With the biopharmaceutical world still buzzing from the latest data presented at the American Society of Hematology meeting, we sat down with industry expert Ivan Kairatov to unpack the results that have sent one company’s stock soaring. At the center of the discussion is TERN-701, an experimental oral treatment for chronic myeloid leukemia that appears to be posting unprecedented efficacy numbers. We explored the nuances of the CARDINAL study data, the critical importance of a clean safety profile in a competitive market, the science behind the drug’s precision targeting, and what these findings could mean for the future of CML therapy.
The CARDINAL study showed 74% of patients achieved a major molecular response, a figure that seems to dwarf Scemblix’s 25% result in a similar study. Could you walk me through the specific patient population and trial design elements you believe contributed to this impressive outcome?
That 74% figure is precisely what has everyone talking, and for good reason. What makes it so stunning is the context of who these patients were. This wasn’t a group of newly diagnosed, treatment-naive individuals. The CARDINAL study enrolled people who were, for lack of a better term, at the end of the line. Nearly all of them had already been on other treatments, like Gleevec or even the current market leader Scemblix, and those drugs had either stopped working or caused unbearable side effects. To see such a deep, major molecular response in this heavily pre-treated population is extraordinary. It tells us the drug has a powerful mechanism that works even when others have failed.
Analysts suggest TERN-701 could “upend Scemblix dominance.” Beyond the efficacy data, what specific aspects of the drug’s safety profile—like the absence of pancreatitis or high blood pressure—do you believe will be most critical for challenging a blockbuster with $4B peak sales projections?
Efficacy gets a drug to the market, but in a chronic disease like CML, tolerability is what keeps it there and helps it grow. Patients may be on these therapies for the rest of their lives, so quality of life is paramount. When you can tell a physician and their patient that this drug doesn’t carry the risk of pancreatitis or high blood pressure seen with other CML drugs, that’s a massive advantage. It means less worry, fewer monitoring visits, and a more manageable daily experience. Furthermore, another drug in this space, Iclusig, carries a terrifying black-box warning for blood clots, heart attacks, and strokes. TERN-701’s clean profile in this regard is a huge differentiator that builds immense confidence.
The article mentions TERN-701 changes the molecule’s shape to reduce “off-target” interactions. Can you elaborate on this mechanism and provide a step-by-step explanation of how this translates to a better safety profile, particularly avoiding the blood clotting events seen with Iclusig?
It’s really a story of elegant engineering at the molecular level. Think of the BCR-ABL protein that drives CML as a machine with a main “on” switch. The first generation of drugs, like Gleevec, were designed to directly block that switch. It worked, but that switch looks a lot like other switches on other important proteins in the body, leading to off-target side effects. What TERN-701 and Scemblix do is fundamentally different and more precise. Instead of hitting the main switch, they bind to a unique little pocket on the side of the protein. By grabbing onto this site, the drug subtly changes the entire shape of the protein, effectively jamming the “on” switch from a distance. Because this side pocket is so specific to the BCR-ABL protein, the drug is far less likely to accidentally interact with other machinery in the cell, which is how you avoid those dangerous off-target events like blood clots.
You stated TERN-701 is “going to raise the bar in efficacy.” Considering the standard caution about cross-trial comparisons, what specific metrics and long-term endpoints beyond the 24-week molecular response rate will be crucial to definitively prove this drug’s superiority in the CML treatment landscape?
It’s absolutely right to be cautious about comparing different trials. However, a gap as wide as 74% versus 25% is more than just statistical noise; it’s a powerful signal. To truly cement its superiority, we need to see durability. The 24-week molecular response is a fantastic early indicator, but the real proof will be seeing if those patients maintain that deep response at one, two, and even five years. The next critical metric will be progression-free survival—showing that the drug not only reduces the cancer’s molecular footprint but also demonstrably stops the disease from advancing over the long term. Ultimately, the gold standard would be a head-to-head trial against Scemblix. That would be the definitive test to prove that a new bar has indeed been set.
The study focused on patients for whom prior treatments stopped working, yet only one patient dropped out from a severe side effect. Could you share any anecdotes or specific patient feedback that highlights the drug’s day-to-day tolerability and what the next key clinical milestones are?
That single dropout is one of the most compelling parts of this story. For a patient population that has already been through the wringer with other therapies, to have such a high retention rate speaks volumes about the drug’s day-to-day livability. While we don’t have direct patient testimonials, that number itself tells a powerful anecdote: this is a treatment people can stick with. It suggests they aren’t being plagued by the kind of side effects that make daily life a struggle. As for what’s next, the immediate milestone is finalizing the optimal dose from this CARDINAL study. After that, the company will need to launch into larger, pivotal trials to confirm these results and gather the data needed for regulatory approval. All eyes will be on the design of their Phase 3 program.
What is your forecast for the treatment landscape for chronic myeloid leukemia over the next five years?
I believe we’re on the cusp of a significant shift. The future of CML treatment is moving decisively towards this class of highly targeted, allosteric inhibitors. The paradigm is no longer just about efficacy at any cost; it’s about achieving a deep and, most importantly, durable molecular response with a pristine safety profile that allows for an excellent quality of life. Over the next five years, I expect to see drugs like TERN-701, if these results hold, not only dominate the later-line settings but also begin to push into earlier lines of therapy. We could see a future where a CML diagnosis is managed with a simple, daily pill that is not only profoundly effective but also remarkably well-tolerated.
