lasmotinib (PHI-101) / Pharos iBio - LARVOL DELTA

AMLM26/T9 INTERCEPT A multi-arm trial for patients with acute myeloid leukemia investigating new treatments which target early relapse and changes in disease characteristics - PHI-101 (ANZCTR) - P1/2 | N=60 | Recruiting | Sponsor: Australasian Leukaemia & Lymphoma Group | Not yet recruiting ➔ Recruiting | N=30 ➔ 60

Enrollment change • Enrollment open • First-in-human • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A Potent Small Molecule Inhibitor of FLT3, PHI-101 Overcomes Resistance in Acute Myeloid Leukemia: Efficacy and PK/PD Profile in Phase 1 First in Human Study (ASH 2022) - P1a/1b | "Seventy percent of enrolled patients had more than 3 prior anti-leukemic treatment attempts, and four patients had relapsed or refractory disease after treatment with other FLT3 inhibitors including gilteritinib, quizartinib, or HM43239. A dose-escalating phase 1a clinical data of PHI-101, which reflects up to cohort 4 of the study, indicates that PHI-101 generated potent FLT3 inhibition leading to encouraging anti-leukemic responses in R/R AML patients, including in those with prior FLT3 TKI therapeutic failure. PHI-101 showed good tolerance and favorable safety profile and reduced leukemic blasts significantly with 28-day dosing. PHI-101 sustained its activity to clear FLT3-ITD and/or FLT3-TKD mutations including D835Y or N676K identified in AML patients."

Clinical • P1 data • PK/PD data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • FLT3

Lasmotinib synergizes with menin inhibition to overcome acquired MEN1 mutation–mediated resistance in FLT3-mutated KMT2A-rearranged AML (EORTC-NCI-AACR 2026) - "Abstract will be available as of 4 November (with consent of the author)"

Acute Myelogenous Leukemia • Oncology • FLT3 • KMT2A • MEN1

Proteomic analysis and efficacy evaluation reveal strong synergistic anti-leukemic activity of lasmotinib combined with menin inhibitors for AML (AACR 2026) - "In conclusion, lasmotinib is identified as a highly promising combination partner for menin inhibitors in AML. The strong synergism observed, both in vitro and in vivo, supports further development of lasmotinib plus bleximenib as a compelling therapeutic strategy for KMT2A-r and FLT3 mutant leukemia."

Clinical • Omic analysis • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • FLT3 • KMT2A • MEIS1 • MYC • NPM1 • STAT5

The third-generation FLT-3 inhibitor, PLM-102, is a promising therapeutic option for venetoclax-resistant AML (AACR 2025) - "Notably, PLM-102 demonstrated the highest tumor growth inhibitory (TGI) efficacy compared with those of other FLT3 inhibitors including tuspetinib, gilteritinib and PHI-101. In conclusion, PLM-102 completely inhibited FLT3 kinase and its downstream signaling including AKT and STAT3, inducing apoptosis in VR AML cells along with significant inhibition of the tumor growth in the VR xenograft mouse model. These findings suggest that PLM-102, a third-generation FLT-3 inhibitor, is a promising candidate for overcoming venetoclax resistance and could serve as a therapeutic option for venetoclax-resistant AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • CASP3 • FLT3 • MCL1 • STAT3

PHI-101 synergizes with chemotherapy and venetoclax in preclinical models of acute myeloid leukemia (AACR 2024) - "Additionally, treatment of mice with low-dose PHI-101 inhibited tumor regrowth and further potentiated venetoclax or azacytidine response in vivo. Our results suggest that the combination of PHI-101 and venetoclax or azacitidine may have the advantage of improving clinical responses in FLT3-ITD AML patients and offers a potential therapeutic option to treat patients with newly diagnosed or relapsed/refractory FLT3-mutant AML."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

PHI-101, a Novel FLT3 TKI, Shows Clinical Efficacy in Relapsed/Refractory FLT3-Mutated AML (ASH 2024) - P1a/1b | "75% of these patients had received prior FLT3 inhibitors (Gilteritinib (7), Midostaurin (3), Sorafenib (1), HM43239 (1)). The recommended phase 2 dose will be 160 mg once-daily which resulted in Cmax and AUC0-24 plasma concentrations in Phase 1b of 259 ng/ml and 3,920 ng/ml at cycle 1 day 1. Conclusion : Once-daily dosing of single-agent PHI-101 had a distinct tolerability profile and showed excellent anti-tumor activity across FLT3i-pretreated and FLT3i-naïve patients with R/R FLT3 mutant AML."

