On December 9, 2015 Flagship Ventures, a leading innovation and venture firm focused on healthcare and sustainability, reported it has launched Rubius Therapeutics, to develop functionalized red blood cells for the treatment of autoimmune conditions, metabolic diseases, cancer, and other serious diseases (Press release, Rubius Therapeutics, DEC 9, 2015, View Source [SID1234520729]). Flagship has made an initial capital commitment of $25 million to enable Rubius to enter clinical testing of its novel therapeutic modality.

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!

Rubius is pioneering Red-Cell Therapeutics (RCTs). RCTs are a new treatment modality and possess pharmacodynamic and pharmacokinetic advantages over traditional therapeutics, in part due to their natural ability to engage and modulate the immune system and circulate for extended periods in the body.
"Working together with our collaborators, technology advances made at Flagship’s innovation foundry, VentureLabs, led to the creation of a completely new therapeutic modality," said Noubar Afeyan, Ph.D., senior managing partner and CEO of Flagship Ventures and a director of Rubius. "We believe Red-Cell Therapeutics will become a new standard of care in many areas of high unmet medical need."
One of the diseases Rubius intends to initially target is phenylketonuria (PKU), a disease of metabolism that affects as many as one in 13,000 births in the U.S. and is responsible for about 300 new cases each year. People born with PKU have a genetic defect that leaves them unable to break down a particular amino acid, one
of the building blocks of proteins. Left untreated, the amino acid, phenylalanine, builds up in the body and causes severe developmental problems and long-term health issues. Newborns are routinely tested for this genetic disease within days of birth.
Currently, the most effective treatment for PKU is a strict diet that lowers the amount of phenylalanine in the body. Rubius has developed and pre-clinically validated a Red-Cell Therapeutic capable of enzymatically reducing phenylalanine levels in human serum. By continually lowering phenylalanine levels in the bloodstream, RCT therapy promises to allow PKU patients to live normally without extremely restrictive diets.
"Red blood cells can now be produced in culture and engineered to possess enormous biotherapeutic properties," said Harvey Lodish, Ph.D., professor of biology and bioengineering at MIT and a member of the Whitehead Institute, who is a scientific founder of Rubius and has joined the firm’s board of directors. "They spend as much as four months in circulation, providing an opportunity for long and tunable therapeutic treatments. Red cells also have profound effects on the immune system and may ultimately transform the way we treat autoimmune diseases and allergies."
"Through its rapid prototyping capability, Rubius has generated and tested over 50 different RCTs for a wide array of indications including autoimmunity, oncology and infectious disease" said Avak Kahvejian, Ph.D., founding CEO of Rubius and Flagship VentureLabs partner. "The company is now poised to drive lead programs into the clinic, build a drug pipeline and further develop the Rubius Erythrocyte Design platform. We are expanding our R&D and management teams, and setting the stage for our next phase of growth."
Besides Dr. Afeyan and Dr. Lodish, the Rubius board of directors includes:

• Jim Gilbert, a healthcare investor and former partner and director at Bain & Co., who serves on several boards, including the board of Nestle Health Sciences. Jim serves as chairman of Rubius.

• Robert S. Langer, Ph.D., Institute Professor at MIT and the holder of more than 1,000 patents

• Dr. Roger Pomerantz, chairman and CEO of Seres Health and former worldwide head of licensing and acquisitions, senior vice president at Merck & Co. Inc.

• Dr. Michael Rosenblatt, executive vice president and chief medical officer of Merck & Co. Inc. , and former dean of the Tufts University School of Medicine.

• Peter Hutt, senior counsel at Covington & Burling and former chief counsel of the U.S. Food and Drug Administration.

Since emerging from Flagship VentureLabs 18 months ago, Rubius has been developing its RCT platform in stealth mode. The company has established a broad patent estate covering its platform and therapeutic products. Rubius is currently testing RCTs in animal models of disease, and plans to initiate human clinical trials in the very near future.

On December 9, 2015 Cancer Research Technology (CRT), the development and commercialisation arm of Cancer Research UK, has reported the appointment of Dr Deborah Harland to its board of directors (Press release, Cancer Research Technology, DEC 9, 2015, View Source [SID1234523200]).

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!

Deborah brings more than 25 years’ experience in the pharmaceutical sector and is currently a partner at SR One – the corporate venture capital arm of GlaxoSmithKline. In addition to her current role Deborah has held various roles spanning clinical development, medical affairs and business development throughout her career. She is currently a board member for several biotech companies in which SR One has invested including MISSION Therapeutics*.

