On November 24, 2025 Rakovina Therapeutics Inc. ("Rakovina" or the "Company") (TSX-V: RKV)(FSE: 7JO0) a biopharmaceutical company advancing cancer therapies through AI-enabled drug discovery, reported impressive results from its AI-enabled ATR program at the 2025 Society for Neuro-Oncology (SNO) Annual Meeting which took place November 19-23 in Honolulu, Hawaii.

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The poster, titled "Discovery and development of a novel CNS-penetrating ATR inhibitor: Dual inhibition of ATR and mTOR in PTEN-deficient tumors," highlights the discovery and early characterization of novel ATR/mTOR dual inhibitors designed using the Enki generative AI platform. The compounds are engineered to modulate two well-established cancer-driving pathways that, despite their importance, have never before been combined in a single therapeutic agent. Notably, Rakovina’s lead molecules were designed specifically to cross the blood–brain barrier and reach tumor cells within the central nervous system, supporting their potential relevance in primary brain cancers and cancers with a high risk of brain metastasis.

Rakovina’s senior management team presented the findings showing that the AI-discovered ATR+mTOR inhibitors achieve meaningful CNS penetration, addressing a key limitation of current clinical ATR inhibitors, which have poor CNS distribution. In direct comparisons, multiple Rakovina compounds showed >50% ATR inhibition at 1 µM and exhibited equal or greater enzymatic potency than leading ATR inhibitors ceralasertib, tuvusertib, and elimusertib, while maintaining similar PIKK-family selectivity.

Importantly, these compounds were engineered with a mechanistic rationale to co-target ATR and mTOR, two pathways on which PTEN-deficient tumors (including those prone to brain metastasis) are highly dependent. By simultaneously blocking ATR-mediated DNA damage response and mTOR-driven survival signaling, these CNS-penetrant inhibitors have the potential to overcome key resistance mechanisms in PTEN-deficient cancers and deliver therapeutic effects not achievable with ATR-only agents.

PTEN deficiency in cancer

PTEN is one of the most frequently lost tumor-suppressor genes in human cancer and serves as a key brake on the PI3K/AKT/mTOR signaling pathway that governs cell growth, metabolism, and survival. Its loss promotes unchecked proliferation, genomic instability, therapy resistance, and aggressive tumor progression.

PTEN deficiency is particularly prevalent in cancers with a high propensity for CNS spread, including ovarian, lung, breast, and melanoma – where tumor cells rely heavily on mTOR-driven growth and survival. In these settings, mTOR becomes an adaptive escape pathway, especially under ATR inhibition, allowing PTEN-deficient tumors to accelerate growth and diminish the effectiveness of ATR-only therapeutic strategies.

Prevalence of PTEN deficiency and CNS metastases in major cancers
Cancer type Approximate frequency of PTEN loss Est. CNS Metastases Prevalence
Lung cancer ~ 35-55 % ~55% in NSCLC
Breast cancer ~ 30-40 % ~40%
Prostate cancer ~ 25-50 % ~8%
Colorectal cancer ~ 10-40 % ~6%
Ovarian cancer ~ 30-50 % ~5%
Endometrial carcinoma ~ 50 % 1-2%
Glioblastoma (brain) ~ 80-85 % n/a (primary brain tumor
Using the ENKI generative AI platform, the Company designed a virtual library of 138 predicted compounds, from which, 43 priority molecules were synthesized for evaluation in biochemical and cellular assays. Multiple compounds demonstrated >50% inhibition of recombinant ATR at 1 µM and exhibited potency comparable to or exceeding ATR inhibitors currently in development including ceralasertib, tuvusertib, and elimusertib.

Pharmacokinetic profiling in mice following a single 5 mg/kg intraperitoneal dose revealed favorable tolerability, metabolic stability in human liver microsomes, and measurable CNS exposure, supporting further evaluation in brain tumor models.

"Sharing these data at SNO is an important milestone for our ATR/mTOR program," said Prof. Mads Daugaard, President and Chief Scientific Officer of Rakovina Therapeutics. "To our knowledge, no company has previously generated a single small-molecule therapeutic designed to combine ATR and mTOR inhibition with CNS penetration. Seeing generative AI propose compounds with this level of precision gives us a fundamentally new way to address these difficult-to-treat cancers with a high risk of brain involvement."

