Diabetic peripheral neuropathic pain

Boston biotech Axonis Therapeutics has raised a $115 million Series A to test whether its oral drug AXN-027 can help patients with focal epilepsy and diabetic neuropathic pain. The financing, disclosed Wednesday morning, will get the biotech into the clinic around the end of this year, or about the same time Ovid Therapeutics expects to begin human trials with a similar approach by way of an AstraZeneca platform it licensed. Both companies are looking at KCC2, a CNS chloride transporter that is key to electrical signaling in the brain. KCC2 allows for neuronal GABA signaling. The GABA pathway has been targeted by multiple drugmakers , including Sage’s postpartum depression medicine Zurzuvae , but biotechs have yet to enter the clinic with a focus on KCC2, CEO Joanna Stanicka told Endpoints News . “Often GABA treatments can induce global inhibition, which leads to this cognitive impairment and sedation often reported by patients,” Stanicka said, adding that focused inhibition should avoid those side effects. The 13-employee biotech also said Wednesday that it added Donald Manning as chief medical officer and Jeff Imbaro as operating chief. Manning previously held the same post at Travecta, Pacira BioSciences and Adynxx. Imbaro was in the same role at stroke-focused Elevian, and before that he was a founding member of Vertex-acquired Semma Therapeutics. Axonis was founded by spinal cord injury patient advocate and board observer Bob Yant about 15 years ago, but it didn’t become “operational” until 2019, Stanicka said. Prior to the Series A, Axonis had raised about $34 million in seed funding and about $9 million in government and foundation money, Stanicka said. Its investors include Cormorant Asset Management, venBio, Sofinnova Investments, Merck’s corporate venture arm and others. The startup anticipates the Series A will fund AXN-027 through Phase 2 proof-of-concept studies, she said.

Analysis Marks the First Study of Spinal Cord Stimulation to Demonstrate Long-term, Significant, and Clinically Meaningful Reductions in HbA1c and Weight in Study Participants with Painful Diabetic Neuropathy and Type 2 Diabetes REDWOOD CITY, Calif., Oct. 29, 2024 /PRNewswire/ -- Nevro Corp. (NYSE: NVRO), a global medical device company that is delivering comprehensive, life-changing solutions for the treatment of chronic pain, today announced the publication of new data in the Journal of Pain Research demonstrating significant, durable pain relief and long-term and clinically meaningful reductions in hemoglobin A1c (HbA1c) and weight in study participants with painful diabetic neuropathy (PDN) and Type 2 diabetes who received 10 kHz high-frequency spinal cord stimulation (SCS) therapy.1 Globally, the number of people with diabetes has quadrupled in the last two decades2, and PDN impacts up to 25% of all people with diabetes.3 PDN can have significant impacts on the quality of life for people living with this condition, with symptoms like numbness, tingling/paresthesia, loss of protective sensation, impaired balance, and reduced response to sensory stimuli.4 Patients typically manage PDN with oral pain medications, but the efficacy of these medications is relatively low and can result in intolerable side effects.5 As a result, people with PDN suffer from significantly reduced health-related quality of life (HRQoL), impaired functionality and other comorbidities like sleep disorders, depression, and anxiety.6 The analysis evaluated 144 patients with Type 2 diabetes and refractory PDN who received 10 kHz SCS therapy during the SENZA-PDN randomized controlled trial (RCT), the largest RCT to evaluate SCS to treat PDN. Changes in pain intensity, HbA1c, weight, and sleep were evaluated over 24 months, with participants stratified according to preimplantation HbA1c. At 24 months, the following benefits were noted1: Significant, durable pain relief: Study participants had a mean pain reduction of 79.8% and the mean visual analog scale (VAS) score for lower limb pain decreased from 7.5 ± 0.1 cm at preimplantation to 1.5 ± 0.2 cm (p < 0.001). Clinically meaningful, statistically significant mean reductions in HbA1c: Participants with preimplantation HbA1c >7% and >8% achieved mean reductions of 0.5% (p = 0.031) and 1.1% (p = 0.004), respectively. Significant mean weight loss: Across all study participants, patients achieved a significant mean weight loss of 3.1 kg (p = 0.003). In participant subgroups with body mass indices (BMI) of ≥ 30 and ≥ 35 kg/m2, mean weight reductions were 