Vall D’Hebron University Hospital

Mª Eugenia Zarabozo, co-founder of aptaTargets, Dr Marc Ribó, interventional neurologist at Vall d'Hebron, Dr Macarena Hernández, CSO of aptaTargets, and David Segarra, CEO and co-founder of aptaTargets, at ISC. ApTOLL is the first TLR4 antagonist neuroprotectant to achieve positive efficacy endpoints in acute ischemic stroke trials, decreasing significantly mortality and long-term functional disability. The Phase 1b/2a clinical trial led by doctor Marc Ribó from Vall d’Hebron University Hospital in Barcelona, Spain, achieved all primary safety outcomes and multiple secondary efficacy outcomes. The data was presented during the opening main plenary session at the International Stroke Conference held this week in Dallas, USA. Dallas (USA) / Madrid (Spain), 9 February 2023 – The drug ApTOLL, developed by the biopharmaceutical company aptaTargets, yielded groundbreaking safety and efficacy results in a Phase 1b/2a clinical trial in patients with acute ischemic stroke in combination with endovascular therapy (EVT). The final data was disclosed yesterday at the opening main plenary session of the International Stroke Conference (ISC) in Dallas, United States, by Dr Marc Ribó, an interventional neurologist at the Vall d’Hebron University Hospital in Barcelona, Spain, principal investigator of the Stroke Research group of the Vall d'Hebron Research Institute (VHIR) and Chief Medical Officer of aptaTargets, and Dr Macarena Hernández, Chief Scientific Officer of aptaTargets. The ISC is organised by the American Heart Association (AHA) and from 8 to 10 February, it brings together leading stroke experts from around the world. ApTOLL is a first-in-class neuroprotective drug that acts on the Toll-like receptor 4 (TLR4) with high specificity, blocking the inflammatory response that occurs after an ischemic stroke. The aptaTargets company developed it using innovative aptamer technology. Stroke can be caused by a significant decrease in blood flow to the brain or by bleeding caused by a ruptured brain vessel. The first instance is an ischemic stroke, the most frequent type, which represents 85% of all strokes. APRIL was designed as a multicentre, double-blind, randomised, placebo-controlled trial, in which 151 patients participated, these patients being men and women between 18 and 90 years of age, from 14 hospitals1 of reference in research and care for neurovascular diseases in Spain and France. The patients were randomly assigned to treatment with intravenous ApTOLL in two different doses or with a placebo. All patients in the study underwent mechanical thrombectomy, with or without a thrombolytic agent, according to the clinical guidelines. The primary aim was to assess ApTOLL’s safety based on four variables: death, symptomatic intracranial hemorrhage, malignant stroke, and recurrent stroke. The secondary, efficacy-related aims included the final infarct volume after 72 hours, the US National Institutes of Health (NIH) stroke score at 72 hours, and the score on the disability assessment scale at 90 days. ApTOLL met the primary safety endpoints, with the high-dose ApTOLL arm demonstrating a decrease in mortality from 18% to 5% compared to the placebo arm. Additionally, high-dose ApTOLL achieved statistical significance in both reduction of final infarct volume and improvement of the National Institute of Health Stroke Scale (NIHSS) measurements at 72 hours. Of note, 64.3% of patients receiving high dose ApTOLL scored 0-2 mRS at 90 days, which is considered functional independence, while only 46.3% of placebo patients scored 0-2 mRS. The results obtained in the APRIL trial, led by Vall d'Hebron, “demonstrate ApTOLL’s neuroprotective effect after a stroke occurs, protecting the brain tissue at risk”, explains Dr Marc Ribó. Furthermore, “ApTOLL did not show any interactions with the drugs that are administered for ischemic stroke, meaning that it could be administered to most patients”, emphasizes Dr Ribó. “We are extremely pleased with the excellent safety, tolerability and efficacy pro in the APRIL Phase 1b/2a trial. The massive patient benefit seen during the APRIL trial excites us for the future of acute ischemic stroke treatment. We plan to rapidly advance ApTOLL to a Phase 2b/3 clinical trial as well as to expand to other conditions”, comments David Segarra, CEO and co-founder of aptaTargets. aptaTargets is currently preparing two new Phase 2a trials: the RaceToll trial for use in ambulances where ApTOLL is administered to patients with suspected stroke, and the ApSTEMI trial to assess the effects of ApTOLL in acute myocardial infarction. ApTOLL has also shown promising preclinical results in haemorrhagic stroke and multiple sclerosis. 1 Vall d’Hebron University Hospital in Barcelona (Spain), La Princesa University Hospital in Madrid (Spain), Germans Trias i Pujol University Hospital in Badalona (Spain), A Coruña University Hospital Complex (Spain), Bellvitge University Hospital in L'Hospitalet de Llobregat (Spain), Ramón y Cajal University Hospital in Madrid (Spain), Virgen del Rocío University Hospital in Sevilla (Spain), La Fe University Hospital in Valencia (Spain), Doctor Josep Trueta University Hospital in Girona (Spain), University Clinical Hospital of Valladolid (Spain), 12 de Octubre University Hospital in Madrid (Spain), Toulouse University Hospital (France), Hospital University Hospital of Lille (France) and Hôpital Fondation Adolphe de Rothschild (France). Session details: April: A Double-blind, Placebo-controlled, Randomized, Phase Ib/IIa Clinical Study Of Aptoll For The Treatment Of Acute Ischemic Stroke Date: 8 February, 2023 Time: 12:15 pm – 12:30 pm Local time (UTC -7) ….......