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Medivir focuses exclusively on oncology and reorganizes to significantly reduce the cost structure

On October 10, 2016 Medivir AB (Nasdaq Stockholm: MVIR) reported a reorganization of the company and a significant cost reduction in both early research and administrative functions. The board has decided that the company onwards will have an exclusive focus on oncology, utilizing both of Medivir´s technology platforms and competences in protease inhibition and nucleotide-/nucleoside science (Press release, Medivir, OCT 10, 2016, View Source [SID:SID1234515722]). Partnering discussions for all remaining infectious disease assets in the R&D pipeline will be initiated by year-end, as well as for MIV-711 once the phase IIa program has been completed.

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The reorganization will result in a total cost reduction of approximately 110 MSEK per year compared to current levels in the affected functions. The exclusive focus on oncology, along with a reduced number of projects in the early stage research portfolio, will lead to a reduction of around 25 positions and cost savings of approximately 60 MSEK vs current spending in the early stages of development. The reduced early research organization creates flexibility to strengthen capabilities in clinical development and will enable broadening the pipeline with oncology projects in clinical phases. At the same time, efficiency improvements in administrative and commercial support functions will generate the additional cost savings of approximately 50 MSEK per year compared to the current levels, impacting around 20 positions.

As a consequence of these changes, a total of around 30 colleagues will unfortunately have to leave the company and affected vacancies will not be filled. A redundancy cost of approximately 20 MSEK related to these organizational changes will be charged in the fourth quarter.

"I believe this reduced cost in early research, and a streamlined therapeutic area focus with a smaller and more cost effective organization, will strengthen Medivir´s position as an efficient oncology company with a growing development pipeline and research platforms for sustainable growth." says Niklas Prager, CEO & President of Medivir. He continues: "Medivir´s ambition is to have a well balanced and broad pipeline from early to late stages of development. We will continue to build on our technology platforms and proven track record of translating projects into value creating partnerships."

Crescendo Biologics and Takeda Enter Collaboration for Humabody®-based Therapeutics Worth up to $790m

On October 10, 2016 Crescendo Biologics Limited (Crescendo), the drug discovery and developer of Humabody-based therapeutics, and Takeda Pharmaceutical Company Limited (TSE: 4502) reported a global, strategic, multi-target collaboration and license agreement for the discovery, development and commercialization of Humabody -based therapeutics for cancer indications with a high unmet medical need (Press release, Takeda, OCT 10, 2016, View Source [SID:SID1234515716]).

Crescendo will use its proprietary transgenic platform and engineering expertise to discover and optimally configure Humabody candidates (Humabody Drug Conjugates and Immuno-Oncology modulators) against multiple targets selected by Takeda.

"We see significant potential in Crescendo and its innovative technology to develop unique, small and customizable Humabody-based therapeutics," said Andrew Plump M.D., Ph.D., Chief Medical and Scientific Officer, Takeda. "Collaborations are critical to helping us achieve our aspiration of curing cancer. Working together with Crescendo will enable us to leverage its important technology to support Takeda’s goal of developing next generation, highly modular and targeted therapies to treat cancer.

"This collaboration with Takeda represents a significant step forward for Crescendo. It provides validation of our transgenic platform and our capabilities to rapidly assemble and configure small, differentiated Humabody-based therapeutics, opening routes to novel biology," said Dr. Peter Pack, CEO, Crescendo Biologics. "As a leading global pharmaceutical company, Takeda brings extraordinary expertise in the oncology area with significant capabilities in developing and delivering novel medicines to patients. This first major collaboration enables us to potentially broaden and accelerate innovative Humabody-based product candidates. "

Under the terms of the agreement, Crescendo is eligible to receive up to $36 million, in a combination of an upfront payment, investment, research funding and preclinical milestones. Takeda will have the right to develop and commercialize Humabody-based therapeutics resulting from the collaboration. Crescendo is also eligible to receive further clinical development, regulatory and sales-based milestone payments of up to $754 million. In addition, Crescendo will be eligible to receive royalties on Humabody-based product sales by Takeda.

