On May 8, 2025 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported financial results for the first quarter of 2025, along with recent product highlights and corporate updates (Press release, Zai Laboratory, MAY 8, 2025, View Source [SID1234652774]).

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"In the first quarter, we continued to advance both our global pipeline and commercial business," said Dr. Samantha Du, Founder, Chairperson, and CEO of Zai Lab. "We are rapidly expanding our global portfolio, having recently presented promising data for two next-generation oncology therapies at AACR (Free AACR Whitepaper), and we look forward to presenting updated results for ZL-1310 (DLL3 ADC) at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting. We remain on track to initiate a pivotal study for ZL-1310 in SCLC this year, with the goal of securing FDA approval in 2027. In parallel, we are also exploring opportunities in first-line SCLC and other neuroendocrine tumors to unlock the full potential of this important global asset. On the commercial front, we continued to expand patient access for key products and are leveraging our existing infrastructure to support upcoming launches and our next wave of blockbuster opportunities. With a strong foundation in place, we are well positioned to drive growth and profitability, and to further our mission of becoming a leading global biopharmaceutical company."

"2025 marks a transformational year for Zai Lab, and we are executing against the key objectives we set at the start of the year," said Josh Smiley, President and COO of Zai Lab. "Following a seasonal slowdown of VYVGART early in the year, we saw patient volumes rebound in March and April, and we anticipate a return to strong sequential growth throughout the rest of the year. Looking ahead, our late-stage pipeline, including bemarituzumab and KarXT, is expected to fuel the next wave of topline growth alongside VYVGART. At the same time, we continue to strengthen our financial position, achieving a 20% year-over-year reduction in operating loss and a 25% year-over-year reduction in adjusted operating loss1, keeping us on track to achieve profitability1 in the fourth quarter of 2025. With a strong cash position,2 a growing commercial business, and an expanding global portfolio, Zai Lab is poised to capitalize on multiple upcoming catalysts and drive long-term shareholder value."

First Quarter 2025 Financial Results

•Product revenue, net was $105.7 million in the first quarter of 2025, compared to $87.1 million for the same period in 2024, representing 21% y-o-y growth, 23% y-o-y growth at constant exchange rate (CER). This increase was primarily driven by increased sales for VYVGART, ZEJULA, and NUZYRA.

–VYVGART and VYVGART Hytrulo were $18.1 million in the first quarter of 2025, compared to $13.2 million for the same period in 2024. Although quarter over quarter growth was impacted by seasonality, sales grew year over year driven by increasing market coverage and penetration since VYVGART’s launch in September 2023 and listing on China’s National Reimbursement Drug List (NRDL) for the treatment of generalized Myasthenia Gravis (gMG) effective January 1, 2024.

–ZEJULA was $49.5 million in the first quarter of 2025, compared to $45.5 million for the same period in 2024. ZEJULA sales remained strong as it continued to be the leading PARP inhibitor in hospital sales for ovarian cancer in mainland China.

–NUZYRA was $15.1 million in the first quarter of 2025, compared to $9.9 million for the same period in 2024. This growth was supported by increasing market coverage and penetration.

•Research and Development (R&D) expenses were $60.7 million in the first quarter of 2025, compared to $54.6 million for the same period in 2024. This increase was primarily due to upfront fees totaling $20.0 million for our license and collaboration agreements. Other R&D expenses decreased as a result of resource prioritization and efficiency efforts.

•Selling, General and Administrative expenses were $63.4 million in the first quarter of 2025, compared to $69.2 million for the same period in 2024. This decrease was primarily driven by decreased personnel costs as a result of resource prioritization and efficiency efforts.

•Loss from operations was $56.3 million in the first quarter of 2025, $37.1 million when adjusted to exclude non-cash expenses including depreciation, amortization, and share-based compensation. A reconciliation of loss from operations (GAAP) to adjusted loss from operations (non-GAAP) is included at the end of this release.

•Net loss was $48.4 million in the first quarter of 2025, or a loss per ordinary share attributable to common stockholders of $0.04 (or loss per American Deposit Share (ADS) of $0.45), compared to a net loss of $53.5 million for the same period in 2024, or a loss per ordinary share of $0.05 (or loss per ADS of $0.55). These decreases in net loss were primarily due to product revenue growing faster than net operating expenses.

