A Randomized, Double-blind, Placebo-controlled Phase 2 Study Using the Rhinovirus Challenge Model to Investigate the Efficacy and Safety of 2-Deoxy-D-Glucose as Pre-exposure Prophylaxis

2-DG-02 is a randomized, placebo-controlled, double-blind Phase 2 study to investigate the efficacy and safety of 2-Deoxy-D-Glucose as a pre-exposure prophylaxis using the rhinovirus challenge model in healthy study participants.

Start Date02 Apr 2024

Sponsor / Collaborator

G.ST Antivirals GmbHStartup

CTIS2023-509311-91-01 / Recruiting

A randomized, double-blind, placebo-controlled Phase 2 study using the rhinovirus challenge model to investigate the efficacy and safety of 2-Deoxy-D-glucose as pre-exposure prophylaxis. - 2-DG-02

Start Date14 Feb 2024

Sponsor / Collaborator

G.ST Antivirals GmbHStartup

NCT05314933 / CompletedPhase 1

A Single/Multiple Ascending Dose Phase 1 Study Of The Safety, Tolerability, And Pharmacokinetics Of Intranasal 2-Deoxy-D-Glucose In Normal Healthy Volunteers

2-DG-01 is a randomized, double-blind, placebo-controlled, single and multiple ascending dose phase 1 study assessing safety, tolerability and pharmacokinetics of 2-DG in normal healthy volunteers (NHV). The safety and pharmacokinetics of 2-DG are assessed after single or multiple intranasal administrations.

Start Date03 Mar 2022

Sponsor / Collaborator

G.ST Antivirals GmbHStartup

100 Clinical Results associated with 2-Deoxyglucose

100 Translational Medicine associated with 2-Deoxyglucose

100 Patents (Medical) associated with 2-Deoxyglucose

4,377

Literatures (Medical) associated with 2-Deoxyglucose

01 Feb 2024·Free radical biology & medicine

Potassium ion efflux induces exaggerated mitochondrial damage and non-pyroptotic necrosis when energy metabolism is blocked

Article

Author: Li, Ya-Ping ; Zhou, Zhi-Ya ; Zha, Qing-Bing ; Ouyang, Dong-Yun ; He, Xian-Hui ; Lu, Na ; Wong, Tak-Sui ; Gan, Ying-Qing ; Yuan, Li-Sha ; Xu, Rong

Damage-associated molecular patterns (DAMPs) such as extracellular ATP and nigericin (a bacterial toxin) not only act as potassium ion (K⁺) efflux inducers to activate NLRP3 inflammasome, leading to pyroptosis, but also induce cell death independently of NLRP3 expression. However, the roles of energy metabolism in determining NLRP3-dependent pyroptosis and -independent necrosis upon K⁺ efflux are incompletely understood. Here we established cellular models by pharmacological blockade of energy metabolism, followed by stimulation with a K⁺ efflux inducer (ATP or nigericin). Two energy metabolic inhibitors, namely CPI-613 that targets α-ketoglutarate dehydrogenase and pyruvate dehydrogenase (a rate-limiting enzyme) and 2-deoxy-d-glucose (2-DG) that targets hexokinase, are recruited in this study, and Nlrp3 gene knockout macrophages were used. Our data showed that CPI-613 and 2-DG dose-dependently inhibited NLRP3 inflammasome activation, but profoundly increased cell death in the presence of ATP or nigericin. The cell death was K⁺ efflux-induced but NLRP3-independent, which was associated with abrupt reactive oxygen species (ROS) production, reduction of mitochondrial membrane potential, and oligomerization of mitochondrial proteins, all indicating mitochondrial damage. Notably, the cell death induced by K⁺ efflux and blockade of energy metabolism was distinct from pyroptosis, apoptosis, necroptosis or ferroptosis. Furthermore, fructose 1,6-bisphosphate, a high-energy intermediate of glycolysis, significantly suppressed CPI-613+nigericin-induced mitochondrial damage and cell death. Collectively, our data show that energy deficiency diverts NLRP3 inflammasome activation-dependent pyroptosis to Nlrp3-independent necrosis upon K⁺ efflux inducers, which can be dampened by high-energy intermediate, highlighting a critical role of energy metabolism in cell survival and death under inflammatory conditions.

