On March 26, 2025 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company utilizing its novel proprietary ARCUS platform to develop in vivo gene editing therapies for high unmet need diseases, reported financial results for the fourth quarter and fiscal year ended December 31, 2024, and provided a business update (Press release, Precision Biosciences, MAR 26, 2025, View Source [SID1234651466]).

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"2024 was a transformational year for Precision BioSciences as we solidified ourselves as a leading in vivo gene editing company, and we now have clinical data from two differentiated ARCUS based programs. Our focus on operational excellence was exemplified by PBGENE-HBV, our lead in vivo gene editing program for chronic Hepatitis B, where we in parallel filed and received approval for three Clinical Trial Applications (CTA) in three markets with world class clinical capabilities," said Michael Amoroso, President and Chief Executive Officer of Precision BioSciences. "Building on that momentum, and consistent with our pursuit of globalizing the ELIMINATE-B trial, Precision has recently received Investigational New Drug (IND) clearance by the U.S. Food and Drug Administration. PBGENE-HBV is the first-ever investigational in vivo gene editing therapy cleared to enter clinical trials for the treatment of chronic Hepatitis B in the U.S. and globally."

"In 2025, our steadfast focus remains on continued clinical execution as we work to deliver on the promise of our ARCUS gene editing technology through robust clinical data," continued Mr. Amoroso. "The recent reported clinical experience for PBGENE-HBV focused on viral editing and elimination of replicating cccDNA and integrated HBV DNA in Hepatitis B, an extremely large patient population, adds to the compelling clinical validation of the ARCUS platform observed in severe OTC deficiency, a rare and extremely dire disease. In January, our partner iECURE announced news from the OTC-HOPE study, where first-in-human data demonstrated a complete clinical response in severe neonatal OTC deficiency using an ARCUS nuclease for in vivo gene insertion. We look forward to building on this clinical momentum throughout 2025."

Wholly Owned Portfolio

PBGENE-HBV (Viral Elimination Program): PBGENE-HBV is Precision’s wholly owned in vivo gene editing program under investigation in a global first-in-human clinical trial, which is designed to potentially cure chronic Hepatitis B infection. Currently, it is estimated that approximately 300 million people worldwide are afflicted with chronic Hepatitis B. Unlike all other downstream targeting modalities, which offer low likelihood of achieving a cure, PBGENE-HBV is the first and only potentially curative gene editing program to enter the clinic that is specifically designed to eliminate cccDNA and inactivate integrated HBV DNA. The ELIMINATE-B trial is designed to investigate PBGENE-HBV at multiple ascending dose levels with three dose administrations per dose level in patients afflicted with chronic Hepatitis B who are HBeAg-negative.

Precision received IND and CTA approvals for its Phase 1 ELIMINATE-B trial in the United States, Moldova, Hong Kong, and New Zealand.

Mr. Amoroso added, "We have already completed dosing of the first patient cohort establishing both safety and early efficacy for PBGENE-HBV at the lowest dose level in the Phase 1 clinical trial and have commenced subsequent administrations. These operational milestones are a tremendous step forward for Precision BioSciences, and we look forward to accelerating patient access to the study by initiating the trial in the U.S. and later expanding to the U.K. Clinical data updates will continue to be shared throughout 2025 at meaningful timepoints."

The Company dosed the first patient in December 2024 and has completed dosing the low-dose cohort (N= 3 patients) with the first dose administration of PBGENE-HBV. The participants treated in cohort 1 possessed different baseline characteristics: age of infection, duration of infection and level of Hepatitis B surface antigen (HBsAg).

The study is primarily designed to test the safety of three dose administrations of PBGENE-HBV. In the first cohort, all three patients dosed with the first dose administration of PBGENE-HBV have completed the initial safety evaluation period. PBGENE-HBV was well-tolerated and none of the patients experienced a Grade ≥2 treatment-related adverse event or serious adverse event.

