On April 3, 2024 Blacksmith Medicines, Inc. (Blacksmith), a leading biopharma dedicated to discovering and developing medicines targeting metalloenzymes, reported that it will present a company overview and participate in 1×1 meetings at the 23rd Annual Needham Healthcare Conference on Thursday, April 11, 2024 at 11:00 am ET (Press release, Blacksmith Medicines, APR 3, 2024, View Source [SID1234641734]).

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"At Blacksmith Medicines, we are developing a pipeline of novel small molecule medicines targeting metalloenzymes of significant unmet need and high pharma interest, but chemistry limitations have hampered previous efforts that we can solve using our technology platform," said Zachary A. Zimmerman, Ph.D., CEO of Blacksmith. "We look forward to presenting our story at the Needham conference and showcasing the vast number of important metalloenzyme targets, the broad therapeutic application of our technology, and our compelling preclinical data."

About metalloenzymes and the Blacksmith platform

Metalloenzymes utilize a metal ion cofactor in the enzyme active site to perform essential biological functions. This diverse class of targets has historically been difficult to drug due to small molecule chemistry limitations that have plagued the industry. The Blacksmith metalloenzyme platform has solved this problem by leveraging the following:

A large proprietary fragment library of metal-binding pharmacophores (MBPs);
A comprehensive database containing a full characterization of the metalloenzyme genome including functions, metal cofactors, and associations to disease;
A first-of-its-kind metallo-CRISPR library of custom single guide RNAs;
An industry-leading metalloenzyme computational toolkit for docking, modeling and structure-based drug design; and
A robust and blocking intellectual property estate covering bioinorganic, medicinal, and computational chemistry approaches for metalloenzyme-targeted medicines.

On April 3, 2024 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer, reported its participation in upcoming investor conferences (Press release, Black Diamond Therapeutics, APR 3, 2024, View Source [SID1234641733]). Presentation details with President and Chief Executive Officer, Mark Velleca, M.D., Ph.D., are as follows:

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23rd Annual Needham Virtual Healthcare Conference presentation at 8:00am ET on Wednesday, April 10, 2024
Stifel Virtual Targeted Oncology Forum fireside chat at 10:00am ET on Tuesday, April 16, 2024
Piper Sandler Spring Biopharma Symposium on Wednesday, April 17, 2024, in Boston, Mass.
Webcasts will be available at the start of the presentations on the investor relations section of the Company’s website, www.blackdiamondtherapeutics.com. Replays of the presentations will also be available and archived on the site for 90 days.

On April 3, 2024 Bio-Techne Corporation (NASDAQ:TECH) reported it will showcase its portfolio of solutions to advance cancer research from target discovery to cell therapy development at the upcoming annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), taking place April 5-10, 2024, in San Diego, California (Press release, Bio-Techne, APR 3, 2024, View Source [SID1234641732]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Bio-Techne will showcase its solutions at booth #541, featuring our market-leading portfolio of high-grade life science reagents, immunoassays, automated proteomic analytical instruments, and multiomics solutions that are enabling new drug discovery research, accelerating immune cell therapy, and supporting the development of better diagnostic tools. We will also be debuting our Journey into the Tumor Microenvironment video experience in our booth this year. We welcome attendees to explore how different cell types in the tumor microenvironment promote tumor escape through this new interactive platform.

Several scientists from the company will be presenting posters at the conference highlighting our in-house studies in the areas of drug discovery research, automated spatial multiomics, and the development of novel diagnostic tools. These include investigations into validating atypical drug combinations, analyzing the tumor microenvironment by integrated RNA and protein profiling with automated spatial multiomics, developing an exosome/cfDNA methylation blood-based screen for colorectal cancer, and monitoring ESR1 mutations by RT-qPCR in longitudinal studies to predict endocrine therapy resistance.

"We are excited to showcase our portfolio of innovative tools, reagents and workflow solutions that enable the scientific discoveries necessary to advance cancer research," said Kim Kelderman, Bio-Techne’s President and Chief Executive Officer. "Bio-Techne’s portfolio plays a critical role in the development of next-generation cancer therapies, including workflows supporting the emerging class of cell and gene therapies. Our broad presence at AACR (Free AACR Whitepaper) will showcase the many roles Bio-Techne plays in catalyzing advances in science and medicine, and ultimately enabling global populations to live healthier and longer lives."

