Good morning and welcome to Beam Therapeutics' conference call. At this time, all participants are in listen-only mode. There will be a question andanswer session at the end. Please be advised that this call is being recorded at Beam's request. I would now like to turn the call over to Holly Manning, Vice President of Investor Relations and External Communications.
Thank you, Operator. Good morning, everyone, and welcome to Beam's conference call to review initial clinical data for the phase I/II t rial of BEAM-302 in patients with alpha-1 antitrypsin deficiency. You can access Slides for today's call by going to the Investor section of our website, beamtx.com. With me on the call today with prepared remarks are John Evans, our Chief Executive Officer, Dr. Giuseppe Ciaramella, our President, and Dr. Amy Simon, our Chief Medical Officer. Our Chief Financial Officer, Sravan K. Emany, will join for Q&A. Before we get started, I would like to remind everyone that some of the statements we make on this call will include forward-looking statements for purposes of the Safe Harbor Provisions under the Private Securities Litigation Reform Act of 1995.
Actual events and results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors, including those set forth in the Risk Factors section of our most recent annual report on Form 10-K and any other filings that we may make with the SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Except as required by law, Beam specifically disclaims any obligation to update or revise any forward-looking statements, even if our views change. With that, I will turn the call over to John.
Thanks, Holly, and good morning, everyone. At Beam, our vision is to provide lifelong cures for patients suffering from serious diseases. We believe that base-editing technology has the potential to enable one-time curative therapies that can bring about a lifelong transformation in the lives of patients, not to mention dramatically reshape treatment and reduce the long-term costs associated with chronic management of diseases.
Today's initial data showing clinical proof of concept for BEAM-302 as a potential treatment for patients with severe alpha-1 antitrypsin deficiency, or AATD, are an important step forward in pursuit of this vision. This is also a milestone for the field of genetic medicine, delivering, to our knowledge, the first-ever genetic correction of a disease-causing mutation in DNA, not just modulating expression of a gene, but rewriting and repairing the genetic code itself. Importantly, we are also building a true platform.
This means that the core elements of our therapies can be reused again and again, and once they are proven to work a first time, we expect to have a higher probability of technical success as we expand to other genes and other diseases over time. Beam's base-editing technology is a next-generation form of CRISPR that allows us to make precise, single-base changes, resulting in predictable edits without the need to make double-stranded breaks in DNA. Through our approach, we aim to reduce or eliminate many of the challenges seen with first-generation CRISPR technology and ultimately enable a superior way to modify genes, leading to entirely new applications for gene editing in a wide range of severe diseases. AATD is a potentially optimal target for base-editing technology for two reasons.
First, if we want to repair the function of a broken gene, we need to avoid making a double-stranded break in DNA because cellular repair disrupts the gene sequence at random and destroys its function. Base-editing's lack of double-stranded breaks allows us to edit directly within the exons, or functional coding sequence, of a gene with the goal of preserving the function and regulation of the gene we are trying to repair. Second, severe AATD is caused almost uniformly by a single point mutation, a one-letter misspelling in the gene, in this case, an A where there should be a G. Fixing this mutation requires precise, predictable, and uniform control of editing outcomes, exactly what our base editors are capable of delivering. Our leadership position in the field of gene editing is underscored by several key elements.
First, our leading base-editing platform now has clinical validation demonstrating proof of concept in three out of three clinical programs with consistent translation from preclinical studies, clearly demonstrating the power of our platform approach. Second, we are strategically deploying this platform toward high-value franchises with assets that we believe have best-in-class potential and indications of major unmet need. Third, we have established a strong track record of rapid execution across our portfolio. Importantly, we have entered a period of multiple anticipated catalysts this year and beyond, driven by the continued progress of our pipeline. Underpinning all of this is our robust financial position, made stronger by this morning's announcement that we have priced a $500 million oversubscribed financing fueled by supportive long-time shareholders as well as key new blue-chip investors.
With proceeds from this raise, along with our $850.7 million in cash, cash equivalents, and marketable securities as of December 31, 2024, our anticipated cash runway extends into 2028. As we have laid out before, given the broad potential of base-editing, it was important for us to strategically focus on areas of unmet need where we believe we can drive significant value creation while also ensuring the greatest impact for patients. Our two core franchises in hematology and liver genetic diseases each feature highly differentiated and potentially best-in-class lead programs. Today, we can now say that clinical proof of concept has been achieved in both areas, first with our potentially best-in-class BEAM-101 ex vivo data in sickle cell disease presented at ASH in December, and now with data from our first-in-class in vivo program, BEAM-302, for the treatment of AATD.
Initial data provide important proof points in two key areas. First, and Amy will dive deeper into the data shortly, today's findings demonstrate the potential of a single treatment with BEAM-302 to correct the most prevalent disease-causing mutation of AATD, leading to dose-dependent increases in total AAT above the protective threshold necessary for clinical benefit at the third dose level. We also show simultaneous lowering of the toxic mutant Z protein. Base-editing outcomes are functional, resulting in corrected M protein levels that demonstrate strong inhibition of neutrophil elastase. Most important, we have early evidence of both safety and tolerability across all dose levels to date for BEAM-302, even as we achieve these important therapeutic targets. The second major implication of today's data is at the platform level.
This is Beam's first clinical data for an in vivo base-editing program targeting the liver, and we are very pleased with the early evidence we are seeing for safety, dose responsiveness, and efficacy. As you'll hear from Pino, we have made significant investments in our state-of-the-art LNP capabilities, including formulation, process development, and most recently, GMP manufacturing in our facility in North Carolina. LNP delivery of base-editing will be a cornerstone of our franchise in liver-targeted genetic diseases, and because of our platform approach, today's data suggests that future liver-targeted programs at Beam may enjoy higher probabilities of technical success from this point forward. I'll now turn the call over to Pino to walk through a disease and program overview.
Thank you, John. We asked ourselves this question: What if we could use base-editing to correct disease-causing mutations in vivo? Today, we're pleased to share with you that we have done just that, a first for Beam and for genetic medicines. Alpha-1 antitrypsin deficiency, or AATD, is a serious genetic disorder caused by mutations in the SERPINA1 gene, which affects the production of alpha-1 antitrypsin, or AAT, a protein made in the liver that is secreted into the bloodstream to protect the lungs from inflammation and damage. The most common severe form of AATD results from mutations in the Z allele, known as PIZ, which is caused by a single G to A point mutation in the SERPINA1 gene. This results in the expression of the pathogenic PIZ variant of AAT, known as Z-AAT, that misfolds and aggregates inside liver cells rather than being secreted.
