Roche Molecular Systems, Inc.

On June 18, 2020, the Food and Drug Administration granted accelerated approval to tazemetostat (TAZVERIK, Epizyme, Inc.), an EZH2 inhibitor, for adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies, and for adult patients with R/R FL who have no satisfactory alternative treatment options. Today, the FDA also approved the cobas EZH2 Mutation Test (Roche Molecular Systems, Inc.) as a companion diagnostic for tazemetostat. Approval was based on two open-label, single-arm cohorts (Cohort 4 - EZH2 mutated FL and Cohort 5 - EZH2 wild-type FL) of a multi-center trial (Study E7438-G000-101, NCT01897571) in patients with histologically confirmed FL after at least 2 prior systemic therapies. EZH2 mutations were identified prospectively using formalin-fixed, paraffin-embedded tumor samples, which were centrally tested using the cobas® EZH2 Mutation Test. Patients received tazemetostat 800 mg orally twice daily until confirmed disease progression or unacceptable toxicity. Efficacy was based on overall response rate (ORR) and duration of response (DOR) according to the International Working Group Non-Hodgkin Lymphoma criteria as assessed by an independent review committee. ORR in 42 patients with EZH2 mutant FL was 69% (95% CI: 53%, 82%), with 12% complete responses and 57% partial response. Median DOR in these patients was 10.9 months (95% CI: 7.2, NE). The ORR in 53 patients with EZH2 wild-type FL was 34% (95% CI: 22%, 48%), with 4% complete responses and 30% partial responses. Median DOR was 13 months (95% CI: 5.6, NE). The most common (≥20%) adverse reactions in patients with follicular lymphoma included fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain. Serious adverse reactions occurred in 30%, most often from infection. Second primary malignancy was the most common reason for treatment discontinuation (2% of patients). The prescribing information includes a warning and precaution for secondary malignancies. The recommended tazemetostat dose is 800 mg taken orally twice daily with or without food. View full prescribing information for TAZVERIK. These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). This application was granted priority review and Fast Track designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088. For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov. For information on the COVID-19 pandemic, see the following resources: FDA: Coronavirus Disease 2019 (COVID-19) NCI: Coronavirus: What People With Cancer Should Know CDC: Coronavirus (COVID-19) Follow the Oncology Center of Excellence on Twitter @FDAOncologyExternal Link Disclaimer. Content current as of: 06/18/2020 Regulated Product(s) Drugs Prescription Drugs 06/18/2020 Drugs Prescription Drugs Drugs Regulatory Science Research and Education Development & Approval Process | Drugs Drug Safety and Availability Emergency Preparedness | Drugs Guidance, Compliance, & Regulatory Information News & Events for Human Drugs Resources | Drugs Science and Research | Drugs Regulatory Science Research and Education Development & Approval Process | Drugs Drug Safety and Availability Emergency Preparedness | Drugs Guidance, Compliance, & Regulatory Information News & Events for Human Drugs Resources | Drugs Science and Research | Drugs

In its lawsuit, Roche claimed Foresight's founders developed the Stanford spinout's tech on a tumor DNA sequencing approach they had sold to the drugmaker about five years prior, before returning to Roche to propose a new commercial deal in 2022. Roche has filed a lawsuit against Stanford University and its spinout Foresight Diagnostics, saying the young cancer test developer was built upon trade secrets it acquired for detecting tumor DNA in the bloodstream. The suit stems from a nearly decade-old deal that Roche inked with some of Foresight’s founders—Stanford professors Maximilian Diehn and Ash Alizadeh, who specialize in oncology, hematology and liquid biopsy. Diehn and Alizadeh previously helped establish Capp Medical, which Roche bought up in 2015 to gain access to its genomic cancer detection platform, dubbed CAPP-Seq.  According to Roche’s molecular diagnostics divisions, Capp’s technology was used to help develop the drugmaker’s Avenio DNA analysis kits, including assays for non-Hodgkin’s lymphoma and recurrence monitoring. Though the financial details were not disclosed at the time, Roche said in its complaint that it paid out tens of millions of dollars for the company. And through the deal, Diehn and Alizadeh signed on as consultants for Roche into mid-2021, while a third Stanford professor, David Kurtz, also contributed as a contractor. In its lawsuit, filed in Northern California federal court, Roche claimed that time overlapped with the trio’s work as they “secretly co-founded” Foresight in 2020—and that the startup used CAPP-Seq to develop an expanded approach to capturing and analyzing circulating tumor DNA.  The resulting tech, called PhasED-Seq, was patented by Stanford before being licensed to Foresight, which so far has raised about $70 million in venture capital funding. In a public statement, Foresight described the suit as “meritless,” saying that Stanford owns the patents under dispute, and that they were developed using Stanford time and resources.  “[Roche Molecular Systems] acquired prior, different technology in 2015 known as CAPP-Seq,” the company said. “We believe that, unfortunately, Roche failed to achieve the full potential of that acquisition. Now, recognizing the strength of Foresight’s new and independently developed technology, Roche has brought litigation as a negotiating tactic to try and force a result to which it is not entitled.” Earlier this year at the annual meeting of the American Society of Clinical Oncology, Foresight presented a poster showing the ability of its Clarity platform to detect minimal residual disease among patients who had surgery to remove early stage non-small cell lung cancer, saying it can capture bloodstream tumor DNA at less than 1 part per million. The company has also studied its approach in blood cancers such as B-cell malignancies. In April 2023, Foresight collected $58.75 million through a series B round, led by Foresite Capital and backed by Civilization Ventures, Bluebird Ventures, Pear Ventures, Agent Capital, Stanford University and The University of Colorado Healthcare Innovation Fund.

