Multi-Centre, Ph IIb Study, Evaluating Safety & Efficacy of Targeted Intraprostatic Admin of PRX302 to Treat Men With Histologically Proven, Clinically Significant, Localised Prostate Cancer Associated With MRI Lesion

The purpose of this study is to determine a safe, effective, and tolerable dose of PRX302 for the treatment of low to intermediate risk prostate cancer.

Start Date07 Jun 2017

Sponsor / Collaborator

Sophiris Bio, Inc.

NCT02499848

/ CompletedPhase 2

Phase IIa Study, Evaluating the Safety and Tolerability of Targeted Intraprostatic Administration of PRX302 With Histologically Proven,Clinically Significant Localised, Low to Intermediate Risk Prostate Cancer Associated With MRI Lesion

To Evaluate Safety, Tolerability and Potential Efficacy of PRX302 effect on clinically significant localised low to intermediate prostate cancer.

Start Date01 Jul 2015

Sponsor / Collaborator

Sophiris Bio, Inc.

NCT01966614

/ CompletedPhase 3

Randomized, Double-Blind, Vehicle-Controlled, Multicenter Safety and Efficacy Study of a Single Intraprostatic Treatment of PRX302 for Lower Urinary Tract Symptoms (LUTS) Secondary to Benign Prostatic Hyperplasia (The PLUS 1 Trial)

The purpose of this study is to evaluate the safety and efficacy of a single treatment of PRX302 for the treatment of Benign Prostatic Hyperplasia (BPH) as compared to placebo.

Start Date01 Oct 2013

Sponsor / Collaborator

Sophiris Bio, Inc.

100 Clinical Results associated with Topsalysin

100 Translational Medicine associated with Topsalysin

100 Patents (Medical) associated with Topsalysin

Literatures (Medical) associated with Topsalysin

01 Nov 2020·Molecular cancer therapeuticsQ2 · MEDICINE

Microparticle Encapsulation of a Prostate-targeted Biologic for the Treatment of Liver Metastases in a Preclinical Model of Castration-resistant Prostate Cancer

Q2 · MEDICINE

Article

Author: Simons, Brian W. ; Levy, Oren ; Joshi, Nitin ; Rosen, D. Marc ; Denmeade, Samuel R. ; Karp, Jeffrey M. ; Antony, Lizamma ; Brennen, W. Nathaniel ; Dalrymple, Susan L. ; Isaacs, John T. ; Lan, Haoyue ; Zheng, Lei ; Ranganath, Sudhir H. ; Howard, S. Peter ; Pickering, Andrew ; Rogers, Oliver C. ; Kuang, Heidi

Abstract:

PRX302 is a highly potent, mutant bacterial pore-forming biologic protoxin engineered for selective activation by PSA, a serine protease expressed by benign and malignant prostate epithelial cells. Although being developed as a local therapy for benign prostatic hyperplasia and localized prostate cancer, PRX302 cannot be administered systemically as a treatment for metastatic disease due to binding to ubiquitously expressed glycosylphosphatidylinositol (GPI)-anchored proteins, which leads to poor accumulation within the tumor microenvironment. To overcome this limitation, poly-lactic-co-glycolic acid (PLGA) microparticles encapsulating the protoxin were developed, which are known to accumulate in the liver, a major site of metastasis for prostate cancer and other solid tumors. A highly sensitive and reproducible sandwich ELISA to quantify PRX302 released from microparticles was developed. Utilizing this assay, PRX302 release from different microparticle formulations was assessed over multiple days. Hemolysis assays documented PSA-dependent pore formation and lytic potential (i.e., function) of the released protoxin. MTT assays demonstrated that conditioned supernatant from PRX302-loaded, but not blank (i.e., unloaded), PLGA microparticles was highly cytotoxic to PC3 and DU145 human prostate cancer cells in the presence of exogenous PSA. Microparticle encapsulation prevented PRX302 from immediately interacting with GPI-anchored proteins as demonstrated in a competition assay, which resulted in an increased therapeutic index and significant antitumor efficacy following a single dose of PRX302-loaded microparticles in a preclinical model of prostate cancer liver metastasis with no obvious toxicity. These results document that PRX302 released from PLGA microparticles demonstrate in vivo antitumor efficacy in a clinically relevant preclinical model of metastatic prostate cancer.

