BMYMP - Bristol-Myers Squibb Company (BMY) Presents at 2023 Virtual ASCO Investor Event Conference (Transcript)

2023-06-06 14:02:06 ET

Bristol-Myers Squibb Company (BMY)

2023 Virtual ASCO Investor Event Conference

June 06, 2023 08:00 AM ET

Company Participants

Tim Power - Investor Relations

Samit Hirawat - Chief Medical Officer

Adam Lenkowsky - Chief Commercialization Officer

Lynelle Hoch - Senior Vice President, Cell Therapy Franchise Lead

Rosanna Ricafort - Vice President Cell Therapy Clinical Development Lead

Conference Call Participants

Chris Schott - JPMorgan

Carter Gould - Barclays

Matt Phipps - William Blair

Dane Leone - Raymond James

Terence Flynn - Morgan Stanley

Steve Scala - TD Cowen

Adam Jolly - Wolfe Research

Hao Shen - Bank of America

Harry Gillis - Berenberg

Olivia Brayer - Cantor

Presentation

Tim Power

Good morning. This is Tim Power from Bristol-Myers Squibb Investor Relations. Welcome to our Investor Event at ASCO 2023. We're presenting important data across our hematology and oncology portfolios this week, so it's exciting news for patients and lots discussed today.

I'm joined for today's discussion by Samit Hirawat, our Chief Medical Officer, and by Adam Lenkowsky, our Chief Commercialization Officer. Samit and Adam will go through our slide presentation followed by Q&A. At the end -- and also be joined by two of our cell therapy leaders Lynelle Hoch, Senior Vice President, Cell Therapy Franchise Lead, and Rosanna Ricafort, Vice President Cell Therapy Clinical Development Lead.

We'll look to Slide 2, and on this slide I'll refer you to our forward-looking statement. And with that, I'll hand over to Samit to begin the presentation on the slide.

Samit Hirawat

Thank you, Tim. Good morning, everyone. ASCO is very important meeting for BMS, and this year, we are excited to share updates spanning both hematologic disease and solid tumor malignancies. Later this month, we will also present important hematology data at both EHA and ICML Congresses.

Turning to Slide 4. What did we show at ASCO? First, our COMMANDS study data shows that Reblozyl is superior to EHA in the first line treatment of patients with transfusion dependent lower risk MDS-associated anemia. For the first time in over 30 years, there is a new option for patients and Reblozyl has the opportunity to become a new standard of care in frontline treatment for this disease.

We are also making great progress in cell therapy, advancing multiple programs across our portfolio. Breyanzi has the potential to expand into new indications like chronic lymphocytic leukemia and our TRANSCEND CLL studies, the first and only pivotal multi-center trial where a CAR-T cell therapy has shown improvement in efficacy and durability in this patient population with considerable medical -- unmet medical need.

We also look forward to presenting new Breyanzi data at ICML in additional indications including follicular lymphoma and mantle cell lymphoma. We saw real-world data from multiple myelomas CAR-T consortium, which further strengthens Abecma's profile and reinforces prescriber's confidence outside the clinical trial setting.

We are also excited about our emerging CAR-T targeting GPRC5D in relapsed and refractory multiple myeloma. We have seen new data for Opdivo across both hematology and oncology with the SWOG cooperative group presenting improved PFS using Opdivo versus the current standard of care brentuximab vedotin on top of our chemo backbone in first line advanced Hodgkin's lymphoma.

Finally, we are progressing our research in lung cancer, reinforcing the long-term benefits seen with three year following. In the neoadjuvant data from study CheckMate-816 and four year updated data in the first line metastatic setting with CheckMate-9LA.

We have also shown that repotrectinib provides a durable clinical benefit in patients with ROS1 positive non-small cell lung cancer, including those with CNS metastasis, which is very meaningful, as we know CNS involvement leads to poor outcomes.

We received priority review status in the U.S. with a PDUFA date of November 27, and look forward to a potential approval later this year. Taken together, this shows the breadth and the depth of our development programs across hematology, cell therapy and oncology.

Let's begin with our Phase 3 COMMANDS study data for Reblozyl, on Slide 5. We know there remains a high unmet need for patients with transfusion dependent lower risk MDS-associated anemia, who need treatments that effectively address chronic anemia better than ESAs with a more durable response.

Chronic anemia and dependence on blood transfusions leads to a greater than 50% increased mortality in these patients with a median survival rates of less than five years. COMMANDS is a randomized head-to-head trial of Reblozyl versus ESAs in the first line treatment of patients who are ESA naive.

The study enrolled an all-comer patient population of RS positive and RS negative, with a composite primary endpoint of red cell transfusions independence for at least 12 weeks with a concurrent increase in mean hemoglobin of at least 1.5 grams per deciliter.

Now looking at COMMANDS study results on Slide 6. Reblozyl showed superiority over ESAs with twice as many patients in the Reblozyl arm, achieving the primary endpoint. In addition to the overall intent to treat benefit, Reblozyl also showed benefit across subgroups regardless of EPO levels, transfusion burden, and common mutations like SF3B1.

As you can see on the right side of the slide, Reblozyl also delivered more durable responses with median transfusion independence of nearly 2.5 years, one year longer than those receiving ESAs.

Turning to Slide 7, we are looking at RS subgroups. An important objective of treatment is to both achieve transfusion independence and even more importantly sustain it. You can clearly see longer duration of response in both subgroups, including in RS negative where the median has not yet been reached.

