GATA2 Deficiency

Immunogeneticists have discovered a new genetic disorder that causes immunodeficiency and profound susceptibility to opportunistic infections including a life-threatening fungal pneumonia. An international consortium co-led by Vanderbilt University Medical Center immunogeneticist Rubén Martínez-Barricarte, PhD, has discovered a new genetic disorder that causes immunodeficiency and profound susceptibility to opportunistic infections including a life-threatening fungal pneumonia. The discovery, reported Jan. 20 in the journal Science Immunology, will help identify people who carry this in-born error of immunity (IEI). "Our findings will provide the basis for genetic diagnosis and preventive treatment for these groups of patients," Martínez-Barricarte said. IEIs, also known as primary immunodeficiencies, are genetic defects characterized by increased susceptibility to infectious diseases, autoimmunity, anti-inflammatory disorders, allergy, and in some cases, cancer. To date, 485 different IEIs have been identified. It is now thought that they occur in one of every 1,000 to 5,000 births, making them as prevalent as other genetic disorders, including cystic fibrosis and Duchene's muscular dystrophy. Despite recent medical advances, about half of patients with IEIs still lack a genetic diagnosis that could help them avoid debilitating illness and death. That's why this research is so important. The error in this case is a mutation in the gene for the protein IRF4, a transcription factor that is pivotal for the development and function of B and T white blood cells, as well as other immune cells. As a postdoctoral fellow at The Rockefeller University, Martínez-Barricarte was part of an international research team that, in 2018, identified an IRF4 mutation associated with Whipple's disease, a rare bacterial infection of the intestine that causes diarrhea, weight loss, and abdominal and joint pain. Martínez-Barricarte is now an assistant professor of Medicine in the Division of Genetic Medicine, and of Pathology, Microbiology & Immunology in the Division of Molecular Pathogenesis. In 2020, after moving his lab to VUMC, he began collaborating with Aide Tamara Staines-Boone, MD, and her colleagues in Monterrey, Mexico. They were caring for a young boy who was suffering from severe and recurrent fungal, viral, mycobacterial, and other infections. Martínez-Barricarte and his team sequenced the protein-encoding regions of the boy's genome and discovered a de novo IRF4 mutation, which originated in the patient and was not inherited from his parents. Upon consulting with IRF4 experts at the Imagine Institute for the study and treatment of genetic diseases in Paris, they were told that seven other groups were independently characterizing the same mutation. They now collaborate as the IRF4 International Consortium. In the current study, the consortium identified seven patients from six unrelated families across four continents with profound combination immunodeficiency who experienced recurrent and serious infections, including pneumonia caused by the fungus Pneumocystis jirovecii. Each patient had the same mutation in the DNA-binding domain of IRF4. Extensive phenotyping of patients' blood cells revealed immune cell abnormalities associated with the disease, including impaired maturation of antibody-producing B cells, and reduced T-cell production of infection-fighting cytokines. Two knock-in mouse models, in which the mutation was inserted into the mouse genome, exhibited a severe defect in antibody production consistent with the combined immune deficiency observed in the patients. The researchers also discovered the mutation had a "multimorphic" effect detrimental to the activation and differentiation of immune cells. While the mutant IRF4 binds to DNA with a higher affinity than the native form of the protein (in a hypermorphic way), its transcriptional activity in common, canonical genes is reduced (hypomorphic), and it binds to other DNA sites (in a neomorphic way), altering the protein's normal gene expression profile. This multimorphic activity is a new mechanism for human disease. "We anticipate that variants with multimorphic activity may be more widespread in health and disease," the researchers concluded. Co-authors from Martínez-Barricarte's lab included graduate students Jareb Pérez Caraballo and Xin Zhen, and research assistant Linh Tran. His research was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (grant #AI171466).