The Z-AAT that is made in the liver is poorly secreted into circulation and less effective in inhibiting neutrophil elastase, leading to total circulating levels of AAT that are 10%-15% of normal in homozygous individuals. As a consequence, the lung is left unprotected from neutrophil elastase and other damaging proteases that can cause progressive destructive changes in the lung, resulting in, among other things, early-onset emphysema. The accumulation of Z-AAT protein aggregates in the liver can cause liver inflammation, hepatocyte injury, and cirrhosis. The PIZ genotype accounts for over 95% of severe AAT cases, and despite affecting more than 100,000 individuals in the U.S., only about 10% of people living with this disease have been diagnosed. As shown on Slide 11, the figures on the left reflect the gradation of AAT levels and disease manifestations across individuals by genotype.
Patients with severe AATD, known as the PIZ genotype, have two copies of the disease-causing mutation, leading to a high risk of developing both progressive emphysema and liver disease. These patients have very low levels of AAT, between 3-7 micromolar, shown in orange, and all of it is the mutant Z-AAT form, which is much less effective. In the middle are individuals with just one mutant PIZ copy, and these individuals do not have disease. At most, they may have low risk for developing either lung or liver disease, but only if they are exposed to other injurious factors such as smoking or obesity. Why is this information important? Because these genotype characteristics help define what the critical goalposts are for an efficacious AATD treatment.
First and foremost, a therapeutic needs to increase total AAT above the protective threshold of 11 micromolar, which is the threshold for AAT levels of people carrying just one copy of the disease-causing Z allele, who do not have progressive AATD. This threshold was also clinically accepted as the basis of augmentation of proof. Second, a therapeutic that can treat the full spectrum of AATD disease manifestations must reduce mutant Z-AAT levels that aggregate in the liver and blood to prevent ongoing organ damage. Finally, AAT needs to be available in a dynamic manner, meaning that during periods of inflammation or infection, AAT levels increase in order to combat lung destruction from adipose proteases generated from inflammatory cells such as neutrophil elastase. This is not possible with existing therapies.
The current standard of care for AATD for patients with lung disease primarily consists of treatment for emphysema, including bronchodilators, inhaled steroids, and oxygen therapy. The only approved treatment today, plasma-derived AAT augmentation therapy, requires weekly intravenous infusions. While it has been shown to slow the lung disease progression, it does not stop it, nor does it prevent ongoing liver damage. Treatment for liver disease is limited to supportive care, as there are currently no approved therapies. In severe cases, liver transplantation remains the only option. Consequently, there is a significant unmet need for new disease-modifying treatments that are effective in treating both the lung and liver disease manifestations of AATD. As John mentioned earlier, the PIZ form of AATD is caused by a single-letter misspelling, where there is an A instead of a G.
BEAM-302 is a potential one-time therapy designed to directly correct this misspelling through the elegance and precision of base editing. BEAM-302 is comprised of a messenger RNA encoding an adenine base editor and the guide RNA targeting the Z mutation on the SERPINA1 gene, encapsulated into a lipid nanoparticle, or LNP for short. The advantages of LNPs as a delivery mechanism for liver genetic diseases are multiple. They can be dosed in an outpatient or even the home setting via an IV infusion. They are titratable and reducible if necessary and benefit from a synthetic and highly scalable manufacturing process. Once optimized, LNPs provide a predictable and reproducible platform for both tolerability and dose projection. LNPs also offer the benefit of being low cost.
At Beam, we have built significant expertise in LNP optimization of both internally developed and externally sourced lipids and have internal GMP capabilities to manufacture at scale LNPs that demonstrate high levels of tolerability and potency in preclinical studies. In summary, BEAM-302 represents a potential breakthrough in the treatment of AATD, addressing both lung and liver manifestations of the disease with a one-time durable solution. By correcting the underlying DNA mutation, BEAM-302 aims to restore normal AAT production at its most proximal point, leading to increased circulating and functional AAT to prevent lung damage while also decreasing toxic Z-AAT in the liver and circulation to reduce organ injury in both the liver and the lung.
BEAM-302 also has the potential to restore physiologic control of AAT, enabling the body to naturally produce corrected M-AAT from the endogenous gene under the regulation of its own promoter, potentially enabling an increase in AAT levels during the acute phase response when the body needs it most, such as during infections. We have previously shown the potential of this approach in our preclinical studies, where administration of BEAM-302 led to increases in total AAT, production of corrected M-AAT, and decreases in mutant Z-AAT. Importantly, the increase in total AAT was accompanied by increases in functional AAT. All of these findings have now been replicated in our clinical trial, which Amy will review now. Amy?
Thank you, Pino. The phase I/II trial of BEAM-302 is designed to establish clinical proof of concept across the full spectrum of AATD disease manifestations. The study is structured in two parts. Part A includes patients with lung disease to establish an understanding of the safety of LNP delivery in patients without clinically evident liver disease, followed by Part B, which will include patients with mild to moderate liver disease with or without AATD-associated lung disease. The trial includes dose exploration phases with up to four dose escalation cohorts in each group, followed by dose expansion. Our goal is to assess early safety and efficacy while identifying the optimal biologic dose for further development. The study has received CTA clearances in four countries to date, with ongoing global site activation and enrollment actively underway.
Today's initial clinical data are from nine adult patients in three dose escalation cohorts in Part A of the trial. We evaluated single ascending fixed doses of 15 mg, 30 mg, and 60 mg of BEAM-302, with three patients in each cohort. We have an additional fourth cohort planned as part of the ascending dose explorations. Key eligibility criteria for Part A required that patients are homozygous for the PIZ mutation with evidence of emphysema and no evidence of liver disease. Shown here are patient demographics across cohorts. We enrolled a mix of males and females, and most patients were in their late 40s or 50s, which is typically when this disease is diagnosed. Baseline FEV1 % predicted levels are consistent with moderate emphysema.
Mean baseline AAT levels were between 4.4 and 5.3 micromolar, with ZZ patients, as mentioned by Pino, typically having levels ranging from 3-7 micromolar. Turning to safety, the preliminary data indicate that BEAM-302 was well tolerated across all dose levels evaluated, with no serious adverse events, dose-limiting toxicities, or Grade 3 or higher adverse events. All treatment-emergent adverse events were mild to moderate. Grade 1 asymptomatic elevations in ALC and AST were seen in all of the cohorts and did not require intervention. Further details will be presented on the next Slide. Three patients had mild infusion-related reactions that resolved without infusion interruption or intervention and did not appear dose responsive. With LNP delivery, we expect some impact on liver transaminases as we increase the dose, as has been seen with other lipid nanoparticles in clinic.
