On April 28, 2025 Edgewood Oncology, a clinical-stage biotechnology company focused on delivering BTX-A51 to patients with hematologic malignancies and genetically-defined solid tumors, reported the presentation of new preclinical data presented by Dana-Farber Cancer Institute and Hebrew University-Hadassah Medical School in support of an ongoing investigator-sponsored Phase 1 study of BTX-A51 in liposarcoma (LPS) at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 25-30, 2025, in Chicago (Press release, Edgewood Oncology, APR 28, 2025, View Source [SID1234652229]).

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BTX-A51 is a first-in-class, small molecule kinase inhibitor that co-targets casein kinase 1 alpha (CK1a) and cyclin-dependent kinases 7 and 9 (CDK7 and CDK9), three master regulators of cancer cell survival and transcriptional control.

The presentation, "Therapeutic potential of combined targeting of casein kinase 1 alpha (CK1a) and CDK7/9 with the inhibitor BTX-A51 in human liposarcomas," highlights new mechanistic and efficacy data in patient-derived cell lines and xenograft models. One of the most significant findings from the presentation is that CK1a is an essential gene for the growth of liposarcomas based on genome-scale RNAi perturbation analysis. The study also used RNAi knockdown and targeted small molecules to confirm that inhibition of CK1a, CDK7, and CDK9 has synergistic impacts on LPS cell survival. As a single agent, BTX-A51 blocked MDM2 and induced P53 expression, stimulating potent apoptosis in LPS models while significantly inhibiting tumor growth in patient-derived xenografts at well tolerated dose levels.

"Well-differentiated and dedifferentiated liposarcomas (WD/DDLPS) remain among the most challenging soft tissue sarcomas to treat," said Geoffrey I. Shapiro, M.D., Ph.D., Professor of Medicine, Harvard Medical School, and director of the Early Drug Development Center at Dana-Farber Cancer Institute. "This study identifies novel, targetable vulnerabilities in LPS and offers a compelling justification for the clinical evaluation of BTX-A51 in this patient population."

BTX-A51 is currently being evaluated in an open-label, investigator-sponsored Phase 1 pilot study at Dana-Farber Cancer Institute in patients with metastatic and/or recurrent liposarcomas characterized by Murine Double Minute Clone 2 (MDM2) amplifications. Additional details about the study can be found at clinicaltrials.gov under the identifier NCT06414434.

"These findings strengthen the rationale for BTX-A51’s mechanism of action and support its potential across a spectrum of genetically defined cancers," said David N. Cook, Ph.D., Chief Executive Officer of Edgewood Oncology. "We’re encouraged by the strength of these preclinical findings, which further support the ongoing clinical advancement of BTX-A51."

Additional Details about the Study
Through computational and experimental methods, including DepMap screening, siRNA silencing, and small-molecule inhibitor profiling, the study confirmed that CK1α, CDK7, and CDK9 are essential for LPS survival. CK1a knockdown by itself was shown to be toxic to LPS cell lines and CDK9 inhibition alone suppressed LPS cell growth and induced apoptosis by downregulating MDM2 and activating p53. When CK1α depletion and CDK9 inhibition were combined, the potency of the individual approaches was amplified. In addition, combining CDK7 and CDK9 inhibitors synergistically inhibited LPS cell lines. These observations led to the evaluation of BTX-A51, which inhibits all three kinases with nanomolar potency. BTX-A51 robustly reduced MDM2 expression and induced expression of p53 and PUMA. The compound also lowered MCL1 expression and sensitized cells to apoptotic signaling through BIM and PUMA, as confirmed by BH3 profiling. In vivo studies in two LPS PDX models demonstrated that BTX-A51 is well tolerated and inhibits tumor growth under clinically relevant dosing conditions.

On April 28, 2025 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that seek to overcome tumor immune evasion and drug resistance, reported that two posters reporting new NT219 data being presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR 2025) Annual Meeting on Sunday and Monday, April 27-28, 2025 (Press release, Purple Biotech, APR 28, 2025, View Source [SID1234652245]).

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NT219, a novel dual inhibitor of IRS1/2 and STAT3, is being evaluated in a Phase 2 study in patients with recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC) in combination with pembrolizumab (anti-PD1) and in combination with cetuximab (anti-EGFR).

"The poster presents a significant upregulation of STAT3, IRS1/2 and b-catenin in HNSCC tumors and tumor microenvironment as compared to normal tissues, and a similar trend per tumor stage. Together with the unique mechanism of NT219 as a suppressor of STAT3 and a degrader of IRS1/2, which blocks IGF1R/IRS and downstream AKT and b-catenin signaling, we revealed that the activated forms of STAT3 and IGF1R are associated with the patient response to NT219-based therapy, suggesting these targets as potential biomarkers," stated Purple Biotech VP R&D Dr. Hadas Reuveni. "STAT3 and b-catenin, as well as cancer stem cells, are major immune evasion and tumor recurrence mechanisms, suppressed by NT219. This mechanistic rationale and preclinical in-vivo and ex-vivo results demonstrating repression of anti-PD1 refractory tumors, support NT219 and anti-PD1 combination therapy that will be administered to R/M HNSCC patients in our Phase 2 clinical study."

