On November 10, 2022 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported its financial results for the quarter ended September 30, 2022 and provided a pipeline update (Press release, Moleculin, NOV 10, 2022, View Source [SID1234623714]). As previously announced, the Company will host its inaugural quarterly conference call and live audio webcast, today, November 10, 2022, at 5:00 PM ET (details below).
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"We have made fundamental progress across our pipeline this past quarter. Of note, we have three active Phase 1/2 clinical trials for Annamycin and patients treated thus far continue to demonstrate no evidence of cardiotoxicity. Additionally, we have gained valuable insight in all of our ongoing development programs and are well-positioned to successfully execute operationally through the remainder of the year. Looking ahead, as we continue delivering on our initiatives, I believe the fourth quarter is poised to be an exciting conclusion of a transformational year and foundational for what is to come," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin.
Recent Highlights
Opened enrollment in the Phase 1/2 Study of Annamycin in combination with cytarabine for the treatment of Acute Myeloid Leukemia ("AML") in Europe.
Initiated and began dosing in the Phase 2 portion of the U.S. Phase 1b/2 clinical trial evaluating Annamycin for the treatment of soft tissue sarcoma lung metastases ("STS lung mets").
An investigator-funded, second Phase 1b/2 clinical trial of Annamycin in STS lung mets in Europe was commenced and began dosing.
Continued expanding the safety profile of Annamycin with a third report from an independent cardiology expert assessing recent subjects. This assessment again confirmed that there was no evidence of cardiotoxicity associated with Annamycin. This brings the total to 42 subjects where no evidence of cardiotoxicity has been identified by an independent expert cardiologist.
Enrolled what is expected to be the final subject in the Phase 1 portion of a clinical trial of WP1066 being conducted in collaboration with Emory University for the treatment of pediatric brain tumors, including medulloblastoma and diffuse interstitial pontine glioma ("DIPG").
Concluded Phase 1a first-in-human clinical trial of WP1122 for the treatment of COVID-19 in the United Kingdom establishing a safe and tolerable dose in healthy volunteers.
Announced the selection of WP1096 (a compound in the WP1122 portfolio) as novel potential antiviral, by the National Institute of Allergy and Infectious Diseases ("NIAID"), part of the National Institutes of Health ("NIH"), for NIH-funded animal studies.
Received U.S. Food and Drug Administration ("FDA") Orphan Drug Designation of WP1122 for the treatment of Glioblastoma Multiforme ("GBM").
Pipeline Update
Next Generation Anthracycline – Annamycin
Annamycin is the Company’s next-generation anthracycline that has been designed to be non-cardiotoxic and has been shown in animal models to accumulate in the lungs at up to 30-fold the level of doxorubicin (a commonly prescribed anthracycline), as well as demonstrating the ability to avoid the multidrug resistance mechanisms that typically limit the efficacy of doxorubicin and other currently prescribed anthracyclines. Annamycin is currently in development for the treatment of relapsed or refractory AML and STS lung metastases and the Company believes it may have the potential to treat additional indications.
STS Lung Mets
The Company recently initiated its Phase 2 portion of the U.S. Phase 1b/2 clinical trial evaluating Annamycin for the treatment of STS lung mets ("MB-107") and has begun enrollment and dosing.
In the Phase 1b portion of the study, 15 subjects were enrolled and treated per the protocol in four cohorts to determine the maximum tolerable dose and/or the RP2D. Each cohort had three subjects, except for the fourth cohort, which (per the protocol) was expanded to six subjects after a dose-limiting toxicity (DLT) occurred in a single subject. The Company concluded the Phase 1b portion after the fourth cohort of 390 mg/m2 was documented to be safe. Based on findings from the Phase 1b position of the trial, 360 mg/m2 demonstrated it may be tolerated by subjects initially, however continued treatment was deemed at risk to be delayed or interrupted due to adverse events (primarily myelosuppression, which is anticipated with high doses of anthracycline therapy), hence lowering the dose from 360 mg/m2 to 330 mg/m2 was contemplated in advance of beginning the Phase 2 expansion pending results from the first three subjects in the expansion phase. Adverse Events, primarily myelosuppression, in the first three subjects at 360 mg/m2 led the Company to lower the RP2D to 330 mg/m2 in October 2022, which the Company believes will enable continued treatment of subjects with fewer interruptions.
The Company expects to treat at least 25 subjects in this Phase 2 portion of the clinical trial. For more information about the Phase 1b/2 study evaluating Annamycin for the treatment of STS lung mets, please visit clinicaltrials.gov and reference identifier NCT04887298.
Additionally, the investigator-funded, second Phase 1/2b clinical trial of Annamycin for the treatment of STS lung mets was recently initiated. The grant-funded clinical trial is being led by Prof. Piotr Rutkowski, MD, PhD, Head of Department of Soft Tissue/Bone Sarcoma and Melanoma at the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland. The trial will use a dosing regimen of once weekly for three weeks in a 28-day cycle rather than once every 21 days as in the US trial. Two subjects have been dosed to date.
AML
Patient enrollment and screening has been initiated in the Company’s Phase 1/2 clinical trial in Poland evaluating Annamycin in combination with Cytarabine (also known as "Ara-C" and for which the combination of Annamycin and Ara-C is referred to as AnnAraC) for the treatment of subjects with AML who are refractory to or relapsed after induction therapy ("MB-106"). Ongoing efforts to open additional clinical sites in Poland and other European countries for the MB-106 clinical trial are underway.
Annamycin currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of STS lung metastases, in addition to Orphan Drug and Fast Track Designation for the treatment of relapsed or refractory AML.
Upcoming Milestones Expectations
Q4 2022: Commence dosing and open additional clinical sites in Poland and other European countries in the Phase 1/2 study of Annamycin in combination with Ara-C in Acute Myeloid Leukemia.
Q1 2023: Report Phase 2 interim data from ongoing Phase 1b/2 study of Annamycin for the treatment of STS lung mets in the US and Europe.
Flagship Immune/Transcription Modulator – WP1066
WP1066 is designed to stimulate the immune response to tumors by inhibiting the errant activity of Regulatory T-Cells (Tregs) while also inhibiting key oncogenic transcription factors, including p-STAT3 (phosphorylated signal transducer and activator of transcription 3), c-Myc (a cellular signal transducer named after a homologous avian virus called Myelocytomatosis) and HIF-1α (hypoxia inducible factor 1α). These transcription factors are widely sought targets that are believed to contribute to an increase in cell survival and proliferation, and the angiogenesis (coopting vasculature for blood supply), invasion, metastasis and inflammation associated with tumors. They may also play a role in the inability of immune checkpoint inhibitors to affect more resistant tumors.
Moleculin is in ongoing discussions with multiple academic institutions in separate programs evaluating WP1066 for the treatment of brain tumors. The Company expects the investigator-sponsored clinical trials or programs for the treatment of adult and pediatric brain tumor to commence in the first half of 2023.
Additionally, WP1066 is currently being evaluated in collaboration with Emory University for the treatment of pediatric brain tumors, including medulloblastoma and DIPG. In October 2022, the Emory trial enrolled the last subject in the last cohort at 8 mg/kg. Discussions are underway to explore WP1066 in combination with radiation on similar tumors in a Phase 2 clinical trial in the near future.
In April 2022, the Company received IND clearance from the FDA to conduct a Phase 1 study of WP1066 for the treatment of recurrent malignant glioma. Since that time, the Company has been evaluating strategic partnerships and collaborations to utilize this IND. WP1066 has received Orphan Drug Designation for the treatment of brain tumors, as well as Rare Pediatric Disease designation for three other pediatric indications. Additionally, WP1066 + radiation is being evaluated, pre-clinically, in the treatment of Glioblastoma Multiforme (GBM).
Upcoming Milestones Expectations
H1 2023: Commencement of investigator-sponsored clinical trials or programs for the treatment of adult and pediatric brain tumors.
Metabolism/Glycosylation Inhibitor – WP1122 Portfolio
WP1122 was developed as a 2-DG prodrug to provide a more favorable pharmacological profile and was found to have greater potency than 2-DG alone in preclinical models where tumor cells require higher glycolytic activity than normal cells. WP1122 has also been shown to have a greater antiviral effect than 2-DG against SARS-CoV-2 in MRC-5 cells in culture. The improved pharmacokinetic and pharmacodynamic (PK/PD) profile of WP1122 compared to 2-DG was noted in mice following oral dosing at equimolar (i.e., equivalent levels of 2-DG) doses. The WP1122 Portfolio includes numerous analogs, including WP1096, which has demonstrated the potential for broad antiviral capabilities in a wide range of in vitro models including multiple arenaviruses, Zika virus, and HIV.
Glioblastoma Multiforme
In September of 2022, Moleculin was granted Orphan Drug Designation of WP1122 for the treatment of GBM from the FDA. Additionally, based on preclinical data indicating the potential for WP1122 as a treatment for GBM, Moleculin received FDA clearance of its Investigational New Drug application to initiate a Phase 1 open label, single arm, dose escalation study of the safety, pharmacokinetics and efficacy of oral WP1122 in adult patients with GBM. The Company is currently evaluating opportunities for collaboration in clinical development.
COVID-19
In October 2022, the Company concluded its Phase 1a, first-in-human, randomized, double-blind, placebo-controlled, overlapping SAD and MAD clinical trial investigating the effects of WP1122 administered as an oral solution in healthy human volunteers. A safe and tolerable dose was established for WP1122 in this trial, which now provides a starting point for a range of potential Phase 2 clinical trials. Approximately 80 subjects were enrolled in the trial.
Upcoming Milestones Expectations
Identify investigators interested in initiating a Phase 1 open label, single arm, dose escalation study of the safety, pharmacokinetics and efficacy of oral WP1122 in adult patients with GBM.
Report preliminary findings of NIH-funded animal testing of WP1096 in the Tacaribe Arenavirus by the end of the first quarter 2023.
Summary of Financial Results for the Third Quarter 2022
Research and development (R&D) expense was $14.8 million and $11.2 million for the nine months ended September 30, 2022 and 2021, respectively. The increase of $3.6 million is mainly related to increased clinical trial activity as described above, a license termination fee, and costs related to manufacturing of additional drug product.
General and administrative expense was $8.7 million and $6.4 million for the nine months ended September 30, 2022 and 2021, respectively. The increase of $2.3 million is mainly related to an increase in regulatory and legal services, consulting and advisory fees.
For the nine months ended September 30, 2022 and 2021, the Company incurred net losses of $22.3 million and $13.1 million, respectively, and had net cash flows used in operating activities of $20.4 million and $14.7 million, respectively.
The Company ended the quarter with $50.4 million of cash. The Company believes that this cash is sufficient to meet its projected operating requirements, which include a forecasted increase over its current R&D rate of expenditures, beyond mid-2024.
Conference Call and Webcast
Moleculin management will host its inaugural quarterly conference call and live audio webcast for investors, analysts, and other interested parties today, Thursday, November 10, 2022, at 5:00 PM ET.
Interested participants and investors may access the conference call by dialing (877) 407-0832 (domestic) or (201) 689-8433 (international) and referencing the Moleculin Biotech Conference Call. The live webcast will be accessible on the Events page of the Investors section of the Moleculin website, moleculin.com, and will be archived for 90 days.