John Simboli
Welcome to BioBoss, Haseeb.
Haseeb Ahmad
Thanks, John. It's great to be here.
John Simboli
How did you come to be the CEO at Purespring?
Haseeb Ahmad
I think, like with most people, there's a professional and there's a personal. Personally, just a bit of kind of background in terms of my origin story. I grew up in the northwest of England in a city called Liverpool. It's a port town. It's a real melting pot of a place. Both of my parents were immigrants, which was an important part of my upbringing. But what they also were were they were both physicians. So my mother was a primary care physician, a GP, in inner city Liverpool, and my father was a hospital physician. So grew up around healthcare. Always really passionate about community, trying to make a positive impact in the world, and then professionally I joined the pharma industry, worked for some really large companies, blue chip companies like Merck and Co,, MSD outside of the U.S. Schering-Plough, and more recently Novartis.
Haseeb Ahmad
And if I look at the last sort of five or six years, there's a few things that kind of professionally and personally brought together this Purespring opportunity. So professionally, I led Novartis's gene therapies unit. So I have an interest in gene therapies. Also, about five or six years ago, I was responsible for commercial input to portfolio strategy at Novartis. I led a team and was one of the sponsors to say we should get into renal disease because there's untapped clinical potential in renal disease. And I guess more personally, my late father, now, so my father passed away about four years ago, was a pioneering nephrologist. So he was a renal physician, passed away about four years ago, invented one of the world's first portable dialysis machines. And through this professional and personal journey, really in the last four or five years, I think as most people get to in middle. their middle years, as you get to this stage in your work and personal life, I think you really start asking the questions around kind of what am I really passionate about, where do I want to make an impact? You start thinking about, like, grandiose terms like legacy. When I say legacy, you know what I want my kids, my grand, I don't have grandkids yet, but what would I want them in the future to think about? And there's definitely something around me wanting to kind of inspire the next generation of Ahmad's, if you like,. But also follow with some areas that I'm passionate about. There's gene therapies, there's renal disease. Clearly, I've been in biopharma for quite a while, and here I am. It's almost if I could have designed a company and a role, it would have been this. There's also obviously the move into biotech as well, which is wanting to have a closer proximity to impact and being closer to patients.
John Simboli
Having two physicians in your family, and of some note, did that make you think that you wanted to be a physician, and if so, if you followed that, how did you make that transition to being a leader of a biopharma company?
Haseeb Ahmad
The answer is yes and no. And the yes part of it is, you know, as a young kid, I used to, I was thinking like you know when I was like say six or seven years of age, around Christmas time, sometimes in the vacations, my father would take my brother and I into the hospital, and we'd walk around, and I'd see him walking the wards, speaking to the patients and the nurses, and I was really attracted to medicine in that respect. But I learned later on that what I was attracted to wasn't medicine per se. The other yes part of it is my mother, who was a GP, was very much in terms of academia, medicine being kind of the route to, as immigrants, the route to a successful career was very much more pro me studying medicine. My father was very much more from the school of do something you're passionate about, do something that you enjoy. And when I decoded it, what I understood from watching my parents' careers is what attracted me to medicine is the fact it's a force for good in the world. This is something that improves people's lives at a micro level, at a macro level in terms of their broader nuclear families. It can bring joy and happiness to people's lives, and what I was attracted to from my father, I mean, he invented one of the world's first portable dialysis machines, a needle that's used in hemodialysis called the Ahmad needle. I think it was the leadership aspect of what he did. You know, seeing him walking around and the positive impact he had on colleagues, people who were more junior to him. He used to have, I remember, like there's a stream of, like, physicians that used to come through the house, he used to mentor. All of that side of what he did really fascinated me.
