Press Releases

Philadelphia, PA, April 30th, 2025 – NodThera, a leading clinical-stage biotech delivering a paradigm shift in the treatment of chronic inflammatory diseases through selective modulation of the NLRP3 inflammasome, today announces the publication of preclinical data demonstrating the potential of its clinical-stage, oral NLRP3 inflammasome inhibitor NT-0796 to augment existing GLP-1 receptor agonist (GLP-1RA) obesity therapies to deliver enhanced weight loss and sustained weight management.  

These data, published in the research journal Obesity, show that combined dosing of NodThera’s NT-0796 with semaglutide (Wegovy^®) drove greater weight loss than either monotherapy in an animal model of obesity. Treatment with the fully brain-penetrating NLRP3 inflammasome inhibitor also sharply limited weight regain following the cessation of semaglutide therapy and reduced multiple cardiovascular, inflammatory and metabolic biomarkers.

Despite the significant achievements of GLP-1RAs in the management of obesity, their use is impacted by challenges related to tolerability and the weight regain following discontinuation of treatment. NodThera is pioneering a new approach to obesity treatment built on the growing understanding of the impact of chronic inflammation on the body and its underlying role in the complex cycle of weight regulation. These new data build on NodThera’s earlier preclinical and clinical work and support the potential of central NLRP3 inhibition to reset multiple dysregulated cardiometabolic pathways, restoring the body’s natural metabolic balance and enabling sustained and healthy weight loss.

Enhanced weight loss effects of NT-0796 and semaglutide in combination

In NodThera’s latest publication, the researchers show that weight loss induced by a combination of NT-0796 and semaglutide was nearly two-fold higher at 23% over 28 days compared to semaglutide monotherapy in a high fat diet murine obesity model. Weight loss was further enhanced on the combination therapy when animals were switched for a further 28 days to a polyunsaturated fatty acid diet, intended to be more reflective of a typical human diet. Animals receiving the combination therapy experienced continued weight loss, completely reversing their obese state, with a weight loss of >30% to achieve a weight comparable to animals fed a standard control diet. Hypothalamic (brain) inflammation was also reversed among animals maintained on the combination therapy.  

Prevention of weight regain post-semaglutide treatment

In animals who were switched to NT-0796 monotherapy, following treatment with either semaglutide alone or the NT-0796 and semaglutide combination, the degree of weight regain was highly reduced compared to animals who stopped all therapy.

Potential of NLRP3 inhibition to enable a healthy weight loss

DEXA scans determined that combination therapy increased fat mass loss whilst preserving lean mass. Calorie intake was also further reduced in animals on the combination therapy, but the degree of fat mass loss observed suggests additional mechanisms, such as enhanced energy expenditure, may contribute. This supports a model consistent with the observed reduction in both peripheral and hypothalamic (brain) inflammation as a druggable mechanism in obesity pathogenesis.

Daniel Swisher, Chief Executive Officer of NodThera, commented: “These data further reinforce our belief in the potential of our brain-targeting NLRP3 inflammasome inhibitor to deliver a step change in the management of obesity. While the efficacy of existing treatments is not in doubt, there are many limitations and challenges to their real-world use by patients. The opportunity to provide patients with a highly effective oral therapy with a well-tolerated safety profile and without titration complexities is compelling and supported by our growing body of evidence indicating NT-0796’s potential as monotherapy and in combination to improve the efficacy and tolerability of existing treatments, or even as a follow-on therapy to sustain weight loss.”

Alan Watt, President and Chief Scientific Officer of NodThera, added: “By harnessing both peripheral and central NLRP3 inhibition to correct multiple dysregulated pathways in the brain and throughout the body we have the potential to bring profound cardiometabolic benefits to patients, establishing an enhanced treatment approach to weight management that would enable sustained and healthier weight loss.”

NodThera is currently preparing to initiate a robust Phase 2 obesity study of NT-0796, expected in 2Q 2025. Details about the trial’s design will be communicated upon initiation of dosing.

For more information about NodThera please contact:

NodThera

Tel: +44 (0) 1223 608130

Email: info@nodthera.com

ICR Healthcare

Amber Fennell, David Daley

Tel: +44 (0)20 3709 5700

Email: nodthera@icrhealthcare.com   

About NodThera

NodThera is a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases. Led by an experienced management team, NodThera is combining a deep understanding of NLRP3 inhibition, pharmaceutical neuroscience expertise and precision chemistry. Its two lead clinical candidates are oral, small molecule NLRP3 inflammasome inhibitors, which have demonstrated differentiated, potentially best-in-class clinical profiles with significant anti-inflammatory effects and high brain penetration, offering distinct opportunities to treat multiple indications. The Company is backed by top-tier investors including 5AM Ventures, Blue Owl Capital, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera is headquartered in Philadelphia, Pennsylvania, with additional operations in Cambridge, UK. Learn more at www.nodthera.com or follow the Company on LinkedIn.

Philadelphia, PA, August 5, 2024 – NodThera, a leading clinical-stage biotech delivering a paradigm shift in the treatment of chronic inflammatory diseases through selective modulation of the NLRP3 inflammasome, today announces that it has been named by Fierce Biotech as one of 2024’s ‘Fierce 15’ biotechnology companies, designating it as one of the most innovative and promising biotechnology companies in the industry.