01 Feb 2024·Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology

Oxidative phosphorylation rather than glycolysis is the primary energy source for sperm motility in the mussels Mytilus edulis

Article

Author: Sokolova, Inna M ; Kong, Hui

Broadcast-spawning marine mussels rely on high sperm motility for successful fertilization in the dynamic seawater environment. Mitochondria are typically considered the primary source of ATP generation via oxidative phosphorylation (OXPHOS); however, the ATP generation pathways of mussel sperm have not been fully characterized. To better understand the importance of both OXPHOS and glycolysis for mussel sperm function, we conducted experiments inhibiting these pathways in sperm from Mytilus edulis. Our results indicate that oligomycin, an inhibitor of the mitochondrial ATP synthase, immediately decreased sperm motility rate, velocity, and ATP content, while 2-deoxy-d-glucose, a glycolysis inhibitor, had no effect. The OXPHOS inhibitor rotenone also partially reduced sperm motility rate and velocity. Interestingly, no evidence was found for the inhibitors' effects on the content of energy-rich compounds (lipids, carbohydrates, and proteins) in the mussels' sperm, indicating only modest energy demand to fuel sperm motility. Based on these findings, we conclude that OXPHOS is the primary energy source for sperm motility in marine mussels. Our study sheds light on the intricacies of mussel sperm physiology and highlights the importance of understanding the energy requirements for successful fertilization in broadcast-spawning marine invertebrates.

01 Feb 2024·The Science of the total environment

Formaldehyde aggravates airway inflammation through induction of glycolysis in an experimental model of asthma exacerbated by lipopolysaccharide

Article

Author: Du, Ping ; An, Zhuoling ; Li, Boyu ; Xuan, Lingling ; Ren, Lulu ; Zhang, Wen

Formaldehyde (FA) exposure has been reported to induce or aggravate allergic asthma. Infection is also a potential risk factor for the onset and aggravation of asthma. However, no study has addressed the effects of FA exposure on asthmatic patients with respiratory infection. FA is ubiquitous in environment and respiratory infections are common in clinics. Therefore, it is necessary to explore whether FA exposure leads to the further worsening of symptoms in asthma patients with existing respiratory infection. In the present study, ovalbumin (OVA) was used to establish the murine asthma model. Lipopolysaccharide (LPS) was intratracheal administrated to mimic asthma with respiratory infection. The mice were exposed to 0.5 mg/m³ FA. FA exposure did not induce a significant aggravation on OVA induced allergic asthma. However, the lung function of specific airway resistance (sRaw), histological changes and cytokines production were greatly aggravated by FA exposure in OVA/LPS induced murine asthma model. Monocyte-derived macrophages (MDMs) were isolated from asthmatic patients. Exposure of MDMs to FA and LPS resulted in increased TNF-α, IL-6, IL-1β, and nitric oxide (NO) production. Lactate produciton and lactate dehydrogenase A (LDHA) expression were found to be upregulated by FA in OVA/LPS induced asthmatic mice and LPS stimulated MDMs. Furthermore, glycolysis inhibitor 2-Deoxy-d-glucose attenuated FA and LPS induced TNF-α, IL-6, IL-1β, and NO production. We conclude that FA exposure can lead to the aggravation of allergic asthma with infection through induction of glycolysis. This study could offer some new insight into how FA promotes asthma development.

