is a precision genetic medicines company committed to developing curative therapeutics for patients using a proprietary next generation gene editing toolbox. Before I go further, I'll just very briefly hit our forward-looking statements. We are going to make forward-looking statements in this presentation. Please refer to our filings on www.sec.gov. So our vision at Metagenomi is to harness the power of our metagenomics platform to create curative genetic medicines for patients. This is really a groundbreaking strategy of trying to create cures, replacing current treatments as therapies. And we've seen a lot of progress in the gene editing companies that are leading the space. The first gene editing program approved last year, as well as programs making their way into the clinic. However, these programs are really first-generation technologies that have limitations on where they can target within the human genome.
At Metagenomi, we are focused on our AI-driven metagenomics platform to create programmable genome editing tools that will make precise human gene modifications, with the goal to translate those tools and modifications into curative genetic medicines. So what is metagenomics? Metagenomics is really the study of genomic material that is found in the environment. It's a very revolutionary kind of science. Here, we start with proprietary sampling, where we go into diverse microbiome-rich ecosystems, and we extract all the DNA that we can find in those environments. We go to environments such as backyard gardens or deep-sea hydrothermal vents. We then bring those samples back to the lab and apply a variety of engineering tools. These include artificial intelligence, ancestral reconstruction, proprietary algorithms, and automation.
Through this, we reveal novel cellular machinery out of the samples that we have found. We then engineer and optimize those samples. We take these novel tools and, through our engineering and optimization, turn them into precision, efficient, and highly capable editing capabilities. This generates for us a metagenomics toolbox. This is a toolbox of metagenomic capabilities, where we are nearing the ability to target any genetic correction anywhere within the human genome. This is a sample of our proprietary toolbox. It covers a wide variety of technologies. On the left, you see our nucleases, base editors, and RIGs. These are for our smaller genetic corrections, up to 100 base pairs.
And then on the right, you see our large RIGs and Cas, and these are for much more significant, very large genome corrections. Starting in detail with our programmable nucleases, these are systems that are able to do knockdowns, knockins, exon skipping. We use them to do very precise gene editing within the genome, and this is an advantage of our systems versus CRISPR-Cas9. We also have uniquely small systems called SMARTs, another advantage of our systems because they are so small, which gives us this ability to increase our targeting. These tools provide a chassis for us, and we build upon this chassis to develop the remaining tools in our toolbox.
So for example, our next tool, which is base editors, we build upon the programmable nucleases, and then we add on a deaminase, which we get from our metagenomics database. Putting these two together, we have the ability to do single nucleotide changes. We have some of the smallest systems in the industry with the potential to make the most specific edits. We then move on to our RIG systems, which are for larger genome editing. With our RIGs, we have been able to show a nine hundred base pair integration, and then with our Cas, which are our largest systems, we have been able to show editing in human cells. We have several partnerships at Metagenomi. The first of those is with Ionis. This is for in vivo gene editing, focused on cardiometabolic diseases.
Within our Ionis partnership, we have up to eight targets, with four of those targets in the first wave and four of those targets in the second wave. When we achieve the second wave and unlock the second four targets, each of those comes with up to a $30 million payment. The Ionis collaboration brought in $80 million for us historically and has the potential for $2.9 billion in potential milestones and royalties. We then move on to our Affini-T collaboration. As opposed to Ionis, which is in vivo gene editing, our Affini-T collaboration is ex vivo, focused on immuno-oncology cell therapies, and here we have the potential to receive options, milestones, and royalties.
Overall, in addition to our existing partnerships, we continue to look for additional partnerships, focused on finding partners that can help us move our medicines into the clinic quickly, bringing development capabilities, complementary technologies, market presence, compatible vision. We are focused on fiscal responsibility, and what that means is that we can't, as Metagenomi, develop all of our programs on our own. So specifically, in the second quarter, we announced that for our PH1 program, we would be looking for a partner. This is a program where we had beautiful preclinical proof-of-concept data in a PH1 disease model. We've also announced in Q2 that we will look for partners in ex vivo gene editing. We will stay focused primarily or focused specifically on in vivo for our holome platform, and be looking for partners, in particular, in the ex vivo area, including multiplex cell editing.
