Revolution Medicines at Barclays Conference: Focus on Pancreatic Cancer Trials

On Tuesday, 11 March 2025, Revolution Medicines (NASDAQ: RVMD) presented at the Barclays 27th Annual Global Healthcare Conference, offering insights into its strategic direction. The company highlighted its focus on clinical trials, particularly the RASOLUT-302 trial for second-line pancreatic cancer, while addressing concerns about tariffs and market conditions.

Key Takeaways

• Revolution Medicines is advancing the RASOLUT-302 trial for the PAN-RAS inhibitor, Duraxon RASib, with enrollment expected to complete this year.
• The company plans to initiate a first-line pancreatic cancer trial in 2025 and a trial in resectable disease this year.
• Combination therapies, especially with Tango’s PRMT5 inhibitors, are being explored for enhanced anti-tumor effects.
• Revolution Medicines reported no direct impact from tariffs or NIH budget cuts but noted a $1 billion market cap loss due to broader market conditions.
• Clinical findings from the RASOLUT-302 trial are anticipated in 2026, with a focus on improving patient quality of life.

Financial Results

• CEO Mark Goldsmith noted an indirect impact from tariffs, contributing to a $1 billion market cap loss.
• Despite market conditions, there has been no direct impact on supply chains.

Operational Updates

• RASOLUT-302 Trial (Second-line Pancreatic Cancer):

- Enrollment is ongoing, targeting 420 patients across the US, EU, and Japan.

- A clinical readout is expected in 2026, with strong interest from investigators and patients.

• First-line Pancreatic Cancer Trial:

- A Phase 3 trial is planned for 2025, with preclinical work guiding the design.

- A trial in resectable early-stage pancreatic cancer is expected to start this year.

• Combination Therapies:

- Collaboration with Tango Therapeutics to evaluate Duraxon RASib with PRMT5 inhibitors.

- Preclinical data has shown additive anti-tumor effects.

• G12D Inhibitor (ZoldonRasib):

- Additional monotherapy and combination data expected in the second or third quarter of this year.

Future Outlook

• Revolution Medicines aims to report findings from the RASOLUT-302 trial in 2026.
• The company is committed to improving patient quality of life and survival outcomes.
• Continued exploration of combination therapies is planned, leveraging internal RAS inhibitor doublets and collaborations.

Q&A Highlights

• Chemotherapy Combinations:

- The main challenge is tolerability; the goal is to find a regimen with minimal dose reductions.

- A three-arm trial is being considered to evaluate Duraxon RASib alone, with chemotherapy, and chemotherapy alone.

• Overall Survival Expectations:

- The ambition is for Duraxon RASib to exceed the 11-month overall survival reported for first-line chemotherapy.

• Safety of Doublets/Triplets:

- Good safety observed in combining oleronrasib with draxonrasib. Zoldonrasib is well-tolerated.

For more details, please refer to the full transcript below.

Full transcript - Barclays 27th Annual Global Healthcare Conference:

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: My name is Peter Lawson. I’m one of the SMIDCAP biotech analysts at Barclays.

And it gives me great pleasure. I’ve got up on stage with me the management team from Revolution Medicine. So we’ve got Mark Goldsmith, the CEO and President. And I guess the first question just topical considering the current administration and the impact. Have you seen any impact from tariffs or any disruption in supply chain that you’re kind of concerned about?

Mark Goldsmith, CEO and President, Revolution Medicine: Thanks, Peter, and thanks to Barclays for the chance to participate in this meeting. Have tariffs impacted us at all? Well, I guess you mean other than the bloodbath in the market and the loss of $1,000,000,000 of market cap that’s occurred as a result of those. We haven’t really experienced any direct impact of tariffs or on supply chain so far. We’re of course monitoring it very closely and will react to it if we see that.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Got you. And then the communication with the FDA, has that changed in any way? Do you anticipate any changes just with staffing cuts or worry about staffing cuts? Sure. Sure.

Mark Goldsmith, CEO and President, Revolution Medicine: I mean, we’ve had some concern about that. But in practice, we have had ongoing, I’d say, business as usual exchange with the FDA clearance of our IND for the three zero one study and so on that have all been essentially on time. So, so far we have not experienced anything. Of course, we’re keeping an eye out for it.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Okay. And then kind of the other concerns we should be thinking about is it like NIH budgets, cuts that have anything in the near to midterm that could impact the industry or your company?

Mark Goldsmith, CEO and President, Revolution Medicine: We fund all of the work for our trials ourselves, so none of it is supported by the NIH or any federal agency. And so as a result, we haven’t had any direct impact from those cuts or proposed cuts. I think it’s conceivable that some of the institutions where clinical trials are conducted might find their financial support affected by any proposed changes. We have not had any manifestation of that in our clinical trials. We’ve been able to activate sites.

We’ve been able to proceed to enroll and have not seen impact yet.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Perfect. Thank you. And then just kind of I guess back to your business or the trials. As we think about your PANRAS inhibitor in second line pancreatic, how’s enrollment tracking? And is that likely to be completed by year end?

I guess that’s a topical question.

Mark Goldsmith, CEO and President, Revolution Medicine: Yes. This is a very exciting trial. It’s called the RASOLUT three zero two trial. It’s a trial comparing patients with second line pancreatic cancer that has previously treated pancreatic cancer receiving either standard of care chemotherapy or randomized to the compound called Duraxon RASib or RMC6236, our RAS multi inhibitor. And we expect to enroll about four twenty patients in that trial.

It is now actively enrolling. We have a number of U. S. Sites that are really doing very well. There’s very high interest in this trial both by investigators and by patients.

There’s really a scramble to get into the trial. We’re expanding the number of sites in The U. S. According to our original operating plan for the trial, so that’s going well. We’re also now activating sites in The EU and in Japan since we received clearance regulatory clearance to do so back in December.

So we expect enrollment to continue to be very strong, and we do anticipate completing enrollment this year for a clinical readout in 2026.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Okay. Perfect. And then as we think about like the Phase onetwo population and the Phase three, how do we kind of bridge that? Will there be any differences as we think about these patients?

Mark Goldsmith, CEO and President, Revolution Medicine: Yes. I think you’re asking about the common trend that Phase three trials tend to take some sort of discount to the Phase III trials. We’re not really anticipating that. Of course, we can’t predict with any certainty, but we have gone to great lengths to make sure that the eligibility criteria for the patient population that we studied and reported on in terms of response rates, median progression free survival, median overall survival that those patients have the same clinical profiles or matching range of clinical profiles as the ones we expect to enroll in the Phase III trial. So the eligibility criteria are very similar and we don’t predict a decrement, but of course that could happen just with the stochastic probabilities.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Perfect. Thank you. And then kind of the mix of second line versus second line plots?

Mark Goldsmith, CEO and President, Revolution Medicine: This is strictly a second line study. So this is patients who have only received one prior treatment for metastatic disease. It’s really the same population as I indicated that we studied in the Phase onetwo trial and reported on. We did also study third line and third line plus patients and reported on those as well, but those are not included in this particular trial.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Got you. Thank you. And then just the expectations that we should have for the median OS for the chemo?

Mark Goldsmith, CEO and President, Revolution Medicine: Well, it’s hard for me to convey expectations. Everybody has to triangulate on that themselves. In the Phase onetwo trial that we’ve reported in the G12X population, that’s patients with a KRAS G12 mutation, the median progression free survival at three hundred milligrams, which is the dose we’re using in the Phase three trial, the median progression free survival was eight point eight months and the median OS was not determined. However, in a larger group of patients, which had received doses below 300 up to and including three hundred milligrams, the median OS was fourteen point five months. These numbers of fourteen point five and eight point eight, I think, compare favorably, albeit with a cross trial comparison and albeit with a single arm trial, compare favorably to what the literature has reported for randomized Phase III trials for median PFS and OS of around three months and six months in a similar population.

So, we’re quite excited about that result. I think patients are enthusiastic about participating and now we just have to let it run its course and we’ll see what happens.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Got you. And it’s come up before on the calls just the sense that the patients are doing really well like you’ve got great quality of life impact. Just if you could walk through that. I know it’s kind of not the normal numbers we kind of think about, but it’s because we’re increasing.

Mark Goldsmith, CEO and President, Revolution Medicine: Yes. Thank you, Peter. It’s a really important topic that we aren’t just trying to extend people’s progression free survival and their overall survival. We’re also trying to improve their lives. Today, the standard of care for really any form of pancreatic cancer other than highly localized resectable cancer is chemotherapy.

And chemotherapy for pancreatic cancer is very harsh. Nearly all patients who receive treatment for pancreatic cancer chemotherapy treatment experience grade three adverse events during the course of their treatment and most of those are treatment related. So it’s a very unpleasant experience. And for patients whose lives may be as short as three to six months to spend the last few months of your life on chemotherapy seems like a really dismal prospect. The experience with RMC6236 or deraxone rasib as reported to us has been very favorable.

