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 that a second scientific abstract from its research and development programs was presented at the 2025 Society for Neuro-Oncology (SNO) Annual Meeting, which took place November 19-23 in Honolulu, Hawaii.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The poster titled "Discovery and development of novel CNS-penetrating PARP1-selective inhibitors," was developed in collaboration with investigators at the Vancouver Prostate Centre and the University of British Columbia, describes the Company’s work applying artificial-intelligence (AI) methods to the discovery and early characterization of novel, PARP1-selective small-molecule drug candidates with properties consistent with central nervous system (CNS) penetration.

The presentation outlines the use of Deep Docking and generative-AI computational approaches to virtually screen large chemical libraries and identify compounds predicted to demonstrate selective inhibition of PARP1, favourable drug-like properties, and characteristics supportive of CNS exposure.

According to the data reported, hundreds of prioritized compounds have been synthesized and evaluated in biochemical assays. A subset demonstrated PARP1-selective activity, as well as in vitro metabolic-stability and pharmacokinetic profiles that will inform additional optimization and testing. Examples of ADME and pharmacokinetic data from the first round of synthesized compounds, including comparisons with existing PARP inhibitors and next-generation benchmark compounds, were also presented.

Prof. Mads Daugaard, President of Rakovina Therapeutics, commented: "The data generated to date provide early insight into our AI-driven discovery platform and its ability to prioritize compounds with the features we are seeking, including PARP1 selectivity and properties supportive of CNS penetration. These results demonstrate timely progress of our PARP1-selective inhibitor program and validate our iterative AI approach."

This SNO 2025 presentation represents the second abstract from Rakovina Therapeutics at the conference and reflects the Company’s ongoing research efforts in the field of DNA-damage-response (DDR) therapeutics.

(Press release, Rakovina Therapeutics, NOV 24, 2025, View Source;utm_medium=rss&utm_campaign=rakovina-therapeutics-inc-announces-presentation-of-second-abstract-at-the-2025-society-for-neuro-oncology-annual-meeting [SID1234660907])

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

(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).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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])