On April 25, 2025 Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, reported the publication of 3 abstracts for poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Obsidian Therapeutics, APR 25, 2025, View Source [SID1234652179]). In addition to a trial-in-progress study design update on the ongoing multicenter study Agni-01 (NCT06060613), Obsidian will share preclinical data from our cytoDRiVE platform demonstrating spatiotemporal regulation of membrane-bound IL12 in syngeneic solid tumor models and preclinical data on OBX-115 TIL phenotype starting from NSCLC tumor tissue.

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Obsidian is presenting new preclinical data from its cytoDRiVE regulation platform, further demonstrating the ability to unlock the therapeutic window of potent cytokines and broaden the reach of armored cell therapies. The poster for abstract LB025 demonstrates the application of Obsidian’s regulatable cytoDRiVE platform to enhance antigen-responsive ("spatial") promoter-induced activation by adding a critical pharmacologically regulatable ("temporal") signal to exert tight "spatiotemporal" control over IL12 expression1, resulting in a positive impact on safety and tumor control in syngeneic solid tumor models.

Obsidian will also present preclinical data from a multimodal phenotyping analysis comparing OBX-115 TIL generated with its proprietary manufacturing process to conventional, non-engineered TIL using NSCLC tumor samples. The poster for abstract LB359 provides evidence that, as observed with melanoma2, the OBX-115 process generates a minimally exhausted, CD8+ enriched and memory "stem-like" T-cell phenotype. Additionally, the tumor reactive gene signature analysis showed that the drug product is enriched for putative tumor-reactive T-cell clonotypes.

Obsidian Posters at AACR (Free AACR Whitepaper) 2025:

Spatiotemporally regulated expression of membrane-bound interleukin 12 (mbIL12) for armored adoptive cell therapy (ACT) shows strong antitumor activity in syngeneic solid tumor models without overt toxicity (Abstract LB025)
Presenting Author: Ross T, Obsidian Therapeutics
Poster: Sunday, April 27, 2:00-5:00pm CT
OBX -115 TIL from non-small cell lung cancer (NSCLC) are enriched for putative tumor-reactive, stem-like T cells with enhanced tumor cytotoxicity: Results from multimodal phenotyping analysis (Abstract LB359)
Presenting Authors: Schoenfeld AJ, Memorial Sloan Kettering Cancer Center
Poster: Tuesday, April 29, 2:00-5:00pm CT
Trial in progress: Phase 1/2 study of OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced solid tumors (Abstract CT244)
Presenting Author: Shoushtari AN, Memorial Sloan Kettering Cancer Center
Poster: Tuesday, April 29, 2:00-5:00pm CT
1 Smith et al., SITC (Free SITC Whitepaper) 2024 (Abstract 463).
2 Bernatchez et al., ISCT 2024 (Abstract 909).

About OBX-115

Obsidian’s lead investigational cytoTIL15 program, OBX-115, is a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15). OBX-115 has the potential to become a meaningful therapeutic option for patients with advanced or metastatic melanoma and other solid tumors by leveraging the expected benefits of mbIL15 and Obsidian’s proprietary, differentiated manufacturing process to enhance persistence, antitumor activity, and clinical safety of TIL cell therapy. Obsidian is investigating OBX-115 in the phase 1/2 Agni-01 multicenter trial in patients with advanced solid tumors (NCT06060613).

On April 25, 2025, Bullfrog AI Holdings, Inc. (the "Company") entered into an At-The-Market Sales Agreement (the "Agreement") with BTIG, LLC ("BTIG"), pursuant to which the Company may offer and sell, from time to time in its sole discretion, shares of its common stock, par value $0.00001 per share (the "Common Stock"), having an aggregate offering price of up to $20,000,000 (the "Shares"), through BTIG as its sales agent (Filing, 8-K, Bullfrog AI, APR 25, 2025, View Source [SID1234652222]). The Shares will be offered and sold pursuant to the Company’s Registration Statement on Form S-3 (Registration No. 333-281341) filed by the Company on August 7, 2024, as amended by Amendment No. 1 thereto filed on August 15, 2024, and declared effective by the U.S. Securities and Exchange Commission on August 21, 2024 (the "Registration Statement") and the Company’s prospectus supplement filed on April 25, 2025 that forms a part of such Registration Statement. The issuance and sale, if any, of the Shares may be made by any method permitted by law deemed to be an "at-the-market offering" as defined in Rule 415 of the Securities Act of 1933, as amended, including, without limitation, sales made directly on the Nasdaq Capital Market, or on any other existing trading market for the Common Stock.

