On May 13, 2025 MaaT Pharma (EURONEXT: MAAT – the "Company"), a clinical-stage biotechnology company and a leader in the development of Microbiome Ecosystem TherapiesTM (MET) dedicated to enhancing survival for patients with cancer through immune modulation, reported a business update and announced its cash position as of March 31, 2025 (Press release, MaaT Pharma, MAY 13, 2025, View Source [SID1234652979]).

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"The first months of 2025 have marked a pivotal moment for MaaT Pharma with the positive results from our Phase 3 trial of MaaT013, our lead asset. This milestone enables us to advance toward a Market Authorization submission in Europe and reflects over a decade of dedication and close collaboration with physicians. We are deeply grateful for the trust and participation of patients, whose support has been essential in achieving this progress," said Hervé Affagard, CEO and co-founder of MaaT Pharma. "We are also making strong progress across our pipeline, with encouraging outcomes for MaaT033 and MaaT034. Additionally, by extending our cash runway to October 2025, we are well-positioned to deliver on our upcoming value-creating milestones."

Pipeline highlights

In Hemato-Oncology

Acute Graft-versus-Host Disease (aGvHD) – MaaT013

In January 2025, the Company announced positive topline results from the pivotal Phase 3 ARES Study evaluating MaaT013 in aGvHD. The study met its primary endpoint with a significant gastrointestinal overall response rate at Day 28 of 62% and demonstrates the unprecedented efficacy of MaaT013 as third-line treatment of aGvHD with gastrointestinal involvement (GI-aGvHD) consistent with previously communicated EAP results. The Company anticipates MAA submission in Europe in June 2025.
In March 2025, the Company received positive opinion from EMA Pediatric Committee on the Pediatric Investigation Plan for MaaT013, a key milestone achieved towards the MAA submission to the EMA.
In March 2025, the Company received a positive outcome from the final DSMB meeting on ARES Phase 3 trial, confirming the remarkable efficacy results and positive risk/benefit profile of MaaT013 in third-line aGvHD.
Earlier this year, the Company announced its intent to partner the distribution of MaaT013 in Europe, while retaining MaaT013 rights in the U.S.
Allogenic Hematopoietic Stem Cell Transplant (allo-HSCT) – MaaT033

In January 2025, the Company announced that the DSMB completed its second safety assessment of the Phase 2b trial PHOEBUS and recommended continuation of the trial without modification.
In April 2025, the Company announced the positive outcome of a key DSMB safety interim analysis for the Phase 2b trial PHOEBUS. As a result of their unblinded analysis, the DSMB recommended the trial to proceed as planned, showing no excessive mortality related to MaaT033 as of today. This additional positive outcome further reinforces MaaT033’s safety profile and supports MaaT033’s integration in the allo-HSCT setting without significant risks of severe adverse events.
In Immuno-Oncology

MaaT034 – Next-generation drug candidates with co-cultured technology (MET-C platform)

In April 2025, MaaT Pharma presented promising preclinical data for MaaT034 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025, demonstrating strong anti-tumor efficacy and immune activation in germ-free mice.
MaaT013– Proof-of-Concept trials with donor derived drugs (MET-N platform)

MaaT013 is currently being evaluated in a Phase 2a randomized clinical trial (NCT04988841) (PICASSO) sponsored by AP-HP and in collaboration with INRAE and Institut Gustave Roussy, in combination with immune checkpoint inhibitors (ICI), ipilimumab (Yervoy) and nivolumab (Opdivo), in metastatic melanoma patients. The Company provided its MaaT013 drug candidate and placebo and contributes to the microbiome profiling of patients using its proprietary gutPrint AI research engine, while the trial investigator sponsor handled recruitment, treatment and oversee data collection and analysis. Data readout is expected in H2 2025.
In Neurodegenerative Diseases

Amyotrophic Lateral Sclerosis (ALS) – MaaT033

In May 2025, MaaT Pharma announced positive final Phase 1b results for MaaT033 in ALS, showing a favorable safety and tolerability profile supported by biomarker and microbiome analyses. Rapid and sustained microbial engraftment was observed, along with a slower rate of disease progression (ALSFRS-R slope to be interpreted with caution. The Company is seeking a partner to further advance clinical evaluation in ALS.
Corporate update

