Ankit Mahadevia, CEO of Spero Therapeutics, on Leadership in Biotechnology and Innovation in Antibiotic Development
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For the third episode of the season, we spoke with Ankit Mahadevia, M.D. MBA
Ankit Mahadevia is the CEO of Spero Therapeutics and a member of the Board of Directors. He was formerly a Venture Partner in the life sciences group at Atlas Venture, located in Cambridge, MA. At Atlas, he led the creation of eight companies focused on novel drug discovery platforms and therapeutic products including Nimbus Therapeutics, Arteaus Therapeutics (acquired by Lilly), and Translate Bio (Nasdaq: TBIO). Prior to joining Atlas in 2008, Ankit worked in business development at Arcion Therapeutics, Genentech, and Vanda Pharmaceuticals after experience in consulting at McKinsey & Company and Monitor Group. Ankit started his career with roles at the U.S. Senate Health, Education, Labor, and Pensions committees, the U.S. Government Accountability Office, and the Mexican Institute of Social Security (IMSS) and later served on the Advisory Council at the NIH National Center for Advancing Translational Studies. He has spoken widely on entrepreneurship at various universities and published “Quiet Leader, Loud Results: How Quiet Leaders Drive Outcomes that Speak for Themselves” in fall of 2022.
Ankit received B.A. degrees in Economics and Biology at Northwestern University, a M.D. from Johns Hopkins University, and an MBA from The Wharton School.
In our conversation, Ankit and I chatted about:
- His career path through healthcare before landing
- The value of seeing different “movies” in biotechnology
- The challenges and opportunities in infectious diseases and antibiotics
- Regulatory structures and potential legislation shaping Spero’s strategy
- Guidance on successful biotech company creation
1:45 to 11:20 Having interest in healthcare but taking a circuitous route to an M.D./MBA education and joining Atlas Ventures post-grad
- Growing up : Ankit knew from a young age he wanted to pursue a career related to medicine and studied both Economics and Biology at Northwestern University nearby his Chicago hometown. Rather than go straight to medical school, he decided to work in healthcare policy and later strategy consulting which began forming his well-rounded perspective on the medical system.
- Ultimately, Ankit attended The Johns Hopkins University School of Medicine during which he continued working in different roles, such as taking a leave to work at McKinsey & Co. He then went on to attend The Wharton School to pursue an MBA in Healthcare Management where he sought out opportunities in business development at Genentech and Vanda Pharmaceuticals. He also began exploring life sciences venture capital through SafeGuard, a Philly-based fund.
- Choosing a starting point: After reflection and a series of discussions with peers/mentors, Ankit chose to join Atlas Venture as an Associate post-graduation to gain experience in company creation.
11:21 to 15:43 Early tenure at Atlas Venture and seeing as many “movies” as possible
- The first company Ankit worked directly on was Nimbus Therapeutics, which now has multiple small molecule assets in clinical trials and he continued to support the portfolio through Board positions (saw over 100 companies over his first year at Atlas).
- Ankit discusses the fallacy of rational planning early in career or during graduate school, he shared how in retrospect he knew very little about what his true goals would be down the line.
“By the nature of a what a VC firm does, you get to see a lot of ‘movies’ at once. Both within the existing portfolio and also the deal flow that came. At the time, Atlas was making its’ transition from a more traditional later stage VC model to early stage company formation.”
15:44 to 18:50 Balancing humility and confidence early in your career
- On his first board experiences: At age 29, Ankit was much younger than many of his colleagues he served on boards with. He spoke about finding ways to provide value to a company in a difficult financial situation and how authenticity is key.
“My advice would be to find the style that works for you, no style is the same and people know immediately if the style you’ve chosen is not the one that is true to you.”
18:51 to 22:20 Transitioning to Spero Therapeutics
- After becoming a venture partner at Atlas, Ankit served as Active CEO for three distinct companies after their formation: 1) Synlogic, a public company with programs in Phase II, 2) Rodin Therapeutics, a company focused on an epigentic mechanism of neurologic disaease that was purchased by Alkermes, and 3) Spero Therapeutics, a company focused on infectious disease with multiple assets in clinic and a partnership with GSK
- On choosing Spero Therapeutics as his next step: Ankit highlights how over time he found himself spread a bit thin between two kids at home and the three companies. Despite not seeing himself as a CEO previously, he decided to put his name in consideration for Spero’s full-time CEO role after realizing he was increasingly drawn to his work there.
