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THURSDAY, Sept. 12, 2024 -- Individuals with sickle cell trait (SCT) have an increased risk for venous thromboembolism (VTE), according to a study published online Sept. 12 in Blood Advances . Keng-Han Lin, Ph.D., from 23andMe in Sunnyvale, California, and colleagues leveraged data from the 23andMe Research cohort (4,184,082 participants) to calculate the ancestry-independent risk for VTE associated with SCT. A meta-analysis of three genetic ancestry groups (European [3,183,142 participants], Latine [597,539 participants], and South Asian [41,257 participants]) was used to calculate odds ratios. The researchers found that 2.25 percent of participants from the full cohort reported a history of VTE. In a meta-analysis, the risk for VTE was increased 1.45-fold among individuals with SCT versus non-SCT carriers, similar to the full cohort estimate. In SCT, the risk for pulmonary embolism (PE) was higher than that of isolated deep vein thrombosis (DVT; odds ratios, 1.95 versus 1.04). Carriers of factor V Leiden had a 3.30-fold increased risk for VTE versus noncarriers, with a higher risk for isolated DVT versus PE (odds ratios, 3.59 and 2.72, respectively). "Our study also provides high-powered data to confirm the PE-predominant pattern of VTE in SCT carriers. These data may inform clinical practice guidelines, future research, and public health initiatives in SCT," the authors write. Several authors are employed by and hold stock or stock options in 23andMe.

23andMe, National Human Genome Research Institute, and Johns Hopkins University conducted collaborative research that studied sickle cell trait in a diverse population SUNNYVALE, Calif., Sept. 12, 2024 (GLOBE NEWSWIRE) -- 23andMe Holding Co. (Nasdaq: ME) (23andMe), a leading genetic health and biopharmaceutical company, in collaboration with lead researchers at National Human Genome Research Institute, part of the National Institutes of Health (NIH), and Johns Hopkins University, conducted one of the largest and most diverse studies on sickle cell trait (SCT). Many prior SCT research studies have only focused on Black/African American populations. This collaborative research leveraged 23andMe’s diverse cohort of research-consented participants. The researchers studied the association of sickle cell trait with venous thromboembolism (VTE) (blood clots) and compared this degree of risk to factor V Leiden (FVL). The results from the study were published today in the journal Blood Advances . Sickle cell trait and sickle cell disease Sickle cell disease is a global public health issue. Individuals with sickle cell disease (SCD) have two genes that cause the production of sickle hemoglobin, and these patients can have severe pain and other organ complications Individuals with sickle cell trait (SCT) carry only one gene that causes the production of sickle hemoglobin, and these individuals are generally healthy. However, SCT can be a risk factor for select health outcomes such as blood clots. One hundred million people worldwide have sickle cell trait. In the United States, three million people have sickle cell trait, and it disproportionately affects the Black community. However, sickle cell trait and sickle cell disease aren’t just a Black issue. Individuals in all communities can have sickle cell trait. This study found that sickle cell trait is a modest risk factor for blood clots across populations. “This study uniquely demonstrates that sickle cell trait’s association with blood clots extends across diverse genetic backgrounds,” said Keng-Han Lin, Ph.D., a Senior Scientist at 23andMe and a co-author of the paper. “It highlights how comprehensive genetic research can reveal health risks relevant to all communities.” Collaborative and diverse sickle cell trait study Most prior sickle cell trait studies have been limited to the Black community because many assume SCT occurs only in a specific race or population. Combining those assumptions with systemic racism can lead to bias. “The power of the 23andMe platform is that it enables research that’s inclusive of communities historically underrepresented in genetics research at an unprecedented scale. This diversity can help uncover novel biology and can also dispel misconceptions,” said Anjali Shastri, Ph.D., a Principal Program Manager at 23andMe who leads research equity programs and advocacy partnerships for research and is a co-author of the study. With this collaborative study, researchers at National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), Johns Hopkins University (JHU), and scientists at 23andMe sought to better understand the connection between sickle cell trait and blood clots. The study was one of the largest sickle cell trait studies to date, leveraging 4.2 million 23andMe research-consented participants, which included 19,000 with SCT. The researchers studied the associations with venous thromboembolism (VTE). To contextualize SCT and VTE, the researchers also studied the association of factor V Leiden and