Amphista Therapeutics is a biotechnology company specializing in targeted protein degradation to develop novel treatments for diseases, with a focus on oncology.
Congratulations on becoming the new CEO of Amphista Therapeutics! Before we dive into your plans, could you share a bit about your background?
I have been in the industry for 35 years, spending the first half in big pharma with Novartis, Merck, and Bristol Myers Squibb. Over time, I felt that the big pharma model had become less effective, so I transitioned to privately held companies and later to Ocular Therapeutics, a publicly traded biotech focused on drug delivery. I have always been passionate about finding alternative ways to target disease-causing proteins.
My interest in protein degradation led me to Amphista. Targeted protein degradation is an exciting field, and I wanted to wait for the technology to mature. Amphista represents a true third-generation approach, and we will soon see in clinical trials whether we have truly figured it out. The goal is to target disease-causing proteins that have traditionally been considered undruggable, and I believe this is the best modality to achieve that.
In your view, the ‘big pharma model’ has ‘burned itself out’. Why do you think that is the case?
Big pharma operates within large bureaucratic structures, requiring significant coordination and multiple layers of approval. This makes it difficult to push things forward efficiently. Additionally, corporate strategies tend to shift frequently. For example, AML was a major focus for big pharma five years ago, but interest waned, only to resurface again. As a result, promising programs can be terminated simply because they no longer align with corporate priorities.
In biotech, however, success or failure is entirely tied to the programs being developed, without excessive bureaucracy slowing things down. Biotech companies function like guided missiles, focusing entirely on bringing their innovations to patients. If the science does not work, the company may fail, but that kind of creative destruction is essential for R&D progress. Big pharma is increasingly recognizing this, leaving early-stage innovation to entrepreneurial companies while stepping in for later-stage development and commercialization.
Let’s discuss targeted protein degradation (TPD). Could you introduce us to the concept?
The concept is quite simple. The body naturally degrades proteins through its own sanitation system, primarily the ubiquitin-proteasome system The idea behind targeted protein degradation is to identify damaged proteins, tag them for recycling, and use the body’s own processes to eliminate them before they cause disease.
This is an elegant way to address disease-causing proteins because it directly removes them from the body rather than just inhibiting their function. Unlike gene editing, which permanently alters DNA and carries unpredictable long-term risks, protein degradation does not permanently alter protein synthesis. Amphista’s technology is particularly advanced in this field, offering specificity to the protein of interest that minimizes off-target effects.
When do you expect to enter clinical trials, and for which indications?
Most diseases are driven by problematic proteins, and the human body contains about 6,000 proteins, many of which remain undruggable. The potential applications of protein degradation are vast, but our immediate focus is oncology. We currently have four programs targeting cancer, with our lead compound in AML expected to enter the clinic in 2026.
Beyond AML, we are developing therapies for solid tumors, including non-small cell lung cancer and hepatocellular carcinoma. While our internal expertise is concentrated in oncology, our platform is broadly applicable. We are also working with strategic partners interested in immunological, neurological, and ophthalmological applications.
Could you share more about your partnerships with BMS and Merck?
Our partnerships with BMS and Merck were established in the early stages of our development, and we have learned a great deal about our chemistry since then. Amphista operates in the targeted protein degradation space using a novel Targeted Glue approach. Unlike first-generation methods that relied on bulky molecules with complex linker structures, our glues are small molecules designed to be orally bioavailable and capable of crossing the blood-brain barrier.
Our platform enables rational drug design, allowing us to create glues specific to particular proteins. This results in greater precision, fewer off-target effects, and increased usability in the human body. Our ability to build Targeted Glues around existing ligands, including inhibitors or radiolabeled molecules, sets us apart in the field.
To execute these plans, you need a supportive biotech ecosystem. How does the UK’s Cambridge biotech environment compare to Massachusetts’s Cambridge?
I have worked in both Cambridge, UK, and Cambridge, Massachusetts, and I have observed a significant evolution in the UK biotech scene. Seven years ago, it was nearly impossible to scale biotech companies in the UK beyond discovery. Many promising projects had to relocate to Boston or San Francisco to access the necessary expertise and infrastructure.
That has changed, largely due to AstraZeneca’s decision to move its headquarters to Cambridge, UK. This, combined with GSK’s existing presence in the UK, has fostered an ecosystem capable of supporting companies from discovery to clinical development. As a result, companies like Amphista can now scale within the UK without needing to transfer operations to the US.
Finally, as the newly appointed CEO, where do you see Amphista three years from now?
In three years, we hope to have meaningful clinical data for our lead AML program. AML is an aggressive cancer with a high mortality rate, but our therapy aims to induce differentiation in cancer cells, allowing them to mature and cease uncontrolled proliferation. If we can combine this with antiproliferative agents, our hope is to turn AML into a manageable condition rather than a fatal disease.
By that time, we also expect to have three additional programs advancing through clinical trials for solid tumors. These next three years will determine whether Amphista can truly make a difference in oncology. If our science holds up, we will have built a powerful company capable of reshaping the landscape of targeted protein degradation.
