Immunocore Holdings PLC

NASDAQ:IMCR

Earnings Call Analysis

Immunocore Reports Strong KIMMTRAK Growth

Immunocore's second quarter performance has continued to rise, with KIMMTRAK revenue reaching $111 million, a testament to its robust commercial traction across over 35 countries. Quarter over quarter, revenue from KIMMTRAK grew from $52 million to $57.8 million, primarily fueled by its expansion in the United States. The company expects further growth through educational efforts and forthcoming three-year overall survival data. They have achieved a significant pricing agreement with Germany, while negotiations in the UK are anticipated to run into 2024. With a resilient cash reserve of $435 million, the company is advancing research with a new Phase 3 melanoma trial as part of its PRAME investment. They uphold a firm commitment to increasing patient access, aiming to reach over 1,000 patients annually by 2025.

Exploration of KIMMTRAK Monotherapy and Combination Therapy

The company plans to conduct a meticulously designed seamless Phase 2/3 trial to explore the efficacy of KIMMTRAK both as a monotherapy and in combination with pembrolizumab. The aim is to determine the necessity of pembrolizumab in the treatment regimen, which could lead to discontinuation of one of the treatment arms depending on the observed treatment effect relative to the control arm.

Cutaneous Melanoma Dosing Strategy Rationale

The discussion on cutaneous melanoma focused on a dosing strategy that employs less frequent administration after initial treatment. This approach was driven by the KIMMTRAK experience and Phase 2 data from the PRAME program. A weekly dosing schedule was considered critical for the first 12 weeks due to the high incidence of progression during this period. After this initial phase, the plan transitions to a less frequent dosing regimen to match the observed stabilization of disease progression.

Revenue Growth and Pricing Strategy for KIMMTRAK

KIMMTRAK's revenue growth, particularly in the U.S., accounted for a 14% quarter-over-quarter increase driven primarily by demand. The company reported no significant changes in stocking patterns and acknowledged a price increase of 2.5% at the start of the year.

PRISM Trial Dose Selection and Efficacy Expectations

Two dosages were chosen for the PRISM trial after a sevenfold dose range was considered from the Phase 1 trial. The company selected a higher dose based on modeling and simulations and a lower dose, avoiding the lowest dose to ensure sufficient exposure for patients. As for efficacy, the company is seeking to achieve a median progression-free survival (PFS) that outperforms current benchmarks of 4.7 to 8 months, with an understanding that a blended median PFS will likely be less than 8 months.

Enrollment and Data Timeline for the PRAME A02 Trial

The enrollment for the PRAME A02 trial is progressing according to plan as the study moves from a Phase 1 to a Phase 2 footing. The company continues to open new sites and recruit patients across various priority expansion cohorts. They intend to share the trial's matured data in the first half of 2024.

Potential Synergy between PRAME Agent and KIMMTRAK in Melanoma

There is a growing interest in understanding how the PRAME agent and KIMMTRAK might work together to treat cutaneous melanoma. This follows observations of disease stabilization in uveal melanoma when PRAME was used post-KIMMTRAK. While the exact mechanisms are yet to be unraveled, the company is optimistic about exploring combinations of both agents to potentially enhance the targeting of melanoma cells.

Earnings Call Transcript 2023-Q2

[Operator]

Greetings. Welcome to the Immunocore Second Quarter 2023 Financial Results and Business Update Conference Call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. [Operator Instructions] As a reminder, this conference is being recorded.

At this time, I would like to hand the call over to Clayton Robertson, Head of Investor Relations. Thank you. You may begin.

[Clayton Robertson, Head of IR]

Thank you. During today's call, we'll be making certain forward-looking statements including about financial projections, development activities, business strategy, and the timing and impact of future events. Actual results could differ materially from those projected by these statements, which are based on management's views as of today and subject to risks and uncertainties, including those noted in our most recent Form 20-F and any 6-Ks we filed with the SEC, in the earnings press release, we issued this morning. You are cautioned not to place undue reliance on these statements and Immunocore disclaims any obligation to update that. We'll also disclose certain non-IFRS measures on today's call which are reconciled to comparable IFRS measures in today's slides.

