From The Trenches

By Arthur Tzianabos, CEO of Lifordi Immunotherapeutics, as part of the From The Trenches feature of LifeSciVC

Building the right team is a popular topic because it is difficult and a company’s success hinges on it. In a cash-crunched biotech environment like today, it is top of mind because as company builders, we are being asked to “do more with less.”LifeSci VC blogs like Pitfalls of the Scarcity Mindset and How Early is Too Early to Establish a Commercial Function in Biotech? have described the impact of limited resources on hiring decisions and what functions are needed when. The debate about building internal capabilities or using external consultants will rage on. But apart from whether you hire or borrow talent, you should be asking yourself what type of individual do I need to complement the team? Given how long it takes to develop a drug, needs will inevitably change and talent pools will vary. Determining the right mix of talented individuals can make or break a team. Are you continually assessing, attracting, and balancing the Jack of All Trades and Utility Players?

The Jack of All Trades (“Jacks”)

Jacks can do many kinds of work across the different functions within a company. The term was first used in the 1600s when performing manual labor was essential for survival. Today, these multi-talented individuals are still valuable contributors to the workplace and society despite the integration of AI into offices and homes. When discussing the theme of this blog, each time I mentioned, ‘Jack of All Trades’ to someone, they felt compelled to add ‘and Master of None.’ The second half of that phrase evolved over time and unfortunately, it gave Jacks a bit of a bad rap. Sometimes misunderstood, Jacks are responsible for the success of many biotechs since ‘wearing many hats’ is essential for survival. Possessing a broad range of skills, Jacks are flexible, adaptable, and reliable. They are often also great leaders, which I believe stems from their willingness to jump into any situation, bring people together and get the job done.

The ‘Jack’ Advantage

Inside the last few biotech startups I have led, I was fortunate to work alongside the same individual who is a quintessential Jack of All Trades. In fact, he was one of my first hires at Lifordi. Performing many functions and mastering more than one at several of the companies, he has assumed the role of real estate agent, IT guru, marketing and sales rep, and KOL relationship manager, among other responsibilities. He locates the ideal office space and knowingly designs a flexible layout because he knows our needs will change over time. At a prior company, when we outgrew the confines and prices of a Cambridge office, he found a great place for us in Waltham —and this was at a time when few biotechs had even considered taking that leap. He is a fierce lease negotiator, insisting on the most favorable tenant improvements I have ever seen. At a previous company, he found a spot for our new headquarters that could accommodate a full-scale gene therapy manufacturing facility and then managed the build out in record time and on budget. A few years later when we entered into a joint venture to monetize this facility, he reconfigured the space without any major disruptions to operations.

From day one, he works alongside technical experts to develop an efficient IT infrastructure.  At Lifordi, this extends across state lines and country borders. He scouts out the right equipment to buy and finds the best price. He can fix most computer or printer problems, saving countless hours of frustration for employees and maintaining productivity for the company. I have also seen him jump in to design marketing materials, partner with colleagues on the commercial team to identify global prospects and then help maintain strong relationships with doctors and clinics using our technology. At Lifordi, he consulted experts and other biotech companies to establish a new entity in a foreign country. Working closely with legal, regulatory, clinical, research, and CMC colleagues inside and outside the organization, he helps to assess needs and the associated costs, which is integral to our planning and budgeting process. A natural leader and organizational ‘go-to-guy, he has earned the highest level of respect from the team.

An Executive Assistant (EA) who is a Jack of All Trades is a rare and coveted team member. She or he can support the entire Management team, manage the office, and even handle essential Human Resources responsibilities. At Lifordi, our EA Jack of All Trades jumped right in to develop and manage our employee onboarding program, learn how to select and administer the health benefits and 401K plans, and execute the company meetings and outings, among a host of other much needed things. Our Lab Manager showed her Jack of All Trades capability by taking on our global procurement and shipping needs. She has fast become the linchpin in directing complex logistics that are required to deliver a high-quality antibody drug conjugate (ADC) to another country on time for our clinical trial. These are just a few examples of the value of the Jacks. We all need them, but do you have them in your network when building a biotech newco?

Spotting a Jack of All Trades

You can usually identify a Jack of All Trades right away. The examples above may be helpful, but you can also find a potential Jack from resumes. While a good resume should be tailored to the job description and focus on the requirements and accomplishments of the position, you should look for his/her contributions across the company and their achievements inside and outside the organization. Has their work helped the company, stakeholders, or perhaps even the field? A variety of seemingly unrelated personal interests can also be a clue to their innate curiosity, affinity for pushing boundaries, and willingness to jump in and get it done.

