Phase 2 Study Evaluating the Efficacy of the Combination of DKN-01 (DKK1 Inhibitor, Leap Therapeutics) and Pembrolizumab in the Treatment of Advanced or Recurrent Endometrial Cancer

To learn if the combination of DKN-01 and pembrolizumab can help to control advanced or recurrent endometrial cancer.

Start Date29 Aug 2023

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+3]

NCT05480306

/ CompletedPhase 2

Randomized Phase 2 Study of DKN-01 Plus FOLFIRI/FOLFOX and Bevacizumab Versus FOLFIRI/FOLFOX and Bevacizumab as Second-line Treatment of Advanced Colorectal Cancer (DeFianCe)

This is a Phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to evaluate efficacy and safety of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus standard of care (SOC) [FOLFIRI/FOLFOX and bevacizumab] as second-line treatment of advanced CRC patients.

Start Date30 Aug 2022

Sponsor / Collaborator

Cypherpunk Technologies, Inc.

NCT04363801

/ TerminatedPhase 2

A Phase 2, Multicenter, Open-Label Study of DKN-01 in Combination With Tislelizumab ± Chemotherapy as First-Line or Second-Line Therapy in Adult Patients With Inoperable, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (DisTinGuish)

A Phase 2, Multicenter, Open-Label Study of DKN-01 in Combination with Tislelizumab ± Chemotherapy as First-Line or Second-Line Therapy in Adult Patients with Inoperable, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Start Date29 Jul 2020

Sponsor / Collaborator

Cypherpunk Technologies, Inc.

[+1]

100 Clinical Results associated with Sirexatamab

100 Translational Medicine associated with Sirexatamab

100 Patents (Medical) associated with Sirexatamab

Literatures (Medical) associated with Sirexatamab

01 Jun 2025·Prostate cancer and prostatic diseases

A Phase 1/2 multicenter trial of DKN-01 as monotherapy or in combination with docetaxel for the treatment of metastatic castration-resistant prostate cancer (mCRPC)

Article

Author: Loomis, Cynthia ; Pachynski, Russell K ; Leis, Dayna ; Griglun, Sarah ; Newman, Walter ; Deng, Jiehui ; Chattopadhyay, Pratip ; Ren, Qinghu ; Kagey, Michael H ; Fedal, Ezeddin ; Waalkes, Erika ; Gargano, Gabrielle ; Febles, Victor Adorno ; Wise, David R ; Sirard, Cynthia A ; Troxel, Andrea B ; Baum, Jason ; Chiriboga, Luis ; Deng, Fang-Ming ; Yang, Nina ; Soamchand, Nadia ; Economides, Minas P ; Denmeade, Samuel R ; Aggarwal, Rahul R ; Selvaraj, Shanmugapriya ; Wong, Kwok-Kin ; Aranchiy, Viktoriya ; Balar, Arjun V ; Haas, Michael ; Puranik, Amrutesh ; Machado, Sabrina ; Melamed, Jonathan

BACKGROUND:

Dickkopf-related protein 1 (DKK1) is a Wingless-related integrate site (Wnt) signaling modulator that is upregulated in prostate cancers (PCa) with low androgen receptor expression. DKN-01, an IgG4 that neutralizes DKK1, delays PCa growth in pre-clinical DKK1-expressing models. These data provided the rationale for a clinical trial testing DKN-01 in patients with metastatic castration-resistant PCa (mCRPC).

METHODS:

This was an investigator-initiated parallel-arm phase 1/2 clinical trial testing DKN-01 alone (monotherapy) or in combination with docetaxel 75 mg/m² (combination) for men with mCRPC who progressed on ≥1 AR signaling inhibitors. DKK1 status was determined by RNA in-situ expression. The primary endpoint of the phase 1 dose escalation cohorts was the determination of the recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 expansion cohorts was objective response rate by iRECIST criteria in patients treated with the combination.

RESULTS:

18 pts were enrolled into the study-10 patients in the monotherapy cohorts and 8 patients in the combination cohorts. No DLTs were observed and DKN-01 600 mg was determined as the RP2D. A best overall response of stable disease occurred in two out of seven (29%) evaluable patients in the monotherapy cohort. In the combination cohort, five out of seven (71%) evaluable patients had a partial response (PR). A median rPFS of 5.7 months was observed in the combination cohort. In the combination cohort, the median tumoral DKK1 expression H-score was 0.75 and the rPFS observed was similar between patients with DKK1 H-score ≥1 versus H-score = 0.

CONCLUSION:

DKN-01 600 mg was well tolerated. DKK1 blockade has modest anti-tumor activity as a monotherapy for mCRPC. Anti-tumor activity was observed in the combination cohorts, but the response duration was limited. DKK1 expression in the majority of mCRPC is low and did not clearly correlate with anti-tumor activity of DKN-01 plus docetaxel.

