A Phase 2b, Dose-ranging, Randomized, Double-blind, PlacebO-controlled, Parallel-GRoup, MulticEnter Study in PatientS with Diabetic Peripheral Neuropathic Pain (PROGRESS)

Evaluation of the efficacy of LX9211 compared to placebo in reducing DPNP. Please see study website: https://diabeticpainstudy.com/

Start Date29 Nov 2023

Sponsor / Collaborator

Lexicon Pharmaceuticals, Inc.

NCT04662281

/ CompletedPhase 2

A Phase 2, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of LX9211 in the Treatment of Postherpetic Neuralgia (RELIEF-PHN1)

Evaluation of the efficacy of LX9211 compared to placebo in reducing pain related to postherpetic neuralgia over an 11 week assessment period.

Start Date29 Dec 2020

Sponsor / Collaborator

Lexicon Pharmaceuticals, Inc.

NCT04455633

/ CompletedPhase 2

A Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of LX9211 in the Treatment of Diabetic Peripheral Neuropathic Pain

Evaluation of the efficacy of a low and high dose of LX9211 compared to placebo in reducing pain related to diabetic peripheral neuropathy over an 11 week assessment period.

Start Date07 Jul 2020

Sponsor / Collaborator

Lexicon Pharmaceuticals, Inc.

100 Clinical Results associated with Pilavapadin

100 Translational Medicine associated with Pilavapadin

100 Patents (Medical) associated with Pilavapadin

Literatures (Medical) associated with Pilavapadin

01 Feb 2025·Journal of Diabetes Investigation

LX9211, a rising star for relieving of diabetic peripheral neuropathic pain

Article

Author: Lee, Chia‐Chin ; Hwu, Chii‐Min ; Ko, Fu‐Shun ; Yen, Fu‐Shun

In a multicenter trial, LX9211 significantly reduced pain in diabetic peripheral neuropathy (DPN) patients, with the 10 mg dose showing notable relief by the first week. Although the higher dose was less effective, side effects like dizziness and nausea were generally mild. These findings highlight the importance of exploring both pharmaceutical and natural treatments, such as flavonoids, for managing DPN.

01 Dec 2024·BIOORGANIC CHEMISTRY

Design, synthesis, and biological evaluation of novel AAK1/HDACs dual inhibitors against SARS-CoV-2 entry

Article

Author: Hui, Zi ; Mao, Nian-Dong ; Che, Hao ; Xu, Yueying ; Hu, Suwen ; Gao, Yuan ; Lu, Jinshan ; Wang, Chenchen ; Yao, Xia ; Ye, Xiang-Yang ; Yu, Jie ; Zhang, Hang

AP2-associated protein kinase 1 (AAK1) is a crucial regulator of clathrin-mediated endocytosis, involved in various cellular processes, including viral infection. Histone deacetylases (HDACs) are essential in regulating gene transcription through the process of histone deacetylation and have become promising therapeutic targets for the treatment of cancer and viral infections. In this study, several AAK1/HDACs dual inhibitors based on our previous reported compounds were designed and synthesized, and the antiviral activity of these dual inhibitors were evaluated. Among them, compound 12 showed remarkable dual inhibitory activity against both AAK1 and HDACs, with IC₅₀ values of 15.9 nM for AAK1, 148.7 nM for HDAC1, and 5.2 nM for HDAC6. Notably, this compound exhibited superior efficacy in suppressing SARS-CoV-2 entry into host cells compared to its close analogs 4, 13a, and 13b. Mechanistically, compound 12 attenuated AAK1-induced phosphorylation of adaptor protein-2 μ subunit (AP2M1) threonine 156, disrupting the direct interaction between AP2M1 and ACE2, thus inhibiting the CME-mediated SARS-CoV-2 endocytosis. Additionally, compound 12 increased the acetylation levels of H3K27 and α-tubulin, suggesting its potential as an epigenetic modulator. Overall, our findings propose compound 12 as a promising dual inhibitor against AAK1 and HDACs, highlighting its therapeutic potential in antiviral infections.

