On December 17, 2018 UroGen Pharma Ltd. (Nasdaq:URGN), a clinical-stage biopharmaceutical company developing treatments to address unmet needs in the field of urology, reported that it has initiated the rolling submission with the U.S. Food and Drug Administration (FDA) of the New Drug Application (NDA) for UGN-101 (mitomycin gel) for instillation as a treatment for patients with low-grade upper tract urothelial cancer (LG UTUC) (Press release, UroGen Pharma, DEC 17, 2018, View Source [SID1234532095]). The company expects to complete its NDA submission by mid-2019, with potential approval in 2019.

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"This is an important milestone in our mission to bring innovative, non-surgical treatment options to patients with urothelial cancers and potentially eliminate the need for repetitive surgical intervention and kidney removal," said Ron Bentsur, Chief Executive Officer of UroGen. "UGN-101 has the potential to be the first non-surgical therapy for LG UTUC, and the first drug ever approved in this indication. We are grateful to our UroGen team and clinical investigators who have worked diligently to advance this potentially paradigm-shifting program."

The NDA submission is supported by clinical data from the Phase 3 OLYMPUS clinical trial of UGN-101 for the non-surgical treatment of LG UTUC. Results from an interim analysis were presented at the American Urologic Association Annual Meeting in May 2018. UroGen plans to present topline data from the OLYMPUS study in January 2019.

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 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 mitomycin to urinary tract tissue, thereby enabling the treatment of tumors by non-surgical means. UGN-101 is delivered to patients using standard ureteral catheters.

On December 17, 2018 C4X Discovery Holdings plc (AIM: C4XD), a pioneering drug discovery company, reported that it has entered into an exclusive target discovery partnership with Horizon Discovery Group plc ("Horizon", AIM: HZD), a global leader in the application of gene editing and gene modulation technologies (Press release, C4X Discovery, DEC 17, 2018, View Source [SID1234533248]). The partnership aims to validate novel synthetic lethal oncology targets that have been identified by Horizon’s cutting-edge CRISPR-Cas9 technology leading to the generation of potential new drugs for patients with limited effective treatments such as colorectal and lung cancer.

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C4XD aims to apply its proprietary 4D shape-based chemistry technology (Conformetrix) to discover drug candidates directed against these high value, novel, synthetic lethality targets and out-license them to clinical development partners. This discovery partnership bolsters C4XD’s oncology pipeline, a high priority therapeutic area for the company.

The therapeutic concept of harnessing synthetic lethality in cancer with tumour-specific mutations has been demonstrated with the recent approval of the poly(ADP-ribose) polymerase (PARP) inhibitors Lynparza Zejula and Rubraca. These drugs are effective in indications that are poorly served by immunotherapy drugs, such as checkpoint inhibitors, and have become an established treatment in ovarian cancer. They work by targeting a specific DNA repair pathway that cancer cells, with mutations such as BRCA, become over-reliant on. Inhibiting this critical DNA repair pathway causes the tumour cells to self-destruct, resulting in the terminology ‘synthetic lethality’. The pharmaceutical industry is now rushing to fill its clinical pipelines with investigational drugs, identified by empirical research, that might produce similar efficacy in cancers where PARP inhibitors are not effective.

However, recent advancements in the gene-editing tool, CRISPR-Cas9, has enabled systematic ‘functional genomic’ screening to identify novel synthetic lethal genes in cancer cells with specific mutations. Horizon has utilised its target discovery platform to conduct high quality CRISPR gene knock-out studies across multiple cancer cell lines, screening around ~3000 genes suitable as the basis for small molecule drug targets. This cutting-edge approach has identified a shortlist of ~20 novel, high value synthetic lethal genes following a secondary screen to further validate them as targets. The partnership has been established to complete the target validation package for these novel targets, leading to the initiation of drug discovery programmes by C4XD should it exercise its options on a target-by-target basis. C4XD will provide the funding for the work plan and Horizon will receive a share of all future revenues C4XD receives should any drug discovery programmes emerging from the partnership be out-licensed for clinical development.

