On September 30, 2019 UroGen Pharma Ltd. (Nasdaq:URGN), a clinical-stage biopharmaceutical company developing treatments to address unmet needs in uro-oncology, reported that it will present at the following conference in October (Press release, UroGen Pharma, SEP 30, 2019, View Source [SID1234539952]):

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2019 Cantor Global Healthcare Conference

Wednesday, October 2nd
8:20AM Eastern Time
New York, NY
A live audio webcast of the event will be available on the Investors section of UroGen’s website, www.urogen.com. A replay of the webcast will be available on the website for approximately two weeks.

On September 30, 2019 Tarveda Therapeutics, Inc., a clinical stage biopharmaceutical company discovering and developing a new class of potent and selective precision oncology medicines for the treatment of patients with a wide range of solid tumor malignancies, reported the presentation of Phase 1 data from an ongoing Phase 1/2a study of PEN-866 at the at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2019 (Press release, Tarveda Therapeutics, SEP 30, 2019, View Source [SID1234539951]). The results presented, which are based on a data cutoff date of July 10, 2019, show that PEN-866 was well tolerated and demonstrated preliminary evidence of anti-tumor activity. Three patients remained on study at the time of data cutoff.

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"Results of the Phase 1 study in heavily treated, advanced patients show that overall PEN-866 was well tolerated with encouraging, early signs of anti-tumor activity," said Dr. Jeffrey D. Bloss, Chief Medical Officer of Tarveda. "Based on these results, we have progressed to an expansion cohort to determine the recommended Phase 2 dose. We are excited about the profile of PEN-866 for its development in solid tumors where new, effective treatments are truly needed. Further, the attributes of PEN-866 are indicative of the opportunity we have with our HSP90 binding miniature drug conjugate platform to enable a wide range of compelling, anti-cancer payloads that are promising but require enhanced penetration, accumulation and residence time in tumor to be effective."

PEN-866 is a small molecule miniature drug conjugate linked to a potent topoisomerase 1 inhibitor (SN-38) payload which targets and binds to Heat Shock Protein 90 (HSP90). HSP90 is activated and upregulated in tumor cells compared to normal tissue allowing the HSP90 miniature drug conjugate to accumulate and be retained in tumor cells. The HSP90 miniature drug conjugate is designed with a slowly cleaving linker resulting in a sustained release of SN-38 in tumor. The Phase 1 study established a MTD and assessed the safety, tolerability, pharmacokinetics and efficacy of PEN-866.

"Investigating new treatment options for patients who are not responding to standard therapies is central to our research efforts," said Johanna Bendell, M.D., Chief Development Officer and Director of the Drug Development Unit at Sarah Cannon Research Institute in Nashville, Tenn. "With PEN-866’s innovative approach to targeting solid tumors, we observed promising early results with stable disease after treatment for some of the participants and a partial response for one additional participant. These preliminary results support the further investigation of PEN-866 for patients living with these difficult-to-treat cancers."

Phase 1 Trial Design
Patients were enrolled in seven dose escalating cohorts of two to six patients with advanced solid tumor malignancies, the most common of which were pancreatic and colon tumor types. Patients received PEN-866 weekly for three of four weeks in a 28-day cycle, and in cohorts 1-5, patients were initially treated with flat dosing. Cohorts 6 and 7 were switched to body surface area dosing based on emerging data indicating variable exposure.

Safety Data
Results of the study show that PEN-866 was well tolerated with no dose limiting toxicities (DLTs) in the first four cohorts (30-240 mg). One DLT was observed in cohort 5 (360 mg) and was resolved with dose reduction. 2 DLTs were observed in cohort 7 (200 mg/m2). One fatal event of dehydration occurred 11 days following the last dose of PEN-866. The most frequent adverse events observed were nausea, fatigue, diarrhea, vomiting, and alopecia and the most common Grade 3 adverse event was neutropenia. The maximum tolerated dose for PEN-866 monotherapy was determined to be 175 mg/m2.

Efficacy Data
There was preliminary evidence of antitumor activity observed in the trial. One patient (5.9%) of 17 evaluable patients per RECIST v1.1, achieved partial response and remains on therapy. Five patients of the 17 patients (29.4%) experienced stable disease (SD). Of the patients who experienced stable disease:

Two patients with pancreatic cancer had prolonged SD (~4 and 5 months, respectively).
One patient with liposarcoma had prolonged SD (>12 months).
One patient with acinar cell cancer of the pancreas remained on therapy after 6 months with SD.
About PEN-866
PEN-866 is a small molecule miniature drug conjugate that selectively binds to the activated form of the intracellular target Heat Shock Protein 90 (HSP90) linked to a topoisomerase 1 inhibitor (SN-38), a potent anti-cancer payload. HSP90 is activated and upregulated in tumor cells compared to normal tissue allowing the HSP90 miniature drug conjugate to accumulate and be retained in tumor cells. The HSP90 miniature drug conjugate is designed with a slowly cleaving linker resulting in a sustained release of SN-38 in tumor which has been shown to cause prolonged DNA damage and tumor regressions in multiple patient-derived and other xenograft tumor models. PEN-866 is in a Phase 1/2a trial and the first miniature drug conjugate from Tarveda’s HSP90 binding conjugate platform.

