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Leap Therapeutics Reports Updated Clinical Data from Sirexatamab Colorectal Cancer Study and Announces Exploration of Strategic Alternatives

On June 23, 2025 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported updated 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 advanced microsatellite stable (MSS) colorectal cancer (CRC) who have received one prior systemic therapy for advanced disease (Press release, Leap Therapeutics, JUN 23, 2025, View Source [SID1234654056]). Due to the Company’s financial position, Leap’s Board of Directors is taking further steps to preserve capital and has initiated a process to explore strategic options to preserve and maximize shareholder value.

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"Sirexatamab demonstrated a statistically significant benefit in patients with high levels of DKK1, no prior exposure to anti-VEGF therapy, or liver metastasis, with a positive trend on ORR and PFS in the full second-line CRC population. With the additional patient follow-up, we believe that the objectives of the DeFianCe study have been achieved. On behalf of everyone at Leap, I thank all the patients and physicians who have participated in our sirexatamab clinical trials," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "However, due to current market conditions, we have decided to wind-down the DeFianCe clinical trial and further reduce internal expenses. In parallel, we have initiated a review of the full range of strategic alternatives to maximize shareholder value."

DeFianCe Study Update

In the updated analysis as of May 22, 2025, sirexatamab demonstrated a positive trend on overall response rate (ORR), by investigator assessment (IA) and blinded independent central review (BICR), and progression-free survival (PFS) in the full second-line CRC population, driven by the statistically significant benefit in patients with high levels of DKK1, no prior exposure to anti-VEGF therapy, or liver metastasis.

· Across the intent-to-treat population (n=188):

Sirexatamab Arm
(n=94) Control Arm
(n=94)
Median PFS 9.2 months 8.31 months HR 0.84
95% CI: 0.57, 1.22
p = 0.1749
ORR by IA 35.1% 26.6% p = 0.1009
ORR by BICR 33.0% 20.2% P = 0.0203
Remaining on study drug 21 15

· In patients with high DKK1 levels (upper quartile, n=44):

Sirexatamab Arm
(n=25) Control Arm
(n=19)
Median PFS 9.36 months 5.88 months HR 0.47
95% CI: 0.22, 1.01
p = 0.0237
ORR by IA 44.0% 15.8% p = 0.0149
ORR by BICR 40.0% 15.8% p = 0.0301
Median OS Not Yet Reached 9.66 months HR 0.19
95% CI: 0.05, 0.73
p = 0.0037
Remaining on study drug 7 1

· In patients with DKK1 levels above the median (upper median, n=88):

Sirexatamab Arm
(n=50) Control Arm
(n=38)
Median PFS 9.03 months 7.23 months HR 0.56
95% CI: 0.33, 0.94
p = 0.0146
ORR by IA 38.0% 23.7% p = 0.0706
ORR by BICR 40.0% 15.8% p = 0.0039
Median OS Not Yet Reached 14.39 months HR 0.48
95% CI: 0.2, 1.16
p = 0.0475
Remaining on study drug 12 3

· In patients who had not received prior anti-VEGF therapy (n=95):

Sirexatamab Arm
(n=49) Control Arm
(n=46)
Median PFS 11.2 months 8.34 months HR 0.61
95% CI: 0.35, 1.06
p = 0.0383
ORR by IA 55.1% 32.6% p = 0.0116
ORR by BICR 44.9% 26.1% p = 0.0252
Median OS Not Yet Reached Not Yet Reached HR 0.47
95% CI: 0.14, 1.6
p = 0.1069
Remaining on study drug 15 5

· In patients with liver metastases (n=138):

Sirexatamab Arm
(n=73) Control Arm
(n=65)
Median PFS 9.03 months 7.26 months HR 0.7
95% CI: 0.46, 1.06
p = 0.0443
ORR by IA 37.0% 27.7% p = 0.1203
ORR by BICR 30.1% 24.6% p = 0.233
Median OS Not Yet Reached 15.74 HR 0.69
95% CI: 0.33, 1.43
p = 0.1584
Remaining on study drug 14 6

Corporate Update

Leap is taking additional steps to reduce spending and preserve capital. Over the next two months as the DeFianCe study completes, the Company will implement a workforce reduction of approximately 75%. The total cash payments and costs related to this reduction in force, including severance payments, are estimated to be approximately $3.2 million. The majority of these costs will be recognized in the third quarter of 2025. The Company’s cash and cash equivalents totaled $32.7 million as of March 31, 2025.

