Moleculin Announces Positive Results from Phase 1 Clinical Trial Evaluating WP1066 for the Treatment of Pediatric Recurrent Malignant Brain Tumors

Rhea-AI Summary

Moleculin (Nasdaq: MBRX) announced positive Phase 1 results for WP1066 in pediatric recurrent malignant brain tumors on Dec 17, 2025. The Emory physician‑sponsored trial at Aflac/Children’s Healthcare of Atlanta treated 10 children (plus 3 compassionate‑use cases) to identify a maximum feasible dose given twice daily for 14 days.

Key findings: no significant toxicity, determination of a maximum feasible dose, suppression of STAT3 with demonstrable anti‑tumor immune responses, and a partial response in a diffuse intrinsic pontine glioma (DIPG) patient. Results were published in Journal of Clinical Investigation Insight. Trial identifier: NCT04334863.

Positive

• No significant toxicity observed in pediatric cohort
• Maximum feasible dose determined in Phase 1
• WP1066 suppressed STAT3 expression and activity
• Clear anti‑tumor immune responses documented
• Partial tumor response observed in a DIPG patient
• Results published in Journal of Clinical Investigation Insight

Negative

• Small cohort size: 10 patients plus 3 compassionate‑use cases
• Phase 1 study not powered to demonstrate survival benefit

Key Figures

Pediatric patients treated 10 children Phase 1 WP1066 trial dosing twice daily

Dosing schedule 14 days WP1066 administered twice daily over 14 days

Compassionate use patients 3 children High-grade glioma patients treated under compassionate use

Survival after diagnosis 9–11 months Average survival for DMG and DIPG pediatric brain tumors

Phase of trial Phase 1 First-in-child WP1066 pediatric brain tumor study

ClinicalTrials.gov ID NCT04334863 Identifier for the WP1066 Phase 1 trial

Market Reality Check

$3.98 Last Close

Volume Volume 101,622 is about 0.33x the 20-day average 311,255, indicating subdued pre-news trading. low

Technical Shares at $4.69 were trading below the 200-day MA $16.24, reflecting a longer-term downtrend before this update.

Peers on Argus 1 Up 1 Down

MBRX was up 4.22% pre-news while peers showed mixed moves, from LPTX up 238.84% to MBIO down 6.14%, suggesting stock-specific rather than broad sector action.

Common Catalyst Multiple oncology-focused biotechs reported clinical updates, including a Phase 2a psoriasis study at peer SNGX.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 10	Warrant exercise financing	Negative	-27.1%	Warrant exercises and new warrants for up to 2,610,823 shares.
Dec 09	Clinical trial progress	Positive	-8.6%	Completion of treatment for first 45 patients in pivotal MIRACLE AML trial.
Dec 08	R&D collaboration	Positive	+0.1%	New Annamycin collaboration in glioblastoma preclinical models.
Nov 26	Investor event	Neutral	-22.0%	Announcement of participation in a virtual investor presentation and Q&A.
Nov 26	Reverse stock split	Negative	-22.0%	1-for-25 reverse split reducing outstanding shares to about 2.1M.

Pattern Detected

Recent news often met with selling, even on positive or neutral items, especially around financing and structural actions.

Recent Company History

Over the last few months, Moleculin has combined capital structure changes and clinical progress. A 1-for-25 reverse split on Nov 26 and warrant exercises for about $6.5M in proceeds on Dec 10 coincided with sharp declines. In parallel, the company advanced its pivotal MIRACLE AML trial, completing treatment of the first 45 subjects and expanding global recruitment, yet related clinical updates in September–December 2025 drew mixed to negative reactions. Today’s pediatric brain tumor data add another clinical asset alongside Annamycin.

Regulatory & Risk Context

Active S-3 Shelf Registration 2025-09-19

The company has an active S-3 shelf filed on 2025-09-19 that remains in effect until 2028-09-19. It is noted as not yet effective and with no recorded usage, indicating capacity for future registered financing once effective but no takedowns so far.

Market Pulse Summary

The stock dropped -11.7% in the session following this news. A negative reaction despite positive pediatric Phase 1 data would fit prior patterns where clinically encouraging headlines coincided with selling pressure. Recent examples include MIRACLE trial updates that saw declines of several percent. Structural concerns such as earlier reverse-split and financing headlines have contributed to a fragile backdrop, so even good trial news might not have fully offset broader risk perceptions in the name.

