Ovarian Serous Adenocarcinoma

Presentations highlight key preclinical data that support investigational new drug application (IND) submissions for ZW220 in 1H and ZW251 in 2H in 2025 VANCOUVER, British Columbia, Oct. 25, 2024 (GLOBE NEWSWIRE) -- Zymeworks Inc. (Nasdaq: ZYME), a clinical-stage biotechnology company developing a diverse pipeline of novel, multifunctional biotherapeutics to improve the standard of care for difficult-to-treat diseases, today announced new preclinical data for Zymeworks’ antibody-drug conjugate (ADC) candidates ZW220 and ZW251 in presentations at the European Organisation for Research and Treatment of Cancer-National Cancer Institute-American Association for Cancer Research (EORTC-NCI-AACR) Conference taking place in Barcelona on October 23-25, 2024. "We are thrilled to present preclinical data for ZW220 and ZW251 at the EORTC-NCI-AACR Conference," said Paul Moore, Ph.D., Chief Scientific Officer at Zymeworks. "These innovatively designed molecules, incorporating our proprietary payload, ZD06519, show significant potential to address critical unmet needs in oncology. The preclinical data presented this week supports our belief that these programs could advance treatment options beyond current standards of care, offering renewed hope for patients battling challenging cancers where therapeutic progress has been limited." Oral Presentation Details An oral presentation titled “ZW220, a NaPi2b-directed topoisomerase I inhibitor Antibody-Drug Conjugate, demonstrates compelling preclinical activity in NSCLC, ovarian and uterine cancer models, with a favorable toxicology profile in non-human primate” highlights preclinical data that continue to support an IND submission in the first half of 2025. Results demonstrate that ZW220 has the potential for improvement over previous NaPi2b ADCs and on the basis of efficacy, tolerability and payload mechanism. ZW220 features a novel, moderate potency TOPO1i payload with strong bystander activity, beneficial for tumors with low and heterogeneous NaPi2b expression. We believe it offers a differentiated safety profile compared to other ADCs currently in the clinic, demonstrating high tolerability in animal studies with MTD ≥90 mg/kg in non-human primates (NHP) and ≥200 mg/kg in rats, suggesting potential for high doses in humans. The low drug-antibody ratio (DAR) and moderate stability of the antibody-linker provide a good balance of stability, tolerability, and anti-tumor activity, while potentially minimizing antibody-driven toxicities. ZW220's strong internalizing antibody enables efficient cellular trafficking and tissue penetration, potentially improving anti-tumor activity even at lower NaPi2b levels. Poster Presentation Details A poster titled “ZW251, a novel glypican-3-targeting antibody-drug conjugate bearing a topoisomerase I inhibitor payload, demonstrates compelling preclinical activity in hepatocellular carcinoma models” highlights preclinical data that continue to support an IND submission in the second half of 2025. Results demonstrate that ZW251 shows promise as a new treatment option for patients, potentially improving upon the current standard of care (SOC). Demonstrating strong anti-tumor activity across a wide range of hepatocellular carcinoma (HCC) models, including those with lower and heterogenous GPC3 expression, ZW251 was designed with a DAR of four, striking a balance between tolerability and broad anti-tumor effectiveness. In NHP studies, ZW251 displayed significant tolerability at doses up to 120 mg/kg. As an ADC, ZW251 offers flexibility in treatment strategies, potentially serving as either a standalone therapy or in combination with existing SOC treatments. About ZW220 ZW220 is an ADC that targets NaPi2b-expressing NSCLC and ovarian cancers, and is built, like ZW191, using our proprietary TOPO1i- payload technology. The NaPi2b-targeting monospecific antibody incorporated in ZW220 was developed in-house and selected based on a favorable binding profile and enhanced internalization properties to enable targeting of both high- and low- NaPi2b-expressing tumors. The antibody in ZW220 is Fc-silenced, containing mutations in its Fc region which abolish FcγR (Fc gamma receptor) binding in normal cells, with the goal of minimizing potential off-target toxicities. A DAR of four and a moderate stability antibody-linker were selected to balance tolerability and efficacy. NaPi2b is reported to be expressed in