Episode 2

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Published on:

25th May 2022

What is n-Lorem?

The first in Dr. Stan Crooke's lesson series to provide knowledge on science and drug discovery and development for patients and their families. With the educational series, listeners will learn the basic science behind drug discovery and development. In this episode, Stan provides an overview of n-Lorem and the progress the Foundation has made in two years.

Transcript
Dr Stan Crooke:

Hello, and welcome to the N-Lorem podcast

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series, a series that focuses exclusively on patients now

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referred to as having nano rare mutations. I'm Stan Crooke, and

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I'm the founder chairman and CEO of n-lorem. n-lorem is a

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nonprofit foundation that I initiated in January of 2020.

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Our mission, and enormous to take advantage of the technology

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we created at Ionis Pharmaceuticals, antisense

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technology or ASO technology to discover, develop and provide

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experimental ASO treatments, to nano rare patients and to do

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that for free for life. So let's begin by defining what a nano

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rare patient is. A nano rare patient is a patient with a

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disease caused by a mutation that is oftentimes unique to

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that individual. That is a single person in the world has

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that particular mutation. In some cases, that mutation may

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cause disease in as many as 30 patients around the world. This

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is the smallest possible patient population. And oftentimes, it

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truly is an n of one, the rarity of the mutations, and therefore

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diseases is the core problem. Most patients with nano rare

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diseases are never diagnosed, and progress without ever

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knowing what's wrong with them. And the fortunate few who are

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diagnosed typically spend years being referred from one

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specialist to the next. While the disease progresses, before

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they're finally genetically sequenced. And and a diagnosis

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achieved a task of sequencing the patient's genome,

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characterizing the function of the gene and understanding the

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patient's symptom complex, are challenging and are really only

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achievable in tertiary care centers, at least today. This

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group of patients is the most isolated, most underserved and

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most desperate population of patients that I have

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encountered. And the limited number of patients means that

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the commercial development of a drug for these patients is

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essentially impossible. And if it were possible to make

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commercial sense of it, these families would have to be

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charged an extraordinary amount of dollars every year. So

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n-lorem is a nonprofit, for all of those reasons. And there is

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today an opportunity to treat many of these patients. And of

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course, that's where n-lorem comes in, though n-lorem is only

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two years old, and more than five years ago, now, I realized

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that ASO technology could in principle help many of these

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patients. But a number of other elements needed to be in place

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before n-lorem could be feasible. The first step in the

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process of treatment is of course diagnosis. diagnosis for

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a patient with a nano rare mutation, as I said, requires

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genomic sequencing. It requires characterization of the function

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of the gene, so that we know that if we manipulate a mutated

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gene of that sort, what sort of issues we might create. And we

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have to understand the manifestations of the disease

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thoroughly in the patient in question. All of these

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activities can really only be achieved today in the most

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sophisticated of settings. And those are tertiary care,

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research focus medical centers. Fortunately, over the last

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decade or so, a consortium of tertiary care centers, called

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the Undiagnosed Disease Network, or UDN, has made great strides

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in identifying patients who are undiagnosed, working them up,

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and identifying the mutations and the and the nature of the

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diseases these patients have that is achieving a diagnosis.

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So among the first collaborations that are more

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established, was a collaboration with the UDN. And the UDN has

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certainly provided a number of patients to n-lorem for

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potential treatment. But and this is, I think, very

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encouraging. We've also received many applications for treatment

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of patients from non UDN institutions. And then that

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speaks to the fact that many Personalized Medicine Centers

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are being created around the world in response to recognizing

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the unique challenges of the unique needs and the unique

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opportunities to help patients with nano rare diseases. The

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next critical element was to ensure that there was a

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supportive regulatory environment because the

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discovery and development of treatments for patients with

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Nano rare diseases is truly urgent and must be very rapid

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and very streamlined, and also has to be cost effective if

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we're to give the medicines away for free for life. Special

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guidance is required from the FDA and other regulatory

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agencies to use to ensure that providing professional treatment

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is actually possible. Fortunately, again, the FDA has

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been highly responsive and has issued guidance specific to the

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provision of experimental ASO treatments at no cost to nano

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rare patients. And that guidance is consistent with the

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suggestions that we made in public commentary phase of the

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process of putting guidelines together. And it certainly is

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sufficient to provide us a pathway to bring experimental

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ASO treatments to many of these patients. Today, the only

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technology for which special guidance has been issued. For

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nano rare patients is the technology that we bring to bear

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to help these patients. That is the ASO technology that we

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created at the company I founded and led for 30 years Ionis

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Pharmaceuticals, the founding donors of n-lorem were then put

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together in the founding donors where Ionis, us our partner in

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the neurosciences, Biogen and my wife and myself since the

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foundation, we've added numerous partners and donors and other

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types of supporters that have supported a very rapid expansion

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to meet the needs, and the demand that we've experienced.

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The name n-lorem derives from an abbreviation for number n, and

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the concept of therapy. So n-lorem, signifies bringing

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treatment to patients who are unique, n of one type patients.

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And our members then of this unique group of patients that we

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call nano rare patients. And indeed, the demand has been

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extraordinary. So when I began n-lorem, I thought that perhaps

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by now, we might have a handful of applicants, and that we would

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be able to manage n-lorem essentially, with all volunteers

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for the first two to three or four years. In fact, while we

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were setting up n-lorem, we had the opportunity to help 14

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patients be treated with personalized experimental ASOs.

