On May 5, 2019 Harbour BioMed and Chia Tai Tianqing Pharmaceutical Group Ltd. (CTTQ) reported they are entering into a strategic alliance to discover, develop and commercialize next-generation biologics for multiple therapeutic targets in oncology and immunology (Press release, Harbour BioMed, MAY 5, 2019, View Source [SID1234535722]).

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The collaboration will combine Harbour BioMed’s discovery capabilities, including its transgenic mouse technologies for generating fully human antibodies, with CTTQ’s preclinical development resources and expertise. The companies will be responsible for clinical development and commercialization of therapeutic candidates emerging from the collaboration in their respective regions. Harbour BioMed will be responsible for the United States, Japan, and the rest of the world outside, while CTTQ will have responsibility for Greater China and Europe. The companies will pay royalties to each other based on sales in their respective territories. Additional financial terms were not disclosed.

"The agreement with CTTQ, is part of our strategy to build a robust therapeutic pipeline for global markets through co-discovery, development and commercialization partnerships that capitalize on our patented platforms for generating fully human antibodies," said Dr. Jingsong Wang, Founder, Chairman and CEO of Harbour BioMed. "CTTQ, a well-known pharmaceutical company that is making strategic investments in therapeutic innovation in oncology and immunology, is a strong partner in that effort and directly complements our internal discovery programs," added Dr. Wang. It is expected that both sides will jointly own the IP and development and commercialization rights for the new drugs coming out of this collaboration.

"CTTQ will be committed to bring valuable treatment agents for diseases with unmet need. The collaboration with Harbour BioMed is well aligned with CTTQ’s strategy for innovative biological medicine development, it also marks significant progress to strengthen our capability of R&D of innovative therapeutic antibodies," said Shanchun Wang, President of CTTQ. CTTQ currently has several monoclonal antibody drugs, including a PD-L1 inhibitor, which have progressed into Phase 2 and Phase 3 clinical development.

On May 5, 2019 UroGen Pharma Ltd. (Nasdaq: URGN), a clinical-stage biopharmaceutical company developing treatments to address unmet needs in the field of urology, reported findings from a secondary analysis from the pivotal Phase 3 OLYMPUS trial which showed that UGN-101 (mitomycin gel) for instillation, an investigational mitomycin formulation, demonstrated a 59 percent complete response rate in a subset of patients with endoscopically unresectable low-grade upper tract urothelial cancer (UTUC) (Press release, UroGen Pharma, MAY 5, 2019, View Source [SID1234535721]). Findings were presented by Seth Paul Lerner, M.D., FACS, Professor of Urology at Baylor College of Medicine, in an oral presentation during the plenary session at the 114th American Urological Association (AUA) Annual Meeting in Chicago.

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The analysis showed that in the OLYMPUS intent-to-treat population, 71 patients had undergone PDE at the time of the analysis and 42 of the 71 patients (59 percent) achieved a CR. Forty-one patients entered follow-up. Of the evaluated complete responses to date, 27 patients have undergone a six-month evaluation, and 24 out of 27 patients (89 percent) have remained disease free at six months. Overall, 5 of 41 patients who achieved a CR have relapsed at any time during the study.

Of these 71 patients, 34 were initially characterized by the treating physician as having endoscopically unresectable tumor at baseline, and 20 of 34 of these patients (59 percent) achieved a CR at the PDE.

*Forty-one patients entered follow-up. At the time of the analysis, 66 percent (27/41) of patients have completed a six-month evaluation.

The most common adverse events observed were urinary tract infection, ureteral narrowing and stricture formation. The majority of ureteral events were reported as mild to moderate and have resolved.

"The results from the OLYMPUS trial continue to be compelling for new and recurrent LG UTUC, as well as for those who have unresectable tumors and would be immediate candidates for kidney removal. For this typically elderly patient population, kidney preservation is paramount, and these findings provide evidence-based support for the concept of chemoablation with UGN-101 as an initial kidney-sparing treatment option for low-grade UTUC," said Mark P. Schoenberg, MD, Chief Medical Officer at UroGen. "The analysis also advances our understanding of durability of response, which we are pleased to see has remained consistent as the number of patients who reach the six-month follow-up timepoint increases."

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 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 primary disease evaluation (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 complete response 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.

On May 4, 2019 ESSA Pharma Inc. (Nasdaq: EPIX; TSX-V: EPI), a pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported new preclinical data on ESSA’s lead Investigational New Drug ("IND") candidate at the 2019 American Urological Association ("AUA") Annual Meeting (Press release, ESSA, MAY 4, 2019, View Source [SID1234535723]).