Many patients, we’ve been told, when they first show up at the doctor’s office are experiencing pain, anorexia, weight loss and really their lives have been markedly affected. And some number of those patients have been reporting back to their physicians on their six week visit. They’re walking in the door having less pain, no anorexia or less anorexia and have gained weight and their lives have been improved. We haven’t quantitated that yet. So those are all really qualitative and anecdotal experiences, but it is commonly described to us by investigators who take care of these patients that this is what they see.

And it gives them great hope that this is really having a biologically important effect for patients and that we might be able to improve their quality of life as well as their quantity of life.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Got you. And I know there are any qualitative comments, but how do physicians kind of talk about your drug versus other KRAS inhibitors for improvement around quality of life?

Mark Goldsmith, CEO and President, Revolution Medicine: We haven’t we don’t have any information. Really, historically, the only other RAS inhibitors that have been tested in pancreatic cancer have been the G12C selective inhibitors. And the results they’ve reported have been modest so far, but we haven’t had any qualitative input from investigators other than that once they see patients on the compound, while some do experience side effects, there are adverse events associated with diaraxone rasib. But nonetheless, their overall report is that patients are doing much better on diaraxone RASA. But again, I can’t quantitate it and I’m just giving you anecdotal vector variance.

Thank you.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: And then given the rapid progression of the disease, how quickly would we expect to see the initial results after enrollment? I

Mark Goldsmith, CEO and President, Revolution Medicine: can’t give you specificity on that. We do expect to be able to report out the clinical findings in 2026. The way the trial is designed, it is the number of events in the OS readout that drives disclosure or opening up of the envelope. So it’s an OS driven trial. And when a certain number of deaths are reached in the trial that will trigger the data monitoring committee to review the data and to determine whether those trials should proceed, whether it should stop, etcetera.

So that’s all we can say today. I don’t have a timeline specifically associated with that.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Got you. And then as you move into the first line kind of and that everyone if you could talk to the trial design and how you’re kind of thinking about the combination use with chemotherapy?

Mark Goldsmith, CEO and President, Revolution Medicine: Yes. Well, there’s been so much excitement about the impact of deraxone rasib monotherapy in previously treated pancreatic cancer patients that the presumption is that if we move to earlier lines of treatment, we would be able to preserve that benefit either in absolute terms or at least in relative terms or in fact might even be able to improve further upon that in absolute terms because the baseline outcomes are better in first line than in second line. And we have seen that trend in moving from third line to second line in the study we’ve reported so far. So, we’ll have to see what happens in first line, but we’re encouraged by that. Based on the results of the second line trial that I just described earlier, those numbers do numerically exceed the reports in first line chemotherapy randomized controlled trials.

Now, I know we really shouldn’t formally make comparisons cross study like that, so there are real limitations to the statement I just made. But just on paper numerically, the median PFS and OS from the second line trial are superior to the literature in first line pancreatic cancer with chemotherapy. So that gives us a lot of reason to believe that we should go study this compound in first line patients. And we have committed to initiating a first line pancreatic metastatic pancreatic cancer trial in 2025. And we’re currently doing the work to help guide the design of that Phase III trial.

And we’re quite excited about it. And we’ve heard from investigators that they can’t wait to start it as well. We also announced just a couple of weeks ago that we expect to initiate a trial in resectable disease, patients who have resectable early stage pancreatic cancer as adjuvant treatment. And we’re also excited about that. We know the investigators have been asking us to do it and we’ve now held hands and agreed that this is an important thing for us to do and we expect to initiate that trial also in this year.

And that would give us coverage for almost all of pancreatic cancer.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: How should we think about how your PANREST behaves with different chemotherapies because the chemotherapy regimen on the standardized as you probably want for a controlled experiment?

Mark Goldsmith, CEO and President, Revolution Medicine: Yes. I think the challenge with combining with chemotherapy is that the chemotherapy itself is harsh. As I mentioned, almost all patients on chemotherapy experience one or more grade three or greater adverse events. That’s sort of a remarkable statement. That means if you start that any of those chemotherapy regimens, you’re very likely to have a grade three event during the course of treatment.

And most of those grade three events are caused by the treatment, which results in very high rates of dose holds, dose reductions and even discontinuation. So many patients don’t complete their chemotherapy cycles because of intolerance. And it gets it’s a cumulative effect. So, after the first cycle, it’s much harder in the second cycle and much harder in the third cycle and so on. So, that’s the baseline that’s occurring in these patients.

Their median dose intensity for really either FOLFIRINOX modified FOLFIRINOX regimen or for gemabraxane, those are the two most common standards in first line metastatic pancreatic cancer. The dose intensity is around seventy percent for both of those, meaning that a lot of doses are being missed or doses reduced drastically. And because chemotherapy has such a steep dose response curve that really does have impact on the overall benefit. If we’re adding Duraxon RASib on top of that, we’re just starting with a very difficult set of patients’ experiences that’s tough for them to get through it even without dexonrasib. And dexonrasib will bring its own generally moderate side effects, but nonetheless some side effects.

So, I think the main goal for us right now and active work that’s underway is to establish a regimen, hopefully one for five FU based chemotherapy and one for gemcitabine based chemotherapy that is tolerated enough that we can provide Duraxonrassib on top of that or in conjunction with that and not cause have the chemotherapy drive significant dose reductions or dose holds or dose continuations. That’s really the issue is that the chemotherapy itself often results in the medicine being withheld and we wouldn’t want deraxonrasib to be withheld during that time unless absolutely necessary. It’s important to keep in mind that deraxonrasib is a targeted therapy. It’s inhibiting the very biologic driver of cancer. If you withhold a dose or a week’s worth of doses or two weeks’ worth of doses, you’re taking the foot off the brakes of the tumor and allowing it to regrow and that can’t be good for patients.

So that’s what we’re trying to determine now is what’s the right regimen or regimens to proceed with.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Got you. Okay. And then in the community setting presumably there’s no real standard of a care for the chemotherapy?

Mark Goldsmith, CEO and President, Revolution Medicine: Well, there is. There is both for modified filferonox and gemabraxane. There’s a well accepted range of doses and schedules that are commonly used that are standards of practice and different physicians may start at different points in those regimens, but because they tend to step down during the course of treatment anyway, pretty much everybody ends up getting the same ultimately the same exposure to chemotherapy across different physicians. Even though they might go about it slightly differently, they’re all working within the same range. So, any protocol that we proceed with will also be within that same range.

And I think it will be perfectly adequate for answering the question of whether Duraxonrasib with chemotherapy is superior to chemotherapy. Now, we also will have a monotherapy arm in this trial, Duraxonrasib alone. And that’s really in direct a direct outcome of the comment I made earlier that Duraxon RASib three hundred milligrams in second line pancreatic cancer already delivers numerically superior outcomes at least in the single arm trial that we’ve reported to first line chemotherapy. And so I think it’s certainly it’s justified to evaluate that and hence I think we’ll have a three arm trial that would be the most likely plan.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Got you. Thank you. Is there any what’s the level of confidence that there’s no cross reactivity for your PAN RAS with other chemotherapies? You mean additive toxicity? Yes.

Additive toxicity and any drug drug interactions.

Mark Goldsmith, CEO and President, Revolution Medicine: Oh, drug drug interactions. I don’t think we have high concerns about a drug drug interaction. I think the main question really is going to be tolerability. Given that the chemotherapy itself is poorly tolerated, adding deraxone or acid could be taken down with it. But I’m not aware of any particular drug interactions that we need to be concerned about.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Are there good examples where you can kind of maintain a backbone therapy despite

Mark Goldsmith, CEO and President, Revolution Medicine: dosing down the chemotherapy? There aren’t good examples because there really are almost no targeted therapies for pancreatic cancer. Pancreatic cancer is treated with chemotherapy except in rare exceptions for BRAF mutations or in fact an EGF receptor antagonist was approved years ago, erlotinib was. But they’re very rarely used because most patients have a RAS driver for their cancer. And therefore in the absence of RAS treatments, it’s been chemotherapy, chemotherapy, chemotherapy.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Got you. What’s the or what are your expectations going into the study for the OS around the chemotherapies?

Mark Goldsmith, CEO and President, Revolution Medicine: Well, I can’t really predict what the outcomes would be, but I certainly would expect or hope maybe would be a better way to put it that we would be able to exceed the OS for first line chemotherapy, which is has been reported to be roughly eleven months for first line metastatic pancreatic cancer patients, six months for previously treated second line patients and eleven months for first line patients. So that certainly would be our ambition is for Duraxone RASB either alone or in combination with chemotherapy to be superior to that number.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Got you. Thank you. And then we’ve got a really interesting combination with Tango’s MTA cooperative PRMT5 inhibitors. Just your thoughts around kind of our expect or what did the preclinical data look like and kind of what are you expecting to see?

Mark Goldsmith, CEO and President, Revolution Medicine: So pancreatic cancer like other RAS driven cancers does often have other co mutations as part of the genetic or genomic landscape within the tumor. And among those is deletion of the MTAP gene, which we now know from preclinical work is synthetically lethal with a PRMT5 inhibitor. And that has driven Tango and several other companies to develop PRMT5 inhibitors. But because of that, there is the possibility that a patient may have both a RAS mutation and an MTAP deletion. And if that’s the case, maybe they would benefit combining a RAS inhibitor with a PRMT5 inhibitor.

We have conducted in collaboration with Tango experiments pre clinically in which we’ve combined those two agents in cell in vivo models of cell lines that carry both of those mutations and we have seen additive anti tumor effects. So, that in our minds justifies biologically evaluating that combination in patients. Tango in this case, Tango is taking the lead. They’re sponsoring a clinical trial and we’re providing Duraxone RASib for that trial and we’re looking forward to seeing what the results might be. Okay.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Will there be further preclinical data disclosures around that? Or is that a Tango question?

Mark Goldsmith, CEO and President, Revolution Medicine: We haven’t really discussed that. It is certainly possible. I think the results are going to be just what I described that in these in vivo models, the antitumor effect is increased in combination, increased over either of the two agents alone. And I’m sure at some point that will be reported. I just don’t know of a timeline for it.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Got you. Perfect. And then your G12D kind of monotherapy additional data this year, what we should expect to see?

Mark Goldsmith, CEO and President, Revolution Medicine: Yes. So, our compound that is selective for the G12D mutation is called ZoldonRasib. It’s been historically known as RMC nine thousand eight hundred and five. Just comment that both Zolto onrasib and Draxonrasib have the onrasib core to their names, onrasib, which alludes to the fact that these compounds all inhibit the active or on state of RAS. And our third compound, which is our G12C selective inhibitors called EleironRASib also with the onRASib as part of the name.

ZoldonRASib is a really exciting compound. It’s again an oral agent. It is highly selective covalently for the G12D mutation. Our scientists were able to do something with chemistry that’s not been done previously, and that is to engineer a warhead and to design the compound in a way that it can covalently bind to the aspartic acid, which is the D in in the G12D mutation. G12D is the most common mutation among RAS driven solid tumors.

So, it’s a very important mutation to target and ZoltonRacib is designed to do so. We reported preclinical data showing very strong activity of ZOLD onRASib in xenograft mice and we reported monotherapy initial monotherapy data in pancreatic cancer at the triple meeting just this fall, which were quite encouraging from a response rate perspective. Now to your question, that’s the background to your question. We expect to report additional monotherapy ZOLDON RASM data sometime in the second or third in the second quarter of this year. And we also expect to report additional combination data involving Zold on RASib or Olear on RASib in combination with Duraxon RASib.

We call this a RAS ON inhibitor doublet, taking two RAS inhibitors and combining them in the same patient. We saw encouraging results when we combined the G12C selective inhibitor with Duraxone RASib and we hope to report additional data in second or third quarter of this year.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Okay. How much data should we expect for that? Like I said, there’s two updates. Is that a handful of patients or

Mark Goldsmith, CEO and President, Revolution Medicine: Don’t know how to quantitate it. We’ll be able to quantitate it when we report it. But we’ve generally reported data when we have enough information that we think it directionally tells us where things should go and when it helps guide future studies.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Got you. And is that

Mark Goldsmith, CEO and President, Revolution Medicine: going to be conference or? I can’t answer that today. We typically try to submit data for medical meetings. That’s our preferred venue. But of course those meetings are very locked in.

And if our data happen to come out at a time when it’s not possible to submit an abstract, then we’ll present it through an investor forum. But I think almost all of our data have been presented at medical meetings either before an investor conference or after we’ve presented it publicly.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: What are the in the final few seconds, what are the expectations around safety for making these doublets and potentially triplets?

Mark Goldsmith, CEO and President, Revolution Medicine: Yes. So far, we’ve seen pretty good safety in combining oleronrasib with draxonrasib. Zolto onrasib is extremely well tolerated. So, I expect it would be able to combine very well.

Peter Lawson, SMIDCAP Biotech Analyst, Barclays: Perfect. Thank you so much. Pleasure to speak to you as always. Thank you.

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