01 Feb 2025·APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY

DKN-01 Suppresses Gastric Cancer Progression Through Activating cGAS-STING Pathway to Block Macrophage M2 Polarization

Article

Author: Qi, Yingying ; Wang, Sisi ; Yang, Xiaohuan

Dickkopf-1 (DKK1) is a secretory antagonist that can bind with the Wnt coreceptor to desensitize cells to canonical Wnt ligands. DKN-01 is a specific antibody targeting secreted DKK1, which has been investigated as a monotherapy or combination therapy for various malignant tumors, including gastric cancer (GC). Tumor-associated macrophages (TAMs) with high plasticity usually present M2 phenotype, which can promote tumor progression. The aim of this study was to investigate the effect of DKN-01 on macrophage polarization in GC and the underlying molecular mechanism. To ascertain the effect of DKN-01 on GC tumor growth, we established a tumor-bearing mouse model and found that DKN-01 treatment suppressed tumor growth efficiently. Through RNA-seq and pathway enrichment analysis, we identified that the differentially expressed genes after DKN-01 treatment are associated with tumor immune-related pathways. Macrophage polarization was assessed using immunohistochemistry and quantitative real-time polymerase chain reaction. DKN-01 and knockdown of DKK1 promoted M1 polarization and inhibited M2 polarization of macrophages, while DKK1 overexpression got the opposite results. Moreover, DKN-01 activated the cGAS/STING pathway, while the inactivation of cGAS-STING pathway using RU.521 reversed the inhibition of tumor growth in vivo and macrophage M2 polarization caused by DKN-01. This study reveals that DKN-01 suppresses GC tumor growth through activating cGAS-STING pathway to block macrophage M2 polarization.

20 Jan 2025·JOURNAL OF CLINICAL ONCOLOGY

DKN-01 in Combination With Tislelizumab and Chemotherapy as First-Line Therapy in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: DisTinGuish

Article

Author: Stilian, Melissa C. ; Thoma, Mathis ; Ajani, Jaffer A. ; Scott, Aaron James ; Chung, Vincent ; Chiu, Vi K. ; Kagey, Michael H. ; Uronis, Hope Elizabeth ; Tejani, Mohamedtaki Abdulaziz ; Baum, Jason ; Sirard, Cynthia A. ; Sonbol, Mohamad Bassam ; Wainberg, Zev A. ; Iqbal, Syma ; Altura, Rachel A. ; Zhang, Ying ; Klempner, Samuel J.

PURPOSE:

The outcomes of anti–PD-1 agents plus fluoropyrimidine/platinum in frontline advanced gastroesophageal adenocarcinomas (aGEAs) remain poor. We investigated the safety, tolerability, and activity of fluoropyrimidine/oxaliplatin and tislelizumab with the DKK1-neutralizing antibody DKN-01 in aGEAs in a phase IIa open-label study.

PATIENTS AND METHODS:

Patients had untreated human epidermal growth factor receptor 2–negative aGEAs, RECIST v1.1 measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and adequate organ function. Patients received intravenous DKN-01 300 mg once every 2 weeks, tislelizumab 200 mg once every 3 weeks, oxaliplatin 130 mg/m 2 once every 3 weeks, and capecitabine 1,000 mg/m 2 twice daily on days 1-15 of each 21-day cycle. The primary end point was safety and tolerability. Key secondary end points included objective response rate (ORR) by RECISTv1.1, progression-free survival (PFS), and overall survival (OS).

RESULTS:

Between September 18, 2020, and April 8, 2021, 25 patients were enrolled. All patients who received at least one dose of DKN-01 were included in the safety analysis. Most patients had gastroesophageal junction tumors, median age was 61 years, 76% were male, and 55% were ECOG of 0. All patients reported at least one treatment-emergent adverse event. The ORR was 73% (95% CI, 49.8 to 89.3), with a disease control rate of 95%. The ORR was 90% (95% CI, 55.5 to 99.7) in the DKK1-high tumor patients and 67% (95% CI, 29.9 to 92.5) in the DKK1-low tumor patients. The median PFS was 11.3 months (95% CI, 5.8 to 12.0) and the 12-month PFS rate was 33%. The median OS was 19.5 months (95% CI, 15.2 to 24.4) with a 12-month OS rate of 76% and an 18-month OS rate of 55%.

CONCLUSION:

DKN-01 can be safely combined with frontline fluoropyrimidine/oxaliplatin and tislelizumab and demonstrates encouraging activity independent of PD-L1 expression levels. A randomized phase II trial is ongoing (ClinicalTrials.gov identifier: NCT04363801 ).

