On September 9, 2025 DeuterOncology, a clinical-stage biotech company focused on developing best-in-class deuterated cancer therapies, reported compelling safety, pharmacokinetic and efficacy results from its ongoing Phase I dose escalation study of DO-2, a novel deuterated MET tyrosine kinase inhibitor (Press release, DeuterOncology, SEP 9, 2025, View Source [SID1234655892]). The results are being presented at the World Conference on Lung Cancer (WCLC) 2025 in Barcelona (Abstract ID-2859).

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The Phase I study enrolled 29 patients (26 RECIST 1.1 evaluable) with advanced solid tumors harboring any known driver alterations, with 86% having non-small cell lung cancer (NSCLC). The study’s primary findings demonstrate that DO-2 treated patients showed a remarkable 100% Disease Control Rate (DCR) and saw tumor shrinkage in 100% of MET exon 14 skip mutation-positive NSCLC patients without alternative oncogenic drivers and reached efficacious drug exposures (10/10 patients). RECIST 1.1 Partial responses (>30% reduction) were observed in 2 out of these 10 patients. Importantly, the study showed a markedly improved safety profile compared to approved MET inhibitors, with only one patient (5%) experiencing grade 1 peripheral oedema versus 68-82% seen with other agents in this class.

"These results represent a significant advancement in MET-targeted therapy," said Dr. Cecilia Ahlin, CMO of DeuterOncology. "Our deuteration strategy has successfully enhanced drug exposure while maintaining efficacy, but most importantly, we have achieved this without the debilitating peripheral oedema that forces many patients to discontinue current MET inhibitors —symptoms that can severely limit daily activities such as walking, dressing, or cooking. This addresses a critical unmet medical need for cancer patients."

The study’s key findings include:

Superior Safety Profile: Only 1 patient (5%) experienced peripheral oedema (grade 1) compared to 68-82% with approved competitors. No grade 3 or 4 peripheral oedema was observed versus ~17% in approved competitors
Enhanced Pharmacokinetics: Deuteration increased plasma exposure compared to the non-deuterated parent compound, enabling once-daily dosing at 60mg with food, versus 450-800mg daily with approved competitors
Promising Efficacy: A 100% disease control rate (DCR) was observed, including two partial responses, in treatment-naïve and previously treated MET exon 14 skipping NSCLC patients without known resistance mechanisms who achieved efficacious drug exposure. Notably, one patient with pleural effusion experienced full resolution and maintained stable disease for over 20 months
Excellent Tolerability: Only two grade 3 treatment-related adverse events (fatigue and reversible creatinine increase) were observed across all dose levels
Dr. Hans Prenen, Principal Investigator at University Hospital Antwerp (UZA), commented: "The clinical data for DO-2 are very encouraging. The fact that we’re seeing robust anti-tumor activity with minimal peripheral oedema represents a potential game-changer for MET-driven lung cancer patients, who currently face difficult treatment tolerability issues with existing therapies."

The study confirms DeuterOncology’s hypothesis that continuous 24/7 MET inhibition is not required for efficacy but is responsible for the class-effect toxicity of peripheral oedema. DO-2’s unique biochemical and pharmacokinetic profile allows for effective target engagement while providing recovery periods that minimize on-target toxicities.

Based on these promising Phase I results, DeuterOncology has initiated an expansion cohort in selected first-line MET exon 14 skip NSCLC patients to further validate the safety and efficacy of the 60mg once-daily regimen.

Details of the poster presentation are as follows:

Title: Preliminary Safety and PK of the MET-TKI DO-2 in Advanced Solid Tumors with MET Aberrations: Phase I Study

Authors: Hans Prenen MD, PhD, Rachel Galot MD, PhD, Alexis Cortot MD, PhD, Aurélie Swalduz MD, PhD, Bernd Dekeyser MD, Peter de Bruijn PhD, Francois Zammit MD, Jean-Pascal Machiels MD, PhD, Brant Delafontaine MD, Sylvie Rottey MD, PhD, Ingrid Desar MD, PhD, Marthe Paats MD, PhD, Barend J. Sikkema3MD, , Florence Wastelin MSc, Cecilia Ahlin MD PhD, Timothy Perera PhD, Jaap Verweij MD, PhD, Carla van Herpen MD, PhD, Debbie G.J. Robbrecht MD, PhD