01 Dec 2024·BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery and evaluation of HW161023 as a potent and orally active AAK1 inhibitor

Article

Author: Li, Lie ; Su, Jiangtao ; Zhang, Xuejun ; Kaushik, Shivansh ; Jia, Yimin ; Li, Jinping ; Liu, Lifei ; Li, Yang ; Yang, Jun ; Jiang, Wen

AAK1, also known as AP2-associated protein kinase 1, is an enzyme that belongs to the family of serine/threonine protein kinases. It regulates the assembly and disassembly of clathrin-coated pits and thereby protein endocytosis, by phosphorylating the μ2 subunit of the AP2 complex, which is a key component of clathrin-coated vesicles. LX9211 is currently the only selective small molecule AAK1 inhibitor at the clinical trial stage for diabetic peripheral neuropathic pain, which was found to be safe and well tolerated in healthy participants in phase I clinical trials. The present manuscript described a series of fused-ring derivatives as a novel class of potent AAK1 inhibitors, resulting in the discovery of compound 5, namely HW161023, which showed high inhibitory potency against AAK1 enzyme and satisfactory oral pharmacokinetic profile with weaker HepG2 cell toxicity and hERG inhibition than LX9211.

119

News (Medical) associated with Pilavapadin

28 Mar 2025

·www.globenewswire.com

Lexicon Pharmaceuticals Announces Exclusive License Agreement with Novo Nordisk for LX9851

Lexicon eligible to receive up to $1 billion in upfront and development, regulatory and sales milestone payments, including $75 million in upfront and near-term milestone paymentsTHE WOODLANDS, Texas, March 28, 2025 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that it has entered into an exclusive license agreement with Novo Nordisk A/S for LX9851, a first-in-class, oral non-incretin development candidate in obesity and associated metabolic disorders. Under the terms of the agreement, Novo Nordisk obtains an exclusive, worldwide license to develop, manufacture and commercialize LX9851 in all indications. Lexicon will be responsible for completing agreed upon Investigational New Drug (IND) application-enabling activities for LX9851. Novo Nordisk will be responsible for filing the IND, all further development, manufacturing and commercialization of LX9851. Lexicon is eligible to receive upfront and near-term milestone payments of up to $75 million. In total, Lexicon will be eligible to receive $1 billion in upfront and potential development, regulatory and sales milestone payments. Lexicon is also entitled to tiered royalties on net sales of LX9851. LX9851, discovered and developed by Lexicon, is a potent and selective oral small molecule inhibitor of Acyl-CoA Synthetase 5 (ACSL5). ACSL5 plays a key role in the metabolic pathway which regulates fat accumulation and energy balance. Additionally, LX9851 may activate the ileal brake mechanism leading to increased satiety by delaying gastric emptying and suppressing appetite. Preclinical in vivo efficacy data presented at Obesity Week 2024 show that LX9851, when combined with semaglutide, significantly reduced weight, food intake and fat mass compared to semaglutide alone. Separately, LX9851 mitigated weight regain and had positive effects on liver steatosis when introduced after semaglutide discontinuation. "We are thrilled that Novo Nordisk, a global leader in diabetes care and obesity management, has recognized the potential of LX9851," said Mike Exton, Ph.D., chief executive officer and director of Lexicon. "This arrangement decisively strengthens our financial position, providing optionality as we further invest and accelerate our R&D portfolio.” “Novo Nordisk is committed to serving the diverse needs of people living with obesity and other metabolic diseases and to build a pipeline of differentiated drug candidates in this space,” Jacob Sten Petersen, Senior Vice President, Diabetes, Obesity and MASH therapeutic area at Novo Nordisk. “We are pleased to enter this agreement with Lexicon as it will allow us to explore a novel biology and potential treatment paradigm further, and we look forward to building on the great work Lexicon has already done with the development of LX9851.” About LX9851LX9851 is an orally delivered small molecule drug candidate for the treatment of obesity and associated cardiometabolic disorders. Lexicon is investigating the pharmacology of LX9851 as a stand-alone therapy and in combination with GLP-1 agonists such as semaglutide. Lexicon scientists identified the function of ACSL5, the target of LX9851, based on their discovery that knockout mice lacking the target enzyme exhibited favorable phenotypes across multiple measures of metabolic syndrome in preclinical models, including resistance to diet-induced obesity and improved body composition. About Lexicon PharmaceuticalsLexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives. Through the Genome5000™ program, Lexicon’s unique genomics target discovery platform, Lexicon scientists studied the role and function of nearly 5,000 genes and identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to treat disease safely and effectively. Lexicon has a pipeline of promising drug candidates in discovery and clinical and preclinical development in cardiology, neuropathic pain, metabolism and other indications. For additional information, please visit www.lexpharma.com. About Novo Nordisk Novo Nordisk is a leading global healthcare company, founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat serious chronic diseases, built upon our heritage in diabetes. We do so by pioneering scientific breakthroughs, expanding access to our medicines, and working to prevent and ultimately cure disease. Safe Harbor Statement This press release contains “forward-looking statements,” including statements relating to Lexicon’s financial position and long-term outlook on its business, growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including Lexicon’s ability to meet its capital requirements, conduct preclinical and clinical development and obtain necessary regulatory approvals of pilavapadin (LX9211), LX9851, sotagliflozin and its other drug candidates on its anticipated timelines, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates. Any of these risks, uncertainties and other factors may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2024 and other subsequent disclosure documents filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise. For Investor and Media Inquiries:Lisa DeFrancesco Lexicon Pharmaceuticals, Inc.lexinvest@lexpharma.com

