PRMT5

Dose escalation ongoing in four clinical-stage precision oncology programs; TNG908 phase 1/2 clinical data expected in 2024 First patient dosed in phase 1/2 clinical trial of TNG348 in patients with BRCA1/2-mutant and other HRD+ cancers FDA Orphan Drug Designation granted for TNG462 for the treatment of soft tissue sarcomas Strong cash position of $337 million as of December 31, 2023, combined with $42 million in proceeds from ATM in January 2024; cash runway into late 2026 expected to fund all clinical programs through proof-of-concept BOSTON--(BUSINESS WIRE)-- Tango Therapeutics, Inc. (NASDAQ: TNGX), a clinical-stage biotechnology company committed to discovering and delivering the next generation of precision cancer medicines, reported its financial results for the fourth quarter and full year ended December 31, 2023, and provided business highlights. “In 2023, we made meaningful progress developing precision oncology treatments and now have four ongoing phase 1/2 clinical trials. These treatments have the potential to reach people with a wide range of cancers, including those with MTAP-deleted solid tumors, STK11 loss-of-function mutations, BRCA 1/2 mutations and other DNA damage repair defects. To support the advancement of our broad clinical portfolio, we expanded our management team, adding members with expertise in regulatory affairs and clinical development,” said Barbara Weber, M.D., President and Chief Executive Officer of Tango Therapeutics. “We are off to a strong start in 2024, marked by dosing the first patient in the phase 1/2 clinical trial for TNG348, receiving Orphan Drug Designation from the U.S. FDA for TNG462 and strengthening our cash position. We remain on track to provide TNG908 clinical data this year." Recent Business Highlights Pipeline Update TNG908 phase 1 dose escalation ongoing Dose escalation and patient enrollment is ongoing in the phase 1/2 clinical trial evaluating TNG908, an MTA-cooperative PRMT5 inhibitor, in patients with MTAP-deleted solid tumors, including glioblastoma (GBM). To date, the safety, tolerability and pharmacokinetics profiles are favorable. MTAP deletions occur in approximately 10%-15% of all human cancers, including 40% of GBM. TNG462, a potentially best-in-class MTA-cooperative PRMT5 inhibitor The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation (ODD) to TNG462 in December 2023 for the treatment of soft tissue sarcomas. ODD is granted to investigational therapies addressing rare medical diseases or conditions that affect fewer than 200,000 people in the United States. This designation provides for a seven-year marketing exclusivity period upon regulatory approval, as well as certain incentives, including federal grants and tax credits. Dose escalation is ongoing in the TNG462 phase 1/2 clinical trial in patients with MTAP-deleted solid tumors except GBM, as TNG462 is not brain penetrant in preclinical models. To date, the preliminary safety, tolerability and pharmacokinetics profiles are favorable. TNG462 has the same mechanism of action as TNG908, but with enhanced potency and selectivity in MTAP-deleted cell lines and patient-derived xenografts. In preclinical studies, TNG462 is 45X selective for MTAP-deleted cancer cells versus normal cells and ~30X more potent than TNG908. TNG260, a first-in-class, highly selective CoREST complex inhibitor Dose escalation is ongoing in the TNG260 phase 1/2 clinical trial evaluating the safety, pharmacokinetics, pharmacodynamics and efficacy of TNG260 in combination with pembrolizumab in patients with locally advanced or metastatic solid tumors with an STK11 loss-of-function mutation. To date, the preliminary safety, tolerability and pharmacokinetics profiles are favorable. STK11 mutations occur in approximately 15% of NSCLC, 15% of cervical, 10% of carcinoma of unknown primary, 5% of breast and 3% of pancreatic cancers. TNG348, a novel USP1 inhibitor Dose escalation is ongoing in the TNG348 phase 1/2 clinical trial evaluating the safety, pharmacokinetics, pharmacodynamics and efficacy of TNG348 as a single agent and in combination with olaparib, a PARP inhibitor, in patients with BRCA1/2-mutant and other HRD+ (homologous recombination deficient) cancers. The first patient dosed was announced in January 2024. HRD+ cancers, including BRCA1/2 mutations, represent