Takeda signed agreements with Crescendo Biologics through its wholly-owned subsidiary, Millennium Pharmaceuticals, Inc.

OncoMed Presents Interim Phase 1b Data for Ipafricept and Vantictumab in Pancreatic Cancer at the ESMO 2016 Congress

On October 10, 2016 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED) reported the presentation of interim clinical data from its ongoing Phase 1b trials of ipafricept (FZD8-Fc, OMP-54F28) and vantictumab (anti-Fzd, OMP-18R5) at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress (Press release, OncoMed, OCT 10, 2016, View Source [SID:SID1234515712]).

Ipafricept and vantictumab are first-in-class Wnt pathways inhibitors that are each being tested in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in patients with previously untreated metastatic pancreatic cancer. Each Phase 1b clinical trial is designed as a dose-escalation study to primarily assess safety and tolerability. Secondary objectives include a preliminary assessment of efficacy and exploratory objectives include the identification of pharmacodynamic and predictive biomarkers.

"In the pancreatic cancer setting, ipafricept and vantictumab in combination with standard-of-care chemotherapy have demonstrated acceptable safety and encouraging early signs of efficacy and biomarker effects," said Jakob Dupont, M.D., Chief Medical Officer. "The data presented at ESMO (Free ESMO Whitepaper), alongside the data presented at ASCO (Free ASCO Whitepaper) for ipafricept and vantictumab, provide evidence supporting the Phase 2 readiness of each drug. Upon the completion of additional dose cohorts and subsequent follow-up, we look forward to presenting an opt-in package to our partner Bayer for these distinct Wnt pathway inhibitors in the first half of next year."

Ipafricept and vantictumab are both part of OncoMed’s collaboration with Bayer Pharma AG. Bayer can elect to exercise its options on ipafricept and vantictumab through completion of Phase 1b trials.

Ipafricept — Interim Phase 1b Data in Pancreatic Cancer
The ipafricept Phase 1b clinical trial has enrolled a total of 22 patients in four dose cohorts. Median follow up for the subjects was 5.9 months (range 0.97-17.5months) as of the data cut-off of August 1, 2016.

Safety
Interim safety results showed that the combination of ipafricept with chemotherapy was well tolerated. The most common toxicities were fatigue, nausea and decreased appetite and vomiting. No Grade 4 or 5 ipafricept-related toxicities were observed. Ipafricept did not appear to enhance chemotherapy-related toxicities.

Following the incidence of bone fractures in the Phase 1a clinical trials of Wnt inhibitors, OncoMed implemented an enhanced bone safety plan that includes monitoring of blood bone markers and bone density, and the administration of zoledronic acid bone protection in at-risk patients. Twelve of 22 patients received bone protective therapy on study and no fragility fractures were observed.

A maximum-tolerated dose has not yet been established and a fourth cohort is currently enrolling.

Efficacy
An interim efficacy assessment demonstrated evidence of anti-tumor effects for the combination of ipafricept with chemotherapy. Of the 18 patients evaluable for response, the overall response rate was 39 percent with seven patients achieving partial response. Another eight patients have achieved stable disease for a clinical benefit rate of 83 percent. Early evidence of durability was observed, with nine patients on study greater than 168 days and two patients on study for greater than one year. Progression-free survival (PFS) and overall survival (OS) data are not yet mature. At the time of the data cut-off eight subjects were still on study treatment.

Biomarker analysis
Interim analysis showed that patients with higher expression of Wnt pathway genes at baseline had greater than 40 percent reduction in tumor size compared to those patients with lower Wnt pathway gene expression at baseline, suggesting activated Wnt pathway signaling at baseline may be predictive of patients with a more favorable response to treatment.

