PHI-501 / Pharos iBT - LARVOL DELTA

Paros I-Bio (CEO Jeong-hyeok Yoon) announced the preclinical study results of its anticancer drug candidate ‘PHI-501' [Google translation] (HIT News) - "Major domestic bio companies have announced the preclinical results of their anticancer drug candidates one after another at the 'American Association for Cancer Research (AACR) 2025'....In preclinical experiments, anticancer activity was demonstrated in various resistance models (BRAF V600E, CCDC6-RET fusion, KRAS Y95D/N·H95Q/B/D·R68S mutations, etc.), and a tumor growth inhibition rate (TGI) of 76% was confirmed in a KRAS mutant non-small cell lung cancer animal model."

Preclinical • Non Small Cell Lung Cancer

PHI-501 as a potent pan-RAF/DDRs inhibitor suppresses lung cancer cell proliferation and overcomes KRAS G12C inhibitor resistance (AACR 2025) - "The growth inhibitory activity of PHI-501 in KRASG12V, KRASG12S, KRASQ61H and NRASQ61K lung cancer cells was superior to that of G12Ci (sotorasib and adagrasib) and BRAF inhibitors (encorafenib and avutometinib). The treatment of PHI-501 alone showed robust growth inhibition in lung cancer cells harboring KRAS wild-type or KRAS and NRAS mutation. Our results suggest that PHI-501 as the pan-RAF/DDRs dual inhibitor is beneficial for the treatment of lung cancer and even helps overcome the resistance of previous G12Ci treatments."

Lung Cancer • Oncology • Solid Tumor • DDR1 • EGFR • KRAS • NRAS

Paros I-Bio announces preclinical results of lung cancer new drug 'PHI-501' at AACR [Google translation] (HIT News) - "Paros I-Bio...announced on the 26th that it will present the preclinical results of 'PHI-501', a candidate for the treatment of intractable lung cancer, at the American Association for Cancer Research (AACR 2025) to be held in Chicago, USA in April....In this announcement, the company explained that PHI-501 showed superior anticancer activity compared to existing BRAF inhibitors in KRAS mutant lung cancer cells. In addition, the company emphasized that it confirmed excellent cancer cell inhibition efficacy in KRAS G12V, G12S, and Q61H mutant lung cancer models that did not respond to the existing FDA-approved treatment, KRAS G12C inhibitor 'sotorasib'."

Preclinical • Lung Cancer

Macrogen, Pharos iBio to co-develop precision companion diagnostics for cancer therapy (Korea Biomedical Review) - "Macrogen said it has signed a memorandum of understanding (MoU) with Pharos iBio, an AI-driven new drug development company, to collaborate on the development of companion diagnostics (CDx) aimed at advancing precision medicine....Under the agreement, Macrogen will provide its circulating tumor nucleic acid (ctNA) analysis technology to support the phase 1 clinical trials of Pharos iBio’s investigational anti-cancer drug, PHI-501, targeting refractory solid tumors. The companies aim to strengthen cooperation in the field of CDx-based precision drug development."

Licensing / partnership • Oncology • Solid Tumor

Parosi Bio, PHI-501 Phase 1 IND Application [Google translation] (HIT News) - "Paros I-Bio...announced on the 5th that it has applied for an IND (clinical trial plan approval) for a phase 1 clinical trial for PHI-501, a treatment for intractable solid cancer, to the Ministry of Food and Drug Safety....'PHI-501's entry into phase 1 clinical trials will be an important opportunity for the birth of an innovative new drug in the solid cancer treatment market where treatment options are limited and unmet medical needs are high'."

New P1 trial • Oncology • Solid Tumor

Paros I-Bio, Full-scale Clinical Trial for Intractable Solid Tumor Treatment [Google translation] (BioTimes) - "Paros I-Bio...announced on the 14th that it plans to apply for an IND (clinical trial plan approval) for a phase 1 clinical trial for its innovative new drug candidate 'PHI-501' to the Ministry of Food and Drug Safety at the end of this month or early next month. This IND filing is an important milestone toward the first-in-human clinical trial of PHI-501, targeting solid tumor therapeutics markets, including malignant melanoma and refractory colorectal cancer....The Phase 1 IND application is scheduled to be submitted in late February or early March, and the possibility of PHI-501 entering the global market will be examined through subsequent clinical trials. In the future, Paros I-Bio plans to expand international collaborations and partnerships to successfully establish PHI-501 in the global anticancer drug market."

