On December 5, 2016 Actinium Pharmaceuticals, Inc. (NYSE MKT:ATNM) ("Actinium" or "the Company"), a biopharmaceutical company developing innovative targeted therapies for cancers lacking effective treatment options, reported that results from its Phase 1 trial of Actimab-A were presented at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper) that is currently ongoing in San Diego, CA (Press release, Actinium Pharmaceuticals, DEC 5, 2016, View Source [SID1234516965]). Data from the previously conducted Phase 1 study pertaining to safety, efficacy and PB burden were highlighted during the poster session. Actimab-A is currently being studied in a 53-patient Phase 2 clinical trial as a monotherapy for patients newly diagnosed with Acute Myeloid Leukemia (AML) age 60 and above who are ineligible for currently used induction therapies. The Phase 2 trial is studying Actimab-A as a monotherapy administered via two fifteen minute intravenous injections of 2.0 μCi/kg/fraction of Actimab-A given a week apart. PB burden below 200 blasts/µL will serve as an inclusion criteria and patients above this threshold will be administered hydroxyurea to reduce their peripheral blasts counts prior to Actimab-A administration. Results from the Phase 1 trial showed that patients with PB burden below 200 blasts/µL who received a dose of 2.0 μCi/kg/fraction of Actimab-A saw a 50% response rate.

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!

Actinium’s PB burden hypothesis states that patients below the key threshold level of 200 blasts/µL have an increased response rate to Actimab-A while patients above the key threshold are unlikely to respond. An analysis of 2 clinical trials with Actimab-A totaling 38 patients, of which 36 were evaluable, showed that 42% (8 of 19) of patients with blasts counts below 200/µL responded to Actimab-A while no patients with blast counts above 200/µL responded to Actimab-A. The Phase 1 trial was a dose escalation study using a 3+3 design. Dose escalation proceeded if dose-limiting toxicities (DLT) were seen in less than 33% of patients. Maximum tolerable dose (MTD) was not reached in the Phase 1 trial.

Dr. Joseph Jurcic, Director of Hematologic Malignancies and Professor of Medicine at Columbia University Medical Center and Principal Investigator of the study said, "Older patients with AML, particularly those that have progressed from MDS, are difficult to treat and have very few treatment options since many have already received lower-intensity therapy with hypomethylating agents. The results from this Phase 1 trial were encouraging in regards to both the safety and efficacy of Actimab-A. We are particularly excited to have identified that patients with peripheral blasts below 200/µL have higher response rates to Actimab-A and that we can reduce blast counts in patients above that level using hydroxyurea. Actimab-A has shown promise in older AML patients, including those previously treated for MDS–a population excluded from trials with most novel agents, including ongoing studies with other CD33-directed therapies. We look forward to continuing to study Actimab-A in the ongoing Phase 2 trial and potentially meeting this critical need."

Of the 18 patients in the Phase 1 trial, 28% (5 of 18) had objective responses (2 CR, 1CRp and 2 CRi). Amongst patients with objective responses, median response duration was 9.1 months (range, 4.1-16.9 months). At the 3 highest dose levels in the Phase 1 trial (1.0 μCi/kg/fraction – 2.0 μCi/kg/fraction) objective responses were seen in 33% of patients (5 of 15). Mean bone marrow blast reduction amongst evaluable patients was 66% with 57% of patients having bone marrow blast reduction of 50% or greater and 79% of patients (11 of 14) had bone marrow blast reductions after Cycle 1 of therapy. The Phase 1 trial enrolled patients newly diagnosed with AML who are age 60 and above who were administered Actimab-A in combination with low-dose Cytarabine. Median patient age was 77 with 67% of patients having prior myelodysplastic syndrome (MDS) of which, 83% received prior therapy consisting of either hypomethylating agents (HMAs) or a hematopoietic stem cell transplant (HSCT).

A formal interim analysis will occur after 31 patients receive Actimab-A, which the Company expects to occur in mid-2017. The Company anticipates the Phase 2 trial to be complete by the end of 2017.

