On April 29, 2025 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat cancers and viral infections, reported that an abstract and poster presentation regarding the Company’s next-generation anthracycline, Annamycin, was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025, on April 28, 2025, at the McCormick Place Convention Center in Chicago, IL (Press release, Moleculin, APR 29, 2025, View Source [SID1234652314]).

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"The case for expanding the potential markets for Annamycin continues to get stronger," said Walter Klemp, Chairman and CEO of Moleculin. "In an environment where more and more cancer treatment regimens are combinations of two or more drugs, it is encouraging to see that Annamycin appears capable of generating synergistic results with so many commonly used drugs. The latest research continues to support our view that, in addition to hematological malignancies, solid cancers including sarcoma and pancreatic cancer also represent important expansion opportunities for Annamycin. These findings may help expand the clinical use of Annamycin and consequently make our drug candidate even more attractive to prospective future partners. 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 advance 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 US Food and Drug Administration (FDA) approved drugs. Usually, 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.

The research shown in the AACR (Free AACR Whitepaper) poster, described below, demonstrates that Annamycin is potentially a highly versatile drug capable of working synergistically with numerous mechanistically different FDA approved anticancer agents both in vitro and in vivo. Ongoing studies are working towards identifying new efficacious clinical applications of L-ANN drug combinations with the long-term goal of developing novel therapeutic strategies for treatment resistant cancers.

Details of the poster presentation are as follows:

Title: Combining Annamycin, a Non-cardiotoxic Potent Topo II Poison, with Azacitidine, Cytarabine, Gemcitabine, Ifosfamide, Trabectedin, or Vincristine to Synergize Anticancer Effects and Identify Potential Clinical Applications
Track: Experimental and Molecular Therapeutics
Session: PO.ET02.03. Drug Combination Strategies for Cancer Treatment
Abstract Number: 1683/ 14
Presenter: Waldemar Priebe, Ph.D., Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center

For more information, visit the AACR (Free AACR Whitepaper) Annual Meeting website.

On April 29, 2025 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported data today from a study showing that its methylation-based Shield multi-cancer detection (MCD) test demonstrated high specificity and clinically meaningful sensitivity across ten tumor types,* while also providing information to guide clinical diagnostic evaluation (Press release, Guardant Health, APR 29, 2025, View Source [SID1234652335]). The study was presented at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting. Results of the study served as the basis for the selection of the blood-based Shield MCD test by the National Cancer Institute (NCI) for inclusion in its upcoming Vanguard Study evaluating emerging MCD technology.

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Data presented in the oral session titled "Evaluation of a plasma cell-free DNA methylation-based multi-cancer detection test" showed that the Shield MCD test demonstrated 98.5% specificity and 60% overall sensitivity, with 74% sensitivity across the six most aggressive cancers (defined as those with the shortest survival rates), including esophageal-gastric, hepatocellular, lung, ovarian and pancreas. The test also demonstrated 89% accuracy for primary or secondary cancer signal of origin (CSO) prediction.

"There are still many types of cancer that are difficult to detect with existing technologies until the late stages. This strong data reinforces the potential of the Shield test to detect multiple cancers earlier through a simple blood draw," said AmirAli Talasaz, Guardant Health co-founder and co-CEO. "This study was a critical step in evaluating this innovative technology as a new screening option we can bring to patients to help reduce cancer deaths."

The blinded case-control study evaluated samples from 778 individuals with either a known diagnosis of cancer or who were cancer free (by self-report). Age range of participants was 40-78 years (median age 62); 55% were female and 79% were white. Across the ten cancer types, overall sensitivity per type ranged from 96% (esophageal-gastric (stomach)) to 21% (prostate) at 98.5% specificity (Table 1).

Table 1: Overall and per cancer Sensitivity and CSO Accuracy Results at 98.5% Specificity (n=403)

Sensitivity, %

Primary or Secondary CSO
Accuracy, %

Overall, 375

60%

89%

Bladder, 13

62%

75%

Breast, 86

45%

92%

Colorectal, 41

83%

94%

Esophageal-Gastric (Stomach) 25

96%

92%

Hepatocellular, 16

94%

73%

Lung, 57

67%

97%

Ovarian, 20

70%

93%

Pancreas, 59

68%

80%

Prostate, 59

21%

83%

"Impressively, this initial cohort analysis of the Shield MCD test met overall performance expectations, with particularly strong sensitivity in the six most aggressive cancers for which early detection is key," said William Greenleaf, Ph.D., study co-author, consultant for Guardant Health and professor of genetics at Stanford University School of Medicine. "These results show this blood-based MCD test holds promise for detection of multiple cancer types, and thus for detection in asymptomatic adults when treatment is more effective."