I will now hand over the call to our CEO, Dr. Bahija Jallal.

[Bahija Jallal, CEO and Director]

Thank you, Clay. Good morning and good afternoon. Welcome everyone.

I'm here today with Brian Di Donato, our CFO; Ralph Torbay, Head of Commercial; David Berman, our Head of R&D; and Mohammed Dar, our CMO. We will answer your questions after my closing remarks.

During this call, we will share an overview of our second quarter and first half of the year performance, as we continue to deliver our mission to radically improve outcomes for patients with cancer, infectious disease, and autoimmune diseases. I am proud to report that we have delivered another excellent quarter of performance, both commercially and in terms of progress with our pipeline.

In the first half of the year, KIMMTRAK revenue was $111 million. That growth reflects a robust commercial execution and the recognized benefit that KIMMTRAK provides to patients. Now approved in over 35 countries, KIMMTRAK has recently launched in four additional countries. Ralph will share some insights on the Q2 commercial execution and the growth drivers for the second half of the year.

Disciplined expense management and our strong cash position allow us to continue to advance and invest in the pipeline in oncology and infectious diseases and we are thrilled to announce that we will start with the first Phase 3 randomized trial with our PRAME-targeted ImmTAC. David will walk you through the trial design today and provide an update on the durability from the melanoma patients we presented at ESMO last year.

And we have continued to treat patients in the PRAME Phase 1 monotherapy and combination cohorts with plans to present data in the first half of next year. We are also randomizing patients in the Phase 2/3 late-line cutaneous melanoma trial with KIMMTRAK.

The expansion of our oncology pipeline continues as our teams are working on IND or CTA application for three new products with PIWIL on track for IND by year's end. And finally, trials with our infectious disease candidates investigating the potential for a functional cure for people living with HIV and HBV are ongoing and enrolling patients as we speak.

I will now hand over to Brian.

[Brian Di Donato, CFO and Head of Strategy]

Thank you, Bahija. Good morning, everyone.

Earlier today, we released our financial results for the second quarter ending June 30. I invite you to review the release and our SEC filings for more details. I'll share some of the key highlights. On Slide 7, you'll see the summary of our financial results. I'm delighted to report that our teams have delivered another impressive quarter of KIMMTRAK sales. Net KIMMTRAK revenue grew to $57.8 million in Q2 from $52 million in Q1, primarily driven by growth in the United States. We have now launched with reimbursement in seven countries, including Italy.

I'm pleased to announce that we have reached a reimbursement agreement with Germany, which is slightly improved from our accounting assumptions. We expect Germany to publish the price in September. Ralph will take you through the launch details.

Both R&D and SG&A expenses for the quarter were broadly flat with Q1 with the net loss for the period of approximately $18 million. Year-to-date, SG&A expense includes approximately $12 million of currency mark-to-market and $14 million of non-cash share-based payment expenses.

So in total, $26 million for net cash, year-to-date SG&A expense of roughly $60 million. Looking ahead, we expect R&D expense to increase gradually over time as we expand our PRAME investment. Including the new Phase 3 melanoma trial announced today. Our cash position of $435 million has continued to increase over the past three quarters, driven by KIMMTRAK revenue, U.K. tax credits, and disciplined expense management.

With that, I'd like to congratulate the teams on another great quarter and we'll turn the call over to Ralph, who will review the KIMMTRAK commercial performance.

[Ralph Torbay, Head of Commercial]

Thank you, Brian, and hello, everyone.

KIMMTRAK is approved in over 35 countries and we have launched in four additional markets this year, including Italy, Austria, Finland, and Israel. With U.S., Germany, and France, we estimate these seven markets represent 3/4 of KIMMTRAK's global potential sales. In Q2, we had our strongest revenue quarter-to-date with $57.8 million in net sales, up 11% quarter-over-quarter. Importantly, this represents the fifth quarter of growth.

