On August 10, 2023 Moleculin Biotech, Inc., (Nasdaq: MBRX) (Moleculin or the Company), a clinical stage pharmaceutical company with a growing pipeline, including Phase 2 clinical programs, for hard-to-treat cancers and viruses, reported an update on recent activity and expected near term milestones across its clinical development pipeline (Press release, Moleculin, AUG 10, 2023, View Source [SID1234634200]).
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"We continue to make solid progress across our development pipeline and ongoing clinical trials and are extremely encouraged by our Annamycin AML and STS programs. Our team remains focused on executing our clinical development and driving recruitment forward in our three ongoing Phase 1b/2 clinical trials to meet the milestones ahead for each program. With the data Annamycin continues to generate, we are excited about the potential for further positive data readouts throughout the remainder of 2023," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin. "Additionally, we continue to have encouraging discussions for externally funded, investigator-initiated trials and believe we are well positioned to bring those discussions to fruition in 2023. I believe Moleculin is poised to build on its momentum and maximize value for both patients and shareholders."
Ongoing Clinical Trial Updates
Next Generation Anthracycline – Annamycin
Annamycin is the Company’s next-generation anthracycline that has been designed to be non-cardiotoxic (unlike currently prescribed anthracyclines) 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. An independent expert has reported no signs of cardiotoxicity in the first 42 subjects in the Company’s three clinical trials, which total includes 32 subjects treated over the lifetime maximum anthracycline dose set by the U.S. Food and Drug Administration (FDA). Annamycin is currently in development for the treatment of STS lung metastases (STS lung mets) as well as both first line therapy and therapy for relapsed or refractory acute myeloid leukemia (AML), and the Company believes the drug may have the potential to treat additional indications.
STS Lung Mets
The Company is currently in the Phase 2 portion of its ongoing U.S. Phase 1B/2 clinical trial evaluating Annamycin for the treatment of soft tissue sarcoma lung metastases (MB-107). clinicaltrials.gov: NCT04887298
Recent Activity Highlights
In the ongoing Phase 2 portion of the study, to date fifteen subjects have been enrolled and treated. Thirteen subjects have been treated with at least two cycles of therapy at the confirmed Recommended Phase 2 Dose (RP2D) of 330 mg/m2 and are evaluable for efficacy. One subject was withdrawn from the study prior to receiving a scan due to the clinician’s assessment. Per the protocol, follow-up imaging and RECIST evaluation is required for a subject to be included in the efficacy population. One subject is pending initiation of the cycle 2 treatment.
Including the three subjects treated at the same dose in the Phase 1B portion of this trial, this equates to fifteen total subjects measurable for efficacy at the 330 mg/m2 dose level. Including all measurable subjects at all dose levels in the Phase 1B portion of the trial, there have been thirty-one subjects treated with at least one cycle in this study and twenty-six have received two cycles of treatment. For these subjects, the median time to entering the MB-107 trial from the time of initial diagnosis is estimated to be approximately 20 months, and these subjects have been mostly heavily treated previously for STS lung mets prior to entering the study.
To date, 67% of the fifteen subjects receiving 330 mg/m2 and that have received end of cycle 2 scans in Phase 1B and Phase 2 have exhibited stable disease (SD) after receiving two cycles. The study has one subject who has not received end of cycle 2 scans and remains to be evaluated. Of the thirty-one subjects in the Phase 1B and Phase 2 portions of the study, 73% (n=26) have exhibited SD after receiving two cycles. Some subjects are continuing with the study so, SD continues to be monitored, and overall survival is being followed for the study. These data are preliminary and subject to change.
An investigator sponsored Phase 1B/2 clinical trial was initiated in Poland in 2022 to study an alternative dosing regimen for Annamycin in the treatment of STS lung mets. This trial continues to enroll subjects and began dosing subjects in late 2022.
AML
The Company is currently conducting its Phase 1B/2 clinical trial 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 as both first line therapy and for subjects who are refractory to or relapsed after induction therapy (MB106). clinicaltrialsregister.eu: EudraCT 2020-005493-10 or clinicaltrials.gov: NCT05319587
Recent Activity Highlights
Announced the publication of data from the successfully completed MB-105 European Phase 1 clinical trial assessing the safety and efficacy of Annamycin as a single agent for the treatment of adults with relapsed or refractory AML. The manuscript titled, "Results of a Phase 1 Study of Liposomal Annamycin for the Treatment of Relapsed or Refractory AML Patients After Induction Therapy," was published in the peer-reviewed British Journal of Cancer Research.
The MB-106 clinical trial began dosing subjects in March 2023. Six clinical sites in Poland and Italy have been activated for the MB-106 trial. The Company is planning for a total of up to eleven sites in the European Union (EU).
In May 2023, the Company announced the completion of the first cohort in the Phase 1B portion of the MB-106 study. In the first cohort, three subjects were treated, all of whom are relapsed from one or more prior therapies. Annamycin was dosed at 190 mg/m2, along with Cytarabine at 2.0 g/m2/day for five days (total dose of 10 g/m2), consistent with the familiar 7+3 regimen, combining daunorubicin and Cytarabine, typically used as a first-line induction therapy. In the Company’s study therapy Annamycin replaces daunorubicin. The Company, at the recommendation of the data safety committee, deemed the first cohort dose as safe and opened the second cohort with the Annamycin dose being increased to 230 mg/m2.
The median of prior therapies for these three subjects were five (one to seven). One of the subjects, who was 78 years of age at the time of the study initiation and enrolled after a single prior multi-year therapy, achieved a complete response (CR) that has continued to be durable at five months. The other two subjects were shown to have disease progression.
On August 7, 2023, Moleculin successfully and safely completed the second cohort at 230 mg/m2 of Annamycin in this combination study. In the second cohort four subjects were treated, one who is believed to be relapsed from multiple prior therapies and three of whom are believed to be refractory from up to three prior therapies. One subject was replaced due to a Serious Adverse Event (SAE) experienced on Day 1 of dosing. The SAE was determined to be unrelated to Annamycin and definitively related to Cytarabine. The Company, at the recommendation of the safety review committee, deemed the second cohort dose as safe and opened recruitment to the Phase 2 portion of the trial. In light of the encouraging efficacy seen throughout the Phase 1B portion of this trial and the final (240 mg/m2) cohort of the MB-105 single agent trial, the safety review committee have concluded (and the Company concurs) that the Phase 2 portion should be conducted at the 230 mg/m2 level of Annamycin dosing.
The median of prior therapies for the three evaluable subjects in the second cohort were two (one to three) and the median age was 67 years of age. One of the subjects, who was 64 years of age at the time of the study initiation with one prior therapy, was preliminary recorded as a complete response with an incomplete recovery of the bone marrow or CRi per the protocol. The other two subjects were shown to have disease progression.
This brings the total CR or complete response with incomplete recovery of peripheral blood count (CRi) out of the Phase 1B portion of this combination trial to two out of six subjects or 33%. The median age of these subjects was 66 years of age.
These data are preliminary and subject to change.
Expected Upcoming Milestones
STS (U.S.): Report Phase 2 interim data.
STS (U.S.): Present a more in-depth review of the topline data on progression free survival, overall survival after entering the study, overall survival, and other data on this study in 2H 2023.
AML: Present CSR for MB-105 Phase 1 results at an upcoming conference.
AML: Updates on the Phase 2 portion of MB-106 on a quarterly basis.
Flagship Immune/Transcription Modulator – WP1066
Moleculin is in ongoing discussions with multiple academic institutions in separate programs evaluating WP1066 for the treatment of glioblastomas and/or pediatric brain tumors. The Company expects to finalize agreements with Northwestern University and FDA filings in the second half of this year (Clinicaltrials.gov ID: NCT05879250).
Recent Activity Highlights
Ongoing progress in development of an intravenous formula for WP1066.
The Company supplied drug product to an externally funded pediatric brain tumor trial with WP1066 up to its conclusion in February 2023 and expects additional externally funded clinically trials for WP1066 (in combination with radiation) in 2023 in the U.S. and, possibly, in Southeast Asia.
Expected Upcoming Milestones
Report topline results from investigator-initiated Phase 1 study in pediatric brain tumors.
Seek external funding opportunities for an investigator-initiated clinical trial in adult and pediatric cancer patients in 2023.
Announce progress regarding an IV formulation by the end of 2023.
Metabolism/Glycosylation Inhibitor – WP1122 Portfolio
WP1122 was developed as a prodrug of 2 deoxy-D-Glucose (2-DG) to provide a more favorable pharmacological profile and was found to have greater potency than 2-DG monotherapy 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, filoviruses, Zika virus, and HIV. The Company looks forward to the potential of additional externally funded research to confirm such activity.
Expected Upcoming Milestones
Report preliminary findings of National Institutes of Health (NIH) funded animal testing of WP1096 in the Tacaribe Arenavirus.
Identify investigators interested in initiating a clinical trial to study the safety, pharmacokinetics and efficacy of oral WP1122 in adult patients with GBM.
General Information on the Company’s Core Technologies
Annamycin currently has Fast Track Status (FTS) and Orphan Drug Designation (ODD) from the FDA for the treatment of soft tissue sarcoma, in addition to ODD for the treatment of acute myeloid leukemia. WP1066 has ODD for the treatment of GBM and has four indications designated for the FDA Rare Pediatric Disease Priority Review Voucher (PRV) Program. WP1122 has ODD and FTS for GBM, as well. For more information about the Company’s trials, please visit clinicaltrials.gov.