This is our pipeline, and before I get into the pipeline, just a little bit of background about how we selected the programs in our pipeline. In particular, we are focused on programs that have disease biology that is compelling to us, where there's a readily available biomarker, where there's a clear development pathway, and where there is a significant unmet medical need. We are also starting with programs in the liver. This is because we have the tools and delivery technologies that are readily available now to go into the liver. Over time, we build upon those tools with programs in exhepatic indications. Specifically, as I talk about Hemophilia A, our lead wholly-owned program, I want to reference that we achieved 12-month durability in non-human primates, and my colleague here, Dr.
Sarah Nuermann will speak more about the recent data that we disclosed. This is a large gene integration in a Hem A program, and we are planning to use this MGX001 platform, so the development candidate that we declared is MGX001. We plan to use this as a development platform for additional targets in secreted protein disorders. Moving on from there, to our Ionis programs, we have four collaboration programs with Ionis. The two that we have announced in transthyretin amyloidosis and refractory hypertension, targeting the AGT pathway, as well as two that are not disclosed. All of these programs are currently in lead optimization, which illustrates our ability to translate our tools into programs that are marching toward the clinic.
We move from our Ionis programs into additional programs in alpha-1 antitrypsin and Wilson's disease, focused on small gene corrections and large gene integration in the liver, and then from there, we go on to programs outside the liver, including neuromuscular and lung and kidney. At the same time, as I mentioned previously, we have got partners in the area of cell therapy, specifically our partnership with Affinity. There, we achieved a milestone, which we announced in the second quarter, relative to supporting Affinity's regulatory filing. We are also supplying materials to Affinity at cGMP standards.
So our milestones for the second half of 2024, in particular, we just did confirm our 12-month durability, and now we will initiate for our Hemophilia A program manufacturing, IND-enabling manufacturing, as well as moving into activities to support our IND in 2026. Relative to our Ionis programs, we plan to demonstrate in vivo proof of concept, supporting our development candidates in 2024, second half, and then moving into 2025, nominate at least one to two development candidates. And then relative to other therapeutic programs, we plan to present multiplex base editing data at a scientific conference in the second half of the year. And then just a little bit about our technology innovations, which continue.
We are continuing to focus on our compact systems, our RIGs, and our Cas systems, with the plan that we will move into in vivo in these systems, in twenty twenty-five and beyond. I'll now turn the presentation to Dr. Sarah Nuermann to talk through our Hemophilia A data.
Thank you, Pam, and it's a pleasure to be here to provide an update on our Hemophilia A program, where we have made tremendous strides toward achieving a single, truly curative approach for adults and children with this disease. And Hemophilia needs very little background introduction. Just briefly, it's the most common X-linked bleeding disorder, arises from the loss of functional Factor VIII from the bleeding and clotting cascade. While intracranial bleeding is the most severe manifestation, the main clinical concern is lifelong bleeding into joints, which, despite improvements in the standard of care, continues to lead to cumulative joint damage. And importantly, there's a really strong correlation between the levels of Factor VIII activity in the blood and your risk of joint bleeding, and that's shown to the graph in the upper left.
And as you get toward above 10-15 IU per deciliter, which equates to 10%-15% of normal, that bleeding phenotype really diminishes, and that sets an important therapeutic benchmark for curative therapeutics. So, despite the improvements in the standard of care for hemophilia, there remains a desire and a strong push from the hemophilia community for a cure. Recent advances in extended Factor VIII half-life recombinant products and Factor VIII mimetics have really improved burden of therapy and improved trough levels. More recently, the first Factor VIII gene therapy, Roctavian, was approved, and this is only approved for adults with hemophilia, being an episomal gene-edited or gene therapy program, which risks dilution over time. And unfortunately, the clinical data failed to demonstrate durability, so that's only a temporary cure.
Our goal is a permanent one-time cure for both adults and children with hemophilia, and really build upon the progress that's been made over the past 50 years. So our approach for gene editing, we've recently had a major milestone in declaring our first development candidate, which we call MGX001. And MGX001 is a two-component system. A lipid nanoparticle delivers a nuclease. It's a novel nuclease from our metagenomics toolbox that creates an efficient and highly specific cut site at a safe harbor locus in the genome, and that's within the first intron of albumin 1. And then, an AAV delivers a promoterless Factor VIII donor template that's then inserted, and integration occurs by normal DNA repair mechanisms.
