I first started off in the career , but now with our network , it's been's been fantastic . So I'm I'm lucky that I have a good management team that you know places the same importance I do on that .

And then I think the other piece of it that's been important for me is always making sure that the an individual understands what their purpose is , uh . So the purpose , uh , being aligned with what the company's purpose is , is very critical because otherwise then people can easily be kind of failing in the way , failing in the winds .

So that alignment in terms of job responsibilities , role with purpose is a key factor that I always stress and I spend the time with the team to kind of continue to enable that .

I love asking this question of my guests who have worked in the VC space and perhaps who were in the VC space when they , you know , planted a stake , you know , stuck their flag in the ground and said , yep , I'm going to , I'm going to , I'm going to really get behind this . One right Like , why ? Why this one ?

You have exposure , and when you're in that role , you have exposure . You have two giant advantages , One being your experience in the space in the , you know , drug development space , working for drug development companies , and then , when you're in a VC capacity , you have exposure to all sorts of programs , indications , modalities , opportunities .

What was it that , I guess , incited you to say , yeah , you know what this metabolic space and sky like this is . This is the one that I'm going to . I'm going to jump behind the wheel of this one .

I was a , I was a board member and an investor , so it it or I already kind of had a , a stake in it , um and uh a responsibility from a fiduciary perspective and then really started putting kind of pen to paper on how do we build a fundamental company off of this , this , this broad area of science .

So the company was historically focused on the endocannabinoid system and we're like , okay , this is that is fascinating , it's great . But you know , if we want to really scale that um , then we're going to have to focus on an area where where we can uh attract capital and uh leverage uh any any opportunities to de-risk , uh .

So I incidentally , I was already exposed to kind of other things that were happening in the space . I was following , uh , uh , I was following CB1 inhibition space even before I joined formally as CEO of this company in 2020 . I did have this vision of focusing on CB1 as a target . Initially .

It was around CB1 agonism and glaucoma , where there was validation of agonism validation of agonism of CB1 helping lower intracranial pressure , and then CB1 inhibition was attractive in terms of broadly in a range of different diseases , including the metabolic health space . But let's fast forward Right now .

In the last year it's really evolved into this really compelling opportunity to innovate in this metabolic health space and that's really where we are today .

I think we can still say that we have a lot of experience with targeting the endocannabinoid system as a company , but specifically in CB1 inhibition , I think it's aligned perfectly with my experience and vision for creating a company and potentially breakthrough treatments that can address critical health challenges .

I finally feel personally in purpose , where I get to work on a therapeutic area where I can relate to this , you know , on a on a really rapidly moving , uh moving scale , and uh we've been , I think , uh pretty successful in the last year of where , where we've come from , of acquiring a company , building on the financial , uh strength of the company , advancing

a clinical pipeline and now just launching a phase two study .

Not everyone can relate to an ultra rare disease , not everyone can relate to a chronic condition , but I think metabolic health becomes a really fundamental pillar of overall well-being .

And you can , I think , now recognize , with so much literature that's out there and the prevalence of the discussion around metabolic disorders and specifically obesity , it does represent a very pressing public health challenge in our time Because there's just , I guess , a more common knowledge and relatability around it .

So , beyond the market opportunity , I think it's a fascinating area Because of the complexity of it and obesity . The more we dig into it we also see this additional causal relationship that it's linked to many other diseases and comorbidity . So I really see this as a space where there's a lot of innovative science that can make a profound impact .

It has the ability to address all the unmet kind of components that come along with pharmacotherapy , but by addressing on the root cause of metabolic dysfunction , with this novel approach that we're taking with CB1 inhibition , we have the potential to not only treat but also prevent a wide range of chronic diseases , and I think that by focusing on metabolic diseases

you get to have this link to improving quality of life . So that's a tough one in healthcare . Quality of life is a very tough definition , but you can do it on a global scale , by by by , by this macro area of metabolic disease .

So I'm really excited for for what that pipeline can enable and , working at Sky , I really , I , you know , I really do feel in purpose on making a radical difference with pharmacotherapy because , although you know , I'm not , you know , knock on wood , I don't , I don't have , you know , have a direct kind of link to a chronic therapeutic condition .