Closed Merger with TYME Technologies and Concurrent PIPE; Proceeds from Combined Transactions Augment Cash Balance, Ending Third Quarter with Approximately $245 Million and Extending Cash Runway into 2025 Initial Data from Safety Lead-in Portion of SELECT-AML-1 Phase 2 Trial to be Presented at ASH Initial Data from Safety Lead-in of Phase 1 Trial of SY-5609 Demonstrates Encouraging Safety and Clinical Activity in Pancreatic Cancer Patients Management to Host Conference Call at 8:30 a.m. ET Today CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, today reported financial results for the quarter ended September 30, 2022 and provided a corporate update. “The third quarter was transformative for Syros. In September, we announced the closing of our merger with TYME Technologies and concurrent oversubscribed PIPE, with combined gross proceeds of approximately $190 million,” said Nancy Simonian, M.D., Chief Executive Officer of Syros. “With this additional capital, we believe we are well-positioned to build Syros into a commercial-stage company. We are now focused on advancing our late-stage hematology programs toward important clinical milestones, beginning with the presentation of initial results, including clinical activity, from the safety lead-in portion of the SELECT-AML-1 Phase 2 trial at the ASH Annual Meeting in December. In addition, we remain on track to report data from the pivotal SELECT-MDS-1 trial in late 2023 or early 2024 and, based on the preliminary data from our dose confirmation study of SY-2101 that we announced in August, expect to initiate a Phase 3 trial in patients with APL in the second half of next year.” Dr. Simonian continued, “Today, we are excited to announce initial data from the safety lead-in portion of our Phase 1 trial evaluating SY-5609 in combination with chemotherapy in patients with relapsed/refractory metastatic pancreatic cancer as well as an update from the single agent portion in advanced solid tumor patients. Importantly, the data reinforce our belief in the promise of selective CDK7 inhibition to benefit many difficult to treat cancers. To maximize the potential of SY-5609, we made the strategic decision to seek partnership opportunities for this program while we continue dose escalation in the ongoing trial, and to focus our internal resources on advancing our late-stage hematology portfolio for the frontline treatment of MDS, AML and APL.” UPCOMING MILESTONES Tamibarotene: Oral RARα agonist Higher-Risk Myelodysplastic Syndrome (HR-MDS) On track to report pivotal data from the SELECT-MDS-1 trial in newly diagnosed HR-MDS patients with RARA gene overexpression in the fourth quarter of 2023 or the first quarter of 2024, with a potential new drug application (NDA) filing expected in 2024. Acute Myelodysplastic Syndrome (AML) Present safety and clinical activity data from the safety lead-in portion of the ongoing SELECT-AML-1 Phase 2 trial in newly diagnosed unfit AML patients with RARA overexpression at the 64th American Society of Hematology (ASH) Annual Meeting in December. The presentation, titled “Initial Results from SELECT-AML-1, a Phase 2 study of Tamibarotene in Combination with Venetoclax and Azacitidine in RARA-positive Newly Diagnosed AML Patients Ineligible for Standard Induction Chemotherapy,” is scheduled to be presented in a poster session on December 10, 2022. Expect to initiate the randomized portion of the SELECT-AML-1 Phase 2 trial in an additional eighty patients evaluating the triplet regimen of tamibarotene, venetoclax and azacitidine compared to venetoclax and azacitidine with data expected in 2023 or 2024. SY-2101: Oral arsenic trioxide (ATO) Expect to initiate the Phase 3 trial of SY-2101 in patients with newly diagnosed acute promyelocytic leukemia (APL) in the second half of 2023. RECENT PIPELINE HIGHLIGHTS Today, Syros announced initial safety and clinical activity data from the safety lead-in portion of the ongoing Phase 1 trial evaluating SY-5609 in combination with chemotherapy in patients with relapsed/refractory metastatic Pancreatic Ductal Adenocarcinoma (PDAC) as well as from the ongoing single agent portion in relapsed/refractory patients with select solid tumors. The data showed: As of October 12, 2022, SY-5609 was generally safe with enhanced tolerability being maintained in the 7 day on/ 7 day off regimen at the highest doses evaluated to date, up to 10 mg when administered as a single agent, up to 5 mg when administered in combination with gemcitabine, and up to 4 mg when administered with gemcitabine/nab-paclitaxel. The single agent 10 mg dose level did not result in any dose limiting toxicities (DLTs), further supporting the tolerability of the 7 day on/7 day off dosing regimen in which 30 patients have been dosed across five dose levels (4, 5, 6, 7, and 10 mg), with only one DLT observed at the 4 mg single agent dose level. A maximum tolerated dose (MTD) has not yet been reached in either the single agent or in the chemotherapy combination cohorts in the 7 day on/ 7 day off dosing regimen. The adverse event pro SY-5609 in combination with