Platinum-Resistant Epithelial Ovarian Carcinoma

Designation is based on preliminary safety and efficacy data from an ongoing Phase 1/2 trial in patients with platinum-resistant ovarian epithelial cancer, fallopian tube, or primary peritoneal cancer1Fast Track designation can facilitate the development and expedite the regulatory review of BNT325/DB-1305 Ovarian cancer is the fourth most common gynecological tumor type2 with over 300,000 cases diagnosed globally each year3; over 90% of ovarian tumors arise from epithelial cells, including the epithelial tissue of the ovary, the lining of a fallopian tube or the peritoneum4 MAINZ, Germany and SHANGHAI, China, January 31, 2024 – BioNTech SE (Nasdaq: BNTX, “BioNTech”) and Duality Biologics (Suzhou) Co., Ltd. (“DualityBio”) today announced that the U.S. Food and Drug Administration (“FDA”) granted Fast Track designation for BNT325/DB-1305 for the treatment of patients with platinum-resistant ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer who have received one to three prior systemic treatment regimens. BNT325/DB-1305 is a next-generation antibody-drug conjugate (“ADC”) candidate targeting the trophoblast cell-surface antigen 2 (“TROP2”), a protein which is overexpressed on a range of tumor types. The candidate is currently being evaluated in an ongoing Phase 1/2 study (NCT05438329) in patients with TROP2-expressing advanced solid tumors. Ovarian cancer is the fourth most common gynecological tumor type, with over 300,000 cases diagnosed globally each year.3 Over 90% of ovarian tumors arise from epithelial cells including the epithelial tissue of the ovary, the lining of a fallopian tube or the peritoneum.4 Ovarian epithelial cancer is often diagnosed at advanced disease stages, leading to a poor prognosis for patients. This makes it one of the most frequent causes of cancer death in women.3 The 5-year survival rate ranges from 26% to 42%, depending on the initial disease stage.3 “The FDA’s decision is an important recognition of the potential of our TROP2-targeting ADC candidate. Platinum-based chemotherapy is the backbone of treatment for ovarian epithelial cancer and related subtypes that form in the epithelial tissue. Patients with platinum resistance who relapse within under six months have a poor prognosis, and effective and well-tolerated treatment options remain a substantial unmet medical need,” said Prof. Özlem Türeci, M.D., Chief Medical Officer and Co-Founder at BioNTech. “Recent studies have indicated the role of TROP2 in aggressive tumor growth and progression in patients with chemotherapy-resistant ovarian tumors. We are committed to further advancing BNT325/DB-1305 and believe that a TROP2-targeted treatment approach has the potential to overcome current limitations in the treatment of advanced ovarian cancers.” “BNT325/DB-1305 is the second investigational asset in our strategic collaboration which has received FDA Fast Track designation highlighting the potential of the candidate to fill an unmet medical need,” said Vivian Gu, M.D., Chief Medical Officer at DualityBio. “Data from the Phase 1/2 clinical trial with BNT325/DB-1305 have demonstrated encouraging anti-tumor signals in heavily pretreated patients with TROP2-expressing solid tumors who had failed standard therapy with an objective response rate of 30.4% and a disease control rate of 87.0%.5 We look forward to progressing the further development of BNT325/DB-1305 within the fast track framework, and hope to be one step closer to potentially improving outcomes for a range of patients.” Fast Track is a process designed to facilitate the development and expedite the review, of new drugs and vaccines that are intended to treat or prevent serious conditions that have the potential to address an unmet medical need. The designation is based on preliminary data from an ongoing Phase 1/2 study with BNT325/DB-1305 in patients with platinum-resistant ovarian epithelial cancer, fallopian tube, or primary peritoneal cancer patients.1 With the Fast Track designation, the development of BNT325/DB-1305 can benefit from more frequent engagement with the FDA, to support the development and expedite the review of BNT325/DB-1305. About BNT325/DB-1305BNT325/DB-1305 is a third-generation topoisomerase-1 inhibitor-based ADC targeting TROP2 which was built from DualityBio’s proprietary Duality Immune Toxin Antibody Conjugates (“DITAC”) platform. TROP2 is a cell surface protein which is expressed in many normal tissues but is overexpressed in a variety of tumors. TROP2 plays an