Personally , I think health and wellness is something I really care about . So being able to apply pharmacotherapy to make that difference , I can just see that link to make that difference . I can , I can , I can just see that link . And I was just being being an avid health nut and athlete most of my life , like I .

I feel like this is , this is kind of my calling in terms of an opportunity to really help lead , lead a , you know , a company that's focused on that and I can . I can see the rest of my management team too . We joke , I think .

I think our management team has the most um uh , you know anyways the , the best , the , the , you , you cut mean figures across the skyline across the landscape of the biotech industry right I would say we , I'd say we would have a pretty strong deadlift uh score combined as a management team .

So it only makes sense that you have a healthy and good-looking management team in the space you're in . But the space you're in , but this space you're in , like I'm going to dumb this down like to , to , to probably what's a terrible analogy ? And if it is a terrible analogy , I want you to call me out on it . But , like , let let's say you know .

Let's say like I have a , let's say I don't , but let's say I have a passion for ridding the world of a household vermin like mice Right , and I think I want to apply that to a business Again . Just bear with the terrible analogy .

You know Victor , the company that has been making mousetraps probably since the 1700s , and you know what , victor , I got a better way , I've got a different way and I think it's a better way . I'm going to fly in the face of Victor and I'm going to tackle this rodent , you know this rodent epidemic .

In a way , the analogy fits , because I'm looking at you guys and I'm going like you're in , in this context , in this time and place . You know , glp ones are just lighting the world on fire and your , your approach , is a contrarian is probably not the right word , but it's a bit against that grain .

Those would never make as much impact as what pharmacotherapy can offer in metabolic diseases , right ? So that's where I see this opportunity and I guess you can say , yeah , sky is taking a contrarian approach by focusing on peripheral CB1 inhibition , because it's really a novel mechanism for treating obesity . So just to put that in context , right ?

So GLP-1 agonists , which is where you see most of the headlines because of Ozempic , zapbound or Manjaro these are all GLP-1 or GLP-1 derivatives and they've shown efficacy . They've also come with significant side effects and limitations .

We believe that targeting CB1 receptor in the peripheral tissue offers a safer and more effective way to really modulate the metabolic process Without some of the central nervous system side effects that this class has historically had a challenge with , so that we can get into that .

So , ultimately , the approach allows us to really differentiate a therapy in a crowded market and address unmet needs in a way that GLP-1 agonists don't do very well .

But maybe it still doesn't sell as well as the 87 cent . You know , classic Victor Victor mousetrap . In order to get that new approach and in your case , to get this new approach out there and develop it , you've got to make some noise of your own in a in a noisy , in a space as very noisy as it is . So tell me a little bit about that .

Like , what's the ? What have you done ? As I , as I said from the outset , I mean , you've got some stout backing and and companies like 5am ventures . Like what have you done to to create some appeal where it's real easy to jump on the super popular ship right ?

Why would we give a look at a CB1 inhibition program when , like , all the momentum's going in a different direction ? So what are you doing to create that momentum ?

So it's basically um , you know , if you , if you think about um fat loss , it's really a relationship of food intake and relative to energy expenditure . So if you reduce the caloric intake , then you should have fat loss and that's at the very basic level . That's what the Incredin approaches have been focused on .

We are focused on more of the opportunity for healthier , sustainable weight loss .

So the regulation of body weight , uh , you know , if it's , if it's in , if it's , if it's involving this food intake and energy expenditure , then pharmacotherapy and lifestyle approaches have really tried to manipulate this balance and promote weight loss through um , uh , through , like we talked about , caloric restriction , uh , these other types of um , um , uh mechanisms

and specifically these incretin hormones , are really driving that . And what we believe is , you know , a coordinated approach , right ? A coordinated neuroendocrine approach , a multi-organ response to weight loss , really helps to mobilize all the mechanisms involved in fat and triggering mechanisms to really prevent further weight gain is an opportunity .

