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Immunome to Present at the 24th Annual Needham Virtual Healthcare Conference

On April 4, 2025 Immunome, Inc. (Nasdaq: IMNM), a biotechnology company focused on developing first-in-class and best-in-class targeted cancer therapies, reported that Immunome management will participate in a fireside chat at the 24th Annual Needham Virtual Healthcare Conference on Thursday, April 10, 2025 at 12:45 p.m. Eastern Time (Press release, Immunome, APR 4, 2025, View Source [SID1234651808]).

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Interested parties can access the live audio webcast for this conference from the Investor Relations section of the company’s website at www.immunome.com. The webcast replay will be available after the conclusion of the live presentation for approximately 30 days.

SkylineDx Presents Landmark Study on Merlin CP-GEP beyond SLNB prediction: Transforming Melanoma Risk Assessment

On April 4, 2025 SkylineDx, an innovative diagnostics company specializing in molecular diagnostics for oncology, inflammatory, and infectious diseases, reported that Dr. Teresa Amaral, MD, PhD, Head of Skin Cancer Clinical Trials Center, University of Tübingen, Germany, will present groundbreaking new data at the 2025 World Congress of Melanoma (WCM) (Press release, SkylineDx, APR 4, 2025, View Source [SID1234651807]). The presentation will highlight the Merlin CP-GEP (Clinicopathologic and Gene Expression Profile) test’s ability to identify high-risk melanoma patients who did not undergo sentinel lymph node biopsy (SLNB), a critical gap in current melanoma staging methods – showing CP-GEP’s potential in predicting relapse and other long-term survival outcomes [1-2].

Key Findings from the Study:

Merlin CP-GEP test successfully stratified 930 stage I/II melanoma patients: 879 (94.5%) were Merlin Low-Risk and 51 (5.5%) were Merlin High-Risk.
Patients identified as Low-Risk showed an impressive 5-year and 10-year relapse-free survival (RFS) rate of 96% and 94.5% respectively.
Patients in the Merlin (CP-GEP) High-Risk group were around 20 times more likely to experience a recurrence, compared to the Merlin Low-Risk group. Their 5-year and 10-year RFS was 37.5% for both endpoints. Additionally, High-Risk patients showed significantly increased rates of distant metastasis and melanoma-specific death, reinforcing the clinical value of CP-GEP in identifying patients at risk for recurrence.
While SLNB remains the standard for melanoma staging, many patients classified as low-risk based on traditional methods still experience relapse or even death. The CP-GEP model, which combines gene expression data with clinical factors age and tumor thickness, effectively identified two distinct risk groups among patients who did not undergo SLNB.

Dr. Teresa Amaral shared her thoughts on the study: "The results of this study highlight the potential of the Merlin CP-GEP test to redefine risk assessment for melanoma patients. By identifying high-risk individuals who may not have undergone SLNB, we can better personalize treatment decisions, ultimately improving long-term outcomes for patients."

Dr. Jvalini Dwarkasing, Chief Scientific Officer at SkylineDx, commented, "These results highlight the power of CP-GEP in helping clinicians identify high-risk patients, even in the absence of SLNB status. Additional research is needed but potentially the Merlin High-Risk patients could benefit from systemic therapy to overcome their risk of recurrence, as their RFS is similar to that of patients who are currently eligible for immunotherapy."

SkylineDx remains committed to advancing innovative molecular diagnostic solutions that offer better insights and more personalized treatment options for melanoma patients, ultimately improving their chances for a better outcome.

About the advanced cutaneous melanoma GEP test (Merlin CP-GEP test)

CP-GEP is a non-invasive prediction model for cutaneous melanoma patients and is the only commercially available GEP test that combines clinicopathologic (CP) variables with gene expression profiling (GEP) into a single integrated algorithm. This CP-GEP model is also the only GEP test that provides a binary stratification of all patients based on being High or Low Risk for metastasis and thereby assign them to the appropriate surgical action categories as listed in evidence-based cancer treatment, prevention and screening guidelines. The advanced CP-GEP model was developed by Mayo Clinic and SkylineDx BV and is the latest commercially launched GEP test, which has been clinically validated in multiple studies on a global basis. More information (including references) may be obtained at www.falconprogram.com and www.merlinmelanomatest.com. The test has been launched in the United States and Europe as Merlin test. SkylineDx collaborates with diagnostic service providers globally to bring this test to market and increase patient access.

