On December 9, 2025 Promega reported a new study published in Nature Communications reveals technological advances that accelerate breakthroughs in precision medicine. Conducted as a collaboration between Promega, the Center for Advanced Study of Drug Action at the State University of New York at Stony Brook, and the Centre for Medicines Discovery at the University of Oxford, the work leverages bioluminescent NanoBRET Target Engagement (TE) technology developed by Promega to characterize inhibitors that selectively target cancer cells without harming noncancerous cells. Their results demonstrate a connection between drug efficacy and tumor metabolic state, offering a mechanistic bridge between cancer metabolism and precision oncology.

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"To our knowledge, this is the first time anyone has characterized this type of uncompetitive inhibitor mechanism directly in live cells." -Ani Michaud, Sr Research Scientist at Promega

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"The methods in this study enable us to characterize inhibitors that bind much more tightly in tumor cells with specific mutations," says Ani Michaud, Sr Research Scientist at Promega and co-first author of the Nature Communications paper. "To our knowledge, this is the first time anyone has characterized this type of uncompetitive inhibitor mechanism directly in live cells."

PRMT5: Top Target for Drug Discovery

The published study focuses on a gene-regulating protein called PRMT5, which has long been considered a top target for drug discovery. In normal cells, PRMT5 interacts with a molecule called SAM. However, in the tumor cells of approximately 10-15% of cancers, a deletion of the MTAP gene leads to PRMT5 interacting with the molecule MTA instead, reducing its function. This difference creates a key vulnerability for targeting cancer cells with a mutation to MTAP while leaving normal cells unaffected.

The University of Oxford team designed and developed CBH-002, a cell-permeable BRET probe that binds to a genetically encoded PRMT5-NanoLuc biosensor to report drug target engagement in live cells.

Dr Elisabeth Mira Rothweiler, Postdoctoral Researcher, Centre for Medicines Discovery, University of Oxford and co-first author, says: "CBH-002 could measure various PRMT5 inhibitor types in live cells, prompting us to test its sensitivity to the cofactor SAM. When we discovered the probe’s ability to sense metabolite levels, it established its utility as a metabolic biosensor. Through collaboration with Promega, we demonstrated how MTA influences drug selectivity, revealing why certain inhibitors are so effective in MTAP-deleted cancers."

Dr Rothweiler’s research further enables a strategy for developing molecules that exploit the metabolic vulnerabilities specific to MTAP-deleted cancers, potentially offering highly targeted treatments with minimal effects on healthy tissue.

Uncompetitive Binding in Live Cells

While past studies have characterized this mechanism-of-action (MoA) in biochemical assays, this is the first to use NanoBRET TE technology to characterize uncompetitive, or cooperative, binding in live cells. Biochemical assays can reveal uncompetitive MoAs, but there is often a discrepancy between biochemical data and functional assays like selective cell killing. The NanoBRET TE assay used in this study bridges the two modalities, showing binding MoA in a cellular context that aligns with functional assay results.

Professor Kilian Huber, Associate Professor, Centre for Medicines Discovery, University of Oxford and co-senior author of the study, says, "The biosensor lets us examine, in living cells, how different PRMT5 inhibitors behave under the specific metabolic conditions that make some tumors uniquely vulnerable. This provides unprecedented insight into why certain inhibitors are much more effective in cancers lacking MTAP and paves the way for highly targeted cancer treatment in the future. It’s like turning on the lights inside the cell so we can finally see which key actually fits the lock."

"Selectivity is one of the most critical challenges in cancer therapy, as most treatments also damage healthy cells, leading to dose-limiting toxicities and reduced therapeutic effectiveness," says Peter Tonge, distinguished professor of chemistry and director of the Center for Advanced Study of Drug Action at the State University of New York at Stony Brook and visiting professor at the University of Rochester. "A new class of tumor-specific drugs addresses this by acting uncompetitively with a metabolite that accumulates only in cancer cells, limiting activity to tumor tissue. We have now developed the first technology to quantify the activity of these drugs directly in live cells, providing a foundation for optimizing and advancing next-generation precision oncology therapeutics."

Collaboration Between Academia and Industry

This study was the result of collaboration between Promega, the Center for Advanced Study of Drug Action at the State University of New York at Stony Brook, and the Centre for Medicines Discovery at the University of Oxford, with additional contributions from researchers at Boston University and the Structural Genomics Consortium at the University of Toronto.

"This work underscores the value of research collaborations between academia and industry," says Matt Robers, Associate Director of R&D at Promega and co-senior author of the study. "By combining our complementary expertise in chemical biology and assay design, we were able to dissect how cooperativity can drive cancer cell selectivity. These findings have real potential to guide the development of future precision medicines."

Read the paper "A BRET biosensor for measuring uncompetitive engagement of PRMT5 complexes in cells" in Nature Communications here: View Source

(Press release, Promega, DEC 9, 2025, View Source [SID1234661337])

On December 9, 2025 Alpha Tau Medical Ltd. (Nasdaq: DRTS, DRTSW) ("Alpha Tau"), the developer of the innovative alpha-radiation cancer therapy Alpha DaRT reported that the first patient has been treated in its pilot study for the treatment of patients with recurrent glioblastoma multiforme (GBM) using the Alpha DaRT technology.