In April 2025, the Company announced the initiation of coverage of its stock by H.C. Wainwright & Co. With a research report named "In With the Gut and Out With the Bad in GvHD; Initiating at Buy With a €21 PT", H.C. Wainwright & Co initiated a Buy recommendation and a Target Price of €21.
Cash position1

As of March 31, 2025, total cash and cash equivalents were EUR 24.4 million, as compared to EUR 20.2 million as of December 31, 2024. The net increase in cash position of EUR 4.2 million during the first quarter of 2025 includes the capital increase of €13 million supported by historical shareholders, while investment in R&D activities continued across the pipeline. The Company believes it has sufficient cash to cover its current needs and planned development programs into October 2025 and is exploring several options to further extend its cash horizon.
Revenues in Q1 20251

MaaT Pharma reported revenues of EUR 1.1 million for the first quarter of 2025 compared with EUR 0.8 million for the same period of 2024 representing a constant growth, quarter to quarter, year to year.
Upcoming financial communications*

June 20, 2025: Annual General Meeting
September 16, 2025: Publication of H1 2025 results
November 4, 2025: Publication of revenues & cash for Q3 2025
*Indicative calendar that may be subject to change.

Upcoming investor and business conferences participation

June 12-15 – European Hematology Association (EHA) (Free EHA Whitepaper) Congress, Milan, IT
June 16-19, 2025 – Bio International Convention, Boston, MA
June 18-19, 2025 – Portzamparc Conference Mid & Small Caps 2025, Paris
September 25, 2025 – KBC Healthcare Conference, Brussels

On May 13, 2025 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage company advancing a pipeline of next-generation CAR T-cell therapies for patients with cancer, reported financial results and business highlights for the first quarter ended March 31, 2025 (Press release, Lyell Immunopharma, MAY 13, 2025, View Source [SID1234652978]). Lyell’s lead clinical program, LYL314 (formerly known as IMPT-314), is an autologous CD19/CD20 dual-targeting CAR T-cell product candidate under evaluation in a Phase 1/2 trial enrolling patients with relapsed and/or refractory large B-cell lymphoma (LBCL). LYL314 was recently granted RMAT designation by the United States FDA in recognition of its potential to address significant unmet needs in patients with aggressive LBCL in the third- or later-line setting.

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"We are pleased with the progress we are making with our LYL314 clinical development strategy and look forward to presenting new clinical data from patients with aggressive large B-cell lymphoma who have not previously received CAR T-cell therapy at the International Conference on Malignant Lymphoma in Lugano, Switzerland in June," said Lynn Seely, M.D., President and CEO of Lyell. "Based on promising clinical data, Lyell remains on track to initiate two pivotal programs for LYL314: one for patients in the third- or later-line setting by mid-2025 and a second for patients in the second-line setting by early 2026. In addition, our LyFE Manufacturing Center in Bothell, Washington is now manufacturing the LYL314 clinical supply following completion of a successful technology transfer and FDA clearance of an IND amendment."

First Quarter Updates and Recent Business Highlights

Lyell is advancing a pipeline of next-generation CAR T-cell product candidates. Its lead program, LYL314, is in Phase 1/2 clinical development for relapsed and/or refractory LBCL and its preclinical programs target solid tumor indications. Lyell’s programs target cancers with large unmet need with substantial patient populations.

