Welcome to Farmer Talk Radio. This podcast is focused on optimizing the value proposition in small companies with limited budgets from the twenty twenty five Chief Medical Officer Summitt three sixty. For more information on the CMO Summit, editorials, podcasts, or webcasts, please visit CMO three sixty dot org. Thank you and enjoy the podcast.
I'd like to introduce myself. I'm Luke dv I'm the CMO of twelve Therapeutics, which is a car t reg company based in London, and I've been there for a couple of years after a career in Big Farmer. Prior to that in academic surgery, and then a more recent gig for me is working's venture partner at SV Health Investors. And so if I can ask my fellow panelist to introduce yourselves to Jen.
Hi, everyone, Jen Sida. I've been almost exclusively on the biotech side for the past twenty five years and the last nine of those with SSI Strategy, and with that team, I've held three CMO roles, but also as part of the company, we do is not just sometimes place cmos in interim acting supplementary roles, but we also wrap around existing cmos, so we have a chance to work with about forty to fifty cmos per year, so we end up seeing a lot of what people do write and
where people might go a little sideways in trying to really optimize their budgets. So have a little bit different perspective there.
Hi, everyone, I'm John Goldberg.
I was the CMO at a publicly traded biotech company called on Chorus.
That's the operating part of my career.
We went public like many other companies in twenty twenty October second, to be exact, and I think what I learned about optimizing the value proposition there really was around maybe as a company strategically not over investing in internal capabilities. But fast forward to now we'll have a chance to get into that more. I'm the chief medical officer at Raphael Holdings, which is a publicly traded but family controlled
holding company based in Newark, New Jersey. We have recently completed a merger and a merger with Psychotherapeutics, and my colleague from Cyclo is here in the audience as well, so we can talk a little bit about how we're keeping that team lean as we approach the value proposition.
And I'm Scott Harris. Excuse me. I'm the chief medical officer of Altimoun. We're a publicly traded company in the mass and obesity space. We have a JLP one dual receptor agonist with the trial readout coming up in this quarter. But I've been in biotech for twenty five years. I've
been in both the public and private sectors. I've been the chief medical officer three private company, two of which were a venture back, one of which I actually founded and started with the Series A. And now I'm currently the chief medical officer of a public company.
So this this topic feels very cogent to today's Everything that we've heard today actually just about the kind of bear market that we're operating in and this sort of tough funding environment, the elevated expectations of what we have to deliver in terms of data packages in order to make compelling investment opportunities.
We've also heard.
Quite a lot about how to articulate our stories in the best possible way in order to make to make them interesting to investors. It's sort of another story that I heard first thing at breakfast was how there's a forty percent vacancy rate in Kendall square at the moment, right. So, I thought that really brought it home to me just how tough a our it is that we're all pracing it now with the sort of wealth of different perspectives
we've got on the panel. I wanted if maybe Scott, you could start off by reflecting on how things are different now and the difference in the story that we need to be able to tell in order to make a compelling investment proposition.
Well, the downfall of the markets are very recent. It's a little hard to tell, although we've seen these rises and falls periodically. You know, we saw this during the pandemic when the markets took a hic and then the biotech market went zooming because of the promise of developing COVID vaccines with a lot of schizophrenic investors. There's really
nothing that we can really do about it. I think that the value proposition for you here and listening to us speak is what we can tell you you can do to create your own value for your own companies. And I'm happy to make other comments, but I'll pass it over to John and see if he wants to add to that.
Thanks, Thank you, Scott.
So I think For me, the canary in the coal mine was I was first time head of development and it was it was citsy of twenty twenty one and we were holding our first investor call and the street did not like it, and in retrospect, knowing what I know now, that was pretty obvious we didn't. We had a call, we had our analysts call in and we basically said that, you know, patients had psychokine release syndrome when they got injected with a virus and maybe somebody's
tomb had gotten smaller. We were really psyched about it. We thought we had executed very well. But I think the lesson there, aside from the fact that it was sparked, things were starting to get very hard from an oncology standpoint.
You needed to have response data.