Next slide, please. There are three factors underpinning our growth this quarter. First, we saw 14% demand growth in the U.S. where we increased our first-line market share from around 50% in Q1 to 60% in Q2. The second driver of growth is that patients are appropriately remaining on therapy. This is a result of our focus on educating healthcare professionals around the importance of continuing treatment in the presence of clinical benefit.

Lastly, in Europe, nearly all first-line patients in Germany and France received KIMMTRAK. We have seen incremental growth driven by our new launches, including Italy, where the team transitioned all patients to reimbursed KIMMTRAK in a record three months.

Looking ahead in the second half of the year, we see two significant revenue drivers for KIMMTRAK. In the U.S., we expect further growth from our continued educational push into the community while supporting patients on therapy. KIMMTRAK's three-year overall survival data expected later this year will be instrumental in achieving this goal. We also expect to grow Italy and continue to launch in several additional European countries by the end of the year.

Let's move on to reimbursement updates. As we shared with you in the July 6-K, the CMS in its draft rule named KIMMTRAK as meeting a unique circumstance for an increased exemption threshold. If this language is maintained in the final rule, expected in Q4, it would functionally exempt KIMMTRAK from a refund.

In Germany, we successfully completed price negotiations and the agreed price will be published in September. We're pleased with the outcome, which is not materially higher than our accruals to date. The price remains confidential until publication.

In the U.K., we expect reimbursement discussions will continue well into 2024. It has become, unfortunately, more common for innovative products to receive a negative funding decision from NICE and the process to be extended.

In France, we're confident going into reimbursement negotiations with KIMMTRAK having had a strong ASMR III rating from the Commission de transparence and plan to have an updated agreement in place in 2024.

So to sum up, I'm delighted with our continued progress in the second quarter and we remain firmly committed to our mission of making KIMMTRAK available to over 1,000 patients per year by 2025.

I'd now like to pass the call to David to walk you through our exciting R&D plans.

[David Berman, Head of R&D]

Thank you very much, Ralph

We continue to make good progress in our oncology and infectious disease clinical pipeline. And today, I'm going to focus on two programs. First, I'm going to share recently published KIMMTRAK data, which we believe provide insights for how we will develop PRAME. And second I'm going to update you on PRAME, including the original 18 melanoma patients from ESMO, and I'm very proud to also introduce our new Phase 3 study in first-line cutaneous melanoma.

We presented the Phase 3 first-line ctDNA data for KIMMTRAK result at AACR earlier this year. And there are two points that I take from these data. First, a majority of patients are benefiting from KIMMTRAK since most patients are having ctDNA reduction. And second, KIMMTRAK has higher activity in first-line compared to second-line based on the three-fold higher rates of ctDNA clearance. This informs for our platform including PRAME, that where possible we should strive to move to earlier lines of therapy.

Also at AACR, we presented that KIMMTRAK at three years has long-term survival benefit in second-line uveal melanoma compared to historical controls. We have been following these patients to look for a long-term survival tale since this is the hallmark of other IO therapies such as checkpoints.

These data are very encouraging and we will share that three-year survival update on the first line Phase 3 study later this year. The emergence of the long-term survival benefit, however, increases our confidence that this platform can be transformative to patients, and we hope to extend with PRAME to other tumors.

Turning to cutaneous melanoma. We recently published the final results for KIMMTRAK plus checkpoint combinations. Most of the data has previously been shared. However, there were several insights I would like to emphasize. First, the durability of partial responses and disease control for this combination is remarkable with some ongoing for over two years. This increases our interest to study PRAME plus checkpoints.

Second, the safety profile was consistent with each therapy alone, providing confidence for combining PRAME safely with checkpoints. And finally, we have historically dosed ImmTAC's monotherapy on a weekly basis. However, we had hypothesized that we can switch to less frequent dosing when impacts are combined on a backbone of an active therapy and after initial disease control.

In this study, we successfully piloted switching from weekly to monthly KIMMTRAK at one year with most of these patients maintaining their disease control. This provides confidence for doing similar with PRAME. These are some of the many insights we are applying to the PRAME program.

