Kura Oncology at ESMO Congress 2025: Promising Cancer Therapies

On Saturday, 18 October 2025, Kura Oncology (NASDAQ:KURA) presented its latest findings at the ESMO Congress 2025. The company showcased its Farnesyl Transferase Inhibitor (FTI) program, with a particular focus on the promising potential of Darlafarnib (KO-2806) in combination therapies. While the clinical data was met with optimism, the absence of financial results left some questions unanswered.

Key Takeaways

• Kura Oncology highlighted the enhanced profile of Darlafarnib, showcasing improved potency and tolerability.
• Promising results were observed in HRAS mutant solid tumors and renal cell carcinoma (RCC) with combination therapies.
• The company is planning further studies to optimize dosing and explore broader applications.
• Kura Oncology aims to address unmet needs in heavily pretreated cancer patients with innovative combination therapies.
• Future data updates are expected, focusing on the combination with cabozantinib and adagrasib.

Operational Updates

• Kura Oncology plans to complete dose escalation of Darlafarnib with cabozantinib in RCC.
• A Phase 1b study is planned to determine the optimal dosing for this combination in RCC.
• Ongoing dose escalation for Darlafarnib with adagrasib in KRAS G12C mutated cancers.
• Development of Darlafarnib with a PIK3CA inhibitor in solid tumors is underway.
• Updated data on RCC cabozantinib arm and preliminary data on Darlafarnib with adagrasib are expected next year.

Future Outlook

• Kura Oncology sees a significant market opportunity, with over 200,000 patients potentially benefiting from Darlafarnib combination therapies.
• The company is developing a strategic plan for collaboration and business development to advance its FTI program.
• Emphasis is placed on enhancing the effectiveness of targeted therapies through innovative combinations.

Q&A Highlights

• The duration of response for the Darlafarnib and cabozantinib combination in RCC is still being evaluated, with more data expected next year.
• Patients previously treated with cabozantinib showed potential resensitization with the combination therapy.
• Comparisons to other treatments suggest promising response rates for the Darlafarnib and cabozantinib combination.
• Manageable neutropenia and limited dose reductions were noted, indicating a favorable safety profile.
• Darlafarnib offers advantages over tipifarnib, including once-daily dosing and a broad therapeutic window.

Readers are encouraged to refer to the full transcript for a detailed understanding of the conference call discussions.

Full transcript - ESMO Congress 2025:

Operator: Good day and thank you for standing by. Welcome to the Kura Oncology Discussion of FTI Clinical Data at the ESMO twenty twenty five Congress. At this time, all participants are in a listen only mode. After the speakers’ presentation, there will be a question and answer session. To ask a question during the session, you would need to press 11 on your telephone.

You will then hear an automated message advising your hand is raised. To withdraw your question, please press 11 again. Please be advised that today’s conference is being recorded. I would now like to turn the conference over to your first speaker, to Troy Wilson, President and CEO of Cora Oncology. Please go ahead.

Troy Wilson, President and CEO, Kura Oncology: Thank you, Dulam. Good morning, good afternoon, good evening, everyone. As Dulam mentioned, I’m Troy Wilson, CURA Oncology’s President and Chief Executive Officer. And it’s a pleasure to have us here with you today to review our Farnesyl Transferase Program, and in particular our clinical updates from ESMO twenty ’25. This is the second in a two part series.

The first part was a discussion of the preclinical data and rationale, which was presented on September 16, last month. For those interested, that webcast and those slides are available on the Kura Oncology website. If we could please go to the next slide. In today’s presentation, we’re going to be making certain forward looking statements. I would refer you either to our website or to the SEC’s website for more information about the risks of an investment in CURA oncology.

If we could go to the next slide, please. Slide three, today’s agenda. We’re going to be reviewing each of the three datasets that are shown here. First, we’ll discuss the darlafarnib monotherapy data in advanced HRAS mutant solid tumors. Then we’ll talk about the combination data of FTIs and TKIs in renal cell carcinoma.

And finally, we’ll conclude with a discussion of the combination of FTIs and PI3 kinase self inhibitors in PIK3CA mutant head and neck. We expect that the prepared remarks should take about thirty minutes or so. There should be plenty of time for a Q and A session at the end. We could go to the next slide, slide four. The participants in today’s call, in addition to me, include Doctor.

Molly Leone, Cura’s Chief Medical Officer. And then we’re very pleased to have with us Doctor. Glenn Hanna. Doctor. Hanna is Director of the Center for Cancer Therapeutic Innovation.

He’s a medical oncologist with a specialty in head and neck at the Dana Farber Cancer Institute. He’s also Associate Professor of Medicine at Harvard Medical School. Doctor. Hanna has been an investigator both with Tipifarnib and Darlafarnib. And he’ll be presenting the data on the HRAS mutant solid tumors as well as the PIK3CA mutant head and neck data.

If you could go to slide number five, please. In our call on September 16, we introduced to you for the first time darlafarnib in the context of preclinical data. Now we’re going to follow that up with the clinical data. But notably, darlafarnib, we took all of the lessons of tipifarnib as well as the other FTIs. We tried to improve everything that we could.

As you’ll see, darlafarnib is an extremely potent, well behaved molecule. We have efficacious doses that are in the single digit milligrams, with anticipated daily dosing, excellent drug like properties. And of course, this is a novel, chemical entity a new chemical entity, excuse me. And so it has an appropriate patent state. And we’re hoping it really forms a foundation for which we can now advance this concept of using FTIs as a companion therapy to various targeted therapies.

