On May 8, 2017 AVEO Oncology (NASDAQ: AVEO) reported that it received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for U.S. patent application number 14/653,684, entitled "notch binding agents and antagonists and methods of use thereof." Allowed under the application are composition of matter and method of use claims related to the Company’s humanized anti-Notch 3 antibodies, including AV-353. The U.S. patent scheduled to issue from this application will expire December 19, 2032, with the potential for extension to December 19, 2037.

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AV-353 is a potent inhibitory antibody specific to Notch 3, a pathway implicated in multiple diseases, including Pulmonary Arterial Hypertension (PAH). In preclinical studies, AV-353 has demonstrated the ability to potentially reverse the PAH disease phenotype, which would represent a potential disease-modifying approach to treatment. PAH is a rare and life-threatening disorder that affects approximately 250,000 people worldwide and is caused by enlargement of the arterial walls in small arteries between the heart and the lungs, resulting in restricted blood flow.

"AV-353’s disease modifying properties have the potential to transform the future treatment of PAH, a debilitating disorder for which current therapies target only symptoms," said Michael Bailey, president and chief executive officer of AVEO. "AV-353’s selectivity and high affinity to Notch 3, which are unique from other approaches targeting the Notch pathway, have enabled us to build an increasingly broad patent estate around the program. Consistent with our strategic focus on oncology, we continue to engage with potential partners around the worldwide development of this important therapeutic candidate."

On May 8, 2017 Array BioPharma Inc. (Nasdaq: ARRY) reported that it has entered into a clinical trial collaboration agreement with Merck (known as MSD outside the United States and Canada) to investigate the safety and efficacy of Array’s MEK inhibitor, binimetinib, with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in metastatic colorectal cancer patients with microsatellite stable tumors (MSS CRC) (Press release, Array BioPharma, MAY 8, 2017, View Source [SID1234518886]).

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The companies are entering into this collaboration based on the growing body of preclinical and clinical evidence that the immune activity of an anti-PD-1 therapy, such as KEYTRUDA, can be enhanced when combined with a MEK inhibitor, such as binimetinib.

"Array is excited to announce this partnership with Merck, an established leader in the field of immuno-oncology," said Ron Squarer, Chief Executive Officer, Array BioPharma. "Given the synergistic activity we have seen with our MEK inhibitor when combined with anti-PD-1 therapy in preclinical models, and based on emerging clinical data, we are optimistic that this combination holds great potential for cancer patients."

Under the terms of the agreement, Array and Merck will collaborate on a clinical trial to investigate the safety and efficacy of the combination of binimetinib with KEYTRUDA, in MSS CRC patients. The trial is expected to establish a recommended dose regimen of binimetinib and KEYTRUDA, as well as explore the preliminary anti-tumor activity of several novel regimens. The study is expected to begin in the second half of 2017. Results from this first study will be used to determine optimal approaches to further clinical development of these combinations.

The collaboration agreement is between Array BioPharma and Merck, through a subsidiary. Under the agreement, the trial will be sponsored by Merck. Additional details of the collaboration were not disclosed.

About Colorectal Cancer
Worldwide, colorectal cancer is the third most common type of cancer in men and the second most common in women, with approximately 1.4 million new diagnoses in 2012. Of these, nearly 750,000 were diagnosed in men, and 614,000 in women. Globally in 2012, approximately 694,000 deaths were attributed to colorectal cancer. In the U.S. alone, an estimated 135,430 patients will be diagnosed with cancer of the colon or rectum in 2017, and approximately 50,000 are estimated to die of their disease. There is wide variation in 5-year survival rates across the globe, with 5-year survival expected to be around 65% in the developed world and dropping to around 20% in some developing countries. The incidence of microsatellite stability in colorectal tumors varies by stage, with nearly 80% of early stage, resectable tumors and approximately 67% of advanced, metastatic tumors exhibiting MSS.

About Binimetinib
MEK is a key protein kinase in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Research has shown this pathway regulates several key cellular activities including proliferation, differentiation, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, such as melanoma, colorectal and thyroid cancers. Binimetinib is a late-stage small molecule MEK inhibitor which targets key enzymes in this pathway.

Binimetinib is being studied in clinical trials in advanced cancer patients, including the Phase 3 COLUMBUS trial in patients with BRAF-mutant melanoma and the Phase 3 BEACON CRC trial in patients with BRAF V600E-mutant colorectal cancer.