So , if you keep it kind of at a simple level , the CB1 receptor .

It's expressed on many different organs and many organs are critical for this broad kind of neuroendocrine response and it suggests that CB1 plays a significant role in coordinating that energy balance and fat storage and we believe that part of the endocannabinoid system it plays a critical role in this metabolic component .

It contributes to obesity but by promoting this inappropriate hormone expression and increase in fat and storage and chronic inflammation and targeting it peripherally , targeting through cv1 inhibition , we're really able to drive these other things , like reducing appetite , through , uh , through a different um , these path , these pathways , we're able to uh drive um , uh , like

the , the conversion of fat metabolism into energy . Uh , we're able to target liver and muscle and offering these other metabolic benefits without some of the other side effects that have been associated with the central side effects that previous CB1 inhibition has been .

So it's a different approach than what the incretins are doing and what we expect out of that is a more productive body composition that helps to really promote , like , lean mass preservation and muscle and really just target the fat .

I've read and I don't know how I'll validate that is or what the scientific evidence is um , but are those kind of the side effects that you're talking about , that you're you're looking to do an end around ?

So it's just the degree of muscle loss is which is which is the concern , and what we are trying to really promote is can you get a better preservation of lean mass and a better body composition at the end ?

So this approach that we're taking through targeting peripheral CB1 , is that you're able to kind of not only convert this fat into energy , you're able to also reintroduce leptin .

Leptin resistance is really induced by a high-fat diet and so you're really helping to restore the effectiveness of leptin and it's it's it's helping promote reducing food intake and and and promoting weight loss . You're also helping to reestablish insulin sensitivity .

So those are all combined kind of metabolic pathways that are working in conjunction with this organ-specific CB1 inhibition that we're targeting .

Right , I think the last time that you and I chatted , we were talking about the regulatory scene and I guess the way I look at it like if I'm , you know , if I'm developing a therapy for a rare disease , I'm developing a therapy maybe for an oncological indication I think I can kind of expect what to expect from the regulatory agencies .

And I think the last time we talked , you were talking a little bit about how that's a little bit different , like the game's a little bit different in the obesity space when it comes to developing a regulatory plan . So tell me a little bit about that . Is it considerably different from when you were working solely in immuno-oncology ?

Now you're in this space where there are many applications , for we'll just call it at its simplest form , weight loss . There are many applications , many approaches , many avenues , whether that's a biologic or an over-the-counter drug . It changes the regulatory paradigm a bit .

Diseases where there is a different bar , where you're usually doing a comparison against an active . Here the comparison has been against placebo and showing at least 5% . So it's different than oncology or other rare diseases in terms of the bar right .

But one of the most significant concerns is the potential for neuropsychiatric side effects , which has been a critical issue in terms of the bar right . But one of the most significant concerns is the potential for neuropsychiatric side effects , which has been a critical issue for the development of CB1 inhibitors .

So just to kind of for the audience understanding , there's a historical context here where the development of first generation CB1 inhibitors , such as Ramonimat , which was developed by Sanofi , didn't get approved by the FDA . It got approved in Europe and it was actually halted due to severe neuropsychiatric side effects .

So that included depression and anxiety and even the case of suicide ideation , and those adverse effects were primarily linked to central inhibition of cb1 receptors in the brain , which which ultimately plays a significant role in mood and emotional processing mood regulation and emotional processing .

So so there has been this regulatory scrutiny and because of that , I think that regulatory scrutiny around CB1 inhibition is actually spilled over to everything that's happening in obesity , because even the incudin class is driving a central mediated kind of response .

So there is a heightened focus on ensuring that any new therapies don't pose similar risks , and I think over the last couple of weeks there's even been some headlines about the case of GLP-1s potentially being linked to this mood regulation and , in some cases , depression , in some cases depression .

So I think this means that the regulatory pathway for drugs like we're developing , like namazumab , is likely to be more stringent , right , requiring a very robust data to demonstrate the peripheral inhibition strategy effectively avoids the central side effects .