But as an introduction, let’s talk a little bit about the data that gave us confidence, really, that darlafarnib was giving us what we expected and what we wanted to see. And with that, if we can go to slide six, I’m going to turn it over to Doctor. Hanna. Glenn?

Glenn Hanna, Director of the Center for Cancer Therapeutic Innovation, Medical Oncologist, Dana Farber Cancer Institute, Harvard Medical School: Thank you, Troy. So as stated, I think the first step is to talk about darlafarnib or KO-two eight hundred six as monotherapy in advanced HRAS mutant solid tumors. And this data is being presented in the poster session at ESMO this weekend. On behalf of my co authors it’s a pleasure and my colleagues here to present the data to you. So KO2806 or DARLI, the mechanism of action for monotherapy is described here.

Just a reminder that in post translational biology we know that prenylation is an important process whereby different carbon chains like little strings are attached to the ends of proteins and flag them for localization to the surface of the cell. This is a key process, right? The signaling process requires for an oscillation. And this is just based on the number of carbons that are added to the end of a molecule to localize it. And this can be important in oncogenic and cancer signaling.

We know that HRAS and REB depends solely on farnesylation. There are other forms of crenulation like duralgerenylation. And again, don’t get mixed up with these names. It just implies the number of carbon chains that are added, whether it’s 10 or 13, like a little tail to the end of proteins. But this has important implications for how these are handled and how cell communications occur.

And so importantly HRAS and REB as we said solely focus on this function whereas other RAS isoforms which are a little bit different are using a different carbon attachment mechanism and enzymatic process for their cleavage. And so this offers an opportunity to target HRAS mutant tumors. And we know from the experience that they’re sensitive to these And Tipifarnib has very well demonstrated encouraging clinical activity in patients with HRAS mutant tumors. So Darley Farnib, as we heard from Troy, is the next generation, hopefully best in class optimized version of Inhibition that offers enhanced potency. It has optimized pharmacokinetic properties.

And importantly, it’s a small molecule with even single agent activity that has the ability to improve outcomes. You can see on the cartoon at the right by blocking this important process in HRAS and red, we disrupt the downstream signaling cascade that allows cancers to grow through the MEKERK pathway. So FIT-one is a monotherapy study design that looks at first in human multicenter open label usage of KO-two thousand eight hundred and six or Darley alone, but also in combination, as we’ll hear soon, in a number of advanced solid tumor types where preclinical data is supportive. So KO-two eight hundred six monotherapy was conducted in RAS altered solid tumors. So we included HRAS mutant and highly amplified.

Generally cutoffs around six to 12 are used, but that can be a point of discussion. HRAS overexpression in head and neck squamous cell cancer was permitted. And in non small cell and colorectal, we did allow other RAF isoforms like NRAS and KRAS primarily because it’s never perfect in science or in biology. There is used in some of the other RAS isoforms. And so there was a rationale in the dose escalation to get data quickly and to expose patients with KRAS and NRAS to the Darley Farnib compound.

This was administered orally once daily on days one through seven and fifteen to 21 in a twenty eight day cycle. So onoff dosing, one week on, one week off. And this data cutoff that we’ll share is as of August 15. You can see the dose levels on the right starting at three milligrams daily dosing up to fifteen as an estimated sort of cap point. And we’ll walk through that in the dose escalation.

We did anticipate monotherapy activity based on the tipifarnib experience and the potency of this molecule. So here are the baseline characteristics and demographics of the population. From left to right, showing you monotherapy dosing, three milligrams sequentially all the way to fifteen milligrams. No need to read the entire slide. As a clinician, this is balanced for what we would expect in this population.

We see a proportion of men and women. The median age is on par. There is a larger proportion of white patients, and that’s typical for the epidemiology of the disease we see with head and neck mucosal disease. As well as an important point about the primary tumor opportunity here. So you can see head and neck was an important enrolling tumor as well as salivary gland and thyroid.

But we also had some colorectal patients, GI with pancreas represented. I think the other important point is prior lines of therapy. So these patients were heavily pretreated. And that’s impressive when you start thinking about monotherapy activity for a novel agent. With some patients between thirty percent and even sixty percent in dose levels with more than three lines of treatment.

And of course, HRAS alteration is highlighted at the bottom across each of the dose ranges as well. So importantly, we see that KO-two thousand hundred and six demonstrates encouraging safety and tolerability. And this is on brand with what we experienced in the clinic with the tipifarnib population. And this is really a clean molecule. And I think the point I would make here as a drug developer and someone who leads a portfolio of more than 60 oncology drugs in development in solid tumor oncology, this is one of the easiest drugs to dose in clinic.

You have very predictable and manageable cytopenias. You can see there rates of treatment expected AEs in terms of neutropenia and anemia, and even thrombocytopenia. But most importantly at the bottom in the blue chunk is the grade three or greater treatment emergent AEs. And you’re noticing that in the dose range of interest, the sort of optimal range between three and eight milligrams, we’re seeing manageable and modest rates of neutropenia, anemia and minimal thrombocytopenia. These other points of interest like fatigue, mild nausea, this is impressive for what you’d expect from contemporary small molecule inhibitors, which are plagued with a lot more issues related to rash, dosing disruptions and GI toxicity.

