On March 11, 2025 Werewolf Therapeutics, Inc. (the "Company" or "Werewolf") (Nasdaq: HOWL), an innovative biopharmaceutical company pioneering the development of conditionally activated therapeutics engineered to stimulate the body’s immune system for the treatment of cancer and other immune-mediated conditions, reported a business update and announced financial results for the fourth quarter and full year ended December 31, 2024 (Press release, Werewolf Therapeutics, MAR 11, 2025, View Source [SID1234651073]).

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"Werewolf made considerable progress in 2024 with promising preliminary evidence of durable anti-tumor activity and tolerability for cytokine therapeutics as we completed the dose-escalation phase of our Phase 1/1b clinical trial in both monotherapy and in combination with pembrolizumab," said Daniel J. Hicklin, Ph.D., President and Chief Executive Officer of Werewolf. "We expect to build on these promising data in 2025, targeting full enrollment in the monotherapy cutaneous melanoma dose-expansion arm of the WTX-124 Phase 1/1b clinical trial by the end of the first half of 2025, and in combination with pembrolizumab by the end of the year. These data will guide conversations with regulators on potential registrational pathways for WTX-124 in the second half of the year. We anticipate providing a clinical data readout for both monotherapy and combination data and providing an update on our plans for further clinical development of WTX-124 in the fourth quarter of 2025. In addition, our PREDATOR platform continues to demonstrate its effectiveness as we presented updated interim safety, pharmacokinetics, biomarker, and efficacy data from the WTX-330 Phase 1 clinical trial at SITC (Free SITC Whitepaper) in November, which demonstrated anti-tumor activity in patients with refractory solid tumors. A Phase 1/2 dose and regimen-finding clinical trial is expected to be initiated by the end of the first quarter of 2025, which includes expansion arms in specific indications."

Recent Highlights and Upcoming Milestones
WTX-124: a systemically delivered, conditionally activated Interleukin-2 (IL-2) INDUKINE molecule being developed as monotherapy and in combination with pembrolizumab in multiple solid tumor types.
•Werewolf continues to evaluate WTX-124 as a monotherapy and in combination with pembrolizumab through the ongoing Phase 1/1b clinical trial evaluating the INDUKINE molecule in multiple solid tumor types.
•WTX-124 has shown promising monotherapy activity and an improved tolerability profile versus high dose IL-2 in heavily pretreated patients refractory to all standard-of-care therapies, including immune checkpoint inhibitors. The Company has selected 18 mg administered intravenously every two weeks (IV Q2W) as the recommended dose for monotherapy expansion arms in metastatic melanoma, renal cell carcinoma (RCC) and cutaneous squamous cell carcinoma (CSCC), as well as combination expansion arms in metastatic melanoma, RCC, and non-small cell lung cancer (NSCLC).

