On October 7, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported the completion of the Verona Pharma plc (Nasdaq: VRNA) ("Verona Pharma") acquisition (Press release, Merck & Co, OCT 7, 2025, View Source [SID1234656484]). Verona Pharma is now a wholly-owned subsidiary of Merck and the American Depositary Shares (ADS) of Verona Pharma will no longer be listed or traded on the Nasdaq Global Market.

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"The Verona Pharma acquisition strengthens and complements our portfolio of treatments for patients with cardio-pulmonary diseases to include Ohtuvayre, while delivering near and long-term growth as well as value for shareholders," said Robert M. Davis, chairman and chief executive officer, Merck. "The addition of Ohtuvayre is another strong example of our business development strategy, which focuses on opportunities where compelling science and value align. Ohtuvayre is a novel, first-in-class maintenance treatment targeting an important unmet need for adult patients with COPD. We look forward to applying our commercial capabilities and working with our talented new colleagues from Verona Pharma to build on the strong uptake and performance to date to reach even more patients with this important medicine."

Through this acquisition Merck has added Ohtuvayre (ensifentrine), a first-in-class selective dual inhibitor of phosphodiesterase 3 and 4 (PDE3 and PDE4), to its growing cardio-pulmonary pipeline and portfolio. The U.S. Food and Drug Administration approved Ohtuvayre in June 2024 for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients. Ohtuvayre is the first novel inhaled mechanism for the maintenance treatment of COPD in more than 20 years and combines bronchodilator and non-steroidal anti-inflammatory effects. Ohtuvayre is also being evaluated in clinical trials for the treatment of non-cystic fibrosis bronchiectasis.

Additional Transaction Details
Under the terms of the acquisition agreement, Merck, through a subsidiary, has acquired all outstanding shares of Verona Pharma for $107 per ADS, each of which represents eight Verona Pharma ordinary shares, for a total transaction value of approximately $10 billion.

As previously disclosed, the acquisition will result in the capitalization of most of the purchase price as an intangible asset for Ohtuvayre (which will be amortized as a GAAP-only charge over the life of the product). The transaction is expected to negatively impact non-GAAP EPS by approximately $0.16 in the first 12 months, representing costs associated with financing the transaction partially offset by Ohtuvayre performance.

Ohtuvayre Indication and Important Safety Information

INDICATION

Ohtuvayre is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients.

IMPORTANT SAFETY INFORMATION
Contraindication: Ohtuvayre is contraindicated in patients with hypersensitivity to ensifentrine or any component of this product.

Warnings and Precautions:
Acute Episodes of Bronchospasm Ohtuvayre should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled, short-acting bronchodilator.

Paradoxical Bronchospasm As with other inhaled medicines, Ohtuvayre may produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with Ohtuvayre, it should be treated immediately with an inhaled, short-acting bronchodilator. Ohtuvayre should be discontinued immediately and alternative therapy should be instituted.

Psychiatric Events Including Suicidality Before initiating treatment with Ohtuvayre, healthcare providers should carefully weigh the risk and benefits of treatment with Ohtuvayre in patients with a history of depression and/or suicidal thoughts or behavior. Patients, their caregivers, and families should be advised of the need to be alert for the emergence or worsening of insomnia, anxiety, depression, suicidal thoughts, or other mood changes, and if such changes occur to contact their healthcare provider. Healthcare providers should carefully evaluate the risks and benefits of continuing treatment with Ohtuvayre if such events occur.

Treatment with Ohtuvayre is associated with an increase in psychiatric adverse reactions. Psychiatric events including suicide-related adverse reactions were reported in clinical studies in patients who received Ohtuvayre (1 suicide attempt and 1 suicide). Additionally, the most commonly reported psychiatric adverse reactions in the pooled 24-week safety population were insomnia (6 patients [0.6%] Ohtuvayre 3 mg; 2 patients [0.3%] placebo), and anxiety (2 patients [0.2%] Ohtuvayre 3 mg; 1 patient [0.2%] placebo). Depression-related reactions including depression, major depression, and adjustment disorder with depressed mood occurred in 4 patients [0.4%] receiving Ohtuvayre and no patients receiving placebo.

Adverse Reactions: The most common adverse reactions ≥1% in Ohtuvayre and greater than placebo in the pooled population were back pain 1.8%, hypertension 1.7%, urinary tract infection 1.3%, and diarrhea 1.0%.

These are not all of the possible risks associated with Ohtuvayre.

