Research Engine

The MindImmune research enterprise lifts off

Drug discovery research firm affiliated with the Ryan Institute for Neuroscience at URI acquires two preclinical research programs from Lundbeck, with the potential to develop new therapeutics capturing a significant share of markets worth more than $39 billion

Photo by Richard Asinof

The MindImmune team: Stevin Zorn, CEO, left; Brian Campbell, VP for Pharmacology, center, and Frank Menniti, CSO, right. Missing from photo: Robert Nelson, VP for Exploratory Biology.

Image courtesy of MindImmune

A slide prepared by MindImmune showing the broad therapeutic potential of its drug development research platform.

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By Richard Asinof
Posted 5/22/18
The acquisition of licenses for two preclinical research platforms by MindImmune Therapeutics positions the drug development research firm to launch a new class of therapeutic targeting the brain’s immune system, catapulting the company’s research enterprise and positioning URI to be a leader in developing new therapeutics to treat brain diseases.
How will MindImmune’s new research partnerships with Lundbeck and Pfizer promote new kinds of collaborative research partnerships in Rhode Island with other pharma companies? Can the model of embedding a drug discovery research firm at a university be replicated at other colleges and universities in Rhode Island? How can Brown University’s neuroscience research program find new common ground with the Ryan Institute for Neuroscience? Is there a possible integration of the work being done by Christopher Moore at Brown around bioluminescent optogenetics to help illuminate the interactions of the therapeutic interventions with the brain immune cells? How will the pending proposals to create an innovation campus in Rhode Island connect with MindImmune’s efforts at URI?
As the Supremes once sang: You can’t hurry love. In that same vein, scientific research takes time, and as promising as the developments in the neuroscience research enterprise appear to be in Rhode Island, it would be a mistake to project the wrong kinds of expectation upon it in terms of job creation and immediate economic development metrics. More than political expectations, the work depends on scientific results.

KINGSTON – MindImmune Therapeutics, Inc., a for profit drug discovery research firm at the University of Rhode Island affiliated with the George and Anne Ryan Institute for Neuroscience, announced on Tuesday, May 22, that they had acquired the licenses for two preclinical research programs from H. Lundbeck A/S, a Danish-based global pharmaceutical company.

Under the licensing agreement, MindImmune will be working on two neuroinflammation targets as part of their broader portfolio to develop novel drug therapeutics targeting the immune system in order to treat brain disease. As part of the agreement, Lundbeck received equity in MindImmune as well as milestone payments and royalties for successful therapeutics developed.

The first preclinical research program, P2X7 receptor antagonists, will focus on the development of non-opioid analgesics for treatment of neuropathic pain, with the potential to serve a large portion of the current unmet and underserved market.

Some 8 percent of adults in the U.S. suffer from neuropathic pain, with as many as 30 percent of those adults not adequately treated, according to MindImmune.

Unlike other approaches, MindImmune will seek to use P2X7 antagonists to block pain sensitization, not pain perception, preventing neural circuits from “ learning to hurt,” without the potential for abuse and addiction.

The leadership team of founding neuroscientists at MindImmune, including Stevin Zorn, CEO, Frank Menniti, CSO, Robert Nelson, VP for Exploratory Biology, and Brian Campbell, VP for Pharmcology, believe that the P2X7 antagonists have a best-in-class potential to capture a significant share of what is estimated to be a $24 billion market for treating neuropathic pain.

The MindImmune value proposition for developing its non-opioid analgesic using P2X7 antagonists is based upon four factors: the “all hands on deck” approach urged by Frances Collins, the former director of NIH, to develop new, non-addictive analgesics; the go/no go decision on the therapeutic efficacy may be able to be demonstrated in a short clinical trial, supported by robust biomarkers; the science underlying the rationale is supported by human genetics research that has shown gain or loss of function mutations in P2X7 have predicted neuropathic pain sensitivity; and the capability of the MindImmune therapeutic candidate to reach its target in the central neervous system.

The second preclinical research program acquired from Lundbeck, KMO inhibitors, will focus on development on a therapeutic target to block neuroinflammation caused by the mutant Huntington Disease protein.

Huntington’s Disease, a deadly orphan neurodegenerative disease, currently has very limited therapeutic options. Blocking formation of toxic KMO metabolites in the brain will halt the neuroinflammation that causes neuronal cell death. The MindImmune scientific team believes the therapeutic approach will reduce Huntington’s Disease symptoms and slow its progression, and with it, the potential to capture a significant share of the market for treatment of Huntington’s Disease, estimated to be worth more than $2.4 billion.

The value proposition offered by MindImmune for its therapeutic targets focused on KMO inhibitors includes: the collaborative relationships being developed with Huntington Disease foundations; the fact that KMO inhibitors have been vetted as an approach for therapeutics for Huntington Disease; and because the approach offers significant potential for value-added therapeutics in the nexus of the central nervous system and immune signaling systems.

Third leg of the research platform
Earlier this year, in January, MindImmune reached a deal with Pfizer on a research collaboration focused on potential outcomes for new therapeutics for Alzheimer’s disease. The approach seeks to block specialized immune cells being recruited into the brain that will, as Bob Nelson described it, “Nip Alzheimer’s disease in the blood.”