Deborah succeeds Dr Ruth McKernan, who was appointed chief executive of Innovate UK earlier this year.

Dr Deborah Harland said: "I’m thrilled to join Cancer Research Technology at a time of exciting progress in our understanding of cancer and the development of vital new therapies for cancer patients.

"I look forward to contributing to CRT’s ambitious plans to drive delivery of the Cancer Research UK research strategy by identifying innovative scientific and business solutions to unmet needs in cancer."

Dr Keith Blundy, Cancer Research Technology’s chief executive officer, said: "I’m delighted to welcome Deborah to Cancer Research Technology. She brings a wealth of experience in industrial drug discovery, licensing and venture financing.

"I have no doubt that CRT will benefit greatly from Deborah’s guidance and expertise as we continue our work to develop and advance discoveries that help beat cancer."

On December 8, 2015 Celator Pharmaceuticals, Inc. (Nasdaq: CPXX) reported positive data for VYXEOS (also known as CPX-351) were presented in two presentations at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, December 5-8, 2015 (Press release, Celator Pharmaceuticals, DEC 8, 2015, View Source [SID:1234508498]).

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!

Abstract Title: CPX-351 ((Cytarabine:Daunorubicin) Liposome Injection, (Vyxeos)) Does Not Prolong QTcF Intervals, Requires No Dose Adjustment for Impaired Renal Function and Induces High Rates of Complete Remission in Acute Myeloid Leukemia

This Phase 2 study was undertaken to support potential marketing applications for VYXEOS worldwide. Twenty-six patients with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) were enrolled. The study showed VYXEOS did not prolong the QT/QTc interval, a positive safety outcome. The drugs remain encapsulated in the nano-scale delivery vehicle while circulating in the plasma ( > 97% over the first 24 hours), which allows the drugs to be delivered directly to leukemia cells at the synergistic 5:1 molar ratio. The study included patients with newly diagnosed AML, relapsed/refractory AML and relapsed/refractory ALL. Thirteen of the 26 patients responded. Responses were seen in each of the three acute leukemia patient populations.

In addition, the study showed that no dose adjustment is required in patients with renal impairment.

Adverse events were similar in frequency and severity to those described in earlier studies.

"We are encouraged to report that CPX-351 did not prolong cardiac repolarization, and the pharmacokinetic results indicate that no dose modification is necessary in patients with renal impairment," said Tara Lin, M.D., Assistant Professor of Medicine at The University of Kansas Cancer Center, the lead investigator of this study. "Also, we are happy to report that this study confirms the broad activity of CPX-351 in multiple populations of acute leukemia patients."

Abstract Title: CPX-351 Enables Administration of Consolidation Treatment in the Outpatient Setting and Increases the Time Spent out of the Hospital after Completion of AML Treatment Compared with 7+3

Health resource utilization (HRU) was assessed using data from a previously published randomized Phase 2 study comparing first-line treatment with VYXEOS vs. the current standard of care, known as the 7+3 regimen, in newly diagnosed older patients (age 60-75) with AML (Lancet, et al. Blood 2014;123(21):3239-3246).

Treatment arms were compared for number of hospitalizations, total hospital days, patients responding following a single induction, responding patients receiving consolidation therapy in the outpatient setting, event-free survival (EFS), and the ratio of EFS per inpatient days.

Phase 2 study data indicate HRU outcomes are favorable for VYXEOS compared to 7+3. VYXEOS-treated patients required fewer inductions to respond and were more likely to be given consolidation treatment in an outpatient setting (47% vs. 19%).

VYXEOS treatment was associated with a substantial increase in EFS days (median: 197 days vs. 60 days), with a slight increase in hospital days (median: 38 days vs. 35 days) resulting in a substantial improvement in the ratio of median EFS days to median hospital days (5.2 vs. 1.7) in favor of VYXEOS.

"The improvement in clinical benefit was associated with favorable health resource utilization outcomes, which is an important feature of CPX-351," said Jeffrey Lancet, M.D., Senior Member and Chief of the Leukemia/Myelodysplasia Program at Moffitt Cancer Center and lead investigator on the study. "We look forward to confirmation of this observation from the pivotal trial, expected in the first quarter of 2016."

The posters are available on Celator’s website (www.celatorpharma.com).

