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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) and Ono Pharmaceutical Co., Ltd (Ono), reported that the two companies have entered into a license agreement in which Ono obtains exclusive global rights for the development and commercialization of sapablursen, an investigational RNA-targeted medicine for polycythemia vera (PV), a rare and potentially life-threatening hematologic disease (Press release, Ionis Pharmaceuticals, MAR 11, 2025, View Source [SID1234651095]). Sapablursen is currently being evaluated in adults living with PV in the fully enrolled Phase 2 IMPRSSION study. Sapablursen was granted Fast Track designation and orphan drug designation in 2024 by the U.S. Food and Drug Administration (FDA).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Under the terms of the agreement, Ionis will receive a $280 million upfront payment, with the potential to earn up to $660 million in additional payments based on the achievement of development, regulatory and sales milestones. Ionis is also eligible to earn royalties in the mid-teen percentage range on annual net sales of sapablursen. Ionis will be responsible for the completion of the ongoing Phase 2 IMPRSSION study, while Ono will be solely responsible for subsequent development, regulatory filings and commercialization. The transaction is subject to the requirements of the Hart-Scott-Rodino Antitrust Improvements Act of 1976 (HSR Act).

"We are pleased to entrust sapablursen to Ono, whose unique capabilities will help maximize its value by ensuring broad access for people living with PV," said Brett P. Monia, Ph.D., chief executive officer, Ionis. "Ionis remains committed to advancing the wholly owned medicines we choose to commercialize ourselves, which includes our first independent launch currently underway and three additional anticipated launches in the next three years. Streamlining our Ionis-owned portfolio provides financial flexibility, supporting our commitment to invest in and focus on our near and mid-term commercial opportunities and generate substantial revenue growth."

"We are delighted to enter into this collaboration with Ionis Pharmaceuticals, a pioneer in RNA-targeted medicines, for sapablursen. This partnership aligns with our strategy to strengthen our pipeline in hematology. We expect sapablursen to become a new treatment option for PV patients worldwide," said Toichi Takino, president and COO, Ono.

About Polycythemia Vera (PV)
PV is a rare and potentially life-threatening hematologic disease characterized by the overproduction of red blood cells, which significantly increases the risk of serious blood clots, especially in critical organs like the lungs, heart and brain. Patients with PV also experience severe iron deficiency and commonly have symptoms of fatigue.

About Sapablursen
Sapablursen is designed to reduce the production of TMPRSS6 resulting in increased expression of hepcidin, which is the key regulator of iron homeostasis. By increasing production of hepcidin, sapablursen has the potential to positively impact blood diseases such as PV.

On March 11, 2025 Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, reported pipeline progress and business updates and announced financial results for the fourth quarter and full year ended December 31, 2024 (Press release, Xilio Therapeutics, MAR 11, 2025, View Source [SID1234651074]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We started 2025 with multiple promising updates across our pipeline, including encouraging initial Phase 2 combination data for vilastobart, our tumor-activated anti-CTLA-4, in patients with late-line MSS CRC, a difficult to treat, immunologically cold tumor type that is increasing in incidence, particularly in younger people," said René Russo, Pharm.D., president and chief executive officer of Xilio. "These data included a preliminary 27% objective response rate in patients without liver metastases and continue to support a differentiated safety profile, including a low incidence of immune-related adverse events and only 5% of patients reporting colitis. We look forward to reporting additional data from the ongoing Phase 2 trial in the middle of this year."

Dr. Russo added, "In addition, we are excited to be advancing multiple novel masked T cell engager programs internally and as part of our recently announced collaboration with AbbVie. Each of these programs leverages our clinically-validated, tumor-activation technology, which we believe has great potential to enhance the activity and tolerability of T cell engagers and open up promising new targets within this class of immunotherapies."

Pipeline and Business Updates

Vilastobart: tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4

Vilastobart is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 monoclonal antibody designed to block CTLA-4 and deplete regulatory T cells when activated in the tumor microenvironment (TME).