On May 6, 2017 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 14th International Symposium on MDS in Valencia, Spain (Press release, Acceleron Pharma, MAY 6, 2017, View Source [SID1234518875]). Luspatercept is being developed as part of the global collaboration between Acceleron and Celgene.

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"These positive data presented in lower-risk MDS confirm our optimism in new opportunities for luspatercept beyond our ongoing Phase 3 trials," said Michael Pehl, President, Hematology and Oncology for Celgene. "We are now planning a Phase 3 clinical trial to expand the development of luspatercept into this lower-risk MDS patient population."

"There is a high unmet medical need for a drug to treat patients earlier in the MDS treatment paradigm," said Habib Dable, President and CEO of Acceleron. "We continue to be motivated to find additional opportunities for luspatercept to treat anemia due to rare blood disorders and remain on track to initiate Phase 2 trials in myelofibrosis and non-transfusion dependent beta-thalassemia by year-end."

Luspatercept Phase 2 Data in First-Line, Lower-Risk MDS Patients

In lower-risk, erythropoiesis-stimulating agent (ESA)-naïve MDS patients, 48% (11/23) of patients treated with luspatercept achieved red blood cell transfusion independence (RBC-TI) and 51% (20/39) of patients achieved a clinically meaningful erythroid hematological improvement (HI-E) response per the International Working Group’s (IWG) criteria. The response rates were positive in patients treated with luspatercept in both ESA-naïve and prior ESA-treated patients.



IWG HI-E, N=82
n (%)

RBC-TI, N=56
n (%)
ESA-Naïve 20/39 (51%) 11/23 (48%)
Prior ESA 22/43 (51%) 11/33 (33%)

Luspatercept Phase 2 Data in RS+ and RS- Lower-Risk MDS Patients

In patients with baseline erythropoietin (EPO) levels ≤ 500 international units per liter (IU/L), RBC-TI and IWG HI-E response rates were positive in both ring sideroblast-positive (RS+) and -negative (RS-) patients.


Baseline
EPO (IU/L)
RS Status
IWG HI-E, N=82
n (%)

RBC-TI, N=56
n (%)
≤ 500 RS+ 30/46 (65%) 16/29 (55%)
RS- 6/14 (43%) 4/7 (57%)
> 500 RS+ 5/9 (56%) 2/9 (22%)
RS- 1/11 (9%) 0/9 (0%)
Unknown 0/2 (0%) 0/2 (0%)
*Table includes both ESA refractory and ESA naïve patients. Patients treated at dose levels ≥ 0.75 mg/kg.

Luspatercept Phase 2 Safety Data

The majority of adverse events (AEs) were grade 1 or 2. AEs at least possibly related to study drug that occurred in at least 3 patients during the studies were fatigue, headache, hypertension, diarrhea, arthralgia, bone pain, injection site erythema, myalgia, and edema peripheral. Grade 3 non-serious AEs possibly or probably related to study drug were ascites, blast cell count increase, blood bilirubin increase, hypertension, platelet count increase, and pleural effusion. Grade 3 serious AEs possibly or probably related to study drug were general physical health deterioration and myalgia.

Luspatercept is an investigational product that is not approved for use in any country.

The oral presentation given at the 14th International Symposium on MDS is available on Acceleron’s website (www.acceleronpharma.com) under the Science tab.

Acceleron MDS Symposium Conference Call Information

Acceleron will host a conference call and live webcast to discuss data presented at the MDS Symposium and its first quarter operational and financial results on May 8, 2017, at 8:00 a.m. EDT. To participate by teleconference, please dial 877-312-5848 (domestic) or 253-237-1155 (international) and refer to the Acceleron Earnings Call.

To access the live webcast, please select "Events & Presentations" in the Investors/Media section on Acceleron’s website (www.acceleronpharma.com) at least 10 minutes beforehand to ensure time for any downloads that may be required.

An archived webcast recording will be available on the Acceleron website beginning approximately two hours after the event.

About the MDS Phase 2 Studies

Data from two Phase 2 studies were presented at the conference: the base study in which patients received treatment with luspatercept for three months and the long-term extension study in which patients may receive treatment with luspatercept for up to an additional five years. In both the three-month base study and the long-term extension study, lower-risk MDS patients were enrolled and treated with open-label luspatercept, dosed subcutaneously once every three weeks.