We were pleased to see that ALT and AST elevations were at most Grade 1 and, importantly, were asymptomatic and did not require intervention. In addition, bilirubin levels remained within the normal range or at baseline across all patients and dose levels. Turning to efficacy, treatment with BEAM-302 led to a dose-responsive increase in total AAT in circulation, as measured by a turbidimetry assay. At day 28, mean total AAT in circulation was 12.4 micromolar for the three patients treated with 60 mg of BEAM-302, exceeding the therapeutic threshold of 11 micromolar. Each patient in this cohort reached levels of greater than 11 micromolar. As you can see, the increase in total AAT was rapid, with peak levels occurring around day 14-21.
In a moment, we'll show on another slide that these elevated levels remain durable, with the longest duration to date being six months of follow-up in the 15 mg cohort. As shown here, we also assessed the fold change in total AAT in circulation for each patient from their own baseline, and we observed an even more dramatic dose response curve with tighter error bars. In the table on the right, you can see that the mean baseline AAT levels for the 60 mg cohort are on the lower end at 4.4 micromolar as compared to 5.3 for cohort 2, with the mean fold change in cohort 3 of 2.8x. BEAM-302 was designed to increase total AAT by inducing production of corrected M-AAT while at the same time driving down mutant Z-AAT.
What we have shown here using an LC-MS assay is that it did just that across all dose levels. Following treatment with BEAM-302, corrected M-AAT was produced in circulation of these patients for the first time ever in a rapid manner, occurring within three days. In the 60 milligram cohort, corrected M-AAT levels reached up to 88% at day 14, the farthest time point available, with data from an LC-MS assay for patients in this cohort. This is a similar AAT profile to what is seen in people with the MZ genotype who have 80% M-AAT and 20% Z-AAT in circulation and do not have disease unless there is a second injurious insult. While MZ individuals have cells that are comprised of 50% M alleles and 50% Z alleles, due to protein misfolding, only a fraction of the Z-AAT protein is secreted into the blood.
Shown another way, here we outline percent change in mutant Z-AAT levels from baseline. The graph on the left demonstrates rapid and dose-dependent decreases in Z-AAT in the circulation. At the highest dose level, Z-AAT levels were reduced up to 78% following treatment with BEAM-302. This illustrates the dual mode of action of BEAM-302, on the one hand, increasing total AAT through the production of corrected M-AAT, while on the other hand, significantly reducing the production of mutant Z protein, which is known to result in toxicity to the liver and to the lungs. Slide 27 puts all the pieces together and confirms that these changes in AAT were durable across both cohorts, where we have more than one month of follow-up. The dose-dependent increases in total AAT are shown in blue, reduction in mutant Z-AAT in orange, and increases in corrected M-AAT in green.
Importantly, in addition to correcting AAT, we also wanted to assess whether the new corrected M-AAT protein created by base editing was functional. Shown here, we demonstrated that all of the increase in total AAT in circulation after treatment with BEAM-302 was also functional AAT in the neutrophil elastase inhibition assay. At the highest dose of 60 mg, the functional and total AAT amounts are superimposable, as the Z-AAT levels are markedly reduced. Additionally, not shown here, increased total AAT in circulation was also found to be functional in a neutrophil elastase binding assay. Restoring higher levels of functional AAT is another important marker to determine whether BEAM-302 has the potential to successfully address the underlying causes of AATD disease.
In summary, we're encouraged by these emerging BEAM-302 clinical data, which we believe are consistent with our preclinical findings and demonstrate the potential for differentiation as a one-time treatment for AATD that could impact both the lung and liver manifestations of the disease. These initial data demonstrate that BEAM-302 was well tolerated with an acceptable safety profile at all doses tested to date. A single dose of BEAM-302 led to durable dose-dependent correction of the PIZ mutation. This was demonstrated by increases in total AAT above the therapeutic threshold of 11 micromolar, production of corrected M-AAT in the circulation for the first time, and decreased mutant Z-AAT up to 78%. Notably, the ratio of M and Z proteins in circulation was similar to that seen in the MZ genotype, people who do not have disease and have just one copy of the mutant Z allele.
Finally, the increased total AAT was functional by both neutrophil elastase inhibition and neutrophil elastase binding assays. These results mark a significant milestone in our mission to develop a novel one-time treatment for AATD that addresses the root cause of the disease, and we look forward to advancing BEAM-302 towards the next phase of development. With today's findings, we're focused on continuing dose escalation in Part A of the trial, for which we plan to present updated data at a medical conference in the second half of this year.
We also expect to initiate the dose exploration portion of Part B in patients with mild to moderate AATD-associated liver disease in the second half of the year. Taken together, we aim to establish the optimal dosing regimen to take into a potential registrational study for BEAM-302. Finally, we will be looking to expand the clinical site network for the program, including opening BEAM-302 in the United States, as we look forward to accelerate development of BEAM-302 for patients with AATD. With that, I will turn the call back over to John.
Thanks, Amy. As you can see, we believe that this early data set already shows BEAM-302 achieving the ideal target product profile that Pino outlined earlier, including correction at the root cause of the disease with normal physiologic regulation because we are repairing the gene itself, increase of total AAT above the therapeutic threshold, significant decrease in mutant Z protein, and durable effects after a single administration of drug. The strength of this early data set strongly suggests that BEAM-302 has the potential to be a transformative one-time treatment for AATD, including both lung and liver manifestations. As Amy outlined, we plan to continue phase one dose escalation and expansion, but in parallel, we are already planning for the further expansion and acceleration of the overall development program for BEAM-302.
In addition to the exciting path forward for BEAM-302 and AATD, this data set also has significant implications more generally for genetic medicine and Beam. First, this again marks a major milestone in genetic medicine, as base editing achieves the first-ever genetic correction of a disease-causing DNA mutation. Previously, gene editing has turned genes on or off. Now, we are rewriting and repairing them, outcomes that were not achievable with earlier technologies. We expect to pursue more highly differentiated editing applications in the future. In addition, for Beam, these results meaningfully de-risk our in vivo LNP capabilities, showing that we have the ability to deliver base editing to the liver and supporting the further expansion of this platform for future liver programs. We look forward to giving more visibility into the growth of our liver pipeline in the future, an important strategic driver for the company.
Finally, these findings validate Beam's strong track record in drug discovery, preclinical development, and clinical translation. We now have delivered clinical proof of concept for three out of three programs that are in line with our preclinical studies. As we look ahead to the rest of the year, 2025 is shaping up to be a milestone-rich period for Beam, with multiple value-driving catalysts on the horizon across our growing clinical portfolio. We plan to rapidly advance the BEAM-302 program, as Amy outlined, continue the pace of dosing in the BEACON trial to meet our target of 30 patients dosed by mid-year, with plans to share updated data for that program as well by mid-year, initiate dosing for our second in vivo program, BEAM-302 for GSD1A imminently, and progress our ESCAPE program to a healthy volunteer study by year-end.
To close, at Beam, everything we do is driven by our commitment to patients. The promise of base editing is not just about innovation. It's about transforming lives, and we are deeply committed to our vision of developing one-time life-changing therapies for patients. I'd like to thank the entire Beam team for their tireless efforts and exceptional teamwork in advancing this program from inception to today. I'd also like to acknowledge that these findings today would not be possible were it not for the individuals whose lives we aim to change, people living with AATD. We'd like to thank all of our partners, including the investigators, the clinical site staff, our clinical research and manufacturing partners, the Alpha-1 Foundation and other advocacy organizations around the world, and above all, each of the patients and caregivers who have taken part in our trials and made today possible. Operator, please open the line for Q&A.
Thank you. If you'd like to ask a question, please press star one one . If your question has been answered and you'd like to remove yourself from the queue, please press star one one again. Our first question comes from Kostas Biliouris with BMO Capital Markets. Your line is open.
Good morning, everyone. Congrats on the strong data. A question from us on the highest alpha-1 antitrypsin levels you can achieve. We know you have one more cohort to evaluate, and you have previously mentioned that the highest dose you will probably want to test is one mg/kg, which corresponds to 75 mg. My first question is, is that still the case? Is 75 mg the highest dose you would want to evaluate? If so, how are you thinking about the dose response, Kev? How much additional AAT do you think these 75 mg can offer on top of the 12.4? Thank you very much.
Sure. Thanks, Costas. Maybe to talk about the dose escalation, I'll ask Amy to weigh in on that, and we can talk more about levels.
Sure. We're not guiding to the exact dose. We still have to meet with our safety review committee and get approval. However, we do think it will not be to the gradation that you've seen in the prior doses of a twofold increase. We think more like a 20%-30% increase, given that we're on the steep portion of the dose response curve now. We do have that optionality in cohort four to go up. We also have the optionality to explore more patients at the 60 mg dose as well, because we think we're seeing a great response there.
Yep. In terms of how high we can go, I mean, a couple of comments. One, the 60 mg cohort actually has a relatively low baseline if you look at it. Those patients are on the low end. If we believe in the full change data that we presented of that 2.8x increase, patients who are more in the 5, 6 range would already be delivering higher levels. I think we're in a really good place already. Nonetheless, we have that additional dose escalation. I think the totality of data really suggests that we're getting patients to that MZ genotype range, particularly if you look at the proportion of M and Z in circulation. That's already, we think, a therapeutic zone. Quite happy to see this, of course, the trial continues and more to come.
Thank you. Our next question comes from Rick Bienkowski with Cantor Fitzgerald. Your line is open.
Hey, good morning, everyone. Congrats on the really impressive data. I just have a couple of questions. First, do you have a sense of how the reduction in Z protein in the serum correlates to the levels of Z protein in the liver? I'm just trying to think through what the reduction in Z protein in the serum could mean for the treatment of liver disease. My second question is just thinking about the next steps for the program. I guess, first off, it sounds like recruitment hasn't started yet for the fourth dose. Could you just walk us through any rate-limiting steps for recruitment and dosing into the cohort? Also, will the currently active clinical sites be sufficient for the dosing of cohort four, or is this dependent on expanding the number of clinical sites?
Great. Let me have Pino then, Amy.
Yeah. In terms of sort of recruitment, Amy's kind of covering the recruitment. You do go first, Amy.
In terms of recruitment, we've opened up multiple sites in multiple countries already and have had really an incredible enthusiasm, both by the patients as well as the sites. We already have patients in line both for the next cohort in Part A as well as, believe it or not, for Part B. That should not slow us down at all. We've had a ton of enthusiasm for the trial. We continue to open more sites, and as mentioned in the presentation, we'll come to the U.S. sometime this year as well.
Yeah. Rick, coming back to your original questions around what does it mean in the liver in terms of the reduction. Of course, we do not have liver biopsy yet in order to confirm that. We plan to have those when we do the Part B part of the study. However, we do believe that what you're seeing in circulation is a very strong surrogate for what you're expected to see in the liver. That is, as you know, in DNA repairing, as we are doing now, we're literally converting the Z gene into an M gene. It is really a one-to-one direct correction of Z to M. We would expect to see a significant reduction in the liver, frankly, like we've seen in preclinical studies as well. Yeah, that's pretty strong evidence that we were able to potentially affect both the lung by increasing the circulating levels as well as the liver by reducing Z significantly.
All right. Excellent. Thanks for taking the question, and congrats again.
Thank you.
Thank you. Our next question comes from Yanan Zhu with Wells Fargo Securities. Your line is open.
Oh, great. Thanks for taking our questions, and congrats on the very exciting data here. Just wanted to maybe ask about, I think, Amy, you mentioned there's a 20%-30% increase in the fourth dose. At this level, current dose level, we see roughly MZ genotype-like distribution of M and Z. I was wondering, for the next dose, what kind of AAT level could we expect? You did mention you were in a steep part of the dose response curve, and the data does seem to suggest that. I guess what I'm asking is, could the next dose level give us an AAT level that's between MZ and is that part of the aspiration here? Thank you.
Thank you. I mean, I think part of why we do this type of study is to understand the safety and efficacy of the drug completely before we take it forward for optimal biologic dose. While we think we already have a drug here, where, as you've indicated, we're at the MZ levels, we do think it's worth exploring another dose given how safe it actually has been to date. With that, to your point, being on the steep portion of the dose response curve, if we think about the 3x increase now and a range of Alpha-1 levels of anywhere from 3-7, you could argue that we're anywhere from what we've seen, 12, all the way up to as high as 18 right now.
