Alligator Bioscience AB (publ) (ATORX) Earnings Call Transcript & Summary

Hello, and welcome to Alligator Biosciences First Quarter 2024 Earnings Call. My name is Greta Eklund, and I am the Investor Relations and Communications Manager, and I will be introducing today's call. With me are CEO, Søren Bregenholt; and CFO, Marie Svensson. They will walk you through the latest development from Q1 2024 and the upcoming news flow, after which they will be happy to answer any questions that you might have. Before we begin, I would like to share a quick reminder with our listeners that during today's call, management may make forward-looking statements that involve known and unknown risks, uncertainties and other important factors beyond the company's control that could cause the company's actual results, performance or achievements to be materially different from the expected results, performance or achievements expressed or implied by such forward-looking statements. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those contained in the forward-looking statements. Actual results and the timing of certain events may differ materially from the results or timing predicted or implied by such forward-looking statements, and reported results should not be considered as an indication of future performance. Please note that these forward-looking statements made during this call speak only as of today's date, and the company undertakes no obligation to update them to reflect subsequent events or circumstances, other than to the extent required by law. This call is being webcast and will also be made available through the Investor Relations section of our website. With the formalities out of the way, I would now like to turn the call over to Søren.

Thank you, Greta. Good afternoon, and good morning, everyone, and welcome to Alligator Bioscience first quarter 2024 earnings call. As Greta mentioned, I'm Søren Bregenholt and I'm the CEO of Alligator Bioscience. I'm very pleased to share with you that Alligator continues to make a strong progress on all fronts. We are bolstering our mid-stage clinical pipeline, while we're also making progress on our earlier programs. Preparation for the Phase III evaluation of our lead asset, mitazalimab, in first-line metastatic pancreatic cancer are underway, and we are looking forward to building on the very positive results from OPTIMIZE-1. You remember, the top line results from the Phase II study, which we reported January 29 demonstrated that mitazalimab in combination with standard of care chemotherapy FOLFIRINOX provided significant survival benefits over standard of care alone, a fact that we are going to discuss in more detail during today's call. This quarter, we also reported positive interim Phase I data from a dose escalation study with ALG.APV-527 in solid tumors. This is a molecule we are codeveloping with Aptevo out of Seattle. We received the first U.S. patent for our Neo-X-Prime platform bispecific antibody, ATOR-4066. And recently, our partner, Orion, selected the lead candidate in our second collaboration program and exercising their development option, which triggered a milestone payment to Alligator. On the financial front, we recently conducted a capital raise, extending our cash runway and applying or adding maneuverability in our efforts to negotiate the best possible deal for mitazalimab. We remain financially disciplined and -- which allow us to continue to invest in our key assets, both proprietary and partner program. Next slide, please. So on January 29, we announced positive top line data from the OPTIMIZE-1 study, which is a Phase II study assessing the safety and efficacy of our CD40 monoclonal antibody, mitazalimab, in combination with standard of care chemotherapy modified FOLFIRINOX in first-line metastatic pancreatic cancer. First of all, the study achieved its primary endpoint with an objective response rate of 40.4% and an unconfirmed objective response rate well above 50% in the 57 evaluable patients. This compares very favorably with the objective response rate of around 30% reported in a similar patient population treated with a chemotherapy backbone alone, thus demonstrating the profound clinical benefits of mitazalimab over standard of care. We also observed a highly durable response with a median overall survival of 14.3 months, with over 50% of the patients still being alive at the time of analysis and an unprecedented durability of response of 12.5 months, together demonstrating the extended survival benefit over standard of care. Both the durability of response and the survival rate will mature further with ongoing treatment and follow-up, and we'll talk a little bit more about the timescale for that in a minute. So we are planning to report 18-month survival follow-up from these patients, the full Phase II population, in the middle of this year. And we can see from the data readout already now that mitazalimab is well underway to potentially changing the treatment benefit -- treatment paradigm in first-line pancreatic cancer. And we believe, as I said, based on the fact that more than half of the patients were alive at the last readout, that the survival data that we'll present midyear will have improved significantly. Now go to the next slide. As we are laser-focused on advancing mitazalimab to the next stage of development, which is naturally in Alligator's view a randomized pivotal Phase III trial, we've had discussions with the U.S. Food and Drug Administration to ensure the development path for mitazalimab. The FDA has confirmed that OPTIMIZE-1 is a Phase III-enabling studies, which allow Alligator to move directly from OPTIMIZE-1 into a pivotal trial. In addition, the FDA has provided guidance on the dose characterization in accordance with their Project Optimus and requested Alligator to add additionally 15 patients on the lower dose in OPTIMIZE-1. I'm happy to announce that we have already