Clinical • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Neutropenia • Thrombocytopenia • FLT3

Evaluation of Synergistic Anti-Leukemic Efficacy of PHI-101 in Preclinical Model of FLT3-ITD Acute Myeloid Leukemia (ASH 2023) - "Study Design and Combination effects of simultaneous versus sequential treatment of PHI-101 with other agents, including daunorubicin, cytarabine, venetoclax (Ven), and azacytidine (Aza) were tested using human leukemia cell lines harboring FLT3-ITD mutations (MV4-11, Molm13, Molm14) or FLT3-wild type as controls...The GI 50 of the gilteritinib was 5... Treatment of AML cells with the combination of Ven or Aza with PHI-101 in vitro induced rapid induction of apoptosis and inhibition of cell growth that showed significant synergy. In vivo data showed improved efficacy for the combination treatment with these agents. In vitro and in vivo data from the preclinical AML models provides a rationale to evaluate the activity of PHI-101 in combination for patients who are ineligible for more intensive chemotherapeutic induction therapy."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • BCL2 • FLT3

PHI-101 As a Potent Next-Generation FLT3 Inhibitor, Overcome Resistances in Previously Treated Patients with FLT3-ITD or TKD Acute Myeloid Leukemia: Results of a Phase Ia/Ib Clinical Trial (ASH 2023) - P1a/1b | "Ten pts were R/R following previous treatment with other FLT3 inhibitors (gilteritinib, quizartinib, midostaurin, or HM43239). In dose-escalating phase Ia clinical trials, PHI-101 was well tolerated at all dose levels with no DLTs. Phase Ib dose-expansion trials with 160 mg daily dosing are currently ongoing. PHI-101 has delivered CRcs at 120 mg and 160 mg."

Clinical • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Paros IBio's AML treatment 'PHI-101' receives approval from the Australian Human Research Ethics Committee for clinical trials. [Google translation] (BioTimes) - "This clinical trial is expected to be a crucial opportunity to further verify PHI-101's potential to overcome MRD, a major challenge in AML treatment, following its efficacy in treating patients with relapsed/refractory AML confirmed in a global Phase 1 clinical trial."

New P1 trial • Acute Myelogenous Leukemia

AMLM26/T9 INTERCEPT A multi-arm trial for patients with acute myeloid leukemia investigating new treatments which target early relapse and changes in disease characteristics - PHI-101 (ANZCTR) - P1/2 | N=30 | Not yet recruiting | Sponsor: Australasian Leukaemia & Lymphoma Group

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Paros I-Bio, PHI-101 Global Phase 1 Final Results "Comprehensive Complete Remission 50%" [Google translation] (HIT News) - P1a/1b | N=42 | NCT04842370 | "Paros I-Bio...announced on the 1st that it has secured the final results report (CSR, Clinical Study Report) of the global phase 1 clinical trial of 'PHI-101', which is currently being developed as a treatment for acute myeloid leukemia (AML)....In phase 1b clinical trials, 50% of evaluable patients achieved a composite complete response (CRc), and the objective response rate (ORR) was 67%. Composite complete response is a concept that includes complete remission (CR), complete remission with incomplete hematological recovery (CRi), and morphologically free leukemia (MLFS)."

P1 data • Acute Myelogenous Leukemia

Pharos iBio designates PHI-101 as orphan drug for acute myeloid leukemia in Europe (Chosun Biz) - "Pharos iBio...announced on the 24th that its treatment for acute myeloid leukemia (AML), 'PHI-101,' has received orphan drug designation from the European Medicines Agency (EMA)....The company expects to benefit from a shortened review period for new drug approval, consulting related to clinical trials, and 10 years of market exclusivity after approval, as PHI-101 has been designated as an orphan drug in Europe. Previously, PHI-101 received orphan drug designation from the U.S. Food and Drug Administration (FDA) in 2019 and was also designated as a development-stage orphan drug by the Korea Food and Drug Administration last year."