•Of the five previously disclosed objective responses, one monotherapy and two combination responses continue to demonstrate no evidence of disease progression, with the monotherapy complete response ongoing at greater than one year off therapy, one combination response improving from a confirmed partial response to a complete response, and both combination responses ongoing at greater than eight months.
•The cutaneous melanoma monotherapy dose-expansion arm of the Phase 1/1b clinical trial evaluating WTX-124 in a more homogeneous, less heavily pre-treated patient population is expected to be fully enrolled in the first half of 2025, and the cutaneous melanoma dose-expansion arm evaluating WTX-124 in combination with pembrolizumab is expected to be fully enrolled by the end of 2025. The Company expects to use the monotherapy and combination data to engage with regulators to discuss potential registrational pathways for WTX-124, including strategies for accelerated approval, in the second half of 2025.
•Anticipated presentation of interim data from monotherapy and combination expansion arms in the fourth quarter of 2025.
WTX-330: a systemically delivered, conditionally activated Interleukin-12 (IL-12) INDUKINE molecule being developed in advanced or metastatic solid tumors.
•Presented an interim update from the Phase 1 clinical trial highlighting the tolerability profile and monotherapy efficacy signals of WTX-330 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 39th annual meeting in November 2024.
•On track to initiate a Phase 1/2 dose- and regimen-finding clinical trial by the end of the first quarter of 2025 to optimize the exposure of WTX-330 in the tumor microenvironment.
•Pending data from Phase 1/2 dose- and regimen-finding trial, anticipate opening expansion arms in selected tumor types.
Preclinical Portfolio: includes development candidates WTX-712 and WTX-518, our Interleukin-21 (IL-21) and binding protein resistant Interleukin-18 (IL-18) INDUKINE molecules, respectively, for treatment of cancer, and WTX-921, a first-of-its-kind Interleukin-10 (IL-10) INDUKINE molecule for the treatment of inflammatory bowel disease (IBD) and potentially other inflammatory diseases.
Financial Results for the Fourth Quarter and Full Year 2024:
•Cash position: As of December 31, 2024, cash and cash equivalents were $111.0 million, compared to $134.3 million as of December 31, 2023. The Company also had restricted cash and cash equivalents of $1.2 million and $21.2 million as of December 31, 2024 and December 31, 2023, respectively. The Company believes its existing cash and cash equivalents at December 31, 2024 will be sufficient to fund operational expenses and capital expenditure requirements through at least the second quarter of 2026.
•Collaboration revenue: No collaboration was recognized during fourth quarter of 2024 due to the fact that Werewolf substantially completed its performance obligations under the collaboration agreement with Jazz Pharmaceuticals (Jazz) during the second quarter of 2024. Comparatively, collaboration revenue was $1.5 million for the fourth quarter of 2023. Collaboration revenue was $1.9 million for the full year 2024, compared to $19.9 million for the same period in 2023. Collaboration revenue consists of revenue recognized from the Company’s licensing agreement with Jazz and includes fixed payments received from Jazz, plus costs incurred for research services to be reimbursed by Jazz.
•Research and development expenses: Research and development expenses were $15.7 million for the fourth quarter of 2024, compared to $9.6 million for the same period in 2023. Research and development expenses were $56.4 million for the full year 2024, compared to $41.8 million for the full year 2023.
•General and administrative expenses: General and administrative expenses were $4.6 million for the fourth quarter of 2024, compared to $4.8 million for the same period in 2023. General and administrative expenses were $19.0 million for the full year 2024, compared to $18.7 million for the full year 2023.
•Net loss: Net loss was $20.4 million for the fourth quarter of 2024, compared to $12.0 million for the same period in 2023. Net loss was $70.5 million for the full year 2024, compared to $37.4 million for the full year 2023.

On March 11, 2025 Peptomyc SL, a Spanish clinical-stage biotech company spin-off of the Vall d’Hebron Institute of Oncology (VHIO) and the Catalan Institute of Research and Advanced Studies (ICREA) in Barcelona, reported that in February the first patient of its Phase 2 clinical trial in pediatric and adult patients with advanced osteosarcoma was successfully treated with OMO-103, the first direct pan-Myc inhibitor to have successfully completed a Phase 1 clinical trial (Press release, Peptomyc, MAR 11, 2025, View Source [SID1234651072]).

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This investigator-initiated trial conducted by VHIO in Barcelona, Spain, is sponsored by The Osteosarcoma Institute (OSI), whose mission is to dramatically increase treatment options and survival rates in osteosarcoma patients through identifying and funding the most promising and breakthrough osteosarcoma clinical trials and science. This trial is also supported in collaboration with Curing Kids Cancer, The Morgan Adams Foundation, and The Kristen Ann Carr Fund.

Dr. Claudia Morales Valverde, Senior Researcher of the Genitourinary, Central Nervous System (CNS) Tumors, Sarcoma, and Cancer of Unknown Primary Site Group at VHIO in Barcelona and Principal Investigator of the trial said, "This is the first use of a MYC inhibitor in osteosarcoma patients, and we are glad to conduct this seminal study at the Vall d’Hebron Institute of Oncology (VHIO) – Vall d’Hebron University Hospital." Peptomyc Chief Medical Officer, Dr. Manuela Niewel added, "MYC is an oncogene deregulated in the majority of human cancers and especially amplified in osteosarcomas. Inhibiting MYC with OMO-103, we hope to make a difference for this underserved patient population."

Peptomyc Chief Executive Officer, Dr. Laura Soucek concluded "We are extremely grateful to the OSI and VHIO for this study and for having enabled this important milestone for osteosarcoma patients."