But the lesson for us was you have to understand what the stakeholders are expecting to hear, and we did not understand that. The market at that point was you have to have responses, and perhaps for good reasons in the ancalitic virus field.
So that was certainly a lesson for me.
And then right sizing your clinical development program to deliver what you think the market is expecting which I hope I have the opportunity to do now. We're working with our new partner, Psycotherapeutics, and I'd.
Love to add, even though it seems like the laboring. A point we heard a lot of today is how to really create more value from every milestone by actually building with the end in mind as early as possible, even if it's pipeline prioritization or into indication selection. Is this something that's truly solving an issue in the market as it stands, not just now, but in development the
timeline until the drug would come to market. And we see a lot of companies that get very insulated thinking very early on, especially from an R and D mindset to CSO founder mindset, that this is our compound and we're going to build everything around it, and then maybe add a few bells and whistles about Okay, there's a big market and if we get a little piece of that, we'll be happy. Versus those that really take the time and effort, which is difficult to do, especially in that
limited resource environment. You want to go, go, go and get to a milestone, but to take a step back and say, are we really telling a compelling narrative about how we're going to creatively approach this situation in something that will really solve an unmet need. And that could be looking like instead of focusing an incredible discipline to
value a creative milestones, not just the next milestone. I know we heard a lot about that, but that could look like instead of every meeting about being about are we hitting that timeline for filling out and submitting the I and D, are we actually sitting back and thinking about how are we optimizing our own resources to creatively get the proof of concept as fast as possible in humans?
Which is a very different conversation to have, and that might be for like a rare and complex a rare disease or and complex modality that I've worked a lot in. We can actually demonstrate we got early advice from multiple jurisdictions to de risk our strategies, so we have a higher chance of success of being clinically and commercially successful across our CDP because we got that input early, we maybe looked at different geographies to say how do we
most efficiently get there? So I actually did want to challenge maybe one of the thoughts we heard of what makes a good CMO was have they done this multiple times? But I want to know have they done it the same way every time versus right now? You might need to be able to do that a little bit more creatively. So I think more of the thrust of that was about de risking and optimizing those individual kind of choices along the way and being disciplined to sticking to that value accretion milestone.
So you know what I'm hearing is three major changes. One is a discipline from investors looking at the end in mind and not only to the next development milestone, but through to approval, through to reimbursement and revenue. Secondly, the macroeconomic limitations with and limitations in investment. And then thirdly this political context that we now all live in, which is thrown up a whole load of other uncertainties.
I'm just wondering whether you see any particular I don't know if you could riff on the you know that on those themes, you know, what are the particular challenges that you see? Do you see any particular solutions to that at the moment in this current environment.
I think that there are themes that run true. I think there are things that you can do. The first is value is not a continuous process. It doesn't gradually go up or gradually go down. It's generally driven by catalysts. Okay, now it's hard to see this as a private company because you don't have those external metrics. But as a public company, you can look at your stock price in market capitalization not only every day but by the minute.
So what drives that value? If it's not continuous, it's catalysts, or you can call it milestones, as Jen said, So what are those milestones. Well, generally they're your data readouts, and depending in the marketplace, that data readout is typically clinical. But during the pandemic, when we had a vaccine company, we read out a pre clinical rats study on an internasal covid vaccine. Based on preclinical data, the stock popped, our market valuation went up to a billion, and we
raised two hundred million dollars on direct financing. But it depends on you where you are in development. But you can also create value based on announcements for example, you had a successful FDA meeting for example, that can also drive value as well. So it's really important to also recognize in the process that words matter. What you say
publicly clearly matters. We had an example from John. I remember we had a successful readout and I mentioned that one of our patients had an elevation of ALT and.
The stock dropped.
You could watch a drop by the minute from the time actually made an announcement. I thought it was irrelevant. I've seen it hundreds of times in phase one trials, but the market was poised to react, So consequently what we said really matters. The bottom line is what you say in your presentations matters. Every word, every title matters. What you say to investors matters, what you say in your press releases matters. So always go and look as if you're looking from the outside in and don't get
interiorized into your message or value. Take the look at value from the outside and be realistic, be brutal, and don't drink your own kooid.
