On February 20, 2025 Signet Therapeutics, a clinical-stage biotech company leveraging organoid- and AI-driven cancer drug discovery, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for SIGX1094, the world’s first potential targeted therapy for diffuse gastric cancer (DGC) (Press release, Signet Therapeutics, FEB 20, 2025, View Source [SID1234650436]). This designation is designed to accelerate the development and regulatory review of therapies addressing serious diseases with unmet medical needs, bringing promising new treatments to patients more quickly. In November 2024, SIGX1094 was also granted Orphan Drug Designation (ODD) from the FDA.

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"Receiving Fast Track Designation for SIGX1094 underscores the FDA’s recognition of both the serious, life-threatening nature of diffuse gastric cancer and the potential of SIGX1094 to address this critical medical need," said Dr. Haisheng Zhang, founder and CEO of Signet Therapeutics. "This milestone highlights our commitment to rapidly advancing innovative cancer treatments through our organoid and AI platform, bringing us closer to offering a breakthrough solution for patients with diffuse gastric cancer."

SIGX1094 is an innovative targeted therapy developed using Signet’s proprietary organoid + AI drug discovery platform. Based on a novel therapeutic target independently identified by Signet, SIGX1094 was discovered and optimized in collaboration with XtalPi (2228.HK), a leading drug discovery platform integrating quantum physics, AI, and robotics. As the world’s first drug developed through the integration of organoid models and AI, SIGX1094 represents a major advance in the treatment of DGC, a highly aggressive cancer with no approved targeted therapies. The drug is currently being evaluated in a Phase I clinical trial at Beijing Cancer Hospital in China.

With Fast Track Designation, Signet Therapeutics will benefit from more frequent interactions with the FDA throughout the drug development process, early regulatory guidance, and potential eligibility for accelerated approval, priority review, and rolling review—all aimed at expediting SIGX1094’s path to market and addressing the urgent need for effective DGC treatments. SIGX1094 received Orphan Drug Designation (ODD) from the U.S. FDA in November 2024. The FDA grants ODD to therapies for rare diseases affecting fewer than 200,000 people in the U.S.

Signet Therapeutics is at the forefront of integrating organoid models with AI to revolutionize drug discovery. By combining AI-driven molecular screening with its proprietary organoid platform, Signet accelerates the identification, evaluation, and optimization of novel therapeutics. This innovative approach significantly enhances drug development efficiency and clinical success rates, representing a paradigm shift in the convergence of AI and biotechnology for precision oncology.

On February 20, 2025 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported data from Phase 2a trial of SLS009 (tambiciclib), a highly selective CDK9 inhibitor, in relapsed/refractory Diffuse Large B-Cell Lymphoma (r/r DLBCL) (Press release, Sellas Life Sciences, FEB 20, 2025, View Source [SID1234650419]).

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The trial, conducted and funded by GenFleet Therapeutics (Shanghai), Inc. ("Genfleet"), was an open-label single-arm multicenter Phase 2a study in China evaluating SLS009 in combination with BTK inhibitor, Brukinsa (zanubrutinib) in r/r DLBCL. The results showed an overall response rate of 67%, more than double the expected overall response rate (ORR) of zanubrutinib alone. Among responders, one achieved complete response (CR), while three had partial response (PR) with target lesion shrinkages of 89%, 78%, and 56%, respectively. As of the last follow-up, after the median of 4.6 (range: 1.4 – 7.4) months follow-up, median overall survival (OS) was not reached, and six out of 9 patients were alive.

"These results represent a promising step forward in improving outcomes for DLBCL patients and underscores the potential of SLS009 in combination with zanubrutinib to deliver meaningful clinical benefits," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "Achieving an ORR that significantly exceeds expectations, along with a complete response and multiple partial responses is a testament to the power of collaboration and innovation in tackling this challenging disease. We believe that the combination of SLS009 and zanubrutinib demonstrates a synergy that could pave the way for more effective treatment options. Moving forward, GenFleet will determine the next steps regarding the trial’s continuation around lymphoma as SELLAS’ focus remains in AML and spliceosome – chromatin mutations, including ASXL1 mutations."