up to 50% of ovarian cancers, 25% of breast cancers, 10% of prostate cancers and 5% of pancreatic cancers. Upcoming Milestones Clinical data from the ongoing TNG908 phase 1/2 trial are expected in 2024. Scientific Presentations American Chemical Society (ACS) Spring 2024, March 17-21, 2024, New Orleans, LA In March 2024, an oral presentation of the discovery and preclinical characterization of TNG348 will be presented at the ACS Spring Meeting, supporting the further development and ongoing phase 1/2 clinical trial of TNG348 as a single agent and in combination with olaparib. American Association of Cancer Research (AACR) Annual Meeting, April 5-10, 2024, San Diego, CA In April 2024, seven posters will be presented highlighting preclinical data from the Company’s clinical-stage precision oncology pipeline and synthetic lethality discovery platform. Ayushi Patel, Ph.D. from NYU Langone Health will present a minisymposium based on a Tango-NYU collaboration to study TNG260 in STK11 mutant non-small cell lung cancer in preclinical models. Leadership Updates: December 2023 Drew Sansone, M.S., was appointed Chief Regulatory Officer. Mr. Sansone brings over 25 years of pharmaceutical regulatory experience to this newly created role. He oversees the Company’s Regulatory Affairs team. Most recently, Mr. Sansone served as Vice President and Head, Global Regulatory Affairs, Regulatory and Quality, North America at Ipsen Pharmaceuticals. Heather DiBenedetto, M.S., was appointed Chief Development Operations Officer. Ms. DiBenedetto joined Tango in July 2020 as Head of Development Operations. She has over 25 years of drug development experience, focused in oncology. Doug Barry, J.D., was appointed Chief Legal Officer. Mr. Barry, who joined Tango in July 2021 as General Counsel, will continue to oversee the Company’s Legal, Compliance, Corporate Governance and Public Reporting functions as a publicly traded entity. Mr. Barry has practiced law for more than 20 years. Financial Results As of December 31, 2023, the Company held $336.9 million in cash, cash equivalents and marketable securities. Combined with $41.7 million in net proceeds from shares sold under the Company’s at-the-market (ATM) stock offering program in January 2024, the Company believes it is sufficiently capitalized to fund operations into late 2026. Collaboration revenue was $5.4 million for the three months ended December 31, 2023, compared to $6.4 million for the same period in 2022, and $31.5 million for the twelve months ended December 31, 2023 compared to $24.9 million for the same period in 2022. The amount of research costs spent under the collaboration directly affects the collaboration revenue that is recorded in the period. License revenue was $0.0 and $5.0 million for the three and twelve months ended December 31, 2023, respectively, compared to $0.0 for both the three and twelve months ended December 31, 2022. The increase is the result of out-licensing a program to Gilead for $5.0 million during the second quarter of 2023. Research and development expenses were $31.3 million for the three months ended December 31, 2023, compared to $29.1 million for the same period in 2022, and $115.2 million for the twelve months ended December 31, 2023 compared to $105.9 million for the same period in 2022. The change is primarily due to increased personnel-related costs to support our research and development activities. General and administrative expenses were $9.1 million for the three months ended December 31, 2023, compared to $7.9 million for the same period in 2022, and $35.5 million for the twelve months ended December 31, 2023 compared to $30.0 million for the same period in 2022. The change was primarily due to increases in personnel-related costs. Net loss for the three months ended December 31, 2023 was $30.8 million, or $0.32 per share, compared to a net loss of $29.1 million, or $0.33 per share, in the same period in 2022. Net loss for the twelve months ended December 31, 2023 was $101.7 million, or $1.08 per share, compared to a net loss of $108.2 million, or $1.23 per share, in the same period in 2022. About Tango Therapeutics Tango Therapeutics is a clinical-stage biotechnology company dedicated to discovering novel drug targets and delivering the next generation of precision medicine for the