Key Terms

stat3 medical

"Tobey MacDonald, MD, who discovered STAT3 is critical to certain childhood brain tumors"

STAT3 is a protein inside cells that acts like a control knob for turning sets of genes on or off, influencing cell growth, survival and immune responses. For investors, STAT3 matters because drugs or tests that block or measure its activity can be used to treat or track cancers and inflammatory diseases, so progress on STAT3-targeted therapies or diagnostics can affect the value and prospects of biotech and pharmaceutical firms.

regulatory t cells medical

"by inhibiting the errant activity of regulatory T cells while also inhibiting key oncogenic"

Regulatory T cells are a specialized type of immune cell that act like a brake on the body’s defense system, preventing it from attacking healthy tissue or causing chronic inflammation. They matter to investors because drugs that increase or block these cells can change treatment success and safety in areas such as autoimmune disease, organ transplants, and cancer immunotherapy, affecting clinical trial results, approval chances, and commercial value.

oncogenic transcription factors medical

"while also inhibiting key oncogenic transcription factors, including p-STAT3"

Proteins that act like on/off switches for genes, controlling which genes are copied into cellular messages; when these switches are mutated or stuck 'on' they can drive the uncontrolled growth and survival of cells that becomes cancer. Investors should care because these faulty switches are common drug targets and diagnostic markers: therapies that fix or block them can create big markets, while failed trials or regulatory setbacks around such targets can sharply affect company value.

p-stat3 medical

"including p-STAT3 (phosphorylated signal transducer and activator of transcription 3)"

p-STAT3 is the activated form of a cellular signaling protein called STAT3, produced when the protein is chemically modified (phosphorylated) and can turn genes on or off. For investors, p-STAT3 is important because its presence or reduction in lab tests or clinical samples can indicate whether a drug is hitting its intended target, predict how aggressive a disease like cancer may be, and help gauge a therapy’s development and commercial potential—think of it as a molecular ‘on’ switch that shows whether a treatment is working.

c-myc medical

"c-Myc (oncogene driving many aggressive cancers) and HIF-1α"

c-myc is a gene that makes a protein acting like a cell’s “gas pedal,” controlling how fast cells grow, divide, and use energy. Because abnormal c-myc activity is common in many cancers, it is a key target and biomarker in oncology drug development; changes in c-myc can influence whether a therapy works, the size of potential patient populations, and regulatory or commercial prospects for treatments.

hif-1α medical

"and HIF-1α (hypoxia-inducible factor 1α). These transcription factors are widely"

HIF-1α is a protein that acts like a cellular oxygen sensor, switching on genes that help cells survive when oxygen is low. For investors, it matters because drugs or diagnostics that target HIF-1α can change disease outcomes in areas like cancer, heart and vascular disease, and is often a focus of clinical trials and regulatory review; success or failure can materially affect a biotech company's value.

angiogenesis medical

"role in cancer cell survival and proliferation, angiogenesis (coopting vasculature"

Angiogenesis is the biological process where the body builds new blood vessels, like laying new roads to deliver oxygen and nutrients to tissues. Investors care because many drugs aim to block or encourage this process to treat cancer, eye diseases, or chronic wounds; success or failure in controlling angiogenesis often determines a therapy’s effectiveness, regulatory approval, safety profile, and commercial potential.

diffuse intrinsic pontine glioma medical

"partial tumor response in a diffuse intrinsic pontine glioma (DIPG) patient"

A diffuse intrinsic pontine glioma (DIPG) is a rare, aggressive tumor that arises in the pons, a critical area at the base of the brain that controls breathing, balance and basic movement. It matters to investors because DIPG represents a severe unmet medical need with high clinical and regulatory risk, long development timelines and the potential for transformative treatments to command significant attention, funding and valuation changes in biotech and pharmaceutical markets.

AI-generated analysis. Not financial advice.

Emory University physician-sponsored clinical trial conducted at the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta

Results demonstrated WP1066 induces anti-tumor immune responses and were recently published in the Journal of Clinical Investigation Insight

WP1066 found to be safe and effective, warranting a Phase 2 trial

HOUSTON, Dec. 17, 2025 (GLOBE NEWSWIRE) -- Moleculin Biotech, Inc., (Nasdaq: MBRX) (“Moleculin” or the “Company”), today announced positive results from the Emory University physician-sponsored Phase 1 clinical trial conducted at the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta led by pediatric oncologist, Tobey MacDonald, MD, who discovered STAT3 is critical to certain childhood brain tumors and currently serves as Professor of Pediatrics and Director of the Pediatric Neuro-Oncology Program.

WP1066 is Moleculin’s flagship Immune/Transcription Modulator designed to stimulate the immune response to tumors by inhibiting the errant activity of regulatory T cells while also inhibiting key oncogenic transcription factors, including p-STAT3 (phosphorylated signal transducer and activator of transcription 3), c-Myc (oncogene driving many aggressive cancers) and HIF-1α (hypoxia-inducible factor 1α). These transcription factors are widely sought targets because of their role in cancer cell survival and proliferation, angiogenesis (coopting vasculature for blood supply), invasion, metastasis, and inflammation associated with tumors.