Aptevo Therapeutics Announces the Closing of $2.1 Million Registered Direct Offering and Concurrent Private Placement Priced At-The-Market Under Nasdaq Rules

On April 4, 2025 Aptevo Therapeutics Inc. (Nasdaq:APVO) ("Aptevo" or the "Company"), a clinical-stage biotechnology company focused on developing novel immune-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported the closing of its previously announced offering of 1,764,710 shares of the Company’s common stock in a registered direct offering and warrants to purchase up to 3,529,420 shares of common stock in a concurrent private placement (together with the registered direct offering, the "offering") at a combined purchase price of $1.19 per share and accompanying warrant (Press release, Aptevo Therapeutics, APR 4, 2025, View Source [SID1234651806]). The warrants issued pursuant to the concurrent private placement have an exercise price of $1.19 per share, will be exercisable upon the receipt of stockholder approval and will expire 5 years from the date of stockholder approval.

Roth Capital Partners acted as the exclusive placement agent for the offering.

Gross proceeds from the offering were approximately $2.1 million, before deducting the placement agent’s fees and other estimated offering expenses payable by the Company. Aptevo intends to use the net proceeds from the proposed offering for the continued clinical development of its product candidates, working capital, and other general corporate purposes.

A shelf registration statement on Form S-3 (File No. 333-284969) relating to the shares of common stock issued in the registered direct offering was previously filed with the Securities and Exchange Commission (the "SEC") and is currently effective. The registered direct offering was made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement, relating to the registered direct offering that will be filed with the SEC. The warrants were issued in a concurrent private placement. Electronic copies of the final prospectus supplement and accompanying prospectus may be obtained on the SEC’s website at View Source or by contacting Roth Capital Partners, LLC at 888 San Clemente Drive, Newport Beach CA 92660, by phone at (800) 678-9147 or by email at [email protected].

The private placement of the warrants and the underlying shares will be made in reliance on an exemption from registration under Section 4(a)(2) of the Securities Act and/or Regulation D thereunder. Accordingly, the securities issued in the concurrent private placement cannot be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws.

This press release does not constitute an offer to sell, or the solicitation of an offer to buy, the shares of common stock or warrants, nor will there be any sale of the shares of common stock or warrants in any state or other jurisdiction in which such offer, solicitation or sale is not permitted.

The Company also amended certain existing warrants that were previously issued on December 12, 2024 to purchase up to 1,647,088 shares of the Company’s common stock and have an exercise price of $9.53 per share, effective upon the closing of the offering, such existing warrants have a reduced exercise price of $1.19 per share, shall become exercisable upon stockholder approval and will expire 5 years from the date of stockholder approval.

Sonnet BioTherapeutics Holdings, Inc. (the “Company”) announced positive safety results of SON-1010

On April 4. 2025, Sonnet BioTherapeutics Holdings, Inc. (the "Company") announced positive safety results of SON-1010 at the highest dose combined with atezolizumab (Tecentriq) in the Phase 1b/2a clinical trial in adult patients with advanced solid tumors or platinum-resistant ovarian cancer (PROC) (the "SB221 study") (Press release, Sonnet BioTherapeutics, APR 4, 2025, View Source [SID1234651805]). Based on positive feedback from a formal evaluation by the Safety Review Committee (SRC) for the SB221 study, the study can now advance to the expansion phase, which will study the preliminary effect of the combination at the maximum tolerated dose (MTD), before proceeding to a Phase 2a randomized comparison with the standard of care in patients with PROC.

The SB221 study was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of increasing doses of SON-1010 administered with atezolizumab. The primary goal for the first part of the study was to establish the MTD in combination with the immune checkpoint inhibitor (ICI). A total of 19 subjects were treated during dose escalation and one patient with PROC had a partial response at the highest dose.

The SB221 SRC review at the completion of dose expansion in combination with atezolizumab concluded that fatigue, fevers, and gastrointestinal symptoms were the most common adverse effects; no dose-limiting toxicity or cytokine release syndrome were seen. The only related serious adverse event (SAE) during dose escalation was Grade 2 pneumonitis, which is a known adverse event with atezolizumab. One patient with PROC had a 44% tumor size reduction, indicating a partial response (PR), along with a more than 2-fold reduction in the CA 125 ovarian cancer biomarker. SON-1010 monotherapy in the SB101 study led to a PR at the same MTD in a patient with sarcoma.