treatment of cancer. Using an approach that starts and ends with patients, Tango leverages the genetic principle of synthetic lethality to discover and develop therapies that take aim at critical targets in cancer. This includes expanding the universe of precision oncology targets into novel areas such as tumor suppressor gene loss and their contribution to the ability of cancer cells to evade immune cell killing. For more information, please visit . Forward-Looking Statements Certain statements in this press release may be considered forward-looking statements. Forward-looking statements generally relate to future events, Tango’s future operating performance and goals, the anticipated benefits of therapies and combination therapies (that include a Tango pipeline product), as well as the expectations, beliefs and development objectives for Tango’s product pipeline and clinical trials. In some cases, you can identify forward-looking statements by terminology such as “may”, “should”, “expect”, “intend”, “will”, “goal”, “estimate”, “anticipate”, “believe”, “predict”, “designed,” “potential” or “continue”, or the negatives of these terms or variations of them or similar terminology. For example, implicit or explicit statements concerning the following include or constitute forward-looking statements: dose escalation is ongoing in all four of Tango’s clinical trials; company is actively enrolling patients in the company’s clinical trials; the objectives and endpoints of each of the clinical trials that are ongoing; data from the TNG908 clinical trial is expected in 2024; cash runway will last into late 2026, such amount expected to fund all clinical programs through proof-of-concept (the company is capitalized to fund operations into late-2026); Tango is committed to discovering and delivering the next generation of precision cancer medicines; each of the company’s four clinical stage assets have the potential to reach people with a wide range of cancers, including those with MTAP-deleted solid tumors, STK11 loss-of-function mutations, and BRCA 1/2 mutations and other DNA damage repair defects; Tango is well-positioned to deliver proof-of-concept data on its four clinical programs; TNG462 is a potentially best-in-class MTA-cooperative PRMT5 inhibitor; certain pre-clinical data support the ongoing phase 1/2 clinical trial of TNG348 as a single agent and in combination with olaparib; Orphan Drug Designation (ODD) to TNG462 for the treatment of soft tissue sarcomas and potential benefits resulting from such designation; and the expected timing of: (i) development candidate declaration for certain targets, (ii) initiating IND-enabling studies; (iii) filing INDs; (iv) clinical trial initiation and (v) disclosing initial, interim, additional and final clinical trial results; and the expected benefits of the Company's development candidates and other product candidates. Such forward-looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon estimates and assumptions that, while considered reasonable by Tango and its management, are inherently uncertain. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: benefits of product candidates seen in preclinical analyses may not be evident when tested in later preclinical studies or in clinical trials or when used in broader patient populations (if approved for commercial sale); Tango has limited experience conducting clinical trials (and will rely on a third party to operate its clinical trials) and may not be able to commence the clinical trial (including opening clinical trial sites, dosing the first patient, and continued enrollment and dosing of an adequate number of clinical trial participants) when expected, may not be able to continue dosing (and dose escalation) on anticipated timelines, and may not generate results (including final, initial or additional safety, efficacy data and proof-of-mechanism and proof-of-concept) in the anticipated timeframe (or at all); Tango’s pipeline products may not be safe and/or effective in humans; Tango has a limited operating history and has not generated any revenue to date from product sales, and may never become profitable; other companies may be able to identify and develop product candidates more quickly than the Company and commercially introduce the product prior to the Company; the