In addition to safety, the ELIMINATE-B protocol is designed to assess the efficacy for three dose administrations at each dose level, with the goal to maximize cumulative viral editing to achieve undetectable levels of HBsAg ultimately enabling patients to stop taking lifelong nucleos(t)ide analog therapy. PBGENE-HBV demonstrated a substantial reduction in HBsAg in two of the three participants following the first administration at the lowest dose. Initial clinical data in the first cohort of patients was consistent with the HBsAg reductions observed in preclinical non-human primate models.

"Given PBGENE-HBV’s novel modality, these data suggest that PBGENE-HBV appears to be working by its intended mechanism of eliminating the source of viral replication in cccDNA while inactivating integrated disease," said Cassie Gorsuch, PhD, Chief Scientific Officer of Precision BioSciences.

With a well-tolerated safety profile and early antiviral activity established after the first administration at dose level 1, Precision expects to complete subsequent administrations in all cohort 1 patients while in parallel expanding to the next higher dose cohorts. The Company plans to provide ongoing updates on the full low-dose cohort, including multiple dose administrations, and data at higher dose levels throughout 2025.

Supporting the ELIMINATE-B clinical study design, Precision presented new preclinical safety and efficacy data at the Global Hepatitis Summit (GHS) on March 21, 2025, showcasing the rationale for administering up to three repeat doses in clinic to safely increase cumulative viral editing and optimize the therapeutic index of PBGENE-HBV for patients with chronic Hepatitis B. The data shared at GHS was supported by definitive preclinical safety and toxicology studies conducted by Precision.

PBGENE-3243 (Mutant Mitochondrial DNA Elimination Program): PBGENE-3243 is a first-of-its-kind potential treatment for m.3243-associated mitochondrial disease that is designed to specifically target and eliminate mutant m.3243G mitochondrial DNA, thereby eliminating the root cause of the disease. Currently, there are no cures for m.3243-associated mitochondrial disease, which affects approximately 20,000 people in the U.S. alone and an even larger prevalent population globally. PBGENE-3243 is designed to alleviate muscular myopathy symptoms, providing a significant quality of life and functional improvement for patients.

The high specificity of ARCUS nucleases enables editing and elimination of mutant mitochondrial DNA while allowing wild-type (normal) mitochondrial DNA to repopulate, thus improving cellular function. Unlike CRISPR/Cas, base editors, and prime editors that require a guide RNA, ARCUS single-component nucleases are able to penetrate the mitochondrial membranes and target mutant mitochondrial DNA. In 2025, Precision plans to present new data for PBGENE-3243 while advancing the program toward a CTA and/or IND.

Wholly Owned Portfolio – Under Assessment

In July 2024, Precision regained the rights for three programs, including its PBGENE-DMD, PBGENE-LIVER, and PBGENE-CNS programs; the following of which are being assessed for either internal development and/or development through new partners.

PBGENE-DMD (Muscle Targeted Excision Program): New preclinical, in vivo efficacy data using the clinical construct, PBGENE-DMD, was presented at the 2025 Muscular Dystrophy Association Clinical and Scientific Conference on March 19, 2025. The oral presentation highlighted significant functional dystrophin protein production across heart, diaphragm and skeletal muscles at levels expected to provide therapeutic benefit. In a humanized DMD-diseased mouse model, PBGENE-DMD demonstrated long-term functional improvement over multiple time points, including achieving 93% of the maximal force output observed in healthy control mice. Importantly, PBGENE-DMD demonstrated the ability to edit Pax7+ cells, a marker for satellite muscle stem cells which are the precursor cells to new muscle cell formation and a potential predictor of durable functional benefit. These in vivo efficacy results further support the therapeutic potential of an ARCUS gene editing approach for the treatment of DMD and ongoing development in clinical trials.
PBGENE-CNS (CNS Targeted Excision Program): Precision expects to publicly present preclinical data on PBGENE-CNS for the first time at a scientific conference in 2025.
ARCUS Platform

At the ESGCT 31st Annual Congress in October 2024, Precision presented preclinical data highlighting ARCUS’s capability for high-efficiency gene editing to achieve a range of gene editing outcomes, including specific base correction, insertions, and the replacement of large segments of DNA within the genome via homology-directed repair (HDR). The presentation also discussed how the ARCUS approach may provide broader therapeutic applicability and address significantly more diseases through gene insertion and repair than other gene editing modalities which primarily target gene deletion or knock out.

