On February 26, 2025 Microbiotica, a clinical-stage biopharma company developing a pipeline of oral precision microbiome medicines called live biotherapeutic products (LBPs), reported that it has presented new data on the mechanism of action of MB097 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) AACR (Free AACR Whitepaper) IO meeting held in Los Angeles, February 23-26 (Press release, Microbiotica, FEB 26, 2025, View Source [SID1234650634]). MB097 is an LBP in development as an adjunct to immune-oncology treatments such as MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy, KEYTRUDA (pembrolizumab).

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Dr Mat Robinson, Microbiotica’s Senior Vice-President of Research, presented data from new pre-clinical studies in a poster entitled "Clinical response to immune checkpoint inhibitors in melanoma is associated with distinct gut bacterial species that promote anti-tumor immunity by different mechanisms". The poster can be accessed here (View Source)

The bacteria comprising MB097 were found to be associated with response to immune-oncology treatments, such as KEYTRUDA (pembrolizumab), in multiple cohorts of melanoma patients. These new data demonstrate that the bacterial strains within MB097 can interact directly with dendritic cells to potently activate cytotoxic T lymphocytes (CTL). In addition, certain MB097 bacteria also produced metabolites that enhanced the tumor cell-killing potential of CTLs. One strain released metabolites that reversed the inhibitory effects of tumor-associated macrophages.

Mat Robinson, Microbiotica’s Senior VP of Research, said, "These data begin to identify the different mechanisms by which gut commensal bacteria drive immunotherapy response."

MB097 is being tested in an international Phase Ib clinical study, in combination with KEYTRUDA (pembrolizumab), MSD’s anti-PD-1 therapy, in patients with cutaneous melanoma who have failed to respond to immunotherapies. Data readout expected by the end of 2025.

On February 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 fourth quarter and full year 2024 financial results and provided a corporate update (Press release, Kura Oncology, FEB 26, 2025, View Source [SID1234650633]).

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"We are very pleased the KOMET-001 registrational trial achieved its primary endpoint. We look forward to sharing topline data at an upcoming medical conference and expect to submit a New Drug Application (NDA) in relapsed/refractory (R/R) NPM1-mutant acute myeloid leukemia (AML) next quarter," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "In parallel, we are advancing ziftomenib into registrational studies in the frontline (1L) setting. Approximately half of patients with newly diagnosed NPM1-mutated (NPM1-m) AML and 80% of patients with KMT2A-rearranged (KMT2A-r) AML will die from the disease within five years. Given this unmet need, we are pleased to have reached alignment with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) on key aspects of our Phase 3 trials, including the use of minimum residual disease (MRD)-negative complete response (CR) as a primary endpoint for potential accelerated approval in the U.S., with topline results anticipated in 2028. Our KOMET-017 trial is breaking new ground, and we and our partners at Kyowa Kirin are working as rapidly as possible to bring ziftomenib to AML patients worldwide."

Recent Highlights

Positive topline results from registration-directed trial of ziftomenib in R/R NPM1-m AML – Kura and Kyowa Kirin announced positive topline results from KOMET-001, the Phase 2 registration-directed trial of ziftomenib in patients with R/R NPM1-m AML. The KOMET-001 trial achieved its primary endpoint, consistent with the targeted 20-30% CR/CR with partial hematological recovery (CRh) rate, and data have been submitted for presentation at ASCO (Free ASCO Whitepaper). The benefit-risk profile for ziftomenib is highly encouraging, and safety and tolerability were consistent with previous reports. Facilitated by the Breakthrough Therapy Designation status of ziftomenib in R/R NPM1-m AML, the Company completed its pre-NDA meeting with FDA and anticipates submitting an NDA in the second quarter of 2025.

Positive feedback from FDA for 1L combination trial designs – Earlier this month, Kura and Kyowa Kirin announced alignment with FDA on the KOMET-017 global trial protocol evaluating ziftomenib in combination with both intensive and non-intensive combination regimens in patients with newly diagnosed NPM1-m and/or KMT2A-r AML. This includes alignment on potential pathways for accelerated approval in the U.S. in both the KOMET-017-IC (intensive chemotherapy) and KOMET-017-NIC (non-intensive chemotherapy) trials by allowing the trials to use MRD-negative CR and CR, as primary endpoints, respectively. The companies also gained alignment with the EMA on the KOMET-017 protocol, and expect to initiate the KOMET-017 Phase 3 trials in the second half of 2025.