On September 30, 2019 AVEO Oncology (NASDAQ: AVEO) reported that it has initiated enrollment in an open-label, multi-center Phase 1b/2 clinical trial evaluating FOTIVDA (tivozanib), the Company’s once-daily, potent and selective vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI), in combination with IMFINZI (durvalumab), AstraZeneca’s human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in patients with hepatocellular carcinoma (HCC) who have not received prior systemic therapy (Press release, AVEO, SEP 30, 2019, View Source [SID1234539950]).

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The study is expected to enroll approximately 50 patients. The Phase 1b portion will evaluate the safety, tolerability, dose limiting toxicity, maximum tolerated dose and preliminary anti-tumor activity starting with 1.0mg of tivozanib for 21 days followed by 7 days rest together with 1500mg of durvalumab every 28 days. Assuming satisfactory completion of the Phase 1b portion of the study, a Phase 2 expansion cohort will enroll at the dose schedule designated in Phase 1b. The primary outcome measure is incidence of treatment emergent adverse events. Secondary outcome measures include objective response rate per RECIST 1.1, progression free survival, duration of response, and overall survival. The trial is being conducted as part of a clinical collaboration between AVEO and AstraZeneca. AVEO is serving as the study sponsor, with study costs shared equally by both parties and clinical drug supplied by each respective company.

"HCC is the fastest rising cause of cancer-related death in the U.S., driven by prevalent diseases that include hepatitis B and C, nonalcoholic steatohepatitis and obesity. With five-year survival at approximately 26%, there remains a desperate need for new therapeutic options," said Michael Bailey, president and chief executive officer of AVEO. "VEGF TKIs and immunotherapy represent current standard of care monotherapies for advanced HCC, and we believe that the combination of tivozanib and durvalumab, both of which have demonstrated single agent activity in HCC, holds great promise as a potential new treatment option for this patient population. Tivozanib’s unique tolerability profile has the potential to make it an attractive VEGF TKI to combine with immunotherapy; in collaboration with AstraZeneca, we look forward to elucidating the potential of the tivozanib-durvalumab combination in patients with previously untreated advanced liver cancer."

About Tivozanib

Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway, New Zealand and Iceland. It is a potent and selective inhibitor of all three VEGF receptors.1,2 Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models3 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC4. Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal, ovarian and breast cancers.

About Durvalumab

Durvalumab (IMFINZI) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is also approved for previously-treated patients with advanced bladder cancer in 10 countries, including the US.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, small cell lung cancer, bladder cancer, head and neck cancer, liver cancer, cervical cancer, biliary tract cancer and other solid tumours.

On September 30, 2019 MiNA Therapeutics, the pioneer in RNA activation (RNAa) therapeutics, reported final Phase 1 clinical data of MTL-CEBPA as a single agent in patients with advanced liver cancer as well as pre-clinical data demonstrating synergistic immunological and anti-tumour activity of MTL-CEBPA in combination with anti-PD1 checkpoint inhibition (Press release, MiNA Therapeutics, SEP 30, 2019, View Source [SID1234539949]). The data will be presented in two posters at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress taking place in Barcelona, Spain on September 28th and September 30th.

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"In addition to the ongoing evaluation of MTL-CEBPA in combination with sorafenib in patients with advanced liver cancer, the new pre-clinical findings support investigating MTL‑CEBPA and anti-PD1 checkpoint combination therapy in patients with other solid tumour cancers."

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"The Phase 1 study, in which immunological activity and tolerability of MTL-CEBPA as a single agent was observed, provides an excellent foundation on which to advance MTL‑CEBPA in combination with other cancer therapies and serves as a strong, general validation of our novel approach to targeting cancer," said Robert Habib, CEO of MiNA Therapeutics. "In addition to the ongoing evaluation of MTL-CEBPA in combination with sorafenib in patients with advanced liver cancer, the new pre-clinical findings support investigating MTL‑CEBPA and anti-PD1 checkpoint combination therapy in patients with other solid tumour cancers."