News (Medical) associated with 2-Deoxyglucose

20 May 2024

·www.prnewswire.com

Studies Show Linked Biological Pathways Driving Skin Inflammation

NEW YORK, May 20, 2024 /PRNewswire/ -- A certain biological pathway, a set of linked reactions in the body, drives the inflammation seen in the skin disease psoriasis, a new study finds. The work could lead to improved therapies for all inflammatory skin diseases, including atopic and allergic dermatitis and a type of boil called hidradenitis suppurativa, say the study authors. Inflammation is the body's natural response to irritation and infection, but when out of control, it can lead to the reddish, flaky, itchy lesions that come with these skin diseases. Led by researchers at NYU Langone Health, the new study found that the interleukin-17 (IL-17) pathway, whose activity is blocked by existing anti-inflammatory drugs, activates a protein called hypoxia inducible factor 1-alpha (HIF-1-alpha) in psoriasis. Researchers say that IL-17 has long been known to be active in inflammation, but the role of HIF-1-alpha has until now been unclear. The research team also found that HIF-1-alpha let inflamed skin cells more actively break down sugar for energy, supporting their metabolism and leading to the production of a waste product called lactate. When consumed by inflammatory T cells, lactate triggered production of IL-17, fueling even more inflammation. Publishing in the journal Immunity online May 20, the findings show that in human skin tissue samples from people with psoriasis, measures of gene activity around IL-17 and HIF-1-alpha were similar, suggesting that these factors are interconnected. Experiments in mice treated to develop psoriasis found that subsequent treatment with an experimental drug that blocks the action of HIF-1-alpha, called BAY-87-2243, resolved inflammatory skin lesions. Further, skin samples from 10 patients successfully treated with anti-inflammatory drug etanercept showed diminished activity for both IL-17 and HIF-1-alpha, suggesting to researchers that when IL-17 is blocked, so is HIF-1-alpha. "Our study results broadly show that activation of HIF-1-alpha is at the crux of metabolic dysfunction observed in psoriasis and that its action is triggered by IL-17, another key inflammatory-signaling molecule," said corresponding study author Shruti Naik, PhD, associate professor at NYU Grossman School of Medicine in the Departments of Pathology and Medicine, and the Ronald O. Perelman Department of Dermatology. Further experiments were performed on skin samples from five patients with psoriasis whose healthy and inflamed skin was separately treated with either BAY-87-2243 or an existing combination of topical drugs (calcipotriene and betamethasone dipropionate). Researchers then compared differences in inflammatory gene activity as a measure of impact and found that the HIF-1-alpha inhibitor had a greater effect than existing topical drugs. Specifically, skin samples that responded to HIF-1-alpha therapy had 2,698 genes that were expressed differently, while standard-of-care–treated samples had 147 differently expressed genes. Genetic analysis of skin samples from another 24 psoriatic patients treated with the IL-17A–blocking drug secukinumab showed only decreased, not heightened, gene activity connected to HIF-1-alpha when compared to HIF-1-alpha gene activity in nine healthy patients with no psoriatic disease. Researchers say this indicates HIF-1-alpha's blocked action was codependent on blockage of IL-17. Additional experiments in mice showed that blocking sugar (glucose) uptake in the skin slowed psoriatic disease growth by limiting glucose metabolism, or glycolysis. Both the number of immune T cells tied to inflammation and the cell levels of IL-17 also decreased. The researchers