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About SillaJen Biotherapeutics Targeting, Attacking, and Eradicating Cancers®

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About SillaJen Biotherapeutics

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SillaJen Biotherapeutics

SillaJen Biotherapeutics is located in San Francisco, one of the largest and most innovative biotech clusters in the world. SillaJen Biotherapeutics focuses on the research, development and manufacturing of oncolytic viruses to treat cancer; we are responsible for Clinical Operations, Regulatory Affairs, Research and Development, Manufacturing, Alliance Management and Accounting for clinical trials.

BAL0891 Dual TTK/PLK inhibitor

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source. BASILEA Non-Confidential Presentation 2022

BAL0891: Advancing Cancer Research with Dual Inhibition of TTK and PLK1

Mechanism of Action

The mitotic checkpoint ensures accurate eukaryotic cell division by monitoring the proper segregation of chromosomes. BAL0891 targets two key phosphorylating enzymes involved in this process:

  • Threonine Tyrosine Kinase (TTK) : Inhibition by BAL0891 induces mitotic override, where cancer cells proceed to divide prematurely, leading to errors in chromosome segregation.
  • Polo-like Kinase 1 (PLK1) : Inhibition results in mitotic block, arresting cells at the G2/M phase and preventing progression to anaphase.

Both mechanisms disrupt the cancer cell cycle, triggering apoptosis and effectively halting tumor growth. BAL0891 is the only molecule currently in development that simultaneously inhibits both TTK and PLK1 positioning it as a potential first-in-class therapeutic.

Ongoing Clinical Development

BAL0891 is undergoing a Phase 1 clinical trial, focusing on dose escalation in patients with relapsed/refractory solid tumors. Key details include:

  • Clinical Trial Identifier : NCT05768932
  • Current Status : Dose escalation stage, evaluating safety, tolerability, and pharmacokinetics.

Study Design

The study design, highlighting the trial's objectives, endpoints, and dosing schedules, can be accessed via the following link : BAL0891 Study Design.

Scientific Insights

Recent publication in Frontiers in Oncology (Aug 9 2024) highlights the scientific rationale and potential f for dual inhibition therapy.
https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1447807/full

SJ-600 Series Wyeth Strain Backbone Pipeline

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The SJ-600 series is SillaJen's next-generation pipeline that dramatically improves the intravenous administration efficiency of anticancer viruses. Intravenous administration is an easy way to deliver drugs quickly to the whole body, but it has the disadvantage of reducing anticancer effects as it is mostly removed by antiviral substances in the blood while moving to the tumor. In response, SillaJen designed proteins that inhibit antiviral substances in the blood to directly display them on the viral envelope to compensate for these shortcomings and produce high anticancer effects.

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In particular, the SJ-600 series is attracting attention as an unrivaled platform that can directly avoid innate immunity, which is differentiated from existing technologies. It has the advantage of aviding the human body's defense mechanism, which maintains stable anticancer activity during intravenous injections, as well as minimizing side effects of anticancer drugs by reducing the dosage of the viruses.

SJ650: An Oncolytic Vaccinia Virus Designed for Systemic Delivery

Challenges to Systemic Delivery

  • Intravenous (IV) delivery remains the primary challenge in advancing oncolytic virus therapies
  • Systemically administered oncolytic viruses are rapidly eliminated from the circulation by the complement system.
  • Repeated administration of oncolytic viruses triggers antibody production, leading to viral neutralization and diminished efficacy of subsequent doses
  • Therefore, the therapeutic efficacy of oncolytic viruses is primarily confined to the window before neutralizing antibodies are produced

Nat Rev Cancer 5: 965, 2005

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SJ-650 is Engineered For Systemic Delivery

Intravenous administration is the best way to deliver oncolytic viruses to the whole body, but the complement system may inactivate much of the virus before it reaches the tumor; furthermore, repeated dosing is less effective after the body produces antibodies that recognize and neutralize the virus without requiring complement. SillaJen’s next generation virus SJ-650 expresses a protein on the virus envelope that inhibits complement activation thereby improving its ability to reach tumors. The engineered changes to SJ-650 dramatically improve the efficiency of intravenous administration, enable repeat dosing, and may allow maximum therapeutic efficacy at lower doses.


Dr. Russell discusses systemic administration of Oncolytic Viruses