Insilico Medicine and Atossa Therapeutics Publish AI-Driven Study in Nature Scientific Reports Identifying (Z)-Endoxifen as a Potential Therapeutic Candidate for Glioblastoma

Atossa Therapeutics (Nasdaq: ATOS) and Insilico Medicine published a joint AI-driven study in Nature Scientific Reports on Dec 2, 2025 identifying (Z)-endoxifen as a potential therapeutic candidate for glioblastoma (GBM).

Rhea-AI Summary

Atossa Therapeutics (Nasdaq: ATOS) and Insilico Medicine published a joint AI-driven study in Nature Scientific Reports on Dec 2, 2025 identifying (Z)-endoxifen as a potential therapeutic candidate for glioblastoma (GBM).

The study used Insilico's PandaOmics across >900 cancer indications and multi-omic methods, ranked GBM as a top opportunity, found >1,400 shared genes reversed by endoxifen, and reported in vitro suppression of GBM cell proliferation exceeding high-dose temozolomide plus tolerable in vivo dosing. Insilico also cited 20 preclinical nominations with a 12–18 month average turnaround.

Positive

• AI screening ranked GBM among top indications from >900 evaluated
• >1,400 genes shared between GBM tumors and endoxifen-treated cells
• In vitro endoxifen suppressed GBM proliferation more than high-dose temozolomide
• In vivo dosing of endoxifen was reported as well tolerated
• Insilico nominated 20 preclinical candidates with 12–18 month average turnaround

Negative

• Findings are limited to preclinical in vitro and in vivo data; no human clinical efficacy reported
• Report notes substantial unpublished collaborative work, indicating early-stage development

Argus Dec 2 session

-5.65% close to close Open Argus

Details

News Market Reaction – ATOS

On Dec 2, the day this news came out, ATOS closed 5.65% below the previous close.

Data tracked by StockTitan Argus for the Dec 2 session.

Market Context

On Dec 2, the day this news came out, the stock closed 5.7% below the previous close. A negative rea...

Analysis

On Dec 2, the day this news came out, the stock closed 5.7% below the previous close. A negative reaction despite this AI-driven GBM publication would fit ATOS’s pattern where science-focused updates sometimes preceded declines, such as the -5.65% move on the prior GBM AI release and weak reactions around DMD and earnings news. The market may be discounting long development timelines and existing cash burn while awaiting clearer clinical or regulatory inflection points for (Z)-endoxifen.

Key Figures

GBM 5-year survival: roughly 4% Cancer indications screened: more than 900 Shared genes identified: more than 1,400 +3 more

GBM 5-year survival

roughly 4%

Background prognosis for glioblastoma multiforme in adults

Cancer indications screened

more than 900

PandaOmics evaluation of oncology indications for endoxifen

Shared genes identified

more than 1,400

Genes shared between GBM tumors and endoxifen-treated cells

Preclinical candidates

20 candidates

Insilico nominations from 2021–2024

Turnaround to PCC

12–18 months

Average time from project start to preclinical candidate nomination

Molecules per program

60–200 molecules

Number synthesized and tested per Insilico program

Historical Context

5 past events · Latest: Dec 09

5 events

1. Dec 09

   Patent issuance

   24h Move

   +3.5%

   USPTO granted a broad U.S. patent with 100 claims for (Z)-endoxifen.

2. Dec 04

   Regulatory strategy update

   24h Move

   +2.7%

   FDA Type C feedback clarified expedited development paths for (Z)-endoxifen.

3. Dec 02

   AI research publication

   24h Move

   -5.7%

   AI-driven Nature paper identified (Z)-endoxifen as a GBM candidate with strong preclinical signals.

4. Nov 17

   DMD opportunity update

   24h Move

   -1.9%

   (Z)-endoxifen highlighted for DMD and carrier patients based on mechanistic hypothesis work.

5. Nov 12

   Earnings/corporate update

   24h Move

   -1.7%

   Q3 2025 results showed higher operating expenses and outlined IND and trial plans.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Key Terms

glioblastoma multiforme, multi-omics, transcriptomic integration, single-cell sequencing, +4 more

8 terms

glioblastoma multiforme medical

"joint study evaluating the potential of (Z)-endoxifen for glioblastoma multiforme (GBM)"

An aggressive form of brain cancer that grows quickly and spreads into nearby brain tissue, often causing severe symptoms and limited treatment options. For investors, glioblastoma matters because it defines a high unmet medical need and a potentially large market for new drugs, devices, or diagnostics; success or failure in clinical trials and regulatory reviews for glioblastoma treatments can dramatically affect the valuation and risk profile of healthcare companies, like a make-or-break product for a small biotech.

multi-omics medical

"By applying multi-omics and AI-enabled methods—including transcriptomic integration"