Haseeb Ahmad
Nephrology is something in the last five or six years that's really raised its head in terms of its importance. Until actually, I've been in the industry now just over 25 years. I'd never worked in renal disease until I joined PureSpring. I had worked on the periphery, so I was at Novartis when we made the decision to enter renal as a therapy area, and was a big sponsor at Novartis to say we should do that. But I think it was with my father passing away that I probably lent a lot more into it. It was only really-I mean, I knew that he'd had certain inventions, but after he'd passed away. I remember once, you know, I put a post on LinkedIn and mentioned that he had invented this portable dialysis machine. And you know, someone on LinkedIn sent me a message telling me that in the 1980s, she went . . . her father had renal disease, and she went on holiday for a first family holiday because of this kidney machine that my dad had developed, which is called I think the Renalaid 1000. That had a huge impact on me. And obviously, you know, unfortunately for these situations. I met people at my father's funeral, and the kind of the wake or the event afterwards were, yeah, people shared with me the impact that he had on them.
John Simboli
And then prior to that, perhaps in academia was there anyone whose influence, in addition to your father, anyone whose influence opened your eyes to the satisfaction you might find in the business world, in inleadership roles?
Haseeb Ahmad
There's two people that stand out. One is a an academic and a management theorist, which was Peter Drucker. So I studied business, and he had great framing for how we would phrase certain topics. So one of the phrases he always used is that profits are like oxygen, essential for life, but not the reason for living. And that really worked for me on so many different levels because, as a part of it, recognizing that within the you know the ecosystem within which we live, regardless of where you're on the political spectrum, we're all investors to some degree. If you've got a pension fund or you're an investor, you need certain industries to be successful, and this is one of those industries. And there's nothing wrong with business success and commercial success. But the, whilst profits are essential, but not the reason for living, that bit really kind of piqued my curiosity in terms of that really helped me to lean into what is my reason for living. I don't just want to work in banking or finance. I want to work in a sector of the industry that is a force for good in the world, and that's what kind of got me into the healthcare part. So that was a bit on the academia side. The other was one of my earliest bosses was a gentleman called Gordon Couttes, at a company called Schering-Plough, early in my career, had a really profound impact on me. He was a physician by training, who would then become a senior pharma executive, and he also had this phrase: "Good medicine is good business." And those two things kind of are two things that I really subscribe to.
John Simboli
I know from my research, you've had very senior positions in large pharma companies. Did you anticipate, in certain parts of your career, did you anticipate higher and higher levels of responsibility, but staying within that general framework of big pharma, or did you have an inkling at some point along the way,I might find myself being the CEO of a biopharma company?
Haseeb Ahmad
I think I've only ever really thought one or two levels ahead. When I was at university because of my personal background, I actually decided when I was about 17 or 18 that I wanted to work in marketing in the biopharma industry. So my dream was to be a brand manager,. And then I think by the time I was 25, I was a brand manager. Then I wanted to be like a business unit director. Then once I got to that, I wanted to be a managing director, you know, running an affiliate company. So I think I've only ever really thought two or three steps ahead, which may surprise people who know me because, particularly early in my career, I think people really saw me as someone very competitive, very driven, very focused on career. But there was also a part that I actually just also wanted to be bloody good at what I did. So I wasn't always necessarily looking that far ahead. I just wanted to be really good at what I did and have the credentials to get the next job or two.
Haseeb Ahmad
The bit about becoming the CEO of a biopharma company, I think, really came in the last 10 or so years. You know, I've obviously aged myself already, as I, you know, in the third in your 30s in particularrI was just very much focused on getting on a career trajectory, all the responsibilities I had in terms of financial responsibilities and getting on the housing ladder, starting a family, all of those kind of things are very much there. It was only really when I got to my 40s I was able to raise my head slightly above the parapet and say, okay, yeah, now I've got a level of well, I have a certain trajectory and a certain level of, I guess you could call it financial independence or stability. If I'm really liberated from just having to put my children through the school and you know pay for my mortgage and all the rest of it. What do I really want to do? And I'd say I would say it's in the last 10 years I've started thinking about it. But the real catalyst, and I don't want to make this all about my father, but clearly he was a very important person in my life. Losing what was not just my father, but a really important role. And I get to reflect on the impact that he had on me was probably the catalyst I needed to make the jump.