Company’s proprietary discovery platform is novel and may not identify any synthetic lethal targets for future development; the Company may not be able to identify development candidates on the schedule it anticipates due to technical, financial or other reasons; the Company may not be able to for development candidates on time, or at all, due to technical or financial reasons or otherwise; the Company may utilize cash resources more quickly than anticipated; Tango will need to raise capital in the future and if we are unable to raise capital when needed or on attractive terms, we would be forced to delay, scale back or discontinue some of our development programs or future commercialization efforts (which may delay filing of INDs, dosing patients, reporting clinical trial results and filing new drug applications); Tango’s approach to the discovery and development of product candidates is novel and unproven, which makes it difficult to predict the time, cost of development, and likelihood of successfully developing any products; the Company may be unable to advance our preclinical development programs into and through the clinic for safety or efficacy reasons or commercialize our product candidates or we may experience significant delays in doing so as a result of factors beyond Tango’s control; the Company may not be able to realize the benefits of ODD or Fast Track designation (and such designations may not advance any anticipated approval timelines); Tango may not identify or discover additional product candidates or may expend limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success; the Company’s product candidates may cause adverse or other undesirable side effects (or may not show requisite efficacy) that could, among other things, delay or prevent regulatory approval; our dependence on third parties for conducting clinical trials and producing drug substance and drug product; and our ability to obtain and maintain patent and other intellectual property protection for our technology and product candidates or the scope of intellectual property protection obtained is not sufficiently broad. Additional information concerning risks, uncertainties and assumptions can be found in Tango’s filings with the SEC, including the risk factors referenced in Tango’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022, as supplemented and/or modified by its most recent Quarterly Report on Form 10-Q. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Tango specifically disclaims any duty to update these forward-looking statements. Consolidated Statements of Operations (In thousands, except share and per share data) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Collaboration revenue $ 5,431 $ 6,411 $ 31,527 $ 24,860 License revenue — — 5,000 — Total revenue 5,431 6,411 36,527 24,860 Operating expenses: Research and development 31,339 29,091 115,198 105,906 General and administrative 9,105 7,887 35,502 30,025 Total operating expenses 40,444 36,978 150,700 135,931 Loss from operations (35,013 ) (30,567 ) (114,173 ) (111,071 ) Other income, net 4,297 1,558 12,563 2,949 Loss before income taxes (30,716 ) (29,009 ) (101,610 ) (108,122 ) Provision for income taxes (47 ) (51 ) (134 ) (54 ) Net loss $ (30,763 ) $ (29,060 ) $ (101,744 ) $ (108,176 ) Net loss per common share – basic and diluted $ (0.32 ) $ (0.33 ) $ (1.08 ) $ (1.23 ) Weighted average number of common shares outstanding – basic and diluted 97,223,183 87,971,485 94,572,448 87,820,037 Consolidated Balance Sheets (In thousands) December 31, 2023 2022 Assets Current assets: Cash and cash equivalents $ 66,385 $ 59,968 Marketable securities 270,500 306,165 Accounts receivable — 2,000 Restricted cash 856 567 Prepaid expenses and other current assets 8,797 6,572 Total current assets 346,538 375,272 Property and equipment, net 9,908 10,884 Operating lease right-of-use assets 43,508 46,886 Restricted cash, net of current portion 2,567 3,423 Other assets 46 5 Total assets $ 402,567 $ 436,470 Liabilities and Stockholders' Equity Current liabilities: Accounts payable $ 2,785 $ 4,453 Accrued expenses and other current liabilities 15,401 17,495 Operating lease liabilities 2,082 1,770 Deferred revenue 25,670 31,792 Income tax payable — 35 Total current liabilities 45,938 55,545 Operating lease liabilities, net of current portion 36,838 39,361 Deferred revenue, net of current portion 66,683 92,088 Total liabilities 149,459 186,994 Total stockholders’ equity 253,108 249,476 Total liabilities and stockholders’ equity $ 402,567 $ 436,470 View source version on businesswire.com: Contacts Investor Contact: Sam Martin/Andrew Vulis Argot Partners tango@argotpartners.com Source: Tango Therapeutics, Inc. 