"Activation of b-catenin or loss of its negative suppressor APC play a key role in colorectal cancer, and we have previously shown that NT219 efficiently blocks the IRS2 to b-catenin pathway, inhibiting CRC metastasis and chemo-resistance," added Hadas Reuveni. "Here we reveal that these elements may serve as potential biomarkers for NT219-based therapy in CRC, based on extended in-vivo and ex-vivo patient-derived screens."

"These biomarker and mechanism data are important guides for study design, patient selection, and combination therapy strategies for NT219," stated Purple Biotech CEO Gil Efron. "This new data is highly encouraging and support our current NT219 Phase 2 study in head and neck cancer. We were pleased to share these data at the prestigious AACR (Free AACR Whitepaper) annual meeting."

Key highlights from the posters include the following:

Poster Title—"NT219 overcomes immune evasion mechanisms in head and neck squamous cell carcinoma (HNSCC)"

● NT219 mitigates several immune evasion mechanisms including cancer stem cell-mediated resistance and resulting tumor recurrence, and sensitizes resistant HNSCC tumors to PD1 and EGFR therapies.

● NT219 inhibits major targets and signaling pathways playing a key role in tumor immune evasion, including STAT3 and IRS-to-β-catenin pathways.

● In a clinical setting, upregulation of pIGF1R and pSTAT3 were correlated with patient response and suggested as potential biomarkers for NT219 treatment.

● Immunosuppressive mechanisms such as IL-10 secretion induced by anti-PD1 treatment, were suppressed by NT219, supporting the synergistic anti-tumor activity observed

● These data demonstrate the potential of NT219 to restore the efficacy of immunotherapies and expand the patient population that can benefit from these drugs.

Poster Title—"APC-loss as a potential biomarker for NT219 treatment in colorectal cancer"

● The anti-tumor efficacy of NT219 monotherapy in screens of about 30 patient-derived xenograft (PDX) models and colorectal (CRC) patient-derived explants (PDE), along with genomic and transcriptomic analysis, suggest that the response to NT219 is associated with enhanced wnt/β-catenin signaling or loss of function mutation of its negative regulator APC (APC-loss).

● The results suggest APC-loss or upregulated β-catenin as a potential biomarker for NT219 treatment in CRC.

● In addition, NT219 reversed chemo-resistance and synergized with approved chemotherapy as demonstrated in multiple models including PDE with APC-loss and activated PI3K mutations, and in-vivo intracranial model with activating mutation in β-catenin.

The NT219’s posters will be available at the Publication section on Purple Biotech’s website following its presentation at the conference.

On April 28, 2025 Elpis Biopharmaceuticals, a clinical-stage cell therapy company developing bispecific armored CAR-T therapies for solid tumors, reported that it will present two posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Elpis Biopharmaceuticals, APR 28, 2025, View Source [SID1234652277]). The presentations, which were accepted as late-breaking submissions, highlight the company’s latest advances in multi-mechanism, armored CAR-T therapies for the treatment of solid tumors and glioblastoma (GBM).

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The first poster, LB363, titled, "Multi-mechanism human B7H3 CAR-T effectively overcome tumor microenvironment resistance in treatment of solid tumors," details research involving EPC-002, Elpis’s novel human B7H3-targeted CAR-T cell therapy developed with a proprietary, precision-engineered multi-mechanism armor to simultaneously overcome multiple tumor microenvironment (TME) resistant mechanisms. B7H3 is overexpressed on a wide range of solid tumors, including skin, pancreatic, lung, breast, colon, kidney, ovarian, and other cancers. As presented at AACR (Free AACR Whitepaper), EPC-002 demonstrated an ability to reduce regulatory T cell proliferation, modulate CAR-T and bystander immune cell activation, enhance TIL infiltration, overcome TME suppression, and mediate anti-tumor activity. These mechanisms were highlighted in preclinical mouse models in which EPC-002 enabled complete tumor regression and long-term persistence with very low dose of 0.3M CAR-T cells in tumor rechallenging studies.

The second poster, LB360, titled, "Discovery and development of fully human IL13Ra2/B7H3 bispecific armored CAR-T for treatment of glioblastoma," describes the ongoing development of EPC-003, Elpis’s first-in-class human bispecific CAR-T cell therapy targeting IL13Ra2 and B7H3, two antigens co-expressed in a majority of GBM tumors. Engineered with Elpis’s proprietary mRNADis and mSCAFold platforms, EPC-003 integrates dual antigen targeting with a secreted multi-functional armor to enhance CAR-T cell persistence, block immune suppression, and penetrate the blood-brain barrier (BBB). As presented at AACR (Free AACR Whitepaper), in an orthotopic GBM mouse model, EPC-003 induced tumor regression as early as day 6 following intracranial injection of 2 × 10⁶ CAR-T cells. Moreover, intravenous injected CAR-T cells successfully penetrated the BBB, achieving significant tumor regression by day 13 post-treatment.