•
In January 2025, Xilio announced encouraging initial data from its ongoing Phase 2 clinical trial evaluating vilastobart at a dose of 100 mg once every six weeks (Q6W) in combination with atezolizumab (Tecentriq) at 1200 mg once every three weeks (Q3W) in patients with metastatic microsatellite stable colorectal cancer (MSS CRC). As of a data cutoff date of January 13, 2025, these data demonstrated a preliminary 27% objective response rate in patients without liver metastases, and responses were accompanied by decreases in levels of serum tumor biomarkers (carcinoembryonic antigen and circulating tumor DNA) as well as improvement in clinical symptoms. In addition, as of the data cutoff date, the combination was generally well-tolerated, with patients experiencing a low incidence of immune-related adverse events and only 5% of patients reporting colitis. These safety data continue to support the potential for vilastobart to be a differentiated next-generation anti-CTLA-4 in combination with PD-(L)1 inhibitors. For more information, read the press release here.

•
Xilio expects to report updated data from the Phase 2 clinical trial in the middle of 2025, including additional response assessments and follow-up. In addition, Xilio continues to enroll patients in Phase 1C (combination dose escalation) evaluating vilastobart at the 150 mg Q6W dose level in combination with atezolizumab at 1200 mg Q3W.

•
Based on the promising initial Phase 2 proof-of-concept data, Xilio plans to seek opportunities for partnering to accelerate and expand further development of vilastobart.

XTX301: tumor-activated IL-12

XTX301 is an investigational tumor-activated IL-12 designed to potently stimulate anti-tumor immunity and reprogram the TME of poorly immunogenic "cold" tumors towards an inflamed or "hot" state. In March 2024, Xilio entered into an exclusive license agreement with Gilead Sciences, Inc. (Gilead) related to Xilio’s tumor-activated IL-12 program, including XTX301.

•
In December 2024, Xilio announced preliminary data from its ongoing Phase 1 clinical trial of XTX301 in patients with advanced solid tumors. As of the data cutoff date of November 25, 2024, XTX301 was generally well-tolerated, and no patients experienced a dose limiting toxicity or a dose reduction due to a treatment-related adverse event. In addition, XTX301 showed evidence of sustained interferon gamma signaling without evidence of tachyphylaxis throughout treatment cycles. Tachyphylaxis has historically limited other IL-12 agents. For more information, read the press release here.

•
A maximum tolerated dose has not yet been established, and Xilio continues to enroll patients in Phase 1A monotherapy dose escalation and Phase 1B monotherapy dose expansion of the ongoing Phase 1 clinical trial of XTX301.

XTX501: masked PD-1/IL-2 bispecific

XTX501 is a novel, tumor-activated bispecific PD-1/IL-2 designed to selectively stimulate PD-1 positive, antigen-experienced T cells and enhance their function. XTX501 incorporates masking designed to overcome IL-2 receptor-mediated clearance and peripheral activity. In preclinical studies, XTX501 demonstrated robust monotherapy activity (including in settings insensitive to PD-1) and tumor-selective pharmacodynamics consistent with its intended mechanism of action. Xilio is currently advancing XTX501 in investigational new drug (IND) application enabling studies and plans to submit an IND application for XTX501 in the middle of 2026.

Masked T Cell Engager Programs

Xilio is leveraging its proprietary, clinically-validated tumor-activation platform to advance multiple preclinical programs for masked T cell engagers, including wholly-owned programs targeting the tumor-associated antigens for PSMA, CLDN18.2 and STEAP1 and an additional program in collaboration with AbbVie.

Xilio’s masked T cell engager programs include bispecific molecules designed using its advanced tumor-activated cell engager (ATACR) format, which consists of a T cell engager with a masked CD3 targeting domain, and tri-specific molecules designed using its selective effector-enhanced cell engager (SEECR) format. The SEECR format builds upon the ATACR format by adding co-stimulatory signaling designed to further enhance potency and T cell activation.

•
PSMA has demonstrated potential as a T cell engager target for prostate cancer. Xilio anticipates nominating a development candidate for its PSMA program in the ATACR format in the third quarter of 2025 and submitting an IND application in the first quarter of 2027.

•
CLDN18.2 has broad potential as a T cell engager target for gastric, pancreatic, esophageal and lung cancers. Xilio anticipates nominating a development candidate for its CLDN18.2 program in the ATACR format in the fourth quarter of 2025 and submitting an IND application in the second quarter of 2027.

•
STEAP1 has broad potential as a T cell engager target for prostate, colorectal and lung cancers. Xilio anticipates nominating a development candidate for its STEAP1 program in the SEECR format in the first half of 2026 and submitting an IND application in the second half of 2027.