found further that levels of lactate, the main byproduct of glycolysis, in psoriatic skin cell cultures dropped once exposed to the glycolysis-inhibiting drug 2-DG. Directly targeting lactate production in psoriatic mice using a topical skin cream containing lactate dehydrogenase, which breaks down lactate, also slowed disease progression in the skin, with reduced numbers of inflammatory gamma-delta T cells and reduced IL-17 activity. Gamma-delta T cells were shown to take up lactate and use it to produce IL-17. "Our findings suggest that blocking either HIF-1-alpha's action or its glycolytic metabolic support mechanisms could be effective therapies for curbing the inflammation," added Naik, who is also the associate director for NYU Langone's Judith and Stewart Colton Center for Autoimmunity. "Evidence of HIF-1-alpha's depressed action, or downregulation, could also serve as a biomarker, or molecular sign, that other anti-inflammatory therapies are working," said study co-senior investigator Jose U. Scher, MD, the Steere Abramson Associate Professor of Medicine in the Department of Medicine at NYU Grossman School of Medicine. Scher, who also serves as director of NYU Langone's Psoriatic Arthritis Center and the Judith and Stewart Colton Center for Autoimmunity, says the team plans to develop experimental drugs that can block HIF-1-alpha and lactate action in the skin "to end the underlying vicious cycle of IL-17–driven inflammation in skin disease. Our research fundamentally expands the scope of feasible therapeutic options." Naik points out that while many available therapies for psoriasis, including steroids and immunosuppressive drugs, reduce inflammation and symptoms, they do not cure the disease. She said further experiments are needed to refine which experimental drug works best, with respect to HIA-1-alpha inhibition, before clinical trials could start. Indeed, Naik and study co-lead investigators Ipsita Subudhi and Piotr Konieczny have a patent application pending (U.S. application number 63/540,794) for inflammatory skin disease therapies derived from their work on HIA-1-alpha inhibition. More than 8 million Americans and 125 million worldwide are estimated to have psoriatic disease. The condition affects men and women equally. Funding support for the studies was provided by National Institutes of Health grants P30AR075043, R01AR080436, R01AI168462, UC2AR081029, K22AI135099, K99AR083536, T32AR069515, TL1TR001447, UL1TR001445, and DP2AR079173. Additional funding was provided by the National Psoriasis Foundation, the Judith and Stewart Colton Center for Autoimmunity, the Beatrice Snyder Foundation, the Riley Family Foundation, the American Association of Immunologists, the International Human Frontier Science Program, the Charles H. Revson Foundation, and the Pew-Stewart Scholar Award 00034119, as well as the New York Stem Cell Foundation. Naik serves on the advisory boards of Seed Inc. and as a consultant for BiomX. She also receives research funding from Takeda Pharmaceuticals. Scher has served as a consultant for Janssen, Pfizer, UCB, and BMS. He also receives research funding from Janssen and Pfizer. All of these arrangements are being managed in accordance with the policies and practices of NYU Langone Health. Besides Naik, Scher, Subudhi, and Konieczny, other NYU Langone investigators were Aleksandr Prystupa, Rochelle Castillo, Erica Sze-Tu, Yue Xing, Daniel Rosenblum, Ilana Reznikov, Ikjot Sidhu, Cynthia Loomis, Catherine Lu, and Aristotelis Tsirigos. Other study co-investigators were Niroshana Anandasabapathy, at Weill Cornell Medicine; Mayte Suarez-Farinas, at the Icahn School of Medicine at Mount Sinai; and Johann Gudjonsson, at the University of Michigan. Contact: Gregory Williams, [email protected] SOURCE NYU Langone Health

