By Dr. Kelly Shepard

We love sharing exciting news about recent discoveries or announcing the launch of a new CIRM-funded clinical trial because they offer tangible signs of progress, but the background work to build a gene and cell therapy “pipeline” is no less important.

Behind the scenes

Important signs of progress also happen behind the scenes—efforts we see at CIRM that aren’t obvious to the untrained eye. These projects may not make headlines or lead to publications, but they spark new ideas and steer the field away from unproductive paths. Many fill knowledge gaps, break technical barriers, and work closely with regulators to define safe routes to the clinic.

These efforts often remain hidden because they sit in the middle of the long, difficult journey from bench to bedside. For CIRM’s pioneering programs, this journey is unique and full of false starts. CIRM tracks each project’s momentum and supports those with strong potential. As a result, we have watched many evolve as they move toward the clinic. We want to share examples of this progress, but first, a bit of background for readers new to medicine development.

Our pipeline

Drug development is often described as a pipeline. It begins with a discovery in the lab and ends with government approval after a therapy proves safe and effective. Between discovery and approval is “Translation,” where researchers shift research‑level methods to clinically compatible ones that use certified materials for human use.

Researchers must also develop ways to manufacture the product at scale and adapt testing methods from animals to humans. A key milestone in Translation is the pre‑IND meeting, where investigators present data and plans to the FDA for early feedback before pivotal testing begins.

IND‑enabling studies support the formal IND application and the start of clinical trials. Phase 1 tests safety in a small group. Phase 2 evaluates early benefit in more patients. Phase 3 tests large numbers to confirm safety and effectiveness before an approval request. A diagram below shows each stage.

A visual illustration of the pipeline

This pipeline is long and complex, with many twists and setbacks. Far more projects enter than exit. Still, as these examples of “works in progress” show, momentum is building.

Caption for Graphic: This graphic shows how many CIRM‑funded projects have advanced through multiple funding rounds. For example, the top arrow shows about 19 translational projects that previously received Discovery‑stage support. Many came from pre‑2016 programs such as Early Translation, Basic Biology, and New Faculty Awards. Another arrow shows about 15 IND‑enabling projects that have moved into Phase 1 or Phase 2 trials. Most began in pre‑2016 programs like the Disease Team Awards, while others advanced from newer “2.0” programs launched in 2016.

The number of CIRM projects that have progressed with agency support is impressive, though undercounted. Some projects advanced outside CIRM’s purview, making tracking harder.

We also monitor projects that spun off or were licensed to commercial groups, another exciting form of progress. Those may be part of a future blog. For now, here are examples of the projects shown in the graphic.

Project: stem cell therapy to enhance bone healing in the elderly

– Currently funded stage: IND enabling development, CLIN1-11256 (Dr. Zhu, Ankasa Regenerative Therapeutics)

– Preceded by preIND-enabling studies, TRAN1-09270 (Dr. Zhu, Ankasa Regenerative Therapeutics)

– Preceded by discovery stage research grant TR1-01249 (Dr. Longaker and Dr. Helm, Stanford)

Project: embryonic stem cell-derived neural cell therapy for Huntington’s Disease

– Currently funded stage: IND enabling development, CLIN1-10953 (Dr. Thompson, UC Irvine)

– Preceded by preIND-enabling studies, PC1-08117 (Dr. Thompson, UC Irvine)

– Preceded by discovery stage research grant (TR2-01841) (Dr. Thompson, UC Irvine)

Project: gene-modified hematopoietic stem cells for Artemis Deficient severe combined immunodeficiency (SCID)

– Currently funded stage: Phase 1 clinical trial CLIN2-10830 (Dr. Cowan, UC San Francisco)

– Preceded by IND enabling development, CLIN1-08363 (Dr. Puck, UC San Francisco)

– Preceded by discovery stage research grant, TR3-05535  (Dr. Cowan, UC San Francisco)

Project: retinal progenitor cell therapy for retinitis pigmentosa

– Currently funded stage: Phase 2 and 2b clinical trials, CLIN2-11472, CLIN2-09698 (Dr. Klassen, JCyte, Inc.)

– Preceded by IND enabling development, DR2A-05739 (Dr. Klassen, UC Irvine)

– Preceded by discovery-stage research grant, TR2-01794 (Dr. Klassen, UC Irvine)