Drug Development and Clinical Trials - The company has six drug candidates, three of which have shown human activity in clinical trials[19] - The company expects to have up to ten clinical trials active or concluded by the end of 2022[25] - The company is seeking collaborative partners for a Phase 2 clinical trial of WP1220 in CTCL[33] - The ongoing geopolitical uncertainties may impact the company's clinical trials and drug supply[36] - The company is focused on developing treatments for highly resistant cancers and viruses, including AML, GBM, STS lung metastases, and COVID-19 variants[38] - The company is exploring additional strategic collaborations and grant-funded opportunities to support its drug candidates[41] - The company is independently funding its WP1122 antiviral program, which has received FDA clearance for a Phase 1 clinical trial[43] - The company plans to initiate a Phase 1 trial of WP1122 for COVID-19 in the UK in the first half of 2022[22] - The company plans to initiate a European Phase 1/2 AML trial with AnnAraC in the first half of 2022, following the successful completion of a single-agent trial[81] - The company is collaborating with WPD and physicians in Poland for a Phase 1b/2 clinical trial of Annamycin, funded by a $1.5 million USD grant[105] Annamycin and Its Efficacy - Annamycin has demonstrated a 60% objective response rate (ORR) in the last cohort of a Phase 1 trial for relapsed and refractory acute myeloid leukemia (AML) in Poland[27] - Annamycin has shown no cardiotoxicity in subjects treated to date in clinical trials[20] - A Phase 1 clinical trial of Annamycin for relapsed and refractory AML successfully concluded in 2020, meeting the primary endpoint of safe administration up to the lifetime maximum allowable dose[54] - The company established a recommended Phase 2 dose (RP2D) of 240 mg/m2 for Annamycin in its ongoing Phase 1/2 trial in Europe, demonstrating an overall response rate (ORR) of 60% in the final cohort[55] - Preclinical studies suggest that the combination of Annamycin with Cytarabine (AnnAraC) may be 68% more effective for R/R AML patients compared to Annamycin alone[55] - Annamycin has shown no cardiotoxicity in three Phase 1 clinical trials, with less than 10% incidence of alopecia compared to 65%-92% for doxorubicin[65] - Annamycin demonstrated a 100% survival rate in a preclinical study for metastatic osteosarcoma, compared to only 10% for untreated animals[78] - Annamycin's uptake in the lungs is over 30-fold higher than that of doxorubicin, suggesting potential effectiveness against STS lung metastases[77] - Annamycin may circumvent multidrug resistance mechanisms, allowing for higher drug uptake in diseased cells[69] - Annamycin clinical trials demonstrated a 60% overall response rate (ORR) with two partial responses (PRs) and one complete response (CRi) at a dose of 240 mg/m2[87] WP1066 and Related Trials - The WP1066 Portfolio includes lead drug candidates WP1066 and WP1220, targeting oncogenic transcription factors, with FDA granting Orphan Drug Designation (ODD) for WP1066 for glioblastoma[110] - WP1066 has shown significant anti-tumor activity in various solid tumors, including head and neck, pancreatic, stomach, and renal cancers, as well as glioblastoma[122] - A physician-sponsored Phase 1 trial of WP1066 for recurrent malignant glioma has generated pharmacokinetic data demonstrating sufficient bioavailability via oral administration[125] - The combination of WP1066 and WBRT resulted in enhanced median survival time in the GL261 glioma model, with a p-value of <0.0001 compared to monotherapy[128] - The Emory trial for pediatric brain tumors has treated three subjects, with one subject showing clinical improvement and a radiologic reduction of tumor size[130] Market Opportunities and Competition - The American Cancer Society estimates 1.9 million new cancer cases and 609,360 cancer deaths in the US for 2022, highlighting the significant market opportunity for oncology drugs[151] - The market for acute myeloid leukemia (AML) therapies is projected to grow from $153 million in 2016 to $1.6 billion by 2025, with the US holding the largest share[153] - The market for soft tissue sarcoma (STS) with lung metastases is expected to increase from $177 million in 2017 to $198 million by 2030[159] - The incidence of cutaneous T-cell lymphoma (CTCL) is estimated to grow from 16,000 in 2020 to 18,000 by 2026, with a significant unmet need for effective treatments[168] - There are currently 551 ongoing clinical trials for pancreatic cancer, indicating intense competition in this therapeutic area[199] Regulatory and Development Challenges - Regulatory approvals for pharmaceutical products are extensive and can be costly and time-consuming, impacting development timelines[204] - The FDA aims to complete the NDA review within 10 months of the 60-day filing date, which translates to within 12 months of submission, although this deadline may be extended under certain circumstances[215] - The FDA may grant Accelerated Approval based on data demonstrating an effect on a surrogate endpoint that is likely to predict clinical benefit[218] - The FDA may require a risk evaluation and mitigation strategy (REMS) to ensure the safe use of the product[217] - The submission of an NDA is subject to a substantial fee under the Prescription Drug User Fee Act (PDUFA), which may be waived under certain circumstances[214]
Moleculin(MBRX) - 2021 Q4 - Annual Report