All enrolled patients have advanced solid tumors and all patients at the higher doses have PROC, including those enrolled in a final 1200 ng/kg dose-escalation cohort. The SB221 trial employed a ‘desensitizing’ first dose of 300 ng/kg to take advantage of the known tachyphylaxis with rhIL-12, with the intention of minimizing toxicity while allowing for higher maintenance doses. The safety and toxicity profile that has developed is typical for a Phase 1 oncology trial, with the majority of adverse events (AEs) being reported as mild and transient and there has been no evidence of cytokine release syndrome. Of the 19 patients dosed to date, 8 of the 15 evaluable patients (53%) had SD at the first follow-up CT scan and 5 of the 15 evaluable patients (33%) remained stable at four months, suggesting SON-1010 is showing clinical benefit. While the follow-up is still early, four of those 15 patients were still on trial at 6 months, including 3 with SD and one with an unconfirmed PD. As noted, one of the PROC patients in the highest SON-1010 dose cohort had a PR at 2 months.

Enhertu approved in the EU as first HER2-directed therapy for patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer following at least one endocrine therapy

On April 4, 2025 AstraZeneca and Daiichi Sankyo reported that Enhertu (trastuzumab deruxtecan) has been approved in the European Union (EU) as a monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low or HER2-ultralow breast cancer who have received at least one endocrine therapy in the metastatic setting and who are not considered suitable for endocrine therapy as the next line of treatment (Press release, AstraZeneca, APR 4, 2025, View Source [SID1234651793]).

The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the DESTINY-Breast06 Phase III trial, which were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and published in The New England Journal of Medicine.

HR-positive, HER2-negative is the most common breast cancer subtype, accounting for approximately 70% of all breast cancers.1 Despite being classified as HER2-negative, many of these tumours still have some level of HER2 expression. Currently, regardless of HER2 expression, endocrine-based therapies are widely used in the early lines of treatment for HR-positive metastatic breast cancer. Following endocrine-based therapy, some patients discontinue treatment, and others are treated with conventional chemotherapy which is associated with poor response rates and outcomes.2-5

Giuseppe Curigliano, MD, PhD, Professor of Medical Oncology at the University of Milan and the Head of the Division of Early Drug Development at the European Institute of Oncology, IRCCS, Italy and principal investigator for the trial, said: "This approval introduces a new treatment option for HR-positive metastatic breast cancers that express HER2. In DESTINY-Breast06, Enhertu outperformed chemotherapy, providing progression-free survival of more than one year for patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer, demonstrating the benefit of treating these patients with Enhertu instead of chemotherapy."

Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: "Enhertu continues to open up new approaches to the diagnosis and treatment of patients with metastatic breast cancer. This approval underscores the importance of testing metastatic breast cancer tumours for any IHC staining to identify patients with HR-positive, HER2-low or HER2-ultralow disease who may be eligible for Enhertu once sustained responses are no longer achieved with endocrine-based therapy."

Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, said: "Enhertu continues to evolve what is possible with breast cancer treatment, becoming the first HER2-directed medicine approved in the EU for patients with HR-positive metastatic breast cancer with HER2-low or HER2-ultralow expression following endocrine therapy. Today’s approval expands the use of Enhertu to now include an earlier treatment setting of HER2-low metastatic breast cancer and broadens the patient population eligible for treatment to those with HER2-ultralow disease."

In the trial, Enhertu showed a 38% reduction in the risk of disease progression or death versus chemotherapy (hazard ratio [HR] 0.62; confidence interval [CI]: 0.52-0.75; p<0.0001) in patients with chemotherapy-naïve HR-positive, HER2-low metastatic breast cancer with a median progression-free survival (PFS) of 13.2 months versus 8.1 months.

In the overall trial population (patients with HER2-low or HER2-ultralow metastatic breast cancer), the median PFS was 13.2 months in patients randomised to Enhertu compared to 8.1 months in those randomised to chemotherapy (HR 0.64; 95% CI: 0.54-0.76; p<0.0001). In an exploratory analysis, results were consistent between patients with HER2-low expression and HER2-ultralow expression.