More than half of all U.S. cervical cancer patients are underscreened1, which makes reducing barriers to sample collection and increasing access to screenings crucial to ultimately helping eliminate this deadly disease.Each year in the U.S., more than 13,000 patients are diagnosed with cervical cancer and approximately 4,000 die from this preventable disease, caused by HPV infection.1Roche’s human papillomavirus (HPV) self-collection solution will improve access to testing by providing women the option to privately collect their own sample. Basel, 15 May 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today the FDA approval of its human papillomavirus (HPV) self-collection solution, one of the first available in the United States. Screening for HPV can help identify women who are at risk of developing cervical cancer so that the disease can be found and treated early before cervical cancer has a chance to develop. HPV self-collection offers an accessible screening option. In a healthcare setting, an individual collects their own vaginal sample, which is sent to a laboratory for analysis with Roche’s cobas® molecular instrument. Those who receive a positive HPV result would then continue their care with a healthcare provider. “With vaccinations, innovative diagnostic tools and screening programs, achieving the WHO’s goal of eliminating cervical cancer by 2030 is within reach,” said Matt Sause, CEO of Roche Diagnostics. “Our HPV self-collection solution helps support this goal by reducing barriers and providing access to HPV screening by allowing people to privately collect their own sample for HPV testing.” More than half the patients diagnosed with cervical cancer in the U.S. have never been screened or have only been screened infrequently, and they do not participate in routine screening.1 Many factors can contribute to individuals not participating in cervical cancer screening programs, such as access to healthcare, social and economic barriers, history of traumatic experience, cultural concerns and embarrassment. Roche’s self-collection solution can help reduce these barriers by offering an alternative to clinician collection procedures, while also providing accurate and reliable results enabling clinicians to make patient care decisions. Roche has collaborated with the National Cancer Institute (NCI), which is part of the National Institutes of Health (NIH), on the Cervical Cancer “Last Mile” Initiative. This public-private partnership has, in part, facilitated the regulatory pathway towards the approval. About the Roche Cervical Cancer PortfolioHPV is the known cause of more than 95% of all cervical cancers.2 Roche’s cervical cancer portfolio includes the cobas HPV Test, used for primary screening and co-testing. While the Pap smear can potentially detect abnormalities in the cervix, the cobas HPV test detects 14 types of high-risk HPV genotypes that put patients at higher risk of cervical cancer. It includes results for HPV 16, HPV 18 and 12 other high-risk pooled genotypes.3 The HPV self-collection solution is approved for use with Roche's cobas HPV test. The cobas HPV test runs on the cobas 4800 and the fully automated cobas 5800/6800/8800 Systems, which offers the fastest time to results, providing up to 96 results in about three hours, and 384 results for the cobas 6800 System and 1,056 results for the cobas 8800 System in an eight hour shift. The portfolio also includes CINtec PLUS Cytology, the only FDA-approved dual-stain product and CINtec® Histology, the only FDA-cleared p16 biomarker technology that can help pathologists confirm the presence of pre-cancerous cervical lesions. The IMPACT trial design, used to validate the clinical benefits of the Roche cervical cancer portfolio, had representation from diverse patient segments, including 21 percent Black, 24 percent Hispanic-Latino and 0.3 percent American Indian or Alaskan Native participants.4 This diversity was critical to accurately assess the performance of dual stain in patient populations with higher incident rates of HPV. Learn more now: http://diagnostics.roche.com 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. In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the fifteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work. 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] https://deainfo.nci.nih.gov/advisory/joint/1219/Sahasrabuddhe.pdf [2] WHO cervical cancer fact sheet[3] cobas® HPV test [package insert]. Branchburg, NJ: Roche Molecular Systems, Inc.; 2020.[4] Safaeian M, Wright TC Jr, Stoler MH, Ranger-Moore J, Rehm S, Aslam S, Fang Q, Volkir P, Ridder R. The IMproving Primary Screening And Colposcopy Triage trial: human papillomavirus, cervical cytology, and histopathologic results from the baseline and 1-year follow-up phase. Am J Obstet Gynecol. 2021 Sep;225(3):278.e1-278.e16. doi: 10.1016/j.ajog.2021.03.047. Epub 2021 Apr 20. PMID: 33852886 Roche Global Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58Sileia UrechPhone: +41 79 935 81 48Nathalie AltermattPhone: +41 79 771 05 25 Simon GoldsboroughPhone: +44 797 32 72 915 Karsten KleinePhone: +41 79 461 86 83 Nina MählitzPhone: +41 79 327 54 74Kirti PandeyPhone: +49 172 6367262 Yvette PetillonPhone: +41 79 961 92 50Dr. Rebekka SchnellPhone: +41 79 205 27 03 Attachment 15052024_MR_HPV cobas test_en