Daniel Swisher, Chief Executive Officer of NodThera, commented: “Over the past year, NodThera has made significant progress towards realizing the full potential of targeting the NLRP3 inflammasome, supported by a proven leadership team, best-in-class molecules and compelling pre-clinical and clinical data. We are incredibly honored to be profiled by Fierce Biotech among the industry’s most exciting and innovative companies. With preparations underway for our Phase II clinical development program in cardiovascular disease, obesity, and neuro-inflammation among other value inflection points, this achievement underscores the strength of our science and commitment to leading a paradigm shift in the treatment of chronic inflammatory diseases.”

Ayla Ellison, Editor-in-Chief, Fierce Life Sciences and Healthcare, said: “For the past 22 years, we have evaluated hundreds of companies for inclusion in the ‘Fierce 15’ special report. Our selection process considers various factors, including technological robustness, strategic partnerships, venture support and market positioning. This report highlights innovation and creativity amid intense competition.”

This year’s full list of winners can be viewed here.

For more information about NodThera please contact:

NodThera

Tel: +44 (0) 1223 608130

Email: info@nodthera.com

ICR Consilium

Amber Fennell, David Daley, Sukaina Virji

Tel: +44 (0)20 3709 5700

Email: nodthera@consilium-comms.com

About NodThera

NodThera is a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases. Led by an experienced management team, NodThera is combining a deep understanding of NLRP3 inhibition, pharmaceutical neuroscience expertise and precision chemistry. Its two lead clinical candidates are oral, small molecule NLRP3 inflammasome inhibitors, which have demonstrated differentiated, potentially best-in-class clinical profiles with significant anti-inflammatory effects and high brain penetration, offering distinct opportunities to treat multiple indications. The Company is backed by top-tier investors including 5AM Ventures, Blue Owl Capital, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera is headquartered in Philadelphia, Pennsylvania, with additional operations in Cambridge, UK and Seattle, WA. Learn more at www.nodthera.com or follow the Company on LinkedIn.

About Fierce Biotech

Fierce Biotech is the biotech industry’s daily monitor, providing the latest news, articles, and resources related to clinical trials, drug discovery, FDA approval, FDA regulation, patent news, pharma news, biotech company news and more. More than 300,000 top biotech professionals rely on Fierce Biotech for an insider briefing on the day’s top stories.

– Greg brings over 25 years of public and private company leadership experience

Philadelphia, PA, August 1, 2024 – NodThera, a leading clinical-stage biotech delivering a paradigm shift in the treatment of chronic inflammatory diseases through selective modulation of the NLRP3 inflammasome, today announces the appointment of Greg Chow as Chief Financial and Business Officer (CFBO), effective immediately.

Greg is an experienced executive with over 25 years of corporate finance, capital markets, investment banking, financial accounting, drug development operations, and business development experience. Over the course of his career, he has led major financing rounds for both public and private companies, as well as supported operations and administrative functions.

Greg joins NodThera from Freenome Holdings, where he served as Chief Financial Officer (CFO) and helped successfully execute the company’s recent $254 million Series F financing round. Prior to Freenome, Greg was CFO at Frontier Medicines, where he helped lead its Series B and C fundraising rounds and headed up Alliance Management for its global, multi-year collaboration with AbbVie.  His leadership across Frontier’s business operations was instrumental in helping the company transition from a discovery-stage to clinical-stage organization. He gained significant public company experience as Executive Vice President and CFO at Aptose Biosciences (Nasdaq: APTO), overseeing the company’s dual listing on the Nasdaq and Toronto stock exchanges in addition to successfully raising over $225 million and attracting multiple new shareholders.

Prior to his time as an industry executive, Greg spent 14 years in investment banking as Managing Director and Director of Private Placements at Wedbush Securities and in senior roles at RBC Capital Markets and Wells Fargo Securities. Greg holds an MBA in Finance from the Wharton School at the University of Pennsylvania and a BA in Business Economics, from the University of California, Santa Barbara. He is a Certified Public Accountant (inactive) in the state of California.

Daniel Swisher, Chief Executive Officer of NodThera, said: “Greg’s financial experience and extensive track record of long-term value creation for both private and public biotechs will be invaluable as NodThera continues to execute its strategy and evolves into a mature, high-value, clinical-stage company. I look forward to working closely with him as part of our executive team. Greg will be a key strategic partner as we continue to unlock the broad potential and maximum value of our highly differentiated brain-penetrant NLRP3 inflammasome inhibitors in the treatment of chronic inflammatory diseases. On behalf of the whole team, I would like to wish him a very warm welcome to NodThera.”  

Greg Chow, Chief Financial and Business Officer of NodThera, added: “I am incredibly excited to join NodThera at such a pivotal time in its development. The potential to modulate inflammation for the treatment of chronic diseases presents a significant opportunity to impact patients’ lives in a meaningful way. I look forward to being immersed in one of the most exciting and rapidly evolving therapeutic categories in biotech today. With a highly accomplished team, positive progression of lead candidate NT-0796 and upcoming Phase II studies in obesity, cardiovascular and Parkinson’s disease, NodThera is well positioned in its current trajectory with some important inflection points on the near-term horizon. I am eager to bring my capital markets, operations, and business development experience to NodThera and look forward to partnering with Dan, the Board of Directors and the wider team.”

For more information about NodThera please contact:

NodThera

Tel: +44 (0) 1223 608130

Email: info@nodthera.com

ICR Consilium

Amber Fennell, David Daley, Sukaina Virji

Tel: +44 (0)20 3709 5700

Email: nodthera@consilium-comms.com 

About NodThera

NodThera is a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases. Led by an experienced management team, NodThera is combining a deep understanding of NLRP3 inhibition, pharmaceutical neuroscience expertise and precision chemistry. Its two lead clinical candidates are oral, small molecule NLRP3 inflammasome inhibitors, which have demonstrated differentiated, potentially best-in-class clinical profiles with significant anti-inflammatory effects and high brain penetration, offering distinct opportunities to treat multiple indications. The Company is backed by top-tier investors including 5AM Ventures, Blue Owl Capital, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera is headquartered in Philadelphia, Pennsylvania, with additional operations in Cambridge, UK and Seattle, WA. Learn more at www.nodthera.com or follow the Company on LinkedIn.