"Actimab-A, given its benign toxicity profile combined with potent efficacy as evidenced by the results presented today along with its ease of administration via 2 injections, represents an exciting therapy for elderly patients with AML," said Sandesh Seth, Executive Chairman of Actinium. "Due to our peripheral blast burden hypothesis and optimized Phase 2 protocol we have great excitement for the current Phase 2 clinical trial and future development pathways for Actimab-A."

About Actimab-A

Actimab-A, Actinium’s most advanced alpha particle immunotherapy (APIT) product candidate, is currently in a 53-patient, multicenter Phase 2 trial for patients newly diagnosed with AML age 60 and above. Actimab-A is being developed as a first-line therapy and is a monotherapy that is administered via two 15-minute injections that are given 7 days apart. Actimab-A targets CD33, a protein abundantly expressed on the surface of AML cells via the monoclonal antibody, HuM195, which carries the potent cytotoxic radioisotope actinium-225 to the AML cancer calls. Actinium-225 gives off high-energy alpha particles as it decays, which kill cancer cells and as actinium-225 decays it produces a series of daughter atoms, each of which gives off its own alpha particle, increasing the chances that the cancer cell will be destroyed. Actimab-A is a second-generation therapy from the Company’s HuM195-Alpha program, which was developed at Memorial Sloan Kettering Cancer Center and has now been studied in almost 90 patients in four clinical trials. Actimab-A has been granted Orphan Drug Designation for newly diagnosed AML age 60 and above

On December 5, 2016 Oxford BioMedica plc ("Oxford BioMedica" or "the Group") (LSE: OXB), a leading gene and cell therapy group, reported the findings from Novartis on their clinical trial (ELIANA) evaluating the efficacy and safety of CTL019, an investigational chimeric antigen receptor T cell (CAR T) therapy, in relapsed/refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL). Oxford BioMedica produces the lentiviral vector expressing CTL019 and has a CAR-T partnership with Novartis.

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 findings were presented during an oral session on Saturday 3rd December 2016 at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting (Abstract #221, December 3, 4:00-5:30 p.m.). Novartis reported that the global Phase II study found that 82% (41 of 50) of infused patients achieved complete remission or complete remission with incomplete blood count recovery at three months post CTL019 infusion. For all patients with complete remission, no minimal residual disease was detected. In addition, the estimated relapse-free rate among responders was 60% (95% CI: 36, 78) six months after infusion with CTL019. Novartis confirmed their intention to file CTL019 with the US Food and Drug Administration (FDA) in early 2017 for pediatric and young adult patients with r/r B-cell ALL.

John Dawson, Chief Executive Officer of Oxford BioMedica, commented: "We are pleased that Novartis has reported exciting progress with its investigational therapy CTL-019, and that Novartis confirm their commitment to advancing CTL019 and working closely with the FDA and EMA in the coming months."

On December 5, 2016 CytomX Therapeutics, Inc. (Nasdaq:CTMX), a biopharmaceutical company developing investigational Probody therapeutics for the treatment of cancer, reported the selection of the fourth target by Bristol-Myers Squibb under the companies’ current strategic oncology collaboration established in 2014 (Press release, CytomX Therapeutics, DEC 5, 2016, View Source;p=RssLanding&cat=news&id=2227453 [SID1234517019]). As a result, Bristol-Myers Squibb will pay CytomX $15 million. This constitutes the final target selection under this agreement.

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!

"We are thrilled with the continued progress in our alliance with Bristol-Myers Squibb that has included two new target selections this year and the recent presentations of strong preclinical proof-of-concept data for our anti-CTLA-4 Probody therapeutic program at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Symposium on Immuno-Oncology and the Society for Immunotherapy in Cancer (SITC) (Free SITC Whitepaper) Annual Meeting," said Sean McCarthy, D.Phil., president and chief executive officer of CytomX Therapeutics. "We look forward to continued progress in each of these collaboration programs as we pursue our vision of transforming lives with safer, more effective therapies."

