On March 18, 2025 IceCure Medical Ltd. (NASDAQ: ICCM) ("IceCure", "IceCure Medical" or the "Company"), developer of minimally-invasive cryoablation technology that destroys tumors by freezing as an alternative to surgical tumor removal, reported that it exhibited at the 19th Annual St. Gallen Breast Cancer Conference in Vienna, Austria from March 12 – 15, 2025 (Press release, IceCure Medical, MAR 18, 2025, View Source [SID1234651238]). Six studies of ProSense in breast cancer were accepted as peer-reviewed abstracts, presented as e-posters during the conference, and are being published in the scientific journal, The Breast after the conference.

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"ProSense received a high level of interest at this prestigious breast cancer conference in Europe where our cryoablation system is gaining increasing commercial traction driven by regulatory approval and a growing body of efficacy and safety data from third party studies," IceCure’s Chief Executive Officer, Eyal Shamir commented. "Among the benefits of these investigator-initiated studies is that each practitioner studies different patient populations in varied settings and circumstances, producing a breadth and depth of data that would simply not be available even in the largest of company-sponsored global studies. We are grateful to the investigators as we all aim toward the same goal of advancing women’s health through innovation and collaboration."

The following studies of ProSense were presented:

The Impact of Adjuvant Treatment After Cryoablation in Early-Stage, Low-Risk Breast Cancer: ICE3 Trial 5-Year Ipsilateral Breast Tumor Recurrence (IBTR)
Lead author Dr. Richard Fine, United States
Summary conclusion: The ICE3 trial suggests that cryoablation with ProSense, complemented by adjuvant therapy, is a viable alternative to surgical excision for selected patients with early-stage, low-risk breast cancer with recurrence rates comparable to those following lumpectomy. The addition of endocrine therapy alone yields similar results to de-escalation trials omitting radiation after surgery, such as CALGB 9343, PRIME II and LUMINA, without sacrificing survival. ICE3 enrolled patients aged ≥60 with unifocal, hormone receptor-positive, HER2-negative invasive ductal carcinomas measuring ≤1.5 cm. At 5 years, the overall IBTR rate was 3.61% (7 recurrences out of 194 patients). The 124 Patients who received only endocrine therapy with cryoablation had a 5-year IBTR rate of 3.22% (4 recurrences out of 124 patients).
Expanding the Use of Cryoablation on T1 Breast Cancers: An Initial Experience
Lead Author Dr. Ava Kwong, Hong Kong
Summary conclusion: This study evaluated expanding ICE3’s inclusion criteria to T1 breast cancer of all IHC subtypes (i.e. luminal, HER2-enriched and triple negative breast cancers). The study found that cryoablation with ProSense can completely ablate T1 breast cancer, including triple negative breast cancer, and younger age range. 35 patients were recruited with a median age of 64 and biopsy proven invasive or in-situ breast cancer of ≤2cm.
The Treatment of Breast Cancer with Percutaneous Thermal Ablation: Results of the THERMAC trial
Lead Author by Dr. Linda Risks, Netherlands
Summary conclusion: Percutaneous thermal ablation has the potential to replace surgical treatment and improve the health-related quality of life of patients with small breast cancers, without jeopardizing current treatment effectiveness or safety. 41 postmenopausal patients, with cT1N0 ER+/Her2- breast cancer, were treated. The study compared radiofrequency ablation ("RFA"), microwave ablation ("MWA") and cryoablation ("CA"). The RFA arm was prematurely terminated. Complete ablation was reached in 72% (95% CI, 49% to 88%) in the MWA arm and in 94% (95% CI, 74% to 0.99) in the cryoablation arm. Adverse events occurred in 44% (95% CI, 25% to 66%) of the patients in the MWA arm and 0% (95% CI, 0% to 18%) of in the cryoablation arm. Of the three thermal ablation methods evaluated, cryoablation with ProSense was the only thermal ablative technique that met the minimum requirements and will therefore be selected for a Phase III trial.
Percutaneous Ultrasound-Guided Cryoablation for the Treatment of Breast Cancer in Non-Surgical Patients
Lead Author Dr. Lucía Graña López, Spain
Summary conclusion: Breast cancer patients who chose not to have surgery or were considered inoperable were treated with ProSense cryoablation, which was found to be a safe and well-tolerated outpatient procedure. The study outcomes suggest that cryoablation is effective and could be an alternative to surgery for the management of luminal breast cancer up to 2.5 cm. 60 breast cancer tumors were treated (median size 21 mm, range 6-46 mm) in 54 patients, median age 87, with ProSense cryoablation. Complete tumoral necrosis was achieved in 49 tumors (81.7%). Axillary progression occurred in two cases of triple-negative breast cancer. Two patients experienced recurrence in different locations. Percutaneous cryoablation was successful in 100% of luminal cancers up to 2.5 cm. The procedure was well tolerated, with no major complications observed.
Cryoablation of Breast Cancer: The Challenge of an Innovative Non-Surgical Treatment for Selected Patients
Lead Author Dr. Francesca Magnoni, Italy
Summary conclusion: The European Institute of Oncology in Italy is evaluating ProSense cryoablation, with the prospective observational study "Percutaneous Cryoablation of Low-risk Early Breast Cancer (PRECICE)". The trial has just started and will enroll 233 patients over the age of 50 years with unifocal, small (≤1.5 cm), clinically node-negative, luminal A and B breast cancer. To date, 11 patients eligible for cryoablation have been enrolled. Cryoablation, performed on an outpatient basis under local anesthesia, completely replaces both breast and axillary surgery, in accordance with recent evidence.
Cryotherapy as a Surgical De-Escalation Strategy in Breast Cancer: A Comprehensive Review of Techniques, Complications, and Oncological Outcomes
Lead author Dr. Kai Lin Lee, Singapore
Summary conclusion: After a review of 276 papers, this study concluded that cryotherapy with systems including ProSense could potentially be a step forward in surgical de-escalation of breast cancer, particularly for elderly patients with early-stage breast cancer or those who are at high risk and might benefit from a less aggressive treatment strategy.

