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Ankit Mahadevia: CEO of Spero Therapeutics · BioBoss

• 0:05
  Ankit Mahadevia: I really rely on the expertise of the team and I value input.
• 0:09
  Ankit Mahadevia: I also value contradiction.
• 0:12
  John Simboli: That's the voice of Ankit Mahadevia,, President and CEO of Cambridge, Massachusetts based Spero Therapeutics.
• 0:20
  John Simboli: Listen in now to hear my conversation with Ankit and hear his thoughts about leadership in biopharma and building a better future for coping with infectious diseases.
• 0:31
  John Simboli: I'm John Simboli.
• 0:31
  John Simboli: You're listening to BioBoss.
• 0:32
  John Simboli: This afternoon I'm speaking with Ankit Mahadevia, President and CEO of Cambridge based Spero Therapeutics.
• 0:41
  John Simboli: Ankit, welcome to BioBoss.
• 0:44
  Ankit Mahadevia: Thank you.
• 0:45
  Ankit Mahadevia: It's a pleasure to be here.
• 0:46
  John Simboli: Ankit, how did you find yourself at Spero Therapeutics?
• 0:51
  Ankit Mahadevia: Nonlinearly;, sort of did one thing after another and I ended up in a place where it's very exciting.
• 0:57
  Ankit Mahadevia: Going all the way back to university, what I did know was that I wanted to have an impact in health care.
• 1:04
  Ankit Mahadevia: Wasn't sure if that was on the science or clinical side or that was on the policy side.
• 1:08
  Ankit Mahadevia: And so, and you'll notice a theme here.
• 1:10
  Ankit Mahadevia: I ended up doing both.
• 1:11
  Ankit Mahadevia: , I studied both biology and health economics and ultimately took my first job out of university universities.
• 1:17
  Ankit Mahadevia: I did that thinking that I could make a difference in the health policy arena.
• 1:21
  Ankit Mahadevia: So I joined the U S government Accountability Office and that plus a subsequent tour of duty in the Senate Health Education Labor, Pensions Committee really gave me a flavor for that.
• 1:35
  Ankit Mahadevia: And I felt I was making a difference but probably not on the pace that got me excited.
• 1:40
  Ankit Mahadevia: The other thing is, certainly, my patients is more limited than that.
• 1:43
  Ankit Mahadevia: And so ultimately after having that experience I moved on to what every other liberal arts major does when they don't know what to do with their career, which is management consulting.
• 1:53
  Ankit Mahadevia: And it was in that period of time, again, focused in health where I continued to be inspired.
• 1:58
  Ankit Mahadevia: One inspiration was some of the cardiologists we work with as we were trying to get drug eluting stents to the market.
• 2:05
  Ankit Mahadevia: And I was just inspired by the way that they could have a profound impact on a patient's life, on a very personal level, just through a particular intervention.
• 2:12
  Ankit Mahadevia: And like a good Asan, I had done all of my prerequisites for medical school and I really had a hard t hink about.
• 2:20
  Ankit Mahadevia: .
• 2:20
  Ankit Mahadevia: .
• 2:20
  Ankit Mahadevia: because, really, for based on where I was in my career at t hat time it was now or never.
• 2:25
  Ankit Mahadevia: And I decided it would be now and I decided to train and I ended up at Johns Hopkins.
• 2:29
  Ankit Mahadevia: But I didn't stop there in terms of parallel processing.
• 2:33
  Ankit Mahadevia: I took a very long and circuitous route through Hopkins, maybe set a record when I was there.
• 2:39
  Ankit Mahadevia: But along with doing my medical training, I went back to Capitol Hill.
• 2:43
  Ankit Mahadevia: I went to McKinsey.
• 2:44
  Ankit Mahadevia: I went to Wharton Business school to get my MBA and then after that was at Genentech and learned how to do business development from the excellent team there.
• 2:55
  Ankit Mahadevia: And after all of those adventures, trying to figure out how I could make a difference in health care, my dean called me and said, look, what are you g oing t o do?
• 3:02
  Ankit Mahadevia: Are you coming back o r a re y ou not?
• 3:03
  Ankit Mahadevia: Because I have folks that want your spot.
• 3:05
  Ankit Mahadevia: So I said, fine, I'm coming back and I'm going to go back.
• 3:08
  Ankit Mahadevia: So I did the rest of my training and it set my sights on being an ophthalmologist because again, it allowed me not to choose.
• 3:15
  Ankit Mahadevia: I could be the eyes surgeon, I can be the eyes physician, I can be the eyes oncologist.
• 3:20
  Ankit Mahadevia: And that was fascinating to me.
• 3:22
  Ankit Mahadevia: But before that I got waylaid by a colleague who was as multi-interested as me, happened to be an entrepreneur as well as the Chair of the Hopkins pain service and was a guy named Jim Campbell who had got funding to start a neuropathic pain company across the street from my apartment in downtown Baltimore.
• 3:40
  Ankit Mahadevia: I had just gotten married at the time and the fact that he was giving me a salary was quite attractive as I was paying off wedding bills.
• 3:50
  Ankit Mahadevia: And so that plus the curiosity of something new motivated me to jump in and help him start the business.
• 3:56
  Ankit Mahadevia: And I got a flavor for starting companies that I've come back to later.
• 4:01
  Ankit Mahadevia: And so after I'd done that, I was ready to begin my future training and got connected with the team at Atlas Venture.
• 4:08
  Ankit Mahadevia: And Atlas was shifting their model from more traditional VC investing to company formation.
• 4:14
  Ankit Mahadevia: And the idea of building something was new and exciting and appealed to me.
• 4:18
  Ankit Mahadevia: Also, my wife and I were ready to see something new after having been in Baltimore for a while.