Positive clinical data for Phase 1 trial of ziftomenib in combination with standards of care – In December 2024, Kura Oncology and Kyowa Kirin announced encouraging clinical data from KOMET-007, a Phase 1 trial of ziftomenib in combination with standards of care, including cytarabine/daunorubicin (7+3) and venetoclax/azacitidine in patients with NPM1-m and KMT2A-r AML. Among response-evaluable patients enrolled in the 7+3 combination cohort for patients with 1L NPM1-m or KMT2A-r adverse risk AML, 91% achieved a CR (100% for NPM1-m, 83% for KMT2A-r patients). Ziftomenib was generally well tolerated in combination at all dose levels evaluated across all cohorts in the Phase 1a dose-escalation portion of the trial. The positive results from KOMET-007 reported at ASH (Free ASH Whitepaper) reinforce the companies’ commitment to evaluating ziftomenib across the continuum of 1L AML treatment options.

Global strategic collaboration with Kyowa Kirin to develop and commercialize ziftomenib in acute leukemias – In November 2024, Kura Oncology and Kyowa Kirin announced they entered into a global strategic collaboration to develop and commercialize ziftomenib (Kyowa Agreement), funding the expansive AML development program through U.S. commercialization in 1L combinations. Under the partnership, Kura retains leadership and key strategic rights to ziftomenib in the U.S. and preserves strategic flexibility, while enabling development and commercialization of ziftomenib across the continuum of care in acute leukemias, including both fit and unfit 1L indications, post-transplant maintenance setting and combinations with targeted therapies.

Preclinical data supporting opportunity for ziftomenib in treatment of gastrointestinal stromal tumors (GIST) – In October 2024, Kura reported preclinical data presented at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, supporting the potential for ziftomenib in combination with KIT inhibitors for GIST patients. The combination of ziftomenib and imatinib demonstrated robust and durable antitumor activity in imatinib-sensitive (1L) and imatinib-resistant (2L/3L) GIST patient-derived xenograft models. Sixty percent of patients develop resistance to imatinib within two years and ziftomenib has the potential to delay the onset of resistance to, or overcome resistance in patients pre-treated with, imatinib. In August 2024, Kura announced clearance by the FDA of an IND application and the Company remains on track to initiate the KOMET-015 trial evaluating ziftomenib plus imatinib in patients with advanced GIST, in the first half of 2025.

Clinical and preclinical data support combinations of farnesyl transferase inhibitors with targeted therapies – Despite multiple advances, innate and adaptive resistance remain a challenge for many classes of targeted therapies in cancer. A growing body of clinical and preclinical data demonstrates the potential of farnesyl transferase inhibitors as companion therapeutic agents to augment the antitumor activities of various targeted therapies and overcome resistance in combination. Enrollment in the FIT-001 trial evaluating our next-generation farnesyl transferase inhibitor KO-2806 continues to progress and the dose-escalation portion of the KURRENT-HN trial with tipifarnib is now complete. Kura expects to present the first clinical data for KO-2806 as a monotherapy and in combination, as well as clinical data from the KURRENT-HN trial, in the second half of 2025.
Financial Results

Collaboration revenue from our Kyowa Kirin partnership for the fourth quarter and full year 2024 was $53.9 million, compared to no revenue in 2023.

Research and development (R&D) expenses for the fourth quarter of 2024 were $52.3 million, compared to $32.5 million for the fourth quarter of 2023. R&D expenses for the full year 2024 were $170.0 million, compared to $115.2 million for the prior year.

General and administrative (G&A) expenses for the fourth quarter of 2024 were $24.1 million, compared to $14.2 million for the fourth quarter of 2023. G&A expenses for the full year 2024 were $77.1 million, compared to $50.6 million for the prior year.

Net loss for the fourth quarter of 2024 was $19.2 million, compared to a net loss of $42.8 million for the fourth quarter of 2023. Net loss for the full year 2024 was $174.0 million, compared to a net loss of $152.6 million for the prior year.

Net loss for the fourth quarter and full year 2024 included non-cash, share-based compensation expense of $8.6 million and $33.9 million, respectively. This compares to $7.2 million and $28.1 million for the same periods in 2023.

