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Provectus Announces Acceptance of PV-10 Poster Presentations at SMR 2019 Congress

On September 24, 2019 Provectus (OTCQB: PVCT) reported that data from an ongoing clinical trial of lysosomal-targeting cancer immunotherapy PV-10 in combination with checkpoint inhibition for the treatment of advanced cutaneous melanoma (NCT02557321) will be presented on two poster presentations at the SMR 2019 Congress (the Society for Melanoma Research annual meeting), held in Salt Lake City, Utah from November 20-23, 2019 (Press release, Provectus Biopharmaceuticals, SEP 24, 2019, View Source [SID1234539748]). The accepted abstracts are:

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"Results from a checkpoint inhibition-naive cohort of patients in a phase 1b study of PV-10 and anti-PD-1 in advanced melanoma" (the study’s main cohort), and

"Initial results from a phase 1b study of PV-10 and anti-PD-1 in melanoma refractory to checkpoint inhibition" (the study’s first expansion cohort).
Intralesional (aka intratumoral) injection with PV-10 can yield immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells.1-4

About PV-10

Better drugging of the druggable and effective drugging of the undruggable starts with the cancer cell and continues with the activation of the immune system in the tumor microenvironment (TME). PV-10 may unlock any TME because it is the first lysosomal-targeting cancer drug. Nearly all types of eukaryotic cells, both diseased and normal, contain lysosomes, which are the central organelles for intracellular degradation of biological materials (e.g., the ‘stomach’ of the cell, the ‘recycle bin’ of the cell, the ‘trash bin,’ etc.).

Provectus has shown that PV-10 selectively accumulates in the lysosomes of only cancer cells upon contact, disrupts them, and causes the cancer cells to die1,5, a mechanism that has been reproduced by external collaborators6. Provectus, external collaborators, and independent researchers have further shown that PV-10 treatment (RB application) can trigger each of the three major and distinct lysosomal cell death pathways of apoptosis, autophagy, and necrosis, and do so in a disease-dependent manner.2,3,6-9

PV-10 causes acute oncolytic destruction of injected tumors (i.e., cell death), mediating several identified immune signaling pathways to date, such as the release of danger-associated molecular patterns (DAMPs) and tumor antigens that initiate an immunologic cascade where local response by the innate immune system facilitates systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. Other mediated immune signaling pathways that have been identified include poly-ADP ribose polymerase (PARP) cleavage, and a third pathway currently being investigated that plays an important role in innate immunity. PV-10 is the first cancer drug that may facilitate multiple, temporally-distinct, immune system signaling pathways.10

PV-10 is undergoing clinical study for adult solid tumor cancers, like melanoma and cancers of the liver (including metastatic neuroendocrine tumors and metastatic uveal melanoma), and preclinical study for pediatric solid tumor cancers (like neuroblastoma5, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma) and pediatric blood cancers (like leukemia).

Orphan drug designation status has been granted to PV-10 by the U.S. Food and Drug Administration for the treatments of metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.

PV-10 is an injectable formulation of rose bengal disodium (RB) (4,5,6,7-tetrachloro-2’,4’,5’,7’-tetraiodofluorescein disodium salt), which is a small molecule halogenated xanthene and PV-10’s active pharmaceutical ingredient. PV-10 drug product is a bright rose red solution containing 10% w/v RB in 0.9% saline for injection, which is supplied in single-use glass vials containing 5 mL (to deliver) of solution and administered without dilution to solid tumors via intratumoral injection.

Provectus’ intellectual property (IP) includes a family of US and international patents that protect the process by which pharmaceutical grade RB and related xanthenes are produced, reducing the formation of previously unknown transhalogenated impurities that exist in commercial grade RB in uncontrolled amounts. The requirement to control these impurities is in accordance with International Conference on Harmonisation (ICH) guidelines for the manufacturing of an injectable pharmaceutical. US patent numbers are 8,530,675, 9,273,022, and 9,422,260, with expirations ranging from 2030 to 2031.