John Simboli
How does one take the stability that comes with the acumen you have from having been in a large pharma company, and that decide I'm going to try something that I think I understand, but maybe I do, and maybe I don't. How do you find that courage, for lack of a better word?
Haseeb Ahmad
I had multiple handbrakes. I think holding me back throughout my career. So one is, and it's a blessing as well. Early in my career, I had a lot of responsibility. I got married young. I started a family young. Wanted to get on the housing ladder. All those things are responsibilities that make you somewhat risk averse. One of the other handbrakes, and it's the shadow side of the blessing I had from my parents, is they were immigrants to the UK. They were, not just from their name, but visibly they were immigrants in the UK, and their medical degrees were almost their kind of route out of probably would have been a much tougher life for them as immigrants in the late in the 1970s, early 1980s in the UK. So in some ways they were quite risk averse when it came to giving me guidance on my career. And one of the other I don't know this is a handbrake, but it was more and more a drive on my side. I think children of immigrants, you become almost an emblem of success for your parents. So, you know, imagine like the Mercedes badge or a Cadillac badge on the end of the bonnet. You become like that for your parents. Working for a blue chip company made them hugely proud. Earlier in my career, I was elected as president and chairman of the board for the Association of the British Pharmaceutical Industry. That probably made my father prouder than anything. It wasn't even a job; it was a, it was a kind of additional board responsibility outside of work. And I say all of these things because, in many ways, it would have been very, it was very difficult for them. Would be very difficult for them to accept that I made this move. And it is curious, and I haven't really rationalized it. It is curious that I made the change after my dad passed away. And part of that is probably me rationalizing it and saying, "Oh well, it's because I managed to reflect on my father's impact, his legacy, and this passion I have for nephrology, bringing medicines to patients and impact. Part of it might have been for the first time I didn't have someone I had to that could still tell me off at the age of 48 or 49 that you're nuts and you shouldn't do it. So multiple dimensions, I think, in terms of the answer to that question, John.
John Simboli
How did you choose Purespring to be the place where you wanted to be the CEO, of all the places you may have chosen with your background? I'm sure you had many different people interested in talking with you, and you probably researched lots. How did you choose Purespring?
Haseeb Ahmad
The choice felt very natural, and it was quite an organic process. But as I reflect back, one of the things I think I've learned on my journey, and I've worked for some very large companies, is that large companies always go through this process of maybe they have relatively tight focus. So I'll just give you kind of just to give you a sense. Most mid to large pharma companies will probably operate in five or six different disease or therapy areas: oncology, cardiovascular, neuroscience, for example. You know, so on and so forth, and then normally within each of those therapy areas, they'll be pursuing five or six indications, and that's actually for a large biopharmaceutical that could be relatively focused. And then what tends to happen over time is they then grow and become more and more diversified because they want to spread risk or spread opportunity. They want more shots on goal. And then they realize as they've got diversified, is that they've lost focus, and then they come back again to a core. And there's this kind of accordion-like kind of movement that happens in companies over like three to five-year periods. But what I've learned, particularly as I've got more and more senior roles, is that impact and success and probability of success is directly related to focus. So if you focus on one disease area or one indication, your probability of success, of technical success, because you've got researchers who've worked with exactly that cell type, they understand the biology, therefore they're going to decide the preclinical studies in the right way. It's going to raise your chances of success when you get into clinical trials., you'll have statisticians who've worked in those disease areas, so they'll help you to design the trials or power the trials in the right way, so on and so forth, all the way through regulatory and medical affairs and commercialization. If you're calling on physicians with a cardiovascular, probably bring another one. You're more likely for it to be successful. So focus is very important. That's just one thing that, as I was looking at which companies do I want to move into, that was a key point. When I started looking at different biotechs, there were some that you know maybe they focused on a couple of different disease areas, and sometimes with different modalities. What I really liked about Purespring is, it is only,we're only focused in renal disease. Specifically, we're focused in glomerular disease, and within that, we're very specifically focused on just delivering genetic therapies directly to a particular cell type, the podocytes. And that really tight scientific thesis is what really attracted me because I think if I want to have impact, and part of the reason I've come here is that I want to see something through to fruition. That level of focus and specificity is what kind of stacks the cards in your favor.