The advantages of a Jack of All Trades are clear, but you also need Utility Players to be successful.

The Value of Utility Players

Utility Players are highly skilled, experienced professionals who are expert within a function but can assume multiple roles within that function. As “Masters of Their Domain” they help define goals, drive strategy, and achieve results. They are experts who know all aspects of their function and how to operate efficiently to achieve the desired results.

While you probably never heard of him, the most famous Utility Player in all of baseball is Bert Campaneris, a shortstop for the California Angels who, in 1965 at the age of 23 years, became the first player to play all nine positions in one game (only four others have achieved this). Bert’s story is worth reading if you have the chance, but suffice it to say it’s a thriller, reminiscent of the famous baseball poem Casey at the Bat. The game began with an incredible start and ended with a 5-3 win in 13 innings. Unfortunately, Campaneris wasn’t there to see how it played out because this ‘super utility player’ was headed to the hospital after his inning-ending save as catcher. While Utility Players perform multiple roles within a function, like Campaneris, they shouldn’t play them all and never on the same day.

To illustrate the versatility and value that a good Utility Player brings to the team, consider the Chief Technology Officer (CTO). The CTO Utility Player can be a sinner or savior of biotech companies. Manufacturing is frequently the reason for significant delays and the subject of CRLs. More often than not, they are among the unsung heroes that get new drug applications (NDAs) accepted. He/she is experienced in process development and Good Manufacturing Practice (GMP) clinical and commercial manufacturing, analytical development and quality control, as well as cold chain logistics and management.

At Lifordi, the level of expertise required for this role is heightened by our need to manufacture an antibody drug conjugate (ADC) with a drug to antibody ratio (DAR) of 8. The ADCs’ three components: the drug, monoclonal antibody and linker, must be optimized and manufactured separately and then assembled into an easy-to- administer subcutaneous injection. Understanding the complexity and long-lead time required, it made sense to hire our CTO Utility Player prior to officially founding the company. This enabled him to begin transforming research grade ADCs into reliable, reproducible and scalable products under the GMP conditions required for IND-enabling studies. However, we are lucky that our CTO is a veteran C-suite team player who also understands the broader business enterprise view of the Lifordi mission, which is also extremely valuable.  Today, our ADC drug is vialed, labeled and ready for shipping to clinical sites despite the fact that CMC is usually on the critical path for a clinical study.

Chief Medical Officers (CMO) are another good example of Utility Players. Many people believe a CMO needs to be a domain expert in particular therapeutic area(s) of interest. This is not always the case. With a strong team of external clinical and regulatory advisors, including former heads of medical societies in relevant disease areas, it may be more important to hire an expert in first-in-human (FIH) studies. This is the case at Lifordi where our CMO Utility Player is an expert ‘clinical trialist’ who has led more than a dozen FIH studies. What’s more, he previously worked with the clinical research organization (CRO) and some clinical sites we selected for our global trials. Expert in designing a highly flexible, easy to follow, patient-centered FIH study protocol, and effectively managing global clinical operations as well as placebo rates, he is essential for success.

Finding the Right Mix of Jacks and Utility Players

Establishing just the right mix of Jack of All Trades and Utility Players cannot be underestimated. Further complicating this equation is that the mix will fluctuate. People learn and grow, company needs change, and market conditions will dictate. With the proper motivation, aptitude, guidance and opportunity, Jacks can also move on to become Utility Players. While this temporarily disrupts the delicate balance and challenges the team to divvy up some desperate responsibilities, overall, it is good for them and the company.

Determining the right mix of Jacks and Utility Players largely depends on a company’s business strategy, stage of development, and available resources. However, understanding how to spot them, attract them and the best way to leverage the value they bring is more than half the battle. Striving to maintain a healthy balance of both is how you build a great team that can deliver revolutionary medicines to patients and caregivers, and ultimately, create the greatest value for all stakeholders.