approximately 96% of ovarian serous adenocarcinoma and 87% of non-small cell lung cancer (NSCLC) adenocarcinoma1, and ZW220 has demonstrated anti-tumor activity in patient-derived xenograft models and robust growth inhibition in 3D spheroid models of these cancers. The bystander effect of the TOPO1i payload may help address NaPi2b heterogeneity across these cancers. ZW220 is well-tolerated in non-human primates (NHP) and rats, reaching maximum tolerated doses (MTDs) of ≥ 90 mg/kg and ≥ 200 mg/kg, respectively. We expect to submit an investigational new drug application (IND) and non-U.S. applications for ZW220 in the first half of 2025. About ZW251 ZW251, a potential first-in-class ADC molecule designed for the treatment of glypican 3 (GPC3)-expressing HCC, incorporates the same Zymeworks proprietary bystander-active TOPO1i payload utilized in ZW191 (anti-FRα) and ZW220 (anti-NaPi2b). A DAR of four and a moderate stability antibody-linker were selected to balance tolerability and efficacy. In preclinical studies, anti-tumor activity for ZW251 was observed in multiple patient-derived xenograft models of HCC reflecting a range of GPC3 over-expression. GPC3, a glycosylphosphatidylinositol (GPI)-anchored cell surface oncofetal antigen, is over-expressed in most HCC patients (>75%2), and displays minimal normal adult tissue expression, making it an appealing ADC target. In NHP studies, ZW251 displayed significant tolerability at doses up to 120 mg/kg, suggesting the possibility of high initial dosing in human trials. We are encouraged by published research demonstrating the potential of GPC3-targeting antibody in HCC patients as evidenced by tumor localization of iodine radiolabeled condrituzumab, a prior clinical-stage anti-GPC3 mAb, and believe that ADC-based targeting of GPC3 could enable a novel and effective approach to treatment of HCC. We expect to submit an IND and non-U.S. applications for ZW251 in the second half of 2025. About Zymeworks Inc. Zymeworks is a global clinical-stage biotechnology company committed to the discovery, development, and commercialization of novel, multifunctional biotherapeutics. Zymeworks’ mission is to make a meaningful difference in the lives of people impacted by difficult-to-treat cancers and other diseases. The Company’s complementary therapeutic platforms and fully integrated drug development engine provide the flexibility and compatibility to precisely engineer and develop highly differentiated antibody-based therapeutic candidates. Zymeworks engineered and developed zanidatamab, a HER2-targeted bispecific antibody using the Company’s proprietary Azymetric™ technology. Zymeworks has entered into separate agreements with BeiGene, Ltd. (BeiGene) and Jazz Pharmaceuticals Ireland Limited (Jazz), granting each exclusive rights to develop and commercialize zanidatamab in different territories. Zanidatamab is currently being evaluated in multiple global clinical trials as a potential best-in-class treatment for patients with HER2-expressing cancers. A Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval for zanidatamab as a treatment for previously-treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC) has been accepted and granted Priority Review. A BLA has also been accepted for review by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China. If approved, zanidatamab would be the first HER2-targeted treatment specifically approved for BTC in the U.S. and China. Zymeworks is rapidly advancing a robust pipeline of wholly-owned product candidates, leveraging its expertise in both antibody-drug conjugates and multispecific antibody therapeutics targeting novel pathways in areas of significant unmet medical need. Phase 1 studies for ZW171 and ZW191 are now actively recruiting. In addition to Zymeworks’ pipeline, its therapeutic platforms have been further leveraged through strategic partnerships with global biopharmaceutical companies. For information about Zymeworks, visit www.zymeworks.com and follow @ZymeworksInc on X. Forward Looking Statements This press release includes “forward-looking statements” or information within the meaning of the applicable securities legislation, including Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements in this press release include, but are not limited to, statements that relate to anticipated preclinical data presentations; the timing and status of ongoing and future studies and the release of