John Simboli
It makes sense to me that as one focuses more and more tightly, one increases the potential or the likelihood of reaching the technical success. The other side of that, I think, the question I would ask would be, gene therapy is high risk, high reward in general. Each case is different, right? But the potential to change the way medicine is done is enormous through gene therapy. The difficulties in getting approvals are perhaps the barriers have traditionally been higher than in other disciplines, other modalities. So, how did you navigate that question about gene therapy?
Haseeb Ahmad
We've learned a lot about gene therapies, particularly in the last five or six years. What's highly differentiated about what Purespring is doing, which has taken a lot of learnings, I think, from other gene therapies, is we're a precision nephrology company. We're focused on local delivery of gene therapies directly to the kidney. Most of the headwinds and some of the concerns that people have seen on the safety side with gene therapies have been with systemic gene therapies. We're not delivering systemically; we're delivering locally, 2 to to 5% of the dose for our lead program are that of a systemic gene therapy, which means we can really optimize for efficacy. So, to a large extent, we've de-risked on the safety side. Most of the challenge with gene therapies is less about target risk because if there's a patient who has a missing or a faulty gene, or there's you know experiencing these genetic mutations. If you can deliver a working copy of a gene, you can. If it's in a monogenetic condition, you can solve the disease. Most of the risk is actually in can you actually deliver enough of it safely? One of the nice things about our platform, the GlomThera platform, is that through local administration, specific podocyte promoters and enhancers, and the platform that we've developed, we feel really good that we've managed to de-risk delivery of gene therapy within renal disease. So I've taken, I think, a lot of the learnings that I've taken from my previous company as I've looked through different companies, put it through the various different filters, and yeah, what we're doing is it's very unique, you know. I think when people talk about gene therapies, they get kind of lump them into this kind of, there's this kind of broad umbrella of gene therapies, but not all gene therapies are the same. You know, there's a big difference between a systemic gene therapy and a locally administered low-dose gene therapy.
John Simboli
What do people think you do, and then how do you tell them what you actually do? Because it's possible to picture someone at at a large pharma company having a nice corner office with windows and giving direction to people. It's a little harder to picture what the head of a biopharma company does each day. Can you give me a couple of examples? I mean, I know it's different every day.
Haseeb Ahmad
One of the greatest achievements of society is that since the Second World War, life expectancy has increased from mid 60s to early 80s. We've increased 17 years worth of life since the Second World War in one generation. So much so that I never met either of my grandfathers, but my kids met both of their grandparents, grandmothers, grandfathers, and there's lots of empirical evidence that demonstrates that life expectancy increase, 50% of that is down to better sanitation, better diet, exercise, but the rest of it is exclusively down to medicines and vaccines. So to work in an industry that is, I think, the biggest single contribution to humanity is something I'm hugely proud of, and that's what we do. I don't start with the answer that you see on slogans. Every company, every biopharma company, within their mission or purpose statement, which I need to honor because it's very true, is all about improving and extending lives. But when you really zoom out and look at the collective impact of this industry, how successful they've been at improving and saving lives-it's-it's mind-blowing. And then you know I go even further into it, you know, particularly with the parents that I had, one of the nice things about, with my mother being a community physician, walking around with her around the, you know inner city Liverpool, she'd bump into patients, family of patients. You could see the individual impact you have on individuals and their families. So that's just kind of what we do as an industry.