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Uzi Sofer, CEO of Alpha Tau, stated, "This is a historic day for Alpha Tau and for GBM patients around the world, with the first treatment ever of a brain cancer using Alpha DaRT. Given the devastating prognosis of GBM, and its high rate of rapid recurrences, generally within 6-9 months, there is a desperate need for new local therapies with an appropriate safety profile for such a critical and sensitive area like the brain. This pilot study is a key part of our broader strategy to bring Alpha DaRT to cancer patients with some of the highest unmet needs, supported by the FDA’s Breakthrough Device Designation and acceptance into the FDA’s prestigious Total Product Life Cycle Advisory Program designed to accelerate the Alpha DaRT treatment to market and to GBM patients who may stand to benefit greatly."

The first patient was treated at The Ohio State University Center in Columbus, Ohio, by a multidisciplinary team led by Principal Investigator and Radiation Oncologist Joshua D. Palmer, MD, Medical Physicist Michael Degnan, MS, DABR and Neurosurgeon J. Bradley Elder, MD, using a novel delivery approach designed specifically for intracranial use.

Dr. Joshua Palmer, commented: "Patients with recurrent glioblastoma face one of the most difficult cancer diagnoses in medicine. There is an urgent unmet need for new therapeutic approaches that can be delivered locally while minimizing harm to surrounding healthy brain tissue. Intratumoral alpha-emitting radiotherapeutics such as Alpha DaRT offer a highly compelling novel scientific approach by delivering potent, short-range radiation precisely where it is needed most."

Dr. J. Bradley Elder, who led the procedure with Dr. Palmer, added: "From a technical standpoint, this procedure demonstrated excellent feasibility. The novel delivery device allowed us to place the Alpha DaRT sources in a precise radial configuration that achieved more than 95% coverage of the tumor volume. Importantly, the system integrates seamlessly as an add-on to the standard brain navigation platform that I use routinely in surgery, making it simple to adopt without disrupting existing workflow."

"This achievement represents the culmination of many years of dedicated teamwork within Alpha Tau – including extensive preclinical research, developing a unique delivery system designed specifically to integrate seamlessly into a standard neurosurgical workflow and, of course, partnership with our wonderful clinical collaborators at OSU," commented Dr. Robert Den, Chief Medical Officer of Alpha Tau. "This is a transformational patient-centric moment of great scientific and clinical significance for the entire field of neuro-oncology."

About the Study

The clinical trial is expected to enroll up to ten U.S. patients with recurrent glioblastoma not amenable for surgical resection who have undergone a prior course of central nervous system radiation. The primary objective of the study is to evaluate the feasibility and safety of the treatment, following the Company’s promising results from pre-clinical studies. Additional information about the trial can be found at View Source

(Press release, Alpha Tau Medical, DEC 9, 2025, View Source [SID1234661306])

On December 9, 2025 Daiichi Sankyo reported first patient has been dosed in the randomization phase of the DESTINY-Ovarian01 phase 3 trial evaluating ENHERTU (trastuzumab deruxtecan) in combination with bevacizumab versus bevacizumab monotherapy as first-line maintenance therapy in patients with HER2 expressing (IHC 3+/2+/1+) advanced high-grade epithelial ovarian cancer following treatment with first-line platinum-based chemotherapy in combination with bevacizumab.

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DESTINY-Ovarian01 is being conducted in collaboration with the European Network of Gynecological Oncological Trial Groups (ENGOT), with the Spanish cooperative group (GEICO) as the lead ENGOT group, The GOG Foundation, Inc. (GOG-F) and Asia-Pacific Gynecologic Oncology Trials Group (APGOT).

ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

The prognosis for patients with ovarian cancer is poor with an estimated five-year survival rate of 31.8% for those with advanced disease.1 Approximately 70% to 80% of patients with advanced ovarian cancer (Stage 3 or 4) will experience disease recurrence following standard treatment with surgery and platinum-based chemotherapy regimens.2 Maintenance therapy may be given to delay relapse and current recommended treatment strategies include bevacizumab or PARP inhibitor monotherapy or bevacizumab/PARP inhibitor combination treatment, depending on the biomarker status of the tumor. 3 There currently are no HER2 directed medicines approved as maintenance therapy despite HER2 expression being present in up to 55% of ovarian cancers.

"Results from the ovarian cancer cohort of DESTINY-PanTumor02 demonstrated clinically meaningful and durable responses in previously treated patients with HER2 expressing advanced ovarian cancer, supporting the development of ENHERTU in earlier lines of therapy," said Abderrahmane Laadem, MD, Head, Late- 2 Stage Oncology Clinical Development, Daiichi Sankyo. "Given the important role first-line maintenance therapy can play in disease control, we have initiated this first phase 3 trial in ovarian cancer to evaluate whether ENHERTU combined with bevacizumab could become a new maintenance strategy for patients with HER2 expressing advanced high-grade epithelial ovarian cancer."