chemotherapy was consistent with the safety pro single agent SY-5609 or gemcitabine monotherapy or gemcitabine/nab-paclitaxel, and the majority of adverse events were low grade and reversible, with no new safety signals identified. The most common related adverse events in the cohort with SY-5609 and gemcitabine, where the highest SY-5609 doses were evaluated in combination with chemotherapy, included fatigue, nausea, decreased appetite and decreased platelet count (all low grade), with one patient experiencing a DLT of grade 3 diarrhea at the 5 mg SY-5609 dose level. No DLTs were reported in patients treated with SY-5609 in combination with gemcitabine/nab-paclitaxel. As of October 20, 2022, in the single agent cohort at 10 mg of SY-5609, two of three enrolled patients with select solid tumors were response evaluable, including one patient with PDAC and one with Colorectal Cancer both achieved stable disease (SD). The one patient with PDAC with SD experienced a 10% tumor reduction. In the cohort evaluating the doublet combination of SY-5609 and gemcitabine in patients with PDAC, one of four (25%) response evaluable patients treated at the 4 mg SY-5609 dose level experienced a confirmed partial response (PR) with a 98% reduction in the CA 19-9 tumor marker from a baseline of 60,357 U/mL to 968 U/mL, and three of four (75%) response evaluable patients treated at the 5 mg SY-5609 dose level had SD, for an overall disease control rate (DCR) of 50% (4 of 8 patients). Data from the doublet and the 10 mg single agent dose support an emerging exposure-response relationship; notably, the patient with the PR demonstrated higher-than-average exposure relative to other patients at that dose. In the cohort evaluating the triplet combination of SY-5609 and gemcitabine/nab-paclitaxel in PDAC patients, one of two response evaluable patients treated at the 4 mg dose level achieved SD. Syros plans to continue dose escalation of SY-5609 to 15 mg as a single agent and to 10 mg in the gemcitabine combination cohort and in parallel, will be seeking a partnership for further development of SY-5609. In September, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to SY-5609 for the treatment of pancreatic cancer. The FDA's Office of Orphan Drug Products grants orphan status to support development of medicines for the treatment of rare diseases that affect fewer than 200,000 people in the United States. Orphan drug designation may provide certain benefits, including a seven-year period of market exclusivity if the drug is approved, tax credits for qualified clinical trials and an exemption from FDA application fees. CORPORATE In September, Syros announced the closing of its merger with TYME Technologies, pursuant to which Syros acquired TYME, including its pipeline assets and net cash at closing of approximately $60 million. Concurrent with the closing of the merger, Syros also closed the previously announced oversubscribed $130 million private investment in public equity (PIPE) financing. New and existing investors in the PIPE, which was led by a life-sciences focused investment fund, include Syros co-founder and founding investor Flagship Pioneering, Avidity Partners, Deep Track Capital, Bain Capital Life Sciences, Invus, Samsara BioCapital, Adage Capital Partners LP, Ally Bridge Group and Cowen Healthcare Investments, as well as other investors. Third Quarter 2022 Financial Results Revenues were $3.9 million for the third quarter of 2022, consisting of $3.7 million in revenue recognized under Syros’ collaboration with Global Blood Therapeutics, Inc. (GBT), now a subsidiary of Pfizer, and $0.2 million recognized under its collaboration with Incyte. Syros recognized $5.7 million in revenue in the third quarter of 2021, consisting of $5.6 million in revenue recognized under its collaboration with GBT and $0.1 million recognized under its collaboration with Incyte. Research and development expenses were $25.8 million for the third quarter of 2022, as compared to $27.3 million for the third quarter of 2021. This decrease was primarily due to a decrease in external costs related to our preclinical programs. General and administrative (G&A) expenses were $8.1 million for the third quarter of 2022, as compared to $5.3 million for the third quarter of 2021. This increase was primarily due to employee-related expenses and recruiting fees. Transaction related expenses were $9.5 million for the third quarter of 2022 and consisted of the PIPE financing transaction cost allocated to warrant classified liabilities and severance paid to former Tyme employees. For the third quarter of 2022, Syros reported a net loss of $30.3 million, or $3.21 per share, compared to a net loss of $26 million, or $4.14 per share, for the same period in 2021. Cash and Financial Guidance Cash, cash equivalents and marketable securities as of September 30, 2022 were $244.5 million, as compared with $143.4 million on December 31, 2021. Syros expects that its existing cash, cash equivalents and marketable securities will be sufficient to fund its planned operating expenses and capital expenditure