A poster discussion of data from the ipafricept Phase 1b clinical trial was presented on Sunday, October 9, during the Developmental Therapeutics session in a poster titled, "Phase 1b study of WNT inhibitor ipafricept (IPA, decoy receptor for WNT ligands) with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients (pts) with previously untreated stage IV pancreatic cancer (PC)" (Abstract #3410).

Vantictumab – Interim Phase 1b Data in Pancreatic Cancer:
The vantictumab Phase 1b clinical trial has enrolled a total of 24 patients in four dose cohorts. As of the data cut-off of August 1, 2016 for results reported at ESMO (Free ESMO Whitepaper), median follow up for subjects was 5.9 months (range: 0.77-28.5 months).

Safety
Interim safety results showed that the combination of vantictumab with chemotherapy was well tolerated. The most common vantictumab-related toxicities were fatigue, nausea and dysgeusia. No Grade 4 or 5 vantictumab-related toxicities were observed. Further, vantictumab did not appear to enhance chemotherapy-related toxicities.

Following the incidence of bone fractures in the Phase 1a clinical studies of Wnt inhibitors, OncoMed implemented an enhanced bone safety plan that includes monitoring of blood bone markers and bone density, and the administration of zoledronic acid bone protection in at-risk patients. Seventeen of 24 patients received bone protective therapy and no fragility fractures have been observed.

A maximum-tolerated dose has not yet been established and a fifth cohort is currently enrolling.

Efficacy
An interim efficacy assessment demonstrated evidence of anti-tumor effects for the combination of vantictumab with chemotherapy. Of the 21 patients evaluable for response, the overall response rate was 48 percent with 10 patients achieving partial response. Further, the clinical benefit rate was 86 percent as an additional eight patients achieved stable disease. PFS and OS data are not yet mature. Nine of 24 patients were on study greater than 168 days with two patients on study for more than a year. At the time of the data cut-off five subjects were still on study treatment.

Biomarker analysis
Exploratory interim analysis of baseline tumors suggested OncoMed’s three-gene predictive biomarker successfully identified patients with better overall responses. Of the eight patients whose tumors were positive for the biomarker, seven achieved partial responses and one achieved stable disease.

Data from the vantictumab Phase 1b clinical trial were presented on Saturday, October 8, during the Gastrointestinal Tumors session in a poster titled, "Phase 1b study of WNT inhibitor vantictumab (VAN, human monoclonal antibody) with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients (pts) with previously untreated stage IV pancreatic cancer (PC)" (Abstract #3412).

Endocyte Presents Data on Two Lead Clinical Programs at European Society for Medical Oncology (ESMO) 2016 Congress

On October 10, 2016 Endocyte, Inc. (NASDAQ:ECYT), a leader in developing targeted small molecule drug conjugates (SMDCs) and companion imaging agents for personalized therapy, reported that it has presented poster updates on its two lead clinical programs at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress, being held in Copenhagen, Denmark October 7-11, 2016 (Press release, Endocyte, OCT 10, 2016, View Source [SID:SID1234515710]).

"We are pleased that both EC1456 and EC1169 have shown anti-tumor activity during the dose escalation phase of their respective trials, even in patients not specifically identified as positive for the drug targets," said Mike Sherman, president and CEO at Endocyte. "The activity we’ve seen to date with EC1169 in prostate cancer patients is particularly exciting, with our first confirmed radiologic partial response (PR). This quarter we expect to move the 6.5 mg/m2 dose into the expansion phase of the study where we will evaluate EC1169 in patients selected as prostate specific membrane antigen (PSMA)-positive using our companion imaging agent, EC0652. We have also moved on to the expansion phase of the EC1456 trial, using our companion imaging agent etarfolatide to select folate receptor (FR)-positive non-small cell lung cancer (NSCLC) patients."