About ProSense
The ProSense Cryoablation System is a minimally invasive cryosurgical tool that provides the option to destroy tumors by freezing them. The system uniquely harnesses the power of liquid nitrogen to create large lethal zones for maximum efficacy in tumor destruction in benign and cancerous lesions, including breast, kidney, lung, and liver.

ProSense enhances patient and provider value by accelerating recovery, reducing pain, surgical risks, and complications. With its easy, transportable design and liquid nitrogen utilization, ProSense opens that door to fast and convenient office-based procedures for breast tumors.

On March 18, 2025 INOVIO (NASDAQ: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, reported its financial results and operational highlights for the fourth quarter and full year ended December 31, 2024 and provided a business update and description of operational highlights during the year (Press release, Inovio, MAR 18, 2025, View Source [SID1234651220]).

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"INOVIO’s recent progress puts us on the cusp of achieving several long-term goals for our DNA medicines, most importantly the submission of our first BLA and potential transition to a commercial-stage company," said Dr. Jacqueline Shea, INOVIO’s President and Chief Executive Officer. "By resolving the previously announced device array component issue, we are back on track to submitting our first BLA for INO-3107 to the FDA. We anticipate starting our submission in mid-2025 with non-device related modules under the agency’s rolling submission program, assuming it is granted, with the goal of having the complete submission accepted for priority review before the end of the year. We continue to believe that INO-3107 has the potential to be the preferred product candidate offering durable clinical benefit, tolerability and a patient-centric dosing regimen and are moving forward with urgency."

Dr. Michael Sumner, INOVIO’s Chief Medical Officer, said "While delivering INO-3107 to patients remains our primary focus, we are extremely pleased with recently announced data from a proof-of-concept trial with our DMAb technology that showed durable in vivo antibody production. DMAbs represent a potential breakthrough as they have the ability to overcome traditional monoclonal antibody production challenges, such as short half-life and anti-drug immune responses. They have the potential to transform treatments for infectious diseases, as well as cancer and metabolic disorders by enabling long-term production of therapeutic antibodies and other proteins. Unlike other delivery platforms, our DNA-based approach has demonstrated sustained antibody production without generating anti-drug antibodies, making it a potentially promising long-term solution for conditions requiring continuous therapeutic protein delivery. We look forward to continuing to advance this technology and other promising pipeline candidates through collaborations and other potential strategic opportunities."