VTE. The study also looked at different types of blood clots: deep vein thrombosis (DVT), which forms in a deep vein like in the legs, and pulmonary emboli (PE), which are caused by blood clots that travel to the lungs. Sickle cell trait study results Study results validated the association of sickle cell trait with blood clots. However, the study found that individuals with sickle cell trait are at a lower risk for VTE than carriers of factor V Leiden. The study also validated the association between having SCT and with developing pulmonary emboli (PE), and it similarly validated that sickle cell trait was not associated with developing deep vein thrombosis (DVT). This pattern of blood clots was the opposite of that found in FVL. In individuals with FVL, the risk of DVT was greater than the risk of PE. “This study suggests a unique mechanism of blood clotting in people with sickle cell trait,” said Rakhi Naik, M.D., M.H.S., Clinical Director for the Division of Hematology at Johns Hopkins University, who co-led the study. “Knowing the risks of blood clots in people with sickle cell trait is important for situations such as surgeries or hospitalizations, which add to the risk of developing serious blood clots.” In addition to suggesting novel biology for individuals with sickle cell trait in the development of PE, this study may inform clinical care. “This study provides valuable information to clinicians counseling individuals with sickle cell trait,” said Julie Granka, Ph.D., a Principal Scientist at 23andMe and a co-author of the paper. “Our study results are applicable across ancestries, and they show valuable comparisons to Factor V Leiden, where there is more established clinical guidance. Notably, the risk of VTE for individuals with SCT is lower than for those with Factor V Leiden.” About 23andMe 23andMe is a genetics-led consumer healthcare and biopharmaceutical company empowering a healthier future. For more information, please visit . Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including. All statements, other than statements of historical fact, included or incorporated in this press release are forward-looking statements. The words “believes,” “anticipates,” “estimates,” “plans,” “expects,” “intends,” “may,” “could,” “should,” “potential,” “likely,” “projects,” “predicts,” “continue,” “will,” “schedule,” and “would” or, in each case, their negative or other variations or comparable terminology, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are predictions based on 23andMe’s current expectations and projections about future events and various assumptions. 23andMe cannot guarantee that it will actually achieve the plans, intentions, or expectations disclosed in its forward-looking statements and you should not place undue reliance on 23andMe’s forward-looking statements. These forward-looking statements involve a number of risks, uncertainties (many of which are beyond the control of 23andMe), or other assumptions that may cause actual results or performance to differ materially from those expressed or implied by these forward-looking statements. The forward-looking statements contained herein are also subject generally to other risks and uncertainties that are described from time to time in the Company’s filings with the Securities and Exchange Commission, including under Item 1A, “Risk Factors” in the Company’s most recent Annual Report on Form 10-K, as filed with the Securities and Exchange Commission, and as revised and updated by our Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. The statements made herein are made as of the date of this press release and, except as may be required by law, 23andMe undertakes no obligation to update them, whether as a result of new information, developments, or otherwise. Contacts Media Contact: press@23andMe.com Investor Relations Contact: investors@23andMe.com

~ 88% reduction in median Annualized Bleeding Rate (ABR) for all bleeds and 94% reduction in median ABR for spontaneous joint bleeds in highest dose tested ~ ~ SerpinPC observed to be well-tolerated ~ ~ Company has initiated planning for global registrational program ~ ~ Conference call and webcast scheduled for today at 8:30 a.m. EDT ~ CAMBRIDGE, Mass. and LONDON, Sept. 09, 2021 (GLOBE NEWSWIRE) -- Centessa Pharmaceuticals plc (“Company”) (Nasdaq: CNTA), together with subsidiary ApcinteX Limited (“ApcinteX”), today announced positive topline results from the Phase 2a part of AP-0101, the six-month repeat dose portion of its ongoing first-in-human proof-of-concept study evaluating SerpinPC in severe hemophilia A and B patients. AP-0101 is a Phase 1/2a proof-of-concept study evaluating SerpinPC, an inhibitor of activated protein C (“APC”), in 23 male subjects with either severe hemophilia A or B who were not on prophylaxis.1 The Phase 2a part of the study assessed the safety, tolerability and pharmacokinetics across three dose cohorts (0.3 mg/kg, 0.6 mg/kg and 1.2 mg/kg) of SerpinPC administered as a subcutaneous (SC) injection every 4 weeks over a 