Please see Prescribing Information for Ohtuvayre (ensifentrine) at: View Source, Patient Information for Ohtuvayre at: View Source

About Chronic Obstructive Pulmonary Disease (COPD)
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition that causes restricted airflow and breathing problems. Emphysema and chronic bronchitis are the two most common types of COPD. Common symptoms of COPD include shortness of breath, an ongoing cough or a cough that produces a lot of mucus, wheezing, chest tightness or heaviness and fatigue. Smoking and air pollution are the most common causes of COPD. More than 390 million people were estimated to be suffering from COPD worldwide as of 2019 and COPD is the fourth leading cause of death worldwide. There is no cure for COPD.

About Ohtuvayre (ensifentrine)
Ohtuvayre is the first inhaled therapy for the maintenance treatment of adults with COPD that combines bronchodilator and non-steroidal anti-inflammatory activities in one molecule. Verona has evaluated nebulized Ohtuvayre in its Phase 3 clinical program ENHANCE ("Ensifentrine as a Novel inHAled Nebulized COPD thErapy") for COPD maintenance treatment. Ohtuvayre met the primary endpoint in both ENHANCE-1 and ENHANCE-2, demonstrating statistically significant and clinically meaningful improvements in lung function. A fixed-dose combination of ensifentrine and glycopyrrolate, a LAMA, is currently under development for the maintenance treatment of COPD.

On October 7, 2025 MaaT Pharma (EURONEXT: MAAT – the "Company"), a clinical-stage biotechnology company and a leader in the development of Microbiome Ecosystem TherapiesTM (MET) dedicated to enhancing survival for patients with cancer through immune modulation, reported that the independent Data Safety Monitoring Board (DSMB) has completed the second pre-planned safety interim analysis of the ongoing PHOEBUS trial, a Phase 2b randomized controlled trial designed to be pivotal, evaluate the efficacy and safety of MaaT033 versus placebo in patients undergoing an Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) (Press release, MaaT Pharma, OCT 7, 2025, View Source [SID1234656483]). The PHOEBUS trial is the world’s largest randomized controlled trial evaluating microbiome therapy in oncology to date.

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"We are pleased to report another positive safety review for MaaT033 with the DSMB’s recommendation to continue the trial without modification marking a key milestone in its development. We remain fully committed to advancing this Phase 2b trial and to delivering a much-needed therapeutic option for patients fighting blood cancers and undergoing allo-HSCT and to shaping a future where microbiome-based therapies become an integral part of hematology-oncology treatment," said Hervé Affagard, Chief Executive Officer and co-founder of MaaT Pharma.

The DSMB reviewed unblinded safety data on 120 enrolled patients (including 60 patients randomized to receive MaaT033) and monitored patients for 90 days after allo-HSCT as per the trial protocol. Patients are especially vulnerable in the early phase after allo-HSCT, with a heightened risk of non-relapse mortality. To ensure patient safety, the study protocol includes a predefined safety review, with a stopping rule if an excess of mortality is detected in the experimental group.

Following its review, the DSMB recommended that the study continue as planned, having identified no safety concerns and no excessive mortality related to MaaT033 as of today.

In addition to this specific safety analysis, routine safety assessments are conducted every six months. All assessments to date have confirmed a favorable safety profile for MaaT033, and recommended continuation of the trial without modifications. These regular safety reviews further support MaaT033’s integration in the allo-HSCT treatment setting, without significant added risk of severe adverse events.

Patient enrollment for the PHOEBUS trial is ongoing in France, Germany, Belgium, Spain, Netherlands and the United Kingdom. The trial is expected to enroll 387 patients and is set to be conducted in up to 60 clinical investigational sites (NCT05762211). Next steps include the routine DSMB review for ongoing safety for MaaT033, conducted every six months, with the next analysis expected for the first quarter of 2026.

MaaT033 is designed to reach an expanded patient population through its oral capsule administration that could address approximately 6.000 patients per year, with an estimated potential market of €500 million (EU5, US). By enabling outpatient use, MaaT033 also supports optimized patient care.

About MaaT033

MaaT033, a standardized, donor-derived, high-richness, high-diversity oral Microbiome Ecosystem TherapyTM containing anti-inflammatory ButycoreTM species, is currently being developed as an adjunctive therapy to improve overall survival in patients receiving HSCT and other cellular therapies. It aims to ensure optimal microbiota function and to address a larger patient population in a chronic setting. MaaT033 has been granted Orphan Drug Designation by the European Medicines Agency (EMA).