Haseeb Ahmad
In terms of what I do today, it's really variable. There's aspects of the job where, as a CEO, I mean, ultimately everything is about leading, aligning, and enabling people. There's aspects of the job that take me back to early in my career in big pharma, where I have to roll my sleeves up and write my own slides, draft my own emails, frame them in the right way, which might sound a little bit strange for people to listen to, but the people in big pharma companies that don't write their own emails, by the way, senior executives. But so there's aspects of the job where which take me back to my early 20s as a single contributor, just rolling our sleeves up, getting stuff done, sitting with maybe my assistant discussing the next staff social, hugely important stuff because it's all about the cultural fabric of the organization, the environment that you create to make sure that really smart people can get stuff done. At the other end of the spectrum, there are aspects of the role which are just like any CEO role of any scale of organization, where I have a very sophisticated board, and I have to make sure that not just within the board meetings, but outside of the board meetings, that they're aligned, they're getting the information that they need, and particularly those investor board members, so that they can satisfy, they have investors as well, so there's a whole kind of continuum of stakeholders that you have to align with, and then obviously future investors. There's a whole ecosystem of people that you have to effectively be keeping them updated on what you're doing, and also interested and curious into kind of what the future is going to be, and make sure they maintain their level of interest and focus on the company.
John Simboli
How much of your time and a day to day, I know it varies, goes into the storytelling part, which is related to the making sure that the oxygen is there. And and how much of it is the science, and how much of it is leading the team. How do you how do you balance that out?
Haseeb Ahmad
I mean, firstly, you could never balance it out over a day or even a week. But if I was to balance it out over a year and take a shot at answering that question, if I just chose those three dimensions-storytelling, slash selling, managing the organisation-and the third one was the science, focusing on scientific or clinical thesis. Over a year, I would say 40% 50% is managing the organization, the leadership team, making sure we have the right operating rhythm within the organization. There's a buzz within the organization. We're recruiting really smart people, and we're making sure the smartest people can be successful. So that's kind of 40 50% of it, I would say 30% is probably, and this can vary, 30-40% is storytelling, which is everything from existing investors and ensuring they're aligned and they're still kind of on track for the exist, within the existing fundraising round and for future fundraising rounds, future investors, potential strategic partners, so pharma companies that may have an interest in our technology. So 30-40% there, and then I'd say 10-20% is the scientific and clinical aspects of the role. Well, it's probably more because of my phenotype. So it's interesting, you know, you kind of you have to set your team up and actually play to your strengths. That's where that's where more of my strength lies. I'm not a scientist. I'm not a physician. So if I tried to spend more than 10 to 20 percent of the time on the scientific or clinical aspects of the program delivery, I'd probably be sending the organization in the wrong direction. And you know, in most companies, people tend to be quite hierarchical. So that for me that's right. For me, it's about the metaphor I have is on that side of the role. For me, it's like knocking on wood, getting to the point where you can ask the right questions and you have enough intuition to know that if you hear the wrong sound for the answer, that you have to go, you have to keep on knocking.
John Simboli
So when when you are leading your team, let's just focus on the direct reports. Do you think if we were they were sitting in on this conversation and I were to say, what is Haseeb's management approach? How do you think they would answer that?
Haseeb Ahmad
I think what they would say is high support and high challenge, which sounds like a polarity, but I think they would say both of those things and in that order.
John Simboli
So high support is taking away the roadblocks and making sure that they have the tools they need to get the job done. What is high challenge?
Haseeb Ahmad
High challenge is a productive challenge. What it's not is trying to be a smartass, trying to be the smartest person in the room. It's about, really, when I knock on wood, and if I hear the wrong sound, it's about continuing to knock to make sure that I'm stretching their thinking. That I'm prepared to risk a bit of the relationship I've developed with them to get a better outcome and to help them grow and help the company grow, and to have the courage to do that. And because I'm supportive and I care about them and the rest of the team, for them to know that even if I create a little bit of tension in the relationship, that I care enough that I'm going to fix it afterwards as well and put a bit of balm on whatever wounds may get created. Now we don't do that all the time, but it is important that that level of high productive challenge exists within an organization.