Going up one more dose, if we are in the steep portion and we happen to be lucky enough to get a four-fold increase, we can do the math again on that and say that, let's say, a four or five-fold increase, you'd be in the normal range. I think it's exciting to think about, and we'll understand a little bit more about both the 60 mg dose as well as about the cohort four dose, because I think we really want to get real deep understanding about both the safety and efficacy of them before we decide what our doses could go forward. Keep in mind, we'll be treating both patients across the spectrum of Alpha-1. We want one dose for patients who have liver and lung disease.
Got it. Got it. If you could also comment on the second half data readout, would we be able to see the fourth dose cohort data? If so, roughly, what is the scope of that data? Thank you.
Yeah. We haven't guided to the shape of that data set yet. I think that now that we are, of course, disclosing this data, I think you can see it clearly, you can have a sense that there will be more regular cadence of updates out of this trial, the first one being in the second half of the year. We'll give more guidance to that. All that said, I think, as Amy said, enrollment here has been really quite swift. We have a great clinical site network, very enthusiastic patients and physicians, and it's a large population from which it's relatively easy to draw patients. I certainly think that the next steps in Part A, kicking off Part B, we do expect those to happen efficiently and look forward to giving another data update later this year.
Great. Thanks for the coloring. Congrats again.
Thank you. Our next question comes from Gena Wang with Barclays. Your line is open.
Thank you for taking my questions. Also, congrats on the great data. Maybe follow up on a previous question. When we look at the total protein level from 15, sorry, from 30 mg to 60 mg, we only saw 2 micromolar improvements. What will make you feel confident you could reach like 18 micromolar by only increasing, say, 10%-20%, what you mentioned, like 20%-30%? That is a rough calculation, about 75 mg. What will make you feel confident that you could reach 18 micromolar?
What matters more in terms of total protein or M protein? With current follow-up, do you expect to further increase for the M protein with the longer follow-up data? Quickly, I'm sorry, it is a little question on the data point. For the M protein level, let me look at the slides. You did show Slide 25. One patient at day 14, you did show meaningful improvement from day 7, 68%- 88%. And that number of patients is from three to one. Do you expect the remaining two patients also reach similar level, close to 80% or 90% level?
Great. Thank you, Gena. All right. I'll go through that. I know there's a lot in here, so there's a lot to dig into. First, just on the point about the 2.5 micromolar change from 3 to 60. I think that's where, again, we point to the full change relative to baseline. I think that the baseline of these patients is going to vary, and you're doing small Ns here. The middle cohort has a higher baseline than the third cohort. If you look at the slide that shows the dose response by full change, rather than just the absolute amounts, it sort of corrects for variations in the baseline. I think you see that the difference from 30 to 60 is quite significant, right? You went from a 90% improvement in AAT to a 2.8x improvement.
I think that's one point. In terms of what's more important, total versus M, I mean, I think the reality is that the high-dose cohort were effectively converting the vast majority of the circulating protein to M. I think they actually converge. We certainly think getting rid of as much Z as possible, both in the liver and systemically, is really important, and it's an important mode of action of this drug. I think we don't need to choose. We're going to be able to get both. Let me ask Pino a little bit to talk about any reasons why this may increase over time.
Yeah. Yeah, Gena, and as you've seen from preclinical data that we've generated, but also many others have done, there is certainly evidence in rodents that over time, you will see a survival advantage of the edited cells, leading to actually a significant increase in percent editing and also cells that are producing M as opposed to Z. In human, there is turnover of the liver. It typically is slower. It takes about a year to manifest itself. There is this possibility that you've seen it. Obviously, we're still only at the maximum six months of follow-up in the 15. I suspect that if you are able to see that survival advantage, it will probably be more prominent in the highest levels that we can achieve.
It remains to be seen with the 60 mg and maybe even the higher cohort that we're going to see that. Having said that, I really would like to stress one point, which is the total number of AAT is definitely an important factor. Certainly, it's been an important factor in the context of enzyme replacement therapy because that's the only thing that really meaningfully you can manage and measure. However, in what we are doing, which is restoring essentially the function of the gene in its own location, I would really encourage you and others to look at the totality of the data that we've generated, which is not just the alpha-1, but it's really the level of M, as you were pointing out, already 88%. Yes, we do expect the additional patients to go to that 88% plus M relative to Z.
Also the point that if you do the calculation and you look at the reduction by 78% of the Z, if we are starting to the left, it's about 1 micromolar or thereabouts. It is that totality of the data that would suggest that we now put these patients already at an MZ genotype-phenotype, maybe even better, actually, when you look at the M relative to Z. Over time, there is the opportunity to see even an improvement on that. It is really sort of a very therapeutic profile here.
Thank you.
Thank you. Our next question comes from Samantha Semenkow with Citi. Your line is open.
Hi, good morning. Thanks for taking the question, and I'll add my congratulations on the good data. I wonder if you could just speak a little bit to the severity of the disease and the emphysema in the patients you've enrolled thus far. I'm wondering how similar the patient population is to those you would look to enroll in the U.S. Just secondarily, looking forward, what impact do you believe 302 could have on a patient's emphysema post-dosing with longer follow-up? Is it possible to envision you could reverse it over time, or would you expect to more halt the progression of the disease as the treatment goal? Thank you.
Great. Go ahead, Amy.
Yeah, those are great questions. In order to get into a clinical trial, you had to have evidence of emphysema. In addition, you had to have an FEV1 greater than or equal to 45% or above with evidence of obstruction. What you can see by the patients thus far in the study is that their FEV1 % predicted is around 60%. That would be consistent with moderate emphysema. To start, I think that is the right population to include in the sense that you're trying to understand safety and tolerability of a brand new drug. Having said that, you asked whether that would be the same as when we come to the United States, and the answer is yes, that we will have a very similar inclusion-exclusion criteria to what is already out there for the studies being conducted outside the U.S. right now.
It'll be a protocol very similar. As far as another good question that you asked, which is, will we reverse any emphysema? Unfortunately, the lung is not like the liver. While we do anticipate lowering Z overall in the liver and throughout the circulation and increasing M will help the lungs, it will not reverse the destruction that's already occurred, unfortunately, in the lungs. From that perspective, what we would hope to be able to see is that you halt any further destruction of the lung or any further loss of lung tissue as might be seen on CT densitometry.