So again, it’s a pleasure to work with this class of drug like it was with tipifarnib, We were happy to see an encouraging safety profile for Darlafarnib. So in terms of monotherapy activity in patients with HRAS mutant solid tumors, this is an important slide showing you that there’s a number of tumor types represented. So this is a tumor agnostic and molecularly selected compound for HRAS altered patients across a number of different HRAS mutants and hotspots. We saw, for example, stable disease with tumor regression and even partial responses with maximum tumor regression in hard to treat tumor types across the five and eight milligram dosing range. So as we heard much lower doses, a more narrow but importantly focused therapeutic index where there’s potency at low dosing.

And we even see a hint of durability at that five milligrams with patients staying on beyond twenty months in some cases at data cutoff. So this was very encouraging, right? I think as a drug developer, we want to see excellent tolerability and now we’re demonstrating in a molecularly selected population monotherapy activity. And that’s exactly what we expected with darlefarmib. Here’s just a clinical case example showing deep and durable response.

One of the comments we often get is, oh, you’re just shrinking tiny tumors down to smaller size. Not in this case. You can see examples of upwards of 4.5 millimeters of disease decreasing by a large percentage in this case. In this case, it’s a salivary gland cancer heavily pretreated excuse me, heavily resected and radiated patient with upfront surgery, who had a very difficult to treat disease that has no standard of care options. And with this molecularly targeted agent had a confirmed PR exceeding 60% and continues on treatment at week eighty.

So well over a year. This is actually one of my patients. And she’s thrilled to have gone on to this study and remains, I can say even to this day, still in response and doing very, very well. So that’s really important, right? A lot of drugs are plagued by the inability to dose consistently, The inability to demonstrate that resistance is not developing.

This is proving on brand mechanism good tolerance and durability. And that’s what we want to see with novel agents. Here’s another example of a deep and early response in a fourth patient. This is now, okay, that patient had come out as a first line or early patient with HRAS targeting. We’re talking about someone who’s already had chemo immunotherapy with advanced head and neck cancer, has already had EGFR modulation.

And now in the fourth line, look at this, this is local regional disease. It’s been radiated. It’s hypoxic, fibrotic. This drug is breaking through and causing local regional regression from 6.8 to 2.7 millimeters. That is drug activity.

That is monotherapy impressive activity with a nice sixty percent response rate in this case, which is excellent. So in summary, darlefarnib has demonstrated a manageable safety profile, no new safety signals, excellent tolerability with a q day or once daily dosing schedule in weeks on and off alternating. We see encouraging monotherapy activity observed at multiple dose levels in that three to eight milligram range in HRAS mutant solid tumors, which span a number of different hard to treat cancer types, as well as some more common tumor types like head and neck cancers and mucosal disease. And we see on target activity through that broad therapeutic range. These data definitely further support evaluation of this compound and make it an optimal partner for a number of different small molecules.

I want to remind people that what’s been very challenging with many small molecule inhibitors is that the time when you start combining, you get dose limiting toxicity. I’ll point you to examples of CDK4six combinations, you name it with MEK and ATR inhibitors, all of these new glamorous drugs, it’s very, very difficult to envision combination intolerance. But this drug is delivering on that account. So it’s really exciting to see this drug move forward. And Molly’s going to talk to us a little bit about some of the emerging data in RCC with CABO.

Molly Leone, Chief Medical Officer, Kura Oncology: Yes. Thank you so much. If we want to go to the next slide. So I’m really happy to share our CABO combination data that were actually shared earlier today at ESMO. And I might like to add, received the Best Poster Award in the session.

So, we’re very proud of our FTI2806 in combination with CABO and renal cell carcinoma. Data’s day was presented by the one affectionately known as Doctor. A. So, as we and others have been emphasizing, an overactive mTOR pathway signaling drives cell growth, proliferation, and survival in RCC tumors. Rapalogs block this pathway and are FDA approved in RCC, but have seen limited use because of tolerability issues, as Doctor.

Hanna was just quoting. As seen on the right, CABO offers clinical benefit to these RCC patients where you see around a twenty five to twenty eight percent expected ORR in this particular line of therapy and stable disease approaching sixty percent. However, this is limited activity, and we see reduced activity with subsequent TKIs, which underscores the need to optimize these VEGF targeted therapies. KO-two thousand eight hundred and six inhibits for an esterlation of RET, which uniquely inactivates mTORC1. Additionally, two thousand eight hundred and six enhances cabozantinib’s antiandrogenic activity in both endothelial cells and parasites in RCC xenografts.

Thus, we tested this combination in RCC patients. Next slide. So, this is our FIT-one trial. In addition to the monotherapy that was just described by Doctor. Hanna, we are evaluating combinations as well.

It is a first in human Phase I open label trial studying 2,006 both alone and in combo in advanced solid tumors. The KO-two and eight plus cabozantinib combination, we enrolled specifically patients with renal cell carcinoma, either clear cell or non clear cell. And for the dosing, the KO-two thousand eight hundred six was dosed at three, five, or eight milligrams once a day, one week on, one week off, plus the continuous dose of cabozantinib. We started at forty milligrams and were soon able to escalate to sixty milligrams. And this is also given every day in twenty eight day cycles.

And just as a reminder, this is data as of the August 15 data cut. We’ve enrolled over 50, close to 60 patients as of this data cut. And as you can see, ClearCell was similarly with the baseline demographics here, there’s nothing of great surprise with the types, ages, or performance status of patients that were enrolled into this. So, I’m just going to draw your attention to a few things. As you can see, clear cell was the majority of patients that were enrolled.

The initial portion of the study was well dominated by patients that were prior cabo exposed, so that’s your forty milligram patient population, while earlier Lyme patients dilated the sixty milligram cohort. And please note that the three milligram plus sixty is still enrolling, and thus, that’s why you’re seeing lower patient numbers in that particular cohort at this time. Next slide. The combination has been well tolerated to date. No apparent overlapping toxicities have been seen, and we really see the safety profiles of each individual agent as if given alone.

Next slide. As a reminder, in this patient setting, we would expect to see maybe a twenty five percent to twenty eight percent response rate with cabo as a monotherapy, and we’d expect a zero percent response rate for 2806 alone. We first filled the forty milligram cohorts, and at that dose saw encouraging activities with, you know, consistently a thirty three percent response rate overall and activity even in prior CABO failures. Of the patients that have cleared efficacy evaluation period at the sixty milligram, preliminary data is demonstrating about a fifty percent response rate in the five milligram combination. Again, those patients were enrolled first.

The three milligram and eight milligram are currently maturing data, and were not sufficiently mature at the time of this data cut to share. But we look forward to sharing them in the future. Next slide. We are definitely encouraged by the overall activity we are seeing. Here, the forty milligram cabo patients are the hash marked patients, and those with prior cabo exposure are marked with stars.

Our non clear cell patients are also included in this particular figure. And as you can see, there are consistent decreases in tumor size across doses and subtypes, which is highly encouraging. It appears as we’ve gone up in the cabo dose, we are seeing increased efficacy, but obviously we still evaluating those patients in these combination settings. Next slide. Just to highlight a patient’s experience, this is a 61 year old male with clear cell.

Previous treatment included pembro in the adjuvant setting, and the patient came on trial in stage IV disease. After eight weeks, the patient had experienced a partial response that actually deepened by week sixteen, and this patient remains on trial as of this data cut. Next slide. We’ve previously shown you preclinical data on RCC xenografts that were non responsive to monotherapy TKIs but that were then responsive to the combination. The results support a potential sensitization to cabo therapy with the use of this combination.

So, if we move to the next slide, we are actually also seeing this on study in our patients. This is a 53 year old with clear cell renal cell carcinoma with two prior lines of therapy, the most recent of which included cabo. This patient enrolled at our cabo forty milligram plus three milligrams, the lowest dose of two thousand eight hundred and six. And the patient quickly obtained a partial response that has been very durable. In fact, this patient is almost going on a year as of the time of data cut, Again, after just having failed cabozantinib therapy in their most immediate prior line.

Next slide. So, what messages should you take away? Well, two thousand eight hundred six and cabozantinib has a manageable safety profile is the most important. And that’s across dose levels tested for both drugs as we were able to explore multiple dosing levels of both drugs. The antitumor activity of two thousand eight hundred six in cabo in combination was observed across all doses, including among patients with prior cabo exposure.

We were seeing an ORR of thirty three percent to fifty percent in clear cell. If they had had prior cabo, we saw seventeen percent to fifty percent responses. And disease control rate was extremely high as one would expect, but maybe even a little bit increased over cabo alone around eighty percent to one hundred percent in the clear cell renal cell carcinoma. So, the activity of 2,806 and cabo combinations really does support the hypothesis that 2,806 is able to enhance this anti angiogenic activity of cabozantinib and supports our further development in this space. With that, I will pass it back to Doctor.

Hannah.

Glenn Hanna, Director of the Center for Cancer Therapeutic Innovation, Medical Oncologist, Dana Farber Cancer Institute, Harvard Medical School: Yes. So we’re going to go a little back and talk about farnold transferase inhibition with tipifarnib because the program from the current trial predates the enrollment of the dose escalation and experience with darleafarnib. And this was a combination study, as we’ll talk about, with a PI3K alpha selective inhibitor in head and neck cancer. So really dual targeted oral small molecule inhibition targeted therapy in head and neck. So this is the current trial in head and neck, tipifarnib and alpelisib in recurrent metastatic head and neck squamous cell cancer.

And this was a Phase I study. So just to remind us that the FTI mechanism of action, we talked about this really targets that HRAS and REB, farnesyltransferase interaction and flagging proteins or carbon chains I should say on proteins for localization. But what we learn and as all of you know is that mechanisms of resistance are significant. And so one pathway that’s up regulated or altered in a co adaptive mechanism is the PI3K mTOR AKT pathway. So a number of preclinical experiments and data from different tumor types has shown that blocking one of these pathways can lead to analogous upregulation or sort of adaptive upregulation of the alternative pathway.

And we see this a lot in oncology as we’ve understood resistance mechanisms. And so the preclinical data supported that we would want to use farnold transferase inhibition to suppress that upregulation of MAPKT signaling and mTOR feedback reactivation. And so this was really strong preclinical rationale for combining these two small molecule targeting agents. So that was the basis of the current head and neck study design, which tested both tipifarnib in combination with alpelacid in PI3K altered or PIK3CA altered, mutated or amplified recurrent metastatic head and neck patients. As it should be familiar, we use tipifarnib in its typical schedule on days one through seven and fifteen to 21 with weekly on off dosing.

Alpelicib however, based on the label and experience from breast cancer was once daily dosing. And together this was given in monthly cycles. I have to say the BLRN mechanism to understand safety and tolerability was an important part and an elegant part of this design, where we incrementally adjusted the dose stepwise for each of the agents using an algorithm based on safety events observed at the prior dose level. And so this allowed us to understand the contribution of safety and potentially efficacy at different dose levels to combine these drugs safely. And additional patients were enrolled in the candidate optimally biologically active dose.

You can see here we started at tipifarnib six hundred milligrams total dosing daily. Remember, Tipi is a twice daily medication, so that would be three hundred twice daily, plus two hundred of alpelasib. And you can see we escalated based on safety and efficacy observation to land on two potential dose levels. Dose level two where we enrolled 16 and dose level four, seventeen patients. And you can see we achieved doses of 1,200 or six hundred BID if you will of TIPI and alpelisib at the two fifty milligram daily dose.

In terms of safety and tolerability, this was one of the main focuses of this Phase one trial, again demonstrating the important power of an FTI for combinatorial potential, given its very predictable and well tolerated safety profile. And even with alpilicib, a drug that has evidence of some hyperglycemia, some maculopapular rash and some electrolyte disturbances and lipase elevation, we were able to safely get up to two fifty milligrams daily and maintain tipifarnib at the twelve hundred milligram total daily dose in dose level four. So this was very encouraging from an investigator standpoint, again resonating the point that combinatorial opportunity has high potential with the STIs that Kura Oncology is developing. So moving forward to activity, we saw encouraging antitumor activity for this combination in patients with alterations or hotspot mutations in PIK3CA. So this is showing you the objective response rate.

And really, I think what was most impressive is when we were in the optimal dose range of interest, particularly at dose level four, where safety wasn’t much greater. We saw at the twelve hundred and two fifty respective dosing of these drugs, almost fifty percent response rate. That’s pretty impressive. Keeping in mind these patients have already been treated with platinum, they’ve already failed immunotherapy. And in many cases, we were allowing patients in later lines as I showed you with the darlefarnib experience.

So we have a good safety and at an optimal biologic dose, we have a very encouraging ORR. And in a prior study, just a reminder that alpellisib monotherapy has been explored in PI3K altered patients and we’re talking about response rates approaching zero percent. So this is impressive activity proving our hypothesis. Median duration of the objective response, do want to point out those numbers are impressive, the high end reaching twenty months in some cases. So again, we’re seeing that durability patients staying on for long periods of time and very nice disease control rates, particularly at that dose level four in complement to our response rates around forty seven percent.

Tipifarnib enhances the activity of alpelasib in preclinical models that I believe you’ve seen before. But we it’s important to show that TIPI does inhibit mTOR signaling rebound that’s observed with valpelasib when dosed alone. And that combination does allow for deep regression. And we saw that in CDx models, but are now demonstrating that in patients. Next slide.

So this is just an example of a deep response in a patient treated with the combination. You can see their imaging on the left. This was a 36 year old HPV positive never smoker. I do want to point out that PI3K alterations are common in HPV positive patients, which is the majority of patients we’re seeing in practice these days in some instances, given the trends in smoking. In the epidemic of HPV, it’s about a thirty percent rate of hotspot alterations in this pathway.

This patient was pretreated with immunotherapy, a novel vaccine and had an R88Q mutation, which is generally sensitive to PI3K and had an 80 plus percent reduction at four weeks. So that’s rapid disease control in distant metastatic disease with durability exceeding a year. Exactly what you want to see in a dual targeted therapy combo. And these deep responses, here’s another example. Again, tough to treat local regional disease, heavily pretreated with radiation.

We said this is a hypoxic and fibrotic environment, and this combination is doing a nice job to overcome resistance of platinum and immunotherapy in this 75 year old patient with PI3K mutated head and neck cancer. This was a rapid regression. This was one of my patients who was immediately able to avoid a feeding tube and get back to swallowing with minimal dysphasia once they were able to start the combination. This is an impressive response in a difficult to treat tumor location for head and neck. So putting this together, in the tipifarnib alpelisib experience for PIK3 mutant patients with head and neck cancer, we see, I would say very nice tolerability and a very manageable safety profile where many combinatorial pairs have failed in the past because of overlapping tox.

We see robust anti tumor activity, fast regression, heavily pretreated patients, and nice deep responses with evidence of durability as shown at that two fifty milligram daily alpilicid dose. And in dose level four twelve hundred daily or six hundred BID of Tippi. So these data really do support that. The mechanism has been addressed in this adaptive resistance scenario and really speaks to the power of this drug in combinatorial states going forward. So very happy to see this data and happy to share it.

So I think the next steps going forward is probably where we will focus before opening it up to questions.

Molly Leone, Chief Medical Officer, Kura Oncology: So obviously, we’re very encouraged by all of these data that we have seen thus far. So our next steps for the darlafarnib, the name for two thousand eight hundred and six, is to obviously complete the escalation of our combination in RCC, so our cabo combination. We’re going to be conducting a Phase Ib for two thousand eight hundred and six plus cabozantinib and using that combo to determine our optimal biologically active dose and select our recommended Phase two dose. We will be completing dose escalation for the two thousand eight hundred and six plus adagrasive in KRAS G12C mutated patients that either have non small cell lung cancer, colorectal cancer, or pancreatic cancer. And we plan to develop data generation options for darlafarinen plus a PIK3CA inhibitor as well in the future in solid tumors.

We’re also looking to be able to share additional data hopefully next year. And that’ll be updated data, of course, for the RCC, the cabozantinib arm, but also the preliminary data, which we’re also very excited about for the two thousand eight hundred and six plus adagrasib. And with that, I’d like to pass it back to Troy.