New P1 trial • Colorectal Cancer • Melanoma

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

“The global market is focused on the development of AI new drugs… “We will strengthen global partnerships” Pharos iBio announces Bio USA corporate IR session [Google translation] (Pharos iBio Press Release) - "Paros iBio...announced on the 3rd that it will participate in the IR session of the '2024 Bio International Convention...Paros iBio will showcase its technology in developing treatments for rare and incurable diseases using the AI ​​new drug development platform Chemiverse, as well as major rare and incurable disease treatment pipelines PHI-101 and PHI-501...PHI-101-OC is currently undergoing phase 1 clinical trials in Korea...Paros iBio plans to complete the phase 1 clinical trial of PHI-101 this year with the goal of entering the phase 2 clinical trial of PHI-101, an acute myeloid leukemia treatment, in the United States, Australia, and Korea in 2025. Once it enters phase 2, we plan to review an early commercialization strategy by applying for conditional product approval as an orphan drug depending on the results. PHI-501, a treatment for solid tumors, will complete preclinical trials around the third quarter of this year and submit an clinical trial plan (IND)."

New P2 trial • Preclinical • Trial completion date • Trial status • Acute Myelogenous Leukemia • Gynecologic Cancers • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Solid Tumor

PHI-501 is a novel potent next-generation pan-RAF/DDRs inhibitor, and overcomes resistance to RAF or MEK inhibitor in melanoma via dual inhibition of RAF and DDR1/2 signaling (AACR 2024) - "In this study, we evaluated the ability of PHI-501 to overcome drug-resistance to RAF or MEK inhibitors in melanoma harboring NRAS or BRAF mutations. Three drug-resistant cell lines were established by long-term treatment of belvarafenib in SK-MEL-2 (SK-MEL2BR) and each of dabrafenib and trametinib in SK-MEL-3 (SK-MEL3DR and SK-MEL3TR, respectively). Novel pan-RAF/DDR dual inhibitor PHI-501 has greater anti-tumor activity in RAF or MEK inhibitor-resistant melanoma, which is through downregulation of MAPK signaling and EMT-related genesets and promoting apoptosis. These data support that the clinical development of PHI-501 for melanoma refractory to MAPK inhibitors."

Melanoma • Oncology • Solid Tumor • BRAF • DDR1 • IL6 • KRAS • NRAS • TNFA

Pharos iBio announces efficacy of combination therapy with targeted anticancer drug PHI-101 at AACR [Google translation] (Medifonews) - "According to the results announced by Pharos iBio, PHI-101 showed differential efficacy in both combination therapy with Venetoclax and triple combination therapy with Venetoclax and Azacitidine...PHI-101 showed a tumor growth inhibition rate (TGI) of 95% when administered in combination with venetoclax in a xenograft animal efficacy evaluation model...when PHI-501 was administered alone to animals xenografted with a BRAF (V600E) mutant melanoma cancer cell line that induced dabrafenib resistance, it showed an effect of inhibiting tumor growth by 72.1%."

Preclinical • Acute Myelogenous Leukemia • Leukemia • Melanoma • Oncology • Skin Cancer

Pharos iBio teams up with Yonsei Cancer Center for translational research of 'solid cancer therapy’ (Korea Biomedical Review) - "Pharos iBio will collaborate with the team of Professor Shin Sang-joon of the Department of Medical Oncology at Yonsei Cancer Center to conduct the translational study of PHI-501 under development for treating solid tumors....Pharos iBio and Professor Shin's research team will test PHI-501 in solid tumors, including malignant melanoma and refractory colorectal cancer, to validate the modulation of immune signaling. They will also evaluate the anti-cancer efficacy of PHI-501 in combination with immunotherapy in animal models, the company said on Monday....Pharos iBio expects to complete preclinical studies of PHI-501 in the third quarter of this year....After completing preclinical studies, the company plans to file a phase 1 IND in the latter half of this year."

IND • Licensing / partnership • Preclinical • Colorectal Cancer • Melanoma

PHI-501 as a potent pan-RAF/DDRs inhibitor suppresses colorectal cancer cell proliferation and overcomes BRAF inhibitor resistance (ESMO-TAT 2024) - "BRAF inhibitor-resistant COLO205ER cells were established by long-term treatment of cells with encorafenib. Kim and G-J. Sung have contributed equally to the study."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • KRAS

Paros iBio participates in the Australian bio conference ‘OS Biotech’ [Google translation] (HIT News) - "Paros iBio...will hold a Korea-Australia pharmaceutical bio exchange at 'AusBiotech 2023', a bio industry conference held in Brisbane, Australia from the 1st to 3rd of next month (local time). They announced on the 10th that they plan to attend as a company....Paros iBio plans to seek opportunities to build global partnerships for the successful commercialization of its rare disease pipeline at OS Biotech. Representative examples include PHI-101 (acute myeloid leukemia), which is undergoing global phase 1b clinical trials, and PHI-501 (solid cancer), which is in the preclinical stage in Korea. Paros iBio was also selected as a presenting company for the 'Korean Biotech Leaping towards Innovative Technology' session during this event."