"The reception to our data at SNO has been very encouraging," added Jeffrey Bacha, executive chairman of Rakovina Therapeutics. "This program showcases how combining Variational AI’s Enki platform with the translational capabilities at the Vancouver Prostate Centre allows us to rapidly pursue differentiated DDR-targeted therapeutics with potential clinical relevance in areas of significant unmet need."

(Press release, Rakovina Therapeutics, NOV 24, 2025, View Source;utm_medium=rss&utm_campaign=rakovina-therapeutics-showcases-compelling-preclinical-data-on-ai-discovered-cns-penetrant-atr-mtor-inhibitors-at-the-2025-society-for-neuro-oncology-annual-meeting [SID1234660906])

On November 24, 2025 PharmaMar (MSE:PHM) reported that the Swiss Agency for Therapeutic Products (Swissmedic) has granted approval for Zepzelca (lurbinectedin) in combination with atezolizumab (Tecentriq) as a maintenance treatment for adults with extensive-stage small cell lung cancer

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(ES-SCLC), with no central nervous system (CNS) metastases whose disease has not progressed after first-line induction therapy with atezolizumab, carboplatin and etoposide. The decision marks the first combination therapy approval in an European country for first-line maintenance treatment of ES-SCLC, a fast growing and aggressive cancer with limited treatment options.

The Swissmedic approval is based on results from the Phase 3 IMforte[i] trial, which showed that the lurbinectedin and atezolizumab combination reduced the risk of disease progression or death by 46% and the risk of death by 27%, compared to atezolizumab maintenance therapy alone. Following four cycles of induction therapy, from the point of randomization the median overall survival (OS) for the combination regimen was 13.2 months versus 10.6 months and median progression-free survival (PFS) by independent assessment was 5.4 months versus 2.1 months, respectively. Safety was consistent with the known safety profiles of both treatments

In 2023, Swissmedic granted Temporary Authorisation for the commercialization of lurbinectedin alone for the treatment of adult patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy without CNS metastases in second line.

Luis Mora, Managing Director of PharmaMar, said: "Switzerland has become the first European country to approve this combination for use as a first-line treatment, giving patients access to this new therapy. We will continue working to ensure that as many patients as possible have access to this new therapy across as many countries as possible."

In October, the U.S Food and Drug Administration (FDA) granted approval for Zepzelca (lurbinectedin) in combination with atezolizumab (Tecentriq) as a maintenance treatment for adults with extensive-stage small cell lung cancer (ES-SCLC). In addition, the National Comprehensive Cancer Network (NCCN) recently updated the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for SCLC to include the combination as a preferred regimen for maintenance.

PharmaMar has also submitted a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA), which is currently under review.

SCLC represents about 15% of all lung cancer cases in Europe, each year, approximately 72,600 new cases of SCLC are reported in Europe. Most of these patients are diagnosed with extensive stage disease, which is aggressive and often difficult to treat, with poor prognosis.

(Press release, PharmaMar, NOV 24, 2025, View Source [SID1234660905])

On November 24, 2025 Pasithea Therapeutics Corp. (Nasdaq: KTTA) ("Pasithea" or the "Company"), a clinical-stage biotechnology company developing PAS-004, a next-generation macrocyclic oral MEK inhibitor for the treatment of neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN), reported positive safety, PK and PD data from Cohort 7 (37mg capsules) in its ongoing first-in-human trial evaluating PAS-004 in patients with MAPK pathway-driven advanced solid tumors with a documented RAS, NF1 or RAF mutation, or in patients who have failed prior BRAF/MEK inhibition (NCT06299839).

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Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea commented, "We are highly encouraged by the initial safety data generated in Cohort 7 (37mg capsules), where zero treatment-related adverse events have been observed during the DLT period. Furthermore, PD data demonstrates the pharmacological profile we believe is necessary to achieve consistent pathway inhibition over the 24-hour dosing period, while avoiding both periods of excessive suppression and periods of insufficient target engagement. We believe this balanced profile will be critical for achieving clinical efficacy while minimizing the most commonly observed adverse events associated with MEK inhibitors. We believe PAS-004 is particularly well suited for the treatment of diseases involving the MAPK pathway that require chronic dosing over long periods of time, where sustained long-term pathway suppression at safe and well-tolerated doses is required."