Clinical Result

13 May 2024

·www.biospace.com

HUTCHMED Initiates the RAPHAEL Registrational Phase III Trial of HMPL-306 for Patients with IDH1- and/or IDH2-Mutated Relapsed/Refractory Acute Myeloid Leukemia in China

HONG KONG and SHANGHAI, China and FLORHAM PARK, N.J., May 14, 2024 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that it has initiated a registrational Phase III clinical trial of HMPL-306 in patients with mutated isocitrate dehydrogenase (“IDH”) 1 or 2 relapsed / refractory acute myeloid leukemia (“AML”) in China. The first patient received their first dose on May 11, 2024. HMPL-306 is a novel dual-inhibitor of IDH1 and IDH2 enzymes. Mutations of IDH1 and IDH2 have been implicated as drivers of certain hematological malignancies, gliomas and solid tumors, particularly among AML patients. Although some IDH inhibitors have been approved in certain markets for AML, isoform switching between the cytoplasmic mutant IDH1 and mitochondrial mutant IDH2 often leads to acquired resistance to single inhibitors of IDH1 or IDH2. Targeting both IDH1 and IDH2 mutations may provide therapeutic benefits in cancer patients by overcoming this acquired resistance. RAPHAEL is a multicenter, randomized, open-label, registrational Phase III clinical trial designed to evaluate the safety and efficacy of HMPL-306 as a monotherapy in patients with relapsed or refractory AML harboring IDH1 and/or IDH2 mutations. The primary endpoint of overall survival (OS) and the secondary endpoints, including event-free survival (EFS) and complete remission (“CR”) rate, will be tested in comparison with current salvage chemotherapy regimens. The Company is looking to enroll approximately 320 patients for this registrational study, which is being led by principal investigator Prof Xiaojun Huang of Peking University People’s Hospital. Additional details may be found at clinicaltrials.gov, using identifier NCT06387069. The study follows positive data from a two-stage, open-label Phase I study evaluating the safety, pharmacokinetics, pharmacodynamics and efficacy of HMPL-306 in this indication (NCT04272957). The first-in-human dose-escalation stage data was presented at the European Hematology Association Congress (“EHA”) in June 2023.1 Results of the dose expansion stage of the study in over 50 patients demonstrated promising CR rates at the recommended Phase II dose are expected to be presented at the EHA Congress in June 2024. About IDH and Hematological Malignancies IDHs are critical metabolic enzymes that help to break down nutrients and generate energy for cells. When mutated, IDH creates a molecule that alters the cell’s genetic programming and prevents cells from maturing. IDH1 or IDH2 mutations are common genetic alterations in various types of blood and solid tumors, including AML with approximately 14-20% of patients having mutant IDH genes, myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), low-grade glioma and intrahepatic cholangiocarcinoma. Mutant IDH isoform switching, either from cytoplasmic mutant IDH1 to mitochondrial mutant IDH2, or vice versa, is a mechanism of acquired resistance to IDH inhibition in AML and cholangiocarcinoma.2,3,4 According to the National Cancer Institute (NCI), there will be approximately 20,380 new cases of AML in the U.S. in 2023 and the five-year relative survival rate is 31.7%5. Currently, the U.S. Food and Drug Administration (FDA) has approved two drugs for IDH1 mutation and one drug for IDH2 mutation, but no dual inhibitor targeting both IDH1 and IDH2 mutants has been approved. There were an estimated 19,700 new cases of AML in China in 2018 and is estimated to reach 24,200 in China in 2030.6 In China one IDH1 inhibitor was approved in 2022. About HUTCHMED HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines now marketed in China, the first of which is also marketed in the U.S. For more information, please visit: or follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of HMPL-306 for the treatment of patients with relapsed or refractory AML and the further development of HMPL-306 in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the timing and outcome of clinical studies and the sufficiency of clinical data to support an NDA submission of HMPL-306 for the treatment of patients with relapsed or refractory AML or other indications in China or other jurisdictions, its potential to gain approvals from regulatory authorities on an expedited basis or at all, the efficacy and safety pro HMPL-306, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for HMPL-306 and the timing of these events. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise. Medical Information This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. CONTACTS Investor Enquiries +852 2121 8200 / ir@hutch-med.com Media Enquiries Ben Atwell / Alex Shaw, FTI Consulting +44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) / HUTCHMED@fticonsulting.com Zhou Yi, Brunswick +852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com Nominated Advisor Atholl Tweedie / Freddy Crossley / Daphne Zhang, Panmure Gordon +44 (20) 7886 2500 _______________________ REFERENCES 1 Hu L et al. P539: A Phase 1 Study of HMPL-306, a Dual Inhibitor of Mutant Isocitrate Dehydrogenase (IDH) 1 and 2, in Patients with Relapsed/Refractory Myeloid Hematological Malignancies Harboring IDH1 and/or 2 Mutations. Hemasphere. 2023;7(Suppl):e86312d3. Published 2023 Aug 8. doi:10.1097/01.HS9.0000969064.86312.d3. 2 S Choe S et al. Blood 2019;134(Supplement_1):545. doi:10.1182/blood-2019-122671. 3 Harding JJ et al. Isoform Switching as a Mechanism of Acquired Resistance to Mutant Isocitrate Dehydrogenase Inhibition. Cancer Discov. 2018;8(12):1540-1547. doi:10.1158/2159-8290.CD-18-0877. 4 Delahousse J et al. Circulating oncometabolite D-2-hydroxyglutarate enantiomer is a surrogate marker of isocitrate dehydrogenase-mutated intrahepatic cholangiocarcinomas. Eur J Cancer. 2018;90:83-91. doi:10.1016/j.ejca.2017.11.024. 5 Source: National Cancer Institute – seer.cancer.gov/statfacts/html/amyl.html. 6 Lin J et al. IDH1 and IDH2 mutation analysis in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. Ann Hematol. 2012;91(4):519-525. doi:10.1007/s00277-011-1352-7.