Summary of Phase 2a data of SLS009 in DLBCL

Patients Characteristics

9 r/r DLBCL patients were enrolled: 3 with germinal center B-cell like (GCB) and 6 with activated B-cell like (ABC) subtype of DLBCL
ABC DLBCL, also known as non-GCB DLBCL, carries a worse prognosis vs. GCB DLBCL
The median age was 55 years old and the median of previous lines of therapy was 2 (range 2-4)
Efficacy and Safety

Among 6 non-GCB DLBCL (ABC DLBCL) patients, 4 had an objective response and one patient achieved stable disease (SD) for the disease control rate (DCR) of 5/6 (83%)
Overall response rate (ORR) was 4/6 (67%), more than double the expected ORR with zanubrutinib alone
One patient achieved complete response (CR), and three patients had partial response (PR) with target lesion shrinkages of 89%, 78%, and 56%, respectively
As of the last follow-up, after the median of 4.6 (range: 1.4 – 7.4) months follow-up, median overall survival (OS) was not reached
Six patients were alive as of the last follow-up, including 5 non-GCB DLBCL and 1 GCB DLBCL. Adverse events (AEs) grade ≥ 3 AEs were reported in 55.6% of patients, comparable to safety outcomes expected with Zanubrutinib alone
Genetic data of 6 out of 9 enrolled patients showed that none of the patients carried MYD88 or CD79B mutations predictive of better response to BTK inhibitors. The patient who achieved complete response (CR) by CT had MYC amplification, which is expected, but interestingly also harbored TP53 mutations, indicating that CDK9 inhibition with SLS009 could circumvent TP53 mutated cancers drug resistance.
"These additional data from yet another indication help us further expand the scope of SLS009," said Dragan Cicic, MD, Chief Development Officer of Sellas. "In parallel with our very advanced clinical development in acute myeloid leukemia, we are continuously working on additional clinical and preclinical programs in other indications and uncovering genetic biomarkers that make all the difference in today’s drug development."

On February 20, 2025 CEL-SCI Corporation (NYSE American: CVM) reported it is in the final stages for the launch of its 212-patient Confirmatory Registration Study for Multikine* (Leukocyte Interleukin, Injection) in newly diagnosed locally advanced head and neck cancer patients (Press release, Cel-Sci, FEB 20, 2025, View Source [SID1234650437]). This final Registration Study is specifically designed to confirm the statistically significant efficacy and safety results from CEL-SCI’s previously completed randomized controlled Phase 3 trial.

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This new Registration Study targets the population of previously untreated resectable stage 3 and 4 head and neck cancer patients who had no lymph node involvement and low PD-L1 tumor expression. During the completed Phase 3 clinical trial, the 5-year survival rate of the target patient population increased to 73% when patients were treated with Multikine vs 45% for control patients who received only the standard of care treatments.

Key aspects of the new Confirmatory Registration Study are as follows:

Enlisting clinical sites and investigators in numerous countries across 3 continents
Full enrollment expected by Q2 2026 with plans to seek early approval at that time based on early tumor responses—Potential to set a new standard of care
FDA concurred with the overall design of the Registration Study in meetings last year
Final clinical protocol submitted to FDA in December 2024
Multikine extended median overall survival by nearly 4 years in prior Phase 3 study
A new model for healthcare—Immunotherapy given before surgery to boost the immune system and make the first cancer treatment more successful – may set the first new standard of care in more than half a century
"Now that the clinical protocol for our final marketing Registration Study has been submitted, we are proceeding to sign up investigators and open clinical sites. We are receiving a very positive response and high levels of interest from head and neck cancer physicians who see the abundance of data on Multikine and want to deliver this option to their patients," stated CEL-SCI CEO Geert Kersten. "We believe that this small 212-patient trial will enroll relatively quickly precisely because Multikine has proven what it can do in terms of safety and efficacy in this specific target patient population which has not had a new option for treatment in decades."