"Despite the current therapy options available for prostate cancer patients, there remains a need for safe and effective alternatives for these patients following treatment with hormone therapies," stated Michael J. Morris, M.D., Associate Professor, Genitourinary Oncology, Memorial Sloan Kettering Cancer Center, New York. "The disease is more challenging to treat at this stage, so the safety data, and at least the preliminary efficacy data, which we’re seeing with Endocyte’s PSMA-targeted agent is encouraging. I look forward to further exploring this novel drug in patients with metastatic prostate cancer."

EC1169 Poster #731P – Phase 1 Study of the PSMA-Targeted Tubulysin Small-Molecule Drug Conjugate EC1169 in Patients with Metastatic Castrate-Resistant Prostate Cancer (mCRPC): Study Update

Data presented in this poster showed that total target tumor burden reduction was observed in 4 of the 6 patients with measurable soft tissue disease treated at doses of 3.8 mg/m2 and higher. One of these patients demonstrated the first confirmed radiologic partial tumor response (PR) as measured by RECIST 1.1 criteria. Two patients also demonstrated confirmed prostate specific antigen (PSA) reductions of greater than 50%, one of whom went on to demonstrate the PR. After observing toxicity at 8.5 mg/m2, the company is in the process of confirming 6.5 mg/m2 as the highest clinical dose. EC1169 was well tolerated without causing dose-limiting hematologic toxicity frequently associated with traditional chemotherapy. Primary toxicities included fatigue and gastrointestinal (GI) toxicity; predominantly grade 1 and 2, reversible and responsive to simple medication.

EC1456 Poster #395P – Dose Escalation Phase 1, Safety and Pharmacokinetic Study of the Folate Receptor-Targeted Drug Conjugate EC1456 in Advanced Cancer Patients: Study Update

A dose of 6.0 mg/m2 was established as the maximum twice per week dose, administered 2 weeks out of a 3 week cycle, which is being used in the expansion phase of the trial in FR-positive NSCLC patients. EC1456 was well tolerated, with primary toxicities including fatigue, GI toxicity, and electrolyte disturbance; predominantly grade 1 and 2, reversible and responsive to simple medication. In spite of the inclusion of patients who were not selected as positive for the targeted FR, most patients demonstrated stable disease as best response and several patients demonstrated a reduction in target tumor volume.

About EC1169 and EC0652

EC1169 is an investigational therapeutic SMDC constructed of a high affinity PSMA-targeting ligand conjugated through a releasable linker system to a potent cytotoxic microtubule inhibitor, tubulysin B hydrazide (TubBH). The high affinity of EC1169 for PSMA allows for the active and specific delivery of TubBH to PSMA-expressing cancer cells, while minimizing exposure to normal cells. PSMA is known to be highly expressed on the majority of prostate cancers with limited expression on normal tissues.

The PSMA-targeted companion imaging agent EC0652 is being co-developed to characterize whole body PSMA expression in real time, to identify patients most likely to benefit from EC1169 therapy. EC1169 and EC0652 are currently being evaluated in a phase 1 study in patients with metastatic, castration-resistant prostate cancer (mCRPC) (ClinicalTrials.gov Identifier: NCT02202447).

About EC1456 and etarfolatide

EC1456 is an investigational therapeutic SMDC constructed of folic acid conjugated through a spacer and releasable linker system to a potent cytotoxic microtubule inhibitor, TubBH. The high affinity of the folic acid ligand for the FR allows for the active and specific targeting of EC1456 to FR-expressing cancer cells. The FR is highly expressed in several epithelial cancers (e.g. ovarian, NSCLC) but is expressed at low levels in most normal tissues.

Etarfolatide is an FR-targeted companion imaging agent being co-developed to characterize whole body FR expression in real time, to identify patients most likely to benefit from EC1456 therapy. EC1456 and etarfolatide are currently being evaluated in a phase 1 study in patients with advanced solid tumors (ClinicalTrials.gov Identifier: NCT01999738).