And this is where Sky and our drug is really differentiated , because we've shown through multiple preclinical studies that our drug doesn't cross into the blood-brain barrier and it stays only in the periphery and the small molecule CB1 inhibitors don't have such exquisite restriction .

So when you're looking at at it , you're going to kind of in contrast to other regulatory uh pathways for other diseases like oncology , uh , the risk benefit ratio is is sometimes a bit more straightforward , because you're dealing with a condition where it's life-threatening and and they may be willing to accept significant side effects for potential survival and which then

lead to a different regulatory approach . And in rare diseases that could also be , you know , a different shift in risk tolerance , I think , for this kind of situation , or it's a chronic condition . Uh , it's not necessarily fatal , but you know you want to have this long-term improvement , long-term prevention .

Um , you know the fda is going to be looking at that from a , from a mood regulation standpoint yeah , um , this , this , uh , peripheral inhibition .

So we're kind of what we define as a first-in-class peripherally restricted CB1 inhibiting antibody that's highly specific for CB1 receptor so it binds in a unique way what's referred to as allosterically to the receptor .

It inhibits the CB1 signaling , independent binding to any other endocannabinoids , and it not only functions as an antagonist but it also functions as an inverse agonist , so it signals the contrary to a CB1 agonist .

So it means that it can reduce CB1 activity and also kind of reverses the signaling that's required to drive that response that we're looking for in this mechanism .

in humans . So tell me a little bit about that , like , um , how has the technology matured ? You ? You talked about , you know previous iterations of CB1 inhibition being problematic . Uh , what have you done ? Uh , how have you matured the technology to the point now where you're building , you know chemistry , manufacturing and controls and putting this thing into ?

You know actual , uh , you know , um , I guess , process practice .

So , yes , like you identified CMC , having a robust kind of CMC framework is important for ultimately transitioning the mass map from clinical development to commercial scale , and that's what we're currently working on .

So we have a two-year plan here to advance what we're doing right now in terms of manufacturing scale to get to commercial scale , and we kind of recently outlined that and that's moving in parallel with our clinical development . So I think we're good . In terms of drug substance formulation development , the next real big step up is the manufacturing scale up .

So , in antibody development , you want to continue to optimize um production of the antibody and then we we need to , you know , ensure we have cdmos in place to continue to um meet the requirements .

So in in the condition of obesity is being such a large market opportunity , I think we're we're really interested in having the eventual commercial distribution scale , uh , to be able to treat this large population . The other side that's attractive for us is that there's going to be opportunities for optimization in our formulation .

So in the current trial we're using a 200 milligram dose as a weekly injection . The ideal product profile can move towards a monthly dose or even a quarterly dose , and that might mean that we're going to go to a higher concentration . So those are kind of happening in parallel . The other side of it is also the delivery .

We're using an auto-injector , so that's the ultimate form factor that patients would utilize the drug .

You talk about auto injectors and sort of the patient experience experience , um , like , at what point um this is just as an aside I'm curious about at what point in sort of the development of the company and since you've been there , did that really become , uh , an important focal point for you ?

You know , for company leadership to say , like you know , this has got to be something that , uh , the patients embrace . The patient experience has to be you know it's it's gotta be . It's gotta be be . You know it's got to be .

It's got to be where you know it's got to be something that they're going to embrace and accept if they're going to make the impact that we want to make .

I think with orals , patients are having to kind of contend with compliance and remembering to take a drug every day , and with injection , there's always the age-old oh , I don't want to get pricked by a needle . So we have been focused on this from day one .

Uh , currently , uh , one of the reasons we've been able to move quickly is we acquired , uh , a bird rock bio , uh , with drug product and it was already in pre-filled syringes in a , in a safe injection unit . So it's a , it's a , it's a unique uh kind of , um , a novel approach to to injection .

It's not the auto injector , but it's just right like a kind of a precursor to auto injector , which is just a safe injection unit . And then we move , uh , and then , as we , as we've been kind of moving in parallel with getting our phase two off the ground , we've also been moving forward on having the next drug product come online .