• 4:22
  Ankit Mahadevia: And so what I thought was going to be a 12-month tour of duty, is now an affiliation that's gone on for over 12 years.
• 4:30
  Ankit Mahadevia: And in that time, the teams that I've worked with have built nine companies,.
• 4:38
  Ankit Mahadevia: Four have gone on to sell to partners and three went public.
• 4:45
  Ankit Mahadevia: And in 2016, I certainly had really enjoyed building companies, but I found that the hardest thing in terms of the process was letting go just as the company was really hitting escape velocity.
• 4:59
  Ankit Mahadevia: And so I decided as we were getting three off of the ground around 2013 to 2015 timeframe that I would pick one and just see what that e scape velocity would feel like.
• 5:09
  Ankit Mahadevia: And so I s ort o f went through this process of trying to assess what would be the best place for me to go.
• 5:14
  Ankit Mahadevia: And ultimately I chose Spero.
• 5:16
  Ankit Mahadevia: And in terms of why, I mean there's both an emotional and a rational component to it.
• 5:20
  Ankit Mahadevia: The rational one is that it was unique in that, rather than sort of starting with a platform technology where you try to apply it to patients, it was a wide world basically.
• 5:31
  Ankit Mahadevia: The thesis was we think infectious disease is underserved.
• 5:37
  Ankit Mahadevia: There's some great products out there that need development and the world's our oyster.
• 5:42
  Ankit Mahadevia: Go forth and find what you can.
• 5:43
  Ankit Mahadevia: And that freedom to build in an arena that really matters, mattered a lot to me.
• 5:49
  Ankit Mahadevia: And going back to medical training, c ertainly cardiology was, interventional cardiology was one place, but surgery and ophthalmology and infectious disease all a ppealed for me for the same reason, which is that in a very short time you can change a patient's life.
• 6:04
  Ankit Mahadevia: As an ophthalmologist, if you take out a cataract, t he patient goes from being blind to sighted.
• 6:09
  Ankit Mahadevia: And in the setting of infectious d isease, if you find the right antibiotic, the patient goes from being intubated to having breakfast with their kids in a matter of days and sometimes even hours.
• 6:20
  Ankit Mahadevia: And so to me that was exciting and also a large opportunity to go where others haven't gone before and create a lot of value.
• 6:29
  Ankit Mahadevia: Emotionally, for me it was also sort of, I liken building companies to making chili.
• 6:35
  Ankit Mahadevia: You start with good ingredients, you make them in sort of a similar fashion and depending on the day and where you got the ingredients from, they taste all good but different.
• 6:46
  Ankit Mahadevia: And somehow I just kept coming back to this bowl of chili and I credit it to the Board that we built and the teammates that we have, many of whom were there at around the time I was trying to figure this out and they're still with us today.
• 6:59
  Ankit Mahadevia: And it's been a really exciting journey.
• 7:02
  John Simboli: When you made that decision to be a CEO, did that feel like a natural decision after it was made?
• 7:08
  Ankit Mahadevia: I wasn't sitting, when I was 10 years old, thinking I was going to be a CEO.
• 7:12
  Ankit Mahadevia: We didn't have any physicians in the family, but I was always interested in medical science.
• 7:19
  Ankit Mahadevia: I always thought I was going to be a physician back then.
• 7:22
  Ankit Mahadevia: But ultimately, the things that appealed to me, both the science but also working with others and the idea of building something bigger than yourself, and just building, period really suit me.
• 7:34
  Ankit Mahadevia: And ultimately to me that is the job, which is to build a set of operational understanding, values, culture and belief in the mission that sustains an organization.
• 7:46
  Ankit Mahadevia: And the joy is doing that and then watching the whole become greater than the sum of the parts.
• 7:52
  Ankit Mahadevia: So that's intoxicating.
• 7:54
  Ankit Mahadevia: And I can't say John, that I had any foresight into this, but as I did it because it's what the companies needed, it really grew on me and there was sort of a both for this and in other companies where I've been operationally involved, you sort of start to realize this is probably what I ought to be doing.
• 8:14
  John Simboli: Of all the choices that you had, of all the different things you are alert to, all the possibilities.
• 8:20
  John Simboli: How was it you decided, I think I want to build this thing at Spero, as opposed to maybe go to a bigger, more established company or create something different?
• 8:30
  Ankit Mahadevia: I'll give you a lot of rational reasons why that was the case.
• 8:33
  Ankit Mahadevia: But there's just something that drew me to this place really.
• 8:35
  Ankit Mahadevia: Both the people as well as the breadth of the mission and the opportunity to take a blank sheet of paper.
• 8:44
  Ankit Mahadevia: I think historically, as we build companies, we often take a technology and identify ways to apply to patients.
• 8:51
  Ankit Mahadevia: Here we start with unmet need and it's really, find whatever need to be able to build a comprehensive approach to that unmet need.
• 8:59
  Ankit Mahadevia: And frankly, there's just a part of me that likes going in places that may be a little less well-traveled.
• 9:05
  Ankit Mahadevia: When I take the kids to their school carnivals and celebrations, I go where the lines aren't.
• 9:14
  Ankit Mahadevia: That appeals to me, as well, just because I think that infectious disease is so broad.
• 9:23
  Ankit Mahadevia: It touches everything.
• 9:25
  Ankit Mahadevia: There's such good medicines that you can learn about early.
• 9:27
  Ankit Mahadevia: And I think that it's been some time since we've had a comprehensive approach to treating the threat of infectious disease.
• 9:37
  Ankit Mahadevia: And it's not that we weren't inspired ahead of the current crisis that our country is facing, but now more than ever, it feels like absolutely what we should be doing in service of what the public health needs.
• 9:51
  John Simboli: I think our listeners are always curious, what is it that a CEO does during the day?