Corvus Pharmaceuticals Announces Biomarker Findings from Phase 1/1b Study of Lead Oral Checkpoint Inhibitor CPI-444 Presented at ESMO 2016 Congress

On October 10, 2016 Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of novel immuno-oncology therapies, reported biomarker findings from its ongoing Phase 1/1b study of CPI-444 as a single agent and in combination with Genentech’s TECENTRIQ (atezolizumab),‎ a fully humanized monoclonal antibody targeting protein programmed cell death ligand 1 (PD-L1). CPI-444 is a selective and potent inhibitor of the adenosine A2A receptor. The data were presented today in a poster session by Ian McCaffery, Ph.D., vice president, Translational Sciences at Corvus, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress at the Bella Center in Copenhagen, Denmark.

"The initial part of our Phase 1/1b trial was designed to provide data on optimum dosing, safety and relevant biomarkers, and we have achieved that goal. We have completed enrollment in the dose-selection part of the trial, which enrolled 48 patients in four cohorts. We now have a solid understanding of dose, schedule, pharmacodynamic parameters and biomarkers," said Richard A. Miller, M.D., an oncologist and co-founder, president and chief executive officer of Corvus. "We have selected the optimum single agent and combination dose of CPI-444 for the disease-specific expansion stage of the trial, which is now enrolling patients at 30 centers in the United States, Canada and Australia. We plan to present preliminary efficacy data from the dose-selection part of the study later this year."

Results presented showed:

Seven of seven patients receiving CPI-444 100 mg twice daily had sustained, complete blockade of peripheral blood lymphocyte A2A receptors.
Plasma levels of CPI-444 of 2 mcg/ml resulted in complete saturation of A2A receptors in peripheral blood lymphocytes.
Treatment-related increases in cytotoxic T-lymphocytes that were both PD-1-positive and CD8-positive (double positive) provided evidence of immune activation of peripheral blood lymphocytes. Previous research from others has shown that PD-1, CD8 double positive T-cells are associated with anti-tumor immune responses.
In 14 patients tested to date, increases in PD-1, CD8 double positive T-cells were observed in seven of seven patients receiving single agent CPI-444 100 mg twice daily, in one of three patients receiving single agent CPI-444 200 mg once daily, and in three of four patients receiving CPI-444 50 mg twice daily combined with TECENTRIQ.
CPI-444 has been well tolerated to date, with one patient experiencing a possibly drug related serious adverse event.
Based on these and other data, Corvus has selected an oral dose of 100 mg twice daily for 28 days for both the single agent and combination arms of the second part of the trial.
ABOUT CPI-444
CPI-444, Corvus’ lead checkpoint inhibitor, is an adenosine A2A receptor antagonist. It is designed to disable a tumor’s ability to subvert attack by the immune system by inhibiting adenosine in the tumor microenvironment. CPI-444 is a small molecule that is taken orally. It is in development as an immuno-oncology therapy for the treatment of patients with solid tumors.

ABOUT THE PHASE 1/1B TRIAL
The Phase 1/1b trial is designed to examine the activity of CPI-444 as a single agent and in combination with Genentech’s TECENTRIQ (atezolizumab), an anti-PD-L1 antibody. Patients with non-small cell lung cancer, melanoma, renal cell cancer, triple-negative breast cancer, colorectal cancer, head and neck cancer, bladder cancer and prostate cancer who have failed all standard therapies are eligible.

The first part of the study (dose-selection) included four cohorts of 12 patients each (N=48) – three cohorts treated with single agent CPI-444 (100 mg twice daily for 14 days; 100 mg twice daily for 28 days; 200 mg once daily for 14 days) and one cohort treated with the combination (CPI-444 50 mg or 100 mg twice daily for 14 days combined with TECENTRIQ). A treatment cycle is 28 days. Based on safety and biomarker analyses, an optimum single agent and combination dose were selected. The second part of the study is evaluating CPI-444 as a single agent in five disease-specific cohorts, and CPI-444 in combination with TECENTRIQ in five additional matched disease-specific cohorts. Corvus expects that each of these 10 cohorts will initially enroll 14 patients, but each cohort may be expanded based on efficacy.