•Cash and cash equivalents, short-term investments, and current restricted cash totaled $857.3 million as of March 31, 2025, compared to $879.7 million as of December 31, 2024.

Recent Pipeline Highlights

Below are key product updates since our last earnings release:

Oncology Pipeline

•ZL-1310 (DLL3 ADC):

–Second-Line+ Extensive-Stage SCLC (ES-SCLC): In April 2025, Zai Lab announced that updated data from an ongoing, global Phase 1a/1b clinical trial of ZL-1310 for the treatment of ES-SCLC, will be presented during a poster session at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The updated results will include additional patients and follow-up from the ongoing trial.

–Other neuroendocrine tumors: In April 2025, Zai Lab initiated a global Phase 1/2 study in patients with selected solid tumors, exploring its therapeutic potential beyond ES-SCLC.

•Tisotumab Vedotin (TIVDAK, Tissue Factor ADC): In March 2025, China’s National Medical Products Administration (NMPA) accepted the Biologics License Application (BLA) for TIVDAK for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy. Zai Lab will leverage its commercial footprint of ZEJULA in women’s cancer to accelerate patient access to this therapy in China if approved.

•Tumor Treating Fields (TTFields): In April 2025, Zai Lab partner Novocure announced that the additional results from the Phase 3 PANOVA-3 trial for pancreatic cancer will be presented as a late-breaking oral presentation at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting. Zai Lab participated in the study in Greater China (mainland China, Hong Kong, Macau and Taiwan, collectively) and plans to file for regulatory approval in China in 2025.

•Repotrectinib (ROS1/TRK): In April 2025, China’s NMPA accepted the supplemental New Drug Application for repotrectinib for patients with NTRK-positive solid tumors. Repotrectinib has the potential to become a next-generation TKI that can be used across a broad range of NTRK fusion-positive solid tumors for both TKI-naïve and TKI-pretreated patients.

•ZL-6201 (LRRC15 ADC): In April 2025, Zai Lab presented new data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025. The findings demonstrate that ZL-6201 efficiently internalizes within and kills tumor cells, while also exhibiting a strong bystander killing effect in the tumor microenvironment where the target is often expressed. Based on these findings, Zai Lab plans to initiate Investigational New Drug (IND)-enabling studies of ZL-6201 as a potential treatment for patients with sarcoma and other LRRC15-positive solid tumors, such as breast cancer and other malignancies, in 2025.

•ZL-1222 (PD-1/IL-12): In April 2025, Zai Lab presented data at the AACR (Free AACR Whitepaper) Annual Meeting 2025, marking the first public disclosure of this global asset. Findings from preclinical studies demonstrate its potent anti-tumor activity in both anti-PD-1 sensitive and resistant tumor models, with improved systemic safety. These results indicate its potential to benefit patients who are unresponsive or resistant to the current immuno-oncology therapies.

Immunology Pipeline

•Efgartigimod (FcRn): In April 2025, Zai Lab partner argenx announced the U.S. Food and Drug Administration (FDA) approved VYVGART Hytrulo prefilled syringe (PFS) for self-injection in gMG and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). It is the third administration option providing additional flexibility and convenience for patients. Zai Lab plans to submit the Chemical Manufacturing and Control (CMC) variation for PFS for these indications in China in 2025.

•ZL-1102 (IL-17 Humabody): Zai Lab has decided to discontinue the global Phase 2 clinical trial of ZL-1102 following a comprehensive review of the data from interim analysis from the first 40 enrolled participants and the subsequent recommendation of the independent Data and Safety Monitoring Board.

•Povetacicept (APRIL/BAFF): Zai Lab partner Vertex has completed enrollment of the interim analysis cohort in the global Phase 3 RAINIER study of povetacicept in IgA nephropathy. Zai Lab participated in the study in Greater China.

Anticipated Major Milestones in 2025

Upcoming Potential NMPA Submissions

•Bemarituzumab (FGFR2b): BLA submission in first-line gastric cancer.