Corporate Updates

•
In February 2025, Xilio announced a collaboration, license and option agreement with AbbVie leveraging Xilio’s proprietary tumor-activation technology and platform to discover and develop novel tumor-activated immunotherapies, including masked T cell engagers. In the first quarter of 2025, Xilio received $52.0 million in upfront payments from AbbVie, including a $10.0 million equity investment, and Xilio will be eligible to receive up to approximately $2.1 billion in total contingent payments for option-related fees and milestones plus tiered royalties. For more information, read the joint press release here.

•
In December 2024, Xilio announced the appointment of Caroline Hensley as chief legal officer.

Year-End and Fourth Quarter 2024 Financial Results

•
Cash Position: Cash and cash equivalents were $55.3 million as of December 31, 2024, compared to $44.7 million as of December 31, 2023. In the first quarter of 2025, Xilio received $52.0 million in upfront payments in connection with the collaboration agreement with AbbVie.

•
License Revenue: License revenue was $1.7 million for the quarter ended December 31, 2024, and $6.3 million for the year ended December 31, 2024, which consisted of revenue recognized under the license agreement and stock purchase agreement with Gilead. No license revenue was recognized for the quarter and year ended December 31, 2023.

•
Research & Development (R&D) Expenses: R&D expenses were $8.8 million for the quarter ended December 31, 2024, compared to $11.7 million for the quarter ended December 31, 2023. R&D expenses were $41.2 million for the year ended December 31, 2024, compared to $52.1 million for the year ended December 31, 2023. The year-over-year decrease was primarily driven by decreased clinical development activities for XTX202, a masked IL-2, as a result of discontinuing further investment in XTX202, decreased spending related to early-stage programs and indirect research and development costs, decreased personnel-related costs and decreased manufacturing costs for XTX301, partially offset by increased clinical development activities for vilastobart and XTX301.

•
General & Administrative (G&A) Expenses: G&A expenses were $6.5 million for the quarter ended December 31, 2024, compared to $6.4 million for the quarter ended December 31, 2023. G&A expenses were $24.8 million for the year ended December 31, 2024, compared to $27.0 million for the year ended December 31, 2023. The year-over-year decrease was primarily driven by decreases in personnel-related costs, professional and consulting fees and directors’ and officers’ liability insurance, partially offset by an increase in legal fees.

•
Net Loss: Net loss was $13.1 million for the quarter ended December 31, 2024, compared to $17.7 million for the quarter ended December 31, 2023. Net loss was $58.2 million for the year ended December 31, 2024, compared to $76.4 million for the year ended December 31, 2023.

Financial Guidance

Based on its current operating plans, Xilio anticipates that its cash and cash equivalents as of December 31, 2024, together with the $52.0 million in upfront payments received in the first quarter of 2025 in connection with the collaboration agreement with AbbVie, will be sufficient to enable it to fund its operating expenses and capital expenditure requirements into the first quarter of 2026.

About Vilastobart and the Phase 1/2 Combination Clinical Trial

Vilastobart is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 monoclonal antibody designed to block CTLA-4 and deplete regulatory T cells when activated in the tumor microenvironment (TME). In 2023, Xilio entered into a co-funded clinical trial collaboration with Roche to evaluate vilastobart in combination with atezolizumab (Tecentriq) in a multi-center, open-label Phase 1/2 clinical trial. Xilio is currently evaluating the safety of the combination in Phase 1C dose escalation in patients with advanced solid tumors and the safety and efficacy of the combination in Phase 2 in patients with metastatic microsatellite stable colorectal cancer with and without liver metastases. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.

About XTX301 and the Phase 1 Clinical Trial

XTX301 is an investigational masked IL-12 designed to potently stimulate anti-tumor immunity and reprogram the tumor microenvironment (TME) of poorly immunogenic "cold" tumors towards an inflamed or "hot" state. In March 2024, Xilio entered into an exclusive license agreement with Gilead Sciences, Inc. for Xilio’s tumor-activated IL-12 program, including XTX301. Xilio is currently evaluating the safety and tolerability of XTX301 as a monotherapy in patients with advanced solid tumors in a first-in-human, multi-center, open-label Phase 1 clinical trial. Please refer to NCT05684965 on www.clinicaltrials.gov for additional details.