requirements into 2025. Conference Call and Webcast Syros will host a conference call today at 8:30 a.m. ET to discuss these third quarter 2022 financial results and provide a corporate update. Participants may register for the conference call here. While not required, it is recommended that participants join the call ten minutes prior to the scheduled start. A live webcast of the call will also be available on the Investors & Media section of the Syros website at . An archived replay of the webcast will be available for approximately 30 days following the call. About Syros Pharmaceuticals Syros is redefining the power of small molecules to control the expression of genes. Based on its unique ability to elucidate regulatory regions of the genome, Syros aims to develop medicines that provide a profound benefit for patients with diseases that have eluded other genomics-based approaches. Syros is advancing a robust clinical-stage pipeline, including: tamibarotene, a first-in-class oral selective RARα agonist in patients with higher-risk myelodysplastic syndrome and acute myeloid leukemia with RARA gene overexpression; SY-2101, a novel oral form of arsenic trioxide in patients with acute promyelocytic leukemia; and SY-5609, a highly selective and potent oral CDK7 inhibitor in patients with select solid tumors. Syros also has multiple preclinical and discovery programs in oncology and monogenic diseases. For more information, visit and follow us on Twitter (@SyrosPharma) and LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, including without limitation statements regarding Syros’ clinical development plans, including with respect to tamibarotene, SY-2101 and SY-5609, Syros’ ability to deliver benefit to patients, the timing and impact of upcoming clinical and preclinical data readouts, the timing for submitting a new drug application to the FDA, the ability to develop into a commercial-stage company, the benefits of receiving an orphan drug designation for SY-5609, the intention to seek a partnership for SY-5609, and the sufficiency of Syros’ capital resources to fund its operating expenses and capital expenditure requirements into 2025. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “hope,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “target,” “should,” “would,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including Syros’ ability to: advance the development of its programs, including tamibarotene, SY-2101 and SY-5609, under the timelines it projects in current and future clinical trials; demonstrate in any current and future clinical trials the requisite safety, efficacy and combinability of its drug candidates; sustain the response rates and durability of response seen to date with its drug candidates; successfully develop a companion diagnostic test to identify patients with the RARA biomarker; obtain and maintain patent protection for its drug candidates and the freedom to operate under third party intellectual property; obtain and maintain necessary regulatory approvals; identify, enter into and maintain collaboration agreements with third parties; manage competition; manage expenses; raise the substantial additional capital needed to achieve its business objectives; attract and retain qualified personnel; and successfully execute on its business strategies; risks described under the caption “Risk Factors” in Syros’ Annual Report on Form 10-K for the year ended December 31, 2021 and Quarterly Report on Form 10-Q for the quarter ended September 30, 2022, each of which is on the Securities and Exchange Commission; and risks described in other filings that Syros makes with the Securities and Exchange Commission in the future. In addition, the extent to which the COVID-19 pandemic continues to impact Syros’ workforce and its clinical trial operations activities, and the operations of the third parties on which Syros relies, will depend on future developments, which are highly uncertain and cannot be predicted with confidence, including the duration and severity of the pandemic, additional or modified government actions, and the actions that may be required to contain the virus or treat its impact. Any forward-looking statements contained in this press release speak only as of the date hereof, and Syros expressly disclaims any obligation to update any forward-looking statements, whether because of new information, future events or otherwise. This press release contains hyperlinks to information that is not deemed to be incorporated by reference in this press release. Syros Pharmaceuticals, Inc. Selected Condensed Consolidated Balance Sheet Data (in thousands) (unaudited) September 30, 2022 December 31, 2021 Cash, cash equivalents and marketable securities (current and noncurrent) $ 244,481 $ 143,407 Working capital 213,881 105,077 Total assets 284,725 182,935 Total stockholders’ equity 129,171 85,218 Syros Pharmaceuticals, Inc. Condensed Consolidated Statement of Operations (in thousands, except share and per share data) (unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2022 2021 2022 2021 Revenue $ 