Press Releases

– 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.

NEWS/INSIGHTS

-Oral, small molecule, clinical candidates NT-0249 and NT-0796 demonstrate differentiated, potentially best-in class clinical profiles with significant anti-inflammatory effects

-Proven to penetrate different areas of the brain, providing opportunity to treat multiple indications

-Pioneering, biomarker-rich Parkinson’s disease study now underway with NT-0796

BOSTON, MA, June 20, 2023 – NodThera, a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases, today announces positive data from first-in-human studies of its lead therapeutic candidates, NT-0249 and NT-0796, and provides an update on the Company’s priority clinical development programme.

In the studies, both candidates were shown to clearly inhibit the NLRP3 inflammasome, a highly

validated drug target that plays a pivotal role in controlling inflammatory diseases. The differentiated design characteristics of each candidate enabled them to penetrate different areas of the brain for optimal drug distribution in a range of NLRP3-driven diseases.

Brain penetration and anti-inflammatory effects across both clinical programmes

Data from the recently completed multiple-ascending dose (MAD) cohorts of NT-0249’s first-in-human study confirm a potentially best-in-class pharmacokinetic/ pharmacodynamic (PK/PD) profile, suitable for once-daily dosing. NT-0249 demonstrated significant anti-inflammatory effects in healthy volunteers, with reductions in key inflammatory biomarkers, C-reactive protein (CRP) and fibrinogen, that were maintained throughout treatment. Levels of NT-0249 measured in the cerebrospinal fluid (CSF) additionally demonstrated high levels of brain penetration.

Findings from the completed first-in-human study of NT-0796, initially disclosed in September 2022, also confirm an excellent PK/PD profile, brain penetration and anti-inflammatory effects in healthy volunteers.

Both candidates were well tolerated, treatment emergent effects were predominantly mild and there were no serious adverse events (SAEs).

Priority development programme underway in Parkinson’s disease

Development of NT-0796 is now progressing in a pioneering, biomarker-rich Phase Ib/IIa study in Parkinson’s disease. The study is exploring the candidate’s effect on inflammatory and disease-specific biomarkers in the blood and CSF using an innovative clinical biomarker panel, designed using the preclinical profile of NT-0796 on cytokines, chemokines and markers of microgliosis and astrogliosis relevant to NLRP3 inhibition.

The initial stage of the study, in healthy, elderly volunteers, is already underway, investigating a

modified formulation of the drug candidate designed for use in the upcoming patient arm of the study.

Alan Watt, Chief Executive Officer of NodThera, said: “As the burden of non-communicable diseases continues to rise globally, targeting chronic low-grade inflammation, through selective modulation of the NLRP3 inflammasome, holds enormous potential for the treatment of these diseases. Our strategy to design highly differentiated and brain penetrant molecules, which combines a deep understanding of NLRP3 inhibition, pharmaceutical neuroscience expertise and precision molecular design, is delivering on the promise that NLRP3 inflammasome modulation can change the treatment paradigm for chronic peripheral and neurodegenerative diseases. These excellent clinical data from both clinical candidates reinforce our confidence that NodThera has the clinical tools to address these challenges.”

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 successfully completes Phase 1 study, demonstrating blood-brain barrier penetration and reduced inflammatory biomarkers supporting advancement in neuroinflammatory and peripheral inflammatory diseases-

-Second clinical candidate NT-0249 achieves positive interim results from its Phase 1 study supporting once daily dosing for peripheral inflammatory disease-

LEXINGTON, MA – September 21, 2022 – NodThera, a clinical-stage biotechnology company developing a new class of potent and selective oral, small molecule NLRP3 inflammasome inhibitors to treat diseases driven by chronic inflammation, today announced positive Phase 1 clinical readouts for its first and second clinical candidates, NT-0796 and NT-0249. NT-0796 has completed its Phase 1 study confirming brain penetration with excellent pharmacokinetic (PK) & pharmacodynamic (PD) profiles and NT-0249 has completed dosing of the Phase 1 single ascending dose cohorts confirming a potentially best-in-class PK/PD profile and the potential for once-a-day dosing. The results collectively support further development and clinical evaluation in a range of CNS and peripheral inflammatory diseases.

“We are delighted that NT-0796 continues to demonstrate an exceptional and differentiated clinical profile,” said Adam Keeney, Chief Executive Officer at NodThera. “Neurological and neurodegenerative diseases are a significant and growing burden to patients and society. This is the first clinical demonstration of a brain penetrant inhibitor of the NLRP3 inflammasome, which represents a major milestone for addressing this urgent medical challenge.”