The full data abstract and a list of all abstracts being presented at the meeting can be found on the AACR (Free AACR Whitepaper) website. For more information on the NCI Vanguard Study, please visit the study website.

On April 29, 2025 AstraZeneca reported that a fixed-duration regimen of Calquence (acalabrutinib) in combination with venetoclax, with or without obinutuzumab, has been recommended for approval in the European Union (EU) for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) (Press release, AstraZeneca, APR 29, 2025, View Source [SID1234652259]).

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The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the AMPLIFY Phase III trial, which were presented at the American Society of Haematology (ASH) (Free ASH Whitepaper) 2024 Annual Meeting and published in The New England Journal of Medicine.1

Results showed Calquence plus venetoclax reduced the risk of disease progression or death by 35% compared to standard-of-care chemoimmunotherapy (investigator’s choice of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab; hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.49-0.87; p=0.0038). Calquence plus venetoclax with obinutuzumab demonstrated a 58% reduction in the risk of disease progression or death compared to standard-of-care chemoimmunotherapy (HR 0.42; 95% CI 0.30-0.59; p<0.0001).2

At three years, 77% of patients treated with Calquence plus venetoclax and 83% of patients treated with Calquence plus venetoclax and obinutuzumab were progression free, versus 67% of patients treated with chemoimmunotherapy.1 Median progression-free survival (PFS) was not reached for either experimental arm versus 47.6 months for chemoimmunotherapy.1

Wojciech Jurczak, MD, Maria Sklodowska-Curie National Institute of Oncology, Kraków, Poland and investigator for the trial, said: "Chronic lymphocytic leukaemia is an incurable cancer which means patients live with the disease and stay on treatment for many years, which can have long-term effects. The fixed-duration Calquence regimens will allow patients to take breaks from their treatment, reducing the risk of long-term adverse events and drug resistance."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "With this recommendation, Calquence plus venetoclax can potentially be the only all-oral second-generation BTK inhibitor option approved in Europe for patients with previously untreated chronic lymphocytic leukaemia. Calquence has demonstrated efficacy and safety in fixed-duration and treat-to-progression regimens providing patients and their doctors more treatment flexibility."

CLL is the most common type of leukaemia in adults, with an estimated 27,000 patients diagnosed in the UK, France, Germany, Spain and Italy in 2024.3

The safety and tolerability of Calquence was consistent with its known safety profile, and no new safety signals were identified.

Regulatory applications for Calquence plus venetoclax, with or without obinutuzumab, in this setting are currently under review in several countries based on the AMPLIFY results.

Notes

Chronic lymphocytic leukaemia (CLL)
CLL is the most prevalent type of leukaemia in adults, with over 117,000 new cases globally in 2021.4 Although some people with CLL may not experience any symptoms at diagnosis, others may experience symptoms, such as weakness, fatigue, weight loss, chills, fever, night sweats, swollen lymph nodes and abdominal pain.5 In CLL, there is an accumulation of abnormal lymphocytes within the blood, bone marrow and lymph nodes. As the number of abnormal cells increases, there is less room within the marrow for the production of normal white blood cells, red blood cells and platelets.6 This could result in infection, anaemia and bleeding. B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.

AMPLIFY
AMPLIFY is a randomised, global, multi-centre, open-label Phase III trial evaluating the efficacy and safety of Calquence in combination with venetoclax, with or without obinutuzumab, compared to investigator’s choice of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) in adult patients with previously untreated CLL without del(17p) or TP53 mutation.7 Patients were randomised 1:1:1 to receive either Calquence plus venetoclax, Calquence plus venetoclax with obinutuzumab for a fixed duration or standard-of-care chemoimmunotherapy.7 Both the Calquence containing arms were administered for a fixed duration of 14 cycles (each 28 days), and the standard-of-care chemoimmunotherapy was for 6 cycles.7

The primary endpoint is PFS in the Calquence and venetoclax arm as assessed by an Independent Review Committee and PFS in the Calquence plus venetoclax with obinutuzumab is a key secondary endpoint.7 Other key secondary endpoints include OS and undetectable measurable residual disease.7 The trial includes 27 countries across North and South America, Europe, Asia and Oceania.7

The AMPLIFY trial enrolled patients from 2019 to 2021, continuing through the COVID-19 pandemic.7 Patients with blood cancer remain at a disproportionately high risk of severe outcomes from COVID-19, including hospitalisation and death compared to the general population.8

Calquence
Calquence (acalabrutinib) is a second-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.9 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.

