By Arthur Tzianabos, CEO of Lifordi Immunotherapeutics, as part of the From The Trenches feature of LifeSciVC
If you ask anyone who has run a drug development program what factors determine whether it succeeds or not, the answer is rarely just “the science.” It often depends on the people running the program and if they work well together, as well as whether the company has clarity on where the goalposts are and who is accountable for what. Program Management should play a critical role in creating that clarity and alignment, ensuring that the organization is aligned on the strategy, goals, development plan, and timelines. This function also drives effective cross-functional decision-making and reinforces accountability for delivering against agreed-upon commitments. This is true within seven-person startups or companies of more than 5,000 people.
Program Management is an essential but often overlooked function that can greatly enhance the success rate of drug development programs. Importantly, a successful Program Management function relies heavily on experienced and savvy operators who comprise this organization. LifeSciVC blogs written by me and many others highlight reasons why drug development often fails. What I believe is one of the most damning and yet avoidable reasons why our medicines can fail to make it to patients lies in the lack of understanding of the value that the Program Management function can bring to companies both large and small. To underscore this point, if you search on ‘Program Management’ under the From the Trenches tab on the LifeSciVC website, you will find ZERO hits on this topic.
As a former VP of Program Management and ultimately SVP and Head of Research and Early Development at Shire ──with over 5,000 employees and programs ranging from discovery to marketed drugs, I learned firsthand how a lack of cooperation, integration and team imbalance could destroy programs. Over my career as a CEO, Board Chair/Member, and Venture Partner, I have worked with companies that have mastered Program Management and who have also successfully hired and developed dozens of program leaders. In reflecting on my own experiences and consulting with some of the best Program Executives in the business, here I have endeavored to convey a clear picture of what separates great Program Management from not-so-great.
Two Roles, One Program
It starts with understanding two very different jobs that have to work as one. In some cases, one person has to serve both roles for a program, which is not ideal but sometimes necessary given resource constraints. Ideally, every development program should have a Program Lead (PL) and a Program Manager (PM), and the simplest way to understand the split is this: the PL functions much like the CEO of the program, and the PM as its Chief Operating Officer (COO).
Typically, the PL is accountable for the program development strategy. They weigh the organization’s goals against technical considerations, the competitive landscape and the disease area. Then they build out scenario plans and alternate pathways, as well as drive cross-functional alignment around the direction the program should take.
The PM works with the team to build the cross-functional operating plan. They ensure key risks are flagged and appropriate mitigation plans are in place, maintain cross-functional timelines, and manage the practical machinery — think of it as running point on how the strategy actually gets executed. This PL/PM partnership is critical to create the right conditions and culture for the broader team to succeed.
What to Look For
A great PL or PM doesn’t necessarily need an advanced degree in health science, though a strong technical foundation certainly helps. What matters most is the ability to bring both a technical and business “lens” to the program — paired with genuine intellectual curiosity. Three things tend to separate the great ones from the rest:
Relevant background — but watch for bias
It helps enormously when someone has “been there, done that” —lived through phased drug development, taken a molecule from Phase 1 to Phase 3 or to market, and understands how the process evolves. But background can cut both ways. A PL who comes up through a single function — say, a Chief Medical Officer (CMO) or clinical lead — can bring real depth, but also real bias, and may struggle to see the full commercial or operational picture. Someone from Research might be light on development experience. The key is in the pairing: the PL and PM should bring complementary strengths, experiences, and perspectives, with each helping to balance the other’s potential gaps or biases.
High Emotional Intelligence (EQ)
Programs run on people, and a PL or PM who rubs people the wrong way will stall a program regardless of technical skill. The best ones are diplomats that do not kowtow or crumble under stress. They learn how each stakeholder operates, and — critically — they bring people together instead of driving them apart or playing one against the other.
Credentialed intelligence aside, these are the people that show up as fast learning, sharp analysis, and a hunger to keep pushing boundaries rather than defaulting to “this is how it’s always been done.” A Program Executive I know once hired a PL that primarily had commercial industry experience to lead an early-stage development program and she was highly successful. Another former Program Executive hired someone from regulatory operations with a psychology degree and no formal science degree. That person became one of the most successful PMs because she worked extremely well with people, knew what she didn’t know and moved fast to close the gap.