The Phase 2 trial (OSTEOMYC) aims at evaluating the safety and clinical activity, pharmacodynamics, and pharmacokinetics of OMO-103 in advanced osteosarcoma. The primary efficacy endpoint is progression-free survival (PFS) at 16 weeks per RECIST criteria. Secondary endpoints include Overall Response Rate (ORR) per RECIST and overall survival. The trial is enrolling patients at Vall d’Hebron University Hospital in Barcelona, Spain. More information about the trial is available at: View Source

On March 11, 2025 Neurocrine Biosciences, Inc. (Nasdaq: NBIX) reported that it will participate at the Stifel 2025 Virtual CNS Forum at 1:30 p.m. Eastern Time on Tuesday, March 18, 2025 (Press release, Neurocrine Biosciences, MAR 11, 2025, View Source [SID1234651071]). Chief Executive Officer Kyle Gano and Chief Medical Officer Eiry Roberts will present at the conference.

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The live webcast can be accessed on Neurocrine Biosciences’ website under Investors at www.neurocrine.com. A replay of the webcast will be available on the website approximately one hour after the conclusion of the events and will be archived for approximately one month.

On March 11, 2025 Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company developing novel, investigational engineered therapies targeting cytokine pathways designed to address areas of unmet need for patients with a variety of cancers, reported its financial results for the fourth quarter and year ended December 31, 2024 and provided a business update (Press release, Mural Oncology, MAR 11, 2025, View Source [SID1234651070]).

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"By prioritizing operational efficiency and execution in 2024, we delivered on our milestones and positioned ourselves for a pivotal 2025, with several key inflection points anticipated for our nemvaleukin program. Late this quarter or early next quarter, we will report the interim overall survival analysis for ARTISTRY-7, a potentially registrational trial in platinum-resistant ovarian cancer. As is typical for interim analyses, the bar for success is high. We believe that either declaring the trial complete at the interim analysis or deciding to progress the trial to a final analysis based on the available overall survival data would be a meaningful step forward both for patients and for Mural. Additionally, topline data from ARTISTRY-6 in mucosal melanoma, expected in the second quarter of 2025, represents another potentially significant opportunity for impact and value creation," said Caroline Loew, Ph.D., CEO of Mural Oncology.

Recent Corporate Highlights

In January 2025, Mural announced that, consistent with the company’s prior timing projections, the phase 3 ARTISTRY-7 trial reached the 75% of overall survival (OS) events necessary for the planned interim analysis. This data remains blinded to the company until after the independent data monitoring committee (IDMC) has reviewed the interim analysis, which is expected to be in late Q1/early Q2 2025.

In January 2025, the company also announced that patient enrollment in cohort 3 of the phase 2 ARTISTRY-6 trial is now complete.

Mural expanded its pipeline in Q4 2024 by nominating two development candidates:

MURA-8518, the company’s interleukin-18 (IL-18) program, is designed to deliver a more sustained immune response by introducing half-life extension and resistance to IL-18 Binding Protein (IL-18BP), which otherwise neutralizes the native cytokine’s efficacy.
MURA-7012, Mural’s IL-12 program, is designed to leverage native IL-12’s anti-tumor potency while mitigating its hallmark toxicity. It splits the IL-12p70 heterodimer into two individual sub-units designed to preferentially self-assemble at the tumor site to limit systemic exposure.
Upcoming Milestones

Late Q1/early Q2 2025: Interim data readout of ARTISTRY-7

ARTISTRY-7 is a potentially registrational phase 3 trial evaluating nemvaleukin alfa in combination with pembrolizumab versus investigator’s choice single agent chemotherapy in patients with platinum-resistant ovarian cancer (PROC). Consistent with interim analyses, there is a higher statistical bar for success at the interim analysis compared to the final analysis. If the hazard ratio at the interim analysis meets this pre-specified higher bar for success at the interim analysis (0.727, or a 27.3% reduction in the risk of death assuming exactly 215 OS events), the company plans to submit a Biologics License Application (BLA) for nemvaleukin in combination with pembrolizumab for the treatment of PROC in 2025. If the hazard ratio does not meet the statistical threshold for success at the interim analysis and the company deems the study to have a high probability of success at the final analysis, Mural expects to continue the trial to the protocol-specified final OS. At the final OS analysis, the maximum hazard ratio for success is 0.788, or a 21.2% reduction in the risk of death, assuming exactly 286 events. In that scenario, the company expects to report final OS result in the second quarter of 2026, subject to event accrual.