LYL314: A next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of response as compared to the approved CD19‑targeted CAR T-cell therapies for the treatment of LBCL

LYL314 is an autologous CAR T-cell product candidate with a true ‘OR’ logic gate to target B cells that express either CD19 or CD20 with full potency and that is manufactured with a process that enriches for CD62L-positive cells to generate more naïve and central memory CAR T cells with enhanced stemlike features and antitumor activity. LYL314 is currently being evaluated in a multi-center, open-label trial that is enrolling patients in the third- or later-line and second-line settings who have not previously received CAR T-cell therapy. The trial is designed to evaluate the tolerability and clinical benefit of LYL314 in patients with relapsed and/or refractory LBCL and determine a recommended Phase 2 dose. The FDA has granted LYL314 RMAT and Fast Track designations for the treatment of relapsed and/or refractory diffuse LBCL in the third- or later-line setting. RMAT provides all the benefits of the Fast Track and Breakthrough Therapy designation programs and enables increased frequency of communications with the FDA on the development of LYL314.

New clinical data from the Phase 1/2 multi-center clinical trial of LYL314 in patients with relapsed and/or refractory LBCL will be presented at the 18th International Conference on Malignant Lymphoma in June, including more mature data from patients treated in the third- or later-line setting and initial data from patients treated in the second-line setting. The data will be highlighted in an oral presentation titled "LYL314, a CD19/CD20 CAR T-cell candidate enriched for CD62L+ stem-like cells, achieves high rates of durable complete responses in R/R large B-cell lymphoma" to be presented on June 18th at 5:40 pm CEST.
Initial clinical data in 23 patients treated with LYL314 from the ongoing Phase 1/2 clinical trial were presented at the American Society for Hematology 2024 Annual Meeting on December 9, 2024. The efficacy evaluable population consisted of 17 patients with relapsed and/or refractory LBCL in the third- or later-line setting who had not previously received a CAR T-cell therapy prior to LYL314 administration. The overall response rate was 94% (16/17) of patients, and 71% (12/17) of patients achieved a complete response by three months. The median follow up was 6.3 months (range 1.2 – 12.5 months) and 71% of patients experienced a response at last follow-up. In the safety evaluable population of 23 patients, no event of Grade 3 or greater cytokine release syndrome was reported. Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 13% (3/23) of patients with a median time to ICANS resolution of 5 days, and rapid improvement to Grade 2 or lower with standard therapy.
LYL314 clinical supply is now manufactured at the LyFE Manufacturing Center in Bothell, Washington following successful technology transfer and clearance by the FDA of an IND amendment. LyFE is a state-of-the-art cell therapy manufacturing facility with the capacity to provide drug supply for Lyell’s ongoing and planned pivotal trials and through potential commercial launch, with a capacity over 1,000 CAR T-cell therapy doses per year.
A pivotal trial in the third- or later-line setting is expected to be initiated in mid-2025 in patients with relapsed and/or refractory LBCL who have not previously received CAR T-cell therapy.
More mature data from the ongoing Phase 1/2 trial in the second-line setting are expected to be presented in late-2025.
A pivotal trial in the second-line setting is expected to be initiated by early 2026 in patients with relapsed and/or refractory LBCL who have not previously received CAR T-cell therapy.
Preclinical Pipeline, Technologies and Manufacturing Protocols

Lyell is advancing next-generation fully-armed CAR T-cell product candidates, each including multiple technologies, designed to overcome T-cell exhaustion and lack of durable stemness, as well as immune suppression within the hostile tumor microenvironment.

The first IND for a fully-armed CAR T-cell product candidate with an undisclosed target for solid tumors is expected in 2026.
An abstract titled "Engineered T Cells Combining Stackable Reprogramming Technologies Enable Durable Anti‑tumor Activity in Xenograft Solid Tumors" has been accepted for an oral presentation at the 28th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper), on May 16, 2025, in New Orleans, LA. The presentation will highlight preclinical data demonstrating that engineered T cells enhanced with c-Jun overexpression, a chimeric co-stimulatory receptor and localized cytokine signaling technologies exhibit potent tumor cell killing in vitro, T-cell viability in vitro and in vivo without cytokine support and effective durable antitumor activity in preclinical solid tumor models.
An abstract titled "Optimizing Stim-R, a synthetic stimulatory agent, for feeder-free tumor-infiltrating lymphocyte manufacturing" was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025. The presented work demonstrated that Stim-R, Lyell’s customizable synthetic T-cell activation reagent designed to emulate natural antigen presentation, has the potential to overcome scalability limitations in tumor-infiltrating lymphocyte manufacturing processes by providing a synthetic replacement for feeder cells.