•Tumor Treating Fields (TTFields): Marketing Authorization Application submissions in first-line pancreatic cancer.

•Efgartigimod (FcRn): submission for the CMC variation for PFS in gMG and CIDP.

Expected Clinical Developments and Data Readouts

Global Pipeline

ZL-1310 (DLL3 ADC)

•Second-Line+ ES-SCLC: Zai Lab to present updated data at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting on June 2, 2025. Zai Lab plans to initiate a pivotal study in the second half of 2025.

•First-Line ES-SCLC: Zai Lab to provide a data readout for dose escalation of ZL-1310 doublet in combination with atezolizumab.

ZL-1503 (IL-13/IL-31R)

•Zai Lab to provide a preclinical data update and advance into a global Phase 1 study in moderate-to-severe atopic dermatitis.

ZL-6201 (LRRC15 ADC)

•Zai Lab to advance into global Phase 1 development for patients with sarcoma and potentially other LRRC15-positive solid tumors, such as breast cancer and other malignancies.

Regional Pipeline

Bemarituzumab (FGFR2b)

•Zai Lab partner Amgen to provide data readout from the Phase 3 FORTITUDE-101 study of bemarituzumab combined with chemotherapy versus chemotherapy alone in first-line gastric cancer in the second quarter of 2025. Zai Lab participated in the study in Greater China.

•Zai Lab partner Amgen to provide data readout from the Phase 3 FORTITUDE-102 study of bemarituzumab plus chemotherapy and nivolumab versus chemotherapy and nivolumab in first-line gastric cancer in the second half of 2025. Zai Lab participated in the study in Greater China.

Xanomeline-Trospium (or KarXT) (M1/M4-agonist)

•Zai Lab partner Bristol Myers Squibb (BMS) to provide data readout from the Phase 3 ADEPT-2 study of KarXT in Alzheimer’s Disease Psychosis in the second half of 2025. Zai Lab participated in the study in Greater China.

Efgartigimod (FcRn)

•Seronegative gMG: Zai Lab partner argenx to provide topline results from the Phase 3 ADAPT-SERON study in seronegative gMG. Zai Lab participated in the study in Greater China.

•Lupus Nephritis (LN): Zai Lab to provide topline results from the Phase 2 study in LN.

Povetacicept (APRIL/BAFF)

•Primary Membranous Nephropathy (pMN): Zai Lab plans to partner with Vertex to execute the global pivotal Phase 2/3 study of povetacicept in pMN in Greater China.

Conference Call and Webcast Information

Zai Lab will host a live conference call and webcast today, May 8, 2025, at 8:00 a.m. ET (8:00 p.m. HKT). Listeners may access the live webcast by visiting the Company’s website at View Source Participants must register in advance of the conference call.

Details of registration links are as follows:

•For webcast: View Source

•For dial-in: View Source

All participants must use the link provided above to complete the online registration process in advance of the conference call. Dial-in details will be in the confirmation email which the participant will receive upon registering.

A replay will be available shortly after the call and can be accessed by visiting the Company’s website.

On May 8, 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 reported financial results for the first quarter ended March 31, 2025 (Press release, Xilio Therapeutics, MAY 8, 2025, View Source [SID1234652773]).

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"In the first quarter, we presented encouraging initial Phase 2 data for vilastobart, our tumor-activated anti-CTLA-4, in combination with atezolizumab in patients with late-line MSS CRC. These data included a preliminary 27% objective response rate in late-line MSS CRC patients without liver metastases accompanied by a differentiated safety profile with a low incidence of colitis and other immune-related adverse events, which are common dose-limiting adverse events for other CTLA-4 agents," said René Russo, Pharm.D., president and chief executive officer of Xilio. "MSS CRC is an immunologically cold tumor type that is very difficult to treat and increasing in incidence, particularly in younger people for whom no immunotherapy treatment options are currently available. We look forward to reporting updated Phase 2 data at the upcoming ASCO (Free ASCO Whitepaper) meeting, including additional response assessments and further follow-up on the previously reported data. This quarter was also marked by strong execution across our pipeline, as we continue to advance XTX301, our tumor-activated IL-12, in monotherapy dose escalation in partnership with Gilead, and multiple novel masked T cell engager programs internally and as part of our recently announced collaboration with AbbVie."