Yeah.
Absolutely, I certainly learned that lesson not to drink the kool aid. And certainly what I'm doing now, Raphael is trying to be a very honest broker of the data that we have. Our principle is a very successful man. He's extremely enthusiastic about the whole biotech sphere. But that means that he can maybe look at things with a
different lens. So part of my job is as an advisor to say, you know, this actually isn't very pressive mouse data, No, we should not invest in this that kind of thing because someone who's really a generalist investor is seeing it.
But turned to him and say, is what we do.
What we can do for you, what is going to create value is we have this great new alliance. We have this, we have a Phase three trial that's fully enrolled. We're going to execute the heck out of this. We're going to make sure that the team has everything that they need to bring this home and have this you know, actionable information. That's what we can do, and do it with a lean team because the team that we've joined with is lean, but they're amazing. So that's what I
can offer, you know. And that's one of the things we talked about was execution is obviously part of this.
Yeah, I want to kind of riff on that execution piece a little bit. Where we see cmos doing well early is a kind of radical discipline not just to the right milestones, but also and in prioritization. But do they have the right seat at the table where these decisions are being made, and how is the organization actually making decisions to remain agile and to not swirl on decisions. The amount of time, energy and money lost on decisions
swirl is you know, really, I mean probably calculable. I haven't done it, but we see that a lot in these early stage companies. And sometimes it's due to the shift of moving an early stage from an R and D organization to a clinical organization, but you also see it from a clinical to a commercial organization. There's new decision makers at the table, there's new skills, and the value that's being created is coming from a new group
of leaders that wasn't there previously. And so we don't see companies adapt quick enough in their governance and their decision making and who's sitting at the table, and it should only be the people necessary and not just continually adding folks on shifting that maybe from CSO founder to CMO and COMO then in handshake with the CEO later in that stage. Is that that decision making process and
governance see that it doesn't sound really sexy. We see that as a huge driver of companies that are successful early on versus companies that are not. So take a look at that, and hand in hand with that is some of the program management. So I think sometimes that's
underthought early on as well. But having robust program management so those decisions that get made are appropriately cascaded, that risks are escalated and discussed at the right forums, that actions can be taken in tract, and the impact of those on other divisions when you're adding a bunch of new functions is approaching. You know, your clinical your clinical stage and clinical trials is massive. So not the sexiest answer, but something really practical that we see making a difference.
So what I'd really like to hear from you guys is how you resource and how you execute in order to get to these value and inflection particularly in the title with the limited budgets, right, short runways, cautious use of that cash, how do you build? Where are the pitfalls? Just hints and tips.
So I would advise this group that your most valuable data, your most valuable asset is your data, and you may not be treating it as well as you should. For example, is your data stored in the cloud, is it backed up? Is it encrypted? Can other people access it? In that cloud who is monitoring your data. I'm going to tell you that through Phase two studies, I employ my own monitors because I want to train them. I want them
to be accountable to me. CROs are useful organizations, but at the level that I want better data, I monitor my own data. I have never done a study in my career where outsource medical monitoring. The decisions are just really too important. And lastly, within Ultimune, I've created my own data management with five programmers and a data manager, and consequently we create our own data sets and generate
our own tables. I think everybody has a story where they ask for the ro biometrics group to get a table and you got it back two weeks later at a cost of two to three thousand bucks. When you're doing this internally, you can reach in, ask the question and get it essentially for free by two o'clock that afternoon, and you know the quality is there and they're going to give you what you want, rather than having that table come back and not really answering your own question.
So I think data is extremely important. The value that you can create for your company is how you manage that data and treating it like a prize.
Yeah, if I could add to that, because the way that you get that data is through your clinical protocol. And we heard a lot yesterday and today as well about how to design protocols that maybe don't have a million billion end points in them or data points, but at the same time being responsive to science and being
responsive to new endpoints like patient reported outcomes. I think this is this is somewhere in the early stage where the chief mountical officer certainly can have a lot of input to say, you know, that patient doesn't really care if you see that specific kind of t sell in that part of their tumor when you buy and see it on you know, three times in the first week,
but that will cost a lot of money. And if the patient doesn't respond, then you're never going to do the assay anyway, because your company's not going to be able to raise capital. I'm being a little facetious, but I think it's important to remember the end points that the patients will care about are probably the same endpoints that regulators and more importantly, the.