First Quarter 2025 Financial Results

Lyell reported a net loss of $52.2 million for the first quarter ended March 31, 2025, compared to a net loss of $60.7 million for the same period in 2024. The $8.5 million decrease in net loss was primarily driven by $13.0 million in impairment expenses recognized in the prior year period that did not occur in 2025, partially offset by lower interest income of $3.0 million primarily driven by lower interest rates in 2025, coupled with lower cash equivalent and marketable securities balances. Non‑GAAP net loss, which excludes stock-based compensation, non-cash expenses related to the change in the estimated fair value of success payment liabilities and certain non-cash investment gains and charges, increased to $46.3 million for the first quarter ended March 31, 2025, compared to $37.5 million for the same period in 2024 due primarily to increased personnel costs and lower interest income in 2025.

GAAP and Non-GAAP Operating Expenses

Research and development (R&D) expenses were $43.4 million for the first quarter ended March 31, 2025, compared to $43.2 million for the same period in 2024. The increase in first quarter 2025 R&D expenses of $0.3 million was primarily due to a $3.1 million increase in personnel expenses, due primarily to severance expenses resulting from Lyell’s 2025 workforce reduction related to the closure of the West Hills manufacturing facility acquired as part of Lyell’s acquisition of ImmPACT in 2024, partially offset by reductions in collaboration agreement and leasehold improvement depreciation costs. Non‑GAAP R&D expenses, which exclude non-cash stock-based compensation and non-cash expenses related to the change in the estimated fair value of success payment liabilities for the first quarter ended March 31, 2025 were $41.1 million compared to $38.9 million for the same period in 2024.
General and administrative (G&A) expenses were $14.0 million for the first quarter ended March 31, 2025, respectively, compared to $13.5 million for the same period in 2024. The increase in first quarter 2025 G&A expenses of $0.6 million was primarily driven by an increase of $2.4 million in personnel‑related expenses due to higher headcount associated with Lyell’s acquisition of ImmPACT and severance expenses related to the West Hills facility closure, partially offset by $1.7 million in decreased stock-based compensation expense due to a decrease in the value of awards granted. Non‑GAAP G&A expenses, which exclude non-cash stock‑based compensation, for the first quarter ended March 31, 2025 were $10.4 million, compared to $8.1 million for the same period in 2024. The $2.3 million increase in first quarter 2025 non-GAAP G&A expenses was primarily driven by increased headcount and severance expenses.
A discussion of non-GAAP financial measures, including reconciliations of the most comparable GAAP measures to non‑GAAP financial measures, is presented below under "Non-GAAP Financial Measures."

Cash, cash equivalents and marketable securities

Cash, cash equivalents and marketable securities as of March 31, 2025 were $330.1 million compared to $383.5 million as of December 31, 2024. Lyell believes that its cash, cash equivalents and marketable securities balances will be sufficient to meet working capital and capital expenditure needs into 2027.

On May 13, 2025 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing novel allogeneic, or "off the shelf", cell therapies for serious neurological and ophthalmic conditions, reported its first quarter 2025 financial and operating results and will host a conference call today at 4:30 p.m. Eastern Time to discuss these results and provide a business update (Press release, Lineage Cell Therapeutics, MAY 13, 2025, View Source [SID1234652976]).

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"Lineage has grown increasingly confident in OpRegen’s potential to address a significant medical need," stated Brian M. Culley, Lineage CEO. "Our optimism is driven in part by OpRegen’s uniquely durable treatment effects, lasting up to 24 months, with a 36-month data update from Roche and Genentech forthcoming next month. We are also encouraged by independent first-in-human results recently reported by competitors, which adds validation to an RPE transplant mechanism of action providing functional improvements beyond the reach of currently approved dry AMD therapies. Together, these findings lend support to one-time dosing, a key advantage over the compliance-challenged monthly injections required for anti-complement therapy. While advancing the OpRegen program and the GAlette Study remains a key area of attention, we are equally excited to have recently initiated the DOSED clinical study of OPC1, while progressing ReSonanceTM for the treatment of sensorineural hearing loss and evaluating other strategically selected early-stage initiatives. As our cell therapy platforms gain further validation, we believe our pipeline and expertise position us as a compelling partner and investment opportunity."