Leap has initiated a process to explore strategic alternatives to preserve and maximize shareholder value, including leveraging its cash balance and exploring potential sale or partnership opportunities for sirexatamab and FL-501. The Company’s Board of Directors has approved the engagement of Raymond James & Associates, Inc. to serve as exclusive financial advisor to assist in the strategic evaluation process.

Multi-institutional team awarded NCI grant to open novel AML trial

On June 23, 2025 The University of Cincinnati Cancer Center (UC), The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) and Jabez Biosciences reported their partnering to open a new phase 1 clinical trial studying JBZ-001, a potential new treatment for acute myeloid leukemia (AML) (Press release, Jabez Biosciences, JUN 23, 2025, View Source [SID1234654054]).

The trial is supported by a more than $3.4 million grant from the National Institutes of Health’s National Cancer Institute awarded to UC and OSUCCC – James. It also offers a new approach for research and industry partnerships that will benefit patients by improving efficiency for the therapeutic pipeline.

AML is diagnosed in more than 20,000 individuals per year in the U.S., with more than half of these patients estimated to die each year. This high mortality rate emphasizes the need for new treatments, and JBZ-001 has demonstrated best in class pharmaceutical properties with worldwide patent protection.

The development of the trial drug is unique, as it was initially developed as part of an undergraduate chemistry class at Hendrix College in Arkansas under the mentorship of Thomas Goodwin, PhD. The class was focused on developing small-molecule inhibitors of dihydroorotate dehydrogenase (DHODH), a critical pathway for cancer cell proliferation, using a novel synthesis method called the Suzuki reaction.

The project progressed when Goodwin approached John C. Byrd, MD, a Hendrix alumnus, board member and former student of his. Byrd, along with Erin Hertlein, PhD, and Ola Elgamal, PhD, performed preclinical testing of the drug at OSU before moving to UC in 2021.

In collaboration with the Drug Development Institute at OSU, many iterations of the initial compounds (originally referred to as the HOSU series for Hendrix and OSU) were tested until HOSU-53 was developed as the lead candidate for human therapy trials. HOSU-53 was licensed by Jabez Biosciences in 2024 and then became JBZ-001.

The development of JBZ-001 marks a significant milestone in Jabez Biosciences’ "bench-to-bedside" academic collaboration, with the compound receiving Investigational New Drug approval for first-in-human trials in solid tumors and non-Hodgkin lymphoma in 2024. A Phase 1 trial is currently underway at the OSUCCC – James.

"Jabez Biosciences is extremely proud and grateful to be partnering with the University of Cincinnati Cancer Center and The James Comprehensive Cancer Center at OSU in a new JBZ-001 phase 1 trial in AML," said Tamara Jovonovich, PhD, chief executive officer of Jabez Biosciences. "The excitement around this potential treatment is growing exponentially and this collaboration exemplifies the commitment each has to realizing the potential of JBZ-001 in oncology care."

The Phase 1 clinical study in AML will open at UC and OSU in 2026. This study aims to assess the safety, tolerability and preliminary efficacy of JBZ-001 in patients with AML. Co-principal investigators Byrd, Hertlein and OSU’s Alice Mims, MD, and Christopher Coss, PhD, will partner to define pharmacokinetic and pharmacodynamic exposure-response relationships in patients with AML treated with JBZ-001.

"We are excited to move JBZ-001 from the bench to the clinic," said Byrd, a University of Cincinnati Cancer Center physician-researcher and the Gordon and Helen Hughes Taylor Professor and Chair of the Department of Internal Medicine at the UC College of Medicine. "This three-institution collaboration has been phenomenal. We are grateful for the NCI support to do this trial."

