Oral Combination Therapies: Navigating Development Complexities
A conversation with Joel Latham, President and CEO, Incannex Healthcare
Route of administration is often discussed as a downstream consideration in drug development, but for many therapies, delivery strategy can shape everything from formulation design and manufacturing to patient adherence and commercial success. As the industry continues to pursue more patient-centric treatments, developers are increasingly being challenged to balance scientific objectives with practical realities such as convenience, tolerability, and long-term persistence on therapy.
Few areas illustrate this challenge more clearly than oral drug delivery, particularly when working with complex molecules, fixed-dose combinations, or emerging therapeutic categories such as cannabinoid-based medicines. In this Q&A, Life Science Connect’s Michelle Raley caught up with Joel Latham, president and CEO of Incannex Healthcare, to discuss how delivery strategy influences development decisions, lessons learned from advancing the oral sleep apnea therapy IHL-42X, and his perspective on the future of patient-centric drug delivery.
When you evaluate a new therapeutic, how much does the route of administration factor into the earliest stages of development? What makes you decide that oral delivery is the right strategy versus pursuing another route, and how do you balance pharmacokinetics, patient adherence, convenience, and ultimate commercial viability?
Route of administration should be considered early because it can influence almost every aspect of a development program, from formulation and manufacturing to patient adherence and how a therapy ultimately fits into clinical practice. At Incannex, the starting point is the patient and the disease. We look at what prevents patients from using existing treatments consistently and what type of therapy could realistically fit into their lives. Pharmacokinetics and clinical performance are fundamental, but convenience, tolerability, and long-term adherence also matter, particularly in chronic conditions.
Oral delivery can be attractive when it provides an effective and practical treatment option without adding unnecessary complexity for patients or healthcare providers. That thinking has informed our approach to IHL-42X, our oral therapy for obstructive sleep apnea, where some patients struggle to maintain device-based therapies over time. The positive Phase 2 RePOSA results we reported last year, together with the FDA's Fast Track designation for the program, reinforced that view. Ultimately, the route has to support the clinical objective, regulatory pathway, manufacturing strategy, and real-world use of the product. All of those considerations should be part of the target product profile from the beginning.
IHL-42X combines dronabinol and acetazolamide in a fixed-dose oral formulation. What are some of the formulation and drug delivery challenges involved in putting two pharmacologically distinct molecules into a single dosage form — and what have you learned about designing fixed-dose combinations that could be useful to other drug developers?
Fixed-dose combinations require a disciplined development strategy. Combining two compounds increases the importance of formulation, dose selection, manufacturing, quality, and consistency, and those considerations need to be addressed early in the program. With IHL-42X, the rationale is based on combining two known agents that target complementary biological pathways in obstructive sleep apnea within a single oral therapy. The objective is to achieve a meaningful therapeutic benefit while maintaining a treatment format that is practical for patients.
One lesson that applies more broadly is that a combination should have a clear clinical rationale. The additional development and manufacturing complexity needs to be justified by the potential benefit of addressing multiple drivers of disease or improving how patients use the therapy. Regulatory planning is also important from the outset. Existing compounds do not automatically create a simple development path. Developers still need clear evidence of safety, efficacy, quality, and consistency for the combination itself.
Cannabinoid molecules can present some interesting delivery challenges, including issues around bioavailability and variability in exposure. What have you learned about delivering cannabinoids orally in a way that produces sufficiently predictable exposure, and what formulation or manufacturing considerations have been most important?
Consistency is critical when developing cannabinoid-based medicines. Moving cannabinoids from early-stage research into regulator-ready pharmaceutical products requires standardized pharmaceutical-grade formulations supported by controlled clinical development and appropriate manufacturing standards. With IHL-42X, which includes dronabinol, our approach has been to build those considerations into development from the beginning. Formulation, dose selection, manufacturing, safety monitoring, and the regulatory pathway need to be aligned so that the therapy administered in clinical trials is consistent, well characterized, and appropriate for the intended patient population. Achieving this alignment begins with a detailed understanding of the product’s pharmacology and how its formulation influences absorption, exposure, duration of effect, tolerability, and potential interactions with other medicines. Dose selection must then be supported by clinical and pharmacokinetic evidence demonstrating that the chosen regimen can deliver a predictable therapeutic effect while maintaining an acceptable safety profile.
