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Item 2. Management’s Discussion and Analysis

2025-05-13 compared with 2024-11-08 · 157 added, 212 removed, 86 unchanged (81% of the section changed)

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Forward-looking statements include, but are not limited to, statements about:

Our ability to continue our relationship with MD Anderson, including, but not limited to, our ability to maintain current licenses and license future intellectual property resulting from our sponsored research agreements with MD Anderson;

Our ability to continue our relationship with the University of Texas MD Anderson Cancer Center (MD Anderson), including, but not limited to, our ability to maintain current licenses and license future intellectual property resulting from our sponsored research agreements with MD Anderson;

The success or the lack thereof, including the ability to recruit subjects on a timely basis, for a variety of reasons, of our clinical trials through all phases of clinical development;

20 unchanged sentences

Furthermore, we cannot guarantee future results, events, levels of activity, performance, or achievements.

We are a Phase 3 clinical stage pharmaceutical company with a portfolio of technologies for hard-to-treat cancers and viruses.

We have three core technologies, each of which have had one or more drugs successfully complete a Phase 1 clinical trial, based substantially on discoveries made at and licensed from the University of Texas MD Anderson Cancer Center (MD Anderson) in Houston, Texas.

We are a late-stage pharmaceutical development company currently conducting a pivotal Phase 3 trial evaluating Annamycin (also known by its non-proprietary name "naxtarubicin") in combination with Cytarabine for the treatment of subjects with relapsed/refractory (R/R) acute myeloid leukemia (AML).

This Phase 3 trial should have an interim unblinding of data by the end of 2025, less than a year from its commencement, and an additional unblinding in the first half of 2026.

We believe such early visibility for a pivotal registration-enabling trial is highly unique in that stakeholders will receive preliminary safety and efficacy data in the “MIRACLE” trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) within one year of dosing the first subject.

Additionally, we have two portfolios of technologies for hard-to-treat cancers and viruses with clinical and preclinical research funded by investigators at academic institutions.

Each of our three core technologies is based substantially on discoveries made at and licensed from MD Anderson in Houston, Texas, and features one or more drugs that have successfully completed a Phase 1 clinical trial.

Three of our six drug candidates have shown human activity in clinical trials and are currently or have been in Phase 1B/2 or Phase 2 clinical trials.

One Phase 2B/3 trials is currently underway.

Since our inception, our drugs have completed, are currently in, or have been permitted to proceed in, fourteen clinical trials.

Annamycin is our lead molecule and we have recently concluded one Phase 1B/2 clinical trial for treating Acute Myeloid Leukemia (AML) and are embarking on a Phase 3 clinical trial for the treatment of AML, which we believe will be pivotal.

Annamycin is also in two Phase 1B/2 clinical trials for treating Soft Tissue Sarcoma metastasized to the lungs (STS lung metastases, STS lung mets, or Advanced STS).

One of our core management beliefs is that anthracyclines represent the most important treatment for AML and Advanced STS, and we believe Annamycin may, for the first time ever, allow a majority of these patients to benefit from this treatment, mainly due to its lack of cardiotoxicity (which is found in currently prescribed anthracyclines) and its ability to avoid multidrug resistance mechanisms.

Annamycin is in a class of drugs referred to as Anthracyclines, which are inhibitors of topoisomerase II, enabling them to cause DNA damage in rapidly replicating tumor cells.

Annamycin, in a unique multilamellar lipid formulation, is our lead molecule and we have recently concluded treating subjects in one Phase 1B/2 clinical trial for treating Acute Myeloid Leukemia (AML) and are embarking on a Phase 3 clinical trial for the treatment of AML, which we believe will be pivotal.

Annamycin has also been in two Phase 1B/2 clinical trials for treating Soft Tissue Sarcoma metastasized to the lungs (STS lung metastases, STS lung mets, or Advanced STS).

Our Phase 1B/2 STS lung mets trial MB-107 is completed, and a clinical study report has been issued.

The other trial is an investigator initiated Advanced STS trial which is closed to recruitment.

One of our core management beliefs is that anthracyclines represent one of the most important treatments for AML and Advanced STS, and we believe Annamycin may, for the first time ever, allow a majority of these patients to benefit from this treatment.

We believe that such a benefit could be disruptive to the competitive landscape for these markets.

This belief, coupled with our limited resources, leads us to currently focus mainly on the development of Annamycin.

We intend to advance our other drug candidates via investigator led studies – both clinically and preclinically.

Our Core Technologies

Focus and Core Technologies

Our core technologies consist of the following programs:

a) Annamycin or L-Annamycin is a “next generation” anthracycline (one of the most widely used classes of chemotherapy), designed to be different than currently approved anthracyclines, which are limited in utility because of cardiotoxicity risks and their susceptibility to multidrug resistance mechanisms.

Annamycin was designed to avoid multidrug resistance and to be non-cardiotoxic and, with intensive cardiac monitoring, has shown no cardiotoxicity in subjects treated in our four Annamycin clinical trials to date.

Furthermore, we have demonstrated safe dosing significantly beyond the dose limitations imposed by regulatory authorities upon commonly prescribed anthracyclines due to their inherent cardiotoxicity.

Annamycin has demonstrated efficacy in two of its Phase 1B/2 trials in subjects with AML and Advanced STS.

We believe that Annamycin has potential to fill an unmet need as a second line therapy (2nd line or 2L) in AML and potentially as first line therapy in Advanced STS.

As part of our Annamycin clinical trials, we have engaged an independent expert to assess cardiotoxicity associated with chemotherapy at the Cleveland Clinic (Expert or Independent Expert).

The data made available to the Expert include left ventricular ejection fraction (LVEF) as determined by echocardiograms, and ECHO strain imaging, as well as serum Troponin levels (a biochemical marker of acute heart damage).

“ECHO strain imaging” is a method in echocardiography (medical ultrasound) for measuring regional or global deformation (contraction or beating) of the myocardium (heart muscle).

By strain rate imaging, the simultaneous function of different regions can be displayed and measured.

Cardiac health biomarkers such as blood Troponin levels are considered an indicator of potential long-term heart damage.

The Expert has issued and will continue to issue periodic reports as additional data are provided to him in batches of subject data.

Such data include some data which are preliminary and subject to change.

In our discussions regarding the lack of Annamycin's cardiotoxicity, we rely on the Expert's assessment.

Annamycin benefits from a promising advancement in lipid enabled drug delivery developed in collaboration with and exclusively licensed from MD Anderson.

The unique patented lipid composition allows us to combine a new concept in chemotherapeutic agents within a lipid structure that helps target the delivery of the payload and reduce the potential for toxicity.

In the case of Annamycin, our unique use of lipid technology enables improved tissue/organ distribution, and as demonstrated in multiple clinical trials, dramatically reduced toxicity, including cardiotoxicity.

Annamycin has composition of matter patent protection through 2040.

Furthermore, we have demonstrated safe dosing significantly beyond the lifetime dose limitations imposed by regulatory authorities upon commonly prescribed anthracyclines due to their inherent cardiotoxicity.

b) Our WP1066 Portfolio includes WP1066, WP1193 and WP1220, three of several Immune/Transcription Modulators in the portfolio designed to inhibit p-STAT3 (phosphorylated signal transducer and activator of transcription 3) among other transcription factors associated with tumor activity.

These also stimulate a natural immune response to tumors by inhibiting the errant activity of Regulatory T-Cells (TRegs).

WP1066, in oral formulation, has been in two clinical trials for central nervous system (CNS) tumors, including compassionate use cases, in pediatric subjects.

WP1066 and WP1193 are being tested in preclinical programs in intravenous (IV) formulations.

WP1066 and WP1220 have been in clinical trials in a topical formulation.

WP1066 and WP1220 have both independently successfully completed Phase 1 clinical trials and have demonstrated efficacy in their varied indications.

c) Our WP1122 Portfolio contains compounds (including WP1122, WP1096, and WP1097) designed to exploit the potential uses of inhibitors of glycolysis such as 2-deoxy-D-glucose (2-DG).

We believe such compounds may provide an opportunity to cut off the energy supply of tumors by taking advantage of their high degree of dependence on glucose in comparison to healthy cells, as well as viruses that also depend upon glycolysis and glycosylation to infect and replicate.

WP1122 has completed a Phase 1 clinical study in normal volunteers, successfully establishing a Recommended Phase 2 Dose or RP2D.

Annamycin and the Lack of Cardiotoxicity

As part of our Annamycin clinical trials, we have engaged an independent expert at the Cleveland Clinic to assess cardiotoxicity associated with chemotherapy (Expert or Independent Expert).

“ECHO strain imaging” is a method in echocardiography (medical ultrasound) for measuring regional or global deformation (contraction or beating) of the myocardium (heart muscle).

By strain rate imaging, the simultaneous function of different regions can be displayed and measured.

Cardiac health biomarkers such as blood Troponin levels are considered an indicator of potential long-term heart damage.

The Expert issued periodic reports during our MB-106 clinical trial and will also issue updated reports after each unblinding in the Phase 2B portions of the MIRACLE trial.

Such data from clinical trials where a clinical study report has not yet been issued include some data which are preliminary and subject to change.

We received several independent assessments for the absence of cardiotoxicity in subjects treated with Annamycin.

We now have independent assessments covering 84 subjects that have been treated with Annamycin in five different clinical trials in the U.S.

and Europe with no evidence of cardiotoxicity.

To date of the 77 subjects treated in our internally funded trials, 56 were treated above the FDA’s lifetime maximum anthracycline limit of 550 mg/m 2 , including one subject whose repeated Annamycin treatments took that subject to a total cumulative anthracycline exposure of 3,420 mg/m 2 (or roughly five times the FDA approved lifetime anthracycline exposure) and there has been no evidence of cardiotoxicity reported.

After review of the data provided, the Independent Expert, in their most recent report and as stated in previous reports, concluded that there was no evidence of drug-related cardiotoxicity in any subjects.

We believe the Expert's reports are particularly relevant in light of a recently published retrospective study showing that the incidence of heart failure more than doubles for cancer patients treated with anthracyclines compared to cancer patients not receiving anthracyclines (C Larson, et al.

Anthracycline and Heart Failure in Patients Treated for Breast Cancer or Lymphoma, 1985-2010.

JAMA Network Open.

2023;6(2):e2254669.

doi:10.1001/jamanetworkopen.2022.54669).

Given the heart-damaging impact of prior treatment with currently prescribed anthracyclines, and considering that the subject population that we are enrolling in our Annamycin trials (multiple prior therapies, including anthracyclines known to be cardiotoxic, many elderly, and other comorbidities) we believe that there is a high likelihood that a cardiac event will eventually occur in the future that we will not be able to disassociate from Annamycin.

We believe that the potential for such future incidences, however, does not outweigh the significant lack of cardiotoxicity to date as reflected in the Expert’s reports.

Although we have not definitively concluded that Annamycin is incapable of cardiotoxicity, we discuss Annamycin’s lack of demonstrated cardiotoxicity in this document, corporate presentations and other public communications.

Such discussions reflect the information in the preceding paragraphs but in summary are based on the following:

1) Annamycin was initially designed to be non-cardiotoxic;

2) Preclinical studies have demonstrated Annamycin lacks cardiotoxicity as compared to a currently prescribed anthracycline;

and, 3) Our Expert’s conclusions from analyzing the data from 84 subjects treated with Annamycin in five clinical studies conducted in the US and in Europe.

Our discussions will reflect any additional data or analyses as they become available.

Clinical Trials Summary

We have multiple active INDs/CTAs ("Investigational New Drug" authorization in the US or "Clinical Trial Authorization" in Europe).

These INDs/CTAs are under development, approved, in progress, or completed and comprise a total of fourteen clinical trials, internally and externally funded.

With Annamycin, we currently have active two AML clinical trials:

MB-106 which is a Phase 1B/2 treating AML with AnnAraC (recruitment is closed and this trial is now in subject follow-up) and MB-108 which is a Phase 2B/3 pivotal clinical trial treating R/R AML as 2 nd line therapy (recruitment has started and additional sites are being added).

Additionally, there is one externally funded Phase 1B/2 trial treating STS Lung Mets with Annamycin as monotherapy.

This trial is closed and is in follow-up on the trial’s subjects.

With WP1066, we have an externally funded Phase 1B/2 trial in combination with radiation treating GBM at Northwestern University that is actively recruiting.

MIRACLE Trial

We have a Phase 3 pivotal trial for the treatment of AML patients who are R/R after induction therapy with Annamycin in combination with Cytarabine.

This Phase 3 “MIRACLE” trial is a global study.

It is an adaptive trial designed with a lead-in Part A portion of the study having three arms (control arm with cytarabine, and two test arms with cytarabine plus two different doses of Annamycin) intended to determine an “optimum dose” to be used in Part B of the study.

Once an optimum dose for the Annamycin is determined the study will continue into Part B with two arms (control arm with cytarabine and a test arm with cytarabine plus Annamycin).

In some contexts, we refer to Part A as Phase 2B and Part B as Phase 3, however the adaptive design enables the combining of data from Part A (for the optimum dose) with Part B such that data from both parts A and B will comprise Phase 3 data.

Recent Business Developments

Below are recent business developments.

Phase 3 MIRACLE Trial

We are in the process of evaluating and visiting potential sites for our Phase 3 pivotal trial for the treatment of AML patients who are refractory to or relapsed after induction therapy (R/R AML) with 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”).

This Phase 3 “MIRACLE” trial (derived from (M)olecul(i)n (R)/(r) AML (A)nnAraC (Cl)inical (E)valuation) will be a global trial.

We plan to focus on sites in the North America, Europe, Eastern Europe, Western Asia, and MENA (Middle East and Africa) for the initial Part A of MIRACLE.

Our initial target will be approximate ly 45 sit es.

We expect that this will enable the enrollment of approximately 45 subjects by the third quarter of 2025 and approximately 90 subjects by the second half of 2026.

The data may also be unblinded after the initial 45 subjects and, as currently planned, the data will be unblinded after approximately 90 subjects complete their efficacy analyses.

We believe that we will have the data for approximately the first 90 subjects by the second half of 2026.

The trial is designed to enable the review of interim analyses for safety and efficacy upon reaching these enrollment milestones.

We held a conference call on August 6, 2024, along with Dr.

Michael Andreeff, a member of our Science Advisory Board, to discuss the results of our most recent meeting with the FDA and the plans for the MIRACLE trial.

That meeting, the MIRACLE trial and the current data from the MB-106 trial are discussed further below.

On August 1, 2024, we announced the discussion in and our resulting plans from our End of Phase 1B/2 (EOP1B/2) meeting held in late June with the FDA supporting the advancement of Annamycin in combination with Cytarabine (AnnAraC to a Phase 3 pivotal trial for the treatment of AML patients who are refractory to or relapsed after induction therapy (R/R AML).

This Phase 3 “MIRACLE” trial will be a global study, including sites in the US and consistent with the FDA’s recommendations, the adaptive Phase 3 trial is expected to rely solely on CR (complete remission) at day 35 (+/- 14 days) as the primary endpoint versus the control arm.

We plan to utilize a double-blind, placebo-controlled design, where the control arm is high dose cytarabine (HiDAC) plus placebo.

The MIRACLE trial will focus on AnnAraC as a 2 nd line treatment for R/R AML subjects, with a subsequent trial to be focused on AnnAraC as a 3 rd line treatment for R/R AML.

Based on our discussions with the FDA, we intend to amend our current investigational new drug application or IND to allow dosing above the lifetime maximum allowable dose (LTMAD) for currently prescribed anthracyclines in this trial in the US.

The MIRACLE study, subject to appropriate future filings with and potential additional feedback from the FDA, their foreign equivalents and/or institutional review boards (IRBs), is expected to initially utilize an adaptive design whereby the first 90 subjects will be randomized to receive HiDAC combined with either placebo, 190 mg/m 2 of Annamycin, or 230 mg/m 2 of Annamycin with such doses recommended by the FDA based on their review of our safety and efficacy data.

At that point, the trial data will be unblinded to select the optimum dose for Annamycin.

For the second half of the trial, approximately 240 subjects will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimum dose of Annamycin.

The selection of the optimum dose by the independent Data Monitoring Committee will be based on the overall balance of efficacy, safety, and pharmacokinetics, consistent with the FDA’s new Project Optimus initiative.

We believe the FDA wants to see the durability of response (DoR) and overall survival (OS) as secondary endpoints.

In addition, we believe the FDA wants to see data for subjects beyond 2 nd line and, accordingly, our plan includes a follow-on MIRACLE2 trial in 3 rd line subjects starting once the optimum dose is established in the MIRACLE trial.

We have established plans for the following milestones with regard to the MIRACLE trial:

2024 2H – Begin contracting with MIRACLE trial sites

2025 Q1 – First subject treated in MIRACLE trial

2025 Q4 – Recruitment and interim data (n=~45)

2H 2026 – Interim efficacy and safety data (n=~90) unblinded and Optimum Dose set for MIRACLE trial

2027 – Begin enrollment of 3 rd line subjects in MIRACLE2

2027 – Enrollment ends in 2 nd line subjects

2028 – Primary endpoint efficacy data for 2 nd line subjects in MIRACLE

2028 2H – Begin submission of a new drug application (NDA) the treatment of R/R AML for accelerated approval on primary endpoint of CR from MIRACLE

Clinical Trial for the Treatment of AML in Combination with Cytarabine (MB-106)

Line of Therapy

All Lines (Range 1 st -7 th )

2 nd and 3 rd Line

Subjects Evaluable To Date

Subjects Evaluable Not Dosed Per Protocol

Median Age - Years (Range)

Complete Remission (CR)

Complete Remission Composite (CRc)

Partial Response (PR)

CRc Relapsed To Date

See Note 1 below

Note 1 for Table 1:

Data from MB-106 is for Intent To Treat (ITT) subjects;

is as of October 24, 2024;

and, is preliminary and subject to change.

Median Durability of all CRc's is ~8 months and climbing.

On May 7, 2024, our management held a Key Opinion Leader conference call with Dr.

Martin Tallman and Dr.

Michael Andreeff.

Management made a presentation of the data above and discussion ensued with Drs Tallman and Andreeff on the significance of this data.

Tallman and Andreeff are members of our Science Advisory Board.

The call included a discussion of the results to date for MB-106.

We believe that the Phase 1B/2 trial has been successful in establishing safety and efficacy of Annamycin in combination with Cytarabine (AnnAraC) for the treatment of AML, and in providing sufficient data to support a Phase 3 registration-directed clinical trial (MB-108) to further provide data for efficacy which we intend to use to support an eventual application for New Drug Approval (NDA).

Preliminary Safety, Efficacy and Durability Data

The preliminary data for MB-106 demonstrate a CR rate of 36% and a CRc rate of 41% for all subjects (N=22), regardless of the number of prior treatments, up to 6 prior treatments.

Segmenting the MB-106 subject population for 2 nd line subjects (N=10) yields a CR rate of 50% and CRc rate of 60%.

Further segmenting for 2 nd and 3 rd line subjects (N=14) yields a CR rate of 43% and a CRc rate of 50%.

We believe the results demonstrated by AnnAraC in 2 nd line subjects substantially exceeds the performance reported by any drug currently approved for use in 2 nd line AML.

Median durability of remission (DoR) for the 9 CRcs is approximately 8 months and developing.

The DoR is being measured from the initiation of treatment to relapse or death.

Cardiovascular safety of Annamycin is thoroughly monitored as independent assessments are made by an independent expert cardio-oncologist from Cleveland Clinic.

As of April 1, 2024, data from 84 subjects across five trials (AML & STS, internal and externally funded trials) have been reviewed.

Of note, most of these subjects have received greater than the lifetime cumulative anthracycline dose above 550 mg/m2 associated with increased risk of cardiomyopathy.

Some subjects have received four times this amount following Annamycin administration(s).

No signal of cardiotoxicity has been identified.

Annamycin as Monotherapy for the Treatment of Soft Tissue Sarcoma Lung Metastases

Additionally, we expect to release in the near future the topline data from the MB-107 trial with Annamycin for the monotherapy treatment of soft tissue sarcoma lung metastases.

This Phase 1B/2 clinical trial in the US is for subjects with STS lung metastases after first-line therapy for their disease.

The trial began in the first half of 2021.

The Phase 1B was concluded in July 2022.

On September 21, 2023, we announced the completion of enrollment in the Phase 2 portion of our U.S.

Phase 1B/2 clinical trial evaluating Annamycin as monotherapy for the treatment of soft tissue sarcoma lung metastases.

Subjects who had stable disease at the time of study discontinuation will continue to be followed for progression free response and overall survival.

The study database is locked and the clinical study report is being written and should be completed in early 2025 and will be released in detail at that time.

The total number of intent to treat subjects in the trial is 36.

U.S Patents for Annamycin

On April 9, 2024, the United States Patent and Trademark Office (USPTO) issued U.S.

Patent number 11,951,118 titled, “ Preparation of Preliposomal Annamycin Lyophilizate ” (the ‘118 patent’) to Moleculin and The University of Texas System Board of Regents.

Additionally on May 14, 2024, the USPTO issued an additional patent (U.S.

Patent number 11,980,634) titled “ Method of Reconstituting Liposomal Annamycin ” (the ‘634 patent’).

We have global, exclusive licenses to both patents.

The ‘118 patent provides claims to compositions that contain Annamycin, and the ‘634 patent, as issued, provides claims to liposomal Annamycin suspension compositions, both with a base patent term extending until June 2040, subject to extension to account for time required to fulfill regulatory requirements for FDA approval.

Moleculin’s novel candidate for the treatment of acute myeloid leukemia (AML) and soft tissue sarcoma lung metastases (STS lung mets) uses a unique lipid-based delivery technology.

In addition to the issued ‘118 and expected ‘634 U.S.

patents, we have additional patent applications pending in major jurisdictions worldwide.

EMA issues ODD to Annamycin for the treatment of AML

We announced that the European Medicines Agency (EMA) has granted Orphan Drug Designation (ODD) to Annamycin for the treatment of AML.

Combined with the Orphan Drug Designation we have in the US and with the new composition of matter and formulation patents just awarded by the US Patent and Trademark Office with coverage through 2040, we believe the commercial exclusivity of Annamycin is now well protected.

The EMA grants orphan drug designation to drugs and biologics intended for the treatment, diagnosis or prevention of rare, life-threatening or chronically debilitating diseases or conditions that affect fewer than five in 10,000 people in the European Union.

Orphan designation potentially allows companies certain benefits, including reduced regulatory fees, clinical protocol assistance, research grants and up to 10 years of potential market exclusivity in the European Union if approved.

Presentation at the International Association for the Study of Lung Cancer 2024 World Conference on Lung Cancer

On September 23, 2024, we announced positive in vivo efficacy data of Annamycin in orthotopic and experimental lung metastatic models of sarcoma at the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer.

Treatment with Annamycin resulted in statistically significant inhibition of tumor growth and extension of survival in orthotopic lung cancer models and continues to be 100% non-cardiotoxic.

The poster titled “ Annamycin:

Opening New Doors for Organotropic Targeting of Primary and Metastatic Lung Cancer , ” authored by Waldemar Priebe, PhD (Founder, Founding Scientist, and Chair of Scientific Advisory Board for Moleculin) and coworkers was presented at the IASLC 2024 World Conference on Lung Cancer.

The presented poster outlined results from the efficacy assessment studies of Annamycin, Moleculin’s next-generation anthracycline in orthotopic models of lung cancer and sarcoma lung metastasis models in comparison with doxorubicin (a commonly prescribed anthracycline.

Key Highlights of the Data Presented:

Annamycin demonstrated high uptake and retention in lung parenchyma of mice and rats.

The therapeutic effects of doxorubicin (DOX) are diminished due to low lung DOX uptake as demonstrated in the tested in vivo models.

In contrast, Annamycin exhibits consistent efficacy in vivo in orthotopic and experimental lung metastatic models of sarcoma, breast, and colon cancer.

This correlated with high Annamycin concentration in lungs, which exceeded DOX levels by 10- to 30-fold.

Preclinical tests clearly demonstrate a better cardiac safety profile of Annamycin when compared to DOX and no cardiotoxicity of Annamycin in the in vivo models.

No cardiotoxicity of Annamycin has been noted in ongoing clinical studies.

The observed organotropic properties of Annamycin, its efficacy in vivo , and its promising safety profile warrant further translational studies to evaluate Annamycin in patients with primary or metastatic lung cancers, as a single agent and in combination with currently used therapeutics.

AACR Presentation of Data Demonstrating High Anti-Cancer Activity of Annamycin and Non-Cardiotoxic Properties

Preclinical data regarding the Company’s next-generation anthracycline, Annamycin, was presented at the American Association for Cancer Research (AACR) Annual Meeting, which took place April 5-10, 2024 in San Diego, CA.

The poster titled, Non-cardiotoxic Properties of Annamycin, a Clinically Evaluated Anthracycline and Potent Topoisomerase 2β Poison, was presented in the “Late-Breaking Research:

Experimental and Molecular Therapeutics 2” session held on Monday, April 8 th .

The presented poster outlined results from the assessment and comparison of the potency of doxorubicin (a commonly prescribed anthracycline) and Annamycin, Moleculin’s next-generation anthracycline, against topoisomerase II-alpha and II-beta and determine their impact on physiology of human cardiomyocytes demonstrating no pathologic changes in mice hearts following chronic in vivo exposure.

We announced on September 9, 2024, the beginning of enrollment and treatment of patients in an investigator-initiated Phase 2 study evaluating WP1066 in combination with radiation therapy for the treatment of adults with glioblastoma (NU 21C06).

The study is being conducted under Northwestern University’s investigative New Drug application (IND) which cross references our own IND, which received clearance from the U.S.

Food and Drug Administration (FDA) in April 2022.

This trial is funded by the National Institutes of Health (NIH) and BrainUp®, a non-profit organization dedicated to bringing awareness to brain cancer.

The NU 21C06 trial is a Phase 2, open-label, multi-arm trial of radiation therapy in combination with WP1066 in newly diagnosed IDH (isocitrate dehydrogenase) wild-type, MGMT-unmethylated glioblastoma patients.

The primary outcome measure for the study is progression-free survival and secondary outcome measures include tumor microenvironment analysis.

Four subjects have been treated as of November 1, 2024.

Regarding an intravenous formula for WP1066, we are pursuing a new patent that is co-owned by us and MD Anderson.

We are in discussions regarding licensing or an option to license the MD Anderson rights to the new formulation.

With the data generated from the MB-301 clinical trial setting an RP2D for WP1122 and additional sponsored research, we continue to explore avenues of external funding for further development of this portfolio.

For this study, we submitted the final clinical study report in late October 2023.

General Business

Science Advisory Board Appointment

We announced on November 4, 2024, the appointment of Daniel D.

Von Hoff, M.D., F.A.C.P., FASCO, FAACR to our Annamycin Scientific Advisory Board.

Von Hoff currently serves as the Distinguished Professor at the Translational Genomics Research Institute (TGen) in Phoenix, Arizona and City of Hope.

August Issuance of Equity

On August 19, 2024, we announced the closing of our previously announced public offering of 283,000 shares of common stock and 2,183,368 pre-funded warrants to purchase shares of common stock, Series A warrants to purchase up to 2,466,368 shares of common stock and Series B warrants to purchase up to 2,466,368 shares of common stock, at a combined public offering price of $2.23 per share (or per common stock equivalent in lieu thereof) and accompanying warrants.

The Series A warrants have an exercise price of $2.23, are exercisable immediately upon shareholder approval (which was received in October 2024) and will expire upon the earlier of (i) the 2 year anniversary of the date of stockholder approval or (ii) the 60 th day following the date we release interim data for the first subject group from the MIRACLE trial whereby the complete remission rate for either doses of the Company’s study drug is greater than placebo.

The Series B warrants have an exercise price of $2.23, are exercisable immediately upon shareholder approval (which was received in October 2024) and will expire upon the earlier of (i) the 5 year anniversary of the date of stockholder approval or (ii) the 6 month anniversary following the date we release final topline data from the MIRACLE trial and documented a statistically significant improvement in the primary efficacy endpoint.

Pursuant to Nasdaq Listing Rule 5635(d), the exercise of the Series A warrants and Series B warrants were subject to shareholder approval, which was received.

The gross proceeds from the offering, before deducting the placement agent’s fees and other offering expenses payable by us, were approximately $5.5 million and we would receive up to an additional approximately $11.0 million in gross proceeds if the warrants are fully exercised for cash.

We are using the net proceeds from this offering to advance Annamycin and our other two drug portfolios through clinical development, advance the remainder of our existing portfolio through preclinical studies and into INDs or their equivalent, sponsor research at MD Anderson and HPI, and for working capital.

Miracle Trial

Clinical and Regulatory

As of April 30, 2025, we have selected 38 sites to conduct the MIRACLE trial in the US, Europe and the Middle East/Africa (MENA) for the MIRACLE trial with one site in Ukraine actively treating subjects.

Besides the one site in Ukraine, we have contracted with two other sites in Georgia and Romania.

In November 2024, we amended our existing US investigational new drug application or IND for inclusion of the MIRACLE trial protocol.

In the amendment with the new MIRACLE protocol, the trial will allow, for the first time in the US for AML subjects, dosing above the lifetime maximum allowable dose for currently prescribed anthracyclines.

Then in February 2025 we received FDA feedback and guidance on that amendment.

Such feedback allowed a reduction in the size of our Part B of the Phase 3 pivotal trial protocol to 222.

Guidance from FDA included a recommendation to alter the statistical plan that reduced the initially proposed size of Part B of our trial by approximately 10%.

Moreover, the nature of the feedback helps us move forward quickly to open sites in the US, in addition to the non-US sites we are expecting to open.

Any reduction in recruitment helps to shorten the time to completion of the trial.

In February through April of 2025, we received a total of five separate communications from the FDA including additional comments and information requests, all of which we believe we have adequately addressed.

These requests focused mainly on safety, subject monitoring, clinical pharmacology, and inclusion/exclusion criteria.

None of the requests focused on the overall trial design or dosing of Annamycin.

Our last response was submitted on April 18, 2025 and we have not received follow-up communication since that time.

However, we cannot be assured that our responses will be adequate for the FDA to continue to allow the amended IND to proceed, or that there will not be additional requests for information.

Because we are amending an existing IND, there is no required time for the FDA to respond to our submissions, but neither is a positive FDA response required for us to proceed with the MIRACLE trial.

At this time, we will proceed with the MIRACLE trial, as amended, in the US.

As with all clinical trials, if at any time the FDA believes there is a safety issue that merits it, the agency may put the MIRACLE trial on clinical hold.

Moleculin Receives European Medicines Agency Approval to Expand Phase 3 MIRACLE Clinical Trial

On May 12, 2025, we announced that the European Medicines Agency (EMA) approved its Clinical Trial Application to conduct its MIRACLE trial in all nine countries submitted in the European Union (EU).

We received the final Report for the Application and Evaluation Assessment (part of the EMA’s Clinical Trial Information System or CTIS process) of "Acceptable" for Belgium, Czechia, France, Germany, Italy, Lithuania, Poland, Romania, and Spain.

Such approval was under the condition that we present results of appropriate nonclinical GLP studies before initiating the Phase 3 portion (Part B) of the MIRACLE study.

Such results will be submitted as a substantial modification .

Along with the individual country committee and/or ethics approvals for these nine countries in the EU allows us to proceed.

While there are minor differences between the US and EU protocols with the FDA and EMA, respectively, we do not view these as a barrier to conducting the study and are working to harmonize the protocols as appropriate.

MB-107 Annamycin in Monotherapy for the Treatment of STS Lung Mets

We plan on hosting a Key Opinion Leader (KOL) call announcing and reviewing the final top line data from the MB-107 trial in May or early June.

Originally scheduled for April, we had to delay due to KOL schedules and availability.

We remain positive regarding the data.

Scientific Presentations of Preclinical Data

AACR Presentation of Pre-Clinical Data for Annamycin Market Expansion Potential, including Pancreatic Cancer

We announced on April 29, 2025, that new pre-clinical data for Annamycin demonstrating market expansion potential including treatment for pancreatic cancer was presented at the American Association for Cancer Research (AACR) Annual Meeting in Chicago, IL.

With five previous or current investigator-initiated clinical trials supporting development of our drug candidates, we believe that our next investigator-initiated trials could be Annamycin for the treatment of pancreatic cancer or advanced soft tissue sarcomas.

The study, presented in poster form, was designed to assess the efficacy of Annamycin in combination with approved anticancer agents in order to identify novel potentially highly efficacious clinical applications of Annamycin alone and with a therapeutic partner.

Annamycin in its non-liposomal form (free drug;

in vitro ) and Liposomal Annamycin (L-ANN;

in vivo ) were tested in combination with selected FDA approved drugs.

Several of the most efficacious drug combinations from the in vitro studies were then tested using well developed in vivo models of leukemia and solid tumors, including sarcoma and pancreatic cancer.

It should be noted that in a separate set of previous experiments, Annamycin activity was tested in vitro , and appeared to be highly active, against drug resistant cell lines, including cells resistant to cytarabine and venetoclax.

Clinical Trial with WP1066 at Northwestern University

With our WP1066 oral formula, an externally funded Phase 1B/2 trial in combination with radiation treating glioblastoma (GBM), a form of brain cancer, is recruiting and treating subjects at Northwestern University (Northwestern).

This is an investigator-initiated trial where our main cost is supplying drug product.

To date Northwestern has recruited and treated 7 subjects.

No data has been released.

Preclinical Studies with WP1066 IV Formula at Emory University

We have signed an agreement with Emory University whereby Emory will study various WP1066 IV formulations in preclinical studies with the goal of selecting the best molecule to move into a clinical setting towards, most likely, brain cancers such as GBM.

Study drug was delivered in April 2025 to Emory with results from such studies expected in the second half of 2025.

Intellectual Property, Licenses and Sponsored Research

World Health Organization Approval of “ naxtarubicin ” as International Non-Proprietary Name for Annamycin

We announced on May 6, 2025 that the International Nonproprietary Names (INN) Expert Committee of the World Health Organization approved “naxtarubicin 1 ” for the non-proprietary name of the Company’s next-generation anthracycline in development, Annamycin.

With this INN now given and prior approval by the United States Adopted Names (USAN), we have the ability to establish a universally recognized and conflict-free nonproprietary drug name for Annamycin.

This is considered the last step of approvals for non-proprietary names.

The use of this name will be merged into our public and clinical documents in the near-term.

Commonly referred to as a generic name, each INN is a unique name used to identify pharmaceutical substances or active pharmaceutical ingredients.

Each active substance that is to be marketed as a pharmaceutical must be granted a unique name of worldwide acceptability to ensure the clear identification, safe prescription and dispensing of medicines to patients.

Nonproprietary names are intended for wide use ranging from labelling and product information to drug regulation and scientific literature.

Additional Patents Issued for Annamycin in the US

On May 5, 2025, we announced that the U.S.

Patent and Trademark Office (USPTO) granted two additional U.S.

patents with claims covering Annamycin.

patent number 12,257,261 titled, “ Preparation of Preliposomal Annamycin Lyophilizate ”, has claims covering methods of making liposomal Annamycin and U.S.

patent 12,257,262 titled “ Method of Reconstituting Liposomal Annamycin “, has claims covering methods of making liposomal Annamycin suspension.

Both patents have a base patent term currently extending until June 2040, subject to adjustment for delays in prosecution and extension to account for time required to fulfill requirements for regulatory approval.

Moleculin has additional patent applications related to Annamycin pending in the U.S., Europe and in major jurisdictions worldwide.

Licenses and Sponsored Research with MD Anderson

We have terminated certain licenses related to WP1122 with MD Anderson and are in discussions to execute an option or options on these technologies along with additional technologies where the term of such options will be tied to the term of our Sponsored Research Agreement with MD Anderson.

Such actions are in line with our efforts to focus our resources on the development of Annamycin.

1 WHO Drug Information, Vol.

Results of Operations

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Condensed Consolidated Statements of Operations

Three Months Ended September 30,

Nine Months Ended September 30,

Three Months Ended March 31,

Operating expenses:

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Other income (loss):

(Loss) gain from change in fair value of warrant liability

Gain from change in fair value of warrant liability

Transaction costs allocated to warrant liabilities

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Interest income, net

Three Months Ended September 30, 2024 Compared to Three Months Ended September 30, 2023

Research and Development Expense.

Research and development (R&D) expense was $4.9 million and $3.3 million for the three months ended September 30, 2024 and 2023 , respectively.

The increase of $1.6 million is mainly related t o costs incurred for clinical trials (clinical research organization and drug production) and sponsored research costs.

General and Administrative Expense.

General and administrative e xpense was $2.2 million and $2.6 million for the three months ended September 30, 2024 and 2023 , respectively.

The decrease of $0.4 million is mainly related to a decrease in regulatory and legal fees.

(Loss) Gain from Change in Fair Value of Warrant Liability.

We recorded a net loss of $1.7 million in the third quarter of 2024 as compared to a net gain of $0.001 million in the third quarter of 2023, for the change in fair value on revaluation of our warrant liability associated with our warrants issued in conjunction with certain of our previous stock offerings.

We are required to revalue our liability-classified warrants at the time of each warrant exercise, if applicable, and at the end of each reporting period and reflect in the statement of operations a gain or loss from the change in fair value of the warrant in the period in which the change occurred.

We calculated the fair value of the warrants outstanding using the Black-Scholes model.

A gain results principally from a decline in our share price during the period and a loss results principally from an increase in our share price.

Transaction costs allocated to warrant liabilities and Loss on issuance of warrant liabilities.

Proceeds of offerings are allocated between common shares and warrants first by allocating to the warrants classified as a liability based on their fair value and then allocating the residual to the equity instruments, which would include pre-funded warrants.

As the fair value of the liability classified warrants in the August 2024 offering exceeded the total proceeds, no consideration was allocated to the Common Shares or Pre-Funded Warrants.

The full proceeds of the August 2024 offering were recorded to warrant liabilities, with an initial liability of $6.1 million, and a loss on initial recognition of $0.8 million.

The loss on modification of certain warrants of $0.4 million was also recorded as a loss on issuance of warrant liabilities in the three months ended September 30, 2024.

Transaction costs related to the offering were correspondingly fully allocated to warrant liabilities, and $1.0 million in related transaction costs were expensed during the three and nine months ended September 30, 2024.

Interest income, net.

Interest income, ne t decreased by approximately $0.2 million f or the comparable quarterly periods due to a decreasing cash balance and decreasing interest rates during the past year.

Nine Months Ended September 30, 2024 Compared to Nine Months Ended September 30, 2023

Three Months Ended March 31, 2025 Compared to Three Months Ended March 31, 2024

Research and Development Expense.

Research and development (R&D) expense was $13.3 million and $12.9 million for the nine months ended September 30, 2024 and 2023 , respectively.

The increase of $0.4 million is mainly related to costs incurred for clinical trials (clinical research organization and drug production) and sponsored research costs.

These increases were offset by a $1.5 million decrease mainly related to the WPD sublicense termination in 2023, which enabled the reacquisition of our intellectual property rights in certain territories including parts of the European Union.

Research and development (R&D) expense was $3.4 million and $4.3 million for the three months ended March 31, 2025 and 2024 , respectively.

The decrease of $0.9 million is mainly related t o the clinical trials activity levels.

General and Administrative Expense.

General and administrative e xpense was $6.6 million and $7.8 million for the nine months ended September 30, 2024 and 2023 , respectively.

The decrease of $1.2 million is mainly related to a decrease in regulatory and legal fees.

General and administrative e xpense was $2.5 million and $2.4 million for the three months ended March 31, 2025 and 2024 , respectively.

The increase of $0.1 million is mainly related to a slight overall increase in regulatory and legal fees.

Gain from Change in Fair Value of Warrant Liability.

We recorded a net gain of $1.4 million in the nine months ended 2024 as compared to a net gain of $0.1 million in the nine months ended 2023, for the change in fair value on revaluation of our warrant liability associated with our warrants issued in conjunction with certain of our previous stock offerings.

We recorded a net gain of $9.1 million in the first quarter of 2025 as compared to a net gain of $1.5 million in the first quarter of 2024, for the change in fair value on revaluation of our warrant liability associated with our warrants issued in conjunction with certain of our previous stock offerings.

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As the fair value of the liability classified warrants in the August 2024 offering exceeded the total proceeds, no consideration was allocated to the Common Shares or Pre-Funded Warrants.

The full proceeds of the August 2024 offering were recorded to warrant liabilities, with an initial liability of $6.1 million, and a loss on initial recognition of $0.8 million.

The loss on modification of certain warrants of $0.4 million was also recorded as a loss on issuance of warrant liabilities in the nine months ended September 30, 2024.

As the fair value of the liability classified warrants in the February 2025 offerings exceeded the total proceeds, no consideration was allocated to the Common Shares or Pre-Funded Warrants.

The full proceeds of the February 2025 offerings were recorded to warrant liabilities, with an initial liability of $19.0 million, and a loss on initial recognition of $7.8 million.

Transaction costs related to the offering were correspondingly fully allocated to warrant liabilities, and $1.8 million in related transaction costs were expensed during the three months ended March 31, 2025.

Interest income, net.

Interest income, ne t decreased by approximately $0.6 million f or the comparable quarterly periods due to a decreasing cash balance and decreasing interest rates during the past year.

Interest income, n e t decreased by approximately $0.2 million f or the comparable quarterly periods due to a decreasing cash balance and decreasing interest rates during the past year.

Liquidity and Capital Resources

The following table sets forth our primary sources and uses of cash for the period indicated (table in thousands):

Nine Months Ended September 30,

Three Months Ended March 31,

Net cash used in operating activities

Net cash used in investing activities

Net cash provided by financing activities

Effect of exchange rate changes on cash and cash equivalents

Net decrease in cash and cash equivalents

As of September 30, 2024, there w as $0.4 million of cash on hand in a bank account in Australia and we know of no related limitations impacting our liquidity in Australia.

Net increase (decrease) in cash and cash equivalents

As of March 31, 2025, there w as $0.6 million of cash on hand in a bank account in Australia and we know of no related limitations impacting our liquidity in Australia.

Cash used in operating activities

Cash used in operations was $18.8 million for the nine months ended September 30, 2024 .

This $0.1 million increase over the prior year period of $18.7 million was primarily due to the timing of costs incurred and associated payments for drug production and clinical trial expenses.

Cash used in operations was $4.6 million for the three months ended March 31, 2025 .

This $2.1 million decrease over the prior year period of $6.7 million was primarily due to the timing of costs incurred and associated payments for drug production and clinical trial expenses.

Cash provided by fin ancing activities

On February 25, 2025, the Company entered into a securities purchase agreement with an institutional investor for the sale by the Company of 1,150,000 shares of common stock, and 2,121,029 pre-funded warrants to purchase shares of common stock, and series D warrants to purchase up to 6,543,058 shares of common stock.

The combined purchase price for the securities was $1.07 per share of common stock (or pre-funded warrant in lieu thereof).

Each pre-funded warrant is exercisable for one share of common stock at an exercise price of $0.001 per share.

The pre-funded warrants are exercisable immediately and may be exercised at any time until all of the pre-funded warrants are exercised in full, subject to the beneficial ownership limitation.

Each common warrant will be exercisable upon the receipt of shareholder approval, will have an exercise price of $1.07 per share, and expire five years from the initial exercise date.

The Company received gross proceeds of $3.5 million.

On February 13, 2025, the Company entered into a warrant exercise inducement offer letter with a holder of certain existing warrants to receive new warrants to purchase up to a number of shares of common stock equal to 200% of the number of warrant shares issued pursuant to the exercise of such existing warrants to purchase up to 5,828,570 shares of common stock (series C warrants) pursuant to which the Holder agreed to exercise for cash their existing warrants at a reduced exercise price of $1.00 in exchange for the Company's agreement to issue the inducement warrants to purchase up to 11,657,140 shares of the Company's common stock.

Each inducement warrant will have an exercise price of $0.75, and will be exercisable as of the date of issuance and may be exercised for a period of five years therefrom.

The Company received gross proceeds of $5.8 million.

This brings the total gross proceeds received in February 2025 to $9.3 million.

On August 19, 2024, we announced the closing of our previously announced public offering of 283,000 shares of common stock and 2,183,368 pre-funded warrants to purchase shares of common stock, Series A warrants to purchase up to 2,466,368 shares of common stock and Series B warrants to purchase up to 2,466,368 shares of common stock, at a combined public offering price of $2.23 per share (or per pre-funded warrant in lieu thereof) and accompanying warrants.

We received gross proceeds of $5.5 million, before deducting the placement agent's fees and other offering expenses.

We believe that our cash on hand and cash equivalents as of September 30, 2024, is sufficient to fund our planned operations into the first quarter of 2025.

We believe that our cash on hand and cash equivalents as of March 31, 2025, is sufficient to fund our planned operations into the third quarter of 2025.

This takes into account cash outlays for preparations for clinical trials beyond the current active trials.

The continuation of our Company as a going concern is dependent upon our ability to obtain necessary financing to continue operations and the attainment of profitable operations.

We must seek additional funding of approximately $15 million to support MIRACLE and our operations into the third quarter of 2025 through a combination of equity offerings, debt financings, government or other third-party funding, commercialization, marketing and distribution arrangements, other collaborations, strategic alliances and licensing arrangements and delay planned cash outlays or a combination thereof to continue our operations in the near term.

We must seek additional funding of approximately $15 million to support MIRACLE and our operations into the first quarter of 2026 through a combination of equity offerings, debt financings, government or other third-party funding, commercialization, marketing and distribution arrangements, other collaborations, strategic alliances and licensing arrangements and delay planned cash outlays or a combination thereof to continue our operations in the near term.

We cannot provide assurance that such events or a combination thereof can be achieved.

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We expensed approximate

ly $0.1 million and $0.4 million in related general and administrative fees and expenses for the three months ended

September 30, 2024 and 2023

, respectively, and approximate

ly $0.2 million and $1.4 million for the nine months ended

September 30, 2024 and 2023

million and $0.1 million in related general and administrative fees and expenses for the three months ended

March 31, 2025 and 2024

respectively .

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What changed 10-Q

Item 2. Management’s Discussion and Analysis