​ About aptaTargets aptaTargets is a clinical stage biopharmaceutical company specialised in developing innovative therapies based on aptamer technology. Its lead drug is ApTOLL, a molecule with an immunomodulatory and anti-inflammatory effect that is being researched for acute ischemic stroke (completed Phase 1b/2a), myocardial infarction (Phase 2a), intracerebral haemorrhage, and multiple sclerosis. Founded in 2014, aptaTargets is based in Madrid, Spain, and has successfully raised 17 million euros, including investments from venture capital (Inveready and CDTI through the Innvierte programme are the current investors of reference), in addition to different competitive programmes in the European Union and the Spanish Ministry of Science and Innovation. More information: aptatargets.com

VANCOUVER, Canada I December 09, 2022 I Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, today presented new clinical data for zanidatamab, the company’s investigational HER2-targeted bispecific antibody, in combination with palbociclib, a CDK4/6 inhibitor, and fulvestrant, a selective estrogen receptor degrader, in patients with heavily pretreated HER2-positive hormone-receptor positive metastatic breast cancer. The data were presented today in a spotlight poster session entitled Treatment of HER2-positive (HER2+) hormone-receptor positive (HR+) metastatic breast cancer (mBC) with the novel combination of zanidatamab, palbociclib, and fulvestrant during the San Antonio Breast Cancer Symposium (SABCS) taking place in San Antonio, Texas and virtually. Clinical Data Highlights The data presented at SABCS are from a clinical study of 45 patients with heavily pretreated HER2-positive HR-positive metastatic breast cancer who received zanidatamab in combination with palbociclib and fulvestrant. Patients had received prior regimens containing HER2-targeted agents including trastuzumab (100%), pertuzumab (80%), T-DM1 (98%), and other available options. In 36 efficacy-evaluable patients, treatment with zanidatamab in combination with palbociclib and fulvestrant resulted in a cORR of 33% and DCR of 92%, and the majority of patients experienced a decrease in tumor size. The mPFS was 9.6 months with seven patients still on study at the time of data cutoff (August 31, 2022). The regimen was generally well-tolerated, with the majority of treatment-related adverse events considered mild to moderate in severity (Grade 1 or 2). “Zanidatamab together with palbociclib and fulvestrant shows encouraging antitumor activity and a manageable tolerability profile in patients with HER2‑positive hormone-receptor positive breast cancer that has progressed after treatment with multiple HER2-targeted agents,” said Neil Josephson, M.D., Chief Medical Officer at Zymeworks. “We are encouraged by the durability of disease control and median progression-free survival in this heavily pretreated patient population indicating that this regimen has the potential to be developed as a chemotherapy-free treatment option for these patients.” The presentation is available to conference registrants on the SABCS conference website and is also available on the publications page of the Zymeworks website at https://www.zymeworks.com/publications . Title: Treatment of HER2-positive (HER2+) hormone-receptor positive (HR+) metastatic breast cancer (mBC) with the novel combination of zanidatamab, palbociclib, and fulvestrant Lead Author: Santiago Escrivá-de-Romani, MD, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital; Barcelona, Spain Program Number: PD18-10 About Zanidatamab Zanidatamab is a bispecific antibody, based on Zymeworks' Azymetric™ platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients. Zymeworks is developing zanidatamab in multiple Phase 1, Phase 2 and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2. Zymeworks has entered into separate agreements with each of BeiGene, Ltd. (BeiGene) and Jazz Pharmaceuticals Ireland Limited (Jazz), granting each of BeiGene and Jazz with exclusive rights to develop and commercialize zanidatamab throughout various counties around world. About Zymeworks Inc. Zymeworks is a clinical-stage biopharmaceutical company dedicated to the discovery, development and commercialization of next-generation multifunctional biotherapeutics. Zymeworks’ suite of therapeutic platforms and its fully integrated drug development engine enable precise engineering of highly differentiated product candidates. Zymeworks’ lead clinical candidate, zanidatamab, is a novel Azymetric™ HER2-targeted bispecific antibody currently being evaluated in multiple Phase 1, Phase 2, and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2. Zymeworks’ second clinical candidate, zanidatamab zovodotin (ZW49), is a novel bispecific HER2 ‑targeted antibody-drug conjugate currently in Phase 1 clinical development and combines the unique design and antibody framework of zanidatamab with Zymeworks’ proprietary ZymeLink™ linker and cytotoxin. Zymeworks is also advancing a deep preclinical pipeline in oncology (including immuno-oncology agents) and other therapeutic areas. In addition, its therapeutic platforms are being leveraged through strategic partnerships with global biopharmaceutical companies. For more information on our ongoing clinical trials visit www.zymeworksclinicaltrials.com . For additional information about Zymeworks, visit www.zymeworks.com and follow @ZymeworksInc on Twitter. SOURCE: Zymeworks

