What is n-Lorem?

Our mission, and enormous to take advantage of the technology we created at Ionis Pharmaceuticals, antisense technology or ASO technology to discover, develop and provide experimental ASO treatments, to nano rare patients and to do that for free for life. So let's begin by defining what a nano rare patient is. A nano rare patient is a patient with a disease caused by a mutation that is oftentimes unique to that individual. That is a single person in the world has

that particular mutation. In some cases, that mutation may cause disease in as many as 30 patients around the world. This is the smallest possible patient population. And oftentimes, it truly is an n of one, the rarity of the mutations, and therefore diseases is the core problem. Most patients with nano rare diseases are never diagnosed, and progress without ever knowing what's wrong with them. And the fortunate few who are diagnosed typically spend years being referred from one

specialist to the next. While the disease progresses, before they're finally genetically sequenced. And and a diagnosis achieved a task of sequencing the patient's genome, characterizing the function of the gene and understanding the patient's symptom complex, are challenging and are really only achievable in tertiary care centers, at least today. This group of patients is the most isolated, most underserved and most desperate population of patients that I have

encountered. And the limited number of patients means that the commercial development of a drug for these patients is essentially impossible. And if it were possible to make commercial sense of it, these families would have to be charged an extraordinary amount of dollars every year. So n-lorem is a nonprofit, for all of those reasons. And there is

today an opportunity to treat many of these patients. And of course, that's where n-lorem comes in, though n-lorem is only two years old, and more than five years ago, now, I realized that ASO technology could in principle help many of these patients. But a number of other elements needed to be in place before n-lorem could be feasible. The first step in the process of treatment is of course diagnosis. diagnosis for a patient with a nano rare mutation, as I said, requires

genomic sequencing. It requires characterization of the function of the gene, so that we know that if we manipulate a mutated gene of that sort, what sort of issues we might create. And we have to understand the manifestations of the disease thoroughly in the patient in question. All of these activities can really only be achieved today in the most sophisticated of settings. And those are tertiary care,

research focus medical centers. Fortunately, over the last decade or so, a consortium of tertiary care centers, called the Undiagnosed Disease Network, or UDN, has made great strides in identifying patients who are undiagnosed, working them up, and identifying the mutations and the and the nature of the diseases these patients have that is achieving a diagnosis. So among the first collaborations that are more

established, was a collaboration with the UDN. And the UDN has certainly provided a number of patients to n-lorem for potential treatment. But and this is, I think, very encouraging. We've also received many applications for treatment of patients from non UDN institutions. And then that speaks to the fact that many Personalized Medicine Centers are being created around the world in response to recognizing the unique challenges of the unique needs and the unique

opportunities to help patients with nano rare diseases. The next critical element was to ensure that there was a supportive regulatory environment because the discovery and development of treatments for patients with Nano rare diseases is truly urgent and must be very rapid and very streamlined, and also has to be cost effective if

we're to give the medicines away for free for life. Special guidance is required from the FDA and other regulatory agencies to use to ensure that providing professional treatment is actually possible. Fortunately, again, the FDA has been highly responsive and has issued guidance specific to the provision of experimental ASO treatments at no cost to nano rare patients. And that guidance is consistent with the suggestions that we made in public commentary phase of the

process of putting guidelines together. And it certainly is sufficient to provide us a pathway to bring experimental ASO treatments to many of these patients. Today, the only technology for which special guidance has been issued. For nano rare patients is the technology that we bring to bear

to help these patients. That is the ASO technology that we created at the company I founded and led for 30 years Ionis Pharmaceuticals, the founding donors of n-lorem were then put together in the founding donors where Ionis, us our partner in the neurosciences, Biogen and my wife and myself since the foundation, we've added numerous partners and donors and other types of supporters that have supported a very rapid expansion to meet the needs, and the demand that we've experienced.