On March 10, 2025 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported financial results for the three months and full year ended December 31, 2024, and provided an update on its corporate progress (Press release, BioNTech, MAR 10, 2025, View Source [SID1234651035]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"From the very beginning, BioNTech’s vision has been to translate our science into survival and become an immunotherapy powerhouse. In 2024, we made significant progress towards our vision through important oncology pipeline advancements, including the initiation of global Phase 3 clinical trials for our anti-PD-L1/VEGF-A bispecific antibody candidate BNT327 and key data updates from our mRNA cancer immunotherapy programs," said Prof. Ugur Sahin, M.D., CEO and Co-Founder of BioNTech. "We expect 2025 to be a data-rich year with multiple important updates from our priority programs, which we believe have disruptive potential and could improve the standard of care, if successfully developed and approved."

Financial Review for Fourth Quarter and Full Year 2024 Financial Results

in millions €,
except per share data Fourth Quarter 2024 Fourth Quarter 2023 Full Year
2024 Full Year
2023
Total revenues 1,190.0 1,479.0 2,751.1 3,819.0
Net profit / (loss) 259.5 457.9 (665.3) 930.3
Diluted earnings / (loss) per share 1.08 1.88 (2.77) 3.83
Total revenues reported were €1,190.0 million for the three months ended December 31, 2024, compared to €1,479.0 million for the comparative prior year period. For the year ended December 31, 2024, revenues were €2,751.1 million, compared to €3,819.0 million for the comparative prior year period. The decrease in revenues was primarily driven by lower sales of the Company’s COVID-19 vaccines due to reduced market demand. In addition, write-downs by BioNTech’s collaboration partner Pfizer Inc. ("Pfizer") significantly reduced the Company’s gross profit share which negatively influenced its revenues.

Cost of sales were €243.5 million for the three months ended December 31, 2024, compared to €179.1 million for the comparative prior year period. For the year ended December 31, 2024, cost of sales were €541.3 million, compared to €599.8 million for the comparative prior year period. Cost of sales were influenced by COVID-19 vaccine sales and inventory write-downs and scrapping.

Research and development ("R&D") expenses were €611.8 million for the three months ended December 31, 2024, compared to €577.8 million for the comparative prior year period. For the year ended December 31, 2024, R&D expenses were €2,254.2 million, compared to €1,783.1 million for the comparative prior year period. R&D expenses were mainly influenced by advancing clinical studies for the Company’s late-stage oncology product candidates. Further contributions to the increase came from higher personnel expenses resulting from an increase in headcount.

Sales, general and administrative ("SG&A")3 expenses, in total, amounted to €132.1 million for the three months ended December 31, 2024, compared to €142.3 million for the comparative prior year period. For the year ended December 31, 2024, SG&A expenses were €599.0 million, compared to €557.7 million for the comparative prior year period. SG&A expenses were mainly influenced by the setup and enhancement of commercial IT platforms and personnel expenses resulting from an increase in headcount.

Other operating results amounted to negative €54.0 million during the three months ended December 31, 2024, compared to negative €53.6 million for the comparative prior year period. For the year ended December 31, 2024, other operating result amounted to negative €670.9 million compared to negative €188.0 million for the prior year period. The decrease was mainly due to the settlement of contractual disputes and related expenses to such disputes and other litigations. The amounts for contractual disputes are net of the related reimbursements expected to be received.

Income taxes were accrued with an amount of €41.7 million in tax expenses for the three months ended December 31, 2024, compared to €205.3 million in accrued tax expenses for the comparative prior year period. For the year ended December 31, 2024, income taxes were realized with an amount of €12.4 million in tax income for the year ended December 31, 2024, compared to €255.8 million of accrued tax expenses for the comparative prior year period.

Net profit was €259.5 million for the three months ended December 31, 2024, compared to €457.9 million net profit for the comparative prior year period. For the year ended December 31, 2024, net loss was €665.3 million, compared to a net profit of €930.3 million for the comparative prior year period.

Cash and cash equivalents plus security investments2 as of December 31, 2024, reached €17,359.2 million, comprising of €9,761.9 million in cash and cash equivalents, €6,536.2 million in current security investments and €1,061.1 million in non-current security investments.

Diluted earnings per share was €1.08 for the three months ended December 31, 2024, compared to €1.88 for the comparative prior year period. For the year ended December 31, 2024, diluted loss per share was €2.77, compared to diluted earnings per share of €3.83 for the comparative prior year period.
Shares outstanding as of December 31, 2024, were 239,970,804, excluding 8,581,396 shares held in treasury.