PAS-004 has demonstrated in Cohort 7 (37mg capsules):

Safety and Tolerability Results:

PAS-004 was safe and well tolerated with no dose limiting toxicities (DLTs), and no treatment-related adverse events observed during the DLT period.

After reviewing cohort 7 data, the Safety Review Committee recommended to proceed to Cohort 8, 45mg capsules, without modification.

Pharmacodynamics (PD) Results:

At steady-state, individual patient plasma data showed PAS-004 inhibiting phosphorylated extracellular signal-regulated kinase (pERK) at a level of 80% near Cmax.

At steady-state, individual patient plasma data showed PAS-004 inhibiting pERK at a level above 60% at Cmin (24-hour postdose).

Pharmacokinetics (PK) Results:

Linear PK and dose-proportionality.

PK curve with Cmax/Cmin ratio <2.

AUC: 6,690 ng*h/mL; Cmax: 313 ng/mL; Cmin: 260 ng/mL.

Graph 1 below represents the complete PAS-004 dose escalation curve at steady state in our ongoing Phase 1 trial in advanced cancer patients.

(Press release, Pasithea Therapeutics, NOV 24, 2025, View Source [SID1234660904])

On November 24, 2025 Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company focused on enhancing the standard of care for bevacizumab for the treatment of retina diseases, reported that Bob Jahr, Chief Executive Officer of Outlook Therapeutics, will participate in a fireside chat at the Piper Sandler 37th Annual Healthcare Conference on Tuesday, December 2, 2025 at 10:00 AM ET.

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In addition to the fireside chat, management will be available to participate in one-on-one in-person meetings with qualified members of the investor community who are registered to attend the conference.

A live webcast of the fireside chat will be accessible on the Events page in the Investors section of the Company’s website (outlooktherapeutics.com). The webcast replay will be archived for 90 days following the event.

(Press release, Outlook Therapeutics, NOV 24, 2025, View Source [SID1234660903])

On November 24, 2025 NANOBIOTIX (Euronext: NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-stage clinical biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer and other major diseases, reported an operational update and financial results for the third quarter of 2025 along with an outlook for clinical updates from studies sponsored by Nanobiotix or The University of Texas MD Anderson Cancer Center ("MD Anderson") expected in 2026 and announced the closing of its non-dilutive royalty financing transaction with HCRx.

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Operational Highlights

Establishing the Financial Foundation for Self-sustained Long-term Growth
Closed the royalty financing transaction with Healthcare Royalty ("HCRx") triggering an upfront payment of $50 million
Nanobiotix expects to receive an additional $21 million in one year, subject to reaching certain conditions
Progressing JNJ-1900 (NBTXR3) Clinical Development
Presented first data from a Phase 1 MD Anderson study evaluating JNJ-1900 (NBTXR3) for patients with esophageal cancer presented at the 2025 Annual Meeting of the American Society for Radiation Oncology (ASTRO), adding another potential indication that warrants further investigation
Completed the sponsorship transfer of Phase 3 study evaluating JNJ-1900 (NBTXR3) for patients with locally advanced head and neck cancer who are ineligible for cisplatin (NANORAY-312) in the majority of regions, along with the transfer of full operational control of the Phase 3 study, to Johnson & Johnson ("J&J")
Advancing the Curadigm Nanoprimer Program
Four new patent applications filed to expand the Curadigm Nanoprimer intellectual property portfolio and support an initial proprietary internal pipeline of Nanoprimer-based products in addition to external collaborations
New in vivo pre-clinical data evaluating the Nanoprimer in combination with therapeutic vaccines presented at the 2025 Partnership Opportunities in Drug Delivery conference (PODD) that could serve as the foundation for an initial internal proprietary pipeline of Nanoprimer-based products
Momentum building for external collaborations featuring Nanoprimer platform combinations with numerous material transfer agreements already in place
Chemistry, Manufacturing, and Controls (CMC) activities launched to support internal pipeline and external collaborations