Bio-Techne Poster Presentations:

Validation of Atypical Drug Combinations Identified from Combination Databases
Sunday, April 7th from 1:30 PM – 5:00 PM
Presenter: Marco Pinheiro, Ph.D.
Poster Section #39, Poster Board #11, Abstract #943

Unveiling the Spatial Dynamics of the Tumor Microenvironment: Integrated RNA and Protein Profiling on the Same Slide through Automated Spatial Multiomics Analysis
Monday, April 8th from 1:30 PM – 5:00 PM
Presenter: Arec Manoukian, Ph.D.
Poster Section #45, Poster Board #20, Abstract #3797

A Kit Targeting Detection of ESR1 Mutations from Circulating Exosomal RNA and Cell-Free DNA Supports Longitudinal Studies into Endocrine Therapy Resistance in a Broadly Accessible RT-qPCR Format
Tuesday, April 9th from 9:00 AM – 12:30 PM
Presenter: Sarah Statt, Ph.D.
Poster Section #26, Poster Board #2, Abstract #4626

Exosome Based Multiomics Combined with cfDNA Methylation Reveals Complementary Signatures in Blood Based Liquid Biopsy that Carry Promise for Minimally Invasive Colorectal Cancer Screening
Wednesday, April 10th from 9:00 AM – 12:30 PM
Presenter: Kyle Manning
Poster Section #51, Poster Board #10, Abstract #LB393

Poster Presentation, In Collaboration

Bladder Cancer Risk Stratification with the Oncuria 10 plex Bead-based Urinalysis Assay Using Three Different Luminex xMAP Instrumentation Platforms
Monday, April 8th from 1:30 PM – 5:00 PM
Presenter: Sunao Tanaka, Ph.D., Postdoctoral Scientist, Cedars-Sinai
Poster Section #44, Poster Board #29, Abstract #3773

On April 3, 2024 Astex Pharmaceuticals, a pharmaceutical company based in Cambridge, UK, dedicated to the discovery and development of novel small molecule therapeutics for oncology and diseases of the central nervous system, reported that it will make five key data presentations at AACR (Free AACR Whitepaper) 2024 focusing on its Phase II-ready MDM2 antagonist, ASTX295 (Press release, Astex Pharmaceuticals, APR 3, 2024, View Source [SID1234641731]). AACR (Free AACR Whitepaper) 2024 will take place from April 5-10, 2024, at the San Diego Convention Center, San Diego, USA.

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ASTX295 data presentations at AACR (Free AACR Whitepaper) 2024

Title Presentation Date/Time/Presenter Link to Abstract
Discovery of ASTX295, a potent, next-generation small molecule antagonist of MDM2 with differentiated pharmacokinetic profile. From concept to clinic Oral Tuesday, April 9
3:20 – 3:35pm PT

Session Title: Novel Antitumor Agents 5

Presenter: Maria Ahn, Astex Pharmaceuticals, UK

6588
View Source!/20272/presentation/4100
ASTX295 engages p53-mediated apoptosis and an inflammatory response in patient derived mesothelioma explants Poster Sunday, April 7
1:30 – 5:00pm PT

Presenter: Dean Fennell, University of Leicester, UK

666
linkView Source!/20272/presentation/4103
Identification of biomarkers of response to MDM2 inhibition in solid tumours using computational, multi-omics approaches

Poster Sunday, April 7
1:30 – 5:00pm PT

Presenter: Matthew Davis, Astex Pharmaceuticals, UK

667
View Source!/20272/presentation/4104
Phase 1 study of MDM2 antagonist ASTX295 in patients with solid tumors with wild-type TP53 Poster Monday, April 8, 9:00 -12:30pm PT
Presenter: Ekaterina Dumbrava, The University of Texas MD Anderson Cancer Center, Houston, TX