The name n-lorem derives from an abbreviation for number n, and the concept of therapy. So n-lorem, signifies bringing treatment to patients who are unique, n of one type patients. And our members then of this unique group of patients that we call nano rare patients. And indeed, the demand has been extraordinary. So when I began n-lorem, I thought that perhaps by now, we might have a handful of applicants, and that we would be able to manage n-lorem essentially, with all volunteers

for the first two to three or four years. In fact, while we were setting up n-lorem, we had the opportunity to help 14 patients be treated with personalized experimental ASOs. And that was really a very important experience for us. It gave us a great deal of of knowledge about how this process actually works. In fact, today, in just two years, we have well over 130 new applications. And we're proceeding toward treating

more than 50 Different nano rare patients. As we look out over the long term, it is clear that we will be treating 1000s of patients. So the technology has to be scalable, and fortunately, antisense technology is and we have to continue to expand so we can meet these patient's needs, and eventually expand well beyond the United States. Because these mutations are expressed in all populations around the world, it has been a real challenge to grow n-lorem at a pace sufficient to meet the

demand. And it has been challenging, but we are optimistic that we will achieve our goal of being able to bring treatments to these patients within 12 to 18 months after the application is received and approved. To put that goal in context for you, the discovery process for a drug to a novel target often takes 10 to 20 years and many, many, many

scores of scientists. And then of course, once the first medicine that comes from that program is identified, the average time from that point to commercial treatment is about 16 years. And so we're condensing decades, into a few months. So it's a real challenge. But we can do it. And we have done it. Not only is there an urgent need for us to do this, we have a technology and we have the experience to actually get this done in a timeframe when that these patients require. Now from

inception, we've known that we can't do this alone. We're a

small nonprofit foundation. So we have been very successful at putting together a growing network of stakeholders, donors, partners, clinical research sites that we call a Partners in Excellence and these partnerships have allowed us to reduce the cost per patient by more than 40%, enhance the efficiency the efficiency with which we discover and develop these medicines, and yet assure that each step in the process is of the absolute highest quality the addition of clinical sites

that are focused on helping an n of one type patients, and

working closely with n-lorem. Now, let's just take the next step in being even more efficient in integrating diagnosis, genomic sequencing, and treatment in a seamless fashion for patients who are suffering with these diseases, I'm also very pleased to tell you that we have established a range of novel systems and approach that assure every patient is treated with the optimal so that each step in the process that may lead to treatment of a patient is of the

very highest quality, and that from every patient, in our aggregate experience, we learn as much as we possibly can, because there's a great tool to be learned, of course, these patients deserve the effort to learn from them and be able to apply that information to new patients that we may encounter in the future. But of course, we've just begun, what we're doing is important and exciting. And the progress that we have

made, I think, is really quite, quite impressive. One of the most important contributions that we hope to make, in addition to all of all that we are doing, including treatment is to create a community for these very isolated patients and their families and provide solid knowledge, experience and an opportunity for their voices to be heard as a part of a holistic approach to providing the support these patients and

families needs. One of the key elements of this process is a podcast series that we will be initiating in April and this podcast series is a part of a program that we call the Patient Empowerment Program or Pep.

In coming months, we will be initiating this process in the format is a mix of interviews with stakeholders, with patients with experts, as well as more lecture like experiences in which we try to elevate the knowledge that's available to patients and parents and families who must deal with these unique mutations and the challenges that they bring. Only

through knowledge comes power. As we provide knowledge and a site for voices to be heard, we'll increase the sense of empowerment that patients and families have and move away from the hopelessness and despair that is the current state of affairs for patients in the nano rare mutation group.

free lifetime treatment. For more information about n-lorem or today's episode, visit nlorem.org any questions can be sent into podcast@nlorem.org search nlorem on Twitter, Instagram, YouTube, LinkedIn and Facebook to connect with us. Please rate and review the podcast on Apple, Spotify, or wherever you listen. This truly helps us climb the charts and allows others to find the show. This podcast is hosted by Dr. Stan Crooke. Our videographer is John Magnussen of Mighty One

productions. Our producers are John Magnuson and Kira Dineen of DNA today. Thank you for listening