When interviewing candidates for these roles, one useful line of questioning is simply:
Tell me about a time you drove a decision. What was at stake? What was your approach? How did you analyze it? What was your process? What was the outcome? What would you do differently? The answers reveal far more about how someone actually thinks and operates than any resume line.
How this Works Day to Day
A well-run PL/PM relationship has a rhythm to it. The PL gets the right people in a room to form the Program Team — representatives from Clinical, Chemistry, Manufacturing and Controls (CMC), Research, Non-clinical, Clinical Pharmacology, Regulatory, and Commercial and potentially folks from additional functions depending on stage of development — and drives toward alignment. That means more than assigning responsibilities on paper; it means people actually acting in their roles, with clear expectations for the behaviors the program needs from them. Program leaders function well when they can act independently reporting directly into the CEO in a smaller company or to the COO in larger organizations. In this way, no one function takes the lead and deliverables for all aspects of the program remain clear.
Often, the default for some companies is to have the Head of Clinical or a representative from Clinical be the PL for a program. It should be no surprise then that his/her needs can drive decisions, and the lack of integration, coordination, and attention to detail can suffer. I’ve seen instances where Clinical may not know things like the difference between drug product and drug substance, how long it takes to get from one to the other, or what the lead time is from start to fill-finish. Conversely, CMC may not know the rationale behind a dosing schedule change, only that it will require more or less drug and when. The misunderstandings and blurred responsibilities often result in missed milestones, wasted drug batches and poor team dynamics — a ‘blame game’ is inevitable.
In the model I have seen work best, the PL or PM takes a holistic view of the program and translates the strategy into an integrated development plan with clear timelines, tracks progress and risks, ensures appropriate mitigation and timely escalation when needed. The PL/PM also keeps the various program activities connected, coordinating across sub-teams and managing program team meetings, communications, and information flow. Program Management works within the company’s established matrix and governance structure to enable effective planning, decision-making, and execution.
A few things distinguish programs that run smoothly from ones that don’t:
- Confidence from leadership. The Executive Team needs to trust how decisions are being made and see clear cross-functional buy-in. Without that, meetings turn into ambushes — a CMO or Head of R&D challenging the PL, or a PM caught flat-footed and unable to defend the plan. This is why the broader team needs to have the PM’s back before they ever walk into that room.
- Executive Team meetings should feel like rubber stamps, not drawn-out debates. If a leadership review turns into an extended argument, something upstream has broken down. Program Management that is too junior for the role will waste leadership’s time and struggle to read the room.
- Clarity on goalposts. Programs stall when leaders aren’t honest about constraints or are afraid to name the pain points — in Regulatory, CMC, Clinical, wherever they exist. There’s no perfect solution in drug development. Pretending otherwise just produces analysis paralysis.
One more thing successful Program Management tends to have: a champion on the Executive Team — ideally the CEO — who understands and values the role. Program Management absorbs a lot of pressure, and functions best when cross-functional alignment happens continuously, not just in the room. The goal is always to avoid surprises at the leadership level, or in one program manager’s words, “the cut your legs out from under you moments.” Once someone gets blindsided in front of the Exec Team that trust is hard to rebuild.
It’s also worth asking what happens to a PL or PM whose program isn’t the company’s top priority — the “stepchild” program, so to speak. The best organizations treat this as a development opportunity rather than a demotion: sharing learnings from the priority programs, keeping the B-team managers engaged with regulatory feedback and cross-functional insights, and actively preparing them to run a priority program when the time comes. Everyone benefits.
Why Decision-Making Breaks Down
Even a strong PL/PM pair can’t fully insulate a program from bad decisions made higher up. In biopharma, decisions themselves are complex, cross-functional, and made under real uncertainty. When decision-making breaks down, it usually follows a few predictable patterns:
Structural Flaws
- No clear owner. When it’s unclear who’s actually driving a decision — and which stakeholders need to weigh in — the result is tension, delay, and duplicated work.
