Rebounding From a Setback With a Transformative Partnership

Ankit Mahadevia, CEO, Spero Therapeutics

One of the well-known rituals at many companies is the holiday party. It’s a way to unwind after a long and demanding year and get to know our colleagues better.

The January gathering was extra special at Spero Therapeutics. This was our first in-person holiday celebration in three years. We gathered at a hotel in Cambridge, not far from the office. We thanked employees and their families for their support of our mission to fight hard-to-treat bacterial infections.

The room was decorated in silver. The mood was festive. The team presented an “Up and Comer” award to a star employee and toasted a long-time employee’s 7-year-anniversary. Some introverted scientists even made it out to the dance floor.

The celebration was extra sweet, given some memories of the venue. This was the same hotel where, last year, our executive team learned from the FDA that the data package for tebipenem, an oral carbapenem for patients with urinary tract infections, may be insufficient to support approval in the current review cycle. It’s also the same hotel where the senior team made the difficult, but necessary decision to restructure the company to focus on our other medicines. In May, we had to lay off about 110 employees – 75 percent of our staff.

What a difference a few months can make. By September, we had turned things around. We announced a transformative partnership with GSK that puts tebipenem on a path to potential FDA approval. The collaboration’s $66 million upfront payment extends Spero’s runway to advance the rest of our late-stage pipeline beyond 2024 and enables over $600 million in potential milestone payments.   

Our stock was depressed, along with most others in the biotech sector. We had to manage through major changes. Even so, we secured this partnership while working in a therapeutic area that has fallen out of favor with many in large pharma.  

As we think back on the past year, we had to ask ourselves: How did we do it?

This doesn’t happen in antibiotics – but fundamentals and strategic fit matter

The popular view on antibiotics is that any drug that kills a microorganism is already cursed from birth. Some high-profile failures several years ago have informed the narrative that antibiotics will never sell, and will never get credit with Pharma or investors. Therefore, the initial reaction to our collaboration was surprise – a transformative collaboration for an antibiotic just didn’t square with most pre-conceived notions.   

Readers of this column know that there’s more to the story – the fundamentals around a medicine matter more than broad, category-level pronouncements. Medicines that work on a true unmet need, and that are commercially viable, have driven momentum for the companies that develop them.

The conviction that we and our partners have in tebipenem comes from doing the work. We, and our partners, spoke to clinicians treating UTIs. We engaged in payor research. We did a thorough analysis of the UTI treatment landscape.

New oral, broader spectrum UTI agents serve a major clinical need. Drug resistance impacts millions of patients. There hasn’t been a new oral therapy for these infections in over 30 years. We heard from patients (even a few on the Spero team and their families) suffering from difficult-to-treat UTIs.

Importantly, we also learned a new oral UTI therapy has commercial potential. It could reduce unnecessary hospitalizations, providing relief to frustrated patients, and enabling distribution of therapy outside the hospital (see here for more on why that matters).

Further, there was a strong strategic fit. GSK is developing gepotidacin, a complementary medicine to tebipenem for patients with uncomplicated urinary tract infections.  

Securing the perimeter quickly created room for creative options

Before we could think about a new regulatory path for tebipenem, we needed the time, resources, and credible alternatives necessary to let collaboration opportunities blossom. Time was of the essence – the longer we waited last spring to restructure, the less time we’d have to operate and deliver on key data milestones. We couldn’t afford to delay the inevitable.

This meant pivoting quickly to focus on delivering near-term data on our orphan disease program SPR720, extending our capital runway, and ensuring the core team stayed.    

The most critical task was focusing on the team we needed for this new chapter. We spent some emotional hours last summer to honor the contributions of departing Sperobes. Our efforts to help departing Sperobes find their next roles helped us process the moment and focus on the future.

I will always be grateful to the Sperobes that stuck with us to deliver on the mission in those most uncertain months following our restructuring. Despite having to reorient themselves on the fly, they stayed focused on the mission and delivered.

Leading a biotech is lonely, and even lonelier when things haven’t gone to plan; having a committed team that didn’t quit when it got hard inspired us to keep finding new ways to move forward.  

Long-term relationships, strengthened by transparency

Successful business partnerships are about relationships. The roots of our partnership go back multiple years. GSK has been a longtime investor in Spero. They know what we do. Over time, as we delivered on what we promised on tebipenem, and GSK continued to advance its own infectious disease portfolio, these discussions broadened and deepened. 

Leading up to the September partnership announcement, there was ongoing dialogue at multiple levels of each organization about what could be possible to bring tebipenem to patients. In a world emerging post-pandemic, this went beyond polite Zoom conversations. Several dinners, and a shared love of single malt scotch and world history paved the way for a shared vision.

Our commitment to transparency deepened the discussions. This isn’t the norm. The tendency following a setback is to close ranks. Instead of doing that, we invited GSK in to join us on key regulatory interactions.

They could see for themselves what the FDA was saying, and help us think about what it would take to win an approval for tebipenem.

We built shared conviction on the importance of the program and the viability of the path forward. This conviction served us well when deal discussions hit inevitable sticking points.

Moving forward

Along with the chance to spend time with our colleagues, our holiday party was special because we could make some positive new memories in the venue and focus on the future.

The urgency of this mission hit close home recently as I helped my mother navigate through a couple of months of cycling through ineffective oral antibiotics. It was a reminder of the importance of what we do. We all know patients are waiting.

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