4.1 kg (p = 0.001) and 5.4 kg (p = 0.005), respectively. Significant, durable reductions in pain interference with sleep: Study participants experienced a highly significant improvement in sleep quality, with pain and sleep questionnaire three-item (PSQ-3) scores decreasing by a mean of 65.2%, corresponding to a mean value of 1.9 ± 0.2 cm (p < 0.001). "People with PDN know that this condition can extend well beyond pain – impacting sleep, sensory functions, and overall quality of life," said Dr. David Klonoff, Medical Director, Diabetes Research Institute at Mills-Peninsula Medical Center. "This is the first study of SCS to demonstrate long-term, significant and clinically meaningful reductions in HbA1c and weight in people with PDN and Type 2 diabetes – suggesting possible metabolic benefits with 10 kHz SCS for these patients." "The SENZA-PDN RCT has already demonstrated the significant pain relief benefit when using Nevro's HFX device for the millions of people suffering from PDN around the world," said Dr. David Caraway, Nevro's Chief Medical Officer. "Now, for the first time, we've observed secondary benefits like improved HbA1c and weight loss, which exhibit potentially disease-modifying effects for people with Type 2 diabetes. I'm grateful for the dedication of the clinical investigators who supported this latest analysis and the broader SENZA-PDN RCT as we continue gathering data to support market access for more patients." The 24-month data from the SENZA-PDN RCT were originally published in Diabetes Research and Clinical Practice in 2023. These data showed that patients who received a high-frequency 10 kHz SCS implant and conventional medical management (CMM), compared to CMM alone, experienced durable pain relief and improvements in HRQoL, neurological function, and sleep at 24 months post-implantation. To learn more about Nevro's 10 kHz Therapy™ for PDN, visit . References Nevro's high-frequency, 10 kHz spinal cord stimulation (SCS) device has not been approved or evaluated by the U.S. Food and Drug Administration (FDA) for the treatment of HbA1c and/or weight loss. World Health Organization. (‎2016)‎. Global report on diabetes. World Health Organization. Shillo P, et al. Painful and Painless Diabetic Neuropathies: What Is the Difference? Curr Diab Rep. 2019 May 7;19(6):32. doi: 10.1007/s11892-019-1150-5. PMID: 31065863; PMCID: PMC6505492. Pop-Busui R, Ang L, Boulton AJM, Feldman EL, Marcus RL, Mizokami-Stout K, et al. Diagnosis and Treatment of Painful Diabetic Peripheral Neuropathy. Arlington (VA): American Diabetes Association; 2022. Yang, M., Qian, C., & Liu, Y. (2015). Suboptimal Treatment of Diabetic Peripheral Neuropathic Pain in the United States. Pain medicine (Malden, Mass.), 16(11), 2075–2083. Alleman, C. J., Westerhout, K. Y., Hensen, M., Chambers, C., Stoker, M., Long, S., & van Nooten, F. E. (2015). Humanistic and economic burden of painful diabetic peripheral neuropathy in Europe: A review of the literature. Diabetes research and clinical practice, 109(2), 215–225. Internet Posting of Information Nevro routinely posts information that may be important to investors in the "Investors" section of its website at . The company encourages investors and potential investors to consult the Nevro website regularly for important information about Nevro. About Nevro Headquartered in Redwood City, California, Nevro is a global medical device company focused on delivering comprehensive, life-changing solutions that continue to set the standard for enduring patient outcomes in chronic pain treatment. The company started with a simple mission to help more patients suffering from debilitating pain and developed its proprietary 10 kHz Therapy™, an evidence-based, non-pharmacologic innovation that has impacted the lives of more than 115,000 patients globally. Nevro's comprehensive HFX™ spinal cord stimulation (SCS) platform includes the Senza® SCS system and support services for the treatment of chronic pain of the trunk and limb and painful diabetic neuropathy. Nevro recently added a minimally invasive treatment option for patients suffering from chronic sacroiliac joint ("SI joint") pain and now provides the most comprehensive portfolio of products in the SI joint fusion space, designed to meet the preferences of physicians and varying patient needs in order to improve outcomes and quality of life for patients. Senza®, Senza II®, Senza Omnia™, and HFX iQ are the only SCS systems that deliver Nevro's proprietary 10 kHz Therapy. Nevro's unique support services provide every patient