As of December 31, 2024, Kura had cash, cash equivalents and short-term investments of $727.4 million, including the upfront payment of $330.0 million from Kyowa Kirin, compared to $424.0 million as of December 31, 2023.

Based on our current plans, we believe our cash, cash equivalents and short-term investments as of December 31, 2024 will be sufficient to enable us to fund our current operating expenses into 2027, and combined with anticipated collaboration funding under the Kyowa Agreement, should support our ziftomenib AML program through commercialization in the 1L combination setting.
Forecasted Milestones

Submit an NDA for ziftomenib in R/R NPM1-m AML in the second quarter of 2025.

Present topline data from KOMET-001 Phase 2 registration-directed trial in R/R NPM1-m AML in the second quarter of 2025.

Present preliminary clinical data from the KOMET-007 Phase 1b expansion cohort evaluating ziftomenib with intensive chemotherapy (7+3) at a medical meeting in the second quarter of 2025.

Initiate the KOMET-015 trial evaluating ziftomenib and imatinib in patients with advanced GIST in the first half of 2025.

Initiate two independent Phase 3 registration-enabling trials in 1L intensive (KOMET-017-IC) and non-intensive (KOMET-017-NIC) AML in the second half of 2025.

Present preliminary clinical data from the KOMET-007 Phase 1b expansion cohort evaluating ziftomenib with venetoclax and azacitidine at a medical meeting in the second half of 2025.

Nominate a development candidate for next-generation menin inhibitor program in diabetes in mid-2025.

Initiate one or more expansion cohorts of KO-2806 and cabozantinib in patients with advanced renal cell carcinoma in the first half of 2025.

Present data from the Phase 1 monotherapy dose escalation of KO-2806 in patients with RAS mutations in the second half of 2025.

Present data from the Phase 1 trial evaluating KO-2806 and cabozantinib in patients with renal cell carcinoma in the second half of 2025.

Present data from the dose escalation portion of KURRENT-HN trial evaluating tipifarnib and alpelisib in PIK3CA-dependent head and neck squamous cell carcinoma (HNSCC) in the second half of 2025.
Conference Call and Webcast

Kura’s management will host a webcast and conference call at 4:30 p.m. ET / 1:30 p.m. PT today, February 26, 2025, to discuss the financial results for the fourth quarter and full year 2024 and to provide a corporate update. The live call may be accessed by dialing (800) 579-2543 for domestic callers and (785) 424-1789 for international callers and entering the conference ID: KURAQ4. A live webcast and archived replay of the event will be available here or online from the investor relations section of the company website at www.kuraoncology.com.

On February 26, 2025 Keros Therapeutics, Inc. ("Keros" or the "Company") (Nasdaq: KROS), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapeutics to treat a wide range of patients with disorders that are linked to dysfunctional signaling of the transforming growth factor-beta ("TGF-ß") family of proteins, reported a business update and announced financial results for the fourth quarter and full year ended December 31, 2024 (Press release, Keros Therapeutics, FEB 26, 2025, View Source [SID1234650632]).

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"The efforts over the past year by the team at Keros have positioned us to continue to advance our promising pipeline of novel therapeutics," said Jasbir S. Seehra, Ph.D., Chair and Chief Executive Officer. "We are excited to report initial data from the ongoing Phase 1 clinical trial of KER-065 in healthy volunteers in the first quarter of 2025, which we believe can inform our advancement into a Phase 2 clinical trial in neuromuscular disease, with our initial focus on Duchenne muscular dystrophy. We continue to expect to report data from the Phase 2 TROPOS trial evaluating cibotercept (KER-012) in patients with pulmonary arterial hypertension, and we plan to evaluate the appropriate development strategy for cibotercept following that data readout."

Recent Corporate Highlights:

•Cash position strengthened: In February 2025, Keros received a $200.0 million upfront payment pursuant to the exclusive license agreement it entered into with Takeda Pharmaceuticals U.S.A., Inc. (the "Takeda Agreement") to further develop, manufacture and commercialize elritercept (KER-050) worldwide outside of mainland China, Hong Kong and Macau, which became effective on January 16, 2025. Based on current operating assumptions, the Company expects that its cash and cash equivalents as of December 31, 2024, together with the upfront payment received from the Takeda Agreement, will enable the Company to fund its planned operating expenses and capital expenditure requirements into 2029.

