On May 5, 2016 Acceleron Pharma Inc. (NASDAQ:XLRN), a clinical stage biopharmaceutical company focused on the discovery and development of novel therapeutic candidates that engage the body’s ability to rebuild and repair its own cells and tissues, reported a corporate update and reported financial results for the first quarter ended March 31, 2016 (Press release, Acceleron Pharma, MAY 5, 2016, View Source [SID:1234511968]).

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"In the first quarter, we continued to build momentum across our entire clinical pipeline, including the start of patient recruitment into our Phase 3 trials of luspatercept in MDS and beta-thalassemia with our partner Celgene," said John Knopf, Ph.D., Chief Executive Officer of Acceleron. "Receipt of the $15 million luspatercept milestone payment and the $140.3 million in net proceeds from our equity follow-on offering in January secured our ability to accelerate the pace of development of our wholly owned programs. To that end, we made significant progress toward the planned Phase 2 trial initiation of ACE-083 in facioscapulohumeral muscular dystrophy in the second half of 2016 and advancing our preclinical work in the area of fibrosis as well as the generation of new product candidates with our IntelliTrap platform."

FIRST QUARTER 2016 HIGHLIGHTS

Development Programs

Hematology

Acceleron received a $15 million milestone payment from collaboration partner Celgene related to the initiation of the luspatercept Phase 3 clinical trials. Luspatercept is being studied in two Phase 3 clinical trials in patients with myelodysplastic syndromes (MDS) or beta-thalassemia, both rare hematologic diseases.
Enrollment is ongoing for both of the Celgene-partnered Phase 3 studies of luspatercept. The MEDALIST trial in MDS is evaluating the efficacy and safety of luspatercept versus placebo in patients with anemia due to very low, low, or intermediate-risk MDS with ring sideroblasts (≥ 15%) who require red blood cell transfusions. The BELIEVE trial in beta-thalassemia is evaluating the efficacy and safety of luspatercept versus placebo in adults who require regular red blood cell transfusions. Luspatercept increases hemoglobin levels and is being developed to help patients reduce or eliminate their need for red blood cell (RBC) transfusions. Luspatercept has been granted Fast Track Designation from the FDA in both indications.
Ongoing Phase 2 trials of luspatercept in MDS and beta-thalassemia continue to generate longer-term safety and efficacy data. The Company expects to report updated results for these trials at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in June 2016.
Enrollment is underway in two additional Phase 2 patient cohorts evaluating luspatercept in low- or intermediate-risk MDS patients who are ring sideroblast negative or are eligible but have not yet received an erythropoietin-stimulating agent (ESA). Initial data from these additional MDS patient cohorts are expected by year-end.
Musculoskeletal Diseases

ACE-083 advancing toward the initiation of a Phase 2 trial in facioscapulohumeral muscular dystrophy (FSHD), a neuromuscular disorder, in the second half of 2016. ACE-083 is a locally acting agent designed to increase muscle mass and strength in the muscles in which it is administered.
We continue to make progress with ACE-2494 toward IND submission. ACE-2494, Acceleron’s first IntelliTrap molecule, is a systemic therapeutic designed to increase muscle mass and strength across a range of musculoskeletal diseases. Preclinical data in mice presented in 2015 showed that after 4 weeks of treatment, ACE-2494 generated substantial dose-dependent mean increases in muscle mass: 41% in rectus femoris, 53% in gastrocnemius, and 87% in pectoralis.
Oncology

Enrollment continues in Part 2 of the Phase 2 DART study, a randomized, double-blind study of dalantercept plus axitinib, compared to placebo plus axitinib in patients with advanced renal cell carcinoma. Dalantercept has been granted FDA Fast Track Designation for this indication.
Nephrology

Acceleron and Celgene assessing the opportunity for the development of sotatercept in the pre-dialysis chronic kidney disease (CKD) setting, and expect to provide an update in the second half of the year.
Corporate Updates

Raised $140.3 million of net proceeds in a follow-on public offering of common stock in January 2016 to advance wholly owned programs.
Financial Results

Cash position – Cash, cash equivalents and investments as of March 31, 2016 were $278.7 million. Net cash provided by operating activities in first quarter 2016 was $0.9 million. As of December 31, 2015 the Company had cash, cash equivalents and investments of $136.0 million. We believe that our existing cash, cash equivalents and investments, including the net proceeds of $140.3 million from our January 2016 common stock offering and the receipt of the $15.0 million Celgene milestone, will be sufficient to fund our projected operating requirements into the second half of 2019.
Revenue – Collaboration revenue for the first quarter was $18.2 million. License and milestone revenue was $15.1 million and includes the $15 million milestone payment received from Celgene related to luspatercept. Cost sharing reimbursement revenue from our Celgene partnership was $3.1 million and is related to expenses incurred by the Company in support of our partnered programs.
Costs and expenses – Total costs and expenses for the first quarter were $22.1 million. This includes R&D expenses of $16.2 million and G&A expenses of $5.9 million.
Other income, net – Other income for the first quarter was $9.0 million and includes an $8.7 million, non-cash, gain on marking our common stock warrant liability to market.
Net income – The Company posted a net income for the first quarter ended March 31, 2016 of $5.1 million.