About DESTINY-Ovarian01

DESTINY-Ovarian01 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) in combination with bevacizumab versus bevacizumab monotherapy as first-line maintenance therapy in patients with HER2 expressing (IHC 3+/2+/1+) advanced high-grade epithelial ovarian cancer following treatment with first-line platinum-based chemotherapy in combination with bevacizumab. The randomized period of the trial was preceded by a non-randomized safety run-in phase to evaluate the safety of ENHERTU in combination with bevacizumab

The primary endpoint is progression-free survival (PFS) as assessed by blinded independent central review (BICR) in the HER2 IHC 3+/2+ population. The key secondary endpoint is overall survival (OS) in the HER2 IHC 3+/2+ population. Additional secondary endpoints include PFS as assessed by BICR and OS in the HER2 IHC 3+/2+/1+ population as well as PFS as assessed by investigator in both the HER2 IHC 3+/2+ and HER2 IHC 3+/2+/1+ populations.

DESTINY-Ovarian01 will enroll approximately 580 patients across multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov.

(Press release, Daiichi Sankyo, DEC 9, 2025, View Source [SID1234661322])

On December 9, 2025 Aprea Therapeutics, Inc. (Nasdaq: APRE) ("Aprea", or the "Company"), a clinical-stage biopharmaceutical company developing innovative treatments that exploit specific cancer cell vulnerabilities while minimizing damage to healthy cells, reported that it has entered into a securities purchase agreement with new and existing healthcare focused investors and certain insiders of the Company to sell an aggregate of 2,623,023 shares of common stock (or pre-funded warrants in-lieu thereof), together with warrants to purchase up to an aggregate 2,623,023 shares of common stock, in a private placement priced at-the-market under Nasdaq rules (the "Offering"). The combined effective offering price for each share of common stock (or pre-funded warrant in-lieu thereof) and accompanying warrant to be issued is $1.165. The warrants to be issued will have an exercise price of $1.04 per share, will be exercisable immediately upon issuance, and will expire on the five-year anniversary of the earlier of the effectiveness date of the registration statement covering the resale of the securities purchased in the Offering and the date the shares underlying the warrants are eligible for resale under Rule 144.

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The gross proceeds to the Company from the Offering are estimated to be approximately $3.1 million before deducting the placement agent’s fees and other estimated Offering expenses. The Company intends to use the upfront net proceeds from the private placement for general corporate purposes and for research and development expenses. The Company believes the aggregate net proceeds from the Offering will be sufficient to fund the Company into 2027 based on current projections. The Offering is expected to close on or about December 10, 2025, subject to the satisfaction of customary closing conditions.

Maxim Group LLC is acting as the sole placement agent in connection with the Offering.

The offer and sale of the foregoing securities are being made in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act"), and/or Regulation D promulgated thereunder, and the securities have not been registered under the Securities Act or applicable state securities laws. Accordingly, the securities may not be reoffered or resold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws. The Company has agreed to file a registration statement with the Securities and Exchange Commission registering the resale of the securities purchased in the private placement.

This press release does not constitute an offer to sell or the solicitation of an offer to buy the securities, nor shall there be any sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such state. Any offering of the securities under the resale registration statement will only be made by means of a prospectus.

(Press release, Aprea, DEC 9, 2025, View Source [SID1234661307])

On December 9, 2025 D3 Bio, a global clinical-stage biotechnology company focused on the discovery and development of innovative oncology therapeutics, reported the completion of a $108 million Series B financing round.

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The funding round was backed by a distinguished group of investors, including IDG Capital and SongQing Capital. Existing investors — WuXi AppTec’s Corporate Venture Fund, Temasek, HSG, MPCi, and Medicxi — also contributed to the round. The robust involvement from both new and current investors highlights widespread confidence in D3 Bio’s innovative pipeline and its global development strategy.

Proceeds from this financing will primarily support the planned global Phase III pivotal program for the company’s lead asset, elisrasib (D3S-001). These pivotal trials will assess elisrasib as both a monotherapy and in combination therapies for KRAS G12C-mutant cancers across key countries and regions, including the United States, China, and the European Union, to facilitate global regulatory submissions.

Furthermore, the funding will facilitate ongoing development of D3 Bio’s comprehensive pipeline of targeted and immuno-oncology programs, which are centred on innovative mechanisms with first-in-class or best-in-class potential.

Dr. George Chen, Founder, Chairman, and CEO of D3 Bio, stated, "The completion of our Series B financing demonstrates the strong confidence our investors place in our vision, scientific approach, business operations, and global development capabilities. This funding enables us to advance our lead program into late-stage clinical trials and further expand our pipeline of innovative therapies designed to benefit patients globally."

Dr. Antoine Yver, Member of the Board of Directors and Scientific Committee of D3 Bio, stated, "This financing demonstrates that the swift and effective pursuit of the best- or first-in-class science is meaningful to society, and validates D3 Bio’s leading innovation, scientific vision and development strategy. It also highlights the unique potential of elisrasib for individuals affected by KRAS G12C-mutant cancers."

(Press release, D3 Bio, DEC 9, 2025, View Source [SID1234661323])