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Jay Short

Thank you, Bruce, and thanks to everyone for joining us for our fourth quarter and full-year 2024 BioAtla earnings call. Additional details related to what we will share today are available in today's press release and our updated company presentation, which are available on our website.
Also, the posters which were recently presented at the Mayo Multidisciplinary Head and Neck Cancer Symposium and the European Lung Cancer Congress on our Phase 2 assets, ozuriftamab vedotin, or Oz-V; and mecbotamab vedotin, or Mec-V, respectively, are also available on our website.
I will begin with updates on our conditionally active biologic, or CAB platform clinical programs that we are advancing internally at BioAtla. All of these CAB-based programs are designed to efficiently increase the potency and safety of our therapeutic candidates, targeting solid tumors in areas of high unmet medical need.
Beginning with our first-in-class, dual conditionally binding CAB EpCAM and CAB CD3 bispecific T-cell engager antibody. EpCAM is an attractive therapeutic target because it is widely expressed in most solid tumors. However, it has been a difficult target to drug with traditional antibody technologies because it is also widely expressed in normal epithelial tissues.
EpCAM's ubiquitous expression in both tumors and normal tissues makes it generally undruggable without a differentiating technology like CABs. Successfully enabling the selective targeting of solid tumors with CAB technology offers the potential for developing one of the first pan-cancer therapies outside of immune checkpoint inhibitors.
Today, our dose escalation is progressing well. As hoped, the maximally tolerated dose has not yet been reached, and multiple patients are already experiencing tumor reduction, including one colorectal cancer patient with continued stable disease for more than one year.
At present, three patients have received the target dose of 100 micrograms weekly. Two of these three patients have already cleared the dose limiting toxicity period, and the third patient is on track to clear the DLT period on April 8. We are now also screening patients for the next cohorts who are anticipated to receive the target dose of 300 micrograms. Details about the dosing schematic can be found in our corporate deck.
It's worth noting that animal modeling data indicate that significant tumor reduction is expected to occur at target doses of approximately 200 micrograms and above. So we believe that we are reaching exposures where we will start observing formal objective responses.
We remain on track for a data readout of the dose escalation portion of the study in mid-2025. We also anticipate a data readout for the cohort expansion portion of the study in the first half of 2026.
CAB T-cell engager bispecifics represent a novel approach to harnessing the body's immune system to target and destroy cancer cells, offering the promise of more precise and effective treatment options for cancer patients.
We believe our dual CAB EpCAM and CAB CD32 T-cell engager has the potential to be at the forefront of this exciting and powerful approach and has the potential to treat a wide range of metastatic tumors, including cancers of the colon, lung, breast, pancreas, and prostate, among others.
Now moving on to CAB AXL-ADC Mec-V. Last quarter, we announced that we are observing ongoing anti-tumor activity with multiple confirmed responses among 21 evaluable patients with tumors expressing mKRAS across nine different KRAS mutations.
As part of today's update, we're excited to share promising results from the 1.8 mg per kg Q2W dosing cohort. From the 16 valuable patients in this cohort, we have observed multiple confirmed responses across different mKRAS variants, while also demonstrating an encouraging clinical benefit risk profile, as well as a patient who had a prior failure of sotorasib who experienced a partial response. In addition, a patient who achieved a complete response remains in complete response now for over two years.
Importantly, our initial findings for overall survival continue to be compelling as we are now seeing an exceptional overall survival with 66% and 58% of patients with mKRAS non-small cell lung cancer alive at a landmark of one year and two years respectively, which we believe exceeds what has been observed with the standard of care.
The median overall survival has not been reached at 35 months from the first dose, with continued follow-up ongoing. Mec-V is associated with a generally well-tolerated safety profile, both with and without nivolumab, and no new safety signals have been identified. Notably, the drug-related treatment discontinuation rate was only 7%. We are presenting these data at the European Lung Cancer Congress and encourage you to visit the poster on our website.
Based on our evaluation of patients with mutant KRAS non-small cell lung cancer, we continue to observe a high correlation of AXL and mKRAS expression and believe the mechanistic link between AXL and MK-RAS that drives tumor resistance, coupled with the exceptional overall survival that we are seeing in the Q2W dosing cohort, supports a potential anti-AXL pan mKRAS strategy.
Now, I'd like to pivot to the Phase 2 clinical programs that we are currently advancing toward corporate partnerships. Beginning with our CAB ROR2-ADC Oz-V, which is being evaluated as a monotherapy and treatment refractory head and neck cancer patients. Last quarter, we reported an emerging clinical profile in treatment refractory patients with a median of 3 prior lines of therapy, with the potential to become the standard of care in the second-line plus head and neck cancer population.
Additionally, we shared that we received a fast track designation and actionable guidance from the FDA on our proposed randomized pivotal trial design with Oz-V monotherapy versus investigators' choice among patients with recurrent or metastatic head and neck cancer with disease progression on or after platinum-based chemotherapy and PD1 antibody therapy.
As part of today's update, the fully enrolled Phase 2 study using Oz-V monotherapy continues to demonstrate new responses in treatment refractory, second-line plus head and neck cancer at the 1.8 mg per kg Q2W dosing regimen.
We also continue to capture efficacy data for several endpoints, including overall response rate, duration of response, progression free survival, and overall survival. A particular interest is that we have observed a compelling signal in patients with metastatic HPV positive head and neck cancer, who represent a high unmet need as they are poorly served by agents that inhibit EGFR.
These new data, as well as evolving data in the overall head and neck cancer cohort, were presented as a poster today at the Mayo Multidisciplinary Head and Neck Cancer Symposium.
To highlight, among the 11 patients with HPV positive head and neck cancer treated with 1.8 mgs per kg Q2W, there was 100% disease control rate, a 45% overall response rate, and so far a 27% confirmed response rate with a duration of response greater than 5.3 months that is ongoing.
Multiple patients remain on treatment and have the potential to have responses that deepen with time. It is noteworthy that an HPV positive patient achieved a complete response that continues in complete remission, now at greater than 16 months and ongoing. We believe Oz-V, especially at the 1.8 mgs per kg Q2W dose, has been remarkably well tolerated, and there are no new identified safety findings.
Further, these results of HPV positive head and neck cancer are mechanistically supported by recent literature showing that HPV associated oncogenes upregulate ROR2 expression, driving proliferation and invasiveness thus now providing a compelling rationale for also targeting ROR2 and cancers associated with human papillomavirus infection.
We believe our extended experience with Q2W dosing of Oz-V also has the potential to satisfy Project Optimus requirements, and we plan to share our results with the FDA to seek confirmation regarding our proposed recommended Phase 3 treatment regimen.
We are encouraged by the differentiated findings in second-line plus head and neck cancer patients, particularly in both HPV negative and HPV positive patients.
For partners, the second-line plus population represents a worldwide commercial opportunity of greater than $1 billion in peak sales, with upside opportunity in the first-line setting, as well as in other HPV positive cancers.
Moving now to our CAB CTLA4 antibody evalstotug. Evalstotug is similar to [EP] with respect to epitope, affinity, and half-life, but differs from [EP] with respect to its ability to avoid binding in the normal tissue environment.
As part of today's update, we have dosed a total of 12 patients with unresectable and/or metastatic melanoma, 8 of whom received 5 mgs per kg; 3 were dose escalated to 10 mgs per kg; and 1 dose escalated all the way to 14.3 mgs per kg. While we continue to observe compelling anti-tumor activity with a differentiated safety profile, 10 of the 11 evaluable patients showed tumor reduction, and with the 11 showing no growth to date. Of these 11 valuable patients with unresectable and/or metastatic melanoma treated with evalstotug in combination with the PD1 antibody, so far, we observed across multiple doses an overall response rate of 64% and disease control rate of 100%.
Notably, we observe a partial response in a patient with acral subungual or under the fingernail melanoma, which is a rare and difficult to treat form of melanoma that generally has a poorer prognosis than cutaneous melanoma.
The safety profile of evalstotug continues to be differentiated with a relatively low incidence and severity of immune-mediated AEs, particularly among patients who receive 5 mgs per kg for less than or equal to 18 weeks in a total of 17 patients. Focusing on these 17 patients, we observed 18% grade 3 immune-mediated adverse events and no grade 4 events, while maintaining strong efficacy. The safety profile compares favorably to ipilimumab with a reported rate of 40%, grade 3 and 4 immune mediated adverse events.
We believe evalstotug has demonstrated a differentiated clinical profile relative to other CTLA4 antibodies, and has the potential to be best in class. As such, we have recently initiated partnering discussions with the intent to align with a partner that can maximize the value of this asset.
Onto our ongoing clinical communications. I am pleased to report our progress with the medical and scientific communities, as acknowledged with numerous publications and presentations at prestigious conferences, including the European Lung Cancer Congress, Mayo Multidisciplinary Head and Neck Symposium, and the American Society of Clinical Oncology.
Finally, for our corporate updates, BioAtla is further extending our runway beyond key clinical readouts in the first half of 2026 by streamlining and realigning resources, which includes a workforce reduction of over 30%.
We estimate that we will incur approximately $0.6 million of one-time cash payments related to the workforce reduction, which will mostly be paid in the second quarter. We intend to retain all employees essential for advancing our two internal priority programs, as well as supporting partnering of other clinical assets, which are improving with the ongoing data readouts.
I also wish to express my deep appreciation and respect to our employees, both past and present, who have contributed so much with their creativity and hard work to advance these important cures for patients.
With that, I would now like to turn the call over to Rick to review the fourth quarter and full-year 2024 financials. Rick?

Richard Waldron

Thank you, Jay. Research and development, that is R&D expenses, were $11.6 million for the quarter ended December 31, 2024 compared to $22.7 million for the same quarter in 2023. The decrease of $11.1 million was due to lower clinical development expenses in 2024 from the lower overall targeted enrollment across our clinical trials in 2024, resulting from our program prioritization in 2023.
We expect our R&D expenses to continue to decrease overall in the first half of 2025 due to our recent restructuring and as we complete Phase 2 trials for several indications and focus our ongoing development on our prioritized programs.
General and administrative expenses were $4.6 million for the quarter ended December 31, 2024 compared to $5.9 million for the same quarter in 2023. The $1.3 million decrease was primarily due to lower stock-based compensation, personnel-related costs, and D&O insurance premiums.
Net loss for the quarter ended December 31, 2024, was $14.9 million compared to a net loss of $26.9 million for the same quarter in 2023. Net cash used in operating activities for the full year ended December 31, 2024, was $72 million compared to net cash used in operating activities of $104 million for the same period in 2023.
Cash used for the quarter ended December 31, 2024, was $7.5 million. Cash and cash equivalents as of December 31, 2024, were $49 million compared to $111.5 million as of December 31, 2023.
Excluding any potential future milestones, we believe that cost reductions to be subsequently realized from the realignment of resources and focus on our two internal priority programs further extends our runway beyond key clinical readouts in the first half of 2026.
And now back to Jay.

Jay Short

Thank you, Rick.
We are encouraged by the clinical outcomes observed from our evolving CAB program data sets, which continue to be differentiated in some of the most challenging solid tumor types. As a result, we continue to advance multiple discussions with potential collaborators on our Phase 2 assets as well as initiate new ones. We believe the compelling results we are obtaining will serve as important catalysts, including our EpCAM T-cell engager program and have the potential to be transformative for our patients and shareholders alike.
Thank you for your attention and continued support. With that, we will turn it back to the operator to take your questions.

Question and Answer Session

Operator

(Operator Instructions) Jeet Mukherjee, BTIG.

Jeet Mukherjee

Great. So just in terms of the partnered programs, I noticed in the corporate deck, you had mentioned the ROR2 program is in the process of partnering while CTLA-4 is initiating partnering. Could you perhaps just give a bit more color on where you are in these discussions and what's perhaps needed to get one or both across the finish line? Thank you.

Jay Short

This is Jay. We have both advanced discussions and newer discussions. This HPV positive data is pretty new to most of the people we're in discussions with, except for just a small number. So we also expect additional interest that prior to this report. So we're pretty encouraged with the discussions that are underway.
And so I think it covers a range, and I'm expecting some new participants to get involved as well because I think this has been a significant problem in the treatment of head and neck cancer is being able to add in effective treatments in these refractory HPV-positive patients.