Calquence is approved for the treatment of chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) in the US, Japan and China, approved for CLL in the EU and many other countries worldwide. Calquence is also approved for the treatment of adult patients with previously untreated MCL in the US and other countries. It is also approved for the treatment of adult patients with MCL who have received at least one prior therapy in China and several other countries. Calquence is not currently approved for the treatment of MCL in Japan.

As part of an extensive clinical development programme, Calquence is currently being evaluated as a single treatment and in combination with standard-of-care chemoimmunotherapy for patients with multiple B-cell blood cancers, including CLL, MCL and diffuse large B-cell lymphoma.

On April 29, 2025 Nouscom, a clinical-stage biotech company developing next-generation neoantigen-targeted off-the-shelf and personalized cancer immunotherapies, reported complete safety and immunogenicity results from a Phase Ib/II study evaluating NOUS-209 in individuals with Lynch Syndrome (LS) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, NousCom, APR 29, 2025, View Source;utm_medium=rss&utm_campaign=nouscom-presents-positive-final-results-from-completed-phase-ib-ii-study-of-neoantigen-immunotherapy-nous-209-at-aacr-2025-demonstrating-a-highly-potent-and-durable-immune-response-in-lynch-syndrome [SID1234652315]). The study found that NOUS-209 monotherapy was safe, well-tolerated and induced potent, broad and durable immune responses in all LS carriers evaluated.

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LS is a common inherited condition that significantly increases a person’s risk of developing microsatellite instability (MSI)-associated cancers over their lifetime. Managing LS is limited to frequent screenings or elective organ removal surgery. NOUS-209 is an investigational off-the-shelf cancer immunotherapy that targets tumors with mismatch repair deficiency (dMMR) and/or MSI. These tumors produce markers known as frameshift peptide neoantigens (FSPs). NOUS-209 is a pioneering approach to cancer interception comprising two proprietary viral vectors that deliver 209 shared FSP neoantigens and train the immune system to recognize and attack cancerous and pre-cancerous cells before tumors can fully develop.

The completed Phase Ib/II trial evaluated safety and immunogenicity in 45 LS carriers demonstrated;

Favorable Safety Profile: NOUS-209 was well tolerated, with no serious treatment-related adverse events across the entire study population.
Potent and Durable Immunogenicity Profile: Neoantigen-specific T cell responses were reported in 100% of evaluable participants (n=37). Responses were robust, reaching a mean of ~1100 interferon-gamma (IFN-γ) spot forming cells (SFC) per million of Peripheral Blood Mononuclear Cells (PBMCs). Immune responses were durable, with tumor-specific T cells detected after 1 year in >85% of participants (n=33).
Broad, Polyspecific T Cell Response: Immune responses were confirmed against 115 different FSP neoantigens to date, validating the ability of NOUS-209 to elicit broad polyspecific immune responses.
Desired T Cell Phenotype: NOUS-209 induced neoantigen-specific CD8 and CD4 T cells, exhibiting an effector memory phenotype associated with long-lived immunity critical for sustained surveillance and ability to eliminate emerging tumor cells.
Demonstration of Tumor Cell Killing: T cells induced by NOUS-209 were shown to directly kill tumor cells ex vivo, confirming functional anti-cancer activity.
Target Validation in LS-Associated Premalignant and Cancer Lesions: The vast majority of the immunogenic FSP neoantigens were shown to be present in both pre-cancerous as well as cancer lesions from independent cohorts of LS carriers.
These data support the further clinical development of NOUS-209 as a monotherapy in LS carriers. Following positive Type B and C meetings with the US Food and Drug Administration (FDA), Nouscom has a clear path forward for the advancement of NOUS-209 to a potentially registration-enabling Phase 2/3 clinical study for cancer interception in those living with LS.

"Currently, individuals with Lynch Syndrome rely on frequent screenings, such as colonoscopies, to manage their markedly increased risk of developing cancer. These latest data are a step toward a completely new approach – leveraging the immune system for cancer interception," said the study’s principal investigator, Eduardo Vilar-Sanchez, M.D., Ph.D., Professor of Clinical Cancer Prevention at The University of Texas MD Anderson Cancer Center. "NOUS-209 has shown clear evidence that the T cells it activates can persist over time, effectively target and kill tumor cells and develop into memory cells that support long-term immune protection. These findings support NOUS-209’s potential as a cancer interception strategy."