On October 7, 2025 Kazia Therapeutics Limited (NASDAQ: KZIA), an oncology-focused drug development company, reported an exclusive collaboration and in-licensing agreement (the "Agreement") with QIMR Berghofer for a first-in-class PD-L1 degrader program (Press release, Kazia Therapeutics, OCT 7, 2025, View Source [SID1234656482]). The lead optimized compound, NDL2, is an advanced PD-L1 protein degrader currently in development and represents a new and innovative frontier of cancer immunotherapy.

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About PD-L1 Degradation and NDL2

Cancer cells frequently express PD-L1 protein to evade immune attack. When PD-L1 on a tumor cell surface binds to PD-1 on a T cell, the T cell becomes inactivated and loses its ability to destroy the cancer. Traditional checkpoint inhibitors such as pembrolizumab (Keytruda) and nivolumab (Opdivo) use monoclonal antibodies to block this surface interaction, helping to restore T-cell activity.

However, research has shown that PD-L1 also exists in post-translationally modified forms that are enriched in patients who fail or relapse on checkpoint inhibitor therapy. These modified proteins are found on the cell surface as well as in the cytoplasm and nucleus, where they contribute to resistance and tumor progression.

NDL2 takes a fundamentally different approach. This novel bicyclic peptide degrader, discovered and developed by Professor Sudha Rao, is designed to specifically recognize and degrade these resistant, post-translationally modified forms of PD-L1. By binding PD-L1 and recruiting the cell’s natural protein disposal machinery, NDL2 drives the breakdown and clearance of the modified PD-L1 across all cellular compartments. Targeting these resistant PD-L1 pools that antibody therapies cannot reach offers the potential to overcome immunotherapy resistance and restore durable immune activity against tumors.

We believe this comprehensive degradation strategy has the potential to offer two major clinical advantages: (1) Overcoming resistance in both primary non-responders and patients who relapse on antibody therapies, and (2) Providing durable immune reactivation by restoring cytotoxic T-cell function and reducing T-cell exhaustion in the tumor microenvironment.

NDL2 Preclinical Evidence

In preclinical models of aggressive triple-negative breast cancer (TNBC), NDL2 monotherapy, as well as in combination with anti-PD-1 therapies, achieved significant tumor growth reduction. Importantly, treated tumors showed reduced T-cell exhaustion and enhanced immune activity, consistent with NDL2’s dual mechanism of action. Across the preclinical work to date, no toxicity has been observed. Professor Rao and QIMR Berghofer are working in parallel with a number of world-leading oncology peptide manufacturers to optimize the stability, potency, pharmacokinetics and pharmacodynamics of the NDL2 formulation.

Development Pathway and Combinations

The program will initially target advanced breast cancer and non-small cell lung cancer (NSCLC), where PD-1/PD-L1 immunotherapies are widely used but resistance remains common. IND-enabling studies are expected to commence within six months, with a goal of initiating first-in-human studies within approximately 15 months. Kazia also intends to explore synergistic opportunities to combine NDL2 with its existing pipeline assets, including paxalisib (a pan-PI3K/mTOR inhibitor) and EVT801 (a selective VEGFR3 inhibitor), given their complementary mechanisms of action in modulating the tumor microenvironment.

Dr. John Friend, Chief Executive Officer of Kazia Therapeutics, commented:

"This Agreement positions Kazia at the forefront of next-generation immuno-oncology. NDL2 is a truly first-in-class asset, representing an advanced PD-L1 degrader, and what we believe one of the most exciting innovations in targeted protein degradation. This program complements our existing pipeline, with clear opportunities for synergy with other immunotherapies as well as paxalisib and EVT801, and we are positioned to rapidly advance it toward the clinic."

Professor Sudha Rao, Principal Investigator at QIMR Berghofer and inventor of the PD-L1 degrader program, added:

"NDL2 has the potential to redefine immunotherapy by targeting all functional pools of PD-L1 protein, not just the surface expression blocked by current antibodies. By eliminating PD-L1 throughout the cell, we can address resistance and other pathways that drive aggressive cancers like TNBC and NSCLC. We are thrilled to partner with Kazia to potentially translate this novel science into a transformative therapy for patients."

Collaboration and Licensing Terms

Under the terms of the collaboration Agreement, Kazia will make a one-time payment of approximately $1.39 million 15 business days after signing and is responsible for all development costs. Kazia will share a percentage of commercialization revenue, which includes any out-licensing payments received from third parties.

