Editas Medicine (NASDAQ:) has reported significant strides in its first quarter of 2024, focusing on delivering innovative treatments for genetic diseases. The company emphasized its strategy, which includes advancing its gene editing therapy reni-cel towards commercialization, developing an in vivo editing pipeline, and enhancing business development to monetize intellectual property.

With a cash reserve of $377 million, Editas is poised to fund operations into 2026. The company plans to present clinical data in mid-2024 and by the end of the year, and is on track to establish in vivo pre-clinical proof-of-concept. Moreover, Editas has extended its collaboration with Bristol-Myers Squibb (NYSE:) and remains confident in its intellectual property amidst an ongoing patent dispute.

Key Takeaways

• Editas Medicine is progressing with its strategy to commercialize reni-cel, develop in vivo editing, and expand business development.
• Clinical data for reni-cel in treating severe sickle cell disease and transfusion-dependent beta thalassemia is expected in mid-2024 and year-end.
• The company has completed enrollment for the adult cohort in the RUBY trial and is enrolling adolescents.
• Editas has extended its collaboration with Bristol-Myers Squibb and is confident in its intellectual property position.
• The company has a cash balance of $377 million, which is expected to fund operations into 2026.

Company Outlook

• Editas Medicine aims to become a commercial-stage company with momentum entering 2024.
• They anticipate providing a clinical update on the reni-cel program in mid-2024 and at year-end.
• The focus remains on delivering differentiated gene editing medicines to patients with serious genetic diseases.

Bearish Highlights

• The company is involved in an ongoing patent dispute, although they express confidence in their intellectual property position.

Bullish Highlights

• Editas Medicine has demonstrated a competitive safety profile and potential differentiation for reni-cel from other treatments.
• They have established over 20 clinical sites in the U.S. and are fostering relationships to support commercial success.
• The company is a fast follower in the ex vivo market, learning from others to potentially become the partner of choice.

Misses

• Specific details on the treatment process for reni-cel, including apheresis cycle numbers and manufacturing efficiency, were not disclosed.

Q&A Highlights

• The company has had positive interactions with the FDA, with alignment on the Phase 3 study for reni-cel to support a Biologics License Application.
• No specific details on the filing strategy for reni-cel, including whether filings for adults and adolescents will be concurrent or sequential.
• Editas is interested in the Middle East market for sickle cell disease and is open to partnerships in various geographies.

Editas Medicine’s earnings call has underscored the company’s commitment to advancing gene editing therapies and leveraging its intellectual property for sustained growth. With a robust cash balance and strategic collaborations in place, Editas is positioning itself to meet key milestones in the coming year and beyond.

InvestingPro Insights

Editas Medicine’s (EDIT) latest financial data and market performance reveal a challenging landscape as the company continues to focus on its strategic initiatives. The InvestingPro data indicates a market capitalization of $444.89 million, reflecting the company’s current market valuation.

Despite impressive revenue growth in the last twelve months, amounting to 204.52%, the company’s financial health shows signs of pressure. The gross profit margin stands at a concerning -155.96%, highlighting the cost-related challenges the company is facing.

InvestingPro Tips suggest that Editas Medicine’s stock is currently in oversold territory according to the RSI, which could attract investors looking for potential value. However, analysts have revised their earnings expectations downwards for the upcoming period, indicating concerns about the company’s near-term profitability.

Moreover, the company’s share price has suffered significant declines over the last week and month, with a 10.41% decrease in the past week and a 28.17% drop over the last month. This performance could be indicative of market sentiment and the challenges ahead for Editas.

For investors seeking a deeper analysis, there are additional InvestingPro Tips available that could provide further insights into Editas Medicine’s financial health and market prospects. By using the coupon code PRONEWS24, investors can get an additional 10% off a yearly or biyearly Pro and Pro+ subscription, gaining access to valuable tips that can inform investment decisions. With these insights, investors can better understand the risks and opportunities associated with Editas Medicine as the company continues to navigate the competitive landscape of gene editing therapies.

Full transcript – Editas Medicine (EDIT) Q1 2024:

Operator: Good morning, and welcome to the Editas Medicine’s First Quarter 2024 Conference Call. All participants are now in a listen-only mode. There will be a question-and-answer session at the end of this call. Please be advised that this call is being recorded at the company’s request. I would now like to turn the call over to Cristi Barnett, Corporate Communications and Investor Relations at Editas Medicine.

Cristi Barnett: Thank you. Good morning, everyone, and welcome to our first quarter 2024 conference call. Earlier this morning, we issued a press release providing our financial results and recent corporate updates. A replay of today’s call will be available in the Investors section of our website approximately two hours after its completion. After our prepared remarks, we will open the call for Q&A. As a reminder, various remarks that we make during this call about the company’s future expectations, plans and prospects constitute forward-looking statements for the purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent Annual Report on Form 10-K, which is on file with the SEC as updated by our subsequent filings. 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, we specifically disclaim any obligation to update or revise any forward-looking statements, even if our views change. Now, I will turn the call over to our CEO, Gilmore O’Neill.

Gilmore O’Neill: Thanks, Cristi, and good morning, everyone. Thank you for joining us today on Editas’s first quarter 2024 earnings call. With me today are four members of the Editas executive team, our Chief Medical Officer, Baisong Mei; our Chief Scientific Officer, Linda Burkly; our Chief Financial Officer, Erick Lucera; and our Chief Commercial and Strategy Officer, Caren Deardorf. We are pleased with Editas’ momentum and progress in the first quarter of 2024. Editas’ goal is to deliver life-changing medicines to patients with previously untreatable or undertreated genetically determined diseases. And our vision and focus strategy is to position Editas as a leader in in vivo programmable gene editing. Three pillars underpin our strategy. The first of those pillars is to drive reni-cel, an edited cell therapy for hemoglobinopathies, and formerly known as EDIT-301, toward BLA and commercialization. The second is to build an in vivo editing pipeline. And the third is to increase business development activities with a particular focus on monetizing our very strong intellectual property. At the start of 2024, we announced the following 2024 objectives. For reni-cel, we will provide a clinical update from the RUBY trial for severe sickle cell disease and the EdiTHAL trial for transfusion-dependent beta thalassemia in mid-2024 and by year-end 2024. We will complete adult cohort enrollment and initiate the adolescent cohort in RUBY and continue enrollment in EdiTHAL. For our in vivo pipeline, we will establish in vivo preclinical proof-of-concept for an undisclosed indication. And for BD, we will leverage our robust IP portfolio and business developed to drive value and complement core gene editing technology capabilities. So how are we executed against this strategy and these objectives in the first quarter? Let us start with reni-cel. First, on enrollment. We’ve been very pleased with the growing patient and healthcare provider interest in reni-cel. Indeed, we are delighted to share that we have completed enrollment in the adult cohort of the RUBY clinical trial. Additionally, we have enrolled multiple patients and have more in screening in the adolescent cohort of a RUBY study, which was launched at the beginning of this year. And we continue to enroll beta thalassemia patients in our EdiTHAL study. Dosing continues in both the RUBY and EdiTHAL studies. Second, on clinical data. We remain on track to present a substantive clinical data set of at least 18 sickle cell patients with 2 to 21 months of clinical follow up in the RUBY study in the middle of 2024. And we will share a further update by year-end. We are also on track to present clinical data from the EdiTHAL study of reni-cel in transfusion dependent beta thalassemia in the middle of 2024 and again by year end. Baisong Mei will share more reni-cel detail later on in this call. On the manufacturing front, I am pleased to share that we have promoted Greg Whitehead to the role of Chief Technology and Quality Officer, leading our technical development, technical operations and quality departments. Greg has more than 25 years of experience in the biotech industry and extensive cell and gene therapy clinical and commercial development expertise. Now, let’s turn to in vivo and our pipeline development, where we continue to strengthen our in vivo discovery capabilities and continue lead discovery work on in vivo therapeutic targets in hematopoietic stem cells and other tissues. Importantly, we remain on track to establish in vivo preclinical proof-of-concept for an undisclosed indication by the end of the year. Our internal development efforts are differentiated by leveraging the indel CRISPR technology we already use to upregulate gamma globin expression through direct editing of the HBG12 promoter site in our ex vivo reni-cel program. Our in vivo approach is aimed at functional upregulation of gene expression in genetically defined diseases with a preliminary focus on rare and orphan patient populations. In the medium to long term, we intend to expand to more common genetically determined diseases. Linda Burkly, our CSO, will share more details on our in vivo strategy and progress towards building an in vivo pipeline later on in the call. Finally, what is happening in business development? In March, we signed a two year extension to the collaboration with Bristol-Myers Squibb to research, develop and commercialize autologous and allogeneic alpha beta T cell medicines for the treatment of cancer and autoimmune diseases. We also have options to extend that collaboration for an additional two years. To date, Bristol-Myers Squibb has opted into 13 different programs across 11 gene targets to date. Two programs are currently in IND enabling studies and four programs are in late stage discovery. And in intellectual property, yesterday, oral arguments were held before the U.S. Court of Appeals for the Federal Circuit regarding an appeal of the Patent, Trial and Appeal Boards, or PTABs, previous decision favoring Broad Institute of the US Patent Interference involving specific patents for CRISPR-Cas9 Editing in human cells between the University of California, University of Siena and Emmanuelle Charpentier, or CDC, and the Broad. We expect a decision on the case in the second half of 2024. Eric will share more BD and IP details later on in the call. We are energized by our progress and execution this quarter. With our sharpened strategic focus, our world-class scientists and employees, our keen drive and execution and strong balance sheets, we continue to build momentum to progress our strategy to deliver differentiated editing medicines to patients with serious genetic disease. Now, I will turn the call over to Baisong, our Chief Medical Officer.

Baisong Mei: Thank you, Gilmore. Good morning, everyone. Let’s talk about reni-cel, which is on the clinical development for severe sickle cell disease and transfusion-dependent beta thalassemia. As Gilmore shared, we are pleased that we have completed enrollment in the adult cohort of the Phase 1, 2, 3 RUBY trial and the dosing continues. In the adolescent cohort of the RUBY study, we have enrolled multiple patients and several more patients in screening. The interest and demand are high. I’m very pleased about how quickly we have moved in screening and enrollment of the adolescent cohort. I’d like to thank colleagues and editors and our clinical trial partners for the collaboration and hard work. And more importantly, I would like to thank patients, their families, investigators, and the study side staff for their trust and support. In the EdiTHAL trial for transfusion-dependent beta thalassemia, we continue to move forward with enrollment and dosing. We look forward to sharing clinical data in the middle of this year and also at the year-end. As I have shared, I visited and continue to visit our RUBY’s EdiTHAL clinical trial site and speak with the investigators. I appreciate the enthusiasm and support from the investigators and study sites. I’m pleased with the momentum of reni-cel in patient recruitment, apheresis and dosing in both studies. I’m excited to hear from the investigators that patients those who use reni-cel have already seen positive changes in their lives. As we shared in our February earning call, we aligned with FDA that RUBY clinical trial is now considered a Phase 1, 2, 3 trial for BLA filing. We also have alignment with the FDA on the study design, endpoints, and sample size. We look forward to future discussions with the FDA and continue the collaboration. Turning to clinical data, as Gilmore mentioned, we are on track to present a substantive clinical data set of sickle cell patients with considerable clinical follow-up in the RUBY study in the middle of 2024 and a further update by year-end 2024. What we will show, the RUBY data set will include clinical data from at least 18 sickle cell patients with a 2 to 21 month of follow-up. And the EdiTHAL data set will include clinical data from seven patients with 4 to 12 month follow-up. We will present efficacy data including total hemoglobin, fetal hemoglobin, and the vessel occlusive event or VOE for sickle cell patients in RUBY study. And the red blood cell transfusion or transfusion-dependent beta thalassemia patients in EdiTHAL study. And safety data including neutrophil and platelet engraftment for both studies. As a reminder, in December 2023, we shared safety and efficacy data from 11 RUBY patients and six EdiTHAL patients. Once again, the data confirmed the observation from our prior clinical readouts, including reni-cel drove early robust correction of anemia to a normal physiological range of total hemoglobin in sickle cell patients. Reni-cel drove robust and sustained increase in fetal hemoglobin level in excess of 40%. All RUBY sickle cell patients remained free of vessel occlusive events following Reni-cel treatment. Reni-cel treated sickle cell patients and transfusion dependent beta thalassemia patients have shown successful engraftment, have stopped red blood cell transfusion. And the safety profile of reni-cel observed today is consistent with myeloablative busulfan conditioning and autologous hemopoietic stem cell transplant. This data reinforce our belief that we have a competitive product and a product potentially differentiated from other treatments with a rapid correction of anemia. Thanks to the deliberate choice of our discovery group have made early in the program. The choice of CRISPR enzyme and the target to edit for increased fetal hemoglobin expression matters. Reni-cel uses our proprietary AsCas12a enzyme to upregulate HBG12 promoter. Based on the clinical data thus far, we believe that sustained normal levels of total hemoglobin could be a potential point of differentiation for reni-cel. Now I’ll turn the call over to Linda, our Chief Scientific Officer.