22:21 to 29:30 The unique aspects of innovating in infectious disease and creating antibiotics
- On technical risk: Ankit shares how he has seen the progression with biologics and how the risks have converged in many ways towards a similar profile as small molecules. Spero Therapeutics has both small molecules and biologics they are working on and he has really enjoyed seeing many of these ideas move all the way from test tubes in a lab to clinical trials serving patients.
Why is infectious disease unique? Unlike most drugs, next-gen antibiotics are often saved for special circumstances to avoid cultivating resistance. Microbial infections are treated and billed for differently than many other conditions, posing potential challenges for biotech business models, and generics are much more commonly deferred to during hospital budgeting. This differs from say oncology where there is minimal payor review and innovative drugs capture economic value with relative ease if significantly effective for survival.
- On a key regulatory change: The particular arm of the FDA focused on antibiotics historically require two large Phase III clinical trials for approval which limited investment interest. In 2013, the GAIN Act gave the FDA permission to treat antibiotic development more like orphan drug development to enable more efficient development pathways.
29:31 to 33:15 Spero Therapeutics’ unique positioning, business model strategy, and indication selection
- On pipeline strategy: Ankit describes how they identified oral administration as a key strategy that had clear reimbursement precedent, which has borne out across their pipeline which contains various oral drugs that addresses unmet need not met by existing generics. This approach has enabled them to pursue multiple rounds of financing, establish pharma partnerships, and continue to build their team.
- On indication selection and patient populations: It has been over 30 years since a new oral agent has been developed for urinary tract infections, where antibiotic resistance is a massive problem. Bioavailability and potency remain key challenges, leading to unnecessary hospitalizations and doctor visits. The Spero team identified tebipenem, a molecule invented in Japan, that cleared a Phase III study published in the New England Journal of Medicine and is now partnered with GSK. Second, non-tuberculous mycobacteria (NTM) which has about 100,000 patients in the US that require treatment for many months. Ankit and his team identified an agent from Vertex Pharmaceuticals to develop for these patients with no current approved therapeutic option.
“Our innovations at Spero were not just about good science, and we have to go where the patients are and where there are no approved drugs, but also about the business model. We knew there had to be potential blockbuster drugs in antibacterials and turns out there are. They all happen to be reimbursed outside of the hospital and that became our grounding philosophy ahead of our IPO.”
33:16 to 36:38 Biotech capital markets and the industry macro-environment
- On managing cash runway and progressing science: Ankit speaks on how antibiotics traditionally do not attract heavy investment, which forced Spero to be judicious in their financial approach since their inception. They have raised over $250 million, excluding pharma and public partnerships, to date. They have been diligent in communicating their focus on the specific indications of choice and oral formulations. To complement their private investment, they have raised over $100M from public entities such as the Biomedical Advanced Research and Development Authority (BARDA) and the National Institutes of Health (NIH). They have also partnered with GSK and Pfizer.
“One, be crystal clear in your value proposition and really refine it based on what investors are telling you. Two, and above all else, execute and deliver. Number three, be creative, proactive, and plan years ahead for money that does not come from investors’ pockets.”
On leveraging his own investing background: Ankit shares how his experience allows him to understand the challenges faced by investors in this high interest rate environment, where great companies with good science may be losing value solely because of these external forces. This puts investors in a precarious position with their own LPs as they try to execute on their funds’ goals.
36:39 to 43:30 Legislation as a lever for antibiotic innovation
- On his view of potential legislation: Ankit discusses how given Spero’s mission to address unmet needs in infectious disease, they support any legislation that can facilitate the develop of needed antibiotics. However, he knows how long these initiatives can take to reach fruition, drawing on his earlier experience developing policy in Washington D.C. Thus, Ankit and his team are focused on building within the current system rather than one they hope we may get to down the line.
- On the PASTEUR Act: PASTEUR represents a subscription-like model where there could be upfront payment to be credited against Medicare reimbursements downstream for antibiotics that address high unmet needs. This enables improved insight on potential returns on investment that can be expected, incentivizing greater investment from the biotech community.
- A link to Ankit’s recently published book “Quiet Leaders, Loud Results”: https://www.quietleader.com/