These requirements are especially important for cannabinoid-based therapies. Differences in formulation, route of administration, purity, composition, and the presence of minor constituents can materially influence how a product performs. Cannabinoids may also present development considerations relating to variable bioavailability, psychoactive effects, impairment, drug–drug interactions, abuse potential, and the stability of active ingredients over time. Unless these factors are carefully controlled, it can be difficult to determine whether a clinical outcome is attributable to the active pharmaceutical ingredient, the formulation, the dose, or variability in the product itself.
Pharmaceutical-grade manufacturing standards, validated analytical methods, clearly defined product specifications, and robust quality controls are therefore essential. These measures help establish consistency between manufacturing batches, support reliable dosing across study sites, and provide regulators with confidence that clinical findings can be reproduced in larger trials and, ultimately, in routine clinical practice. Early regulatory engagement is also valuable in ensuring that the evidence generated throughout development is relevant to the requirements for potential approval.
The field will be judged by the same standards as any other pharmaceutical category, with clear evidence of safety, efficacy, quality, and reproducibility. For us, the priority is developing cannabinoid-based therapies as medicines, with the clinical and regulatory rigor required to support potential approval and real-world use.
Your pipeline takes a fairly deliberate approach to oral delivery across multiple therapeutic areas. How much of that is driven by the underlying science versus a strategic decision to pursue dosage forms that are easier for patients and healthcare systems to adopt? In other words, when does patient-centric delivery become a key part of your target product profile?
Patient-centric delivery should be part of the target product profile from the beginning. At Incannex, we consider it alongside the underlying biology and clinical objective when evaluating how a therapy should be developed. Strong science is essential, but a therapy also needs to be something patients can realistically use and clinicians can confidently prescribe. The underlying biology and clinical objective determine whether an oral approach is appropriate. Once that is established, we also consider how the treatment will fit into a patient's daily life, how it will be manufactured and delivered, and whether it can integrate into existing care.
This is important in chronic conditions, where long-term persistence can determine long-term outcomes. Convenience, tolerability, and patient preference can have a significant impact on whether a therapy that performs well in clinical development delivers the same value in practice. That thinking is reflected in programs such as IHL-42X. Developing an oral pharmaceutical option for obstructive sleep apnea could provide another treatment choice for patients whose needs are not fully met by existing approaches.
There is increasing interest in alternative routes of administration to improve bioavailability, reduce systemic exposure, or make difficult-to-deliver molecules more practical. Looking across the broader pharmaceutical landscape, which emerging delivery technologies or administration routes do you think are genuinely capable of changing clinical development — and which ones do you think are receiving more attention than the science currently warrants?
The delivery technologies with the greatest potential are those that solve a clear clinical or patient problem. That could mean making administration simpler, reducing dosing frequency, improving tolerability, or helping patients remain on therapy over time. Drug-device combinations and digital tools can all add value when they reduce effort for patients or providers or generate information that improves clinical decisions.
Looking ahead, I think we will see drug delivery become much more closely tied to how, when, and where a therapy is intended to act. Long-acting formulations and more convenient administration routes will continue to gain importance, particularly in chronic conditions where patients may otherwise need to take medication every day for years. I also expect greater interest in technologies that can provide more consistent drug exposure over time, rather than relying on the peaks and troughs that can come with conventional dosing.
We may also see the distinction between the drug and its delivery system become less pronounced. In some cases, the delivery technology could become a central part of the therapeutic strategy itself, helping determine where a drug acts, how long it remains active, or how reliably patients receive it. That creates the potential to revisit compounds that may have shown promise pharmacologically but were limited by how they could be administered or tolerated.
New administration routes can also be important when they meaningfully improve the therapeutic profile or make a treatment practical for a patient population that does not have a good option today. The key is demonstrating that the technology improves the product in a clinically meaningful way. Added complexity creates additional development, manufacturing, and regulatory considerations, so there needs to be a clear benefit behind it.
My prediction is that some of the most important therapeutic breakthroughs of the next decade will come not from discovering new molecules, but from delivery technologies that transform existing compounds into more precise, durable, and practical medicines.
Ultimately, I think the next generation of drug delivery will be judged less by how novel the technology is and more by whether it can make an effective therapy meaningfully easier, safer, or more practical to use. The most successful platforms will be the ones that turn delivery from a limitation into part of the therapeutic advantage.
About The Expert
Joel Latham has served as the chief executive officer, president, and director of Incannex Healthcare Inc. since July 2023. He brings more than 20 years of senior management and operations experience in both public and private sectors. Previously, he was the CEO and managing director of Incannex Australia, where he played a key role in the company’s growth and its successful transition to Nasdaq. Joel has also held senior leadership roles in corporate strategy and global market development at Mars Foods, Tabcorp, and Philip Morris International.