Select Business Highlights

RG6501 (OpRegen)
RG6501 (OpRegen) Phase 1/2a Clinical Study 36 Month Results to be featured at Clinical Trials at the Summit (CTS) 2025, and will be presented by Christopher D. Riemann, M.D., Vitreoretinal Surgeon and Fellowship Director, Cincinnati Eye Institute (CEI) and University of Cincinnati School of Medicine, on behalf of Roche and Genentech, a member of the Roche Group.
Ongoing execution of Lineage’s contributions to its collaboration with Roche and Genentech across multiple functional areas, including support for the ongoing Phase 2a clinical study (the "GAlette Study") in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) at sites in the U.S. and Israel.
In addition to testing of other surgical parameters, Genentech currently plans to evaluate two proprietary surgical delivery devices that have potential advantages over available off-the-shelf devices in the GAlette Study.
Ongoing efforts to further support development of OpRegen RPE cell therapy under a separate services agreement with Genentech, including: (i) activities to support the ongoing Phase 1/2a study long term follow-up and currently enrolling GAlette Study; and (ii) additional technical training and materials related to our cell therapy technology platform to support commercial manufacturing strategies.
OPC1
DOSED (Delivery of Oligodendrocyte Progenitor Cells for Spinal Cord Injury: Evaluation of a Novel Device) clinical study in subacute and chronic spinal cord patients initiated in February 2025; UC San Diego Health is the first participating study site.
Lineage and OPC1 program featured on CNN: "He was paralyzed his last day of high school. How an experimental trial is showing ‘unexpected improvement’."
3rd Annual Spinal Cord Injury Investor Symposium (3rd SCIIS) announced in partnership with the Christopher & Dana Reeve Foundation.
The 3rd SCIIS will be fully virtual, with interactive and on-demand sessions available starting June 27, 2025.
Event aims to bring together those working on treatments for spinal cord injury (SCI), including regulators, key opinion leaders, persons with lived experience, patient and community advocacy organizations and the investment community, to discuss perspectives on current and future treatments, impact and support SCI disease awareness and clinical trial participation through the implementation of patient appropriate clinical endpoints, and importantly, broaden awareness of and investment capital into SCI.
Balance Sheet Highlights

Cash, cash equivalents, and marketable securities of $47.9 million as of March 31, 2025, is expected to support planned operations into Q1 2027.

First Quarter Operating Results

Revenues: Revenue is generated primarily from collaboration revenues, royalties, and other revenues. Total revenues for the three months ended March 31, 2025 were $1.5 million, a net increase of $0.1 million as compared to $1.4 million for the same period in 2024. The increase was primarily driven by more collaboration revenue recognized from deferred revenues under the collaboration and license agreement with Roche.

Operating Expenses: Operating expenses are comprised of research and development ("R&D") expenses and general and administrative ("G&A") expenses. Total operating expenses for the three months ended March 31, 2025 were $8.0 million, a decrease of $0.1 million as compared to $8.1 million for the same period in 2024.

R&D Expenses: R&D expenses for the three months ended March 31, 2025 were $3.1 million, an increase of $0.1 million as compared to $3.0 million for the same period in 2024. The net increase was primarily driven by $0.2 million for our preclinical programs, partially offset by $0.1 million for our other research and development programs.

G&A Expenses: G&A expenses for the three months ended March 31, 2025 of $4.9 million were primarily in line with expenses for the same period in 2024.

Loss from Operations: Loss from operations for the three months ended March 31, 2025 was $6.5 million, a decrease of $0.2 million as compared to $6.7 million for the same period in 2024.

Other Income/(Expenses): Other income/(expenses) for the three months ended March 31, 2025 reflected other income of $2.4 million, compared to other income of $0.1 million for the same period in 2024. The net increase was primarily driven by changes in fair value of the warrant liabilities.