News (Medical) associated with Sirexatamab

16 Mar 2026

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Cypherpunk Reports Full Year 2025 Financial Results

CAMBRIDGE, Mass., March 16, 2026 /PRNewswire/ -- Cypherpunk Technologies Inc., (Nasdaq: CYPH) ("Cypherpunk"), today reported financial results for the year ended December 31, 2025. "2025 was a transformational year. Following a $58.88 million private placement led by Winklevoss Capital, we rebranded as Cypherpunk to become a privacy technology company with a digital asset treasury strategy focused on Zcash, while advancing sirexatamab for the treatment of patients with colorectal cancer through our Leap Therapeutics subsidiary," said Douglas E. Onsi, President and CEO of Cypherpunk. "Since we began operating as Cypherpunk in October, we have purchased 294,743.10 ZEC for our treasury and made a $5 million strategic investment in Zcash Open Development Lab ("ZODL"), the development team behind Zodl, the leading Zcash wallet. In the year ahead, we will remain focused on advancing the adoption of Zcash and expanding our efforts across a broad set of technologies that defend privacy," said Will McEvoy, Chief Investment Officer of Cypherpunk. Cypherpunk Highlights: Closed a $58.88 million private placement in cash led by Winklevoss Capital In October 2025, the Company raised $58,888,888 in cash led by Winklevoss Capital to become the leading public company focused on advancing privacy preserving technologies. In the transaction, the Company issued: (i) 15,212,311 shares of common stock, (ii) pre-funded warrants to purchase up to an aggregate of 80,768,504 shares of common stock at an exercise price of $0.001 per share, and (iii) warrants to purchase an additional 71,985,605 shares of common stock at an exercise price of $0.5335 per share. Appointed digital asset executives and industry leaders as board members and strategic advisors In November 2025, the Company appointed Khing Oei as Chairman of the Board of Directors, and Will McEvoy as Chief Investment Officer and a Board member. In December 2025, the Company announced that industry pioneer Zooko Wilcox, the founder of Zcash, former CEO of the Electric Coin Company, and current Chief Product Officer of Shielded Labs, joined the company as a Strategic Advisor. In December 2025, the Company announced that Josh Swihart, Chief Executive Officer of ZODL, joined the company as a Strategic Advisor. In January 2026, the Company announced that Arjun Khemani, a prominent voice in the Zcash ecosystem and the "philosophy of progress" movement, joined the company as a Strategic Advisor. Increased treasury holdings to 294,743.10 ZEC As of March 12, 2026, Cypherpunk holds a total of 294,743.10 ZEC, at an average purchase price of $335.89, representing approximately 1.78% of the total circulating supply of the Zcash network. The Company believes that privacy-protecting assets and related technologies will be critical in the increasingly digital and AI driven world. The Company intends to acquire and hold ZEC, the native coin of Zcash, as its primary digital asset and to be an active participant in the Zcash community. ZEC is a digital currency that can be transmitted over a peer-to-peer payment system. Zcash uses a cryptographic method called "zero-knowledge proofs" to allow users to engage in financial transactions while maintaining greater privacy. Invested $5 million into ZODL In March 2026, the Company expanded its holdings with a $5 million investment in Zcash company, ZODL, alongside key investors including a16z, Winklevoss Capital, Coinbase, Paradigm, Chapter One, David Friedberg, Balaji Srinivasan, and others. This marks Cypherpunk's first technology investment outside of ZEC. ZODL, which now houses the top Zcash wallet, Zodl, aims to make Zcash easier to use with continued development of the wallet and support of the Zcash protocol. Leap Therapeutics Subsidiary Highlights: Presented final clinical data from Part B of the DeFianCe study of sirexatamab plus bevacizumab and chemotherapy in colorectal cancer ("CRC") patients In a Mini Oral session at the ESMO Congress in October 2025, the Company presented the final results from Part B of the DeFianCe study, a Phase 2 study of sirexatamab, an anti-DKK1 monoclonal antibody, in combination with bevacizumab and chemotherapy compared to bevacizumab and chemotherapy in patients with microsatellite stable CRC who have received one prior systemic therapy for advanced disease. Sirexatamab demonstrated a statistically significant benefit on overall response rate ("ORR"), progression-free survival ("PFS"), and Overall Survival ("OS") in patients with high levels of DKK1, along with a positive trend on ORR and PFS in the full intent-to-treat population. Across the DKK1-high (upper quartile) patients (n=44): ORR was 44.0% in the Sirexatamab Arm vs. 15.8% ORR in the Control Arm, p-value = 0.0149. mPFS was 9.36 months in the Sirexatamab Arm vs. 5.88 months in the Control Arm, HR 0.46, p-value = 0.0168. mOS was not reached in the Sirexatamab Arm vs. 9.66 months in the Control Arm, HR 0.17, p-value < 0.001. Advancing DKK1 biomarker diagnostic test and engaging with regulatory authorities Leap is engaging with regulatory agencies to discuss the registrational pathway for sirexatamab in DKK1-high CRC patients. Leap is also working with a leading diagnostics research laboratory to optimize the DKK1 biomarker diagnostic test that could be used to identify DKK1-high CRC patients with poor prognosis and to select patients for treatment with sirexatamab. Leap expects to provide an update on the next steps in sirexatamab development and on the registrational pathway in the coming weeks. Selected Year-End 2025 Financial Results Net Income was $4.8 million for the year ended December 31, 2025, compared to a Net Loss of $67.8 million for the year ended December 31, 2024. The increase was primarily due to $50.4 million of unrealized gains on the fair value of the Company's ZEC treasury holdings which are marked to market at the end of each period, as well reductions in research and development expenses and general and administrative expenses due to the