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The Company is not obligated to make any sales of the Common Stock, and BTIG is not required to sell any specific number or dollar amount of shares of the Common Stock, under the Agreement. The Company and BTIG may suspend or terminate the offering of Shares upon notice to BTIG or the Company, as applicable, and subject to other conditions.

Subject to the Company’s request to sell Shares, BTIG will act as the Company’s sales agent and use commercially reasonable efforts, consistent with its normal trading and sales practices, to sell on the Company’s behalf, from time to time, such Shares based upon instructions from the Company (including any price, time or size limits or other customary parameters or conditions that the Company may impose). The Company will pay BTIG a commission fee of 3% of the gross sales price of any Shares sold through BTIG under the Agreement, and also has provided BTIG with customary representations and warranties and indemnification under the Agreement.

The foregoing description of the Agreement is not complete and is qualified in its entirety by reference to the full text of the Agreement, a copy of which is filed as Exhibit 1.1 to this Current Report on Form 8-K and incorporated herein by reference. The opinion of Ballard Spahr regarding the validity of the Shares that will be issued pursuant to the Agreement is also filed herewith as Exhibit 5.1.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the securities discussed herein, nor shall there be any offer, solicitation, or sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

On April 25, 2025 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, reported multiple preclinical presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2025 Annual Meeting supporting several programs, each with different drug targets for indications with central nervous system (CNS) involvement (Press release, Nurix Therapeutics, APR 25, 2025, View Source [SID1234652147]). The AACR (Free AACR Whitepaper) Annual Meeting is being held from April 25-30, 2025, in Chicago, IL.

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"The data we are presenting at AACR (Free AACR Whitepaper) highlight the power of our DEL-AI platform to design and create potent, orally available degraders that overcome the limitations of inhibitors, target difficult to treat mutations, and access the CNS, a feature which is particularly important for patients whose tumor has metastasized to the brain," said Gwenn M. Hansen, Ph.D., chief scientific officer of Nurix. "We look forward to advancing these programs in pursuit of novel therapeutic options for the benefit of patients living with cancer."

In a poster titled: "NX-5948 is a CNS-penetrant catalytic Bruton’s tyrosine kinase (BTK) degrader that breaks established design rules for CNS drugs," data were presented that highlight the unique physico-chemical properties of NX-5948, now called bexobrutideg, that differentiate it from traditional brain penetrant drugs. Bexobrutideg exhibits CNS exposure in several preclinical models and, most importantly, is detectable in the cerebrospinal fluid of patients where it has demonstrated clinically meaningful responses in patients with primary CNS lymphoma or chronic lymphocytic leukemia with CNS involvement. An important feature of protein degraders compared to small molecule inhibitors is their catalytic nature. In vitro experiments enabled calculation of the catalytic efficiency of bexobrutideg, demonstrating that a single molecule can degrade approximately 10,000 copies of BTK protein per hour at clinically relevant concentrations, which means that activity and efficacy can be achieved at much lower concentrations of a degrader as compared to an inhibitor.

In a second poster titled: NRX-0305: a pan-mutant BRAF degrader with broad preclinical efficacy, brain penetrance, and synergistic potential with MEKi across class 1/2/3 BRAF-mutant cancers, preclinical data were presented from Nurix’s differentiated BRAF degrader, NRX-0305, which degrades all three classes of mutant oncogenic BRAF proteins while sparing wildtype BRAF in healthy cells. Mutations in BRAF, a key component of the mitogen-activated protein kinase (MAPK) pathway, drive oncogenic transformation and are commonly found in a variety of cancers including melanoma, non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). BRAF mutations are categorized into three mutational classes (Class 1-3). While approved BRAF inhibitors (BRAFi) provide survival benefit to Class 1 patients, drug durability and efficacy are limited by the emergence of primary and acquired resistance. Furthermore, patients who have progressed on BRAFi, especially in melanoma, frequently present with brain metastases, for which there are limited treatment options due to poor CNS penetrance of available drugs. New data demonstrate that BRAF degradation correlates with reduced tumor cell viability across a panel of clinically relevant BRAF mutations, supporting the role of degradation in driving antiproliferative effects. In disease models, data demonstrated broad anti-tumor efficacy of NRX-0305 across all three BRAF mutation classes and in tumors that are resistant to existing therapies. Specifically, NX-0305 demonstrated superior anti-tumor efficacy in a xenograft (PDX) model derived from a patient with a class 1 BRAF mutation whose tumor was resistant to both pembrolizumab + BRAFi compared to a competitor BRAF degrader CFT1946. In addition, the data showed anti-tumor efficacy as a single agent and in combination with MEKi in class 3 (G466V) NSCLC cell-derived xenograft (CDX) models.