• 9:55
  John Simboli: And I know the easy answer to that is, it depends what day, but tell me what's it like to be a CEO of a biopharma company?
• 10:01
  Ankit Mahadevia: It's the most fun that I've ever had.
• 10:03
  Ankit Mahadevia: Like you say, every day is different.
• 10:07
  Ankit Mahadevia: On the one hand, one may be thinking about the supply chain issues in Asia.
• 10:14
  Ankit Mahadevia: One may be thinking about the statistical analysis of a particular clinical trial or thinking about interviewing ad agencies for a potential drug launch.
• 10:22
  Ankit Mahadevia: And so the variety of one's diet is intoxicating depending on how you're wired.
• 10:27
  Ankit Mahadevia: And I really do like that variety.
• 10:29
  Ankit Mahadevia: I think that the job speaks to—and we had an opportunity to write about this as well—if one is delegating effectively, there's really three things that a CEO does.
• 10:39
  Ankit Mahadevia: One is Motivator in Chief.
• 10:44
  Ankit Mahadevia: And that's setting a culture and values and ensuring that all decisions that are made stay true to those.
• 10:51
  Ankit Mahadevia: A second is Focuser in Chief.
• 10:54
  Ankit Mahadevia: And that's setting the strategy that's in service of the mission and those values.
• 11:00
  Ankit Mahadevia: And then finally is what we like to call Balancer in Chief, which is making those tough calls only a CEO can make that balance benefits and costs at an enterprise level because the CEO is uniquely positioned across all of the functions and disciplines to make those calls.
• 11:18
  Ankit Mahadevia: And sometimes those calls are big enough that, ultimately for every call, the CEO's accountable, but in some one needs to be directly hands on.
• 11:26
  Ankit Mahadevia: But that's it.
• 11:27
  Ankit Mahadevia: If you're doing more, it's our opinion that you're probably not delegating effectively.
• 11:32
  John Simboli: 've heard it also described as a Chief Education Officer.
• 11:36
  Ankit Mahadevia: That's a good point, John.
• 11:41
  Ankit Mahadevia: You asked me how I decided to take this line of work, there's also an element in my experience that both from, as much education as we've been through as well prior careers, in college I was training to be a teacher.
• 12:01
  Ankit Mahadevia: I was a graduate assistant in business school.
• 12:05
  Ankit Mahadevia: There's an element of, as you note, teaching that really permeates the culture at Spero, not just with me, but also more broadly.
• 12:12
  Ankit Mahadevia: I think people really have a joy of sharing what they know and ensuring that folk both incorporate that and are enabled to do it..
• 12:20
  Ankit Mahadevia: And I think that that's an energizing part of the job whereby, something that you or a colleague may have thought was important sort becomes part of the DNA of the organization a nd you see that gene expression everywhere.
• 12:34
  Ankit Mahadevia: That's great.
• 12:36
  John Simboli: That makes me think of management style.
• 12:37
  John Simboli: Different people find the different ways of working with people, work for them, not for somebody else.
• 12:43
  John Simboli: How would you describe what works for you as far as a management style?
• 12:46
  Ankit Mahadevia: It's keeping with the culture we built.
• 12:48
  Ankit Mahadevia: It's very collaborative.
• 12:50
  Ankit Mahadevia: We have a couple of sayings at Spero that sort of permeate our values.
• 12:56
  Ankit Mahadevia: One is be the expert.
• 13:00
  Ankit Mahadevia: The way that we like to run our teams collectively, and that includes me is, really building upon the expertise of each individual team member.
• 13:12
  Ankit Mahadevia: Certainly in a small company it's true that any expertise you bring in is typically the foremost expert in your company in that, as you grow that starts to be less the case, but certainly, during t his stage.
• 13:24
  Ankit Mahadevia: And so we have the saying,"Be the expert." No one's going to know more about your discipline than you.
• 13:31
  Ankit Mahadevia: And so we really build off of that expertise.
• 13:33
  Ankit Mahadevia: Our team certainly in our broader company, generally, has just so much experience in the anti-infective space that we really respect each other's expertise that way.
• 13:44
  Ankit Mahadevia: Secondly is that I'm very fastidious about the involvement I have in the calls that I actually make versus the experts.
• 13:53
  Ankit Mahadevia: My view is that the closer you are to the data, whether that's scientific or market data or otherwise, the better equipped you are to make decisions.
• 14:02
  Ankit Mahadevia: I can certainly be helpful in terms of enterprise context or unconscious biases that might come to play.
• 14:08
  Ankit Mahadevia: But ultimately, if it's a clinical decision, our chief medical officer has decades of experience in, is probably best equipped to make the recommendation.
• 14:17
  Ankit Mahadevia: And that's sort of the statement that we make and maybe your call, but it's my accountability.
• 14:21
  Ankit Mahadevia: So my job is to ensure that we're making the decision with the right unity of motivation and with the right understanding of the goals.
• 14:28
  Ankit Mahadevia: But in terms of, for example, deciding whether our study should be 1,200 patients or 1,300 I'm not that guy.
• 14:34
  Ankit Mahadevia: That's a clinical call.
• 14:36
  Ankit Mahadevia: And the same as it goes with commercial and development and science and finance.
• 14:41
  Ankit Mahadevia: All of those, I really rely on the expertise of the team and I value input.
• 14:45
  Ankit Mahadevia: I also value contradiction.
• 14:47
  Ankit Mahadevia: I'm mindful of the"intimidation" and awe of the office.
• 14:56
  Ankit Mahadevia: Just by having the title CEO can quell dissent and not create a healthy debate.
• 15:02
  Ankit Mahadevia: It's one of my requirements as we add to the team.