"Having two presentations detailing our lead product candidates, EPC-002 and EPC-003, accepted as late-breaking submissions at AACR (Free AACR Whitepaper) is tremendous validation of Elpis’s technologies and the potential that each offers in the treatment of solid tumors and glioblastoma, which have thus far proven resistant to most CAR-T therapies," said Yan Chen, MD, Ph.D., CEO of Elpis Biopharmaceuticals. "Our multi-mechanism approach is designed to address the challenges of tumor microenvironment resistance and antigen heterogeneity, unlocking the full potential of CAR-T in solid tumors and hard-to-treat cancers like glioblastoma. We now look forward to advancing each product into the clinic, including a soon-to-be initiated proof of concept, investigator-initiated trial of EPC-003 in resistant/relapsed glioblastoma patients."

Presentation Details:

Session Title:

Late-Breaking Research: Clinical
Research 3(LB363)

EPC-002: Multi-mechanism human B7H3
CAR-T effectively overcome tumor
microenvironment resistance in treatment
of solid tumors

Session:

4/29/2025 2:00-5:00 PM

Location:

Poster Section 53

Poster Board Number:

7

Session Title:

Late-Breaking Research: Clinical
Research 3(LB360)
EPC-003: Discovery and development of
fully human IL13Ra2/B7H3 bispecific
armored CAR-T for treatment of
glioblastoma

Session:

4/29/2025 2:00-5:00 PM

Location:

Poster Section 53

Poster Board Number:

4

On April 28, 2025 Evaxion Biotech A/S (NASDAQ: EVAX) ("Evaxion"), a clinical-stage TechBio company specializing in developing AI-Immunology powered vaccines, reported new data underscoring the ability of cancer vaccine EVX-01 to drive a targeted and robust immune response (Press release, Evaxion Biotech, APR 28, 2025, View Source [SID1234652230]). Designed with Evaxion’s AI-Immunology platform, EVX-01 is a personalized cancer vaccine currently being evaluated as a treatment for advanced melanoma (skin cancer).

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New immune data from the ongoing phase 2 trial with EVX-01 will be presented at a poster session tomorrow at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place in Chicago. The data demonstrates that 80% of EVX-01 vaccine targets triggered a tumor-specific immune response.

In earlier interim analyses presented at the ASCO (Free ASCO Whitepaper) and ESMO (Free ESMO Whitepaper) 2024 meetings, a vaccine target hit rate of 71% and 79%, respectively, was demonstrated. Now, with more long-term patient samples analyzed, we’ve improved this hit rate to 80%, reinforcing the potential of EVX-01 as a new and effective treatment for a broad range of solid tumors.

"We are excited to report yet another positive set of data for our lead vaccine candidate EVX-01. Its ability to trigger an immune response is unprecedented compared to what has been reported by others. We are further encouraged by the data showing this response to be strong and long-lasting and increasing with additional booster immunizations. The data package for EVX-01 gets stronger and stronger and we are eagerly anticipating the two-year clinical readout," says Birgitte Rønø, CSO of Evaxion.

The trial previously yielded strong interim one-year clinical data and remains on track for readout of two-year clinical data in the second half of 2025. Additionally, the trial has been extended with a third year, allowing for a more comprehensive assessment of the full potential of EVX-01.

The phase 2 trial investigates EVX-01 in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in patients with advanced melanoma (skin cancer). Each patient enrolled in the trial has received a unique vaccine designed and manufactured based on their individual biology. KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

AACR presentation details:

Abstract title: T-cell immunogenicity and biomarker profiling in advanced melanoma patients receiving the personalized vaccine EVX-01 in combination with pembrolizumab
Abstract#: 4538
Poster#: 9
Session (category): Immune responses to therapies including chemotherapy and radiotherapy (Clinical research)
Location: Poster section 28
Date/Time: April 29, 2025, at 9am-12pm CST/16-19 CET
Presenter: Mads Lausen Nielsen, PhD, Project Manager at Evaxion

About EVX-01
EVX-01 is a personalized peptide-based cancer vaccine intended for first-line treatment of multiple advanced solid cancers. It is Evaxion’s lead clinical asset.

EVX-01 is designed with our AI-Immunology platform and is tailored to target the unique tumor profile and immune characteristics of each patient. It engages the patient’s immune system to fight off cancer by mounting a targeted response against tumors.

In clinical trials, EVX-01 has demonstrated 69% and 67% Overall Response Rates in patients with advanced melanoma. Further, significant correlations between clinical responses and AI-Immunology predictions have been observed, underlining the predictive power of the platform.

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.

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.