Multi-omics is a comprehensive approach that combines different types of biological data—such as genetic information, proteins, and other molecules—to gain a detailed understanding of how living systems function. For investors, this approach can reveal insights into health, disease, or biological processes that may influence the development of new treatments or technologies, potentially impacting market opportunities and innovation in healthcare.

transcriptomic integration medical

"methods—including transcriptomic integration, computational modeling, single-cell sequencing"

Combining RNA-based measurements from different experiments, tissues or patient groups into a single, consistent dataset to reveal which genes are active and how their activity patterns change. For investors, it matters because this clearer, broader picture can speed discovery of drug targets, help match therapies to the right patients, and reduce the chance of costly clinical failures — like assembling many partial maps into one accurate navigation chart.

single-cell sequencing medical

"computational modeling, single-cell sequencing, survival analysis, and experimental validation"

Single-cell sequencing is a laboratory method that reads the genetic or activity profile of individual cells instead of averaging many together, like listening to each musician in an orchestra rather than the blended sound. For investors it matters because it reveals rare cell types and precise molecular targets that can drive new diagnostics, drugs or personalized treatments, potentially changing a company’s development risk, timelines and valuation.

protein–protein interaction networks technical

"PandaOmics combined differential expression, pathway enrichment, protein–protein interaction networks"

Protein–protein interaction networks map how proteins in a cell connect and work together, like a social network that shows who talks to whom. Investors care because these maps reveal critical biological pathways that drug developers can target, help predict how therapies will affect disease processes, and guide research priorities; clearer networks can reduce scientific risk and make biotech programs more attractive or valuable.

apoptosis medical

"(Z)-endoxifen significantly suppressed GBM cell proliferation and induced apoptosis"

Apoptosis is a controlled, built‑in process where cells deliberately shut down and are safely removed, like a person retiring and clearing out their belongings so the house stays orderly. Investors care because many drugs and diagnostics target or measure this process: how well a therapy triggers or avoids apoptosis can determine clinical trial success, safety profiles, regulatory approval, and ultimately a company’s valuation.

in vitro medical

"Laboratory validation closely matched the computational predictions. In vitro, (Z)-endoxifen"

In vitro describes laboratory tests performed on cells, tissues, or biological molecules outside a living body—literally “in glass,” such as in test tubes or dishes. For investors, in vitro results are an early sign that a drug or technology has a desired effect under controlled conditions, but they don’t guarantee it will work or be safe in animals or people; think of them as a prototype tested on a bench rather than in real-world use.

in vivo medical

"In vivo studies confirmed that endoxifen was well tolerated across all doses"

In vivo describes tests or experiments performed inside a living organism, such as an animal or human, to observe how a drug, device or biological process behaves in a real, functioning body. Investors care because in vivo results reveal safety, effectiveness and possible side effects that lab tests cannot, much like road-testing a prototype car in traffic rather than only on a bench — outcomes can strongly influence regulatory approval, clinical success and a company’s valuation.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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CAMBRIDGE, Mass., Dec. 2, 2025 /PRNewswire/ -- Insilico Medicine ("Insilico"), a global leader in AI-powered drug discovery, and Atossa Therapeutics ("Atossa") (Nasdaq: ATOS), a clinical-stage biopharmaceutical company developing novel treatments for breast cancer and other serious conditions, announce the publication of a joint study evaluating the potential of (Z)-endoxifen for glioblastoma multiforme (GBM). The peer-reviewed article, now published in Nature's Scientific Reports, represents one of the most comprehensive AI-enabled analyses to date exploring whether endoxifen, an active metabolite of tamoxifen with known activity in endocrine-resistant breast cancer, may offer new therapeutic opportunities for one of the deadliest malignant brain tumors in adults. The study aimed to identify new oncology indications with high therapeutic potential for endoxifen, as monotherapy or in combination, by applying Insilico's AI-powered PandaOmics platform across a wide range of cancer types based on its mechanisms of action. Through this systematic evaluation, GBM emerged as a top candidate for further investigation.

The publication highlights progress in understanding glioblastoma, an aggressive primary brain tumor with a five-year survival rate of roughly 4%. By applying multi-omics and AI-enabled methods—including transcriptomic integration, computational modeling, single-cell sequencing, survival analysis, and experimental validation—the study offers mechanistic insights that support further exploration of endoxifen's potential role in this setting.

(Z)-Endoxifen, already clinically active in hormone-resistant breast cancer and known to act through both estrogen-dependent and estrogen-independent mechanisms, has long been considered a promising molecule for broader oncology applications, but has not been systematically explored in GBM. Using PandaOmics, researchers evaluated more than 900 cancer indications with weighted transcriptomic signatures from endoxifen-treated datasets. PandaOmics combined differential expression, pathway enrichment, protein–protein interaction networks, mechanistic NLP, and disease unmet-need modeling, ultimately ranking GBM among one of the highest-opportunity indications.