Partnered Programs

iECURE-OTC (Gene Insertion Program): Led by iECURE, ECUR-506 is an ARCUS-mediated in vivo gene editing program currently in a first-in-human Phase 1/2 trial (OTC-HOPE) evaluating ECUR-506 as a potential treatment for neonatal onset ornithine transcarbamylase (OTC) deficiency. In January 2025, iECURE reported clinical efficacy and safety data in the first patient dosed showing a complete clinical response from three months post exposure to the end of study at six months post exposure, as demonstrated by the removal of standard of care ammonia scavenger medicines, an absence of hyperammonemic crises, and normalization of protein intake to age-appropriate levels. ECUR-506 was generally well tolerated with no significant clinical safety concerns apart from asymptomatic transaminitis experienced at four weeks. The asymptomatic transaminitis was managed with a short course of immunosuppressive therapy and resolved within four weeks. Twelve weeks after a single dose of ECUR-506, ammonia scavenger medication was discontinued and mean daily protein intake was increased to age-appropriate levels.

The OTC-HOPE study is ongoing in the United Kingdom, the United States, Australia, and Spain, and iECURE expects to finish enrollment in 2025 and provide complete data for the program in the first half of 2026.

PBGENE-NVS (Gene Insertion Program): Precision continues to advance its gene editing program with Novartis to develop a custom ARCUS nuclease for patients with hemoglobinopathies, such as sickle cell disease and beta thalassemia. The collaborative intent is to insert, in vivo, a therapeutic transgene as a potential one-time transformative treatment administered directly to the patient to overcome disparities in patient access to treatment with other therapeutic technologies, including those that are targeting an ex vivo gene editing approach.

Corporate Updates

Strengthened Senior Leadership Team: In January 2025, Precision announced the appointments of Cindy Atwell as Chief Development and Business Officer, and Dr. Cassie Gorsuch, PhD as Chief Scientific Officer, significantly strengthening the Company’s research and development capabilities to support clinical execution for its lead PBGENE-HBV program and advancement of other programs towards the clinic.

Business Updates – Monetization of CAR T Investments:

Equity Investment as Part of 2024 Deal with TG Therapeutics:
In January 2025, Precision received a deferred cash payment of $2.5 million as an equity investment in Precision’s common stock at $11.33 per share, a 100% premium to the then 30-day VWAP prior to purchase. This stock purchase by TG Therapeutics followed receipt of $7.5 million in February 2024 upon closing of the agreement with TG Therapeutics to develop azercabtagene zapreleucel (azer-cel) for autoimmune disorders.

In January 2025, TG Therapeutics announced its intention to enroll participants into the Phase 1 azer-cel trial in autoimmune disease, beginning with primary progressive Multiple Sclerosis in 2025. Upon the achievement of certain near-term clinical milestones, Precision will receive an additional $7.5 million payment in cash and the purchase of Precision common stock by TG Therapeutics at a 100% premium to the then current 30-day VWAP.

Quarter Ended December 31, 2024 Financial Results:

Cash, Cash Equivalents, and Restricted Cash: As of December 31, 2024, Precision had approximately $108.5 million in cash, cash equivalents, and restricted cash. The Company expects that existing cash and cash equivalents, upfront and potential near-term cash from CAR T transactions, along with expected operational receipts, continued fiscal and operating discipline, and availability of Precision’s at-the-market (ATM) facility are expected to extend Precision’s cash runway into the second half of 2026. Based on its expected cash runway, Precision believes it is sufficiently capitalized to operate the two wholly owned programs to Phase 1 data readouts.

