On April 11, 2025 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast cancers (mBC), and Quantum Leap Healthcare Collaborative reported that in the Phase 2 clinical trial evaluating lasofoxifene as a neoadjuvant endocrine therapy in molecularly selected HR+/HER2-, locally advanced breast cancer, the investigational drug was well tolerated and demonstrated promising early activity in suppressing the Ki67 protein in both premenopausal and postmenopausal patients (Press release, Sermonix Pharmaceuticals, APR 11, 2025, View Source [SID1234651888]).

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Results from the study, an arm of the Endocrine Optimization Pilot Protocol (EOP), a sub-study of Quantum Leap’s ongoing I-SPY 2 TRIAL (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis 2), were initially shared yesterday in a poster presentation at RISE UP for Breast Cancer.

Twenty patients (10 pre- and nine postmenopausal women, and one male) were enrolled in the lasofoxifene arm of the study, during which early Ki67 suppression in premenopausal patients was seen in the absence of ovarian function suppression (OFS). Ki67 is a marker that measures how fast cancer cells are dividing.

"Lasofoxifene continued to demonstrate a strong tolerability profile while showing promising Ki67 suppression in this Phase 2 study, supporting our plans to further explore its potential in the neoadjuvant setting," said Dr. David Portman, Sermonix founder and chief executive officer. "We are currently studying lasofoxifene in the ELAINE-3 Phase 3 combination study with abemaciclib in the ESR1-mutated metastatic breast cancer setting. We are excited to see it continue to demonstrate broad potential while offering unique quality of life benefits for people confronted with breast cancer."

Patients were enrolled in the I-SPY 2 arm from March 2023 to May 2024. Median total days of treatment was 154 days. At the time of data analysis, three patients were still on treatment and two discontinued treatment due to physician or patient preference.

Median Ki67 expression went from 10% at baseline (range 1.0-40%) to 4% (1.0-18.0%) at Week 3. At three weeks, Ki67 expression was suppressed to <10% in 14 out of 16 (88%) patients, and to <2.7% in 6 out of 16 (38%) patients. Adverse events (AEs) were all grade 1-2. Most common AEs include hot flushes (65%), constipation (40%), fatigue (40%) and nausea (25%).

"The I-SPY 2 EOP provides a biomarker-rich platform to test novel endocrine agents in the neoadjuvant setting in a molecularly selected group of patients with tumors that are predicted to have little to no benefit from chemotherapy," said Dr. Jo Chien, principal investigator of the sub-study. "Lasofoxifene has demonstrated significant activity based on early Ki67 suppression, not only in postmenopausal women, but also in 10 premenopausal women without concomitant ovarian function suppression, with baseline Ki67 of 12.5% (1.0-40.0%) going to 3.0% (1.0-15%) at Week 3. It is exciting to see that lasofoxifene is well-tolerated even in our youngest patients who are often most impacted by the debilitating side effects of current standard endocrine therapy options."

Quantum Leap partners with a consortium that includes the U.S. Food and Drug Administration (FDA), industry, patient advocates, philanthropic sponsors and clinicians from 41 major U.S. cancer research centers.

About Lasofoxifene
Lasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with a CDK4/6 inhibitor in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies, with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc., has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue selective oral endocrine therapy, could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.

On April 11, 2025 Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of novel oncolytic immunotherapies, reported the grant of inducement equity awards to newly hired non-executive employees (Press release, Replimune, APR 11, 2025, View Source [SID1234651887]).

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The Company granted equity awards to 53 employees as a material inducement to commencing their employment with the Company. The inducement awards consist of non-qualified stock options to purchase an aggregate of 98,450 shares of the Company’s common stock and restricted stock units representing an aggregate of 155,875 shares of the Company’s common stock. Each option has an exercise price of $7.49 per share, which is equal to the closing price of the Company’s common stock on April 7, 2025 (the "Date of Grant"). Each option has a 10-year term and will vest over four years, with 25% of the underlying shares vesting on the one-year anniversary of the Date of Grant, and the remainder vesting in monthly installments for three years thereafter. The restricted stock units vest in approximately four equal annual installments beginning on May 15, 2026.