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). Vilastobart is currently being evaluated in combination with atezolizumab (Tecentriq ) in Phase 1C combination dose escalation in patients with advanced solid tumors and in a Phase 2 clinical trial in patients with MSS CRC.

● In January 2025, Xilio announced encouraging initial Phase 2 data for vilastobart in combination with atezolizumab in patients with MSS CRC. As of a data cutoff date of January 13, 2025, the combination of vilastobart at 100 mg once every six weeks (Q6W) in combination with atezolizumab at 1200 mg once every three weeks (Q3W) demonstrated a preliminary 27% objective response rate in patients without liver metastases accompanied by a generally well-tolerated safety profile. Patients experienced a low incidence of colitis and other immune-related adverse events, which have historically limited the potential for anti-CTLA-4 therapies. For more information, read the press release here. Based on the promising initial Phase 2 data for vilastobart, Xilio is seeking opportunities to partner the vilastobart program to accelerate and expand further development.

● Xilio plans to report updated data from the ongoing Phase 2 clinical trial in patients with metastatic MSS CRC, including additional response assessments and further follow-up on the previously reported data, at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago from May 30 to June 3, 2025.

Title: Vilastobart (XTX101), a tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody, in combination with atezolizumab in patients with MSS CRC

Abstract ID: 3553

Poster Session: Gastrointestinal Cancer – Colorectal and Anal

Poster Board: 222

Session Date and Time: Saturday, May 31, from 9:00 a.m. to 12:00 p.m. CDT

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.

● 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) 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.

● 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. PSMA has demonstrated potential as a T cell engager target for prostate cancer.

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

Corporate Updates

● In the first quarter of 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, and received $52.0 million in total upfront payments from AbbVie. Under the agreement, Xilio is also 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.

First Quarter 2025 Financial Results

● Cash Position: Cash and cash equivalents were $89.1 million as of March 31, 2025, compared to $55.3 million as of December 31, 2024. In the first quarter of 2025, Xilio received $52.0 million in total upfront payments in connection with the collaboration agreement with AbbVie.

● Collaboration and License Revenue: Collaboration and license revenue was $2.9 million for the quarter ended March 31, 2025, which consisted of $2.9 million of total revenue recognized in connection with the collaborations with AbbVie and Gilead. No collaboration and license revenue was recognized for the quarter ended March 31, 2024.

● Research & Development (R&D) Expenses: R&D expenses were $8.3 million for the quarter ended March 31, 2025, compared to $10.4 million for the quarter ended March 31, 2024. The 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 personnel-related costs due to lower headcount and decreased manufacturing costs for XTX301, partially offset by increased spending related to early stage programs and indirect research and development, increased clinical development activities for vilastobart and manufacturing activities for XTX501 in connection with IND-enabling studies.

● General & Administrative (G&A) Expenses: G&A expenses were $8.5 million for the quarter ended March 31, 2025, compared to $6.1 million for the quarter ended March 31, 2024. The increase was primarily driven by an increase in legal fees and personnel-related costs, partially offset by a decrease in costs related to directors’ and officers’ liability insurance.

● Net Loss: Net loss was $13.3 million for the quarter ended March 31, 2025, compared to $17.2 million for the quarter ended March 31, 2024.

Financial Guidance

Based on its current operating plans, Xilio anticipates that its cash and cash equivalents as of March 31, 2025 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 May 8, 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 first quarter ended March 31, 2025 (Press release, Werewolf Therapeutics, MAY 8, 2025, View Source [SID1234652772]).