As far as the liver, there is evidence from other therapeutics, both in the hepatitis C space as well as in RNAi now being administered for alpha-1 antitrypsin deficiency patients in clinical trials, that in fact, you can reverse fibrosis if you remove the offending agent and, frankly, can even reverse aspects of cirrhosis, something we never thought was possible before. I think what this gets at is the point that for the lung disease patients, the earlier we treat them, the better, because once you lose lung tissue, it is gone.
Thank you. Our next question comes from Manny Farooq with Leerink Partners. Your line is open.
Good morning. This is CJ on for Manny. Thanks for taking our question. Congrats on the data. We have two questions. First is, since the corrected SERPINA1 gene is remaining under control of the native promoter, AAT levels should theoretically be upregulated under external stressors such as infection or inflammation, which would be an advantage over RNA editing modalities. Understanding this is early data, did you happen to see any evidence of this at any time point among patients? Our second question is, how should we think about the level of editing efficiency achieved? In other words, what proportion of hepatocytes are edited at each dose level? Thank you.
Great. Great questions. Yes, because we're editing the gene in its normal location, it should turn on when needed. That is the beauty of editing at the DNA level. We will be watching that. It's difficult to catch. You have to catch a patient in a moment of inflammation or infection or crisis, but we'll absolutely be gathering that data over longer-term follow-up here. It is, as you said, I think, an important differentiator and core part of the value proposition of this potential mechanism for these patients to correct the gene at its root cause. In terms of level of editing, we have a lot of speculation. Of course, we haven't done any biopsies yet. I'll let Pino maybe speculate on this.
Yeah. Obviously, as you know, we do not have liver biopsies yet where we could directly measure the editing rates in these hepatocytes. However, we can make some inferences. In particular, I guess the strongest evidence that I can point to and I can sort of think to is the MZ situation. If you think about it, in those patients, you've got one copy of M and one copy of Z. You could roughly speak about 50% editing in that case. Yet, they have about 80% of M in circulation. What we have shown in the data is that we're already at that level. We're actually 88% of M in circulation. Just by extrapolation, one could at least speculate that we have approximately 50% editing in the liver, maybe a little bit more if you think the 88% is a meaningful difference from 80. Yeah, we will see. We will measure it when we get the biopsy in part B.
Okay. Great. Thank you so much.
Thank you. Our next question comes from Michael Yee with Jefferies. Your line is open.
Hi, good morning. Congrats on the data, efficacy, and safety. We had a question as it relates to the liver cohort that I know you want to get started. My view with that is those patients could be at even a higher therapeutic need and greater urgency. I just wanted to think about how that dose escalation would go, how you think the therapeutic effect would look in those patients, and how you think about the overall importance of that cohort. Thank you.
Great. Yeah. Amy, you want to cover that one?
Sure. I mean, we agree with you that there's a huge unmet need, and that's why we're trying to develop a drug that really addresses the spectrum of AATD and not just one or the other. I think it'll be very important as we head into cohort B to understand if the safety that we're seeing with the LNPs is preserved. We have reasons to believe it will be because, as you saw from our slides, we have a very good safety profile to date. We will have to step back to some lower doses now and just kind of do a little bit of a dose escalation in this cohort to understand both the safety and efficacy.
Importantly, we will have a chance to also look at liver biopsies, not frequently, but we will be able to see this prior to being treated and then at time periods of, let's say, six months, similar to what's been done in the RNAi therapeutics. We really anticipate, if you think about what Pino has been saying about carriers who are MZ who have 50/50, they tend not to get liver disease unless there's another hit such as obesity or other things. We think even a 50% reduction, even what we're seeing, what we're speculating, we're seeing now of MZ would be very helpful to these patients. Granted, we want to keep, which is why we're dose escalating, understanding if we can get even higher. We fully agree with you and plan to do really rigorous testing in both of these populations and then go forward with one optimal biologic dose for the entire spectrum of disease.
Great. Thank you.
Thank you. Our next question comes from Eric Joseph with JP Morgan. Your line is open.
Hi, good morning. Let me add my congrats on these data. Maybe just piggybacking from that last question on the outlook in liver disease patients. Amy, you noted sort of wanting to, I guess, for safety reasons, evaluate lower-dose cohorts to start. To the extent, first, I guess I am curious about sort of how sensitive those patients might be to LFTs with this regimen relative to the profile you are showing so far and whether you anticipate any need to kind of proceed with redosing to sort of manage tolerability. Does the protocol in part B allow for redosing of patients? Maybe if I could, with a more forward-looking question, I guess when we think about a pivotal program supporting accelerated approval, how should we think about sort of sizing of a trial there? Would it be an all-encompassing trial for both lung and liver disease patients, or would you sort of take a bifurcated approach? Thank you.
Amy, why don't you start off, and then I'll help you with that.
Sure. As far as tolerability, we do not necessarily know what we are going to see. It is kind of comforting that even in the patients in part A who came in and had high normal or even at times went above the upper limit of normal during their screening samples, when they got LNP, they were not necessarily the ones who had the largest X change from baseline. It is possible that we will see a very similar safety profile. However, we are prepared, as you have indicated, to let's say we go forward and we say we really want to do the 60 mg dose. It is perfect. If we find, for some reason, the tolerability is lesser in that population, we do have optionality in the future to explore split doses should that be necessary. That is a really good point.
We do think that ultimately, we'll be able to safely treat both populations, keeping in mind that this is a one-time treatment, which is very different than having to have continued ongoing treatment with something that could be irritating to the liver. Because as you know, these patients have a liver that's already under a lot of stress. Given the one-time nature of an infusion and possibly, as you mentioned, the split, it would be at most two, I think that we can find a dose that works for the entire spectrum of disease. I think I'll turn it back to John to get a little bit more at the development questions going forward.
Yeah. Thanks, Amy. It's a great question, Eric, and something that's very much on our minds. Obviously, with a dataset like this, with clear proof of concept at a therapeutic level, we're already thinking about how to get this to patients as quickly as possible. That said, there's a lot of work to do and a lot of dialogue to have with regulators and physicians to figure out the best path there. I'm comfortable saying that in our experience as drug developers, we do think that more accelerated options could be appropriate here. We have great biomarkers from total AAT and MAT, functional AAT, reduction of Z, all going in the right directions and telling a coherent story.
Of course, we know the mechanism of the drug is operating on the root cause of disease. In our experience, having that set of attributes does tend to open up the doors to more accelerated approaches. That is for sure what we will be discussing. The first step is to get data like this. We now have it, and now we can begin that work. I think it is too early to speculate on end, so we will have to have those conversations. Again, I think we are more in the precision medicine fast path bucket here with this dataset, which is where we expect it to be.