Troy Wilson, President and CEO, Kura Oncology: Thanks, Molly. If we can just go to the next slide, the large potential opportunity. So as you’ve heard, one of the pleasant surprises is that the FTIs combine well with each of these targeted agents. While we’re not showing you the combination today with adagrasib, we are encouraged there again by the ability to combine darlafarnib with a KRAS G12C inhibitor. Importantly, as we showed you in the with the preclinical data, if this mechanism works with one drug candidate, it likely works with the entire class.

That is both an opportunity and a challenge. The way that we think about darlafarnib and FTIs in general is they’re making good drugs better. They’re driving better outcomes for patients. And that’s what’s giving us this large total addressable market here of greater than 200,000 patients across all potential indications. So there’s a lot that we can do.

We have to be have a thoughtful development strategy. We have to have a thoughtful collaboration and business development strategy. And we’ll have much more to say in the months ahead. With that, we’ll conclude the prepared remarks, and we’re preparing to open it up to questions. I will say based on the feedback that we got from our last presentation, we’re going to do this one a little bit differently.

We have a long queue of people who want to ask questions. I would ask those who want to ask a question to please just ask one question. We’re going to try to get through everyone. If there’s time, please feel free to get back in the queue and you can ask additional questions. But we want to make sure that everyone gets an opportunity to ask a question.

So with that, Dulam, we’re happy to turn it over to you for the Q and A session.

Operator: Thank you, sir. We ask that you please limit your questions to no more than one, but And I show our first question comes from the line of Jonathan Chang from Leerink Partners.

Jonathan Chang, Leerink Partners: Hi, guys. Thanks for taking my question. On the cabozantinib combination data, can you give us a sense of what the duration of response and or time on treatment metrics look like? Is there anything you can comment on there? Or is it still too early?

Thank you.

Troy Wilson, President and CEO, Kura Oncology: Molly, would you like to take that?

Molly Leone, Chief Medical Officer, Kura Oncology: Sure. Thankfully, it’s still a little bit too early, especially because I think we’re going to be seeing the selected dose come out of your sixty milligram cohorts, so cabo cohorts. So, I’d say stay tuned. We’re not disappointed thus far. We’ve had patients stay on for significant periods of time.

But it’s still time for some to let the data mature. And like I said, we’ll present more next year.

Operator: Thank you. And I share our next question in the queue comes from the line of Charles Xu from LifeSci Capital. Please go ahead.

Peter Green, LifeSci Capital: Hi, this is Peter Green on for Charles. Congrats on the data. Just a question on patients treated with cabo and darlafartan. Any color on whether those four or 12 responders that have had prior best response of stable disease, whether they stopped cabo due to progressive disease or for some other reason like toxicity? And then of those 12, did any of them have progressive disease or I guess how many on cabo?

Thanks. Molly?

Molly Leone, Chief Medical Officer, Kura Oncology: Yes. Sure. So, best response tended to be stable disease, and they would come off usually for progression prior to coming on to our treatment. As we said with that one patient, their best response had been stable disease, and then they were losing control when they came onto the combination. So, I can’t give you the details on every single patient with prior cabo.

We saw some stable disease. We saw at least two PRs that looked very good thus far. Again, I think let’s look towards these individual cases and the data we plan to develop even more in the future. But we certainly are seeing, like I said, anywhere from seventeen percent to fifty percent response rate in prior treated cabo patients that are receiving the combination.

Glenn Hanna, Director of the Center for Cancer Therapeutic Innovation, Medical Oncologist, Dana Farber Cancer Institute, Harvard Medical School: The other point I would just make about that is you’ll notice we were able to go up to sixty milligrams of cabo in combination. So if patients had come off for safety issues, we wouldn’t be getting to sixty milligrams. So to Molly’s point, it was progression issue, not a safety issue.

Operator: Thank you. And I show our next question in the queue comes from the line of Reni Benjamin from Citizens Bank. Please go ahead.

Peter Green, LifeSci Capital: Hey, thanks guys for taking the questions and congratulations on the combination data. I guess my one question maybe it’s for Doctor. Hanna is, how do you view these combo results when compared to let’s say the HIF-two alpha plus cabo combinations? Any sort of color would be great. Thanks.

Glenn Hanna, Director of the Center for Cancer Therapeutic Innovation, Medical Oncologist, Dana Farber Cancer Institute, Harvard Medical School: Yes. I think the HIF-two alpha story is still evolving and certainly there’s a difference in toxicity probe file. But I do think seeing the potential around even that window that Molly shared was 33 ish to 50%. That’s impressive. And we’re from my understanding of the emerging data with HIF alpha or HIF2 alpha inhibitors, we’re not necessarily seeing anything outside that ballpark.

This would be equal or better.

Molly Leone, Chief Medical Officer, Kura Oncology: Yes. And just to add to that, the HIF2 alphas are focused obviously, at least currently on developing in renal. But we do have a firm belief that wherever cabo goes, we can go as a combination. So we think that there is broader opportunity as well.

Operator: Thank you. And I show our next question comes from the line of Syed from Mizuho. Please go ahead.

Eric, Mizuho: Hi, this is Eric on for Salim. Congrats on the data and thanks for taking the question. Just eyeballing the waterfall plot on the CABO plus 02/1400, it looks like the prior CABO experienced are kind of leaning towards lower responses. Just wanted to see if there’s any color on that, how we should be thinking about that. Thanks.

Molly Leone, Chief Medical Officer, Kura Oncology: I think that’s tough for you to really be able to interpret because in addition to these patients being prior cabo pretreated, they’re much more heavily pretreated if you look at the baseline characteristics for these patients as well. So, they’ve been through additional lines, and we’re still seeing some at least some tumor regression in these patients. So, you have to wonder, is it a function of having prior cabo exposure? Is it a function of having, their disease hit in so many different ways by multiple different lines of therapy? Tough to interpret at this point, but we hope to gain additional data so that we can answer that question a little bit more clearly.