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Total operating revenues for the full year 2023 were $16.3M, compared to $15.8M for the same period in 2022. As of March 7, 2024, Ryvu's cash position was $57.2M, excluding the first tranche of €8M in venture debt from the EIB, expected imminently. Together with other already secured funding sources, this cash position provides a runway through Q1 2026. Ryvu will present preclinical data from its synthetic lethality pipeline, RVU120, and MEN1703 (SEL24) at the upcoming 2024 American Association for Cancer Research (AACR) Annual Meeting (April 5-10, San Diego, California). After announcing the hematology-focused RVU120 development plan in Q4 2023, Ryvu launched two Phase II studies in early 2024. An additional two Phase II clinical trials for RVU120 are expected to be launched in mid-2024. By the end of the year, the company plans to enroll over 100 patients across all RVU120 Phase II studies and aims to present initial Phase II data. KRAKOW, Poland, March 13, 2024 /PRNewswire/ -- Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small-molecule therapies that address emerging targets in oncology, summarizes its 2023 fiscal year and provides a corporate update. Pawel Przewiezlikowski, co-founder, largest shareholder, and Chief Executive Officer of Ryvu Therapeutics, said: - In 2023, we made significant progress in all key business areas and look forward to multiple catalysts in 2024. We have already started two Phase II studies of RVU120, and around mid-year, we plan to launch two more Phase II studies in hematology. By the end of the year, we plan to enroll more than 100 patients across these clinical trials. We also plan to launch a new Phase II study of MEN1703 (SEL24) in DLBCL, which is being developed under a license agreement with the Menarini Group. Study start-up activities for new trials of both RVU120 and MEN1703 are proceeding quickly. Krzysztof Brzozka, Ph.D., Executive Vice President, and Chief Scientific Officer, said: - We are pleased with the significant progress made in our early-phase projects. Among the most advanced projects from our synthetic lethality platform – PRMT5 and WRN – we plan to identify a clinical candidate in 2024. We are also seeing progress in the programs being developed by our partners – particularly BioNTech and Exelixis. We were excited to achieve the second milestone in the Exelixis collaboration, and we look forward to presenting data on our synthetic lethality assets and novel platform at AACR. 2023 SUMMARY AND RECENT CORPORATE EVENTS RVU120 clinical development plan In 2023 Ryvu prepared for the launch of two Phase II RVU120 trials, which then initiated in early 2024: 1) RVU120 as monotherapy in genetically defined cohorts of patients with relapsed/refractory acute myeloid leukemia (r/r AML) and high-risk myelodysplastic syndromes (HR-MDS, RIVER-52 study), and 2) RVU120 in combination with venetoclax for patients with relapsed/ refractory AML (RIVER-81 study). Ryvu will financially support the REMARK study's Phase II clinical trial of RVU120 in patients with low-risk myelodysplastic syndromes (LR-MDS). REMARK will be conducted as an investigator-initiated study through the EMSCO network, with Prof. Uwe Platzbecker, a globally renowned expert in the field of LR-MDS, as the Coordinating Principal Investigator. Start-up activities have already been launched, and patient enrollment will start in mid-2024. Study start-up is also underway for POTAMI-61, a Phase II study evaluating the efficacy of RVU120 in patients with myelofibrosis (MF). Initiation of patient recruitment is scheduled for mid-2024. Translational research on RVU120 in solid tumors will continue, including combination studies, as well as academic collaborations in the areas of medulloblastoma (MB) and sarcoma-related research. The company plans to enroll more than 100 patients across all RVU120 Phase II trials this year and aims to