important role in tumor cell proliferation, apoptosis, and invasion, thereby impacting the prognosis and treatment of cancer patients.6,7 BNT325/DB-1305 has exhibited antitumor activity in tumor models as well as in several advanced solid tumor indications, including non-small cell lung cancer (”NSCLC“) and ovarian epithelial cancer.8 Preclinical data and preliminary clinical data for BNT325/DB-1305 indicate its potential to target TROP2 receptors on solid tumors irrespective of expression level with a manageable safety profile and a potentially expanded therapeutic window.5 About BioNTechBiopharmaceutical New Technologies (BioNTech) is a next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. The Company exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor (“CAR”) T cells, several protein-based therapeutics, including bispecific immune checkpoint modulators, targeted cancer antibodies and antibody-drug conjugate (“ADC”) therapeutics, as well as small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global pharmaceutical collaborators, including Duality Biologics, Fosun Pharma, Genentech, a member of the Roche Group, Genevant, Genmab, OncoC4, Regeneron and Pfizer. For more information, please visit www.BioNTech.com. About DualityBioDualityBio is a clinical-stage company focusing on the discovery and development of the next generation ADC therapeutics for patients with cancer and autoimmune diseases. DualityBio has successfully established a number of next generation Antibody-Drug Conjugate (ADC) technology platforms with global intellectual property rights. Building upon deep understanding of disease biology and translational capability, DualityBio has advanced 4 assets into global clinical studies, and developed more than 10 innovative product candidates which are currently in preclinical stage. Additionally, DualityBio is continuing evolving its novel protein engineering and ADC technology platforms for the next wave of “super ADC” molecules including diverse payload classes, bispecific ADCs and dual payload ADCs. For more information, please visit www.dualitybiologics.com. BioNTech Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, but not be limited to, statements concerning: the collaboration between BioNTech and DualityBio to jointly clinical develop antibody-drug conjugates (ADCs), including BNT325/DB-1305; the registrational potential of any trial we may initiate for BNT325/DB-1305; the nature and characterization of and timing for release of clinical data across BioNTech’s platforms, which is subject to peer review, regulatory review and market interpretation; the planned next steps in BioNTech’s pipeline programs, including, but not limited to, statements regarding timing or plans for initiation or enrollment of clinical trials, or submission for and receipt of product approvals with respect to BioNTech’s product candidates; the ability of BioNTech’s mRNA technology to demonstrate clinical efficacy outside of BioNTech’s infectious disease platform; the potential safety and efficacy of BioNTech’s other product candidates; and BioNTech’s anticipated market opportunity and size for its product candidates. Any forward-looking statements in this press release are based on BioNTech’s current expectations and beliefs of future events 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 discussions with regulatory agencies regarding timing and requirements for additional clinical trials; and the ability to produce comparable clinical results in future clinical trials. In some cases, forward-looking statements can be identified by terminology such as “will,” “may,” “should,” “expects,” “intends,” “plans,” “aims,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “continue,” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond BioNTech’s control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to: the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as risks associated with preclinical and clinical data, including the data discussed in this release, and including the possibility of unfavorable new preclinical, clinical or safety data and further analyses of existing preclinical, clinical or safety data; the nature of the clinical data, which is subject to ongoing peer review, regulatory review and market interpretation; the timing of and BioNTech’s ability to obtain and maintain regulatory approval for BioNTech’s product candidates; BioNTech’s and its counterparties’ ability to manage and source necessary energy resources; BioNTech’s ability to identify research