– Brain-penetrant NLRP3 inflammasome inhibitor demonstrates highly significant and rapid reduction of key inflammatory marker CRP compared to placebo

– Reductions in multiple markers of cardiometabolic risk confirm profound anti-inflammatory effect of NT-0796

– Most pronounced weight loss seen among high-risk subgroups

– Planning is underway for Phase II studies in obesity, Parkinson’s disease and other cardiometabolic indications

BOSTON, MA, June 12, 2024 – NodThera, a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases, today announces positive data from its Phase Ib/IIa cardiovascular risk study in inflamed obese subjects, evaluating the effects of its oral, brain-penetrant NLRP3 inflammasome inhibitor NT-0796, on inflammatory, cardiovascular and metabolic risk parameters.

Obese subjects with elevated baseline C-reactive protein (CRP), measured using an hsCRP assay, were recruited. Elevated CRP is a key marker of chronic inflammatory diseases such as coronary artery disease, and one or more cardiovascular risk factors (e.g. metabolic syndrome, prediabetes, diabetes, hyperlipidemia or hypertension). The study was conducted in-clinic for 28 days and energy intake was limited to 2000 kCal per day. At study end, a highly statistically significant and rapid CRP reduction in NT-0796 dosed subjects was observed compared to placebo, meeting the primary endpoint of the study. Furthermore, more than 75% of NT-0796 dosed subjects achieved a CRP reduction at day 28 to ≤2mg/L compared to less than 25% among the placebo group, a value generally regarded as a threshold for reducing cardiovascular risk.

NodThera’s study also demonstrated reductions in additional pro-inflammatory and cardiometabolic biomarkers, secondary endpoints that build on the previously reported diet-induced obesity preclinical study and Phase Ib/IIa Parkinson’s disease clinical study. Key reductions in cardiovascular and metabolic biomarkers were found to be highly translatable and consistent with the importance of targeting both brain and peripheral NLRP3. While all subjects lost weight due to calorie restriction in both the active and placebo groups, the most pronounced placebo-adjusted reductions in body weight were among high-risk subgroups of NT-0796 dosed subjects, and, with the Company’s earlier preclinical data, support the anti-obesity potential of the molecule.

Preparations are underway for a Phase II study in obesity and other Phase II studies including additional cardiometabolic diseases and Parkinson’s disease.

Alan Watt, President & Chief Scientific Officer of NodThera, said: “This is an impressive data set, made all the more remarkable by being achieved within 28 days. In addition to the profound anti-neuroinflammatory effects in Parkinson’s disease patients demonstrated previously, the data generated in this study of NT-0796 show improvements in inflammatory and metabolic biomarkers of CV risk that go beyond that seen with antibody and peptide therapies. With additional reductions in body weight that should be enhanced with longer-duration dosing, NT-0796 is confirmed as a highly promising therapeutic agent for chronic inflammatory indications.”

As before, NT-0796 was generally safe and well tolerated; adverse events (AEs) were mainly mild and transient, and no serious adverse events (SAEs) were observed.

Taken together, the findings demonstrate that NT-0796 successfully delivered anti-inflammatory changes in an obese inflamed population, amelioration of cardiometabolic risk factors and reductions in body weight within 28 days, indicating excellent potential for long-term, oral dosing in obese subjects.

For more information about NodThera please contact:

NodThera

Tel: +44 (0) 1223 608130

Email: info@nodthera.com

ICR Consilium

Amber Fennell, David Daley, Sukaina Virji

Tel: +44 (0)20 3709 5700

Email: nodthera@consilium-comms.com 

About NodThera

NodThera is a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases. Led by an experienced management team, NodThera is combining a deep understanding of NLRP3 inhibition, pharmaceutical neuroscience expertise and precision molecular chemistry. Its two lead clinical candidates are oral, small molecule NLRP3 inflammasome inhibitors, which have demonstrated differentiated, potentially best-in-class clinical profiles with significant anti-inflammatory effects and the ability to penetrate different areas of the brain, offering distinct opportunities to treat multiple indications. The Company is backed by top-tier investors including 5AM Ventures, Blue Owl Capital, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera is headquartered in Boston, MA, with additional operations in Cambridge, UK and Seattle, WA. Learn more at www.nodthera.com or follow the Company on LinkedIn.

– Dan joins NodThera with over 30 years of pharmaceutical industry leadership experience, including as President and COO of Jazz Pharmaceuticals and CEO of Sunesis Pharmaceuticals

– Interim CEO Alan Watt becomes President and CSO including leadership of R&D to further build out NodThera’s pioneering work in CNS modulation of chronic inflammatory diseases

BOSTON, MA, May 28, 2024 – NodThera, a leading clinical-stage biotech delivering a paradigm shift in the treatment of chronic inflammatory diseases through selective modulation of the NLRP3 inflammasome, today announces the appointment of Daniel Swisher as Chief Executive Officer (CEO), to strengthen the Company’s commercial capabilities, effective immediately. Alan Watt, the interim CEO moves to an expanded role as President and Chief Scientific Officer (CSO).