NT-0796 is a novel chemotype, designed as an orally bioavailable, brain penetrant NLRP3 inhibitor. The Phase 1 study showed exposures of NT-0796 and its bioactive metabolite NDT-19795 increased linearly with dose. A dose-dependent pharmacodynamic effect was also observed through inhibition of stimulated IL-1β and IL-18 in ex vivo blood samples, which translated into an anti-inflammatory effect via reduction of key inflammatory biomarkers, including C-reactive protein (CRP). Blood-brain barrier penetration of NT-0796 was verified with cerebrospinal fluid (CSF) drug concentrations in excess of anti-inflammatory free blood concentrations. Overall, NT-0796 was safe and well tolerated and no drug-related liver function test (LFT) abnormalities were observed.

NodThera’s second clinical compound, NT-0249, is a peripherally restricted NLRP3 inflammasome inhibitor that has successfully completed its Phase 1 single ascending dose study. NT-0249 was safe and well tolerated with proportional increases in drug exposure with increasing dose. This profile has the potential to be best-in-class as a peripheral NLRP3 inflammasome inhibitor, demonstrating pharmacokinetics consistent with a once-a-day therapy and pharmacodynamics confirming a low clinical dose for efficacy.

“From design to development, the success of our Phase 1 data represents a breakthrough in targeting the NLRP3 inflammasome both peripherally and in the CNS” said Alan Watt, NodThera’s CSO and President of R&D. “Delivery of NT-0796 into the CNS and the positive interim data for NT-0249 continues to reinforce NodThera’s leadership in the NLRP3 inflammasome field.”

About NodThera

NodThera is a clinical-stage biotechnology company developing a new class of potent and selective NLRP3 inflammasome inhibitors for the treatment of diseases driven by chronic inflammation. Led by an experienced management team, NodThera is leveraging new insights into inflammasome biology and chemistry to build a clinically advanced portfolio of highly differentiated small molecule NLRP3 inflammasome inhibitors. The company was founded in 2016 by Epidarex Capital and financed by 5AM Ventures, Cowen Healthcare Investments, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera is headquartered in Lexington, MA, with additional locations in Cambridge, UK and Seattle, WA. Learn more at www.nodthera.com or follow us on LinkedIn.

Media Contact

Darby Pearson
Verge Scientific Communications
dpearson@vergescientific.com

-Lead candidate NT-0796 achieves positive interim results from Phase 1 study, supporting further progression for the treatment of a range of inflammatory diseases-

-Second lead candidate NT-0249 advances into first-in-human Phase 1 study to enable clinical development in peripheral chronic inflammatory disease-

-Third candidate NT-0527 is announced as a novel brain-penetrant NLRP3 inflammasome inhibitor advancing through IND-enabling studies-

LEXINGTON, MA – May 10, 2022 – NodThera, a clinical-stage biotechnology company developing a new class of potent and selective oral, small molecule NLRP3 inflammasome inhibitors to treat diseases driven by chronic inflammation, today announced several key advancements across the portfolio. NodThera’s lead candidate, NT-0796, demonstrated positive interim results from its Phase 1 single-ascending dose (SAD) study. Additionally, the company has commenced first-in-human dosing in the Phase 1 study of its second lead candidate, NT-0249, and announced the selection of its third pipeline candidate, NT-0527 – a brain-penetrant NLRP3 inflammasome inhibitor from a novel chemotype.

The positive interim results from the SAD portion of the Phase 1 trial with NT-0796 represent early clinical proof-of-mechanism for NT-0796 as a potent NLRP3 inflammasome inhibitor. Across all dosing cohorts, NT-0796 was safe and well tolerated and shown to be orally bioavailable with a dose-proportional pharmacokinetic (PK) profile. This portion of the study also showed a dose-dependent pharmacodynamic (PD) effect through the ability to lower IL-1β and IL-18 levels in an ex vivo NLRP3-stimulation assay. These results confirm the criteria to advance NT-0796 further in development and continue the ongoing multiple-ascending dose (MAD) portion of the Phase 1 study to assess brain exposure through cerebrospinal fluid (CSF) sampling.

“NT-0796 has demonstrated robust proof of mechanism and translation from preclinical studies to humans, both validating and further de-risking the development of NT-0796 as a potentially best-in-class, oral, small molecule NLRP3 inflammasome inhibitor,” said NodThera’s Chief Executive Officer, Adam Keeney. “We are encouraged by these first-in-human results as we work to progress NT-0796 in inflammatory diseases impacting millions of patients, many with limited to no treatment options.”

Building on successful clinical progress with NT-0796, NodThera has also initiated dosing of the first healthy volunteers in the Phase 1 trial of the company’s second lead candidate, NT-0249. NT-0249 is a potent inhibitor of the NLRP3 inflammasome with favorable development characteristics supporting advancement to treat chronic inflammatory diseases of the body. The primary objective of this study will be to assess the safety and tolerability of NT-0249, with secondary objectives to assess the PK and PD (ability to lower IL-1β and IL-18 levels) after single and multiple ascending doses.

