Bacteria-Based Technology Could Revolutionize Solid Tumor Treatment

Neobe Therapeutics is a preclinical startup based in the UK, focused on addressing a major unsolved challenge in oncology. Despite the availability of several drugs with curative potential for solid tumors, many of them remain ineffective.

We need to enable the curative potential of existing drugs – many are already transformative when they work, but they only do so in a tiny minority of cancer patients.

One of the main reasons these drugs don’t work in solid tumors is, as the name suggests, their solid nature. These tumors are difficult to penetrate. Most are highly fibrotic, and because of this dense fibrotic tissue, it’s challenging for drugs to reach their target. Equally important, it's very hard for immune cells to penetrate these tumors or for the right immune cells to be recruited. The culprit is the extracellular matrix, which forms a dense, fibrous barrier that physically blocks infiltration.

If we can’t get past these barriers, it’s nearly impossible to break down the tumors effectively. At Neobe, we’re tackling this issue by using synthetic biology to design microscopic 'Trojan horses' – bacteria that can infiltrate these tumors and break down the barriers from within.

These bacteria have an inherent ability to colonize tumors, which we engineer to respond to the tumor microenvironment. The bacteria are activated by the tumor, releasing enzymes that degrade the fibrotic material, softening the dense tumor and making it much easier to penetrate. As a result, drugs that were previously ineffective can begin to work in these patients.

We’ve known since the early 20th century that certain bacteria have a natural affinity for tumors. These solid, dense tumors create a unique microenvironment that’s rich in nutrients, hypoxic and protected from the immune system – a perfect setting for bacteria to thrive.

At Neobe, we use safe, commensal-derived bacterial strains that aren’t pathogenic and lack any virulent factors. Rather than engineering them to target tumors – they already know where to go – we leverage their innate ability to colonize tumors.

What we focus on is containment – ensuring the bacteria is only active within the tumor. We achieve this by engineering a biosensor library in the lab. We design synthetic promoters that respond to factors like low oxygen, low pH and metabolite availability. When these conditions are met, the promoters activate, triggering the bacteria to produce an enzyme payload. This enzyme is then linked to a secretion system that releases it directly into the tumor’s extracellular space.

Funding is one of the biggest challenges, especially in such a tough market. However, there’s a growing understanding that this issue needs to be addressed and that’s helped us get to where we are today. I’ve always been confident that if we could make the technology work, it could be transformative.

The key element we needed to get right was the biosensor aspect. It’s crucial to ensure that the bacteria are only active within the tumor and that they are sufficiently activated to produce a meaningful payload. The activation of these promoters must be specific to the tumor and powerful enough to generate enough of the enzyme payload.

This has been the focus of much of our work in the first couple of years of technological development and we’re now very confident in where the technology stands.

The biggest operational challenge we face is that we’re developing a completely new modality. As such, the proof-of-concept threshold is quite high. We need to demonstrate that this works – not just in theory, but in patients – and, of course, we need to prove its safety.

We’ve designed the entire technology with clinical translation in mind, ensuring both safety and efficacy. The proof, as they say, is in the pudding. We’re moving quickly toward our first human clinical trials and we’re actively fundraising to make that a reality. Our goal is to begin phase one trials in 2027. Once we have that data, we believe we’ll see exponential growth.

Our technology has the potential, once proven, to deliver any biologic more effectively into solid tumors. It’s not limited to one specific cancer type; it applies to all solid tumors and the approach is easily adaptable.

We’re designing biosensors and enzymatic payloads, and currently, we have four prototypes in our pipeline. This is an area of ongoing work and we plan to incorporate computational methods to ensure we’re aligning the correct product with the appropriate tumor.

Once we perfect this, we’ll have the ability to open up all solid tumors to biologic efficacy. This will impact a broad range of precision oncology treatments currently under development, from antibody-based therapies to antibody-drug conjugates, bispecific therapies aimed at immune infiltration and even cell therapies.

One of the biggest challenges with cell therapy in solid tumors is delivering enough of the therapy into the tumor in an active form. By addressing this, we’re essentially opening the door to enabling biologic efficacy in solid tumors, making us a universal enabler for a wide range of treatments. It’s an ambitious vision, but it’s one we’re very committed to.