Linda Burkly: Thanks, Baisong. And good morning, everyone. I’m happy to be talking to you this morning to share more details about our in vivo strategy and our progress towards building an in vivo pipeline. I would like to take a moment to remind you why we believe in vivo medicines will be a disruptive transformative development in medical history with the potential to address genetically determined diseases with durable and curative outcomes for patients. First, in vivo medicines may reduce the administration burden of delivering editing medicines to patients in need, which will provide for broader access to patients all around the world. Second, off the shelf administration may allow for scalable manufacturing and lower costs to produce. Based on these two principles, we believe that in vivo gene editing will provide accessible cures for genetic diseases and therefore may be the most disruptive development in medical history. So how will Editas position itself? There are many monogenic diseases that can potentially be cured with gene editing approach. We have said that we will at first target the development of treatments that are clearly differentiated from current standard of care and that will leverage the aspects of CRISPR editing that give it a unique advantage over other therapeutic modalities. Our internal development efforts are differentiated by leveraging the indel CRISPR technology we use to upregulate gamma globin expression through direct editing of the HBG12 promoter site in our ex vivo reni-cel program. Our in vivo approach is aimed at functional upregulation of gene expression in genetic diseases in rare and orphaned patient populations from which we intend to expand to more common diseases. I’m also pleased to share several progress updates as we advance our in vivo capabilities towards our long-term vision of being a leader in in vivo programmable gene editing. First and most importantly, as Gilmore mentioned, we remain on track to establish in vivo pre-clinical proof-of-concept for an undisclosed indication by the end of the year. Editas is well positioned with established capabilities in the four main components of in vivo gene editing medicine. One, guide RNA, two, editing enzyme, three, messenger RNA, and four, delivery technology. And we are currently evaluating lipid nanoparticles for delivery of gene editing cargo into multiple tissue types with multiple companies. Additionally, we’re evaluating next generation delivery technology. Second, our in vivo capabilities with the potential to be used in developing transformative in vivo gene editing medicines are demonstrated by the preclinical data we are presenting at the American Society of Gene and Cell Therapy or ASGCT Annual Meeting in three presentations taking place on Thursday and Friday of this week. On Friday, in an oral presentation, we will share in vivo preclinical data from mouse studies using lipid nanoparticle mediated delivery of an optimized guide RNA and engineered ASCAS12a messenger RNA. In post-presentations on Thursday and Friday, we will share preclinical data demonstrating ASCAS12a guide RNA modifications that enable high potency gene editing in multiple cell types, including in the liver, and improve gene editing outcomes in vivo, enabling the development of in vivo gene editing medicines. And research on identifying potent large serine recombinases, LSRs, as a foundation to develop novel in vivo gene editing technologies for whole gene knock-in, expanding potential in vivo gene editing targets for developing medicine. Third, Editas CRISPR-based in vivo gene editing capability has been clinically validated. Notably, in 2020, Editas was the first company ever to treat a human with an in vivo delivered CRISPR-based gene editing medicine, EDIT-101. In fact, earlier this week, the New England Journal of Medicine published a manuscript entitled, Gene Editing for CEP290-Associated Retinal Degeneration, detailing our former lead development candidate, EDIT101, for the treatment of Leber’s congenital amaurosis type 10, or LCA10. Editas established clear in vivo human proof-of-concept in 2022, and we are pleased that the results from this groundbreaking clinical trial were published by the New England Journal of Medicine. These progress updates demonstrate Editas’ execution on our in vivo strategy and our proven in vivo gene editing capabilities. And I look forward to sharing more details about our in vivo development strategy and our progress towards building an in vivo pipeline later this year. Now, I will turn the call over to Erick, our Chief Financial Officer.

Erick Lucera: Thank you, Linda, and good morning, everyone. I’m happy to be speaking to you, and I’m excited to provide updates on our business development achievements, intellectual property, and financial results for the first quarter of 2024. First, in regard to business development, as Gilmore mentioned, in March, we announced a two-year extension to the collaboration with Bristol-Myers Squibb to research, develop, and commercialize autologous and allogeneic alpha beta T cell medicines for the treatment of cancer and autoimmune diseases. We also have options to extend the collaboration for an additional two years. To date, Bristol-Myers Squibb has opted into 13 different programs across 11 gene targets to-date. Two programs are currently in IND enabling studies, and four programs are in late stage discovery. As a reminder, for each new experimental medicine that Bristol-Myers Squibb develops and commercializes using opted-into genome editing tools, Bristol-Myers Squibb will pay Editas Medicine potential future milestone payments. Following the approval of any products resulting from the collaboration, Editas Medicine is also eligible to receive tiered royalties on net sales. We are pleased that our Bristol-Myers collaboration has proved to be a productive partnership, and we are committed to future collaborations and partnerships that will allow for the continued access and advancement of gene editing. And in IP, as Gilmore mentioned, yesterday the oral arguments were held before the U.S. Court of Appeals for the Federal Circuit regarding the CBC’s appeal of the PTAB’s decision involving patents for CRISPR-Cas9 editing in human cells. As you know, the Broad Institute has previously prevailed three times against the CBC, twice with the PTAB, and once at the Federal Circuit. The Federal Circuit’s review will determine whether the PTAB correctly applied the law. It is important to remember the Court will not hear new evidence. An appellate court decision in the Broad’s favor would reaffirm Editas’ position as the exclusive licensor of the patents covering Cas9 use in human medicines in the U.S. It is also important to remember that only a small fraction of the IP we licensed from the Broad are involved in the ongoing USPTO interference proceedings. We expect a decision on the case in the second half of 2024. We remain confident that the Broad will once again prevail. Our IP portfolio of foundational U.S. and international patents covering Cas9 and Cas12 use in human medicines are a source of meaningful value as we believe that globally there are more than 100 Cas9, Cas12a programs in development worldwide, with the majority of the programs being developed by 10 companies. We believe these potential deals represent a potential material source of non-dilutive capital, as evidenced by our deal in the fourth quarter of 2023 that extended our cash runway by two quarters. We look forward to future discussions. And now I’d like to refer you to our press release issued earlier today for a summary of our financial results for the first quarter of 2024. I’ll take this opportunity to briefly review a few items for the quarter. Our cash, cash equivalents, and marketable securities as of March 31, $377 million compared to $427 million as of December 31, 2023. We expect our existing cash, cash equivalents, and marketable securities, together with the near-term annual license fees and contingent upfront payment payable under our license agreement with Vertex (NASDAQ:), to fund our operating expenses and capital expenditures into 2026. Revenue for the first quarter of 2024 was $1.1 million compared to $9.9 million for the same period in 2023. The decrease relates to the January 2023 one-time sale of the company’s wholly owned oncology assets and related licenses. R&D expenses this quarter increased by $11 million to $49 million in the first quarter of 2023. This increase relates to additional clinical and manufacturing costs that support the continued progression of the company’s reni-cel program. The increase is also attributable to one-time payments related to sub-license and license obligations. Editas will continue to incur these types of payments, as we and our collaboration partners advance certain license programs in the gene editing space. G&A expenses for the first quarter of 2024 were $19 million, which decreased from $23 million in the first quarter of 2023. The decrease in expense is primarily attributable, to one-time professional service expenses related to the 2023 strategic initiatives, and business development activities, as well as reduced legal and patent costs. With our BD and IP activity and a cash runway into 2026, Editas remains in a strong financial position. We have ample resources to continue the advancement of our reni-cel program, support the progression of our in vivo capabilities to develop our pipeline, and leverage our strong IP position for additional business development and licensing opportunities. With that, I’ll hand the call back to Gilmore.

Gilmore O’Neill: Thank you, Erick. We are proud of our progress in the first quarter of 2024, and we look forward to continue to accelerate the momentum in 2024. As we continue to evolve from a development stage technology platform company into a commercial stage gene editing company, we look forward to continuing our transformation and sharing our progress with you. As a reminder of our 2024 strategic objectives, for reni-cel, we will provide a clinical update from the reni-cel RUBY trial for severe sickle cell disease and the EdiTHAL trial for transfusion-dependent β-thalassemia in mid-2024 and year-end 2024. We have now completed the adult cohort enrollment, and have started enrolling patients in the adolescent cohort in RUBY. We will also continue enrollment in EdiTHAL and dosing in both trials. For our in vivo pipeline, we will establish in vivo preclinical proof-of-concept for an undisclosed indication, and for BD, we will leverage our robust IP portfolio and business development capabilities to drive value and complement core gene editing technology capabilities. As we share today, we are making significant progress in all three pillars of our strategy this quarter, including reni-cel, in vivo, and business development, including intellectual property. We enter 2024 with great momentum, and I am proud of the Editas team’s significant progress towards becoming a commercial-stage company, and on developing clinically differentiated transformational medicines for people living with serious previously untreatable diseases. As always, we could not achieve our objectives without the support of our patients, caregivers, investigators, employees, corporate partners, and you. Thanks very much for your interest in Editas. And we’re happy to answer questions. Thank you.

Operator: Thank you. [Operator Instructions] Our first question comes from Samantha Semenkow from Citi. Please proceed.

Samantha Semenkow: Hi. Good morning, and thanks very much for taking my question. I’m wondering about your in vivo pipeline and the proof-of-concept that you’re expecting, by the end of this year. And what would be the bar for success that you’re looking for in this program? Thank you.

Gilmore O’Neill: Thanks very much, Samantha. I’m going to ask Linda to address that.

Linda Burkly: Thank you, Sam. Thank you for the question. We are looking for proof-of-concept for high efficiency delivery and editing for our target of interest in vivo in this preclinical POC. That will give us confidence in our ability, to target the target of interest. We are going to be sharing more information on this at a future date. Thank you for the question.

Operator: Our next question comes from Joon Lee from Truist Securities. Please proceed.

Joon Lee: Hi. Congrats on the progress, and thanks for taking our question. An interesting update on your disclosure, is the plan to identify large serine recombinases, which implies sort of a newer approach to many of your – that many of your peers are also developing, you know, some call it gene mating, some call it pasting. Does the size of the recombinase-mediated insertion allow for, you know, inserting a coding sequence for dystrophin, for example? And are you able to comment on whether DMD is out of the question regarding your in vivo aspirations? Thank you.

Gilmore O’Neill: Thanks very much, Joon. I’m going to have Linda take that.