Orphan drug • Acute Myelogenous Leukemia

Paros I-Bio applies for designation of ’PHI-101’ as orphan drug to the European Medicines Agency…Expanding global target market [Google translation] (Pharos iBio Press Release) - "Pharos iBio...announced on the 28th that it has submitted an application for orphan drug designation (ODD) for PHI-101, a treatment for acute myeloid leukemia (AML), to the European Medicines Agency (EMA). With this ODD application, Pharos iBio plans to expand the global development and early commercialization potential of PHI-101."

Orphan drug • Acute Myelogenous Leukemia

Paros I-Bio announces phase 1 clinical trial results for acute myeloid leukemia treatment [Google translation] (Nate) - P1 | N=42 | NCT04842370 | "Paros I-Bio...announced on the 9th that it had participated in the American Society of Hematology...and presented the comprehensive research results of the phase 1 clinical trial of 'PHI-101'...According to the results of this phase 1 clinical trial, PHI-101 was confirmed to show safety, tolerability, and therapeutic efficacy in patients with AML who are refractory or have relapsed due to resistance to existing approved treatments...According to the results of the phase 1 study, despite the participation of many patients with high levels of severity and difficulty who had received multiple previous treatments, including FLT3 inhibitors, 50% of the evaluable patients showed comprehensive complete response (CCR)...In addition, the overall response rate (ORR), which indicates a decrease or disappearance of tumor size through PHI-101 administration, was 67%....'We plan to enter full-scale procedures for a global Phase 2 clinical trial in 2025.'"

New P2 trial • P1 data • Acute Myelogenous Leukemia

Hanmi Pharmaceutical, ABL, Aptamer, 'Blood Cancer Treatment' Clinical Results Announced at American Society [Google translation] (Chosun Biz) - "Aptamer Science plans to present an abstract of its blood cancer treatment 'AST-202', which it is developing, at this year's conference....This presentation is expected to confirm the pharmacological characteristics of AST-202 and detailed animal experiment data. In the case of Paros I-Bio, the clinical phase 1 results will be presented as a poster this year as the research abstract for the acute myeloid leukemia treatment 'PHI-101' was adopted last year."

Clinical data • Preclinical • Acute Myelogenous Leukemia

Pharos I-Bio, Conditions for Rebound… Possibility of AI New Drug Technology Transfer [Google translation] (Nate) - "Pharos iBio announced on the 12th that it has completed recruiting patients for the phase 1 clinical trial of its acute myeloid leukemia treatment, 'PHI-101-AML', and that it plans to disclose the research results data for all patients who participated in the clinical trial at the American Society of Hematology (ASH) in December....During the IPO process, it was projected that sales of 55.1 billion won and operating profit of 22.9 billion won would be achieved, led by the global technology transfer contract for PHI-101 in 2025."

Enrollment closed • P1 data • Sales projection • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Korean AML drug shows 50% overall complete response rate in P1 trial (Korea Biomedical Review) - P1 | N=42 | NCT04842370 | "Pharos iBio said Wednesday that it would present poster data from the phase 1 clinical trial of PHI-101 for AML at the American Society of Hematology Annual Meeting, ASH 2024....The meeting will present results from the expanded phase 1b study of PHI-101-AML at the recommended expanded dose of 160 mg monotherapy, along with comprehensive results from the final patient recruitment in the phase 1b study. According to Pharos iBio's study abstract, 75 percent of patients in the phase 1b study relapsed or failed after prior FLT3 inhibitor therapy, and 50 percent of evaluable patients achieved a complete response....Pharos iBio plans to complete the phase 1 clinical trial of PHI-101-AML within the year..."

P1 data • Trial completion date • Acute Myelogenous Leukemia

…Pharos I-Bio to complete phase 1 of leukemia treatment within the year… Aiming for early commercialization [Google translation] (Newspim) - "The company plans to complete phase 1 clinical trials within the year, enter phase 2 trials next year, and pursue early commercialization based on the results. As the phase 1 trials have yielded significant results, phase 2 trials are also expected to proceed smoothly."

Commercial • New P2 trial • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

PHI-101 synergizes with chemotherapy and PARP inhibitors in preclinical models of ovarian cancer (EORTC-NCI-AACR 2024) - P1 | "Niraparib showed different activities: 0.264 μM in the UWB1.89 parental cells and 0.722 μM in the UWB1.289+BRCA1 cells, with synergy confirmed only in the parental UWB1.289 cells.In vivo efficacy of PHI-101 and Olaparib combination therapy was evaluated using a patient-derived xenograft model...The combination efficacy of PHI-101 with Cisplatin or Topotecan was confirmed across four cells, demonstrating synergism...PHI-101 demonstrates a synergistic effect when combined with both platinum-based and non-platinum-based chemotherapy agents as well as PARP inhibitors. These combinations effectively induce cell death, enhancing anti-tumor activity through PARP cleavage and DNA damage in a dose- and time-dependent manner. This indicates that PHI-101 has significant potential as a combination partner to enhance apoptosis and inhibit DNA repair in OC."

