On April 28, 2025 Privo Technologies, Inc., a clinical-stage biopharmaceutical company pioneering nanotechnology-based cancer therapies, reported the activation of multiple premier clinical sites across the United States for its ongoing CLN-004 trial (Press release, Privo Technologies, APR 28, 2025, View Source [SID1234652262]). This Phase 2/3, open-label, two-arm study is evaluating the safety and efficacy of two of Privo’s lead assets—PRV111 and PRV211—in patients with head and neck squamous cell carcinoma (HNSCC).

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The trial is now actively recruiting at the following esteemed institutions:

University of Chicago Medicine (Chicago, IL)

City of Hope (Los Angeles, CA)

Miami Cancer Institute (Miami, FL)

Cleveland Clinic (Cleveland, OH)
Additional leading cancer centers are in the process of being activated and will be announced in the coming weeks.

"We are honored to collaborate with some of the nation’s leading head and neck oncology experts at these top-tier institutions," said Dr. Manijeh Goldberg, CEO of Privo Technologies. "Their participation underscores the potential impact of our novel therapies in transforming the treatment landscape for patients with HNSCC."

About the CLN-004 Trial

The CLN-004 study comprises two distinct arms:

Arm 1: Evaluates PRV111, a nanoengineered, self-adhesive patch designed for the topical delivery of cisplatin directly to the tumor site. This arm targets patients with carcinoma in situ (CIS) and high-grade dysplasia of the oral cavity, aiming to improve local control and potentially reduce the extent of surgical intervention.

Arm 2: Assesses PRV211, an intraoperative chemotherapy system intended for application into the resected tumor bed during surgery. This approach seeks to eliminate residual microscopic disease and reduce the risk of tumor recurrence in patients with stages T1-T4 HNSCC.
Both PRV111 and PRV211 are part of Privo’s proprietary PRV platform, which utilizes nanotechnology to enhance the locoregional delivery of chemotherapeutic agents, aiming to maximize therapeutic efficacy while minimizing systemic toxicity.

On April 28, 2025 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), reported data from preclinical studies of three exatecan-based antibody drug conjugates (ADCs) targeting Claudin-6 (CLDN6), prostate-specific membrane antigen (PSMA), and Alanine, Serine, Cysteine Transporter 2 (ACST2) as presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, ADC Therapeutics, APR 28, 2025, View Source [SID1234652278]).

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"We believe these presentations demonstrate the strong potential of our exatecan-based ADCs to treat a wide range of solid and hematologic cancers beyond lymphoma. The data from the oral presentation of our CLDN6-targeted ADC show its potential, both as a single agent and in combination, to treat ovarian and non-small cell lung cancers," said Patrick van Berkel, PhD, Chief Scientific Officer of ADC Therapeutics. "Our additional presentations showcase compelling data validating the potency and tolerability of our PSMA-targeting and ASCT2-targeting ADCs."

Data from the preclinical investigation of ADCT-242, a novel exatecan-based ADC targeting CLDN6, were presented in an oral presentation titled, "Preclinical investigation of ADCT-242, a novel exatecan-based antibody drug conjugate targeting Claudin-6, as single agent or in combination in ovarian and non-small lung cancer models." Key highlights from this presentation include:

ADCT-242 demonstrated potent anti-tumor activity in vivo in PA-1 and OVCAR-3 xenograft models with medium CLDN6 expression
CLDN6-dependent anti-tumor activity of ADCT-242 was observed in lung patient-derived tumor models
ADCT-242 was tolerated in mice or cynomolgus monkeys at doses up to 150 mg/kg or 40 mg/kg, respectively, indicative of a good therapeutic index
Data from the preclinical investigation of ADCT-241, a novel PSMA-targeting ADC, were presented in a poster presentation titled, "Preclinical Development of ADCT-241, a Novel Exatecan-based Antibody-Drug Conjugate Targeting PSMA for the Treatment of Prostate Cancer." The data demonstrated antitumor activity in both xenograft and patient-derived PSMA-expressing prostate cancer models as well as synergy with enzalutamide. ADCT-241 was well tolerated in both rats and cynomolgus monkeys.

Data from the preclinical investigation of HuB14-VA-PL2202, a novel ASCT2-targeting ADC, were presented in a poster presentation titled, "HuB14-VA-PL2202, a novel antibody-drug conjugate targeting ASCT2, a novel ADC target over-expressed in both solid and hematological cancers." The data demonstrated potent and specific in vitro and in vivo antitumor activity of HuB14-VA-PL2202 in ASCT2-positive solid and hematological cancer cell lines, and HuB14-VA-PL2202 was well-tolerated in cynomolgus monkeys.