opportunities and discover and develop investigational medicines; the ability and willingness of BioNTech’s third-party collaborators to continue research and development activities relating to BioNTech’s development candidates and investigational medicines; unforeseen safety issues and potential claims that are alleged to arise from the use of products and product candidates developed or manufactured by BioNTech; BioNTech’s and its collaborators’ ability to commercialize and market, if approved, its product candidates; BioNTech’s ability to manage its development and expansion; regulatory developments in the United States and other countries; BioNTech’s ability to effectively scale BioNTech’s production capabilities and manufacture BioNTech’s products and BioNTech’s product candidates; risks relating to the global financial system and markets; and other factors not known to BioNTech at this time. You should review the risks and uncertainties described under the heading “Risk Factors” in BioNTech’s Report on Form 6-K for the period ended September 30, 2023, and in subsequent filings made by BioNTech with the U.S. Securities and Exchange Commission (“SEC”), which are available on the SEC’s website at www.sec.gov. Except as required by law, BioNTech disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on BioNTech’s current expectations and speak only as of the date hereof. CONTACTS BioNTechInvestor Relations Victoria Meissner, M.D. +1 617 528 8293 Investors@biontech.de Media Relations Jasmina Alatovic +49 (0)6131 9084 1513 Media@biontech.de DualityBio Business Development bd@dualitybiologics.com 1 Data on file. Based on October 30, 2023, data cut-off from the Phase 1/2 trial.2 Cabasag CT, Fagan PJ, et al. Int J Cancer. 2022 Nov 1;151(9):1535-1541.3 Havasi A et al. Medicina (Kaunas). 2023 Mar; 59(3): 544.4 Sankaranarayanan R., Ferlay J. Best Pract Res Clin Obstet Gynaecol. 2006 Apr;20(2):207-25.5 Marathe O. et al. Annals of Oncology (2023) 34 (suppl_2): S458-S497. 10.1016/annonc/annonc13246 Wen Y, Ouyang D et al. Ann Transl Med. 2022 Dec; 10(24): 1403.7 Wu B, Yu C et al. Exp Ther Med. 2017 Sep;14(3):1947-1952.8 Data on file: https://investors.biontech.de/static-files/bf304f1c-3c61-47bf-b3b3-2efb5373a3b9

Pictured: Cancer cell surrounded by cytokines/iStock, Marcin Klapczynski Alkermes on Wednesday announced that it has completed the spinoff of its oncology business to become a pure-play neuroscience company. Mural Oncology will begin trading on the Nasdaq starting Thursday, with Alkermes shareholders receiving a share of Mural for every 10 shares of Alkermes. Mural is launching with $275 million, which is expected to fund it through the fourth quarter of 2025, and an interleukin-2 cytokine as its most advanced asset. Nemvaleukin alfa is being studied as a monotherapy for advanced mucosal or cutaneous melanoma in Phase II and is in a Phase III study in combination with Keytruda for platinum-resistant epithelial ovarian cancer. The therapeutic is designed to avoid the hallmark toxicities of IL-2 immunotherapies. The studies are potentially registrational with readouts expected in early 2025. Additional assets include therapies targeting IL-18 and IL-12. Mural will nominate a development candidate for each program in 2024. The new company’s CEO Caroline Loew said their reimagination of pro-inflammatory cytokine-based therapeutics could “address the key limitations with current cancer immunotherapies.” Loew takes the helm with significant biopharma experience. She came to Mural from Glympse Bio, which was scooped up by Sunbird Bio in August 2023 for its protein-based technologies for neurological disorders and early-stage cancer. Previously, Loew was in leadership roles at Bristol Myers Squibb and Merck. With the spinoff of its oncology business, Alkermes is now expecting better results for 2023, with a reduction of operating expenses thanks to no longer footing the bill for R&D. Net income is now projected in the range of $250 million to $280 million, up $25 million from previous forecasts. The company’s sales are driven by its lead products which include Vivitrol for alcohol and opioid dependence as well as two schizophrenia drugs. The motivation to split off businesses, streamline operations, decrease operating expenses and increase profits has been a trend in the industry. Sanofi, Novartis, Johnson & Johnson, GSK and more have spun off their generics or consumer health businesses in recent years as part of their pure-play growth strategies. Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.