with an HFX Coach™ throughout their pain relief journey and every physician with Nevrocloud™ insights for enhanced patient and practice management. SENZA, SENZA II, SENZA OMNIA, OMNIA, HF10, the HF10 logo, 10 kHz Therapy, HFX, the HFX logo, HFX iQ, the HFX iQ logo, HFX Algorithm, HFX CONNECT, the HFX Connect logo, HFX ACCESS, the HFX Access logo, HFX COACH, the HFX Coach logo, Nevrocloud, RELIEF MULTIPLIED, HFX AdaptivAI, the X logo, NEVRO, and the NEVRO logo are trademarks or registered trademarks of Nevro Corp. Patents covering Senza HFX iQ and other Nevro products are listed at Nevro.com/patents. Bluetooth® and the Bluetooth symbol are registered trademarks of their respective owners. To learn more about Nevro, connect with us on LinkedIn, X, Facebook, and Instagram. Investors and Media: Angie McCabe Vice President, Investor Relations & Corporate Communications [email protected] SOURCE Nevro Corp. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Top-line Data Now Anticipated in Q1 2025 LX9211 has previously received Fast Track designation from the U.S. Food and Drug Administration (FDA) for DPNP THE WOODLANDS, Texas, Oct. 22, 2024 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that it has closed screening and expects to complete enrollment ahead of schedule in PROGRESS (A Phase 2b, Dose-ranging, Randomized, Double-blind, PlacebO-controlled, Parallel-GRoup, MulticEnter Study in PatientS with Diabetic Peripheral Neuropathic Pain) studying LX9211, an orally-delivered, potent, selective, investigational small molecule inhibitor of adaptor-associated kinase 1 (AAK1). The Company also updated its expectations for the timing of anticipated top-line data, from the second quarter of 2025 to the first quarter of 2025. “We are excited to be ahead of schedule for a near-term completion of PROGRESS for LX9211, with top-line data now anticipated in Q1 of next year,” said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer. “There have been no new, non-opioid medications approved for neuropathic pain in more than two decades, and there is an urgent need for novel treatment options. We believe that LX9211 has the potential to positively impact the lives of people suffering with neuropathic pain and we thank the investigators, study sites, Lexicon clinical team members and especially the patients for their participation in this important study.” PROGRESS commenced in December of 2023 with the goal of enrolling adult patients with a diagnosis of diabetes (type 1 or type 2) with moderate to severe DPNP, with patients allowed to continue their current pain therapy. The primary endpoint of PROGRESS is a reduction of Average Daily Pain Score (ADPS) at 8 weeks. About Lexicon Pharmaceuticals Lexicon 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 commercially launched one of these medicines, INPEFA® (sotagliflozin) in the United States, and has a pipeline of other promising drug candidates in discovery and clinical and preclinical development in neuropathic pain, diabetes and metabolism and other indications. For additional information, please visit www.lexpharma.com. About LX9211 Discovered using Lexicon’s unique approach to gene science, LX9211 is a potent, orally delivered, selective, investigational small molecule inhibitor of AAK1. Lexicon identified AAK1 in its target discovery efforts as a promising approach for the treatment of neuropathic pain. Preclinical studies of LX9211 demonstrated central nervous system penetration and reduction in pain behavior in models of neuropathic pain without affecting opiate pathways. LX9211 received Fast Track designation from the U.S. Food and Drug Administration for development in diabetic peripheral neuropathic pain. 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, including the commercialization of its approved products and the clinical development of, regulatory filings for, and potential therapeutic and commercial potential of LX9211 and its other drug candidates. In addition, this press release also contains forward looking statements relating to Lexicon’s growth and future operating results, discovery, development and commercialization 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, successfully commercialize its approved products, successfully conduct preclinical and clinical development and obtain necessary regulatory approvals of 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 approved products and other 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, 2023, as 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