Operational Highlights

INO-3107 – Recurrent Respiratory Papillomatosis (RRP)

•Made significant progress toward submitting the BLA by completing the drafting of all non-device modules and resolving the previously announced manufacturing issue involving the single-use array component of the CELLECTRA device and enabling the final step of FDA-required device verification (DV) testing.
•Reported data from a retrospective trial (RRP-002) showing that patients continued to improve into years two and three following their initial dosing regimen when compared to their response at Week 52. In the trial, one-half of RRP patients treated with INO-3107 achieved a complete response (CR) and required no surgery in the second 12-month period when evaluated at the end of year two.
•Published and presented the full safety and efficacy data for the Phase 1/2 trial, as well as new immunology data demonstrating the ability of INO-3107 to induce antigen-specific T cell responses against HPV-6 and HPV-11 and drive recruitment of those T cells into airway tissues and papilloma of RRP patients, which could potentially slow or eliminate papilloma regrowth. This data was published in Nature Communications in February 2025.
•The European Medicines Agency’s Committee for Advanced Therapies (CAT) certified the quality and non-clinical data for INO-3107, confirming that CMC data and nonclinical results available to date comply with the scientific and technical standards to be used in evaluating a potential European Marketing Authorization Application.
•INO-3107 was designated an innovative medicine as part of the U.K.’s Innovative Licensing and Access Pathway (ILAP).
•Progressed commercial readiness plans, including refining go-to-market strategy focused on patient and physician needs; driving key strategic decisions on pricing and access, product distribution, targeting and segmentation, and product positioning; and developing plans for the build out of the commercial organization.

Next Steps:
•Complete FDA-required design-verification testing – anticipated to be complete in first half of 2025.
•Update IND and initiate confirmatory trial.
•Submit BLA to the FDA – anticipate beginning rolling submission process mid-2025 and requesting priority review with goal of completing submission in second half of 2025 and receiving FDA acceptance of submission by year end.
•Submit a long-term study protocol to the FDA following BLA submission.
•Present and publish clinical, immunology and durability data at targeted scientific and medical conferences in 2025.

INO-3112 – Oropharyngeal Squamous Cell Carcinoma (OPSCC)

•Advanced development plans for a Phase 3 trial for INO-3112 in combination with LOQTORZI (toripalimab-tpzi), a recently approved PD-1 inhibitor in the U.S. and Europe.
•Gained alignment with FDA on the planned Phase 3 trial design and received initial feedback from European regulatory authorities on proposed trial design.
•Entered into a clinical collaboration and supply agreement with Coherus BioSciences, Inc. for the use of LOQTORZI in the trial.

Next Steps:
•Finalize protocol of the Phase 3 trial in consultation with the FDA. INOVIO anticipates it will conduct the trial in North America and Europe in patients with locoregionally advanced, high-risk, HPV16/18-positive OPSCC.
•Complete ongoing manufacture of drug supply for trial.

Other Pipeline Updates

•Top-line interim results were announced from an ongoing Phase 1 proof-of-concept trial evaluating DMAbs targeting COVID-19. In the trial, 100% (24/24) of participants who reached week 72 maintained biologically relevant levels of DMAbs, confirming the durability of in vivo antibody production. Notably, no participant developed anti-drug antibodies, a common challenge observed in other gene-based delivery platforms, such as adeno-associated virus mediated antibody expression. Additionally, the DMAbs were well tolerated in the trial, with the most common side effects being mild, temporary injection site reactions, such as pain and redness. The trial is being led by The Wistar Institute in collaboration with INOVIO, AstraZeneca, and the University of Pennsylvania and funded by the Defense Advanced Research Projects Agency (DARPA) and the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND). INOVIO and its partners anticipate additional data to be presented at upcoming scientific conferences and published in a peer-reviewed journal.

