Ileadbms

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Creating Better Therapies for a Better Tomorrow iLeadBMS

At iLeadBMS, we are building a pipeline of innovative drugs to address the huge unmet needs in various therapeutic areas including oncology, fibrosis, neurodegeneration, and autoimmune diseases. Our core competencies are as follows:

R&D Strategy
Multiple, simultaneous targeting of key drivers of diseases to create highly de-risked molecules with ideal properties for clinical use
Proven Track Record
Team of discovery experts with great depth of knowledge and experience in molecular design and medicinal chemistry [10+ discovery programs where 3 of these has advanced to clinical stage: (1) FXR agonist for MASH – Out-licensed to Yunovia, currently in phase 1, (2) A1A2a agonist for Parkinson’s disease – Out-licensed to Yunovia, currently in phase 1, (3) Venadaparib for gastric and breast cancer – Our-licensed to Idience, currently in phase 2]
Global Collaboration for Development
Active collaborations with various partners around the globe to maximize the development success rates

Pipeline

Updated: May 2024

iLeadBMS is innovative research-intensive pharma company with a robust globally competitive R&D pipeline

Fibrotic & Autoimmune Disease

CXCR 7 Agonist
First-in-class, orally available, small molecule, chemokine receptor type 7 (CXCR7) agonist for treatment of various fibrotic and autoimmune diseases.

Chemokines play crucial roles in many physiological and pathological processes. Chemokine receptor 7 (CXCR7) is a receptor that binds to CXCL12, a known pro-inflammatory factor under pathological conditions such as inflammation, hypoxia, tumor, autoimmune disease and it activates angiogenesis and regeneration process as a part of the repair mechanism.

In acute tissue (e.g. lung, liver) injuries, CXCR7 is upregulated to stimulate endothelial proliferation in lung and also, promotes hepatocyte proliferation in liver as a part of repair process. However, with chronic injuries, CXCR7 is downregulated, leading to a decreased repair function of injured tissues and also, promotes binding of CXCL12 with CXCR4 in fibroblasts, which contributes to the fibrotic process.

iLeadBMS is developing a first-in-class CXCR7 agonist that reduces CXCL12 levels and currently, there are no other CXCR7 agonists in development (in any stage), on a global basis.

Unlike CXCR4 antagonists, which are being researched and/or developed for various inflammatory & fibrotic diseases, CXCR7 agonist can activate the β-arrestin signal which in turn activates tissue regeneration & cell proliferation function (evidence shown in cardiac research) for a potentially disease modifying properties.

The lead candidate has favorable oral pharmacokinetic profile including a long half-life and therefore, once-a-day formulation will be possible.
Our CXCR7 agonist demonstrated superior efficacy over reference drugs In the bleomycin mouse IPF (both prevention and therapeutic) & CCl4-induced liver fibrosis mouse models. Also, additional in vivo efficacy models including bleomycin induced skin fibrosis, kidney fibrosis, BDL liver fibrosis, PAH & ischemia reperfusion (I/R) models are in progress.
Novel MoA allows potential expansion to a broad types of indications ranging from fibrotic diseases to autoimmune, and CNS disorders.
This candidate is ready for IND-enabling GLP toxicity studies.

Oncology

(1) Cyclin-K Degrader for Solid Tumors
Potentially first-in-class, orally available, small molecule Cyclin-K Degrader with strong anti-cancer activities for difficult cancers including those without identifiable drivers.

We are developing a potent Cyclin-K Degrader (through CDK 12 binding) which can be used for cancers without known drivers including HER2-negative gastric cancer, HER2-negative TNBC, colorectal cancer, etc.

The lead candidate acts as a Cyclin-K molecular glue, a highly promising type of targeted protein degradation (TPD) and has a potential to be developed as an intermittent oral monotherapy.

The lead candidate has exhibited potent growth inhibition in various cancer cells (induced significant tumor regression in the HER2-negative metastatic gastric cancer and triple-negative breast cancer in vivo models.

This candidate is ready for IND-enabling GLP toxicity studies.

(2) SOS1 Inhibitor for RAS Driven Cancers

Potentially best-in-class, orally available, small molecule SOS1 inhibitor for any RAS driven cancers which has shown strong activity against various KRAS mutants and wild types including KRAS G12C, G12D, G12V and KRAS G13C.

SOS1 is a pivotal switch that converts RAS from its inactive (off) state to its active (on) state, representing a novel therapeutic target in RAS-driven cancers Inhibition of the GTP exchange factor (GEF) SOS1-KRAS interaction impairs oncogenic signaling independently of the specific KRAS mutations; pan-KRAS inhibitor.

IL2102 exhibited excellent PK profiles both in rodents and non-rodents and low plasma protein binding, offering high unbound drug concentration.

IL2102 has demonstrated significant in vivo activity as a single agent in a lung tumor xenograft model (G12C sensitive). Additionally, combination of IL2102 with a KRAS G12C inhibitor led to a significant synergistic anti-tumor activity, resulting in complete tumor regression in all animals of the combination groups (24 out of 30 animals) with favorable safety profile (no deaths observed in all 30 animals), in a dose dependent manner.

IL2102 can be developed as a combination agent with any type of KRAS inhibitors (specific mutation or pan-type) due to its broad activity profile in most type of KRAS mutants and wild types.

This candidate is ready for IND-enabling GLP toxicity studies.

Neurodegenerative Disease

CXCR 7 Agonist
Potentially first-in-class, orally available, small molecule CXCR7 agonist with a high permeability for the blood–brain barrier (BBB) for various neurodegenerative diseases such as ALS, Multiple sclerosis (MS), Parkinson’s Disease (PD), etc.

Brain injury triggers the accumulation of microglia via the CXCL12/CXCR4 pathway, while concurrently inducing the attenuation of the CXCR7/PI3K/Akt signaling cascade in astrocytes.

Activation of CXCR7 holds promise in treating neurodegenerative disorders such as ALS, MS, and Parkinson's disease through dual mechanisms: (i) Induction of A2 astrocyte phenotype (anti-inflammatory) and (ii) suppression of microglial activity mediated by CXCR4/CXCL12 via CXCL12 scavenging or degradation.

Thus far, the lead candidate has demonstrated good efficacy in the Mog-EAE (encephalomyelitis) mice model for the MS and additional neurodegeneration animal models are either ongoing or being planned.

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