Payers will care about.
So I think really a focus on trial design is important in a company with a limited budget.
I like those answers and I'm going to go a totally different direction here with not just thinking about some of those concrete things, but also as a CMO, prioritizing your time that what you're spending things on. And I think it's a big bit of a fallacy of a lean team early on that cmos by nature and training, are high performers, and there are a lot of things we are supposed to be experts out and a lot of things we can do. It doesn't mean we should
be doing all of them all of the time. And then we see a lot of companies or cmos that struggle early on because they can be the medical monitor, because they can write the protocols, because they can talk to the KOLs, because they can do all of this, that they think that they should do that and are either burning themselves out and don't have any time time to sit back and creatively think about the protocol or creatively think about how to manage their own data, or
having the time for the investor conversations that are really critical, and almost they reach a point of being underwater before then getting help or delegating or finding creative ways, whether it's insourcing, outsourcing, appropriate vendor management, which we all know takes a little bit of time to get up and going, so it becomes a bit more work before less work. So it's almost thinking early, how are you going to prioritize your time not just today, but a month from
now when the trial is actually kicking off. You know, when the data is coming in, you're going to need that time available. Are you going to be surrounded and are you arguing? And do you have a seat at the table for getting the budget that you need or the time that you need, and is everyone aligned to what those key milestone drivers are so you can be focused on that and have the time for that instead
of that kind of period of overwhelm. So I want to how to bring your best self and what is most critical for the CMO to do sometimes requires that extra discipline of time. Also just a little bit to pre as comment, I think we do really well when we also have some time for the milestones that really matter in our children's lives, personal lives, whatever those things are,
so we can actually come back refresh and creative. I know you don't always get that luxury of time, but it's an important point.
I wanted to make brilliant points. Scott was just wanting to pick up on your comment about insourcing some of the work, because one of the counter points that I've heard from colleagues at this conference is just how hard it is to hire at the moment and how hard it is to justify that headcount. So running really lean, so it'd be really and actually then that also speaks to your spot there with SSI about how you resource that in alternative ways. So I'm just really interested in that theme.
Well, there's a lot of tension in the job, and what I mean by that is not an emotional tension, but decision making tension. Try to be lean and mean, but not over exert yourself. Try to run with a small team, but now expand it enough to do the core functions. I mean, we could be go on schizophrenically here for hours talking about that. I'm being going to
this conference now for fourteen or fifteen years. I think the first one of these that I attended with about one eighth of the amount of people here, was like in twenty eleven, and I remember the conference organizers standing up and saying that the CMO position is the loneliest position in the world. And I've thought about that through the years. And what it means is that when you go to bed at night, who's going to console you?
What are you going to do about your problems? So the answer is is that a dynamic and you have to decide for your own situation, bosting your own resources. If you don't have the money to hire a biometrics team, don't do it. But I'm telling you that if you can, you're going to create This is the topic of the session. You're going to create value.
Right.
You can create value by managing yourself properly so you don't go crazy. I'd say the one piece of advice I would give regarding jen is to surround yourself with a lot of different people and ask for a lot of advice and if you can't get it internally, go out and get it. There are plenty of people out there who can help you a variety of functions, people in the next rooms who have expertise that you don't have. You can't know everything.
Yeah, I would agree with that. I think in a way it's a case by case basis. In our case at Raphael Holdings, we have this great new team that's joined us, So that does free me to think about some of the big things. In fact, Karen and I were talking about a project that I may be able to help with because I'm not as in the weeds executing, and I can spend time thinking about what is our invest stir strategy now now that we are a joint entity and have this rare disease program going, who are
we going to educate? So I think that is the way that we're trying to create value by apportioning duties as necessary, not necessarily bringing on a huge new team. We may need to, you know, I hope we need to, but really thinking sensibly about who's doing what, and.