In addition to advancing two novel candidates into clinical trials, NodThera is further expanding its diverse portfolio with the announcement of NT-0527 as the third oral small molecule NLRP3 inflammasome inhibitor from a novel chemotype to be added to its pipeline. NT-0527 is uniquely designed to inhibit the NLRP3 inflammasome in the brain, with potential to treat a broad range of neuroinflammatory diseases.

“Each of NodThera’s three portfolio candidates feature unique chemotypes that are distinct from one another, offering specific benefits that can be collectively used to cover a range of inflammatory diseases of the brain and body” shares NodThera’s Chief Scientific Officer, Alan Watt. “With the recent addition of NT-0527 as the third candidate in our growing pipeline, NodThera is now advancing novel CNS-penetrant and peripherally-restricted NLRP3 inflammasome inhibitors with differentiated chemistry unlike any other portfolio in the field.”

About NodThera

NodThera is a clinical-stage biotechnology company developing a new class of potent and selective NLRP3 inflammasome inhibitors for the treatment of diseases driven by chronic inflammation. Led by an experienced management team, NodThera is leveraging new insights into inflammasome biology and chemistry to build a portfolio of highly differentiated small molecule NLRP3 inflammasome inhibitors. The company was founded in 2016 by Epidarex Capital and financed by 5AM Ventures, Cowen Healthcare Investments, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera is headquartered in Lexington, MA, with additional locations in Cambridge, UK and Seattle, WA. Learn more at www.nodthera.com or follow us on LinkedIn.

Media Contact

Darby Pearson
Verge Scientific Communications
dpearson@vergescientific.com

-Study of lead candidate to provide important information on safety, pharmacokinetics and pharmacodynamics to inform further clinical development in chronic inflammatory diseases-

-Highlights continued progress advancing a differentiated portfolio of novel NLRP3 inflammasome inhibitors to treat both peripheral- and neuro- inflammatory diseases-

BOSTON and SEATTLE and CAMBRIDGE, England, Nov. 4, 2021 /PRNewswire/ — NodThera, a clinical-stage biotechnology company developing a new class of medicines that inhibit the NLRP3 inflammasome to treat chronic inflammation, today announced that the first healthy volunteers have been dosed in a Phase 1 clinical trial of its lead investigational candidate, NT-0796.

NT-0796 is a small molecule NLRP3 inflammasome inhibitor with differentiated novel chemistry that provides unprecedented potency and potential for prolonged pharmacodynamic (PD) effect, with the ability to cross the blood brain barrier in preclinical species. NT-0796 selectively inhibits NLRP3, the upstream regulator of the body’s inflammation response, to reduce levels of both IL-1β and IL-18 – pro-inflammatory cytokines known to play a role in chronic inflammation underlying a wide range of chronic diseases. Pharmacokinetic (PK) and PD data from an ex vivo IL-1β/IL-18 stimulation assay and cerebrospinal fluid (CSF) sampling in the Phase 1 study will inform further clinical development.

“The recent convergence of key insights into innate immunity, IL-1β/IL-18 and the NLRP3 inflammasome have revolutionized our understanding of chronic disease,” said Adam Keeney, Ph.D., CEO of NodThera. “As one of the first companies to recognize the importance of NLRP3 in the inflammation cascade, we look forward to gathering important human data from the Phase 1 clinical study of our lead candidate NT-0796 so we can accelerate innovation for patients with limited treatment options.”

The primary objective of this study is to assess the safety and tolerability of NT-0796, while secondary objectives include assessment of PK and PD (ability to lower IL-1β and IL-18 levels) and CSF sampling to assess NLRP3 target engagement and compound exposure after single and multiple ascending doses.

“NT-0796 leverages novel chemistry that is unlike any other NLRP3 inflammasome inhibitor in the field. It is designed to deliver key advantages in PK and PD, with the potential to cross the blood brain barrier,” said Donald Johns, M.D., Chief Medical Officer of NodThera. “The NLRP3 inflammasome is a key driver of diseases that span different parts of the body, from common ailments such as osteoarthritis, to cardiovascular disease, Alzheimer’s Disease, cancer, and beyond. Unlocking this treatment potential provides the opportunity to impact many patients whose quality of life is negatively affected by chronic inflammatory disease.”

About NodThera
NodThera is a clinical-stage biotechnology company developing a new class of potent and selective NLRP3 inflammasome inhibitors for the treatment of diseases driven by chronic inflammation. Led by an experienced management team, NodThera is leveraging new insights into inflammasome biology and chemistry to build a portfolio of highly differentiated small molecule NLRP3 inflammasome inhibitors. The company was founded in 2016 and financed by 5AM Ventures, Cowen Healthcare Investments, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera is headquartered in Lexington, MA, with additional locations in Cambridge, UK and Seattle, WA. Learn more at www.nodthera.com or follow us on LinkedIn.