Phase 1Phase 2Clinical ResultPhase 3Immunotherapy

24 Jan 2024

·www.prnewswire.com

Moleculin Announces 2023 Year-End Annamycin Clinical Trials Preliminary Data and 2024 Expectations for Multiple Data Readouts and Transition to Pivotal Phase 2B/3

– MB-106 AML Phase 1B/2 trial (MB-106) preliminary data readout: Reached 67% recruitment – MB-106 preliminary results: Intent to Treat CR rate of 40% plus a CR/ CRi rate of 47% (N=15); Dosed Per Protocol CR rate of 46% plus a CR/CRi rate of 54% (N=13) – First 1st line AML subject treated and resulted in a CR in MB-106 – No CR/CRi's in MB-106 have relapsed to date – MB-107 STS Lung Mets Phase 1B/2 trial preliminary data readout: Phase 1B median extended overall survival of 11 months for heavily pre-treated subjects (N=15); Phase 2 data continues to develop – 100% of Annamycin subjects in multiple studies (N=62) continue to show no signs of cardiotoxicity during study as evidenced by an independent expert's reports – Company provides 2024 business outlook and updates its upcoming milestones HOUSTON, Jan. 24, 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 2023 year-end Annamycin clinical trials preliminary data and 2024 expectations for multiple data readouts and a transition to pivotal Phase 2B/3 clinical studies. The Company also updated its upcoming milestones. "Over the course of 2023, we delivered on our promise for a year of important data from our Annamycin clinical development programs. We are well-positioned to continue building upon our encouraging growing body of preliminary clinical data and transition to pivotal Phase 2B/3 clinical trials by year-end 2024. We believe that Annamycin should be positioned as a 2nd line therapy for acute myeloid leukemia or AML, and for the first time ever, should enable a clear majority of patients to benefit from anthracyclines. Anthracyclines continue to represent one of the most important treatments for AML and advanced soft tissue sarcoma," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin. Mr. Klemp continued, "Our progress is accelerating. Last month, we reported strong results from our first 11 patients in our AML clinical trial. Now, just weeks later our evaluable patients have increased to 15 and the results are even stronger. Enrollment continues to be robust, and we expect to announce the completion of enrollment of 2nd line patients by the time we announce financial results at the end of March, if not sooner. We believe that data will present a clear picture of the approvability of Annamycin and will support our discussions with the FDA for developing an accelerated approval pathway as a 2nd line therapy for relapsed and refractory AML, including a pivotal approval clinical trial we expect to begin before the end of 2024. With our recent financing in December 2023, we have extended our runway into the fourth quarter of 2024, as well. We thank our investors and collaborators for their support in 2023 and we look forward to an exciting and prosperous 2024." Preliminary 2023 Year-End Annamycin Clinical Trials Data AML The Company is currently conducting its Phase 1B/2 clinical trial evaluating Annamycin in combination with Cytarabine (also known as "Ara-C" and for which the combination of Annamycin and Ara-C is referred to as AnnAraC) for the treatment of subjects with AML as both first line therapy and for subjects who are refractory to or relapsed after induction therapy (MB-106). clinicaltrialsregister.eu: EudraCT 2020-005493-10 or clinicaltrials.gov: NCT05319587. The Company has also begun recruiting 1st line subjects into this trial. The Company continues to treat subjects in the Phase 2 portion of the study. Below is a summary of the data to date on this trial which is preliminary and subject to change. Among subjects who had an evaluable post treatment bone marrow biopsy, or who dropped out due to an adverse event (AE), there have been 6 complete responses (CR's) and 1 complete response with incomplete recovery of platelets and/or neutrophils or 40% CR and 47% CR/CRi's of the intent to treat (ITT) subjects (N=15) and 46% CR's and 54% CR/CRi's of the subjects treated (dosed with Annamycin) (N=13). Two subjects experienced adverse events and were not dosed per protocol with one having an allergic reaction to Annamycin, the first the Company has seen in over 70 subjects dosed in the Company's multiple Annamycin clinical trials; the second adverse event was due to an allergic reaction to cytarabine. The CR/CRi's have been spread across 3 different sites in two different countries (Poland and Italy) and 7 out of 9 sites participating in the study have recruited subjects to date. The Company has expanded the study protocol to include a cohort of 1st line subject which should provide data to enable the designing of a potential confirmatory Phase 3 post-approval study, however it does not expect the addition of this cohort to delay its End of Phase 2 (EOP2) Meeting with the FDA, which will focus primarily on securing an accelerated approval pathway for the treatment of 2nd line patients (those who were relapsed from or refractory to a 1st line AML therapy). The first 1st line therapy AML subject for Annamycin was recruited, treated, and upon evaluation it was determined that the treatment resulted in a CR. The first CR subject was treated in February of 2023. The Company has not been notified of any relapses to date, indicating significant durability of the CRs being generated in this study. There continues to be no evidence of cardiotoxicity as reported by an independent expert's reports following assessments of ejection fractions, strain analyses, ECGs, and cardiac biomarkers including Troponin-I and T cross all trials (N=62). Most subjects have experienced myelosuppression, febrile neutropenia and/or thrombocytopenia, which are common adverse events with other anthracyclines. Currently, the median age of the 15 intent to treat subjects in MB-106 is 69 years (range of age is 32 to 78 years) with a median number of prior therapies for AML of 1 (range of 0 to 6). The Company has recruited 19 subjects to date with 2 subjects withdrawing from the trial due to adverse events and 4 other subjects not yet having a bone marrow aspirate fully evaluable. The Company may recruit up to 28 