Presenter: Timothy Perera

Session date and time: 09 September 2025. 10.00AM CEST

Poster ID number: Abstract ID-2859. P3.18.66

About MET-Driven Lung Cancer

Lung cancer remains the most common form of cancer worldwide, affecting approximately 2.2 million individuals annually. MET exon 14 skipping mutations occur in ~3% of NSCLC patients—equating to an estimated 60,000–70,000 new cases worldwide annually—and represent a validated therapeutic target. However, current approved MET inhibitors suffer from high rates of peripheral oedema (>50% of patients), leading to frequent dose reductions, treatment interruptions, and discontinuations that compromise patient outcomes.

On September 9, 2025 ARTBIO, Inc. ("ARTBIO"), a clinical-stage radiopharmaceutical company developing a new class of Pb212 alpha radioligand therapies (ARTs), reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for AB001, and confirmed the study may proceed (Press release, ARTBIO, SEP 9, 2025, View Source [SID1234655891]). The news follows a recent Series B capital raise to advance the company’s pipeline and proprietary technology platform for Pb212-based therapies.

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"AB001 is a novel PSMA-targeted and Pb212-based radioligand therapy designed to treat patients with metastatic prostate cancer, one that we believe has the potential to increase the radioligand dose rate to tumors without higher toxicity to normal tissues," said Margaret Yu, M.D., Chief Medical Officer of ARTBIO. "Following FDA review, our Phase 1 study may now move ahead. This is welcome news for patients who are eagerly awaiting new targeted treatment options and for investigators who are ready to begin screening patients for this trial."

AB001 had been previously administered to patients in a Phase 0 study conducted in Norway with encouraging biodistribution results in those participants. The report on this study was included as part of the IND.

"Despite the availability of many treatment options, metastatic prostate cancer is still not a curable disease, requiring additional innovative treatments," said Oliver Sartor, M.D., Director of the Transformational Prostate Cancer Research Center at East Jefferson General Hospital Cancer Center and ARTBIO Scientific Advisory Board Member. "I’m grateful for ARTBIO’s dedication and passion in this area and am excited about the difference that AB001 could make for patients."

ARTBIO plans to initiate the Phase 1 clinical trial for AB001 across multiple sites in the U.S. by leveraging its distributed manufacturing network of production hubs, including leading radiopharmaceutical CDMOs like SpectronRx, PharmaLogic, and Nucleus Radiopharma.

Clinical trial supply will be enabled by ARTBIO’s proprietary Pb212 generator technology, AlphaDirect, with precursor isotopes being sourced from the U.S. Department of Energy. The company plans to enroll patients outside of the U.S. once additional regulatory approvals are secured.

"This IND clearance represents critical progress in translating the unique biology of Pb212 into patient care," said Dr. Michael Morris, Professor of Medicine, Prostate Section Head at Memorial Sloan Kettering Cancer Center and ARTBIO Clinical Advisory Board Member. "With the ability to target radiation at the cellular level, this program has the potential to establish a new standard of care in metastatic prostate cancer."

About AB001
AB001 is an Alpha Radioligand Therapy (ART) consisting of a prostate-specific membrane antigen (PSMA)-targeted small molecule radiolabeled with Pb212. PSMA is commonly overexpressed in mCRPC and has become an attractive target for imaging agents and therapies.

On September 9, 2025 XtalPi Inc. (Stock Code: 2228.HK) reported that PEP08, a next-generation PRMT5 inhibitor candidate developed through its AI drug discovery collaboration with PharmaEngine, Inc. (TWO:4162), has received regulatory clearances to initiate Phase 1 clinical trials in solid tumors (Press release, XtalPi, SEP 9, 2025, View Source [SID1234655890]). Approvals include Australia’s Human Research Ethics Committee (HREC), recognized by the Australian Therapeutic Goods Administration (TGA), and the food and drug authority of the Taiwan region (TFDA). This milestone triggered a payment to XtalPi under the partnership agreement.