"We are very confident in this Registration Study’s chance of success since we already know that this type of patient showed an almost 4 year increase in median survival in our last study. The many studies we have done have helped us figure out who benefits from the drug and who does not. Early tumor responses measured after treatment with Multikine and prior to surgery have been shown to be correlated with 5-year overall survival outcomes. We plan to seek accelerated and/or conditional marketing approval based on this finding. Data regarding early tumor responses following Multikine treatment should become available shortly after the last patient has been treated, expected by the second quarter of 2026," Kersten concluded.

CEL-SCI has been advised by a biostatistician with expertise in the design and analysis of oncology studies that this final Confirmatory Registration Study has an over 95% chance of success because it will include only the target population of patients who benefited most from Multikine in the prior Phase 3 study. These patients had much longer overall survival and had tumor responses including size reduction and total tumor elimination confirmed by pathology following three weeks of Multikine treatment. The favorable efficacy results in this target patient population exhibited a hazard ratio of 0.35 with an upper 95% confidence interval of 0.66, therefore CEL-SCI can expect (at 95%) to reach a favorable hazard ratio in the Confirmatory Registration Study.

There were no safety signals identified, Multikine administration did not interfere with disease directed treatment/therapy, and Multikine did not add to the treatment burden imparted by the standard of care.

Following the U.S. Food and Drug Administration’s (FDA) go-ahead to conduct the Registration Study, CEL-SCI finalized the clinical protocol based on constructive comments from FDA reviewers and senior staff. The final clinical protocol was submitted to the FDA in December 2024. The study is titled:

"A Phase III, Open Label, Randomized, Controlled, Multi-Center Study of the Effects of Neoadjuvant Leukocyte Interleukin, Injection (LI) Plus Standard of Care Versus Standard of Care Only in Treatment Naïve Adults With Resectable Locally Advanced Primary Squamous Cell Carcinoma of the Head and Neck (Oral Cavity) Who Present With No Nodal Involvement and Low Tumor Programmed Death Ligand 1 Expression (Defined as Tumor Proportion Score <10)"

Ergomed, the clinical research organization (CRO) for the Registration Study, is currently identifying clinical sites and investigators. Sites are initially expected to open in four countries across three continents, with the first clinical site expected to initiate in the United States.

On February 20, 2025 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has obtained regulatory approval today from the Ministry of Health, Labour and Welfare for the anti-cancer agent/humanized anti-PD-L1 monoclonal antibody Tecentriq Intravenous Infusion [generic name: atezolizumab (genetical recombination)] for an additional indication of unresectable alveolar soft part sarcoma (Press release, Chugai, FEB 20, 2025, View Source;category= [SID1234650398]). Tecentriq is the first immune checkpoint inhibitor in Japan for the treatment of this disease.

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"We are very pleased that we can offer Tecentriq as a new treatment for unresectable alveolar soft part sarcoma in adults and children over 2 years. This very rare disease, which occurs most often in the adolescents and young adults (AYA) generation, is known to have a poor prognosis with no standard treatment if it becomes unresectable. We will continue our efforts to provide information on the proper use of Tecentriq in order to contribute to the patients with unresectable alveolar soft part sarcoma," said Chugai’s President and CEO, Dr. Osamu Okuda.

This approval is based on the results from a phase II ALBERT study initiated by investigators in Japan including National Cancer Center Hospital and an overseas phase II clinical study conducted by the National Cancer Institute (NCI), which evaluated the efficacy and safety of Tecentriq in patients with unresectable alveolar soft part sarcoma.

Chugai Pharmaceutical, a leading company in the oncology field, remains committed to addressing unmet medical needs in cancer treatment with innovative medicines, supporting patients and healthcare professionals.