Net Loss Attributable to Lineage: The net loss attributable to Lineage for the three months ended March 31, 2025 was $4.1 million, or $0.02 per share (basic and diluted), compared to a net loss of $6.5 million, or $0.04 per share (basic and diluted), for the same period in 2024.

Conference Call and Webcast

Interested parties may access the conference call on May 13, 2025, by dialing (800) 715-9871 from the U.S. and Canada and should request the "Lineage Cell Therapeutics Call". A live webcast of the conference call will be available online in the Investors section of Lineage’s website. A replay of the webcast will be available on Lineage’s website for 30 days and a telephone replay will be available through May 20th, 2025, by dialing (800) 770-2030 from the U.S. and Canada and entering conference ID number 1789489.

On May 13, 2025 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported financial results for the first quarter of 2025 (Press release, Leap Therapeutics, MAY 13, 2025, View Source [SID1234652975]).

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Leap Highlights:

· Reported positive data from the randomized, controlled Part B of the Phase 2 DeFianCe study of sirexatamab (DKN-01) plus bevacizumab and chemotherapy in second-line colorectal cancer (CRC) patients demonstrating significantly higher overall response rate (ORR) and longer progression-free survival (PFS) across DKK1-high and VEGF-naïve subgroups

· Hosted virtual key opinion leader (KOL) event featuring Zev A. Wainberg, MD, to further discuss the positive data and patient benefit from the DeFianCe study

· Presented preclinical data of FL-501, a novel GDF-15 neutralizing antibody, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2025 Annual Meeting

· Strategic restructuring to prioritize clinical development of sirexatamab in CRC and advancing FL-501 in preclinical development, resulting in an approximately 50% reduction in workforce

"In the first quarter of 2025, sirexatamab, our novel anti-DKK1 antibody, continued to demonstrate encouraging efficacy, including statistically significant higher ORR and longer PFS in both DKK1-high and VEGF-naïve second-line CRC patients. With 42 patients currently remaining on study drug, 25 in the sirexatamab arm and 17 in the control arm, we continue to be optimistic about the maturing dataset in the full population and look forward to upcoming data updates this quarter," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "In this difficult market environment, we focused our resources to position Leap to advance sirexatamab in CRC and FL-501 preclinically in order to provide the greatest value for our shareholders. I would like to personally thank all of our colleagues who have been impacted by this decision and express my appreciation for their contributions and dedication to provide meaningful new treatment options to cancer patients."

DKN-01 Development Update

· Reported updated clinical data from Part B of the DeFianCe Study of sirexatamab plus bevacizumab and chemotherapy in CRC patients. In March 2025, the Company announced updated preliminary data from Part B of the DeFianCe study (NCT05480306), a Phase 2, open-label, global study of sirexatamab in combination with bevacizumab and chemotherapy (Sirexatamab Arm) compared to bevacizumab and chemotherapy (Control Arm) in patients with MSS CRC who have received one prior systemic therapy for advanced disease. Updated data from the study is expected this quarter.

o In patients with high DKK1 levels (upper quartile, n=44), the Sierxatamab Arm had a statistically significant 32% higher ORR, 3.5 month longer PFS, and OS compared to the Control Arm

o In patients who had not received prior anti-VEGF therapy (n=95), the Sirexatamab Arm had a statistically significant 22% higher ORR and 2.6 month longer PFS compared to the Control Arm, with OS not mature but favoring the Sirexatamab Arm

o With a higher number of patients remaining on study drug in the Sirexatamab Arm compared to the Control Arm (25 vs. 17), PFS in the full intent-to-treat population continues to mature with a tail population advantage for the Sirexatamab Arm

o The strong signal from the DeFianCe study supports a registrational Phase 3 clinical trial to evaluate sirexatamab plus bevacizumab and chemotherapy in second-line MSS CRC patients with high DKK1 levels or in patients who have not received prior anti-VEGF therapy

· Hosted a virtual KOL event featuring Dr. Zev Wainberg, Co-Director of the UCLA GI Oncology Program and a globally recognized leader in gastrointestinal cancer research, to discuss sirexatamab in second-line patients with advanced MSS CRC. Dr. Wainberg discussed the unmet need and how sirexatamab may improve upon the current treatment landscape for previously treated patients with advanced MSS CRC and reviewed the positive data from Part A and Part B of the Phase 2 DeFianCe study.

