Expanding Therapeutic Targets For Injection And Inhalation With Phillips Medisize's Geraldine Venthoye

Chief Scientific Officer Geraldine Venthoye from Phillips Medisize joins Supplier Horizons host Tom von Gunden in a conversation about advancements in inhalation and injection for targeting a broader range of patient needs. The two discuss formulation and delivery system challenges for complex, large molecule biologics, including vaccines, immunotherapies, and cell and gene therapies. Venthoye comments on patient access and affordability, digital health and connected devices, chronic disease management, and social and environmental stewardship. 

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Episode Transcript

Tom von Gunden, Chief Editor, Drug Delivery Leader:

Welcome to another episode of Supplier Horizons. My name is Tom von Gunden, chief editor at Drug Delivery Leader and your host for the series. Today I am joined by Geraldine Venthoye, who is Chief Scientific Officer at Phillips Medisize, a CDMO whose offerings include drug delivery systems.

Welcome, Geraldine.

Geraldine Venthoye, Chief Scientific Officer, Phillips Medisize:

Hi, Tom. Thanks for the opportunity to speak to you today.

Well, thanks for joining; it's my pleasure to have you here. So, let's start by looking out over the patient landscape. What's out there in terms of patient needs and therapeutic targets? And what's front of mind for you and the folks at Phillips Medisize when you do look out there at the patient landscape?

Venthoye: It’s a really broad topic, obviously, and it's a constantly evolving landscape. We try to keep that top-of-mind at Phillips Medisize by doing a lot of market insights, frequent engagements with key opinion leaders and subject matter experts. That helps inform our strategic thinking around investments in innovation and capability builds.

But if I was to think of the broad holistic healthcare trends that we see and medical trends, and then really drill down into the therapeutic trends of what it means for drug delivery, what we see is that — in line with healthcare 5.0 and what we understand is healthcare 5.0, which is the next major transformation of healthcare systems — we should expect more and more personalization of healthcare, greater social and environmental stewardship, with better health equity and resilience in healthcare systems in the future. What that means in terms of medicines is that we should expect greater accessibility and affordability in healthcare.

So, real focus on lower cost of goods sold, more generics and biosimilar approvals to lower costs in healthcare, and a rationalization of supply chains, also to reduce costs and simplify, and more local manufacturing.

We should see also a continued decentralization of healthcare provision, so less being centered on the expensive hospital and specialists, driven more towards the localized clinics, pharmacies and to the homes of the patients. So, patients will be taking more control of their own therapy, sharing decision making also with the healthcare providers. And for that, we need to facilitate that by having more intuitive, portable, and self-administered drug delivery. And that includes dealing with the needs of elderly as well as very young patients in that patient group.

We should see healthcare more as preventative care, so maintaining good health and wellness as opposed to just sick care. So, we should expect that digital healthcare is going to be important in the future with interoperability of data coming from various healthcare sources and from the devices themselves. So, having connected devices is still going to be important for the future along with companion diagnostics and biomarkers to allow us to be more preventative. That will mean that software will become more and more a medical device as it intervenes in therapy.

So, that greater patient-centricity and personalization of care is also going to be seen in the types of molecules and therapies. So, more gene and cell therapy, and with that, more biologics, more complex molecules having to be delivered.

Now, these molecules tend to be delivered more on a weekly or monthly basis. The whole pathology of dosing is going to change more to being less frequently dosed. We're not going to see as many multiple times a day, every day type dosing, and that will drive a need for higher payload delivery systems.

And that's all in the context of an aging, growing, and migrating population with a need to be more aware of the impact of their medicines on the environment. So, we should also expect that there will be greater focus on the materials that we use, the complexity of our manufacturing, and the overall impact of our medicines on the environment. So, those are the more general trends that we see.

Great. Thanks for the coverage there. So yeah, thinking about those medicines and treatments and therapies that are being developed for patients: Is there more to say about any of the particular challenges or opportunities related to delivering them to those patients?

Venthoye: So, if I can focus in on some of [the] therapeutic trends that we see and some major medical trends. We will see a continued focus on chronic disease management, especially with the aging population and all the comorbidities that come with that, and the associated polypharmacy challenges that come with comorbidity treatment.

Obesity and diabetes, for example, will continue to be [on] the rise in terms of prevalence. And with that, we've had the global success of the GLP-1s. They're obviously moving towards becoming generic and lifecycle managed. Right now, we have our own pen injector platform within Phillips Medisize — it's called Envoi — in order to address those kinds of opportunities, which are so large, still.

We also expect some of those GLP-1s to be repositioned into other dosage forms. So, nasal delivery of GLP-1s is being looked at, for example. Or, for novel weight management, including novel GLP-1s, that they will be formulated as oral products by first intent. Regardless, we expect to see a still very high volume of injectable use of weight management and diabetes-associated therapeutics.

A second trend that we see is an increasing management of mental health. With the rise in better diagnosis and less stigma and better targeting of therapies for mental health diseases, we should expect to see, for example, the fast-onset-of-action type drug delivery systems, like inhalation and nasal products, being used more for CNS [central nervous system] type developments, including things like treating migraines, anxiety, PTSD [post-traumatic stress disorder], addiction, crisis management.

We see a lot of nasal drug delivery developments in those areas, for example. Nasal drug delivery is an area that is primed for innovation around devices. In the past, very little innovation was really seen in those types of devices. But there's a need for more targeted formulations, [and] also better targeting through devices to areas of the nose that will facilitate better systemic uptake into the circulation. Also, the possibility of blood-brain barrier traversal so that you can actually target the brain directly through nasal drug delivery.