On March 26, 2025 Nkarta, Inc. (Nasdaq: NKTX), a clinical-stage biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported financial results for the fourth quarter and year ended December 31, 2024 (Press release, Nkarta, MAR 26, 2025, View Source [SID1234651464]).

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"As the validation of cellular therapy in autoimmune disease expands to include CAR NK cells, we remain confident that the potential safety and accessibility advantages of NKX019 will allow it to occupy an important place in the future treatment of autoimmune disease," said Paul J. Hastings, CEO of Nkarta. "The opportunity that novel B-cell targeting therapies like NKX019 have to become transformative is substantial, creating a highly competitive development landscape. The integration of cellular therapy into traditionally outpatient-based specialties has been challenging and has required time and investment. We plan to provide our initial clinical update from the Ntrust-1 and Ntrust-2 studies in the second half of 2025."

"To ensure that Nkarta is strongly positioned financially to achieve multiple value-generating milestones within our existing cash and to set the stage for an efficient regulatory pathway for NKX019, we have implemented a restructuring plan, including a significant reduction of our workforce. The restructuring prioritizes investment in clinical execution and impacts every level of the organization, including reducing the executive leadership team by over 50%."

"We believe that this decision is necessary in today’s challenging financial and competitive environment to fulfill Nkarta’s vision of bringing potentially life-saving cellular therapies to people with autoimmune disease. Saying goodbye to cherished and talented team members is very difficult, and we pay tribute to them and their families for their dedication to Nkarta."

NKX019 is an allogeneic, off-the-shelf, chimeric antigen receptor (CAR) NK-cell therapy candidate engineered to deplete CD19-positive cells in B-cell mediated autoimmune disease. The approach leverages the potential advantages of NK cell therapy, including deep and rapid B-cell killing, a lower risk of cytokine release syndrome and neurotoxicity, the opportunity for potential fludarabine-free lymphodepletion to reduce toxicity, the added utility of on-demand dosing allowing for better accessibility, and the opportunity for repeated dosing as needed.

Clinical Program Progress and Upcoming Milestones

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Dosing of the first patient in Ntrust-1, a clinical trial of NKX019 for the treatment of lupus nephritis, reported in November 2024.
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Opening of enrollment for Ntrust-2, a clinical trial of NKX019 for the treatment of systemic sclerosis (SSc), idiopathic inflammatory myopathy (IIM, myositis) and ANCA-associated vasculitis (AAV), reported in December 2024.
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Dosing of the first patient in the investigator-sponsored trial (IST) of NKX019 for the treatment of systemic lupus erythematosus (SLE) led by researchers at the Columbia University Irving Medical Center, reported in November 2024.
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Clearance of the IND for the IST of NKX019 for the treatment of myasthenia gravis (MG) led by researchers at the University of California, Irvine and the University of Kansas Medical Center, reported in December 2024.
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The dosing schedule of NKX019 was harmonized across all four clinical trials in the fourth quarter of 2024. Patients receive NKX019 on Days 0, 3 and 7 following single-agent lymphodepletion with cyclophosphamide.
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Preliminary clinical data from the Ntrust-1 and Ntrust-2 clinical trials is planned for the second half of 2025. The update is expected to include clinical response with available follow-up from a group of patients in the Ntrust-1 and Ntrust-2 studies.