Q2 2025: Top-line data readout of ARTISTRY-6, Cohort 2

ARTISTRY-6, cohort 2 is a potentially registrational phase 2 trial of nemvaleukin monotherapy in patients with unresectable or metastatic mucosal melanoma previously treated with immune checkpoint blockade. Nemvaleukin has been granted Orphan Drug Designation by the United States Food & Drug Administration (FDA) for the treatment of mucosal melanoma. The target response rate in the ARTISTRY-6 trial is 25%. Mural believes that in this rare and highly aggressive tumor, which has historically had poor outcomes even in the first line setting, demonstrating durable responses with a response rate of 20-25% would be meaningful for patients, and would support a discussion with the FDA regarding a BLA submission and potential accelerated approval.

1H 2025: Preliminary data readout of ARTISTRY-6, Cohort 3

This trial is an evaluation of less-frequent intravenous (LFIV) dosing of nemvaleukin monotherapy in patients with cutaneous melanoma. The company is conducting the trial to evaluate the activity and further characterize the safety of nemvaleukin with LFIV dosing in patients with cutaneous melanoma.

2H 2025: Preliminary data readout of ARTISTRY-6, Cohort 4

This trial is an evaluation of LFIV dosing of nemvaleukin in combination with pembrolizumab in patients with cutaneous melanoma.

1H 2026: Submission of Investigational New Drug or Clinical Trial Application for a phase 1 trial of MURA-8518

MURA-8518 is Mural’s IL-18 development candidate. Native IL-18 is a potent immune-stimulating cytokine, but its activity is blunted by IL-18BP, a high affinity decoy protein that neutralizes IL-18, thereby rendering it ineffective. The native cytokine’s potency is also limited by its short half-life. MURA-8518 aims to address these shortcomings in two ways. First, through the introduction of mutations designed to minimally impact the native structure while eliminating binding to IL-18BP. Secondly, half-life extension via fusion to a protein scaffold increases the cytokine’s exposure, allowing for sustained immune stimulation. Together, these have demonstrated more durable immunological effects in preclinical studies.

Financial Results for the Quarter Ended December 31, 2024

Cash Position: As of December 31, 2024, cash, cash equivalents, and marketable securities were $144.4 million.

R&D Expenses: Research and development expenses were $28.7 million for the fourth quarter of 2024 compared to $42.2 million for the fourth quarter of 2023. This decrease was primarily due to a decrease in employee-related expenses, including a non-cash share-based employee compensation charge in the fourth quarter of 2023 as a result of the impact of the modification of our share based-awards in connection with the separation from Alkermes plc ("Alkermes"), our former parent.

In addition, the timing of patient enrollment in the ARTISTRY-7 trial, as well as the winding down of the ARTISTRY-1 and ARTISTRY-2 trials during 2024 also contributed to the decrease in R&D expenses in the fourth quarter of 2024, as compared to the fourth quarter of 2023.

G&A Expenses: General and administrative expenses were $7.2 million for the fourth quarter of 2024 compared to $16.3 million for the fourth quarter of 2023. This decrease in G&A expenses was primarily due to a decrease in employee-related expenses compared to those previously allocated to us by Alkermes prior to the separation and to one-time increases in employee related expenses in 2023, including a non-cash share-based employee compensation charge in the fourth quarter of 2023 as a result of the impact of the modification of our share based-awards in connection with the separation.

Net Loss: Net loss was $34.3 million for the fourth quarter of 2024 compared to $59.5 million for the fourth quarter of 2023. The net loss for the fourth quarter of 2023 included $11.7 million resulting from one-time charges related to the separation from Alkermes and conversion of Alkermes employee equity awards into Mural equity.

Financial Guidance: Mural’s cash, cash equivalents, and marketable securities as of December 31, 2024 are expected to fund its operations into the first quarter of 2026.

On March 11, 2025 MaaT Pharma (EURONEXT: MAAT – the "Company"), a clinical-stage biotechnology company and a leader in the development of Microbiome Ecosystem TherapiesTM (MET) dedicated to enhancing survival for patients with cancer through immune modulation, reported that the European Medicines Agency (EMA) Pediatric Committee (PDCO) has approved the Pediatric Investigation Plan (PIP) for MaaT013 for the treatment of acute Graft-versus-Host Disease (aGvHD) (Press release, MaaT Pharma, MAR 11, 2025, View Source [SID1234651069]).

