LAST WEEK TODAY!

A summary of what was published on ProstateWarriors.com during the past week

Hi fellow warriors! I hope this collection of very promising clinical and preclinical research makes a nice Easter gift for you. Wishing you all a warm hug and a Happy Easter!Stay strong and fight on!

As usual, we also have a podcast if you prefer to listen to the newsletter, you can find it HERE.​

Clinical Research

• GEN1057 (DuoBody-FAPαxDR4), a bispecific antibody, is currently in a Phase 1 clinical trial for patients with advanced solid tumors. This therapy targets death receptor 4 (DR4) on cancer cells and fibroblast activation protein alpha (FAPα) on cancer-associated fibroblasts. Research indicates that FAPα expression is elevated in advanced or metastatic prostate cancer.GEN1057 is designed to activate DR4 only when FAPα is nearby, aiming for precise cancer cell death while sparing healthy tissues.
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• MK-2400 (Ifinatamab Deruxtecan/I-DXd), an antibody-drug conjugate (ADC) targeting TROP2, has shown notable activity in early trials for other tumor types and is expanding its evaluation to metastatic castration-resistant prostate cancer (mCRPC). A Phase 1 clinical trial focused specifically on patients with mCRPC is reported to be enrolling soon (est. June 2025). This trial will primarily focus on establishing the safety, tolerability, and recommended dose of MK-2400 in this patient population. TROP2 is a protein overexpressed on various solid tumors, including advanced prostate cancer.
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• Kesonotide, a first-in-class dual anti-inflammatory and chemotherapy drug, will be evaluated in the ADVICE Phase Ib/IIa clinical trial, starting mid-2025. This adaptive, multi-center, open-label study will enroll up to 80 patients with advanced solid cancers, including prostate cancer, who have progressed despite standard treatments or are unable or unwilling to use them. The trial will administer daily oral kesonotide monotherapy for up to six months, aiming to identify cancer types most responsive to treatment. Kesonotide targets both cancer cells and their supportive tumor microenvironment (TME) by inhibiting vimentin, which is essential for cancer cell survival and TME formation. A successful first-in-human pilot study in 12 men with advanced prostate cancer confirmed its oral bioavailability, safety, and tolerability.

Preclinical Research

• BTE-EN1 has demonstrated remarkable results in mouse studies for advanced prostate cancer with bone metastasis. In mice with well-established bone metastases, weekly BTE-EN1 treatments led to a stunning 62% reduction in bone destruction compared to untreated mice. In a separate experiment simulating widespread metastasis, BTE-EN1 significantly extended life in a dose-dependent manner. Notably, traditional bone-protecting drugs failed to show similar survival benefits in these models. Lab tests confirmed that BTE-EN1 effectively blocks cancer cell movement while targeting bone lesions, and it showed no toxicity even at doses 4,000 times higher than effective doses in mice. BTE-EN1 also inhibits cell movement in various cancer types that destroy bone.
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• CD-001, a novel dual-targeting immunotherapy, has been approved to move to clinical trial stage for solid tumors. While prostate cancer was not specifically tested in early preclinical studies, the mechanism of CD-001 is considered relevant to this disease. CD-001 simultaneously blocks the PD-1 immune checkpoint and delivers a mutated form of the cytokine IL-21 directly to PD-1 positive T cells. This dual action aims to enhance the body’s immune response against tumors, which could be particularly beneficial in the immunosuppressive environment often found in prostate tumors.
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• Early animal tests suggest that SDV2102, an ADC targeting PSMA, could be a promising treatment for mCRPC. In patient-derived tumor models with even low to moderate PSMA levels (as few as 25,000 PSMA receptors per cell), SDV2102 still showed strong anti-tumor effects. In rat studies, SDV2102 circulated effectively without premature breakdown, and non-human primate studies indicated a wide safety margin with no major side effects observed even at high doses. SDV2102 has a unique design with a drug-to-antibody ratio of one, allowing for potentially higher doses with manageable toxicity.
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And…that’s all folks! For today at least!
Please let me know if there is anything I can improve in my newsletters, and let me know if you have enjoyed the podcast.

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Have a great weekend!

Max