Dan joins NodThera with significant leadership expertise of over 30 years in the life sciences industry. During his career, he has led the advancement and commercialization of novel therapeutics across geographic regions and in multiple therapeutic areas, including neuroscience, oncology and rare diseases. He brings to NodThera significant private and public company experience driving cross functional, high-performing teams and building relationships with investors, analysts and corporate partners.

Dan joins NodThera from Jazz Pharmaceuticals (NASDAQ: JAZZ), where he recently served as President and Chief Operating Officer. At Jazz, he was instrumental in the geographic and therapeutic expansion of the company’s commercial and R&D pipeline, as well as playing a critical role in many key corporate development transactions. Prior to his time at Jazz, Dan was CEO and President of Sunesis Pharmaceuticals, guiding the evolution of its early-stage chemistry platform into a multi-asset development platform. During his CEO tenure at Sunesis, he oversaw equity capital market fundraises totaling over $400 million and led the Group to an IPO on the Nasdaq stock exchange.

Earlier in his career, Dan served as Senior Vice President of Sales and Marketing at ALZA Corporation, where he was responsible for its flagship pharmaceutical businesses based in the United States. He also played a pivotal role in the company’s growth into a fully integrated specialty pharmaceutical company and eventual $10.5 billion acquisition by Johnson & Johnson.

Alan Watt, who as the Company’s founder has also served as NodThera’s interim CEO, becomes President and CSO. He will be responsible for the growing R&D organization and focused on strengthening NodThera’s world-leading position in NLRP3 inflammasome inhibition research, with a focus on modulation of neuroinflammation for the treatment of obesity, cardiometabolic disease and neurodegeneration.

Don Nicholson, Executive Chair of the Board of Directors of NodThera, said: “Dan is an accomplished, results-driven leader with a proven track record in developing and commercializing novel therapeutics and building strong, successful businesses. We look forward to drawing on his deep understanding of the biopharmaceutical and financial markets, as well as his substantial experience in advancing clinical-stage assets towards commercialization, as we progress our broad pipeline of NLRP3 inflammasome inhibitors to deliver a paradigm shift in the treatment of chronic inflammatory diseases.

“We are extremely grateful for Alan’s strategic and scientific leadership during his tenure as interim CEO. His creativity, determination and integrity have been invaluable to NodThera in shaping the Company’s strategy and we are delighted that NodThera will continue to benefit from his expertise in his new role.”

Daniel Swisher, newly appointed Chief Executive Officer of NodThera, said: “NodThera is leading the NLRP3 inflammasome space with its best-in-class molecules and a wealth of pre-clinical and clinical data that is setting the tone for the field. NodThera has the potential to drive a positive and meaningful difference to the lives of patients suffering with obesity, cardiometabolic and neurodegenerative diseases and I am delighted to be leading the team at such an exciting point in the Company’s development, ahead of the readout from our ongoing cardiovascular risk trial in an inflamed obese population. I look forward to working alongside Alan, the Board and the wider team to achieve NodThera’s full potential.”

Alan Watt, President of Clinical & Preclinical R&D of NodThera, said: “I would like to extend the warmest welcome to Dan, who joins us at an exciting and pivotal moment. Our sector leading research in the field of NLRP3 inflammasome inhibition, our pioneering and demonstrated approach to reversal of neuroinflammation in humans and the strength of the NodThera team, provide an opportunity to bring about profound change in the management of obesity and multiple cardiometabolic and neurodegenerative diseases. I have the utmost confidence that, together, we will deliver on this opportunity.”

For more information about NodThera please contact:

NodThera

Tel: +44 (0) 1223 608130

Email: info@nodthera.com

ICR Consilium

Amber Fennell, David Daley, Sukaina Virji

Tel: +44 (0)20 3709 5700

Email: nodthera@consilium-comms.com 

About NodThera NodThera is a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases. Led by an experienced management team, NodThera is combining a deep understanding of NLRP3 inhibition, pharmaceutical neuroscience expertise and precision molecular chemistry. Its two lead clinical candidates are oral, small molecule NLRP3 inflammasome inhibitors, which have demonstrated differentiated, potentially best-in-class clinical profiles with significant anti-inflammatory effects and the ability to penetrate different areas of the brain, offering distinct opportunities to treat multiple indications. The Company is backed by top-tier investors including 5AM Ventures, Blue Owl Capital, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera is headquartered in Boston, MA, with additional operations in Cambridge, UK and Seattle, WA. Learn more at www.nodthera.com or follow the Company on LinkedIn.

– Brain-penetrant NLRP3 inflammasome inhibitor NT-0796 reduced key neuroinflammatory and inflammatory biomarkers in Parkinson’s disease patients to the levels found in healthy elderly controls over 28 days

– Demonstrates potential to change the treatment paradigm and halt disease progression with a disease-modifying approach

– Trial results will be presented at AD/PD^TM 2024 on Friday March 8 in Lisbon, Portugal

– Preparations for a Phase IIa/IIb study in Parkinson’s disease are ongoing

BOSTON, MA, March 7, 2024 – NodThera, a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases, today announces positive data from its Phase Ib/IIa study in Parkinson’s disease patients, evaluating the effects of its oral, brain-penetrant NLRP3 inflammasome inhibitor NT-0796, on inflammatory and disease-specific biomarkers in the blood and cerebrospinal fluid (CSF).

NodThera’s study demonstrated mean reductions of key pro-inflammatory biomarkers in CSF (e.g. IL-1β, IL-6, CCL2, CXCL1 and CXCL8) over 28 days compared to baseline to levels approximating those of healthy elderly controls, demonstrating reversal of NLRP3-mediated neuroinflammation. In addition, reductions in neurodegenerative markers were also observed following oral dosing of NT-0796, including NfL and soluble TREM (sTREM2). In subjects with elevated acute phase biomarkers CRP and fibrinogen, levels were reduced significantly, consistent with the peripheral anti-inflammatory effects of NT-0796 seen in elderly healthy volunteers studied in an earlier stage of the trial.

