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In a world where most people are reluctant to confront the biggest challenges, Dr. Rajesh Khanna is taking the opposite approach.

Dr. Khanna is a professor of pharmacology and anesthesiology at the University of Arizona in Tucson and chief science officer at Regulonix, LLC, an early-stage biotechnology company. He and Regulonix CEO Mike Sember are leading a team of researchers taking on one of the biggest public health challenges of all: Creating an effective, non-opioid alternative for severe, chronic pain.

Dr. Aude Chefdeville and Dr. Rajesh Khanna, UA College of Medicine and Regulonix

The challenge could not be any more daunting. In the U.S. alone, about 20 million people suffer from ‘high-impact,’ chronic pain. This is pain severe enough to limit daily activity, according to the Centers for Disease Control and Prevention, the CDC. Worldwide, the number of people suffering from chronic pain in general is close to 1.5 billion people according to estimates from Boston University’s School of Public Health.

So the need for effective pain medication is great. And opioid-based prescription drugs like hydrocodone (Vicodin) and oxycodone (OxyContin) are very effective in relieving severe pain in the short term. The downside is that they can be very addictive when used long-term. Up to one in four persons who take opioid medication long-term become addicted. That’s why these drugs are called narcotic analgesicsin the world of pharmacology.

And addiction can lead to death from overdose. Daily news reports deliver grim reminders of this public health epidemic. The CDC estimates that on average 130 Americans die every day from opioid overdoses. This includes deaths from prescription drug and heroin overdoses. This is the wave of deaths from opioid abuse that hasswept across the  American landscape. And motivates Dr. Khanna and his Regulonix team.“

We started Regulonix to combat the opioid epidemic by designing new drugs that would bypass the need for opioids, or at least, diminish the need for opioid use,” Dr. Khanna says. “The opioid crisis is continuing unabated. The FDA, the CDC, everybody’s weighing in. But we can’t undercut the physician’s ability to prescribe drugs to people in pain.” Which means finding effective drugs for pain that are non-addictive. That’s the big challenge.

On a spring morning, Dr. Khanna is explaining the science that serves as the foundation for the approach his research team is taking. He speaks quickly, the voice trying hard to keep up with the rush of thoughts flowing from his brain. The words are propelled by an energy you might not expect from a world-class expert in the microscopic world of ‘ion channel biology’ This a scientist who has found something very much worth pursuing.

Dr. Khanna and his team have isolated compounds shown in animal models to be non-addictive and more effective than morphine by indirectly targeting the well-established, genetically-validated pain target, the Nav1.7 sodium channel, and focusing on signaling pathways that control channel activity. “Our approach has been different. What we’re doing is regulating, hence the name Regulonix, regulators of ion channels.”

“We’re trying to subtly change the activity, not by physically attacking the channel, but in an indirect manner. By finding out who the channel is talking to on the inside of the cell, we’re able to change that conversation.” “We’re hoping to achieve the same control as if you were to physically block the channel,” Dr. Khanna says. “What is different is our ability to regulate the channel by understanding and regulating something else.”

This targeted Nav1.7 sodium channel approach is what he believes gives Regulonix a clear advantage over the direct-block-of-channels approach used by other researchers. “We hope this is an approach that will achieve pain without tolerance, without addiction, without many of the things that encumber opioids.” And he points to the game-changing benefits of compounds that deliver potency with no addictive properties.

At the same time, Dr. Khanna acknowledges the inherent difficulty of targeting the Nav1.7 sodium channel. Even the most promising targets can be very challenging when it comes to the tough work of producing a safe, effective drug for chronic pain. In recent years, scientists at major pharmaceutical firms have conducted world-class research based on the Nav1.7 sodium channel and still come up short.

For Dr. Khanna, these results simply means pushing ahead and doubling down on rigorous lab processes and testing. He emphasizes the critical element of constant testing across categories of species to identify small problems before they become major roadblocks. “The other big thing we’re doing is checking,’ he says. “Why is that important? Well, that translational divide is there when you test all compounds.

And one way to de-risk our compounds has been this early strategy. For our lead compound 194, we do see inhibition in mouse, in rat, in pig and in human. Which gives us great confidence that this compound should be able to regulate across the species. And so that’s a very important feature that allows us to really be confident about the potential of our compound.”

Another thing that Dr. Khanna feels confident about is the continuing support he receives from Regulonix CEO Mike Sember. “We met Mike in December about three years ago through Tech Launch Arizona. He was an entrepreneur-in-residence. I’m not a business person, so we needed somebody to develop a business plan.”

Mike Sember, Regulonix CEO

Mike Sember has had a long and successful career as a pharmaceutical industry executive. He has worked with a number of biotech startups and emerging companies. He describes the division of labor between his role as Regulonix CEO and Dr. Khanna’s role as chief science officer. “I think it’s very complimentary. We don’t have any hard and fast guard rails on how we cooperate.”