AMG 714 is a human monoclonal antibody that binds to Interleukin-15 (IL-15), a cytokine molecule appearing early in the cascade of events that ultimately leads to inflammatory disease (Company Pipeline, Genmab, MAY 5, 2016, View Source [SID:1234511965]). AMG 714 was created by Genmab, as HuMax-IL15, under a collaboration with Amgen. Amgen has sub-licensed AMG 714 to a private company, Celimmune, LLC. Celimmune is developing AMG 714 for nonresponsive and refractory celiac disease.

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As part of its disciplined approach to funding innovation, Amgen carefully evaluates each internal program to determine which ones will receive much-coveted development funding (Company Web Page, Amgen, MAY 5, 2016, View Source [SID:1234511964]). Occasionally, a program will come along that does not make Amgen’s resource allocation cut in their intended indication but shows great promise in other areas. This presents a dilemma. Does Amgen provide more funding to explore this new promising area? Or, does Amgen put this asset in the hands of a committed outside party? In one recent deal, Amgen found some middle ground. When a particular molecule showed promise outside its intended area, an external team committed to moving it forward was located, while Amgen holds an option to take it back at a later stage. This is how startup company Celimmune came to develop AMG 714.

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A New Direction for AMG 714
AMG 714 is an anti-IL-15 monoclonal antibody that, following a series of rheumatoid arthritis and psoriasis studies, Amgen deprioritized. But there was a scientist outside of Amgen who hadn’t forgotten about anti-IL-15. Dr. Francisco Leon, a leading expert in the development of therapeutics for celiac disease, had been following this antibody and a growing body of scientific literature suggesting IL-15’s central role in refractory celiac disease and non-responsive celiac disease. Dr. Leon believed AMG 714 was a ready tool to test the hypothesis that blocking IL-15 could benefit celiac patients.

Praise in Partnership
Intrigued, Amgen struck an agreement with Celimmune, where Dr. Leon serves as CEO and chief medical officer. Amgen has licensed AMG 714 to Celimmune, which has rights to develop, manufacture and commercialize AMG 714 on a worldwide basis excluding Japan. In connection with the license, Celimmune granted Amgen an exclusive option to acquire Celimmune, and thus to reacquire AMG 714, upon completion of certain clinical studies in patients with celiac disease. "We do not hesitate in going on record to speak to the ‘best-in-industry’ licensing and post-transactional alliance management support we have been so privileged to experience to date with Amgen," said Ashleigh Palmer, Executive Chairman, Celimmune weeks after the deal’s completion.

"Dr. Leon’s conviction was so strong and his credentials so compelling, we couldn’t help but take notice," said Jeremy Grunstein, an executive director from Amgen’s Business Development team. "Celimmune provided not only an avenue to test this important hypothesis, but also a mechanism for Amgen to reprioritize the program in its pipeline. It’s the kind of deal structure we’d like to replicate."

Celiac disease is a chronic hereditary systemic autoimmune and inflammatory disease triggered by gluten consumption, which can cause gastrointestinal dysfunction and debilitating symptoms including nutritional malabsorption. Celimmune plans to initiate Phase 2 studies of AMG 714 for the treatment of diet non-responsive celiac disease and type II refractory celiac disease (RCD-II), an in situ small bowel T-cell lymphoma.

Dr. Leon stated, "Celiac disease is the only common autoimmune disease without any approved medication. Published literature demonstrates that a gluten-free diet is not a solution for the majority of patients. As such, Celimmune is delighted to have an opportunity to license an experimental therapeutic that will test one of the main hypotheses in the pathophysiology of celiac disease, namely that IL-15 plays a central role in RCD-II and non-responsive celiac disease."

Ashleigh Palmer, Celimmune’s Executive Chairman, concurred, "AMG 714 could be the first drug to market for a celiac indication and there’s room for growth. In addition to celiac, AMG 714 could have longer-term expansion and life cycle management opportunities within adjacent gastrointestinal autoimmune diseases."