data; expectations regarding future regulatory filings and approvals and the timing thereof; the timing of and results of interactions with regulators; Zymeworks’ preclinical pipeline; the anticipated benefits of the collaboration agreements with Jazz and BeiGene; the commercial potential of technology platforms and product candidates; Zymeworks’ clinical development of its product candidates and enrollment in its clinical trials; the potential addressable market of zanidatamab; potential safety profile and therapeutic effects of zanidatamab and Zymeworks’ other product candidates; the ability to advance product candidates into later stages of development; and other information that is not historical information. When used herein, words such as “plan”, “believe”, “expect”, “may”, “anticipate”, “potential”, “will”, “continues”, and similar expressions are intended to identify forward-looking statements. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon Zymeworks’ current expectations and various assumptions. Zymeworks believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. Zymeworks may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various factors, including, without limitation: clinical trials and any future clinical trials may not demonstrate safety and efficacy of any of Zymeworks’ or its collaborators’ product candidates; any of Zymeworks’ or its partners’ product candidates may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; regulatory agencies may impose additional requirements or delay the initiation of clinical trials; the impact of pandemics and other health crises on Zymeworks’ business, research and clinical development plans and timelines and results of operations, including impact on its clinical trial sites, collaborators, and contractors who act for or on Zymeworks’ behalf; the impact of new or changing laws and regulations; market conditions; inability to maintain or enter into new partnerships or strategic collaborations; and the factors described under “Risk Factors” in Zymeworks’ quarterly and annual reports filed with the Securities and Exchange Commission (copies of which may be obtained at www.sec.gov and www.sedar.com). Although Zymeworks believes that such forward-looking statements are reasonable, there can be no assurance they will prove to be correct. Investors should not place undue reliance on forward-looking statements. The above assumptions, risks and uncertainties are not exhaustive. Forward-looking statements are made as of the date hereof and, except as may be required by law, Zymeworks undertakes no obligation to update, republish, or revise any forward-looking statements to reflect new information, future events or circumstances, or to reflect the occurrences of unanticipated events. Contacts: Investor Inquiries: Shrinal InamdarDirector, Investor Relations(604) 678-1388 ir@zymeworks.com   Media Inquiries: Diana PapoveSenior Director, Corporate Communications(604) 678-1388 media@zymeworks.com 1Lin et al. 2015. Clin Cancer Res 2Wang HL et al., Arch Pathol Lab Med 2008

A Groundbreaking Assay Using Short-Read Sequencers to Comprehensively Detect Large Structural Variants SCOTTS VALLEY, Calif., Sept. 4, 2024 /PRNewswire/ -- Dovetail Genomics, a leading innovator in genomic solutions, today announces new findings on its VariLink™ assay that will be presented in a poster at the AGBT Precision Health Conference in Denver, CO. The VariLink assay, built on Dovetail's novel LinkPrep™ technology, enables ultra-high sensitivity, de novo detection of large structural variants alongside SNVs, indels and CNVs on a short-read sequencer. The presented study features the VariLink assay's sensitivity and precision in an ovarian tumor sample, highlighting its utility in clinically relevant sample types. Continue Reading "Detection of large structural variants has been a challenge using short-read platforms. We have solved this problem using VariLink, our single-day library preparation workflow. By generating high-quality, unbiased Hi-C libraries, we capture the full spectrum of genetic variants enabling oncology researchers to more fully understand the drivers of human cancer," said Mathew Easterday, Ph.D., J.D., CEO of Dovetail Genomics. "We are now excited to be putting the technology in the hands of research partners as part of a technology early access program". "Detection of large structural variants has been a challenge using short-read platforms. We