Importantly, the strength and constitutive nature of the albumin promoter leads to therapeutically relevant and high levels of factor VIII, despite relatively low integration rates, so that you don't impact albumin levels. I wanna emphasize that gene editing is mechanistically distinct from gene therapy in two important ways, and both of these ways are meant to address the decline in durability seen with Roctavian. First, the gene-edited approach is integrated rather than episomal, so as cells divide, the gene replicates along with those cells, as opposed to gets diluted. Our gene-editing approach uses a native promoter in its natural chromosomal context, rather than a synthetic exogenous promoter, which can trigger cellular mechanisms to induce transcriptional silencing. Both of these differences were meant to address the main limitations seen with AAV-based gene therapies.
Now I'm gonna go into some really exciting data that we recently disclosed. This is a preclinical non-human primate study, where we tested our investigational gene-editing approach in three non-human primates and followed them for a 12-month period, and each of the animals is indicated in a different color. What we were really pleased to see, that was across 12 months, we saw the Factor VIII levels did not decrease over time, and that in two of the three animals, we achieved normal or near normal Factor VIII levels, so 81% and 41% in two animals of normal, again, putting them in the normal to near normal range, the third animal achieving Factor VIII levels in the mild hemophilia range, roughly 9% at 12 months.
If you look at mean values between 3-6 months and 9-12 months, they're highly comparable. Again, underscoring that durability that's so critical for a true cure. We were also really pleased with the safety data that we saw in this non-human primate study, and I'll summarize by saying that the only notable findings were transient and moderate elevations of transaminases, or ALT or AST, seen shortly after treatment administration that did not recur over time. There were no changes in total bilirubin levels, and as expected from the low integration rates, we only saw minimal changes right at the beginning of albumin, just reflecting of inflammation, and then levels remained stable over time. So again, these animals are now being followed over 12 months now. They've had no clinical observations.
They appear healthy and continue to gain weight as expected. So now, moving toward plans for the clinic, this was our very first non-human primate study, and we've continued to make optimizations and really look to create a development candidate that can be differentiated in the clinic. And these optimizations can fall into two categories: those that enhance efficacy and those that are meant to enhance safety. And I won't touch on all of them, but just point out a few. We're using a type five nuclease to make the highly efficient cut site, and a type five nuclease has inherent increased specificity over CRISPR-Cas9 or type two systems. We've optimized the mRNA of our nuclease to enhance nuclear localization and expression, and also, we are using a bioengineered B-domain-deleted variant for factor VIII to enhance factor VIII activity levels.
On the safety side, we've performed orthogonal specificity analyses, as outlined by the FDA guidance document, and to date, have seen no off-target editing. Our delivery components were optimized to minimize on-target editing at safe harbor locus sites outside of the liver. And all of our enhancements made for enhancing potency are going to have important safety implications because they will allow us to reduce the dose of AAV and LNP. So to summarize where we are now and where we're going, we have now performed multiple rodent and non-human primate studies that demonstrate integration and expression of Factor VIII at therapeutically relevant levels, and this includes with our development candidate for human Factor VIII. We've engaged with the FDA at an INTERACT meeting, and we feel like we have a clear understanding of the roadmap to an IND and first-in-human studies.
We've broadened our community of experts in the hemophilia space. We've held multiple clinical advisory boards internationally, and we've initiated GLP and GMP manufacturing to support our IND-enabling studies and ultimately our clinical manufacturing, and material supply. So, moving forward, we're gonna continue to follow these animals for up to two years. So future updates, you'll see that are meant to show continued durability. We'll be performing dose-response studies in non-human primates to define the minimally effective dose of AAV and LNP, continue to engage regulators as well as international key opinion leaders and advocacy groups, and as well our manufacturing efforts. So, a really exciting time for our hemophilia program, and it is well on our way. We continue to feel confident about our guidance and having an IND in 2026.
I'll just summarize that our Hemophilia A program is a great example of how we rapidly harness the power of our metagenomics toolbox to create truly curative therapeutics. This is just one of a number of programs in our pipeline that are advancing quickly. We have multiple programs that are moving ahead with Ionis, and we look forward to providing future updates. Thank you for your time and attention.
Thank you, both Sarah and Pam. It's a very exciting story, and we're very happy to be able to follow it with you guys. Unfortunately, we do not have time for questions in this session, but I'm sure that the Metagenomi team would be happy to answer any of your questions if you can chase them down at the conference. Otherwise, you can also submit questions online. Thank you, guys.