And that is will be part of our plans for our next phases of development.

Operator: Thank you. And I show our next question comes from the line of Lee Watsak from Cantor Fitzgerald. Please go ahead.

Lee Watsak, Cantor Fitzgerald: Hey, guys. Thanks for taking our questions. Very interesting data. I wonder if you can just comment on neutropenia, whether you have seen any Fabryo neutropenia and whether this impact the dosing intensity of cabo and maybe just more information on the dose modifications in the trial?

Glenn Hanna, Director of the Center for Cancer Therapeutic Innovation, Medical Oncologist, Dana Farber Cancer Institute, Harvard Medical School: Molly? I would say, I do recall, I mean, can just speak to this more broadly, but there is the element of anemia that’s a little more focused generally in FTI mechanism and then some concern that neutropenia may play in as well. From my recollection of the RCC data, we didn’t see any synergistic concerns around cytopenias or cytotoxicity issues that cause dosing problems. And I’ll again turn to the point that we’ve been able to escalate to the sixty milligram dose of cabo in combination with DARLI, which speaks to the fact that neutropenia hasn’t been a significant issue. We haven’t had to turn to growth factor support or long periods of interruption.

So I can at least say that from the combo. Yes.

Molly Leone, Chief Medical Officer, Kura Oncology: And I fully agree. We’ve seen limited dose reductions in the cabo. I do not think we’ve actually seen dose reductions in this particular combination in the two thousand eight hundred and six as of yet. But overall, I’d say you’re really just seeing non cumulative tox.

Operator: Thank you. And I show our next question in the queue comes from the line of Phil Nadeau from TD Cowen. Please go ahead.

Phil Nadeau, TD Cowen: Good afternoon. Thanks for taking our question and congrats from us also on the data. Can you discuss in a bit more detail the design of the Phase 1b of 2806 in cabo? And in particular what cabo patients will you be recruiting to the study? Will they be mostly cabo naive, cabo experienced or a mix of the two?

Thanks.

Troy Wilson, President and CEO, Kura Oncology: Holly, you want to take that?

Molly Leone, Chief Medical Officer, Kura Oncology: Sure. We haven’t really released the details yet. But suffice it to say, this is going to be a very robust Phase Ib so that it allows us to not only select the dose that we think is probably best for this combination, but also to evaluate even more some of these potentials to resensitize patients to cabo. We’re going to more than likely focus on the sixty milligram cabo dose, which means that we’re going to see less patients or no patients that have seen higher cabos in their treatment paradigm. But we’ll be getting more data out on that as the time comes closer.

Operator: Thank you. And I show our next question comes from the line of Jason Zemanski from Bank of America. Please go ahead.

Jason Zemanski, Bank of America: Afternoon. Congrats on the data and thanks so much for taking our question. I just wanted to hone back to the waterfall plot for the 2,806 cabo combination. I appreciate it’s still somewhat early, but it looks like the majority of responses here are from the five milligram dose and appreciating still dose escalating here. But curious, does that sort of imply that there’s a saturation point on what you can get from an FTI in this case?

Or do you think if you could increase the dose meaningfully, you could see more responses? Thanks.

Troy Wilson, President and CEO, Kura Oncology: Marlene, you want to take that?

Molly Leone, Chief Medical Officer, Kura Oncology: We certainly see a linear dose response curve for the PK. And we’re still evaluating. Like I said, the eight milligrams, especially at the sixty plus 60 is still ongoing. So let’s give it a little more time for these data to mature so we can really understand what the sixty milligram efficacy looks like. We understand what the sixty milligram safety looks like, and it doesn’t look prohibitive for the dosing of these patients.

But let’s see what the efficacy turns out as we continue to fill these cohorts.

Operator: Thank you. And I show our next question comes from the line of Roger Song from Jefferies. Please go ahead.

Troy Wilson, President and CEO, Kura Oncology0: Great. Congrats for the data and thank you for taking my questions. So maybe just a clarification. In terms of the sixty milligram cabo combo cohort, since you are nearing more cabo naive patients, I think, Marty, you mentioned earlier, if you pick the sixty milligram, you’re more than likely going to focus on the carbon naive. Just want to confirm that moving forward for the Phase 1b and then the future development, you’re focusing on the carbon naive patients.

Thank you.

Molly Leone, Chief Medical Officer, Kura Oncology: Absolutely. We obviously haven’t absolutely finalized the protocol. But yes, you’re correct that we would probably be focusing on the cabo naive. So earlier stage patients, cabo naive patients.

Operator: Thank you. And I show our next question comes from the line of Peter Lawson from Barclays. Please go ahead.

Troy Wilson, President and CEO, Kura Oncology1: Great. Thanks so much for taking my questions and congrats on all the data. On the dose response relationship, to the combination with cabo, that do you kind of interpret that kind of flat as a kind of exposure? Is this just still kind of reflection of limited sample size?

Troy Wilson, President and CEO, Kura Oncology: Peter, I think your question relates to the 40 cabo with different doses of two thousand eight hundred and six, if I’m understanding

Eric, Mizuho: correctly. Thank

Troy Wilson, President and CEO, Kura Oncology1: you. And this kind of around thirty three percent.

Troy Wilson, President and CEO, Kura Oncology: I mean, I’ll just say it’s too small an N, I think to draw any kind of conclusion. Interestingly, each of those dose cohorts is better than what you would expect from even cabo monotherapy. As Molly said, we’re not probably going to spend a lot of time optimizing at a forty milligram dose. I think encouraging. But Molly, you should add your thoughts.

Molly Leone, Chief Medical Officer, Kura Oncology: No, that’s exactly right. We’re not going to spend too much time optimizing the forty milligrams. And when we refer to that twenty five to twenty eight percent response rate of cabo monotherapy, we’re referring to the sixty milligram dose. So the fact that we’re seeing these thirty three percent in previous cabo failures, it implies that things are certainly going in a better direction than one would expect for either therapy alone. Still think it’s small numbers, but we will continue to update the data.

Troy Wilson, President and CEO, Kura Oncology: Yes. Maybe I’ll just add before we prompt the next question. One of the things that gives us confidence again as we look across these different tumor types is, you know, this goes back to the way that Doctor. Hanna laid it out. Is TORC1 pathway reactivation the key mechanism of action.

And as you look at both the RCC data and the PIK3CA mutant data, and of course, you’re not seeing the KRAS data, but hopefully you will next year, that’s what gives us confidence that we’re on to something significant here. That we’ve known as the TORC1 is a validated clinical target, this may just be a much better way to inhibit its activity. I will say before we take the last question, if anyone else would like to ask another question, please get back in the queue. And we have time for just a few more questions. But, Dylan, over to you for the next questioner or two.

Operator: Thank you, sir. Thank you. And I show our next question in the queue comes from the line of David Dye from UBS. Please go ahead.

Troy Wilson, President and CEO, Kura Oncology2: Great. Hey, thanks for taking my questions and congrats on the data. So for the cabo combo, we did see pretty good safety with no overlap in toxicity, but we did see slightly higher levels of diarrhea at sixty milligrams cabo dose. So maybe a question for Doctor. Hanna.

From a clinician’s point of view, what do you think about the rate of diarrhea in this combo? And how do you actually manage them?

Glenn Hanna, Director of the Center for Cancer Therapeutic Innovation, Medical Oncologist, Dana Farber Cancer Institute, Harvard Medical School: Yes. I mean, I think as Molly sort of or Doctor. Leon, he alluded, we’re not seeing an uptick in these types of side effects. It’s on par with what you would expect. We don’t generally see a lot of GI toxicity by partnering with darlafarnib.

So whatever we are seeing in the RCC cohort at 60, which is small numbers at present is going to from the cabo alone, just given its mechanism of action. But because these drugs have been around for some time, these are generally manageable and predictable side effects. You would give someone Imodium or Lamodil, encourage them to take magnesium and hydrate. So I can’t say that having seen the data that I’ve been to date that there’s been any concern that there’s enhanced GI tox. That has not been my observation.

Molly Leone, Chief Medical Officer, Kura Oncology: And just to keep in mind, a lot of this a lot of the data you’re seeing is from the dose limiting toxicity period, where you don’t necessarily prophylactically treat for a lot of these things that we would be able to treat for in normal life or in later lines of our development program. So, think that there’s a lot of room for improvement in how we approach pretreating and prophylactically treating these patients once we’re through this particular phase.

Operator: Thank you. And I share our next question in the queue comes from the line of Jonathan Chang from Leerink Partners. Please go ahead.

Jonathan Chang, Leerink Partners: Hi, guys. Thanks for taking the follow-up. Maybe for Doctor. Hanna, how would you compare your experience with darlifarnib versus tipifarnib? I know it’s not apples to apples here given the differences in the settings, but it would be great to hear your thoughts here.

Thank you.

Glenn Hanna, Director of the Center for Cancer Therapeutic Innovation, Medical Oncologist, Dana Farber Cancer Institute, Harvard Medical School: Yes, there’s I think I highlighted in the earlier presentation of the escalation monotherapy data that they’re both very well tolerated molecules. I think the properties that were outlined by Troy initially and then the preclinical work and now in patient dosing exhibits that very nice activity level at low a broad therapeutic range, but at low dosing levels and allows for a more predictable PK profile in PD that give us a once daily dosing option. So I think that’s very important. I think another point to make is that in our experience with salivary gland cancer where we’re seeing some patients as I showed you with durable and impressive partial response rates. I actually put together the tipifarnib salivary cancer population data a number of years ago and we weren’t actually seeing, I think there was only one short lived PR in that cohort.

So we’re seeing more evidence of antitumor activity in comparable diseases with the darlifarnib sort of more modern STI. So I think for that reason, it’s starting to become appealing as sort of the preferred agent, not just a ME2.

Operator: Thank you. I’m showing no further questions in the queue at this time. This concludes our Q and A. At this time, I’d like to hand the conference back over to Troy Wilson, President and CEO for closing remarks.

Troy Wilson, President and CEO, Kura Oncology: Thank you, Dulam. I want to thank in particular Doctor. Hanna for being generous with his time and his experience. He’s been an incredibly valued partner, from the very first days of our FTI program and we’re at an exciting inflection point. I want to thank all of you for your attention and your questions.

Glad we were able to get at least one question from everyone. We will be available for follow-up. If people would like, you can contact Greg or me. And we’ll look forward to talking to you next time, at least at our next earnings call, which is for early November. But we appreciate it.

We hope everyone has a very productive and successful ESMO. And with that, we’ll conclude the call. Thanks very much.

Operator: Thank you. This concludes today’s conference call. Thank you for participating. You may now

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