Radiopharmaceuticals have emerged as one of the most transformative modalities in oncology.
Unlike localized radiation or broadly acting chemotherapies, these therapies deliver radioactive isotopes directly to tumors throughout the body via small molecules or peptides that selectively bind cancer-specific targets.
Co-Founder and CSO
Ratio Therapeutics
Dr. John Babich, Co-Founder and Chief Scientific Officer of Ratio Therapeutics, describes their unique value: they are designed to treat disseminated disease: cancer that has spread beyond surgical or localized radiotherapy options.
“We’re looking to treat disseminated cancers; cancers that are found throughout the body,” he explained. “We make drugs that are typically small molecules or peptides … that can find their way and bind to tumors after they’re injected into the bloodstream.”
By linking a radioactive isotope to these targeting molecules, the therapy deposits energy precisely where it’s needed, destroying tumor cells while largely sparing healthy tissue.
“You wind up with very selective localization of radiation in the tumors,” said Dr. Babich. “Everything else is basically excreted, meaning that the tumor-killing is a function of that molecule sitting in the tumor for a fairly long period of time. The lower toxicity is a result of the remaining radioactive molecules clearing the blood and normal tissues in a timely fashion.”
The result is a high therapeutic index, a favorable ratio between tumor and normal-tissue radiation dose, and, for many patients, a more tolerable experience.
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Engineering Precision: Inside the Science of Radiopharmaceutical Design
Behind each successful radiopharmaceutical lies intricate chemistry and engineering. “Every target has unique features and obstacles,” said Dr. Babich.
“Nature doesn’t hand you solutions on a platter, so you have to figure out how those solutions work.”
At Ratio Therapeutics, founded by Babich and CEO Dr. Jack Hoppin in 2021, the team focuses on optimizing pharmacokinetics — the circulation, binding and clearance of radiopharmaceuticals — through proprietary molecular design.
Their platform, called Trillium™, uses a tri-functional structure: one component binds the tumor target, another carries the radionuclide payload and the third interacts reversibly with albumin to modify how long the compound remains in the bloodstream.
“Tumors are typically poorly perfused; they don’t get a lot of blood flow,” Dr. Babich explained. “If you inject a drug and it clears too quickly, all that radioactivity is now in the pipes, in your house or the hospital. You’d like it to stick around a little longer to have more chances to interact with the targets on the cancer cells.”
The ability to modulate plasma half-life gives Ratio a way to balance efficacy and safety, ensuring sufficient tumor exposure without prolonged radiation in healthy tissue.
Across the field, additional innovations are emerging. Researchers are exploring heterobifunctional ligands that can bind two distinct targets within a tumor, increasing the likelihood of tumor localization. Advances in chelation chemistry (molecular “baskets” that hold radioactive metals securely during circulation) are improving stability and manufacturability.
Meanwhile companies like Nusano and IBA are developing next-generation accelerator systems capable of generating diverse isotopes at previously unattainable scales.
“There’s a huge investment now in isotope production methods and scale-up,” said Dr. Babich. “That’s critical for the future of this field.”
The Innovation Ecosystem: Small Biotech and Large Pharma in Synergy
Ratio Therapeutics’ trajectory shows how innovation and scale coexist in radiopharma. “We’ve been fortunate since the beginning of the company to have several relationships with large pharma,” said Dr. Babich. Prior ventures led by his team produced molecules that are now advancing through mid-stage clinical studies under major pharmaceutical sponsors.
The company has also established collaborations spanning diagnostic imaging and novel peptide analogs. “We in-licensed a molecule that would allow us potentially to image the activation of the immune system,” he noted. “That’s a highly novel diagnostic with potential both in the development of immuno-oncology therapies, but also for autoimmune disease.”
Dr. Babich sees this dynamic — nimble startups driving discovery while larger partners fund late-stage trials and manufacturing scale-up — as a healthy balance.
“The world thrives on innovation,” he said. “It’s a beautiful time right now in radiopharmaceutical development because all these players are coming together in a very nice ecosystem.”
Building for Scale: Manufacturing and Logistics at Speed
While the science of radiopharmaceuticals is intricate, manufacturing them is equally complex.
Each drug is radioactive the moment it’s made, creating unique safety, timing and logistics challenges.
“Most of these are injectable drugs, and they’re made with a significant amount of radioactivity,” said Dr. Babich. “You have to protect the staff from exposure while protecting the product.”
Unlike conventional injectables that can sit on pharmacy shelves for months, radiopharmaceuticals have a rapidly decaying isotope and, therefore, a limited shelf life.
“As soon as you finish all the manufacturing and all the quality control to release that product, you have a certain shelf life before it’s no use anymore,” Dr. Babich explained. “During that decay, it may be breaking chemical bonds in the actual drug substance.”
