Podcast Transcript

David Brühlmann [00:00:38]:
Engineering a cell to carry two payloads is one thing. Making it find a tumor, do its work, and stop before harming anything else is another challenge entirely.

In this second part, Jun Yung Woo takes us deeper into AGEM Bio’s approach—from the mechanisms behind their lead candidate, AGEM-102, to the questions of control, persistence, and manufacturing that determine whether a promising platform becomes a real therapy. All of it points toward a potential new source of hope against glioblastoma, one of the most aggressive cancers in medicine.

In your Phase I study, you chose a challenging target—glioblastoma, one of the most aggressive cancers. Why go after such a difficult indication?

Jun Yung Woo [00:02:43]:
Most people ask us why we chose glioblastoma first. Actually, I think the question should be: why wouldn’t we choose glioblastoma first? Glioblastoma represents one of the clearest examples of a disease where current therapies struggle. It is highly invasive, highly heterogeneous, and profoundly immunosuppressive. Once the disease recurs, treatment options become very limited.

So if our platform truly has the ability to deliver localized chemotherapy and localized immune activation, then GBM is exactly the type of disease that should matter.

What also intrigued us is the biology itself. Many GBMs have defects in innate immune signaling. Some have STING silencing; others have deletions in chromosomal regions. For example, loss of the 9p21 locus or deletion of components of the interferon cluster. In other words, these tumors are often deficient in the very pathways we are trying to engage. We did not choose GBM because it was easy. We chose it because the biology is compelling, and we believe we can make a meaningful difference in its treatment.

David Brühlmann [00:03:53]:
And how does the treatment look from a patient’s perspective? Also, what are the challenges? For example, you have the blood–brain barrier. How do you deliver what you need to deliver into the brain? How does that work?

Jun Yung Woo [00:04:05]:
From a patient’s perspective, everything begins with surgery. As you may know, even in recurrent cases, the standard of care is surgery. So the tumor has to be surgically debulked.

For recurrent patients who are eligible for a second surgery—because they have already undergone a first surgery that failed—and who consent to participate in the clinical trial, AGEM-102 would be administered during the surgical resection. The cells are prepared before surgery and are delivered directly into the resection cavity after the tumor is removed.

From our perspective, this is one of the best approaches. The surgeon has direct access to the tumor bed and the residual disease. Most likely, there will still be residual disease, because in brain surgery you cannot resect with large margins. This is exactly where we want to place the MSCs—to target the remaining disease.

After surgery and cell administration, the patient takes oral 5-FC. The engineered MSCs then act as local bioreactors, converting the 5-FC prodrug into the active chemotherapeutic agent 5-FU within the surgical bed. The primary goal of this Phase I study is safety. But we will also naturally look for signals of biological activity, including progression-free survival and other clinical indicators.

For a disease like GBM, where survival is very low, even modest improvements can be highly meaningful for patients.

David Brühlmann [00:05:41]:
Absolutely. That is a huge unmet medical need, no doubt about it. How do you handle the diversity of this cancer? There are many different pathways involved. How can you treat such a wide variety of patients?

Jun Yung Woo [00:05:58]:
GBM has two defining characteristics, and interestingly, these are also the reasons why we believe MSCs can be effective in this setting.

The first is that GBM is highly infiltrative. Even after what appears to be a complete surgical resection, microscopic disease almost always remains. This is one of the reasons recurrence is nearly inevitable in many patients. We try to address this by placing MSCs directly into the surgical cavity so they can target residual disease. The second is heterogeneity. GBMs are notoriously heterogeneous.

This is where our strategy differs significantly from antigen-directed approaches such as CAR-T cells and other engineered immune cells. We are not relying on recognition of a specific tumor antigen. Instead, we target biological vulnerabilities that are broadly shared across tumor subclones—such as DNA damage susceptibility, immune suppression, and interferon pathway deficiencies. These are common hallmarks across GBM cells, even across diverse subpopulations within the tumor. That is why we believe this approach has the potential to remain effective even in such a heterogeneous tumor environment.

David Brühlmann [00:07:27]:
With your allogeneic therapy, how do you overcome immune rejection?

Jun Yung Woo [00:07:32]:
One of the main reasons MSCs are so attractive clinically is their unique immunological profile. Unlike many other cell types, MSCs express relatively low levels of MHC molecules, which are key mediators of immune recognition. In addition, MSCs secrete a range of factors that actively modulate immune responses.

As a result, allogeneic MSCs have been used extensively in clinical trials and have demonstrated a strong overall safety profile. Approximately 50% of MSC trials worldwide use allogeneic sources.

Interestingly, tumors themselves often contain MSC-like stromal populations. In some ways, the tumor microenvironment is already accustomed to interacting with cells of this lineage. This does not mean immune rejection is impossible, but MSCs likely provide a uniquely favorable starting point for developing off-the-shelf cellular therapies.

David Brühlmann [00:08:36]:
Assuming your clinical trials are successful, at some point you will need more material to treat more patients. This directly correlates with larger production volumes.