completion of the sirexatamab Phase 2 clinical development program and a reduction in force of full-time employees. Research and development expenses were $25.7 million for the full year 2025, compared to $57.2 million for the same period in 2024. The decrease for the full year 2025 was primarily due to a decrease in clinical trial costs and manufacturing costs during the year ended December 31, 2025. There was also a decrease in payroll and other related expenses due to a decrease in headcount, a decrease in stock based compensation expense, and a decrease in consulting fees. General and administrative expenses were $10.9 million for the full year 2025, compared to $12.8 million for the same period in 2024. The decrease for the full year 2025 was primarily due to a decrease in payroll and other related expenses due to a decrease in incentive based compensation expense and a decrease in headcount. This decrease was partially offset by an increase in stock based compensation expense due to RSUs granted, and an increase in professional fees during the year ended December 31, 2025. During the year ended December 31, 2025, the Company recorded a $50.4 million unrealized gain on the change in fair value of the Company's ZEC treasury holdings. Cash and cash equivalents totaled $14.0 million on December 31, 2025, and ZEC treasury holdings, categorized as a digital asset receivable, totaled $147.4 million on December 31, 2025. About Cypherpunk Cypherpunk Technologies is a privacy technology company. The Company's mission is to advance technologies that guarantee privacy for humans on the internet. Cypherpunk pursues this mission through two primary strategies: accumulating Zcash (ZEC); and investing in, acquiring, and building technologies that push the frontier of privacy forward. Additionally, through its subsidiary Leap Therapeutics, Inc., the Company is developing novel therapies for patients with cancer, continuing the development of sirexatamab and FL-501. For more information about the Company, visit our websites at and or view our public filings with the SEC that are available via EDGAR at or via . About Winklevoss Capital Winklevoss Capital is an investment firm founded in 2012 by Cameron and Tyler Winklevoss that invests in frontier technologies. FORWARD-LOOKING STATEMENTS This press release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements generally can be identified by the use of words such as "anticipate," "expect," "plan," "could," "may," "will," "believe," "estimate," "forecast," "goal," "project," and other words of similar meaning. Forward-looking statements address various matters including statements relating to the value of the Company's ZEC holdings, the investment in ZODL, or digital assets held or to be held by the Company, the expected future market, price, and liquidity of ZEC or other digital assets the Company acquires, the macro and political conditions surrounding Zcash or digital assets, the Company's plan for value creation and strategic advantages, market size and growth opportunities, regulatory conditions, competitive position and the interest of other corporations in similar business strategies, technological and market trends, and future financial condition and performance. Risks and uncertainties of the digital asset treasury strategy include, among others: (a) risks relating to the Company's operations and business, including the highly volatile nature of the price of ZEC; (b) the risk that material changes in the price of ZEC, such as decreases in price, will result in significant changes to the Company's financial statements, such as unrealized losses on fair value of ZEC holdings and net loss; (c) the risk that the price of the Company's Common Stock may be highly correlated to the price of ZEC; (d) the risk that the Company will fail to realize the anticipated benefits of the ZEC digital asset treasury strategy or the investment in ZODL; (e) risks related to the custody of our ZEC and our reliance on Gemini Space Station and its affiliates for trading and custody services; (f) changes in business, market, financial, political and regulatory conditions; (g) risks related to increased competition in the industries in which the Company does and will operate; (h) risks relating to significant legal, commercial, regulatory and technical uncertainty regarding digital assets generally; (i) risks relating to the treatment of crypto assets for U.S. and foreign tax purposes; and (j) the ability to comply with the continued listing requirements of the Nasdaq Capital Market. With respect to our biotechnology operations, important factors that could cause actual results to differ materially from our plans, estimates or expectations could include, but are not limited to: (i) our ability and plan to develop and commercialize sirexatamab; (ii) our estimates regarding our capital requirements and our ability to raise additional financing to support continued development; (iii) the success of other competing therapies that may become available; (iv) the manufacturing capacity for sirexatmab; and (v) our ability to maintain and protect our intellectual property rights. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. The Company may not actually achieve the forecasts disclosed in such forward-looking statements, and you should not place undue reliance on such forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in the Company's most recent Annual Report on Form 10-K filed with the SEC, or as may be included in other reports or information we file with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in its subsequent filings with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither the Company, nor any of its affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date hereof. CONTACT: Douglas E. Onsi President & Chief Executive Officer Cypherpunk Technologies Inc. 617-714-0360 For Investors: Matthew DeYoung Investor Relations Argot Partners 212-600-1902 [email protected] For Media: Jacqueline Ortiz Ramsey It Factor Strategies 954-294-3249 [email protected] SOURCE Cypherpunk Technologies Inc. 21% more press release views with Request a Demo