On April 28, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the European Commission (EC) has granted conditional marketing approval of Lynozyfic (linvoseltamab) to treat adults with relapsed and refractory (R/R) multiple myeloma (MM) (Press release, Regeneron, APR 28, 2025, View Source [SID1234652246]). The indication is specific to those who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy. Lynozyfic is a bispecific antibody designed to bridge B-cell maturation antigen (BCMA) on MM cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing.

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Lynozyfic is the first BCMAxCD3 therapy approved that can be dosed every four weeks due to a response-adapted regimen if a very good partial response (VGPR) or better is achieved following completion of at least 24 weeks of therapy. The regimen includes monitoring in close proximity of a qualified treatment center for safety during the step-up dosing period (one 24-hour period after the first step-up dose and another 24-hour period after the second step-up dose, if certain safety events occur).

"Despite treatment advances, patients with multiple myeloma inevitably endure relapses, reduced responses to subsequent therapies, and increasingly shorter remissions. For those who develop relapsed and refractory disease after having been exposed to the three major drug classes, it’s important to have new therapies with different mechanisms of action like linvoseltamab," said Paula Rodriguez-Otero, M.D., Department of Hematology, Cancer Center Clínica Universidad de Navarra, Pamplona, Navarra, Spain. "In a clinical trial, linvoseltamab demonstrated compelling and impressive efficacy with the potential for complete remission in this patient population, including those with high disease burden. Furthermore, its response-adapted schedule will provide patients a convenient treatment option."

The EC approval is based on results from the pivotal LINKER-MM1 trial (n=117 at the 200 mg dose of Lynozyfic), which demonstrated robust and durable responses in patients with R/R MM. Results showed a 71% objective response rate (ORR), with 50% of patients achieving a complete response (CR) or better, as determined by an independent review committee. The minimal residual disease (MRD) negativity rate in patients achieving a CR or stringent CR was 41% (24 of 58 patients; 95% confidence interval [CI]: 29 to 55). The median duration of response (DOR) was 29 months (95% CI: 19 to not estimable).

The most frequent adverse reactions were musculoskeletal pain (52%), cytokine release syndrome (CRS; 46%), neutropenia (43%), cough (42%), diarrhea (39%), anemia (38%), fatigue (36%), pneumonia (32%), and upper respiratory tract infection (30%). The majority of CRS cases were Grade 1 (35%) or Grade 2 (10%), and there was one case of Grade 3 CRS (0.9%) and no cases of ≥Grade 4 CRS. The median time to first CRS onset was 11 hours (range: -1.1 to 184 hours), with the median time to resolution within 1 day (16 hours; range: 1-96 hours). Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS; 2.6%) and infections that were Grade 3 or 4 (36%) or fatal (4%) also occurred.

"Lynozyfic is our second approved bispecific antibody – in this case for relapsed/refractory multiple myeloma patients – reinforcing our relentless commitment to transforming cancer care for those who need it most," said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer of Regeneron. "We are excited by the potential of Lynozyfic and its differentiated clinical profile, dosing and administration. Given the strength of the data, we are pursuing a robust clinical development program exploring its use – in earlier lines of therapy as monotherapy and in novel combinations – with the hope of further advancing care for patients."

In the U.S., the FDA accepted for review the Biologics License Application for linvoseltamab in adults with R/R MM with a target action date of July 10, 2025.

About Multiple Myeloma
As the second most common blood cancer, there are over 35,000 new cases of MM diagnosed in Europe and 187,000 new cases of MM diagnosed globally every year. The disease is characterized by the proliferation of cancerous plasma cells (MM cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Despite treatment advances, MM is not curable and while current treatments are able to slow the progression of the cancer, most patients will ultimately experience cancer progression and require additional therapies.

About the Lynozyfic (linvoseltamab) Clinical Development Program
Lynozyfic as monotherapy is indicated for the treatment of adult patients with R/R MM who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy. For complete product information, please see the Summary of Product Characteristics that can be found on www.ema.europa.eu in due course.

The ongoing, open-label, multicenter Phase 1/2 dose-escalation and dose-expansion LINKER-MM1 trial is investigating linvoseltamab in more than 300 enrolled patients with R/R MM. The Phase 1 dose-escalation portion of the trial – which is now complete – primarily assessed safety, tolerability and dose-limiting toxicities across nine dose levels of linvoseltamab and explored different administration regimens. The ongoing Phase 2 dose expansion portion is assessing the safety and anti-tumor activity of linvoseltamab, with the primary endpoint of ORR. Key secondary endpoints include DOR, progression-free survival, rate of MRD negative status and overall survival.

