Cardiff Oncology, Inc. Price & Performance (CRDF)

Well, thank you, Kiki, and good afternoon, everyone. And thank you for joining our business update conference call. The fourth quarter of twenty twenty four was significant for Cardiff Oncology. On December 10, we released an initial cut of data in first line RAS mutated metastatic colorectal cancer, or MCRC, which we believe was highly encouraging and served as a basis for us to successfully complete a $40,000,000 capital raise. On today's call, we address four topics. First, will briefly review the data we previously released from our lead program in MCRC and then provide an update on Cardiff four in registrational plans for Advansertib. Second, we'll discuss our intellectual property strategy including the advances made in 2024 what we expect for 2025. Third, we will share highlights from two preclinical posters we presented at the San Antonio Breast Cancer Symposium in December. And finally, we'll discuss our financial position that we disclosed today in our Form 10 ks [indiscernible] I begin with a review of the previously disclosed data from Cardiff. Which is our ongoing randomized Phase two trial in first line RAS mutant MCRC evaluating two dose levels of unvansertib combined with current standard of care regimens [indiscernible] plus bevacuimumab or BEV versus standard of care alone.

In December, we released an initial dataset as of 11/26/2024 for the first 30 patients on the trial. Overall, we were pleased with the efficacy signal observed in the trial. First, as of the data cutoff date, patients on the thirty mg dose of unvansertib demonstrate a sixty four percent ORR compared to a thirty three percent ORR in the control arm. Second, the thirty mg arm demonstrated deeper tumor responses than the other arms. Specifically the five deepest tumor regressions seen across the entire trial, are in patients receiving the thirty mg dose of unvansertib. Based on the data released, we believe this correlation and the magnitude of therapeutic effect serves as an initial signal that ombansertib is a biologically active drug candidate for the treatment of NCRC. Finally, I would like to highlight on Vansertip's favorable safety profile. Which is an important differentiating factor over previous PLK1 inhibitors that have failed in the clinic due to toxicity concerns. Over three eighty patients have been dosed with ombansertib across multiple clinical trials to date. And the treatment has been well tolerated. For the full Cardiff T-four clinical trial results from the initial data cut, please refer to our corporate presentation or the investor call from December 10, posted on our Investor Relations website.

We continue to expect to release additional clinical data from the CARDOV-four trial in the first half of twenty twenty five. Next, I will share the current status of our MCRC program as it pertains to enrollment, and our registrational strategy. First, regarding enrollment, in December, we mentioned that we expected to complete enrollment of the 90 of valuable patients planned in the CARDOV-four trial in early twenty twenty five. Today, I can share that this week, we closed the trial to new patients entering screening we anticipate complete enrollment of the trial Secondly, there is an important FDA approval and Q4 twenty twenty four from another company that validates our registrational strategy, for the approval of onvansertib and MCRC. Specifically, Pfizer announced the results from a MIST Breakwater trial evaluating its drug, encorafenib, In first line mCRC patients with a BRAF mutation, And to be clear, this is a totally separate patient population from our RASK mutated MCRC focus. Pfizer's Breakwater trial achieved accelerated approval using ORR from a subset of patients at an interim time point. And subsequently achieved a statistically significant and clinically meaningful improvement in progression free survival, which is their endpoint for full approval, The regulatory pathway used by Pfizer to pursue accelerated full approval for encorofenib from a single trial is the same as our registrational plans agreed with FDA for Advansertip.

And therefore reinforces the validity of our strategy. I now move on to our second agenda, topic, our intellectual property strategy. In Q4 twenty twenty four, we strengthened our intellectual property portfolio for INVANSERTIV with the issuance of a new patent. The claims cover the method of using Envansertib in combination with BEH for the treatment of KRAS mutated MCRC patients, who have not previously been treated with BEV. The patent aligns with the target patient population of our lead MCRC program and has an expected expiration date of no earlier than 02/1943. We believe the new patent underscores the groundbreaking nature of our discovery demonstrate on Vansertip's powerful synergy with BEV in inhibiting angiogenesis. We continue to explore new opportunities to convert the novel discoveries we have made regarding the role of TLK1 inhibition into new intellectual property, and you could expect to hear more on these efforts later this year. Now I will move to the third item of our agenda, In December, we presented two poster presentations at the San Antonio Breast Cancer Symposium reporting preclinical data from our breast cancer program.