Investigational therapeutics developed with CytomX’s Probody platform are designed to be active in the tumor while sparing healthy tissue. By restricting activity to the tumor microenvironment, investigational Probody therapeutics directed against both validated and novel targets have been shown preclinically to enable anti-tumor efficacy with an enhanced safety window, relative to traditional antibody-based therapies.

About the Collaboration Agreement
Under the terms of the agreement, which was entered into in May of 2014, CytomX granted Bristol-Myers Squibb exclusive worldwide rights to develop and commercialize Probody therapeutics for up to four oncology targets. Bristol-Myers Squibb made an upfront payment of $50 million to CytomX in 2014, and provides research funding over the course of the research term. Upon the selection of the third and fourth targets, Bristol-Myers Squibb pays CytomX selection payments. CytomX is also eligible to receive additional preclinical payments and up to $298 million in future development, regulatory and sales milestone payments for each collaboration target, as well as tiered royalties rising from mid-single digit to low double digits on net sales of each product commercialized by Bristol-Myers Squibb.

On December 4, 2016 ArQule, Inc. (Nasdaq: ARQL) reported that preclinical data was presented on Bruton’s tyrosine kinase (BTK) inhibitor, ARQ 531, in a poster presentation by The Ohio State University at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The presentation highlighted preclinical studies of ARQ 531 in Chronic Lymphocytic Leukemia (CLL) (Press release, ArQule, DEC 4, 2016, View Source [SID1234516920]). ARQ 531 is an investigational, orally bioavailable, potent and reversible BTK inhibitor.

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!

ARQ 531 Poster Presentation Highlights

Title: The Bruton’s Tyrosine Kinase (BTK) Inhibitor ARQ 531 Effectively Inhibits Wild Type and C481S Mutant BTK and Is Superior to Ibrutinib in a Mouse Model of Chronic Lymphocytic Leukemia

Multi-targeted inhibition of cytokine, chemokine, and BCR pathways by ARQ 531 decreases activation, migration, and viability of CLL cells.
Unlike ibrutinib, ARQ 531 inhibits activation of C481S mutated BTK variants and maintains cytotoxicity in ibrutinib resistant clones.
ARQ 531 demonstrates remarkable efficacy in an in vivo TCL1 adoptive transfer model, improving survival to a greater extent than ibrutinib and restoring granulocyte production.
The company plans to complete preclinical studies and file an Investigational New Drug (IND) application in early 2017 to begin clinical testing later in the year.
The presentation can be viewed at View Source

"Irreversible kinase inhibitors directed at BTK have really changed the landscape of CLL but at extended follow up, we are beginning to see a subset of high risk patients who are relapsing," said Dr. Jennifer Woyach, M.D., of The Ohio State University College of Medicine. "Small molecules that target BTK that are not dependent upon the C481 site represent an exciting option for future clinical trials. We are excited to be working with ArQule on this project and look forward to initiating the first in man study with ARQ 531."

"We began our BTK discovery program in 2011 which ultimately lead to the selection of ARQ 531, a potent reversible inhibitor of both wild type and mutant BTK," said Dr. Giovanni Abbadessa, M.D., PhD., Vice President of Clinical Development, Translational Medicine and Medical Affairs at ArQule. "With the recent emergence in 2015 of BTK resistance we concentrated our efforts in this growing CLL patient population. We are pleased to be working with The Ohio State University to finish preclinical studies on this exciting program. We remain on track to file an IND application early next year."

About BTK and ARQ 531

ARQ 531 is an investigational, orally bioavailable, potent and reversible Bruton’s tyrosine kinase (BTK) inhibitor. Biochemical and cellular studies have shown that ARQ 531inhibits both the wild type and C481S-mutant forms of BTK. The C481S mutation is a known emerging resistance mechanism for first generation irreversible BTK inhibitors. ARQ 531 has high oral bioavailability as well as good ADME, pharmacokinetic and metabolic properties. The company plans to file an IND for ARQ 531 in early 2017. BTK is a therapeutic target that has been clinically proven to inhibit B-cell receptor signaling in blood cancers.