The Company’s IP also includes a family of US and international patents that protect the combination of PV-10 and systemic immunomodulatory therapy (e.g., anti-CTLA-4, anti-PD-1, and anti-PD-L1 agents) for the treatment of a range of solid tumor cancers. US patent numbers are 9,107,887, 9,808,524, and 9,839,688, and a US patent application number is 15/804,357 (allowed, but not yet awarded), with expirations ranging from 2032 to 2035.

Akebia Therapeutics to Present at the 2019 Cantor Global Healthcare Conference

On September 24, 2019 Akebia Therapeutics, Inc. (Nasdaq: AKBA), a biopharmaceutical company focused on the development and commercialization of therapeutics for people living with kidney disease, reported that John P. Butler, President and Chief Executive Officer of Akebia, will present at the 2019 Cantor Global Healthcare Conference at 8:55 a.m. ET on Thursday, October 3, 2019 in New York City (Press release, Akebia, SEP 24, 2019, View Source [SID1234539747]).

A live audio webcast and replay of the presentation will be available on the Company’s website at www.akebia.com.

UroGen Reports Positive Data from Two Important Studies: UGN-101 OLYMPUS Pivotal Trial in LG UTUC and UGN-102 Phase 2b OPTIMA II Trial in LG Bladder Cancer

On September 24, 2019 UroGen Pharma Ltd. (Nasdaq: URGN), a clinical-stage biopharmaceutical company developing treatments to address unmet needs in the field of uro-oncology, reported updated findings from the UGN-101 Phase 3 OLYMPUS Trial in patients with low-grade upper tract urothelial cancer (LG UTUC), as well as initial CR data from the UGN-102 Phase 2b OPTIMA II Trial in patients with intermediate risk low-grade non-muscle invasive bladder cancer (LG NMIBC) (Press release, UroGen Pharma, SEP 24, 2019, View Source [SID1234539746]).

Results from a final analysis of the primary endpoint for pivotal Phase 3 OLYMPUS showed that investigational UGN-101 (mitomycin gel) for instillation demonstrated a 59 percent CR rate in patients with LG UTUC. Findings were consistent with previously presented results.

The final analysis of the primary endpoint showed that in the OLYMPUS intent-to-treat population, 42 of the 71 patients (59 percent) achieved a CR. Forty-one patients entered follow-up, which is still ongoing. Durability of response was determined by Kaplan-Meier to be 89 percent at 6 months and 84 percent at 12 months after primary disease evaluation (PDE). The estimated median time-to-recurrence was 13.0 months. Thirty four of the 71 patients treated in the study were initially characterized by the treating physician as having endoscopically unresectable tumor at baseline. Twenty of 34 patients (59 percent) achieved a CR at the PDE assessment and 12-month durability was identical for this subgroup.

In OLYMPUS, the most common treatment emergent adverse events (TEAE) included ureteral stenosis, urinary tract infection, hematuria, flank pain, dysuria, renal impairment, hydronephrosis and frequency. Most TEAEs were characterized as mild to moderate and transient. Sixty-seven percent (48/71) of patients in the trial experienced an adverse event involving the renal/urinary tract. Of these, 23 percent (11/48) did not require surgical intervention, 50 percent (24/48) required temporary ureteral stent placement, 23 percent (11/48) required a long-term ureteral stent and 4 percent (2/48) required nephroureterectomy. At the time of database lock, the most common Grade 3 TEAE’s included ureteral stenosis (8.5 percent), hematuria, flank pain, and urinary tract infection (3 percent each). There was one Grade 4 TEAE of subdural hematoma (1.4 percent).

"We are pleased that the six-month durability from this analysis remains consistent with previously presented results and are very pleased with the durability observed at 12 months in evaluated

patients. These findings provide further support for the concept of chemoablation with UGN-101 as an initial kidney-sparing treatment option for patients with LG UTUC," said Liz Barrett, President and Chief Executive Officer of UroGen. "We are on track to complete our New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in Q4 2019 and will be prepared for anticipated approval and launch in 1H 2020 of the first drug for the non-surgical treatment of LG UTUC."