COM701 + nivolumab + BMS-986207 (anti-TIGIT) resulted in clinically meaningful durable partial responses > 16 months in platinum resistant ovarian cancer patients COM701 dual and triple combinations mediated clinical benefit in platinum resistant ovarian cancer patients, independent of baseline inflammatory status and was associated with an increase in T cell infiltration to the tumor Metastatic breast cancer adds to previous indications in which COM701 combinations show clinical benefit in tumors typically not responding to immunotherapy PVRL2, the PVRIG ligand, identified as potential predictive biomarker for certain indications Data presented at the SITC conference held on November 1-5, 2023 will be discussed during the Company's Q3 results conference call on Tuesday, November 7, 2023 at 8:30 AM ET HOLON, Israel, Nov. 6, 2023 /PRNewswire/ -- Compugen Ltd. (Nasdaq: CGEN) (TASE:CGEN) a clinical-stage cancer immunotherapy company and a pioneer in computational target discovery, today announced data presented at the Annual Meeting of the Society for Immunotherapy of Cancer (SITC), held on November 1-5, 2023. The results reinforce previous data suggesting COM701 mediated anti-tumor activity in patients typically not responding to immunotherapy. For the first time, initial data showing the association between baseline PVRL2 levels and clinical benefit was presented, suggesting the potential of PVRL2 as a predictive biomarker for clinical benefit in certain indications helping to inform future direction of studies with a biomarker driven strategy. "We were delighted to present at SITC clinical data which reinforces data previously presented, suggesting that COM701 mediated anti-tumor activity in patients typically not responding to immunotherapy", said Anat Cohen-Dayag, Ph.D., President, and CEO of Compugen. "The clinical benefit shown in patients with platinum resistant ovarian cancer was associated with infiltration of T cells into the tumor microenvironment and independent of baseline inflammatory status, suggesting a COM701 mediated mechanism of action. In addition, we presented data in metastatic breast cancer, another indication in which patients who typically do not respond to immunotherapy, derived clinical benefit from COM701 combinations." Dr. Cohen-Dayag added, "We are also excited with the progress we have made on the predictive biomarker front, consistent with our deep understanding of the biology of PVRIG. At SITC, we presented for the first time initial data suggesting an association between baseline levels of the ligand for PVRIG, PVRL2, and clinical benefit, suggesting PVRL2 may be a predictive biomarker to help enrich for patients who may derive clinical benefit from our COM701 combinations. We are continuing to assess this association in our ongoing proof-of-concept study in platinum resistant ovarian cancer in which biopsies are mandatory. Acknowledging the competitive evolving platinum resistant ovarian cancer treatment landscape, we believe a biomarker that would help to enrich for patients who could derive clinical benefit, and together with durable responses and safety profile of our triplet combination, could support us in building a unique development path of our triplet regimen in these patients." Stephanie Gaillard, M.D., Ph.D. Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, and first author of the study added, "Durable partial responses lasting more than 16 months is clinically meaningful in patients with high grade epithelial platinum resistant ovarian cancer. While the numbers are small, typical median duration of response is 3-4 months with standard chemotherapy and 6.9 months reported in patients treated with the recently approved antibody drug conjugate. What is also notable is the favorable safety profile of this triple blockade of PVRIG, TIGIT and PD-1. I look forward to the results of the ongoing proof-of-concept study evaluating the combination of COM701, COM902 and pembrolizumab in platinum resistant ovarian cancer patients." Ecaterina Dumbrava, M.D., The University of Texas MD, Anderson Cancer Center, Houston, Texas, and first author of the study continued, "Following treatment with COM701 in combination with nivolumab, it is encouraging to see a complete response of greater than 21 months and a partial response of 10 months in patients with metastatic breast cancer, which is notoriously difficult to treat. Both patients had low PD-L1 expression and low tumor mutation burden at baseline. The patient who responded for 21 months and remains on treatment at the time of data cut off is HER 2 negative, a tumor which is considered as immune cold. The patient who responded for 10 months had a triple negative breast cancer, which is the fastest growing and most aggressive kind of breast cancer. It is also notable that the combination has favorable safety and tolerability profile. These data warrant further investigation of this combination with the addition of the anti-TIGIT, COM902, in tumors not typically responding to immunotherapy to address a significant unmet medical need." Poster presentation details: The posters are available on the publication section of Compugen's website. Title: Immune modulation and baseline biomarker correlation with clinical benefit following treatment with COM701 + nivolumab +/- BMS-986207 in patients with