On December 8, 2015 CELLIPSE reported that during the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Congress held in Orlando, the teams from U. of Indiana Wells Center led by Pr Kapur and Institut Albert Bonniot led by Dr Lafanechère presented the results of their work in the session dedicated to Oncogene and Tumor Suppressors in Myeloïd malignancies (Press release, CELLIPSE, DEC 8, 2015, View Source [SID:1234508500]). This new data reinforces the rationale for looking into LIM Kinase inhibition to stop downstream oncogene signaling of specific mutations of Tyrosine Kinase Receptors.

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!

CELLIPSE is developing selective and highly potent LIM Kinase small molecule inhibitors to bring new targeted therapies against cancer indications with poor overall prognosis and high medical need such as Acute Myeloïd Leukemia and Myeloproloferative Neoplasms.

On December 08, 2015 Oncothyreon Inc. (Nasdaq:ONTY), a clinical-stage biopharmaceutical company dedicated to the development of therapeutic products that can improve the lives and outcomes of patients with cancer, reported updated data from the company’s ongoing trials of ONT-380, an orally active, reversible and selective small-molecule HER2 inhibitor being developed for the treatment of HER2-positive metastatic breast cancer (Press release, Oncothyreon, DEC 8, 2015, View Source [SID:1234508502]). The data will be the subject of two presentations at the San Antonio Breast Cancer Symposium (SABCS) being held December 8-12, 2015 in San Antonio, TX.

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 first presentation (Abstract P4-14-20) highlights data from a Phase 1b trial of ONT-380 in combination with Kadcyla (ado-trastuzumab emtansine or T-DM1) in patients who have previously failed treatment with Herceptin (trastuzumab) and a taxane for HER2-positive breast cancer ( ClinicalTrials.gov Identifier NCT01983501). The data demonstrate an overall response rate of 41% and a clinical benefit rate (CBR) of 59% in an advanced stage patient population, 60% of whom have a history of central nervous system (CNS) metastases. The CNS CBR for patients with response assessable CNS metastases was 64%. The second presentation (Abstract P4-14-19) combines data for patients with response assessable brain metastases from two trials, the Phase 1b trial in combination with Kadcyla and a Phase 1b trial of ONT-380 in combination with Herceptin and/or Xeloda (capecitabine) (ClinicalTrials.gov Identifier NCT02025192). The analysis includes patients with previously untreated CNS metastases as well as patients with progressive or new CNS metastases after prior treatment with radiation or surgery. Responses and clinical benefit in the CNS were seen for both groups and in all combinations tested.

"We are pleased by the response rate and clinical benefit rate we have seen in the combination trial of ONT-380 and Kadcyla, including in patients with brain metastases," said Robert L. Kirkman, M.D., President and CEO of Oncothyreon. "In addition, the analysis of patients with response assessable brain metastases from both our trials reinforce and expand upon our previously reported results, increasing our commitment to exploring ONT-380 in this indication. Our planned Phase 2 trial of ONT-380 in combination with Xeloda and Herceptin includes significant CNS-focused endpoints. We also plan to explore additional options to develop ONT-380 in combination with Kadcyla in patients with CNS metastases."

"CNS metastases occur in up to 50 percent of women with HER2-positive metastatic breast cancer, and these patients have limited options for systemic treatment," said Stacy Moulder, M.D., Associate Professor, Section Chief of Clinical Research, Breast Medical Oncology, University of Texas MD Anderson Cancer Center. "The level of clinical activity seen in the expanded data set for ONT-380 in these advanced stage patients is encouraging and worthy of urgent further development."

About the Clinical Results

The Phase 1b trial of ONT-380 in combination with Kadcyla is a dose escalation trial in patients with HER2-positive metastatic breast cancer who have been previously treated with Herceptin and a taxane. Patients with a history of CNS metastases, including patients with untreated asymptomatic metastases and patients with progression following prior local therapy, were eligible for enrollment in the trial. The trial enrolled a total of 57 patients. The maximally-tolerated dose (MTD) of ONT-380 in this trial was determined to be 300 mg given twice per day, and the detailed safety and efficacy results included here are for 50 patients treated at this dose. For this patient population, the median number of prior non-hormonal systemic treatments was two (range 0-6). Twenty-three (46%) of the patients had received prior Perjeta (pertuzumab) therapy and 10 (20%) had received prior Tykerb (lapatinib) therapy. Thirty (60%) of the patients had CNS metastases, of whom 19 had prior therapy for those metastases.