"Through strategic investments in our priority programs like our next-generation immunomodulator candidate BNT327, we strive to meaningfully improve treatments for patients," said Jens Holstein, CFO of BioNTech. "Our strong financial position enables us to fuel our R&D activities and to prepare for multiple product launches in the coming years. With our targeted investments we aim to create long-term value for the benefit of BioNTech’s stakeholders."

2025 Financial Year Guidance4

Total revenues for the 2025 financial year €1,700 million – €2,200 million
BioNTech expects its revenues for the full 2025 financial year to be in the range of €1,700 – €2,200 million and revenue phasing similar to 2024, primarily concentrated in the last three to four months, driving the full year revenue figure. The revenue guidance assumes: relatively stable vaccination rates, pricing levels and market share compared to 2024; estimated inventory write-downs and other charges by BioNTech’s collaboration partner Pfizer that negatively influence BioNTech’s revenues; anticipated revenues from a pandemic preparedness contract with the German government; and anticipated revenues from the BioNTech Group service businesses.

Planned 2025 Financial Year Expenses and Capex

R&D expenses €2,600 million – €2,800 million
SG&A expenses €650 million – €750 million
Capital expenditures for operating activities €250 million – €350 million
BioNTech expects to continue to focus investments on R&D and scaling the business for late-stage development and commercial readiness in oncology, while continuing to be cost disciplined. Strategic capital allocation will remain a key driver of the Company’s trajectory. As part of BioNTech’s strategy, the Company may continue to evaluate appropriate corporate development opportunities with the aim of driving sustainable long-term growth and create future value.

The full audited consolidated financial statements as of and for the year ended December 31, 2024, can be found in BioNTech’s Annual Report on Form 20-F filed today with the United States Securities and Exchange Commission ("SEC") and available at www.sec.gov.

Endnotes
1 Calculated applying the average foreign exchange rate for the year ended December 31, 2024, as published by the German Central Bank (Deutsche Bundesbank).

2 Payments associated with the closing of the Biotheus acquisition and with the resolved settlement of a contractual dispute with the National Institutes of Health ("NIH") are expected to result in a cash outflow of approximately $1.6 billion to be reflected in cash & cash equivalents in the Company’s first quarter 2025 financial results. The settlement payment of $467 million related to a contractual dispute with the University of Pennsylvania is expected to be reflected in the Company’s second quarter 2025 financial results. In connection with these settlements, BioNTech expects to be reimbursed approximately $535 million by its partner during 2025 and 2026.

3 Sales, general and administrative expenses ("SG&A") include sales and marketing expenses as well as general and administrative expenses.

4 Excludes external risks that are not yet known and/or quantifiable, including, but not limited to the effects of ongoing and/or future legal disputes and related activities, certain potential one-time effects and charges related to portfolio prioritization, as well as potential changes to the law or governmental policy, including public health policy, at the state or national level, and evolving public sentiment around vaccines and mRNA technology, in the United States and/or elsewhere. It includes effects identified from licensing arrangements, collaborations or potential M&A transactions to the extent disclosed and may be subject to update. The Company does not expect to report a positive net income figure for the 2025 financial year.

Operational Review for the Fourth Quarter 2024, Key Post Period-End Events and 2025 Outlook

Selected Oncology Pipeline Updates
In 2024, the Company’s pipeline continued to mature towards later stages of clinical development with a focus on two priority programs: our investigational next-generation immunomodulator candidate BNT327 and mRNA cancer immunotherapies. BioNTech’s oncology pipeline currently contains over 20 ongoing Phase 2 and 3 clinical trials. In 2025, the Company plans to continue progressing its pipeline towards commercialization, with its first oncology launch expected in 2026.

Next-Generation Immunomodulators

BNT327 is a bispecific antibody candidate combining PD-L1 checkpoint inhibition with VEGF-A neutralization.