Linda Burkly: Yes. Thank you for commenting. We’re excited about the LSR technology that we’re disclosing here. We are identifying many different novel LSRs. We’re not disclosing at the moment the size of the integrations that can be accommodated by these large serum recombinases, but we have quite a few novel LSRs that we’ve identified and we’re further characterizing them. Thank you for the question.

Operator: Our next question comes from Mary Kate Davis from Bank of America. Please proceed.

Mary Kate Davis: Good morning. Thanks for taking my question. Looking at the reni-cel program here, how are you guys looking at the mid-year reni-cel update, compared to the year-end update here? As follow-up time progresses, what should we look for from treated patients in terms of safety and efficacy moving forward? Thank you.

Gilmore O’Neill: Thanks, Mary Kate. Baisong is going to take that one.

Baisong Mei: Yes. Thanks, Mary. In this middle-year release, we expect to have at least 18 patient data for RUBY study. Within the 18 patients, and four of them will have 12 or longer, 12 to 21 months of exposure, and seven will have five months to 12 months exposure, and another seven with two to five months exposure. With that, we feel this data is very meaningful to see the direction, not only the increase of total hemoglobin normalization of total hemoglobin and increase of fetal hemoglobin, but also the durability of the study and the impact from efficacy perspective, for example, the free of vessel occlusive events. For the EdiTHAL study, we will have patients from at least seven of those patients with four to 12 months of exposure, which also will be very meaningful. That is compared to the December release. We’ll have 11 RUBY patients and six EdiTHAL patients. That substantial more data will help us to understand RUBY much better. Thank you.

Operator: Our next question comes from Jack Allen from Baird. Please proceed.

Jack Allen: Hi. Congratulations to the team on the progress, and thanks for taking the question. I’m going to stick with the reni-cel program. I was hoping you could provide some color on dosing of the pivotal cohort. I know you’ve commented on the adult cohort being fully enrolled, but have all of those patients received therapy? Any other comments you can provide, as it relates to the size of the cohort that you’ve agreed to, with regulators would be very helpful? Thanks so much.

Gilmore O’Neill: Thanks very much, Jack. I’ll answer the first part and then pass it to Baisong to provide maybe give it a little more color to regulatory interactions. We have obviously completed the adult enrollment, which we’re actually very excited about, not least because that is in the context of two approved therapies. So it really is a very concrete reflection of the enthusiasm that Baisong has found and described, indeed, increasing enthusiasm about our program with his visits to sites and conversations with investigators, healthcare providers, and indeed with patient efficacy groups. We have scheduled many of those patients already for dosing, and we’ll give you further updates on the progress of dosing at a later date. And with regard to the regulatory color, I think, Baisong, you might want to maybe just share a little more of that.

Baisong Mei: Yes. For regulatory, as we shared, we have alignment with FDA that the RUBY study is a Phase 1, 2, 3 study for BLA filing. And we also have alignment on the sample size, duration, and study design of that. So we continue to have a collaboration with FDA, on the further discussion about this program.

Jack Allen: Great. Thank you.

Operator: Our next question comes from Gena Wang from Barclays. Please proceed.

Gena Wang: Thank you. If I may, very quick two questions. First, should we read into your ASGCT presentation for in vivo indication, such as glaucoma? And second, I know you mentioned also a little bit, but when we look at the current approved genomic therapy for sickle cell, we still have a 10% patient relapse with VOE events. What do you think is the key factors that we should look into for the potential differential durability with hopefully 100% control rate?

Gilmore O’Neill: Thanks very much, Gena. I’m going to ask Linda to handle the first part of your question around the ASGCT and then Baisong can talk about durability, what we’re seeing today?

Linda Burkly: Yes, thank you very much, Gena. Primary open-angle glaucoma is obviously an area of very high inmate need, and while we conducted those studies, because of that, we are not currently pursuing that indication, but we were able through those studies to really demonstrate impressive preclinical POC and showcase our in vivo capabilities with respect to three components. Our ability to deliver lipid nanoparticles in vivo, with our gene editing cargo, our proven capability of our proprietary enzyme, AsCas12a, to edit in vivo and our guide modifications, to enhance a gene editing potency. So these capabilities really position us well for delivering in vivo gene editing medicines, and we’re really pleased with the ASGCT disclosures. Thank you.

Baisong Mei: Yes, I can now take up on the question about the VOE relapse for sickle cell patients. First, I would like to say, I want to congratulate the entire field for the effort in treating sickle cell disease, including the recent approval of the two molecules. And so, I think what we see is that with the continued effort of all of us, we will continue to improve and transform the treatment for sickle cell disease patients. Within reni-cel, and we are still continuing to collect the clinical data, as I mentioned, we expect that this is, not only a competitive, but differentiated molecule. And with the normalization of the total hemoglobin correction of anemia. So, we’re looking forward to see our own data on the VOE. As we reported so far, we have seen all those patients, those with reni-cel, is free of VOE event.

Gena Wang: Thank you.

Operator: Our next question comes from Mani Foroohar from Leerink Partners. Please proceed.

Unidentified Analyst: Hi, good morning. This is [CJ] for Mani. Thanks for taking our question. I was just following the agreement with Vertex last year. Just how are you thinking about future IP monetization opportunities?

Gilmore O’Neill: Thanks very much. I’m going to ask Erick to address that question.

Erick Lucera: Yes, thanks for the question. Obviously, as we said in the transcript, we view the future potential royalty monetization and licensing activities as an integral, and very important source of non-dilutive capital. As you know, these are foundational IP patents which are applied to just about everybody’s projects in Cas9, Cas12. And we expect to have conversations with those folks as soon as we can.

Unidentified Analyst: Thank you.

Operator: Our next question comes from Brian Cheng from JPMorgan. Please proceed.

Brian Cheng: Hi, guys. Thanks for taking our question this morning. Can you just remind us, what’s your latest thinking around the timing of holding a discussion with regulators on sickle cell? And just given the data that you’re going to present mid-year, any updates and color on the timing of holding a productive conversation with regulators would be appreciated? Thank you.

Gilmore O’Neill: Thanks very much, Brian. I’m going to ask Baisong to talk about that sort of – I think your two questions, really which is about what the data are in the middle of year and how they integrate with our discussions with regulators?

Baisong Mei: Yes. So, Brian, as I mentioned, we are very pleased with the data we’re going to release in the middle of the year, and which is substantive, and also give us good direction how much we will get and to have, for example, a data set to have equivalent to the CASGEVY BLA filing, for example. So, that’s kind of one part of that. We’re very happy to see the amount of data and the patient outcome from the data. And then the other thing, is about the regulatory engagement. As I mentioned, we already have a line of this Phase 3 study to support the BLA, and we have continued engagement with FDA. We have not disclosed all those details of the interaction yet, but as a reminder, we have RMAT designation, and which allows us to have frequent interaction with agency. But also with the high-level interaction with agency. And this, of course, give us opportunity for potential priority review enrolling submission. So, we’re very excited to the direction. We’ll continue to have engagement and collaboration with FDA.

Brian Cheng: Thank you, Baisong.

Operator: Our next question comes from Eric Schmidt from Cantor Fitzgerald. Please proceed.

Eric Schmidt: Thanks for the question and congrats on the progress. Are you able to give the approximate number of patients, who are enrolled in the RUBY trial with sickle cell disease? And then it sounds like you’ve been able to make pretty good progress in enrollment in that study, despite the availability of commercial cell therapies. I was just wondering at centers that have both experimental and commercial cell therapy available, maybe Baisong could talk a little bit about what’s driving the decision to use the Editas product over others? Thanks.

Gilmore O’Neill: Thanks very much, Eric. Baisong would kind of date you on where our clinical trials.gov sets as a target for the cohort in our trial. And then obviously build on his perceptions of why we’re doing so well with enrollment even in the context of commercial therapies being available.

Baisong Mei: Yes. Yes, thanks Eric. We are very pleased with the momentum by the enrollment in both the EdiTHAL cohort and the adolescent cohort. And for the EdiTHAL cohort, we shared that in February with those we enrolled 40 patients. Now we enroll slightly more than 40 patients and therefore we closed the EdiTHAL cohort enrollment. And for adolescent cohort, we started like the beginning of this year. We already enrolled a multiple patients, and have multiple patient experience. We’re very pleased with that. Then as I mentioned, I’m on the road all the time to visit our investigators and the study sites. And then, they really feel that when is actually there our belief the reni-cel based on the MOA based on the data we have continued to sharing on that. I also give credit the entire field in working on that with the two gene therapy approved for sickle cell, is also increased the interest in the direction of the gene therapy for sickle cell disease. So that’s how we see over the last year or so we see really great momentum that for reni-cel enrollment, especially after we release our data.

Operator: Our next question comes from Jay Olson from Oppenheimer & Company. Please proceed.

Jay Olson: Oh hi, congrats on all the progress and thank you for taking the question. Can you talk about the timing of the collaboration extension with Bristol? Was there some new data that triggered the new collaboration and is there any color on what new data Bristol may have seen? And then separately, can you talk about any work that you’ve done on developing a milder conditioning agent? Thank you.

Gilmore O’Neill: Well, what I would do is ask Erick to address the question about the BMS. What I do want to say, I can address the conditioning, which is that just at our last earnings, we talked that we are going to continue monitoring the space. We have significant contacts in the academic and non-academic worlds around the field. But we have actually really deployed our efforts, and our resources internally to focusing on our in vivo pipeline, including developing hematopoietic stem cells. The rationale for that being that, we see that where a milder conditioning therapy is actually approved, it would be used universally and adopted universally in transplant centers across multiple indications, including stem cell transplantation with hemoglobinopathies. And with that, I’m just going to pass to Erick, just to talk about the BMS deal.

Erick Lucera: Yes, thanks for the question. With respect to the timing of the renegotiation – or the extension, obviously, we put out a press release in the very recent past, a week or two ago, something like that. And that would give you an update on the timing. I’d say with respect to the data, Bristol-Myers, as you know, recently completed a portfolio review. And we were pleased to see that all of the projects that were working on them, are continuing to move forward. I think if – we would leave discussion of specific programs to them to talk about anything that they’re seeing in those programs, I would highlight the fact that at their most recent R&D day last September, which I think was the first one they’ve done in several years, they did mention six products on their pipeline chart, which were using our technology. So I would refer you to their R&D disclosures from that meeting, to get an update on the work that they’re doing with us. But we are very excited about working with them. This has been a partnership that has survived several mergers and several portfolio reviews. So, we’re very excited about what we’re seeing.

Jay Olson: Thank you.

Operator: Our next question comes from Phil Nadeau from TD Cowen. Please proceed.

Unidentified Analyst: Hi, this is [Alex] on for Phil. Thanks for taking my question. So given the association between total hemoglobin levels and organ function, do you plan to utilize any quantitative endpoints, basically assessing end organ function in the RUBY trial? And if so, what might those look like? And when can we maybe expect initial data? Thanks.

Gilmore O’Neill: Thanks very much, Alex. I’m going to ask Baisong to address that question.

Baisong Mei: Yes, thanks, Alex. We certainly have measurements for the end organ function. We look into the several major organ system, to monitor the function improvement. For example, we monitor the liver function, not only with these different lab values, we look into pulmonary function to check the respiratory system. And we also have cardio echo and other measures talking to – measure the cardiovascular system and that too. So, we are looking forward to seeing more data on that and give us more understanding of the end organ function, may behave after the treatment. Just a reminder that we also, of course, look into the not only sickle cell, but also other area in terms of the anemia, how that impact function and how that correction of anemia may be able to improve that function after the treatment. And in sickle cell specifically, over the last couple of years, you already see more publications about end organ function given after the allogenic transplant, to treat sickle cell patients. We are very excited on that. But just to be very honest to ourselves, right, this field is still fairly new and we see some really good publication and direction in this. And we’re looking forward to our own study, as well as the literature on this field.

