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ORLANDO, Fla. — In October, Terns Pharmaceuticals made an announcement that seemed to run counter to every popular sentiment in biotech: It got out of obesity to focus on cancer. The 9.4% stock drop that day showed investors’ disappointment. But in the months since, the company’s decision has been more than proven to be the right one. Soon after dropping the obesity program, it released data for its rare leukemia treatment that has more than tripled the company’s value. And it believes it may be able to compete with an emerging Novartis blockbuster. On Monday, Terns announced updated data from the leukemia program, called TERN-701, showing that 64% of patients in its trial hit a benchmark known as major molecular response after earlier drugs stopped working. The data were an update from the release in November, and from the American Society of Hematology’s annual meeting, that helped drive up the stock. In an interview with Endpoints News at ASH, Terns CEO Amy Burroughs said that trying to move forward in obesity would have required a partnership, and the company was more confident — and had better data — in chronic myeloid leukemia. “It was easier for us that it wasn’t gray. It just clearly was not a best-in-class type of asset,” Burroughs said. “We’d already planned, from an operational standpoint, to move people into oncology, and so it wasn’t very disruptive to the company. It really was just a loss of potential.” There are about 17,000 new CML diagnoses a year in G7 countries, and Novartis’ drug Scemblix — the product Terns believes it can compete with — is on pace to reach $1 billion in full-year sales for the first time in 2025. Success in CML patients is not measured the same way as most other oncology studies, because the disease is a slow-progressing cancer and patients can live with it for years, trial investigator David Andorsky told Endpoints. Rather than using progression-free survival or overall survival, clinicians use the major molecular response, or MMR, metric to track deep responses over long periods of time. Patients achieve a major response when the ratio of a genetically mutated protein, compared to all healthy cells, falls below 0.1%. In CML, the mutation is caused by an abnormality between chromosomes 9 and 22, promoting the overproduction of white blood cells. The 38 evaluable patients in the trial had at least two prior treatments: 28 entered who had cancer that had worsened already, while 10 were still in a major response. Of the patients whose cancer had resurged, 64% reached a major response within 24 weeks of starting TERN-701. All 10 who started the trial with a major response kept it, and in some cases their response got even deeper. That appears to be stronger than Novartis’ results at the same time point: In 2020, Scemblix had a 25.5% major response rate at 24 weeks, though the trial was larger and placebo-controlled. The study eventually ran for 96 weeks and hit a rate of 37.6%. The last two decades have revolutionized care for CML. Before 2001, the only option for patients was a bone marrow transplant, Andorsky said. That changed with the approval of Novartis’ Gleevec, which shifted treatment to one or two pills per day — and much longer prognoses. “Within five years, patients were gonna die from it, versus ‘Take this drug every day, and you’ll live a normal life,’” Andorsky said of Gleevec. “That was really paradigm-shifting.” Novartis has a substantial head start — Scemblix was first approved in 2021. And Terns wants to try and compete solo: Burroughs said she believes Terns can take the drug to market itself and that it’s “unlikely” the company seeks a partner. Terns is now deciding between one of two doses to take into pivotal trials, the first of which will likely start by the end of 2026 or early 2027. The company is also still considering whether to test TERN-701 directly against Scemblix in its studies. For second-line-plus patients, Burroughs said the company thinks it can conduct a study similar to the one Novartis ran for Scemblix, enrolling about 250 patients and comparing TERN-701 to second-generation TKI inhibitors. But Burroughs was non-committal about a head-to-head study against Scemblix in the first-line setting. “We definitely want to get that data. We could do that in a pivotal trial, we could do that in other ways,” Burroughs said. The company will likely raise more money to fund its studies. Terns has about $300 million in cash that should last it into 2028, but that’s not enough for Terns to support multiple studies and a commercial launch. “We’re likely to raise money sometime before we start pivotals,” she said.

ORLANDO An experimental drug from Terns Pharmaceuticals is showing it may emerge as a threat to multiple established medicines for a slow-growing blood malignancy known as chronic myeloid leukemia.According to results presented at the American Society of Hematology meeting on Monday, Terns drug, codenamed TERN-701,helped a majority of study participants with CML who had received previous treatments significantly reduce the number of diseased white blood cells in their bloodstream. The findings suggest the drug, a type of targeted, oral treatment, may eventually be competitive with widely used medicines like Novartis Scemblix, which is expected to generate more than $4 billion in peak yearly sales.Terns first announced a small cut of data from the trial in early November, claiming at the time that the efficacy findings were unprecedented among marketed and experimental treatments for CML. Company shares have more than tripled since then, heightening anticipation for the detailed results being presented at ASH. TERN-701 could potentially upend Scemblix dominance in CML, wrote William Blair analyst Andy Hsieh, in a research note last month.The study, called CARDINAL, is primarily evaluating the safety of TERN-701 in people whove received prior treatments such as Scemblix or another Novartis medicine, Gleevec,as well as determining which dose to advance into further testing. Nearly all of the study recruits joined the trial because their previous treatments stopped working or had too many side effects.But investigators also measured molecular response, or how much the drug reduces the share of cells containing the aberrant BCR-ABL gene that drives the disease. Molecular response rates are frequently used as a study endpoint for CML trials because its predictive of longer-term benefits, such as a reduced risk of disease progression.Among 38 patients who were evaluable for efficacy, TERN-701 helped 74% attain a major molecular response a 1,000-fold reduction in the percentage of white blood cells with the BCR-ABL gene by 24 weeks. Of those who werent classified as being in major molecular response at the studys start,64% achieved it afterwards. All patients at that level when the trial began maintained that status, too.In a similar study population, Scemblix helped 25% of trial volunteers achieve a major molecular response at 24 weeks. Cross-trial comparisons can be misleading, however, and the two drugs havent been tested head to head.Still, what it's telling us is that this is a better drug, said Terns CEO Amy Burroughs, in an interview with BioPharma Dive. This is going to raise the bar in efficacy.Updated data presented at ASH show that the occurrence of side effects and severe side effects remains low among TERN-701 recipients, with 32% of the 63 patients who entered the trial having a Grade 3 adverse event. Only one patient dropped out of the study due to a severe side effect. No signs of high blood pressure or pancreatitis side effects associated with Scemblix and another CML drug, Iclusig have occurred. Iclusig also has a black box warning of blood clotting events that have included heart attacks and strokes.Drugs like TERN-701 and others in its class work by blocking a signaling molecule that produces the diseased white blood cells in CML. Early drugs like Gleevec worked by blocking the active part of the molecule that prevents its signaling, while Scemblix and TERN-701 grab onto a site that changes the shape of the molecule.The latter approach reduces the number of off-target interactions that can trigger severe side effects, Burroughs said. '