“The results of this first-in-child trial show some encouraging signals of activity in a highly aggressive chemotherapy resistant brain cancer, such as partial tumor response in a diffuse intrinsic pontine glioma (DIPG) patient and clear anti-tumor immune changes,” said Dr. MacDonald.

For the Phase 1 trial, 10 children were treated with WP1066 twice daily for 14 days to determine the maximum feasible dose. Compassionate use treatment in three children with high-grade glioma was also evaluated. Results showed there was no significant toxicity, and a maximum feasible dose was determined. Importantly, WP1066 suppressed the expression of STAT3, inhibiting its activity and demonstrating anti-tumor immune responses.

While the preclinical efficacy of WP1066 had been previously demonstrated, and its effectiveness had been studied among adults, this trial was the first to test it in children. Dr. MacDonald and his team recruited pediatric patients with high-grade glioma, which include diffuse midline glioma (DMG) and DIPG, and account for most pediatric brain tumor-related deaths. Both DMG and DIPG have an average survival rate of nine to 11 months following diagnosis. Additionally, patients with relapsed medulloblastoma and ependymoma who have no accepted standard therapy following a relapse were also included in the study. Thus, Dr. MacDonald’s research helps fill a critical need to identify new treatment options for patients with these incurable tumors.

Mr. Walter Klemp, Chairman and CEO of Moleculin, “We are very encouraged by the positive results from our Phase 1 clinical trial evaluating WP1066 in children with recurrent malignant brain tumors. These early data show that WP1066 has the ability to activate meaningful anti-tumor immune responses, an important proof of mechanism in a patient population with extremely limited treatment options. While still early, these findings reinforce the potential of WP1066 as a novel immunomodulatory approach for some of the most difficult-to-treat pediatric brain cancers. We are deeply grateful to Dr. MacDonald and his team, and the patients and families who participated in this study. We look forward to the continued advancement of WP1066 as a potential therapy that can make a real difference for children facing these devastating diseases.”

Results from the study were recently published in the Journal of Clinical Investigation Insight. For more information about the WP1066 Phase 1 clinical trial, visit clinicaltrials.gov and reference identifier NCT04334863.

The results of this study are the foundation of the Phase 2 concept Dr. MacDonald’s team would like to pursue in a follow-up trial. The current study was funded by Peach Bowl LegACy Fund and CURE Childhood Cancer.

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 highly efficacious and well tolerated anthracycline designed to avoid multidrug resistance mechanisms and to lack 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 has begun 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 (the combination of Annamycin and cytarabine, also referred to as “Ara-C”) and, 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 remains 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 also has in its pipeline 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, statements regarding the continued recruitment, treatment, and receipt of the unblinded data for the first 45 subjects of the MIRACLE clinical trial and the timing to complete Part A of the MIRACLE trial with up to 90 patients, each as described above. Moleculin will require significant additional financing, for which the Company has no commitments, in order to conduct its clinical trials as described in this press release, and the milestones described in this press release assume the Company’s ability to secure such financing on a timely basis. 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
(908) 824-0775
MBRX@jtcir.com

FAQ

What did Moleculin (MBRX) announce about WP1066 on December 17, 2025?

Moleculin announced positive Phase 1 results showing no significant toxicity, a maximum feasible dose, STAT3 suppression, immune responses, and a partial DIPG response.

How many children were treated in the WP1066 Phase 1 trial (MBRX) and what was the dosing?

10 children were treated in the dose‑finding study, with WP1066 given twice daily for 14 days; 3 additional compassionate‑use patients were evaluated.

Did the WP1066 trial for MBRX show safety or efficacy signals in pediatric brain tumors?

The trial reported no significant toxicity and showed biological activity: STAT3 suppression and anti‑tumor immune responses, plus a partial response in one DIPG patient.

Where were the WP1066 Phase 1 results for MBRX published and how can I find the trial record?

Results were published in Journal of Clinical Investigation Insight; the clinical trial record is NCT04334863 on clinicaltrials.gov.

Will WP1066 move to a Phase 2 trial after the MBRX Phase 1 data?

Investigators intend to pursue a Phase 2 concept based on these Phase 1 results; the announcement says the Phase 1 findings form the foundation for a follow‑up trial.

Who funded the WP1066 pediatric Phase 1 trial reported by MBRX?

The study was funded by the Peach Bowl LegACy Fund and CURE Childhood Cancer.