present initial Phase II data by the end of 2024. RVU120's updated clinical development plan includes studies (RIVER-52, RIVER-81, and POTAMI-61) that could lead to three drug approvals between 2026 and 2027. Key data presented during 2023 conferences In 2023, Ryvu Therapeutics presented data from the RVU120 program at several international conferences, including EHA 2023, ESMO 2023, and ASH 2023: RVU120 monotherapy demonstrated clinical activity in a Phase Ib study in which 50% of evaluable patients with r/r AML or HR-MDS achieved clinical benefit, including a complete response, morphologically leukemia-free status, clinically significant reduction of blasts including reductions that allowed bridging to a bone marrow transplantation, two-year disease stabilization, hematologic improvements, as well as reduction in bone marrow fibrosis. In particular, early signs of efficacy were observed in patients with an NPM1 mutation, DNMT3a mutation, and HR-MDS. The recommended Phase II dose (RP2D) of 250 mg was found to be safe and well-tolerated, achieving RVU120 concentrations in the pharmacologically active range, with a level of target inhibition between 50% and 70%. This level of target inhibition is expected to result in therapeutic efficacy in selected patients or in combinations with synergistic therapies. RVU120 is emerging as a potential candidate in the first-line treatment of AML, supported by its activity against leukemic stem cells. RVU120 acts synergistically with venetoclax in both sensitive and venetoclax-resistant models. At the ENA conference in October 2023, Ryvu presented preclinical data for PRMT5 and the synthetic lethality platform, and Ryvu's partner – Menarini Group, presented preclinical data for MEN1703 in advanced diffuse large B-cell lymphoma (DLBCL). Ryvu has developed potentially best-in-class MTA-cooperative PRMT5 inhibitors with outstanding drug-like physicochemical properties and the ability to block methyltransferase activity of PRMT5 with nanomolar concentrations and bioavailable upon oral administration. The novel, optimized inhibitors exhibit a significantly improved pharmacokinetic profile. In addition, the compounds show antitumor efficacy and target engagement in vivo, providing a solid foundation for further development towards clinical trials. MEN1703 (SEL24) has shown promising antitumor activity in translational studies in various types of DLBCL. These data justify the development of MEN1703 in Phase II clinical trials in this indication. Expansion of MEN1703 (SEL24) development by Ryvu's partner – Menarini Group, to include a new Phase II clinical trial in DLBCL. In September 2023, Ryvu announced the Menarini Group's decision to expand the development of MEN1703 (SEL24) by initiating a new Phase II clinical trial in patients with DLBCL. A Phase II study in DLBCL is scheduled to begin in mid-2024. The goal is to evaluate the activity of MEN1703 (SEL24) as monotherapy and in combination with standard therapy in patients with DLBCL. The study will be initiated based on the potent activity of MEN1703 (SEL24) observed in preclinical lymphoma models. Clinical trials have confirmed the acceptable safety profile and early signs of activity of MEN1703 (SEL24) as a monotherapy. Based on the available data, further program development will continue in patients with DLBCL and potentially in additional indications. Recent financial events On February 3, 2024, Ryvu received notice that the second financial milestone was achieved under the collaboration agreement with Exelixis, resulting in a $2M payment to Ryvu. Ryvu and Exelixis are working under a research collaboration and license agreement to develop antibody-drug conjugates (ADCs) with Ryvu's portfolio of STING agonists. On March 5, 2024, Ryvu received notice from the European Investment Bank (EIB) that it had met the conditions for disbursement of the first venture debt tranche of €8M. These funds are not yet included in the cash balance reported in this press release, but Ryvu expects to receive the funds on March 13, 2024. As part of the agreement announced in August 2022, Ryvu still has access to an additional €14M in venture debt from the EIB. UPCOMING EVENTS Ryvu will attend the AACR Annual Meeting (San Diego, USA) from April 5-10, 2024, to present preclinical data from its synthetic lethality pipeline, RVU120, and MEN1703 (SEL24). 