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"Werewolf continues to build on our promising data and progress across our clinical-stage programs," said Daniel J. Hicklin, Ph.D., President and Chief Executive Officer of Werewolf. "We remain on track in our Phase 1/1b clinical trial evaluating WTX-124 to share interim data and meet with the FDA to discuss potential registrational pathways in the second half of this year. Additionally, in recognition of Skin Cancer Awareness month, Werewolf is launching an educational campaign in May to highlight the differentiation of Werewolf’s conditionally activated therapeutics and patient experiences to date in the WTX-124 clinical trial. I am also pleased to report that we recently initiated a Phase 1b/2 clinical trial of WTX-330 to explore antitumor activity and optimize the exposure of our IL-12 INDUKINE molecule in the tumor microenvironment. Finally, Werewolf has been making significant progress towards nominating its first INDUCER T cell engager development candidate in the second quarter of 2025, with preclinical data demonstrating that PREDATOR masking technology successfully silenced peripheral activity and prevented cytokine release. We believe that our proprietary PREDATOR masking and targeting technology distinctly positions us to build a robust pipeline of T cell engagers with potentially best-in-class potency and safety profiles, filling a gap in the current immuno-oncology landscape."

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.
•All expansion arms are actively enrolling patients in the ongoing Phase 1/1b clinical trial at a recommended dose of 18 mg administered intravenously every two weeks (IV Q2W).
•During the second half of 2025, Werewolf plans to present interim data from the monotherapy and combination expansion arms, including tolerability, response rate, and durability, and to engage with regulatory authorities to discuss potential registrational pathways for WTX-124, including strategies for accelerated approval.
•The data continue to demonstrate clinically meaningful anti-tumor activity with a tolerable safety profile in patients who have previously been treated with immune checkpoint inhibitors.
•Launching a skin cancer awareness campaign educating various stakeholders on WTX-124 patient outcomes to date and the innovative science underlying Werewolf’s IL-2 cytokine therapy.
WTX-330: a systemically delivered, conditionally activated Interleukin-12 (IL-12) INDUKINE molecule being developed in advanced or metastatic solid tumors.
•Initiated patient dosing in a Phase 1b/2 clinical trial (WTX-330×2102) to optimize the exposure of WTX-330 in the tumor microenvironment, following the encouraging clinical activity and tolerability seen in the WTX-330×2101 first-in-human study.

Preclinical Portfolio:
•Werewolf’s previously announced development candidates WTX-712, its Interleukin-21 (IL-21) INDUKINE molecule, and WTX-518, its binding protein resistant Interleukin-18 (IL-18) INDUKINE molecule, for the 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, are available for partnering.
•Werewolf has extended its conditional activation technology to T cell engagers, utilizing a novel and highly effective anti-CD3 masking strategy for its INDUCER T cell engager molecules. Preclinical data demonstrate that the Company’s PREDATOR masking technology successfully silenced peripheral activity and prevented cytokine release in its INDUCER molecules. The Company’s first INDUCER development candidate is expected to be nominated in the second quarter of 2025.
Financial Results for the First Quarter of 2025:
•Cash position: As of March 31, 2025, cash and cash equivalents were $92.0 million, compared to $111.0 million as of December 31, 2024. Based on updated forecasting, the Company now believes its existing cash and cash equivalents as of March 31, 2025, will be sufficient to fund operational expenses and capital expenditure requirements into the fourth quarter of 2026.
•Research and development expenses: Research and development expenses were $13.1 million for the first quarter of 2025, compared to $12.9 million for the same period in 2024.
•General and administrative expenses: General and administrative expenses were $4.9 million for the first quarter of 2025, compared to $5.0 million for the same period in 2024.
•Net loss: Net loss was $18.1 million for the first quarter of 2025, compared to $16.2 million for the same period in 2024.

On May 8, 2025 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, reported that the U.S. Food and Drug Administration (FDA) has approved AVMAPKI FAKZYNJA CO-PACK (avutometinib capsules; defactinib tablets) for the treatment of adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who received prior systemic therapy (Press release, Verastem, MAY 8, 2025, View Source [SID1234652771]). AVMAPKI FAKZYNJA CO-PACK is the first and only FDA-approved medicine for this disease. This indication is approved under accelerated approval based on the tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. AVMAPKI plus FAKZYNJA is only commercially available in the U.S. as an oral combination co-pack with the two prescription products, known as "AVMAPKI FAKZYNJA CO-PACK."

