Genomic Medicine Initiative (GEMINI) targets unmet needs in rare disease treatment

This is a transcript of the St. Jude GEMINI roundtable conversation. Each speaker is identified by full name and title upon first speaking, and only by surname for any later contributions to the conversation.

J. Paul Taylor, MD, PhD, Executive Vice President, Scientific Director, Chair of the Department of Cell & Molecular Biology and Director of the St. Jude Pediatric Translational Neuroscience Initiative (PTNI):

It became evident, going back a decade, that opportunities were arising to address one large problem, and that is catastrophic neurological diseases of children. Our answer to that has been the Pediatric Translational Neuroscience Initiative. It’s a natural outgrowth of the St. Jude mission, which is unchanged for 63 years.

There are a small number of diseases that have a large number of children that are affected, but that only accounts for a small portion of the total number of children that have neurological diseases, and the conventional model of therapeutic development doesn’t work because we don’t have a ready partner who is willing to take the baton and run with it.

In recognizing this, we needed to put together a brand-new type of mechanism. That’s called the Genomic Medicine Initiative (GEMINI) program. 

For this initiative to work, it really needs three components: a pre-clinical component, a clinical component, and then to leverage the St. Jude infrastructure and to partner appropriately with stakeholders outside of St. Jude to make this as effective as possible.

Richard Finkel, MD, Director of the Center for Experimental Neurotherapeutics (CENT) and member of the Department of Pediatric Medicine:

We’ve taken several different strategies to try to make sure that we are, first and foremost, patient-focused. So, we’ve tried to identify diseases with high unmet need, trying to identify children that we see in the clinic. Because, typically, when we see one patient, there may be others that would benefit from this kind of treatment. And then we had to think about, well, what are the different technologies out there that we can leverage?

There are several, but the one we have adopted initially is an antisense oligonucleotide (ASO) therapy.

Peter McKinnon, PhD, Director of the Center for Pediatric Neurological Disease Research (CPNDR) and Vice-Chair of the St. Jude Department of Cell & Molecular Biology:

The disease indications that we’re working on, we identify the gene mutation, and then we have AI-supported software that can determine the amenability of these particular mutations to an ASO approach. 

Kristin Stephenson, MHA, JD, Director of the Office of Strategy & Alliances (OSA):

Every step along that pathway, which we are building internally, we have built a component of that with input from one or more external stakeholders. For example, it’s working very closely with both industry and nonprofit organizations on thinking about what’s the right strategy for doing ASO design internally, leveraging technology capabilities from industry partners and from nonprofit drug development partners.

Finkel:

We’re trying to make sure that this is really scientifically sound, that we do it in a rigorous way, and, ideally, to develop a sustainable model, something that can build upon itself over time.

Stephenson:

So, the focus initially was on neurological diseases with an ASO strategy, but what we’re really building is an integrated approach systemically so that we can identify mutations of interest, develop whatever the intervention may be, whether it’s a drug or some other kind of therapy, and then take it all the way through manufacturing, testing and clinical trial right here at St. Jude.

McKinnon:

Because it’s in-house, we’re not waiting for somebody else to do it for us, because we have the control of design, safety and synthesis. We’re minimizing the time between mutation identification and therapeutic delivery in a way that I think is fairly unique.

Taylor:

The GEMINI program now has a series of a small number of flagship projects that are being used to build out the pipeline. Specifically, we have four projects that are in the works at various stages. 

What we would like to see is to scale this up and increase the number of projects. We also want to expand, laterally, the clinical indications. We want to continue to move beyond neurological indications to include other prosecutable targets that are genetic in origin.

The long-term goal is to sort out a way in which we can capitalize on this type of approach for children that are in far-flung places that don’t have access to therapies today.

It’s part of the St. Jude culture, and it’s part of the St. Jude history.