Licensing / partnership • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Pharos iBio, upper limit for full-scale clinical preparation for malignant melanoma [Google translation] (BioTimes) - "...Pharos iBio announced on the 31st that it had signed a CDMO contract with Daewoong Bio for the development of raw materials for clinical trials of the solid cancer treatment 'PHI-501', which seems to have affected the stock price...'PHI-501', a solid cancer treatment under development by the company, is a target anticancer drug under development as a dual inhibitor of pan-RAF and DDR1. Pharos iBio's own AI platform 'Chemiverse™' was used to expand indications. The target indications are malignant melanoma, refractory colorectal cancer, and triple negative breast cancer, and are currently in the preclinical stage."

Licensing / partnership • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor • Triple Negative Breast Cancer

PHI-501, a novel and potent pan-RAF inhibitor in metastatic melanoma (AACR 2023) - "Regardless of the therapeutic effect of class I BRAF inhibitors such as vemurafenib, dabrafenib and encorafenib, melanoma patients with BRAF non-V600/RAS mutations remain limited response...The effect of PHI-501 on anchorage independent growth and cell proliferation compared to vemurafenib or belvarafenib (pan-RAF inhibitor) were tested in A375 (BRAFV600E), C8161 (BRAFG464E) and SK-MEL-2 (NRASQ61R) melanoma cell lines by soft agar assay, western blot and FACS analysis... PHI-501, a novel pan-RAF inhibitor, has potent oral anti-tumor activity. Melanoma cells harboring BRAF non-V600/NRAS or BRAF common V600E mutations exhibited significantly reduced proliferation, increased apoptosis and inhibited migration upon treatment with PHI-501. The results of this study suggest that PHI-501 has a potential to overcome the limited response in the treatment of melanoma, and warrant evaluation of PHI-501 as a single agent to treat both BRAF-and NRAS-mutated metastatic melanoma."

Metastases • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Melanoma • Oncology • Oral Cancer • Solid Tumor • ANXA5 • NRAS

PHI-501, a novel pan-RAF/DDRs dual kinase inhibitor, overcomes BRAF or MEK inhibitor resistance in melanoma (AACR 2023) - "Long-term therapy with dabrafenib (BRAF inhibitor), cobimetinib or trametinib (MEK inhibitor) led to the establishment of the drug-resistant SK-MEL-3 (BRAF V600E) and SK-MEL-30 (NRAS Q61K) melanoma cell line. PHI-501 demonstrated potent growth inhibition (GI50 <1 µM) in seven melanoma cell lines harboring BRAF V600E or NRAS mutations. Melanoma cells resistant to RAF or MEK-targeted treatments or harboring NRAS mutation exhibited strong antiproliferative activity when treated with PHI-501, a highly potent pan-RAF/DDR dual inhibitor. The results of this study suggest that PHI-501, as a single agent, has the potential to overcome the restricted response in the treatment of melanoma."

Melanoma • Oncology • Solid Tumor • ANXA5 • BIRC5 • CCND1 • DDR1 • NRAS

The world's top three cancer societies 'AACR' opens next month… K-Bio gun dispatch (Newsis) - "Pharos iBio plans to disclose preclinical data of 'PHI-501', which is being developed as a melanoma treatment. PHI-501 is being studied as a treatment material for skin malignant melanoma, refractory colorectal cancer, and triple-negative breast cancer....Lunit will present 5 research abstracts applying AI biomarkers (biomarkers) to various types of cancer. It plans to introduce research using the AI ​​biomarker platform 'Lunit Scope' in more diverse types of cancer." "

Preclinical • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Skin Cancer • Triple Negative Breast Cancer

PHI-501, a potent and novel inhibitor of NRAS mutated acute myeloid leukemia (AACR 2022) - "The preclinical evaluation of PHI-501, a novel N-RAS inhibitor, showed clear evidence of anticancer activity for AML and improved efficacy in both in vitro and in vivo models. Consequently, PHI-501 is a new potent multi-kinase inhibitor with characteristics that warrant entry into human trials for the treatment of AML in patients expressing the N-RAS activating mutation."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pancreatic Cancer • CASP3 • HRAS • KRAS • NRAS

Pharos iBio’s AML drug candidate wins FDA’s orphan drug status (Korea Biomedical Review) - "Pharos iBio said its PHI-501, a next-generation anticancer drug for acute myeloid leukemia (AML), has won orphan drug designation from the U.S. Food and Drug Administration (FDA). It was the U.S. regulator’s second orphan drug designation of the Korean company’s product. FDA granted similar status to Pharos iBio’s main pipeline, PHI-101, a next-generation FMS-like tyrosine kinase 3 (FLT3) inhibitor for AML, in 2019."

Orphan drug • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology