Trontinemab

New data highlight the potential of the Roche Elecsys® Amyloid Plasma Panel and Elecsys ptau181 for ruling out Alzheimer’s disease related amyloid pathology with very good accuracy.In the largest worldwide clinical trial of its kind, the blood-based test showed very good accuracy in ruling out Alzheimer's pathology in those being investigated for the disease, potentially avoiding the need for further invasive and unnecessary tests.Results further demonstrate Roche’s commitment to bringing diagnostic clarity for Alzheimer’s disease to people at an early stage of cognitive decline. Basel, 31 October 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today new late-breaking data on its Elecsys Amyloid Plasma Panel (combination of pTau181 and ApoE4), for Alzheimer’s disease, at the 17th Clinical Trials in Alzheimer’s Disease congress (CTAD) in Madrid, Spain. Results show that the test, currently in development, could accurately rule out amyloid pathology – a hallmark of Alzheimer’s disease – in a broad population with varying cognitive impairment, as seen in routine clinical practice.1 This could allow clinicians to rule out Alzheimer’s disease as a possible cause of cognitive symptoms with a simple blood test, offering certainty and reassurance. In the prospective, multicentre study, which included 492 patients across the US and Europe, the Roche Elecsys Amyloid Plasma Panel was able to rule out Alzheimer’s disease with a high negative predictive value (NPV) of 96.2% based on a 23.4% prevalence of amyloid positivity according to positron emission tomography (PET) scans, with 91.0% sensitivity and 69.8% specificity. The performance of the test was only minimally impacted by the patients’ age, sex, body mass index or impaired kidney function. Roche’s pTau181 biomarker performed similarly as a standalone assay. “The data from this large-scale study in cognitively impaired individuals suggests that a fast and simple blood test could reliably rule out amyloid pathology, offering much-needed reassurance to patients and their families,” commented Matt Sause, CEO of Roche Diagnostics. “Alzheimer’s disease is one of the most challenging health issues of our time, and its impact on society is growing as the world’s population ages. For many people, getting a clear and timely diagnosis remains challenging. This test could help patients to receive the right care at the earliest opportunity.” The Elecsys Amyloid Plasma Panel, which received FDA Breakthrough Device Designation in July 2023, is a minimally invasive blood test that measures phosphorylated Tau (pTau) 181 protein and apolipoprotein (APOE) E4 in plasma. This is the first industry trial of its kind (globally prospectively collected diagnostic registrational clinical trial) to investigate the test’s clinical performance in a patient population that reflects as closely as possible the patients who could benefit from the test. It involved a subset of patients from a wider trial looking at a highly diverse set of patients with broad inclusion criteria, to ensure the test could be used effectively across different geographies and ethnicities. Further potential uses for the test are being explored with the rich patient population. In addition to data on the Elecsys Amyloid Plasma Panel and pTau181, Roche also presented data for its Elecsys pTau 217 assay which is currently in development and also received FDA Breakthrough Device Designation earlier this year. The results from this latest study demonstrate high accuracy of amyloid pathology detection in comparison with another available pTau 217 test. Today, barriers to early and accurate diagnosis of Alzheimer’s disease exist across the globe, with up to 75% of people living with the symptoms of Alzheimer’s but without a diagnosis. Those who have received a diagnosis waited, on average, 2.8 years after symptom onset.2 To address the growing strain that Alzheimer’s disease is putting on healthcare systems, it will be essential to make a person’s journey to diagnosis faster and more accessible. This will ultimately enable access to appropriate new therapies as they become available. With an unmatched base of installed solutions worldwide, Roche is uniquely placed to rapidly scale testing once approved, ensuring that patients can benefit from the test as soon as it has been cleared for use. Roche is committed to using its diagnostic and pharmaceutical capabilities in an effort to better detect and treat Alzheimer’s disease as early as possible, and working toward preventing the disease altogether. To achieve this, the company is developing and delivering solutions to more effectively detect, diagnose, and monitor the disease and progressing research into investigational medicines for different targets, types, and stages of the disease. This includes trontinemab, a novel Brainshuttle™ Aβ antibody that is currently in development and is specifically engineered for enhanced access to the brain to enable rapid reduction of amyloid in people with Alzheimer’s disease. Further data on progress in the Alzheimer’s disease pipeline will be shared with investors. Click here to access the investor presentation. About the Elecsys Amyloid Plasma PanelThis product is currently under development and not commercially available. The below information reflects Roche’s plans for these products if they are approved by regulatory bodies for clinical use in the future: The Elecsys Amyloid Plasma Panel measures phosphorylated Tau (pTau) 181 protein assay and apolipoprotein (APOE) E4 assay in human blood plasma. Elevations in pTau181 occur in the early stages of Alzheimer’s disease, while the presence of APOE4 constitutes the most common genetic risk factor for Alzheimer’s disease. The result is intended for consideration in conjunction with other clinical information to advise for further confirmatory testing with amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) testing. Patients testing negative with the Elecsys Amyloid Plasma Panel are unlikely to be amyloid positive and should be investigated for other causes of cognitive decline. About Elecsys pTau217This product is currently under development and not commercially available. The below information reflects Roche’s plans for these products if they are approved by regulatory bodies for clinical use in the future: Elecsys Phospho-Tau (217P) is intended to be an in-vitro diagnostic immunoassay for the quantitative determination of the protein Phospho-Tau (217P) (pTau217) in human plasma from individuals aged 60 years and older. The test is intended for use as an aid in identifying amyloid pathology, a pathological feature of Alzheimer’s disease. A positive Elecsys pTau217 result indicates a high likelihood of having a positive amyloid PET/CSF result.A negative Elecsys pTau217 result indicates a high likelihood of having a negative amyloid PET/ CSF result.An indeterminate pTau217 result indicates uncertainty on the amyloid PET/CSF result. The pTau217 result should be used in the diagnostic pathway in conjunction with other clinical information. About Roche in Alzheimer’s diseaseWith more than two decades of scientific research in Alzheimer’s disease, Roche is working towards a day when we can detect and treat the disease early, in order to stop or even prevent its progression to preserve what makes people who they are. Today, the company’s Alzheimer’s disease portfolio spans investigational medicines for different targets, types and stages of the disease, including trontinemab. On the diagnostics side, it also includes approved and investigational tools, including digital and blood-based tests and CSF assays, aiming to more effectively detect, diagnose and monitor the disease. Yet the global challenges of Alzheimer’s disease go well beyond the capabilities of science, and making a meaningful impact requires collaboration both within the Alzheimer’s community and outside of healthcare. Roche will continue to work together with numerous partners with the hope to transform millions of lives. About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com. All trademarks used or mentioned in this release are protected by law. References[1] Kirste I, et al, Revamping Alzheimer's Disease Diagnostics: Evaluating Future IVD Plasma p-Tau 181 and ApoE4 Immunoassays for Amyloid Detection in a Multi-Center Study Reflective of Routine Clinical Practice, presented at CTAD, October 2024.[2] Life Expectancy Following Diagnosis Of Alzheimer’s Disease Depends On Age At Diagnosis, Johns Hopkins Bloomberg School of Public Health, November 18, 2002, https://publichealth.jhu.edu/2002/alzheimer-age Roche Global Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58 Sileia UrechPhone: +41 79 935 81 48 Nathalie AltermattPhone: +41 79 771 05 25 Lorena CorfasPhone: +41 79 568 24 95 Simon GoldsboroughPhone: +44 797 32 72 915 Karsten KleinePhone: +41 79 461 86 83 Nina MählitzPhone: +41 79 327 54 74 Kirti PandeyPhone: +49 172 6367262 Yvette PetillonPhone: +41 79 961 92 50 Dr Rebekka SchnellPhone: +41 79 205 27 03 Roche Investor Relations Dr Bruno EschliPhone: +41 61 68-75284e-mail: bruno.eschli@roche.com Dr Sabine BorngräberPhone: +41 61 68-88027e-mail: sabine.borngraeber@roche.com Dr Birgit MasjostPhone: +41 61 68-84814e-mail: birgit.masjost@roche.com Investor Relations North America Loren Kalm Phone: +1 650 225 3217 e-mail: kalm.loren@gene.com Attachment 31102024_MR_CTAD_DiaAlzheimer_en

Dive Brief:Roche may seek an accelerated U.S. approval of its experimental Alzheimers disease drug trontinemab if the therapy continues to show in testing it can significantly lower levels of a protein linked to cognitive decline, executives said in a presentation to investors Thursday.The Food and Drug Administration has been willing to grant speedy approvals to Alzheimers drugs that can reduce the amount of sticky amyloid protein in the brains of people with the condition. Roche could lean on that precedent to seek an abbreviated approval path, as the company plans to look for an opportunity to get trontinemab to market before the final readout from a Phase 3 trial, said Hanno Svoboda, the drugs lifecycle leader.Two Alzheimers drugs, Eisai and Biogens Leqembi and the now-withdrawn Aduhelm, gained initial approvals based on their effects on amyloid, although the FDA rejected a similar request from Eli Lilly before eventually clearing Kisunla. Trontinemab is currently in Phase 2 testing and, earlier this week, Roche released early data suggesting it could clear amyloid more quickly than Kisunla.Dive Insight:Unlike trontinemabs predecessors, it is designed to more easily slip past the blood-brain barrier, which could theoretically lead to more powerful and precise drug effects at a lower dose.That hypothesis hasnt been proven in the kind of large, late-stage trials typically needed to secure an approval. But data from a Phase 2 study this week demonstrated the drugs potential.In the highest two dose groups tested so far, amyloid was cleared from the brains of a majority of volunteers after 28 weeks of treatment. Though comparing drugs across trials can be difficult, 17% of people in Kisunlas Phase 3 trial had a similar outcome at 24 weeks.The drugs apparently speedy effects could allow Roche to evaluate a potential low-frequency, patient friendly maintenance dosing regimen to keep amyloid levels from rebounding, Svoboda said.Roche is currently moving forward with an expansion phase of its mid-stage trial, which will double the number of trial volunteers to 120, some of whom would receive a placebo.To date, the company has only accrued safety data from that part of the study. Roche disclosed one volunteer who received treatment died from brain bleeding. However, the company said the volunteer had a condition, superficial siderosis, that increased her risk, and has since adjusted its enrollment criteria going forward.Still, the results indicated trontinemab treatment led to lower rates than other drugs of an imaging abnormality called ARIA that indicates brain swelling. According to Roche, less than 10% of trial volunteers treated with trontinemab have experienced ARIA in the trial so far. By comparison, more than 20% of those who received Kisunla in its Phase 3 trial had ARIA, while for Leqembi that figure was above 10%.Trontinemab had higher rates of infusion-related reactions than Leqembi and Kisunla. However, Roche has reduced the rate of those reactions to below 40% at the two highest doses tested.This week, Lilly also released data showing changes to the dosing regimen of Kisunla could lessen rates of ARIA. '