With this deal, Amgen is still making a bet on external innovation, but with science that originated from within Amgen.

"This deal is win-win-win. If Celimmune is successful, both parties will be rewarded and most importantly, patients will be one step closer to the first medicine available for celiac disease," said Grunstein.

On May 05, 2016 Radius Health, Inc. ("Radius" or the "Company") (Nasdaq:RDUS), a science-driven biopharmaceutical company that is committed to developing innovative therapeutics in the areas of osteoporosis, oncology and endocrine diseases, reported its financial results for the first quarter ended March 31, 2016, and provided recent corporate highlights (Press release, Radius, MAY 5, 2016, View Source [SID:1234511959]). As of March 31, 2016, Radius had $439.8 million in cash, cash equivalents and marketable securities.

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"We are extremely pleased to have submitted our first New Drug Application to the U.S. FDA for abaloparatide-SC for the treatment of postmenopausal osteoporosis and our MAA is currently under review in Europe. In anticipation of our first potential launch, we are developing our commercial plans and building our marketing organization in the U.S.," said Robert Ward, President and Chief Executive Officer of Radius. "To maximize the potential of this new investigational drug outside the U.S., we are continuing our productive partnering discussions and anticipate entering into a marketing collaboration prior to a potential first commercial launch."

Pipeline Updates

Abaloparatide-SC

In March 2016, Radius submitted a new drug application ("NDA") in the United States for the treatment of postmenopausal women with osteoporosis. In November 2015, Radius submitted a marketing authorisation application ("MAA") to the European Medicines Agency ("EMA"), which subsequently was validated and is currently undergoing regulatory review. We anticipate a CHMP scientific opinion in 2016.

Abaloparatide-TD

Radius also is developing abaloparatide-transdermal, which it refers to as abaloparatide-TD, based on 3M’s patented Microstructured Transdermal System technology for potential use as a short wear-time transdermal patch. Radius commenced a human replicative clinical evaluation of the optimized abaloparatide-TD patch in December 2015 with the goal of achieving comparability to abaloparatide-SC.

RAD1901

In December 2014, Radius commenced a Phase 1 multicenter, open-label, two-part, dose-escalation study of RAD1901 in postmenopausal women with advanced estrogen receptor positive and HER2-negative breast cancer in the United States. The Phase 1 study is designed to evaluate escalating doses of RAD1901 in Part A. The Part B expansion cohorts allow for an evaluation of additional safety, tolerability and preliminary efficacy. In addition, in December 2015, Radius commenced a Phase 1 FES-PET study in patients with metastatic breast cancer in the European Union, which includes the use of FES-PET imaging to assess estrogen receptor occupancy in tumor lesions following RAD1901 treatment. Upon completion of these studies, we plan to submit to present the data at an appropriate scientific meeting.

Radius Expects the Following Upcoming Milestones

Abaloparatide-SC
Receive opinion from the Committee for Medicinal Products for Human Use regarding the EMA’s review of the abaloparatide-SC MAA
FDA determination on acceptance of NDA for abaloparatide-SC for filing in the second quarter of 2016
Enter into a collaboration for the potential commercialization of abaloparatide-SC prior to a commercial launch
Abaloparatide-TD
Planned mid-year update on human replicative study of optimized abaloparatide-TD patch
RAD1901
Initiate expansion cohorts for Phase 1 dose escalation study in metastatic breast cancer patients
Report results at upcoming scientific meeting
Radius Expects To Make Presentations at the Following Upcoming Conferences

Bank of America Merrill Lynch 2016 Healthcare Conference, May 10-12, 2016, in Las Vegas, NV.
Abstract presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting, June 3-7, 2016 in Chicago
"A Phase I study of RAD1901, an oral selective estrogen receptor degrader, in ER positive, HER2 negative, advanced breast cancer patients".
Recent Corporate Highlights

On April 1, 2016, at the 2016 Endocrine Society Annual Meeting, Dr. Felicia Cosman, an osteoporosis specialist and Professor of Medicine at Columbia University, presented "Abaloparatide-SC Significantly Reduces Vertebral and Nonvertebral Fractures and Increases BMD Regardless of Baseline Risk"

On April 15, 2016, three oral presentations were made from the abaloparatide-SC development program at the 2016 World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases meeting in Malaga, Spain:

Dr. Lorie Fitzpatrick, Chief Medical Officer of Radius Health presented "Effects of Abaloparatide on Vertebral, Non-Vertebral, Major Osteoporotic and Clinical Fracture Incidence in Postmenopausal Women with Osteoporosis: Results of the Phase 3 Active Trial"