HER2 testing in the trial was conducted by a central laboratory. Approximately 85-90% of patients with HR-positive, HER2-negative metastatic breast cancer screened were determined to be HER2-low or HER2-ultralow.6

The safety profile of Enhertu in DESTINY-Breast06 was consistent with previous clinical trials of Enhertu in breast cancer with no new safety concerns identified.

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Enhertu was approved in the US earlier this year based on the DESTINY-Breast06 results. Regulatory applications are under review in Japan and several other countries for this indication.

Enhertu is already approved in more than 75 countries, including the EU, for patients with HER2-low metastatic breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Financial considerations

Following this approval for Enhertu in the EU, an amount of $125m is due from AstraZeneca to Daiichi Sankyo as a milestone payment for the HER2-low and HER2-ultralow chemotherapy-naïve breast cancer indication. The milestone will be capitalised as an addition to the upfront payment made by AstraZeneca to Daiichi Sankyo in 2019 and subsequent capitalised milestones and will be amortised through the profit and loss statement.

Sales of Enhertu in most EU territories are recognised by Daiichi Sankyo. AstraZeneca reports its share of gross profit margin from Enhertu sales in those territories as alliance revenue in the Company’s financial statements. AstraZeneca will record product sales in respect of sales made in territories where AstraZeneca is the selling party.

Further details on the financial arrangements were set out in the March 2019 announcement of the collaboration.

Notes

Breast cancer and HER2 expression
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.7 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally.7 In Europe, approximately 557,000 cases of breast cancer are diagnosed annually.8 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis.1

HR-positive, HER2-negative is the most common breast cancer subtype, accounting for approximately 70% of all breast cancers.1 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast cancer.9 Patients with high levels of HER2 expression (IHC 3+ or 2+/ISH+) are classified as HER2-positive and treated with HER2-directed therapies, representing approximately 15-20% of all breast cancers.10 Historically, tumours that were not classified as HER2-positive were classified as HER2-negative.11

Despite being classified as HER2-negative, many of these tumours may still have some level of HER2 expression detected by IHC.11 In the DESTINY-Breast06 trial, approximately 85-90% of patients with HR-positive, HER2-negative metastatic breast cancer screened were determined to be HER2-low or HER2-ultralow.6

Prior to the approval of Enhertu in HER2-low and HER2-ultralow metastatic breast cancer based on the DESTINY-Breast04 and DESTINY-Breast06 trials, there were no HER2-targeted therapies approved specifically for patients with HER2-low or HER2-ultralow expression.12,13

DESTINY-Breast06
DESTINY-Breast06 is a global, randomised, open-label Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus investigator’s choice of chemotherapy (capecitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) advanced or metastatic breast cancer. Patients in the trial had no prior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrine therapy in the metastatic setting. Patients were also eligible if they had received one prior line of endocrine therapy combined with a CDK4/6 inhibitor in the metastatic setting and experienced disease progression within six months of starting 1st-line treatment or received endocrine therapy as an adjuvant treatment and experienced disease recurrence within 24 months. HER2 status in the trial was confirmed by a central laboratory and was performed on a tumour sample obtained at the time of initial metastatic diagnosis or later.

The primary endpoint is PFS in the HR-positive, HER2-low patient population as measured by blinded independent central review (BICR). Key secondary endpoints include PFS by BICR in the overall trial population (HER2-low and HER2-ultralow), overall survival (OS) in the HER2-low patient population and OS in the overall trial population. Other secondary endpoints include objective response rate, duration of response, time to first subsequent treatment or death, time to second subsequent treatment or death and safety.

DESTINY-Breast06 enrolled 866 patients (n=713 for HER2-low and n=153 for HER2-ultralow) in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Enhertu (5.4mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC 3+ or in-situ hybridisation [ISH]+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

Enhertu (5.4mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Enhertu (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HR-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

Enhertu (5.4mg/kg) is approved in more than 50 countries worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (5.4mg/kg) is approved in Brazil, Isreal, Russia and the US for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on the results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication in the US may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu development programme
A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers. Trials in combination with other anti-cancer treatments, such as immunotherapy, also are underway.