At ESMO '22, we shared the initial PRAME monotherapy Phase 1 data that led to the expansions in melanoma, lung, endometrial, and ovarian carcinoma as a monotherapy in heavily pretreated patients and in combination with standards of care, since this will allow us to move into early lines of therapy.

We always anticipated to see signals earlier in some tumors that would provide confidence to start registrational trials. And today, I am very pleased to announce our first Phase 3 registrational trial, PRISM-301 in first-line cutaneous melanoma.

Here with the ESMO melanoma data we shared last year, which included 18 melanoma patients; seven cutaneous melanoma, all had prior ipilimumab and either nivolumab or pembrolizumab; and 11 uveal melanoma patients, roughly half of which were tebentafusp naive and have had prior tebentafusp.

Here is an update on those original 18 melanoma patients. We continue to see strong durability, including partial responses ranging from 6 months to 17 months. Even in some patients with tumor shrinkage did not meet the criteria for a RECIST partial response, we see durable disease control. Some of these patients are still on therapy.

The cutaneous melanoma activity is remarkable to me given these patients are heavily pretreated and the fact that F106C is being administered as a monotherapy. As a monotherapy, the durable responses and disease control from F106C in melanoma were clearly compelling. This, coupled with the well-tolerated safety profile, our belief in combinability with checkpoints and the insights that our platform will work best in a first-line setting let us to consider opening a Phase 3 first-line melanoma trial with the primary endpoint of progression-free survival.

In additional to the original 18 patients, the emerging data from the newly enrolled cutaneous melanoma patients, which although has less follow-up, increases our conviction to start the Phase 3 trial now. Finally, the platform insights into how we can design a more patient friendly and less frequent dosing regimen in first-line solidified our decision to move forward.

We had a successful Type B meeting with the FDA who agreed to the Phase 3 design and for us to start the study now. And I will walk you through that study design. PRISM-MEL301 was designed with help from global melanoma experts and input from the FDA. We will randomize previously untreated metastatic cutaneous melanoma patients who are HLA-0201 positive in two arms, the experimental arm, nivolumab plus F160C versus a control arm of either nivolumab or nivolumab plus relatlimab. The selection of therapy within the control arm will be country-specific and will not be investigator choice. This is the first Phase 3 trial we are aware of to randomize to a controller that includes checkpoint doublet.

The primary endpoint is progression-free survival and the secondary endpoint are survival and response rate. The F106C regimen, shown on the slide, reflects a growing confidence on how to dose ImmTAC when in combination with an active backbone. Because we had multiple doses that were clinically active and well tolerated, we agreed with the FDA to include an initial randomization to two F106C doses, 40 micrograms and 160 micrograms. This approach is consistent with FDA's Project Optimus.

We will drop one of the two F106C doses after an initial interim analysis. But importantly, there is no pause in their recruitment and all patients in the go-forward dose are included in the intent-to-treat analysis. This is a really exciting time for us at Immunocore. The PRISM-MEL-301 study represents the first Phase 3 study for the PRAME target and for a TCR therapeutic in first-line cutaneous melanoma, which is one of the largest melanoma indications, an opportunity of over 10,000 patients per year. The Phase 1/2 Study 101 is still enrolling the four monotherapy expansions at the 160-microgram dose. And we continue to look at the other tumors, lung, ovarian, and endometrial for the next tumor for development.

Per the Project Optimus FDA discussions, we will also enroll some more patients with the same tumor types in the 40-microgram cohort, which will serve to help confirm the dose. The combinations with standard of care are also progressing and these will provide safety that will allow us to move into the early lines where we believe our platform will be most active.

Finally, based on our excitement for PRAME, we are building a franchise around this target with our half-life extension and our PRAME-A24 programs on track for regulatory submissions next year.

I'm now going to hand it back to Bahija.

[Bahija Jallal, CEO and Director]

Thank you, David. Thank you, Brian and Ralph. As you can see, the team is not letting up, and I'm grateful for everything they do.