"2025 has been a year of strong execution against our strategic priorities, further accelerated by the momentum we built in the third quarter and to date," said Laurent Levy, Chief Executive Officer and Chairman of the Executive Board at Nanobiotix. "We took another disciplined financing step toward self-sustained, long-term growth through the closing of a non-dilutive strategic royalty monetization with HCRx. Clinically, we saw continued advancement of the JNJ-1900 (NBTXR3) program with completion of the Phase 3 head and neck cancer study sponsorship transfer to J&J in the majority of regions and first data from a Phase 1 esophageal cancer study supporting evaluation in yet another indication. In parallel, our Curadigm Nanoprimer program is rapidly emerging as a long-term growth driver for Nanobiotix. We are well positioned to accelerate our trajectory in 2026 and beyond."

Closing of the Royalty Financing Transaction

The closing of this royalty financing transaction with HCRx marks a significant milestone for the Company with an upfront payment of $50 million. The Company expects an additional $21 million in one year, subject to reaching certain conditions.

HCRx will be compensated and repaid out of a capped portion of milestones and royalties on sales of JNJ-1900 (NBTXR3) payable to Nanobiotix under the Janssen license agreement. This repayment and compensation will be implemented through a trust established between (i) Nanobiotix as settlor and beneficiary, (ii) HCRx funds as beneficiaries, and (iii) European Investment Bank ("EIB") as beneficiary. Furthermore, contractual covenants granted by Nanobiotix to HCRx regarding the proper implementation by Nanobiotix of the Janssen license agreement shall also benefit to EIB.

2026 JNJ-1900 (NBTXR3) Clinical Data Outlook for Studies Sponsored by Nanobiotix or MD Anderson

Final data from Nanobiotix Study 1100 evaluating JNJ-1900 (NBTXR3) followed by pembrolizumab or nivolumab anti-PD-1 checkpoint inhibitors for patients with primary cutaneous melanoma resistant to anti-PD-1
Updated data from a Phase 1 MD Anderson study evaluating JNJ-1900 (NBTXR3) for patients with locally advanced non-small cell lung cancer (NSCLC) who are amenable to re-irradiation
New data from expansion cohort of a Phase 1 MD Anderson study evaluating JNJ-1900 (NBTXR3) in combination with standard-of-care chemotherapy (capecitabine) for patients with locally advanced or borderline resectable pancreatic cancer
Updated results and establishment of the recommended Phase 2 dose (RP2D) from the proton therapy cohort of a Phase 1 MD Anderson study evaluating JNJ-1900 (NBTXR3) activated by photon or proton therapy for patients with locally advanced esophageal cancer
Third Quarter Financial Updates

Cash, Cash Equivalents and Operating Runway:

€20.4 million in cash and cash equivalents as of September 30, 2025
$50 million upfront payment to be received by Nanobiotix given the closing of the HCRx agreement, plus the additional $21 million expected one year post-closing upon reaching certain conditions, would extend cash visibility into early 2028
About JNJ-1900 (NBTXR3)

JNJ-1900 (NBTXR3) is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. Its proof-of-concept was achieved in soft tissue sarcomas through a successful randomized Phase 2/3 study in 2018. The product candidate’s mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that JNJ-1900 (NBTXR3) could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.

Radiotherapy-activated JNJ-1900 (NBTXR3) is being evaluated across multiple solid tumor indications as a single agent or combination therapy. The program is led by NANORAY-312—a global, randomized Phase 3 study in locally advanced head and neck squamous cell cancers. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of JNJ-1900 (NBTXR3) activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy—the same population being evaluated in the Phase 3 study.

Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3, Nanobiotix has engaged in a collaboration strategy to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several Phase 1 and Phase 2 studies evaluating JNJ-1900 (NBTXR3) across tumor types and therapeutic combinations. In 2023, Nanobiotix announced a license agreement for the global co-development and commercialization of JNJ-1900 (NBTXR3) with Janssen Pharmaceutica NV, a Johnson & Johnson company.

(Press release, Nanobiotix, NOV 24, 2025, View Source [SID1234660902])