The drugs now under research will act in the blood, and do not need to cross the blood brain barrier, according to MindImmune, which said it was the first to link this particular specialized peripheral immune cells to Alzheimer’s disease pathology. The novel approach to reduce brain inflammation that is driving Alzheimer’s disease offers a potential breakthrough in the Alzheimer’s disease market estimated to be about $13 billion.

Altogether, MindImmune is seeking to raise a total of about $25 million from a variety of sources in the next two to three years to support its research platform.

The success to date of MindImmune reflects the fact that its founding scientific team has more than 100 years of success in researching and discovering neuroscience medicines. It also highlights the innovative relationship developed between URI and the for-profit drug development research firm.

A deeper dive
At the heart of the research platform of MindImmune is the innovative focus on the brain’s immune system and the role that it plays in central nervous system diseases, combining what has been learned about immunology, neuroscience, and human genetics in the last decade.

As Stevin Zorn explained it, during a recent conversation with ConvergenceRI at the MindImmune offices at the Ryan Institute for Neuroscience at the University of Rhode Island, including the research firm’s scientific team of Frank Menniti, Brian Campbell and Robert Nelson [on speakerphone]: “When you look at all of the trillions of cells in the brain, 10 percent of those cells are microglia, the resident immune cells that live in the brain and that participate very actively in maintaining [the biological stability] of the brain.”

For many years, Zorn continued, “Scientists looked at those microglia cells and said, they’re just structural cells, they are not doing anything. But, in fact, they are incredibly active.”

Thirty years ago, Nelson said, “When some of us started working in the pharmaceutical industry, that’s what we thought about glia, they were structural elements that held the nervous system together. They might suck up some neurotransmitters that got in the way, as a way of getting them out of the synapse.”

But, the notion of them [being a key part of] neural transmissions, in helping disease, that is knowledge that has been accrued during the last dozen years, according to Menniti.

“We had a wonderful teacher here, and that was cancer biology,” Zorn added. “Because cancer biology blazed the trail in understanding the role of the immune system and what it does in disease not previously thought to have an immune system component.”

New, better understanding of the brain’s immune system
When many of us started in the industry, Zorn continued, “The brain was considered immuno-privileged, that these cells didn’t get into the brain, because you had this wonderful blood brain barrier that kept everything out, including the immune cells.”

In fact, the immune cells were already there, and they had a very elegant way of communicating with cells in and outside of the nervous system, Zorn explained further. “And, they can go back and forth at will.”

And, Campbell said: “The immune cells play a critical role in shaping neural networks.”

Convergence of genetics, neuroscience
Many of the things being learned about the brain’s immune system linked up with developments in human genetics, according to the MindImmune team.

“There isn’t a central nervous system disease pathology that we’ve looked at that doesn’t have some kind of immune marker associated with it,” Zorn said.

That didn’t necessarily mean that MindImmune would launch a drug discovery research project based on that information, Zorn continued.

The evidence is very persuasive; the immune markers are associated with the pathology across a spectrum of brain disease, Zorn said. “There are immune cells surrounding hallmark features of the pathologies in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis, pain, depression, schizophrenia, the list goes on and on.”

The MindImmune team said that a set of patient biomarkers that have been identified that confirm chronic immune system activation and are associated with the pathology of a whole host of these disorders.

And, in recent years, there has been an explosion of human genetics data that showed that this immune regulation in networks of immune cells regulation of the central nervous system showed a clear cause or an increased risk of central nervous system disease, according to Zorn.

“If inflammation is a common drive of central nervous system diseases, then the corollary is that we want to stop it as a treatment for central nervous system diseases,” Zorn said. “It is now where the field is starting to go, and it is where we are taking it.”

The brain immune system and the body’s immune system are integrally linked, explained Menniti. The body does not make any differentiation. “Given that the immune system is an effector, all of a sudden, you realize that when it is out of whack, no wonder it has a role in all of these diseases,” he said.

Translated, the first defenders and protectors are in the brain, the brain immune cells called microglia. So, the vision of MindImmune and its drug development research is to focus on the neuroimmune system, focusing on the cells that are involved in the immune regulation of neurons. The two preclinical research programs acquired from Lundbeck are focused on these cells, the microglia.

The Lundbeck legacy
Three of the founding scientific team at MindImmune, Zorn, Nelson and Campbell, had all previously worked at Lundbeck, and had been involved in brain inflammation research.

“We started the industry’s first neuroinflammation research unit at Lundbeck,” explained Zorn. Unfortunately, just when we got cooking, they closed and consolidated everything to Denmark.”

According to Zorn, Lundbeck decided not to take their own neuroinflammation projects associated with Huntington's disease and pain with them. “So, they ended up on the shelf,” he said. “Knowing these projects, we worked with Lundberg to acquire them.”

“Lundbeck focuses on treatments for depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, so we are pleased to divest these two promising programs that falls outside our focus areas in line with our strategy. This agreement ensures the continued development of the programs building on our research and hopefully leading to new and better treatments for patients”, said Kim Andersen, senior vice president, Research, at Lundbeck.

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