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"We are very pleased with the productive dialogue with the EMA Pediatric Committee and the positive PIP opinion. This approval marks a major regulatory milestone towards the submission of our Marketing Authorization dossier with the EMA," said Gianfranco Pittari, MD, PhD, Chief Medical Officer at MaaT Pharma. "Through our Early Access Program, we have already successfully and safely treated two pediatric patients with aGvHD. We are committed to bringing MaaT013 to pediatric patients suffering from aGvHD, who currently have limited options."

The EMA PDCO approved the clinical program to evaluate the safety and efficacy of MaaT013 in patients from 6 years old to less than 18 years old, with the initiation, in 2026, of a single-arm trial in third-line treatment for 18 patients with aGvHD and in line with the Company’s cash projections.

Based on this positive opinion, MaaT013 would be eligible for up to an additional two years of marketing exclusivity in Europe, on top of the ten-year European market exclusivity as an orphan drug if the Marketing Authorization is granted by the EMA. This also confirms the Company’s ability to reach the full patient population.

"With this approval of our Pediatric Investigation Plan, we are now on track to submit our Marketing Authorization dossier in June this year. If approved, the Company could be positioned to generate revenues as soon as late 2026 with MaaT013 in third-line treatment in aGvHD," stated Hervé Affagard co-founder and CEO of MaaT Pharma. "Additionally, the Company will continue to provide the product through its Early Access Program for all patients in need."

About the Pediatric Committee (PDCO)
The Pediatric Committee (PDCO) is the European Medicines Agency’s (EMA) scientific committee responsible for activities on medicines for children and to support the development of such medicines in the European Union by providing scientific expertise and defining pediatric needs. The PDCO issues an opinion on PIP as part of the regulatory process and the EMA adopts a final decision based on the PDCO’s opinion.

About the Pediatric Investigation Plan (PIP)
A pediatric investigation plan (PIP) is a development plan aimed at ensuring that the necessary data are obtained through studies in children, to support the authorization of a medicine for children. As part of the regulatory process for the registration of new medicines in Europe, the EMA requires pharmaceutical companies to provide a PIP detailing their strategy for investigation of the new medicinal product in the pediatric population. An approved PIP is a prerequisite for filing a Marketing Authorization Application (MAA).

About acute Graft-versus-Host Disease

Acute Graft-versus-Host Disease occurs in patients within 100 days of undergoing a stem cell or bone marrow transplant, where the transplanted cells initiate an immune response and attack the transplant recipient’s organs, causing inflammation of the skin, liver and/or gastro-intestinal tract and leading to significant morbidity and mortality. GI involvement is associated with severe complications such as profound diarrhea, abdominal pain, intestinal bleeding, and death. These complications are often life-threatening, with increased mortality risk, due to the challenges of managing severe GI inflammation and the associated risks of infection, malnutrition, and organ failure. The standard first line therapy for treating aGvHD is the use of systemic steroids. If patients do not respond to steroids, they are considered Steroid Resistant (SR) and other agents can be administered. Currently, the second-line treatment for steroid-refractory acute graft-versus-host disease (SR aGvHD) is ruxolitinib. Recently, remestemcel—L-rknd was approved in December 2024 in the US specifically for use in the paediatric population as a second-line treatment.

About MaaT013

MaaT Pharma’s Microbiome Ecosystem TherapiesTM (MET) are designed to leverage a full microbiome ecosystem to restore balance and maximize clinical benefits for patients with severe, treatment-induced dysbiosis in acute diseases. MaaT013 is a full-ecosystem, off-the-shelf, standardized, pooled-donor, enema Microbiome Ecosystem TherapyTM for acute, hospital use. It is characterized by a consistently high diversity and richness of microbial species and the presence of ButycoreTM (a group of bacterial species known to produce anti-inflammatory metabolites). MaaT013 aims to restore the symbiotic relationship between the patient’s functional gut microbiome and their immune system to correct the responsiveness and tolerance of immune functions and thus reduce steroid-resistant, gastrointestinal (GI)-aGvHD. MaaT013 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).