So looking ahead to the second half of 2023 and into next year, the commercial and medical teams will be focused on maintaining the momentum to reach patients who could benefit from KIMMTRAK globally. By the end of this year, we expect to launch in additional European countries and to achieve reimbursement agreements in France in 2024.

As you have heard, our commitment to people living with cancer is expanding as we embark on our first Phase 3 trial with our PRAME-targeted therapy with the aim to randomize the first advanced cutaneous melanoma patients by first - by Q1 2024. We will also continue enrolling more patients in the monotherapy and combination cohorts of the Phase 1 PRAME trial as we investigate the potential and further indications, and will share updated data at congresses during the first half of 2024.

Finally, in oncology, we plan to submit three INDs or CTAs over the next 18 months starting with the PIWIL-targeted candidates in Q4 this year. In infectious diseases, we intend to present data next year in our multiple ascending dose trial in HIV, and we continue enrolling patients with HBV as well as with hepatocellular carcinoma in the HPV trial.

To conclude, Immunocore continues to execute on our strategy, and we remain really excited by the potential to reach even more patients with our ImmTACs platform.

We will now open the call for questions.

[Operator]

Thank you. We will now be conducting a question-and-answer session. [Operator Instructions] Our first question comes from the line of Michael Yee with Jefferies. Please proceed with your question.

[Michael Yee, Jefferies]

Good morning. Thanks and congrats on the progress and congrats on Phase 3 PRAME program. I guess keep my one question to PRAME. David, can you just talk a little bit about your plan to start the Phase 3 in melanoma? I know you gave an update on the ESMO data and the duration. I think I just saw the curves. And how much of the ongoing expansion cohort data played a role on that. Are you seeing similar response rates? I think you had 33%. Are you seeing same number of patients? Just talk a little bit about the totality of that, particularly in the expansion that you were seeing going on now?

And then as a follow-up to that, you did comment that you're thinking about the next tumor type, can you just talk a little bit about what you're looking at and what you're seeing in front of you in ovarian and maybe lung cancer for PRAME? Thank you.

[Bahija Jallal, CEO and Director]

Thank you, Michael. David?

[David Berman, Head of R&D]

Yes. Sure. So two questions. So number one, Michael, again, we looked at the ESMO data, which we showed a very promising update in terms of durability. We're enrolling the expansion, although it's still early, we looked at this data. And in a - from a general drug development point of view, I won't speak specifically to the data, which we'll share next year. But from a general drug development point of view, Michael, we ask two questions. What are the percent of patients that are benefiting? And can the treatment effect in that population support the primary endpoint we're interested in, in this case, PFS? For us, it was clearly yes, based on that data plus the original ESMO.

We took that to the FDA who agreed with us when they reviewed the data. We shared that data with global KOLs and so, I think it became clear to us and everyone who sought to move forward with the Phase 3 study.

With regard to the other tumor types, we saw the activity in ovarian, which triggered us to do that expansion. That's still ongoing. We are very interested, of course, in lung and endometrial as well. So those expansions are still ongoing, and I think more to come on that as we review the data.

[Operator]

Thank you. Our next question comes from the line of Tyler Van Buren with TD Cowen. Please proceed with your question.

[Tyler Van Buren, TD Cowen]

Hi guys, good morning. Congrats on the strong KIMMTRAK quarter, and it's exciting to see all the new updates. Just a follow-up on PRAME and the cutaneous durability update. So clearly, the initial response rate is higher than KIMMTRAK, but again, just to follow up on durability. How confident are you that the durability you are seeing with PRAME, even though it's early, is what you saw with KIMMTRAK? And I guess the same question just asked another way, based on the PRAME construct and design relative to KIMMTRAK when you consider TCR and CD3 potency, is there any reason why you wouldn't see similar durability?

[David Berman, Head of R&D]

Tyler, so the only direct comparison we can do, and it's limited is in the uveal melanoma because that's where KIMMTRAK monotherapy has been mostly dosed and where we have PRAME data. And we have the three PRs with durations of 12-month, 16-plus and 17 months on PRAME. In the Phase 3 KIMMTRAK study, the median duration of response was 11 months. So that's Phase 3, and this is Phase 1. But I think the data for PRAME is very promising in terms of tolerability.

