On February 14, 2023 Propella Therapeutics, Inc. ("Propella"), a private, clinical-stage biopharmaceutical company developing best-in-class oncology therapeutics, reported that Dr. Jose Avitia of the New Mexico Cancer Center will present updated data from the Company’s ongoing Phase 1/2a study of PRL-02 for the treatment of advanced prostate cancer on Thursday Feb 16 from 11:30AM to 1:00PM PST at the 2023 ASCO (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium, which is being held in San Francisco, CA from February 16-18, 2023 (Press release, Propella Therapeutics, FEB 14, 2023, View Source [SID1234627180]). Details on the poster presentation are below:
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2023 ASCO (Free ASCO Whitepaper) Genitourinary (GU) Cancer Symposium:
Session Type: Poster Session
Session Title: Poster Session A: Prostate Cancer
Track: Prostate Cancer – Advanced, Prostate Cancer – Localized Poster Session A: Prostate Cancer
Sub Track: Therapeutics
Abstract Title: "Phase 1/2a study of PRL-02, a long-acting intramuscular (IM) depot injection of abiraterone decanoate in patients (pts) with advanced prostate cancer."
Presenting Author: Jose Avitia, M.D.
Presentation Time: February 16, 2023, at 11:30 AM PST
Abstract Number: 141
Poster Bd#: E2
Venue: Moscone Center, West Hall Level 1
Abstract link: View Source
The presentation will highlight results from the ongoing dose-escalation part of the Phase 1/2 study (NCT04729114). At the time of abstract submission, safety, tolerability and activity results were available from 17 patients who had been treated at five different dose levels of PRL-02 (180mg; 360mg; 720mg; 1260mg; 1800mg). PRL-02, administered as an intramuscular injection every 12 weeks, was well tolerated; dose-dependent androgen suppression was associated with clinical benefit including PSA responses and radiographic improvement.
Based upon historical comparisons, the plasma concentrations of potentially harmful progesterone and corticosterone are significantly lower than with Zytiga, which appear to be due to greater PRL-02 CYP17 lyase selectivity. The emerging clinical data suggests that long-acting PRL-02 has the potential for a superior therapeutic index and safety profile compared to oral Zytiga, a standard of care for the patient populations treated.
"The PRL-02 Phase 1 data suggest both clinical efficacy advantages as well as safety and tolerability benefits for advanced prostate cancer patients who may have received approved androgen receptor inhibitor therapy," said Neal Shore, MD, FACS, a presentation author, Phase 1 investigator and the Medical Director for the Carolina Urologic Research Center. "I am very encouraged by the emerging PRL-02 profile and its clinically meaningful potential which could broaden our current armamentarium for patients with metastatic prostate cancer."
PRL-02 is being evaluated in an ongoing Phase 1/2a study for patients with metastatic prostate cancer. The Phase 1 portion is an open-label, multi-center, dose-escalation study designed to assess the safety, tolerability, pharmacokinetics, and preliminary clinical activity of PRL-02 and establish a recommended dose for the Phase 2a portion. The recommended Phase 2 dose will likely be a single injection of 1260mg every 12 weeks based upon pharmacokinetic, safety, clinical pharmacology, and efficacy results.
Expansion of patent estate for PRL-02
Separately, Propella also announced the United States Patent and Trademark Office (USPTO) issued U.S. Patent No. 11,559,534, titled "Abiraterone Prodrugs," on January 24, 2023. The ‘534 patent protects the abiraterone decanoate compound and its related pharmaceutical compositions, unit dosage forms comprising abiraterone decanoate, and methods of treating prostate cancer with pharmaceutical compositions comprising abiraterone decanoate. The ‘534 patent also discloses related methods of treating other androgen-dependent disorders, combination therapies, methods of reducing serum testosterone using a pharmaceutical composition comprising a lipophilic abiraterone prodrug. The ‘534 expires on March 4, 2040.
"Securing additional patent protection for PRL-02 is essential towards protecting and growing the value of this unique and potentially best-in-class therapy," said William Moore, Ph.D., Chief Executive Officer of Propella Therapeutics. "The issuance of the ‘534 patent provides additional protections with claims that cover PRL-02 pro-drug compositions of matter, and proprietary manufacturing processes. Together with the ‘282 patent, we have now built a formidable patent estate surrounding PRL-02 that should afford comprehensive IP protection out to 2040."
The ’534 patent builds upon Propella’s previously issued foundational intellectual property, U.S. Patent No. 10,792,292, which covers the composition of matter protection for multiple novel abiraterone prodrugs including abiraterone decanoate (PRL-02), claims for the PRL-02 IM route of administration, methods of treating prostate cancer and other androgen-dependent disorders, and methods of manufacturing. The ‘292 patent was issued on October 6, 2020, and expires in 2040.
About ASCO (Free ASCO Whitepaper) GU Cancer Symposium
The ASCO (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium is a three-day scientific and educational meeting designed to provide attendees with in-depth, multidisciplinary analysis of the most timely topics in the study, diagnosis, and treatment of GU malignancies. All members of the cancer care and research community will benefit from the Symposium’s exploration of the latest science in the field and its clinical application.
About Metastatic Prostate Cancer
Prostate cancer is the most common non-skin cancer in men, and the second leading cause of cancer death, developing most often in older men. Metastatic disease occurs when prostate cancer cells travel through the lymphatic system or blood stream to other organs and tissues such as lymph nodes, liver, bone, and lungs. While early or localized prostate cancer remains highly curable, advanced prostate cancer remains difficult to treat, with a 5-year survival rate of only 30%. Although there are several treatment options for metastatic prostate cancer, the reduction of androgen activity remains the most effective approach.
About PRL-02
PRL-02 is a next generation androgen biosynthesis inhibitor being developed for the treatment of prostate cancer. A large body of both historic and modern data support a role for androgens in prostate cancer pathogenesis and progression. The only approved androgen biosynthesis inhibitor approved for the treatment of prostate cancer, Zytiga (oral abiraterone acetate), blocks the CYP17 lyase enzyme that is required for the biosynthesis of androgens, including testosterone, but also unnecessarily blocks the CYP17 hydroxylase enzyme activity, resulting in a large accumulation of mineralocorticoids that can produce a constellation of side effects (hypertension, hypokalemia, edema) and upstream steroids such as progesterone that can further stimulate prostate cancer growth. PRL-02 is a patented prodrug of abiraterone designed for lymphatic targeting of tissues and tumors that express the CYP17 lyase enzyme. PRL-02 is an intramuscular depot that, when given along with a gonadotropin releasing hormone agonist or antagonist, precisely releases the concentration of abiraterone needed to block CYP17 lyase activity for 3 months. IM PRL-02 avoids adverse liver and drug-drug interaction effects, the accumulation of steroids (e.g., progesterone) that can further stimulate prostate cancer or produce the symptoms of mineralocorticoid excess (e.g., corticosterone) that arise from unwanted CYP17 hydroxylase inhibition.