Additional studies will be performed to study the specific mechanism(s) of action, and single cell sequencing technologies will explore potential resistance mechanisms.

"We are thrilled to work with UC and Jabez Biosciences to explore JBZ-001 as a potential new therapeutic option for patients with AML," said Mims, professor of internal medicine and co-leader of the OSUCCC – James Leukemia and Hematologic Malignancies Program. "Though there have been advances made in the past 10 years for new therapeutic options for patients with AML, most patients are still not cured of their disease. Novel treatments to improve patient outcomes remain a high need in these patient populations."

At UC, the trial will join more than 40 additional open trials for blood cancers operating at the Blood Cancer Healing Center. Other UC investigators involved with this study include Emily Curran, MD, and Shesh Rai, PhD.

Illumina to acquire SomaLogic, accelerating its proteomics business and advancing the company’s multiomics strategy

On June 23, 2025 Illumina, Inc. (NASDAQ: ILMN) reported it has entered into a definitive agreement with Standard BioTools (NASDAQ: LAB) under which Illumina will acquire SomaLogic, a leader in data-driven proteomics technology, and other specified assets for $350 million in cash payable at closing, subject to customary adjustments, plus up to $75 million in near-term performance-based milestones and performance-based royalties (Press release, Illumina, JUN 23, 2025, View Source [SID1234654052]).

"The acquisition of SomaLogic will enhance Illumina’s presence in the expanding proteomics market and advance the multiomics strategy we announced in 2024. This will strengthen the value of the NovaSeq X product today and unlock greater capabilities in the future," said Jacob Thaysen, chief executive officer of Illumina. "Illumina and SomaLogic have partnered closely for more than three years, and this combination increases our ability to serve our customers and accelerate our technology roadmap towards advanced biomarker discovery and disease profiling."

This transaction builds on a co-development agreement Illumina established with SomaLogic in December 2021 to bring the SomaScan Proteomics Assay onto Illumina’s high-throughput next-generation-sequencing (NGS) platforms. Illumina Protein Prep is currently in use with nearly 40 early-access customers globally and will become available to all customers starting in the third quarter of 2025. Combining SomaLogic’s proteomics technology with Illumina’s scalable NGS ecosystem, DRAGEN software, and Illumina Connected Multiomics will accelerate the technology development roadmap for proteomics and reduce time and cost of proteomic research.

"We are taking the scalability of NGS into proteomics," continued Thaysen. "Illumina will remain an open, accessible, and enabling NGS platform. The Company is committed to maintaining and supporting its existing proteomics partnerships as well as continuing to develop the sequencing ecosystem and supporting a wide variety of multiomics solutions."

Scientific evidence* presented over the past year demonstrates the strength of SomaLogic’s proteomics offerings in the areas of plexity, scalability, and technical reproducibility. In addition, researchers can generate significant and pivotal insights with high sensitivity, high throughput, and thousands of protein markers in a single experiment.

SomaLogic has approximately 250 employees worldwide working in commercial, R&D, lab operations, manufacturing, and other roles. The company’s Boulder, Colorado, facilities—including a CLIA- and CAP-certified lab, office, and manufacturing space—will be part of the purchase. SomaLogic has a global footprint serving customers.

This transaction brings SomaLogic’s aptamer-based affinity proteomics platform into Illumina’s portfolio, enhancing Illumina’s presence in a high-growth area within the proteomics market. The kitted NGS-based panels business will add a high-margin consumables revenue stream. Based on the projected closing date, Illumina expects this business to become profitable in 2027 on a non-GAAP operating income basis, and for non-GAAP operating margins to be in line with Illumina in 2028.

Completion of the transaction is subject to customary closing conditions, including the receipt of required regulatory clearance. The parties intend to make the necessary filing under the Hart-Scott-Rodino Act in the United States in due course. Illumina expects to close the transaction in the first half of 2026. Until then, the companies will continue to operate as separate and independent entities.

