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spk05: Good morning, ladies and gentlemen. Welcome to the Appleomics full year 2023 results conference call. Before we begin, we want to advise you that over the course of the call and question and answer session, forward-looking statements will be made regarding events, trends, business prospects, and financial performance, which may affect Appleomics future operating results and financial position. All such statements are subject to risk and uncertainties, including the risk and uncertainties described under the risk factors section included in APALOMIC's annual report on Form 20F, registration statement on Form F1, and other reports filed with the Securities and Exchange Commission. APALOMIC advises you to review these risk factors in considering such statements. APALOMIC assumes no responsibility to update or revise any forward-looking statements to reflect events, trends, or circumstances after the dates they are made. It is now my pleasure to turn the floor over to Dr. Guoliang Yu, Appleomics Chairman and Chief Executive Officer. Sir, you may begin.
spk01: Thank you, Shannon. Good morning, everyone, and thank you for taking the time to join us today as we provide an overview of recent business highlights and discuss our four-year 2023 financial results. Joining me for the call today is Dr. Sanjeev Radhika, our President, Dr. Peony Yu, our chief medical officer, and Dr. Matthew Plunkett, our recently appointed chief financial officer who joined us earlier this month. Matt brings to Appleomics an outstanding track record of executive leadership in financial strategy and business development. We look forward to his contributions as we continue to execute on our vision of bringing Vibratinib or APL-101 and our other pipeline candidates towards regulatory approvals to better serve patients with a number of underserved indications. I'll begin the call with some introductory remarks, which will be followed by a review of our recent Corporate and Development Progress by Sanjeev. Matt will also cover our four-year 2023 financials, and then we'll open the call for Q&A. We recently reviewed interim data from our Global SPADA Trial and Kunpeng China Trials with the FDA in February 2024 and received informative and encouraging feedback on our lead product candidate, Vibratinib. But first, before we go into that, I want to remind everyone our strategic focus and what we accomplished in 2023. 2023 was a year of significant accomplishment as we made substantial progress in our two lead drug candidates, Vibrotinib and Apsilicillin. Both have shown promising clinical results. First, we substantially advanced our Phase II registrational trial of our lead product candidate, Vibrotinib, in non-small cell lung cancer and other solid tumors with MAD dysregulation. Vibrotinib is a novel oral active, brain-penetrated, highly specific CMAT inhibitor being evaluated in global clinical trials, including the U.S., Europe, and China. Dysregulation in CMAT signaling can play an essential role in the development, progression, and survival of cancer. Vibratinib has the potential to treat cancers with MAT or HGF dysregulations beyond MAT exon 14 skipping. Our multi-cohort global SPADA trial, which includes over 90 clinical sites in North America, Europe, and Asia. Together with our partner, Everstone Pharmaceuticals Technology Company, known as Everstone, More than 500 patients have been treated to date and have observed encouraging efficacy from Vibratinib in clinical trials. The safety profile is generally similar to other met tyrosine kinase inhibitors on the market. At this time, given our encouraging clinical data on Vibratinib monotherapy to date, we are focused on three initial indications. We expect the first to be non-small cell lung cancer with MAD exon 14 skipping mutation for which vibratinib has the potential to be best in class to further improve patient treatment beyond available therapies. And the other two indications are expected to be first in class targeted treatments including non-small cell lung cancer with CMAT amplification and glioblastoma metafome with PTPRZ metafusion. Sanjeev will provide further update on where we are in clinical and regulatory development with each of the indication in a moment. In December 2023, we reported the overall response rate of vibratinib by gene copy number or GCN subgroup analysis in 83 non-small cell lung cancer patients from the ongoing multi-cohort phase 2 QAN-PEN trial in China and the ongoing global multi-cohort phase 2 SPADA trial. The interim data demonstrated vibrotinib efficacy in non-small cell lung cancer patients with MAD exon 14 skipping mutation provide a robust overall response rate and an acceptable safety profile in patient with and without co-occurring MAD amplification. In November 2023, Everstone received a conditional approval from the National Medical Product Administration of China for the commercialization of Vibratinib to treat patients with MAD exon 14 skipping, non-small cell lung cancer. Note, under our partnership agreement, Everstone holds the exclusive rights to Vibratinib in Greater China, while Apolomix retains the exclusive rights in the US, Europe, and the rest of the world. partners have access to each other's data. In addition, in January 2024, we announced the completion