platinum resistant ovarian cancer First Author: Gady Cojocaru Title: The combination of COM701 + nivolumab demonstrates preliminary antitumor activity in patients with metastatic breast cancer First Author: Ecaterina Dumbrava Title: Durable responses with triple blockade of the DNAM-1 axis with COM701 + BMS-986207 + nivolumab in patients with platinum resistant ovarian cancer First Author: Stephanie Gaillard The data will be discussed during the Compugen's Q3 conference call tomorrow November 7, 2023 at 8:30AM ET. To access the live conference call by telephone, please dial 1-866-744-5399 from the U.S., or +972-3-918-0644 internationally. The call will be available via live webcast through Compugen's website, located at the following link. Following the live webcast, a replay will be available on the Company's website. About Compugen Compugen is a clinical-stage therapeutic discovery and development company utilizing its broadly applicable predictive computational discovery capabilities to identify new drug targets and biological pathways for developing cancer immunotherapies. Compugen has developed two proprietary product candidates: COM701, a potential first-in-class anti-PVRIG antibody and COM902, a potential best-in-class antibody targeting TIGIT for the treatment of solid tumors. Compugen also has a clinical stage partnered program, rilvegostomig (previously AZD2936), a PD-1/TIGIT bi-specific derived from COM902, in Phase 3 development by AstraZeneca through a license agreement for the development of bi-specific and multi-specific antibodies. In addition, the Company's therapeutic pipeline of early-stage immuno-oncology programs consists of programs aiming to address various mechanisms of immune resistance. The most advanced program, COM503 is in IND enabling studies. COM503 is a potential first-in-class, high affinity antibody which blocks the interaction between IL-18 binding protein and IL-18, thereby freeing natural IL-18 to inhibit cancer growth in the tumor microenvironment. Compugen is headquartered in Israel, with offices in San Francisco, CA. Compugen's shares are listed on Nasdaq and the Tel Aviv Stock Exchange under the ticker symbol CGEN. Forward-Looking Statement This press release contains "forward-looking statements" within the meaning of the Securities Act of 1933 and the Securities Exchange Act of 1934, as amended, and the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements are based on the current beliefs, expectations, and assumptions of Compugen. Forward-looking statements can be identified using terminology such as "will," "may," "expects," "anticipates," "believes," "potential," "plan," "goal," "estimate," "likely," "should," "confident," and "intends," and similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements include, but are not limited to, statements regarding the possibility that COM701 may mediate anti-tumor activity in patients typically not responding to immunotherapy, statements regarding the association between baseline PVRL2 levels and clinical benefit and the potential of PVRL2 as a predictive biomarker for clinical benefit in certain indications, statements regarding future direction of studies with a biomarker driven strategy, statements regarding the development of Compugen's triplet regimen in certain patients and statements regarding the favorable safety profile of this triple blockade of PVRIG, TIGIT and PD-1. These forward-looking statements involve known and unknown risks and uncertainties that may cause the actual results, performance, or achievements of Compugen to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Among these risks: the clinical trials of any product candidates that Compugen, or any current or future collaborators, may develop may fail to satisfactorily demonstrate safety and efficacy to the FDA, and Compugen, or any collaborators, may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of these product candidates; Compugen's business model is substantially dependent on entering into collaboration agreements with third parties and Compugen may not be successful in generating adequate revenues or commercializing aspects of its business model. Compugen's approach to the discovery of therapeutic products is based on its proprietary computational target discovery infrastructure, which is unproven clinically; general market, political and economic conditions in the countries in which Compugen operates, including Israel; the effect of the evolving nature of the recent war in Gaza; and Compugen does not know whether it will be able to discover and develop additional potential product candidates or products of commercial value. These risks and other risks are more fully discussed in the "Risk Factors" section of Compugen's most recent Annual Report on Form 20-F as filed with the Securities and Exchange Commission (SEC) as well as other documents that may be subsequently filed by Compugen from time to time with the SEC. In addition, any forward-looking statements represent Compugen's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. Compugen does not assume any obligation to update any forward-looking statements unless required by law. Company contact: Yvonne Naughton, Ph.D. Head of Investor Relations and Corporate Communications Email: [email protected] Tel: +1 (628) 241-0071 SOURCE Compugen Ltd.