• 15:06
  Ankit Mahadevia: I want people to challenge me because if I'm the one that has the best idea in the room, and I'm not the expert, that's probably not the right place to be.
• 15:15
  Ankit Mahadevia: I sort of th ink of it like an art gallery where our ex perts, whether they be—regardless of discipline—are the artists.
• 15:24
  Ankit Mahadevia: My job is to make sure that the lights are on and if they need paint, they should ask me.
• 15:28
  Ankit Mahadevia: If they need canvas, they should ask me.
• 15:31
  Ankit Mahadevia: If they need me to clean the floor, so that they have space to paint, they should ask me.
• 15:36
  Ankit Mahadevia: That's my job, right?
• 15:37
  Ankit Mahadevia: Is to ensure that that's the case.
• 15:40
  Ankit Mahadevia: The other thing I can do for them is tell them what the artist do wn the hall was painting, so they don't paint the same thing.
• 15:46
  Ankit Mahadevia: But that's my job, right?
• 15:48
  Ankit Mahadevia: Really, the beautiful work that we do and ma king medicines comes from them, not from me.
• 15:55
  Ankit Mahadevia: And that's sort of ho w I think about it.
• 15:57
  John Simboli: And I would say also there's probably a tradition among gallery owners that they had a fairly disciplined eye and a fairly acute sense of the work itself.
• 16:07
  John Simboli: So we'll just assume that that's just something you've got as well.
• 16:11
  Ankit Mahadevia: I think that's right, and though, what I would say is that if we've chosen the right team members and delegated well, we have even better trained eyes than me on a specific discipline.
• 16:23
  John Simboli: What's new at Spero Therapeutics?
• 16:25
  Ankit Mahadevia: We have a very exciting program.
• 16:28
  Ankit Mahadevia: It's as exciting a time, as any, at Spero.
• 16:32
  Ankit Mahadevia: So we are developing multiple medicines, treating large unmet needs in infectious disease, all of which are in the clinic and all of which are delivering important results coming forward.
• 16:44
  Ankit Mahadevia: Our lead program is an oral agent called Tebipenem.
• 16:49
  Ankit Mahadevia: It's designed with the potency of IV medicines we use for patients with serious gram negative infections, but available in pill form.
• 16:57
  Ankit Mahadevia: And the fundamental need we're trying to address is that for millions of patients in the U.S.
• 17:03
  Ankit Mahadevia: alone, each year, there are infections that should and could be treated outside of a health care institution that are not, but for the lack of an effective oral therapy,, The entire infectious disease establishment has really pushed to try to drive outpatient treatment of important infections just because of a logistics and patient safety, patient convenience and outcomes perspective.
• 17:29
  Ankit Mahadevia: What's been missing for gram negative infections is an effective tool to do so.
• 17:33
  Ankit Mahadevia: And Tebipenem is in the midst of enrolling its pivotal study for the treatment of complicated urinary tract infections that we expect in the third quarter of this year.
• 17:42
  Ankit Mahadevia: And should we be successful, we'll be in the process of developing a new drug application to get that launched in the market in the U.S.
• 17:49
  Ankit Mahadevia: Now more than ever.
• 17:50
  Ankit Mahadevia: It's incredibly important to acknowledge the frustration that patients and physicians feel when they really shouldn't be treating their patients in the hospital.
• 18:01
  Ankit Mahadevia: Or if you're a patient, you really shouldn't be there, but you have to be.
• 18:05
  Ankit Mahadevia: And I think that the recent events, but also just generally, the capacity constraints and cost implications of treating our patients within the walls of a health care institution, have been laid bare.
• 18:19
  Ankit Mahadevia: We really should be treating as many patients as possible outpatient.
• 18:24
  Ankit Mahadevia: We just need the tools to do it.
• 18:26
  Ankit Mahadevia: Along with that, we have a pipeline of medicines to treat complementary unmet needs.
• 18:30
  Ankit Mahadevia: 720 helps our patients with a really debilitating lung disease called NTM disease that shows up in your shower head.
• 18:39
  Ankit Mahadevia: Most people are able to inhale it and clear it, but some folks, either with anatomic or immunological or other difficulties with their lung can't, and it becomes a slow growing infection that really upends patients entire lives.
• 18:53
  Ankit Mahadevia: And we were lucky to have three very brave women come and share their experience with their disease, and the pain and the discomfort and the side effects of the treatment that she was having moved her to tears.
• 19:04
  Ankit Mahadevia: So we did what we instinctively do, and would just hand her a tissue.
• 19:08
  Ankit Mahadevia: She couldn't even accept the tissue because depending on the tissue, it can exacerbate her symptoms.
• 19:14
  Ankit Mahadevia: So these patients are in a prison made by this mycobacterial infection.
• 19:19
  Ankit Mahadevia: We have an oral agent that can do better than what these patients have.
• 19:22
  Ankit Mahadevia: And then finally, we have an IV medicine that's helping patients with serious infections in the ICU, which where evolution continues to drive worse and worse infections that k ill people and we have an option.
• 19:34
  Ankit Mahadevia: So really what we pride ourselves on at Spero is really being about the mission, which is to provide better options for patients and to build a comprehensive leader in the field.
• 19:46
  Ankit Mahadevia: And as we see these drugs perform in the clinic, it just feels very tangible and real and it's inspiring for us to see what the future holds.
• 19:56
  John Simboli: When you have the opportunity to tell the story, as you've been telling it to me here, sometimes in a really condensed version, sometimes more opportunity, more time, there will be those times when people will come up afterward—and I'm sure they will say,"Oh, thank you, Ankit.
• 20:10
  John Simboli: Now I understand what Spero's about." But you'll think to yourself, based on what they say,"No, that's not what I was intending." Sometimes they will have filters or biases and then your job, sometimes, is to say,"Well, actually it's, let me redirect.