Dr Craig Fox, Chief Scientific Officer of C4XD, said: "PARP inhibitors are transforming the treatment of ovarian cancer, particularly in patients with BRCA mutations and so identifying the next generation of synthetic lethality drug targets is a key priority to develop new therapies for cancers patients who are not responsive to current treatments. This partnership with Horizon gives C4XD access to a comprehensive proprietary CRISPR screening dataset that has selected the most promising novel drug targets in colon and lung cancer. We look forward to working with the highly experienced team at Horizon to complete the target validation package for these novel genes and initiate drug discovery programmes to generate high value pre-clinical licensable assets for partnering."

Dr Jon Moore, Horizon’s Chief Scientific Officer added: "Drugging the cancer genome now requires new synthetic lethal therapies that can exploit the vulnerabilities in patient’s tumours that are created by mutations in undruggable cancer driver genes. Horizon’s internal research program has used powerful CRISPR technology to open a new window into how cancer cells are wired and has identified a cohort of novel targets. We are delighted to have secured this collaboration with C4X Discovery, which applies a powerful drug discovery engine to the first-in-class opportunities for transformational medicines represented by the targets Horizon has found and allows Horizon to share in the upside."

On December 17, 2018 Gossamer Bio, Inc., a privately held, clinical-stage biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutics in the disease areas of immunology, inflammation and oncology, reported that it has appointed Jakob Dupont, M.D. as Chief Medical Officer (Press release, Gossamer Bio, DEC 17, 2018, View Source [SID1234532096]). Dr. Dupont has nearly 20 years of academic, biotechnology and pharmaceutical drug development experience, from early clinical phase through post-commercialization.

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"Gossamer has grown rapidly during the past year and has a meaningful pipeline of exciting clinical and preclinical drug candidates," said Sheila Gujrathi, M.D., Gossamer Bio’s Co-Founder and Chief Executive Officer. "Jakob’s extensive clinical development and regulatory expertise comes at a critical time for the company as we accelerate our development and look ahead to multiple significant clinical milestones. Jakob’s deep experience across the spectrum of therapeutic clinical development is an ideal fit, and we are thrilled to welcome him to the Gossamer team."

"Gossamer’s program pipeline addresses a number of significant disease areas that continue to be underserved by currently available therapies," said Dr. Dupont. "I am excited to be joining the team to advance these important potential new treatments in an environment that combines a rare blend of the nimbleness of an early-stage biotech company with the resources, expertise and rigor of a much more mature company."

Dr. Dupont most recently served as Vice President and Global Head of Breast and Gynecologic Cancer Development and was a member of the Oncology Leadership Team for Genentech/Roche. He was responsible for global development of Herceptin, Perjeta, Kadcyla, ipatasetib, taselisib, and Tecentriq, among others, and co-led the Genentech/Roche Breast Cancer Disease Area Strategy Team. Prior to his recent role at Genentech/Roche, Dr. Dupont was Chief Medical Officer and Senior Vice President of OncoMed Pharmaceuticals, Inc. where he oversaw clinical development and regulatory activities in oncology and other therapeutic areas. These activities included investigational new drug applications (INDs), clinical trials initiation, conduct and analysis. Dr. Dupont also participated in the execution of corporate initiatives, including OncoMed’s initial public offering and a partnership agreement with Celgene. Dr. Dupont began his career in the biotechnology industry with Genentech/Roche where he served as Global Medical Director of Avastin and was Group Director and Medical Director overseeing the angiogenesis pipeline, playing a key role in the development and approval of Avastin in ovarian, cervical and breast cancers as well as IND filings of novel anti-angiogenic agents. Prior to first joining Genentech/Roche in 2006, Dr. Dupont was a faculty member and laboratory researcher at Memorial Sloan-Kettering (MSK) Cancer Center and oversaw a solid tumor and GYN oncology clinic and a tumor immunology laboratory. He also served as adjunct clinical faculty in medical oncology at Stanford University, overseeing a GYN Oncology clinic.

Dr. Dupont received his undergraduate degree in philosophy from Vassar College and an M.A. in philosophy from New York University. He studied pre-medical science at Columbia University and received his M.D. from the Joan & Sanford I. Weill Medical College of Cornell University. He also served as Assistant Chief Resident at MSK and completed his Medical Oncology Fellowship at MSK Cancer Center, his Internal Medicine Residency at the New-York Presbyterian Hospital—Cornell Campus, and his Internal Medicine Internship at The University of Michigan Medical Center in Ann Arbor.

