Target Product Profile 101 for Biopharma Startups
Target product profile (TPP) is a term that is used a lot in the biopharma world. For many biotech startups that are founded by scientists or technologists who were never involved in drug development, especially in clinical stage, this might be a foreign concept. Based on experiences developing TPPs for both large pharmaceutical companies and small biotech startups, I have decided to write an article to explain the what, why, and when of TPP so that biotech startups can fully understand, embrace, and leverage it to truly turn their groundbreaking science into life-saving and life-transforming therapies.
What is a TPP?
In the biopharma world, it is a document that outlines the key attributes of a therapeutic product a company is trying to develop. Some of the key attributes include:
Indication: What is the disease and patient population a drug is designed to treat? Some key elements of an indication statement include disease, stage or severity, line of therapy, biomarkers, etc.
Efficacy: What kind of efficacy a drug is expected to deliver? Depending on the stage of development, a TPP could have just one primary efficacy endpoint that matters the most from the clinical, regulatory, and commercial perspectives for a preclinical-stage asset or multiple efficacy endpoints for a mid-to-late-stage clinical asset.
Safety and tolerability: While efficacy is important for a drug, so is the safety and tolerability profile of a drug. Similar to efficacy, the safety and tolerability section of a TPP generally does not have too many details at the preclinical stage. As more and more data become available during preclinical and early clinical testing, more details can be provided in this section.
Route of administration: For many chronic diseases, dosing convenience is of great importance to patients. This is the section where a company sets the target for how the drug will be administered and in what frequency. Depending on the modality of a drug, a company might not have too much flexibility in terms of route of administration. For example, currently it is still not technically feasible to make an oral drug out of a monoclonal antibody.
Why do you need a TPP?
Imagine you go to device engineers at Apple and tell them you want a new smart phone, but you do not tell them anything about what you want the new smartphone to be able to do. It is the same thing if you, as a CEO of a biopharma startup, just tell your scientists to develop a drug against a novel drug target, without providing the specifications of the new drug. What do you expect them to do? They might struggle to initiate the work, or worse yet, they might spend millions of your previous dollars developing a drug that is not effective or even harms patients. Here are a few important reasons for developing a TPP:
Provide goalposts for product development: Baseball legend Yogi Berra once said, “If you don’t know where you’re going, you’ll end up somewhere else.” This is so true for drug development. Only after you develop your TPP, your drug development team will know what kind of drug molecule they need to deliver and your clinical development team what kind of clinical trials they need to design.
Facilitate internal go/no-go decision-making: Another important utility of a TPP is to facilitate internal go/no-go decision-making regarding an asset. If the readout from a clinical study does not meet the pre-specified thresholds in the TPP, it is often the basis for a no-go decision. Without a TPP, a company could kill an otherwise promising asset, or continue to advance an asset that is not going to be clinically or commercially viable.
Communicate product vision externally: This is particularly important for startups. Oftentimes, investors might not have intimate knowledge of a therapeutic space. It is up to the startups to communicate the vision of their potential drug, how it will fit in the future treatment paradigm, and why it will be differentiated. TPP is the basis for a product story.
When do you need a TPP?
The simple answer is YESTERDAY! OK, that is a terrible consultant joke because clients always say they want something yesterday. But in all seriousness, a TPP should be developed before a company starts a new therapeutic development program. It is important to remember that a TPP is a living document. A team should periodically review the internal and external data and make necessary changes to its TPP so that it remains clinically and commercially attractive. It is also worth noting that a TPP for a preclinical-stage asset is much simpler than for a clinical-stage asset. Many startups decide not to develop a TPP because they are overwhelmed by a granular TPP that is often associated with a late-clinical-stage asset. In doing so, they miss an opportunity to set early goalposts for their scientists to design a differentiated molecule.
With that said, it is never too late to start developing a TPP no matter the stage of an asset. Yes, a company might have missed some early opportunities of leveraging the TPP for internal and external purposes, but it can still use a TPP to make sound future decisions and effectively communicate its product story to investors and pharma partners.
The Five Most Common Mistakes in Developing a TPP
#1: Neglect TPP development
Many preclinical-stage companies, especially technology platform companies, never develop a TPP despite boasting dozens of therapeutic programs in their internal pipeline. This is a dangerous practice for a number of reasons.
Without goalposts in the form of a TPP, discovery scientists don’t know what kind of molecules to deliver for human testing. The company could end up with a sub-optimal molecule that is destined for clinical or commercial failure from day one.
Without a TPP, a target compound profile cannot be developed. As a result, there are no goalposts when it comes to the biochemical and biophysical properties of a molecule. Discovery scientists could spend years perfecting a molecule, when in fact the optimized lead from 2 years ago is good enough to progress into non-GLP tox studies.
If a company does not have a TPP for a therapeutic program, chances are it does not understand the therapeutic space it is planning to compete in. That might have been OK two years ago at the peak of the biotech boom, but now you are likely to be laughed out of the room if you are proposing a therapeutic drug without articulating the unmet needs, target patient population, and your asset’s differentiation.
Based on my experience working with biotech startups, TPP is an area where I see the separation between a sophisticated drug development team vs. one that has little collective drug development experiences – the mentality between TPP guiding everything they do vs. TPP being an afterthought.