Fourth Quarter and Full Year 2024 Financial Highlights

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Nkarta had cash, cash equivalents, restricted cash, and investments in marketable securities of $380.5 million as of December 31, 2024.
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Research and development (R&D) expenses were $96.7 million for the full year 2024 and $23.1 million for the fourth quarter of 2024. Non-cash stock-based compensation expense included in R&D expense was $8.0 million for the full year 2024 and $1.8 million for the fourth quarter of 2024.
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General and administrative (G&A) expenses were $31.5 million for the full year 2024 and $7.8 million for the fourth quarter of 2024. Non-cash stock-based compensation expense included in G&A expense was $8.8 million for the full year 2024 and $2.1 million for the fourth quarter of 2024.
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Net loss was $108.8 million, or $1.60 per basic and diluted share, for the full year 2024. This net loss includes non-cash charges of $22.9 million that consisted primarily of share-based compensation and depreciation expenses. Net loss was $25.9 million, or $0.35 per basic and diluted share, for the fourth quarter of 2024. This net loss includes non-cash charges of $4.9 million that consisted primarily of share-based compensation and depreciation expenses.

Restructuring Expenses and Financial Guidance

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Cash payments resulting from the restructuring are estimated to be $5.5 to $6.5 million.
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Nkarta anticipates its cash and cash equivalents to be sufficient to fund its current operating plan into 2029, an extension of its cash runway by more than one year based on cost reductions to be realized from the restructuring.

About NKX019

NKX019 is an allogeneic, cryopreserved, off-the-shelf immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed chimeric antigen receptor (CAR) for enhanced cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal B cells as well as those implicated in autoimmune disease and B cell-derived malignancies. Nkarta is evaluating NKX019 in multiple autoimmune conditions.

About the Ntrust Clinical Trials in Autoimmune Disease

Ntrust-1 (NCT06557265) and Ntrust-2 (NCT06733935) are multi-center, open label, dose escalation clinical trials that build on academic studies of durable, drug-free remissions in patients with autoimmune disease after CD19-targeted cell therapy. Both trials will assess the safety of NKX019 in people living with autoimmune diseases as well as its ability to enable long-term remissions via a "reset" of the immune system through the elimination of pathogenic B cells.

Ntrust-1 is enrolling patients with lupus nephritis. Ntrust-2 is enrolling patients with systemic sclerosis (scleroderma), idiopathic inflammatory myopathy (myositis), or ANCA-associated vasculitis (AAV).

In both studies, patients receive a three-dose cycle of NKX019 on Days 0, 3 and 7 following single-agent lymphodepletion with cyclophosphamide, an agent with an established safety profile across autoimmune diseases. Leveraging the engineering of NKX019, no patients in either trial will receive supplemental cytokines or antibody-based therapeutics. This approach is designed to evaluate the single-agent activity of NKX019 and facilitate a more rapid path to regulatory approval. Patients in Ntrust-1 may also receive additional cycles to restore response. Each trial is designed to initially enroll up to 12 patients.

About the Investigator-Sponsored Clinical Trial of NKX019 for Systemic Lupus Erythematosus

The single-center, single-arm, open-label Phase 1 investigator-sponsored clinical trial (NCT06518668) is designed to enroll up to 6 patients with systemic lupus erythematosus, regardless of renal involvement, and will evaluate safety and clinical outcomes in a potentially different population than Ntrust-1. Translational and biomarker studies, including autoantibodies, cytokine profiles and pharmacokinetics are also planned. Patients receive NKX019 following single-agent lymphodepletion with cyclophosphamide. The clinical trial is being led by Anca D. Askanase, M.D., M.P.H., Director, Lupus Center at Columbia University Irving Medical Center and the Director of Rheumatology Clinical Trials.

About the Investigator-Sponsored Clinical Trial of NKX019 for Generalized Myasthenia Gravis
The single-arm, open-label Phase 1 investigator-sponsored clinical trial is designed to enroll patients with generalized myasthenia gravis, and will evaluate safety and clinical outcomes. Translational and biomarker studies, including autoantibodies, cytokine profiles and pharmacokinetics are planned. Patients will receive NKX019 following single-agent lymphodepletion with cyclophosphamide. The clinical trial is being co-led by Ali A. Habib, M.D., Clinical Professor of Neurology at the University of California, Irvine, and other investigators.