subjects in the Phase 1B/2 clinical trial. At the Company's current rate of recruitment for the study, Moleculin expects to complete recruitment and report topline data in 1H 2024, if not by the end of the first quarter. STS Lung Mets On September 21, 2023, Moleculin announced the completion of enrollment in the Phase 2 portion of its U.S. Phase 1B/2 clinical trial evaluating Annamycin as monotherapy for the treatment of soft tissue sarcoma lung metastases (MB-107) clinicaltrials.gov: NCT04887298. All subjects had pulmonary metastasis from soft tissue sarcoma (STS Lung Mets or STS) and at least one prior therapy. There was no limit on how many prior therapies a subject could have prior to entering this study. Most subjects were heavily treated with other therapies prior to entering our trial with our treatment representing the 4th median therapy for all subjects in the Phase 1B and Phase 2 portion of the trial (range of 2 to 12). Below is a summary of the data to date on this trial which is preliminary and subject to change. The Company previously announced the preliminary data from the Phase 1B portion of the study showing median progression free survival (PFS) for 67% of the Phase 1B subjects of over 2 months (N=15) and median overall survival (OS) of 11.3 months. Not including the one subject that withdrew from OS follow-up the median OS increased to 13 months. Additionally, the Company noted that Phase 1B subjects with less than or equal to 2 prior treatments and treated at the recommended Phase 2 dose or lower demonstrated a higher percentage of subjects with PFS of 2 months or greater at 78% (N=9). Of the 17 subjects in the Phase 2 portion of the study, all treatments have ceased, and subjects are being followed for PFS and OS. A majority of subjects remain alive at this time. The Company believes that the data will be similar to or better than the Phase 1B portion of the study and will announce the results once the study has substantively concluded. 2024 Expected Upcoming Milestones The Company announces the updated expected upcoming milestones for 2024. Annamycin AML 1H 2024: In-depth data review and presentation of topline data on MB-106 clinical trial. 1H 2024: MB-106 End of Phase 2 (EOP2) Meeting with the FDA and/or its European equivalent. Mid 2024: Identify next phase of development/pivotal program. Late 2024 into 1H 2025: Initiate pivotal program. STS Lung Mets 2H 2024: Final MB-107 data readout. 2024: Identify next phase of development/pivotal program. Late 2024 into 1H 2025: Initiate 1st line STS study with an investigator-initiated trial. Other Drug Candidates Moleculin is in ongoing discussions with multiple academic institutions in separate programs evaluating WP1066 for the treatment of glioblastomas and/or pediatric brain tumors. The Company expects to finalize agreements with Northwestern University for an investigator-initiated and funded trial in early 2024 (clinicaltrials.gov: NCT05879250). Expected Upcoming Milestones Report topline results from investigator-initiated Phase 1 study in pediatric brain tumors. Announce results of formulation efforts for intravenous delivery. Expect the commencement of an externally funded investigator-initiated adult clinical trial to be announced in 1H 2024. Seeking investigator-initiated pediatric cancer clinical trial in 2H 2024. WP1122 was developed as a prodrug of 2 deoxy-D-Glucose (2-DG) to provide a more favorable pharmacological profile and was found to have greater potency than 2-DG monotherapy in preclinical models where tumor cells require higher glycolytic activity than normal cells. WP1122 has also been shown to have a greater antiviral effect than 2-DG against SARS-CoV-2 in MRC-5 cells in culture. The improved pharmacokinetic and pharmacodynamic (PK/PD) profile of WP1122 compared to 2-DG was noted in mice following oral dosing at equimolar (i.e., equivalent levels of 2-DG) doses. WP1122 successfully completed a Phase 1 clinical trial, which established a recommended safe dose for future potential Phase 1B or Phase 2 clinical trials. The WP1122 Portfolio includes numerous analogs, including WP1096, which has demonstrated the potential for broad antiviral capabilities in a wide range of in vitro models including multiple arenaviruses, filoviruses, Zika virus, and HIV. The Company looks forward to the potential for additional externally funded research to confirm such activity. Expected Upcoming Milestones Report preliminary findings of National Institutes of Health (NIH) funded animal testing of WP1096 in the Tacaribe Arenavirus. Identify investigators interested in initiating a clinical trial to study the safety, pharmacokinetics, and efficacy of oral WP1122 in adult patients with GBM. About Moleculin Biotech, Inc. Moleculin Biotech, Inc. is a clinical stage pharmaceutical company with a growing pipeline, including Phase 2 clinical programs, for hard-to-treat tumors and viruses. The Company's lead program, Annamycin is a next-generation anthracycline designed to avoid multidrug resistance mechanisms with little to no cardiotoxicity. Annamycin is currently in development for the treatment of acute myeloid leukemia (AML) and soft tissue sarcoma (STS) lung metastases. 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, and WP1220, an analog to WP1066, for the topical treatment of cutaneous T-cell lymphoma. Moleculin is also engaged in the development of a portfolio of antimetabolites, including WP1122 for the potential treatment of COVID-19 and other viruses, as well as cancer indications including brain tumors, pancreatic and other cancers. For more information about the Company, please visit and connect on Twitter, 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, the Expected Upcoming Milestones set forth above, the pace of enrollment in Moleculin's clinical trials, the timing of Moleculin's ability to report topline data from its studies, the timing of the commencement of investigator-sponsored and/or externally funded clinical trials which are outside the control of Moleculin, and whether the results of Moleculin's preclinical animal models can be replicated in human 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, LLC Jenene Thomas (833) 475-8247 [email protected] SOURCE Moleculin Biotech, Inc.