In December 2024, BioNTech initiated a global randomized Phase 3 clinical trial (NCT06712355) evaluating BNT327 plus chemotherapy compared to atezolizumab plus chemotherapy in first-line extensive-stage small cell lung cancer ("ES-SCLC").
In December 2024, BioNTech initiated a global randomized Phase 2/3 clinical trial (NCT06712316) evaluating BNT327 plus chemotherapy compared to pembrolizumab plus chemotherapy in first-line non-small cell lung cancer ("NSCLC").
In December 2024, at the San Antonio Breast Cancer Symposium ("SABCS"), interim data were presented from the Phase 1/2 clinical trial (NCT05918133) evaluating BNT327 in combination with chemotherapy in a cohort of patients with locally advanced, previously untreated triple-negative breast cancer ("TNBC"). In 42 patients, first-line treatment with BNT327 combined with nab-paclitaxel chemotherapy showed encouraging antitumor activity and survival outcomes regardless of PD-L1 status, together with a manageable safety profile.
A global randomized Phase 3 clinical trial evaluating BNT327 in first-line TNBC is on track to start in 2025.
Data from the ongoing global Phase 2 dose optimization clinical trials evaluating BNT327 in combination with chemotherapy in first-line small cell lung cancer ("SCLC") (BNT327-01, NCT06449209) and TNBC (BNT327-02, NCT06449222) are planned to be published in 2025.
Data from two Phase 2 clinical trials conducted in China in first- and second-line SCLC (NCT05844150, NCT05879068, respectively) are expected to be presented at the European Lung Cancer Congress ("ELCC") taking place March 26-29, 2025 in Paris, France.
Title: Phase 2 study of the efficacy and safety of BNT327 plus systemic chemotherapy as first-line therapy for ES-SCLC
Presentation Date: March 28, 2025
Poster Number: 302P
Author: Y. Cheng

Title: Updated Phase 2 efficacy and safety results of BNT327 combined with paclitaxel as second-line therapy in SCLC
Presentation Date: March 28, 2025
Poster Number: 332P
Author: Y. Cheng

First clinical data from the ongoing global Phase 1/2 expansion cohorts (NCT05438329) evaluating the combination of BNT327 and BNT325/DB-1305, a TROP2-targeted antibody-drug conjugate ("ADC") candidate, are planned to be published in 2025.
Additional clinical trials exploring novel combinations of BNT327 with the ADC candidates BNT323/DB-1303 (trastuzumab pamirtecan) targeting HER2, BNT324/DB-1311 targeting B7-H3 or BNT326/YL202 targeting HER3 are planned to start in 2025.
BNT316/ONC-392 (gotistobart) is an anti-CTLA-4 monoclonal antibody candidate being developed in collaboration with OncoC4, Inc. ("OncoC4").

In December 2024, the U.S. Food and Drug Administration ("FDA") lifted the partial clinical hold on the OncoC4-sponsored Phase 3 clinical trial (PRESERVE-003; NCT05671510) evaluating the efficacy and safety of BNT316/ONC-392 as monotherapy in patients with metastatic NSCLC that progressed under previous PD-(L)1-inhibitor treatment. Based on the available clinical trial data and upon alignment with the FDA, the companies will solely continue enrollment of patients with squamous NSCLC.
mRNA Cancer Immunotherapies

Autogene cevumeran (BNT122/RO7198457) and BNT111 are investigational immunotherapies for the treatment of cancer based on BioNTech’s systemically administered uridine mRNA-lipoplex technology.

Autogene cevumeran is an individualized neoantigen-specific mRNA cancer immunotherapy candidate being developed in collaboration with Genentech, Inc. ("Genentech"), a member of the Roche Group ("Roche").

In December 2024, the first patient was treated in a global randomized Phase 2 clinical trial (IMCODE004; NCT06534983) evaluating autogene cevumeran in combination with nivolumab compared to nivolumab alone as an adjuvant treatment in high-risk muscle-invasive urothelial carcinoma ("MIUC").
In January 2025, a manuscript summarizing the results of a Phase 1 clinical trial (NCT03289962) evaluating autogene cevumeran in combination with atezolizumab in patients with advanced solid tumors was published in Nature Medicine (Lopez et al., 2025). In February 2025, a manuscript denoting follow up data from an investigator-initiated Phase 1 clinical trial (NCT04161755, Rojas et al., 2023) evaluating autogene cevumeran in combination with atezolizumab in patients with pancreatic ductal adenocarcinoma ("PDAC") in an adjuvant treatment setting was published in Nature (Sethna et al., 2025).
First data from the ongoing global randomized Phase 2 clinical trial (NCT04486378) evaluating autogene cevumeran as an adjuvant treatment compared to watchful waiting after standard of care chemotherapy in resected circulating tumor DNA+ ("ctDNA") stage II (high-risk) and III colorectal cancer ("CRC") are anticipated in late 2025 or early 2026.
BNT111 is based on BioNTech’s fully owned, off-the-shelf FixVac platform, and encodes four melanoma-associated antigens.