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PRMT5 (Protein Arginine Methyltransferase 5) is a validated synthetic lethality target in tumors harboring homozygous MTAP deletion, which is related to poor prognosis and present in 10-15% of human cancers, including small cell lung cancer (NSCLC), mesothelioma, pancreatic cancer, glioblastoma multiforme (GBM), head and neck cancer, esophageal cancer, and bladder cancer. While PRMT5 inhibition offers a potent mechanism for targeted therapy, first-generation inhibitors face significant challenges in selectivity, resulting in dose-limiting toxicities and unmet medical needs.

Leveraging its integrated drug discovery platform that combines quantum physics, AI, and large-scale robotic experiments, XtalPi partnered with PharmaEngine’s scientific team to conduct de novo drug design. The AI platform generated a multi-million compound library for PRMT5, identifying novel lead series with exceptional potency and selectivity. Following iterative optimization through quantum physics and AI-powered ADMET screening, PEP08 emerged as the preclinical candidate (PCC) and advanced through IND-enabling studies by PharmaEngine.

As a second-generation PRMT5 inhibitor with a novel scaffold, PEP08 demonstrates superior activity and selectivity. Its MTA-cooperative binding mode stabilizes a ternary complex with PRMT5, enabling highly selective target inhibition. This mechanism drives potent synthetic lethality efficacy against MTAP-deleted tumor cells while minimizing off-target effects on normal cells, highlighting significant therapeutic potential.

Preclinical studies revealed PEP08’s markedly improved safety profile compared to first-generation PRMT5 inhibitors, alongside favorable blood-brain barrier penetration and overall developability characteristics. The compound achieved robust in vivo efficacy across multiple animal models. Compared to other clinical-stage second-generation candidates, PEP08 exhibits potential best-in-class properties and compelling combination therapy opportunities. PharmaEngine presented these findings at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

PEP08’s successful regulatory clearance and milestone achievement underscore XtalPi’s platform-driven innovation capabilities and mark a pivotal advancement in its partnership with PharmaEngine. XtalPi remains committed to empowering partners to discover novel drug candidates addressing complex targets, accelerate the development of competitive pipeline projects, and deliver transformative medicines to patients worldwide.

On September 9, 2025 Akeso Inc. (9926.HK) reported that data from a Phase Ib/II clinical study evaluating the combination of cadonilimab and pulocimab (an anti-VEGFR-2 antibody) in patients with immunotherapy (IO)-resistant NSCLC were presented in a Mini Oral session at the 2025 World Conference on Lung Cancer (WCLC) (Press release, Akeso Biopharma, SEP 9, 2025, View Source [SID1234655889]). This marks the first clinical data release for cadonilimab in IO-resistant lung cancer. The cadonilimab combination therapy for advanced squamous non-small cell lung cancer (NSCLC) progressing after PD-(L)1 inhibitor treatment, has previously received Breakthrough Therapy Designation from the NMPA.

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The combination of cadonilimab and pulocimab also offers a potentially chemo-free option for advanced IO resistant NSCLC patients. The data presented at the 2025 WCLC demonstrated that the cadonilimab plus pulocimab regimen shows encouraging efficacy and broad clinical potential in patients with advanced or metastatic NSCLC who progressed after first-line standard immunotherapy-based treatment, offering a promising effective and safe therapeutic option for IO-resistant lung cancer patients:

As of January 13, 2025, with a median follow-up of 16.7 months, the cadonilimab-based combination achieved a median overall survival (mOS) of 15.6 months and a median progression-free survival (mPFS) of 5.8 months in IO-resistant NSCLC.
In the squamous NSCLC (sqNSCLC) subgroup, mOS was 16.7 months, mPFS was 7.1 months, the disease control rate (DCR) reached 96.2%, and the objective response rate (ORR) was 11.5%. In the non-squamous NSCLC (nsq-NSCLC) subgroup, mOS was 12.8 months, mPFS was 5.5 months, DCR was 95.2%, and ORR was 14.3%.
Based on the promising clinical efficacy and safety data, preparation is underway for a Phase III clinical study evaluating the combination of cadonilimab and pulocimab for IO-resistant lung cancer. Additionally, ivonescimab (PD-1/VEGF), another novel bispecific antibody developed by Akeso, has shown unique efficacy and significant expansion potential in the IO-resistant NSCLC population. A registrational Phase III trial for ivonescimab has already been initiated.