Manufacturers must coordinate near-real-time delivery from production to patient infusion. “How do you plan to make enough for the patients that are in need at the moment in your region? How do you arrange the logistics to get these out in just-in-time delivery?” he said. “There’s a huge amount of investment in time and intelligent design to get this done.”
Salt Lake City: A New Radiopharma Hub
Salt Lake City is emerging as a hub for radiopharmaceutical manufacturing, and for Ratio Therapeutics, it represents a strategic opportunity shaped by proximity and collaboration.
“It’s got a lot of layers,” Dr. Babich said. “There’s a company called Nusano, which has really developed a rather remarkable technology: a high-intensity linear accelerator with the potential to make very large quantities of many isotopes we need for the field.”
Setting up manufacturing adjacent to that source offers efficiency and logistical advantages. “If someone has to buy isotopes and ship them overnight, everything’s radioactive, everything is decaying,” Dr. Babich explained. “So if I need a hundred units for my manufacturing, I have to buy two hundred units because by the time it gets to me, it’s decayed down to a hundred.”
The city’s proximity to a major airport and central location west of the Rockies make it ideal for the distribution of short-lived isotopes across the US. “There are efficiencies of scale due to the proximity of a manufacturer like Nusano, and it has other logistical attractions that we like,” he added.
The Power of Imaging
One of the defining advantages of radiopharmaceuticals is the ability to visualize where a therapy goes, a built-in diagnostic capability that unites therapy and imaging in what’s often called theranostics.
“You can see where the drug goes,” said Dr. Babich. “You can actually test how well your preclinical data predicts human behavior.”
Before moving into therapy, researchers can label candidate molecules with isotopes suitable for PET or gamma-camera imaging to study biodistribution in real time. These scans reveal how long a compound stays in the blood, how it’s excreted and how much accumulates in tumors. This information guides both candidate selection and dosing.
“Imaging is integral to radiopharmaceutical therapy, both for understanding your drug and as a biomarker to allow patients to be selected for therapy.”
— Dr. John Babich
Imaging also underpins patient selection. Before enrolling in a clinical trial, patients can be scanned to determine whether their tumors express the target that the radiotherapeutic is designed to bind.
“Not everyone wants a biopsy of their tumor,” Dr. Babich noted. “Sometimes it’s impossible, and it’s certainly never convenient.” Molecular imaging can serve as a non-invasive alternative, ensuring only appropriate candidates receive treatment.
He believes these same imaging principles could improve the development of other targeted modalities, such as antibody-drug conjugates, by confirming target expression and optimizing trial design.
Redefining Endpoints and the Patient Experience
While regulatory frameworks for oncology remain stable, Dr. Babich expects radiopharmaceuticals to heighten attention to patient quality of life.
“Our philosophy here is that we want to extend life with quality,” he said. “If you have to go through a severe battery of chemotherapeutic treatments and your life is miserable even though you’re alive six months later, that’s quite different from being able to go out and play tennis, visit your grandchildren or just go for a walk.”
Because these therapies often produce minimal side effects, patient monitoring focuses more on hematologic safety than on acute toxicity. “You may not feel that your platelets are dropping, but that could be very serious in terms of bleeding,” he cautioned. “So we’re always monitoring, just as in any trial.”
Imaging, again, can play a role in follow-up, not only for measuring response but for early detection of recurrence.
“Maybe the imaging biomarkers we use to find tumors and identify patients for therapy can also be used for follow-up assessments,” Dr. Babich said. “Even if the tumor hasn’t grown much, a PET scan might identify whether something else is popping up unexpectedly.”
The Road Ahead: From Molecules to Medicine
Looking five to ten years ahead, Babich envisions more advanced isotope supply chains and automation.
“Manufacturing techniques will get smarter and more automated, that’s inevitable,” he said. “Ten years from now, there may be some very cool chemical scaffolds better than anything we have today.”
He imagines fit-for-purpose molecules that can self-destruct if they don’t bind to the tumor or covalently attach to targets for sustained delivery. He also predicts growth in community-based radiopharma treatment clinics, allowing patients to access these treatments closer to home. “That will be the big leap, bringing these technologies to patients in their hometowns,” he said.
For emerging biotech founders, Babich offers clear advice: understand the complexity. “It is not for the faint of heart,” he cautioned. “You need expertise across chemistry, radiochemistry, pharmacology, biology and radiation physics.”
Strong partnerships and pragmatic execution, he added, are essential. “Everything takes longer than you think and costs more than you think,” he said. “You need multiple shots on goal and early kill studies are a good thing.”
Despite the challenges, his outlook remains optimistic. “Innovators and large pharma are coming together, and that’s very healthy for patients, because we need both sides: the innovators who are willing to take risks and the larger players who can scale manufacturing and late-stage trials.”
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