Unidentified Analyst: Good. Thank you.

Operator: Our next question comes from Yanan Zhu from Wells Fargo. Please proceed.

Yanan Zhu: Thanks for taking our questions. So first on the differentiation of total hemoglobin normalization, I was wondering, have you had feedback from sickle cell treaters on that differentiation and whether there’s any hesitancy or pushback that perhaps the current level of hemoglobin achieved by the marketed product is sufficient? How much of that kind of thinking is out there? And on the in vivo side, I was wondering, are you focused on first in class targets, or perhaps not first in class targets, but hoping to have a differentiation on, specificity and transduction efficiency, et cetera? Thanks.

Gilmore O’Neill: Thanks very much, Yanan. So I’m going to ask Baisong to talk about the differentiation of total hemoglobin. And then I’ll ask Linda just to talk about our approach to first in class, or clear differentiation and where we would see that with our approach to function upregulation?

Baisong Mei: Thanks, Yanan. I mean, certainly we talk about the investigators as well as the KOLs and sickle cell treaters for our differentiation. And how we may be able to see and what is the position of this molecule. And when we’re talking to those hematologists and sickle cell treaters that see our data, and when hematologists mentioned that it is no brainer, it is better if you have a 16-gram per deciliter versus 10-gram per deciliter of total hemoglobin. And then they also, I mentioned that they introduced as of our study, and there are quite a few knowledgeable hematologists. They see the difference among several molecules. And one investigator said that he was waiting for our trial and did not participate other. So those are the anecdotal examples on that. As I mentioned earlier, we certainly want to look forward to see the clinical data.

Gilmore O’Neill: It’s also worth highlighting, of course, that the FDA has recognized that a 1-gram per deciliter difference is meaningful, or certainly likely to predict a clinically meaningful benefit and that they use that threshold to give an extended approval to Oxbryta in the past.

Baisong Mei: Yes. Talking about that, this is also, when we communicate with FDA, this is also a point we have been discussing with FDA too.

Gilmore O’Neill: So thanks very much, Baisong, Linda, just regarding in vivo and where our focus is.

Linda Burkly: Yes. In vivo, our in vivo approach is aimed at functional up-regulation of gene expression in genetically determined diseases. And this strategy positions us very well to be differentiated from others in terms of our targets and our target editing strategies. And what this means, is that we can go after targets that others can’t go after. And so from an indication perspective, we can go after indications that perhaps others can’t go after. And so we could have a first in class strategy. Also, within a given indication, we could devise a targeting strategy that would be best-in-class, if you will. So we can have first in class strategies as well as best-in-class opportunities. I hope that answers your question.

Yanan Zhu: Yes. Thank you. Very helpful. Thanks for all the answers.

Operator: Our next question comes from Luca Issi from RBC Capital. Please proceed.

Luca Issi: Oh, great. Thanks so much for taking my question and congrats on all the progress. Maybe just a quick one on reni-cel and the filing strategy. What’s the vision here for the BLA? Are you planning to file adults and adolescents concurrently or sequentially? Any color there, much appreciated. And then maybe quickly on the Middle East. Can you just talk about the opportunity for sickle cell disease in the Middle East? Vertex seems really, really excited about that market. So wondering what’s your strategy there to potentially tap that market? Are you still focused on partnership? Can you potentially access that via distributor? Again, any thoughts there, much appreciated. Thanks so much.

Gilmore O’Neill: Happy to do. Thanks very much, Luca. So I’ll ask Baisong just to talk about our regulatory strategy as far as we have shared it. And then Caren can talk about just how we’re looking at and thinking about the Middle East. And frankly, in the context of the rest of the world.

Baisong Mei: Yes, yes. Thanks, Luca. We are very pleased with the interaction with the agency and continued interaction with the agency about the reni-cel and for the RUBY study as a Phase 3 study to support the BLA, and all the front of the Phase 3 study, we have alignment on that. And we have continued conversation with FDA on this route. We have not shared the specifics about the date of the BLA, or the indication of adult alone or adolescent. But as we shared, we are very pleased with the enrollment for both adult cohort as well as adolescent cohort. So that gives us a great position for this molecule. Thank you.

Caren Deardorf: Great, Luca. Thanks for the question about Middle East and certainly just the populations outside the United States. And there’s absolutely a number of geographies where there is a significant population of sickle cell patients, and really high unmet need beta cell ischemia as well. What I’d say is our continued drive to execute in the U.S., and to move reni-cel forward with differentiation, just continues to support the opportunity for us to partner at the appropriate time. And that’s certainly something that we’ve said we are open to and will certainly provide more color in the future as appropriate.

Luca Issi: Thanks so much.

Operator: Our next question comes from Steve Seedhouse from Raymond James. Please proceed.

Unidentified Analyst: Hi, thank you. This is [Nick] on for Steve. We actually had a longer term question. To what extent can you leverage the infrastructure that Vertex is already building out for CASGEVY will EdiTHAL won’t be able to plug into the existing authorized treatment centers once launched? Thank you.

Gilmore O’Neill: Thanks very much. And Nick. I’m going to ask Caren to address that.

Caren Deardorf: Yes, thank you, Nick, for the question. First, we’d say – I’d say that I’m really pleased to see some of the initial progress for the other therapies and being able to get patients started. We always anticipated that it would be a dipping, many centers starting to dip their toe. As they build the infrastructure and they gain the confidence. So to answer your question, absolutely. We’ve always said that in this kind of market of the complexity, of the ex vivo, being a fast follower is absolutely an advantage. We also, on our own, have a really strong base of over 20 clinical sites in the U.S. with very strong enrollment and relationships that we’re leveraging. And those relationships and the guidance they’re giving us will be really pivotal for us as well. But this is a field that will benefit, from the increase in education with patients, which Baisong mentioned, also helps with our enrollment and just building the infrastructure. But we are engaged on the KOL, the patient advocacy, as well as on the payer front to ensure that we’re prepared. So thanks for the question.

Unidentified Analyst: Thank you. Our next question comes from Jack Allen from Baird. Please proceed.

Jack Allen: Great. Thanks so much for taking the quick follow-up here. I just wanted to touch on reni-cel one more time, and ask when we might hear a little bit more about the differentiation, as it relates to the treatment process. Have you provided any color on the number of apheresis cycles, and how editing efficiency of the Cas12a enzyme may allow you to be more efficient in manufacturing the process?

Gilmore O’Neill: Thanks very much, Jack. So I’m going to ask Baisong to talk about that.

Baisong Mei: Yes. Thank you. We have not shared specifics about the number of cycle and the apheresis. What I mentioned before was since I joined, we actually work together with our internal as well as a apheresis external – apheresis expert. We actually have protocol amendment, to improve the apheresis cycle and also provide assistance to study site for the apheresis cycle, which is significant, because it’s reduced the patient burden. It’s a smoother manufacturing process. We’re very pleased to see the progress in that front. And just to add on that, we are hoping this clinical experience will be very much helpful for commercial endeavor.

Operator: Our next question comes from Mani Foroohar from Leerink Partners. Please proceed.

Mani Foroohar: Hi. Thank you for taking our follow-up question. Kind of similar to the last question, you previously talked about optimizing the vein-to-vein process. Would you be able to walk us through how reni-cel could provide advantages from either both operational or logistics perspective? Thank you.

Gilmore O’Neill: So Baisong I’m going to ask, I’ll ask Baisong to address that.

Baisong Mei: Yes. Happy to. We are over this process, really working together that with the study sites to optimize this process. And that coming from multiple factors. One of the factors just mentioned is bio- apheresis. The other factor is the logistics. And we provide support on that. The third factor is actually patient condition. As we know that we are treating the severe sickle cell disease. And before the reni-cel treatment, they can have multiple VOE per year. And that also can impact the vein-to-vein time.

Caren Deardorf: Mani, this is Caren. I would just add that, again, in the fast follower position, one of the things that it gives us the opportunity to do is to really understand as the first two therapies are commercialized, what’s working, what’s not working, what they need to see differently, and really making sure that Editas sets ourselves up as the partner of choice. And so, we’re working very hard on that. And we’ll certainly talk about that at a later time.

Mani Foroohar: Great. Thanks so much for taking questions.

Operator: Ladies and gentlemen, this concludes today’s call. Thank you once again for your participation. You may now disconnect.

This article was generated with the support of AI and reviewed by an editor. For more information see our T&C.

Syndax Pharmaceuticals , Inc. (NASDAQ: NASDAQ:) has efficiently executed its corporate strategy in the first quarter of 2024, as highlighted in its recent earnings call. The company has made significant strides with its revumenib and axatilimab drugs, securing priority review from the FDA for their respective filings.

With a strong cash position of $522 million, expected to last through 2026, Syndax is gearing up for the anticipated launch of these drugs in Q3 2024. The company is also preparing to report pivotal trial data later in the year and has detailed its financial guidance for upcoming quarters.

Key Takeaways

• Syndax Pharmaceuticals reported progress in its corporate strategy with FDA priority review for revumenib and axatilimab.
• Enrollment completed for Augment-101 pivotal trial’s NPM1 AML cohort, with data expected in Q4 2024.
• The company is on track for Q3 launches of revumenib and axatilimab, focusing on disease awareness and market access.
• Syndax anticipates significant commercial opportunities within the $750 million and $1 billion US markets for revumenib and axatilimab, respectively.
• Financial guidance for Q2 includes R&D expenses between $50 million and $55 million, and $240 million to $260 million for the full year.
• Syndax will report 50% of axatilimab revenues net of costs and has $450 million in milestones due from Incyte (NASDAQ:).

Company Outlook

• Cash reserves are robust, with $522 million on hand, sufficient through 2026.
• Syndax is actively pursuing business development to bring new molecules into the pipeline.

Bearish Highlights

• The company has not provided specific details on the size of the sales force for commercialization efforts.
• No specific timelines were given for the enrollment and data of the IPF trial for axatilimab.

Bullish Highlights

• Positive anticipation for revumenib and axatilimab with expected quick uptake in academic centers.
• Syndax is exploring the potential for revumenib as a maintenance treatment, increasing its use case.

Misses

• The company has not provided further details on their ongoing business development activities.

Q&A Highlights

• Syndax does not anticipate an advisory committee review for revumenib or axatilimab.
• The potential for off-label use of revumenib in the NPM1 subset was discussed.
• Executives expect a unique launch trajectory for axatilimab due to its characteristics and data.

Syndax Pharmaceuticals has displayed a strong commitment to advancing its product pipeline and preparing for the successful launch of its key drugs, revumenib and axatilimab. As the company anticipates approval and inclusion in medical guidelines, it continues to engage with healthcare stakeholders and payers to ensure broad access to its treatments.

With upcoming investor events in May and June, Syndax aims to maintain its momentum and further communicate its strategic initiatives to the market.

InvestingPro Insights

Syndax Pharmaceuticals’ financial health and market performance are crucial elements to consider alongside its promising drug developments. With a market capitalization of $1.89 billion, the company demonstrates a significant presence in the biopharmaceutical sector.

Despite not having a positive P/E ratio, which currently stands at -6.88, the company’s strategic moves in the drug development pipeline could be a harbinger for future profitability. The adjusted P/E ratio for the last twelve months as of Q1 2024 is -7.87, reflecting the company’s ongoing investments in research and development.

A noteworthy InvestingPro Tip is that Syndax holds more cash than debt on its balance sheet, which is a positive sign of financial stability. This aligns with the company’s reported cash reserves, ensuring operational funding through 2026. Additionally, Syndax’s liquid assets surpass its short-term obligations, providing further evidence of its financial robustness.