•Advanced development plans for a Phase 2 trial for INO-4201 as a potential booster to ERVEBO (rVSV-ZEBOV), including gaining alignment with FDA on the trial’s protocol and path to potential approval. In 2025, the company anticipates finalizing the trial protocols and seeking funding to support trial activities. INOVIO also plans to submit the data from its completed Phase 1b trial to a peer-reviewed publication for publication, including FANG assay data indicating that boosting with INO-4201 can elicit neutralizing antibody response comparable to that achieved by ERVEBO, an approved primary series vaccination against Ebola.

•Continued efforts to move INO-5401 into its next stage of development for glioblastoma (GBM), which the company believes will be a controlled Phase 2 trial. INOVIO plans on completing manufacture of drug supply for the next trial during 2025.

•The Basser Center at the University of Pennsylvania continues evaluating the tolerability and immunogenicity of INO-5401 in a fully enrolled Phase 1 study exploring the potential to prevent cancer in people with BRCA1 or BRCA2 mutations.

•INOVIO’s collaborator, ApolloBio, continues recruitment into its Phase 3 trial evaluating INO-3100 as a potential treatment for HPV 16/18 positive cervical dysplasia in China.

Operational and Financial Updates

•Announced appointment of Steven Egge as Chief Commercial Officer in July 2024. Mr. Egge has broad commercial and therapeutic area experience, including in HPV-related diseases and cancers, vaccines and rare diseases, and has overseen or contributed to more than a dozen commercial product launches throughout his career.

•Raised over $72 million in gross proceeds from ATM and two offerings of equity securities in April and December 2024.

2024 Financial Results

•Cash, Cash Equivalents and Short-term Investments: As of December 31, 2024, cash, cash equivalents and short-term investments were $94.1 million compared to $145.3 million as of December 31, 2023.

•Revenues: Total revenues were $117,000 and $218,000 for the quarter and year ended December 31, 2024, respectively, compared to $103,000 and $832,000 for the same periods in 2023.

•Research and Development (R&D) Expenses: R&D expenses for the quarter and year ended December 31, 2024 were $12.9 million and $75.6 million, respectively, compared to $17.3 million and $86.7 million for the same periods in 2023. The decrease in R&D expenses was primarily the result of lower employee and consultant compensation, including stock-based compensation, lower drug manufacturing and clinical trial expenses related to INO-4800, partially offset by an increase in drug manufacturing costs related to INO-3107 and higher engineering professional and outside services related to device development, among other variances.

•General and Administrative (G&A) Expenses: G&A expenses were $7.6 million and $37.0 million, respectively, for the quarter and year ended December 31, 2024, versus $10.2 million and $47.6 million, respectively, for the same periods in 2023. The decrease in G&A expenses was primarily related to a decrease in employee compensation, including stock-based compensation, and a decrease in legal expenses, among other variances.

•Total Operating Expenses: Total operating expenses were $20.5 million and $112.6 million for the quarter and year ended December 31, 2024, respectively, compared to $27.5 million and $144.8 million for the same period in 2023.

•Net Loss: INOVIO’s net loss for the quarter and year ended December 31, 2024 was $19.4 million, or $0.65 per basic and diluted share, and $107.3 million, or $3.95 per basic and diluted share, respectively, compared to net loss of $25.0 million, or $1.10 per basic and diluted share, and $135.1 million, or $6.09 per basic and diluted share, for the quarter and year ended December 31, 2023, respectively.

•Shares Outstanding: As of December 31, 2024, INOVIO had 36.1 million common shares outstanding and 50.0 million common shares outstanding on a fully diluted basis, after giving effect to the exercise, vesting, and conversion, as applicable, of its outstanding common stock warrants, pre-funded warrants, stock options, restricted stock units and convertible preferred stock.

INOVIO’s balance sheet and statement of operations are provided below. Additional information is included in INOVIO’s annual report on Form 10-K for the year ended December 31, 2024, which can be accessed at: View Source

Cash Guidance
INOVIO estimates its current cash, cash equivalents and short-term investments balances to support the company’s operations into the first quarter of 2026. This projection includes an operational net cash burn estimate of approximately $27 million for the first quarter of 2025. These cash runway projections do not include any further capital-raising activities that INOVIO may undertake.