2023 Fiscal Year Financial Update [1] Cash Position – On December 31, 2023, Ryvu Therapeutics held $63.7M in cash, cash equivalents, and bonds, compared to $23.2M at the end of 2022. On March 7, 2024, Ryvu Therapeutics held $57.2M in cash, cash equivalents, and bonds, which excludes €8M in venture debt from the EIB to be received imminently. Operating Revenues – In 2023, Ryvu recognized total operating revenues (including grants) of $16.3M, compared to 2022, when the total operating revenue amounted to $15.8M. Operating costs, excluding the non-cash cost of valuation of the Incentive Program ($2.0M) and valuation of NodThera shares ($0.9M) in the full year 2023, amounted to $37.6M, representing an increase compared to $26.4M in the previous year. Net Loss Attributable to Common Shareholders – In 2023, the net loss attributable to common shareholders, excluding the non-cash cost of valuation of the Incentive Program, amounted to $20.0M, compared to $13.8M in the previous year. About Ryvu Therapeutics Ryvu Therapeutics is a clinical-stage drug discovery and development company focused on novel small-molecule therapies that address emerging targets in oncology. Internally discovered pipeline candidates use diverse therapeutic mechanisms driven by emerging knowledge of cancer biology, including small molecules directed at kinase, synthetic lethality, and immuno-oncology targets. Ryvu's most advanced programs include RVU120, a selective CDK8/CDK19 kinase inhibitor with the potential to treat hematological malignancies and solid tumors, currently in Phase II development (i) as a monotherapy for the treatment of patients with relapsed/refractory acute myeloid leukemia (r/r AML) and high-risk myelodysplastic syndromes (HR-MDS) as well as (ii) in combination with venetoclax for the treatment of patients with r/r AML. Another clinical program, SEL24 (MEN1703), is a dual PIM/FLT3 kinase inhibitor licensed to the Menarini Group. Ryvu Therapeutics has signed multiple partnering and licensing deals with global companies, including BioNTech and Exelixis. The Company was founded in 2007 and is headquartered in Kraków, Poland. Ryvu is listed on the Warsaw Stock Exchange and is a component of the mWIG40 index. For more information, please see . [1] USD figures are provided at a conversion rate of: for the period from 01/01/2023 – 31/12/2023: PLN 4.1823; for the period from 01/01/2022 – 31/12/2022: PLN 4.4679; as of 7/03/2024: PLN 3.9485 as of 31/12/2023: PLN 3.9350 as of 31/12/2022: PLN 4.4018 SOURCE Ryvu Therapeutics

BERKELEY HEIGHTS, N.J., March 07, 2024 (GLOBE NEWSWIRE) -- Cyclacel Pharmaceuticals Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative medicines based on cancer cell biology, today announced that preclinical proof-of-concept data with the Company’s fadraciclib will be presented at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2024, being held April 5-10 in San Diego, California. The data will be presented at three poster sessions and report activity and antitumor effects of fadraciclib in biliary tract cancer, lung cancer, Richter transformation and lymphoma cell lines. Details of the presentations are as follows: Title: The CDK2/9 inhibitor fadraciclib is active in Richter transformation and lymphoma cell lines by targeting both cell survival and proliferation Abstract No: 518 / 15 Session Topic: Session PO.ET05.01 - Cell Cycle, Transcription Regulation, and Anticancer Drug Action Date and Time: April 7, 2024, 1:30 PM - 5:00 PM PT Location: Exhibition Hall, Section 21 Title: Elucidation of the fates of CDK2 inhibited aneuploid and residual lung cancers Abstract No: 2117 / 8 Session Topic: Session PO.ET07.02 - Pharmacodynamic Biomarkers of Drug Response Date and Time: April 8, 2024, 9:00 AM - 12:30 PM PT Location: Exhibition Hall, Section 30 Title: Anti-tumor effects of fadraciclib, CDK2/9 inhibitor, in biliary tract cancer Abstract No: 5711 / 11 Session Topic: Session PO.MCB01.01 - Pharmacologic Targeting of Cell Cycle Proteins Date and Time: April 9, 2024, 1:30 PM - 5:00 PM PT Location: Exhibition Hall, Section 18 About Cyclin-Dependent Kinases and Fadraciclib Cyclin-dependent kinases (CDKs) are critical for cell cycle control and transcriptional regulation. Dysregulated CDKs have been linked to the cancer hallmarks of uncontrolled proliferation and increased cancer cell survival. Fadraciclib is a highly selective, potent, orally and intravenously available, next generation inhibitor of CDK2 and CDK9. By inhibiting CDK2 and CDK9 fadraciclib causes apoptotic death through anaphase catastrophe of cancer cells at sub-micromolar concentrations. To date single agent activity, including CR, PR and SD, has been observed in patients with advanced endometrial, squamous NSCLC lung cancer and T-cell lymphoma. Encouraging signals of activity were observed in patients with advanced cervical, hepatocellular, ovarian and pancreatic cancers. 