- No overarching strategy. Without a clear portfolio-level strategy, program decisions drift away from corporate priorities because there’s no framework to weigh them against.
- Under-resourced programs. A program that isn’t treated as a priority often doesn’t get the leadership attention it needs to make timely calls, which becomes a self-fulfilling prognosis.
Unrealistic Planning
- Shifting goalposts. Decisions get revisited endlessly when success criteria, risk tolerance, and financial constraints were never made explicit up front. Sometimes that reflects new data. Just as often, it reflects not being realistic early enough about what’s actually feasible.
- Unrealistic assumptions. Timelines, budgets, and probability-of-success estimates that aren’t grounded in reality set programs up to fail.
Execution Resistance
- Fear of the imperfect option. Some decisions only offer tradeoffs. Leaders who keep searching for a perfect option end up stuck in analysis paralysis instead.
- Limited trust in the team. When executives do not trust a team’s recommendation — often because the team is under-experienced or under-coached — they re-litigate decisions in the weeds instead of trusting the process.
Tips for Developing Cross-Functional Alignment
Drawing from experiences running early-stage to late-stage drug development including rare-disease programs, these core principles will help round out the picture:
Operational Best Practices
- Build relationships before you need them: Cultivate cross-functional relationships early — gather signal from discovery research long before it becomes formal data and understand each function’s real constraints (how long certain experiments take, when CMC material can realistically be available) rather than assuming timelines can simply be compressed.
- Stagger programs deliberately: Programs succeed and fail at different points in their lifecycle. Careful staggering avoids “dead space” where the organization has nothing moving forward.
- Be skeptical of data used to defend a position: Teams often present data to support their preferred conclusion, but the underlying data are rarely as clean as the narrative suggests. Good program leadership knows the difference.
Strategic Approach
- Start with the patient and work backward: The strongest programs pair patient need with the promise of the biology and work out from there — what the preclinical program needs to demonstrate, what the clinic can realistically deliver, and what regulators will actually require. Example: A past program needed to show a direct clinical benefit, but the relevant disease phenotype in animal models only emerged too late for the company’s timeline to sustain. That mismatch between biological reality and program feasibility must surface early.
- Involve all functions from day one: Biology, Clinical, Regulatory, CMC, Business Development, Commercial, and Patient Advocacy should be at the table from the start. Waiting to loop in Commercial or Patient Advocacy almost always costs more.
- Track competitors but don’t be limited by them: A differentiated technology or approach can solve what others couldn’t. Just because it hasn’t been done before doesn’t mean it can’t be done now if the right science, tools, and regulatory environment are finally converging. Challenging the status quo and leaving room for serendipity is valuable — but have a clear ‘go/no-go’ timeframe so exploration doesn’t become indefinite delay.
With all this laid out, you might ask what we do at Lifordi Immunotherapeutics for Program Management? We are a very small company (<15 people) working on developing ADCs for I&I indications. The Phase 1a healthy participant study was completed earlier this year in Australia. We are now enrolling patients with Rheumatoid Arthritis in Eastern Europe and initial data is expected at the end of this year. So there are a lot of moving parts with the program including global supply chain challenges caused by the ongoing conflicts in this region of the world.
Currently, we have external consulting PM support with our CMO serving as the PL and the management team working together to review the program every week. As we transition to a global Phase 2 trial, we will need to re-evaluate how the Program Team is set up to maximize efficiency and communication between the functions. Ultimately, Program Management needs to be flexible to meet the needs of the company and its goals.
Getting with the Program
None of this is really about process for its own sake. It’s not about just knowing how to develop and manage a Gantt chart — although I’ve always been impressed by people who maneuver these well, especially on the fly during team meetings. It’s really all about understanding the power of Program Management. Get the team right, back them with leadership support, and build a solid structure with clear governance, honest constraints, and genuine cross-functional trust. This will enable a lot of the decision-making and execution problems that plague drug development programs to become more efficient, and you dramatically increase your probability of success. When you ‘Get with the Program’ you can ‘Manage’ to get good science to patients.