24-week period (6 total doses). Reduction in the annualized bleeding rates (ABRs) were exploratory outcomes. Although eligible, none of the patients in the study had inhibitors. SerpinPC was well-tolerated. As previously disclosed, one subject with a history of a skin disorder discontinued treatment on SerpinPC due to an injection site reaction. No other SerpinPC-related adverse events have been recorded. There was no reported sustained elevation in D-dimer, a sensitive measure of excess thrombin generation, throughout the 24-week study. Two subjects had anti-drug antibodies and remained on treatment without apparent impact on ABRs. In the highest dose cohort, SerpinPC reduced the self-reported all bleeds ABR by 88% during the last 12 weeks of treatment (pre-specified primary assessment period) as compared to the all bleeds ABR prospectively measured during the pre-exposure observation period. In the highest dose cohort, five out of eight subjects had zero or one bleed during the 12-week pre-specified primary assessment period. Self-reported spontaneous joint bleeds ABR was reduced by 94% in the highest dose cohort. ABR reductions were similar between patients with either hemophilia A or hemophilia B. Dose Tested Exploratory Efficacy Endpoints 0.3 mg/kg n=7 0.6 mg/kg n=7 1.2 mg/kg n=8 All Bleeds ABR (median percent change) -80% p=0.016 -70% p=0.031 -88% p=0.016 Spontaneous Joint Bleeds ABR (median percent change) -76% p=0.016 -69% p=0.031 -94% p=0.023 Above analyses compared last 12 weeks of treatment (pre-specified primary assessment period) to pre-exposure baseline measures. Bleeding events were self-reported. p-values presented are based on small numbers and are exploratory in nature. The median number of target joints (joint with >3 bleeds in any 6-month period) was reduced to zero at the end of the study from a pre-exposure baseline of 2.5. All subjects had target joints at the start of the study and 15 subjects had zero target joints at the end of the study. All 22 patients who completed the Phase 2a portion of the study have elected to enroll into the 48-week open label extension (“OLE”) portion of the study in which a single flat 60 mg subcutaneous dose of SerpinPC will be administered every 4 weeks over a period of 48 weeks (13 doses total). Centessa expects to report results from the OLE portion of this study in the second half of 2022. “The compelling reduction in bleeds and continued tolerability that we observed in both hemophilia A and hemophilia B patients in this proof-of-concept study are very encouraging, and we are eager to move SerpinPC into a global development plan aimed at pursuing one or more registrations. We see broad utility of SerpinPC across the hemophilia landscape and will seek the most rapid path to bring this potential subcutaneous therapy to hemophilia patients,” said Antoine Yver, M.D., M.Sc., Chief Medical Officer of Centessa Pharmaceuticals. “The results of this Phase 2a study of SerpinPC continue to show an excellent tolerability pro this molecule, and the exploratory efficacy results seen in this study of severe hemophilia A and B patients are also very promising. A safe, subcutaneous, prophylaxis option for both hemophilia A and B patients would be an important addition to our treatment choices,” said David Lillicrap, M.D., Professor of Pathology and Molecular Medicine at Queen's University, Kingston, Ontario, Canada and previously a World Federation of Hemophilia Advisory Board member. ¹ Clinicaltrials.gov identifier: NCT04073498 ( ) Conference Call and Webcast Centessa Pharmaceuticals will host a webcast and conference call today, September 9, 2021, at 8:30 a.m. EDT to discuss topline data from the proof-of-concept trial. To access the audio webcast with slides, please visit the "Events & Publications" page in the Investors & Media section of the Company's website at . The call can also be accessed by dialing (855) 493-3565 (domestic) or (929) 517-9002 (international) with conference ID 8459296. An archive of today's webcast will be available on the Company’s website. About Centessa Pharmaceuticals Centessa Pharmaceuticals plc aims to bring impactful new medicines to patients by combining the strengths of an asset-centric model with the benefits of scale and diversification typical of larger R&D organizations. The asset-centric model refers to a highly specialized, singular-focused company that is led by a team of well-recognized subject matter experts. Centessa’s asset-centric companies’ programs range from discovery-stage to late-stage development and include diverse therapeutic areas such as oncology, hematology, immunology/inflammation, neuroscience, hepatology, pulmonology and nephrology. For more information, visit . About ApcinteX Limited ApcinteX Limited is focused on developing SerpinPC for the treatment of hemophilia A and hemophilia B. Hemophilia is a rare bleeding disorder that is caused by a deficiency of thrombin generation upon vascular damage. About SerpinPC SerpinPC, a biologic based on the serpin family of proteins, is