Investors may also be interested in the company’s stock performance, which has seen a substantial price uptick of 66.02% over the last six months, indicating strong investor confidence. Still, it is important to note that analysts do not anticipate the company will be profitable this year, and net income is expected to drop. This could be a point of caution for investors, weighing the potential of upcoming drug launches against the current financial metrics.

For those seeking a deeper dive into Syndax Pharmaceuticals’ financials and stock performance, InvestingPro offers additional insights and metrics. There are 8 more InvestingPro Tips available that can provide further guidance on the company’s outlook. To access these tips and enhance your investment strategy, visit https://www.investing.com/pro/SNDX and use the coupon code PRONEWS24 to get an additional 10% off a yearly or biyearly Pro and Pro+ subscription.

Full transcript – Syndax Pharmaceuticals (SNDX) Q1 2024:

Operator: Good day, everyone, and welcome to the Syndax First Quarter 2024 Earnings Conference Call. Today’s call is being recorded. At this time, I’d like to turn the call over to Sharon Klahre, Head of Investor Relations at Syndax Pharmaceuticals.

Sharon Klahre: Thank you, operator. Welcome, and thank you all for joining us today for a review of Syndax’s first-quarter 2024 financial and operating results. I’m Sharon Klahre. And with me this afternoon to provide an update on the company’s progress and discuss financial results are Michael Metzger, Chief Executive Officer; Dr. Neil Gallagher, President and Head of R&D; Steve Closter, Chief Commercial Officer; Keith Goldan, Chief Financial Officer. Also joining us on the call today for the question-and-answer session are Dr. Peter Ordentlich Chief Scientific Officer; and Dr. Anjali Ganguli, Chief Business Officer. This call is accompanied by a slide deck that is posted on the Investor page of the company’s website. You can now turn to our forward-looking statements on slide 2. Before we begin, I’d like to remind you that any statements made during the call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the risk factors section in the company’s most recent quarterly reports on Form 10-Q as well as other reports filed with the SEC. Any forward-looking statements made represent our views as of today, May 8, 2024, only. A replay of this call will be available on the company’s website, www.syndax.com following its completion. With that, I am pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax.

Michael Metzger: Thank you, Sharon, and good morning, everyone, and thank you for joining us on the call today. I’d like to begin by welcoming Steve Closter to the call. Steve joined us in March as Chief Commercial Officer. He brings over 30 years of commercial experience to Syndax, which includes establishing winning teams and leading successful product launches. Steve is building on the excellent framework that was in place prior to his arrival, and we are already benefiting from his keen insights as we prepare for commercialization. In the quarter, we made significant progress on executing against our corporate strategy. As you can see on slide 3, we achieved several significant milestones this quarter, including securing priority review from the FDA for both revumenib NDA filing and the axatilimab BLA filing. We also completed enrollment in the NPM1 AML cohort of Augment-101, pivotal trial, bringing us one step closer to expanding the market opportunity for revumenib. We look forward to reporting data from the initial trial in the fourth quarter of this year, which could serve as the basis for a supplemental NDA filing in the first half of 2025. These accomplishments set us up for an eventful 2024 that we expect will include two full US regulatory approvals, NPM1 pivotal data readout, additional combination data for recommended for revumenib in KMT2A and NPM1, initiation of a pivotal trial for revumenib in frontline KMT2A and NPM1 acute leukemia in combination with venetoclax, as well as the initiation of two combination trials for axatilimab in frontline chronic graft versus host disease. As we approach our expected approvals, we are working to ensure that we are fully prepared to successfully launch at any time during the third quarter with an ability to reach all patients in need as rapidly as possible. Steve will provide additional details on our launch preparations later in the call. Syndax has a differentiated profile as a smid-cap biotech with two first and best-in-class drugs on the cusp of their potential first approvals. Notably, revumenib has a potential second significant indication and near-term expansion opportunity in relapsed or refractory NPM1 that meaningfully extends the target patient population in acute leukemia. This is unique in a launch year as it quickly broadens the market opportunity for revumenib in the relapsed or refractory setting to up to 6,500 patients. Multiple opportunities beyond the initial relapse or refractory indication exists for both assets. And trials are ongoing that can drive significant long-term value for these franchises for years to come. We are well-funded with $522 million in cash as of March 31, that we expect will provide significant capital through 2026. Our current balance sheet not only supports our planned commercial launches and clinical trials, but also allows us to expand beyond our core registration indications and pursue select business development opportunities. I’ll now ask Neil to provide an overview of the pipeline. Neil?

Neil Gallagher: Thank you, Michael. In the first quarter, the NDA filing for revumenib of a highly selective menin inhibitor was granted priority review by the FDA for the treatment of adult and pediatric relapsed or refractory KMT2A rearranged or MT2Ar acute leukemia and issued a PDUFA date — target date of September 26, 2024. The filing is being reviewed under the Real-Time Oncology Review, which provides a more efficient review process and has historically led to earlier approval . The submission is based on data from the pivotal AUGMENT-101 trial outlined on slide 4 where single-agent revumenib induced a high percentage of blastfree responses in heavily pretreated KMT2Ar acute leukemia patients, thereby, enabling many of them to undergo potentially curative stem cell transplant and to continue revumenib monotherapy following transplant. We’ve also completed enrollment in the final pivotal cohort of the AUGMENT-101 trial of 64 adult relapsed refractory NPM1 AML patients in March and expect to report the pivotal results from this population in the fourth quarter of this year. I’ll take a moment to review the Phase 1 data on slide 5 that underlines our confidence in the pivotal results for patients with relapsed or refractory NPM1 AML. Multiple presentations generated by us in both the relapsed or refractory and frontline settings have highlighted the consistency of menin inhibition across NPM1 mutations and KMT2A rearrangements, and we see the enthusiasm building for the revumenib in NPM1. The Phase 1 NPM1 data that we’ve reported supports our conviction that revumenib could be an important treatment for this AML population. In the Phase 1 part of AUGMENT-101, 50% of NPM1 patients achieved an overall response and 36% achieved complete remission or CR with partial hematological recovery. And importantly, all patients with CR/CRh were MRD-negative. Consistent with the KMT2Ar population, revumenib also enabled a high percentage of NPM1 responders to proceed to transplant 43% and responses have been durable. This is despite many of the patients having failed prior venetoclax therapy and prior stem cell transplants. It’s worth noting that revumenib has been well tolerated in patients with relapsed or refractory NPM1 AML. In the Phase 1, there were no Grade 4 or 5 QT prolongation events, no patient experienced greater than Grade 2 differentiation syndrome, and no patients discontinued due to treatment-related adverse events. We believe that revumenib will form the backbone of treatment for patients who have both KMT2Ar and NPM1 acute leukemias. Our clinical strategy extends beyond the initial relapsed or refractory populations and into the frontline and post transplant maintenance settings, including combinations of approved therapies. We have several combination trials ongoing with different standards of care across the continuum of patients, including in the fit and unfit settings that are listed on slide 6. Investigators presented data from multiple Phase 1 combination trials, including Beat AML, SAVE AML, and AUGMENT-101 during the American Society of Hematology Conference in December, demonstrating revumenib’s ability to safely and effectively combine with the standards of care. We expect to provide updated data from these trials later this year. In the first quarter, we initiated another Phase 1 combination trial with standard-of-care intensive chemotherapy, also known as 7+3. Beyond acute leukemia, we are investigating the opportunity to expand to solid tumors. Our proof-of-concept signal seeking Phase 1 clinical trial in metastatic colorectal cancer is ongoing, and we expect to provide an update on the progress of the dose escalation phase of the trial later this quarter. Turning to axatilimab on slide 7. Also in the first quarter, the BLA filing for axatilimab or CSF-1R antibody was granted priority review by the FDA for the treatment of chronic graft versus host disease or chronic GVHD after failure of at least two prior lines of systemic therapy with the PDUFA date of August 28, 2024. This submission is based on data from the pivotal AGAVE-201 trial for treatment with single-agent axatilimab led to an overall response rate or ORR of 74% with 60% of responders didn’t respond for one year. Importantly, axatilimab has a differentiated mechanism of action from currently approved therapies for chronic GVHD. It is the first investigation of chronic GVHD agent to target inflammation and fibrosis through the inhibition of disease-associated macrophages. We’re excited about the opportunity to expand axatilimab into the frontline setting in combination with standards of care and other fibrotic diseases where monocyte macrophage lineage plays a key role, including idiopathic pulmonary fibrosis or IPF, where we are currently enrolling a Phase 2 clinical trial. The team has been working hard to increase awareness of the compelling regimen of AUGMENT-101 and the axatilimab AGAVE-201 data ahead of the respective potential approvals. In April, investigators presented pediatric data from AUGMENT-101 in a plenary session of the American Society of Pediatric Hematology/Oncology that further supports the consistency of the data across subgroups. Also in April, investigators presented additional analyses from AGAVE-201 at the European Society for Blood and Marrow Transplantation Congress highlighting axatilamab’s impressive clinical activity in fibrosis-dominant organs, which, as I mentioned earlier, is a key point of differentiation. We have ambitious publication plan underway, and we look forward to detailing more of the clinical benefits of axatilimab and revumenib to the prescribing community. I’ll now turn the call over to Steve to talk about preparation for a planned commercial launches on the market opportunity. Steve?