Pipeline Updates

· Presented new preclinical data of FL-501 at the AACR (Free AACR Whitepaper) 2025 Annual Meeting. FL-501 is a first-in-class GDF-15 neutralizing antibody targeting the cachexia pathway, a condition commonly associated with poor outcomes in cancer patients.

o In humanized FcRn mouse studies, FL-501 demonstrated a 2-3-fold longer half-life and 50% reduced clearance compared to its wild-type precursor and ponsegromab

o In mouse cachexia models using GDF-15-overexpressing colorectal cancer cells, FL-501 fully restored body composition, comparably or better than clinical-stage antibodies visugromab and ponsegromab

o In a non-small cell lung cancer patient-derived xenograft model, FL-501 effectively countered cisplatin-induced weight loss, restoring body weight, composition, and condition scores

o These findings, as well as a favorable safety profile and strong pharmacodynamic activity, support advancing FL-501 as a potentially best-in-class molecule

Business Updates

· Engaged leading financial advisor to explore business development opportunities to further the development of sirexatamab. Strong signals from the DeFianCe study supports a registrational Phase 3 clinical trial in second-line CRC, which represents a significant potential global market opportunity.

· Announced strategic restructuring to prioritize clinical focus on the development of sirexatamab in CRC. Leap is realigning its resources in order to prioritize the clinical development of sirexatamab in CRC and advancing FL-501 preclinically. As part of the strategic restructuring, the Company has reduced its workforce by approximately 50%.

Selected First Quarter 2025 Financial Results

Net Loss was $15.4 million for the first quarter 2025, compared to $13.8 million for the first quarter 2024. The increase was primarily due to an increase in research and development expenses.

Research and development expenses were $12.9 million for the first quarter of 2025, compared to $11.3 million for the same period in 2024. The increase was primarily due to an increase of $1.4 million in clinical trial costs due to the expansion of the size of Part B of the DeFianCe study and the increase in activity associated with the end of Part C of the DisTinGuish study. There was also an increase of $0.1 million in manufacturing costs related to clinical trial material and manufacturing campaigns and an increase of $0.1 million in consulting fees associated with research and development activities.

General and administrative expenses were $3.0 million for the first quarter 2025, compared to $3.5 million for the same period in 2024. The decrease was primarily due to a $0.4 million decrease in professional fees and a $0.1 million decrease in stock based compensation expense.

Cash and cash equivalents totaled $32.7 million at March 31, 2025.

On May 13, 2025 Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage biotechnology company developing novel small molecule therapeutics to treat unmet needs in immune-mediated diseases, reported financial results for the first quarter ended March 31, 2025, and provided a business update (Press release, Kezar Life Sciences, MAY 13, 2025, View Source [SID1234652974]).

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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

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"We shared exciting results this quarter from the PORTOLA trial, the first successful randomized study in treatment-refractory AIH," said Chris Kirk, CEO and co-founder of Kezar. "There has been almost no change over the last three decades in the treatment of this serious chronic disease, and patients and physicians are in need of new and effective therapies. We are encouraged by the promising safety and efficacy data in this difficult-to-treat patient population, in particular the durable and steroid-sparing remissions observed in patients treated with zetomipzomib. We continue to respond to the FDA Division of Hepatology and Nutrition on the partial clinical hold and are working toward achieving alignment on an appropriate trial design to demonstrate the clinical benefit of zetomipzomib in AIH."
Zetomipzomib: Selective Immunoproteasome Inhibitor
PORTOLA – Phase 2a clinical trial of zetomipzomib in patients with AIH (ClinicalTrials.gov: NCT05569759)
•In March, Kezar reported topline results from the PORTOLA Phase 2a clinical trial evaluating zetomipzomib in patients with autoimmune hepatitis. In relapsed AIH patients who entered screening on steroid-based therapy, 36% (5 of 14) of zetomipzomib-treated patients achieved a complete biochemical response (CR) and clinically significant steroid taper to 5 mg/day or less, compared to 0 of 7 of placebo patients. In the intention-to-treat (ITT) population, 31% (5 of 16) of zetomipzomib patients achieved a CR and steroid taper (5 mg/day or less), compared to 1 of 8 placebo patients. The median duration of response in zetomipzomib patients achieving a CR was 27.6 weeks (including the ongoing open-label extension at the time of the data cutoff), and no disease flares were reported in any zetomipzomib-treated patient achieving CR during study. A favorable safety profile was observed during the 6-month blinded treatment period.

