Heidelberg Pharma develops innovative cancer treatments using proprietary Antibody-Drug Conjugate (ADC) technologies, including an unique platform using the Amanitin toxin from green death cap mushrooms. Its lead product candidate HDP-101 targets multiple myeloma.
Heidelberg Pharma is the first company to use the amanitin toxin from the green death cap mushroom in its therapies for cancer. Could you explain the theory and practice behind that?
The idea started here in Heidelberg with a professor from the Max Planck Institute who initially aimed to develop an antidote for amanitin. He was unsuccessful, but since the German Cancer Research Center was nearby and he had collaborators there, they teamed up to explore its potential in oncology. This was the beginning of the ATAC (technology.
The key aspect of amanitin is its unique mode of action—it inhibits eukaryotic transcription, a fundamental process in all cells. Surprisingly, it is the only known inhibitor in the world that targets this process. This uniqueness is what led us to develop a therapy making amanitin available to cancer patients through ADC technology.
Today you are working with third-generation ADCs called ATACs, which have an improved efficacy and action against dormant tumor cells. How do ATACs work?
ATAC technology combines the best of two worlds. Traditional chemotherapeutics, which have been around for nearly a century, are effective but come with severe side effects—vomiting, hair loss, and a narrow therapeutic window. On the other hand, antibody technology has advanced rapidly over the past 50 years, allowing us to create highly specific antibodies, but they lack strong biological activity on their own.
The core idea is to merge these two approaches into a “magic bullet”. We conjugate a highly toxic compound to a cancer-targeting antibody, turning the antibody into a cruise missile that delivers the toxin directly to the tumor cells. The goal is for the payload—the toxin—to be released only in the tumor, sparing healthy cells.
Heidelberg Pharma recently advanced its Phase I/IIa study for HDP-101, its lead ATAC candidate for treating relapsed or refractory multiple myeloma. What results have you seen so far?
2Since moving into the clinical trial with HDP-101, we have already seen objective responses, including one patient with a complete response—her tumor became undetectable. This was particularly remarkable because she had multiple myeloma for over 20 years, had undergone nine different lines of therapy, and was resistant to all existing treatments. Even the investigators were astonished that our drug could eradicate the tumor in such a heavily pre-treated patient.
One of the advantages of ADC technology is that, in theory, it has applications in all cancers. By reprogramming the antibody—the "missile"—we can target different types. We started with multiple myeloma, but the same approach could be applied to prostate cancer or other malignancies. We have built a platform that we call "plug-and-play," allowing us to swap in different antibodies while keeping the amanitin payload, enabling us to target various tumor cells. So far, we have not encountered a tumor cell that was resistant to amanitin.
Heidelberg Pharma licenses its platform to other pharmaceutical companies to develop their own ATACs. How is the technology being received by industry peers?
In the early days, there was significant hesitation because people associated amanitin with the deadly green death cap mushroom. If you ingest the mushroom, there is a high chance of fatal poisoning, and this scared people. The pharmaceutical industry is risk-averse, so many watched from the sidelines, waiting to see if we could demonstrate safety in patients.
That perception started shifting last year when we showed strong clinical data, including the case of complete tumor remission. Now, people recognize that amanitin is a safe and effective drug for cancer treatment. As a result, we are seeing a surge in interest, not just from the pharmaceutical industry but from investors eager to be part of Heidelberg Pharma’s journey.
How would you compare Germany’s academic environment in life sciences with that of the U.S.?
Germany is strong academically, but its investment landscape is far more conservative. Biotechnology is not as deeply embedded in the business community here. While startups can secure initial funding, Germany and even Europe as a whole struggle to support later-stage growth. In contrast, the U.S. offers significantly more funding and enthusiasm for breakthrough technologies. Many German-founded biotech companies list on Nasdaq rather than in Germany because Nasdaq remains the best place to attract investors and grow.
A key difference I have observed is in investor attitudes. In Germany, investors often ask when a company will become profitable. In the U.S., the focus is on innovation—investors want to know what is new and disruptive. They are better educated in the science itself and prioritize potential over immediate profitability. Germany excels in engineering, but in biotech commercialization, we still have room to grow.
What milestones can we look forward to from Heidelberg Pharma in 2025?
Our main goal is to complete our Phase I trial and begin dosage expansion for the Phase II part, allowing us to treat more patients and, hopefully, see more cases of complete remission. We are also launching a second program in Non-Hodgkin’s lymphoma this year, marking another application of our technology.
Additionally, we are beginning to explore non-oncology applications, and while it is still early, we hope to generate exciting data demonstrating the broader potential of our approach beyond cancer treatment. I truly believe we are working with a highly disruptive technology. Ultimately, we aim to develop a drug for the entire world.