2024 Financial Results

Keros reported a net loss of $46.0 million for the fourth quarter and $187.4 million for the year ended December 31, 2024, as compared to a net loss of $40.2 million for the fourth quarter and $153.0 million for the year ended December 31, 2023. The increase in net loss for the fourth quarter and the year was largely due to increased research and development efforts as well as additional investments to support the achievement of Keros’ clinical and corporate goals.

Keros generated revenue of $3.0 million for the fourth quarter and $3.6 million for the year ended December 31, 2024 compared to $0.1 million for the fourth quarter and $0.2 million for the year ended December 31, 2023. Revenue in 2024 was largely related to a milestone achieved under Keros’ license agreement with Hansoh (Shanghai) Healthtech Co., Ltd. ("Hansoh").

Research and development expenses were $45.6 million for the fourth quarter and $173.6 million for the year ended December 31, 2024, as compared to $37.5 million for the fourth quarter and $135.3 million for the year ended December 31, 2023. The increase in research and development expenses for the fourth quarter and the year was driven by the continued advancement of the Company’s pipeline, notably the TROPOS trial, the ongoing Phase 1 clinical trial of KER-065 and the progression of two Phase 2 clinical trials and the Phase 3 clinical trial of elritercept, as well as an increase in personnel costs and infrastructure to support operations and expansion of the Company’s pipeline.
General and administrative expenses were $10.7 million for the fourth quarter and $40.8 million for the year ended December 31, 2024, as compared to $9.1 million and $34.8 million for the fourth quarter and year ended December 31, 2023, respectively. The increase was primarily due to an increase in personnel expenses to support the Company’s organizational growth and achievement of its corporate goals, an increase in facilities, supplies and other office expenses due to the growth of the Company’s organization and an increase in professional fees.

Keros’ cash and cash equivalents as of December 31, 2024 was $559.9 million compared to $331.1 million as of December 31, 2023. Based on current operating assumptions, Keros expects that its cash and cash equivalents as of December 31, 2024, together with the $200 million upfront payment from the Takeda Agreement, which the Company received in February 2025, will enable the Company to fund its planned operating expenses and capital expenditure requirements into 2029.

On February 26, 2025 Kairos Pharma, Ltd. (NYSE American: KAPA), a clinical-stage biopharmaceutical company, reported that the company presented preclinical data on its investigational compounds KROS 101 and KROS 401 during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Immuno-Oncology (AACR IO) conference held in Los Angeles from February 23-26, 2025 (Press release, Kairos Pharma, FEB 26, 2025, View Source [SID1234650631]). The data highlighted positive preclinical outcomes with the Company’s glucocorticoid-induced tumor necrosis factor receptor (GITR) agonist KROS101 in melanoma and glioblastoma as well as its peptide inhibitor for macrophages KROS 401 in glioma animal models.

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In the presentation, titled "KROS 101: A Next Generation GITR agonist boosting anti-tumor T cell responses and reprogramming the tumor environment," study authors demonstrated that KROS significantly inhibited tumor growth in a preclinical melanoma model. The same team of scientists also showed that KROS 101 increased the proliferation of helper and cytotoxic T cells (CD4+ and CD8+), while decreasing T reg cell growth in a melanoma model. Further, T cells treated with KROS 101 showed cytotoxicity against glioblastoma cell lines and glioma cancer cells, which study authors, Admasu, et. al., concluded KROS 101 demonstrated potent anti-tumor activity compared to a previously used antibody against the GITR receptor TRX518 that was in clinical trials. Most importantly, the authors demonstrated KROS 101 but not TRX518 to prevent the exhaustion of T cells in the tumor.

The second presentation, titled "Targeting M2 macrophage polarization: The anti-tumor effects of IL-4/IL-13 blocking peptide and iron oxide nanoparticles," demonstrated the Company’s peptide inhibitor KROS 401 may effectively reprogram macrophages — types of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances – to inhibit tumor growth. The preclinical study demonstrated that KROS 401 exhibited an anti-tumor effect in glioma-bearing mice following a decrease in M2 macrophages, which are known to facilitate tumor growth.