On December 4, 2016 Acceleron Pharma Inc. (NASDAQ:XLRN) and Celgene Corporation (NASDAQ:CELG), reported preliminary Phase 2 results from the ongoing three-month base and long-term extension studies with investigational drug luspatercept in patients with lower risk myelodysplastic syndromes (MDS) at the 58th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, California (Press release, Acceleron Pharma, DEC 4, 2016, View Source [SID1234516906]). Luspatercept is being developed as part of the global collaboration between Acceleron and Celgene.

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!

"We are encouraged by the additional luspatercept data from the ongoing Phase 2 studies," said Michael Pehl, President, Hematology and Oncology for Celgene. "These data further support luspatercept’s potential in treating a broader spectrum of MDS patients. We are evaluating opportunities to expand our clinical program to include additional MDS patient populations, as we advance our Phase 3 MEDALIST trial in RS+ patients."

Luspatercept Phase 2 Data in First-line, ESA treatment-naive MDS Patients

In lower-risk MDS patients who have not received prior treatment with an erythropoiesis-stimulating agent (ESA) and have erythropoietin (EPO) levels ≤ 500 IU, luspatercept three-month base study data demonstrated encouraging rates of transfusion independence and International Working Group Hematologic Improvement – Erythroid (IWG HI-E) response criteria.

Transfusion Burden IWG HI-E, n/N (%) RBC-TI, n/N (%)
Base N=64 Extension N=42 Base N=49 Extension N=28
All 12/20 (60%) 13/16 (81%) 9/12 (75%) 8/10 (80%)
Low Transfusion Burden 6/13 (46%) 8/11 (73%) 5/5 (100%) 5/5 (100%)
High Transfusion Burden 6/7 (86%) 5/5 (100%) 4/7 (57%) 3/5 (60%)

Luspatercept Phase 2 Data in Ring Sideroblast Positive (RS+) and Negative (RS-) in MDS Patients

In patients with EPO levels < 200, response rates were similar in both RS+ and RS- patients
In the patients with EPO levels ≥ 200 to ≤ 500, luspatercept response rates remained encouraging in those patients who are RS+

Baseline EPO
(U/L)

RS
Status
IWG HI-E, n/N (%) RBC-TI, n/N (%)

Base
N=64*

Extension
N=42*

Base
N=49*

Extension
N=28*

< 200 RS+ 18/29 (62%) 19/23 (83%) 13/19 (68%) 10/14 (71%)
RS- 2/5 (40%) 3/3 (100%) 1/4 (25%) 1/2 (50%)
≥ 200 to ≤ 500 RS+ 5/11 (46%) 7/8 (88%) 3/9 (33%) 3/5 (60%)
RS- 0/3 (0%) 0/1 (0%) 2/2 (100%) 1/1 (100%)
*Table includes both ESA refractory and ESA naïve patients. Subjects treated at dose levels ≥ 0.75 mg/kg.

Luspatercept Phase 2 Safety Data

The majority of adverse events (AEs) were grade 1 or 2
There were four grade 3/serious AEs possibly or probably related to study drug as of November 28, 2016: blast cell count increase, myalgia, worsening of general condition, progression to AML
Adverse events at least possibly related to study drug that occurred in at least 2 patients during studies were diarrhea, fatigue, headache, hypertension, arthralgia, bone pain, injection site erythema, myalgia and peripheral edema.
Luspatercept is an investigational product that is not approved for use in any country.

The MEDALIST Trial, a global Phase 3 study in patients with very low, low, or intermediate risk, MDS with ring sideroblasts who require red blood cell transfusions, is currently enrolling.

The poster presentation of the ongoing Phase 2 studies is available on Acceleron’s website (www.acceleronpharma.com) under the Science tab.