designed to allow more thrombin to be generated by inhibiting activated protein C (APC) thus rebalancing coagulation in hemophilia patients. SerpinPC has the potential to treat all types of hemophilia regardless of severity or inhibitor status, and may also prevent bleeding associated with other bleeding disorders. About AP-0101 AP-0101 is an ongoing Phase 1/2a open-label clinical trial to investigate the safety, tolerability and pharmacokinetics of intravenous and subcutaneous doses of SerpinPC in healthy male volunteers and male persons with severe hemophilia ( ). About Hemophilia A (HA) and Hemophilia B (HB) HA and HB are X-linked genetic disorders affecting one in 5,000 and one in 20,000 live male births, respectively, resulting in spontaneous internal bleeding that can be life-threatening. More than 70% of bleeds occur into joints (hemarthrosis) causing chronic joint damage (arthropathy) with musculoskeletal destruction. The bleeding associated with these disorders is the result of a defect or deficiency in factor VIII (in the case of HA) or factor IX (in the case of HB), the two components of the intrinsic tenase complex. Normal blood coagulation (hemostasis) is a crucial part of the physiological response to tissue damage. When blood components come into contact with extravascular cells and proteins, platelets accumulate and ultimately lead to the formation of thrombin, the effector enzyme of blood coagulation. Prothrombinase activity is required for the rapid, localized production of thrombin needed for adequate blood clotting. Prothrombinase is continuously degraded by APC, which is present in the circulation at low concentrations. In the setting of deficient intrinsic tenase activity (hemophilia), the natural anticoagulant activity of the circulating APC results in insufficient prothrombinase activity for normal blood clotting. Forward Looking Statements This press release contains forward-looking statements. These statements may be identified by words such as "believe," "anticipate," "plan," "expect," "intend," "will," "may," "goal," "project," "estimate," "potential," and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. These statements include discussions of the open label extension study of SerpinPC and its design and conduct; plans for continued development of SerpinPC, including our global development plan and registrational path for this candidate; our expectations with respect to the treatment paradigm for hemophilia A and B; our ability to deliver impactful medicines to patients; the ability of our key executives to drive execution of our portfolio of programs; our asset-centric business model and the intended advantages and benefits thereof; research and clinical development plans; the scope, progress, results and costs of developing our product candidates or any other future product candidates; strategy; regulatory matters, including the timing and likelihood of success of obtaining approvals to initiate or continue clinical trials or market any products; market size and opportunity; and our ability to complete certain milestones. Any forward-looking statements in this press release are based on our current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the safety, tolerability and efficacy pro SerpinPC observed to date may change adversely in future clinical trials, ongoing analyses of trial data or subsequent to commercialization; foreign regulatory agencies may not agree with our regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted; risks inherent in developing products and technologies; risks related to our ability to protect and maintain our intellectual property position; business, regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about the Company; our ability to obtain adequate financing to fund our planned clinical trials and other expenses; trends in the industry; the legal and regulatory framework for the industry; future expenditures risks related to our asset-centric corporate model; the risk that any one or more of our product candidates will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies; and risks related to the COVID-19 pandemic including the effects of the Delta variant. These and other risks concerning our programs and operations are described in additional detail in our most recent Form 10-Q, which is on the SEC and available on the SEC’s website at . We operate in a very competitive environment in which new risks emerge from time to time. These forward-looking statements are based on our current expectations, and speak only as of the date hereof. We explicitly disclaim any obligation to update any forward-looking statements except to the extent required by law. Contacts: Investor Contact: Media Contacts: Jennifer Porcelli, Head of Investor Relations US Centessa Pharmaceuticals Dan Budwick, 1AB jennifer.porcelli@centessa.com dan@1abmedia.com UK/Greater Europe Mary Clark, Optimum Strategic Communications centessa@optimumcomms.com Switzerland Marcus Veith, VEITHing Spirit marcus@vspirit.ch M: +41 79 20 75 111