John Simboli
When someone asks you who is Purespring Therapeutics, how do you like to answer?
Haseeb Ahmad
PureSpring Therapeutics is a precision nephrology company. What we're doing is very unique. We're delivering genetic therapeutics directly to the kidney to target glomerular disease and to set a whole new standard in terms of efficacy.
John Simboli
Could you tell me about how that is different from the previous approaches and standard of care? Why is this approach that you're following through your platform. Why is it needed, and how does it work?
Haseeb Ahmad
We have a proprietary platform called GlomThera. It's an AAV capsid, which has been developed by us specifically for kidney disease, specifically to target a cell within the glomerulus called the podocyte. The podocyte is a cell within the glomerulus, which has a number of uses, but primarily it's about maintaining correct kidney filtration within the glomerulus and overall glomerular health. So, if the podocyte is not healthy or there is dysfunction within the podocyte, that's how you get kidney disease. So we've developed this proprietary capsid, which has specific promoters and enhancers for the podocyte, and we will load it with a genetic therapy. In this case, a working copy of a gene, and we deliver it locally to the kidney, which again is different and unique. So this is not a systemic gene therapy. So we deliver it locally, and you get uptake into the podocyte, and that gene sits as within a nuclear episome, so it doesn't get integrated into the cell genome, and it produces protein. So we're using the podocyte as a factory for protein production. So that's very different to what anyone else is doing, both in terms of local delivery, but also delivery of genes directly to the glomerus and specifically the podocyte.
Haseeb Ahmad
Why it's needed? For a couple of reasons. Clearly, for monogenic conditions, if you've got a missing or faulty gene, having a platform that can deliver in humans a working copy of a gene to the cell of interest is hugely needed, and potentially, if you identify patients early enough and you treat them early enough, you can have knockout efficacy. Potentially even curative, if you were to, if you could identify a patient before they were even symptomatic with the disease that they have a faulty or missing gene, you can have a completely new standard of efficacy in terms of the impact you can have. But also for non-monogenic conditions, there are conditions such as our lead program is for IgA nephropathy, which is a multi-dimensional disease. There's not just one particular genetic reason why this disease occurs. We've got the opportunity to use the podacyte as a factory for protein production, so we know with that particular program, IgA nephropathy is an inflammatory disease. IgA complexes deposit in the kidney, that creates a inflammatory cascade, which is called complement activation. And what we can do is by delivering a gene that produces a complement factor I, which is a deactivator of complement. We can effectively downregulate that inflammatory cascade within the kidney. That's a very differentiated way to treat immunological condition.
John Simboli
When you tell the story, a variation on what you were just telling me about what distinguishes the Purespring approach, and people understand it. Some will be interested because they have understood it accurately. Some people will not be interested. There are some people who will probably filter it through their own experience and perhaps see it in a different light than you intended, so that's what I'm trying to get at. When people misunderstand the story, is there a pattern of misunderstanding, and then how do you help them get back on track as to what it is you're really after?
Haseeb Ahmad
I think what people get right about Purespring, if you think of their spontaneous response when they hear of Purespring, anywhere. Within the renal, cardio-renal metabolic space, there's pretty good spontaneous awareness of PureSpring and what we're doing. What they get right is that we are a, the modality is a gene therapy, and the disease area focus is nephrology. What they get wrong is the specificity. What they don't understand is that we're a locally administered precision gene therapy approach, where we're delivering low-dose therapeutics directly to the kidney. So we're optimizing for efficacy, and we're de-risking for safety. The other thing they don't have the correct specificity on is that we have this really tight thesis that we know that the majority of kidney dysfunction is created by podocyte dysfunction, but it's a very difficult cell to target and to get therapeutics to. So understanding, we're not just about renal disease, but was specific about glomerular disease and getting targets to the podocyte. That level of specificity is also missing, I think, in terms of people's initial response.