Eligibility in the Phase 2 portion requires patients to have received at least three prior lines of therapy or have triple-class refractory MM. Linvoseltamab is administered with an initial step-up dosing regimen followed by the full 200 mg dose administered weekly. After week 14, all patients transition to every two-week dosing. A response-adapted regimen further enables patients to shift to every four-week dosing if they achieve a VGPR or better and have completed at least 24 weeks of therapy. The regimen requires a total of two 24-hour hospitalizations for safety monitoring.

Linvoseltamab is being investigated in a broad clinical development program exploring its use as a monotherapy as well as in combination regimens across different lines of therapy in MM, including earlier lines of treatment, as well as plasma cell precursor disorders. They include evaluating linvoseltamab in a Phase 1b trial (LINKER-MM2) in combination with other cancer treatments in R/R MM as well as a Phase 3 confirmatory trial (LINKER-MM3) as a monotherapy in R/R MM. For more information on Regeneron’s clinical trials in blood cancer, visit the clinical trials website, or contact via [email protected] or 844-734-6643.

On April 28, 2025 Accent Therapeutics, a clinical-stage biopharmaceutical company pioneering novel, targeted, small molecule cancer therapeutics, reported new preclinical data on its first-in-class oral DHX9 inhibitor, ATX-559, and its potentially best-in-class KIF18A inhibitor, ATX-295, in poster and oral presentations, respectively, at the AACR (Free AACR Whitepaper) Annual Meeting 2025 taking place April 25-30 in Chicago, Illinois (Press release, Accent Therapeutics, APR 28, 2025, View Source [SID1234652263]). ATX-559 and ATX-295 are currently under investigation in Phase 1/2 clinical trials.

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"Our presentations at the AACR (Free AACR Whitepaper) annual meeting showcase the outputs of Accent’s precision oncology approach to drug development, with strong foundational data that inform our current and future clinical development plans for our lead programs, ATX-559 and ATX-295," said Serena Silver, Ph.D., Chief Scientific Officer of Accent Therapeutics. "These preclinical data reinforce our assets’ therapeutic potential across several cancer indications with high unmet need."

The company’s poster presentation includes preclinical data supporting continued clinical evaluation of ATX-559, a first-in-class potent, selective, and orally bioavailable small-molecule inhibitor of DHX9. Results within characterize the compound’s activity in cancer cell lines with genomic instability and elevated replication stress spanning several indications, including dMMR/MSI-H colorectal cancer and BRCA-altered triple negative breast cancer, and in subtypes of lung, gastric, ovarian, and prostate cancers. ATX-559 was shown to be well tolerated in vivo, leading to robust and dose dependent tumor growth inhibition and regression in BRCA deficient breast cancer and dMMR/MSI-H cell- and patient-derived xenograft models.

ATX-559 is currently under investigation in a first-in-human, Phase 1/2, open-label, dose-escalation and expansion study, with a focus on advanced or metastatic patients with BRCA-1 and/or BRCA-2-deficient breast cancer or MSI-H and/or dMMR solid tumors (NCT06625515). Additional undisclosed solid tumor indications undergoing replicative stress and representing significant patient populations may be explored either in parallel or in subsequent studies.

For Accent’s second lead program, preclinical data included in the company’s oral presentation demonstrates sensitivity to KIF18A inhibition across several solid tumor indications with high chromosomal instability, signaling significant opportunity for patient impact by leveraging KIF18A as a selective oncology target. Results further characterize ATX-295 as a potent and selective KIF18A inhibitor capable of inducing mitotic arrest, cell death, and anti-tumor activity in cancer models with high chromosomal instability. Studies in relevant cellular and xenograft models exhibiting whole genome doubling confirm selective anti-cancer activity, providing rationale for whole genome doubling as a predictive biomarker of ATX-295 sensitivity in ovarian and triple negative breast cancer.

Accent recently initiated clinical evaluation of ATX-295 in a first-in-human Phase 1/2 open-label, dose-escalation and expansion study designed to evaluate the molecule’s safety, tolerability, and preliminary efficacy in patients with locally advanced or metastatic solid tumors, including high-grade serious ovarian cancer (NCT06799065).