Moving on Slide 8, we see that Reblozyl had a manageable and predictable safety profile that is consistent with what was seen in previous clinical studies.

On Slide 9, you see the ongoing studies which are part of the Reblozyl development plan. INDEPENDENCE is a Phase 3 trial in the first line treatment of patients with transfusion dependent myelofibrosis-associated anemia, who are also receiving a JAK inhibitor. This trial is currently recruiting, and we anticipate data to read out in 2025.

The second trial is an ex-U.S. Phase 2 study in patients with both transfusion and non-transfusion dependent alpha-thalassemia. Data is also anticipated in 2025. Lastly, we will initiate a Phase 3 ELEMENT trial later this year in first line non-transfusion dependent lower risk MDS-associated anemia.

Shifting now to cell therapy on Slide 10. Later today, we will be presenting our TRANSCEND CLL data for Breyanzi in patients with relapsed or refractory CLL or SLL, whose disease has progressed on a BTK inhibitor. The study also explored a sub-group of patients, which we call the primary efficacy analysis who in addition to progressing on a BTKi have disease that has also failed venetoclax.

This is a patient population with significant unmet medical need, as there are no other approved treatments or established standard-of-care once both BTKi and venetoclax treatment options have been exhausted. Patients have poor outcomes with other available therapies with very low complete response rates and duration of response of less than six months. The primary endpoint of TRANSCEND CLL was complete response rate and key secondary endpoints included overall response rate and MRD.

On Slide 11, you see the efficacy in the subset of patients included in the primary efficacy analysis set. The study met the primary endpoint with a complete response rate of 18.4% with a median duration of response of over 35 months, and the upper bound not yet reached. In this heavily pre-treated, high-risk population, this is a very encouraging outcome. It means that Breyanzi is the first CD19 CAR-T to demonstrate a benefit in a pivotal CLL trial and is a potential new treatment option in this patient population.

Turning to Slide 12. Breyanzi demonstrated a safety profile consistent with prior studies with no new signals observed. Rates of Grade 3/4 CRS and neurological events were low and manageable. Now before we move on, TRANSCEND CLL is the first and only pivotal study where a CAR-T cell therapy has shown a significant improvement in this patient population with no approved options after filling up BTKi and venetoclax.

Additionally, we are excited about expanding Breyanzi even further into new potential indications, as we announced the positive top-line data in relapsed refractory follicular form and mantle cell lymphoma earlier this year. We will present both datasets later this month, as late breaking oral presentations at ICML.

Starting on the Abecma on Slide 13. Here, you see the real world efficacy and safety data published by the multiple myeloma CAR-T consortium earlier this year. In the real world setting, the study showed that despite 75% of commercially treated patients not meeting eligibility criteria for the pivotal KarMMa study, they still observed comparable efficacy and safety results. There were similar overall response rates and complete response rates, and Grade 3/4 CRS and neurotoxicity events were all in the low to mid single-digits.

Furthermore, Abecma demonstrated strong manufacturing reliability in this commercial setting with a 94% success rate. These data support the confidence prescribers have in the reliability of Abecma's profile in patients treated in the commercial setting and we continue to see important real world evidence in BCMA targeted cell therapies at ASCO this year.

Turning to Slide 14, our GPRC5D targeting CAR-T is a potential first-in-class agent in relapse or refractory multiple myeloma. While BCMA targeting therapies have transformed the treatment landscape in multiple myeloma, there is a need for new agents with novel mechanisms in the post-BCMA setting. As more patients become relapsed or refractory to BCMA targeting agents. GPRC5D is an attractive target as it is highly expressed selectively on multiple myeloma cells, but not expressed on most other tissues.

Slide 15 shows our Phase 1 study design, which is a dose finding study evaluating five dose levels followed by a dose expansion cohort. The study enrolled patients who are post-transplant and triple-class exposed to an IMiD proteasome inhibitor and anti-CD38 targeting agent and allowed patients who received a prior BCMA targeted therapy onto the study. The dose expansion cohort is currently ongoing and we anticipate initiating registration trials in early 2024.

Moving to Slide 16, as a reminder of what we presented at ASH, we see encouraging depth and duration of response in heavily pre-treated relapsed refractory multiple myeloma patient population. The efficacy and durability in patients who are both naive and exposed to prior BCMA-directed therapy look promising. Particularly in the subgroup of patients who have received a prior BCMA targeting agent, the overall response rate is 78% with a complete response rate of 44%.

Our GPRC5D CAR-T was also well tolerated with low rates of Grade 3/4 CRS and infrequent neurotoxicity. We saw encouraging tolerability with respect to on-target of tumor adverse events affecting the skin, nails, swallowing or taste, potentially because targeting GPRC5D with a well-designed CAR-T relieves the continuous target pressure seen with other modalities such as the bispecifics. We look forward to presenting updated data at EHA on June 10th.

Now turning our attention to Slide 17, we see a new opportunity for Opdivo with the results of the SWOG 1826 cooperative group study. This is a Phase 3 trial of Opdivo versus brentuximab vedotin, each on top of AVD chemotherapy in first line advanced stage classical Hodgkin's lymphoma. While classical Hodgkin's lymphoma is a highly curable disease that remains a need for improved first line options as 7% to 20% of patients with advanced cHL stage disease still failed treatment.