Goldman Sachs and Co. LLC is serving as financial advisor and Cravath, Swaine & Moore LLP is serving as legal advisor to Illumina. Centerview Partners LLC is serving as financial advisor to Standard BioTools, and Freshfields LLP and Richards, Layton & Finger P.C. are serving as its legal counsel. UBS Investment Bank is serving as financial advisor to the Special Committee of the Standard BioTools Board of Directors.

Enterome presents positive Phase 2 interim results in relapsed/refractory indolent non-Hodgkin lymphoma after EO2463 OncoMimics™ immunotherapy treatment at ICML

On June 23, 2025 Enterome SA, a clinical-stage company developing first-in-class OncoMimics immunotherapies to treat cancer, reported positive interim results for its OncoMimics immunotherapy EO2463 from Cohorts 1 and 4 of the ongoing open label Phase 1/2 SIDNEY trial in patients with indolent non-Hodgkin lymphoma (iNHL), at the International Conference on Malignant Lymphoma (ICML) in Lugano (Press release, Enterome, JUN 23, 2025, View Source [SID1234654050]). Interim data including 24 patients with follicular and marginal zone lymphoma (relapsed/refractory iNHL) showed that treatment with EO2463 in combination with lenalidomide and rituximab (R2) was well tolerated and demonstrated encouraging signs of efficacy that appear better than historical data in similar patients treated with R2.

Importantly, EO2463 showed direct anti-lymphoma activity, including partial responses to the OncoMimics monotherapy, during the first six weeks of the study, a short time period during which just the first three doses of EO2463 were administered, before the protocol called for initiation of treatment with lenalidomide (followed subsequently by adding rituximab). Moreover, once lenalidomide and rituximab were added, the effect of EO2463 appeared to support a deepening of responses, resulting in a complete response rate of 60%, higher than would have been expected with R2 alone, based on historical data[1].

Pierre Belichard, CEO of Enterome said, "The EO2463 interim results are very encouraging, demonstrating exceptional tolerability for an active immunotherapy, and showing a clear signal that the combination with R2 can provide more robust responses in this patient population over R2 alone. This is consistent with the strong response rate we observed with EO2463 monotherapy in patients with low tumor burden disease, the so-called ‘watch-and-wait’ population, included in Cohort 2 of SIDNEY. While we plan to focus our near-term efforts on initiating a registrational Phase 3 trial of EO2463 for the watch-and-wait population, this evidence of a complementary effect in combination with R2 in relapsed/refractory iNHL is very exciting and offers new hope for this patient group, most of whom still see insufficient efficacy with available therapeutics."

EO2463 is designed to expand pre-existing memory CD8+ T cells recognizing non-self-protein sequences from gut bacteria, which mimic several purposefully selected B cell antigens. The interim SIDNEY data from Cohorts 1 and 4 presented at ICML show fast, robust, and durable expansion of the specific CD8+ T cells that were active against EO2463 mimic peptides and the targeted B cell epitopes. Most important, the magnitude of the EO2463-driven expansion of specific CD8+ T cells correlated with the probability of complete remission upon treatment with EO2463 combined with R2 in the SIDNEY study. EO2463 in combination with lenalidomide and rituximab (R2 ) is well tolerated in patients with follicular and marginal zone lymphoma.

Jan Fagerberg, Chief Medical Officer of Enterome, said, "These early efficacy results suggest EO2463 offers additional benefit when used together with the R2 regimen in patients with relapsed/refractory iNHL. We previously reported data from Cohort 2 of SIDNEY, at ASH (Free ASH Whitepaper) in December 2024, showing that EO2463 OncoMimics monotherapy generated a 46% objective response rate in patients who are usually proposed ‘watchful waiting’ and no active anti-lymphoma therapy – and also had an excellent tolerability profile. In short, taken together, these SIDNEY data indicate that this well tolerated novel active immunotherapy may well have broad potential across hematological malignancies."

EO2463 is an innovative, off-the-shelf OncoMimics active immunotherapy that combines four synthetic peptides. These non-self, microbial-derived peptides correspond to CD8 HLA-A2 epitopes that exhibit molecular mimicry with the B lymphocyte-specific lineage markers CD20, CD22, CD37, and CD268 (BAFF receptor). It also includes the helper peptide (CD4+ epitope) universal cancer peptide 2 (UCP2).

