coramitug (NN6019) / Prothena, Novo Nordisk - LARVOL DELTA

Etiological Treatment of Cardiac Amyloidosis: Standard of Care and Future Directions. (PubMed, Curr Heart Fail Rep) - "The standard of care for ATTR-CA include agents capable of selectively stabilizing the precursor protein (e.g., tafamidis), whereas the plasma cell clone is the main target of chemotherapy for AL-CA...Recent data from ATTRibute-CM led to the approval of acoramidis, whereas patisiran received refusal based on the APOLLO-B trial. Novel CRISPR-Cas9-based drugs (i.e., NTLA-2001) hold great potential in the setting of ATTR-CA...However, the investigation of monoclonal antibodies targeting misfolded ATTR (e.g., PRX004, NI301A) or AL (e.g., birtamimab, anselamimab) has led to encouraging results. Various cutting-edge strategies are being tested for treatment of CA and may change the prognostic landscape of this condition in the next years."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Hematological Disorders

Prothena Reports Fourth Quarter and Full Year 2024 Financial Results, and Provides Financial Guidance and Business Highlights (Businesswire) - "PRX019: Phase 1 clinical trial expected to complete in 2026. Birtamimab: The ongoing confirmatory Phase 3 AFFIRM-AL clinical trial is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA with a primary endpoint of all-cause mortality (time-to-event) at a statistical significance level of 0.10. Topline results from confirmatory Phase 3 AFFIRM-AL clinical trial expected in 2Q 2025. Coramitug: Phase 2 clinical trial has completed enrollment of approximately 99 patients with trial completion expected in 1H 2025."

P3 data: top line • Trial completion date • Amyloidosis • Cardiomyopathy • CNS Disorders

New therapies to treat cardiac amyloidosis. (PubMed, Curr Opin Cardiol) - "The therapeutic landscape for ATTR-CM and AL-CM is rapidly evolving, driven by novel therapies targeting diverse mechanisms. Ongoing clinical trials promise to further refine the standard of care and improve outcomes for patients with cardiac amyloidosis."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiovascular

Prothena Reports Third Quarter 2024 Financial Results and Business Highlights (Businesswire) - "'From our wholly-owned programs we expect to complete our confirmatory Phase 3 AFFIRM-AL clinical trial evaluating birtamimab, which is being conducted under a SPA agreement with the FDA at a significance level of 0.10, in 1H 2025. We also expect to announce multiple clinical readouts from our ongoing Phase 1 ASCENT clinical trials evaluating PRX012 for Alzheimer’s disease starting in mid-2025 and continuing throughout the year. In collaboration with Roche, we expect results from the Phase 2b PADOVA clinical trial evaluating prasinezumab for Parkinson’s disease in 4Q 2024 and with Novo Nordisk, we expect results from the Phase 2 signal-detection clinical trial evaluating coramitug for ATTR amyloidosis with cardiomyopathy in 1H 2025.'"

P1 data • P2 data • P2b data • Trial completion • Alzheimer's Disease • Amyloidosis • CNS Disorders • Metabolic Disorders • Parkinson's Disease

PRX004 in variant amyloid transthyretin (ATTRv) amyloidosis: results of a phase 1, open-label, dose-escalation study. (PubMed, Amyloid) - P1, P2 | "PRX004 was well tolerated in patients with ATTRv amyloidosis and demonstrated potential clinical activity. A phase 2 randomised controlled trial in ATTR cardiomyopathy is ongoing (NCT05442047)."

Journal • P1 data • Amyloidosis • Cardiomyopathy • Cardiovascular • Pain

Prothena Reports Second Quarter 2024 Financial Results and Business Highlights (PRNewswire) - "Topline results from confirmatory AFFIRM-AL Phase 3 clinical trial expected between 4Q 2024 and 2Q 2025...Coramitug (formerly PRX004)...Phase 2 clinical trial has completed enrollment of approximately 99 patients with topline data expected in 1H 2025..."

P2 data • P3 data: top line • Amyloidosis • CNS Disorders • Metabolic Disorders

A Research Study to Look at Long-term Treatment With a Medicine Called NNC6019-0001 for People Who Have Heart Failure Due to Transthyretin Amyloidosis (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Novo Nordisk A/S | Trial completion date: Feb 2028 ➔ Aug 2028

Trial completion date • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

A Research Study to Look at How a New Medicine Called NNC6019-0001 Works and How Safe it is for People Who Have Heart Disease Due to Transthyretin (TTR) Amyloidosis (clinicaltrials.gov) - P2 | N=99 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Trial primary completion date: May 2024 ➔ May 2025

Trial primary completion date • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

A Research Study to Look at Long-term Treatment With a Medicine Called NNC6019-0001 for People Who Have Heart Failure Due to Transthyretin Amyloidosis (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

A Research Study to Look at Long-term Treatment With a Medicine Called NNC6019-0001 for People Who Have Heart Failure Due to Transthyretin Amyloidosis (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P2 trial • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

A Research Study to Look at How a New Medicine Called NNC6019-0001 Works and How Safe it is for People Who Have Heart Disease Due to Transthyretin (TTR) Amyloidosis (clinicaltrials.gov) - P2 | N=99 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting

Enrollment closed • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

A Research Study to Look at How a New Medicine Called NNC6019-0001 Works and How Safe it is for People Who Have Heart Disease Due to Transthyretin (TTR) Amyloidosis (clinicaltrials.gov) - P2 | N=99 | Recruiting | Sponsor: Novo Nordisk A/S | Trial completion date: Sep 2024 ➔ Jan 2025

Trial completion date • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

Prothena Reports Fourth Quarter and Full Year 2022 Financial Results, and Provides Financial Guidance and Business Highlights (Businesswire) - “Research and development (R&D) expenses totaled $36.9 million and $135.6 million for the fourth quarter and full year of 2022, respectively, as compared to $22.1 million and $82.3 million for the fourth quarter and full year of 2021, respectively….For the full year of 2022, the higher costs were offset in part by lower collaboration expenses with Roche and lower manufacturing expenses related to the NNC6019 (formerly PRX004) program.”

Commercial • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • CNS Disorders

Prothena Reports Fourth Quarter and Full Year 2022 Financial Results, and Provides Financial Guidance and Business Highlights (Businesswire) - “PRX012: Significant presence at upcoming International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) in March/April 2023 highlighted by oral presentation of preclinical data showing superior binding characteristics of PRX012 and a symposium featuring key thought leaders. Ongoing Phase 1 SAD and MAD studies; topline data expected year end 2023….PRX005: Ongoing Phase 1 MAD study; topline data expected year end 2023. PRX123: Investigational new drug (IND) application filing expected by year end 2023….NNC6019: Ongoing Phase 2 study in patients with ATTR cardiomyopathy is being conducted by Novo Nordisk (NCT05442047); topline data expected in 2024.”

IND • P1 data • P2 data • Preclinical • Alzheimer's Disease • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • CNS Disorders

Prothena Announces Achievement of $40 Million Clinical Milestone Payment from Novo Nordisk for PRX004/NNC6019 Under Investigation for the Treatment of ATTR Cardiomyopathy (Businesswire) - "Prothena Corporation plc...announced that the Company has earned a $40 million milestone payment from Novo Nordisk related to the continued advancement of NNC6019 (formerly PRX004) in a Phase 2 clinical study for the treatment of ATTR cardiomyopathy. There remains a high unmet medical need in moderate to advanced ATTR amyloidosis patients at high risk for early mortality due to amyloid deposition in vital organs."

Commercial • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • CNS Disorders

"Novo Nordisk's #cardiovascular charge continues (via @ByMadeleineA) https://t.co/HrvJmusYON $NVO #ESCCongress #ziltivekimab #PRX004 #amyloidosis #semaglutide #HS001" (@evaluatevantage)

Amyloidosis • Cardiovascular

NNC6019-0001, a humanized monoclonal antibody, in patients with transthyretin amyloid cardiomyopathy (ATTR-CM): rationale and study design of a phase 2, randomized, placebo-controlled trial (ESC 2022) - "Disease-modifying treatments are needed for patients with ATTR-CM, where treatment is often limited to managing symptoms and best supportive care; the first disease-modifying therapies recently became available. This phase 2 trial will be used to determine the appropriate dose for the phase 3 trial of NNC6019-0001, a novel antibody therapy designed to deplete amyloid in patients with ATTR-CM."

Clinical • P2 data • Atrial Fibrillation • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

A research study to look at how a new medicine called NNC6019-0001 works and how safe it is for people who have heart disease due to TTR amyloidosis (clinicaltrialsregister.eu) - P2 | N=99 | Ongoing | Sponsor: Novo Nordisk A/S

New P2 trial • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Heart Failure

A Research Study to Look at How a New Medicine Called NNC6019-0001 Works and How Safe it is for People Who Have Heart Disease Due to Transthyretin (TTR) Amyloidosis (clinicaltrials.gov) - P2 | N=99 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

A Research Study to Look at How a New Medicine Called NNC6019-0001 Works and How Safe it is for People Who Have Heart Disease Due to Transthyretin (TTR) Amyloidosis (clinicaltrials.gov) - P2 | N=99 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P2 trial • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

Prothena Reports First Quarter 2022 Financial Results and Business Highlights (GlobeNewswire) - “Neurodegenerative Diseases Portfolio: Alzheimer’s disease (AD): PRX012…Topline Phase 1 data expected in 2023; ATTR Amyloidosis: PRX004…Novo Nordisk expects to initiate a Phase 2 study of PRX004 for the treatment of ATTR cardiomyopathy in 2Q 2022.”

New P2 trial • P1 data • Alzheimer's Disease • Amyloidosis • Cardiomyopathy • CNS Disorders

Prothena Reports Second Quarter 2021 Financial Results and Business Highlights (GlobeNewswire) - "Upcoming Milestones: PRX004: $40 million milestone payment from Novo Nordisk for Phase 2 initiation expected 1H 2022."

Commercial • New P2 trial • Amyloidosis • CNS Disorders

Prothena and Novo Nordisk Announce Acquisition Agreement for Prothena’s ATTR Amyloidosis Programme (GlobeNewswire) - “Prothena Corporation…and Novo Nordisk…today announced that the companies have entered into a definitive purchase agreement under which Novo Nordisk has acquired Prothena’s clinical stage antibody PRX004 and broader ATTR amyloidosis programme….Novo Nordisk acquires Prothena’s wholly-owned subsidiary and gains full worldwide rights to the intellectual property and related rights of Prothena’s ATTR amyloidosis business and pipeline. Prothena is eligible to receive development and sales milestone payments totalling up to 1.2 billion US dollars including 100 million dollars in upfront and near-term clinical milestone payments."

Licensing / partnership • Amyloidosis • CNS Disorders

Prothena Reports First Quarter 2021 Financial Results and Provides Updated Financial Guidance and R&D Update (GlobeNewswire) - "Upcoming Milestones: Birtamimab: Phase 3 AFFIRM-AL study initiation expected mid-2021...Prasinezumab: Results from Part 2 of the PASADENA study expected to be presented at an upcoming medical conference...PRX004: Phase 2/3 study in patients with ATTR-cardiomyopathy expected to initiate 4Q 2021...PRX005: IND expected by 3Q 2021 $80 million potential payment from Bristol Myers Squibb upon exercising their US license option in 2021...PRX012, a potential treatment for Alzheimer’s disease...IND expected by 1Q 2022...Research and development (R&D) expenses totaled $21.1 million for the first quarter of 2021..."

Commercial • Financing • IND • New P2/3 trial • New P3 trial • P2 data • Alzheimer's Disease • Amyloidosis • CNS Disorders • Frontotemporal Lobar Degeneration • Parkinson's Disease • Progressive Supranuclear Palsy • Tauopathies And Synucleinopathies

Novel Treatment Approach in Transthyretin Amyloidosis (Medscape) - "Commenting on the study for Medscape Medical News, Morie Gertz, MD...who was not involved in the current work, said this was a completely new approach to treatment. 'PRX0004 represents a monoclonal antibody that binds to the amyloid fibrils and stimulates phagocytosis dissolving existing amyloid deposits,' he explained....'The ability to eliminate existing amyloid deposits is a completely new approach and would offer synergy with current therapies that stabilize the TTR tetramer and silence the gene responsible for TTR production,' Gertz said."

Media quote • Amyloidosis • Cardiomyopathy