On October 7, 2025 Kairos Pharma, Ltd. (NYSE American: KAPA), a clinical-stage biopharmaceutical company dedicated to addressing resistance to current cancer therapeutics, reported that it has been selected to present at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (Press release, Kairos Pharma, OCT 7, 2025, View Source [SID1234656481]). Kairos’s presentation, titled, "Preliminary safety and clinical activity from a Phase 2 study of apalutamide and carotuximab in advanced, castration-resistant prostate cancer" will take place in Berlin, Germany on October 17–21, 2025.

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Prostate cancer remains one of the most diagnosed cancers in men, with over a million new cases annually in the U.S. alone. Resistance to androgen-targeted therapies represents a major clinical challenge in patients with metastatic castration-resistant prostate cancer (mCRPC).

The presentation will highlight results from an interim analysis of the randomized Phase 2 trial evaluating ENV105 (carotuximab), a first-in-class CD105 antagonist. The trial is enrolling 100 men at Cedars-Sinai Medical Center, City of Hope, and Huntsman Cancer Institute at the University of Utah with mCRPC who had progressed on prior hormone therapies. Patients are randomized to receive apalutamide in the presence or absence of ENV105.

"The data we will be presenting at the 2025 ESMO (Free ESMO Whitepaper) Congress demonstrates encouraging safety and early efficacy findings from our Phase 2 trial," said Neil Bhowmick, PhD, Kairos Pharma CSO. "This is an important venue for us to share the therapeutic potential of ENV105 for patients with few remaining treatment options after hormone therapy resistance develops."

On October 7, 2025 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported that findings highlighting the strong potential of circular single-stranded DNA (CssDNA) as a universal, efficient non-viral template for gene therapy, along with a comprehensive study of TALE base editors (TALEB) off-targets in the nuclear genome, will be presented at the European Society of Cell and Gene Therapy (ESGCT) annual congress, that will take place on October 7-10, 2025, in Sevilla, Spain (Press release, Cellectis, OCT 7, 2025, View Source [SID1234656480]).

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Poster presentation:

Title: Circularization of Single-Stranded DNA Donor Template Unleashes the Power of Non-Viral Gene Delivery for Long-Term HSCs editing

Presenter: Julien Valton, Ph.D., Vice President Gene Therapy at Cellectis

Date/Time: Wednesday, October 8, 2025 from 2:00 p.m. to 3:30 p.m. CET

Poster number: P0439

Over the past decade, non-viral DNA template delivery has been used with engineered nucleases to target single-stranded DNA sequences in hematopoietic stem and progenitor cells (HSPCs).

While developed for gene therapy purposes, so far this method has been restricting to gene corrections. To expand this scope, Cellectis developed an editing process using its gene editing technology and kilobase-long circular single-stranded DNA donor templates.

Research data show that:

· CssDNA editing process achieved high gene insertion frequency in viable HSPCs.

· CssDNA-edited HSPCs show a higher propensity to engraft and maintain gene edits in a murine model than adeno-associated viruses (AAV)-edited HSPCs.

These data highlight the strong potential of CssDNA as a universal and efficient non-viral DNA template for gene therapy applications.

The research was also presented as an oral presentation at the Homology-Directed Repair: The Path Forward Workshop in Sevilla on October 6, 2025.

Poster presentation:

Title: Comprehensive analysis of TALEB off-target editing

Presenter: Maria Feola, Ph.D., Senior Scientist, Team Leader Gene Editing at Cellectis

Date/Time: Thursday, October 9, 2025 from 2:00 p.m. to 3:30 p.m. CET

Poster number: P0506

TALE base editors (TALEB) are fusions of a transcription activator-like effector domain (TALE), split-DddA deaminase halves, and an uracil glycosylase inhibitor (UGI).

These recent additions to the genome editing toolbox can directly edit double strand DNA, converting a cytosine (C) to a thymine (T) through the formation of an uracil (U) intermediate without the need of DNA break. Base editing has great potential in therapeutic applications. However, being able to avoid potential off-target effects is key toward this goal.

To evaluate TALEB safety, Cellectis combined advanced bioinformatic predictions with multiple experimental approaches to investigate potential off-target effects in the nuclear genome of primary T cells.

The study found no evidence of biases towards off-site C-to-T editing at sites flanked by CTCF binding sites, a key DNA-binding protein that regulates genome organization and gene expression at genome wide level.

These results provide a strong framework for the safe development of TALEB in therapeutic cell engineering, supporting their potential for future nuclear and mitochondrial applications.