Clinical ResultFinancial StatementPhase 2Executive ChangeIPO

09 Mar 2026

·www.prnewswire.com

Cypherpunk Makes $5M Investment into Zcash Open Development Lab (ZODL)

Cypherpunk expands its holdings with new $5M investment in Zcash company, ZODL, alongside key investors including a16z, Winklevoss Capital, Coinbase, Paradigm, Chapter One, David Friedberg, Balaji Srinivasan, and others CAMBRIDGE, Mass., March 9, 2026 /PRNewswire/ -- Cypherpunk Technologies Inc., (Nasdaq: CYPH) today announced the company has invested $5M into Zcash Open Development Lab (ZODL) marking its first technology investment outside of ZEC. ZODL was founded and is led by former Electric Coin Company (ECC) CEO Josh Swihart. At ECC, Josh and his team, who have joined him at ZODL, launched the top Zcash wallet, Zashi, now rebranded to Zodl. Zashi was arguably the single biggest factor responsible for putting Zcash back on the map last year. In particular, its simple UX allowed for the Orchard shielded pool to grow from ~1M ZEC to ~4M ZEC during the span of 2025. ZODL, which now houses the Zashi wallet technology and related intellectual property, aims to make Zcash easier to use with continued development of the wallet, as well as supporting Zcash at the protocol level. The new investment strongly aligns with Cypherpunk's mission of advancing technologies that guarantee privacy for all humans on the internet and gives its shareholders exposure to a private company building critical privacy infrastructure on the frontier. "True to their name, Cypherpunk is backing the builders who will put shielded ZEC in the hands of billions. We're grateful for their support and proud to partner with them in bringing private digital money to the global mainstream." – Josh Swihart, CEO of ZODL The investment in ZODL is highly synergistic with Cypherpunk's ZEC treasury. "As ZODL makes Zcash easier to use, we expect adoption of the protocol to grow alongside demand for ZEC." – Cameron and Tyler Winklevoss Swihart joined Cypherpunk in December as a strategic advisor. Cypherpunk's current total ZEC holdings stand at 294,743.10, at an average price of $335.89, bringing the company's total network ownership to ~1.78%. "ZODL and Cypherpunk are the two most important companies in privacy. We're excited to embark together on this mission of accelerating technology that defends self-sovereignty and secures human freedom." – Will McEvoy, Chief Investment Officer of Cypherpunk About Cypherpunk Cypherpunk Technologies Inc. is a privacy technology company implementing a digital asset treasury strategy anchored by Zcash and, through its subsidiary Leap Therapeutics, Inc., is developing novel therapies for patients with cancer. The Company is aiming to build long-term shareholder value by acquiring ZEC, participating in the development of privacy technologies and Zcash, and continuing the development of sirexatamab and FL-501 to treat patients with cancer. For more information about the Company, visit our websites at and or view our public filings with the SEC that are available via EDGAR at or via . About Winklevoss Capital Winklevoss Capital is an investment firm founded in 2012 by Cameron and Tyler Winklevoss that invests in frontier technologies. FORWARD-LOOKING STATEMENTS This press release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements generally can be identified by the use of words such as "anticipate," "expect," "plan," "could," "may," "will," "believe," "estimate," "forecast," "goal," "project," and other words of similar meaning. Forward-looking statements address various matters including statements relating to the investment in Zcash Open Development Lab ("ZODL"), ZEC, or digital assets held or to be held by the Company, the expected future market, price and liquidity of ZEC or other digital assets the Company acquires, the macro and political conditions surrounding Zcash or digital assets, the Company's plan for value creation and strategic advantages, market size and growth opportunities, regulatory conditions, competitive position and the interest of other corporations in similar business strategies, technological and market trends, and future financial condition and performance. Risks and uncertainties of the digital asset treasury strategy include, among others: (a) the risk that the Company will fail to realize the anticipated benefits of the investment in ZODL and the digital asset treasury strategy; (b) changes in business, market, financial, political and regulatory conditions; (c) risks relating to the Company's operations and business, including the highly volatile nature of the price of cryptocurrencies, including ZEC; (d) the risk that the price of the Company's Common Stock may be highly correlated to the price of ZEC or other digital assets that it holds; (e) risks related to increased competition in the industries in which the Company does and will operate; (f) risks relating to significant legal, commercial, regulatory and technical uncertainty regarding digital assets generally; and (g) risks relating to the treatment of crypto assets for U.S. and foreign tax purposes. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. The Company may not actually achieve the forecasts disclosed in such forward-looking statements, and you should not place undue reliance on such forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in the Company's most recent Annual Report on Form 10-K filed with the SEC, or as may be included in other reports or information we file with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in its subsequent filings with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither the Company, nor any of its affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date hereof. CONTACT: Douglas E. Onsi President & Chief Executive Officer Cypherpunk Technologies Inc. 617-714-0360 [email protected] For Media: Jacqueline Ortiz Ramsay It Factor Strategies 954-294-3249 [email protected] For Investors: Matthew DeYoung Investor Relations Argot Partners 212-600-1902 [email protected] SOURCE Cypherpunk Technologies Inc. 21% more press release views with Request a Demo