Details for the presentations are as follows:

Presentation Title: Activity of the Novel KIF18A Inhibitor, ATX-295, is Enriched in Whole Genome Doubled Ovarian Cancer Pre-Clinical Models

Abstract Number: 3784
Session Type: Minisymposium
Session Title: Novel Antitumor Agents
Session Date and Time: Monday, April 28, 2:30 pm – 4:30 pm CT
Location: Room S103 – McCormick Place South (Level 1)
Presenter: Maureen Lynes, Ph.D.
Poster Title: ATX-559, a First in Class DHX9 Inhibitor, and Targeted Therapeutic for Molecularly Defined Tumors with Genomic Instability and Replicative Stress

Abstract Number: 1758
Session Title: Novel Antitumor Agents 1
Session Date and Time: Monday, April 28, 9:00 am – 12:00 pm CT
Location: Poster Section 22
Poster Board Number: 10
Presenter: Jennifer Castro
About ATX-559
ATX-559 is a first-in-class potent and selective inhibitor of DHX9, a novel and previously undrugged RNA and DNA/RNA helicase, shown to play a critical role in tumors with high levels of replication stress (including breast, ovarian, colorectal, endometrial, gastric, and others), representing large patient populations with significant unmet medical need. DHX9 has been reported to play important roles in replication, transcription, translation, RNA splicing, RNA processing, and maintenance of genomic stability, making it a compelling novel oncology target. In addition to exploiting key tumor vulnerabilities in DNA repair deficient backgrounds (e.g., BRCA) and hyper-mutated states (e.g., MSI-H/dMMR), Accent is exploring the sensitivity of other tumor types to DHX9 inhibition, and the potential to combine DHX9 inhibitors with other cancer treatments to maximize its full potential for helping patients. Accent retains full worldwide rights to ATX-559, currently being evaluated in a Phase 1/2 clinical trial (NCT06625515), and the DHX9 program.

About ATX-295
Accent’s second lead program is a potential best-in-class inhibitor for KIF18A which may address a large patient population across several cancer indications, including ovarian and triple negative breast cancer (TNBC). KIF18A is a mitotic kinesin motor protein critical for cell division in select tumors with chromosomal instability, but not in healthy cells. KIF18A inhibitor treatment results in rapid cell death for cancers with an abnormal number of chromosomes (aneuploid) in vitro and in vivo, while cells with normal numbers of chromosomes (euploid) are unaffected. Accent retains full worldwide rights to ATX-295, which is currently being evaluated in a Phase 1/2 clinical trial (NCT06799065), and the KIF18A program.

On April 28, 2025 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for precision oncology, reported new interim analysis results of the VICTORI study showing strong performance of its ultra-sensitive NeXT Personal assay in detecting early signs of residual or recurrent colorectal cancer (CRC) (Press release, Personalis, APR 28, 2025, View Source [SID1234652279]).

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The study, led by Dr. Jonathan Loree’s team at BC Cancer in Vancouver, Canada, utilized NeXT Personal to look for small traces of circulating tumor DNA (ctDNA) in blood samples from a cohort of 71 patients with resectable Stage I-IV CRC. The data was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, Illinois by Emma Titmuss at BC Cancer, in an oral presentation titled Detection of post-surgical minimal residual disease (MRD) in colorectal cancer; preliminary results from the VICTORI study.

"After surgery, ctDNA-based liquid biopsies may help identify patients who would benefit most from additional treatment," said Jonathan Loree, MD, MS, a medical oncologist at BC Cancer and the senior investigator of the study. "Alternatively, this may help patients with good prognosis avoid toxicities from unnecessary chemotherapy. By monitoring patients for recurrences, liquid biopsies can continue to support clinical care and allow more patients to undergo second curative intent surgeries to remove early recurrences."

Key findings presented from the interim analysis for VICTORI:

100% of patients who have recurred were detected as ctDNA positive by NeXT Personal prior to detection on imaging.
100% of patients who have been ctDNA negative throughout the study remain disease-free.
87% of clinical recurrences were detectable within the early "landmark window" 2 to 8 weeks after surgery, with 85% detectable by 4 weeks.
64% of detections within the landmark window were in the ultrasensitive range (under 100 ppm).
100% of distant metastatic recurrences were detected prior to imaging, including lung metastasis, an area which has traditionally been more challenging to detect by ctDNA testing.
70% of the first ctDNA detections were in the ultrasensitive range, with a median of 24.4PPM and as low as 2.45 PPM.
Median patient follow-up at the time of the interim analysis was 15.75 months, with the patients continuing to be followed clinically.

"The initial results from our study show the importance of using a highly sensitive MRD assay like NeXT Personal in colorectal cancer," said Dr. Loree.

"We are encouraged by the preliminary results from the VICTORI study, which show the ability of our ultrasensitive ctDNA assay NeXT Personal to detect residual and recurrent colorectal cancer at high rates in the early landmark window after surgery," said Dr. Richard Chen, Chief Medical Officer and Executive Vice President, R&D at Personalis. "We continue to expand this prospective study as we strive towards helping patients with colorectal cancer detect and treat recurrence earlier."