John Simboli
As people understand that, that perhaps course correction, and you help them to understand what it is. Purespring is focused on, how do you talk about your vision for the company in terms of the pipelineHow does the pipeline express your vision for the company?
Haseeb Ahmad
I'll go back to the Peter Drucker quote. In fact, there's two quotes I've shared with you, and I'll share a third. So there's Peter Drucker, which is that profits are like oxygen, essential for life, but not the reason for living. There's Gordon Coutts, a previous boss of mine, he said, "Good medicine is good business." And then, the first company I ever worked for was Merck & Co. George Merck in the 1950s, at an investor event, was once asked about, h"e's been challenged about the, I think, the net margin performance that particular quarter, and I'm paraphrasing now, but he says something along the lines of, "We must remember that medicines are not solely for profits; they're for patients, and the better we remember them, the more profitable that we are." So all these three phrases say a couple of things: you've got to have huge impact for patients, but you've also got to, if you're going to build a business, have big ambition in terms of commercial success and viability. And in terms of our ambition, I obviously come from a commercial background as well. We are targeting indications are going to have a huge patient impact in terms of the size of populations we can get after, the fact that they're going after true clinical unmet need, but they're also all indications that have true, clear, unambiguous commercial potential that you can build successful companies on the back of.
John Simboli
When you do allow yourself to think, you know, if this succeeds in the way that I hope it will, either the short-term view or the longer-term view, or both. If it succeeds the way I hope it will, what will it mean for a patient who doesn't have those, you know, those opportunities now? How will it affect their life?
Haseeb Ahmad
So let me start with Ig nephropathy. So Ig nephropathy is a disease area where, up until a couple of years ago, there really had been no innovation and no licensed treatments. Patients were just on supportive care, and they were really staring down the barrel of typically from diagnosis to dialysis, 10 years, and eventually basically looking at dialysis and then eventually a transplant. What's come through now, and typically patients with Ig nephropathy, when they get diagnosed, they will have a level of proteinuria. So you're probably familiar in many other diseases like hyperlipidemia, you have an LDL cholesterol level in diabetes. You have an HbA1c level. In nephrology and renal disease, people are very focused on how much proteinuria have you got. So typically, a patient would be diagnosed and they'd have, let's say, typically one and a half grams per day of protein in the urine. Normal levels for you and I, is zero grants today. So there's a new wave of therapies that are now coming through the markets. So majority of them are called APRILLS, APRILL/BAFF therapies, which are demonstrating they can achieve a 40 to 50 percent reduction in proteinuria. That's a significant improvement versus what existed previously with supportive care, maybe you'd be getting low single digit, maybe early double digit percentage reductions in protenuria. So these are it's really exciting. These treatments are coming through.
Haseeb Ahmad
But the international guidelines, as there are in other diseases in renal diseases, they call the KDIGO guidelines for Ig natropathy say. You should aspire to get below 0.3 grams per day of proteinuria,, and at the very least 0.5. So it's very clear that there's many patients who, even with these new treatments coming through, aren't going to get to target with existing therapies. So there's a patient population that these treatments, these B cell depleters that are coming through, they're all injectable, so it's once weekly, once monthly injections. And ultimately, what they're doing is they're just delaying the time to dialysis. What's highly differentiated approach that we're taking is rather than the B cell therapies, which are targeting the upstream part of the disease, which is preventing the production of these IgA complexes, which eventually get deposited and create the inflammation, what we're focused on is, irrespective of whether that gets created or not, we'll make sure that we can deactivate complement and stop the inflammatory cascades. We have a different approach in terms of mode of action,.