20 Oct 2025

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Leap Therapeutics Presents Final Data from DeFianCe Study at ESMO 2025

Sirexatamab demonstrated statistically significant improvement in PFS and OS in DKK1-high population Increasing DKK1 levels further improved PFS, OS, and ORR advantage for the Sirexatamab Arm Leap to continue supporting development of sirexatamab in DKK1-high CRC patients CAMBRIDGE, Mass., Oct. 20, 2025 /PRNewswire/ -- Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today announced final results from Part B of the DeFianCe study (NCT05480306), a Phase 2 study of sirexatamab (DKN-01), an anti-DKK1 monoclonal antibody, in combination with bevacizumab and chemotherapy (Sirexatamab Arm) compared to bevacizumab and chemotherapy (Control Arm) in patients with microsatellite stable (MSS) colorectal cancer (CRC) who have received one prior systemic therapy for advanced disease. The final clinical results were presented on behalf of the DeFianCe study investigators by Zev Wainberg, MD, Professor of Medicine and Co-Director of the GI Oncology Program at UCLA in a Mini Oral session at the European Society for Medical Oncology (ESMO) Congress 2025 in Berlin, Germany. "Circulating DKK1 is a negative prognostic factor and elevated in patients with advanced, metastatic CRC. The data presented at ESMO demonstrate that sirexatamab, which binds to and removes free DKK1, has significant potential to provide a survival benefit for CRC patients who have high DKK1 levels and who are likely to have poor outcomes receiving the current standard of care alone," said Dr. Wainberg. "Sirexatamab has the potential to be a valuable addition to the CRC treatment paradigm as a targeted therapeutic for patients with high DKK1 and should move forward to be evaluated in a biomarker-focused registrational trial." The DeFianCe study was a two part, open-label, multi-country study. Part A of the DeFianCe study enrolled 33 patients, including a significant number of patients who had early progression on first-line therapy, previous exposure to bevacizumab, tumors with RAS mutations, or liver and lung metastases. The study expanded into a 188 patient Part B randomized controlled trial. The primary objective of the study was progression-free survival PFS. Secondary objectives included objective response rate (ORR), duration of response, and overall survival (OS). A key pre-defined exploratory population was those patients who had high levels of circulating DKK1, as measured by a biomarker assay. Key Part B DeFianCe Study Findings: Across the DKK1-high (upper median) patients (n=88): ORR was 38.0% in the Sirexatamab Arm compared to 23.7% ORR in the Control Arm. mPFS was 9.03 months in the Sirexatamab Arm compared to 7.06 months in the Control Arm, Hazard Ratio (HR) 0.61, p-value = 0.0255. mOS was not reached in the Sirexatamab Arm compared to 14.39 months in the Control Arm, HR 0.42, p-value = 0.0118. Across the DKK1-high (upper quartile) patients (n=44): ORR was 44.0% in the Sirexatamab Arm compared to 15.8% ORR in the Control Arm. mPFS was 9.36 months in the Sirexatamab Arm compared to 5.88 months in the Control Arm, HR 0.46, p-value = 0.0168. mOS was not reached in the Sirexatamab Arm compared to 9.66 months in the Control Arm, HR 0.17, p-value < 0.001. In the full intent-to-treat population (n=188): ORR was 35.1% in the Sirexatamab Arm compared to 26.6% ORR in the Control Arm. mPFS was 9.2 months in the Sirexatamab Arm compared to 8.3 months in the Control Arm, HR 0.84, p-value = 0.1712. Event-free rate favors Sirexatamab Arm beginning at month 9 (53 vs 47%) with further separation at month 12 (34 vs 23%). Sirexatamab, in combination with chemotherapy and bevacizumab, was safe and well tolerated Overall treatment-emergent adverse effects (TEAE) profile was similar between the Sirextamab and Control Arms, suggesting sirexatamab did not impact the safety profile when combined with the standard of care. "The DeFianCe study results demonstrate the significant potential of sirexatamab in patients with advanced CRC. Patients with this aggressive cancer, particularly those with high DKK1 levels, have poor overall survival outcomes and few promising second-line or later options," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "Sirexatamab has repeatedly demonstrated its potential as a novel, first-in-class antibody targeting DKK1 that provides deep and durable benefit for patients in desperate need of new therapies. With support from a recently completed financing, Leap plans to engage with regulatory authorities over the registrational path for sirexatamab in CRC and to optimize the DKK1 biomarker diagnostic test that could be used to identify these CRC patients with poor prognosis." About Leap Therapeutics Leap Therapeutics (Nasdaq: LPTX) is focused on developing targeted and immuno-oncology therapeutics. Leap's pipeline includes sirexatamab (DKN-01), a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein, and FL-501, a humanized monoclonal antibody targeting the growth and differentiation factor 15 (GDF-15) protein. Leap initiated a digital asset treasury strategy following a $58.88 million private placement led by Winklevoss Capital, aiming to build long-term shareholder value and continue the development of sirexatamab and FL-501. For more information about Leap Therapeutics, visit or view our public filings with the SEC that are available via EDGAR at or via . FORWARD-LOOKING STATEMENTS This press release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements generally can be identified by the use of words such as "anticipate," "expect," "plan," "could," "may," "will," "believe," "estimate," "forecast," "goal," "project," and other words of similar meaning. These forward-looking statements, including statements regarding the potential safety, efficacy, and regulatory and clinical progress of sirexatamab; regulatory feedback that Leap may receive from U.S. Food and Drug Administration (FDA) or equivalent foreign regulatory agency or from site institutional review boards; the intended use of proceeds from the recent private placement offering; the assets to be held by the Company; the expected future market, price and liquidity of the digital assets the Company acquires; the macro and political conditions surrounding digital assets; and the Company's plan for value creation and performance. Each forward-looking statement contained in this press release is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statement. Applicable risks and uncertainties include, among others, any regulatory feedback that Leap may receive from FDA or equivalent foreign regulatory agency or from site institutional review boards; failure to realize the anticipated benefits of the digital asset treasury strategy; changes in business, market, financial, political and regulatory conditions; risks relating to the Company's operations and business, including the highly volatile nature of the price of cryptocurrencies; the risk that the price of the Company's common stock may be highly correlated to the price of the digital assets that it holds; risks related to increased competition in the industries in which the Company does and will operate; risks relating to significant legal, commercial, regulatory, and technical uncertainty regarding pharmaceutical development and digital assets generally; and risks relating to the treatment of crypto assets for U.S. and foreign tax purposes. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Leap may not actually achieve the forecasts disclosed in such forward-looking statements, and you should not place undue reliance on such forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Leap's most recent Annual Report on Form 10-K filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in its subsequent filings with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither Leap, nor any of its affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing Leap's views as of any date subsequent to the date hereof. CONTACT: Douglas E. Onsi President & Chief Executive Officer Leap Therapeutics, Inc. 617-714-0360 [email protected] Matthew DeYoung Investor Relations Argot Partners 212-600-1902 [email protected] SOURCE Leap Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultPhase 2ASCOImmunotherapy

