What is n-Lorem?
n-Lorem provides an opportunity for a better life, renewed hope and brighter dreams, one patient, one family at a time. Our mission is to provide personalized experimental antisense oligonucleotide (ASO) medicines to treat nano-rare patients – for free, for life. Nano-rare patients describe a very small group of patients (1-30 worldwide) who, because of their small numbers, have few if any treatment options. We take advantage of the efficacy and versatility of ASO technology. ASO technology is the only technology with regulatory guidance to treat nano-rare patients. Rare diseases often cause people to do things that they’re completely untrained to do. With this series, we’re building a community for nano-rare and bringing the basic science behind drug discovery and development directly to patients and their families.
Transcript
Hello, and welcome to the N-Lorem podcast
Dr Stan Crooke:series, a series that focuses exclusively on patients now
Dr Stan Crooke:referred to as having nano rare mutations. I'm Stan Crooke, and
Dr Stan Crooke:I'm the founder chairman and CEO of n-lorem. n-lorem is a
Dr Stan Crooke:nonprofit foundation that I initiated in January of 2020.
Dr Stan Crooke:Our mission, and enormous to take advantage of the technology
Dr Stan Crooke:we created at Ionis Pharmaceuticals, antisense
Dr Stan Crooke:technology or ASO technology to discover, develop and provide
Dr Stan Crooke:experimental ASO treatments, to nano rare patients and to do
Dr Stan Crooke:that for free for life. So let's begin by defining what a nano
Dr Stan Crooke:rare patient is. A nano rare patient is a patient with a
Dr Stan Crooke:disease caused by a mutation that is oftentimes unique to
Dr Stan Crooke:that individual. That is a single person in the world has
Dr Stan Crooke:that particular mutation. In some cases, that mutation may
Dr Stan Crooke:cause disease in as many as 30 patients around the world. This
Dr Stan Crooke:is the smallest possible patient population. And oftentimes, it
Dr Stan Crooke:truly is an n of one, the rarity of the mutations, and therefore
Dr Stan Crooke:diseases is the core problem. Most patients with nano rare
Dr Stan Crooke:diseases are never diagnosed, and progress without ever
Dr Stan Crooke:knowing what's wrong with them. And the fortunate few who are
Dr Stan Crooke:diagnosed typically spend years being referred from one
Dr Stan Crooke:specialist to the next. While the disease progresses, before
Dr Stan Crooke:they're finally genetically sequenced. And and a diagnosis
Dr Stan Crooke:achieved a task of sequencing the patient's genome,
Dr Stan Crooke:characterizing the function of the gene and understanding the
Dr Stan Crooke:patient's symptom complex, are challenging and are really only
Dr Stan Crooke:achievable in tertiary care centers, at least today. This
Dr Stan Crooke:group of patients is the most isolated, most underserved and
Dr Stan Crooke:most desperate population of patients that I have
Dr Stan Crooke:encountered. And the limited number of patients means that
Dr Stan Crooke:the commercial development of a drug for these patients is
Dr Stan Crooke:essentially impossible. And if it were possible to make
Dr Stan Crooke:commercial sense of it, these families would have to be
Dr Stan Crooke:charged an extraordinary amount of dollars every year. So
Dr Stan Crooke:n-lorem is a nonprofit, for all of those reasons. And there is
Dr Stan Crooke:today an opportunity to treat many of these patients. And of
Dr Stan Crooke:course, that's where n-lorem comes in, though n-lorem is only
Dr Stan Crooke:two years old, and more than five years ago, now, I realized
Dr Stan Crooke:that ASO technology could in principle help many of these
Dr Stan Crooke:patients. But a number of other elements needed to be in place
Dr Stan Crooke:before n-lorem could be feasible. The first step in the
Dr Stan Crooke:process of treatment is of course diagnosis. diagnosis for
Dr Stan Crooke:a patient with a nano rare mutation, as I said, requires
Dr Stan Crooke:genomic sequencing. It requires characterization of the function
Dr Stan Crooke:of the gene, so that we know that if we manipulate a mutated
Dr Stan Crooke:gene of that sort, what sort of issues we might create. And we
Dr Stan Crooke:have to understand the manifestations of the disease
Dr Stan Crooke:thoroughly in the patient in question. All of these
Dr Stan Crooke:activities can really only be achieved today in the most
Dr Stan Crooke:sophisticated of settings. And those are tertiary care,
Dr Stan Crooke:research focus medical centers. Fortunately, over the last
Dr Stan Crooke:decade or so, a consortium of tertiary care centers, called
Dr Stan Crooke:the Undiagnosed Disease Network, or UDN, has made great strides
Dr Stan Crooke:in identifying patients who are undiagnosed, working them up,
Dr Stan Crooke:and identifying the mutations and the and the nature of the
Dr Stan Crooke:diseases these patients have that is achieving a diagnosis.