have solved this problem..." Post this Using a clinical ovarian serous adenocarcinoma sample, the authors compared the performance of the VariLink assay for detecting a continuum of large and small structural variants compared to whole genome shotgun sequencing (WGS) and RNA-seq. Compared to WGS, the VariLink assay demonstrated enhanced sensitivity and precision for SV detection while maintaining a high concordance for capturing SNVs and indels. The VariLink data demonstrated increased sensitivity for breakpoint detection while reducing the number of false positives that plague short-read WGS data. Illustrating this capability, three translocations linked to known oncogenes known to drive oncogenesis were discovered with high confidence and confirmed by PCR and Sanger sequencing. Minimal to no evidence for each was observable in WGS and RNA-seq datasets. "In the past, we have seen interest in using Hi-C for detecting large structural variants, however, the assay complexity, multiday workflow, and sequence coverage gaps associated with traditional Hi-C have limited its broad adoption. Our LinkPrep technology on which the VariLink assay is built addresses these shortcomings," stated Ericca Stamper, Ph.D., Genomic Science Liaison at Dovetail Genomics and lead author on the poster. "I look forward to sharing more on this with researchers at the AGBT Precision Health conference." The detailed findings will be presented in the poster titled " VariLink: a novel assay for comprehensive variant detection and genome characterization" (Poster Number : 506) on Thursday, September 5th, from 4:40pm-6:40pm. Dovetail Genomics is seeking additional projects that highlight the unique sensitivity and precision offered by the VariLink assay for inclusion in the early access program. Researchers interested in being considered for this program are encouraged to contact Dovetail Genomics at dovetailgenomics.com. About Dovetail Genomics Dovetail Genomics, a subsidiary of Cantata Bio and an Edenroc Sciences company, is a leading provider of genomics solutions focused on understanding the complex organization of the genome. Through Dovetail Genomics' proprietary proximity ligation technologies, the 3D architecture of the genome is captured alongside primary sequence information using standard next-generation sequencing (NGS) approaches. Researchers are using Dovetail Genomics' unique methods to solve complex problems including chromatin topology analysis, small and large structural variant detection, de novo chromosome assembly, haplotype phasing, and microbiome analysis in the fields of epigenetics, developmental biology, cancer research, evolutionary biology and more. For more information on Dovetail, its technology, and service offerings, visit . Follow Dovetail on X/Twitter: @DTGenomics. Media Contact Vikki Herrera Oak Street Communications for Dovetail Genomics [email protected] SOURCE Dovetail Genomics

Multiple Years for Diagnosis, Limited Treatment Options, Treatment Side Effects, and Cancer Recurrence Main Concerns of Respondents Survey Developed Through a Global Collaboration Among Patient Advocacy Groups and Medical Leaders to Uncover and Address the Urgent Needs of Patients BOSTON--(BUSINESS WIRE)-- Verastem Oncology, (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, today announced results of the first-ever LGSOC Patient Impact Survey that reveal the particular challenges with diagnosis, disease management and mental, physical, and emotional well-being experienced by people living with low-grade serous ovarian cancer (LGSOC)*.1 This multi-national, online survey was conducted by The Harris Poll on behalf of the LGSOC Patient Impact Advisory Committee – a global collaboration among patient advocacy groups, including STAAR Ovarian Cancer Foundation (STAAR), Cure Our Ovarian Cancer and the World Ovarian Cancer Coalition (Coalition) as well as leaders in the medical community – with the aim to better understand and address the needs of those living with this rare and difficult to treat disease. This press release features multimedia. View the full release here: The biggest challenges women with LGSOC face in managing their condition (Graphic: Business Wire) LGSOC is a rare, highly recurrent ovarian cancer associated with slow but persistent tumor growth and a high mortality rate and is known to be relatively resistant to chemotherapy.2,3,4 In 2014, LGSOC was classified as a separate disease compared