100 Deals associated with Sirexatamab

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Adenocarcinoma of large intestine	Phase 2	United States	Cypherpunk Technologies, Inc.	30 Aug 2022
Adenocarcinoma of large intestine	Phase 2	Germany	Cypherpunk Technologies, Inc.	30 Aug 2022
Adenocarcinoma of large intestine	Phase 2	South Korea	Cypherpunk Technologies, Inc.	30 Aug 2022
Advanced Colorectal Adenocarcinoma	Phase 2	United States	Cypherpunk Technologies, Inc.	30 Aug 2022
Advanced Colorectal Adenocarcinoma	Phase 2	Germany	Cypherpunk Technologies, Inc.	30 Aug 2022
Advanced Colorectal Adenocarcinoma	Phase 2	South Korea	Cypherpunk Technologies, Inc.	30 Aug 2022
Gastroesophageal junction adenocarcinoma	Phase 2	United States	BeOne Medicines Ltd.	29 Jul 2020
Gastroesophageal junction adenocarcinoma	Phase 2	United States	Cypherpunk Technologies, Inc.	29 Jul 2020
Gastroesophageal junction adenocarcinoma	Phase 2	Germany	BeOne Medicines Ltd.	29 Jul 2020
Gastroesophageal junction adenocarcinoma	Phase 2	Germany	Cypherpunk Technologies, Inc.	29 Jul 2020