The Company also presented interim results from the Phase 2b OPTIMA II trial of investigational UGN-102 (mitomycin gel) for intravesical instillation for patients with intermediate risk LG NMIBC, defined as those with one or two of the following criteria: multifocal disease, large tumors and rapid rates of recurrence. The single-arm, open label study trial recently completed enrollment of 62 patients at clinical sites across the U.S. and Israel. Patients are treated with six weekly instillations of UGN-102 and undergo assessment of CR (the primary endpoint) four to six weeks following the last instillation. In an interim cohort of 32 patients, 63 percent (20/32) achieved a CR.

Response Rate
Overall (n=32)
CR at PDE 63% (20/32)
"Achieving our enrollment goal ahead of schedule is a testament to the enthusiasm and need for this type of innovative approach to treatment in LG NMIBC. ‘Intermediate risk’ patients experience what can be viewed as a form of surgical failure, and many undergo multiple surgical procedures, known as transurethral resection of bladder tumor (TURBT), to manage these recurrences. We are encouraged by the data observed in this tough-to-treat population for whom the standard of care is really not effective," said Mark Schoenberg, MD, Chief Medical Officer of UroGen. "While OPTIMA II remains ongoing and a Phase 3 study is anticipated, the results presented today further support our belief that UGN-102 has the potential to be an effective treatment option for this patient population of approximately 80,000, as there are no other options for these patients aside from repetitive surgical intervention. Based on literature, these patients have a high likelihood of recurrence at one year due to the chronicity of this disease, so we will continue to follow them and assess durability at 12 months."

In the interim data from OPTIMA II, the most common adverse events observed were dysuria, pollakiuria, fatigue, hematuria and urinary tract infection. The majority of these treatment-emergent adverse events were characterized as mild or moderate and transient.

The Company intends to initiate a pivotal Phase 3 trial in 2020 following discussion with the FDA.

About The Phase 3 OLYMPUS Trial

OLYMPUS (Optimized DeLivery of Mitomycin for Primary UTUC Study) is a pivotal, open-label, single-arm Phase 3 clinical trial of UGN-101 (mitomycin gel) for instillation to evaluate the safety, tolerability and tumor ablative effect of UGN-101 in patients with low-grade UTUC. The trial enrolled 71 patients at clinical sites across the United States and Israel. Study participants were treated with six weekly instillations of UGN-101 administered via a standard catheter. Four to six weeks following the last instillation, patients underwent a PDE to determine response, the primary endpoint of the study. PDE involved a ureteroscopy and wash cytology, a standard microscopic test of cells obtained from the urine to detect cancer. Patients who achieved a CR at the PDE timepoint were then followed for up to 12 months to determine the durability of disease control with UGN-101.

About UGN-101

UGN-101 (mitomycin gel) for instillation is an investigational drug formulation of mitomycin in Phase 3 development for the treatment of low-grade upper tract urothelial cancer (LG UTUC). Utilizing the

RTGel technology platform, UroGen’s proprietary sustained release, hydrogel-based formulation, UGN-101 is designed to enable longer exposure of urinary tract tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-101 is delivered to patients using standard ureteral catheters. The Company initiated its rolling submission of the UGN-101 New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in December 2018. The FDA previously granted Orphan Drug, Fast Track, and Breakthrough Therapy Designations to UGN-101 for the treatment of UTUC. If approved, UGN-101 would be the first drug approved for the non-surgical treatment of LG UTUC.

About The Phase 2b OPTIMA II Trial

OPTIMA II (OPTimized Instillation of Mitomycin for BlAdder Cancer Treatment) is an open-label, single-arm, multi-center Phase 2b clinical trial of UGN-102 (mitomycin gel) for intravesical instillation to evaluate the safety and efficacy of UGN-102 in patients with intermediate risk low-grade non-muscle invasive bladder cancer (LG NMIBC) at intermediate risk of recurrence. Intermediate risk of progression is defined as one or two of the following: multiple tumors, solitary tumor >3 cm, or recurrence (³ 1 occurrence of LG NMIBC within 1 year of the current diagnosis). The trial enrolled 62 patients at clinical sites across the United States and Israel. Study participants were treated with six weekly instillations of UGN-102 administered via a standard intravesical catheter. Four to six weeks following the last instillation, patients undergo a PDE to determine response, the primary endpoint of the study. PDE involves a cystoscopy and wash cytology, a standard microscopic test of cells obtained from the urine to detect cancer. Patients who achieve a CR at the PDE timepoint are then followed for up to 9 months to determine the durability of disease control with UGN-102.