Okay. Great. Thanks for taking the questions, and congrats again.
Thank you.
Thank you. Our next question comes from Ry Forseth with Guggenheim Securities. Your line is open.
Hi, this is Ry from [audio distortion] team. Two questions from us. Number one, how many of the cohort 3 60-mg patients ended up achieving greater than 11 micromolar AAT by day 28? Number two, we're curious about the liver biopsy and how you will avoid biased measures of editing efficiency and pathological protein given factors such as fibrosis in the liver.
Yeah. These are great questions. Yes, all of the patients in the 60-mg cohort were over 11 micromolar. That is to answer the first part. The second part is we'll be working with gastroenterologists who have extensively done liver biopsies and are aware of some of the limitations and probably will wind up including two separate biopsy areas as a way to kind of help reduce any kind of confounding. Because, as you know, a liver biopsy is probably simply one four-thousandth of the actual liver.
We have been working very closely with the experts in the field now who have worked on alpha-1 associated liver disease for a long time and know kind of what some of the issues are related to biopsies, both from a safety and also just tolerability. On top of that, how can you actually use them in a way that overcomes some of the issues? While it's the gold standard, it has some limitations. Again, we're going to use that expertise. These are people who've been involved in some of the other RNAi therapeutic trials looking at a therapeutic for AAT-associated liver disease.
Maybe if I could add one thing, though, even though it obviously will be very useful to have biopsy data, I think the mechanism of action that we are deploying, which is a direct correction of Z to M, is also a very meaningful, frankly, evidence that basically the liver is being adequately corrected. I think while biopsies are definitely an added data point that we are very keen to generate, I would say that it's not absolutely necessary in order to demonstrate the ability of our treatment to actually correct the liver as well as the lungs.
Thank you. Our next question comes from David Nierengarten with Wedbush Securities. Your line is open.
Hey, thanks for taking the question. I guess continuing on the liver theme, in your animal models and things like that, were there any differences in dosing? I know maybe it's tricky to extrapolate from animal livers or anything like that, but were there any differences in dosing or expression levels in animal models? I don't know if you could isolate the lung from the liver or anything like that to help guide you on dosing in liver patients and expectations around ultimate protein expression levels in those patients. One last question on the liver there.
Yeah. Sure. Maybe I'll take it. Hi, David. It's Pino. Yeah. So pre-clinic, what we've done, we've actually done editing experiments in cirrhotic animals, and we have seen no difference in dose and efficacy levels in that. There is also, I would say, clinical evidence to suggest that actually individuals who have some liver involvement do respond well, just like normal to LNPs, onpatro as evidence of that in many patients now. I know that Amy has done some work in Porphyria in the past and also seen that. Obviously, we will not know until we have that data in our hands, but there is good pre-data, if you will, both pre-clinically and clinical, to suggest that we should be able to see very similar responses in those individuals.
Okay. Thanks.
Thank you. Our next question comes from Sami Corwin with William Blair. Your line is open.
Hi there. I'm going to share my congrats as well on this great data. There's been a couple of questions on liver biopsies, but I was actually curious if you plan on conducting any kind of bronchoscopies and looking at AAT diffusion into the lung as well as neutrophil elastase activity there. I was also curious if you could share any additional detail on early discussions with FDA and if they've seen this data yet. Thank you.
Great. Maybe I'll ask Amy, our resident pulmonologist, to answer the first question, and then maybe Pino, you can talk about some of the FDA interactions with them.
Great. Great question. We do know that all of the circulating AAT should get into the lung. However, your point is well taken. Once we get to the optimal biologic dose, we will have a cohort of patients at a couple of sites that have expertise in doing bronchoscopy in patients with AATD-associated emphysema because it is not a trivial process. We will have those samples to confirm that what we are seeing in circulation, the increase, also translates to an increase in functional AAT in the lungs as well, where it is most needed.
In terms of interactions with the FDA in particular, obviously, we've interacted with other regulators already in New Zealand, in Australia, in the Netherlands, very recently also with Ireland. We have had a pre-IND with the FDA. It was actually pretty successful. We now understand essentially what we need to see. Remember, we also have an open IND with our 301 program. Really no major differences between that. Importantly, they've also not shut down the door to an accelerated approval on the basis of biomarker data that we generate.
Of course, the FDA will never commit to anything until you give them a pretty robust data package to be able to opine upon, and we definitely plan to do that. We're really hopeful to be able to make that argument to them. If anything, I think by going and repairing the gene on it at its site, I think we have the most scientifically cogent argument to be able to justify that.
Great. Thank you.
Thank you. Our next question comes from William Pickering with Bernstein. Your line is open.
Hi, good morning. Congrats on the data, and thank you for taking my question. I also had a question on redosing. Is that something that you could explore to maximize efficacy, for example, with two 60-mg doses rather than just a way to think about splitting for tolerability purposes? Another question on the FDA, what data would you want to have in hand before you would engage with them on the path to registration? Thank you.
Great. Why don't we do Pino on redosing and then Amy on data in hand?
Yeah. Redosing is certainly an option with LNP. That's why we like LNPs as an opportunity. We will explore it at least in the lower cohorts. Obviously, those individuals have not received an optimal dose, and we intend to be able to provide that as soon as we have identified what the optimal dose is like. We are not necessarily planning for that as the initial sort of out-of-the-gate option for us, but we definitely retain the opportunity to do so.
As far as what we'll have in hand when we meet with the FDA, I think it's important when you go to the FDA that you have a compelling dataset with enough safety and efficacy data that the conversation can really be guided on facts and not, "We suspect we can get to X." I think right now, it would be good if we had a little bit more—I'm not guiding to exact numbers, etc.—about what potentially is our optimal biologic dose that we're planning to take forward. When we do that, we can get some guidance on, for example, is there an accelerated path here with just enrolling some more patients after our expansion cohort for an accelerated approval, or is there some other path in play which could be a separate registrational trial?
All of this is the type of thing where, in my past experience, and I'm sure others have had this, the more data you bring, the more able the FDA is to work with you. They really want to get these therapeutics to patients who are in great unmet needs, such as this population. We really look forward to working with them. In addition, we will try to work with them on breakthrough designations and other things which allow that more back and forth that is really required here.
Thank you. Our next question comes from Luca Issi with RBC Capital Markets. Your line is open.