enrolled the first patient in this backfill cohort of OPTIMIZE-1 and expect to have this cohort fully enrolled in the early part of Q3. We are continuing our partnering activities, both with due diligence and with negotiations in our effort to find the best possible global partner to take mitazalimab through Phase III regulatory approval, bring it to the patients for their benefit and hopefully also for commercial success. And we are on track to initiate a Phase III study in 2025 together with a partner. Could I have the next slide, please? So an important point to note about the planned Phase III evaluation is whereas the primary endpoint in the Phase II study, as you can see here on the left of the slide, was overall objective response rate, the agreed endpoint with the regulators on the Phase III study will be overall survival. You can see the chart on the right that the 14.3 months overall survival reported so far compares very favorably with the 11.1 months obtained for both classical FOLFIRINOX and the new NALIRIFOX chemotherapy in first-line metastatic pancreatic cancer. And maybe this is a good time to remind ourselves that Onivyde, the novel component of the NALIRIFOX regime was recently approved based on a 1.9-month difference in overall survival on top of -- or in comparison to gemcitabine, paclitaxel. Therefore, we believe that more than 3 months survival benefit that we've already now seen with mitazalimab is not only believed to be clinically meaningful, but also approvable by the regulators. And finally, when we look at this slide, we can see from the middle chart that the durability of response of 12.5 months compares extremely favorable with approximately 7 or -- 6 or 7 months that you see with the chemotherapy backbone. And together with the data that we recently announced on the pharmacodynamic activity of mitazalimab, these data will support the continued clinical development of mitazalimab in first-line metastatic pancreatic cancer. Next slide, please. So here, we have a full overview of our prepared proprietary programs mitazalimab we just discussed in Phase II and on its way into Phase III in metastatic pancreatic cancer. Importantly, the next-generation CD40 agonist based on our Neo-X-Prime platform, the first of which is called 4066 is in early preclinical development. We see this as a significant growth opportunity for the company as we go forward. And when we look at the 4-1BB part of our portfolio, our collaboration with Aptevo recently have resulted in solid interim -- or intermediate Phase I data from the dose escalation trial in 5T4 positive solid tumors. And if we take the next slide, we can follow -- we can continue on 527. So in March, we announced the positive interim data from the study. So this is a third-generation tumor-directed 4-1BB agonist. And we are evaluating the molecule in tumors that express 5T4. This asset was developed using Alligator's internal libraries, combining with Aptevo's bispecific platform, and preclinical studies have highlighted at the differentiated design of this molecule minimize the systemic immune activation, while maximizing in-tumor immune activation, thus allowing for highly efficacious tumor-specific responses as demonstrated by potent activity in a range of preclinical models. So the interim data from the Phase I study showed that the treatment has been well tolerated. So far, the dose escalation is reaching the top cohorts, the top dose levels, and biomarker analysis have indicated that the expression of both targets 4-1BB and 5T4 in the tumors, which underlines the potential of the molecule to treat multiple indications that are 5T4 specific. Of particular interest, we saw clinical signs of early activity in patients with heavily pretreated breast cancer. These patients demonstrated measurable levels of drug in circulation and reproducible elevation of serum pharmacodynamic markers, which together suggested that the drug is biologically active. Alligator and Aptevo have currently enrolled more than half of the patients, and we are on track for the final readout of top line data from this study in the second half of the year. Now let's go to the next slide. So as I just mentioned a few slides ago, the third generation bispecific CD40 agonist is really what we believe will drive long-term value for Alligator. And we are -- I'm happy to announce continuing to make great progress with 4066. This quarter, we strengthened the IP protection of the molecule with the first U.S. patent for 4066, which, of course, is vital to the commercial development of any molecule. And we expect to strengthen the protection around the molecule with more patents, both in the U.S. and in other regions of the world. At the end of the quarter, we presented the key preclinical data at the ACR Meeting, suggesting an even more specific and efficacious activation of CD40, further opening the way for an even more targeted therapeutic approach with 4066 that really supports the continued development of the molecule in clinical trials, which we will continue to work towards. Now can I have the next slide, please? We also announced the good news on our collaboration with Orion. This collaboration is now running on its third year. The common name here is to develop bispecific antibody leveraging Alligator's antibody, cloning and screening technologies, together with our proprietary bispecific Ruby format against a target of strategic interest for Orion. We have been working on two programs. And now recently, Orion exercised the development options for the second program, triggering a milestone for Alligator. We will continue to work with Orion and support their efforts to bring these molecules further into human clinical trials and eventually to provide novel treatment opportunities for people with hard-to-treat cancers. And with these words, I will leave the word to Marie, our Chief Financial Officer. Marie, please take it away.

Thank you, Søren. Next slide, please. Going over the financial figures. We start with the net sales for the first quarter '24 that amounted to SEK 6.97 million, down from SEK 9.59 million in the prior year period, and that comprised primarily to the collaboration agreement with Orion Corporation. Operating loss for the quarter resulted in negative SEK 59.64 million and decreased from SEK 62.19 million in the prior year period. Cash flow for the quarter amounted to negative SEK 26.2 million compared to negative SEK 52.2 million in the prior year period. The cash flow in the quarter was positively affected by the company, taking up a bridge loan amounting to SEK 58.8 million. Operating expenses mainly pertain to the cost of the ongoing clinical trials for mitazalimab and 527 as well as Phase III-enabling activities for mitazalimab. In February, Alligator announced a restructuring plan to reduce costs and allow the company to prioritize its preclinical and early stage assets. The reconstruction plan was completed in March, and the SEK 1.9 million was reserved in the quarter as the cost for -- related to the personnel reductions. In the figure down to the right, you can see how expenses were distributed between our projects in Q1. And not surprisingly, 48% of our resources have been focused on the mitazalimab project. An important point I would like to bring to your attention is the focus of financial resources behind our R&D efforts. While Alligator dedicated around 70% of its operational expense to R&D in 2020 and '21, this level was significantly increased in 2022 reaching 81%, and our efforts has continued, leading us to dedicate 83% as March 31, 2024. Next slide, please. Through our preferential rights issue conducted in the first quarter 2024, we extended our cash runway receiving SEK 107.1 million before deduction of costs, of which SEK 59.5 million relates to the set-off against the outstanding bridge loan. This additional financing allows Alligator to continue pursuing our goals, including the continuation of the Phase II development of mitazalimab in pancreatic cancer, the continued 527 Phase I study and the ongoing development of our other pipeline candidates, including ATOR-4066. Next slide, please. If we look at Alligator operating cost on a rolling 12 months basis, we note a slight decrease as the patient recruitment peak is behind us in OPTIMIZE-1 study. Expenses for -- in our ongoing clinical trials are still high due to the number of patients staying on longer in OPTIMIZE-1, but also due to the ongoing investment in various Phase III-enabling activities for mitazalimab. On March 31, liquidity was SEK 40 million. The result of the rights issue was announced on April 9, with around 70% of the total issued subscribed. In order to support the continued development of our key assets, the company is continuously working on opportunities for partnerships, collaborations, out-licensing deals, loans and equity financing to secure the financing on the operations. And with that, I will turn the call back to Søren.

Thank you, Marie. Could I have the next slide, please? So Q1 has provided a strong start for Alligator on our various milestones. You can see we have already read out the top line data from mitazalimab and also the interim Phase I data from 527, as we call it. This leads to a significant news flow in the rest of the year. We expect, as I've alluded to a couple of times, to provide the next survival update from the OPTIMIZE-1 study around the mid of the year. We expect that the recruitment of the additional patients on 450 micrograms per kilogram to align with the FDA's request for additional dose characterization will be completed in the first half of Q3. In Q4, we expect to deliver top line data from the Phase I study with 527. And then throughout Q3, but ending in Q4, we will conduct further dialogues with the U.S. and European regulators to get a clear agreement on the Phase III study for mitazalimab in first-line metastatic pancreatic cancer, which will then lead to Phase III initiation in the first half of 2025. Next slide, please. So if we take a broader look on Alligator and our strategic intent for 2024, we have already provided data, we have raised additional cash and extended our cash runway, but it's clear that the current efforts we have with identifying and negotiating deals with a partner for mitazalimab is of crucial importance for the continued speed development of that molecule. Next year, we expect to initiate Phase III together with a partner. We expect to go beyond CD40 and bringing 527 into the second phase of clinical development following positive Phase I data later this year. And then we will, of course, continue to deliver on our partnerships with Orion, MacroGenics and others. And beyond 2025 and mitazalimab deal, we will broaden our proprietary and partnered clinical pipeline, and we will start to generate the first sustainable revenues and reaching operational profitability by an approval of mitazalimab in -- before at least 2030. The numbers here might be a little bit on the optimistic side. So with this, I thank you for your attention and take any questions that may have arisen from today's presentation.

And we have a couple of questions here. We have one from [ Luisa ] from Kempen and the question goes as such. You mentioned in today's report that preparations for a Phase III study with mita in pancreatic cancer is ongoing. And what do those preparations entail? That's a very important question. So these preparations are basically threefold. Of course, we are engaging our key opinion leaders and other experts to get the right Phase III design in order to be able to discuss it with the regulators in the second half of the year. We are finalizing the manufacturing process development for Phase III, something that has sort of at its final stages and somewhat taking significant costs for that. Previously, that will sort of taper off during the next quarters. And of course, we are recruiting the last 15 patients in the low-dose optimized -- or the low-dose cohort in OPTIMIZE-1. Then we have a couple of questions here from Richard at Redeye, and I think this one is also, to me, could further improve results in the midyear readout from OPTIMIZE-1 assist business development. Yes. I think any positive data will, of course, help advancing the discussions and the negotiations that are already ongoing. We expect those data to come out during the second half of June this year. And there's another question here. Sorry that I'm reading it from my phone. What are the main takeaways from the ACR Meeting this year? What is the interest in pancreatic cancer among practitioners and pharmaceutical companies? That's also a very good question. Obviously, with a very high unmet medical need in metastatic pancreatic cancer, practitioners are very keen on testing new molecules like mitazalimab in the appropriate clinical setting. For us, the clear message from practitioners and our key opinion leaders is that the next obvious step for mitazalimab is a randomized pivotal trial. Companies are probably a little bit more hesitant for pancreatic cancer, in general. It's a disease with a, as I said, high unmet medical need. It's also a disease where it's difficult to develop new drugs. But there is a number of incumbents already in the disease or in other gastric -- gastrointestinal cancers that have shown a strong interest in mitazalimab. And we expect that we will be able to further these talks in the months to come, leading to a partnership agreement for mitazalimab. We have another set of questions here. This is more about Orion. Will Orion take over the second bispecific antibody? And do the development work from now on, meaning that Alligator will have no cost and no reimbursement from the program? And can we talk about the financials? Unfortunately, based on terms of the agreement, we cannot talk about the specific financials. But as Orion has exercised the development milestone for -- the development option for the second program, they will take over the molecule and lead the development from here on. Alligator will, of course, continue to assist Orion in the areas where we have specific and unique competencies. And the last question from Richard here. What is the plan for 527? Do you want to out-license that and 1017 as a package individually or continue development in-house? For 1017, we have previously stated and will continue to state so that until we have either our partner or an substantial free cash flow to support the development, we will not engage in further development of 1017. 527 is codeveloped with Aptevo, and we are leading discussions with potential partners, while we are also exploring opportunities for continuing the molecules development in the current setup. And then we -- there's a lot of questions here. Let's stay with the -- with questions here on mitazalimab. When will you report the data for the additional cohort of the 15 patients in OPTIMIZE-1? As I said, we expect to have recruited these patients by the beginning of Q3, hopefully. And we expect to be able to put out the first set of data from this study probably in the beginning of Q1 2025. We are primarily evaluating these patients for pharmacokinetic, pharmacodynamic and exposure response ratios and not necessarily for full survival parameters. But around Q1 next year, and we are still continuing both our dialogues with potential partners and our Phase III preparations with the assumption that OPTIMIZE-1 is -- or based on the agreement that OPTIMIZE-1 is Phase III enabling. So here is a question from another investor. The objective response rate of mitazalimab for the first few patients increased meaningfully from the first interim to the second interim, but you did not provide an update on how this ORR involved for these 23 initial patients. Could you provide us with an update on that? No, I cannot. We decided to not continue to follow this particular cohort when we did the full top line analysis in January. This was an analysis of the initial futility cohort that we thought was interesting to see, whether the study would continue to provide mature data at that early point. We have not further analyzed that. But when we look at the data, we can see that some of these patients that were the early ones included are still alive in the study, and that is, of course, very encouraging. And we are looking very much forward to provide the 18-month follow-up data on mitazalimab in -- during June. So Marie, you have been waiting patiently. Here is a couple of questions for you. How far does your current cash runway take you in your proprietary and partner programs?