Dr Stan Crooke:So among the first collaborations that are more
Dr Stan Crooke:established, was a collaboration with the UDN. And the UDN has
Dr Stan Crooke:certainly provided a number of patients to n-lorem for
Dr Stan Crooke:potential treatment. But and this is, I think, very
Dr Stan Crooke:encouraging. We've also received many applications for treatment
Dr Stan Crooke:of patients from non UDN institutions. And then that
Dr Stan Crooke:speaks to the fact that many Personalized Medicine Centers
Dr Stan Crooke:are being created around the world in response to recognizing
Dr Stan Crooke:the unique challenges of the unique needs and the unique
Dr Stan Crooke:opportunities to help patients with nano rare diseases. The
Dr Stan Crooke:next critical element was to ensure that there was a
Dr Stan Crooke:supportive regulatory environment because the
Dr Stan Crooke:discovery and development of treatments for patients with
Dr Stan Crooke:Nano rare diseases is truly urgent and must be very rapid
Dr Stan Crooke:and very streamlined, and also has to be cost effective if
Dr Stan Crooke:we're to give the medicines away for free for life. Special
Dr Stan Crooke:guidance is required from the FDA and other regulatory
Dr Stan Crooke:agencies to use to ensure that providing professional treatment
Dr Stan Crooke:is actually possible. Fortunately, again, the FDA has
Dr Stan Crooke:been highly responsive and has issued guidance specific to the
Dr Stan Crooke:provision of experimental ASO treatments at no cost to nano
Dr Stan Crooke:rare patients. And that guidance is consistent with the
Dr Stan Crooke:suggestions that we made in public commentary phase of the
Dr Stan Crooke:process of putting guidelines together. And it certainly is
Dr Stan Crooke:sufficient to provide us a pathway to bring experimental
Dr Stan Crooke:ASO treatments to many of these patients. Today, the only
Dr Stan Crooke:technology for which special guidance has been issued. For
Dr Stan Crooke:nano rare patients is the technology that we bring to bear
Dr Stan Crooke:to help these patients. That is the ASO technology that we
Dr Stan Crooke:created at the company I founded and led for 30 years Ionis
Dr Stan Crooke:Pharmaceuticals, the founding donors of n-lorem were then put
Dr Stan Crooke:together in the founding donors where Ionis, us our partner in
Dr Stan Crooke:the neurosciences, Biogen and my wife and myself since the
Dr Stan Crooke:foundation, we've added numerous partners and donors and other
Dr Stan Crooke:types of supporters that have supported a very rapid expansion
Dr Stan Crooke:to meet the needs, and the demand that we've experienced.
Dr Stan Crooke:The name n-lorem derives from an abbreviation for number n, and
Dr Stan Crooke:the concept of therapy. So n-lorem, signifies bringing
Dr Stan Crooke:treatment to patients who are unique, n of one type patients.
Dr Stan Crooke:And our members then of this unique group of patients that we
Dr Stan Crooke:call nano rare patients. And indeed, the demand has been
Dr Stan Crooke:extraordinary. So when I began n-lorem, I thought that perhaps
Dr Stan Crooke:by now, we might have a handful of applicants, and that we would
Dr Stan Crooke:be able to manage n-lorem essentially, with all volunteers
Dr Stan Crooke:for the first two to three or four years. In fact, while we
Dr Stan Crooke:were setting up n-lorem, we had the opportunity to help 14
Dr Stan Crooke:patients be treated with personalized experimental ASOs.
Dr Stan Crooke:And that was really a very important experience for us. It
Dr Stan Crooke:gave us a great deal of of knowledge about how this process
Dr Stan Crooke:actually works. In fact, today, in just two years, we have well
Dr Stan Crooke:over 130 new applications. And we're proceeding toward treating
Dr Stan Crooke:more than 50 Different nano rare patients. As we look out over
Dr Stan Crooke:the long term, it is clear that we will be treating 1000s of
Dr Stan Crooke:patients. So the technology has to be scalable, and fortunately,
Dr Stan Crooke:antisense technology is and we have to continue to expand so we
Dr Stan Crooke:can meet these patient's needs, and eventually expand well
Dr Stan Crooke:beyond the United States. Because these mutations are
Dr Stan Crooke:expressed in all populations around the world, it has been a
Dr Stan Crooke:real challenge to grow n-lorem at a pace sufficient to meet the
Dr Stan Crooke:demand. And it has been challenging, but we are
Dr Stan Crooke:optimistic that we will achieve our goal of being able to bring
Dr Stan Crooke:treatments to these patients within 12 to 18 months after the
Dr Stan Crooke:application is received and approved. To put that goal in
Dr Stan Crooke:context for you, the discovery process for a drug to a novel
Dr Stan Crooke:target often takes 10 to 20 years and many, many, many
Dr Stan Crooke:scores of scientists. And then of course, once the first
Dr Stan Crooke:medicine that comes from that program is identified, the
Dr Stan Crooke:average time from that point to commercial treatment is about 16
Dr Stan Crooke:years. And so we're condensing decades, into a few months. So
Dr Stan Crooke:it's a real challenge. But we can do it. And we have done it.