License out/in

20 Mar 2025

·www.biospace.com

Purdue Files for Bankruptcy Anew to Support $7.4B+ Opioid Settlement

iStock, Besiki Kavtaradze The Supreme Court last year blocked a previous settlement proposal from Purdue, arguing that the plan would afford the Sackler family too much protection. Purdue Pharma on Wednesday filed another Chapter 11 Reorganization Plan with an eye toward delivering more than $7.4 billion in opioid settlement payments. Last year, the Supreme Court in a slim 5–4 vote blocked Purdue’s previous attempt to claim bankruptcy. The pharma’s prior plan, according to the justices, would have seen the Sacklers hand over up to $6 billion, but would also protect the family from future litigation. This would afford the Sacklers too much protection from fallout in the company’s role in the U.S. opioid epidemic, according to the justices, who noted that such safeguards are not backed by federal bankruptcy laws. Under Wednesday’s new reorganization proposal, the Sacklers would contribute between $6.5 billion and $7 billion to the total settlement value, of which $1.5 billion would be disbursed upfront while the remaining balance would be payable over the next 15 years. In turn, a public benefit company would deliver the money to creditors “to compensate victims and abate the opioid crisis,” according to Purdue’s Wednesday release. Of note, the new plan “does not contain non-consensual third-party releases.” Creditors will instead have to opt in to the plan to receive payments. Otherwise, creditors that choose to not participate in the program will retain their right to sue the Sacklers. Purdue’s new plan is set to come before a bankruptcy court in May 2025 for confirmation or amendments. If approved, Purdue will then put the plan up for an internal vote before it can be implemented. Purdue, once owned by the Sackler family, is widely considered the chief architect of the opioid crisis in the U.S. Many allege that its synthetic opioid painkiller Oxycontin was marketed aggressively —with its side effects and addictive nature downplayed—leading to the wave of overdoses across the country. The pharma in November 2020 pleaded guilty to criminal charges related to the epidemic, in a plea deal that included accepting responsibility for it, but the Sacklers themselves have since tried to evade accountability. In December that same year, the family apologized to victims in a virtual appearance at a hearing but stopped short of admitting their own personal role in the crisis. Purdue’s proposal comes as change may be on the horizon in the pain space. In January, the FDA handed a landmark approval to Vertex Pharmaceuticals’ Journavx, the first non-opioid painkiller in more than 20 years. Several other biopharma players are following in Vertex’s footsteps, advancing their own non-addictive analgesics. One of these is Latigo Bio, which is running a Phase II trial for its sodium channel blocker LTG-001. Lexicon Pharmaceuticals, meanwhile, is advancing the small-molecule painkiller pilavapadin, which targets the AAK1 protein, a mechanism that has been shown to alleviate neuropathic pain. Pilavapadin is in Phase IIb development for diabetic peripheral neuropathic pain, topline results from which showed the candidate could meaningfully reduce pain through 8 weeks.