• 20:23
  John Simboli: It's actually this." So when that happens, what do people mis-hear or misunderstand?
• 20:25
  John Simboli: And how do you help them to understand?
• 20:29
  Ankit Mahadevia: So to me, John, the most fundamental misunderstanding about the Spero pipeline is where it's positioned and how that speaks to the growth of both the products and the companies.
• 20:41
  Ankit Mahadevia: I think that there's been much in the lay press, even, about challenges that some specific antibiotic products have had as they move from development to commercialization.
• 20:53
  Ankit Mahadevia: And I think that what's important to understand is that we have built our pipeline with that in mind.
• 20:59
  Ankit Mahadevia: And the fundamental drivers of sustainability, as we look historically at the data,is number one—being positioned outside of the hospital, and I'll go into that in a minute.
• 21:10
  Ankit Mahadevia: And secondly, and this is most important, is going after unmet needs for which there's no generic comparator.
• 21:17
  Ankit Mahadevia: Those two have been the hallmarks of sustainability for infectious disease products, whether that's Cubicin or that's drugs like Sovaldi or drugs lik, as there's emerging, Insmed's Arikayce, and others.
• 21:30
  Ankit Mahadevia: All of those have those elements in common.
• 21:33
  Ankit Mahadevia: And I think that where the headlines really magnify is the challenges we face, particularly, for hospital-based drugs.
• 21:40
  Ankit Mahadevia: So those hospital-based drugs have two particular challenges that our pipeline doesn't share: one is that they're reimbursed in the hospital, which is a fixed payment system.
• 21:51
  Ankit Mahadevia: So essentially a patient admitted with a given diagnosis is reimbursed at a fixed level, no matter how long they stay, no matter what agents are used in their care.
• 22:01
  Ankit Mahadevia: And that really curtails the innovation that can be invested in by the hospital because essentially the more expensive the medication, the more it comes directly out of that hospital's bottom line.
• 22:13
  Ankit Mahadevia: Number two is that a number of these IV-based hospital agents are designed to treat infections that are, still, fortunately for society, relatively rare.
• 22:24
  Ankit Mahadevia: And medicine has evolved to the point where we don't use new agents where old agents could do the trick.
• 22:30
  Ankit Mahadevia: We only use new agents where new agents are necessary and fortunately for society, but unfortunately for these products, there aren't enough of these types of infections that only these medicines can treat to be financially sustainable.
• 22:44
  Ankit Mahadevia: So what we've done, learning from all of that, is we curated our pipeline to focus on large unmet needs.
• 22:50
  Ankit Mahadevia: So the the patients that need new oral agents for cUTI number in the millions, over 2 million, in fact, that's number one.
• 22:58
  Ankit Mahadevia: Number two is we're not reimbursed in that same fixed fee setting.
• 23:03
  Ankit Mahadevia: So what people get wrong is that infectious disease isn't a monolith.
• 23:07
  Ankit Mahadevia: There are different sub-sectors within infectious disease, each with their challenges and opportunities.
• 23:12
  Ankit Mahadevia: And the key to leadership in the field is to focus on those arenas in infectious disease that are synonymous with sustainability and work with partners on those that aren't.
• 23:22
  Ankit Mahadevia: And that has been our philosophy from day one is to build our story on the basis of agents like Tebipenem and 720 that are sustainable and collaborate with folks as wide ranging as Gates, to the department of defense,on agents that aren't, for drugs like for TB or for very rare, serious infections like pseudomonas infections.
• 23:44
  John Simboli: What kind of partners make a good fit to Spero?
• 23:48
  Ankit Mahadevia: So we're fortunate, essentially everything that we built at Spero is partnered.
• 23:52
  Ankit Mahadevia: We partnered to bring it to clinic, our oral carbapenem, Tebipenem, is partnered with a Japanese fi rm t hat initially developed it for a different indication.
• 24:05
  Ankit Mahadevia: Our NTM program comes from Vertex and we're proud to partner with them to advance it, as an example.
• 24:11
  Ankit Mahadevia: Also every program that we advance has a partner.
• 24:16
  Ankit Mahadevia: So our oral carbapenem is partnered with BARDA, which is helping us support the development of this, and in turn, we a re sup porting their vision and building a broad arsenal against future infectious threats.
• 24:28
  Ankit Mahadevia: And our NTM programs part ner wit h the Gates Foundation where we'r e par tnered with them to explore what 720 can do for TB patients in the developing world.
• 24:39
  Ankit Mahadevia: And we're proud to work with them as well, as an example.
• 24:41
  Ankit Mahadevia: And then 206, also partnered with the Department of Defense and with Everest medicines in China.
• 24:47
  Ankit Mahadevia: So we've had a lot of experience both being a partner and partnering.
• 24:52
  Ankit Mahadevia: And what matters for us is folks that fit in with our values.
• 24:56
  Ankit Mahadevia: I think good partners have a fundamental commitment to building a better future for infectious disease.
• 25:05
  Ankit Mahadevia: And so really believing in the power of the medicine and thinking about the broader implications of what we do.
• 25:10
  Ankit Mahadevia: I think second is those that have a strong scientific and commercial understanding of those patients that we're trying to serve, that is incredibly important.
• 25:22
  Ankit Mahadevia: And then thirdly, are those with whom we can collaborate well.
• 25:26
  Ankit Mahadevia: Our model and our style at Spero is very collaborative and we expect, and we have, and we're fortunate to have that type of collaborative relationship with our partners.
• 25:39
  Ankit Mahadevia: And that's what works well.
• 25:40
  Ankit Mahadevia: Developing drugs and medicine, in general, is a nonlinear challenge that we have to face and, in those settings, my strong belief is in a nonlinear setting you need more opinions rather than fewer before you make a decision.
• 25:59
  John Simboli: It sounds like a lot of those qualities that make good partners for you and you a good partner to those companies, it sounds like probably a good number of those characteristics would be also in the kinds of people you're looking to bring on tp your team full time.
• 26:13
  John Simboli: So to that point, what kinds of people thrive at Spero?
• 26:17
  Ankit Mahadevia: The"Sperobes," as we call them—the sort of mix between Spero and microbe—the"Sperobe" that really does well here is mission-driven.
• 26:25
  Ankit Mahadevia: I think that with all of the twists and turns with drug development, if you don't get up in the morning because you can make patients feel better, ultimately, because of your work, you're probably in the wrong business.
• 26:39
  Ankit Mahadevia: And so,, the mission is such a strong driver what we do at Spero, in terms of creating a better future for infectious disease medicine.
• 26:47
  Ankit Mahadevia: So that's one.
• 26:47
  Ankit Mahadevia: I think, secondly is somebody that is humble.
• 26:50
  Ankit Mahadevia: Humility is a major part of our core values at Spero.
• 26:55
  Ankit Mahadevia: And humble means not necessarily sort of self-effacing, but it is having the humility to understand that you may not have the only good ideas in the room and that humility lends itself to collaboration.
• 27:07
  Ankit Mahadevia: It lends itself to intellectual curiosity, and it lends itself to really thinking rigorously through issues at all angles.
• 27:18
  Ankit Mahadevia: Having the humility that your first instinct may not capture everything and ensuring that you are doing it right.
• 27:25
  Ankit Mahadevia: So really these are folks that are curious, humble and believe in a world larger than themselves that they can make a difference in.
• 27:34
  John Simboli: When you're not dealing with the here and now, and the day-to-day, and all the details that require your attention, when you do have that moment from time to time to sit back and recall,"This is why I'm doing this.
• 27:47
  John Simboli: If this company does the things I believe it will do, we're going to really do some good in the world." At what level do you picture that?
• 27:54
  John Simboli: How significant is the potential, do you think, for the work that you're doing?
• 27:59
  Ankit Mahadevia: Well, I think that both in terms of the medicines we are developing and then the sum total of those medicines, the potential for Spero is vast.
• 28:07
  Ankit Mahadevia: Really starting at a macro level, infections touch everything we do.
• 28:15
  Ankit Mahadevia: Every hip replacement, every chemotherapeutic dose, assumes that we have effective control of microbial infection.
• 28:25
  Ankit Mahadevia: And increasingly that is not the case.
• 28:28
  Ankit Mahadevia: So when we think about the vision of Spero, we believe that choosing the right products ultimately positions a company well to be a leader.
• 28:37
  Ankit Mahadevia: And we believe strongly in Tebipenem and the rest of our pipeline's ability to touch many millions of patients' lives and also help us build Spero.
• 28:47
  Ankit Mahadevia: And as we build Spero, we have a vision to become a leader in the field and continue to build the pipeline, both late stage and in early stage over time.
• 28:57
  Ankit Mahadevia: But again, it all starts with the success of the products that we have.
• 29:00
  Ankit Mahadevia: And successful products build a platform to do even more good in the world, both by developing future medicines, but also shaping the infrastructure on infection.
• 29:11
  Ankit Mahadevia: Now more than ever, there's, I think, a realization that we likely haven't done enough in terms of comprehensively addressing the infectious disease needs of society.
• 29:26
  Ankit Mahadevia: I'm confident that we will prevail over coronavirus, specifically, but nature doesn't stop.
• 29:34
  Ankit Mahadevia: It's already cooking up the next infectious threat.
• 29:37
  Ankit Mahadevia: So neither can we.
• 29:38
  Ankit Mahadevia: And I think that the multifaceted impact that infection has had on our society, of late, really invites a reexamination of our priorities and how do we prevent this from happening again.
• 29:52
  Ankit Mahadevia: And so, sort of going back to Spero's mission, we're inspired by really having a platform that can be a large part of that solution.
• 30:01
  Ankit Mahadevia: Ultimately, what's required is sustained expertise on a forward looking basis, continuing to improve what we can deliver to treat patients with infection.
• 30:10
  Ankit Mahadevia: That has been our mission from day one.
• 30:12
  Ankit Mahadevia: And we're committed now more than ever to do it.
• 30:15
  John Simboli: And what's required in terms of long term vision?
• 30:18
  Ankit Mahadevia: Back in the 1950s and 1960s, advances in antibiotic development, in particular, really revolutionized the way that we treat patients in the United States and in the world.
• 30:31
  Ankit Mahadevia: And it's one of the drivers of improvements in overall mortality and society in general.
• 30:38
  Ankit Mahadevia: And I think that spurred several decades of really fruitful research, finding newer and newer ways to treat these infections and over time, in part because the science is sometimes hard, we hit a wall, number one and I think number two is that the infectious disease medicine has an added challenge relative to treating other diseases, which is that one needs to design a drug that can be delivered just as well to a prokaryotic organism, the microbe or virus, while at the same time having good safety, potency and tolerability to be in a human.
• 31:20
  Ankit Mahadevia: And that dual challenge is can be a difficult one.
• 31:25
  Ankit Mahadevia: And so the science can be hard.
• 31:26
  Ankit Mahadevia: I think secondly is that fundamentally, we have not prioritized forward-looking infectious disease, from a policy or r eimbursement perspective.
• 31:37
  Ankit Mahadevia: And so that has sort of slowed down the flow of novel medicines.
• 31:42
  Ankit Mahadevia: I think that, in particular, that's exacerbated by the way we pay for hospital stays, number one.
