HUTCHMED (China) Limited (HCM) Earnings Call Transcript & Summary

Hello. Good morning and good evening. Welcome to HUTCHMED ASCO investor call. I believe some of you have already seen our ASCO data readout, among which such as that it must be the most exciting one with amazing PFS and HR. So today, we are doing this call to further help you analyze some of the data so you can better understand its implication. As you know, before the presentation, we need to remind you of our safe harbor statement and disclaimer. The performance and results of the operations of the HUTCHMED Group contained within this presentation are historical in nature, and past performance is no guarantee of future results. For better identification, please change your Zoom name to your name plus institution name. We'll keep you muted during the presentation. There will be a Q&A session for you to ask questions after the presentation. Okay. Now let's invite our CEO and CFO, Dr. Su, to give the presentation.

Thank you, Ming, for the introduction. Hello, everyone. Welcome to the call. With me today are Michael Shi, CMO and Head of R&D, who will be available for Q&A as well. So I'll be happy to give you a very quick run-through of the key data of SACHI and also SAVANNAH as well to some extent, and we can all discuss. Next slide, please. SACHI study was terminated following a positive interim analysis and subsequently, an NDA was submitted in China, which is currently under review. Clearly, the study met the primary endpoint of PFS with a statistically significant and clinically meaningful improvement in PFS in comparison to standard of care. Here is the clinical study design of the SACHI study. When we started the study in China in the first-line setting in EGFR mutant non-small cell lung cancer population, all first-generation, second-generation and third-generation EGFR TKIs were available. So the study was designed to allow all patients resistant to first-line EGFR TKI due to MET amplification. The patients were randomized to receive savolitinib plus osimertinib in comparison to standard double chemo platinum plus pemetrexed in a 1:1 randomization. The study was stratified based on brain metastases, TKI and also EGFR mutation types. The primary endpoint also upon confirmed disease progression crossover was allowed. And this study was an adaptive design. And the data will be first analyzed for patients who progress on first-generation and second-generation EGFR TKI followed by the ITT patient population. The primary endpoint is the PFS. Next slide, please. The key demographic information you can see fairly well balanced of note, almost just under 40% of patients enrolled had brain metastases. Next slide, please. This is the primary endpoint. As I mentioned, the study was an adaptive design. The first analysis was patients who progressed on first, second-generation EGFR TKI. Median PFS improved from the chemo group of 5.4 months to savo plus OSI of 9.8 months, hazard ratio -- stratified hazard ratio of 0.34, obviously, highly significant. And this was followed by the ITT population analysis and the same hazard ratio and obviously highly statistically significant. In the next slide, when you look at the patients who progressed on third-generation EGFR TKI, obviously, with the approval of osimertinib and many other third-generation EGFR TKI during the study, in a real-world situation, there was a very quick switch in the first-line setting from first, second-generation EGFR TKI to third-generation EGFR TKI. So when we look at the third-generation EGFR TKI resistant patient population, as you can see here, very consistent clinical benefit for OSI plus savo treatment. TFS improved from 3.0 months for chemo group to 6.9 months for the savo plus OSI treatment, hazard ratio of 0.32 again, highly significant, both investigator-assessed and IRC assessed results were very consistent. The looking at the predefined subgroups, as you can see the PFS benefit was very consistent for almost all predefined subgroups in favor of OSI plus treatment. Next slide, please. This is more of a benchmark -- marking comparing SACHI versus MARIPOSA-2 study in second-line setting and in patients progressed on third-generation EGFR TKI with amplification. Obviously, cross-study comparison and also the small sample sizes should take into consideration. First off, the MET detection difference. MARIPOSA 2 used NGS to detect ctDNA MET amplification. SACHI study, FISH was used and fresh tissue biopsy was required. First off, in the MARIPOSA-2 study, only 14% ctDNA positive, while for the SAI study using the FISH, greater than 30% of MET amplification was detected. And this actually was consistent with the unpublished HUTCHMED data that not every FISH positive patient will be tested ctDNA positive. As a matter of fact, only about 30% of patients FISH positive will detect ctDNA. So a threefold difference roughly and consistent here as well between the 2 studies. Sample size, as I mentioned, relatively small. These are subgroups of the big studies, 32 versus 12 versus 30 for the MARIPOSA 2 study and in the SACHI study was 37 versus 37 patients. Obviously, clear difference in route of administration, MARIPOSA-2 all injections and SACHI study or oral administration and the MARIPOSA-2 had double chemo doublets platinum plus pemetrexed and SACHI study was chemo-free. Looking at the clinical benefits, median PFS, 4.2 versus 3.1. So 4.2 for the Ami plus chemo versus 3.1 months for the chemo alone and hazard ratio of 0.51. There was 0.078 for the p-value, obviously probably due to the small sample sizes. But as you can see, comparing to SACHI study, median PFS, 6.9 for the savo plus OSI versus 3.0 for the chemo. And you can see here, for these patients who progressed on third-generation EGFR TKI with MET amplification, the chemo PFS were very consistent, 3.1 for the MARIPOSA and 3.0 for the SAI study. And the clinical benefit was numerically greater for the SACHI study, OSI -- savo plus OSI 6.9 months. So comparing to -- for the chemo comparator, looking at MET amplified versus ITT in the MARIPOSA study, as you can see, 3.1 months for patients with MET amplification and 4.2 months for the ITT patient population, suggesting MET amplification is a driver and denotes poor prognosis. Evidence of CNS activity, no data was reported from MARIPOSA-2 as of yet. For SACHI study on OSI -- on savo plus OSI treatment, we have noted clear clinical benefit from both the SAVANNAH study and also the SACHI study. I'll go into this a bit further with the data. But let's look at the next slide. So this is the -- you're looking at brain mets study -- brain mets subgroup in the SACHI study, you look at the median PFS, 6.9. And this is very consistent with the broader patient population and highly statistically significant as well. Obviously, not surprising given what we know about the brain penetration ability of both osimertinib and savolitinib, but this was published before in many publications. Let's go to the next slide. So this is a few other key secondary endpoints -- on this slide, response rate, disease control rate and median duration of response, all significantly improved and all consistent with previously published SAVANNAH data as well. Very good response rate, close to 60% and disease control rate and the response was durable. Next slide. So on the safety, no new signal was detected and the combination [indiscernible] was well tolerated and AEs can be readily managed. Let's go to the next slide. So in conclusion, the combination of savolitinib and osimertinib shows clinically meaningful improvement in PFS, ORR and duration of response versus chemo in the second-line setting for patients who progressed on EGFR TKI. Median PFS for the ITT patient population, 8.2 months for the savo plus RSI treatment versus 4.5 months for the chemo treatment group has a ratio of 0.34. Looking at the third-generation EGFR TKI resistant patient population, median PFS 6.9 for the savo plus OSI treatment versus 3 months for the standard chemo treatment, hazard ratio of 0.32. And the safety profile for the savo plus OSI combination treatment was consistent with previously reported safety profile of savolitinib and osimertinib. No new safety signal was detected in the study. Okay. Next slide. So the other abstract presented by AstraZeneca, our partner at ASCO focused on CNS, again, the CNS activity of the -- savo plus OSI treatment. And actually, this was a study, a sub-study to determine the contribution of component in this patient population. Okay. Let's go to the next slide. As you can see next again. So if you look at the efficacy parameters in patients with brain metastasis first comparing savo plus OSI versus savolitinib alone, as I mentioned, this was a subcomponent of the study to determine contribution of component. And when you look at the study as a whole, overall was 58%, again, very consistent when you compare this to the SACHI study, median duration of response, 11.8 months and the onset of response, 6 weeks, so fairly rapid. The next slide. Again, you see these patients with brain metastases, median PFS for the savo plus OSI combination 8.3 months. They're also very comparable to the SACHI study, the ITT patient population. So these patients with brain metastases benefit equally from the savo plus OSI combination treatment. Next slide. Again, when you look at the CNS confirmed versus 43% CNS PFS also events all very consistent with the level of efficacy seen with the greater ITT patient population. Next slide. Also of interest looking at patients who develop brain metastasis on treatment. And in the plus treatment group, there were 13 patients who had PFS events or whose disease will progress. Out of the 13 patients, 0 had the CNC -- new CNS lesions or progression due to CNS lesions. In contrast, savolitinib single-agent treatment out of the 11 patients who progressed, 6 had CNS -- new CNS lesions. So the OSI plus savo group had a very good CNS disease control. Next slide. Again, safety profile, very consistent across all studies and across all different patient population, Chinese versus -- or Asian versus non-Asians, all very consistent, and it can be easily managed. Next slide. So again, savo plus OSI provided meaningful clinical benefit to patients who progressed on EGFR TKI with MET amplification and demonstrated CNS activity or CNS disease control using this combination. Next slide. So I think this wraps up the data summary, and we'll take questions from the audience, if any.