•Kezar is responding to the information request from the FDA Division of Hepatology and Nutrition to resolve the partial clinical hold on the PORTOLA Phase 2a clinical trial.

PALIZADE – Phase 2b clinical trial of zetomipzomib in patients with active lupus nephritis (LN) (ClinicalTrials.gov: NCT05781750)
•In February, Kezar presented an update from the PALIZADE Phase 2b clinical trial evaluating zetomipzomib in patients with active LN. At the time of study termination, no patients had completed the full 52 weeks of treatment. Of the 12 patients receiving 60 mg of zetomipzomib who reached week 25, 42% achieved a urine protein-to-creatinine ratio (UPCR) of 0.5 or less, and the median UPCR was reduced by 79% from baseline. Marked improvements in serologic markers were observed in patients who received a 60 mg dose of zetomipzomib.
•In October 2024, Kezar made the strategic decision following a clinical hold by the FDA to terminate PALIZADE and focus the clinical development of zetomipzomib in AIH.
Financial Results
•Cash, cash equivalents and marketable securities totaled $114.4 million as of March 31, 2025, compared to $132.2 million as of December 31, 2024. The decrease was primarily attributable to cash used in operations.
•Research and development (R&D) expenses for the first quarter of 2025 decreased by $5.0 million to $12.2 million, compared to $17.2 million in the first quarter of 2024. This decrease was primarily due to the decreased clinical activities resulting from the Company’s strategic decision to terminate the PALIZADE trial in October 2024, a decrease in manufacturing expense related to the timing of drug manufacturing runs and a decrease in facility related expenses.
•General and administrative (G&A) expenses for the first quarter of 2025 decreased by $1.1 million to $5.4 million compared to $6.5 million in the first quarter of 2024. The decrease was primarily due to a decrease in legal and professional service expenses and non-cash stock-based compensation.
•Net loss for the first quarter of 2025 was $16.6 million, or $2.27 per basic and diluted common share, compared to a net loss of $21.7 million, or $2.98 per basic and diluted common share, for the first quarter of 2024.
•Total shares of common stock outstanding were 7.3 million shares as of March 31, 2025.
About PORTOLA
PORTOLA is a placebo-controlled, randomized, double-blind Phase 2a clinical trial evaluating the efficacy and safety of zetomipzomib in patients with AIH that are insufficiently responding to standard of care or have relapsed from a previous CR. The trial enrolled 24 patients, randomized (2:1) to receive 60 mg of zetomipzomib or placebo in addition to background therapy for 24 weeks, with a protocol-suggested steroid taper. All patients were required to receive a starting daily steroid dose of 20-40 mg/day of prednisone (or budesonide equivalent) and physicians were encouraged to taper daily steroid usage to 5 mg/day consistent with AIH treatment guidelines established by the American Association for the Study of Liver Diseases (AASLD). The primary efficacy endpoint of PORTOLA, which was not powered for efficacy, evaluated the proportion of patients who achieved a CR by Week 24, measured as normalization of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and Immunoglobulin G (IgG) values (if elevated at baseline), with steroid dose levels not higher than baseline. A key secondary endpoint was the proportion of patients who achieved a CR by Week 24 with a steroid dose of 5 mg/day or less.