As first-in-class bispecific antibodies, both cadonilimab and ivonescimab are showing increasing advantages across a broadening range of disease areas. By leveraging dual-targets with synergistic mechanisms, they both address critical clinical challenges, such as limited efficacy or resistance to single-target agents like PD-1 inhibitors. This positions the bispecific antibodies as superior treatment options for patients worldwide.

In recent years, immunotherapy has made significant progress in lung cancer treatment. PD-1/L1 inhibitors, either alone or with platinum-based chemotherapy, are the first-line treatment for driver-negative advanced NSCLC. However, 60%–70% of patients experience disease progression within a year. Docetaxel is the standard therapy for IO-resistant patients, but its effectiveness is limited. Improving outcomes for NSCLC patients after IO resistance remains a critical unmet need. Previous Phase III trials for IO-resistant lung cancer, including those with PD-1 inhibitors and ADCs, have not demonstrated meaningful clinical benefits. There is currently no approved standard treatment for NSCLC after resistance to IO therapies.

The combination of cadonilimab and pulocimab has shown strong clinical potential in IO-resistant lung cancer, notably extending patient survival. The cadonilimab and pulocimab combination has also shown promising clinical data in other treatment-resistant cancers, including IO-resistant hepatocellular carcinoma and gastric cancer. Cadonilimab’s proven efficacy for patients across all levels of PD-L1 expression, positions it as a key solution for IO-resistant cancers. This breakthrough offers a potentially new option for NSCLC patients that currently have limited treatment options after resistance to cancer immunotherapies.

On September 9, 2025 iOnctura, a clinical-stage precision oncology company focused on neglected and hard-to-treat cancers, reported the expansion of its clinical trial program for lead candidate roginolisib into the United States (Press release, iOnctura, SEP 9, 2025, View Source [SID1234655888]). Several US trial sites are now enrolling patients in the OCULE-01 Phase II study in metastatic uveal melanoma, with an additional study, led by Dr Jennifer Brown, underway in chronic lymphocytic leukemia (CLL) at Dana-Farber Cancer Institute.

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Catherine Pickering, CEO and co-founder of iOnctura said, "We are proud to begin the next phase of iOnctura’s global growth by making roginolisib available to US patients in our clinical studies. The enthusiastic response from US investigators, leading research centers, and patient communities highlights the significant opportunity to impact outcomes for individuals with limited treatment options."

Roginolisib, an orally dosed small molecule allosteric modulator of PI3Kδ, is being investigated in multiple randomized Phase II studies in solid and hematological malignancies. The global Phase II randomized OCULE-01 study (NCT06717126) will assess whether roginolisib improves overall survival in patients with metastatic uveal melanoma who have progressed on prior therapy. Patients from both the US and Europe are now being treated in the study, which started in March 2025.

Roginolisib is also being investigated in patients with non-small cell lung cancer (NSCLC) (NCT06879717) and myelofibrosis (NCT06887803). In these diseases, targeting the PI3Kδ pathway in combination with standard therapies has potential to reverse resistance[1],[2].

Seeing the promise of roginolisib as a combination therapy, the US Department of Defense (DoD) recently awarded a substantial grant to Dr. Jennifer Brown at Dana-Farber Cancer Institute in Boston, MA, to explore the potential of roginolisib in relapsed / refractory CLL in a Phase I / II study (NCT06644183).

Dr. Jennifer R Brown, M.D. Ph.D., Director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute and Principal Investigator on the study and grant said, "We are enthusiastic about the potential of roginolisib in enhancing treatment outcomes for CLL patients who have relapsed after prior Bruton’s tyrosine kinase inhibitor therapy. We feel roginolisib offers a promising avenue to improve remission depth and duration in combination with venetoclax and rituximab, whilst minimizing treatment-related side effects."

Recently published preclinical evidence by Sasi, Tarantelli et al. supports the synergistic potential of roginolisib and venetoclax in the treatment of CLL[3].