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05480306 (DeFianCe, ESMO2025)	Phase 2	Microsatellite Instability cancer Second line MSS \| BRAF wildtype	188	Sirexatamab (DKN-01) + FOLFIRI/FOLFOX + bevacizumab	poncbppccf(nrfqmzzfxc) = hzymkmgxvh pqqwckxuxw (lxklluxibv ) View more	Positive	17 Oct 2025
				FOLFIRI/FOLFOX + bevacizumab	poncbppccf(nrfqmzzfxc) = yxqqpdebfx pqqwckxuxw (lxklluxibv ) View more
NCT04363801 (DisTinGuish, Pubmed) Manual	Phase 2	Gastroesophageal junction adenocarcinoma Second line DKK1 Expression	52	DKN-01+tislelizumab	bjbcclxmzk(nrpvrymrkf) = dcfyvnhnuy rzysntxmas (jdvmpdpzkr ) Met View more	Positive	10 Jul 2025
NCT05480306 (DeFianCe, Company_Website) Manual	Phase 2	Colorectal Cancer Second line DKK1 Expression \| Microsatellite Stable (MSS)	188	Sirexatamab + bevacizumab + chemotherapy (high DKK1 levels)	squbmozzty(opbzxtwmum) = genvqyhekp odxwvhjgnt (dgqabejyih ) View more	Positive	26 Mar 2025
				bevacizumab + chemotherapy (high DKK1 levels)	squbmozzty(opbzxtwmum) = lhbwqkybfp odxwvhjgnt (dgqabejyih ) View more
NCT04363801 (DisTinGuish, PRNewswire) Manual	Phase 2	Gastrooesophageal junction cancer \| Advanced gastric carcinoma First line HER2 Negative	170	Sirexatamab + tislelizumab + chemotherapy	mmmvfmqiyc(jbjyijdcai) = zuvkglsjhf oxvlbqmtiq (kbwbueuqmd ) View more	Positive	28 Jan 2025
				Tislelizumab + chemotherapy	mmmvfmqiyc(jbjyijdcai) = ycjkhqaqui oxvlbqmtiq (kbwbueuqmd ) View more
NCT05480306 (DeFianCe, PRNewswire) Manual	Phase 2	Microsatellite Stable Colorectal Carcinoma Second line Microsatellite Stable (MSS)	188	Sirexatamab + bevacizumab + chemotherapy	jzhjmmqjzn(mwkgnmkgws) = zdtkbtcoop vctinllwsv (abazhujnrp ) View more	Positive	28 Jan 2025
				bevacizumab + chemotherapy	jzhjmmqjzn(mwkgnmkgws) = rauhwkrmat vctinllwsv (abazhujnrp ) View more
NCT04363801 (DisTinGuish, Pubmed \| J Clin Oncol)	Phase 2	Advanced Gastroesophageal Junction Adenocarcinoma First line DKK1-high tumor \| DKK1-low tumor	25	DKN-01	nldapqtfcj(jqeekvlhdt) = gvqtzilnlq ubzzlcgoer (byhovxqoxq, 49.8 - 89.3) View more	Positive	21 Oct 2024
NCT05480306 (DeFianCe, NEWS) Manual	Phase 2	Microsatellite Stable Colorectal Carcinoma	33	DKN-01	ywbilkjuts(iagtugzecr) = atulnhofgz toigpxokld (iimsopoapu ) View more	Positive	03 Jun 2024
				DKN-01 (左结肠肿瘤)	ywbilkjuts(iagtugzecr) = bksvyfoczk toigpxokld (iimsopoapu ) View more
NCT04057365 (CTgov)	Phase 2	Advanced Bile Duct Carcinoma	15	Nivolumab+DKN-01 (DKN 01 and Nivolumab Safety Run in)	irskzrghaf = mqydmbnbwj cxxbqxnnli (vhovzxsowo, luhdcvpjyj - nhpxsjgpbh) View more	-	10 Apr 2024
				Nivolumab+DKN-01 (DKN 01 and Nivolumab)	urmpkuhttl(mszfzvkjop) = jaqwuogcax paiqgyvmfq (clxdvqffei, nhyoctvylc - wkimcsfvme) View more
NCT05480306 (DeFianCe, ASCO_GI2024) Manual	Phase 2	Microsatellite Stable Colorectal Carcinoma Second line Microsatellite Stable (MSS)	33	DKN-01 + FOLFIRI/FOLFOX + bevacizumab	dvpiovjkro(xushehfrmf) = umkforcuft zmprhavdvu (nbajyygwhw ) View more	Positive	18 Jan 2024
NCT03837353 (CTgov)	Phase 1/2	Advanced Prostate Carcinoma	18	DKN-01+Docetaxel (Cohort 1A.1 (DKN-01 300mg, Docetaxel 75 mg/m2))	gfallkbhgg(onbbzynevv) = zpadqupdai ganwljoldx (apstnajazw, 0) View more	-	18 Dec 2023
				DKN-01+Docetaxel (Cohort 1A.2 (DKN-01 600mg, Docetaxel 75 mg/m2))	gfallkbhgg(onbbzynevv) = qgbyvrajpd ganwljoldx (apstnajazw, 0) View more

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