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"Today’s approval of AVMAPKI FAKZYNJA CO-PACK for patients with KRAS-mutated recurrent low-grade serous ovarian cancer represents not only the first-ever FDA-approved treatment specifically for this rare cancer but also a new day for people living with this disease who have been in desperate need of new treatment options," said Dan Paterson, president and chief executive officer of Verastem Oncology. "We are very proud to bring two innovative medicines in one combination treatment to the LGSOC community. We thank the researchers, patients, and their families participating in our clinical trials, the patient advocacy community, the FDA, and everyone at Verastem for their dedication and commitment to helping us bring AVMAPKI FAKZYNJA CO-PACK to patients in the U.S."

The accelerated approval of AVMAPKI FAKZYNJA CO-PACK is based on the Phase 2 RAMP 201 clinical trial, which evaluated the combination of AVMAPKI and FAKZYNJA in adult patients with measurable KRAS-mutated recurrent LGSOC.

"Low-grade serous ovarian cancer is a rare and highly recurrent cancer with limited effective treatment options. This first-ever FDA approval in this disease was based on the primary analysis of the Phase 2 RAMP 201 trial, in which the combination of avutometinib and defactinib resulted in a significant overall response rate for patients with a KRAS mutation while being generally well tolerated," said Rachel Grisham, M.D., Section Head, Ovarian Cancer at Memorial Sloan Kettering Cancer Center in New York, NY and Global Lead Principal Investigator of GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301. "The approval of avutometinib plus defactinib brings a much-needed therapeutic option to patients and establishes this combination as the new standard of care for women with recurrent low-grade serous ovarian cancer harboring a KRAS mutation. I look forward to progressing the confirmatory Phase 3 trial, RAMP 301, where we look to continue to support the ongoing body of research of this combination in women with and without a KRAS mutation."

"To see our early research in both the FRAME and RAMP 201 trial in recurrent low-grade serous ovarian cancer advance the combination of avutometinib and defactinib to now be the first-ever FDA-approved therapy for this disease is what gives us real hope when treating patients with rare or difficult-to-treat gynecological cancers," said Professor Susana Banerjee, M.B.B.S., M.A., Ph.D., F.R.C.P, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Team Leader in Women’s Cancers at The Institute of Cancer Research, London and Global Lead Principal Investigator of ENGOTov60/GOG3052 /NCRI/RAMP201. "With this approval, we thank all of the patients and researchers who participated in this trial, and the low-grade serous ovarian cancer community for their contributions to help bring the first FDA-approved treatment for KRAS-mutated recurrent LSGOC and changing the treatment possibilities for RAS/MAPK-pathway-driven cancers. We now need to build on this milestone to bring this new treatment to patients around the world."

Prior to this approval, there were no FDA-approved treatments specifically for KRAS-mutated recurrent LGSOC, a rare and distinct ovarian cancer that differs from high-grade serous ovarian cancer in both its biology and how it responds to treatment.

"One of the most devastating aspects of my LGSOC diagnosis was learning there are no FDA-approved treatments for this rare cancer. While there were some treatment options at the time that I could try, I made it my mission to advocate for research specific to my disease," said Nicole Andrews, chair of the STAAR Low-Grade Serous Ovarian Cancer Foundation. "Today we’re celebrating a milestone with the first-ever FDA-approved treatment option specifically for patients with recurrent LGSOC with a KRAS mutation. The low-grade serous ovarian cancer community is hopeful and excited about the potential benefits of this treatment and the progress toward improving the diagnosis, awareness, and research for LGSOC."

AVMAPKI FAKZYNJA CO-PACK is the first treatment to receive regulatory approval anywhere in the world, specifically for KRAS-mutated recurrent LGSOC. The Company believes AVMAPKI FAKZYNJA CO-PACK is also the first-ever oral, novel/novel combination therapy approved in oncology. Verastem initiated a rolling new drug application (NDA) with the FDA in May 2024 and completed its NDA submission in October 2024. The FDA granted Priority Review, and the approval was received in advance of its Prescription Drug User Fee Act (PDUFA) action date of June 30, 2025. The FDA granted Breakthrough Therapy Designation for the treatment of patients with recurrent LGSOC after one or more prior lines of therapy, including platinum-based chemotherapy, in May 2021. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC.