Oh, great. Thanks so much for taking our questions. This is Lisa on for Luca, and congrats on the data here. Just a few ones from us. Are there any plans to explore additional higher doses beyond cohort 4? Just on the assays used, we noticed there were two different assays employed to measure A1AT, terpidimetry and LCMS. Just wondering if you can comment on which assay is clinically validated and has been used in the past for approval of augmentation therapy. The last one, for the 60-mg dose, the total AAT levels are shared up to day 28, but for the ratio of N to Z, we only have data up to day 14. Can you add any color as to why you did not share the longer follow-up here for the 60-mg dose? Any color here would be helpful. Thanks so much.
Great. Maybe just first on higher doses, I mean, the drug is very well tolerated. We clearly have the room to explore more. We've generally felt that around 1 mg per kg, which would be a little bit higher from here, called one more dose cohort, you might be getting into that range. Maybe a limit, but again, the LNP looks great. We will make a database decision when we get to that point. Amy, why don't you talk a little bit about the assays and some of the data points there?
Sure. Typically in clinical settings, turbidimetry or nephelometry is used. That's used often to check levels to make the diagnosis, etc. We use turbidimetry, and we use the LCMS. Both of these have been validated and developed by our internal bioanalytical and biomarker group. As you mentioned, what has been used with augmentation therapies is typically the turbidimetry assay. The reason that we have both is that the LCMS enables us to actually look at the amount of corrected M and corrected, so the corrected M has to be seen. We wanted to show you that because we're increasing it, but we also wanted to look at what happened to Z. Getting on that level of granularity, you can't just use turbidimetry. You really need to now add LCMS for that precision.
The reason that we only have, let's say, one sample at, let's say, you called out 60-mg cohort at day 14 is because LCMS is a much more difficult and much more kind of intensive process where samples have to then be shipped to another lab and then run. It is not as instant as the terpidimetry as far as the turnaround times. We do think that ultimately we will obviously show that complete dataset when we have that data, so.
Got it. Thanks so much. Congrats again on the data.
Thank you.
Thank you. Our next question comes from Greg Harrison with Scotiabank. Your line is open.
Hey, good morning. Congrats on the data, and thanks for taking the question. How should we think about the trend in total AAT and the % corrected in the 60-mg cohort from here, just given that if you look at the 15-mg, there was still a pretty significant increase from either day 14 or day 28 to six months? Would you expect something similar in the 60-mg cohort? I know the N is small, but if that were to continue to increase, I'm just curious if that would be your expectation. Yep. Great questions, Pino.
Yeah. The pre-clinical data, frankly, in rodents, by us and others, would suggest that editing cells, actually edited cells have got survival advantage. You know, we have seen in rodents an increase over time, actually as much as twice editing rates to be more precise. There is definitely that expectation, and that expectation is supported by the pre-clinical data as well as by the fact that it is known that hepatocytes in the liver of humans do turn over over time.
They turn over more slowly than in rodents. It takes about a year for a human hepatocyte to turnover. If anything, we may expect to see that over a longer period of follow-up, and in particular in the higher-dose cohorts, even more so than the lower-dose cohorts because those have more corrected M than the others. At the moment, we're not necessarily—yeah, we're not stating that that's going to be the case. We're just going to monitor and look at it as we go along in the future.
That's helpful. Would you say the increase is mostly driven by that survival advantage? And how long do you know, or do you have a good sense of how long 302 remains active?
Due to the early datasets and the slow turnover of the hepatocytes, we do believe that what you're seeing initially is really a direct switch of the Z gene to an M gene and the production of that. Z has a half-life of about five days, but the alpha-1 is a little bit longer as part of that. What you're seeing there is a sort of gradual optimization of the steady state of production, and now you have alpha-1. That takes about—I would say you start to see a peak around day 14, but maybe stabilize around day 21. Over time, we'll see what happens.
Yeah. I would characterize this dataset more as once it kind of settles in, it's more stable. I think the effects of the survival advantage Pino mentioned may be more longer term. In terms of the reagents themselves, they're washed out of the body within days. That's the beauty of gene editing. You literally do an acute dose, the editors make the change, and then they're gone. At that point, it's just the system reacting to the new genotype that you've created. Great. Thanks again.
Thank you. Our last question comes from Alex Janahan with Bank of America. Your line is open.
Hey, guys. Thanks for taking our questions, and I want to offer my congrats on the data as well. Maybe just to put a finer point on an answer you gave to a previous question on dose escalation in part A, do you think the 60-mig cohort could actually be a candidate for expansion given the data you're seeing? Or I guess, would you be willing to take maybe multiple doses forward for expansion if, say, cohort 4 also looks good? Is there anything in particular you think the safety monitoring committee will be looking for selection of cohort 4 for the dose? Is it really around the LNP or maybe something else like the edits, or is it just the overall profile? Maybe just last quick one, with the new proof of concept and the bolstered cash, are there opportunities or disease areas that you feel more confident to pursue now, either in the current pipeline or maybe beyond as well?
Thank you. Yeah. Great questions, and thank you. I think the dose escalation, absolutely. We think that 60 mg is a clearly potentially therapeutic dose, and we are very confident that this would be a potentially transformative treatment for patients. Nonetheless, we think we have a safety profile to explore more. We're still exploring for just exactly what that optimal dose is. As much as we escalate, absolutely, 60 is on the table, and we'll be exploring it. We have the potential to expand there as well. In terms of the safety committee, I think, I mean, as always, they look at sort of the totality of data, but I think if you've seen it's such a benign profile, we certainly don't anticipate there's much to be discussed.
In terms of the proof of concept, to your point, and obviously, yes, with the cash, I mean, the primary use of the cash is to extend the runway significantly into 2028, which lets us get through a number of meaningful milestones, of course, on our hematology franchise with sickle and now with BEAM-302 moving forward through some significant accelerated development. That said, as we noted on the call, this does, we think, provide additional de-risking of liver delivery of base editing using BEAM LNPs. We do have additional programs even beyond BEAM-302 that we're working on and look forward to expanding that part of our strategy going forward.
Thanks, and congrats again.
Thank you.
Thank you. This concludes the question and answer session. I'd like to turn the call back over to John for closing remarks.
Thank you. Really appreciate the time and attention today. Hopefully, you understand how excited we are about this early, but I think very promising dataset. Most impactful is what we think it can do for patients who have this incredibly serious disease. We look forward to continued development and updating you in the future.
Thank you for your participation. You may now disconnect. Everyone, have a great day.