The trial enrolled both adult and pediatric patients 12 years old and up with newly diagnosed stage three or four classical Hodgkin's lymphoma. Progression-free survival is the primary endpoint with overall survival as a key secondary endpoint. Patients were randomized one to one and it is important to note that prophylactic G-CSF was required in the brentuximab vedotin arm per the product label where G-CSF was optional in the Opdivo arm.

Looking at the results of the SWOG study on Slide 18, the Opdivo+chemo arm showed superior PFS at 12 months and a hazard ratio of 0.48.Opdivo is currently approved in classical Hodgkin's lymphoma for adult patients who have relapsed or progress post-transplant, and we believe the use of Opdivo-chemo in first line advanced classical Hodgkin's lymphoma provides a potential new treatment option for pediatric and adult patients.

This study is still ongoing, and we'll collect longer follow up data, but we are very encouraged by the data presented here at ASCO. We are working closely with SWOG on next steps as we analyze the full data set and prepare for future discussions with the regulators.

On Slide 19, the safety profile of the Opdivo+AVD arm was manageable and differentiated from the brentuximab arm in rates of neuropathies. We see lower rates of peripheral neuropathy in the Opdivo arm 29% versus 55%, which may improve tolerability and adherence in patients.

Next on Slide 20, I want to switch gears and talk to you about the lung cancer data we shared at ASCO, starting with the three year follow-up results from the CheckMate-816 study for Opdivo+chemo in neoadjuvant setting in the non-small cell lung cancer indication. The proportion of patients who had definitive surgery was numerically hired in the Opdivo+chemo arm versus the chemo along arm.

Neoadjuvant Opdivo continues to demonstrate sustained clinical benefit in the metastatic lung setting. We are also pleased with what we saw in the CheckMate-9LA four year follow-up data, particularly in the non-PD-1 expression population, where a significant unmet need still exists. The hallmark of I-O is prolonged survival, which we see in the flattening of the curve. These data show long-term survival benefits in first line lung cancer with 21% of patients alive at four years.

Lastly, repotrectinib is our next generation potential best-in-class TKi targeting ROS1 positive non-small cell lung cancer. Repotrectinib continues to demonstrate high response rates and durable responses to patients with or without CNS metastases. We are pleased with a continued progress we have made in lung cancer.

And now before I hand over to Adam, I'm sure you can see why we are very encouraged by our progress. We have a new potential option with Reblozyl in the first line transfusion dependent lower risk MDS-associated anemia. We're expanding our leadership in cell therapy with Breyanzi and Abecma, and we continue to improve outcomes for patients with lung cancer.

I will now hand it over to Adam to share his thoughts from the commercial perspective, and thank you. Adam?

Adam Lenkowsky

Thank you Samit, and good morning everyone. It's been a very good ASCO for Bristol-Myers Group so far. And as you've just heard from Samit, we continue to make progress and generate compelling data advancing our hematology cell therapy and oncology franchises.

Now, if we could turn to Slide 22, we continue to demonstrate a strong presence at both ASCO and EHA with significant disclosures across a broad range of diseases. Today, I'm excited to cover some of our commercial opportunities that are essential to both the current and future growth of Bristol-Myers Squibb.

So starting on Slide 23 and our opportunity with Reblozyl. Reblozyl has the potential to be the first approved treatment and a new standard of care in first line lower risk MDS-associated anemia. And what we hear from our customers is that the current treatment options with ESAs have significant limitations.

Few patients achieved transfusion independence, and when they do, they don't achieve a durable response. We know this is important because transfusion dependence increases mortality rates therefore more effective and durable treatment options are needed.

Reblozyl has a strong profile demonstrating superiority over ESAs in the COMMANDS trial, with twice as many patients achieving a response and showing a durability improvement of one year over ESAs, the durable benefit that was observed across RS subgroups. Additionally, we heard from Samit and we hear from physicians, that in every three week dosing schedule is more convenient over weekly ESA treatment.

So let's turn to Slide 24 to highlight our go-to-market strategy. COMMANDS has the opportunity to more than double the market and drive adoption for first line use of Reblozyl in MDS based on its clinical profile and superiority over ESAs. So we plan to position Reblozyl as a new standard-of-care displacing ESAs as physicians want to provide the most effective and durable therapy available to their patients in frontline.

We have demonstrated strong performance in the second line setting, and the COMMANDS data is to strengthen our confidence and continue to de-risk Reblozyl to achieve our goal of an excess of $4 billion of potential revenue in 2030. Our teams are launch-ready in the United States with the priority review PDUFA date of August 28th.

So turning your attention to cell therapy on Slide 25, we continue to focus on growth and building our long-term leadership position in cell therapy. Bristol-Myers Squibb is the only company with two approved and commercialized CAR-T therapies addressing two distinct targets: Breyanzi, which targets CD19; and Abecma the first approved cell therapy to target BCMA have made significant impact on improving patients' lives and has demonstrated strong demand in the market.

Physicians clearly recognize Breyanzi's best-in-class strong clinical profile that's further strengthened by its safety profile as a truly differentiated asset. Now Breyanzi continues to generate strong demand with the broadest label in second line plus large B-cell lymphoma. We now have the potential to expand the patient population beyond our large B-cell lymphoma indication in areas of high unmet need including CLL as well as follicular lymphoma and mantle cell lymphoma, where patients need more options.

Abecma also continues to generate strong demand in relapsed refractory multiple myeloma, as we continue to increase our supply. First, let me just remind you, we recently published results from our KarMMa-3 study highlighting deep and durable responses in difficult-to-treat, triple class exposed patients in the New England Journal of Medicine. And these data are now under regulatory review across the United States, Europe and Japan. We think is really important is that our customers value the reliability of a veterans profile.

So what do I mean by reliability? First, Abecma's strong clinical profile has been strengthened by the real world experience as noted by Samit earlier. Second, Abecma has a reliable safety profile, which is now clearly understood by physicians. And third, we continue to see strong manufacturing reliability with an outstanding manufacturing success rate of greater than 90%.

We continue to make a number of investments to increase our capacity for both of our cell therapy products, including vector sourcing, as well as drug products with our future new facilities in Devens, Massachusetts as well as Leiden Netherlands, which will expand our footprint internationally.

We are very pleased with the progress we are making on enhancing our manufacturing capabilities to bring these transformational innovations to more and more patients. And we remain confident that both products will yield significant commercial opportunity overtime.

Our cell therapy platform continues to extend its potential beyond the success with Abecma and Breyanzi, as we look to providing more updates on our GPRC5D CAR-T in multiple myeloma next week or later this week. We are well positioned with our current commercialized product and pipeline to lead in cell therapy into the future.

So now let's turn to Slide 26. We're all discussing the important cHL data that was presented. What you heard during the presentation on Sunday is that these data are practice changing. We've heard from our physicians, it's been very, very consistent. Opdivo+AVD could be a paradigm shift for patients with first line advanced cHL based on the data generated by the SWOG cooperative group.

Now recall, Opdivo is currently approved under accelerated approval in the United States in adults in post-transplant relapse refractory in that setting, and this is the confirmatory study that was agreed upon with the FDA. There remains a high unmet need in the frontline setting where patients and HCPs continues to look for more effective and tolerable treatment options.

This year, they're estimated to be about 8,500 new cases of cHL in the U.S. alone, and the strong data, which demonstrated 12 month PFS superiority over brentuximab vedotin gives great promise in this disease that despite being highly curable, still has a need for more effective and tolerable options for patients.

We continue to collaborate with SWOG on next steps and prepare for discussions in the future with regulators. We also look forward to sharing these data with NCCN as we believe these results are clinically meaningful and could potentially be a new standard of care in treating cHL.

Finally, as we turn to Slide 27 where we continue to provide options for patients for lung cancer, we have consistently said that the benefit of Opdivo and Yervoy comes with a hallmark of a flattening of the overall survival part.

Now, we see this clearly in the four-year overall survival data for CheckMate-9LA, which gives us an important opportunity to grow our first line non-small cell lung cancer business, especially in the PD-L1 negative patients, as there still remains a significant unmet need in that patient population.

In early stage lung cancer, we've already established Opdivo as the standard of care in neoadjuvant disease with CheckMate-816 data, which positions us very well for the future, and we look forward to potentially expanding into the per adjuvant setting with our CheckMate-77T data that's expected next year. Now, these deals will be very important to help physicians understand the optimal role of immunotherapy in the early lung cancer treatment setting, and which patients may actually need to go on to additional treatment in the adjuvant setting.

Finally, as Samit mentioned, repotrectinib was added to our portfolio from the Turning Point acquisition last year. We believe we have the opportunity to double the ROS1 market, and we're so excited about our opportunity to achieve best-in-class share based on the durable responses seen in patients with the ROS1 mutation. And we're pleased with the recently announced priority review PDUFA date of November 27th as the teams are currently preparing for launch in the U.S.

So finally on Slide 28, if I take a step back and tie it together. At BMS, we continue to make meaningfully advancements in our leadership in oncology, hematology and cell therapy with a broad set of programs across cancers. Importantly, the data percent here not only advanced the science across our franchise, but also support our near term and long term commercial opportunities.

We continue to deliver strong execution and largely de-risk our new product portfolio. We see significant expansion opportunities for Reblozyl, moving to the first line with the COMMANDS data, advancing our differentiated cell therapy business with the Abecma, Breyanzi and more data to come with our novel GPRC5D, as well as expanding opportunities across our important lung cancer business.

I am excited for the future of Bristol-Myers Squibb with our young and diverse portfolio and continued opportunities to solidify our leadership across hematology, cell therapy and oncology.

Now I'll turn the discussion back over to Tim. Tim?

Tim Power

Thanks very much, Adam. And we're going to start getting ready for Q&A now, so just give us a minute to get the lines connected. And once we do, if you can put your hand up, if you're in the Q&A room so we know to call that would be great.

Operator

We are now ready for Q&A.

Question-and-Answer Session

A - Tim Power

Terrific. Can we go to our first question from Chris Schott at JPMorgan, please.

Operator

[Operator Instructions]

Tim Power

Great. Thanks again. Can we go to our first question for Chris Schott at JPMorgan, please.

Chris Schott

Do you guys hear me now?

Tim Power

We can hear you now.

Chris Schott

Okay. Perfect. So just from our perspective, may I just have a two-parter on the CAR-T portfolio. Maybe just first on Abecma, in light of what we saw from CARTITUDE-4, can you just talk about how you're thinking about the competitive landscape on the BCMA side of things? And maybe the second part of this with the GPRC5D CAR-T, how quickly can you move this forward? I think I heard 2024 registrational studies, I just wanted to confirm that. And maybe -- just maybe more holistically talk about how you see that asset fitting in the treatment paradigm as we think about, I guess, bispecifics versus the CAR-T approach for that target?

Lynelle Hoch

Samit, do you want me to start with that one?

Samit Hirawat

Yes. Maybe, Rosanna, if you can start with the GPRC5D and then of course Lynelle for the Abecma versus the CARTITUDE data would be the two follow-ups.

Rosanna Ricafort

Absolutely. So, I will say that really proud of our multiple myeloma portfolio, having multiple targets and multiple modalities of therapy. We are seeing a really rapidly evolving treatment landscape in multiple myeloma as always, and we've seen intriguing data sets here at ASCO. Relating to the question on GPRC5D, we're extremely excited to progress this program forward. Related to the bispecifics, we've seen really interesting data here at ASCO of different bispecific therapies, targeting both BCMA and GPRC5D and the combination of both.

And with this increase in modalities and targets that are available for the treatment of relapsed/refractory multiple myeloma, I think it's important to think about the optimal way to sequence these different assets. And we've seen some data here and a nice discussion at the myeloma education session about the optimal way to sequence therapies. And what we see is that we know with BCMA therapies from our own data in KarMMa, that antigen loss is rare. And so you can sequence BCMA, post BCMA.

And with the data that we have on hand, we do believe that having an employing a CAR-T therapy prior to a bispecific is the way to go. We've seen that with real-world evidence. We've seen that with CARTITUDE-2, and we've seen activity with T cell engagers in that post BCMA setting. That said, there is -- there can be antigen lower expression and immunogenicity that we need to take into account when we are sequencing in the post BCMA setting and this is where having a different target is really attractive.

And so we are excited with the GPRC5D CAR-T that we have. We think it's differentiated from the bispecific in terms of the safety profile, and that may be due in part to the cellular genetics of giving a cell therapy where you have an initial rapid expansion and then a nice down recognition versus given the continuous target pressure with the bispecific and we are seeing more on-target off-tumor effects with the bispecifics.

So the combination data that we've seen with tech and talc is also validated using both BCMA and GPRC5D. And we have as our BCMA -- as our GPRC5D program progresses, we are thinking about combination therapies. And then we also have our bispecific CAR-T that's in the pipeline that we are excited to progress into clinical trials.

Lynelle Hoch

And from there, I'll take the competitiveness. Actually, we've always felt Abecma to be a very competitive asset. And actually, the data that we have seen here at ASCO actually even brings greater confidence in our competitiveness. For one, the real data that Adam had spoken about, we're seeing consistent and reliable results across efficacy, safety and manufacturing. And what does that mean for customers? What it means for them is what they can expect from Abecma is something that no matter what patients they're putting on, they really can rely on what efficacy and safety and more importantly, that they can get the product successfully from a successful manufacturing process.

Further, what I would say, as we have seen additional data here at ASCO, it really also makes us confident in KarMMa 3. Remember, this is a patient population with a very high unmet need. We had 95% of our patients that were data refractory. So this is a highly -- I'm sorry, consistent with what the patients we see today and the treatment paradigm that we see today. So when you think about that patient population and the efficacy we saw in KarMMa 3, we're quite confident. In addition, I think most of you know about the statistical methodology that is required by the FDA when assessing CAR-Ts, and we're quite confident that our data also looks very strong from that prism as well.

Tim Power

Okay. Thanks very much, Lynelle. Can we go to our next question, please, from Carter Gould at Barclays, please.

Carter Gould

Great. I hope you can hear me. Good morning, everyone. I wanted to come back to the commentary on luspatercept. Samit, I appreciate your comments and you're highlighting sort of the longer duration of treatment, but I think there's been some critique that hazard ratio, definitely a lot impressive. The confidence intervals are fairly broad, and the denominators get rather small towards the tail end. Could you maybe just address your confidence in the face of that commentary? And maybe also comment how ELEMENT fits into the strategy and if that maybe addresses any of the shortcomings of COMMANDS?

Samit Hirawat

Sure. Thank you. And Carter, I'll start off and certainly Adam will add on a commercial perspective. So look, number one, this is a study, an intent-to-treat population where all-comer population was enrolled in the first-line setting and prepared directly against an active treatment arm, which is ESAs. When we think about when the trial read out, it still had the interim analysis that the trial read out.

From an efficacy perspective, we crossed the boundary and therefore, we were unblinded, and you've seen the results. We've also seen the results from a subgroup analysis perspective, which trend in the right direction for all of the subgroups. You've also seen the forest plot, which shows very clearly that no matter how you look at it from EPO levels, from mutation status as well as from a durability perspective as well, you'll see the equal efficacy across all the subgroups.

So the beauty of doing Phase 3 trials in a randomized fashion, especially when you're comparing your drug against an active competitor, these are exactly the results that you want to see. And if you think about what was presented at ASCO and what the investigators that did the study and the presenter said as well as the discussions, they all said that these are truly the data that they were looking for as they think about applying them to their clinical practice.

And now of course, when we submitted the data to the FDA, we've got our priority review as well. So we're looking forward to that and then bringing it to patients as soon as possible. From the ELEMENT's perspective, again, we are taking a step further now to apply these learnings and bringing it to the non-transfusion-dependent population so that patients can stay off of that transfusion, which creeps in, in patients with MDS because the bone marrow does get impacted.

And we want to get these red cells to continue to mature that the anemia doesn't creep in and the patients don't have to go on to transfusion because as I said during the presentation, patients who become transfusion dependent have increased mortality and the overall survival rate, over five years, it continues to decline. And so the longer we can stave off that transfusion dependence, the better it would be and that's why ELEMENT becomes important in the conduct. Adam?

Adam Lenkowsky

Yes. Just coming back to COMMANDS. As we said, remember, COMMANDS are studied in an all-comers patient population. And it really was the first time in over 30 years where therapy showed superiority versus ESAs in low-risk MDS. And so as we've shared these data now with hematologists post the presentation, what they're telling us is that it's the durability of the transfusion -- durability and transfusion dependence have been really key regardless of RS status. And so we do believe that Reblozyl will become a new standard of care in the first-line setting regardless of RS status. And as I mentioned, this significantly provides the opportunity to grow the addressable patient population. So our teams are launch ready for our PDUFA date, and they're ready for an RS agnostically.

Tim Power

Thanks, Adam. Could we take our next question from Matt Phipps at William Blair, please?

Matt Phipps

Yes, Adam, I mean, maybe just following up, can you contextualize a little bit of maybe how you see the market opportunity or how the market opportunity compares between RS-positive and RS-negative patients?

Adam Lenkowsky

Yes. Thanks. You're cutting out a little bit. But RS-positive represents around 25% to 30% of the patient population. But as I talked about, when you look at the totality of the first-line business, we believe that this opportunity will more than double the addressable patient population that we see in second line, which is the MEDALIST patient population.

We've been out there since 2020 with the second line plus indication where we've established Reblozyl as the standard of care in second line with our shares across most of the markets are north of 70% in that second line RS-positive setting. So we feel really good about our opportunity to really move into the first-line setting, which is a much greater opportunity for patients to achieve transfusion dependence and durability of response with Reblozyl.

Tim Power

Thanks, Adam. Thanks, Matt, for the question. Can we take our next question from Dane Leone from Raymond James, please?

Dane Leone

Yes. So sorry to keep on this topic, but I think what we're all getting at here is there was a trend favoring ESAs on the primary endpoint for the RS-negative patient population. And I think we're just trying to understand why the enrollment of the study actually skewed towards RS-positive, given the patient population just skewed towards RS-negative. I mean does that actually infer clinical bias to the RS-positive patient? Or is this incorrect and your team does think we should be modeling adoption in the RS-negative patient population based upon the COMMANDS' data?

Samit Hirawat

Thank you for the question. The way we have thought about it is, number one, there are two ways of looking at the overall data. One is the overall response rate. And the second is the longevity of transfusion independence. I think the mistake that many people make is to look at just the response rate part of it. But it is, I think, more important because what we said earlier, transfusion dependence equals mortality in terms of the overall outcome for patients.

So if we can continue to stay off that transfusion for the longer duration, it is better for the patients. The trial was an intent to treat. Trial, meaning all-comer patient population was the primary analysis and we have shown statistic significance as well as clinically meaningful outcome overall from all patients' perspective. And in a similar way, as I said earlier, across the subgroups, you've seen all of that.

Now from a trial enrollment perspective, certainly, geographical differences do occur. It's a heterogenous population. And it is not just about RS-positive and RS negativity in the clinical trial. There are a number of inclusion and exclusion criteria that patients have to fit to be able to get enrolled in the clinical trial. So all of that has to be taken into account, and that's why we -- it is important to look at the forest plot as well as the stratified analysis that we conduct. And therefore, the application of the results applies to the overall population and not only in a subset.

So the way we look at it is how the study was conducted, and that's why we've submitted the overall data sets to the FDA. We'll continue, of course, to follow up, and we'll do an updated analysis at a later date and present the data in the future because this was an interim analysis based outcome where the study already met the outcome and the endpoints that were predefined. So you'll continue to see the data. But of course, more excitedly, we are looking forward to the approval date on August 28.

Adam Lenkowsky

And I'll just add, again, remember, this is an all-comer ITT patient population and you look at the -- not just the durability of response, but also the safety which is superior to ESAs. And so we believe that the $4 billion projection is not impacted at all. And so that's what we're continuing to model because we believe that this will be in an RS-agnostic label in the United States.

Tim Power

Thanks, Adam. Can we take the next question from Terence Flynn at Morgan Stanley, please?

Terence Flynn

Maybe just two quick ones for me. Samit, just wondering if you can confirm you don't anticipate an AdCom for luspatercept ahead of the PDUFA date here? And then on Opdivo in Hodgkin's lymphoma, congrats on the data there, I know you talked about a potential compendia listing. Can you just confirm how long that might take to get that on board here? What the time lines would be for compendia in first-line Hodgkin's?

Samit Hirawat

So on the first one, and -- I'll take that one and then, of course, I'll ask Adam to comment on the compendia listing part of it for AdCom. For luspa, look, we are -- as we've said already that we anticipate the outcome to be declared as per the PDUFA date in August. So at this time, we do not anticipate, but these are regulatory discussions, and we don't comment specifically on what the outcomes could be and we'll certainly be communicating as we look to the approval in August of this year.

Adam Lenkowsky

As it relates to the first-line cHL data. As I mentioned, first, we're hearing from physicians that this is truly practice-changing data showing superiority versus ADCETRIS in the first-line setting. And as Samit and I both mentioned, this is a SWOG study. And so not only we were discussing these data with regulatory authorities, but working with SWOG.

We will be submitting these data to NCCN for guideline adoption. Now as you're probably aware, each NCCN panel has their own criteria and takes different time to make an assessment around placement on guidelines. But we believe that guideline adoption will happen for first-line Opdivo in the coming weeks to months.

Rosanna Ricafort

And maybe, Adam, if I can add a little bit more of the clinical context around this data because at Sunday's plenary, we were really excited to see the data for a lot of reasons. First of all, this was an intergroup study that really harmonized the adult and pediatric cooperative groups. And that's important, right, because this is a classical Hodgkin's lymphoma, which is predominantly a disease of adolescents and young adults.

And why that's important is that the goals of therapy are not only to improve efficacy, but to limit toxicities. And we've seen really compelling efficacy with the hazard ratio of 0.48 that crosses the superior boundary with a p-value of 0.0005. And that was accompanied by a safety profile that's better than what the standard of care is.

You have a limit in the G-CSF that's used, and that can cause bone pain. So that really affects quality of life and then also that decrease in peripheral neuropathy is because you don't have the overlapping toxicities of brentuximab vedotin within vinblastine and that is important in terms of being able to continue therapy, and that was shown in the study.

I think we'll see longer-term data to see if there's any effects on, the late effects, but the PFS advantage is important for adolescent and young adult population because what that means is that less patients will need salvage therapy, which includes radiation therapy, high-dose chemotherapy and transplant. So we've heard from physicians on both the adult and pediatric side, but this is really a practice-changing data.

Tim Power

Terrific. Thanks, Rosanna. And just a quick reminder, if you want to ask a question, to put your hand up in the Q&A room, can we take our next question, please, from Steve Scala with TD Cowen.

Steve Scala

Can you hear me?

Tim Power

Yes.

Steve Scala

The question is, to what extent do you view Merck's KEYNOTE 671 periadjuvant regimen as a risk to Opdivo in the neoadjuvant setting? The Merck data is stronger but not by much, and demands a higher treatment burden. I guess it could be concluded that the value of periadjuvant therapy is debatable. I'm wondering if you agree. And are there any key differences in your periadjuvant trial versus MK 671?

Adam Lenkowsky

I'll take the first part of the question and then turn it over to Samit. But thank you for the question. As I mentioned, I mean, 816 is the standard of care in the market today. We have over a 70% share and physicians continue to tell us that the Opdivo plus really limited dose chemo is a significant advantage. Now you're right. When you look at the data that Merck presented over the weekend, the data looks very similar. PCR rates are almost identical.

And I do think that the CheckMate-77T data that we will be -- that we will read out sometime early next year, we'll answer a lot of questions to understand which patients would require, for example, Opdivo chemo upfront and would not need to go on to additional adjuvant therapy and which of the patients might need additional therapy in the adjuvant setting, and we look forward to receiving that data next year.

Samit Hirawat

Yes, I think you've covered it all, Adam. There's is no -- and the trials are very similar, so not much to add on top of what Adam already said.

Tim Power

Thanks very much. I believe Adam Jolly from Tim Anderson's team at Wolfe Research. So we go to Adam for Tim, please.

Adam Jolly

This is Adam on for Tim. Looking at ct.gov, it appears that the primary endpoint for Part 2 of your Phase 2 LAG 3 trial in long change from PFS to ORR last August. Can you clarify why this has changed?

Samit Hirawat

When we are conducting a Phase 2 study, we look at a multitude of endpoints. PFS is part of the inclusion in terms of the endpoints that will be assessed. It's only that ORR data will be available faster than the PFS data. So from a decision-making point of view, we'll utilize that. But it doesn't mean that we don't look at PFS. In fact, we will be looking at PFS as well, and make decision in looking at the overall data set from the Part 1 of the study, which was the dose finding and then the Part 2, which is the randomized portion of the study where we will be looking at all parameters, not just ORR, not just PFS, but also biomarker analysis and others. So it's the totality of that data within the clinical trial that will constitute our decision-making parameters.

Tim Power

I believe Hao Shen from Geoff Meacham's team at Bank of America. So can we go to Hao please? We can hear you now.

Hao Shen

Okay. Okay. This is Hao Shen for Geoff Meacham. Thank you for the question. So back to SWOG and congrats on the data. Could you talk about the path forward for regulatory approval? Is that one-year PFS data sufficient? Or you will have to wait for longer term?

Samit Hirawat

Sure. Thank you. As Adam and Rosanna both mentioned, this is an intergroup study. So when I've been -- studies at SWOG cooperative group study, while as Adam had also mentioned during his presentation that this is a study that was agreed upon as a next step in terms of conversion of accelerated approval to full approval.

It is important to understand that this is an intergroup study. So we have to get the data from the SWOG group, analyze that data and then obviously engage the regulators in terms of our conversations with them. So we'll continue to keep you updated as we move forward in those. At the current time, we're looking forward to actually getting the data and analyzing that in a more complete way.

Tim Power

I believe that Harry Gillis from Luisa's team at Berenberg. Can we go to Harry, please?

Harry Gillis

I hope you can hear me. So I was just wondering how confident you are that CheckMate-77 will actually determine, which patients should continue with adjuvant therapy after neoadjuvant and then perhaps which factors are likely to be important in this decision?