Best responses were measured using RECIST 1.1 criteria in 48 evaluable patients. In 34 patients with measurable disease, a best response of a confirmed partial response (cPR) was seen in 14 (41%), stable disease (SD) in 15 (44%) and progressive disease (PD) in 5 (15%). Fourteen patients had non-target lesions, primarily bone metastases, none of whom had a best response of PD (all were non-CR/non-PD by RECIST 1.1). The CBR, defined as patients with a complete response (CR), a cPR, or either SD or non-CR/non-PD for at least 6 months, was 59% (23/39). Patients active on study at the time of the analysis with SD for less than six months were excluded from the calculation of CBR. Twenty patients had response assessable CNS metastases. Of these patients twelve had measurable lesions and a follow-up scan, with a best CNS response of one CR, three PRs and eight SDs, for an overall response rate of 33%. One patient did not have a follow-up CNS scan as a result of progressive systemic disease. All seven patients with assessable non-target lesions had non-CR/non-PD as a best response. The CNS CBR was 64%. A calculation of progression free survival is not yet possible in this trial, as 25 of the 50 patients enrolled at the MTD remained active on the study at the time of the analysis.

Combination therapy with ONT-380 and Kadcyla was well-tolerated in this trial. The most common clinical adverse events were nausea, vomiting, diarrhea, vomiting and constipation, the majority of which were Grade 1 in severity. The most common laboratory abnormality was elevation in liver function tests (ALT/AST), the majority of which were Grade 1 or 2. All elevations in ALT/AST which were Grade 3 or greater were reversible with dose interruption, except in the setting of progressive metastatic liver disease, and most patients with Grade 3 or greater elevations were able to resume treatment with reduced dose ONT-380 and/or Kadcyla.

The role of ONT-380 in the treatment of CNS metastases from HER2-positive breast cancer was further evaluated in a combined analysis of 34 patients with response-assessable CNS metastases from both the Phase 1b trial of ONT-380 in combination with Kadcyla and the Phase 1b trial of ONT-380 in combination with Herceptin and/or Xeloda. CNS metastases were considered response assessable if they were either untreated with radiation or surgery, or were new or progressive lesions following prior radiation or surgery. Of 14 patients with previously untreated lesions, eight had measurable disease, with a best CNS response of one CR, two cPRs and four SDs. One patient did not have a follow up CNS scan secondary to progressive systemic disease. Six patients with previously untreated lesions had non-target lesions only, of whom five were non-CR/non-PD and one was not evaluable. The CNS CBR for the previously untreated CNS metastases was 44%. Of 20 patients with new or progressive lesions following prior therapy, 17 had measurable disease, with a best CNS response of five cPRs, nine SDs, and one PD. Two patients remain too early to evaluate. Three patients with non-target lesions only had non-CR/non-PD. The CNS CBR for patients with new or progressive lesions following prior therapy was 59%. Of note, responses and clinical benefit were seen when ONT-380 was combined with each of Kadcyla, or Herceptin and/or Xeloda.

About the Planned ONT-380 Clinical Development Program

Oncothyreon plans to initiate a Phase 2 randomized, double-blind, controlled study of ONT-380 versus placebo in combination with capecitabine and trastuzumab in patients with unresectable locally advanced or metastatic HER2-positive breast cancer (ClinicalTrials.gov Identifier: NCT02614794). The trial is expected to enroll approximately 180 patients in multiple centers located in the United States, Canada and Western Europe. Eligible patients must have centrally confirmed HER2-positive breast cancer and must have been previously treated with a taxane, trastuzumab, pertuzumab and TDM-1. The primary endpoint of the trial is bi-compartmental progression free survival, both CNS and non-CNS, as assessed by independent review using both RECIST 1.1 and Response Assessment in Neuro-Oncology – Brain Metastases (RANO-BM) criteria. Secondary endpoints include time to CNS progression, objective response rate, CBR rates for both CNS and non-CNS metastatic disease and overall survival. Oncothyreon currently expects to initiate the first clinical sites for the Phase 2 trial before the end of 2015 and to treat the first patient in early 2016.

Based on the results of the Phase 1b trial of ONT-380 in combination with Kadcyla discussed above, Oncothyreon is considering an additional Phase 2 or Phase 3 trial of this combination potentially focused on patients with CNS metastases. Oncothyreon plans to discuss potential designs for this trial, together with the overall registration strategy for ONT-380, with regulatory authorities, including the United States Food and Drug Administration, in the first part of 2016.