I'd say I don't think there's a one size fits all for insourcing versus outsourcing versus vendor array versus complete internal build. I do think that having these all those options on the table and considering who are we as an organization, what's our cash on hand, what are our milestones coming up? Who do we have available? Where does it make sense that we full time hire versus where does it make sense that we reach externally? What kind
of external relationship does that actually look like? But we do find companies who are most successful are thinking creatively about it, even if their actual answer is a little bit different from one to the other. So you know, being able to you don't you're suddenly working in an area that has a complex manufacturing you want to get ten hours of manufacturing expertise from C and C reg and how you're going to address that versus hiring inside great?
Do that go go buy that expertise in a limited fashion of high level expertise rather than maybe relying on a junior person to go take the time to kind of research. So I just think thinking creatively about what the needs are and who you are as an organization and what your ultimate, immediate and long term goals are. Are you thinking that you'd want to hire a big team if you know you've got a potential acquisition on
the on the front? Do you want to have a big SGNA if you're going to be limited and you've got a you know, some concern about what the data is actually going to read out? Is it better to have more vendors or outsourcer insight kind of partners to help take off some of that risk and you won't lose people right before that readout and then have to do all that work yourself.
Just taking it taking a slightly different direction at the end. Here, Johnny raised a really interesting point about protocol design and what the critical data elements where and how do different parts of the data play, and particularly if you need to get to stepping stone readouts to keep people engaged, keep the investors engaged, even if you've not, maybe got a runway that gets you all the way to the end. Just what's the relative value of the buyomarker data at
the clinical end points? How do you think about that?
Yeah, thanks for that question, Luke.
I grew up in phase one translational medicine, so I love biomarkers. I didn't mean to make it sound like I don't, but I also recognize that if the stakeholder, if the audience doesn't understand and why a certain readout is important, then it doesn't really matter if I think it's important, it's not going to move the needle. So if I believe that something's important and this needs to
be pressure tested internally like this is. You know, we had arguments around some of these with our CEO at on Chorus, then I really need to be able to explain why. And then the next job is to go out and educate stakeholders. You can start with your investigators, because certainly if they're not bought in.
You're not going to be able to do the study.
But then once once it's a real live entity and you're going forward, you do need to meet with investors. And I'm sure everyone in this room has done this where you may have to meet with the same investor four times, but you kind of explain this is the biology and if I see this readout in my phase one, that gives me confidence that this other endpoint of clinical response or survival or what have you could be impacted. That's how you do it. I mean, it's about educating.
It's like educating your patients.
I like to blend that comment an idea with something that Scott was mentioning earlier, which is the value of external validation on that piece of education. So you can say, we did these studies and this is what we think.
It's a lot more potent or powerful. And also knowing which stakeholder you're engaging in, what their level of education, what they need to understand about it is also if there's that external validation that there is a raft of literature, that there is precedent, that there's something else, even if it's in a slightly different disease, but there's precedent for the impact of this biomarket and it all goes back to de risking your clinical development strategy and plan.
Yeah, I would recommend that you take a position and you hold it right. You research it, you have the courage, you spend money on it, you develop it, and then you hold on to it. You hold that position, and holding that position is a repetitious process. Talking to investors is not easy. You're going to talk to investors four or five times each over the course of six months, whether you're in the public space or the private space, and you have to have that durability and stamina to
do it. It's very, very tiring, but it takes that conviction and courage to take your endpoint, whether it's a clinical endpoint or a biomarker endpoint, and present it in such a way. Words matter, right. Your presentations, your slides have to be clear, your presentations, your press releases have to be clear, and then announce on it because you believe in you know what, never argue with yourself. You have to believe in what you're doing and you have to say it in that way.
Well, what a brilliant note to enfluentchion. So I'd love to thank Jen, John and Scolt for your expertise and insights.
We hope you enjoyed the podcast. For more information about the CMO submit three sixty editorials, podcasts, or webcasts, please visit CMO three sixty dot org. Thanks for listening.