Next drug product will have a pre-filter range with an auto injector unit , and that's been a parallel process that we've been working on , and then we're already kind of have our eyes set on okay , what's what's next after that ?

I mean , it may not be required for commercial , because there's a regulatory consideration here , but perhaps post-commercialization , there is also auto-injectors with some future kind of technology or smart technology that can be integrated .

delivery of the of the therapy down the road , um , that that's closely related to you know , closely related to patient acceptance is , uh , is is healthcare provider acceptance and payer acceptance , and this is a sort of a uh , I don't want to say murky , but you know it's a it's not well trod , it's not a well trodden path right In obesity .

And that's why I think that this is very attractive in terms of a product profile that gets to a monthly dosing or even a quarterly dosing . So that's the opportunity here is that compliance would make it easier .

Patients are going to be more accepting of taking it because they don't have to kind of be worried about taking it daily and forget and you still get the efficacy out of it .

So we're lucky here with a product profile that has a very favorable PK-PD relationship and a very strong half-life , and we're continuing to look at ways where we can optimize that , where we can make this easier amenable pharmacotherapy for life for patients .

And then , along with clinically meaningful weight loss , if you can have lean muscle preservation and if you keep patients on drug longer , then you can also address comorbidities . So those are the broad level , are the kind of winning factors and I think that's what payers want to see as well .

So the way we look at the path to success for us is that CB1 blockade will become a monotherapy approved and it's going to be very additive to the incretin approach .

And we believe that in the anti-obesity medication landscape that the GLP-1 drugs will be widely available and there'll be probably price compression based on the wide availability of GLP-1 drugs because of patent life , because of just so many companies that are focused on developing GLP-1 drugs and the dominant players advancing their pipeline .

So insurance is probably going to cover that and that price is going to be an acceptable price point . There'll probably be a step through because insurance would be like , hey , that's all we can manage , and then you have the additional kind of second line therapy that would be like a CB1 .

And in some cases CB1 gets applied with GLP-1 because that's an attractive price point . But we don't expect that the price would be higher than what patients are paying right now and and that that price seems to be becoming more competitive .

I mean , maybe you know , in a way that you might be able to offer some hints to , you know , to other folks who are out there developing therapies and looking for , for investment partners . I mean , you know , you can obviously rehash the yeah , you can obviously rehash the appeal of the science .

Uh , that we have with this drug and the previous safety data generated with phase one that you know gives everybody the confidence they're gonna have some level of de-risk associated with it . Of course , you know there's the , there's the rudimentary stuff .

We , we , we did do a polished or that wouldn't say it was a completely polished first one , but we pitched right and like we did the conventional pitch 101 where I was like this is what we want to do and this is why we think this is going to be a valuable opportunity .

And then there was an iteration to that in terms of the subsequent pitch , so to get VC involved . There is the rudimentary stuff , but ultimately it's about de-risking right and de-risking for us came down to okay , novel mechanism , first in class , differentiated . It does show really strong potency against small molecules .

It shows really strong distribution , it has a really strong safety profile . And then here's the development plan .

It has a development plan that can meet an unmet need in the obesity market and Sky's approach is advancing the development at a rapid clip and we can fork it in terms of advancing a broader metabolic focus pipeline and that's what I think made it very attractive for our cap table .

So these buy-side firms , I think , recognize the transformative potential of an approach like CB1 and Ambition . It helps that large pharma is interested in CB1 and Ambition .

So Novo Nordisk making an investment in this area Nordisk , you know , making an investment in this area and prior to Novo making that investment , other buy side had funded you know another company in CB1 inhibition . So you see , kind of you know a lot of smart players I guess you know , attracted to the space .

So that all feeds into the opportunity to invest in a program that can really redefine the treatment landscape for metabolic disorders . But all of this is still risky right until we get further along . I think every step of the way we're working hard to de-risk it for ourselves , for our stakeholders , for investors .

But today I think what sets us apart is a really strong benchmark in terms of preclinical data , a strong strategic development plan . We've been very aggressive in terms of our speed and bets that we made . If you look at our phase two study , it's the first phase two study that's going to have a combination of GLP-1 .