On March 26, 2025 Mereo BioPharma Group plc (NASDAQ: MREO) ("Mereo" or the "Company"), a clinical-stage biopharmaceutical company focused on rare diseases, reported its financial results for the full year ended December 31, 2024, and provided recent corporate highlights (Press release, Mereo BioPharma, MAR 26, 2025, View Source [SID1234651463]).

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"2024 was a year of focused execution and strategic advancement at Mereo, driving our lead programs closer to key milestones," said Dr. Denise Scots-Knight, Chief Executive Officer of Mereo. "The Phase 3 Orbit study of setrusumab in osteogenesis imperfecta (OI) is set to read out at the upcoming second interim analysis mid-year or at the final analysis during the fourth quarter of 2025. This could set the stage for us, alongside our partner Ultragenyx, to file for regulatory approvals in the U.S. and EU. Our European pre-commercial activities are ongoing, where we are focused on laying the foundation for a successful and efficient commercial launch, following potential regulatory approval. On alvelestat, the recent receipt of European Orphan Designation and the Phase 3 readiness activities have been highly supportive for our ongoing partnering process. With a strong financial position, we look forward to a transformative 2025, focused on bringing life-changing therapies to patients with rare diseases."

2024 Highlights, Recent Developments, and 2025 Anticipated Milestones

Setrusumab (UX143)

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Continued progress in two global studies, the Phase 3 portion of Orbit (Phase 2/3) and Cosmic (Phase 3), of setrusumab in OI patients, led by our partner Ultragenyx.
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The Phase 3 portion of the Orbit Study is continuing to dose pediatric and young adult patients, with the second interim analysis expected mid-2025 and potential final analysis in the fourth quarter of 2025.
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Treatment is ongoing in the open-label Phase 3 Cosmic study evaluating setrusumab against intravenous bisphosphonate therapy in patients aged 2 to <7 years. Data from this study will be evaluated in parallel with the interim or final analysis from the Orbit study.
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Pre-commercial activities to lay the foundation for launch ongoing.
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Scientific advice obtained from GBA in Germany and NICE in the U.K.
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Progress on project SATURN with existing registries that are appropriate sources of data on the natural history of OI and longitudinal data with the standard-of-care.

Alvelestat (MPH-966)

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In the first quarter of 2025, the European Commission granted Orphan Designation to alvelestat for the treatment of AATD-LD. This designation followed a positive recommendation from the EMA Committee for Orphan Medicinal Products in January 2025.
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Alvelestat previously received Orphan Drug Designation and Fast Track Designation from the U.S. FDA in 2021 and 2022, respectively.
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The Company remains in discussion with multiple potential partners for the development and commercialization of alvelestat.

Full Year 2024 Financial Results

Total research and development ("R&D") expenses increased by $3.5 million from $17.4 million in 2023 to $20.9 million in 2024. The increase was primarily due to increases of $6.2 million and $2.6 million in R&D expenses for alvelestat and setrusumab, respectively, partially offset by a $5.5 million decrease in R&D expenses for etigilimab. The increase in program expenses for alvelestat is due to the preparatory work for the Phase 3 study. This principally comprised drug formulation and manufacturing activities, SGRQ validation activities and regulatory interactions. The increase in program expenses for setrusumab was primarily due to higher levels of ongoing activities in Europe, including real-world evidence programs and medical affairs activities, and amounts under the manufacturing and supply agreement with our partner, Ultragenyx, along with input into development, regulatory and manufacturing plans with Ultragenyx, who fund the global development of the program pursuant to our license and collaboration agreement. The reduction in program expenses for etigilimab was primarily due to the winding down and completion of the open label Phase 1b/2 basket study in combination with an anti-PD-1 in a range of tumor types.