Clinical ResultPhase 2Phase 1

100 Deals associated with 2-Deoxyglucose

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB08831

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
COVID-19	IN	Dr. Reddy's Laboratories Ltd.	01 May 2021

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Common Cold	Phase 2	NL	G.ST Antivirals GmbHStartup	02 Apr 2024
Rhinovirus infection	Phase 2	NL	G.ST Antivirals GmbHStartup	02 Apr 2024
Prostatic Cancer	Phase 2	US	Defense Language Institute Foreign Language Center	01 Nov 2006
Advanced Malignant Solid Neoplasm	Phase 1	US	Threshold Pharmaceuticals, Inc.	01 Feb 2004
Breast Cancer	Phase 1	US	Threshold Pharmaceuticals, Inc.	01 Feb 2004
Head and Neck Neoplasms	Phase 1	US	Threshold Pharmaceuticals, Inc.	01 Feb 2004
Lung Cancer	Phase 1	US	Threshold Pharmaceuticals, Inc.	01 Feb 2004
Pancreatic Cancer	Phase 1	US	Threshold Pharmaceuticals, Inc.	01 Feb 2004
Stomach Cancer	Phase 1	US	Threshold Pharmaceuticals, Inc.	01 Feb 2004

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ERS2019	Not Applicable	Mesothelioma	-	Cisplatin+Pemetrexed	awoghjtyxk(uzkaugkxfd) = ecyvgqkhrq pkaseyvxba (wsvhuxsevw )	-	28 Sep 2019
ERS2019	Not Applicable	Mesothelioma	-	2-Deoxy-glucose (2DG)+Cisplatin+Pemetrexed	awoghjtyxk(uzkaugkxfd) = ubgcmldjdo pkaseyvxba (wsvhuxsevw )	-	28 Sep 2019
MP88-06 (AUA2016)	Not Applicable	Bladder Cancer	-	2-deoxyglucose (2DG)	oighqtitpf(vkgkgprvau) = zasxvpwceo dbowtijfbn (zteiqhjhwd ) View more	-	01 Apr 2016
ASN2014	Not Applicable	Polycystic Kidney Diseases	-	2-deoxyglucose (2DG)	dwtuvehybn(lqlzhjxwly) = kbiiyqyipr eeqpwumuzi (vsxycmzndy ) View more	-	11 Nov 2014
ASN2014	Not Applicable	Polycystic Kidney Diseases	-	Vehicle treatment	dwtuvehybn(lqlzhjxwly) = zlvpowacjt eeqpwumuzi (vsxycmzndy ) View more	-	11 Nov 2014
SP018 (ERA2014)	Not Applicable	Polycystic Kidney Diseases	-	2-deoxyglucose (2-DG)	rflvtzeiaj(eurpzxbcgv) = inhibited izdrqqkdsf (imhbggyxmn ) View more	Positive	01 May 2014
NCT00633087 (CTgov)	Phase 1/2	Advanced cancer \| Castration-Resistant Prostatic Cancer	12	2-deoxyglucose	zbxfzhqmsd(dyueiuxnpi) = kyynflzazo lpjqkwsgxw (ricgcisler, ylnvyxdupl - oyhweidbsj) View more	-	07 Jan 2014
NCT00096707 (Pubmed \| Cancer Chemother Pharmacol)	Phase 1	HR-positive/HER2-low Solid Tumors	-	2-deoxy-D-glucose	nbjaxyopda(vtbyxbebso) = zkrkwgfabn jvginmhnnd (cyhrevqsot ) View more	-	01 Feb 2013
AACR2010	Phase 1/2	HR-positive/HER2-low Solid Tumors \| Castration-Resistant Prostatic Cancer	12	2-Deoxyglucose	ckwtczacqt(jeznrbizel) = ladgzqnznq crqstzmhjo (sgwuvhsalr ) View more	-	15 Apr 2010
ARVO2003	Not Applicable	Ganglion Cysts	-	2-deoxy-D-glucose (2DG)	pzzqxddnhg(dfmuifgcdp) = zyvvgglygn kezwxpcivv (lfpeguibrl )	-	01 May 2003
ARVO2003	Not Applicable	Ganglion Cysts	-	Saline	pzzqxddnhg(dfmuifgcdp) = waxltxfdel kezwxpcivv (lfpeguibrl )	-	01 May 2003

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