On Tuesday, April 29, 2025, Nurix scientists will also present data from the company’s ongoing collaboration sponsored by Alex’s Lemonade Stand Foundation (ALSF), a leading funder of pediatric cancer research, to develop a drug to potentially treat aggressive childhood cancers including neuroblastoma and medulloblastoma. As part of the collaboration, Nurix has identified a panel of selective, orally bioavailable degraders of Aurora A kinase (AURKA), an oncogene frequently overexpressed in these pediatric cancers and in adult solid tumors and hematologic malignancies. While several AURKA inhibitors are effective in preclinical tumor models, this activity has failed to translate into clinical efficacy, which may be explained by recent studies that found that AURKA has kinase-independent scaffolding functions that are not effectively blocked through enzymatic inhibition. In an oral presentation titled "Identification of selective, orally bioavailable Aurora A degraders for treatment of pediatric and adult cancers," Nurix will highlight preclinical data from studies of NRX-4972, an orally bioavailable and highly selective brain penetrant AURKA degrader. The data demonstrate that daily oral administration of NRX-4972 resulted in downregulation of MYCN as well as induction of DNA damage, apoptosis, and G2/M arrest, the latter set of effects being more pronounced in the context of degradation rather than AURKA inhibitor, which translated into significant efficacy in a model of neuroblastoma. Data comparing AURKA degradation to inhibition in a second efficacy model will be included in the upcoming oral presentation on Tuesday, April 29, 2025.

About Bexobrutideg (NX-5948)
Bexobrutideg is an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK. Bexobrutideg is currently being evaluated in a Phase 1a/b clinical trial in patients with relapsed or refractory B cell malignancies. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022).

About NRX-0305
NRX-0305 is a potent, selective, and orally bioavailable mutant-specific BRAF degrader that Nurix is exploring for use in oncology. Nurix has reported preclinical data demonstrating potent anti-tumor activity in multiple cell line-derived and patient-derived xenograft disease models representing Class I, Class II and Class III B-RAF mutations. Anti-tumor activity was also observed in the setting of CNS disease and treatment-resistance, suggesting the potential for utility across a broad range of solid tumor types.

About Aurora A Kinase
Aurora A kinase (AURKA) is an oncogene frequently overexpressed in adult solid tumors, hematologic malignancies, and pediatric cancers. Several AURKA inhibitors are effective in preclinical tumor models, but this activity has failed to translate into clinical efficacy. To address the limitations of inhibitors, Nurix has designed bifunctional targeted protein degraders of AURKA that enable removal of both enzymatic and scaffolding functions.

On April 25, 2025 DELFI Diagnostics, Inc., developer of innovative blood-based tests that leverage cell-free DNA (cfDNA) fragmentomics for cancer detection and monitoring, reported its team is presenting at the upcoming 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL (Press release, Delfi Diagnostics, APR 25, 2025, View Source [SID1234652163]). DELFI is showcasing its groundbreaking DELFI-TF technology for treatment response monitoring alongside its early detection capabilities.

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"Our presentations at AACR (Free AACR Whitepaper) highlight how DELFI’s fragmentomics platform is transforming both early cancer detection and treatment monitoring," said Victor E. Velculescu, MD, PhD, DELFI Diagnostics Founder and Board Director. "The DELFI technology represents a paradigm shift in how we detect cancer by combining genome-wide fragmentomics of DNA in the blood with AI algorithms for high sensitivity in the screening setting as well as for noninvasively measuring treatment efficacy in advanced cancer patients. "

DELFI is presenting multiple podium and poster sessions at AACR (Free AACR Whitepaper), including:

Genomic and fragmentomic landscapes of cell-free DNA for early cancer detection presented by Victor E. Velculescu, MD, PhD

Tuesday, April 29, 11:06 AM – 11:26 AM CT
Room S100 BC (Grand Ballroom BC) – McCormick Place South
Leveraging the cfDNA fragmentome to predict immunotherapy response presented by Valsamo Anagnostou, MD, PhD

Monday, April 28, 3:05 PM – 3:20 PM CT
Room S105 – McCormick Place South
Analysis of lung cancer clinical characteristics using cell-free DNA fragmentomes presented by Lorenzo Rinaldi, PhD

Monday, April 28, 9:00 AM – 12:00 PM CT
Section 28, Poster 29
Cell-free DNA fragmentomes for treatment response monitoring in patients with metastatic colorectal cancer: the DOLPHIN study presented by Denise E. Van Steijn

Monday, April 28, 2:00 PM – 5:00 PM CT
Section 29, Poster 6
DELFI Diagnostics has clinically validated FirstLook Lung, its blood test designed to improve early detection of lung cancer, which remains the leading cause of cancer deaths in the United States. At the AACR (Free AACR Whitepaper) Annual Meeting, DELFI will present research data on early detection in additional cancer types, including liver, ovarian, and other cancers.