"Nouscom’s proprietary viral vector platform is uniquely positioned to deliver rapid, potent and broad immune activation against a large number of shared neoantigens, with minimal reactogenicity and durable immune responses," said Dr. Elisa Scarselli, Chief Scientific Officer of Nouscom. "These compelling Phase Ib/II data further reinforce our confidence in NOUS-209 monotherapy to safely and effectively prime the immune system to recognize and intercept pre-malignant and cancer lesions before they progress into tumors in LS carriers."

Dr. Marina Udier, Chief Executive Officer of Nouscom, added: "We are enormously pleased with these robust Phase Ib/II data and look to progress toward a potentially registration-enabling Phase 2/3 clinical study for cancer interception in LS. We remain deeply committed to advancing NOUS-209 and bring better solutions for people living with LS who urgently need and deserve a better way to manage their cancer risk."

The study was led by researchers at MD Anderson, in collaboration with the Cancer Prevention Clinical Trials Network and sponsored by the National Cancer Institute (grant # UG1CA242609) of the National Institutes of Health. These data were presented during the Hot Topics in Cancer Prevention session, and the abstract is available on the AACR (Free AACR Whitepaper) website here.

On April 29, 2025 SOTIO Biotech, a clinical-stage biopharmaceutical company owned by PPF Group, this week reported preclinical data on two of its leading antibody-drug conjugate (ADC) candidates, SOT109 and SOT106, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL (Press release, SOTIO, APR 29, 2025, View Source [SID1234652336]).

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Preclinical data on SOT109 (anti-CDH17 ADC) and SOT106 (anti-LRRC15 ADC) demonstrate strong anti-tumor activity and favorable tolerability profiles across multiple tumor models, supporting their potential as groundbreaking ADC therapies for various solid tumor types.

SOT109 is tailored to be a best-in-class ADC exploiting the highly promising target of CDH17 for treatment of gastrointestinal cancers including colorectal cancer (CRC), where unmet need remains very high. ADCs have shown limited clinical success in CRC to date largely due to a lack of ideal target antigens. CDH17 is a highly promising target antigen homogenously overexpressed in more than 90% of CRC and abundantly expressed in other GI cancers. Its expression in normal adult tissues is largely restricted to the GI tract, reducing the risk of off-target toxicity. SOT109 utilizes a proprietary, highly internalizing and fully human antibody combined with Synaffix B.V.’s leading ADC technology platform. Both the antibody and the epitope it is targeting, as well as the linker/payload design, have been selected to maximize its efficacy and safety.

SOTIO’s poster presentation on SOT109 showed the following:

SOT109 exhibited potent efficacy, producing significant and sustained tumor regressions in several in vivo colorectal tumor models, including cell-derived and patient-derived xenografts.
The doses tested in these studies were well tolerated in mice, with no dose-limiting toxicities observed. Subsequent studies in non-human primates confirmed a favorable pharmacokinetic and safety profile.
SOT106, leveraging LigaChem Biosciences’ clinically validated ConjuAll ADC platform for tumor-specific MMAE release, is a potentially best-in-class ADC for the clinically-validated target LRRC15. SOTIO’s oral presentation on SOT106 showed the following:

SOT106 demonstrated exceptional efficacy in an LRRC15 low-expressing patient-derived xenograft model of pediatric osteosarcoma, achieving significant tumor regression where a first-generation LRRC15-targeting ADC benchmark therapy was ineffective. This further supports its therapeutic potential across a broad range of target expression levels.
Complete responses and potent antitumor efficacy were also observed across a range of other models where LRRC15 is expressed directly on tumor cells, including multiple subtypes of soft tissue sarcoma, a therapy-resistant non-small-cell lung cancer model, and head and neck squamous cell carcinoma.
SOT106 displays a favorable pharmacokinetic and safety profile, good stability in vivo, and a high therapeutic index.
"The data we presented at AACR (Free AACR Whitepaper) this week highlights the strength of our next-generation ADCs by addressing areas of high unmet need in oncology," said Martin Steegmaier, Ph.D., chief scientific officer at SOTIO. "SOT109 continues to show excellent tolerability and strong anti-tumor activity across multiple preclinical models of colorectal cancer, while SOT106 offers a novel precision approach with broad applicability in LRRC15+ sarcomas and other solid tumors. These findings mark important progress in our pipeline and reinforce our commitment to developing highly differentiated ADCs for difficult to treat solid tumors."

Presentation materials will be available here after the presentation concludes.