Dr. Serge Ferrari, Professor of Medicine, Geneva University presented "Eighteen Months of Treatment with Abaloparatide Followed by Six Months of Treatment with Alendronate in Postmenopausal Women with Osteoporosis- Results of the ACTIVExtend Trial"

Dr. Eugene McCloskey, Professor in Adult Bone Diseases, University of Sheffield presented "Effect of Investigational Treatment Abaloparatide for Prevention of Major Osteoporotic Fracture or Any Fracture is Not Altered by Baseline Fracture Probability"
Abaloparatide-SC as a treatment for postmenopausal women with osteoporosis is an investigational product and its safety and efficacy have not been established.

First Quarter 2016 Financial Results

For the three months ended March 31, 2016, Radius reported a net loss of $40.5 million, or $0.94 per share, as compared to a net loss of $17.1 million, or $0.47 per share for the three months ended March 31, 2015. The increase in net loss for the three months ended March 31, 2016 as compared to the three months ended March 31, 2015 was primarily due to an increase in research and development and general and administrative expenses, partially offset by a decrease in interest expense and an increase in interest income.

Research and development expenses for the three months ended March 31, 2016 were $27.5 million, compared to $11.6 million for the same period in 2015. The increase for the 2016 period as compared to the 2015 period was primarily attributable to an increase in professional contract services costs associated with the development of RAD1901 to support a Phase 1 study in metastatic breast cancer that commenced in late 2014 and a Phase 2b study in postmenopausal vasomotor symptoms that commenced in December 2015. This increase was also a result of an increase in compensation expense, including stock-based compensation, due to an increase in headcount from March 31, 2015 to March 31, 2016.

General and administrative expenses for the three months ended March 31, 2016 were $13.6 million, compared to $4.8 million for the same period in 2015. The increase for the 2016 period as compared to the 2015 period was primarily attributable to an increase in professional support costs and legal fees, including the costs associated with increasing headcount and preparing for the potential commercialization of abaloparatide-SC, subject to a favorable regulatory review.

As of March 31, 2016, Radius had $439.8 million in cash, cash equivalents and marketable securities. Based upon Radius’ cash, cash equivalents and marketable securities balance, Radius believes that, prior to the consideration of revenue from the potential future sales of any of its investigational products, it has sufficient capital to fund its development plans, U.S. commercial scale-up and other operational activities into 2018.

About Abaloparatide

Abaloparatide is an investigational therapy for the potential treatment of women with postmenopausal osteoporosis who are at an increased risk for a fracture. Abaloparatide is a novel synthetic peptide that engages the parathyroid hormone receptor (PTH1 receptor) and was selected for clinical development based on its favorable bone building activity.

Abaloparatide has completed Phase 3 development for potential use as a daily self-administered injection (abaloparatide-SC). In the fourth quarter of 2015, Radius’ Marketing Authorisation Application (MAA) for abaloparatide-SC for the treatment of patients with postmenopausal osteoporosis was validated and is currently undergoing regulatory review by the European Medicines Agency (EMA). Radius submitted a New Drug Application (NDA) for abaloparatide-SC to the US Food and Drug Administration (FDA) at the end of the first quarter of 2016.

Radius also is developing abaloparatide-transdermal (abaloparatide-TD) based on 3M’s patented Microstructured Transdermal System technology for potential use as a treatment for osteoporosis.

About RAD1901

RAD1901 is a selective estrogen receptor down-regulator/degrader (SERD), which at high doses is being evaluated for potential use as an oral non-steroidal treatment for hormone-driven, or hormone-resistant, breast cancer. RAD1901 is currently being investigated for potential use in postmenopausal women with advanced estrogen receptor positive (ER+), HER2-negative breast cancer, the most common form of the disease. Studies completed to date indicate that the compound has the potential for use as a single agent or in combination with other therapies for the treatment of breast cancer.

RAD1901 also is being evaluated in a Phase 2b study at low doses for potential relief of the frequency and severity of moderate to severe hot flashes in postmenopausal women with vasomotor symptoms. Additional information on the clinical trial program of RAD1901 is available on www.clinicaltrials.gov.

RAD140

RAD140 is a non-steroidal selective androgen receptor modulator (SARM) that is currently in preclinical development for potential use in multiple indications including cancer. RAD140 resulted from an internal drug discovery program focused on the androgen receptor pathway, which is highly expressed in many breast cancers. Due to its receptor and tissue selectivity, potent oral activity and long half-life, RAD140 could have clinical potential in the treatment of conditions where androgen modulation may play a role.