3,891 $ 5,697 $ 15,634 $ 15,686 Operating expenses: Research and development 25,759 27,262 84,030 73,077 General and administrative 8,076 5,346 21,970 16,606 Transaction related expenses 9,510 — 9,510 — Total operating expenses 43,345 32,608 115,510 89,683 Loss from operations (39,454 ) (26,911 ) (99,876 ) (73,997 ) Interest income 392 32 539 56 Interest expense (1,051 ) (984 ) (3,008 ) (2,921 ) Change in fair value of warrant liability 9,860 1,836 12,465 14,117 Net loss applicable to common stockholders $ (30,253 ) $ (26,027 ) $ (89,880 ) $ (62,745 ) Net loss per share applicable to common stockholders - basic and diluted $ (3.21 ) $ (4.14 ) $ (11.93 ) $ (10.06 ) Weighted-average number of common shares used in net loss per share applicable to common stockholders - basic and diluted 9,417,069 6,292,830 7,536,149 6,239,482

BOULDER, Colo.--(BUSINESS WIRE)-- Clovis Oncology, Inc. (NASDAQ: CLVS) today announced the presentation of data from the TRITON3 Phase 3 trial in men with metastatic castration-resistant prostate cancer with BRCA or ATM mutations. The presentation titled, “TRITON3: A Phase 3 Study of Rucaparib vs. Physician’s Choice of Therapy in mCRPC Associated with Homologous Recombination Deficiency (HRD)” is being presented by Alan H. Bryce, MD, chair of the Division of Hematology and Medical Oncology at the Mayo Clinic and co-principal investigator of the TRITON3 trial during the session titled, “Novel Clinical Trial Updates” at the 29th Annual Prostate Cancer Foundation (PCF) Scientific Retreat. The presentation is available at . “We believe that the positive results from TRITON3 further demonstrate the important role that Rubraca may play as a treatment option for men with metastatic castration-resistant prostate cancer associated with homologous recombination deficiency. This is the first and only PARP inhibitor that has demonstrated superior radiographic PFS compared to a control arm containing docetaxel chemotherapy, which is today the standard of care for these patients,” said Patrick J. Mahaffy, President and CEO of Clovis Oncology. “We look forward to submitting additional data for presentation during a medical meeting in 2023.” Earlier this month, the Company reported top-line data from the TRITON3 (NCT02975934) study evaluating Rubraca monotherapy versus chemotherapy or second-line second-generation androgen pathway inhibitor in patients with chemotherapy-naive mCRPC with mutations in BRCA or ATM achieved the primary endpoint of improved radiographic progression-free survival (rPFS) by independent radiology review (IRR). About the TRITON3 Clinical Trial TRITON3 (NCT02975934) is a Phase 3, multicenter, open-label, randomized trial of Rubraca in patients with chemotherapy-naïve mCRPC. Patients with a mutation in BRCA or ATM were randomized to Rubraca or the control group, which consisted of physician’s choice of docetaxel, abiraterone acetate, or enzalutamide. The primary objective was efficacy, as analyzed by independent radiology review (IRR) of radiographic progression-free survival (rPFS) in patients with mutations in BRCA1, BRCA2 or ATM. TRITON3 was designed as a Phase 3 trial to confirm and expand the efficacy data from TRITON2 in an earlier treatment setting against a relevant control arm. About Prostate Cancer The American Cancer Society estimates that approximately 268,000 men in the US will be diagnosed with prostate cancer in 2022, and the GLOBOCAN Cancer Fact Sheets estimated that approximately 473,000 men in Europe were diagnosed with prostate cancer in 2020. Castrate-resistant prostate cancer has a high likelihood of developing metastases. Metastatic castrate-resistant prostate cancer (mCRPC) is an incurable disease, usually associated with poor prognosis.i Approximately 43,000 men in the US were expected to be diagnosed with mCRPC in 2020.ii According to the National Cancer Institute, the five-year survival rate for mCRPC is approximately 30%. BRCA1, BRCA2 or ATM mutations have been detected in approximately 19% of patients with mCRPC according to articles published in JCO Precision Oncology in 2017 and in Clinical Cancer Research in 2021. These molecular markers may be used to select patients for treatment with a PARP inhibitor.iii About Rubraca (rucaparib) Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway. Rubraca is an unlicensed medical product outside of the US and Europe. Rubraca US FDA Approved Indications Ovarian Cancer Rubraca is indicated for the maintenance treatment of adult women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Prostate Cancer Rubraca is indicated for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Select Important Safety Information Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) have occurred in patients treated with Rubraca and are potentially fatal adverse reactions. In 1146 treated patients, MDS/AML occurred in 20 patients (1.7%), including those in long term follow-up. Of these, 8 occurred during treatment or during the 28-day safety follow-up (0.7%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 53 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA damaging agents. In TRITON2, MDS/AML was not observed in patients with mCRPC (n=209) regardless of homologous recombination deficiency (HRD) mutation. Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Rubraca. Based on its mechanism of action and findings from animal studies, Rubraca can cause fetal harm when administered to a pregnant woman. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca. For males on Rubraca treatment who have female partners of reproductive potential or who are pregnant, effective contraception should be used during treatment and for 3 months following the last dose of Rubraca. Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1-4) were nausea (76%), fatigue/asthenia (73%), abdominal pain/distention (46%), rash (43%), dysgeusia (40%), anemia (39%), AST/ALT elevation (38%), constipation (37%), vomiting (37%), diarrhea (32%), thrombocytopenia (29%), nasopharyngitis/upper respiratory tract infection (29%), stomatitis (28%), decreased appetite (23%), and neutropenia (20%). Most common adverse reactions in TRITON2 (≥ 20%; Grade 1-4) were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%). Co-administration of rucaparib can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring. Because of the potential for serious adverse reactions in breast-fed children from Rubraca, advise lactating women not to breastfeed during treatment with Rubraca and for 2 weeks after the last dose. Please Click here for full Prescribing Information for Rubraca. You may also report side effects to Clovis Oncology, Inc. at 1-415-409-7220 (US toll) or 1-844-CLVS-ONC (1-844-258-7662; US toll-free). About Clovis Oncology Clovis Oncology, Inc. is a biopharmaceutical company focused on acquiring, developing, and commercializing innovative anti-cancer agents in the US, Europe, and additional international markets. Clovis Oncology targets development programs at specific subsets of cancer populations, and simultaneously develops, with partners, for those indications that require them, diagnostic tools intended to direct a compound in development to the population that is most likely to benefit from its use. Clovis Oncology is headquartered in Boulder, Colorado, with additional office locations in the US and Europe. Please visit for more information. To the extent that statements contained in this press release are not descriptions of historical facts regarding Clovis Oncology, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Examples of forward-looking statements contained in this press release include, among others, statements regarding our expectations concerning future regulatory activities, expectations for submission of regulatory filings, our plans to present final or interim data on ongoing clinical trials, our plans to submit additional data to, or meet with, the FDA with respect to the status of or plans for ongoing or planned trials, the potential for marketing authorizations for new indications, our expectations regarding the suitability of Rubraca, and our plans to develop Rubraca in additional indications and tumor types. Such forward-looking statements involve substantial risks and uncertainties that could cause our future results, performance, or achievements to differ significantly from that expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in our clinical development programs for our drug candidates and those of our partners, whether future study results will be consistent with study findings to date, the timing of availability of data from our clinical trials and the initiation, enrollment, timing and results of our planned clinical trials and the corresponding development pathways, effectiveness and suitability of diagnostic tests, the risk that final results of ongoing trials may differ from initial or interim results as a result of factors such as final results from a larger patient population may be different from initial or interim results from a smaller patient population, the risk that additional pre-clinical or clinical studies may not support further development in certain additional indications or tumor types, and actions by the FDA, the EMA or other regulatory authorities regarding data required, including that of secondary endpoints such as overall survival, and the maturity of such data, to support drug applications and whether to approve drug applications. Clovis Oncology does not undertake to update or revise any forward-looking statements. A further description of risks and uncertainties can be found in Clovis Oncology’s filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K and its reports on Form 10-Q and Form 8-K. i Sumanasuriya S. and Bono J., Treatment of Advanced Prostate Cancer—A Review of Current Therapies and Future Promise, Cold Spring Harb Perspect Med, 2018, June; 8(6); a030635. ii Scher H. et al, Prevalence of Prostate Cancer Clinical States and Mortality in the United States: Estimates Using a Dynamic Progression Model, PLoS One, 2015; 10(10) iii Congregado B., PARP Inhibitors: A New Horizon for Patients with Prostate Cancer, Biomedicines, 2022 Jun; 10 (6)