Preclinical • Endometrial Cancer • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • HRD

Pharos I-Bio Releases Data on Combination Therapy for Relapsed and Refractory Ovarian Cancer [Google translation] (Medipana) - "Pharos I-Bio...announced on the 10th that it will present combination therapy data of its recurrent ovarian cancer treatment drug, PHI-101-OC, at the EORTC-NCI-AACR (ENA), an international cancer conference...Pharos I-Bio plans to present combination therapy data of its recurrent ovarian cancer treatment drug, PHI-101-OC, which was selected as the presentation topic at this conference, in a poster presentation....According to the research abstract to be presented at this conference, PHI-101-OC has been confirmed to have a synergistic effect in inhibiting the growth of cancer cells when administered in combination with not only platinum-based chemotherapy, which is the standard first-line treatment for ovarian cancer, but also PARP inhibitors or non-platinum chemotherapy."

Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor

Paros I-Bio, PHI-101 Investigator Clinical Trial Contract for Treatment of Microscopic Residual Disease [Google translation] (Medifonews) - "Paros I-Bio...announced on the 26th of last month that it signed an investigator-led clinical trial contract with ALLG (Australasian Leukaemia and Lymphoma Group), a leukemia and lymphoma specialized clinical research group in Oceania, for 'PHI-101', which is being developed as a treatment for acute myeloid leukemia (AML)....This PHI-101 investigator-initiated clinical trial (clinical trial name: ALLG AMLM26 INTERCEPT) will be conducted simultaneously in hospitals located in Australia, New Zealand, and the United States with the support of ParosiBio and ALLG....The company also plans to use the results of this MRD treatment study as reference material for conditional approval and accelerated approval from the Ministry of Food and Drug Safety and the U.S. Food and Drug Administration (FDA) in the future."

Commercial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Paros I-Bio “Acute Myeloid Leukemia Treatment PHI-101, Designated as Orphan Drug by the Ministry of Food and Drug Safety” [Google translation] (ET news) - "ParosiBio announced on the 4th that its relapsed and refractory acute myeloid leukemia (AML) treatment drug 'PHI-101' is scheduled to be designated as an orphan drug in the development stage by the Ministry of Food and Drug Safety (hereinafter referred to as the MFDS)....It is ParosiBio's core pipeline that completed recruitment of patients for phase 1 clinical trials in July of this year and is expected to end within the year."

Orphan drug • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Paros I-Bio signs MTA for two new drug pipelines with Australian Childhood Cancer Research Institute [Google translation] (Hankyung) - "ParosiBio...announced on the 12th that it has signed a material transfer agreement (MTA) with Dr. David Zigler, a brain tumor researcher at the Children's Cancer Institute Australia in Sydney, Australia, to expand the indications and conduct translational research for its core pipelines, PHI-101 and PHI-501. This agreement was conducted for the purpose of verifying the efficacy of two of ParosiBio's pipelines, radiosensitizer PHI-101-RS and pan-RAF mutation inhibitor PHI-501, in patient samples derived from pediatric brain tumors, a rare disease....The Australian Childhood Cancer Institute and Dr. David Ziegler plan to study the efficacy of PHI-101-RS as a CHK2 inhibitor in diffuse intrinsic pontine glioma (DIPG), a severe pediatric disease."

Licensing / partnership • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Solid Tumor

Paros I-Bio, Phase 1 clinical trial for leukemia treatment begins in earnest [Google translation] (Pinpoint News) - "According to industry sources on the 1st, Paros I-Bio has completed the recruitment of patients for the multinational phase 1 clinical trial of 'PHI-101', an acute myeloid leukemia treatment targeting FLT3 mutations...This clinical trial is being conducted in Korea and Australia for patients with acute myeloid leukemia who have relapsed or are refractory to other treatments....Currently, 30 patients have been registered, and a phase 1b clinical trial is underway with the expanded recommended dose of 160 mg as a single therapy."

Enrollment status • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology