Moleculin(MBRX) - 2024 Q4 - Annual Report

Clinical Trials and Drug Development - The company is conducting a pivotal Phase 3 trial for Annamycin in combination with Cytarabine for relapsed/refractory acute myeloid leukemia (AML), with interim data expected by the end of 2025[22]. - The company has completed or is currently conducting fourteen clinical trials for its drug candidates, with three candidates showing human activity in clinical trials[23]. - The Phase 2B/3 trial for Annamycin is expected to be pivotal, with the first site initiated for the global trial[34]. - The FDA's EOP2 meeting in July 2024 resulted in a positive discussion and the design of a Phase 2B/3 pivotal trial (MIRACLE) for R/R AML patients, which will be a global trial including sites in the US, Europe, Western Asia, and the Middle East[39]. - The MIRACLE trial will utilize a double-blind, placebo-controlled design, comparing Annamycin to high-dose cytarabine (HiDAC) with complete remission (CR) as the primary endpoint[39]. - The company completed recruitment and treatment in the MB-107 Phase 1B/2 clinical trial using Annamycin for STS lung mets in 2023, with follow-up for progression-free survival (PFS) and overall survival (OS) during 2024[38]. - The company plans to initiate a follow-on MIRACLE2 trial for third-line patients once the optimum dose is established in the MIRACLE trial[39]. - The company completed recruitment of 22 subjects for the MB-106 clinical trial, focusing on Annamycin in combination with Cytarabine for AML treatment[84]. - The Phase 1 clinical trial of Annamycin (MB-104) successfully demonstrated safety at the lifetime maximum allowable dose of anthracycline, with no signs of cardiotoxicity observed[67]. - The Phase 1B/2 clinical trial for Annamycin in STS lung metastases has completed enrollment with 36 subjects, and results are anticipated by the end of April 2025[100]. Drug Efficacy and Safety - Annamycin has shown a complete response (CR) rate of 50% and a composite complete response (CRc) rate of 60% in combination with Cytarabine for the treatment of R/R AML, which is higher than other approved second-line therapies[25]. - Annamycin has demonstrated non-cardiotoxicity in clinical trials, with some patients safely dosed at five times the typical lifetime maximum allowed anthracycline dose[25]. - Annamycin's overall survival (OS) rate is approximately 11 months, which is climbing, in combination with Cytarabine for the treatment of R/R AML[25]. - Annamycin has shown no signs of cardiotoxicity in clinical trials, allowing for higher dosing and potential treatment of traditionally "Unfit" patients[64]. - In the MB-106 trial, 41% of subjects achieved a complete response (CR) or CR with incomplete recovery (CRi) when treated with Annamycin and Cytarabine[76]. - The combination of Annamycin and Cytarabine (AnnAraC) demonstrated a 68% improvement in median overall survival (OS) compared to Annamycin alone and a 241% increase compared to Cytarabine alone in animal models[72]. - The company has received independent assessments covering 84 subjects treated with Annamycin, showing no evidence of cardiotoxicity, even with doses exceeding the FDA's lifetime maximum anthracycline limit[56]. Regulatory Designations and Market Potential - The company has received orphan drug and fast track status for Annamycin, with patent protection extending through 2040[25]. - The FDA and EMA have granted Orphan Drug Designation (ODD) to Annamycin for AML and soft tissue sarcoma, indicating a medically plausible basis for its use[48]. - The company has obtained orphan drug designations (ODD) from the FDA for Annamycin, WP1066, and WP1122 for various cancer treatments[147]. - The FDA granted orphan drug designation (ODD) for WP1066 for glioblastoma treatment, indicating a medically plausible basis for its use[105]. - The FDA granted "Rare Pediatric Disease" designation for WP1066, which may lead to a Priority Review Voucher valued at up to $100 million[170]. - The US market for anthracyclines, including Annamycin, was estimated at approximately$1.3 billion in 2023 and is expected to grow to $2 billion by 2032[158][159]. - The global market size for soft tissue sarcoma (STS) is projected to grow from$1.58 billion in 2024 to $2.57 billion by 2030[164]. - The American Cancer Society projects 2.0 million new cancer cases and 618,120 cancer deaths in the US in 2025, highlighting the significant market potential for oncology drugs[156]. Competitive Landscape and Challenges - The company faces significant competition in the oncology market from larger pharmaceutical and biotechnology firms, as well as academic institutions[185]. - FDA approved targeted therapies for AML patients with specific gene mutations, but they only serve subsets of the population[189]. - Only 20$0.2 million and $0.3 million, respectively[175]. - The company has a sponsored research agreement with MD Anderson, with expenses of$2.0 million and $0.8 million for the years ended December 31, 2024, and 2023, respectively[176]. - The reverse stock split on March 22, 2024, reduced the number of authorized shares from approximately 33 million to 2 million[182]. Drug Mechanism and Research - Annamycin is designed to avoid multidrug resistance and has shown no cardiotoxicity in subjects treated in five clinical trials to date[28]. - WP1066 has shown significant anti-tumor activity in various animal models, with the ability to inhibit key transcription factors such as c-Myc and HIF-1α, and boost immune response by reducing TRegs[107]. - WP1066 has demonstrated potential for combination use with checkpoint inhibitors, with preclinical evidence suggesting it may reverse immune tolerance in brain tumor patients[109]. - The company believes WP1122 has the potential to enhance the effectiveness of checkpoint inhibitors and impact hard-to-treat viruses reliant on glycolysis[131].