The aforementioned inducement awards were approved by the compensation committee of the Company’s board of directors in reliance on the employment inducement exception under Nasdaq Listing Rule 5635(c)(4). While the inducement awards were granted outside of the Company’s 2018 Equity Incentive Plan, the awards will have terms and conditions consistent with those set forth under such plan.

On April 11, 2025 Circio Holding ASA (OSE: CRNA), a biotechnology company developing powerful circular mRNA technology for next generation nucleic acid medicine, reported that its subsidiary Circio AB has entered a research evaluation agreement with Lonza, one of the world’s largest contract development and manufacturing organizations (Press release, Circio, APR 11, 2025, View Source [SID1234651886]).

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The research license enables Circio to test the circVec circular mRNA expression technology in Lonza’s proprietary transient expression system for protein production. Further updates will follow as necessary as the project progresses.

On April 10, 2025, Cue Biopharma, Inc. (the "Company") reported to have entered into a Collaboration and License Agreement (the "Collaboration and License Agreement") with Boehringer Ingelheim International GmbH ("BI") to research, develop and commercialize differentiated B cell depletion molecules, including the Company’s CUE-501 product candidate, which the Company is developing as a B cell depletion therapy for autoimmune diseases (Filing, Cue Biopharma, APR 10, 2025, View Source [SID1234651913]).

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Under the terms of the Collaboration and License Agreement, BI and the Company will conduct collaborative research focused on CUE-501 during a four year period or, if earlier, the completion of activities under the research plans (the "Research Term"). In addition to, or instead of, CUE-501, BI may elect, at its sole discretion, to include additional or alternative compounds targeted at B cell depletion. BI will have an exclusive, royalty-bearing, worldwide, sublicensable license, under the Company’s applicable patents and know-how, to develop, manufacture and commercialize such compounds and their derivatives ("Licensed Products") for all uses, and BI shall be responsible for all further research, preclinical and clinical development, manufacturing, regulatory approvals, and commercialization of Licensed Products at its expense. During the Research Term, the Company is prohibited from developing or commercializing any molecule for applications in B cell depletion.

Pursuant to the terms of the Collaboration and License Agreement, the Company will receive an upfront payment of $12.0 million and will be eligible to receive up to an aggregate of approximately $345.0 million in success-based research, development and commercial milestone payments, beginning with two preclinical development milestones, as well as royalty payments on net sales. The royalty payments will be subject to reduction due to patent expiration, payments made under certain licenses for third-party intellectual property and generic competition. During the Research Term, BI will also make research support payments to the Company.

The Collaboration and License Agreement will continue, on a product-by-product and country-by-country basis, until the expiration of the applicable royalty term, unless earlier terminated. BI has the right to terminate the Collaboration and License Agreement for any reason after a specified notice period. Each party has the right to terminate the Collaboration and License Agreement on account of the other party’s bankruptcy or material, uncured breach.

The foregoing description of the Collaboration and License Agreement and the transactions contemplated thereby does not purport to be complete and is subject to, and qualified in its entirety by reference to, the complete text of the Collaboration and License Agreement, which will be filed with the U.S. Securities and Exchange Commission as an exhibit to the Company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2025.

Amendment to Einstein License Agreement

On April 10, 2025, the Company entered into an amendment (the "Amendment") to its Amended and Restated License Agreement, dated July 31, 2017, with Albert Einstein College of Medicine ("Einstein"), as amended by the First Amendment to the Amended and Restated License Agreement with Einstein, dated October 30, 2018, and the Second Amendment to the Amended and Restated License Agreement with Einstein, dated January 13, 2024 (as so amended, the "Einstein License"). Pursuant to the Amendment, Einstein consented to the Company’s entry into the Collaboration and License Agreement and granted the Company the right to sublicense to BI. In addition, Einstein and the Company agreed to amend specified upstream payment obligations that may be owed to Einstein by the Company, solely in connection with the sublicense to BI.

The foregoing description of the Amendment does not purport to be complete and is subject to, and qualified in its entirety by reference to, the complete text of the Amendment, which will be filed with the U.S. Securities and Exchange Commission as an exhibit to the Company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2025.