General and administrative expenses increased by $8.0 million from $18.4 million in 2023 to $26.4 million in 2024. The increase primarily reflects $2.7 million higher pre-commercial activities to lay the foundation for the commercial launch of setrusumab in Europe, including activities to support pricing and reimbursement by HTA authorities and payor decision-makers in Europe. The remaining increase is driven by additional corporate expenses, including employee-related costs and legal and professional fees in respect of compliance with the U.S. domestic reporting regime, and reductions in reimbursements of certain expenses from our depository in respect of our ADR program and settlement of a claim under our D&O insurance policy in the prior year.

Net loss for the full year ended December 31, 2024 was $43.3 million, compared to $29.5 million during the comparable period in 2023, primarily reflecting an operating loss of $47.4 million, partially offset by interest income and the benefit from R&D tax credits.

As of December 31, 2024, the Company had cash and cash equivalents of $69.8 million, compared to $57.4 million as of December 31, 2023. The Company’s guidance remains unchanged, and it continues to expect, based on current operational plans, that its existing cash and cash equivalents balance will enable it to fund its currently committed clinical trials, operating expenses, and capital expenditure requirements into 2027. This guidance does not include any potential upfront payments associated with a partnership for alvelestat or business development activity around any of the Company’s non-core programs.

Total ordinary shares issued as of December 31, 2024 were 775,728,034. Total ADS equivalents as of December 31, 2024 were 155,145,606, with each ADS representing five ordinary shares of the Company.

On March 26, 2025 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported financial results for the fourth quarter and year ended December 31, 2024 (Press release, Leap Therapeutics, MAR 26, 2025, View Source [SID1234651462]).

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Leap Highlights:

· Reported positive updated data from Part B of the Phase 2 DeFianCe study of sirexatamab (DKN-01) in second-line patients with advanced microsatellite stable (MSS) colorectal cancer (CRC) confirming:
o Statistically significant 32% higher overall response rate (ORR), 3.5 month longer progression-free survival (PFS), and longer overall survival (OS) in patients with high DKK1 levels
o Statistically significant 22% higher ORR and 2.6 month longer PFS in patients who had not had prior anti-VEGF therapy
· FL-501 abstract accepted for poster presentation at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

"In 2024, we continued to advance sirexatamab, our anti-DKK1 antibody, through Phase 2 randomized controlled clinical trials as part of our mission to bring personalized medicines to patients fighting against cancer. In particular, the updated data from Part B of the DeFianCe study that we announced today demonstrated significantly higher ORR and longer PFS for sirexatamab in patients who have high levels of DKK1 or who have not had prior anti-VEGF therapy, two exploratory populations with strong scientific rationale that each represent 25-50% of the second-line CRC market," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "We believe that there is a compelling opportunity to move forward with a registrational study for sirexatamab in patients with CRC and to advance FL-501 towards clinical trials."

DKN-01 Development Update

· Reported updated clinical data from Part B of the DeFianCe Study of sirexatamab plus bevacizumab and chemotherapy in CRC patients. Today, 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 (Experimental Arm) compared to bevacizumab and chemotherapy (Control Arm) in patients with MSS CRC who have received one prior systemic therapy for advanced disease. In the updated data announced today,

o Patients with high DKK1 levels, either at the upper quartile or above the median, treated in the sirexatamab Experimental Arm had significantly improved ORR, PFS, and OS compared to the Control Arm.

o In patients who had not received prior anti-VEGF therapy, the sirexatamab Experimental Arm had significantly improved ORR and PFS compared to the Control Arm, with an early advantage in OS.

o Across the intent-to-treat population, the sirexatamab Experimental Arm had improved ORR compared to the Control Arm, with PFS and OS maturing with a higher number of patients continuing to benefit on the sirexatamab Experimental Arm.

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.