Steve Closter: Thank you, Neil. This is an exciting time to be at Syndax, and we’re looking forward to launching two first-in-class and meaningfully differentiated agents this year. As Michael indicated earlier, we’ll be ready to launch revumenib and axatilimab in the third quarter. And we’ve made significant progress so far this year to prepare ourselves in the market to realize the full potential of these medicines for patients or health care professionals and the company. Our key focus areas are highlighted on slide 8. Our pre-commercialization strategy has focused on developing an efficient, effective, and purpose-built infrastructure to support the business and prioritize relationships with important external stakeholders [Technical Difficulty] and the health care provider as well as the payer space to accelerate uptake at launch. For revumenib, our prelaunch activities have been centered around disease awareness, mechanism of disease education, and market access, as well as ensuring patient support services are in place at the time of launch. The customer facing leadership team has been in the field for some time and focus on disease state awareness and building relationships with health care providers. The team is actively profiling accounts, understanding workflows and identifying the patient journey at the largest and most influential academic centers in the country. This has allowed us to have important conversations with health care providers and other health care organization decision makers and gained valuable insights on the market, which has helped us define our outreach strategy. We launched a non-branded campaign last year, focused on improving the knowledge and understanding around the role of menin inhibition across key segments of acute leukemia, including KMT2A rearrangements, as well as follow-on indications like NPM1 AML. This effort will expand as we approach a potential launch. We’ve recruited a talented and highly experienced sales team with an average of 22 years of experience, primarily in hematology/oncology with an average of six product launches per representative. This is obviously a very experienced group with existing relationships and proven past success. The customer facing field team will play a multidisciplinary role in supporting health care professionals and patients. With regard to market access, our team has been educating commercial and Medicare payers on the burden of relapsed or refractory acute leukemia to prepare them to conduct timely and evidence-based reviews and ultimately access decisions upon potential FDA approval while formulary approval builds over time. We have little doubt that revumenib will be covered for reimbursement, while plans to review the product for formulary inclusion. We’ve been meeting with pharmacy benefit managers and payers since 2023, sharing relevant market and product information and expect to reach plans covering more than 90% of all lives prior to revumenib’s anticipated approval. Payers are telling us that they recognize the significant unmet need in KMT2Ar acute leukemia patients and the benefit that revumenib could provide as supported by the AUGMENT-101 data. This is important due to the acute nature of the disease and the high mortality and morbidity in relapsed or refractory KMT2Ar acute leukemia, making the urgency to treat quickly absolutely critical. I’m excited about our progress to date and look forward to sharing more about our ongoing efforts in the future. Turning now to slide 9, KMT2Ar and NPM1 acute leukemias represent up to 40% of all AML patients. And there are no FDA approved targeted therapies for this population. We believe relapsed or refractory KMT2Ar acute leukemia alone represents a total addressable market of approximately $750 million in the US. The annual incidence of KMT2Ar acute leukemia is about 2,600 patients and the majority are refractory to front-line standard-of-care treatments. We estimate a median duration of therapy across the treated population of approximately nine months, and we believe the clinical data supports pricing competitively to other targeted therapies in AML, such as the FLT3 or IDH inhibitors. Physicians we’ve spoken with indicate an eagerness to prescribe revumenib early during an eligible patient’s treatment journey to bring more patients to transplant and then extend responses by continuing with revumenib line of therapy following transplant engraftment. We expect that our first mover advantage and the early experience physicians will gain treating patients with revumenib will be vitally important to the long-term success of our brand. Our significant market share is likely to extend meaningfully beyond KMT2Ar, especially as we will be the first to deliver meaningful pivotal data in other indications such as NPM1 AML. We estimate that the two distinct market segments in acute leukemias, KMT2Ar and NPM1 available accessible population of 5,000 to 6,500 patients in the relapse or refractory setting and an addressable market opportunity that approaches $2 billion in the US. Turning now to slide 10, approximately 14,000 US patients suffer from chronic GVHD, 50% of whom require treatment beyond second line due to disease progression, inadequate response, or disease manifestations that aren’t wholly addressed with current treatments. There are no cures for this advanced chronic GVHD patient population. Patients initially treated with corticosteroids are then cycled through a variety of additional therapies based on the physician’s experience and manifestations of the disease being addressed. The successful commercial launches of Jakafi and , and importantly, the speed by which both these agents gained adoption really speak to the unmet need in chronic GVHD. We also know that despite these recent advances, the disease is still inadequately treated and physicians are looking for an agent that can better address the underlying fibrosis that ultimately leads to organ damage. Further, they are excited to have a drug with such a fast onset of action and impressive durability of response. These key points of differentiation should enable axatilimab to carve out a sizable commercial opportunity within the estimated $1 billion US refractory chronic GVHD market. As you know, Incyte is our partner for axatilimab and really the leader in the GVHD space. As of last year, we exercised our option with Incyte to co-commercialize axatilimab in United States and provide 30% of the commercial efforts as we believe there is a considerable benefits of [indiscernible] two products simultaneously to a highly overlapping and targeted physician prescriber universe. We’re working closely with Incyte to develop our go-to-market strategy for axatilimab and plan to align more fully with Incyte before sharing additional details. However, we expect to follow a similar set of strategic imperatives as we’ve just outlined for revumenib. Now I’ll turn the call over to Keith to review our financial results.

Keith Goldan: Thank you, Steve. Turning to slide 11, as Michael mentioned earlier, the $522 million in cash equivalents and short- and long-term investments on our balance sheet at March 31, expected to provide runway through 2026. Our financial strength allows us to appropriately invest to maximize the value of our pipeline, and importantly, to transition into a commercial stage organization this year. Turning to the income statement, operating expenses in the first quarter was $79.5 million, comprised of $56.5 million of research and development expense and $23.0 million of selling, general, and administrative expense. Keeping in mind that we’ve always embraced a disciplined approach to resource allocation, we’d like to provide financial guidance for the second quarter and full year of 2024. For the second quarter, the company expects research and development expenses to be $50 million to $55 million and total operating expenses to be $80 million to $85 million. For the full year 2024, there is no change to the existing guidance, and the company continues to expect research and development expenses to be $240 million to $260 million and total operating expenses to be $355 million to $375 million. Note that the guidance range for operating expenses for the full year 2024 is inclusive of an estimated $43 million of non-cash stock compensation expense. And preparing for launch, I want to take a minute to lay out how we plan to recognize revenue for axatilimab. Slide 12 includes an illustrative example of accounting for sales of axatilimab and is not intended to provide any margin or other guidance. Commercially, our partnership with Incyte is a 50/50 split of the economics in the US. We will report 50% of revenues earned, net of cost of sales and commercial expenses. During the period where there is a net commercial profit for axatilimab, as in the top example on this slide, our 50% share of the net profit will be recognized on our P&L as collaborative arrangement revenue. During a period where there’s a net commercial loss for axatilimab, as in the bottom example on this slide, our 50% share of the net commercial loss would be included in operating expenses designated as a separate line item called share of collaboration loss. We also have various future US commercial and regulatory milestones owed to us from Incyte that would be recorded as partnership or milestone revenue on our income statement.Development expenses are shared 55/45 in the US and our 45% share is included in the income statement as part of R&D expense. Outside of the US, Incyte is responsible for 100% for the development and regulatory expenses, and we are entitled to receive a milestones plus royalties on ex-US sales. With that, let me now turn the call back over to Michael.

Michael Metzger: Thank you, Keith. As you’ve heard during the call, 2024 is shaping up to be a historic year for Syndax as we prepare to launch two first-in-class products. And I’m confident that we have the expertise, resources, and determination to bring these products to market. As an organization, we are truly excited to evolve into a commercial organization, and we are laser focused on bringing these important treatment options to patients in need. On slide 13, we lay out our key upcoming milestones for the balance of the year, and I look forward to updating you on our progress in the coming months. As always, I would like to express my sincere appreciation to the Syndax team, our collaborators, and most importantly, the patients, trial sites, and investigators involved with our clinical programs. Through our work and dedication, we are getting ever so close to delivering on our mission of improving the lives of patients with cancer. I’d also like to thank our committed, long-term investors who continue to share in our vision and support us in building Syndax. With that, I’d like to open the call for questions. Operator?

Operator: [Operator Instructions]. Our first question is from Peter Lawson at Barclays.

Peter Lawson: Just first question is around how important NCCN guidelines will be for new additional indications after you get the initial approval for revumenib.

Michael Metzger: Peter, thanks for the question. Maybe I’ll ask Neil to comment on the importance of the guidelines.

Neil Gallagher: Yeah. Thanks, Peter. So as you know, the first approval — we’re anticipating that the first approval for revumenib will come in the third quarter, and that will be for KMT2A rearranged acute leukemias in adults and children. So the approval will be — should be sufficient to actually have that indication included in the guidelines. And in addition to that, we’ve also guided to the fact that we will — in fact, I referenced agenda — prepared remarks that we anticipate reporting pivotal data from the NPM1 cohort by the end of the year. So suffice to say that we have a plan. I mean, prior to approval, presentation at medical congress along with publication of the data could position us to at least start conversations with the NCCN committee regarding inclusion in the guidelines, as you’re aware the committee meets twice a year. These disease-specific committees meet at least once a year, but they also meet ad hoc, once important new data become available. So we’re considering all of that. And clearly, we want to make sure that the best possible information is made available to the committee as well as to prescribers when we publish our data.

Peter Lawson: And then as we think about expansion of revumenib to solid tumors, kind of, just if you could detail the expectations around the CRC data — that’s still 2Q, when we should expect to see that data at medical conference and number of patients?

Neil Gallagher: Thanks, Peter. Thanks for the follow-up. So question was related to solid tumor is in our plans there. And as we’ve disclosed and mentioned in the prepared remarks, we are continuing to work in the area of colorectal cancer. This is metastatic colorectal cancer, third line, plus these are — and we are conducting a Phase 1 trial. We had said that we had planned to disclose some information, update everyone on our progress there in the second quarter, and that remains to be the case. Let me remind everyone, this is a dose escalation trial. So this is roughly 10 to 20 patients heavily pretreated. And what we’re essentially looking for — looking to see is activity of revumenib again in this patient population, looking for prolonged stable disease in four to six month, so call it, a range with perhaps around 15% of the patients in that stable disease category. So that’s the signal that would be — we think impactful. Of course, patients don’t do very well in this setting. And certainly, standard of care doesn’t yield prolonged stable disease of that nature. So we’ll obviously update when we’re ready to do so in the second quarter.

Operator: Our next question is from Anupam Rama at JPMorgan.

Anupam Rama: Hey, guys. Thanks so much for taking the question. Maybe a quick one for Stephen. Just wondering, you know, before you join Syndax and you doing assessments for the opportunities for revumenib and axatilamab, what really attracted you to these products? And then the second one is also actually for Stephen, you mentioned very broadly what some of the levers for success in slide 8 are for both of these launches, but anything more specific to revumenib in KMT2A that you’d highlight? Thank you so much.

Steve Closter: Yeah, thanks for the question. I’ll answer both. First is why did I probably come here. And it’s truly a combination of things. I’ve been pretty careful over the course of my career, and I think this is my fourth organization in 30 years, so the bar is pretty high. I look at all opportunities in three different factors. The first is that needs to be great products, product set, addressed unmet need, products that have a great amount of clinical data, and really provides differentiated attributes. And I think both revenueand axa have that. I knew that coming in. And as I’ve seen the data and as I’ve reviewed lots of market research and actually engaged with KOLs, that’s only been amplified. I think the second thing that I really think about is really who I work with, right, wanting to be a companies with great people and great leaders. And that’s exactly what we have here. Michael, the entire , the Board are all top-tier, very supportive. And even walking in the commercial leadership team that was in place was strong as well. And the third thing for me is really the willingness to invest and plan for success, and we have that here too. So I’d say my expectations have been exceeded coming in and I’m more excited now than I was even before I started, I think I mean, we . The second question is really around levers for success on revumenib. There’s a lot we’re building as a commercial organization and all of that will be in place. I think as Neil mentioned and Michael mentioned in his remarks, we’ll be ready in Q3. So infrastructure processes, all those things will be done. I think from a strategic point of view, well, the three things that I think about that we are very focused on, really the first is the population of patients is limited. We know that, righ? And that opportunity will grow over time, but finding them is critical. Patients are fragile. They need treatment immediately. So we’ve got focus there. I think the second thing is just the landscape of health care delivery. There’re multiple stakeholders out there that deliver care to patients. Physicians, nurses, advanced practice providers, pharmacy, reimbursement, pathology, you name it. We have a customer-facing footprint that will address and directly engage with that dynamic. And the third piece, third point is really access, sight? Neil mentioned NCCN guidelines, which will be important. Payers are looking for that. They’re looking for other published data. The patients need access to treatment. So we’ve been deployed against the payer space for some time on calls directly with payers, and that is in an effort to really expedite formulary review. And in addition, we’ve built a support program to meet the needs of patients, which we know their need. So thanks for the question. I hope that was a good answer.

Operator: Our next question is from Brad Canino at Stifel.

Brad Canino: Hi, good morning. Relating to the plan for the pivotal ven/azac combo trial to be initiated by year end. This will move the emphasis of clinical endpoints from CR towards remission, durability, and OS. And I want to ask how does the company plan to evaluate data from the uncontrolled trial updates later this year, both from the combos and also the NPM1 pivotal monotherapy, in order to gain confidence in the randomized endpoints for the frontline pivotal? Thank you

Michael Metzger: Brad, thanks for the question. I’m going to turn it over to Neil to address that.