In terms of differences between the molecules, I think that was your second question. The TCR end has the same picomolar potency, the CD3 end is the same. The peptide density for PRAME is higher than it is for gp100, but that's essentially what we know right now.

[Operator]

Thank you. Our next question comes from the line of Justin Zelin with BTIG. Please proceed with your question.

[Justin Zelin, BTIG]

Thanks for taking the question. Maybe for David, can you just walk us through - obviously, you're moving forward PRAME here in the first line versus KIMMTRAK in - and second and third in cutaneous melanoma. Can you just walk us through just the numbers for the accessible market for gp100 versus PRAME and cutaneous.

[David Berman, Head of R&D]

Yes, Justin. So the current Phase 2/3 study TEBE-AM and KIMMTRAK, we estimate to be 2,000 to 4,000 patients per year, and that patients have progressed on ipilimumab and BRAF-targeted therapy and anti-PD-1s. For PRAME in first-line, part of the reason we're so excited about this, the opportunity is greater than 10,000 patients per year. That's the difference in terms of size.

[Operator]

Thank you. Our next question comes from the line of Graig Suvannavejh with Mizuho. Please proceed with your question.

[Graig Suvannavejh, Mizuho]

Thank you and good morning. Congrats on the progress from me as well. A lot of questions on PRAME, but I would just want to focus on KIMMTRAK and the cutaneous melanoma opportunity. Well, actually, uveal, I know that there's been developments on the competitive landscape, and I know that there are thoughts around potentially combining KIMMTRAK with PRAME. So can you just give us your overall strategy there in uveal melanoma? Thanks so much.

[David Berman, Head of R&D]

Yes, I'm happy to take that and invite anyone else to join also. So KIMMTRAK had a great survival benefit and there's a lot of patients who benefit. We are really excited about our combination of KIMMTRAK plus PRAME. It's - we're currently doing the dose escalation optimization. They're both very active drugs and the idea there would be to study KIMMTRAK plus PRAME in the first-line setting. So once we have that data available and we can have a good regimen, we'll be able to share that data.

[Operator]

Thank you. Our next question comes from the line of Justin Kim with Oppenheimer. Please proceed with your question.

[Justin Kim, Oppenheimer]

Hi. Good morning and thanks for taking the question. Maybe just to pivot a little bit to the HIV program. We're hearing a lot more interest in sort of the program as we see potential data near term. Can you just frame for us how we should expect the initial data cut to look? And what exactly is the expectation for patients who withdraw ART over a 12-week time frame?

[Bahija Jallal, CEO and Director]

Thanks. David, you are -

[David Berman, Head of R&D]

Yes, I'm happy to take that. So in terms of the data, we were doing the multiple ascending dose where we treat patients for 12 weeks with intra-patient escalation and then at a target dose. We expect to have multiple cohorts completed, multiple-dose escalations completed when we share the data. The data will include, of course, safety and biomarkers during the initial 12-week run in. After 12 weeks, we will interrupt both our bispecific as well as the antiretroviral therapy, and there we'll look for a rebound of the virus.

Historically, I think the virus will rebound usually within a few weeks. I think most of the patients usually rebound within four weeks. We have a 12-week planned interruption. And so, in terms of what we're looking for there, it's a new field. I mean no one has ever really had a functional care in HIV. So we're really excited to see where this data leads us.

[Operator]

Thank you. Our next question comes from the line of Michael Schmidt with Guggenheim. Please proceed with your question.

[Michael Schmidt, Guggenheim]

Hi guys. Good morning and thanks for taking my question. I had a question going back to the planned Phase 3 study for PRAME and melanoma. So it sounds like the decision to go into first line was driven partially by the KIMMTRAK ctDNA data. And so I was just wondering about the concept, why the activity on ctDNA was higher in first-line patients and whether that is something that would be the case for other tumor types as well.

[Brian Di Donato, CFO and Head of Strategy]

Yes. David or Mohammed, you can?