065-101 Study of Oral Fadraciclib Oral fadraciclib is being tested in a Phase 1/2 trial for the treatment of advanced solid tumors and lymphoma (065-101; NCT#04983810). A total of 29 patients have been treated as monotherapy in this ongoing study. The study is enrolling unselected, all comer patients with advanced solid tumors and lymphoma. The Phase 2 part of the 065-101 study is designed to further evaluate fadra safety and efficacy in up to 8 cohorts defined by histology and/or NGS. The study is powered to demonstrate response in the molecular subtype suggested by the Phase 1 data and others that may be sensitive. CDKN2A, CDKN2B, MTAP deletions CDKN2A gene deletions occur in over 40% of several solid tumors, including glioma, head and neck, pancreatic, esophageal, lung (incl. squamous), bladder, melanoma, and others. CDKN2B deletions occur in over 30% of several solid tumors, including bladder, glioma, pancreatic, esophageal, lung (incl. squamous), head and neck, melanoma, and others. MTAP deletions occur in over 25% of several solid tumors, including glioma, mesothelioma, pancreatic, bladder, esophageal and others. MTAP deletion confers dependency on the PRMT5 enzyme in cancer cells which was identified as a synthetic lethal target for MTAP deleted cancers. About Cyclacel Pharmaceuticals, Inc. Cyclacel is a clinical-stage, biopharmaceutical company developing innovative cancer medicines based on cell cycle, transcriptional regulation and mitosis biology. The transcriptional regulation program is evaluating fadraciclib, a CDK2/9 inhibitor, and the anti-mitotic program CYC140, a PLK1 inhibitor, in patients with both solid tumors and hematological malignancies. Cyclacel's strategy is to build a diversified biopharmaceutical business based on a pipeline of novel drug candidates addressing oncology and hematology indications. For additional information, please visit . Forward-looking Statements This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and intended utilization of Cyclacel’s product candidates, the conduct and results of future clinical trials, plans regarding regulatory filings, future research and clinical trials and plans regarding partnering activities. Factors that may cause actual results to differ materially include the risk that product candidates that appeared promising in early research and clinical trials do not demonstrate safety and/or efficacy in larger-scale or later clinical trials, trials may have difficulty enrolling, Cyclacel may not obtain approval to market its product candidates, the risks associated with reliance on outside financing to meet capital requirements, the potential effects of the COVID-19 pandemic, and the risks associated with reliance on collaborative partners for further clinical trials, development and commercialization of product candidates. You are urged to consider statements that include the words "may," "will," "would," "could," "should," "believes," "estimates," "projects," "potential," "expects," "plans," "anticipates," "intends," "continues," "forecast," "designed," "goal," or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to our most recent Annual Report on Form 10-K and other periodic and other filings we the Securities and Exchange Commission and are available at . Such forward-looking statements are current only as of the date they are made, and we assume no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Contacts Company: Paul McBarron, (908) 517-7330, pmcbarron@cyclacel.com Investor Relations: Grace Kim, IR@cyclacel.com © Copyright 2024 Cyclacel Pharmaceuticals, Inc. All Rights Reserved. The Cyclacel logo and Cyclacel® are trademarks of Cyclacel Pharmaceuticals, Inc.