So that's a second area — mental health.

The third area that I would mention would be the unmet therapeutic needs in rare diseases, where we still have lots of diseases with unlicensed medication. Neurogenerative disorders, where there are still no cures, and a lot of investment into those diseases. Antibiotic resistance, the need to overcome the resistance that we see, still.

And then, of course, next-pandemic readiness. We still have a focus on where the next pandemic could come from and how best we could respond better this time in terms of therapies.

Drug delivery has a role to play in all of these areas in terms of being ready with appropriate delivery systems but also providing IP protection in terms of exclusivity that we can bring through combination product developments.

Then the last one I want to talk about — probably the most important one — is more personalization of therapies. So, immunotherapeutics, for example, in oncology and infectious disease — harnessing your own immune system to fight the disease. These are generally cell and gene therapies, which come with the associated challenges in drug delivery of intracellular targeting and transfection. We need to formulate these biologics to deliver them in a way that keeps them stable and conserves their potency, but also allows them to get into the cells and then be released and transfect in the way that they should. That is quite a challenge in terms of delivery systems and formulations, and there's a lot of R&D going on in that area right now.

So overall, we should see a shift from high-volume to high-value type products going forward. There will still be the GLP-1 type opportunities of high volume. But more and more, through the biologics coming on board, we will see lots of high-value type products potentially dosed [with] less frequency, with less volume, therefore, associated with them. Those are the major therapeutic trends that we see.

Gotcha. If you don't mind, let's take a deeper dive into the science and technology. Is there anything you can comment on in terms of the challenges and opportunities when it comes to making advances right down to the science and the technology itself?

Venthoye: Yes, as I mentioned before, the delivery of novel biologics efficiently, while conserving the potency of those biologic molecules, is a huge area of R&D, in terms of both the injectable and inhalation fields. Formulations are becoming far more complex, with nanotechnology and novel matrices being used in those formulations to encapsulate and protect the biologic molecule, whether it be an oligonucleotide or a monoclonal antibody or a therapeutic protein, for example, and then release them, as I said before, intracellularly for transfection.

They will require novel excipients and novel manufacturing techniques to formulate them both in the liquid and the dry powder state to be delivered by inhalation or injection. These products will be of much higher payload because of the degree to which the excipients will need to be there to protect the molecules, but also the dosing of those molecules themselves requires much higher mass.

And so, we should be expecting higher volume injections of higher viscosity. This is an area where novel injection delivery, autoinjectors — looking at delivering those types of systems. But also, in inhalation — higher payloads being delivered through engineered particles to the lung to also affect the transfection in a targeted way.

So, that's an area for a lot of innovation. We have our own mechanical and electromechanical novel autoinjector to be able to dose flexibly to quite a high volume. I think it's 2.25 milliliters and a much higher viscosity, about 200 centipoise, being able to be delivered in a tolerable and user-friendly way. That flexibility in dosing is really important when you are doing clinical studies and trying to look at dose ranging.

And then, in inhalation, we also have a novel dry powder, high payload inhaler to be able to deal with these high payloads coming from the biologic opportunities. The lung and the nose have a large mucosal surface area for absorption, and that's why we see a lot of repurposing from injection to inhalation. We have vaccines that have been repurposed with a COVID vaccine in China, for example, having been approved [for delivery] by inhalation.

We should expect to see more repurposing, both in the parenteral field from IV to subcutaneous and IM [intramuscular] injections, allowing those administrations to come out of the hospital setting into settings that can be more local. But also repurposing from injection to inhalation; we should see more of those types of developments coming to the fore.

Great. Well, as I like to conclude these episodes, I'm going to ask you to look out over the horizon and at the future state and tell us what you see out there in terms of: Should these advances and innovations move forward and take hold, what do you think the landscape of patient lives and health will look like?

Venthoye: Yes, so as I said before about healthcare 5.0, we should expect patients to be more involved in their healthcare, with greater access to their own data. So, taking decisions alongside their healthcare professionals because they have more data coming from multiple sources of their healthcare — both from connected healthcare apps and connected devices, from companion diagnostics that they might be using. And all of this data to be interoperable data amongst all of their healthcare.

We should expect this urgent need to lower the financial burden of care to go into the future. So, we should see that this greater focus on cost reduction and making sure that we have health equity — [that] we have accessibility of medicines by all — is going to be a real focus for years to come. That will mean that we have a really acute need to look at reducing our costs, increasing our efficiencies, and lowering the development timeframes associated with getting our products to market.

As I said before, these products will be highly personalized to patients and more precise in their delivery. Therefore, there will be a bunch of disruptive technologies that will be involved, in terms of the formulations, manufacturing technology, and device technology. We will be using things like microfluidics, 3D printing, and a greater use of automation. Even at the lower scales of development and even at the bench scale, there will be a continued greater leveraging of digital tools in general with artificial intelligence, big data analytics. But also, simulation and modeling data with digital twins being used to cut down the number of experiments that we do physically and to be more predictive to aid the experiments that we do and bring those products to market quicker.

And to conclude, the point about environmental stewardship: Novel materials will become important —materials that are more biocompatible and sustainable. And we will design and manufacture more robust devices that can be used intuitively by the patients so that we can reuse them and recycle them rather than discard them each and every time that we dose a patient.

Gotcha. Well, Geraldine, thank you for joining me to share your perspectives and insights with our Drug Delivery Leader audience. And to that audience, I want to say thank you for joining for another episode of Supplier Horizons. And we'll see you next time.