Conference Call / Webcast Information
INOVIO’s management will host a live conference call and webcast with slides at 4:30 p.m. ET today to discuss INOVIO’s financial results and provide a general business update. The live webcast and replay may be accessed by visiting INOVIO’s website at View Source

On March 18, 2025 Hoth Therapeutics, Inc. (NASDAQ: HOTH), a clinical-stage biopharmaceutical company, reported breakthrough preclinical findings demonstrating the efficacy of HT-KIT, a novel targeted therapy for gastrointestinal stromal tumors (GIST) (Press release, Hoth Therapeutics, MAR 18, 2025, View Source [SID1234651239]). The results highlight HT-KIT’s ability to significantly reduce tumor burden in humanized mouse models, disrupt KIT signaling pathways, and induce tumor cell death.

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"These exciting findings mark a significant milestone in the development of HT-KIT as a potential new therapeutic for patients with GIST," said Robb Knie, CEO of Hoth Therapeutics.

"By targeting KIT mutations, which are a major driver of GIST progression, HT-KIT has shown remarkable efficacy in preclinical models, demonstrating its potential as a transformative treatment option for this difficult-to-treat cancer."

Key Findings from the Preclinical Study:

Significant Reduction in KIT Expression – HT-KIT effectively reduced KIT receptor expression within 24 hours, with effects sustained for 72 hours.
Induction of Tumor Cell Death – HT-KIT triggered significant tumor cell death as early as 24 hours post-treatment, while the lower dose led to delayed but substantial cell death at 72 hours.
Decreased Tumor Cell Proliferation – HT-KIT treatment inhibited cell growth and proliferation in GIST-T1 cells, as confirmed by cell count reductions and decreased fluorescence intensity in proliferation assays.
Marked Tumor Volume Reduction in GIST Mouse Models – In a humanized xenograft model, HT-KIT treatment led to a significant reduction in tumor growth, with differences becoming statistically significant by day 8 and increasing over time.
Consistent Tumor Size Reduction – Excised tumors from HT-KIT-treated mice were smaller and lighter than those in the control group, reinforcing tumor volume measurements.
HT-KIT: A Potential New Treatment for GIST

GIST is a rare but aggressive cancer often driven by activating mutations in the KIT receptor. Current treatment options, including tyrosine kinase inhibitors (TKIs), can face resistance over time, leading to disease progression. Hoth Therapeutics’ HT-KIT offers a novel approach by effectively reducing KIT receptor expression, disrupting tumor survival pathways, and inhibiting tumor growth in vivo.

"These results provide compelling preclinical proof-of-concept for HT-KIT in GIST treatment," said Robb Knie. "By directly targeting the underlying genetic drivers of GIST, HT-KIT has the potential to overcome limitations of existing therapies and provide a new therapeutic strategy for patients with KIT-driven malignancies."

Next Steps in Development

Hoth Therapeutics is committed to advancing HT-KIT toward clinical evaluation. The company is currently conducting additional preclinical studies to further validate HT-KIT’s efficacy and safety profile, with plans to initiate regulatory discussions for first-in-human trials.

On March 18, 2025 Medison Pharma , a global company focused on accelerating access to highly innovative therapies in international markets, and Immunocore Holdings plc (NASDAQ: IMCR), a commercial-stage biotechnology company pioneering the delivery of transformative immunomodulatory medicines to radically improve patient outcomes for cancer, infectious diseases and autoimmune diseases, reported that KIMMTRAK (tebentafuspe) has received approval for health registration by the National Health Surveillance Agency (ANVISA), under the regulatory approval pathway for rare diseases (Press release, Medison Pharma, MAR 18, 2025, View Source [SID1234651240]).

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Tebentafuspe is indicated for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mum). This is the first therapy approved by ANVISA for metastatic uveal melanoma in Brazil [1],[2] .
Uveal melanoma is a rare and aggressive eye cancer with limited treatment options available at an advanced stage. Once metastasized, it carries a poor prognosis, and survival rates have remained largely unchanged for decades [ 3] . Developed by Immunocore,
tebentafuspe is an innovative immune mobilization monoclonal T-cell receptor therapy against cancer (ImmTAC) [ 4] designed to engage the body’s immune system to specifically target and destroy uveal melanoma cells.
As part of their long-standing global partnership, Medison and Immunocore are collaborating to bring this therapy to Latin America and beyond the U.S., Japan and Western Europe. Brazil has become the first country in the region to obtain approval for the drug, which offers a new treatment option for patients living with this disease [ 5] .