Alan Watt, Chief Executive Officer of NodThera, said: “Our new findings in Parkinson’s disease, a condition with substantial unmet medical needs, are profound and highly encouraging. They bolster our confidence in the ongoing program, with Phase II studies now in advanced planning stages. The correlation between Parkinson’s disease and neuroinflammation is well-documented, with alpha-synuclein fibrils triggering microglial NLRP3 activation, leading to neuroinflammation and subsequent neurodegeneration. This is the inaugural demonstration of an NLRP3 inhibitor’s potential to not only address Parkinson’s disease but also offer a broader impact on neurodegenerative diseases. Given that existing Parkinson’s treatments primarily manage symptoms, our innovative, disease-modifying strategy presents a significant shift, aiming to stop the disease progression. NT-0796’s demonstrated efficacy in reducing neuroinflammation in patients heralds a substantial advancement towards halting this devastating disease.”

NT-0796 was safe and well tolerated; adverse events (AEs) were mainly mild and transient, and no serious adverse events (SAEs) were observed. Pharmacokinetics indicated the drug candidate’s potential for once-daily dosing and levels of the drug candidate in the brain, determined by measuring the concentration in CSF, were found to be maintained over 24 hours.

Taken together, the findings demonstrate that NT-0796 successfully delivered anti-neuroinflammatory and anti-inflammatory changes within 7 days and sustained for 28 days, indicating excellent potential for long-term, oral dosing in Parkinson’s disease patients.

Prof. Thomas Foltynie BSc, MBBS, MRCP, PhD, Professor of Neurology in the Department of Clinical and Movement Neurosciences, UCL Institute of Neurology and Consultant Neurologist at the National Hospital for Neurology and Neurosurgery, Queen Square, London, said: “These results are particularly promising for the future of Parkinson’s disease treatment, providing a compelling approach to the modulation of inflammation in the brain, a key driver in the development of this disease. Such an approach has the potential to change the face of treatment – actually stopping the disease in its tracks, that would be of enormous value to those living with Parkinson’s disease.”

The findings from NodThera’s study will be presented on Friday March 8 at AD/PD^TM 2024, the international conference on Alzheimer’s and Parkinson’s diseases and related neurological disorders, taking place in Lisbon, Portugal.

Additionally, following the recently published preclinical data demonstrating NodThera’s NLRP3 inflammasome inhibitors reversed diet-induced obesity (DIO) and inflammation in mice the Company’s pioneering Phase Ib/IIa clinical study of NT-0796 in obese subjects with cardiovascular risk is in progress with results expected by end of 2Q24. This biomarker-rich study is measuring the change in baseline to Day 28 of CRP levels, a key peripheral inflammatory marker and known predictor of risk of developing atherosclerotic cardiovascular (CV) disease as well as the potential for modification of body weight over 28 days.

For more information about NodThera please contact:

NodThera

Tel: +44 (0) 1223 608130

Email: info@nodthera.com

ICR Consilium

Amber Fennell, David Daley, Sukaina Virji

Tel: +44 (0)20 3709 5700

Email: nodthera@consilium-comms.com 

About NodThera

NodThera is a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases. Led by an experienced management team, NodThera is combining a deep understanding of NLRP3 inhibition, pharmaceutical neuroscience expertise and precision molecular chemistry. Its two lead clinical candidates are oral, small molecule NLRP3 inflammasome inhibitors, which have demonstrated differentiated, potentially best-in-class clinical profiles with significant anti-inflammatory effects and the ability to penetrate different areas of the brain, offering distinct opportunities to treat multiple indications. The Company is backed by top-tier investors including 5AM Ventures, Blue Owl Capital, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera is headquartered in Boston, MA, with additional operations in Cambridge, UK and Seattle, WA. Learn more at www.nodthera.com or follow the Company on LinkedIn.

-Data published in Journal of Pharmacology and Experimental Therapeutics

-NodThera’s brain-penetrant NLRP3 inhibitors matched weight loss driven by GLP-1 receptor agonist semaglutide (Wegovy^®) or calorie restriction, while also providing enhanced improvements in disease-relevant biomarkers of cardiovascular inflammation and lipid metabolism

-Findings indicate NLRP3 activation in the brain is implicated in driving obesity which can be reversed with brain penetrant NLRP3 inhibitors

-Additionally, combinations of an NLRP3 inhibitor and a GLP-1 receptor agonist were shown to be additive on weight loss in as-yet unpublished data

-NodThera’s lead candidate NT-0796 is currently in Phase Ib/IIa development in cardiometabolic disease and Parkinson’s disease

BOSTON, MA, February 19, 2024 – NodThera, a leading clinical-stage biotech developing brain-penetrant NLRP3 inhibitors to treat chronic inflammatory diseases, today announces the publication of preclinical data demonstrating its clinical-stage investigational compounds reversed diet-induced obesity (DIO) and inflammation in an animal model of disease.

The data are published in the Journal of Pharmacology and Experimental Therapeutics in a paper titled ‘Reversal of high fat diet-induced obesity, systemic inflammation and astrogliosis by the NLRP3 inflammasome inhibitors NT-0249 and NT-0796’¹.