Final results of the first-in-human evaluation of MTL-CEBPA as a single agent demonstrated MTL-CEBPA to be well tolerated at all dose levels with clear pharmacological activity. In the study, MTL-CEBPA was evaluated as a single agent in 39 patients with advanced liver cancer and liver disease across escalating dose levels and dose frequencies in which no maximum tolerated dose was identified. Pharmacological activity was observed in patients with significant activation of CEBPA target gene and subsequent changes in white blood cell count. Analysis of paired biopsies indicated repopulation of the tumour microenvironment from immuno-suppressive to mature myeloid cells. In 35 patients evaluable for efficacy, partial tumour response was achieved in 1 patient, and stable disease was achieved in 15 patients. Following discontinuation of MTL‑CEBPA, 8 patients received subsequent tyrosine kinase inhibitor therapy. Of 5 patients treated with sorafenib, 4 experienced durable, objective tumour responses including 3 complete tumour responses durable for over 1 year. The ongoing OUTREACH Phase 1b study continues to evaluate MTL-CEBPA in combination with sorafenib standard of care.

Separately, a new pre-clinical study described the synergistic benefits of combining MTL‑CEBPA with anti-PD1 checkpoint inhibition in an immunocompetent mouse model of colon cancer. Compared to single agent treatments, the combination treatment resulted in synergistic improvements in tumour growth inhibition. Synergistic increases in infiltration of cytotoxic T lymphocytes (TILs) evidenced the immunological role of MTL-CEBPA in the tumour microenvironment.

The posters will be made available on the Company’s website in the Publications section under "RNA Activation".

Presentation information

Title: First-in-human, first-in-class phase I study of MTL-CEBPA, a RNA oligonucleotide targeting the myeloid cell master regulator C/EBP-α, in patients with advanced hepatocellular cancer
Poster no: 455PD (Abstract 2878)
Session: Poster Discussion – Developmental therapeutics
Date / time: 16:30 – 18:00 CET, Saturday 28 September 2019
Location: Alicante Auditorium (Hall 3)

Title: Targeting myeloid-derived suppressor cells and T cells: combination treatment with MTL-CEBPA and PD-1 antibody in a mouse syngeneic CT26 model
Poster no: 1230P (Abstract 3089)
Session: Poster Display Session 3, Immunotherapy of cancer
Date / time: 12:00 – 13:00 CET, Monday 30 September 2019
Location: Poster Area (Hall 4)

About MTL-CEBPA
MTL-CEBPA is the first therapy to specifically up-regulate CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of myeloid cell lineage determination and differentiation. Dysregulated myeloid cells have been implicated in several diseases and identified as a critical barrier for many therapies to induce clinical responses in solid tumour cancers. In pre-clinical studies MTL-CEBPA has been shown to improve the anti-tumour activity of cancer therapies by targeting dysregulated myeloid cells and reducing their suppression in the tumour microenvironment.

On September 30, 2019 Iksuda Therapeutics (Iksuda), a developer of next generation Antibody Drug Conjugates (ADCs), reported the first data on its lead ADC, IKS01. IKS01, an ADC targeting the folate receptor, has shown significant anti-tumour efficacy in pre-clinical models of ovarian and lung tumours, each of which included a broad range of folate-receptor alpha (FRA) expression (Press release, Iksuda Therapeutics, SEP 30, 2019, View Source [SID1234539947]). The data is currently being presented at ESMO (Free ESMO Whitepaper) Congress 2019 in Barcelona, Spain.

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ADCs allow for the targeted delivery of a potent cytotoxic payload to tumours, resulting in selective killing with increased efficacy and less off-target toxicity than standard-of-care chemotherapies. Frequent over-expression of FRA in ovarian and non-small-cell lung cancer (accounting for 80% of lung cancer cases) and relative lack of expression in normal tissue, make it an attractive therapeutic target. However, anti-tumour activity is generally limited to patients whose tumours express high levels of FRA.

IKS01 is an ADC comprised of an FRA-targeting antibody conjugated via Iksuda’s PermaLink technology to Femtogenix’s highly potent FGX2-62 payload. IKS01 is target specific and these new data confirm that it is highly effective in causing tumour regression in FRA-expressing models at doses that are well-tolerated, significantly more active than a benchmark ADC and caused complete regressions in low/moderate FRA-expressing models.

The IKS01 data is a major advancement of Iksuda’s ADC drug pipeline, from which it aims to progress multiple candidates towards first clinical studies in 2020.

Dave Simpson PhD, Chief Executive Officer, Iksuda Therapeutics, said: "Ovarian cancer is one of the most deadly gynaecological cancers and lung cancer remains a leading cause of cancer-related death. The IKS01 data highlight the potential impact of our ADC pipeline by targeting difficult-to-treat tumours and advancing current standard of care."

Iksuda Therapeutics’ will be exhibiting its poster: ‘IKS01, a next generation antibody drug conjugate (ADC) designed to be efficacious in tumors with low and moderate levels of folate receptor alpha (FRA) expression’ until 1st October at ESMO (Free ESMO Whitepaper) Congress 2019, presentation number 58P.