• 31:50
  Ankit Mahadevia: And number two is the way that we pay for medicines generally.
• 31:54
  Ankit Mahadevia: So at a macro level, I think number one is we need to fix some of those cross incentives.
• 32:01
  Ankit Mahadevia: So the worst infectious threat we're going to see is probably one that doesn't have that many patients suffering today.
• 32:08
  Ankit Mahadevia: Before January, there weren't any coronavirus patients.
• 32:13
  Ankit Mahadevia: So then the commercial incentive to develop coronavirus therapies was rather limited at the time.
• 32:19
  Ankit Mahadevia: So, there has to be a way to address that.
• 32:21
  Ankit Mahadevia: The same is true for bacterial infections whereby some infections for which we're creating future weapons don't happen all that often, fortunately.
• 32:30
  Ankit Mahadevia: But that means that there's also not a market for them.
• 32:32
  Ankit Mahadevia: And this is in particular in the hospital, where on top of that, hospitals get a fixed payment no matter how long the hospital stays, no matter what they use.
• 32:42
  Ankit Mahadevia: So it's like the difference, and I remember this from being a government employee and a consultant, when I was a government employee, I got a per diem for dinner and when I was a consultant I got reimbursed for my dinner up to a limit and I definitely ate better as a consultant than as a per diem government employee.
• 32:57
  Ankit Mahadevia: But the same is true, which is that hospitals are in this difficult position where if they're going to pay for an innovative drug that's coming right out of their bottom line.
• 33:05
  Ankit Mahadevia: And so there's a disincentive for innovation there as well.
• 33:08
  Ankit Mahadevia: But at a macro level, so if we can fix the science hurdles, which I think I'm optimistic we can—us and others are working on that— and there's pockets of infectious disease that need better incentives, which I'm confident will also happen.
• 33:21
  Ankit Mahadevia: Ultimately though, the real solution to having a comprehensive infectious disease infrastructure is picking products that can sustain the types of institutions that need to be there to develop these new drugs.
• 33:33
  Ankit Mahadevia: All of the policy investments will help.
• 33:37
  Ankit Mahadevia: But really you need what we call hero products, products that are broad enough to sustain and build companies.
• 33:43
  Ankit Mahadevia: And what are these products?
• 33:44
  Ankit Mahadevia: Historically, they're like Sovaldi that helped build the next chapter of Gilead, like Cubicin, which really built Cubist into a leader.
• 33:51
  Ankit Mahadevia: other things that really help build a franchise that allows us to go ahead.
• 33:58
  Ankit Mahadevia: So it goes back to our fundamental mission at Spero which is pick good products that allow the breadth to be able to build a leader in the field.
• 34:10
  Ankit Mahadevia: And given the Tebipenem, both reimbursed outside of the hospital and affecting the lives of at least 2 million patients a year, it's broad enough for us to help fulfill that vision.
• 34:22
  Ankit Mahadevia: So my long answer, the short one is if we pick good products and then we have complementary public incentives for those medicines that are socially critical but privately unprofitable like IV medicines in the hospital, and those for future infectious threats, we're going to be i n excellent shape.
• 34:40
  Ankit Mahadevia: And the current crisis that we're in invites a deep reexamination of how we've systematically approached that.
• 34:49
  Ankit Mahadevia: And I think that, the analogy that I use, who's a former Homeland security official giving h is take on corona, we still take off our shoes at the airport in relation to something that happened almost 20 years ago.
• 35:02
  Ankit Mahadevia: I think c oronavirus is going to change the way we think about investing in our defense against infection forever.
• 35:08
  Ankit Mahadevia: And good products are part of that solution.
• 35:11
  Ankit Mahadevia: And so i s smart policy.
• 35:13
  John Simboli: Infectious disease seems to be the kind of thing that is a global problem as we're learning right now How does one adapt a system of payments and a system of incentives t hat's based on where we live, a nd in other parts of the world where those systems are developed, how does one then connect that with a global n eed?
• 35:32
  Ankit Mahadevia: I think what you're asking about is, the virus is attacking our society globally, yet we are attacking it back often in in a regional basis.
• 35:45
  Ankit Mahadevia: AndI think that's absolutely necessary and coordination at the international level is critical,.
• 35:56
  Ankit Mahadevia: Now, more than ever, we do need organizations that have an international reach to really help us share information and coordinate.
• 36:06
  Ankit Mahadevia: I think that at least as it relates to how we think about some of these policy supports for antibacterials, I think that there actually are some excellent ideas around the world and in particular in the U.S.
• 36:18
  Ankit Mahadevia: and in Europe, that sort of t r y to find that balance.
• 36:23
  Ankit Mahadevia: And so I'm actually very pleased with the global response to the policy challenges that have im pacted how comprehensive we can be in effecting treatment for infection.
• 36:38
  Ankit Mahadevia: So with all of the barriers that there are in international coordination, I think there has been a very good international dialogue at places like Davos and among the G7 and both in the UK and in mainland Europe and the U.S,.
• 36:52
  Ankit Mahadevia: that's been p retty thoughtful.
• 36:53
  Ankit Mahadevia: And now we just need the wherewithal to take that next step.
• 36:58
  Ankit Mahadevia: The good ideas are there.
• 37:00
  Ankit Mahadevia: We just need to act on one of them.
• 37:02
  Ankit Mahadevia: And in the meantime though, as I mentioned, what's required on a global basis is that companies like ours and others pick the right products, succeed with them, because we need to be part of the solution.
• 37:15
  Ankit Mahadevia: As much as a government can incentivize, they are not drug developers.
• 37:20
  Ankit Mahadevia: Ultimately, drug developers have to come together and maintain the right expertise to be ready.
• 37:28
  Ankit Mahadevia: I think for us, as a team of drug developers, we build the base on those infectious disease needs that are here today.