On one hand, you have an advantage because this is an allogeneic therapy, so scaling is potentially easier than with an autologous therapy. On the other hand, there are still challenges because it is donor-dependent—you have variability in donors and variability in the manufacturing process itself.

How does scale-up and GMP production work for this as you move toward commercial manufacturing?

Jun Yung Woo [00:09:16]:
When we present ourselves as a modified MSC therapy, many people think the modification step is the hardest part. But I think the real challenge is not transfection itself—the hardest part is reproducibility.

Anybody can make a good batch once, but can you consistently make high-quality batches hundreds of times under GMP conditions? As you rightly pointed out, every donor is slightly different, every expansion behaves differently, and every manufacturing step introduces variability.

The challenge is to create a process that is robust enough so that the final product remains functionally equivalent despite these sources of variation. One thing we are particularly proud of is that we designed the engineering platform with translation in mind from the very beginning.

Many technologies work beautifully at bench scale but become extremely difficult to scale under GMP conditions. We have spent years simplifying the workflow, defining critical process parameters, and developing potency assays to ensure smooth technology transfer.

So we do have a process in place, and we have iterated it many times to ensure it performs reliably in a GMP setting. Along the way, we have developed significant know-how to fine-tune the process. That is what makes the system robust and reproducible at scale.

David Brühlmann [00:10:50]:
That’s fantastic, and I’d like to commend you for starting with the end in mind. This is something I often emphasize on this podcast: smart biotech scientists should always consider GMP manufacturing from the very beginning of development. So thank you for highlighting that. This is exactly the right approach.

Now let’s talk about the potential of this therapy. You are currently focusing on glioblastoma, but beyond that, do you have other indications in mind? And ultimately, where do you see this platform evolving?

Jun Yung Woo [00:11:27]:
Honestly, GBM is just the beginning. When we think about AGEM-102, we don’t see it as a glioblastoma therapy—we see it as a platform cancer therapy. The real question is whether engineered MSCs can become a generalizable delivery technology.

If the answer is yes, then the possibilities are quite broad. In solid tumors such as sarcomas, liver cancers, and peritoneal malignancies, we have already explored these in preclinical studies. There is also potential beyond oncology, in regenerative medicine and chronic inflammatory diseases.

The exciting part is that once the engineering and manufacturing challenges are solved, changing the payload becomes relatively straightforward. The cell remains the same—the MSC—but the biological program encoded within it can be changed. That is what we hope to develop, and that is the essence of MSC 2.0.

David Brühlmann [00:12:37]:
As we are wrapping up, what additional question should I have asked?

Jun Yung Woo [00:12:41]:
One question we often get is: after the Phase I clinical trial, what is the next step for AGEM Bio and AGEM-102? Coming from Singapore, we are very aware that it is a small country. It has an excellent healthcare system, but a limited patient population.

Even for our glioblastoma trial, we are planning around 10 to 12 patients, and clinicians estimate that recruitment may take one to two years. To move beyond this stage, we will need to look internationally and collaborate with partners to expand access and conduct further studies.

When developing a biotech therapy, it is important to think beyond the present—beyond the immediate trial. What do we envision for this therapy if it succeeds, and what do we do if it does not?

For AGEM and AGEM-102, we recognize this limitation and are actively seeking international partners, clinicians, and cancer centers interested in collaborating to bring this therapy to a larger patient population.

David Brühlmann [00:14:06]:
What is the most important takeaway from our conversation?

Jun Yung Woo [00:14:10]:
I think if there is one thing I would like people to remember, it is this: For a very long time, we have treated stem cells as the therapy. I think the next chapter is treating stem cells as programmable therapeutic vehicles.

Once you can reliably engineer them, manufacture them, and preserve their function, you are no longer limited to what the cell naturally does. You are limited only by what biology you can encode into these cells. That is the vision behind MSC 2.0. For us, I think we are only beginning to scratch the surface of what is possible with these cells.

David Brühlmann [00:14:48]:
Fantastic, Jun. Where can people get in touch with you and learn more about MSC 2.0?

Jun Yung Woo [00:14:55]:
You can find me on LinkedIn—Jun Yung Woo. I’m also on LinkedIn under that name. You can also visit our website at AGEM Bio, and you can reach me directly via email at AGEM Bio. Thank you.

David Brühlmann [00:15:10]:
Excellent. Thank you so much, Jun, for being on the show today, for sharing your passion, and for working on solutions in a therapeutic area where there is still so much unmet need. We need people like you to help move the field forward. Smart Biotech Scientists, you have all the notes and information in the show notes. Please reach out to Jun and his team. And Jun, thank you once again for being on the show today.

Jun Yung Woo [00:15:34]:
Thank you so much, David. It was definitely a pleasure talking with you.

David Brühlmann [00:15:38]:
The story of engineered MSCs is, at its core, a story about precision: directing a cell to the right place, controlling what it does once it arrives, and proving that what works at the bench can be made reliably at scale.

If this episode was worth your time, please leave a review on Apple Podcasts or your favorite platform. It helps others find the show. Thank you so much for tuning in, and I’ll see you next time.