Neil Gallagher: Yeah, thank you for the question. I mean, all of this combination studies that we reported on the one specific, scenario. In other words, initiating the Phase 3 revumenib ven/azac study by the end of the year is the Beat AML study. And as you’re aware, we — the group reported data around the ASH meeting last year and anticipate updating those data during the course of this year. Those data are exciting, not only to the company, but also to the investigators and actually not just the Beat AML investigators, but the broader community. So people are highly enthusiastic, when initiating the Phase 3 study. Just to remind you the response rates, including the CR/CRh rates that were observed and the Beat AML studies to date have exceeded the historical controls observed in , including in terms of CR, in particular, molecular MRD-negative CR was much, much higher in the Beat AML study compared to VRA. So the emergent data, including the observation that revumenib is highly combinable. It’s not adding. It doesn’t appear to be adding toxicity to the backbone therapy as well as being — providing incremental efficacy in the target patient population. And that’s bolstered also by the observations from, for instance, SAVE. The SAVE study, which is a combination of revumenib with venetoclax and/or azacitidine in a relapsed refractory setting as well as our own AUGMENT-102 trial, the combination trial, with relapsed refractory population in combination with chemotherapy. So the body of the evidence is that revumenib is combinable with backbone standards of care is not adding toxicity. In the target population for the Phase 3 trial in the newly diagnosed unfit population, the BAML data providing evidence that revumenib is also adding in a notable efficacy through the backbone therapy. So obviously, we will be having conversations with health authorities as we design the trial. We don’t typically comment on those, but we look forward to presenting more details around the study prior to initiation later in the year.

Operator: Our next question is from Phil Nadeau at TD Cowen.

Phil Nadeau: Morning. Congrats on progress. Thanks for taking our questions. A few for us. First, in terms of the Phase 2 doses in the combo trials or validating the Phase 2 doses in the combo trials. This morning’s press release notes that some of the trials have been expanded to validate the Phase 2 doses. Just curious whether you’d be willing to disclose whether the full monotherapy dose of revumenib is being used in those combinations at this point?

Michael Metzger: Neil?

Neil Gallagher: Yeah, thanks for the question. So I’ll just remind everyone the 3 studies that I just referenced and the three — and answer to the previous question are the studies under discussion. So I won’t repeat what those are. In all three of those studies — in all three of those trials, there are two doses of revumenib that were investigated: 113 milligrams and 163 milligrams. 163 milligrams is the presumptive monotherapy dose in combination with the strong that will be included in the label. So revumenib has been given at full dose in all three trials. By the time we talked about them at the event around the ASH last December, in all three, the dose-limiting toxicity windows for both doses have been cleared and both doses are being expanded in all three trials at this point in time. So we haven’t — when we talked about RP2D, we’re continuing to characterize the two doses. But in general, our anticipation is that revumenib — our observation to date is that revumenib is combinable at full monotherapy dose with backbone standards of care.

Phil Nadeau: That is very helpful. Thank you. And then second question, based on the milestone tables that you just presented, it doesn’t seem like you’re anticipating an advisory committee review for either revumenib or axatilimab. Is that accurate? And can you remind us did the FDA explicitly, say, in acceptance letters that would not be necessary for both drugs?

Michael Metzger: Yes, Phil, thanks for the question. And I think our expectation is that neither axatilimab nor revumenib will require an AdCom, but we haven’t explicitly stated or nor do we comment on regulatory correspondence from the agency relative to things like that. So but that is our expectation that neither will need an AdCom.

Phil Nadeau: Perfect. Then last question from us, you referenced the nine months expected median duration of use for KMT2A patients, can you remind us what proportion of patients go into transplant is assumed in that nine-month figure?

Michael Metzger: Phil, thanks for the question. It’s roughly about a third of that half, right — of the patients that go transplant.

Phil Nadeau: So a third of patients who get a relapse refractory line or go to transplant is the assumption?

Anjali Ganguli: Yeah, Phil, it’s Anjali. I think what we’ve been saying is there’s usually three groups of patients that seem — based on the trials seem to all be about an equal sized population. There were a third of patients that did not respond. Of the two-thirds of patients that responded, half went to transplant. So overall, the entire population is third that go to transplant.

Operator: Our next question is from Michael Schmidt with Guggenheim.

Michael Schmidt: Hey, guys. Good morning. Thanks for taking my questions. I just had one on the axatilimab launch, now that we’re obviously closing in on the PDUFA date later this year. And as we think about the $1.5 billion to $2 billion opportunity in a relapsed refractory setting, just wondering how we should think about perhaps the early launch trajectory, subsequent approval? Are there any good proxies we should look at, for example? And then, what are your expectations for potential off-label use in the NMP1 subset. Obviously, we will have data later this year. Could that help next year to accelerate the launch early on? Thanks so much.

Michael Metzger: Yeah, Michael, thank you for the questions. I’m going to ask Anjali to comment on the launch.

Anjali Ganguli: Yeah, thanks, Michael. No, we’re really excited about this opportunity. I think what revumenib has been — certainly, this is a very unique situation. As you know, we got through the clinical development in record time, first patient dose to NDA filinng in four years. We generated data that support indications across AML and ALL, adults and pediatrics. And as you said, we’re anticipating an approval in the third quarter of this year, and we’ll have data for another very important patient population treated by the exact same set of health care providers in a disease where physicians can choose the best options for their patients. And then on top of that, we also talked about all the combination data we’ve generated with revumenib that allow them to think about multiple ways to use this drug and fit it into their treatment plans as they think best. So I think we have a very unique launch curves that we’re going to be generating in real time. I don’t think there’s a perfect analogue that addresses all of these aspects of what’s coming in the next 12 months. But we have seen very significant excitement around revumenib around this new class of agents and how they can utilize it to bring care to patients that have had nothing. And I think you’ll recall the last two ASH meetings have been very focused on the data that we’ve been generating. And I think that shows how much education is already out there. And Steve talked about, there’s a lot more that we’re doing to make sure everybody’s aware of the drug or the support and patient support is in place to allow utilization. And we’re really excited to have a really strong launch of revumenib.

Michael Schmidt: Maybe just a follow-up. Can you just remind us what percentage of the AML market is under Medicare? And how do you think about pricing in the Medicare population or any sort of expectations for free drug programs as we think about the early launch again later this year?

Michael Metzger: Yes. Let me ask — thanks, Michael. Let me ask Steve to comment on those questions.

Steve Closter: Yeah. I mean, it’s a good question. And the payer space is different for KMT2Ar versus NPM1. It will be more of a commercial patient for the KMT2A launch just based on the age of the patient. We’ll expect coverage honestly at launch. Formulary acceptance will happen overtime, right? Typically, takes six to nine months for that to happen. But in the meanwhile, for health care providers, their staff are very fluent on how to get through the medical exception process. That’s where the NCCN guidelines are helpful and all the other published data, Medicare payers will be less important for KMT2Ar but for NPM1 patient population, which is a little bit older, it’s going to change. So our approach has been really over the last nine months, even a year is really to to all plans. We’ve been delivering a and information exchange, if that’s the preapproval information exchange. So we’ve had some very good interactions with payers. They recognize the unmet need and the criticality of patient care, I think, is largely set its unique launch where you’ve got a launch followed by what seen other launch in a year. So we’re prepared for both at the same time. It takes time to build coverage. So we’ve got the whole payer space. I think, in my prepared remarks, we will talk to payers that cover 90% of covered lives in this country, which is as good as it gets, in advance of approval. So we’re prepared for success.

Michael Schmidt: Okay, great. And then maybe just a housekeeping question. As we think about the time of filing and potential approval, are there any milestones due from Incyte for that that we should incorporate in our models this year?

Michael Metzger: Yes. Thank you, Michael. Keith?

Keith Goldan: Yeah, Michael, we do — as disclosed in this Q and as we’ve disclosed in past Qs and Ks, we do have not only development regulatory milestones, but commercial milestones to us from Incyte. Total milestones for development regulatory under the agreement were $220 million. Total commercial milestones were $230 million. So a total of $450 million due us. You can expect those to come at major — certainly major regulatory events such as approval. I think that’s a reasonable expectation. But we haven’t been more specific as to the amounts.

Operator: Our next question is from Yigal Nochomovitz with Citigroup.

Yigal Nochomovitz: Yeah, hi. Thanks very much for taking the question. Just on NMP1 regulatory pathway [Technical Difficulty] breakthrough or given sNDA, is that — are those options not really necessary?

Michael Metzger: Yigal, thank you for your question. You broke up a little bit, but I think I captured it. So as you know, we’ve had breakthrough therapy designation for KMT2A. For NPM1, we have the opportunity to potentially get breakthrough therapy, probably most importantly, your first indication. and I think the engagement around KMT2A and the molecule and the submission package has been very strong. We have priority review as well. I think for NPM1, we’ll look to leverage some of the same access points with the agency. But we’re, I’d say, pretty well advantaged by what we’ve — what’s come our way already. But I will say we don’t generally comment on regulatory strategy, but the opportunity to submit for BTD at a point in the future is open to us. So I think it’s obviously a program that we’ll have data on later this year. We’ll have a submission, we hope, by — in the not too distant future beyond that and then look to get the drug approved in 2025. So that will be through an sNDA process. So it’s all, I’d say, call it an expedited pathway through some of the designations we have in hand already or some of the things that we may avail ourselves in the future.

Yigal Nochomovitz: Okay, thanks. And then when you think more broadly about the revumenib in terms of the spectrum of care in AML, both in the frontline and in relapsed refractory, and given the fact that there’s a good chance that you’re going to be initiating a pivotal trial in the frontline in combo with venetoclax. When you start to think about the commercial build there, are you making assumptions around the potential pretreatment revumenib for patients that received revumenib in the frontline in a combination setting, whether it be with [indiscernible] or perhaps even with the 7+3, including those patients in the builds for revumenib in a relapsed refractory setting? Or once they are treated in the frontline, that wouldn’t be a part of your assumption set? Thank you.

Michael Metzger: Yes, thanks, Yigal. I think our assumption is that once you’re treated with revumenib, at least from our vantage point, the way we see it today, I think once you’re treated with the — in the frontline setting, it’s less likely that you’re going to be treated in the relapsed refractory setting, again with another revumenib inhibitor. And Neil, do you want to make a comment?

Neil Gallagher: Yeah, I agree with Michael’s comments there that I think that it is a little bit nuanced because I think longer term or I can foresee situations where patients could, for instance, have either been treated and relaxed along time later on NMP1 [Technical Difficulty] positive or came to a positive market might be very exposed. But I think, in general, I agree with Michael’s points. We shouldn’t be expecting a lot of patients to [indiscernible]

Yigal Nochomovitz: And just one on axa, do you have any timelines for the IPF trial in terms of enrollment and data?

Michael Metzger: Thanks, Yigal. No, not at this point. I think we are enrolling. As you know, we started recently bringing up sites and enrolling patients, and it’s going nicely. And so we’ll have more to say in terms of milestones, both for enrollment as well as data as we get further into the year, maybe into next year.

Operator: Our next question is from Kalpit Patel with B. Riley Securities.

Kalpit Patel: Can you comment on what proportion of patients that you estimate might be eligible to receive revumenib as a maintenance treatment after induction and consolidation. I’m trying to understand if that median duration of treatment in that specific frontline setting would be higher than the nine months that you expect in the relapsed refractory setting. Thank you.

Michael Metzger: Yeah, thanks for the question. I think if I interpret your question correctly, I think in terms of patients who would be eligible for maintenance going in the relapsed refractory setting. I think if you’re getting — if you had a successful transplant, there’s no reason that all patients wouldn’t necessarily be eligible. They need to have — be stable and graft well, and I think that usually the first step in pitching the physicians, remind us of that that there’s an engraftment period. But for all intents and purposes, all patients should be eligible for maintenance. So I think that’s our assumption. And that’s, I think, been discussed with physicians on an ongoing basis. I think when you get to the frontline setting, the assumptions for long-term maintenance and how that would play out in the fit population could very well differ if you are able to get to patients earlier and treat them successfully through transplant and put them back on therapy. I think the expectation is treat patients earlier they stay on — they do better and they stay longer and so that should change how the assumptions work on the time on maintenance in the frontline compared to relapsed refractory. We don’t have a good estimate of that yet. Obviously, we’re generating that data. But over time, we’ll understand that a little bit better.