• 37:38
  Ankit Mahadevia: So when we think about patients with complicated UTI that need oral options, there are 2 million today, so we build the base with those unmet needs that exist today, that help us build the momentum as a company that's necessary to take a comprehensive approach to infection.
• 37:59
  Ankit Mahadevia: Then we move from there, and this is a good example of our pipeline, we've focused our efforts on Tebipemem and SPR 720 for NTM disease, those are needs that exist today that need solutions.
• 38:12
  Ankit Mahadevia: If we could wave a magic wand and get both drugs approved, there would be millions of people and many thousands o n the NTM side, that would be eligible today.
• 38:23
  Ankit Mahadevia: Then we build from there to our commitment to public health.
• 38:26
  Ankit Mahadevia: And so we do that with collaborators.
• 38:29
  Ankit Mahadevia: So as an example, SPR 206 is an IV a gent that treats serious infections, including acinetobacter a n d p seudomonas.
• 38:37
  Ankit Mahadevia: And because 206 is focused on the hospital and pseudomonas and acinetobacter are important problems but aren't necessarily broad enough to be sustainable on their own, we collaborate.
• 38:47
  Ankit Mahadevia: So we can collaborate with the Department of Defense.
• 38:50
  Ankit Mahadevia: We collaborate with Everest Medicines to ensure that we have the wherewithal to both put our talents to the use of this important need, but also balance that with product sustainability.
• 38:58
  Ankit Mahadevia: In addition, for 720 we're partnered with Gates to explore the public health opportunities that 720 allows for tuberculosis.
• 39:09
  Ankit Mahadevia: So the big picture is build the base on sustainable products and then collaborate both with public and private organizations to advance the ball forward for public health needs.
• 39:18
  Ankit Mahadevia: That is consistent with the vision that we had when we built this place.
• 39:27
  John Simboli: What are we learning as a society about how to keep going during this process?
• 39:33
  John Simboli: Here I am today working from my home studio and, and yet we're carrying on and,, we're all looking forward to going back to work.
• 39:42
  Ankit Mahadevia: Well, I think that, certainly, we've seen it first hand amongst our team, but then just also generally, this crisis that we've been in has tested our resilience in a way that nothing else has, in particular because of the unpredictability and the prolonged nature of it.
• 40:06
  Ankit Mahadevia: And we've been through crises before, but you can't see this enemy, number one.
• 40:13
  Ankit Mahadevia: And number two, you don't know when this enemy is go ing away.
• 40:15
  Ankit Mahadevia: And I've been inspired certainly, at Spero, by folks that continue to go above and beyond, not just do their jobs but then go the extra mile even though so many things we take for granted—when ar e th e kids going to school next?
• 40:30
  Ankit Mahadevia: How am I getting groceries for the family without exposing myself?
• 40:35
  Ankit Mahadevia: I'm sick, do I even want to go to the doctor?
• 40:37
  Ankit Mahadevia: Things that we take for granted every day we've put aside and we're able to deliver.
• 40:43
  Ankit Mahadevia: And I speak for all the folks in the community we see, and especially, our heart goes out to those frontline workers.
• 40:52
  Ankit Mahadevia: Certainly, our colleagues in the infectious disease community that are on the front lines, folks like Helen Boucher and others here in Boston.
• 41:01
  Ankit Mahadevia: but also the folks that take out our trash folks that check me out at the grocery store.
• 41:08
  Ankit Mahadevia: They are enabling our way of life and doing so with the resilience that's amazing, particularly because I know, comparing notes with my clinician colleagues, it's frightening to go to work every day.
• 41:20
  Ankit Mahadevia: Something as simple as going to work every day.
• 41:23
  Ankit Mahadevia: So I, I think that despite all the negative news that one may read, I am inspired by the resilience, both of our community in pharma, our community in Spero, but just our community at large.
• 41:37
  Ankit Mahadevia: We're finding a way to persevere and I think that what's going to help us continue is to just realize, mourn and admit that life's not going to be the same after this for some time, if ever.
• 41:52
  Ankit Mahadevia: And I think that rather than go back to"the way it was," we can all focus on how to make it the way it should be going forward.
• 42:01
  Ankit Mahadevia: And for us here at Spero, we're going to try to do our part both in terms of modeling how we think it should be in terms of how we work together, a s well as continuing to develop our medicines because that's going to be part of the solution.
• 42:17
  John Simboli: Ankit, thanks for making time to speak with me today.
• 42:21
  Ankit Mahadevia: It was a pleasure, John.
• 42:22
  Ankit Mahadevia: Thank you so much.
• 42:23
  John Simboli: Ankit Mahadevia has a seemingly unquenchable thirst for knowledge.
• 42:28
  John Simboli: He's seen the world of health care through the lenses of both biology and health economics and his multifaceted perspective may have something to do with his approach to leadership and why he values both input and contradiction.
• 42:43
  John Simboli: At the same time Ankit guides Spero Therapeutics towards development of drugs for patients with multidrug resistant bacterial infections, his eyes are also focused over the horizon on the global threat of infectious diseases.
• 42:57
  John Simboli: Ankit's vision is that we can learn from the coronavirus pandemic.
• 43:02
  John Simboli: Rather than go back to the way it was, we can focus on how to make it the way it should be going forward.
• 43:10
  John Simboli: He reminds us, the worst infectious threat we're going to see in the future is probably one that doesn't have many patients suffering today.
• 43:18
  John Simboli: That's why he thinks the time is now to change, forever, the way we think about investing in our defense against infection and building the sustained expertise needed to improve what we can deliver to treat patients with infection.
• 43:32
  I'm John Simboli.
• 43:34
  You're listening to BioBoss.