Objective of the first poster was to evaluate on Vansertib in combination with paclitaxel as a potential therapeutic strategy for hormone receptor positive, or HR positive, breast cancer patients after progression on endocrine therapy and CDK4six inhibitors. In vitro, onvansertib demonstrated synergistic activity with paclitaxel in HR positive breast cancer cell lines. In vivo, the combination exhibited robust antitumor activity in eight models resistant to first line therapies. The second poster evaluated the combination of onvansertib and in HER2 in drug resistant HR positive breast cancer PDX models. The combination of ombansertib plus in HER2 was well tolerated overcame inherto resistance, and displayed enhanced antitumor activity compared to each monotherapy. Overall, the combination of ANHERTU with unvansertib represents a promising therapeutic strategy for HR positive breast cancer patients resistant to first line therapies. We believe these posters highlight the broad potential of ONVANSERTIG. Some of which we are currently evaluating through our investigator initiated trials. For our last agenda item, I will turn the call over to Jamie, to talk about our fourth quarter Thank you, Mark. Earlier today, we issued a press release and filed a Form 10 ks with the SEC, which contain our financial results for the full year ending 12/31/2024.

Turning to our balance sheet. Cash and short term investments as of 12/31/2024 totaled $91,700,000 which includes the net proceeds of the $40,000,000 capital raise we successfully completed in December. With new and existing healthcare dedicated institutional investors. Our cash used in operating activities was $10,300,000 in Q4 twenty twenty four, which is in line with our typical quarterly cash burn. Based on the cash spend forecasted for our ongoing clinical programs, we believe that our current cash resources provide us with runway into the first quarter of twenty twenty seven. Finally, I'd like to point out that today we also filed a shelf registration statement on Form S-three which replaces our previous shelf that was due to expire in April of this year. It has always been our practice to maintain an active shelf registration statement and for clarity, the S3 we filed today did not involve the issuance of any shares. With that, I'll turn the call back over to Mark.

Thank you, Jamie. As you could hear from our remarks today, we are highly encouraged by the efficacy results the CARDINAL-four Cardiff. And we that we shared in December and we look forward to sharing additional updates from the trial in the first half of this year. With that, I would like to take a moment to thank the clinical investigators and importantly the patients and their families whose participation in the trial is enabling our clinical development efforts We continue to believe that onvansertib has the potential to change the treatment paradigm for the large number of patients who are diagnosed with RAS mutated MCRC each year. With that, I will now open the call up for questions. Operator?

Great. Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you will need to press Our first question comes from Mark Frum with TD Cowen.

Hi, this is Alex on for Mark.

Thanks for taking my question. Can you give us any sense of when exactly in the first half that data update is coming and in what context? And then in that update, how many new patients do you expect will become a valuable for ORR and also how mature do you expect those PFS curves to be? Thank you.

Thanks, Alex, for that question. At this point in time, what our goal is is to really to our next update to to actually give a more mature and substantive update since the 30 patient update. So at this point, that's really what we have planned to do. When it comes to PFS, I think that this is probably [indiscernible] too early for PFS. Within the first half of this year. But that's something that obviously we will be updating beyond this half, this first half. Great.

Thank you.

Our next question comes from Joe Catanzaro at Piper Sandler. Your line is now open.

Great. Hey, everybody. Thanks for real estate. Thanks for taking my questions. Maybe a couple from me here. Can you just sort of speak to your thoughts around when you will make the dose selection decision And whether that will come together with your interactions with the FDA and converting four to potential registrational trial, just maybe walk through The cadence of those decision points and I have a follow-up. Thanks.

Thanks, Joe, for that question. Really our goal as you know this is the [indiscernible] based on Project Optimus And our goal really is to get in front of the FDA as soon as possible And there's really two topics that we will be talking to the FDA about.

First of course is the dose which is thirty versus twenty. And then the second really is the really finalizing the trial design for the registrational trial, the zero zero five. So I mean from our point of view, our goal is to get to the FDA as soon as possible. This may or may not be all 90 patients, could be less. Of course, it will depend on looking at that signal between with thirty and twenty. So I think that that's really where we are right now. And of course, after that meeting with the FDA, that will give us clarity and that will be the gate gating factor for going into the registrational five trial.

Okay, got it. So my follow-up relates to your comments, Mark, on the breakwater trial of the engorafenib Yes. Not terribly familiar with the data off the top of my head, here. So my question is whether the response rate delta that they have served in that trial that supported an accelerated approval aligns with what you've seen thus far in the four study?

Yes, certainly, Joe, great question. Certainly, it's consistent Their ORR was 61 versus 40. So I think that it's certainly consistent with what we have shown so far with the first 30 patients.

Okay, great. That's it. For me. Thanks for taking my questions. Thank you, Joe.

Appreciate it.

Thank you. Please standby for the next question.

Our next question comes from Andy Tsai at William Blair. Your line is now open.

Thanks for the update taking our questions. Two for me, if you don't mind. One is Really kind of your evolving thinking in terms of of the velocity of tumor size reduction. So basically looking at the December data, one of the most obvious observations is really that the slope of the control arm is relatively flat over time. And then it deepens, as you alluded to Mark, on the call, for the twenty milligram and thirty milligram. So I'm curious that if that data based on some of the prior CRC experience could derisk or inform how you think about [indiscernible] PFS and OS. So that's question number one.

Question number two has to do with also also breakwater. So in that trial, the patient number that's required for the accelerator approval was about 100 patients each arm. So I'm curious if that's kind of potentially form the framework of your upcoming discussion with the FDA in the context of of the accelerate approval pathway? Thank you. Thanks, Andy, for both of those questions. Going after that first one, clearly there has been data in CRC first line in previous trials showing that earlier responses and deeper responses have a correlation and are associated with greater PFS and OS. So that's something that is known. And I think moving on to the Breakwater well certainly, there are 110 per arm was what they went after for their interim. Certainly, we are looking at that. We will be, of course, talking to the FDA to finalize The specifics around our assumptions and our our trial design when we do meet with them. But certainly one point that you make Andy, which is a good one is that what Breakwater showed was a fewer patients are needed for the accelerated and of course the full approval. So thank you for both those questions.

Great. Thank you. Thank you.

Our next question comes from Robert Burns at H. C. Wainwright.

Hi guys. Thanks for taking my questions. And again, congrats on the amazing data that you reported late last year. Guess just one follow-up from me. So obviously, we know about the Codebreak-three zero one trial. And although KRASG TOLC is a minor component in colorectal cancer, I wanted to get your thoughts as to how you view that agent, especially also the pan RAS agents that are also being developed in the space Great, Robert. Thanks for both those questions. The G12C inhibitors, as you mentioned, There is an approval of the Amgen's drug last year but that was really in second line and that of course is just with G12 which you know is a very small sliver of the KRAS and RAS mutated patients. It's about makes up about four percent of RAS mutated patients So I think that from what we look at there, it's really, it's not really too doesn't really impact what we're doing in first line since they are in second a G12C mutations patients with those mutations within our trials. So that's the with the RevMed, the G12x program, clearly, the signal is in the non small cell as well as pancreatic or the PDAC.

And so we don't see as much activity with their agents or for what they've reported in the colorectal. But we certainly are keeping an eye on their progress and what they're doing. This space.

Awesome. Thanks for taking my questions and congrats again.

Thank you, Robert.

Thank you. Please standby for the next question. The next question comes from Albert Lowe with Craig Hallum. Your line is now open.

Hi, everyone. Thanks for taking my question. I was just wondering it's great to see the enrollment is going to complete over the next few weeks here. So do you think we'll be able to see all of the 90 patients included in this first half update?

Yes, Albert, thank you for that question. Yes, we are very pleased and excited that we're really within a couple of weeks of finishing the enrollment We did have 60 patients dose by in December when we reported out the 30 patients who would chat at least one post baseline scan. And so we continue Obviously, we'll be continuing to treat these patients and our goal really for this first half and reporting out the next update is really to make sure as a a substantive and really more mature update from the trial. So we leave it at that at this point. Okay, I see. Thank you. Thanks, Albert.

Please standby while we compile the Q and A roster. All right. I'm showing no other questions at this time. So this will conclude the question and answer session. I would now like to turn it back to Mark for closing remarks.

Thank you, operator, and thank you all again for everyone here for joining us this afternoon for this call. [indiscernible]