Dr. John Yu, CEO of Kairos Pharma and co-inventor, commented, "We continue to receive validation of our preclinical data demonstrating our KROS platform’s development of anti-tumor therapies. KROS 101 addresses an Achille’s heel of all T cell immunotherapies and that is the development of exhaustion in anti-tumor T cells. KROS 101 appears to prevent the development of exhaustion by T cells enabling them to continue to kill tumor cells."

Dr. Ram Murali, VP of Research and Development stated, "KROS 401 is designed to reverse the M1 to M2 transition of macrophages in the tumor microenviroment. What this translates to is changing pro-tumor macrophages into anti-tumor macrophages. This leads to tumor-killing activity by both macrophages and T cells."

The American Association for Cancer Research (AACR) (Free AACR Whitepaper) Immuno-Oncology (AACR IO) encompasses the very best of basic, translational, and clinical research in immunology, inflammation, and immunotherapies for cancer, including immuno-oncology (IO) drugs, inflammatory modulators, vaccines, and cellular therapies. The cutting-edge AACR (Free AACR Whitepaper) IO 2025 program will appeal to a wide audience of basic scientists, translational researchers, clinical investigators, regulators, industry, investors, and lay press. A mix of keynote lectures, major symposia, spotlight sessions, educational sessions, special sessions, and poster sessions with exhibits will cover the spectrum of the IO field—including late-breaking clinical trials sessions highlighting new agents and IO combinations, and the results of practice-changing clinical trials.

On February 26, 2025 IngenOx Therapeutics the Oxford-based biopharmaceutical company, reported positive interim results from its Phase 2 clinical trial investigating zabadinostat in combination with a PD-1 inhibitor for advanced hepatocellular carcinoma (HCC) (Press release, IngenOx Therapeutics, FEB 26, 2025, https://ingenox.com/interim-phase-2-results-suggest-zabadinostat-combination-improves-overall-survival-in-advanced-liver-cancer [SID1234650630]). The findings were presented at The Lancet Summit 2025 in Shanghai, China.

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Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced HCC. While some patients experience lasting responses, resistance to therapy is a common challenge. Collaborative preclinical research has shown that IngenOx’s zabadinostat reversed resistance to immune checkpoint inhibition in a clinically relevant orthotopic mouse HCC model (Tu et al., 2024). This study provided a strong scientific rationale for the clinical development of zabadinostat in combination with an ICI as a treatment for HCC patients who have become resistant to checkpoint blockade.

IngenOx is supporting a randomised Phase 2 clinical trial conducted by the Chinese University of Hong Kong (CUHK) to evaluate the safety and efficacy of zabadinostat combined with geptanolimab in ICI-resistant HCC patients (Experimental Arm), compared with a tyrosine kinase inhibitor such as lenvatinib or sorafenib (Control Arm). Geptanolimab is an ICI that targets the programmed cell death-1 (PD-1) receptor.

Interim results were presented by investigators at The Lancet Summit on Cancer Control in China, recently held in Shanghai (https://thelancetsummit.com/cancer-control-china/index.html). The results showed that the experimental combination with zabadinostat was associated with a higher disease stabilisation rate (61.5%; 95% CI 35–88%; n = 13) compared to the control group (46.2%; 95% CI 19–73%; n = 13). No difference in progression-free survival was observed between the groups. Median overall survival was 13.9 months (95% CI 8–14) in the Experimental Arm, compared to 9.3 months (95% CI 2–NR) in the Control Arm (HR 0.16, 95% CI 0.08–1.36, p = 0.12). These preliminary findings indicate that the combination therapy is well tolerated, associated with a higher disease control rate, and suggests a trend towards improved outcomes. The positive clinical results support the continued development of zabadinostat combinations for advanced cancer treatment.

David Kerr, CMO of IngenOx and Professor of Cancer Medicine at the University of Oxford commented:

"These promising clinical trial findings give us great confidence that we can recapitulate in patients the extraordinary results seen in mice models and deliver a telling blow to this awful disease. Our sophisticated trial design gives us the necessary clinical data to continue recruitment and stays true to our commitment to precision medicine as we interrogate the serial biopsies from our patients to discover potentially predictive biomarkers to further improve clinical outcomes."

Nick La Thangue, CEO of IngenOx and Professor of Cancer Biology at the University of Oxford commented:

"These encouraging early results continue to endorse zabadinostat as a potentially significant drug in resistant liver cancer. We are pleased to support this trial and look forward to continuing our important collaboration with colleagues in Hong Kong."