On December 16, 2018 Innovent Biologics, Inc. (Innovent) (HKEX: 01801) and Incyte (NASDAQ:INCY) reported that the companies, through their respective subsidiaries, have entered into a strategic collaboration agreement for three clinical-stage product candidates discovered and developed by Incyte—pemigatinib (FGFR1/2/3 inhibitor), itacitinib (JAK1 inhibitor) and parsaclisib (PI3Kδ inhibitor) (Press release, Incyte, DEC 16, 2018, View Source [SID1234532118]). Under the terms of the agreement, Innovent will pay Incyte US$40 million in cash up front, and Incyte shall be eligible to receive an additional US$20 million in consideration in connection with the first investigational new drug (IND) application by Innovent in China, which is expected to be achieved in 2019. Innovent will receive the rights to develop and commercialize the three assets in hematology and oncology in Mainland China, Hong Kong, Macau and Taiwan.

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"The collaboration and partnership with Innovent provides us with an important and strategic opportunity to further serve the oncology community around the world by potentially bringing new, innovative medicines to patients with high unmet medical needs in China," said Hervé Hoppenot, Chief Executive Officer of Incyte. "We believe Innovent’s experienced leadership team and sizeable clinical network will expand our clinical trials for itacitinib, pemigatinib and parsaclisib, and, if any of these product candidates are approved, will provide access to our innovative therapies to patients and healthcare providers in China."

"We’re very pleased to enter into this collaboration with Incyte, a well-recognized innovative global biopharmaceutical company. This collaboration not only strengthens our portfolio by adding three potentially best-in-class clinical-stage targeted therapies, but, we believe, also proves that Innovent is an ideal partner for world-class pharmaceutical companies coming to China—transforming Innovent from a company primarily focused on monoclonal antibodies to one with a broader oncology focus that develops potentially innovative treatments regardless of molecule size," said Michael DC Yu., Ph.D., Chief Executive Officer and President of Innovent. "Based on the compelling clinical data reported to-date, we believe pemigatinib, itacitinib and parsaclisib may be poised, if further development is successful and approvals in China are granted, to dramatically alter the treatment landscape for patients in China with FGFR-altered cholangiocarcinoma and urothelial carcinoma, graft-versus-host-disease after bone marrow transplant and non-Hodgkin lymphoma, respectively, and other cancers. These three novel medicines from Incyte complement our rich pipeline of immune-oncology-focused monoclonal antibodies and also enable the exploration of combination treatment approaches with the potential to further improve patient outcomes worldwide."

Per the terms of the collaboration agreement, Innovent will pay Incyte US$40 million in cash up front and Incyte will be eligible to receive an additional US$20 million in consideration in connection with the first IND filing in China, which is expected to be achieved in 2019. Innovent will receive rights to develop and commercialize three product candidates (pemigatinib, itacitinib and parsaclisib) in hematology and oncology in the Innovent territory of Mainland China, Hong Kong, Macau and Taiwan. In addition, Incyte will be eligible to receive up to US$129 million in potential development and regulatory milestones, and up to US$202.5 million in potential commercial milestones. Incyte will also be eligible to receive tiered royalties from the high teens to the low twenties on future sales of products resulting from the collaboration. Incyte retains an option to assist in the promotion of the three product candidates in China.

The transaction is effective immediately upon the execution of the strategic collaboration agreement. Further financial details were not disclosed.

About Pemigatinib (INCB54828, FGFR inhibitor)

Fibroblast growth factor receptors (FGFRs) play an important role in tumor cell proliferation and survival, migration and angiogenesis (the formation of new blood vessels). Activating mutations, translocations and gene amplifications in FGFRs are closely correlated with the development of various cancers. Pemigatinib is an oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated potency and selective pharmacologic activity against cancer cells with FGFR alterations. Phase 2 studies investigating the safety and efficacy of pemigatinib monotherapy across several FGFR-driven malignancies are ongoing—the FIGHT (FIbroblast Growth factor receptor in oncology and Hematology Trials) clinical trial program currently comprises FIGHT-201 in patients with metastatic or surgically unresectable bladder cancer, including with activating FGFR3 alterations; FIGHT-202 in patients with metastatic or surgically unresectable cholangiocarcinoma who have failed previous therapy, including with activating FGFR2 translocations; and FIGHT-203 in patients with myeloproliferative neoplasms with activating FGFR1 translocations. FIGHT-302, a randomized Phase 3 trial in newly-diagnosed patients with cholangiocarcinoma and activating FGFR2 translocations, is expected to be initiated before the end of 2018 (NCT03656536).