About UGN-102

UGN-102 (mitomycin gel) for instillation is an investigational drug formulation of mitomycin in Phase 2b development for the treatment of low-grade non-muscle invasive bladder cancer (LG NMIBC). Utilizing the RTGel Technology Platform, UroGen’s proprietary sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using standard intravesical catheters. The Company completed enrollment in the Phase 2b OPTIMA II trial of UGN-102 for the treatment of LG NMIBC in September 2019 and intends to advance the program to a pivotal study to further investigate UGN-102 in the treatment of this condition.

ImmunoPrecise’s Talem Therapeutics Enters into an LOI with AgonOx Pharma in the Advancement of Novel, Immuno-Oncology Therapeutics

On September 24, 2019 IMMUNOPRECISE ANTIBODIES LTD. (the "Company" or "IPA") (TSX VENTURE: IPA) (OTCQB: IPATF), an industry leader in the discovery of novel, therapeutic antibodies, reported that Talem Therapeutics, its wholly-owned subsidiary, has entered into an LOI to form a Joint Venture as it partners in the continued development of antibody therapeutics to target T cell mediated anti-tumor activity, with AgonOx, a clinical-stage biopharma company (Press release, ImmunoPrecise Antibodies, SEP 24, 2019, View Source [SID1234539745]). AgonOx specializes in identifying and developing immuno-oncology therapeutics.

AgonOx’s approach to target discovery begins with genomic and proteomic analyses of tumor-infiltrating lymphocytes isolated from human tumor biopsies. Candidates are further validated in the laboratory by utilizing an array of in vitro and in vivo systems. The partnership with Talem is addressing targets involved in T cell mediated anti-cancer activity, with therapeutics that, in preliminary, in vivo-validated animal models of established tumors, have demonstrated significant tumor reduction.

This partnership will advance two of AgonOx’s top 10 candidates to emerge from its translational science platform focused on modulation of the tumor microenvironment and, if commercialized, may result in approximately $720 million USD comprised of licensing fees, as well as development and commercial milestones in addition to royalties on worldwide sales.

Andrew Weinberg, President and CSO of AgonOx, stated, "Collaborating with Talem strengthens our efforts to develop immuno-oncology drug candidates by leveraging IPA’s ability to address challenging targets, with the deep mining of the immune repertoire in a species agnostic manner. This LOI supports AgonOx’s mission of discovering and delivering science that can change the standard of care for patients with cancer. ImmunoPrecise has first-rate scientists that we hope to work with for years to come."

Talem will leverage the internal development capabilities of ImmunoPrecise, including high throughput, rapid identification of candidates through single cell interrogation, as well as accessing synthetic and natural immune phage libraries, and its bispecific platform, Abthena. All of these technologies integrate seamlessly with IPA’s integrated Artemis Intelligence Metadata (AIM) capabilities to enable rapid turnaround on additional outputs in therapeutic optimization, stability, affinity, and manufacturability.

Both companies will aid in the functional analyses of the candidates, while AgonOx also pulls from its experience in pre-clinical and clinical development, built, in part, on access to physicians and relevant samples through their alignment with the Earl A. Chiles Research Institute at the Providence Cancer Institute.

"We look forward to advancing the development of these candidates toward an Investigational New Drug filing. AgonOx has extensive expertise in validating the expression and function of biologically relevant immuno-oncology targets" said Jennifer Bath, CEO of ImmunoPrecise. "We see significant advantages from Talem and AgonOx leadership sharing knowledge across antibody discovery, development, pre-clinical and clinical trials. This partnership will enhance the companies’ pipelines of novel, monoclonal antibodies that could transform the standard of care for patients with advanced cancers."

Corporate presentation

On September 24, 2019 Constellation Pharmaceuticals presented the Corporate presentation (Presentation, Constellation Pharmaceuticals, SEP 24, 2019, View Source [SID1234539744]).