The AVMAPKI FAKZYNJA CO-PACK is expected to be available for adult patients with KRAS-mutated recurrent LGSOC in the U.S. in one week.

On May 8, 2025 Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, reported financial results for the first quarter ended March 31, 2025, and highlighted recent corporate progress (Press release, Tyra Biosciences, MAY 8, 2025, View Source [SID1234652770]).

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"In 2025, we are focused on clinical execution across our portfolio of next-generation precision therapies for oncology and skeletal dysplasia. We continued to advance TYRA-300 for ACH and intermediate risk non-muscle invasive bladder cancer and will begin dosing in BEACH301 and SURF302 in the second quarter," stated Todd Harris, CEO of TYRA. "In addition, our SURF431 study is now underway, and we dosed the first HCC patient with TYRA-430, our oral FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers."

First Quarter 2025 and Recent Corporate Highlights

TYRA-300

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Advanced Clinical Evaluation of TYRA-300 and Published Preclinical Research. TYRA continued to progress TYRA-300, an oral, investigational FGFR3-selective inhibitor, for the treatment of intermediate risk non-muscle invasive bladder cancer (IR NMIBC), pediatric achondroplasia (ACH), and metastatic urothelial cancer (mUC).
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Advanced Phase 2 ACH Study – BEACH301 – Open for Enrollment. The study is a Phase 2, multicenter, open-label, dose-escalation/dose-expansion study evaluating TYRA-300 in children ages 3 to 10 with achondroplasia with open growth plates. The study will enroll children who are treatment-naïve (Cohort 1) and those who have received prior growth-accelerating therapy (Cohort 2) at multiple sites across the globe. Each of these cohorts is expected to enroll up to 10 participants per dose level (0.125, 0.25, 0.375, 0.50 mg/kg) for up to 12 months. The study is now enrolling a safety sentinel cohort of up to 3 treatment-naïve participants per dose level in children ages 5 to 10.
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Advanced Phase 2 NMIBC Study Activities – SURF302. SURF302 is an open-label Phase 2 clinical study evaluating the efficacy and safety of TYRA-300 in participants with FGFR3-altered low-grade, IR NMIBC. The study will enroll up to 90 participants at multiple sites primarily in the United States. Participants will be randomized initially to treatment with TYRA-300 at 50 mg once-daily (QD) (Cohort 1) or treatment with TYRA-300 at 60 mg QD (Cohort 2). Following a review of efficacy and safety, an additional dosing cohort may be evaluated. The primary endpoint is complete response (CR) rate at three months. Secondary endpoints include time to recurrence, the median duration of response, recurrence free survival (RFS), progression free survival (PFS), safety and tolerability.
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Advanced Phase 1/2 mUC Study – SURF301. TYRA-300 is currently being evaluated in Part B of SURF301 (NCT05544552) at potentially therapeutic QD doses in preparation for potential future Phase 2 studies.
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Preclinical Results with TYRA-300 Published in JCI Insight. In April 2025, preclinical results with TYRA-300 were published in JCI Insight 2025 in a manuscript titled "TYRA-300, an FGFR3 selective inhibitor, promotes bone growth in two FGFR3-driven models of chondrodysplasia." TYRA-300 was evaluated in three genetic contexts: wild-type mice, the Fgfr3Y367C/+ mouse model of ACH, and the Fgfr3N534K/+ mouse model of HCH. In each model, TYRA-300 treatment increased naso-anal length, tibia and femur length. In the two FGFR3-altered models, TYRA 300-induced growth partially restored the disproportionality of long bones. Histologic analysis of the growth plate in Fgfr3Y367C/+ mice revealed that TYRA-300 mechanistically increased both proliferation and differentiation of chondrocytes. Importantly, TYRA-300 also significantly improved the size and shape of the skull and foramen magnum in Fgfr3Y367C/+ mice. These studies demonstrate that TYRA-300 led to a significant increase in bone growth in two independent FGFR3-driven preclinical models, as well as in wild-type mice.