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In an oral poster presentation, "A New Generation of N-terminal Domain Androgen Receptor Inhibitors in Castration-Resistant Prostate Cancer Models", a deeper preclinical characterization of EPI-7386 was presented. The studies demonstrate that, pre-clinically, EPI-7386:

Displays similar in vitro IC50 potency compared to the ‘lutamide class of antiandrogens in an in vitro androgen receptor (AR) inhibition assay.
Shows in vitro activity in several enzalutamide-resistant prostate cancer cell models in which enzalutamide is resistant.
Exhibits a favorable metabolic profile across three preclinical animal species, which suggests that EPI-7386 will have high exposure and a long half-life in humans.
Provides similar antitumor activity to enzalutamide in the enzalutamide-sensitive LNCaP prostate cancer xenograft model.
Provides superior antitumor activity to enzalutamide, as a single agent or in combination with enzalutamide, in the enzalutamide-resistant VCaP prostate cancer xenograft model.
AR inhibition with both an N-terminal domain inhibitor (EPI-7386) and a ligand binding domain inhibitor (enzalutamide), induces deeper and more consistent anti-tumor responses in the enzalutamide-resistant VCaP xenograft model.
"The variety of in vitro and in vivo studies examining both antiandrogen sensitive models and antiandrogen-resistant xenograft mouse models show a favorable preclinical profile of EPI-7386. From this and an aggregate of other preclinical data, we nominated EPI-7386 as the IND candidate to be used in the clinic in mCRPC patients failing current antiandrogen therapy. EPI-7386 represents a novel approach to targeting the androgen receptor, one of the most validated targets in oncology," said Dr. David R. Parkinson, President & Chief Executive Officer. "We look forward to providing further details of the preclinical profile of EPI-7386 later in the year as we move close to our anticipated IND filing in the first quarter of 2020."

On May 3, 2019 Oncoceutics, Inc. reported the publication of two scientific research articles demonstrating that members of the imipridone family ONC201 and ONC212 directly activate a mitochondrial protease called caseinolytic protease P (ClpP) (Press release, Oncoceutics, MAY 3, 2019, View Source [SID1234558356]).

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One research article, featured on the cover of the journal Cancer Cell, demonstrates that ONC201 and ONC212 hyperactivate ClpP by altering its structural conformation, leading to mitochondrial dysfunction and apoptosis in leukemia. In AML, ClpP is over-expressed in patient samples and its hyperactivation selectively kills cancer cells independent of p53 status, while not affecting normal cells.

Another research article, published in the journal ACS Chemical Biology, similarly demonstrates that ONC201 and ONC212 directly bind to and activate ClpP.

ClpP is a protease located in the mitochondrial matrix that is overexpressed in tumor cells and plays a central role in mitochondrial protein quality control by degrading misfolded proteins. Modulating the activity of ClpP can cause impaired oxidative phosphorylation that selectively kills cancer cells in vitro and in vivo without affecting normal cells.

The two research studies concordantly demonstrate that imipridones are capable of targeting ClpP in tumor cells, which has emerged as a therapeutic target in oncology. ClpP activation by imipridones is consistent with select downstream effects of these compounds that have been previously reported, such as integrated stress response activation and disruption of mitochondrial structure and function in tumor cells.

"The unique phenotypic effects of ONC201 and its imipridone family members that have been studied in a broad range of cancers point to a novel mechanism of action," said Dr. Joshua Allen, PhD, Senior Vice President of R&D at Oncoceutics. "The discovery that ONC201 targets ClpP, in addition to DRD2, expands the biomarker panel for the molecule and other impridones. ClpP activation also helps us interpret downstream effects of imipridones on the mitochondria, as well as their activity in tumor types beyond those that depend on the dopamine pathway."

"ClpP activation in cancer and disruption of the resulting mitochondrial dysfunction by ONC201 provides a mechanism of action that reinforces the basis for its efficacy spectrum across cancer that differentiates from other DRD2 antagonists," said Dr. Keith Flaherty, MD, Director of Clinical Research at Massachusetts General Hospital and Member of Oncoceutics’ Scientific Advisory Board.

On May 3, 2019 Palatin Technologies, Inc. (NYSE American: PTN) reported that it will announce its third quarter, fiscal year 2019 operating results on Thursday, May 9, 2019 before the open of the U.S. financial markets (Press release, Palatin Technologies, MAY 3, 2019, View Source [SID1234535707]).

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Palatin will also conduct a conference call and live audio webcast hosted by its executive management team on May 9, 2019 at 11:00 a.m. ET. The conference call will include a review of the company’s operating results and an update on programs under development.

Schedule for the Operating Results Press Release, Conference Call / Audio Webcast

Q3 Fiscal Year 2019 Financial Results Press Release

5/9/2019 at 7:30 a.m. ET

Q3 Fiscal Year 2019 Conference Call-Live

5/9/2019 at 11:00 a.m. ET

US/Canada Dial-In Number:

1-800-667-5617

International Dial-In Number:

1-334-323-0509

Conference ID:

7024541

Q3 Fiscal Year 2019 Conference Call-Replay

5/9/2019-5/16/2019

US/Canada Dial-In Number:

1-888-203-1112

International Dial-In Number:

1-719-457-0820

Replay Passcode:

7024541

Audio Webcast Live and Replay Access

View Source

The audio webcast and replay can be accessed by logging on to the "Investors-Webcasts" section of Palatin’s website at View Source.