Operator: Our next question is from Jason Zemansky with Bank of America.

Jason Zemansky: Perfect. Thank you. Good morning and congratulations on the progress. Appreciate you taking our questions. Regarding the commercialization plans for revumenib and your initial outreach, I have to imagine there’s already quite a bit of excitement across at least the more academic-focused community. But what sort of division between rapid adopters and non do you expect? How quickly do you expect maybe the more community-based prescribers to come on board as far as awareness and education goes? And maybe bolus isn’t quite the right descriptor, given patient dynamics this late in treatment, but do you expect an initial large bump in patient numbers or more of a straight line uptake?

Michael Metzger: Jason, thank you for the question. I’m going to turn it over to Steve to address your questions.

Steve Closter: Yeah, hey, Jason. Thanks for the question. I mean, there’s a lot of excitement. I think predating, coming to the company, the company has done quite a bit of research, market research, advisory boards, and that with KOLs and the field medical team has been out there. So there’s a lot of, well to say, demand that’s there because of lack of treatment options. I’ve recently — I actually was out in New York yesterday at Cornell and and meeting with KOLs, so they’re ready for the drug. Literally cannot wait till it hits the market. So I think certainly the academic centers, Jason, there will be quick uptake. They are ready for this product. Awareness is already fairly high, whether it’s revumenib or menin inhibitor. I think downstream, in the community, it’s going to take a little bit of time. Part of it is just they may not see a lot of patients initially. So it’s up to us to be there. So from a commercialization standpoint, we’ll have a adequately sized team that’s going to cover 95%-plus of the opportunity. I will have a nonpersonal promotional program that will reach folks in places that we may not be at as frequently. So I think you’ll see quick uptake across the board. And a lot of it’s just patients in the office ready to be treated. Leads to your second question, and there’s not going to be much of a bolus. We have an EAP that’s in place. I can’t give the number, but it’s a certain number of patients. No one’s withholding treatment for eligible patients, to your point. The criticality is just too high. So it will be a little, I will say, actually initially coming EAP, that will burn out over the beginning months of the launch. And then after that, we’ll expect the typical uptick just based on our assumptions and available patients.

Jason Zemansky: Got it. Makes sense. And then maybe just a quick follow up on your Phase 1 and metastatic colorectal cancer. In terms of the go, no-go decision, I know you mentioned disease stabilization as important, but was curious, is there a specific signal, I don’t know, maybe a biomarker what you’re looking for in terms of menin’s potential or hypothetical role in driving solid tumors that would just make you feel confident about investing significantly in this potential expansion opportunity?

Michael Metzger: Jason, thanks for the follow-up on CRC. I’m going to turn it over to Neil to address.

Neil Gallagher: Yeah, thanks. And so in the part of the study that has been conducted to date, I just — to reiterate Michael’s point, this is primarily the safety part of the study. We are looking at in addition to clinical responses, I mean, primarily, it’s a safety study. We’re also looking at clinical responses. We’re also looking at biomarker data. And anticipation is that as we get to a point in the future where we could make a decision on future development in this space, but this to be taken into consideration. We haven’t specifically set colorectal data we’re looking at, but at some point in the future, we will provide more details around it. I wouldn’t expect necessarily too much data in in our update in the second quarter, for instance, colorectal data. But rest assured that we are pursuing colorectal studies. And as I said, we’ll take the totality of the evidence into consideration.

Operator: Our next question is from Justin Zelin with BTIG.

Justin Zelin: Thanks for taking the question and welcome to Steve. So ahead of two launches this year, I wanted to ask how large of a sales force you’re looking to build here. And could you talk to the overlap of providers who treat both leukemia and chronic graft versus host disease from promotion of both products?

Michael Metzger: Sure. Maybe I’ll let Steve take that question.

Steve Closter: Yeah, I appreciate the question, Justin. In terms of salesforce size, we’re not prepared to provide the exact color and size of the team. But it will be a team that I think can really address customer needs. Our goal, whether it’s providers or anybody within the health care delivery system that it’s a great customer experience. So we’re prepared to link up to all different aspects of health care organizations to make sure we’re meeting the needs and supporting providers in their treatment of patients. So I think I use the term plus 95% coverage. So we’ll cover the opportunity. There is no doubt about that. In terms of overlap between on GVHD and rev, there’s high overlap. I mean, we’re likely along with Incyte calling on the same treatment centers, right, whether it’s treatment of AML or treatment of transplant, and we’ll leverage that call point. Yeah, there’s probably a third overlap right now of our rev audience with the axa audience. We’ll obviously provide 30% of the effort. So we’ll leverage our footprint and we will cover the market opportunity in really both opportunities.

Operator: Our next question is from Chris Shibutani with Goldman Sachs.

Chris Shibutani: Thank you. Good morning. A lot of questions on the focus have already been asked. So perhaps if I can ask a bigger-picture, longer-term question, it ties a little bit to your guidance in terms of operating expense spend on R&D. The near term question is it looks as if to reach your full-year guidance, we’ll have a considerable step-up in the second half. Is that primarily attributed to the combination studies. just to give us a sense there, Keith? And then secondly, , I think you’ve done a tremendous amount of work in building this portfolio and the company is now very focused on trying to launch two products but as you know, investors are impatient to trying to figure out what to come next. What is your thought on capital allocation priorities further business development? What are you seeing out there. What’s your appetite? Thank you.

Michael Metzger: Great. Thank you, Chris. Good questions. Maybe, Keith, you want to take the first one on the longer-term?

Keith Goldan: Yeah, sure. So Chris, I wouldn’t necessarily agree that it’s a big step up, to use your words. We did — total operating expenses in 1Q approached to $80 million. The guidance range from second quarter is $80 million, $85 million. So if we were just to stay on that trajectory, we’d be $320 million-ish. So there is some increase that I think we would anticipate in the back half of the year. And I think, yes, certainly as PF ramps as the first line 7+3 combination trial with ramp continues to accrue and as we get ready to launch the pivotal Phase 3 ven/aza combo trial with rev, that’s certainly going to add to some of our R&D expenses in the back half of the year. But also don’t forget, we’re building out a commercial organization. So on the SG&A side, we would expect still some growth there for the sales force of the customer-facing individuals that Steve commented on earlier, as well as the G&A support for field force.

Michael Metzger: And in terms of your second question, Chris, on business development, maybe I’ll start and turn it over to Anjali. So look, I think our strategy has been — and we’ve been pursuing the same business model for quite some time, which is to in-license and develop new molecules with differentiated profiles. I think we’ve been fortunate to have great success with our in-licensing strategy and having these two molecules that are nearing approval. And so the bar is always quite high with regard to new opportunities and it gets incumbent upon us to be thoughtful about how we allocate capital. And so we do think that additional molecules bringing them into the pipeline, backfilling the earlier part of the pipeline is quite important. And we are interested in doing that. And so, I don’t know, if Anjali want to make a comment on our activities, but we remain quite disciplined about what we’re doing.

Anjali Ganguli: No, I think you said it well, Michael. We’re very actively engaged in the market looking across a variety of sources for new opportunities and spending a lot of time on diligence and hopefully we’ll have some exciting news to share. But there is definitely a lot to look at.

Operator: Our next question is from George Farmer with Scotiabank.

George Farmer: Hi, good morning. Thanks for taking my question. A competitor of yours has talked about combining their menin inhibitor with other targeted therapies like inhibitors and the like. Is — there hasn’t been too much conversation on the call about that this morning. Is that something that you’re thinking about as well in a greater detail?

Michael Metzger: George, thanks for the question. So in terms of combinations, maybe I’ll let Neil comment on what else is going on with targeted therapies. Obviously, we have the trials ongoing, the pillars of our strategy being ven/aza in the unfit population, and then [indiscernible] if you will, as another interesting option for patients with relapsed refractory and perhaps in earlier patients as well. So just think about it in terms of — then combos. And then on the fit side of the equation, in combination with that chemotherapy, we’ve already demonstrated the drug’s ability to be combined with chemotherapy in relapsed refractory study. We’ll have data updates on that. We’ll also have additional data, as we talked about on the ven combos this year, which so far, it looks extremely good. But I think there’s options open to us. And Niel, I don’t know if you want to comment on some of those?

Neil Gallagher: Yeah, sure. So we have investigator-initiated trials either planned or ongoing, which were — in which revumenib in combination with [indiscernible] or will be — either are or will be investigated. To Michael’s point on, conducting, for instance, a pivotal program in the frontline fit population in patients with both NPM1 and premutations is technically very challenging. It’s not really core to our strategy. Of course, we haven’t revealed overall what our strategy is, but it’s not core to our strategy. What we’ve said is that, obviously, in addition to the unfit Phase 3 that will initiate — we plan to initiate by yearend that we’re dose ranging in combination with 7+3, which will position us then to initiate a Phase 3 during 2025. You can anticipate that that will not be in dual mutation patients because that’s a very large and complicated study. So we prefer to generate evidence in that population as opposed to potentially pursuing a registration strategy.

Operator: This concludes our question-and-answer session. I will now turn the floor over to Mr. Michael Metzger for any additional comments or closing remarks.

Michael Metzger: Thank you, operator, and thank you, all, for your questions. Appreciate you tuning in today, and we look forward to seeing you all at our planned investor events, including the Bank of America Conference in May and the Goldman Sachs Conference in June. And with that, we wish you a great day.

Operator: The meeting has now concluded. Thank you for joining. You may now disconnect.

This article was generated with the support of AI and reviewed by an editor. For more information see our T&C.

BEIJING (Reuters) – China’s new yuan loans likely dropped sharply in April from March due mainly to seasonal factors, a Reuters poll showed, even as the central bank keeps policy support for the economy.

Chinese banks are expected to have issued 800 billion yuan ($110.7 billion) in net new yuan loans last month, compared with 3.09 trillion yuan in March, according to the median estimate in the survey of 21 economists.

But the expected new loans would be higher than 718.8 billion yuan issued in the same month a year earlier.

The People’s Bank of China (PBOC) is expected to release April credit data between May 10 and 15.

“April is a low season for new credit,” analysts at Citi said in a note. “Even with the PBOC’s new re-lending tool, new RMB loans could stay low at 800 billion yuan in April amid property weakness.”

China’s central bank said last month that it would set up a 500-billion yuan re-lending programme to support the country’s science and technology sectors.

China’s economy grew 5.3% in the first quarter, faster than expected, offering some relief to officials as they try to shore up growth in the face of protracted weakness in the property sector and mounting local government debt. However, some March indicators showed that demand at home remains frail, weighing on overall momentum.

The Communist Party’s top decision-making body, the Politburo, said in late April that China would step up support for the economy with prudent monetary and proactive fiscal policies, including interest rates and bank reserve requirement ratios (RRR).

China will issue ultra-long term special treasury bonds as soon as possible and speed up the issuance of local government special bonds to maintain the necessary intensity of fiscal expenditure, it said.

China has pledged that the growth of total social financing (TSF), a broad measure of credit and liquidity, and money supply will match expected goals on economic growth and inflation this year.

Outstanding yuan loans were expected to grow by 9.7% in April from a year earlier, up from 9.6% in March, the poll showed. Broad M2 money supply growth in April was seen at 8.3%, the same as in March.

Any acceleration in government bond issuance could help boost total social financing (TSF), a broad measure of credit and liquidity.

Outstanding TSF was 8.7% higher at the end of March than a year earlier, growing slower than the 9.0% annual rate seen at the end of February.

In April, TSF is expected to fall to 1.00 trillion yuan from 4.87 trillion yuan in March.

($1 = 7.2241 renminbi)