Approval Information *Newly added description
Indications: unresectable alveolar soft part sarcoma
Dosage and administrations: The usual adult dosage is 1200 mg atezolizumab (genetical recombination) administered by intravenous infusion over 60 minutes once every 3 weeks. The usual dose for children over 2 years old is 15 mg/kg (weight) (max 1200 mg) atezolizumab (genetical recombination) administered by intravenous infusion over 60 minutes once every 3 weeks. If the initial infusion is well tolerated, subsequent infusions can be delivered over 30 minutes.

About the ALBERT study1
The ALBERT study is a domestic Phase II, multicenter, open-label, single-arm study led by physicians including National Cancer Center Hospital in Japan to evaluate the efficacy and safety of Tecentriq in patients aged 16 years and older with unresectable alveolar soft part sarcoma. The study enrolled 20 patients to investigate safety and efficacy.

The ALBERT study is being conducted as a substudy of the MASTER KEY project, which promotes the development of treatments for rare cancers through industry-academia collaboration with the National Cancer Center Hospital.

About alveolar soft part sarcoma
Alveolar soft part sarcoma is one of the ultra-rare cancers accounting for less than 1% of soft tissue sarcomas. It is estimated to occur in 15-40 Japanese people annually. It most commonly affects the limbs, mainly the thighs, and is more common among adolescents and young adults (15-35 years old, AYA (Adolescent and Young Adult) generation). Unresectable alveolar soft part sarcoma has a poor prognosis, and no standard treatment has been established.

About Tecentriq
Tecentriq is a cancer immune checkpoint inhibitor targeting PD-L1, which is a protein expressed on tumor and tumor-infiltrating immune cells. PD-L1 blocks T cell activity by binding with PD-1 and B7.1 receptors on T cell surface. By inhibiting PD-L1, Tecentriq may enable the activation of T cells and boost immune response against cancer cells. In Japan, Tecentriq was launched in April 2018 and has obtained approval for 4 indications (extensive-stage small cell lung cancer, non-small cell lung cancer, breast cancer, and hepatocellular carcinoma).

On February 20, 2025 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported financial results for the fourth quarter and full year periods ended December 31, 2024 and provided an update on recent company developments (Press release, SpringWorks Therapeutics, FEB 20, 2025, View Source [SID1234650420]).

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"We are very pleased with the strong execution of OGSIVEO in 2024 and believe that we are still in the early stages of realizing the full potential of our opportunity to serve the desmoid tumor community. With the recent FDA approval of GOMEKLI for adults and children with NF1-PN, we believe we are ready to deliver another strong launch and are delighted that the broad label enables us to help patients throughout their treatment journey," said Saqib Islam, Chief Executive Officer of SpringWorks. "In parallel with our U.S. launches, we are working with urgency to bring our medicines to patients globally and are advancing a diversified pipeline across a variety of indications that provide the potential for us to develop important therapeutic advances for patients who are currently underserved."

Recent Business Highlights and Upcoming Milestones

OGSIVEO (Nirogacestat)

Continued strong commercial execution of the OGSIVEO launch in the U.S. with fourth quarter and full-year 2024 U.S. net product revenue for OGSIVEO of $61.5 million and $172.0 million, respectively.
A Marketing Authorization Application (MAA) for nirogacestat for the treatment of adult patients with desmoid tumors is under review with the European Medicines Agency (EMA). If approved, SpringWorks expects to launch OGSIVEO following reimbursement authorization in individual EU countries, beginning with Germany in mid-2025.
Presented long-term follow-up data from the Phase 3 DeFi trial of nirogacestat in adults with progressing desmoid tumors at the 2024 Connective Tissue Oncology Society Annual Meeting, which highlighted further reductions in tumor size, increase in objective response rate, sustained improvement in desmoid tumor symptoms, and consistent safety profile. SpringWorks expects to publish these data in a peer-reviewed journal in 2025.
SpringWorks expects to report initial data from the Phase 2 trial evaluating nirogacestat as a monotherapy in patients with ovarian granulosa cell tumors in the first half of 2025.
SpringWorks continues to support several industry and academic collaborator studies evaluating nirogacestat as part of B-cell maturation antigen (BCMA) combination therapy regimens across treatment lines in patients with multiple myeloma.
GOMEKLI (Mirdametinib)