01 May 2018·CURRENT OPINION IN UROLOGY

Investigational procedures in benign prostatic hypertrophy

Review

Author: Borofsky, Michael S ; Acquaye, Joseph

PURPOSE OF REVIEW:

As benign prostatic hypertrophy (BPH) becomes a more common disease, there has been a dramatic rise in the number of investigational procedures being developed to manage it. We seek to present an overview of the most recently developed treatments and present clinical data related to application wherever available.

RECENT FINDINGS:

As a greater number of treatments become available for BPH, improved diagnostic testing could prove beneficial in helping guide patient selection. Efforts are underway to identify serum biomarkers associated with BPH as well as new classifications strategies, specifically with MRI, to determine both the anatomy of BPH as well as its histologic distribution. Outpatient-based procedures for BPH currently being developed include the temporary implantable nitinol device as well as intraprostatic injections such as Botox and PRX302. Aquablation is a novel technique that uses robotically guided high-pressured saline to ablate prostate tissue. Early data suggests noninferiority compared with TURP. Finally, efforts are underway to apply robotics to BPH with the advent of a robotic transurethral platform being designed for prostate enucleation.

SUMMARY:

Many new techniques are poised to be introduced to the BPH market over the coming years. The unique risk/benefit profiles as well as associated clinical outcomes of each will need to be studied in detail in order to help identify proper roles in the management of patients with symptomatic disease.

01 Dec 2017·EUROPEAN UROLOGY

Emerging Minimally Invasive Treatment Options for Male Lower Urinary Tract Symptoms

Review

Author: Chapple, Christopher R ; Woo, Henry H ; Elhilali, Mostafa ; Gratzke, Christian ; Magistro, Giuseppe ; Roehrborn, Claus G ; McVary, Kevin T ; Stief, Christian G ; Gilling, Peter

CONTEXT:

Lower urinary tract symptoms (LUTS) are one of the most common and troublesome nonmalignant conditions affecting quality of life in aging men. A spectrum of established medical and surgical options is available to provide relief of bothersome LUTS. Both the adverse events of medication and the morbidity with surgical treatment modalities have to be counterbalanced against efficacy. Novel minimally invasive treatment options aim to be effective, ideally to be performed in an ambulatory setting under local anaesthesia and to offer a more favourable safety profile than existing reference techniques.

OBJECTIVE:

A comprehensive, narrative review of novel minimally invasive treatment modalities for the management of male LUTS due to benign prostatic enlargement is presented.

EVIDENCE ACQUISITION:

Medline, PubMed, Cochrane database, and Embase were screened for randomised controlled trials (RCTs), clinical trials, and reviews on novel minimally invasive treatment options for male LUTS due to benign prostatic enlargement.

EVIDENCE SYNTHESIS:

With regard to newly devised intraprostatic injectables (botulinum neurotoxin A, NX1207, PRX302), PRX302 is currently the only substance that was superior to placebo in a phase 3 RCT providing proof of efficacy and safety. The prostatic urethral lift technique has been evaluated in several phase 3 trials showing rapid and durable relief of LUTS without compromising sexual function in carefully selected patients without a prominent median lobe. The first clinical experience of the temporary implantable nitinol device demonstrated that implantation of this novel device is a safe procedure, easy, and fast to perform. Further studies are required to evaluate efficacy, durability, and to define appropriate patient selection. New ablative approaches like the image guided robotic waterjet ablation (AquaBeam) or procedures based on convective water vapour energy (Rezūm) are in the early stages of development. Prostatic artery embolization performed by interventional radiologists at specialised centres shows a high technical success rate in the treatment of bothersome LUTS. However, a substantial clinical failure rate and a particular spectrum of complications not commonly seen after urologic interventions do occur and need to be critically evaluated.

CONCLUSIONS:

Initial promising clinical results on novel minimally invasive treatment options indicate efficacy comparable to standard techniques, often associated with a more favourable safety profile, in particular with preservation of sexual function. Many of these techniques are in their infancy and based on experience of new developments in the past. Further RCTs are required to evaluate efficacy, safety, and durability of novel techniques with long-term follow-up and careful evaluation of the selection criteria, which have been applied in clinical trials. The prostatic urethral lift is the only procedure with Level 1 evidence data and that can therefore be recommended for treatment of male LUTS in clinical practice for selected patients.