On April 10, 2025 Arima Genomics, Inc. (Arima), a company leveraging 3D genomics to reveal actionable insights that will empower researchers and clinicians to improve human health, reported the publication of a study in The Journal of Molecular Diagnostics showing its proprietary technology detected clinical structural variants missed by conventional clinical tests (Press release, Arima Genomics, APR 10, 2025, View Source [SID1234651881]). Conducted in collaboration with researchers from NYU Langone Health, Weill Cornell School of Medicine, Scripps Cancer Center, Moores Cancer Center at the University of California, San Diego, and the University of Colorado School of Medicine, the retrospective study found that Arima’s technology identified gene fusions or rearrangements in 71% of cases where standard molecular techniques failed. Importantly, in 14% of these cases where no driver had been found by other techniques, a clinically actionable variant was identified.

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"Structural variants like gene fusions are central to cancer diagnostics, but current clinical tests miss many events that are crucial to diagnostic and therapeutic decision-making," said Matija Snuderl, MD, Professor of Pathology and Director of Molecular Pathology and Diagnostics at NYU Langone Health and corresponding author of the study. "Arima’s technology allowed us to detect hidden variants — many of them clinically actionable — in cases where standard tests came up empty. This provided important information to our understanding of the cancers and directly impacted patient care in some cases, confirming diagnoses and improving treatment options."

In the current study, researchers analyzed 71 formalin-fixed, paraffin-embedded (FFPE) specimens across ten solid tumor types, comparing results using Arima’s technology to results from prior clinical testing via fluorescence in situ hybridization (FISH), RNA sequencing, and DNA sequencing. Arima’s technology demonstrated 98% concordance with positive cases detected by conventional methods. Among the 14 samples negative by standard techniques, structural variants in 71% (10/14) were uncovered. Among these:

14% (2/14) harbored gene fusions or rearrangements listed in current clinical guidelines, directly impacting patient care.
14% (2/14) involved rearrangements affecting therapeutically targetable genes, potentially expanding treatment options even though they are not currently classified as actionable in guidelines.
Several cases described in the paper highlight the utility of Arima’s technology in achieving proper diagnosis and enabling appropriate therapeutic intervention.

For example, one young patient experiencing seizures was initially believed to have a non-tumorous brain abnormality called focal cortical dysplasia. DNA methylation results hinted at a possible low-grade glioma but remained inconclusive following two commercial RNA sequencing panels, which did not identify a diagnostic fusion for low-grade glioma. Only when the patient’s sample was analyzed with Arima’s technology did doctors detect a MYBL1::MAML2 fusion, confirming a low-grade glioma diagnosis and allowing the patient to receive the proper treatment.

In another case involving a pediatric glioblastoma patient, Arima’s technology detected a complex rearrangement involving PD-L1 that standard RNA and DNA tests missed. Later confirmatory testing using immunohistochemistry showed that PD-L1 was overexpressed on the tumor cells and provided an opportunity for immunotherapy treatment based on PD-L1 expression—an option that would have been overlooked without the enhanced sensitivity of Arima’s technology.

Arima’s technology uses high-throughput chromosome conformation capture (Hi-C) sequencing to map the spatial architecture of the genome within FFPE tumor samples. By revealing how DNA is organized in 3D space, it detects gene fusions, rearrangements, and translocations with 100-1000 times higher signal compared to standard methods like RNA or DNA sequencing or FISH, resulting in superior sensitivity.

Beyond actionable findings, the study also described how Arima’s technology offers deep insights into tumor biology by detecting complex genomic rearrangements such chromothripsis and extrachromosomal DNA (ecDNA). Recent literature has suggested ecDNA may be involved in treatment resistance, but may also be targetable with on-market therapies.

"Our technology provides a unique method to amplify the signal of rearrangements," said Anthony Schmitt, PhD, Senior Vice President of Science at Arima Genomics. "This allows us to capture structural rearrangements with far greater sensitivity and detail in FFPE samples—bringing both immediate clinical benefit and new avenues for research."

This new publication adds to a growing body of clinical evidence supporting Arima’s technology, building on recent studies conducted in collaboration with institutions such as Yale School of Medicine, Harvard Medical School, and Seattle Children’s Hospital.