With approximately 30,000 second-line treated CRC patients in the US and 160,000 in the next 7 largest markets, sirexatamab has a large market opportunity in the 25-50% of patients who have high DKK1 levels or in the approximately 50% of patients who did not receive prior anti-VEGF therapy. In addition, the outcomes in patients with no prior anti-VEGF therapy provides an opportunity to move into treating first-line CRC patients, where there are an estimated 45,000 patients in the US and 265,000 in the next 7 largest markets who receive therapy for their advanced disease.

Leap has engaged a leading financial advisor to explore business development opportunities to further the development of sirexatamab.

Pipeline Update

· Presenting preclinical FL-501 data at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. Preclinical data from FL-501, a potential best-in-class monoclonal antibody designed to neutralize GDF-15 to treat patients with cachexia and other GDF-15-driven diseases, will be featured during a poster session at the 2025 AACR (Free AACR Whitepaper) Annual Meeting taking place April 25-30 in Chicago. In addition, manufacturing and non-clinical development continues with the goal of beginning a clinical trial in 2026.

Conference Call

· Leap’s management team will host a conference call today, March 26, 2025 at 8:00 a.m. Eastern Time to further discuss the data. The conference call will be broadcast live in listen-only mode and can be accessed via the webcast URL: View Source A replay of the event will be available for a limited time on the Investors page of the Company’s website at View Source

Selected Year-End and Fourth Quarter 2024 Financial Results

Net Loss was $67.6 million for the year ended December 31, 2024, compared to $81.4 million for the year ended December 31, 2023. The decrease was primarily due to a decrease in research and development expenses.

Research and development expenses were $57.2 million for the full year 2024, compared to $73.2 million for the same period in 2023. Research and development expenses were $13.1 million for the fourth quarter ended 2024, compared to $11.7 million for the same period in 2023. The decreases for the full year 2024 were primarily due to in-process research and development acquired in the Flame merger which were expensed in the year ended December 31, 2023.

General and administrative expenses were $12.8 million for the full year 2024, compared to $13.8 million for the same period in 2023. General and administrative expenses were $3.0 million for the fourth quarter ended 2024, compared to $3.1 million for the same period in 2023. The decreases for the full year 2024 were primarily due to a decrease in professional fees due to lower finance and legal costs.

Cash and cash equivalents totaled $47.2 million at December 31, 2024.

On March 26, 2025 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported that an abstract containing preclinical data for KO-2806, the Company’s next-generation farnesyl transferase inhibitor (FTI), in combination with cabozantinib, a tyrosine kinase inhibitor (TKI), in clear cell renal cell carcinoma (ccRCC), has been accepted for an oral presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL on April 28, 2025 (Press release, Kura Oncology, MAR 26, 2025, View Source [SID1234651461]).

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"The latest findings for our next-generation farnesyl transferase inhibitor, KO-2806, being presented at this year’s AACR (Free AACR Whitepaper) Annual Meeting, add to the growing body of data demonstrating the potential of FTIs as companion therapeutic agents to augment the antitumor activities of various targeted therapies and to overcome resistance in combination," said Francis Burrows, Ph.D., Chief Scientific Officer of Kura Oncology. "We continue to make good progress in our FIT-001 trial evaluating KO-2806 in solid tumor indications where there is unmet medical need, and we look forward to presenting the first clinical data for KO-2806 as monotherapy and in combination with cabozantinib for the treatment of RCC later this year."

The title and session information for the oral presentation are listed below. Full abstract details including title and text are currently available to registrants via the AACR (Free AACR Whitepaper) online itinerary planner. Details of the oral presentation, entitled "Farnesyl transferase inhibitor KO-2806 enhances the antitumor activity of cabozantinib in ccRCC tumors that progress on anti-VEGFR agents" (oral 6370), are as follows:

Session Date and Time: Monday, April 28, 2025; 2:30 PM – 4:45 PM CT
Session Title: Minisymposium Novel Antitumor Agents
Presentation Time: 4:25 PM – 4:40 PM CT

A copy of the presentation will be available in the Posters and Presentations section on Kura’s website at the beginning of the presentation session.