Okay. Thank you very much for the great presentation. Now we are open for the Q&A session. [Operator Instructions] Due to time, please limit your number of questions to 1 or 2 and only questions about our ASCO data. Now the first question comes from Alec Stranahan from Bank of America.

Guys, can you hear me?

Yes. Okay. Great.

Okay. Great. Yes. Thanks for running through the data at ASCO and congrats on the progress from SACHI and SAVANNAH. I guess on the SACHI combo of savo plus osimertinib, I appreciate the OS profile is still evolving. But do you think you'll need static benefit on OS for approval? Or is PFS enough given sort of this is how the study was designed? And curious if you see OS as maybe feeding into physician decision to describe over other options if approved?

Okay. Thank you, Alex. Obviously, for the SACHI study, as I mentioned, crossover treatment was allowed for the study design. So OS statistic significant OS improvement is not allowed -- I'm sorry, is not required for the approval. And it's not even a primary endpoint. So we don't expect that OS -- significant OS is required. And we did see a trend of improvement in OS. I think it will be further published.

Okay. Next question comes from Jonah Chen at China Merchant Securities International.

I have a question on the, especially on the patient selection. So I remember you have a slide showing the comparator versus the MARIPOSA and J&J and you show the ctDNA landed from the -- left from the [indiscernible] patients that we included in the trial, not from the general non-small cell lung cancer patients. Is that right?

Sorry, I didn't get your question. Can you repeat your question?

Yes. I mean the MET amplification detection, you still hear it is a data set from the samples that we recruited for the trial, right? It's not the amplification detection rate for the real-world population. Is that right?

The amplification right here, like 30% for SACHI, 14% for MARIPOSA-2. These are study patient population and the savo patients who progress on the third-generation EGFR TKI treatment. So it's not in novo, it's not for like -- it's not for the first-line patients. These are patients who progress on the third-generation EGFR TKI treatment.

So the second question is that in the upcoming second line third-gen TKI, we've seen lots of new modalities targeting various targets like PD-1 VEGF or [indiscernible] or any other candidates. So Frankly, I think the MET amplification is the most direct [indiscernible] assay problem that we need to target. So how do you compare our SACHI over the [indiscernible] combination versus the current available other dual target or some other ADC target?

So again, we believe MET amplification is an oncogenic driver and patients not poor prognosis. The only way to compare the data is you have to compare with the biomarker detection of MET amplification, for instance. All other studies, they have not published data on the MET amplified patients as we pointed out, right, the IT or the all-comer data is not very useful for comparison. MARIPOSA-2, they just revealed their subgroup data on patients with MET amplification, so we can do the comparison. I would expect based on the hypothesis that MET amplification is an oncogenic driver and these patients will do worse than all comers or all the ITT patient population. So all other studies chemo plus, VEGFR or VEGF plus PD-1, they need to reveal -- they need to publish the MET amplified subgroups for better comparison. So I can't tell you how the SA data compared to all other possible treatments in second-line setting. But overall, I think for patients, I think that what's important in the clinics for patients who progress on the third-generation EGFR TKI, they need to get their tumor samples tested. And if they are MET amplified, I think OSI plus savolitinib offers a very good treatment for them.

One last question on the CNS subset of the Phase II SAVANNAH. I think it's quite encouraging for us to read the PFS data, the separation for our -- the SAVANNAH combination. And what is the current available statement for all the post-TKI treatment, but they have the CNS metastatic patients? Is there any available kind of care for these subject?

I think always, right, patients with brain metastases, the prognosis is much worse than CNS is absent. So that's why we are highlighting the CNS activity of savo plus OSI treatment. I think it's really important, the disease control in the CNS patients. I think this -- a lot of patients ultimately die because of the brain metastases. So again, I think clinically clinicians will pay attention to the patient's brain or CNS status. It's -- unfortunately, chemotherapy -- standard chemo, they don't -- currently, the standard chemotherapy does not offer very good coverage in the CNS. You can imagine all the chemo plus PD-1 plus VEGF or anti-VEGF. I think ultimately, we need to accumulate more data to do pooled analysis looking at CNS control. But we are very happy that savo plus OSI for these patients, at least they benefit very well from the treatment.

Next question from Adam McCarter at Cavendish.

Congratulations on the data as well. And the one question for me is more of a commercial sort of market opportunity one. So you previously disclosed that the EGFR non-small lung cancer MET aberration market in China is worth around $850 million to $1.2 billion. I'm assuming that estimate likely included both MET amplification and MET overexpression. So could you provide any guidance or assumptions around the market opportunity specifically for MET amplification in China, which is the target population for SACHI's potential approval?

Well, Adam, I think at this point, what we do know is in the first -- in the second-line setting, we were just talking about SACHI study, the MET amplification following third-generation EGFR TKI treatment is about 34% in the SAVANNAH study and about 35% from the SACHI study. You are right that overexpression can also be targeted. As a matter of fact, the SAVANNAH study target both MET amplification and MET overexpression together based on the criteria set forth for SAVANNAH study, it was about 40%. So that information is what we know today. So you can kind of estimate the patient population size following the first-line treatment. In the first-line setting, which we have a study ongoing called SANOVO study targeting MET overexpression, which is depending on the cutoff, MET overexpression in EGFR mutant non-small cell lung cancer is rather high based on the reports available, it ranges from 40% to 80% in that range, again, depending on the cutoff. So the majority of patients who are EGFR mutation positive will have MET overexpression as well. Whether that's a targetable patient population using savolitinib osimertinib combination remains to be seen. The study is still ongoing. So from that, I think you can estimate the patient population size. I think in terms of commercial sales, where it's going to peak or -- it's a lot more complicated because depending on the -- again, depending on the various markets, the pricing, the duration of treatment, all these remains to be seen from the SANOVA study in first-line setting. But second line, we have more information, as I said, right, roughly about 40% of patients Duration of response is about somewhere between 8 and 9 months. So I think you can probably do your model using the information available from the SACHI study and SAVANNAH study and -- but again, pricing can vary widely from markets to markets.

Excellent. And if I could just follow up with one more question. With the SACHI data now accepted under priority review in China and a potential approval over the next 12 months, could you share how you're preparing for a potential launch? And I'm thinking particularly around biomarker testing infrastructure for amplification and an overall positioning with the EGFR TKI treatment landscape.

Yes. I think we are working very closely with our partner in China, AstraZeneca China team. So there will be a companion diagnostic kit to go with the final approval. And MET amplification diagnostic kit is relatively mature. It's widely used in hospitals already. I think Astra team will -- they're obviously responsible for commercialization, and they will be providing the kit to train the pathologists in the hospitals. But it's been widely used already in the hospitals in China. So yes, I think we will be working closely with Astra team in China as soon as it's approved.

Thank you, Adam. Due to the limited time, we'll take the last question. it's from Khalil Fenina at Goldman Sachs. No. I think she's not offline. Okay. your line is open.

Hi, everyone can hear me?

Yes.

This is Khalil in for Paul from Goldman Sachs. Just a really quick one from us. Just on the MET amplification testing. We really appreciate the slide on the comparison between MARIPOSA-2 and SACHI. Could you just talk about like the implications that has for studies going forward, whether it's SAFFRON or others in terms of the participation criteria? Are you or is there any planning to require testing via FISH instead of ctDNA? And then what about, and what implication does it have for like the commercial landscape in terms of testing patients once the drug is on the market?

Thank you. Yes, that's a very good question. the SACHI study, fresh biopsy was required and the tissue FISH was a standard test. SAFFRON study, again, fresh biopsy required, but both FISH and IHC for overexpression were used. So the study -- the SAFFRON study is still ongoing. Ultimately, there will be 2 companion diagnostic kits for the SEPFRON study, Standard FISH, same as SACHI, but also IHC for MET overexpression as well. So -- as I talked about, NGS for ctDNA MET amplification that is convenient, but it under detects by almost 70%. It can only detect about 30% based on our published data. Patients with FISH MET amplification, only 30% of those will test NGS positive. So for patients who are -- who progress on EGFR TKI at this point of time, I think FISH test on biopsy is most reliable.

Got it. So is that going to be the requirement going forward? Sorry, I just missed what you said on the 2 companion diagnostics. Is that specifically just for SAFFRON or in general?

That's for SAFFRON. And for SACHI, MET FISH is the only CDx. And the patient population size, it basically FISH alone is about 30% -- somewhere between 30% and 35% when you add overexpression in IHC, it increases to about 40%. So greater majority of patients overlap basically 90% of patients overlap.

Okay. Thank you, everyone, and thank you, Dr. Su. Sorry for the, we have to end the call to time of limited time. So you may end the call, and have a nice day.

Buh-bye. Thank you.

m,anak you. Thank you.