“When it comes to the scientific decisions of the company, I’m always going to defer to Raj. And he will tend to defer to me on the more business-related aspects of things that we have to decide,” Sember says. “But there’s a lot of crossover and we discuss virtually everything between us. And we’re completely open to each other’s input in that regard.”

There is more than a little give and take in their conversations according to Dr. Khanna. “I’m always butting heads with him, always arguing about what direction we should take. I think it’s a healthy argument. I think we need that to thrive. And Mike is very seasoned. There’s a lot of experience, probably three, four decades worth of experience which he brings to the table.”

CEO Sember offers this insider’s perspective on the science developed by Dr. Khanna and the Regulonix research team. “I think the science of what we’re doing is exquisite. I think it’s unique. And those are very compelling features for people who are involved with startup companies like this. More importantly, it’s the contribution we can make to society, if we’re successful. That’s the critical distinguishing factor.”

Sember does not minimize the challenge Regulonix faces, but he is confident nonetheless. “Delivering new drugs to market is a very difficult business,” he admits. “But we do think that the odds of this compound making it to market and being a successful entry are very high. Because we understand the ‘mechanism of action.’ It’s one
scientific target that should be pursued for pain relief.”

Looking at the road ahead for Regulonix, Mike Sember sees real progress and points to human clinical trials as an important next step. “We are well along in terms of understanding the mechanism and action of this drug, how it works in the body. We’re convinced that it works in relevant animal models. We’ve got significant amounts of data in that regard. So the next step for us to take it to human trials.”

Dr. Khanna shares the view of his Regulonix partner and CEO. “We are a small company and we’re dedicated to moving this forward as far as we can, but we’re not in a position to run the clinical trials. We will gather all the critical data to get to the pre-investigational, new-drug-enabling studies and partner with the right firm and then take this to human trials.”

From Sember’s perspective, Regulonix has already surpassed the biggest obstacle. “We’ve already overcome the toughest hurdle and that was raising the first amount of capital needed,” he says. “Capital is the lifeblood of what we do. So the investment from UA Venture Capital and the Desert Angels of $2M was the critical step for us in terms of moving forward to achieving success.”

Mike Sember’s belief in the science developed by Dr. Khanna and his research team is shared by Regulonix Board Chairman, Fletcher McCusker. He is one of co-founders of UAVenture Capital Fund, LLC, a Tucson-based investment fund designed to help finance enterprises connected to the University of Arizona and led by university faculty involved in launching innovative startups.

McCusker recalls his initial reaction on first meeting Dr. Khanna and listening to his idea for developing a non- opioid alternative for severe chronic pain relief. “I was sold. It’s probably the most topical issue in this country today. Opioid abuse and deaths related to opiate abuse. It’s reached crisis proportions. Raj has an alternative. We were very excited about it, and it was one of our first investments.”

The Regulonix board chairman offers this perspective on the science developed by Dr. Khanna and his research team and the progress they’ve made in their first two years of operation. “We know it works in the lab. It works in mice. We know it’s efficacious. We know it’s not toxic. The money we’ve advanced them, the money we’ve invested in them, it’s designed to move the drug into human clinical trials.”

Like a proud father looking forward to the graduation of a son or daughter, he envisions what the impact might be if Regulonix is able to bring a safe, effective, non-opioid alternative to market. “It would be huge benefit for the UA campus and faculty if we can change the way pain is treated. If we can resolve and eliminate the opiate crisis, it would be probably the most important drug discovery in the last hundred years.”

“And the fact that we’re all involved in that, and it’s coming from Tucson, Arizona, and it’s coming out of the University of Arizona, is unbelievable, really,” McCusker says. “So I think this is some of our most important work, not only in terms of what we do, but in terms of what’s happening on our campus, and the opportunity to relieve the dependency people have on opiates. It’s going to be a world changer.”

In the high-risk world of launching biotechnology companies, everything has to line up perfectly in order to achieve the science that produces the drug that addresses the critical public health need. Pharmaceutical firms spend hundreds of millions of dollars investing in emerging biotech firms they hope will make it to final FDA approval. Knowing full well that they may not produce the successful outcome everyone envisions.

From their perspective, what is essential is identifying the serious public health need, the innovative quality of the underlying science and the problem-solving skills and drive of the lead scientist and research team. And, last but not least, the financial investment needed to sustain the emerging company as it works through all the challenges of bringing a breakthrough drug to market.

Regulonix has all these essential elements and more. A committed scientist who decided to take on one of the biggest public health challenges of all. A pharmaceutical industry veteran who makes sure the team has what they need to validate the critical path chosen. And a venture capitalist who decided to back this ambitious effort with a deep-pocket investment.

Because he believes in the scientist. And wants to give back to his alma mater. And is committed to tackling the world-wide opioid epidemic. Even if you’re a cynical, Las Vegas oddsmaker, how in the world do you bet against this team? You don’t.

©Copyright, 2019 Regulonix Holding, Inc.