Phase 2Drug Approval

03 Mar 2025

·www.fiercebiotech.com

Lexicon feels the pain as midphase non-opioid data underwhelm investors

The biotech is preparing to meet with the FDA and start a phase 3 program this year. \n Lexicon Pharmaceuticals is yet again defending a mixed set of data on its non-opioid pain prospect. The biotech focused on low-dose results from its latest phase 2 trial, rather than the overall primary endpoint miss, but investors took a much more downbeat view of the data.Texas-based Lexicon published data from two phase 2 trials in 2022. Based on the findings, the biotech dropped the loading dose from the regimen for its third midphase study to improve tolerability. Monday, Lexicon shared topline results from the third study, which compared three regimens of the AAK1 inhibitor LX9211 to placebo in adults with diabetic peripheral neuropathic (DPN) pain.Pooling data from all the treatment arms, LX9211 was no better than placebo at improving average daily pain score (ADPS) after eight weeks. Lexicon blamed the primary endpoint miss on the high-dose cohort.Mean ADPS fell 1.74 and 1.38 points, respectively, in the low- and high-dose cohorts. People who began on the high dose and then switched to the low dose experienced a 1.7-point reduction. The results look solid compared to Lexicon’s earlier DPN trial, when the biotech saw reductions of 1.4 and 1.3 points, respectively. The problem, for Lexicon, is that placebo performed better in the latest trial too. The mean ADPS reduction on placebo in the latest study was 1.31, compared to 0.7 in the earlier trial. The upshot is the placebo-adjusted change at the low dose fell from around 0.7 to 0.4 between the two trials. Analysts were already questioning whether a 0.7-point delta was meaningful. Steve Edelman, a professor of medicine at the University of California San Diego, made the case that the data point was indeed meaningful at a Lexicon event in January.Investors made their own feelings about this morning\'s results clear, sending Lexicon’s share price down 40% to 42 cents when the markets opened Monday. Lexicon is publicly more positive about the study, which, in its eyes, delivered on its goal of identifying a phase 3 dose. Lexicon has seen separation from the control at the low dose in two trials and a placebo-like dropout rate in the latest study.Buoyed by those findings, the biotech is preparing to meet with the FDA and start a phase 3 program this year. Craig Granowitz, M,D., Ph.D., chief medical officer at Lexicon, made the case that the candidate can hit in phase 3 on a call with analysts to discuss the data, noting that increasing enrollment to the 300 to 350 subjects per arm planned for the phase 3 and extending the study’s duration will bring benefits.“We feel pretty confident that first of all, the trends in pain reduction will continue with the treatment arm, especially with a much lower dropout rate and with many more patients,” Granowitz said. “The variance of the data should also shrink, which should improve the statistical reliability of the dataset.”

Phase 2Clinical ResultPhase 3

100 Deals associated with Pilavapadin

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Neuralgia, Postherpetic	Phase 2	United States	Lexicon Pharmaceuticals, Inc.	29 Dec 2020
Neuralgia, Postherpetic	Phase 2	Czechia	Lexicon Pharmaceuticals, Inc.	29 Dec 2020
Neuralgia, Postherpetic	Phase 2	Poland	Lexicon Pharmaceuticals, Inc.	29 Dec 2020
Diabetic peripheral neuropathic pain	Phase 2	United States	Lexicon Pharmaceuticals, Inc.	07 Jul 2020
Neuralgia	Phase 1	-	Bristol Myers Squibb Co.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06203002 (PROGRESS, Company_Website) Manual	Phase 2	Diabetic peripheral neuropathic pain	496	Pilavapadin 10 mg	wgnivthvvk(hpfeasvnoi) = pyszrzmdmq dcryqucwcc (thsrnhxvlu ) Met	Positive	03 Mar 2025
				Pilavapadin 20 mg	wgnivthvvk(hpfeasvnoi) = jbjybqmhxn dcryqucwcc (thsrnhxvlu ) Met
NCT04455633 (RELIEF-DPN 1, EASD2023)	Phase 2	Diabetic peripheral neuropathic pain	319	LX9211 10 mg	fowsoswblk(jsmvbjpkbv) = no treatment-related SAEs or deaths gxighorxes (jnilwyorss )	Positive	03 Oct 2023
				LX9211 20 mg

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Pilavapadin

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation