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Moleculin Announces Positive In Vivo Efficacy Data Of Annamycin In Orthotopic And Experimental Lung Metastatic Models Of Sarcoma

Data recently presented at the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer

Treatment with Annamycin results in statistically significant inhibition of tumor growth and extension of survival in orthotopic lung cancer models

Annamycin continues to be 100% non-cardiotoxic

HOUSTON, Sept. 23, 2024 /PRNewswire/ -- Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, today announced the recent presentation of positive in vivo efficacy data of Annamycin in orthotopic and experimental lung metastatic models of sarcoma.

(PRNewsfoto/Moleculin Biotech, Inc.) (PRNewsfoto/Moleculin Biotech, Inc.)

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 recently 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).

"Annamycin continues to exhibit consistent activity against different type of cancers including therapy resistant cancers such as soft tissue sarcoma lung metastases while also avoiding cardiotoxicity, which continues to be a significant side effect limiting the clinical use of anthracyclines. Importantly, the presented data demonstrates that treatment with Annamycin results in statistically significant inhibition of tumor growth and extension of survival in orthotopic lung cancer models, which is consistent with the preliminary results we are seeing in our sarcoma clinical trials. This further underscores Annamycin's potential to provide a much-needed treatment option for patients with primary or metastatic lung cancers, as a single agent and in combination with currently used therapeutics. Combined with the encouraging growing body of clinical data from our ongoing studies, we remain confident in Annamycin's potential to address significant unmet needs in a wide range of cancers," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin.

Key Highlights

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.

Story continues

Annamycin is currently being evaluated in ongoing clinical trials for the treatment of relapsed or refractory acute myeloid leukemia (AML) and soft tissue sarcoma (STS) lung metastases. Annamycin currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of relapsed or refractory acute myeloid leukemia, in addition to Orphan Drug Designation for the treatment of soft tissue sarcoma. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia from the European Medicines Agency (EMA).

About Moleculin Biotech, Inc.

Moleculin Biotech, Inc. Is a Phase 3 clinical stage pharmaceutical company advancing a pipeline of therapeutic candidates addressing hard-to-treat tumors and viruses. The Company's lead program, Annamycin, is a next-generation anthracycline designed to avoid multidrug resistance mechanisms and to eliminate the cardiotoxicity common with currently prescribed anthracyclines. Annamycin is currently in development for the treatment of relapsed or refractory acute myeloid leukemia (AML) and soft tissue sarcoma (STS) lung metastases.

The Company is initiating the MIRACLE (Moleculin R/R AML AnnAraC Clinical Evaluation) Trial (MB-108), a pivotal, adaptive design Phase 3 trial evaluating Annamycin in combination with cytarabine, together referred to as AnnAraC, for the treatment of relapsed or refractory acute myeloid leukemia. Following a successful Phase 1B/2 study (MB-106), with input from the FDA, the Company believes it has substantially de-risked the development pathway towards a potential approval for Annamycin for the treatment of AML. This study is subject to appropriate future filings with potential additional feedback from the FDA and their foreign equivalents.

Additionally, the Company is developing WP1066, an Immune/Transcription Modulator capable of inhibiting p-STAT3 and other oncogenic transcription factors while also stimulating a natural immune response, targeting brain tumors, pancreatic and other cancers. Moleculin is also engaged in the development of a portfolio of antimetabolites, including WP1122 for the potential treatment of pathogenic viruses, as well as certain cancer indications.

For more information about the Company, please visit www.Moleculin.Com and connect on X, LinkedIn and Facebook.

Forward-Looking Statements

Some of the statements in this release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995, which involve risks and uncertainties. Forward-looking statements in this press release include, without limitation, whether the results shown in the animal models can be replicated in clinical trials. Although Moleculin believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. Moleculin has attempted to identify forward-looking statements by terminology including 'believes,' 'estimates,' 'anticipates,' 'expects,' 'plans,' 'projects,' 'intends,' 'potential,' 'may,' 'could,' 'might,' 'will,' 'should,' 'approximately' or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors, including those discussed under Item 1A. "Risk Factors" in our most recently filed Form 10-K filed with the Securities and Exchange Commission ("SEC") and updated from time to time in our Form 10-Q filings and in our other public filings with the SEC. Any forward-looking statements contained in this release speak only as of its date. We undertake no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events.

Investor Contact:

JTC Team, LLCJenene Thomas(908) 824-0775MBRX@jtcir.Com

Cision

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Biological Findings Open The Door To Improved Outcomes For Young Adults With Sarcoma

Overview of the adolescent and young adult (AYA) and older adult (OA) patients in the cohort. A Distribution of patient sex, anatomical site, and histological subtype within the AYA and OA cohorts. B Kaplan–Meier plot of overall survival (OS) for AYA and OA patients. Hazard ratio (HR), 95% confidence intervals (CI) and p value determined by univariable Cox regression. AS angiosarcoma, ASPS alveolar soft part sarcoma, CCS clear cell sarcoma, DDLPS dedifferentiated liposarcoma, DSRCT desmoplastic small round cell tumor, DE desmoid tumor, EPS epithelioid sarcoma, LMS leiomyosarcoma, SS synovial sarcoma, UPS undifferentiated pleomorphic sarcoma. Credit: Communications Medicine (2024). DOI: 10.1038/s43856-024-00522-x

A recent study has answered the long-standing question of why improvements in survival outcomes for young people with cancerous soft tissue tumors have lagged behind those of their pediatric and older adult counterparts. By analyzing the protein profiles of different types of soft tissue tumors, known as sarcomas, researchers have shown that there are distinct biological differences between these age groups.

Furthermore, the team has identified a potential biomarker that could help predict which adolescent and young adult (AYA) patients are likely to have aggressive forms of sarcoma that will spread to other areas of the body.

In the future, this may help guide treatment decisions for people of this age, improving outcomes for patients predicted to need more intensive treatment and sparing those with less aggressive cancer from the side effects of overtreatment.

Researchers at The Institute of Cancer Research, London, led the study, which has been published in the journal Communications Medicine.

Age affects outlook for people with soft tissue tumors

Soft tissue tumors develop in the connective and supporting tissues of the body, such as muscle and fat. They are relatively rare but can affect people of any age. Those that are malignant (cancerous) are called sarcomas.

Despite the incidence of sarcoma being higher among the AYA age group than among older adults (representing 8% of cancer diagnoses vs. Just 1%), improvements in survival rates in the AYA age group, defined as people aged 16 to 39 at the time of diagnosis, have not kept pace with those for patients belonging to other age groups.

The study authors note that there are multiple reasons for this disparity, including inadequate age-specific services and under-representation of people in the AYA age group in clinical trials. These factors mean that the current treatments are optimized for older adults—those aged 40 and older—and do not always work effectively for AYA patients.

Believing that biological differences between the age groups must play a part in these inconsistent outcomes, the researchers set out to retrospectively analyze the features of the sets of proteins expressed in patients of different ages.

They used data from 309 people with soft tissue sarcomas or benign soft tissue tumors, known as desmoid tumors. Nine sarcoma types were represented across the cohort, including angiosarcoma, clear cell sarcoma and leiomyosarcoma.

Identifying a new way to predict cancer spread

The researchers identified a total of 8,148 proteins across all the patient samples and quantified 3,299 of them. They found that 32 of the proteins were more abundant in the AYA patients than in the older adults, while 35 were more abundant in the older adults. Once the researchers had adjusted the results to account for other variables, including tumor size, anatomical site and sarcoma subtype, five of these proteins remained significant.

Overall, the older patients had higher levels of a protein involved in regulating the cell cycle, while the proteins that were more abundant in the AYA patients have a role in structural support and the function of mitochondria, which generate energy for cells.

These differences could affect how sarcomas respond to treatment, which will in turn influence people's likelihood of survival.

In the next part of the study, the team wanted to determine whether there was a correlation between any biological factors and the survival rates of the participants. The analysis showed that high expression of specific subunits of the cellular machinery responsible for splicing—an important step in the process of protein synthesis—were associated with better metastasis-free survival (MFS). MFS is the time from the start of treatment until the cancer begins to spread.

This splicing "signature" could potentially be used by clinicians to identify the AYA patients most likely to need intensive treatment to prevent their cancer from spreading.

'This could lead to substantial improvements in survivorship'

First author Yuen Bun Tam, a Ph.D. Student in the Molecular and Systems Oncology Group at the ICR, said, "The lack of therapies tailored to adolescent and young adult patients is a key barrier to improving survival rates in this age group, representing a significant unmet need. In this study, we not only characterized the biological differences between young people and older adult patients but also identified an age-specific signature that may serve as a risk stratification tool in the clinical setting.

"By demonstrating the importance of age-specific studies in the discovery of more tailored strategies, such as targeted agents, we hope that our findings will encourage future studies and clinical trials to include more adolescents and young adults. In the long term, this could lead to substantial improvements in survivorship and the management of late effects for this age group."

Senior author Dr. Paul Huang, Leader of the Molecular and Systems Oncology Group at the ICR, said, "Although we predicted that there would be inherent biological differences between the tumors in the two patient groups, we were surprised to see that many of these findings were independent of other clinical factors that differed between the two age groups, including the type of sarcoma.

"We are planning further work to validate our findings in larger cohorts and to measure our splicing signature, with the hope of making it feasible to use as a clinical test. We will also work on better understanding the link between this splicing signature and the ability of the tumor to spread.

"This knowledge could aid the identification of new treatment options to manage soft tissue tumors in adolescents and young adults."

More information: Yuen Bun Tam et al, Proteomic features of soft tissue tumours in adolescents and young adults, Communications Medicine (2024). DOI: 10.1038/s43856-024-00522-x

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Northwestern Performs 1st-of-its-kind Double-lung Transplant

Surgeons at Chicago-based Northwestern Medicine have performed a double-lung transplant for a patient with stage 4 colorectal cancer through its double-lung replacement and multidisciplinary care program, a first-of-its-kind initiative reserved for patients whose cancers do not respond to standard treatments. 

The patient was a 42-year-old woman. Originally diagnosed with stage 4 colorectal cancer in 2017, she had previously undergone a liver transplant after the cancer had spread to her liver in 2020. Six months after the liver transplant, the cancer was found to have spread to her lungs, according to a Sept. 25 news release from Northwestern. 

The double-lung transplant was performed on June 3 and the patient was discharged one week later. Based on available testing, the patient has no remaining signs of cancer, Ankit Bharat, MD, chief of thoracic surgery and director of the Northwestern Medicine Canning Thoracic Institute, said in the release. 

"While we're optimistic about her future, it's important to approach this with cautious optimism as further research is needed to understand the long-term outcomes," Dr. Bharat said.

The procedure was performed at the Northwestern Medicine Canning Thoracic Institute in Chicago. It involves removing the cancerous lungs and lymph nodes, and washing the airways and chest cavity to reduce the risk of cancer cells spreading, the release said. 

The institute is the only center in the U.S. Offering this treatment to lung cancer patients "without any options," according to the release. 

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