to the more common high-grade serous ovarian cancer (HGSOC) by the World Health Organization, yet awareness and knowledge of the disease remains low.5 Eighty-five percent of people with LGSOC have their cancer come back after remission.4 Few treatment options are available for LGSOC and no treatments specifically for LGSOC have been approved to date.6 “Not only is LGSOC a rare disease, its classification as a distinct type of ovarian cancer was established within the last 10 years. With no medicines specifically approved by the U.S. Food and Drug Administration for LGSOC, along with limited research and published data about the patient experience and its impact, managing this disease is challenging for healthcare professionals and patients. This survey is an important collective effort to gather valuable insights and opinions to help better serve those living with LGSOC,” said Dr. David Gershenson, expert researcher in rare ovarian cancers and LGSOC Patient Impact Advisory Committee member. “As a physician dedicated to finding better ways to manage LGSOC, I witness how the long journey to diagnosis and the uncertainty of this disease takes a toll on my patients and their loved ones. These survey results underscore the urgency of educating on this unique form of ovarian cancer and provide important information to guide that effort.” Delayed Diagnoses and Low Awareness Results from the survey revealed the challenges people with LGSOC face in obtaining a timely and accurate diagnosis. Among the 81% of participants surveyed who experienced disease symptoms, it took an average of nearly three years to get an accurate diagnosis and most reported their path to diagnosis as difficult (73%) or frustrating (68%).1 Nearly seven-in-ten (68%) people surveyed who experienced symptoms, experienced a misdiagnosis and nearly two-thirds (66%) reported having their symptoms dismissed by a healthcare provider (HCP).1 Younger respondents (ages 18-49)** were more likely than their older peers (age 50+) to report that their symptoms were misdiagnosed (77% vs. 56%) and to feel that their symptoms were dismissed by their HCP (52% strongly agree vs. 32%).1 LGSOC often affects younger women compared to the more common high-grade serous ovarian cancer (HGSOC), with a median age at diagnosis between 45-55.3 Nearly all those surveyed (99%) had no awareness of LGSOC prior to diagnosis, and 60% did not feel that their HCP was “very knowledgeable” about this rare cancer.1 When it comes to educating about LGSOC, 87% want others to know that symptoms can be easily misdiagnosed as another disease, and 82% feel they should know that it’s important to listen to your body and seek medical attention as soon as possible.1 Challenges with Disease Management, Uncertainty and Anxiety In the survey, 60% of respondents reported that one of the biggest challenges in managing their disease is that their treatment options are limited, with most (90%) feeling like they are getting the “treatment leftovers” instead of regimens studied in LGSOC.1 More than half (52%) reported experiencing side effects from treatment as a challenge and 25% reported having to pause or stop treatment because they couldn’t tolerate the side effects.1 The data also revealed the impact on respondents of navigating a recurrent disease with limited treatment options. Nearly seven-in-ten (68%) respondents reported that their biggest challenge is living with uncertainty that their cancer will return, more than two-in-five (41%) feel like their lives revolve around their cancer, and nearly half (48%) reported that their biggest challenge is experiencing anxiety or worry.1 “Since my LGSOC diagnosis, it has been so important to have my community around me. Although LGSOC is classified as a rare cancer, we have seen this community come together to provide support for each other, raise awareness of symptoms, and improve outcomes,” said Nicole Andrews, Board of Directors Chair, STAAR Ovarian Cancer Foundation and a member of the LGSOC Patient Impact Advisory Committee. “What this survey reveals is critical, because there are too many women like me who have had to navigate this experience on their own, with very few resources and low awareness of the disease. Having this measurable, actionable data that sheds new light on the challenges we face because of LGSOC is an important step toward education and awareness that can hopefully improve care.” About the LGSOC Patient