Фармацевтические компании должны пересмотреть стратегию ко-разработки препаратов на ранних этапах

Co-development is an established concept. The practical question is how early its logic should shape candidate selection, development planning, and portfolio governance. Combination therapy is routine in oncology, and investigational co-development is not a new concept. Regulatory frameworks have long addressed circumstances in which two or more investigational therapies may appropriately be developed together. The practical question is organizational: What should R&D do differently when the biology suggests from the beginning that the intended therapy may require multiple components? Drug development is usually organized around individual assets. A molecule is discovered, optimized, selected, and advanced. If later evidence suggests that greater activity requires another therapy, a combination strategy may follow. For many programs, that sequence is exactly right. But in selected cases, the therapeutic hypothesis may point to a combination much earlier. If meaningful activity appears likely to require simultaneous intervention against complementary mechanisms, R&D leadership may need to ask a different question: What are we actually trying to develop: an individual drug that may later be combined, or a therapeutic strategy whose components need to be developed with one another in mind? That distinction can influence decisions well before a combination reaches the clinic. Start With The Therapeutic Hypothesis The starting point should not be combination development itself. It should be the strength of the therapeutic hypothesis. Cancer biology is interconnected, and resistance or bypass mechanisms can limit the effect of inhibiting a single target. But biological plausibility, pathway interaction, or an interesting synergy experiment is not enough to justify coordinated development. The threshold should be high. The evidence should support a compelling expectation that simultaneous intervention will produce a meaningfully better therapeutic result and that developing the components principally as independent agents may not adequately test that hypothesis. If that threshold is reached, the organizational question becomes relevant. Instead of asking only, “Is this molecule an attractive development candidate?” teams can also ask, “What intervention does this biology appear to require?” Most of the time, the answer will still be one drug. Sometimes it may be more than one. Candidate Selection May Need To Reflect The Intended Therapy Traditional candidate selection appropriately considers the pharmacology, pharmacokinetics, safety, and overall developability of an individual molecule. If the therapeutic hypothesis depends on multiple components, those considerations remain necessary, but they may not be sufficient. The individually strongest molecule does not automatically produce the strongest therapeutic strategy. A component with modest single agent activity could still be important if it blocks a mechanism essential to the activity or durability of the combination. Conversely, two individually attractive molecules do not automatically make an attractive combination. The evidence package therefore needs to answer a broader set of questions. Does simultaneous intervention produce materially greater or more durable activity? Is the effect reproducible across relevant models? What does each component contribute? Are the required exposures compatible? Can a biomarker identify the biological context in which the combination is most likely to matter? The objective is not to lower the bar for individual molecules. It is to ensure that candidate selection decisions reflect the therapy that the organization ultimately intends to test. Build The Development Case Across Functions If a therapeutic hypothesis involving multiple components is being considered seriously, cross functional development questions should influence the program earlier. Translational teams need to establish whether the mechanistic rationale is robust enough to guide candidate selection. Clinical pharmacology needs to assess compatible exposures and schedules. Biomarker strategy needs to identify the patients most likely to depend on the combined intervention. Safety teams need to understand whether overlapping toxicities could make the strategy impractical. Clinical development needs a credible way to establish the contribution of the individual components. Manufacturing needs to know whether both can be supplied on compatible timelines. These activities are not new. The difference is when they begin shaping the definition of the program. Under a coordinated approach, functions do not simply support a combination strategy after it has emerged. They help determine whether the strategy is scientifically and operationally viable before the organization becomes committed to developing each asset independently. That feasibility assessment matters. A scientifically compelling combination can still fail as a development strategy if the components cannot be manufactured on workable timelines, their regulatory paths cannot be aligned, intellectual property or partnering constraints are prohibitive, or the clinical program cannot generate interpretable evidence. The biology may define the opportunity, but the organization still has to determine whether it can execute it. Make It A Portfolio Decision This is where the framework moves beyond project team execution. Pharmaceutical companies are understandably structured around assets. Individual molecules have owners, budgets, milestones, development plans, regulatory strategies, and valuation assumptions. A therapeutic strategy involving multiple investigational components can cut across those structures. The components may sit in different project teams or research groups. One may look stronger as a standalone asset than the other. They may compete for resources or carry different partnering and intellectual property considerations. If the therapeutic hypothesis depends on both, evaluating them entirely independently creates a governance problem. Each asset team can make a rational decision for its own molecule while the organization fails to optimize the therapeutic strategy as a whole. Coordinated development therefore becomes a portfolio decision. Leadership may need to determine whether the components should share a therapeutic hypothesis, major decision points, investment assumptions, and governance, even while each retains the scientific and regulatory work required for an individual investigational drug. The key question is accountability: Who owns the performance of the therapy when success depends on more than one asset? If no one does, each team will naturally optimize its own molecule, timeline, budget, and milestones. The organization also needs accountability for optimizing the intervention as a whole. Create An Explicit Decision Gate The implication is not that combination development should become the default. The practical change is to make the definition of what is being developed an explicit leadership decision. Before a program becomes fully organized around individual assets, ask these four questions: What does the biology suggest the intended therapy actually requires? Is one mechanism reasonably expected to produce meaningful activity, or is there compelling evidence that another must be addressed simultaneously? Is the evidence strong enough to justify a different development model? Mechanistic plausibility or isolated synergy should not be sufficient. The expected therapeutic advantage must justify the additional scientific, regulatory, operational, and financial complexity. Can the components be developed as a coherent program? That includes component contribution, biomarkers, exposure, safety, manufacturing, regulatory strategy, intellectual property, partnering, and clinical execution. Should leadership govern and invest in the intervention as one therapeutic strategy? If success depends on multiple components, accountability should exist for the whole strategy, not only for each asset. In many programs, these questions will reinforce the conventional answer: advance the individual drug and allow combinations to emerge as the evidence develops. But in selected cases, they may lead to a different conclusion, with the biology influencing development architecture much earlier. Follow The Logic Upstream Investigational co-development is already an established concept. The purpose here is not to rename it or suggest a new scientific principle. It is to consider what happens when its logic is applied further upstream in R&D. If the intended therapy appears to depend on multiple mechanisms from the beginning, that assumption may need to influence preclinical validation, candidate selection, translational strategy, clinical pharmacology, biomarkers, manufacturing, regulatory planning, portfolio governance, partnering, and capital allocation. Seen this way, co-development is not only the point at which two investigational drugs enter the same clinical trial. In selected programs, its logic can begin with the therapeutic hypothesis and extend through the decisions that determine which molecules are selected, what evidence is generated, how resources are allocated, and who is accountable for the program as a whole. The individual drug will appropriately remain the primary unit of development in most cases. The question is whether it should automatically be assumed to be the right unit before the biology has answered that question. When the evidence strongly suggests that meaningful therapeutic activity depends on multiple coordinated interventions, R&D leadership should at least ask whether it is developing separate drugs that may someday be combined, or whether it is developing a therapy whose components need to be considered together from the beginning. About The Author: Professor David Adler, M.D./Ph.D., MBA, is a senior pharmaceutical leader in oncology clinical drug development and translational medicine with more than 15 years of industry and academic leadership experience. He spent a decade in senior leadership at Bayer AG’s Global Oncology Clinical Development organization and currently serves as Chief Scientific & Medical Officer of the PATHORA Institute of Pathology & Tissue Medicine. He also holds academic appointments at the Hebrew University of Jerusalem, Ben-Gurion University of the Negev, and the University of Bonn.