CT066
View Source!/20272/presentation/11530
Targeting the MDM2-p53 interaction: Time-and concentration-dependent studies in tumor and normal human bone marrow cells reveal strategies for an enhanced therapeutic index

Poster Monday, April 8
1:30 – 5:00pm PT

Presenter: Steve Wedge, Newcastle University, Newcastle upon Tyne, UK

3333
View Source!/20272/presentation/5680
ASTX295 is an oral, potent inhibitor of the p53-MDM2 protein-protein interaction that was discovered by Astex using its proprietary structure-based drug design approach. The compound was specifically designed to overcome the on-target toxicity seen in the first generation MDM2 antagonist compounds which have shown dose-limiting haematological toxicities in the clinic. In contrast, ASTX295 is a potent MDM2 antagonist with a clean CYP/hERG profile and a shorter human half-life allowing for pulsatile pathway modulation while avoiding myelosuppression. ASTX295 therefore has bone-marrow sparing characteristics which permit a differentiated safety profile to be presented at AACR (Free AACR Whitepaper). Astex is interested in discussing the further development of ASTX295 with potential partners.

On April 3, 2024 Vopec Pharmaceuticals and Agastiya Biotech reported topline results from the Phase 1 study of AB001, an investigational small molecule, PDL1 immunotherapy for patients with metastasized and locally advanced solid tumors (Press release, Agastiya Biotech, APR 3, 2024, View Source [SID1234641730]).

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Unlike current standard of care immuno- and chemotherapy drugs AB001’s novel immunotherapy mechanism of action selectively destroys tumors without harming healthy cells.

Study Design

A total of 33 patients [3+3 Design], 7 with breast cancer, 5 with ovarian cancer, and 21 with other solid tumors, received AB001. AB001 was administered orally twice daily (at BID doses ranging from 40 to 800 mg) in patients with advanced or metastatic solid tumors. The study’s primary and secondary objectives were safety and efficacy. Safety parameters include MTD, PK, and other standardized toxicology protocols. The efficacy study included investigator-evaluated anti-tumor activity (PD) and biomarker responses correlated with pre- and post-treatment PET-CT and mRNA expression studies.

Toxicity Study

The Phase 1 study showed that AB001 was well-tolerated. The adverse events (AEs) were mild to moderate in severity. No dose-limiting toxic (DLT) effects or treatment-related deaths were reported. Treatment-related adverse events occurred in 9 patients at an instance rate of 2.9%; the most common adverse events were 5 patients with diarrhea (1%), 3 patients with vomiting (1%), and 1 patient with fatigue. Six adverse events were graded as mild in severity, and 3 adverse events were found to be moderate in severity. On investigation, the AEs were determined to be of unrelated causes to the treatment drug and resolved with medications, including over-the-counter medicines.

Efficacy Study

AB001 met secondary efficacy endpoints and demonstrated clinical benefit. The 14-day dose escalation studies showed notable improvements at all dosages in tumor biomarkers, immune markers, and tumor size, as confirmed by 21-day PET SCANs. Among patients with solid tumors, a favorable response was observed in 63.64%, a stable response in 19.39%, and disease progression in 16.36%. Partial responses (PR) were also observed in patients with other solid tumors. Serial assessment of tumor biomarkers showed a significant reduction from baseline. CA19.9 showed a 42% reduction (p=0.2), compared to a 38.4% drop in the CA125 markers (p=0.9), and the overall CEA markers revealed a reduction of 58.6% (p=0.6). mRNA studies showed significant changes in the expression of immunomodulation genes and Treg genes, which were associated with the anti-tumor response of AB001.

The superfast treatment impact within 21 days is attributed to the femto-scale metabolism and tumor DNA damage. MiRNA ad mRNA degradation add to the efficacy of the drug.

AB001 is the first Anti-cancer molecule to be released in India by Vopec Pharmaceutical with R&D and clinical collaboration with US-based Agastiya Biotech. Phase 2 is anticipated to begin in May 2024 in India.

The US FDA has awarded Orphan Drug Designation for AB001 for pancreatic, glioblastoma multiforme (GBM), and acute myeloid leukemia (AML) cancer indications. The companies will present the AB001 Phase 1 data at a future scientific forum.