Tvardi Therapeutics, Inc.

Tvardi’s previously announced merger with publicly traded Cara Therapeutics is on-track to close in 1H 2025 TTI-101 is currently being evaluated in a Phase 2 study in patients with idiopathic pulmonary fibrosis (REVERTIPF) and a Phase 2 study in patients with hepatocellular carcinoma (REVERTLIVER CANCER) March 19, 2025 -- Tvardi Therapeutics, Inc. (“Tvardi”), a clinical-stage biopharmaceutical company developing novel STAT3 inhibitors for fibrosis-driven diseases, announced today that results from the first-in-human Phase 1 study of TTI-101 in patients with advanced solid tumors have been published in the journal Clinical Cancer Research. Imran Alibhai, Ph.D., Chief Executive Officer of Tvardi Therapeutics, stated, “The positive results of this Phase 1 study speak to the potential broad clinical utility of our lead candidate, TTI-101, across a range of fibrosis-driven diseases in which STAT3-mediated proliferation is implicated. Perhaps most notable, in addition to its biological activity in advanced treatment-refractory hepatocellular carcinoma, was a pharmacodynamic reduction of TTI-101’s target, activated STAT3, within paired tumor biopsies. We believe these findings provide very strong rationale for our ongoing Phase 2 studies in IPF and liver cancer.” The publication, titled, “Phase 1 Trial of TTI-101, a First-in-Class Oral Inhibitor of STAT3, in Patients with Advanced Solid Tumors,” describes a Phase 1 study in which patients, who received a median of three prior systemic therapies, were treated with TTI-101 monotherapy orally twice daily (NCT03195699). By targeting both intrinsic tumorigenesis and extrinsic immune suppression, TTI-101 showed promising antitumor activity across tumor types, particularly in patients with hepatocellular carcinoma who were refractory to immune checkpoint inhibitors and anti-angiogenic agents. TTI-101 showed dose-linear pharmacokinetics and, at the recommended Phase 2 dose, the trough exposure levels were above the IC90 for STAT3-induced growth. No dose-limiting toxicities or treatment-related adverse events greater than grade 3 were observed. Pharmacodynamic analysis demonstrated TTI-101 decreased levels of phosphotyrosine (pY) STAT3 within paired tumor biopsies. Tvardi is a clinical stage, biopharmaceutical company focused on the discovery and development of oral, small molecule therapies targeting STAT3 to treat fibrosis-driven diseases. STAT3 is a central mediator across critical fibrotic signaling pathways that drive uncontrolled deposition, proliferation, survival and immune suppression. STAT3 is also positioned at the intersection of many signaling pathways integral to the survival and immune evasion of cancer cells. The company is conducting Phase 2 clinical trials in fibrosis-driven diseases with high unmet need: idiopathic pulmonary fibrosis (NCT05671835) and hepatocellular carcinoma (NCT05440708). The content above comes from the network. if any infringement, please contact us to modify.

iStock/wildpixel If the attention generated by BioSpace ’s coverage of this landmark approval is any indication, Americans are hungry for non-opioid pain treatments that could help quell the still raging opioid epidemic. Last week, a post I shared on LinkedIn highlighting the FDA approval of Vertex’s Journavx netted around 9,000 impressions—a new record for me and an indication of the significance of this new pain therapeutic. The greenlight for Journavx—a first-in-class non-opioid analgesic—came just a week after Purdue Pharma and the infamous Sackler family agreed to pay $7.4 billion to settle lawsuits stemming from the company’s opioid-based painkiller OxyContin. In 2022, nearly 82,000 Americans died from opioid overdoses, according to the CDC ; 15,000 of those deaths involved prescription opioids, per ICER . Between 1999—four years after OxyContin’s FDA approval—and 2022, opioid overdoses were responsible for the loss of some 727,000 lives in the U.S., as the Sacklers cashed in . In a Jan. 30 investor note, Leerink Partners analysts called Journavx’s approval “the start of something big,” and predicted that Vertex will “serially innovate and launch additional non-opioid pain medicines over the medium-long term.” And Vertex isn’t the only one. Journavx’s approval was almost immediately followed by the news that Algiax Pharmaceuticals’ non-opioid drug AP-325 elicited persistent drops in pain within two weeks of treatment in a mid-stage trial . Also book-ending Vertex’s regulatory victory was a positive Phase III readout showing that Tris Pharma’s own non-opioid candidate cebranopadol demonstrated a statistically significant drop in pain intensity 44 hours post-operation. Others, including South Rampart Pharma, Latigo Biotherapeutics and Cara Therapeutics, are all vying for a piece of a global pain therapeutics space that could exceed $106.7 billion by 2032. Analysts expressed uncertainty regarding the uptake of Journavx, with William Blair analysts suggesting in an investor note last week that it may face “initial inertia” from clinicians. The group does ultimately expect it to become a blockbuster, reaching $1 billion in sales by 2028. Journavx’s list price—$15.50 per pill or $420 for a two-week course—is half the cost of ICER’s expectations for cost-effectiveness, according to William Blair, but it is still considerably more expensive than generic opioids, which the firm said cost about $0.50 per pill. Insurance coverage for Journavx is still unclear. While the opioid epidemic is unsparing in its reach, it is more pervasive in rural communities where employment opportunities are limited, according to the U.S. Department of Agriculture —as are funds to pay for a more expensive medicine. Vertex has set up a patient savings program , where eligible individuals—including military veterans and those on Medicare and Medicaid—can access Journavx for as low as $30 per prescription. Journavx is an important start, but acute pain—the indication for which it’s approved—is only one segment of a much larger pain population, and the opioid crisis overall. Chronic pain is the leading cause for seeking medical aid in the U.S., according to Avise Analytics , which referenced a 2016 study by the CDC, NIH and others that estimated 20.4% percent of U.S. suffered from this condition. Vertex has conducted studies of Journavx in patients with chronic pain conditions like lumbosacral radiculopathy. Unfortunately, Journavx failed to significantly outperform placebo in a Phase II trial in this indication in December 2024, delivering Vertex a 13% stock hit, though Jefferies analysts shared their belief that it “is still an active drug and has promise as a chronic pain drug.” Vertex is also studying the drug as a possible treatment for pain associated with diabetic peripheral neuropathy . Here at BioSpace , we will keep covering—and sharing—advances and setbacks in this space. It is clear there is an appetite for these non-opioid options and the news that stems from their development, with Journavx’s approval easily taking the spot as our top story last week. More often, the articles that draw the most eyeballs are those highlighting late-stage trial failures, stock crashes and political theater, so it’s refreshing to see positive, potentially game-changing news generate this much attention.

Stock, hapabapa The greenlight for Journavx (suzetrigine), which comes on the heels of a $7.4 billion opioid settlement, could spark momentum in the fledgling non-opioid pain space. A week after Purdue Pharma and the Sackler family agreed to pay $7.4 billion to settle lawsuits stemming from the company’s opioid-based painkiller OxyContin, the FDA approved Vertex’s suzetrigine as the first new mechanism for acute pain in more than 20 years—possibly turning a new page in this treatment space. Suzetrigine—to be marketed as Journavx—is a first-in-class non-opioid analgesic intended to treat moderate to severe acute pain in adults. “A new non-opioid analgesic therapeutic class for acute pain offers an opportunity to mitigate certain risks associated with using an opioid for pain and provides patients with another treatment option,” Jacqueline Corrigan-Curay, acting director of the FDA’s Center for Drug Evaluation and Research, said in a statement. Vertex will price Journavx at $15.50/pill or $420 for a two-week course, according to William Blair analysts, who also noted the drug’s broad label which does not restrict Journavx prescribing by setting. Meanwhile, Leerink analysts in a Thursday note called the approval of Journavx “the start of something big.” “We believe that suzetrigine will beat consensus sales expectations and that VRTX will serially innovate and launch additional non-opioid pain medicines over the medium-long term,” the analysts wrote. Leerink went on to project peak sales of over $10 billion for Journavx and follow-on NaV1.8 inhibitors for acute and neuropathic pain. Editor’s note (Jan. 31): This story has been updated to include commentary from William Blair and Leerink. Original article published Jan. 30 at 9:56 a.m.: Vertex Awaits FDA Verdict on Landmark Non-Opioid Pain Drug In one of the year’s most closely watched decisions, the FDA is expected to render a verdict Thursday on Vertex’s suzetrigine, which—if approved—would provide the first new mechanism for the treatment of acute pain in over two decades. The action date comes just a week after Purdue Pharma and the Sackler family agreed to pay $7.4 billion to settle lawsuits stemming from the company’s opioid-based painkiller OxyContin. Vertex is one of several companies looking to bring non-opioid options to the market in the midst of a still-ongoing opioid epidemic that kills tens of thousands per year. Suzetrigine is an orally available pain signal inhibitor that selectively targets the NaV1.8 voltage-gated sodium channel, a genetically validated pain target found on peripheral neurons. NaV1.8 is believed to play a role in sensing pain and transmitting signals back to the central nervous system. Vertex is supporting suzetrigine’s New Drug Application with data from two Phase II and three Phase III studies, including the NAVIGATE 1 and NAVIGATE 2 trials, which assessed the drug’s analgesic efficacy in patients who had undergone bunion removal or tummy tuck surgery (bunionectomy and abdominoplasty, respectively). In these late-stage trials, suzetrigine had greater efficacy in patients following abdominoplasty, improving pain scores by 48.4 points, while patients undergoing bunionectomy saw their pain scores lowered by 29.3 points. Not all of suzetrigine’s results have been so robust, however. In December, Vertex revealed data from a Phase II trial studying the drug in nearly 220 patients with lumbosacral radiculopathy, a disorder that causes pain the lower back and hips, often radiating down the leg. At 12 weeks, patients taking Vertex’s drug saw a mean reduction of 2.02 points in the numeric pain rating scale (NPRS). While this result met the study’s primary endpoint, the placebo group also saw a 1.98-point drop in mean NPRS score, giving analysts pause. In an investor note at the time, Truist Securities analysts wrote that the results were “worse than anticipated as no numeric separation can be seen between [suzetrigine] and [placebo] arms.” An approval for suzetrigine would generate momentum for a non-opioid pain space that also includes companies like Tris Pharma, Latigo Biotherapeutics and SiteOne Therapeutics. Last week, Tris reported positive Phase III data for its non-opioid painkiller, cebranopadol, which showed strong efficacy as well as a solid safety pro patients who had just undergone abdominoplasty. Meanwhile, Latigo launched in February 2024, raising $135 million in a series A round for its NaV1.8 inhibitor, LTG-001, and SiteOne secured a $100 million series C round for its selective ion channel modulators. Elsewhere, Collegium Pharmaceuticals leverages its patented DETERx platform to provide extended release drug-delivery while deterring abuse and tampering and Cara Therapeutics is developing new chemical entities that target the body’s peripheral kappa opioid receptors to treat pruritus. And Protega Pharmaceuticals recently won approval for an abuse-deterrent opioid. Editor’s Note: This article has been updated to include comments from William Blair and Leerink Partners.