Strengthens senior leadership team with appointments of Donald Johns, M.D., as Chief Medical Officer and Katina Dorton, J.D., MBA, as Chief Financial Officer

CAMBRIDGE, UK, BOSTON and SEATTLE – December 15, 2020 – NodThera, a biotechnology company developing a new class of medicines that inhibit the NLRP3 inflammasome to treat chronic inflammation, today announced the expansion of its senior leadership team with the appointments of Donald Johns, M.D., as Chief Medical Officer and Katina Dorton, J.D., MBA, as Chief Financial Officer.

Dr. Johns is an accomplished drug development leader and board-certified clinical neurologist who previously served as Chief Medical Officer and Executive Vice President of Medical and Scientific Affairs at Syntimmune, prior to the company’s acquisition by Alexion Pharmaceuticals. Ms. Dorton is a recognized and internationally experienced financial executive, corporate director and public company CFO. Ms. Dorton’s industry expertise includes roles in healthcare, life sciences and investment banking, including experiences at Repare Therapeutics and AVROBIO, Inc.

NodThera is advancing a portfolio of potent and selective inhibitors of the NLRP3 inflammasome that reduce both IL-1β and IL-18, pro-inflammatory cytokines which are known to play a role in chronic inflammation underlying a wide range of diseases. The pipeline includes brain penetrant NLRP3 inhibitors for central nervous system (CNS) indications.

“We welcome Don and Katina to the team as we continue to advance our portfolio of differentiated NLRP3 inhibitors to capitalize on the opportunity to exploit the well-understood, but still untapped therapeutic potential of the NLRP3 inflammasome across a broad spectrum of diseases,” said Adam Keeney, Ph.D., President & Chief Executive Officer of NodThera. “Don is an accomplished clinician with an impressive track record who brings a wealth of innovative clinical development experience. Katina brings capital markets experience and has built financial, legal and operational functions to support companies through aggressive growth, including IPO preparation. Their combined contributions will add significant value as we continue to advance NodThera’s portfolio through clinical development and additional financing rounds.”

“The NLRP3 inflammasome is one of the most exciting emerging areas of therapeutic science. NodThera’s best-in-class molecules have great potential to address the unmet medical need in patients with a wide range of inflammatory disorders,” said Dr. Johns. Ms. Dorton adds, “By leveraging innate immunity, NodThera’s platform has the potential to blaze a new path forward in a wide range of disorders, and I am excited to join the rest of the experienced leadership team in this effort.”

Dr. Johns brings more than 25 years of experience in the development of novel treatments for serious diseases, including autoimmune and CNS disorders. Prior to his role at Syntimmune, Dr. Johns served in key leadership positions at Biogen and the Novartis Institutes for Biomedical Research (NIBR). He has contributed to numerous investigational new drug applications (INDs), first-in-human studies and conclusive proof-of-concept studies in a broad spectrum of CNS and autoimmune diseases, as well as four successful new drug applications (NDAs). Prior to joining the pharmaceutical industry, he was a neurologist clinician-scientist at Johns Hopkins and Harvard Medical School. Dr. Johns earned his B.A. from Vanderbilt University and his M.D. from the Yale University School of Medicine.

Ms. Dorton currently serves on the board of directors for Fulcrum Therapeutics (Nasdaq: FULC), Pandion Therapeutics, Inc. (Nasdaq: PAND) and US Ecology (Nasdaq: ECOL). She most recently served as Chief Financial Officer of Repare Therapeutics, a synthetic lethality and DNA repair-focused oncology company. Prior to Repare, Ms. Dorton served as Chief Financial Officer of AVROBIO, a lentiviral gene therapy company. Earlier in her career, she served as a managing director in investment banking for Morgan Stanley and Needham & Company and as an associate attorney at Sullivan & Cromwell. Ms. Dorton received her J.D. from the University of Virginia School of Law, her MBA from George Washington University and her B.A. from Duke University.

About NodThera

NodThera is a biotechnology company developing a new class of potent and selective NLRP3 inflammasome inhibitors for the treatment of diseases driven by chronic inflammation. Led by an experienced management team, NodThera is leveraging new insights into inflammasome biology and chemistry to build a platform of highly differentiated small molecule NLRP3 inhibitors. The company was founded by Epidarex Capital and further financed by 5AM Ventures, Cowen Healthcare Investments, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera was founded in 2016 and maintains offices in Cambridge, UK, Seattle, WA and Boston, MA. For more information please visit www.nodthera.com.

Media Contact

Gina Nugent
Ten Bridge Communications
(617) 460-3579
gina@tenbridgecommunications.com