Impact Survey The LGSOC Patient Impact Advisory Committee, supported by Verastem Oncology, worked with The Harris Poll to conduct a survey on behalf of leaders in the medical and advocacy communities. They surveyed 186 women ages 18+ who have been diagnosed with LGSOC across 10+ countries. The survey was conducted July 31st - August 29th, 2023. Raw data were not weighted and are therefore only representative of the individuals who completed the survey. Additional data from the survey were submitted to an upcoming medical congress. The sampling precision of Harris online polls is measured by using a Bayesian credible interval. For this study, the sample data is accurate to within ± 7.1 percentage points using a 95% confidence level. This credible interval will be wider among subsets of the surveyed population of interest. All sample surveys and polls, whether or not they use probability sampling, are subject to other multiple sources of error which are most often not possible to quantify or estimate, including, but not limited to coverage error, error associated with nonresponse, error associated with question wording and response options, and post-survey weighting and adjustments. To view survey details, including methodology, audience demographics, survey data and more, click here. Visit for more information. *For the purposes of this survey, the term LGSOC refers to people diagnosed with low-grade serous carcinoma of the ovary or peritoneum (the thin layer of tissue lining the abdomen). **Caution: small sample size (n<100). Results should be interpreted as directional. About Low-Grade Serous Ovarian Cancer (LGSOC) Low-grade serous ovarian cancer (LGSOC) is a highly recurrent, chemotherapy-resistant cancer, associated with slow tumor growth and high mortality rate.3 Approximately 6,000 women in the U.S. and 80,000 worldwide are living with this disease.7 Mutations in the KRAS gene are present in 30% of cases of LGSOC.8,9 LGSOC is most often diagnosed in women between the ages of 45-55 years and has a median survival of approximately ten years.7 The majority of patients experience severe pain and complications as the disease progresses. Chemotherapy is one of the preferred treatments for this disease, and there are limited treatment options currently available.7 About Verastem Oncology Verastem Oncology (Nasdaq: VSTM) is a development-stage biopharmaceutical company committed to the development and commercialization of new medicines to improve the lives of patients diagnosed with cancer. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition and focal adhesion kinase (FAK) inhibition. For more information, please visit . 1 LGSOC Patient Impact Survey Research Findings. Harris Poll. 2023. 2 WHO Classification of Tumours, 5 Edition, Volume 4: Female Genital Tumours. 3 Grisham, R. Low Grade Serous Carcinoma of the Ovary. Oncology. 2016. 30(7):650-652. . Accessed March 2023. 4 Corrado G, Salutari V, Palluzzi E, Distefano MG, Scambia G, Ferrandina G. Optimizing Treatment in Recurrent Epithelial Ovarian Cancer. Expert Rev Anticancer Ther. 2017; 17:1147-1158. doi: 10.1080/14737140.2017.1398088. 5 Kurman RJ, Carcangiu ML, Herrington CS, Young RH, editors. WHO Classification of Tumors of Female Reproductive Organs, 4th ed; 2014. 6 Ovarian Cancer Guidelines. National Comprehensive Cancer Network. . Accessed October 2023. 7 Slomovitz B, Gourley C, Carey S. M, Malpica A, Shih I, Huntsman D, et al. Low-grade serous ovarian cancer: State of the science. Gynecol Oncol. 2020;156(3):715-725. . 8 Timar J, Kashofer K. Molecular epidemiology and diagnostics of KRAS mutations in human cancer. Cancer and Metastasis Reviews. 2020;39:1029–1038. . 9 Baines T. A, Xu D, Der C. J. Inhibition of RAS for cancer treatment: the search continues. Future Medicinal Chemistry. 2011;3(14):1787–1808. . View source version on businesswire.com: Contacts Source: Verastem Oncology Smart Multimedia Gallery Photo The biggest challenges women with LGSOC face in managing their condition (Graphic: Business Wire) Document LGSOC Patient Impact Survey Infographic (Graphic: Business Wire) Document LGSOC Patient Impact Advisory Committee (Graphic: Business Wire) Document LGSOC Patient Impact Survey Research Findings (Graphic: Business Wire) Document LGSOC Patient Impact Survey Patient Perspectives (Graphic: Business Wire) Video LGSOC Patient Impact Survey Patient Perspectives Video Logo View this news release and multimedia online at: