ABECMA-related Excerpts from BMY's BCMA CAR-T partner 2seventy bio (TSVT) 2Q2022 Earnings Call | BMY Message Board Posts

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Msg  10138 of 10312  at  8/11/2022 2:34:27 PM  by


The following message was updated on 8/12/2022 8:08:11 AM.

ABECMA-related Excerpts from BMY's BCMA CAR-T partner 2seventy bio (TSVT) 2Q2022 Earnings Call

My Take: BMY's massive portfolio of blockbusters, new launches and key milestones provide less opportunity to gain deeper color on any one program, thus it is helpful to track partner communications. The timing of TVST's earnings call was the same day as the press release announcing early success hitting PFS Primary Endpoint in Phase III KarMMa-3 for Multiple Myeloma (MM) patients with 2-4 prior lines of therapy. The commentary during prepared remarks and during Q&A provided a rich tapestry to better appreciate understand ABECMA dynamics.
Discussions with several constituents at ASCO2022 support the view that there is a tremendous demand for BCMA CAR-T in MM that fare outstrips demand with plenty of room for multiple players. Moving into earlier lines of therapy expands that opportunity once approved.
ABECMA-related excerpts from TVST's 2Q2022 earnings CC:

Our commercial business is growing with significant demand for ABECMA. We continue to treat as many patients as we can and as previously stated, we're committed to capacity improvements which we've been able to achieve. We're tracking towards the high end of our anticipated 2022 revenues for ABECMA sales.

We continue to evolve to meet the needs of the growing ABECMA opportunity that BMS recently outlined in their earnings call, including exciting top line growth.

On the cost side this quarter, we saw an increased investment in ABECMA ramp up activities and higher than anticipated vector costs. You will hear more detail from Chip on how this has impacted our near-term guidance.


Shifting gears, we are extremely excited to share the great news regarding our earlier line study, Phase 3 study for ABECMA called KarMMa-3, studying patients with two to four prior lines of therapy. After performing a pre-planned interim analysis and receiving the recommendation by the data safety monitoring board, the study was unblinded and has met its primary endpoint of demonstrating a statistically significant improvement and progression-free survival. It's hard to overstate our excitement for patients with myeloma. And along with BMS, this news certainly increases our conviction of the potential of ABECMA over the long term. It is both exciting and humbling.

It is an incredibly exciting day indeed. So to expand on the updates that Nick shared this morning, 2seventy and BMS issued a press release announcing positive top-line results from a pre-specified interim analysis of KarMMa-3, which is a Phase 3 Global, randomized, multicenter, open label will study that evaluates ABECMA in relapse and refractory multiple myeloma patients who have had two to four prior lines of therapy. They must have been refractory to their last regimen and have been previously exposed to a proteasome inhibitor and IMiD and daratumumab also called triple-exposed and the outcome of these patients was compared to that of standard combination regimens.

This makes ABECMA the first BCMA directed CAR T therapy to demonstrate clinical superiority versus standard regimens in a randomized controlled trial. Indeed these results came ahead of schedule compared to our original timing guidance of data in 2023, and we are so pleased for what these data could mean in terms of potential paths to treat earlier line patients. The study met the primary endpoint of progression-free survival and the safety results were consistent with the well established and predictable profile demonstrated in the pivotal KarMMa trial. We, along with Bristol Myers Squibb, expect to present additional data from this study at a medical meeting in the future and discuss these findings with health authorities.

We also presented additional data for ABECMA in June at the 2022 ASCO annual meeting, including the largest data set to date for ABECMA patients treated in the commercial setting by the multiple myeloma cell therapy consortium of academic institutions. The data presented were consistent with what was seen in the pivotal KarMMa study despite the fact that the overwhelming majority of such patients would not have met the eligibility criteria of KarMMa reinforcing the efficacy and safety profile of ABECMA.

Looking forward, we expect to share proof-of-concept data for our KarMMa-2 study in high-risk early-stage multiple myeloma in 2022 that will further inform our earlier line development plans.

During the second quarter, ABECMA generated $72 million in U.S. commercial revenue, up 29% compared to the prior quarter. As a reminder, we share all profits and losses related to ABECMA equally with BMS for the development, manufacturing and commercialization of ABECMA in the U.S.

We continue to see very strong demand for ABECMA and we're pleased with the growth trajectory there. We remain on track to achieve the high end of our 2022 U.S. ABECMA revenue guidance of between $250 million and $300 million. We reported our share of collaboration loss of $4.3 million for the second quarter, which includes our share of gross profit less costs associated with commercialization of ABECMA in the U.S..

Given the strong demand for ABECMA and our growing belief in the potential for this therapy to play an important role in earlier lines, we've been making significant investments to increase manufacturing capacity across the supply chain. In addition to our manufacturing capacity investments, we have experienced cost for vector that were higher than anticipated. This does not affect our 2022 revenue target as we believe we have sufficient vector to achieve that target and we are continuing to invest in increasing manufacturing capacity in the future.

That said, we are partnering closely and supporting BMS in their efforts to lower manufacturing -- sector [ph] manufacturing costs and continue to increase manufacturing capacity.

Q: GS - This is Elizabeth on for Salveen. Just wondering if you could kind of comment on the powering or how stringent the criteria was to stop [ph] with the pre-specified interim analysis? And then if there's any comment on CR rates that you could provide? And then a follow up on vector supply for 2023 and how to think about that?
A: It was a pre-specified analysis. This was our interim analysis for superiority and the DSMB recommended that we unblind the study and it was a positive result.

In terms of response rates, I can share that its secondary endpoint of overall response rate was met and was statistically significant. But at this time, that's all that I could share.

We've continued to make step ups throughout this year in terms of our weekly capacity, in terms of patients that we can provide drug product to. We continue to work with the regulators to make additional step ups and we have plans to make step ups later this year and in '23 as well. So that is a picture that month-to-month, quarter-to-quarter continues to improve and we should have more to share in terms of our outlook for '23 as you get closer to the end of this year.

Q: Can you just remind us the statistical design for KarMMa-3, in particular, what triggered the events that triggered this interim? And what were the primary and secondary? And if you will, since you said the ORR is secondary but how far down the secondary hierarchy you were able to get?

And then on costs, can you just help break down this net cash spends you expect the $245 million to $265 million, Chip? Can you help us understand how much of that is on discovery, on your early clinical program and then on ABECMA program? And then how much is being spent as you said on supporting sort of scale up and manufacturing for ABECMA? Thank you.

A: As Nick mentioned, the primary endpoint was PFS and that was the primary endpoint for which the interim analysis statistics were driven. The key secondary endpoints were response rate. And as we mentioned, we can say that both the PFS and the overall response rate was significantly improved. Overall, survival is a key secondary endpoint, and the follow-up for overall survival remains ongoing.

From a development perspective, ide-cel remains our biggest investment with the various KarMMa studies and investments in manufacturing scale up. 

On the manufacturing side, I can just comment, we've invested both on the drug product side together with BMS in terms of scaling that capacity. And then as I mentioned, continuing to work on vector supply and increasing skill there. 

Q: Cowen Yaron Weber: Good morning, and congrats on the data. I know you can't say a lot, but I wanted to just probe a little bit. When you're thinking about second to fourth line, I mean, you could have doubled it or you really have triplet therapies here. It could be again, did you expect some patients to get Darzalex again? Or they're typically getting another (inaudible) and sort of another PI? And if you can, what do you think is a comp in terms of prior data with respect to PFS and ORR? I mean, these are obviously triple exposed. So the question is, what they were getting at that point?

And then, secondly, for Chip. We're beginning to see a little bit of a range for you now, for the collaboration with Bristol on OpEx, and I know that's going to be obviously variable depending on spending, and clinical supplies, et cetera. But can you give us some brackets to kind of where you are on toward profitability and sustainability, because it sounds like the clinical spend is now getting a lot more manageable and sort of predictable. We only have essentially one big study and one small study ongoing. Thank you.

A: That is an excellent question. So, let me reply and make two points in that regard. The first point is that the standard of care arm in the randomization was a choice of five approved combination therapies, and the investigators chose which combination therapy that they would use if patients were randomized to that arm. And it's a regimen that they could not have had before, so that it increases the potential likelihood of benefit.

In terms of your question what would be expected, I think that is an important question because these patients are, one, have been refractory to their last line of therapy, which means that they have progressed within 90 days of their last line of therapy. And second, as you alluded to, they were triple exposed.

And if you look at the literature and across the studies, there's not an awful lot of large databases on the outcome of patients who are triple exposed. But the totality of the data suggests that if you fail daratumumab, your overall response and your performance status, both were extremely poor. So, we had some ideas of what this might look like and really built our study upon that. But what we were very encouraged was in this study that ABECMA really had a statistically significant what we believe is a clinically significant improvement over the poor response rate and poor performance status seen in patients who had failed daratumumab.

In terms of how to think about the ABECMA spend, you're right. On the non-commercial side, those OpEx related to the clinical studies are in a more predictable range. We, for the existing studies, we would predict that that glide path continues. Although, I would refer you to the quote in today's press release, so I think we are thinking together with BMS about future investments in ABECMA. And you'll hear more from us on that throughout the second half of this year as those plans develop. But these data today I think give us increasing conviction in the long- term role of ABECMA and the treatment of myeloma.

And Yaron, I mean, you and I have talked about this a couple of times but I think if you zoom back up, right, there are a lot of questions around the myeloma market opportunity for CAR T products, and I think that's been dispelled, right? The interest is there. Then there are sort of where does ABECMA fit relative to cell to cell and there's a room for both, et cetera, et cetera. I think, that also is becoming quite clear in our opinion saying there's ample room here to sort of service on unfortunately big market opportunity with these patients who are just desperate for help. And now as we start thinking about earlier lines, I think we have that growing conviction and excitement.

So pretty much on every turn that we've taken, I'm getting more excited. But you're absolutely right, it's still bouncy, a lot less bouncy that it was 6-12 months ago, still a little bouncy right now as far as the execution side and build a level there off. But as we get into '23 here, we feel a high degree of confidence along with BMS. And that we're very pleased with BMS and they are paying attention, frankly like can we possibly imagine a better partner in this regard and I think they're certainly very committed to cell therapy space in that regard. So hopefully Yaron, that helps.


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10143 Re: ABECMA-related Excerpts from BMY's BCMA CAR-T partner 2seventy bio (TSVT) 2Q2022 Earnings Call JBWIN 6 8/13/2022 2:25:58 PM

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