Mark Moyer , Senior Vice President of Regulatory Sciences at Immunocore said: "Following the approval of the registration, HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in Brazil can now access tebentafuspe. With approvals in 39 countries, this underscores Immunocore’s firm commitment to providing our medicines to patients who can benefit from them around the world."

The approval of tebentafuspe in Brazil underscores Medison’s commitment to expanding access to innovative oncology treatments in Latin America. Victor Papamoniodis , Chief Commercial Officer of Medison Pharma, said: "We are proud of our global partnership with Immunocore that allows us to bring this treatment to Brazilian patients who have not had access to an approved therapy until now. Medison is dedicated to providing the most advanced therapies for rare and serious diseases to patients around the world."

Edson Paixão, General Manager of Medison Pharma in Brazil, Andean Region, Central America and the Caribbean , reinforced: "Medison remains committed to accelerating access to highly innovative therapies for Brazilian patients. The approval of tebentafuspe is an important milestone, and we are proud to make this therapy available to patients who can benefit from it."

About KIMMTRAK (tebentafuspe)

Solution for dilution for infusion with 100 micrograms/0.5 mL in a pack containing 1 vial of 0.5 mL.

INTRAVENOUS USE

ADULT USE

WARNING: Cytokine Release Syndrome (CRS), which can be serious or life-threatening, has occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours after the first three infusions and then as clinically indicated.

Indications: As monotherapy for the treatment of adult patients with unresectable or metastatic uveal melanoma positive for human leukocyte antigen (HLA) A*02:01.

Patients treated with KIMMTRAK must have an HLA-A*02:01 genotype determined by any validated HLA genotyping assay.

Contraindications: Hypersensitivity to the active substance or to any of the excipients listed.

Warnings and Precautions: Most patients experienced CRS following tebentafuspe infusions. The diagnosis of CRS was most frequently based on pyrexia followed by hypotension and infrequently on hypoxia. Other symptoms commonly observed with CRS included chills, nausea, vomiting, fatigue, and headache. In most cases, CRS began on the day of infusion, with a median time to resolution of 2 days. Pyrexia was observed in nearly all cases of CRS, and in these patients, an increase in body temperature typically occurred within the first 8 hours after tebentafuspe infusion. CRS rarely (1.2%) led to discontinuation of treatment. Patients should be monitored for signs and symptoms of CRS for at least 16 hours after the first three tebentafuspe infusions in a hospital setting with immediate access to resuscitation drugs and equipment to manage CRS. If CRS is observed, immediate supportive care, including antipyretics, intravenous fluids, tocilizumab, or corticosteroids, should be initiated to prevent worsening of the syndrome or potential fatality, and monitoring should continue until resolution. With subsequent doses, patients should be closely monitored after treatment for early identification of signs and symptoms of CRS. Patients with comorbidities, including cardiovascular disorders, may be at increased risk of sequelae associated with CRS. Tebentafuspe treatment has not been studied in patients with clinically significant cardiac disease. Depending on the persistence and severity of CRS, tebentafuspe treatment should be withheld or discontinued. Acute skin reactions with infusion have been reported, including rash, pruritus, erythema, and skin edema. Cardiac events, such as tachycardia and sinus arrhythmia, have been observed in patients on treatment. Cases of QT prolongation have been reported following treatment with tebentafuspe. An electrocardiogram (ECG) should be performed on all patients before and after treatment, during the first 3 weeks and thereafter as clinically indicated. This medicine may potentiate QT interval prolongation, which increases the risk of serious ventricular arrhythmias such as "torsades de pointes", which is potentially fatal (sudden death). This medicine may cause hepatotoxicity. Therefore, it requires careful use, under strict medical supervision and accompanied by periodic controls of liver function, at the physician’s discretion.

Pregnancy and lactation: Women of childbearing potential must use effective contraception during treatment and for at least 1 week after the last dose of treatment. The drug is not recommended during pregnancy and in women of childbearing potential who are not using contraception. Pregnancy in women of childbearing potential should be ascertained before starting treatment. There is insufficient information on the excretion of tebentafuspe/metabolites in human milk. A risk to the newborn/infant cannot be excluded. Breast-feeding should be discontinued during treatment with tebentafuspe.