In addition to the company’s early detection efforts, DELFI launched the DELFI-TF* research service in February 2024. DELFI-TF actively guides critical oncology drug development decisions at five top 20 pharmaceutical companies. The technology is designed to deliver critical insights at every stage of the metastatic cancer journey, from baseline assessment and response monitoring to resistance detection and continuous insight across all treatment lines. Requiring just 800µl of plasma, DELFI-TF offers a mutation-independent monitoring solution with a 99% success rate and results typically available in 10-14 business days.

DELFI-TF’s performance has been validated through clinical studies across multiple cancers, including colorectal, lung, pancreatic, breast, melanoma, and head and neck. It has demonstrated its ability to quantify tumor burden without requiring mutation profiling. This strongly correlates with Mutant Allele Frequency (MAF) measurements even when specific mutations are undetectable.

"Lack of efficacy is still the most common reason for Oncology Phase II clinical trials to fail during development, demonstrating the need for improved methods for detection of efficacy of new medical entities in early clinical trials," said Nicholas C. Dracopoli, PhD, Chief Scientific Officer and Co-Founder. "DELFI-TF offers pharmaceutical developers a streamlined, cost-effective solution for monitoring treatment response earlier and more efficiently than traditional methods."

To learn more about DELFI Diagnostics and its innovative fragmentomics platform, visit them at AACR (Free AACR Whitepaper) Booth #2060 or visit www.delfidiagnostics.com.

*The DELFI-TF Assay and related services are for Research Purposes Only and are not intended for diagnostic procedures or applications.

On April 25, 2025 Parabilis Medicines (formerly Fog Pharmaceuticals), a clinical-stage biopharmaceutical company committed to creating extraordinary medicines for people living with cancer, reported preclinical data demonstrating first-in-industry targeted degradation of ERG at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which begins today in Chicago, Illinois (Press release, Parabilis Medicines, APR 25, 2025, View Source [SID1234652180]).

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ERG has been a long-recognized high-value target in prostate cancer, where ERG fusions have been implicated in 40-50% of all cases. In metastatic castrate-resistant prostate cancer (mCRPC) specifically, the TMPRSS2-ERG gene fusion is associated with more aggressive disease and may predict resistance to certain therapies, such as PARP inhibitors. However, ERG has been undruggable by conventional inhibitors or first-generation degraders because it lacks small molecule binding pockets.

Potent and specific degradation of ERG has been achieved with Helicon peptide degraders both in vitro and in vivo, leading to substantial tumor growth inhibition in multiple mouse models of prostate cancer. The data represent the first pharmacological proof-of-concept for ERG dependency in preclinical models of ERG-fusion prostate cancer.

"Parabilis’s Helicon peptide degraders have thrilling potential to expand the reach of targeted protein degradation to traditionally ‘undruggable’ targets," said Mathai Mammen, M.D., Ph.D., Chairman and CEO of Parabilis Medicines. "These first compelling data from our ERG program validate our novel approach to degradation. The data also support the continued progress of our ERG degrader toward clinical trials, where it has the potential to be a meaningful therapeutic for patients with metastatic prostate cancer."

Highlights of the data presented at AACR (Free AACR Whitepaper) include:

In mice implanted with prostate cancer cell-derived xenograft (CDX) tumors, administration of the ERG degrader produced >90% tumor ERG degradation through 7 days post dose. This corresponded to suppression of ERG’s downstream effects on target gene ARHGDIB.
In both patient- and cell-line derived xenograft (PDX and CDX) models of TMPRSS2-ERG fusion prostate cancer, Parabilis’s ERG degrader significantly inhibited tumor growth.
RNA sequencing expression analyses indicated that Parabilis’s ERG degrader downregulated Myc target genes.
Parabilis’s ERG degrader uses Helicon technology to bind directly to the ERG protein and, through its attached E3 ligand, directs the ERG protein to the ubiquitin-proteasome pathway for degradation. The company anticipates entering IND-enabling toxicology studies in 2025.

Parabilis’s prostate cancer franchise additionally includes a selective degrader of active androgen receptor (AR), which binds at a different site from approved drugs, and circumvents known resistance mechanisms that arise in response to AR antagonist therapies. Together, Parabilis’s degraders of ERG and AR could potentially provide novel therapeutic approaches for patients with mCRPC.