On April 21, 2025 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-class1 targeted and immune-mediated therapeutics to fight cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to TPST-1495, the company’s novel dual receptor inhibitor of prostaglandin (PGE2) signaling, for the treatment of patients with Familial Adenomatous Polyposis (FAP) (Press release, Tempest Therapeutics, APR 21, 2025, View Source [SID1234651994]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"Receiving orphan drug designation for TPST-1495, our second clinical program, is a significant milestone in our mission to bring innovative therapies to patients with unmet medical need," said Stephen Brady, President and CEO of Tempest. "This designation for the treatment of FAP underscores Tempest’s mission to make a meaningful difference in the lives of patients and builds on the momentum from prior designations received for amezalpat in hepatocellular carcinoma."

A Phase 2 study evaluating TPST-1495 in patients with FAP is set to begin this year, conducted by the Cancer Prevention Clinical Trials Network and funded by the National Cancer Institute (NCI) Division of Cancer Prevention. Data from this study are expected in 2026.

About Familial Adenomatous Polyposis

FAP is a high-risk inherited syndrome associated with the development of cancer in affected patients and has no approved medical therapies. In the US, the disease affects approximately one in 5,000 to 10,000 individuals2. FAP is caused by autosomal dominant inactivating mutations in the tumor suppressor gene APC. Patients with FAP develop large numbers of adenomatous polyps throughout the gastrointestinal tract, often starting in their teenage years. These growths have a high risk of malignant transformation and can give rise to invasive cancers of the colon, stomach, duodenum, rectum, and other tissues. Standard of care treatment for patients with FAP is surgical removal of the colon (colectomy) early in life to reduce the likelihood of cancer development. Even after colectomy, patients must receive careful surveillance for development of cancer elsewhere in the GI tract throughout their lifetime. While surgical management and surveillance have improved the prognosis for patients with FAP, cancer remains a major cause of death for patients with FAP.

On April 21, 2025 Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company pioneering a differentiated approach to treating cancer and Alzheimer’s disease (AD) through the inhibition of Semaphorin 4D (SEMA4D), reported that it will present exciting new data characterizing the unique mechanism of pepinemab to enhance immune responses to checkpoint therapies, corresponding with improved survival benefit in patients with melanoma and head and neck cancer at the 2025 Annual Meeting of American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Chicago on April 29, 2025 (Press release, Vaccinex, APR 21, 2025, View Source [SID1234651995]). Elizabeth Evans, PhD, Senior VP Discovery and Translational Medicine, will present results of these studies in two presentations.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

AACR Conference Information:

Date: Tuesday, April 29, 2025
Presentation title: Regulating dendritic cells to promote mature tertiary lymphoid structures and enhance anti-tumor immunity. Presentation #3975
Time: 9-12 AM CDT/10 AM – 1 PM EDT.
Session Title: The Tumor Immune Interplay as a Driver of Progression

Presentation title: Neoadjuvant pepinemab enhances DC function associated with mature tertiary lymphoid structures and activity of immune checkpoint blockade in patients with metastatic melanoma. Presentation #6007
Time: 2-5 PM CDT/ 3-6 PM EDT.
Session Title: Therapeutic Antibodies, Including Engineered Antibodies 2
Access: Posters will be presented in-person on Tuesday, April 29 at McCormick Place Convention Center, Chicago, Illinois, and on AACR (Free AACR Whitepaper) 2025 virtual meeting platform at 1:00 PM ET on Friday, April 25, 2025.

Previously reported data from these two clinical studies suggest a crucial role of pepinemab to facilitate immune cell interactions within highly organized and robust centers of immunity, called tertiary lymphoid structures, or TLS. By blocking the SEMA4D inhibitory signal to Dendritic Cells (DC), pepinemab allows productive, coordinated interactions between SEMA4D+ T cells, key effector cells capable of eradicating tumors, and DC, regulatory cells that promote immune cell interactions within TLS so as to amplify mature T cell responses. New data will characterize clinical outcomes, biomarkers, and mechanisms of these interactions in patients treated with pepinemab in combination with immune checkpoint therapy.

Boosting TLS within tumors is an area of growing excitement because the presence of TLS has been shown to correlate with clinical benefit and positive response to immune checkpoint therapy. A limitation in the field has been identification of safe and effective therapies that can induce formation and harness the potential of TLS to enable durable benefit to patients. Pepinemab may represent a solution to this problem, as our data demonstrate the potential of pepinemab to turn immunologically cold tumors, such as HPV-negative and PD-L1-low head and neck cancer, into hot immune centers by inducing robust and mature TLS.

Neoadjuvant immunotherapy has emerged as a promising approach in the treatment of various cancers, showing improved immune and clinical benefit in the preoperative setting compared to standard post surgery adjuvant treatments. Despite these advances, many patients who initially benefit from antibodies that block inhibitory checkpoint molecules (e.g. PD-1, CTLA 4) will progress. More effective combination therapies are needed. Neoadjuvant treatment with pepinemab enhanced TLS maturity and correlated with longer recurrence-free survival when combined with immune checkpoint inhibitors in patients with metastatic melanoma. Evaluation of pepinemab in the neoadjuvant setting for patients with head and neck cancer is ongoing and will be reported at upcoming scientific meeting this Spring.

About Pepinemab
Pepinemab is a humanized IgG4 monoclonal antibody designed to block SEMA4D, which can otherwise bind to plexin-B1 receptors to trigger collapse of the actin cytoskeleton in cells and lead to loss of homeostatic functions of dendritic cells in immune tissue and of astrocytes and other glial cells in the brain. Pepinemab appears to be well-tolerated with a favorable safety profile in multiple clinical trials in different cancer and neurological indications.