PATIENT SUMMARY:

Minimally invasive treatment options have been developed to provide relief of lower urinary tract symptoms comparable to standard surgical techniques with a more favourable safety profile. However, long-term clinical evaluation is still needed for most of these innovations before they can be recommended to be an effective replacement for standard surgical treatment.

News (Medical) associated with Topsalysin

23 Aug 2016

·www.biospace.com

SoCal’s Sophiris Bio Evaluating Options, Will Not Pursue New Clinical Trials Unless New Financing is Obtained

August 23, 2016 By Mark Terry , BioSpace.com Breaking News Staff Sophiris Bio , located in La Jolla, California, announced yesterday that it plans to offer and sell its common shares and warrants in order to buy additional common shares in an underwritten public offering. Piper Jaffray & Co. is the book-running manager. Warrants are a type of security that lets the holder buy the company’s underlying stock at a fixed price. Sophiris Bio is focused on developing topsalysin, a clinical-stage drug to treat urological diseases. It has successfully finished a Phase III clinical trial to treat symptoms of benign prostatic hyperplasia (BPH). The drug has also successfully wrapped up a Phase IIa trial to treat clinically significant, localized low to intermediate risk prostate cancer prior to radical therapy. At the company’s second-quarter financial report on Aug. 9, the company stated that on May 11 it had closed a registered offering where it raised net proceeds of $4.6 million. And during June and July, it received proceeds of $2.4 million from the exercise of warrants, which brought the total up to $7 million. “2016 is proving to be a transformational year for Sophiris,” Randall Woods , the company’s president and chief executive officer, said in a statement. “In the past quarter, we completed a Phase IIa proof of concept trial of topsalysin in localized prostate cancer in which topsalysin demonstrated the ability to ablate tumor cells in 50 percent of patients, including two men who experienced complete ablation of their targeted tumor with no evidence of any tumor remaining at six months post treatment. We also presented complete results from the Phase III BPH study in a late breaking presentation at the AUA 2016 Annual Meeting, demonstrating that topsalysin met the primary endpoint of a reduction in symptom score compared to the vehicle control arm.” As of June 30, the company had 9.3 million in cash and cash equivalents, and net working capital of $5.7 million. The company believes that will be enough to fund operations for the next 12 months if it doesn’t begin any new topsalysin studies. “We do not plan to initiate any new clinical trials,” the company stated, “including a second Phase III trial in BPH or a second Phase II trial in localized prostate cancer unless we obtain additional financing. We are actively evaluating strategic alternatives, including potential partnering arrangements, financings or a strategic transaction.” Sophiris Bio has been doing fairly well recently, although it dropped 28.87 percent in after-market trading after the news of the new offering was made. Shares traded on Nov. 11, 2015 for $3.20, dropped to $0.88 on May 18, 2016, and spiked to $5.95 on July 25, 2016. Shares dropped to $4.31 on Aug. 16, and is currently trading for $5.82. The consensus price target estimates for the next year is $8.25, according to Review Fortune .

Phase 2Phase 3Clinical ResultFinancial Statement

13 May 2016

·www.biospace.com

Only Days After a Follow-On Offering, San Diego’s Sophiris Bio Hires Oppenheimer to Explore Strategic Options