The unique ability of EO2463 active immunotherapy to selectively target multiple B cell markers enables the destruction of malignant B lymphocytes. By ensuring broad target coverage across malignant B cells, this novel approach aims to simultaneously improve safety and maximize efficacy, reducing the tumor cells’ capacity to develop immune-resistance mechanisms such as antigen escape.

SIDNEY is an ongoing open label Phase 1/2 study that aims to assess safety, tolerability, immunogenicity, and preliminary efficacy of EO2463 monotherapy and combination therapy with lenalidomide/rituximab in up to 55 patients with follicular lymphoma and marginal zone lymphoma including four cohorts of three patient populations:

Cohort 2: patients with newly diagnosed, previously untreated low tumor burden disease, not in need of standard of care therapy, i.e., the "watch-and-wait" setting; treatment = EO2463 monotherapy
Cohort 3: patients with newly diagnosed, previously untreated low tumor burden disease, in need of therapy; treatment = EO2463 in combination with rituximab
Cohorts 1 and 4: patients with relapsed/refractory disease and at least one prior treatment; treatment = EO2463 in combination with lenalidomide and rituximab (R2)
OncoMimics are synthetically produced peptides designed in silico using AI and machine learning to mine Enterome’s extensive proprietary database of microbial bacteria. Unlike cancer antigens, OncoMimics bypass a gating process, known as thymic deletion, that prevents the immune system from mounting an attack against the "self" proteins (e.g. antigen) on tumor and blood cancer cells. Furthermore, that they trigger a more targeted, rapid and robust immune response than would otherwise be possible, because very early in human development the immune system learns to protect the body from microbiome bacteria. This means that OncoMimics call up memory CD8+ T cells that selectively target the cancer cells that carry the mimicked antigen(s). This therapeutic strategy takes inspiration from and is de-risked by emulating the gut microbiome’s causal role in certain autoimmune diseases.

OncoMimics are easy to manufacture, store, distribute and administer as an "off-the-shelf" subcutaneous injection. In clinical testing to date they have been shown to be extremely well tolerated, especially compared to other potent immunotherapies.

Cidara Announces Proposed Public Offering of Common Stock

On June 23, 2025 Cidara Therapeutics, Inc. ("Cidara") (Nasdaq: CDTX), a biotechnology company using its proprietary Cloudbreak platform to develop drug-Fc conjugate (DFC) therapeutics, reported its plans to commence an underwritten public offering, subject to market and other conditions, to issue and sell $250.0 million of shares of its common stock (Press release, Cidara Therapeutics, JUN 23, 2025, View Source [SID1234654049]). All of the shares are being offered by Cidara. In connection with the proposed offering, Cidara expects to grant the underwriters a 30-day option to purchase up to an additional 15% of the shares of its common stock sold in the public offering. There can be no assurance as to whether or when the proposed offering may be completed or as to the actual size or terms of the proposed offering.

J.P. Morgan, Morgan Stanley, Guggenheim Securities and Cantor are acting as joint book-running managers for the proposed offering.

The proposed offering is being made pursuant to a shelf registration statement on Form S-3 that was filed with the U.S. Securities and Exchange Commission (the "SEC") on May 8, 2025, and declared effective by the SEC on May 15, 2025. A preliminary prospectus supplement and accompanying prospectus relating to the proposed offering will be filed with the SEC and will be available for free on the SEC’s website located at View Source Copies of the preliminary prospectus supplement and the accompanying prospectus relating to the proposed offering may be obtained, when available, from: J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (866) 803-9204, or by email at [email protected]; Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, New York 10014, or by email at [email protected]; Guggenheim Securities, LLC Attention: Equity Syndicate Department, 330 Madison Avenue, New York, NY 10017 or by telephone at (212) 518-9544, or by email at [email protected]; or Cantor Fitzgerald & Co. by mail at Attention: Capital Markets, 110 East 59th Street, New York 10022 or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.