Haseeb Ahmad
Where we're also very different, there is a complement inhibitor on the market right now, which is an oral therapy. It's twice a day, and therefore, by definition, as an oral therapy, it's systemic. We're only locally active, so based on our preclinical package and the bio distribution data, the FDA have said and the EMA have said in our studies, you don't need to be vaccinated, so you don't have the, you don't have the kind of the, risk of infection you get with systemic complement inhibitors. It's also a one and done therapy. So the podocyte is a terminally differentiated cell. What that means is it doesn't turn over. Therefore, if you can deliver a therapy to that cell, there's the premise of durable efficacy, which goes to the one and done approach. So what this does, you know, if you're a patient, you know, if you go forward 5, 6, 7,years, you know, if a product like this is on the market and you're sitting with a physician, you would hopefully, and the clinical data has to play out, but hopefully you would be sitting there and you'd be saying there's these different medicines. There's this one which gives you this level of efficacy, and it's a once weekly or it's a once monthly injection you'll be taking for a number of decades. There's this one which shows a comparable or potentially even better level of efficacy. Targeted therapy, works locally, and it's a one and done approach. And if you're in your 40s or 50s, or no, sorry, many of these patients are in their 20s and 30s. You know, your big concern is that you're staring down the barrel of dialysis and going in and out of hospital. Even having to inject yourself weekly or monthly is not something patients want.
Haseeb Ahmad
So, primarily from an efficacy perspective, but also in terms of, you know, patient preference., this kind of, this is a very unique and differentiated approach. And I think will, these are people you know if you're in your 20s and 30s, goes back to something we were discussing before about starting your careers. The rate of unemployment amongst people who are on dialysis is greater than 50% So to get access to a treatment which effectively could potentially put you into clinical remission without daily, weekly, monthly treatment is, I think, really exciting for patients. It means that they can just enjoy what many of us take for granted, which is just like everyday life. So that's our gene nephropathy.
Haseeb Ahmad
Alport syndrome. Alport syndrome is alongside ADPKD is the largest genetic kidney disease that we know. There are no licensed treatments available. Typically, it will affect kids late childhood, where they'll start seeing some protein and blood in their urine, they can progress into their early 20s to get to be in kidney failure. This is a monogenic condition. Typically, it's a function of one of three genes is mutating, is faulty, and if you can replace that gene, you can have a transformative impact on those patients.
John Simboli
Haseeb, thanks for speaking with me today.
Haseeb Ahmad
Thank you, John. It's great to spend time with you.
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John Simboli
As a second generation American, I’m attuned to Haseeb Ahmad’s story about his parents’ life as immigrants in the UK, and how their achievements as physicians in Liverpool in the 1970s helped shape Haseeb’s life. It must have taken courage, and self-awareness, for Haseeb to choose the world of business management, rather than the practice of medicine—though his advance through the ranks of blue-chip pharmaceutical companies did form a connection back to his parents’ education and contribution to their community.
The managerial skills Haseeb honed at big pharma companies seem to have translated directly to his leadership approach at Purespring Therapeutics—his understanding that success is correlated with focus, and that CEOs play to their strength when they create an environment where really smart people can get stuff done.
Haseeb built on this idea of high support for his team, by sharing the mirror image of leadership—high challenge. In the words of Haseeb, he “knocks on wood,” and listens for the returning sound. If it’s what he expects to hear, he’s confident the team is aligned. If his knock on wood doesn’t produce the anticipated tone, Haseeb continues to knock, with the goal of stretching everyone’s thinking.
It takes courage to challenge in this way. For Haseeb, the result is worth it—a better outcome for the immediate need, for personal growth of his colleague, and to help realize the company’s mission. For people who lead organizations, this kind of “courageous conversation,” is a worthy test of how to guide the ship. I admire the conviction of biopharma CEOs I’ve known, who seek this balance.
I’m John Simboli. You’re listening to BioBoss.