VANCOUVER, British Columbia--( BUSINESS WIRE )--Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, today presented new clinical data for zanidatamab, the company’s investigational HER2-targeted bispecific antibody, in combination with palbociclib, a CDK4/6 inhibitor, and fulvestrant, a selective estrogen receptor degrader, in patients with heavily pretreated HER2-positive hormone-receptor positive metastatic breast cancer. The data were presented today in a spotlight poster session entitled Treatment of HER2-positive (HER2+) hormone-receptor positive (HR+) metastatic breast cancer (mBC) with the novel combination of zanidatamab, palbociclib, and fulvestrant during the San Antonio Breast Cancer Symposium (SABCS) taking place in San Antonio, Texas and virtually. Clinical Data Highlights The data presented at SABCS are from a clinical study of 45 patients with heavily pretreated HER2-positive HR-positive metastatic breast cancer who received zanidatamab in combination with palbociclib and fulvestrant. Patients had received prior regimens containing HER2-targeted agents including trastuzumab (100%), pertuzumab (80%), T-DM1 (98%), and other available options. In 36 efficacy-evaluable patients, treatment with zanidatamab in combination with palbociclib and fulvestrant resulted in a cORR of 33% and DCR of 92%, and the majority of patients experienced a decrease in tumor size. The mPFS was 9.6 months with seven patients still on study at the time of data cutoff (August 31, 2022). The regimen was generally well-tolerated, with the majority of treatment-related adverse events considered mild to moderate in severity (Grade 1 or 2). “Zanidatamab together with palbociclib and fulvestrant shows encouraging antitumor activity and a manageable tolerability profile in patients with HER2‑positive hormone-receptor positive breast cancer that has progressed after treatment with multiple HER2-targeted agents,” said Neil Josephson, M.D., Chief Medical Officer at Zymeworks. “We are encouraged by the durability of disease control and median progression-free survival in this heavily pretreated patient population indicating that this regimen has the potential to be developed as a chemotherapy-free treatment option for these patients.” The presentation is available to conference registrants on the SABCS conference website and is also available on the publications page of the Zymeworks website at https://www.zymeworks.com/publications . Title: Treatment of HER2-positive (HER2+) hormone-receptor positive (HR+) metastatic breast cancer (mBC) with the novel combination of zanidatamab, palbociclib, and fulvestrant Lead Author: Santiago Escrivá-de-Romani, MD, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital; Barcelona, Spain Program Number: PD18-10 About Zanidatamab Zanidatamab is a bispecific antibody, based on Zymeworks' Azymetric™ platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients. Zymeworks is developing zanidatamab in multiple Phase 1, Phase 2 and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2. Zymeworks has entered into separate agreements with each of BeiGene, Ltd. (BeiGene) and Jazz Pharmaceuticals Ireland Limited (Jazz), granting each of BeiGene and Jazz with exclusive rights to develop and commercialize zanidatamab throughout various counties around world. About Zymeworks Inc. Zymeworks is a clinical-stage biopharmaceutical company dedicated to the discovery, development and commercialization of next-generation multifunctional biotherapeutics. Zymeworks’ suite of therapeutic platforms and its fully integrated drug development engine enable precise engineering of highly differentiated product candidates. Zymeworks’ lead clinical candidate, zanidatamab, is a novel Azymetric™ HER2-targeted bispecific antibody currently being evaluated in multiple Phase 1, Phase 2, and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2. Zymeworks’ second clinical candidate, zanidatamab zovodotin (ZW49), is a novel bispecific HER2 ‑targeted antibody-drug conjugate currently in Phase 1 clinical development and combines the unique design and antibody framework of zanidatamab with Zymeworks’ proprietary ZymeLink™ linker and cytotoxin. Zymeworks is also advancing a deep preclinical pipeline in oncology (including immuno-oncology agents) and other therapeutic areas. In addition, its therapeutic platforms are being leveraged through strategic partnerships with global biopharmaceutical companies. For more information on our ongoing clinical trials visit www.zymeworksclinicaltrials.com . For additional information about Zymeworks, visit www.zymeworks.com and follow @ZymeworksInc on Twitter. Cautionary Note Regarding 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 the potential therapeutic effects of zanidatamab and Zymeworks’ other product candidates; Zymeworks’ clinical development of its product candidates and enrollment in its clinical trials; anticipated clinical data presentations; expectations regarding future regulatory filings and the timing thereof, the commercial potential of technology platforms and product candidates; and other information that is not historical information. When used herein, words such as “plan”, “believe”, “expect”, “may”, “anticipate”, “potential”, 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: 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 the COVID-19 pandemic 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, may be more severe and more prolonged than currently anticipated; 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, including its Quarterly Report on Form 10-Q for its quarter ended September 30, 2022 (a copy 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.