Jeet Mukherjee

Understood. And maybe if I could just ask a follow-up for the AXL program. I believe last time you were still analyzing some patient samples for both AXL and KRAS expression. So in your hands, what percentage of patients are double positive for mutant KRAS and AXL? And have any patients on the study to date been treated with a pan-RAS inhibitor?

Jay Short

I'll share some of this question with Eric. I'll just start off by saying in our immunohistochemical analysis, we saw a bit over 70% that were positive across all types of KRAS mutants. And I think the G12C was, I think, 100%. Also, we know that if you look at mRNA levels that it's much, much higher than even that. So it's a very strong correlation, keeping in mind that mRNA is likely to be more sensitive than immunohistochemical data.
But it's a very strong correlation. And further, there's a fundamental mechanistic alignment. If you refer to the corporate deck, you'll see that laid out there on slide 23 within that deck.
Eric, do you want to add anything to this?

Eric Sievers

Sure. Thank you, Jay, and thanks for the question, Jeet. On slide 24, we indicate that one of the patients had prior treatment with sotorasib, and they did experience a response. And we did not treat anyone with a known prior exposure to a pan-KRAS inhibitor, which was your question. Thank you.

Operator

Kelly Shi, Jefferies.

Hi, this is [Hanse] for Kelly. As the near-term data coming out with BA-31882, just curious what kind of data we're expecting? And have you reached a recommended Phase 2 dose? And what we're looking for in the next follow-up data and expansion portion of the study?

Jay Short

Eric, do you want to take that one?

Eric Sievers

Sure. Thank you, Kelly. I appreciate the question.
On slide 19 of our recently released corporate deck, we have the BA3182 dose escalation schema. So just to remind everyone, this is the EpCAM targeted T-cell engager where it's conditionally binding both on the EpCAM arm and the CD3 T-cell binding arm to really drive the therapeutic window even further to benefit.
This gives you a sense of the dose escalation. We've achieved cohorts A1, B1, and B2, and then we're moving up with a one-step priming dose and a two-step priming dose. We're doing that concurrently. And you can see there's schema for Cohorts C and B that are both enrolling concurrently. And you asked about the recommended Phase 2 dose.
We think we're in a zone where we're seeing meaningful tumor control. And as the animal model suggests that tumor reduction would occur right around 200 micrograms given weekly it's really consistent with that. So we're enthusiastic to be able to report more fully on this Phase 1 data set in the coming months.
I'll note that two of the three patients in Cohort C4, as you see on the slide, have already cleared the DLT observation window and the third patient will clear very shortly, as Jay just mentioned, in early April.

Operator

Reni Benjamin, Citizens.

Hi, this is Sam on for Reni. Just a quick one on 3182 as well. Are there any partnership ongoing partnership discussions ongoing for this asset? And if so, are these contingent upon the mid-'25 data?

Jay Short

Sheri, do you want to touch on that one?

Sheri Lydick

Sure, sure. Thanks for the question. We currently have had interest in this program. Our goal is to get through Phase 1 and also the expansion cohorts so that we have a data set that can really drive a lot of value for this program. So while we've had interest, we're not at a point where we necessarily would engage in discussions until we have a look at what the dose escalation and expansion data look like.

Operator

(Operator Instructions) Tony Butler, Rodman & Renshaw.

Tony Butler

Eric, one question on the HPV-positive patients for the head and neck cancer program. Were all of those patients that responded smokers that's actually somewhat important.
And second, Jay, you had mentioned a partnering program, but in the deck, again, it makes reference to moving toward discussions with mid-tier companies. And I just wonder why that strategy? Or is it, in fact, an argument such that the market opportunity may be somewhat smaller than a large pharma would engender and a mid-tier company would like very much?

Eric Sievers

Why don't I start with the last one, and then we'll go to the other one. We think that it's a $1 billion opportunity, over $1 billion in the second line. And so we did experience one larger company that indicated that they were wanting a multibillion-dollar opportunity.
And so we recognize from that discussion that there maybe we'll add in more of the mid-tier companies. And that's really where that's derived from. But let's face it, a $1 billion opportunity in a refractory patient population with a fairly efficient trial and a big differential from others from the standard of care is still pretty exciting.
I would also note, even in an HPV-positive subpopulation, it's over $0.5 billion risk adjusted. So I think either way you cut it, it's pretty good. And you still have the opportunity to advance to first line, have the opportunity to advance to other indications as well. But you're right in this regard, Tony, that we said we recognize that adding in some of these mid-tier players matters.
And actually, I would say it does matter because we're seeing some people that have capital that have really not been able to perform with their late-line drugs and are very interested in getting into some strong Phase 2 compounds that can move to efficient Phase 3. So hopefully, that helps address some of it.

Jay Short

Tony, so you have a really interesting question about smokers amongst the patients that have the p16 positive protein, the HPV analysis. We have a total of 26 patients in this that had the HPV of 40 total. And as you know, the HPV-negative patients were really more associated with smoking and alcohol exposure, the environmental exposure form and HPV is much more the oncogene-driven side with a particular unmet need amongst patients when they reach second and third-line setting because of the lack of EGFR benefit.
And I don't have the smoking correlation set up, but that's something I can try to obtain for you after the call. So thank you.

Tony Butler

I appreciate that. The key is whether it's smokers and non-smokers, that's really where I want to go with that HPV-positive cohort.

Jay Short

Yes, we have the smoking data. It's just we haven't made a correlation with the HPV, but it's a great question, and we'll get right on it.

Operator

Arthur He, H.C. Wainwright.

Arthur He

So I guess I have three quick questions. So first for the EpCAM program. Regarding the data upcoming mid this year, is that -- which kind of dose level of the data we can see? Can we go up to the 3,300 milligram -- microgram, sorry, microgram cohort data? Or it's probably more at the lower dose levels?

Jay Short

Well, certainly, in the 300, we should have, assuming all the dosing goes well. Is there a chance to see 900? Possibly if we do it in July. So we're still -- we'll just make sure -- it also depends a little bit on patient recruitment, but I'm very comfortable that the 300 will be there and potentially higher.

Arthur He

So Jay, when you're talking about 300, you mean 300 from both C and D arms or just --?

Jay Short

No, I'm talking about C. I think the B formally is just behind the other but tends to reinforce. But yes, I'm focused on C right at the moment.

Arthur He

And my second question is regarding the AXL program. So maybe correct me if I was wrong. So are we going -- are you guys going to treat more patients for the -- in terms of the AXL program? Or I mean, is there any more additional patient data we can see in the future?

Jay Short

I think our hope -- I mean, EpCAM is a priority right now because of many reasons and because of the safety that we're seeing, which we're liking and the broad applicability. I mean, it's a pan-cancer drug, and it's hard to ignore how big this could be. With AXL, though, we see some advantage of being able to do a few more patients on that. So our hope is to add in a few more patients that haven't been added yet.
We're in the process of amending our trial to allow more patients. But we're going to have a pretty good picture of what happens on EpCAM. So our intent is to drive some additional patients there, but I will allow that EpCAM could turn into something so exciting that we may decide to double down there. But for now, yes, that's our plan.

Arthur He

And my last question is regarding the BD or strategic wise. So besides you think about to part out the ROR2 and CTLA-4 program, are you open to any other strategy to maximize the shareholder value?

Jay Short

Yes. I mean we certainly would be open if the partner decided that they want to drive AXL instead of ROR2. I mean both are pretty exciting. We're also always looking at backup strategies. We're partnering timing sometimes as we've learned and be hard to exactly forecast, but we're definitely doing both of those things.

Arthur He

Congrats on the progress.

Jay Short

I think they're coming in very nicely, and I think it's kind of rare in this world where everything is working.

Operator

Thank you. It appears that we have no further questions at this time. I will now turn the program back over to Jay Short for any additional or closing remarks.

Jay Short

I just want to thank you all for your time. And I think, hopefully, you've heard some of this data. We're pretty excited about the differentiation we're seeing in the ROR2 programs. EpCAM, we think we're pioneering there.
We also think AXL is also as well as CTLA-4 are showing the differentiation that we expect from CAB, and I think that's going to translate into partnerships sooner than later. So thank you for your time.

Operator

Thank you. This does conclude today's program. Thank you for your participation. You may disconnect at any time.