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By Ankit Mahadevia, founder and board director of Spero Therapeutics, as part of the From The Trenches feature of LifeSciVC

Biotech leaders love talking about ‘margin of safety’—but what if the safety nets we build are just illusions? In The Intelligent Investor, Ben Graham defines the margin of safety —the cushion that a decision leaves for the unexpected—and its singular importance for the “rightness” of that decision.  I was recently part of a discussion with a NewCo on the trade-off between waiting for a better molecule versus declaring a candidate now and pushing it to the clinic. It dawned on me that many tough calls in biotech—cash runway, quality of a molecule, pipeline breadth, and team construction—are all margin-of-safety choices. Since buying safety in one place often compromises it elsewhere, it’s essential to invest in areas that truly mitigate risk. I’ve highlighted tradeoffs from my experience as a CEO and Board member where, contrary to my initial thinking, one side of that trade wasn’t as helpful as I thought.

Cash runway vs. pipeline breadth

The choice: Concentrate on one program to extend cash or keep multiple to diversify risk.

In my experience, the margin of safety created by a pipeline is often false.  Great programs are rare, and the chances that a company has multiple, truly exceptional lead programs are even rarer.  To gamble on that low probability, a team needs to accept the certainty of burning extra cash and taxing focus. Even platform companies typically deliver a significant amount of their value from their most advanced drug. Very early (early LO or earlier) assets can be an exception – the cost of failure is usually lower, and some data-driven processes (for example, with assays that correlate with clinical efficacy) can yield a more informed choice. In a previous company, setting expectations with our Board on this evolutionary process gave us the time to choose our lead program wisely, even though it took a little extra time for one program to catch up. As we learned, board and investor management are essential in this process; prospectively communicating the bar to beat for a drug can support tough decisions on programs when they reach a decision point.  There is another circumstance where pipeline breadth makes sense – with a substantial cash cushion and enough capacity on the team. Lately, this has not been the privilege of early-stage company builders, and the onus is still on a team to prove that multiple programs are truly extraordinary.

Speed to clinic vs. quality of a drug

The choice: Get to the clinic fast with a good drug, or take extra time to get to a great drug

Being ahead of competitors is often discussed as a margin of safety for multiple reasons – it may unlock a company’s next round and ensure a seat at the table in the competitive landscape if things take longer.    That said, it will require millions to get a molecule through first-in-patient studies, and that molecule must deliver.  I think about tradeoffs in terms of which end is recoverable.  It’s a lot easier to find cash later than to deal with a lukewarm efficacy result because your compound could have had better PK or potency. When speed is the only optimizing variable, there’s also an incentive to shortchange key steps (CMC, for example) in ways that ultimately prove costly. Furthermore, there is evidence suggesting that second-in-line compounds can perform well commercially, especially if they have advantages over the incumbent.  Some judgment is required when testing this; if waiting is not feasible from a capital perspective, of course, follow the 80/20 rule and proceed. In the competitive landscape, being first can sometimes matter greatly – for example, in an ultra-orphan indication where first to clinic has a decided advantage in enrollment.

Depth and breadth of team vs. Burn rate

The choice: Hire a full-thickness team to plan for success, or stay lean/fractional and preserve cash

There is a perception that a full-time C-suite (comprising a CEO, CSO, etc.) is a required margin of safety.  This is generally true, but it may not be right for the earliest stages (such as prior to entering the clinic). First, team building depends on strategy, which is fluid at the earlier stages. At one platform company I advise, primate data on biodistribution changed our TA strategy completely over a few weeks. A team mismatched to the strategy may create confusion or require transitions downstream.  Second, experienced leaders have options, and data can drive conviction. It may not be possible to recruit a top-quality team at an early stage; searches can be time-consuming, costly, and low-yielding if the data is not yet available to build conviction.  There’s also a danger of locking the company into a team that is OK for now, but not the long term.  Finally, cash is precious in the early stage. Often, an experienced, fractional team can drive a company towards key go/no go data efficiently, and the lower investment required creates its own margin of safety by preserving cash for pivots and delays.  There’s often a “chicken or egg” conversation in boardrooms, about whether a strong C-team is required to raise capital, or capital is required to recruit a strong C-team. Both are right, and in my experience, the right fractional leadership in the short term can solve this quandary until the team signs up full-time or helps recruit their replacements. Half of the right team is far better than all of the wrong leadership.

Tradeoffs between a company’s cash, time, and human resources are tough, with no right answers. Sometimes, though, tradeoffs that seem wise and safe in the moment do not actually build more cushion against the unexpected.  Knowing the difference can leave you even better prepared for all the challenges and opportunities ahead.

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