On April 21, 2025 Veracyte, Inc. (Nasdaq: VCYT), a leading cancer diagnostics company, reported that data from its market-leading Decipher Prostate Genomic Classifier are available in a new specialized database that the National Cancer Institute’s (NCI’s) Surveillance, Epidemiology, and End Results (SEER) Program just released (Press release, Veracyte, APR 21, 2025, View Source [SID1234651996]). This database will enable eligible researchers to evaluate Decipher Prostate test results in the context of real-world patient outcomes, prostate cancer characteristics, treatment protocols, demographics and other factors.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"We are excited about the numerous opportunities that our collaboration with the NCI SEER Program will enable for prostate cancer researchers and, ultimately, for patients," said Philip Febbo, M.D., Veracyte’s chief scientific officer and chief medical officer. "It also reinforces Veracyte’s commitment to building clinical evidence for our tests and to advancing scientific understanding of cancer and its biological underpinnings."

The NCI SEER Program is an authoritative source of population-based information on cancer incidence and survival in the United States. The SEER specialized database containing de-identified Decipher Prostate Genomic Classifier data is based on a linkage conducted by the SEER registries and included over 560,000 prostate cancer cases diagnosed from 2010 to 2018. The Decipher Prostate test has been available for use on radical prostatectomy specimens since 2013 and on biopsy tissue since 2016.

About Decipher Prostate

The Decipher Prostate Genomic Classifier is a 22-gene test, developed using RNA whole-transcriptome analysis and machine learning, that helps inform treatment decisions for patients with prostate cancer. The test is performed on biopsy or surgically resected samples and provides an accurate risk of developing metastasis with standard treatment. Armed with this information, physicians can better personalize their patients’ care and may recommend less-intensive options for those at lower risk or earlier, more-intensive treatment for those at higher risk of metastasis. The Decipher Prostate test’s performance and clinical utility has been demonstrated in over 85 studies involving more than 200,000 patients. It is the only gene expression test to achieve "Level I" evidence status and inclusion in the risk-stratification table in the most recent NCCN Guidelines* for prostate cancer. More information about the Decipher Prostate test can be found here.

On April 18, 2025 SparX Biopharmaceutical Corp. reported that it will present clinical updates on its lead asset, SPX-303, a first-in-class anti-LILRB2/PD-L1 bispecific antibody, during the Trial-in-Progress poster session at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 28, from 2:00 PM to 5:00 PM (Press release, Sparx Therapeutics, APR 18, 2025, View Source [SID1234651986]). The presentation marks the one-year anniversary of the first patient dosing of this novel bispecific antibody in its ongoing Phase 1 clinical trial.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

A more comprehensive overview of SPX-303’s dual mechanism, which targets both myeloid and T-cell immune checkpoints, will be featured at a Satellite Symposium themed "Harnessing Super Immunotherapy and ADCs to Redefine the Standard of Care." Co-hosted by the University of Illinois at Chicago Cancer Center and Yao Yuan—Academy for Pharma Innovation, the symposium will convene expert clinicians, academic investigators, and industry leaders to discuss how next-generation immuno-oncology, known as "Super IO," can be synergized with antibody-drug conjugates (ADCs). This innovative approach combines the tumor-targeting precision of ADCs with the immune-activating power of checkpoint inhibitors, aiming to deliver deeper and more durable anti-tumor responses.

SPX-303, a first-in-class bispecific antibody targeting LILRB2 and PD-L1, is currently enrolling patients with resistant or refractory solid tumors at a dose level of 20 mg/kg. "This innovative program represents a significant advancement in macrophage checkpoint blockade and T cell co-engagement strategies," said Dr. Gui-Dong Zhu, CEO of SparX. "It holds promise as a potential next-generation immuno-oncology therapy—or ‘Super IO’ booster—for patients with limited treatment options."

The SPX-303 poster will be presented at Poster #CT116-11 in the Phase I Clinical Trials in Progress session at McCormick Place, Chicago, on April 28, from 2:00 to 5:00 PM. The Satellite Symposium will be held at the Trump International Hotel & Tower Chicago (401 N Wabash Ave, Chicago, IL 60611). SparX welcomes attendees to visit its exhibition booth during the symposium and strongly encourages early registration via the [registration portal] to secure a seat.

About SPX-303

SPX-303 is a first-in-its-class bispecific antibody therapy designed to simultaneously inhibit LILRB2 and PD-L1, two critical immune checkpoint proteins often hijacked by cancer cells. The program represents a novel immunotherapy approach aimed at activating both myeloid and lymphoid immune responses.

On April 18, 2025 Ymmunobio AG (YB), a Swiss-based global biotech company dedicated to the development of new cancer therapeutics, reported that its two-antibody drug conjugate (ADC) assets, YB-800ADC1 and YB-800ADC2, have completed the preclinical proof of concept studies (Press release, Ymmunobio, APR 18, 2025, View Source [SID1234651987]). Both in vivo and in vitro studies have reached this important milestone by demonstrating the anti-tumor efficacy of both ADCs.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

The ADCs are derived from YB’s lead antibody YB-800 which targets a novel and first in class tumor marker. They utilize established payloads and a third-generation linker, demonstrating a tumor growth inhibition of 90%.

"These excellent results allow YB to move forward swiftly to prepare for the pivotal toxicology studies. This is a major step towards the clinical development of our ADCs in solid tumors and demonstrates the potential for YB’s ADCs to address unmet needs for cancer patients expressing the new novel tumor marker. In addition, the proof-of-concept data support the preclinical development of the two YB-800 based radiopharmaceuticals developed in collaboration with the Paul Scherer Institute," said Peter Schiemann, CEO.