[David Berman, Head of R&D]

Yes. I'm happy to start. So the data was based on the ctDNA, but also based on the survival and first line is better. I think we have two hypotheses, the first is that perhaps newly diagnosed first-line patients have a better immune fitness. And the second hypothesis is that the patient's tumors might not have been edited as much in contrast to after anti-PD-1. So that's a pretty standard phenomena, by the way, for all immunotherapies. And so we do expect - I mean, we haven't treated first-line patients, but we do expect that the activity will be larger in the first line for cutaneous as well.

[Operator]

Thank you. Our next question comes from the line of Patrick Trucchio with H.C. Wainwright. Please proceed with your question.

[Patrick Trucchio, H.C. Wainwright]

Thanks and good morning, good afternoon, and congrats on all the progress here. Just a follow-up question on the Phase 2/3 trial with KIMMTRAK in second-line or later cutaneous melanoma. With the randomization of Phase 3 portion to commence immediately following completion of accrual into a Phase 2 portion, I'm wondering if you can discuss how efficacy from the Phase 2 portion might inform changes to the Phase 3 design. What changes could you implement? Would there be potentially accelerated pathway depending on what you see in that Phase 2 portion of the study?

[David Berman, Head of R&D]

Yes, Patrick, that's a great question. And we specifically spent a lot of time designing this seamless Phase 2/3. So what we'll look at in the Phase 2 is, number one, we have a KIMMTRAK monotherapy, we have a KIMMTRAK-plus pembrolizumab. Do we need to have the pembrolizumab on board, yes or not. So we can decide to discontinue one of those arms. Number two, we'll be looking at the treatment effect relative to the control arm because we may need - may be clear that we can decrease the size of the trial if the treatment effect is larger.

[Operator]

Thank you. Our next question comes from the line of Ahu Demir with Ladenburg Thalmann. Please proceed with your question.

[Ahu Demir, Ladenburg Thalmann]

Good morning. Congratulations on the progress and thanks for taking my questions. Two on our side. First one is on the cutaneous melanoma. Could you elaborate more on the less frequent dosing? What led you to take that leap and is it only driven by KIMMTRAK or is it driven by the Phase 2 data you got from the PRAME program?

[Bahija Jallal, CEO and Director]

Go ahead, David?

[David Berman, Head of R&D]

Yes, I'm happy to do that. So there's a couple of things that led us to the dosing. Number one was we talked about the KIMMTRAK experience. Number two is if you look at the - if you look at the Kaplan-Meier curves for first-line PD-1s, including nivolumab, you see that most of the progression - in fact, the majority, 2/3 of progressions occur during the first 12 weeks. So that's where we plan to have the weekly dosing because that's where the trial PFS is one and last. After 12 weeks, the Kaplan-Meier curves really plateau out.

And so, we didn't think you need to have a weekly dosing regimen after 12 weeks. And then, of course, by one year, it moves to a once-monthly regimen. And then I think just finally one other point. When we look at the PRAME data, but also KIMMTRAK we see the majority of the tumor shrinkage occurs in the first 12 weeks. So that's the time to have the weekly dosing.

[Operator]

Thank you. Our next question comes from the line of Peter Lawson with Barclays. Please proceed with your question.

[Unidentified Analyst]

Hi, good morning. This is [Jay] on for Peter. Thanks for taking our question. I just want to get a little more color around the organic growth for the second quarter for KIMMTRAK? And if you could give any - talk to the volume of - volume growth versus price growth? And any one-timers we should be thinking about here stocking orders and pricing benefits for U.S. versus ex- U.S.? Thank you.

[Brian Di Donato, CFO and Head of Strategy]

Thank you for that question. So most of the growth was driven from the U.S. with the 14% quarter-over-quarter growth. That was pure demand growth. We did not see any difference in patterns of stocking per se. And you have to consider that we took a price increase at the beginning of the year in January of 2.5%.

[Operator]

Thank you. Our next question comes from the line of Nick [indiscernible] with Goldman Sachs. Please proceed with your question.

[Unidentified Analyst]

Hi, there. It's Nick on for Rajan. And thanks for taking my questions. If we could just come back to the PRISM trial and the design there. I was just wondering what the rationale was for the selection of the two doses, they seem to - or at least optically, they look quite far apart. Is - why was there not a dose in between? Is that something that you've agreed with the FDA? And then looking further ahead, could you just give us an idea of what you see as the bar for efficacy and what good data would delight you. Thank you.

[Bahija Jallal, CEO and Director]

David?

[David Berman, Head of R&D]

Yes. So with the selection of the two doses, we had multiple doses that were active and well tolerated in Phase 1. In fact, we had a sevenfold dose range. We have 20 micrograms all the way up to 160 micrograms. And we chose the 160 originally based on modeling and simulation, although we had fewer patients at the lower doses.

And I think that was the reason for the need to explore a lower dose. When it came to the selection of the lower dose, we had two choices, 20 or 40. 20 was the threshold dose and we felt just in general, a good drug development never to choose the lowest dose because of variability in PK, you'll end up with some patients having too low of exposure. And so, that really set us on choice of 40.

With regard to the bar for efficacy, the nivolumab median PFS has really ranged, I think, between 4.7 months to, I think, 8 months. The most recent RELATIVITY-047 was 4.7 months from a median perspective, we're going to have a blended median PFS because we'll have some patients who are on Opdualag or some patients who are on nivo, but I think that the median PFS blended is probably still going to be less than 8 months. It just will depend on how many patients are randomized to the Opdualag.

[Operator]

Thank you. Our next question comes from the line of Jeff Hung with Morgan Stanley. Please proceed with your question.

[Jeff Hung, Morgan Stanley]

Thanks for taking my question. How is enrollment going for the PRAME, A02 trial? And what should we expect to see in the first half '24 data? Thanks.

[Clayton Robertson, Head of IR]

Great. Mohamed, do you want to take that?

[Mohammed Dar, CMO]

Sure. As we had said earlier, we have moved from a Phase 1 footing to a Phase 2 footing. So we continue to open up additional sites and continue to accrue to our multiple priority expansion cohorts as well as the standard of care combination. So all of that continues to go according to plan. And as we've said, we plan to share the data as it matures in the first half of next year?

[Operator]

Thank you. Our next question comes from the line of Gil Blum with Needham & Co. Please proceed with your question.

[Gil Blum, Needham & Co.]

Good morning, everyone, and thanks for taking our question. So this is a bit of a hypothetical at this point, but it'd be interesting to see kind of what you expected the play would be between the PRAME agent and the KIMMTRAK agent in cutaneous melanoma. When you did previously PRAME post KIMMTRAK data and it suggested there was a ton of activity, but what happens the other way around? Thank you.

[David Berman, Head of R&D]

Yes. So in cutaneous mel - so the PRAME after KIMMTRAK was in uveal and although we didn't see RECIST part response was really remarkable, the disease stabilization that we saw there. Now why was it disease stabilization and not RECIST partial responses like we saw in first line? We don't know that. We can speculate, but we don't know. I think we really are excited to study PRAME plus KIMMTRAK to understand how our platform works when you do multiple combinations. It makes sense to study it initially in uveal melanoma because we have a lot of KIMMTRAK experience there.

But I think clearly, cutaneous melanoma would be the next step. I think there are two ways to think about it, Gil. One is because both PRAME and gp100 are broadly expressed, we could target more cells within the tumor. And you could also think for cells that co-express both, there might be more peptide HLA targets on the cell for the T cell to kill. So I think both of those are active hypotheses.

[Operator]

Thank you. There are no further questions at this time, I would now like to turn the floor back over to Bahija Jallal for any closing comments.

[Bahija Jallal, CEO and Director]

Yes. Thank you, operator. I just want to thank everyone for taking the time today and listening to the progress that we've made. So thank you very much.

[Operator]

Thank you. This does conclude today's teleconference. We appreciate your participation. You may disconnect your lines at this time. Enjoy the rest of your day.