Samit Hirawat

So if you look at the overall data sets that are being generated, I think -- I don't think any one study will answer it. The question is to be analyzing the data set across clinical trials because of the clinical characteristics that you really want to understand as well as other markers of efficacy that one would isolate.

So if you think about neoadjuvant setting, now there are multiple studies that have read out showcasing that neoadjuvant study is very important and already starts to impact the event-free survival. And then, of course, longer-term follow-up that we'll continue to have, will there be a change or impact on the overall survival? We are now also getting the data from the adjuvant trials as well as periadjuvant trials.

So it ultimately will lead to a meta-analysis of some sort where we will be able to work with the investigators and other clinical trial statisticians to be able to conform all the data sets together and then come to and draw conclusion. So it's not just about 77T, but rather amalgamation of the clinical trial data from various studies that will start to define the characteristics that may lead to that decision-making by investigators.

Tim Power

Thanks, Samit. Could we go next to Olivia Brayer from Cantor, please.

Olivia Brayer

Hopefully, you can hear me, and thank you for the question. Can you share any FDA feedback on the ROS1 submission and maybe just your level of confidence coming out of those meetings? And is it fair to say that they've been supportive of a single-arm study now that you do have priority review? Or is that still a potential risk here?

Samit Hirawat

Olivia, of course, we comment on the specifics of the conversations we have with the FDA. But as you've seen, we've submitted those single-arm trial data to the FDA. You already know that there are -- there is breakthrough therapy designation that has been granted to repotrectinib. And you know the submission has been accepted, and we have a priority review. So, that is a conclusion to be drawn from those things, how FDA is looking in these data. But beyond that, we will not be able to comment on the specifics of the conversations we have, as we never have. Thank you.

Tim Power

Can we take our next one from, I think, Mohit Bansal's team. I think Serena might be representing Mohit from Wells Fargo.

Unidentified Analyst

Since Geron's Imetelstat also showed positive data in lower-risk MDS, can you guys talk about the relative profiles of Reblozyl versus Imetelstat in the study?

Samit Hirawat

Yes. So there obviously more and more data that are emerging of the lower risk MDS. Remember, luspatercept was the first one to show as a new class of agent that showed an impact on transfusion independence in the second-line setting first. And now we have the data in the first-line setting. We also obviously have an approval in beta-thalassemia as well for the transfusion-dependent population and in Europe also in the transfusion-independent population.

So, the overall data set that, are available for luspatercept remains much larger than anybody else. Second thing to note is how you look at the patient populations enrolled in the various programs as well as the endpoints that are analyzed. Some have analyzed a shorter duration of transfusion independence. So if you think about eight week transfusion independence versus the one that we've looked at 12 and 24 weeks of transfusion independence, it's easier to achieve eight-week transfusion independence as opposed to 12 or 24 weeks. So those longevities are important.

The second, we also looked at what was presented in terms of the EPO levels. We've obviously created a much difficult-to-treat population who have less than 500 EPO, whereas others have created more than 500, so another differentiating features. So I think overall, we are very confident and very energized and excited about the data that we have continued to generate. And as I said earlier during the presentation, we still have a multitude of other studies that are ongoing that will add on to the data sets for luspatercept, whereas the safety profile remains very consistent across the clinical trials.

Adam Lenkowsky

Samit, I think just a couple of things I might add as we look at the data. Number one, when you see the adverse event profile for luspatercept versus Imetelstat, there's an extremely high rate of cytopenia in the Geron study that we know are rate limiting. There was a discontinuation rate of almost 80% in that study. So patients are unable to tolerate the product.

Also, we know when we look at the administration route. Remember, Imetelstat is administered as a two-hour IV infusion and when you look at the subcu every week dose for Reblozyl is seen as being very, very convenient for patients. So we believe that our COMMANDS data in first line and first setting really are going to be standard of care in that setting. And then when you look at patients who might need a secondary treatment, that's potentially where they could use Imetelstat.

Tim Power

Terrific. Thanks, Adam. I believe Colin Bristow's team from UBS or can we go to them, please.

Unidentified Analyst

This is Yihan on for Colin. Congrats on the progresses. So we have one question on the Opdivo lag. So should we still expect the Phase 2 data readout in the first line non-small cell lung cancer later this year, you previously guided? Or it is actually more realistic to see that data early next year? And also, we are wondering what kind of data set should we expect to see?

Samit Hirawat

So, we obviously have the ongoing study in non-small cell lung cancer, randomized study, it's a Phase 2 study. We anticipate to see the data either very late this year or more likely to be early next year.

In terms of what kind of data set, of course, when we present the data, it is going to be inclusive of a multitude of things in terms of patient population enrolls at clinical characteristics as well as from our safety and efficacy end points that we've included in the clinical trial and some levels of biomarkers.

So, if it's a study and if it's a data presentation then, of course, we will be more comprehensive because we also have to make decisions in terms of where we go from once we have the data from there to when we have the data in our hands. So looking forward to that ourselves, and we'll keep you posted as the data is.

Tim Power

Great. Thanks. I understand that we sort of -- we've run out of questions at this point. So I just want to thank everybody for your participation today. If you got follow-ups, you know where to find us in the IR team.

Have a good day.

Samit Hirawat

Thank you.

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Bristol-Myers Squibb Company (BMY) Presents at 2023 Virtual ASCO Investor Event Conference (Transcript)