Dr Stan Crooke:Not only is there an urgent need for us to do this, we have a
Dr Stan Crooke:technology and we have the experience to actually get this
Dr Stan Crooke:done in a timeframe when that these patients require. Now from
Dr Stan Crooke:inception, we've known that we can't do this alone. We're a
Dr Stan Crooke:small nonprofit foundation. So we have been very successful at
Dr Stan Crooke:putting together a growing network of stakeholders, donors,
Dr Stan Crooke:partners, clinical research sites that we call a Partners in
Dr Stan Crooke:Excellence and these partnerships have allowed us to
Dr Stan Crooke:reduce the cost per patient by more than 40%, enhance the
Dr Stan Crooke:efficiency the efficiency with which we discover and develop
Dr Stan Crooke:these medicines, and yet assure that each step in the process is
Dr Stan Crooke:of the absolute highest quality the addition of clinical sites
Dr Stan Crooke:that are focused on helping an n of one type patients, and
Dr Stan Crooke:working closely with n-lorem. Now, let's just take the next
Dr Stan Crooke:step in being even more efficient in integrating
Dr Stan Crooke:diagnosis, genomic sequencing, and treatment in a seamless
Dr Stan Crooke:fashion for patients who are suffering with these diseases,
Dr Stan Crooke:I'm also very pleased to tell you that we have established a
Dr Stan Crooke:range of novel systems and approach that assure every
Dr Stan Crooke:patient is treated with the optimal so that each step in the
Dr Stan Crooke:process that may lead to treatment of a patient is of the
Dr Stan Crooke:very highest quality, and that from every patient, in our
Dr Stan Crooke:aggregate experience, we learn as much as we possibly can,
Dr Stan Crooke:because there's a great tool to be learned, of course, these
Dr Stan Crooke:patients deserve the effort to learn from them and be able to
Dr Stan Crooke:apply that information to new patients that we may encounter
Dr Stan Crooke:in the future. But of course, we've just begun, what we're
Dr Stan Crooke:doing is important and exciting. And the progress that we have
Dr Stan Crooke:made, I think, is really quite, quite impressive. One of the
Dr Stan Crooke:most important contributions that we hope to make, in
Dr Stan Crooke:addition to all of all that we are doing, including treatment
Dr Stan Crooke:is to create a community for these very isolated patients and
Dr Stan Crooke:their families and provide solid knowledge, experience and an
Dr Stan Crooke:opportunity for their voices to be heard as a part of a holistic
Dr Stan Crooke:approach to providing the support these patients and
Dr Stan Crooke:families needs. One of the key elements of this process is a
Dr Stan Crooke:podcast series that we will be initiating in April and this
Dr Stan Crooke:podcast series is a part of a program that we call the Patient
Dr Stan Crooke:Empowerment Program or Pep.
Dr Stan Crooke:In coming months, we will be initiating this process in the
Dr Stan Crooke:format is a mix of interviews with stakeholders, with patients
Dr Stan Crooke:with experts, as well as more lecture like experiences in
Dr Stan Crooke:which we try to elevate the knowledge that's available to
Dr Stan Crooke:patients and parents and families who must deal with
Dr Stan Crooke:these unique mutations and the challenges that they bring. Only
Dr Stan Crooke:through knowledge comes power. As we provide knowledge and a
Dr Stan Crooke:site for voices to be heard, we'll increase the sense of
Dr Stan Crooke:empowerment that patients and families have and move away from
Dr Stan Crooke:the hopelessness and despair that is the current state of
Dr Stan Crooke:affairs for patients in the nano rare mutation group.
Narrator:n-lorem is a nonprofit committed to discovering and
Narrator:providing personalized experimental treatments for free
Narrator:for life to patients with genetic diseases that affect one
Narrator:to 30 patients worldwide, referred to by n-lorem. As nano
Narrator:rare. Many of these patients progress and die without ever
Narrator:achieving a diagnosis. This is where n-lorem comes in. They do
Narrator:the impossible by providing hope and for those that they can help
Narrator:free lifetime treatment. For more information about n-lorem
Narrator:or today's episode, visit nlorem.org any questions can be
Narrator:sent into podcast@nlorem.org search nlorem on Twitter,
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Narrator:Please rate and review the podcast on Apple, Spotify, or
Narrator:wherever you listen. This truly helps us climb the charts and
Narrator:allows others to find the show. This podcast is hosted by Dr.
Narrator:Stan Crooke. Our videographer is John Magnussen of Mighty One
Narrator:productions. Our producers are John Magnuson and Kira Dineen of
Narrator:DNA today. Thank you for listening