May 13, 2016 By Mark Terry , BioSpace.com Breaking News Staff La Jolla, California-based Sophiris Bio yesterday hired Oppenheimer & Co. Inc. to help it develop strategic plans that could include a partnership or other financial transactions. Sophiris is developing PRX302 for the treatment of urological diseases, and is currently in Phase III trials for benign prostatic hyperplasia (BPH), otherwise known as enlarged prostate. The compound is also in a Phase IIa proof of concept study for localized low to intermediate risk prostate cancer. “Our Phase III BPH clinical trial met its primary endpoint and the initial data from our Phase IIa proof of concept trial in localized prostate cancer was encouraging, both of which create attractive strategic opportunities for moving the programs and the company forward,” said Randall Woods , president and chief executive officer of Sophiris, in a statement. “Data from all 18 patients treated with topsalysin in the Phase IIa prostate cancer study is still expected this quarter. With the totality of the topsalysin data, Oppenheimer’s experience advising companies in our field will be immensely valuable as we evaluate strategic alternatives to maximize opportunities from our topsalysin programs.” Earlier this week, the company reported that it has closed its previously announced public offering at $1.40 per share for total gross proceeds of $5 million. Sophiris indicated it plans to use the net proceeds, about $4.6 million, for general corporate purposes and to pay down outstanding debt. The company’s fourth quarter and full year financial results were released on March 23, when Sophiris reported that on Dec. 31, 2015 it had $8.4 million in cash, cash equivalents and securities with a net working capital of $5.6 million. The company said this cash was enough to fund operations through September 2016, but it would need more capital to fund a second Phase III trial of topsalysin for BPH and for any future development of the drug for the treatment of localized prostate cancer. On Dec. 31, 2015, the outstanding principal balance of its term loan was $5.3 million. “Compelling data have been announced from both topsalysin programs over the past few months,” said Woods in a statement at time. “Topsalysin demonstrated promising therapeutic activity in four of the initial seven patients with localized prostate cancer—including one with a complete tumor ablation. This encouraging data follows the announcement in November of 2015 that topsalysin met the primary endpoint in a Phase III study in BPH. We believe that these robust and consistent BPH results will help us secure the capital needed to advance the BPH program into the final clinical study required for marketing approval, in a non-dilutive manner such as through a development and/or commercial partner.” Sophiris Bio’s are currently trading for $0.98. Zacks gives the stock a consensus price target of $4 within the year.

Phase 2Phase 3Financial StatementClinical Result

15 Jan 2008

·www.biospace.com

Protox Therapeutics Inc. Initiates Phase 2 Prostate Cancer Study

VANCOUVER, Jan. 15 /CNW/ - Protox Therapeutics Inc. (TSX-V:PRX), a leader in the development of targeted therapeutic proteins, today announced that the Company has received Institutional Review Board (IRB) approvals to proceed with its Phase 2a clinical trial evaluating PRX302 for the treatment of localized recurrent prostate cancer. Activities associated with patient screening have commenced and the Company expects to enroll the first patient in the first quarter of 2008.

100 Deals associated with Topsalysin

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Prostatic Hyperplasia	Phase 3	United States	Sophiris Bio, Inc.	01 Oct 2013
Prostatic Hyperplasia	Phase 3	Australia	Sophiris Bio, Inc.	01 Oct 2013
Prostatic Hyperplasia	Phase 3	Canada	Sophiris Bio, Inc.	01 Oct 2013
Prostatic Hyperplasia	Phase 3	New Zealand	Sophiris Bio, Inc.	01 Oct 2013
Prostatic Hyperplasia	Phase 3	Russia	Sophiris Bio, Inc.	01 Oct 2013
Prostatic Hyperplasia	Phase 3	Ukraine	Sophiris Bio, Inc.	01 Oct 2013
Lower Urinary Tract Symptoms	Phase 3	United States	Sophiris Bio, Inc.	01 Oct 2013
Lower Urinary Tract Symptoms	Phase 3	Australia	Sophiris Bio, Inc.	01 Oct 2013
Lower Urinary Tract Symptoms	Phase 3	Canada	Sophiris Bio, Inc.	01 Oct 2013
Lower Urinary Tract Symptoms	Phase 3	New Zealand	Sophiris Bio, Inc.	01 Oct 2013

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AUA2016	Phase 3	Prostatic Hyperplasia	479	PRX302	rvinkbpftj(dqhheqdvka) = kzoivedvsk lycmuvdogy (qqrwjyrqow )	Positive	01 Apr 2016
NCT01966614 (PLUS-1, Biospace) Manual	Phase 3	Prostatic Hyperplasia	479	Topsalysin	vxhbwdixwh(pnuvhhyvkn) = zaklulxvgq dygrbqktft (sagmupwnaq ) View more	Positive	10 Nov 2015
NCT01966614 (PLUS-1, Biospace) Manual	Phase 3	Prostatic Hyperplasia	479	Vehicle	vxhbwdixwh(pnuvhhyvkn) = zncycskpiv dygrbqktft (sagmupwnaq ) View more	Positive	10 Nov 2015
1787 (AUA2010)	Phase 1/2	Prostatic Hyperplasia PSA	-	PRX302	hnbuebpqys(avmiljrhem) = pugzukrquj iqgkjoehzs (gnftensldd )	-	01 Apr 2010

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