AI-driven analyses identified more than 1,400 genes shared between GBM tumors and endoxifen-treated cells, revealing strong reversal of biological programs that drive tumor growth and treatment resistance. Endoxifen was predicted to counteract pathways associated with uncontrolled proliferation, inflammation, metabolic dysregulation, and aggressive tumor behavior. Single-cell sequencing further pinpointed key malignant-cell genes linked to poor survival and aggressive subtypes, all of which were downregulated by endoxifen.

"This collaboration with Insilico Medicine provides a whole new indication in which we might explore the utility of endoxifen, and potentially significant new opportunities to address an extremely underserved set of cancer patients," said Steven Quay, M.D., Ph.D., CEO of Atossa Therapeutics. "Most of our joint projects have focused on advancing women's health, but this study allowed us to extend our work into glioblastoma, a disease with an urgent and unmet need, and not unlike other highly ranked indications, including but not limited to Duchenne muscular dystrophy (DMD) and multiple gynecologic-related cancers for which (Z)-Endoxifen may have excellent therapeutic outcomes. The results of our collaboration with Insilico highlight how AI-enabled discovery can uncover entirely new opportunities for a well-characterized molecule like endoxifen."

Laboratory validation closely matched the computational predictions. In vitro, (Z)-endoxifen significantly suppressed GBM cell proliferation and induced apoptosis, demonstrating greater cytotoxic activity than high-dose temozolomide and showing enhanced effects in combination. In vivo studies confirmed that endoxifen was well tolerated across all doses. Together, the multi-omic analyses and experimental findings highlight endoxifen as a promising therapeutic candidate for GBM and showcase how AI-powered discovery can reveal new opportunities for drug repurposing and cancer treatment innovation.

"Atossa is deeply committed to scientific leadership in the prevention and treatment of high risk breast cancers, and Insilico is honored to collaborate with the company to advance genuine innovation and expand indications across different areas of oncology," said Alex Zhavoronkov, Ph.D., Founder and CEO of Insilico Medicine. "This publication represents one of the early fruits of our joint research, and much of our collaborative work remains unpublished. We are hopeful that these efforts will ultimately translate into meaningful therapeutic programs."

Harnessing state-of-the-art AI and automation technologies, Insilico has significantly improved the efficiency of preclinical drug development. While traditional early-stage drug discovery typically requires 3 to 6 years, from 2021 to 2024 Insilico nominated 20 preclinical candidates, achieving an average turnaround - from project initiation to preclinical candidate (PCC) nomination - of just 12 to 18 months per program, with only 60 to 200 molecules synthesized and tested in each program.

About Insilico Medicine

Insilico Medicine, a leading and global AI-driven biotech company, utilizes its proprietary Pharma.AI platform and cutting-stage automated laboratory to accelerate drug discovery and advance innovations in life sciences research. By integrating AI and automation technologies and deep in-house drug discovery capabilities, Insilico is delivering innovative drug solutions for unmet needs including fibrosis, oncology, immunology, pain, and obesity and metabolic disorders. Additionally, Insilico extends the reach of Pharma.AI across diverse industries, such as advanced materials, agriculture, nutritional products and veterinary medicine.

For more information, please visit www.insilico.com.

About Atossa Therapeutics

Atossa Therapeutics, Inc. (Nasdaq: ATOS) is a clinical-stage biopharmaceutical company developing innovative therapies for significant unmet needs in breast cancer. Atossa's strategy emphasizes disciplined capital allocation, focusing resources on programs and data packages that can enable future regulatory submissions and potential commercialization.

For more information, visit www.atossatherapeutics.com and refer to Atossa's filings with the U.S. Securities and Exchange Commission (SEC).

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SOURCE Atossa Therapeutics Inc

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Atossa (ATOS) and Insilico announce on Dec 2, 2025 about (Z)-endoxifen and GBM?

They published an AI-driven study in Nature Scientific Reports identifying (Z)-endoxifen as a potential GBM candidate after multi-omic analyses and laboratory validation.

How did Insilico's PandaOmics rank glioblastoma for (Z)-endoxifen in the Dec 2025 study?

PandaOmics evaluated >900 indications and ranked GBM among the highest-opportunity indications for endoxifen.

Did the Dec 2025 study report clinical trial results for (Z)-endoxifen in GBM?

No; the publication reported in vitro and in vivo preclinical results only, with no human clinical efficacy data.

How did (Z)-endoxifen perform versus temozolomide in the Atossa/Insilico preclinical work?

(Z)-endoxifen showed greater cytotoxic activity than high-dose temozolomide in vitro and enhanced effects in combination.

What investor-relevant development timelines did Insilico report in the Dec 2025 announcement?

Insilico reported nominating 20 preclinical candidates from 2021–2024 with an average 12–18 month turnaround per program.