In the expanding landscape of "-omics," a new field is gaining momentum: metallomics, the study of how metals act within biological processes. This emerging field focuses on understanding the essential roles that metals, like zinc, play in maintaining health, influencing everything from protein function to cell signaling.
Metallomix Inc., a pioneering biotech and Cure Collaboration Residency company, is harnessing this knowledge to create disease-modifying treatments. The team, led by Sergei Petukhov, DVM, CEO of Metallomix, combines its biochemistry and biophysics expertise to leverage the intricate interplay between the body’s "metallome," its broader molecular networks and other "omes" — such as the genome, proteome and microbiome.
With innovations that target diseases from cancer to neurodegenerative and metabolic disorders, Metallomix is spearheading a new approach to health that could redefine how we view metals in medicine. The company, founded in 2021, is developing disease-modifying drugs based on isotopically modified zinc (64Zn) for diseases such as:
Solid tumors (melanoma, prostate cancer and pancreatic cancer) and chronic lymphocytic leukemia: phase 1 clinical trials;
Neurologic diseases (Parkinson's disease, Alzheimer's disease, Lewy body dementia, ALS and major depression): transitioning from the completed preclinical animal models into clinical trials in patients; and
Metabolic disorders (obesity, insulin disorders, type 2 diabetes and non-alcoholic fatty liver disease): preclinical studies.
Cure spoke with Petukhov about the field of metallomics and the company's approach and mission.
This interview has been edited for length and clarity.
Cure: Can you explain how metals influence protein function?
Petukhov: Metals are a very important part of our own biochemical processes. They attach to proteins, shaping them in ways that impact structural integrity and function.
About half of the proteins in our body are metalloproteins, meaning they require metals for correct protein synthesis, folding, function and degradation.
Cure: Why did Metallomix choose to focus on zinc?
Petukhov: We chose to focus on zinc because it plays a role in transcription-translation machinery and DNA damage repair. But zinc is not really one metal: it’s a mixture of five different isotopes [atoms of zinc that differ in their number of neutrons, reaction rates and binding preference in the body]. The lightest isotope is zinc-64 and the heaviest one is zinc-70.
We discovered that isotopic fractions of metals in the body are different from their natural abundance fractions outside of the body. When we are young and healthy, our cells and tissues present a higher concentration of lighter zinc isotopes relative to heavy ones. But in the presence of diseases such as cancer and neurodegeneration, that ratio shifts. We see more heavy isotopes.
This is called isotopic dysfractionation, and it can cause the inflammation and oxidative stress associated with cancer, neurodegenerative diseases and metabolic disorders. So lighter isotopes have beneficial properties and heavier ones are present in the disease and aging.
Metallomix is the first company to create a drug candidate using non-radioactive light isotope 64Zn and metallomics approach. About 3,000 proteins need zinc to function. We created a compound coded KLS-1, an enriched fraction of 64Zn, attached to a carrier molecule. It's designed to isotopically modulate zinc’s metallome function inside our cells. The goal is to induce proper proteomics and repair numerous cellular functions.
Cure: What have your preclinical data shown and where are you in the clinical trials process?
Petukhov: Our preclinical work in cell cultures and animal models has produced some interesting results, including the shrinkage of tumors. But nothing beats human data.
That's why we’re really excited about being the first clinical stage company working in the isotopic metallomics space. We just dosed our first patient in a phase 1 cancer clinical trial in October 2024. The next clinical trial will be a safety trial in healthy people, followed by a clinical trial of patients with neurodegenerative diseases and another study of people with metabolic disorders.
Cure: How is this treatment approach different from other therapies?
Petukhov: This is a whole-body approach, rather than taking aim at one target. The advantage of our approach is that we're starting with a metal that has always inherently been a part of the normal functioning of our bodies and which gets depleted with age.
Our goal is to provide weakening cells with the zinc isotope to restore the body to its healthy zinc balance. By doing this, we hope to slow down inflammation and oxidative stress, and in doing so, mitigate the effects of related medical conditions.
The body is like a car. It runs at peak performance when it's new, but with inevitable wear and tear, it will need intervention to ensure it can continue to run smoothly. We're trying to retune the human body using our understanding of isotopic fractionation and the role of isotopes in biological processes.
Cure: Does someone have to take these drugs for the rest of their lives?
Petukhov: We don't think so. Our bodies are designed to repair themselves. We believe that by using our isotope-selective modulation drugs, patients can bring their cellular functions to a healthy state, so bodies can start functioning normally on their own.
Cure: How do you like being part of the Cure community?
Petukhov: I am a scientist by training and have been part of the venture capital community since 2008. As a New Yorker of 30 years, I have a deep appreciation for this city’s unparalleled biotech community — it’s a real wellspring of intellectual property, benefiting enormously from world-class medical schools and renowned biotech centers like the Alexandria Center for Life Science, Biolabs at NYU Langone and others.
I learned about Cure through some past projects with the Deerfield team, and I really appreciated the role a hub like that can play in fostering the next generation of innovators. Startups with great science and great vision have so much to gain from being in the same place, pushing our respective disciplines forward in parallel and finding synergisms where our work overlaps. Cure’s lineup of events and conferences does a great job keeping us collectively on the cutting edge of industry.
Metallomix is really excited to be here, and we look forward to being part of the Cure community for years to come.
Sergei Petukhov is speaking at the 2024 BioFuture conference, taking place at Cure starting October 28, 2024. Learn more and register.