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And that was really a very important experience for us. It

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gave us a great deal of of knowledge about how this process

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actually works. In fact, today, in just two years, we have well

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over 130 new applications. And we're proceeding toward treating

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more than 50 Different nano rare patients. As we look out over

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the long term, it is clear that we will be treating 1000s of

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patients. So the technology has to be scalable, and fortunately,

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antisense technology is and we have to continue to expand so we

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can meet these patient's needs, and eventually expand well

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beyond the United States. Because these mutations are

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expressed in all populations around the world, it has been a

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real challenge to grow n-lorem at a pace sufficient to meet the

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demand. And it has been challenging, but we are

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optimistic that we will achieve our goal of being able to bring

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treatments to these patients within 12 to 18 months after the

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application is received and approved. To put that goal in

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context for you, the discovery process for a drug to a novel

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target often takes 10 to 20 years and many, many, many

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scores of scientists. And then of course, once the first

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medicine that comes from that program is identified, the

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average time from that point to commercial treatment is about 16

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years. And so we're condensing decades, into a few months. So

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it's a real challenge. But we can do it. And we have done it.

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Not only is there an urgent need for us to do this, we have a

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technology and we have the experience to actually get this

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done in a timeframe when that these patients require. Now from

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

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small nonprofit foundation. So we have been very successful at

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putting together a growing network of stakeholders, donors,

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partners, clinical research sites that we call a Partners in

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Excellence and these partnerships have allowed us to

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reduce the cost per patient by more than 40%, enhance the

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efficiency the efficiency with which we discover and develop

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these medicines, and yet assure that each step in the process is

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of the absolute highest quality the addition of clinical sites

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

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working closely with n-lorem. Now, let's just take the next

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step in being even more efficient in integrating

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diagnosis, genomic sequencing, and treatment in a seamless

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fashion for patients who are suffering with these diseases,

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I'm also very pleased to tell you that we have established a

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range of novel systems and approach that assure every

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patient is treated with the optimal so that each step in the

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process that may lead to treatment of a patient is of the

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very highest quality, and that from every patient, in our

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aggregate experience, we learn as much as we possibly can,

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because there's a great tool to be learned, of course, these

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patients deserve the effort to learn from them and be able to

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apply that information to new patients that we may encounter

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in the future. But of course, we've just begun, what we're

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doing is important and exciting. And the progress that we have

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made, I think, is really quite, quite impressive. One of the

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most important contributions that we hope to make, in

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addition to all of all that we are doing, including treatment

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is to create a community for these very isolated patients and

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their families and provide solid knowledge, experience and an

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opportunity for their voices to be heard as a part of a holistic

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approach to providing the support these patients and

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families needs. One of the key elements of this process is a

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podcast series that we will be initiating in April and this

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podcast series is a part of a program that we call the Patient

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Empowerment Program or Pep.

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In coming months, we will be initiating this process in the

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format is a mix of interviews with stakeholders, with patients

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with experts, as well as more lecture like experiences in

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which we try to elevate the knowledge that's available to

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patients and parents and families who must deal with

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these unique mutations and the challenges that they bring. Only

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through knowledge comes power. As we provide knowledge and a

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site for voices to be heard, we'll increase the sense of

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empowerment that patients and families have and move away from

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the hopelessness and despair that is the current state of

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affairs for patients in the nano rare mutation group.

Narrator:

n-lorem is a nonprofit committed to discovering and

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providing personalized experimental treatments for free

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for life to patients with genetic diseases that affect one

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to 30 patients worldwide, referred to by n-lorem. As nano

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rare. Many of these patients progress and die without ever

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achieving a diagnosis. This is where n-lorem comes in. They do

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the impossible by providing hope and for those that they can help

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free lifetime treatment. For more information about n-lorem

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or today's episode, visit nlorem.org any questions can be

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sent into podcast@nlorem.org search nlorem on Twitter,

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Instagram, YouTube, LinkedIn and Facebook to connect with us.

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Please rate and review the podcast on Apple, Spotify, or

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wherever you listen. This truly helps us climb the charts and

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allows others to find the show. This podcast is hosted by Dr.

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Stan Crooke. Our videographer is John Magnussen of Mighty One

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productions. Our producers are John Magnuson and Kira Dineen of

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DNA today. Thank you for listening

Show artwork for Patient Empowerment Program: A Rare Disease Podcast

About the Podcast

Patient Empowerment Program: A Rare Disease Podcast
Learn about Nano-Rare Diseases with biotech titan Dr. Stan Crooke of n-Lorem.
Join the nano-rare disease community! Interviews features leading physicians, scientists, biotech experts, and patient advocates. Lessons teach core concepts about drugs. Our host Dr. Crooke has led the creation of antisense technology and his foundation, n-Lorem, is using this powerful technology to discover, develop, and provide personalized experimental antisense oligonucleotide medicines to nano-rare patients for free, for life.

n-Lorem is a non-profit organization established to apply the efficiency, versatility and specificity of antisense technology to charitably provide experimental antisense oligonucleotide (ASO) medicines to treat patients (less than 30 patients) that are the result of a single genetic defect unique to only one or very few individuals. The advantage of experimental ASO medicines is that they can be developed rapidly, inexpensively and are highly specific. n-Lorem was founded by Dr. Stan Crooke, who founded IONIS Pharmaceuticals in 1989 and, through his vision and leadership, established the company as the leader in RNA-targeted therapeutics.

This podcast is produced by n-Lorem Foundation and hosted by Dr. Stanley T. Crooke, who is our Founder, CEO and Chairman. Our videographer is Jon Magnuson. Our producers are Kira Dineen, Jon Magnuson, Kim Butler, and Amy Williford. To learn more about n-Lorem, visit nlorem.org. Contact us at podcast@nlorem.org.

About your host

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Kim Butler