Drug, food and alcohol interactions: No formal interaction studies have been performed with tebentafuspe. Initiation of tebentafuspe therapy causes a transient release of cytokines that may suppress CYP450 enzymes . The highest risk of drug-drug interactions occurs within the first 24 hours of the first three doses of tebentafuspe in patients who are receiving concomitant CYP450 substrates , particularly those with a narrow therapeutic index. These patients should be monitored for toxicity (e.g., warfarin) or drug concentrations (e.g., cyclosporine). The dose of concomitant medications should be adjusted as necessary.

Dosage: Hospitalization is recommended for at least the first three infusions. The recommended dose is 20 micrograms on Day 1, 30 micrograms on Day 8, 68 micrograms on Day 15, and 68 micrograms once weekly thereafter. Treatment should continue as long as the patient derives clinical benefit and in the absence of unacceptable toxicities. To minimize the risk of hypotension associated with CRS, intravenous fluids should be administered prior to initiating the infusion, based on clinical assessment and the patient’s volume status. Tebentafuspe should be withheld or discontinued to manage adverse reactions. The recommended infusion period is 15 to 20 minutes.

Adverse reactions and laboratory test abnormalities: The most common adverse reactions in patients treated with tebentafusp were CRS (88%), rash (85%), pyrexia (79%), pruritus (72%), fatigue (66%), nausea (56%), chills (55%), abdominal pain (49%), edema (49%), hypo/hyperpigmentation (48%), hypotension (43%), dry skin (35%), headache (32%), and vomiting (34%). Adverse reactions led to permanent discontinuation in 4% of treated patients. The most common adverse reaction resulting in discontinuation of tebentafusp was CRS. Adverse reactions resulting in at least one dose interruption occurred in 26% of treated patients (weekly dosing) and resulted in a median of one missed dose. Adverse reactions requiring dose interruption in ≥2% of patients included fatigue (3%; Grade 1-3), pyrexia (2.7%; Grade 1-3), alanine aminotransferase increased (2.4%; Grade 1-4), aspartate aminotransferase increased (2.4%; Grade 1-3), abdominal pain (2.1%; Grade 1-3), and lipase increased (2.1%; Grade 1-3). Adverse reactions leading to dose modification in ≥1% of patients were CRS (1.9%; Grade 1-3) and hypotension (1.1%; Grade 2-4). Very common adverse reactions were: CRS, decreased appetite, hypomagnesemia, hyponatremia, hypocalcemia, hypokalemia, insomnia, headache, dizziness, paresthesia, tachycardia, hypotension, flushing, hypertension, cough, dyspnea, nausea, vomiting, diarrhea, abdominal pain, constipation, dyspepsia, rash, pruritus, dry skin, hypo/hyperpigmentation, erythema, arthralgia, back pain, myalgia, pain in extremity, pyrexia, fatigue, chills, edema, influenza-like illness, increased aspartate aminotransferase, increased alanine aminotransferase, increased serum bilirubin, increased lipase, anemia, decreased lymphocyte count, decreased serum phosphate, increased serum creatinine. See other adverse reactions in the full product leaflet.

Registration: 1.9132.0001/ Medison Pharma Brasil Produtos Farmacêuticos LTDA /CNPJ 48.682.588/0001-37/ Rua Nelson Pontes , 125 Bloco 5 e 6. Jardim Margarida. Vargem Grande Paulista/SP/Indústria Brasileira/ KIMMTRAK/SAC: 0800-633-4766. SALE UNDER PRESCRIPTION. USE RESTRICTED TO HEALTHCARE ESTABLISHMENTS. If symptoms persist, a physician should be consulted. Scientific documentation and additional information are available from Customer Service and the service department for prescribers and dispensers of medication. Product information approved by Anvisa is available at View Source

On March 18, 2025 Alphamab Oncology (stock code: 9966.HK) and CSPC Pharmaceutical Group Co., Ltd. ("CSPC") (Stock Code: 1093.HK) reported that anti-HER2 biparatopic antibody-drug conjugate (ADC) JSKN003 has been granted Breakthrough Therapy Designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). The designation is for the treatment of platinum-resistant recurrent epithelial ovarian cancer (PROC), primary peritoneal cancer, or fallopian tube cancer, not restricted to HER2 expression levels.