About Itacitinib（INCB39110, JAK1 inhibitor）

Itacitinib (INCB039110) is a novel, potent, and selective JAK1 inhibitor currently in clinical studies for the treatment of treatment naïve acute and chronic GVHD, and non-small cell lung cancer in combination with osimertinib, an EGFR inhibitor. A Phase 3 study (GRAVITAS-301) of itacitinib for the treatment of acute GVHD is underway, with data expected in 2019. GRAVITAS-309 (NCT03584516) is a randomized, double-blind, placebo-controlled pivotal Phase 3 study evaluating itacitinib or placebo in combination with corticosteroids as a first-line treatment for patients with chronic graft-versus-host disease (cGVHD) which is expected to be initiated early in 2019.

About Parsaclisib (INCB50465, PI3Kδ inhibitor)

Parsaclisib (INCB50465) is an investigational novel oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ) isoforms. PI3Kδ is an important anticancer target implicated in malignant B-cell growth, survival and proliferation which, in preclinical studies, has demonstrated potency and selectivity in preclinical studies and has potential therapeutic utility in the treatment of patients with hematologic malignancies such as lymphoma. Emerging data suggest that PI3Kδ may also be an important target in the solid tumor microenvironment. The CITADEL (Clinical Investigation of TArgeted PI3K-DELta Inhibition in Lymphomas) clinical trial program is currently evaluating parsaclisib in several ongoing Phase 2 trials as a treatment for non-Hodgkin lymphomas (follicular, marginal zone and mantle cell) Parsaclisib is also being studied in Phase 1 and Phase 2 trials as part of a combination therapy for patients with myelofibrosis, advanced or metastatic solid tumors and diffuse large B-cell lymphoma.

On December 16, 2018 Incyte (NASDAQ:INCY) and Innovent Biologics, Inc. (Innovent) (HKEX: 01801) reported that the companies, through their respective subsidiaries, have entered into a strategic collaboration agreement for three clinical-stage product candidates discovered and developed by Incyte—pemigatinib (FGFR1/2/3 inhibitor), itacitinib (JAK1 inhibitor) and parsaclisib (PI3Kδ inhibitor) (Press release, Incyte, DEC 16, 2018, View Source [SID1234532077]). Under the terms of the agreement, Innovent will pay Incyte US$40 million in cash up front, and Incyte shall be eligible to receive an additional US$20 million in consideration in connection with the first investigational new drug (IND) application by Innovent in China, which is expected to be achieved in 2019. Innovent will receive the rights to develop and commercialize the three assets in hematology and oncology in Mainland China, Hong Kong, Macau and Taiwan.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The collaboration and partnership with Innovent provides us with an important and strategic opportunity to further serve the oncology community around the world by potentially bringing new, innovative medicines to patients with high unmet medical needs in China," said Hervé Hoppenot, Chief Executive Officer of Incyte. "We believe Innovent’s experienced leadership team and sizeable clinical network will expand our clinical trials for itacitinib, pemigatinib and parsaclisib, and, if any of these product candidates are approved, will provide access to our innovative therapies to patients and healthcare providers in China."　

"We’re very pleased to enter into this collaboration with Incyte, a well-recognized innovative global biopharmaceutical company. This collaboration not only strengthens our portfolio by adding three potentially best-in-class clinical-stage targeted therapies, but, we believe, also proves that Innovent is an ideal partner for world-class pharmaceutical companies coming to China—transforming Innovent from a company primarily focused on monoclonal antibodies to one with a broader oncology focus that develops potentially innovative treatments regardless of molecule size," said Michael DC Yu., Ph.D., Chief Executive Officer and President of Innovent. "Based on the compelling clinical data reported to-date, we believe pemigatinib, itacitinib and parsaclisib may be poised, if further development is successful and approvals in China are granted, to dramatically alter the treatment landscape for patients in China with FGFR-altered cholangiocarcinoma and urothelial carcinoma, graft-versus-host-disease after bone marrow transplant and non-Hodgkin lymphoma, respectively, and other cancers. These three novel medicines from Incyte complement our rich pipeline of immune-oncology-focused monoclonal antibodies and also enable the exploration of combination treatment approaches with the potential to further improve patient outcomes worldwide."

