Cardiff Oncology - Earnings Call - Q4 2024

Executive Summary

• Robust interim efficacy signal in first‑line RAS‑mutated mCRC: 64% ORR at the 30mg onvansertib dose vs 33% control; clear dose‑response and deeper tumor regressions supported the December financing and registrational plans.
• Strengthened balance sheet and runway: $91.7M cash + short‑term investments at 12/31/24 and runway projected into Q1 2027; oversubscribed $40M offering priced at $2.60 per share in December.
• Q4 operating cash burn ~$10.3M, consistent with typical quarterly burn; full‑year net cash used in operations rose to $37.7M from $30.9M YoY.
• Near‑term catalyst: additional CRDF‑004 clinical data (more mature ORR dataset) planned in 1H 2025; PFS readout expected later (too early in 1H).
• Regulatory pathway confidence: Management cites Pfizer’s BREAKWATER as validation for an ORR‑based accelerated approval followed by PFS for full approval; CRDF’s observed ORR delta aligns with that precedent.

What Went Well and What Went Wrong

What Went Well

• Efficacy signal and dose‑response: “Patients on the 30mg onvansertib dose arm demonstrated a 64% response rate, compared to a 33% response rate in the control arm… deeper tumor regression compared to the 20mg dose”.
• Operational progress: Trial closed to new screening with enrollment completion expected within weeks; ~60 patients had been dosed by December, setting up a more mature update in 1H 2025.
• Capital and IP: $40M oversubscribed financing and issuance of a new patent (expected expiry ≥2043) covering bev‑naïve KRAS‑mut mCRC treated with onvansertib + bevacizumab.

What Went Wrong

• Elevated cash usage: FY24 net cash used in operating activities increased to ~$37.7M from ~$30.9M in FY23, reflecting higher clinical spend and staffing.
• Net loss widened: FY24 net loss of $45.4M vs $41.4M in FY23; quarterly royalty revenue remains de minimis (Q4 ~$0.151M).
• PFS timing pushed: Management indicated PFS curves will be too immature for 1H 2025; investors must wait for durability endpoints beyond the near‑term ORR update.

Transcript

Operator (participant)

Welcome to the Cardiff Oncology Fourth Quarter 2024 Financial Results and Business Update Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone, and you will then hear an automated message advising your hand is raised. Please be advised that today's conference is being recorded. I would now like to turn the conference call over to Kiki Patel of Gilmartin Group. My reading. Please go ahead.

Kiki Patel (Managing Director)

Thank you, Operator. Joining us on the call today from Cardiff Oncology are Chief Executive Officer Mark Erlander and Chief Financial Officer Jamie Levine. During the conference call, management will make forward-looking statements, including without limitation, statements related to guidance, results, and timing of data readouts for Onvansertib clinical trials. These forward-looking statements are based on the company's current expectations and inherently involve significant risks and uncertainties. Our actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties. Factors that could cause results to be different from these statements include factors the company describes in the section titled Risk Factors in its annual report on Form 10-K filed with the SEC for the year ended December 31, 2024.

Cardiff Oncology undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events, or changes in its expectations. With that, I turn the call over to Chief Executive Officer Mark Erlander. Mark.

Mark Erlander (CEO)

Thank you, Kiki, and good afternoon, everyone, and thank you for joining our Business Update Conference Call. The fourth quarter of 2024 was significant for Cardiff Oncology. On December 10th, we released an initial cut of data from our ongoing Cardiff 004 trial 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 million capital raise. On today's call, we address four topics. First, we will briefly review the data we previously released from our lead program in mCRC, and then provide an update on Cardiff 004 enrollment activity and our registrational plans for Onvansertib. Second, we'll discuss our intellectual property strategy, including the advances made in 2024 and 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. Finally, we'll discuss our financial position that we disclosed today in our Form 10-K filing. I begin with a review of the previously disclosed data from Cardiff 004, which is our ongoing randomized Phase II trial in first-line RAS mutant mCRC, evaluating two dose levels of Onvansertib combined with current standard of care regimens, FOLFIRI or FOLFOX, plus bevacizumab or BEV versus standard of care alone. In December, we released an initial data set as of November 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 30 mg dose of Onvansertib demonstrated a 64% ORR compared to a 33% ORR in the control arm.

Second, the 30 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 30 mg dose of Onvansertib. Based on the data released, we believe this correlation between the dose of Onvansertib and the magnitude of therapeutic effect serves as an initial signal that Onvansertib is a biologically active drug candidate for the treatment of mCRC. Finally, I would like to highlight Onvansertib'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 380 patients have been dosed with Onvansertib across multiple clinical trials to date, and the treatment has been well tolerated.