BioNTech plans to present data from the ongoing Phase 2 clinical trial (BNT111-01; NCT04526899) at a medical conference in 2025. In 2024, an initial topline readout was provided noting that the clinical trial had met its primary efficacy outcome measure, demonstrating a statistically significant improvement in overall response rate ("ORR") in patients with anti-PD-(L)1 refractory/relapsed, unresectable stage III or IV melanoma treated with BNT111 in combination with cemiplimab as compared to historical control in this treatment setting.
Antibody-Drug Conjugates

BNT323/DB-1303 (trastuzumab pamirtecan) is an ADC candidate targeting HER2 that is being developed in collaboration with Duality Biologics (Suzhou) Co. Ltd. ("DualityBio").

BNT323/DB-1303 is being evaluated in a Phase 1/2 clinical trial (NCT05150691) in patients with advanced/unresectable, recurrent or metastatic HER2-expressing solid tumors. Data from patients with HER2-expressing (IHC3+, 2+, 1+ or ISH-positive) advanced endometrial carcinoma are expected in 2025. A confirmatory Phase 3 clinical trial (NCT06340568) is planned to start in 2025.
Preparation of a potential Biologics License Application ("BLA") submission for BNT323/DB-1303 as a second line or subsequent therapy in HER2-expressing advanced endometrial cancer in 2025.
BNT324/DB-1311 is an ADC candidate targeting B7-H3 that is being developed in collaboration with DualityBio. The program has received Fast Track designation from the FDA for the treatment of patients with advanced castration-resistant prostate cancer ("CRPC") who have progressed on or after standard systemic regimens and Orphan Drug designation for the treatment of patients with advanced esophageal squamous cell carcinoma.

In December 2024, preliminary data from the first-in-human, open-label Phase 1/2 clinical trial (NCT05914116) were presented at the 2024 European Society for Medical Oncology ("ESMO") Asia Congress, demonstrating encouraging efficacy and a manageable safety profile across a range of advanced solid tumors.
Cell Therapies

BNT211 consists of a CAR-T cell product candidate targeting CLDN6-positive solid tumors in combination with a CAR-T cell-amplifying RNA cancer immunotherapy encoding CLDN6.

In January 2025, the FDA granted Regenerative Medicine Advanced Therapy ("RMAT") designation for BNT211. The RMAT designation is designed to expedite the development and review process for promising pipeline products, including cell therapies.
A pivotal Phase 2 clinical trial in patients with testicular germ cell tumors is expected to start in 2025 based on encouraging clinical activity observed in this patient population in the ongoing Phase 1 clinical trial (NCT04503278). The Phase 1 clinical trial is ongoing to evaluate BNT211 in other CLDN6+ cancer types, including NSCLC and gynecologic cancers.
Selected Infectious Diseases Pipeline Updates

BioNTech and Pfizer developed, manufactured and delivered JN.1- and KP.2-adapted COVID-19 vaccines which received multiple regulatory approvals and marketing authorizations in more than 40 countries and regions. In 2024, BioNTech and Pfizer delivered approximately 180 million variant-adapted COVID-19 vaccine doses worldwide.

BioNTech and Pfizer continue to invest in the research and development of next-generation and combination COVID-19 vaccine candidates.

Corporate Update for the Fourth Quarter 2024 and Key Post Period-End Events

In November 2024, BioNTech signed an agreement to acquire Biotheus and obtain full global rights to BNT327 and to all other candidates from Biotheus’ pipeline, as well as to its in-house antibody generation platform and bispecific ADC capability. The transaction amounted to an upfront consideration of $800 million, plus additional performance-based payments of up to $150 million. The acquisition was completed in February 2025.
Upcoming Investor and Analyst Events

Sustainability Report 2024 Publication: March 24, 2025
Annual General Meeting: May 16, 2025
Innovation Series AI Day: October 1, 2025
Innovation Series R&D Day: November 18, 2025
Conference Call and Webcast Information
BioNTech invites investors and the general public to join a conference call and webcast with investment analysts today, March 10, 2025, at 8:00 a.m. EDT (1:00 p.m. CET) to report its financial results and provide a corporate update for the fourth quarter and full year 2024.

To access the live conference call via telephone, please register via this link. Once registered, dial-in numbers and a PIN number will be provided.

The slide presentation and audio of the webcast will be available via this link.

Participants may also access the slides and the webcast of the conference call via the "Events & Presentations" page of the Investor section of the Company’s website at www.BioNTech.com. A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call.