Per the terms of the collaboration agreement, Innovent will pay Incyte US$40 million in cash up front and Incyte will be eligible to receive an additional US$20 million in consideration in connection with the first IND filing in China, which is expected to be achieved in 2019. Innovent will receive rights to develop and commercialize three product candidates (pemigatinib, itacitinib and parsaclisib) in hematology and oncology in the Innovent territory of Mainland China, Hong Kong, Macau and Taiwan. In addition, Incyte will be eligible to receive up to US$129 million in potential development and regulatory milestones, and up to US$202.5 million in potential commercial milestones. Incyte will also be eligible to receive tiered royalties from the high teens to the low twenties on future sales of products resulting from the collaboration. Incyte retains an option to assist in the promotion of the three product candidates in China.

The transaction is effective immediately upon the execution of the strategic collaboration agreement. Further financial details were not disclosed.

About Pemigatinib (INCB54828, FGFR inhibitor)

Fibroblast growth factor receptors (FGFRs) play an important role in tumor cell proliferation and survival, migration and angiogenesis (the formation of new blood vessels). Activating mutations, translocations and gene amplifications in FGFRs are closely correlated with the development of various cancers. Pemigatinib is an oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated potency and selective pharmacologic activity against cancer cells with FGFR alterations. Phase 2 studies investigating the safety and efficacy of pemigatinib monotherapy across several FGFR-driven malignancies are ongoing—the FIGHT (FIbroblast Growth factor receptor in oncology and Hematology Trials) clinical trial program currently comprises FIGHT-201 in patients with metastatic or surgically unresectable bladder cancer, including with activating FGFR3 alterations; FIGHT-202 in patients with metastatic or surgically unresectable cholangiocarcinoma who have failed previous therapy, including with activating FGFR2 translocations; and FIGHT-203 in patients with myeloproliferative neoplasms with activating FGFR1 translocations. FIGHT-302, a randomized Phase 3 trial in newly-diagnosed patients with cholangiocarcinoma and activating FGFR2 translocations, is expected to be initiated before the end of 2018 (NCT03656536).

About Itacitinib（INCB39110, JAK1 inhibitor）

Itacitinib (INCB039110) is a novel, potent, and selective JAK1 inhibitor currently in clinical studies for the treatment of treatment naïve acute and chronic GVHD, and non-small cell lung cancer in combination with osimertinib, an EGFR inhibitor. A Phase 3 study (GRAVITAS-301) of itacitinib for the treatment of acute GVHD is underway, with data expected in 2019. GRAVITAS-309 (NCT03584516) is a randomized, double-blind, placebo-controlled pivotal Phase 3 study evaluating itacitinib or placebo in combination with corticosteroids as a first-line treatment for patients with chronic graft-versus-host disease (cGVHD) which is expected to be initiated early in 2019.

About Parsaclisib (INCB50465, PI3Kδ inhibitor)

Parsaclisib (INCB50465) is an investigational novel oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ) isoforms. PI3Kδ is an important anticancer target implicated in malignant B-cell growth, survival and proliferation which, in preclinical studies, has demonstrated potency and selectivity in preclinical studies and has potential therapeutic utility in the treatment of patients with hematologic malignancies such as lymphoma. Emerging data suggest that PI3Kδ may also be an important target in the solid tumor microenvironment. The CITADEL (Clinical Investigation of TArgeted PI3K-DELta Inhibition in Lymphomas) clinical trial program is currently evaluating parsaclisib in several ongoing Phase 2 trials as a treatment for non-Hodgkin lymphomas (follicular, marginal zone and mantle cell) Parsaclisib is also being studied in Phase 1 and Phase 2 trials as part of a combination therapy for patients with myelofibrosis, advanced or metastatic solid tumors and diffuse large B-cell lymphoma.