For the full Cardiff 004 clinical trial results from the initial data cut, please refer to our corporate presentation or the investor call from December 10th posted on our investor relations website. We continue to expect to release additional clinical data from the Cardiff 004 trial in the first half of 2025. 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 evaluable patients planned in the Cardiff 004 trial in early 2025. Today, I can share that this week we closed the trial to new patients entering screening. We anticipate complete enrollment in the trial in the next few weeks.

Secondly, there is an important FDA approval in Q4 2024 from another company that validates our registrational strategy for the approval of Onvansertib in mCRC. Specifically, Pfizer announced the results from its Breakwater trial evaluating its drug encorafenib in first-line mCRC patients with a BRAF mutation. To be clear, this is a totally separate patient population from our RAS-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 encorafenib from a single trial is the same as our registrational plans agreed with FDA for Onvansertib and therefore reinforces the validity of our strategy.

I now move on to our second agenda topic, our intellectual property strategy. In Q4 2024, we strengthened our intellectual property portfolio for Onvansertib with the issuance of a new patent. The claims cover the method of using Onvansertib in combination with BEV 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 2043. We believe the new patent underscores the groundbreaking nature of our discovery, demonstrating Onvansertib'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 PLK1 inhibition into new intellectual property, and you can 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. The objective of the first poster was to evaluate Onvansertib 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 CDK4/6 inhibitors. In vitro, Onvansertib demonstrated synergistic activity with paclitaxel in HR positive breast cancer cell lines. In vivo, the combination exhibited robust anti-tumor activity in eight patient-derived xenograft or PDX models resistant to first-line therapies. The second poster evaluated the combination of Onvansertib and Neratinib in drug-resistant HR positive breast cancer PDX models. The combination of Onvansertib plus Neratinib was well tolerated, overcame Neratinib resistance, and displayed enhanced anti-tumor activity compared to each monotherapy.

Overall, the combination of Neratinib with Onvansertib 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 Onvansertib, 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 financials. Jamie.

Jamie Levine (CFO)

Thank you, Mark. Earlier today, we issued a press release and filed a Form 10-K with the SEC, which contained our financial results for the full year ending December 31, 2024. Turning to our balance sheet, cash and short-term investments as of December 31, 2024, totaled $91.7 million, which includes the net proceeds of the $40 million capital raise we successfully completed in December with new and existing healthcare-dedicated institutional investors. Our cash used in operating activities was $10.3 million in Q4 2024, 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 2027.

Finally, I'd like to point out that today we also filed a shelf registration statement on Form S-3, 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. For clarity, the S-3 we filed today did not involve the issuance of any shares. With that, I'll turn the call back over to Mark.

Mark Erlander (CEO)

Thank you, Jamie. As you could hear from our remarks today, we are highly encouraged by the efficacy results from the Cardiff 004 trial 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.

Operator (participant)

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 star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from Marc Fromm with TD Cowen. Your line is now open.

Alex Sakhno (Director of Private Capital Markets)

Hi, this is Alex Sakhno from Marc. 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? In that update, how many new patients do you expect will become available for ORR? Also, how mature do you expect those PFS curves to be? Thank you.

Mark Erlander (CEO)

Oh, thanks, Alex, for that question. You know, at this point in time, what our goal is, is to really to our next update 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, you know, this is probably early, too early for PFS within the first half of this year. But that's something that obviously we will be updating, you know, beyond this half, this first half.

Alex Sakhno (Director of Private Capital Markets)

Great. Thank you.

Operator (participant)

Please stand by for the next question. Our next question comes from Joe Catanzaro at Piper Sandler. Your line is now open.

Joe Catanzaro (Director and Senior Biotech Equity Analyst)

Great. Hey, everybody. Thanks for the update. Thanks for taking my questions. Maybe a couple for 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 004 to a potential registrational trial? Just maybe walk through sort of the cadence of those decision points and I have a follow-up. Thanks.

Mark Erlander (CEO)

Oh, thanks. Thanks, Joe, for that question. You know, really, our goal, as you know, this is the Cardiff 004 is based on Project Optimus. Our goal really is to get in front of the FDA as soon as possible. There are really two topics that we will be talking to the FDA about. The first, of course, is the dose, which is, you know, 30 versus 20. The second really is finalizing the trial design for the registrational trial, the 005. 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. It could be less. Of course, it'll depend on, you know, looking at that signal between with the 30 and 20. I think that that's really where we are right now.

Of course, after that meeting with the FDA, that will give us clarity and that will be the gating factor for going into the registrational 005 trial.

Joe Catanzaro (Director and Senior Biotech Equity Analyst)

Okay. Got it. My follow-up relates to your comments, Mark, on the Breakwater trial of Encorafenib.

Mark Erlander (CEO)

Yes.

Joe Catanzaro (Director and Senior Biotech Equity Analyst)

Not terribly familiar with the data off the top of my head here. My question is whether the response rate delta that they observed in that trial that supported an accelerated approval aligns with what you've seen thus far in the 004 study.

Mark Erlander (CEO)

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

Joe Catanzaro (Director and Senior Biotech Equity Analyst)

Okay. Great. That's it for me. Thanks for taking my question.

Mark Erlander (CEO)

Thank you, Joe. Appreciate it.

Operator (participant)

Thank you. Please stand by for the next question. Our next question comes from Andy Hsieh at William Blair. Your line is now open.

Andy Hsieh (Biotech Analyst)

Thanks for the update and taking our questions. Two for me, if you don't mind. One is really kind of your evolving thinking in terms of the velocity of tumor size reduction. Basically looking at the December data, you know, 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 20 mg and 30 mg. I'm curious if that data, based on some of the prior CRC experience, could de-risk or inform how you think about endpoints, approval endpoints such as PFS and OS. That's question number one. Question number two has to do with also Breakwater. In that trial, the patient number that's required for the accelerated approval was about 100 patients each arm.

I'm curious if that's kind of that could potentially form the framework of your upcoming discussion with the FDA, you know, in the context of the accelerated approval pathway. Thank you.

Mark Erlander (CEO)

Thanks, Andy, for both of those questions. Yeah, you know, 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. That is something that is known. I think moving on to the Breakwater, certainly, you know, their 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 trial design when we do meet with them. Certainly, one point that you make, Andy, which is a good one, is that, you know, what Breakwater showed was that fewer patients are needed for the accelerated and, of course, the full approval. Thank you for both those questions.

Andy Hsieh (Biotech Analyst)

Great. Thank you.

Mark Erlander (CEO)

Thank you.

Operator (participant)

Please stand by for the next question. Our next question comes from Robert Burns at H.C. Wainwright. Your line is now open.

Robert Burns (Managing Director and Biotech Equity Research Analyst)

Hi guys. Thanks for taking my questions. Again, congrats on the amazing data that you reported late last year. I guess just one follow-up from me. Obviously, we know about the CodeBreak 301 trial. Although, you know, KRAS G12C 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.

Mark Erlander (CEO)

Great, Robert. Thanks for both those questions. You know, the G12C inhibitors, as you mentioned, there is an approval of the Amgen drug last year, but that was really in second line. That, of course, is just with G12C, which you know is a very small sliver of the KRAS and RAS-mutated patients. It makes up about 4% of RAS-mutated patients. I think that, you know, from what we look at there, it's really not really too, it doesn't really impact what we're doing in first line since they are in second line and it's such a small. You know, we also do have G12C mutations, patients with those mutations within our trials. That's the, you know, with the RevMed, the G12X program, clearly, you know, their signal is in the non-small cell as well as the pancreatic or the PDAC.

We do not see as much activity with their agents for what they have reported in the colorectal. We certainly are keeping an eye on their progress and what they are doing in this space.

Robert Burns (Managing Director and Biotech Equity Research Analyst)

Awesome. Thanks for taking my questions and congrats again.

Mark Erlander (CEO)

Thank you, Robert.

Operator (participant)

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

Albert Lowe (Senior Biotech Equity Research Analyst)

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

Mark Erlander (CEO)

Yeah. Albert, thank you for that question. You know, yes, we are very pleased and excited that, you know, we're really within a couple of weeks of finishing the enrollment. We did have, you know, 60 patients dosed by in December when we reported out the 30 patients who had, you know, at least one post-baseline scan. You know, we continue to, you know, obviously, we'll be continuing to treat these patients. You know, our goal really for this first half in reporting out the next update is really to make sure it's a substantive and really more mature update from the trial. We leave it at that at this point.

Albert Lowe (Senior Biotech Equity Research Analyst)

Okay. I see. Thank you.

Mark Erlander (CEO)

Thanks, Albert.

Operator (participant)

As a reminder, if anyone would like to ask an additional question, you will need to press star one one on your telephone and wait for your name to be announced. Please stand by while we compile the Q&A roster. All right. I'm showing no other questions at this time. This will conclude the question and answer session. I would now like to turn it back to Mark for closing remarks.

Mark Erlander (CEO)

Thank you, Operator. Thank you all again for everyone here for joining us this afternoon for this call.

Operator (participant)

Thank you for your participation in today's conference. This does conclude the program, and you may now disconnect.