Avista Therapeutics and Forge Biologics are kicking off a new strategic partnership centered around the advancement, development, and manufacturing of AVST-101, Avista’s lead gene therapy candidate for X-linked retinoschisis (XLRS).
First, a look at these players.
Starting with Avista, the Pittsburgh, Pennsylvania-based biotechnology company launched in 2021 as a spinout of the University of Pittsburgh Medical Center (UPMC).
Its focus: Developing adeno-associated virus (AAV)-based gene therapies for rare ophthalmic conditions (specifically retinal diseases) with cell-type specific delivery, reduced dosages, and a minimally invasive intravitreal (IVT) approach.
The basis for its science: The in vivo scAAVenger, a single-cell AAV engineering platform designed to accelerate and advance the development of AAV vectors designed exclusively for retinal gene therapies.
- How it does this: The computational platform utilizes single-cell ribonucleic acid (RNA) sequencing to—rapidly and quantitatively—identify various AAV vectors and determine their suitability for delivering gene therapy to specific areas of the retina.
And its pipeline?
Its proprietary pipeline consists of three candidates (with just one indication [XLRS] identified so far), while its candidate pipeline in partnership with Roche includes two capsids (with two unidentified indications).
- About these candidates: Based on AAV variants, these gene therapies are intended to target gene delivery to individual retinal cell types.
- Chief among these: AVST-101.
Give me the rundown on this lead asset.
The next-generation ocular gene therapy is under clinical development for treating XLRS via a combination of several components (per Avista):
- Advanced capsid engineering
- IVT delivery
- Low-dose efficacy
- Broad retinal coverage
Its potential: To serve as a safer and more accessible treatment option for patients diagnosed with inherited retinal diseases (IRDs) such as XLRS.
- And before you ask: No, there aren’t yet any reports of a clinical investigation conducted on AVST-101—however, an investigational new drug (IND) filing is expected by the end of the year.
Noted. Now to Forge.
Founded in 2020, headquartered in Columbus, Ohio, and a member of Ajinomoto Bio-Pharma Services, Forge is a gene therapy contract development and manufacturing organization (CDMO).
Its specialty: AAV and plasmid manufacturing (including developing a pipeline of AAV-based gene therapies for rare genetic diseases)
Its end-to-end manufacturing services: Extend to gene therapy development, finished dosage formulations, and both viral vector and plasmid supplies—all in-house.
- How: Through Hearth, the company’s 200,000 square foot manufacturing facility featuring 20 custom-designed Current Good Manufacturing Practices (cGMP) suites
Any technologies to know about?
In the context of this new partnership: the proprietary Foundation for Unleashing Excellence in Life-changing Therapies (FUEL) platform and two specific advanced technologies:
- HEK293 suspension Ignition Cells
- pEMBR 2.0 adenovirus (AV) helper plasmid
Explain these, please.
Forge’s FUEL platform is an AAV manufacturing platform offering advanced technologies, processes, and flexible, product-specific optimizations—all with the intent to increase productivity (reportedly by 6-22x) and recovery of AAVs while maintaining product quality.
- Notably: It’s also designed to support all serotypes (including novel capsids).
As for those advanced technologies:
- HEK293 suspension Ignition Cells
- What they are: Consists of the suspension-adapted HEK293 cell line engineered for efficient and scalable AAV vector production
- Their purpose: Enables industrial-scale production of AAVs and can achieve +90% full capsids post-enrichment, resulting in more usable AAVs per batch
- pEMBR 2.0 adenovirus (AV) helper plasmid
- What it is: One of the smallest commercially-available AV helper plasmids
- Its purpose: Increases manufacturing efficiency and offers an improved safety profile by reducing unnecessary adenoviral components for AAV production
That’s pretty advanced … so how does this all factor into the Avista partnership?
Let’s remember: The focus of this collaboration is to advance Avista’s AVST-101 gene therapy for XLRS.
To do this: Forge will provide Avista with the following services:
- Process development
- cGMP manufacturing
- Toxicology
- Analytical development
Plus: Avista will also utilize Forge’s FUEL technologies (the platform and those two techs we just discussed) to support AVST-101’s advancement.
And where will this be done?
All activities included in this partnership will be conducted at Forge’s aforementioned Columbus-based gene therapy and manufacturing facility.
As Avista’s CEO, Robert Lin, PhD, commented, “Forge’s AAV-specific manufacturing expertise and platform technologies give us confidence in a smooth path forward in the development of AVST-101.”