The NLRP3 inflammasome is a highly validated anti-inflammatory drug target, and these findings demonstrate that NLRP3 plays a key role in controlling obesity and obesity-associated inflammation through the modulation of hypothalamic gliosis. Both NT-0796 and NT-0249, two structurally distinct NLRP3 inhibitors in clinical development by NodThera, have generated a wealth of preclinical and clinical data demonstrating brain-penetration and broad anti-inflammatory effects, with NT-0796 being the first NLRP3 inhibitor to show reduced neuroinflammation in the clinic.

In this latest publication, NodThera’s researchers show for the first time the ability of NT-0796 and NT-0249 to reverse DIO in a murine model, providing comparisons against the effects of the GLP-1 receptor agonist (GLP-1RA) semaglutide (Wegovy®) and calorie restriction. While all three therapeutic approaches led to statistically significant reductions in body fat in DIO mice, only the NLRP3 inhibitors reduced disease-relevant cardiovascular inflammatory biomarkers such as fibrinogen, sVCAM-1, suPAR, and PCSK9 suggesting their potential to further reduce cardiovascular risk in obese populations. NodThera has additionally explored alternative treatment scenarios where NLRP3 inhibitors can be combined with a GLP1-RA or used as a follow-on therapy for patients who do not tolerate GLP-1RA drugs. Yet-to-be-published preclinical findings have demonstrated an additive weight loss effect when combining the brain-penetrant NLRP3 inhibitors with low dose GLP-1RAs, and stable weight maintenance following cessation of GLP-1RA therapy by dosing of a brain penetrant NLPR3 inhibitor, thereby preventing body mass regain.

Obesity is a global health concern that predisposes individuals to chronic disease such as diabetes and cardiovascular disease at least in part by promoting systemic inflammation.

Alan Watt, Chief Executive Officer of NodThera, said: “These remarkable findings – the first in the field of NLRP3 inflammasome research – suggest that in obese mice consuming a high-fat diet, brain-penetrant NLRP3 inhibition and the resulting anti-inflammatory effect confers not only reversal of obesity but metabolic benefits that extend well beyond this. While GLP-1 receptor agonists have undoubtedly delivered significant achievements in the management of obesity, their adverse event profile is well established, presenting difficulties for some patients. Our brain penetrant NLRP3 inhibitors deliver robust weight loss and broad cardiometabolic benefits by targeting a novel molecular mechanism with the convenience of oral dosing and an exceptional safety profile. Our ongoing Phase IIa study in obese individuals at cardiovascular risk will further validate these pre-clinical findings.”

References:

1. Reversal of High Fat Diet-Induced Obesity, Systemic Inflammation, and Astrogliosis by the NLRP3 Inflammasome Inhibitors NT-0249 and NT-0796. Peter Thornton, Valérie Reader, Zsofia Digby, Pamela Smolak, Nicola Lindsay, David Harrison, Nick Clarke and Alan P. Watt. Journal of Pharmacology and Experimental Therapeutics March 2024, 388 (3) 813-826; DOI: https://doi.org/10.1124/jpet.123.002013

For more information about NodThera please contact:

NodThera

Tel: +44 (0) 1223 608130

Email: info@nodthera.com

ICR Consilium

Amber Fennell, David Daley, Sukaina Virji

Tel: +44 (0)20 3709 5700

Email: nodthera@consilium-comms.com 

About NodThera

NodThera is a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases. Led by an experienced management team, NodThera is combining a deep understanding of NLRP3 inhibition, pharmaceutical neuroscience expertise and precision molecular chemistry. Its two lead clinical candidates are oral, small molecule NLRP3 inflammasome inhibitors, which have demonstrated differentiated, potentially best-in-class clinical profiles with significant anti-inflammatory effects and the ability to penetrate different areas of the brain, offering distinct opportunities to treat multiple indications. The Company is backed by top-tier investors including 5AM Ventures, Blue Owl Capital, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera is headquartered in Boston, MA, with additional operations in Cambridge, UK and Seattle, WA. Learn more at www.nodthera.com or follow the Company on LinkedIn.

BOSTON, MA, February 5, 2024 – NodThera, a leading clinical-stage biotech developing brain-penetrant NLRP3 inhibitors to treat chronic inflammatory diseases, today announces the appointment of Thomas Jaecklin, M.D., M.Sc., FMH as Chief Medical Officer (CMO), with effect from today.

With more than 20 years of experience across global large pharma, biotech and academic medicine, Dr. Jaecklin is an accomplished late-stage drug development leader. He brings deep expertise across multiple therapy areas, including neuroscience and inflammation, with a strong track record in the execution of integrated drug development programs, progressing clinical assets through to regulatory and commercial success.

Dr. Jaecklin most recently served as Vice President, Global Program Head of the Small Molecule Portfolio at the global biotechnology company Galapagos NV (Euronext & NASDAQ: GLPG), where his strategic guidance led to multiple successful regulatory submissions and approvals. Prior to this, he was Senior Vice President, Head of Clinical Development at global biopharmaceutical company Mirum Pharmaceuticals (NASDAQ: MIRM). At Mirum, he initiated and drove the spin-off of two rare disease assets from Shire to successful registration and oversaw the regulatory submission and approval of Livmarli® (maralixibat chloride) less than 3 years later. He also played a pivotal role in the company’s creation and build-up, assisting in its $120 million Series A Financing and subsequent IPO. Earlier in his career, Thomas served in key leadership roles in clinical and medical assessment, business development and market access at Novartis.

Dr. Jaecklin earned his M.D. from the University of Geneva, followed by a M.Sc. from the University of Toronto. He is Swiss board-certified in paediatrics, neonatology and critical care medicine.

Alan Watt, Chief Executive Officer of NodThera, said: “We are delighted to welcome Thomas to the NodThera team, with his wealth of sector experience and successful execution of drug development programs across multiple therapeutic areas. These will be critical to us delivering our vision of a paradigm shift in the treatment of disease through the selective modulation of the NLRP3 inflammasome.”

Dr. Thomas Jaecklin, newly appointed Chief Medical Officer of NodThera, added: “The NLRP3 inflammasome is one of the most exciting emerging areas of therapeutic science, and NodThera’s best-in-class molecules hold great potential to address the unmet medical need in multiple neurodegenerative and cardiometabolic diseases. With a wealth of excellent data and two ongoing Phase Ib/IIa studies, I am excited to be joining the Company at such a critical juncture and look forward to working with the leadership team and Board to advance our clinical programs.”

NodThera’s pioneering, biomarker-rich Phase Ib/IIa study investigating the potential of its lead candidate NT-0796 in Parkinson’s disease, announced in June 2023, has successfully dosed all patients and is on track to read out in Q1 2024. This readout will be closely followed in 2Q24 with results from the Company’s ongoing Phase Ib/IIa cardiovascular risk trial in an inflamed obese population, further reinforcing NodThera’s leadership position in the field.

For more information about NodThera please contact:

NodThera

Tel: +44 (0) 1223 608130

Email: info@nodthera.com

ICR Consilium

Amber Fennell, David Daley, Sukaina Virji

Tel: +44 (0)20 3709 5700

Email: nodthera@consilium-comms.com 

About NodThera

NodThera is a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases. Led by an experienced management team, NodThera is combining a deep understanding of NLRP3 inhibition, pharmaceutical neuroscience expertise and precision molecular chemistry. Its two lead clinical candidates are oral, small molecule NLRP3 inflammasome inhibitors, which have demonstrated differentiated, potentially best-in-class clinical profiles with significant anti-inflammatory effects and the ability to penetrate different areas of the brain, offering distinct opportunities to treat multiple indications. The Company is backed by top-tier investors including 5AM Ventures, Blue Owl Capital, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera is headquartered in Boston, MA, with additional operations in Cambridge, UK and Seattle, WA. Learn more at www.nodthera.com or follow the Company on LinkedIn.

-Aberrant NLRP3 activation is recognised as a critical driver of cardiometabolic disease

-A Phase Ib/IIa trial of lead candidate NT-0796 will assess inflammatory biomarkers and other cardiometabolic endpoints in an inflamed obese population

-Sub-cohort will examine potential of NLRP3 modulation to reduce neuroinflammation as a contributor to cardiometabolic disease in these patients

BOSTON, MA, October 16, 2023 – NodThera, a leading clinical-stage biotech developing brain-penetrant NLRP3 inhibitors to treat chronic inflammatory diseases, today announces that the first patients have been dosed in a Phase Ib/IIa clinical trial evaluating the potential of its lead candidate, NT-0796, to assess cardiometabolic biomarkers in obese patients with risk factors for atherosclerotic cardiovascular disease. This follows the U.S. Food and Drug Administration’s (FDA) ‘safe to proceed’ letter in response to the Company’s Investigational New Drug (IND) application.

The NLRP3 inflammasome is a highly validated drug target that plays a pivotal role in controlling inflammatory diseases. NLRP3 activation is recognised as a critical driver of cardiometabolic disease with strong data supporting a role in atherosclerosis, myocardial infarction and heart failure.

Emerging evidence also suggests that NLRP3 activation can drive neuroinflammation (reactive gliosis) leading to dysregulated storage of body fat, energy utilisation and obesity. NodThera’s trial of its brain-penetrant candidate NT-0796 will explore the potential of central NLRP3 inhibition in the brain to reduce gliosis and other consequences of obesity.

The randomised, double-blind, placebo-controlled Phase Ib/IIa trial will evaluate the pharmacokinetic and pharmacodynamic (PK/PD) profile of NT-0796 in inflamed obese patients over 28 days. Up to 60 patients will be enrolled and randomised into two cohorts receiving either NT-0796 or placebo. The study’s primary endpoint is the change in baseline to Day 28 of high-sensitivity C-reactive protein (CRP) levels, a key peripheral inflammatory marker and known predictor of risk of developing atherosclerotic cardiovascular (CV) disease. Secondary endpoints include multiple inflammatory and CV-risk specific biomarkers.

Alan Watt, Chief Executive Officer of NodThera, said: “Atherosclerosis is the leading cause of death in Western populations and inflammation is increasingly recognised as playing a major role in all stages of the disease.” Modulation of the NLRP3 inflammasome consequently holds great potential for the development of novel treatment approaches. Our strategy at NodThera has been to develop small molecule NLRP3 inhibitors that penetrate both tissues and brain, not just for treating neurological disease but for treating the central components of peripheral disease that are caused by neurological dysfunction.

“Novel in-house preclinical findings have confirmed the importance of inhibiting brain NLRP3 in cardiometabolic disease models. In evaluating an obese population at high risk of cardiovascular disease we aim to assess the impact of NLPR3 inhibition on both peripheral inflammation and reactive gliosis, both of which contribute to cardiometabolic dysfunction.”

An earlier first-in-human study of NT-0796 has confirmed the candidate’s excellent PK/PD profile, brain penetration and anti-inflammatory effects in healthy subjects. A Phase Ib/IIa study in Parkinson’s disease patients is ongoing following NT-0796’s demonstration of a reduction of multiple neuroinflammatory and inflammatory biomarkers in plasma and cerebrospinal fluid (CSF) of elderly volunteers.

For more information about NodThera please contact:

NodThera

Tel: +44 (0) 1223 608130

Email: info@nodthera.com

ICR Consilium

Amber Fennell, David Daley, Sukaina Virji

Tel: +44 (0)20 3709 5700

Email: nodthera@consilium-comms.com 

About NodThera

NodThera is a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases. Led by an experienced management team, NodThera is combining a deep understanding of NLRP3 inhibition, pharmaceutical neuroscience expertise and precision molecular chemistry. Its two lead clinical candidates are oral, small molecule NLRP3 inflammasome inhibitors, which have demonstrated differentiated, potentially best-in-class clinical profiles with significant anti-inflammatory effects and the ability to penetrate different areas of the brain, offering distinct opportunities to treat multiple indications. The Company is backed by top-tier investors including 5AM Ventures, Cowen Healthcare Investments, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera is headquartered in Boston, MA, with additional operations in Cambridge, UK and Seattle, WA. Learn more at www.nodthera.com or follow the Company on LinkedIn.

NT-0796 demonstrates reduction of multiple neuroinflammatory and inflammatory biomarkers in plasma and CSF of elderly volunteers in just 7 days

Individuals with the highest baseline levels of inflammation demonstrate greatest reductions, including reductions in CSF neurofilament light chain (NfL), a key biomarker of neurodegeneration

Recruitment into patient arm of pioneering Phase Ib/IIa study in Parkinson’s disease with extensive biomarker analysis ongoing

BOSTON, MA, July 11, 2023 – NodThera, a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases, today announces positive, initial data from four subjects in the elderly volunteer stage of its Phase Ib/IIa study evaluating the effects of its lead candidate NT-0796 on inflammatory and disease-specific biomarkers in the blood and cerebrospinal fluid (CSF). 

Alan Watt, Chief Executive Officer of NodThera, said: “Taken together, these initial findings represent the first unambiguous demonstration of modulation of neuroinflammation in a human population with an NLRP3 inflammasome inhibitor. In designing our Parkinson’s disease study, we deliberately chose to measure the effects of NT-0796 in an elderly volunteer population as the first stage, since age is a clear factor in increased neuroinflammation. 

“Demonstrating such rapid decreases in just 7 days, across a broad range of neuroinflammatory biomarkers in the CSF, particularly NfL, is a striking result, as other drugs have required an extended timeframe of months or even years to show reduction of this biomarker. Our data provide clear validation of our strategy to take highly differentiated brain penetrant molecules into the clinic and justify our confidence in the potential of NT-0796 to treat diseases such as Parkinson’s disease and Alzheimer’s disease.”

Professor Paul Matthews, Head of the Department of Brain Sciences in the Faculty of Medicine of Imperial College London, said: “These data, while still very preliminary, provide promising evidence of the potential of NLRP3 inhibition to modulate the neuroinflammation associated with Parkinson’s disease. This is an exciting area. Development of molecules based on this concept could lead to a step change in the treatment landscape for neurodegenerative diseases more generally.” 

Significant anti-inflammatory effects in both plasma and CSF

Initial data from the ongoing study confirm earlier findings from the completed first-in-human and preclinical studies with NT-0796 showing excellent pharmacokinetics with a novel capsule formulation.

Subjects in the study were cannulated and CSF-sampled on Day 1 (pre-dose) and Day 7 following daily NT-0796 dosing. CSF drug levels were confirmed as consistent with previous observations and a range of inflammatory CSF biomarkers demonstrated meaningful reductions. 

Neurofilament light chain (NfL), exclusively synthesised in the central nervous system (CNS), decreased by approximately 25% over 7 days in the most inflamed subject and by 13% on average. NfL is now recognised by the Food and Drug Administration (FDA) as a key biomarker of neuroaxonal damage and neurodegeneration.

A full panel of cytokines, chemokines and adhesion molecules known to be associated with neuroinflammation were determined in the CSF, with the most inflamed individuals again demonstrating the most robust reductions. As previously observed, the most inflamed subjects at baseline showed the largest decreases in key peripheral inflammatory markers, C-reactive protein (CRP) and fibrinogen. Consistent reductions in circulating levels of unstimulated IL-1β, IL-18 and TNFα were also seen in subjects on Day 7 compared to Day 1.

NodThera’s pioneering, biomarker-rich Phase Ib/IIa study in Parkinson’s disease, previously announced in June 2023, is currently recruiting into the patient arm of the study. This innovative clinical biomarker panel was designed using the preclinical profile of NT-0796 which demonstrated modulation of cytokines, chemokines and markers of gliosis relevant to neuroinflammatory disease.

For more information about NodThera please contact:

NodThera

Tel: +44 (0) 1223 608130

Email: info@nodthera.com 

Consilium Strategic Communications

Amber Fennell, David Daley, Sukaina Virji 

Tel: +44 (0)20 3709 5700

Email: nodthera@consilium-comms.com  

About NodThera

NodThera is a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases. Led by an experienced management team, NodThera is combining a deep understanding of NLRP3 inhibition, pharmaceutical neuroscience expertise and precision molecular chemistry. Its two lead clinical candidates are oral, small molecule NLRP3 inflammasome inhibitors, which have demonstrated differentiated, potentially best-in-class clinical profiles with significant anti-inflammatory effects and the ability to penetrate different areas of the brain, offering distinct opportunities to treat multiple indications. The Company is backed by top-tier investors including 5AM Ventures, Cowen Healthcare Investments, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera is headquartered in Boston, MA, with additional operations in Cambridge, UK and Seattle, WA. Learn more at www.nodthera.com or follow the Company on LinkedIn.