In a capital-constrained world like we live in today, it is imperative to have a well-thought-out TPP before you invest millions of previous investor dollars on a therapeutic program!
#2: Over-think a TPP
One of the common pushbacks I heard from startups on TPP development is we are so early in our development and there is so much we don’t know about our molecule yet, so it’s impossible to develop a TPP. While this pushback has some merit, it is based on a wrong assumption – TPP should be as granular as possible. But the truth is at this early stage a TPP should focus on high-level goals rather than granular details.
For example, if you are trying to develop a small molecule for Alzheimer’s disease, at the discovery stage, it is impossible to know what the potential off-target liabilities might be, so it would be pointless to try to spell out detailed safety parameters such as liver enzyme elevation. But what you can do at this stage is to set some high-level goals, such as no boxed warning. With this goal, at least discovery scientists know they have to deliver a rather selective molecule.
Another example is around dosing frequency. Based on the disease state and competitive landscape, you should have a good idea early on whether a three-time-a-day dosing would be viable. For a chronic inflammatory disease with a once daily oral pill already available, a three-time-a-day dosing is not a good idea unless the drug works wonders. Once you put once daily or twice a day dosing frequency in your TPP, your discovery scientists at least know they have to develop a molecule with decent metabolic stability.
In a nutshell, at discovery stage, you just need a simple TPP to guide discovery scientists for their design of a molecule. It is very different from clinical stage, where you need a more granular TPP to guide clinical researchers for their design of clinical trials and enable leadership team to make go/no-go decisions at each stage gate.
#3: Lack of cross-functional collaboration in TPP development
Based on my past experiences working for two large pharmaceutical companies and two startups and consulting for numerous biotech clients, different companies have different philosophies about TPP and which function is accountable for TPP development.
Having observed diverse approaches to TPP development, I think the best approach is through cross-functional collaboration, where one function may lead TPP development, but inputs from other relevant functions are incorporated. This is the only way to make TPP truly a North Star for a therapeutic program. Here are a few reason:
For a clinical-stage asset, clinical development function is often tasked to develop a TPP. Their top priority is to achieve technical and regulatory success. Without inputs from commercial and market access functions, the TPP will reflect the singular focus on achieving technical and regulatory success. Consequently, the drug might not satisfy the requirements for commercial success.
TPP can be thought of a contract between various functions within a biopharma company – that is unless the asset achieves pre-specified goals in the TPP, a company should not proceed to the next stage of development. As you can imagine, if this contract has only one “signature” from the function leading TPP development, a company can easily get into a very messy situation during a stage-gate where different functions argue whether an asset’s data meet the requirements for further development.
Lastly, having a TPP agreed upon by a cross-functional team means the entire team aligns to the same vision for the product, minimizing confusion and conflicts internally and enabling better communication externally.
In short, TPP development is an ultimate team sport, requiring key functional stakeholders' involvement regardless of the leading function.
#4: Failure to make TPP future-proof
When a company develops a TPP, it is usually dealing with an asset that will reach the market years later, so it is important to consider what the future treatment landscape would look like and what kind of drug would be competitive in that future state.
Unfortunately, many companies are too focused on developing a TPP that is competitive against the current standard of care. While this might serve the purpose of having goalposts for a therapeutic development program, it most likely will not lead to a clinically and commercially attractive product by the time the product launches.
What a company must do instead is start out with the current standard of care as TPP benchmark, but also research what clinical performance other promising pipeline assets might be able to deliver in the future. There is no hard and fast rule about which pipeline assets should be included and how early a clinical trial dataset is too early to be considered. Ideally, you should consult with clinical experts in the therapeutic space for inputs.
Another important aspect of TPP development is consider payer needs in the future. Market access has become more and more challenging over the last decade or so, and this trend is unlikely to reverse. Therefore, a TPP must consider what kind of data will be needed to ensure optimal access when the product launches. For example, if the current standard of care is a branded twice-a-day pill, you might think a once daily pill with slightly better efficacy might ensure good access. That might be true if you were launching the drug today, but once the current standard of care goes generic, chances are payers will require patients to fail the current standard of care first, which will shrink your market share considerably.
#5: Failure to update a TPP
Many companies put in the effort to develop a TPP but made the mistake of not updating it periodically. The consequence is the TPP becomes outdated in the context of changing competitive environment and new data for their assets. Those companies most likely will discover their products are no longer clinically and commercially competitive only when it is too late. Here are some examples:
A competitor’s drug in the same class just revealed its Ph3 data with efficacy better than what is in your TPP. If you decide to not increase efficacy bar in your TPP or identify any other points of differentiation, chances are you will be wasting a lot of time and money to develop and launch an inferior drug with little return on investment.
From your Phase 1 trial, you saw elevation of certain liver enzymes. Your previous TPP might be plain vanilla when it comes to safety and tolerability, but now is the time to conduct some market research to understand the thresholds of liver enzyme elevation, below which the product is still clinically and commercially viable and put them into your TPP. Better yet, given this new information, should you think about what target patient population is more appropriate?
Updating TPP periodically is not rocket science, but the hard part is to establish a process within a company to ensure everyone understands the what, when, who, and how.