of patient enrollment for our Phase III bridging study in China for Aplacelin or APL106 in patients with relapsed or refractory acute myeloid leukemia or AML. Apolomix licensed Apolysilin from Glycomimetics, including the right to clinical development, production, and commercial sales in greater China market. Apolysilin is a first-in-class E-selectin inhibitor being used in combination with standard-of-care chemotherapy in patients with AML. It has the potential to improve efficacy and tolerability of chemotherapy. Aplacilin has been granted breakthrough therapy designation by both the FDA and the NMPA. Glycomyometics US and the global phase three aplacilin study in the reflex and the refractory AML patient was fully enrolled as of November 2021. Glycomyometics expects top line results from this trial in the second quarter of 2024. Finally, in March 2023, we successfully transitioned to a public company by completing our business combination and listing on NASDAQ. With that, I will turn the call over to Sanjeev.
spk00: Thank you, Ruolian. In February 2024, we sought feedback from the FDA in a type C meeting with the objectives to review our development plan as well as our registration pathway of febrile tinib for the treatment of three conditions. The first was non-small cell lung cancer with Medexon 14 skipping mutation. The second, non-small cell lung cancer with CMET amplification. And the third, glioblastoma, or GBM, with PTPRZ1-CMET fusion. Now, the interim results in the first indication, MedExon 14 skipping mutation, included 107 non-small cell lung cancer patients with centrally confirmed MedExon 14 skipping mutation. Now, of the 107 patients, 71 were treatment naive and 36 previously treated patients with no prior MET inhibitor and no immune checkpoint inhibitor treatment immediately prior to MRI. Now, in the 71 treatment night on small cell lung cancer patients, about half are from Sparta and half are from the Kunpun trial. The objective response rate, ORR, was 66.2%, supported by median duration of response of 16.5 months. In the 36 previously treated patients, of which 19 are from Sparta and 17 from Kunpun, The ORR was 61.1%, with a median duration of response of 16.7 months. An updated efficacy analysis by gene copy number, or GCN subgroup, continues to show similar web relatinib activity in the treatment of non-small cell lung cancer patients with medexon protein skipping mutation, regardless of overlapping MET amplification. that is, in the absence of overlapping CMET amplification. With GCN gene copy number less than four, the ORR was 67% in a pooled analysis of 86 patients from the SPARTA and Kuhn-Pung trials. Now, in the treatment naive patients with GCN less than four, the ORR was 64.3% in 28 SPARTA patients, and The ORR was 71.4 in 28 Kunpun patients. Based on the feedback from the FDA from this Type C meeting, we will continue to enroll in the SPARTA cohorts and review additional information on patients from the SPARTA and Kunpun trials with the FDA on the NDA readiness for this indication. We will analyze data after all patients have achieved a 12-month follow-up to support a traditional approval. Now, based on the discussions with the FDA, we believe that pre-treated non-small cell lung cancer patients with CMED amplification, they remain an unmet medical need, and that the preliminary data presented could represent an improvement over available therapy. We'll continue to enroll non-small cell lung cancer patients with CMED amplification in the SPARTA study to increase the precision around the point estimate for the ORR and provide geographic diversity in the NDA package for supporting an accelerated approval. The primary efficacy analysis could potentially be based on the single-arm trial results from Kunpeng and SPARTA. We expect enrollment of these incremental patients in SPARTA will continue into 2025, and if these results are positive, we could potentially submit an NDA in 2026 to seek accelerated approval of webraltinib as a second-line treatment for non-small cell lung cancer patients with CMET amplification. Now, for patients with GBM with PDPR-Z1 MET fusions, the agency acknowledged that PDPRZ1 met fusion positive high-grade glioma is a serial illness with an unmet medical need. We do need additional study data and additional to determine if the randomized phase 2, 3 study completed by Avistone, which showed a 48% reduction in risk of death, supported by data from the SPARTA study, could support a marketing authorization for this indication in the US. For the remainder of 2024 and into 2025, we look forward to the following milestones and updates. We look forward to disclosing exciting new preclinical data on Vibraltinib at the AACR meeting in San Diego next week. We are planning to present results from multiple preclinical studies in two posters. Now on APL106 at Upper Lesserland, Apalomic's partner in the U.S., Glycomimetics, expects to report top-line results from its pivotal phase III study of aprolexaline in the relapsed refractory AML in the second quarter of 2024. Our phase III bridging study in relapsed refractory AML in China was fully enrolled at the end of 2023. While waiting for data to mature in this event-driven study, we expect to report top-line data in the first half of 2025. I'll now turn the call over to Matt who will review the financials.
spk02: Thank you, Sanjeev. Please refer to our press release issued earlier this morning, March 28, 2024, for a summary of our financial results for the year ended December 31, 2023. As of December 31, 2023, cash, cash equivalents, bank deposits, and money market funds were $37.8 million as compared to $58.9 million as of December 31, 2022. In March 2023, the company raised $23.7 million before transaction expenses in a pipe financing in conjunction with the business combination enlisting on NASDAQ. Based on current projections, we believe our cash position is sufficient to fund planned operations through the first quarter of 2025. For the year ended December 31, 2023, research and development expenses were $34.2 million, including stock-based compensation of $5.9 million. This compares to $35.4 million, including stock-based compensation of $2.4 million for the full year 2022. General and administrative expenses were $20.6 million, including stock-based compensation of $6.8 million for the full 2023 year. This compares to $9.9 million, including stock-based compensation of $0.6 million for the full year 2022. The increase was primarily from administrative expenses related to our business combination in 2023, directors and officers insurance as a result of being a publicly listed company, and an increase in employee stock-based compensation. Net loss for full 2023 was $172.6 million, or $2.32 per diluted share, as compared to a net loss of $240.8 million, or $8.44 per diluted share, for the full year 2022. The net loss includes a non-cash expense for change in fair value of convertible preferred shares of $76.4 million in 2023 and $189.6 million in 2022 and also includes expenses related to capital markets activities of $46.0 million in 2023 and $6.6 million in 2022. For the year ended December 31, 2023, net cash used in operating activities was approximately $43.2 million, as compared to $42.8 million in the prior year. At this point, I'll now turn it back over to the operator for our Q&A session.
spk05: Thank you. To ask a question, please press star 1 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1 1 again. please stand by while we compile the Q&A roster. Our first question comes from the line of Tim Moore with EF Hutton. Your line is now open.
spk03: Thanks. Prior press release and your prepared comments on the call, it's great that you want to move forward with enrolling the SPARTA cohorts. So I just want to maybe clarify the timing. You know, you want to you need to reach the 12-month follow-up period. It sounds like you will expect the enrollment to be finished by maybe early 2025. So does that mean you'd have more data that you're pretty confident on submitting to the FDA sometime, I guess, maybe early 2026? Does that timeline make sense?
spk01: Maybe, Puni, would you be able to answer Tim's question here?
spk05: Your line may be on mute.
spk03: I can do another question if you want. Come back to that one.
spk04: Sure.
spk03: Great. So it's good that you might seek the NDA application route. That was good news. And is there anything else you can maybe share on feedback from the FDA meeting? Is there anything that they want you to do or follow up on or any kind of request that they had?
spk01: Yeah, so I think the key message is that, you know, FDA basically we need to continue to enroll more patients to kind of identify results that we already have. So we will just continue what we're doing. I think Peony is on. Could you answer the previous question Tim has asked?
spk04: Peony, are you on? If he's not, okay.
spk01: Yeah, so actually maybe I'll give you a high-level answer. I think the timeline might be a little shorter than what you think. with the current patient that we have presented to FDA, the 12 months follow-up time will coming up in this summer. But if we need additional patient to be enrolled, that will basically extend, you know, another 12 months. So we are thinking of, you know, in the year of 2025 rather than 2026. Hope that answers your question.
spk03: Yeah, no, that's why I was kind of curious because these extra patients might push out that timeline a bit, right, for the 12-month. I'm just wondering if the FDA is going to redefine the 12-month follow-up, you know, if it's not this summer and it gets moved out to, you know, early 2026.
spk01: Yeah, so for the non-small cell lung cancer with exon 14 skipping, because we're going after the traditional approval, therefore... you know, 12-month follow-up is required.
spk03: Okay. Okay. I got it. One other question I had was, you know, you added the CFO role last week. You know, Dr. Plunkett spoke a bit. I'd just love to hear from him, you know, what is he expected to enhance and improve at the company? You know, is he bringing over some best practices of commercialization, regulatory approval learned, you know, at Imago and Carta Therapeutics? Great question.
spk01: Matt, would you be able to share your thoughts?
spk02: Yes, I certainly can. Tim, thanks for the question. Near-term focus here is really to help the existing team with our 20F filing, which you'll see come out later today. As you've seen, I do have some extensive experience variety of finance and business roles in various small biopharma companies, ranging from capital formation to strategic collaborations. And those are some of the things that I'll be looking to work on in the coming months. So stay tuned there.
spk03: Great, great. Not to put Matt on the spot, but whoever wants to answer financial expense questions, I'm just trying to update my model for this year and Now, I've got to imagine that your R&D expense climbs. I think it was $34 million for 2023. Is it reasonable for me to expect, you know, because you've got enrollments and other expenses and clinical trials going on, is $50 million this year maybe too much? And, you know, just kind of curious about the R&D number.
spk02: Yeah, happy to answer that for you. What I would really do is look at our guidance for – for cash runway and kind of back into it from there. So 37.8 million in cash bank deposits and mutual fund balances at the beginning of 2024. And we said we've got cash through the first quarter of 2025. So five quarters there. So basically you can just do the math there and kind of get a total expense. I would point out that with the completion of enrollment in the APROLISON Phase 3 trial, obviously those expenses, one would expect, are not going to be as great in 2024 as 2023. So, you know, hopefully that gives you a little bit of help there. And then obviously with some significant one-time expenses related to the D-SPAC transaction in 2023, first time ever public reporting, et cetera, we're going to expect some of those G&A things not to be as large in 24 as 23. But really the best thing to do is just look at the overall cash burn guidance and runway guidance. So I think that should get you where you need to be.
spk03: Yeah, that's what I was thinking originally. It's just I was kind of curious, you know, it was really helpful to say through the first quarter next year, it makes you feel comfortable on the cash burn, but I didn't know how much that, Does that factor in the additional patient's enrollment if that's the route you're going to go, you know, the extra patients? It sure does, Tim. Okay, good. Good, good. Anything else to add on the rest of the pipeline? I know you touched on, you know, a couple other indications. Anything else going on with some of the other drug candidates?
spk01: Not really. You know, we try to stay focused with Vibrantinib and Aplasmin at this time, you know, especially Aplasmin. with limited cash that we have. So we really kind of try to stay focused and get our first drug approved.
spk03: Good, good. No, I like the focus. I think that's very good. Too many biotechs try to fund five or six things at once, and you're focusing on your two top ones. So I appreciate it, and that's it for my questions. Thanks.
spk01: Thank you very much. Thank you, Tim.
spk05: Thank you. As a reminder, to ask a question at this time, please press star 1-1 on your touch-tone telephone. And I'm currently showing no further questions at this time. I'd like to hand the call back over to Dr. Goli and you for closing remarks.
spk01: Okay. Thank you, everyone, for joining today. We appreciate your interest in the company, and thank you for the questions. I look forward to updating you on our business in the near future.
spk05: This concludes today's conference call. Thank you for your participation. You may now disconnect.
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