On February 11, 2025, SpringWorks received U.S. Food and Drug Administration (FDA) approval for GOMEKLI, an oral MEK inhibitor, for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection. GOMEKLI is the first and only medicine approved for both adults and children with NF1-PN. With the approval, SpringWorks was granted a rare pediatric disease priority review voucher (PRV) by the FDA.
GOMEKLI is now available through a specialty pharmacy and specialty distributor network in the United States.
An MAA for mirdametinib for the treatment of adults and children with NF1-PN is under review with the EMA. If approved, SpringWorks expects to begin its initial launch in the European Union in 2025.
A Phase 2 study evaluating mirdametinib in pediatric and young adult patients with low-grade gliomas (LGG) is ongoing and enrolling patients.
Emerging Pipeline

A Phase 1b trial of brimarafenib and Amgen’s EGFR inhibitor, panitumumab, in colorectal and pancreatic cancer patients with known MAPK pathway mutations is ongoing. Brimarafenib is an investigational, selective RAF dimer inhibitor being developed by MapKure, LLC, a joint venture between SpringWorks and BeiGene, Ltd.
SpringWorks is continuing to enroll patients in a Phase 1 trial of SW-682, an investigational novel, oral, potent, and selective pan-TEAD inhibitor, in Hippo-mutant solid tumors.
SpringWorks obtained an exclusive, global license from Rappta Therapeutics Oy for a first-in-class molecular glue of specific Protein Phosphatase 2A (PP2A) complexes. PP2A mutations represent a class of targetable oncogenic drivers in molecularly defined subsets of uterine cancer patients with high unmet need. In preclinical models of PP2A mutant uterine cancer, SW-3431 (formerly RPT04402) showed rapid, deep and durable tumor regressions as a monotherapy. SpringWorks expects to file an Investigational New Drug (IND) application for SW-3431 by the end of 2025.
Fourth Quarter and Full Year 2024 Financial Results

Product Revenues: OGSIVEO net product revenues were $61.5 million and $172.0 million in the fourth quarter of 2024 and full year 2024, respectively.
Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $77.1 million and $256.7 million for the fourth quarter and full year 2024, respectively, compared to $59.8 million and $197.6 million for the comparable periods of 2023. The increase in SG&A expense for the fourth quarter and the full year 2024 were largely attributable to commercial readiness activities to support the U.S. launch of GOMEKLI as well as commercial activity supporting the U.S. launch of OGSIVEO.
Research and Development (R&D) Expenses: R&D expenses were $60.2 million and $200.5 million for the fourth quarter and full year 2024, respectively, compared to $43.7 million and $150.5 million for the comparable periods of 2023. The increase in R&D expense for the fourth quarter and year ended 2024 was primarily attributable to an increase in external costs related to licensing fees, drug manufacturing, clinical trials, other research, consulting and professional services.
Net Loss Attributable to Common Stockholders: SpringWorks reported a net loss of $77.3 million, or $1.04 per share, for the fourth quarter of 2024 and a net loss of $258.1 million, or $3.48 loss per share, for the year ended December 31, 2024. This compares to a net loss of $94.3 million, or $1.44 per share, for the fourth quarter of 2023 and a net loss of $325.1 million, or $5.15 per share for the year ended December 31, 2023.
Cash Position: Cash, cash equivalents and marketable securities were $461.9 million as of December 31, 2024.
Additional Information

Additional information on the Company’s results can be found on the Investors and Media section of the SpringWorks website at View Source The previously scheduled conference call and webcast has been cancelled.