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Ovarian cancer (OC) ranks as the third most common gynecologic malignancy in China and continues to show a rising incidence, with the highest mortality rate among all malignant gynecologic tumors. The standard treatment regimens recommended by authoritative guidelines both domestically and internationally include surgery combined with platinum-based chemotherapy and targeted therapy maintenance. However, about 80% of OC cases recur, and eventually progress to platinum-resistant ovarian cancer (PROC), leaving patients with limited effective treatment options and poor prognosis. Non-platinum chemotherapy, with or without bevacizumab, is the standard treatment for PROC. Previous studies have shown that the objective response rate (ORR) of PROC treated with non-platinum chemotherapy is only 10% to 15%. The median progression-free survival (PFS) is only 3 to 4 months, and the median overall survival (OS) approximately 12 months, highlighting an urgent need for new treatment options.

The grant of Breakthrough Therapy Designation is based on the pooled analysis of two clinical studies, JSKN003-101 and JSKN003-102. JSKN003-101 (NCT05494918) is an open-label, multicenter, dose-escalation Phase I clinical study conducted in Australia, enrolling patients with advanced solid tumors expressing HER2 (IHC≥1+) or with HER2 mutations. JSKN003-102 (NCT05744427) is a Phase I/ II study conducted in China. The Phase I part enrolled patients with histologically confirmed HER2 expression (IHC≥1+) or HER2 mutations advanced solid tumors. The Phase II part enrolled patients with advanced solid tumors regardless of HER2 expression or mutation status. Pooled results have demonstrated that JSKN003 monotherapy has a favorable tolerability and safety profile, with promising efficacy signals in patients with advanced PROC, and the efficacy was observed across patients with (IHC 1+/2+3+) or without (IHC 0) HER2 expression, with or without prior bevacizumab and prior PARP inhibitor. Preliminary data from the pooled analysis of these two studies were presented at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress.

The Phase III clinical study of JSKN003 for this indication is currently in the enrollment phase and the study is progressing smoothly. As a novel bispecific ADC, JSKN003 leverages the synergistic mechanism of enzyme catalysis and click chemistry to enhance serum stability and bystander effects, while demonstrating superior efficacy. The grant of Breakthrough Therapy Designation is expected to accelerate the clinical development, review and approval process of JSKN003, enabling more patients with PROC to benefit sooner.

About JSKN003

JSKN003 is an anti-HER2 bispecific antibody-drug conjugate (bis-ADC), which is developed inhouse with Alphamab’s proprietary Glycan-specific conjugation platform. JSKN003 can bind HER2 on the surface of tumor cells and release topoisomerase I inhibitors (TOPIi) through cellular endocytosis, thereby exert anti-tumor effects. Compared with its ADC counterparts, JSKN003 demonstrated better serum stability and stronger bystander effect, which effectively expands the therapeutic window.

Multiple clinical studies at various stages of JSKN003 are currently being conducted in China and Australia. Clinical research results have demonstrated favorable tolerability and safety profile, with promising efficacy of JSKN003 in heavily pretreated patients with advanced solid tumors, especially in patients with HER2-expressing breast cancer, platinum-resistant ovarian cancer (PROC), or high HER2-expressing solid tumors.

In September 2024, the Company entered a licensing agreement with JMT-Bio Technology Co., Ltd. ("JMT-Bio"), a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd. ("CSPC") (stock code: 1093.HK), pursuant to which, JMT-Bio was granted the exclusive license and sublicense rights to develop, sell, offer for sale and commercialize JSKN003, for the treatment of tumor-related indications (the "Field") in mainland China (excluding Hong Kong, Macau or Taiwan) (the "Territory") and become the sole marketing authorization holder for JSKN003 for the Field in the Territory. Alphamab retains the sole right to supply JSKN003.

(Press release, Alphamab, MAR 18, 2025, View Source [SID1234657003])