And it's a novel approach with the antibody and explain kind of the differentiation from the small molecule . So I think all of these components , with a management team that's very focused on farm operational excellence , it's instilled the confidence in the buy side to invest and we're going to continue executing against that plan .

You know it's a and I'm not going to say it's a politically correct answer , but it makes perfect sense , you know . Hey , it's indicative of momentum behind this approach . Right Like , it's a good thing . The rising tide lifts all ships . There's got to be a little bit of a balance there , though .

Right Like , you walk a balance between competition and being on the right side of momentum .

Timing for us because we acquired BirdRock at the same time . So it validated our strategy and I think you know not to give ourselves a pat on the back , it was just very unique timing and it underscored the potential for Namasumab . It does introduce competition but it also reinforces the market opportunity and the need for differentiated therapies like ours .

So Novo's interest in CB1 , it helps pave the way but it also helps us really push for other strategic partnerships in the field as it continues to evolve . Because when you look at the anti-obesity medication landscape , the majority of the pipeline is all built on the incretin-based approach .

Like over 50% of the drugs in development , they're all focused on incretin .

If you look at the non-incretin space , the non-GLP-1 space , there's like six companies in phase two right now right , and in that you look at really amlin as a combination with glp1 , which is what novo is advancing , and then there's others like these myostatin inhibitors and kind of muscle preservation specific mechanisms , and then there's cb1 .

So if you , in terms of mid-stage programs , cv1 is really in a unique spot in the anti-BCT medication landscape and it has a unique mechanism that's targeting kind of these underlying metabolic pathways that really hopefully show the additive effect with the existing drugs .

You know you lift . You told me that you've , you've , you've invested in , you know gyms and gotten into that business a little bit . You've told me that you'd , you know you'd love to run a gym , you'd love to own a gym .

I mean , how do you , how do you rationalize sort of that old school , you know , do it the hard way mentality about staying fit and healthy and fighting and avoiding obesity with a therapeutic approach . I know it's , it's like a . It's . It's like a just a , a totally like visceral , not visceral , but it's like a . You know , I don't know it's just it's .

It's like a baseline question about how you fundamentally sort of rationalize this , uh , this approach .

I think maintaining fitness through diet and exercise is ideal , right , but I recognize that not everyone has the same starting point or the ability to achieve the health goals through lifestyle , lifestyle changes alone and and a lot of it . You know , I think we talked about this last time a lot of it's like just privilege , right , like it's like .

You know , some of us are in a unique spot where we can devote the time to do that . Not everyone has that same same level of resources or bandwidth . So what is important is obesity is complex .

It's a very multifactorial disease with genetic , environmental , behavioral components , and for many individuals , even the best efforts in diet and exercise may not be enough due to underlying metabolic dysfunctions may not be enough due to underlying metabolic dysfunctions .

So I think therapeutic interventions , like what we're working on with the mass map or other anti-PC medications , provide the tool to really help those individuals manage their weight and improve their metabolic health and and then also complimenting it with lifestyle changes , are then offering a path to to this , this better quality of life that we talked about .

So I think it's , it's an important piece of the puzzle of pharmacotherapy applying and I think , as the pharmacotherapy makes a difference , we their in their weight loss . That allows them to then continue that momentum with the required lifestyle changes and makes it easier . So I think it's , it's both , and pharmacotherapy has a very important role to play .

Right , like you want someone who walks the walk , talks the talk and understands the science behind it .

They take their um , both like mental and physical side , very seriously . Um , and it's a . It's a good , good environment to be around for us to continue to emphasize what we're trying to do from our drug development standpoint too .

We have a milestone associated with clinical readout there , expected in 2025 . So those are the critical kind of things that are value drivers here , because efficacy and safety of our therapy in a larger patient population , showing that monotherapy as well as a combination can really open up and advance our clinical development , and so that's what we're geared towards .

There's some other stuff that we're keeping close to our vest right now that we're getting to do . You know , naturally , as a biotech with a startup culture , there's a lot to continue to create value , but the major value driver is execution on our phase two study .