TYRA-200

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Advanced Phase 1 SURF201 Study. TYRA-200 is an FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. SURF201 (Study in PrevioUsly Treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors) (NCT06160752) is a multi-center, open label study designed to evaluate the safety, tolerability, and pharmacokinetics of TYRA-200 and determine the optimal and maximum tolerated dose and recommended Phase 2 dose, as well as evaluate the preliminary antitumor activity of TYRA-200. The SURF201 study continues to enroll and dose adults with unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating FGFR2 gene alterations.

TYRA-430

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Initiated Patient Dosing in Phase 1 Study – SURF431. TYRA-430 is an oral, investigational FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers. Patient dosing has commenced in SURF431, a Phase 1, multicenter, open-label, first-in-human study of TYRA-430 in advanced hepatocellular carcinoma (HCC) and other solid tumors with activating FGF/FGFR pathway aberrations (NCT06915753). SURF431 is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of TYRA-430 and determine the maximum tolerated dose and recommended Phase 2 dose, as well as evaluate the preliminary antitumor activity of TYRA-430. We believe TYRA-430 has the potential to address a significant unmet need in HCC, where there are no approved biomarker-driven, targeted therapies.

SNÅP Platform and Pipeline

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TYRA continued to advance its in-house precision medicine discovery engine, SNÅP, used to develop therapies in targeted oncology and genetically defined conditions.

First Quarter 2025 Financial Results

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Cash, Cash Equivalents and Short-Term Investments. As of March 31, 2025, TYRA had cash, cash equivalents, and marketable securities of $318.9 million. The Company’s current cash, cash equivalents and marketable securities are expected to allow TYRA to execute on its plans through at least 2027.
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Research and Development (R&D) Expenses. R&D expenses for the three months ended March 31, 2025 were $25.0 million compared to $17.2 million for the same period in 2024. The increase was primarily driven by higher clinical costs associated with start-up activities for BEACH301, SURF302 and SURF431, as well as increased CMC and personnel-related costs, including non-cash stock-based compensation.
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General and Administrative (G&A) Expenses. G&A expenses for the three months ended March 31, 2025 were $6.9 million compared to $5.1 million for the same period in 2024. The increase was primarily driven by higher personnel-related costs, including non-cash stock-based compensation.
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Net Loss. First quarter net loss was $28.1 million compared to $18.2 million for the same period in 2024.

Upcoming Anticipated Milestones and Events

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BEACH301: dose first child with ACH with TYRA-300 – Q2 2025
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SURF302: dose first IR NMIBC patient with TYRA-300 – Q2 2025

About TYRA-300

TYRA-300 is the Company’s lead precision medicine program stemming from its in-house SNÅP platform. TYRA-300 is an investigational, oral, FGFR3-selective inhibitor currently in development for the treatment of cancer and skeletal dysplasia, including achondroplasia and hypochondroplasia. In oncology, TYRA-300 is being evaluated in mUC and IR NMIBC. In mUC, TYRA-300 is being evaluated in a multi-center, open label Phase 1/2 clinical study, SURF301 (Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors) (NCT05544552). The study is designed to determine the optimal and the recommended Phase 2 dose of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. In October 2024, TYRA reported interim clinical proof-of-concept data in mUC from SURF301. TYRA has received IND clearance from the US FDA to proceed with its SURF302 clinical trial in patients with IR NMIBC. In skeletal dysplasia, TYRA-300 has demonstrated positive preclinical results in achondroplasia and hypochondroplasia, and its BEACH301 clinical trial in children with achondroplasia is now enrolling.

About TYRA-200

TYRA-200 is an oral, investigational, FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. The Phase 1 clinical study of TYRA-200, SURF201 (NCT06160752), is a multi-center, open label study designed to evaluate the maximum tolerated dose and the recommended Phase 2 dose of TYRA-200, as well as to evaluate the preliminary antitumor activity of TYRA-200. SURF201 is currently enrolling and dosing adults with advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating alterations in FGFR2.

About TYRA-430

TYRA-430 is an oral, investigational FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers. The Phase 1 study (SURF431) is a multicenter, open-label, first-in-human study of TYRA-430 and is currently enrolling and dosing adults with advanced HCC and other solid tumors with activating FGF/FGFR pathway aberrations (NCT06915753).