On March 10, 2025 REVEAL GENOMICS, a pioneering Barcelona-based biotech company dedicated to advancing precision oncology, reported the publication of a groundbreaking study demonstrating the clinical impact of HER2DX, its genomic diagnostic test designed for early-stage HER2-positive (HER2+) breast cancer (Press release, REVEAL GENOMICS, MAR 10, 2025, View Source [SID1234651052]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The study, now published in ESMO (Free ESMO Whitepaper) Real World Data and Digital Oncology, is the first prospective real-world investigation assessing the impact of HER2DX results on treatment decision-making in clinical practice.

The study, led by Dr. Olga Martínez-Sáez, Dr. Juan Miguel Cejalvo, and Dr. Antonio Llombart-Cussac, evaluated how HER2DX impacted treatment decisions in a cohort of 297 patients with stage I-III HER2+ breast cancer across multiple hospitals in Spain. The primary findings reveal that HER2DX led to a modification in the treatment plan in 48.1% of cases, with most changes (75.5%) leading to a reduction in treatment intensity, reducing chemotherapy and/or anti-HER2 without compromising outcomes.

HER2DX also demonstrated strong predictive capability, accurately identifying patients with a higher likelihood of achieving a pathologic complete response (pCR), reinforcing its role as a crucial tool in therapy selection.

Additionally, oncologists reported a significant increase in confidence when making treatment decisions based on HER2DX data. Finally, the study also underscored the economic benefits of incorporating HER2DX into clinical practice, with healthcare cost savings when drug costs and type of vein access were taken into account, further validating its role in optimizing treatment strategies and reducing unnecessary interventions.

Dr. Olga Martínez Sáez, breast medical oncologist at Clinic Barcelona Comprehensive Cancer Center and Principal Investigator (PI) of the study, added: "This study represents a significant step forward in personalized oncology. HER2DX enables physicians to make precision-guided decisions with greater confidence, improving patient care."

Dr. Juan Miguel Cejalvo, breast medical oncologist at Hospital Clínico Universitario de Valencia/INCLIVA, and co-PI of the study, emphasized the importance of integrating genomic tools into routine clinical practice, "These results confirm that HER2DX provides valuable information that can refine treatment strategies, allowing for more personalized care while maintaining excellent outcomes."

Dr. Antonio Llombart-Cussac, head of the medical oncology department at Hospital Arnau de Vilanova in Valencia, and investigator of the study, highlighted the impact on clinical practice, "The capacity to forecast a patient’s therapeutic response prior to treatment initiation allows oncologists to adjust treatment intensity appropriately, effectively reducing unnecessary toxicity and healthcare costs."

Patricia Villagrasa, CEO of REVEAL GENOMICS, underscored the company’s mission, "Our goal is to revolutionize cancer care with cutting-edge genomic insights, helping oncologists make more informed decisions and benefiting patients. The results of this first clinical utility study confirms HER2DX as a key tool in precision medicine for HER2+ breast cancer."

About HER2DX

HER2DX is the world’s first diagnostic test formulated specifically for HER2+ breast cancer. Marketed by REVEAL GENOMICS since January 2022, HER2DX is a standardized 27-gene expression test for patients with early-stage HER2+ breast cancer.

HER2DX is a prognostic and, predictive assay based on clinical and genomic data. The test integrates clinical information (i.e. tumor size and nodal status) with biological information tracking immune response, luminal differentiation, tumor cell proliferation, and expression of the HER2 17q12-21 chromosomal amplicon, including the ERBB2 gene.

HER2DX predicts:

Risk of relapse score (high vs. low): the risk of recurrence in patients with newly diagnosed HER2+ breast cancer.
pCR likelihood score (high vs. medium vs. low): the likelihood of a patient responding to anti-HER2-based treatment before surgery.
ERBB2 score (high vs. medium vs. low): the quantitative expression of ERBB2 mRNA across HER2-negative, HER2-low and HER2+ breast cancer.
About HER2+ breast cancer

HER2+ breast cancer accounts for 20% of all diagnosed breast tumors. This represents more than 390,000 new cases diagnosed worldwide every year, meaning that, on average, 3 women are diagnosed with HER2+ breast cancer every 4 minutes. HER2+ breast cancer is clinically and biologically heterogeneous, and standard clinical-pathological assessment has proven insufficient in capturing this heterogeneity. Understanding this biological heterogeneity is key to identifying the prognosis of each patient and the benefit from systemic therapies that target HER2.