The outcome measures for the studies included the proportion of patients who had an erythroid response (IWG HI-E) or achieved RBC transfusion independence (RBC-TI). IWG HI-E was defined as hemoglobin increase ≥ 1.5 g/dL sustained for ≥ 8 weeks in patients with < 4 units RBC / 8 weeks transfusion burden at baseline and hemoglobin levels below 10 g/dL. For patients with a ≥ 4 units RBC / 8 weeks transfusion burden at baseline, erythroid response was defined as a reduction of ≥ 4 units RBC sustained for ≥ 8 weeks. RBC-TI was defined as no RBC transfusions for ≥ 8 weeks in patients with a ≥ 2 units RBC / 8 weeks baseline transfusion burden.

About Luspatercept

Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members in the transforming growth factor-beta superfamily involved in the late stages of erythropoiesis (red blood cell production). Luspatercept regulates late-stage erythrocyte (red blood cell) precursor cell differentiation and maturation. This mechanism of action is distinct from that of erythropoietin (EPO), which stimulates the proliferation of early-stage erythrocyte precursor cells. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. Acceleron and Celgene are enrolling Phase 3 clinical trials that are designed to evaluate the safety and efficacy of luspatercept in patients with myelodysplastic syndromes (the "MEDALIST" study) and in patients with beta-thalassemia (the "BELIEVE" study). For more information, please visit www.clinicaltrials.gov.

On May 5, 2017 TG Therapeutics, Inc. (NASDAQ:TGTX) reported its financial results for the first quarter ended March 31, 2017 and recent company developments (Press release, TG Therapeutics, MAY 5, 2017, View Source [SID1234518881]).

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, stated, "2017 has been an exciting and busy year for us already, with both the announcement of the positive topline data from the Phase 3 GENUINE trial and the subsequent $89M capital raise. Having achieved these two important milestones, we believe the company is well positioned for a successful remainder of the year and beyond." Mr. Weiss continued, "We plan to focus our attention on advancing our clinical programs towards success and look forward to a data and news rich summer where we will be presenting a more detailed analysis of the GENUINE data, announcing the interim analysis data from both our UNITY-CLL Phase 3 trial and UNITY-DLBCL trial, as well as commencing our global Phase 3 program in MS."

Recent Developments and Highlights

Received orphan drug designation for the combination of TG-1101 and TGR-1202 for the treatment of CLL and DLBCL
Announced the publication of clinical data from the Phase 1/2 trial of TG-1101 monotherapy in the British Journal of Haematology
Announced positive topline data from Phase 3 GENUINE study of TG-1101 in combination with ibrutinib in patients with high risk CLL
Solidified the Company’s balance sheet raising approximately $89M in gross proceeds through the combination of a public offering and an at-the-market sales facility
Presented preclinical data on our anti-PD-L1 monoclonal antibody at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting
Presented preliminary results, including B-cell depletion data from ongoing Phase 2 study of TG-1101 in patients with MS at the American Academy of Neurology (AAN) annual meeting
Reaffirming 2017 Milestones

Present updated clinical data including the full Phase 3 GENUINE data at a major medical meeting in the first half of 2017
Present clinical data from the Phase 2 Multiple Sclerosis (MS) trial
Initiate a global Phase 3 trial in MS
Complete the first interim analysis in the UNITY-CLL Phase 3 trial
Complete the first interim analysis in the UNITY-DLBCL trial
Meet with the FDA to review the Phase 3 GENUINE data and discuss suitability for filing for accelerated approval
Present new and updated data from ongoing trials at various scientific meetings throughout the year, including the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December
Financial Results for the First Quarter 2017

Cash Position: Cash, cash equivalents, investment securities, and interest receivable were $109.5 million as of March 31, 2017.

R&D Expenses: Research and development (R&D) expense was $22.7 million for the three months ended March 31, 2017 compared to $11.6 million for the three months ended March 31, 2016. Included in research and development expense for the three months ended March 31, 2017 and 2016, was $5.3 million and $4.3 million, respectively, of manufacturing and CMC expenses for Phase 3 clinical trials and potential commercialization. The increase in R&D expenses for the three months ended March 31, 2017, is primarily due to the ongoing clinical development programs and related manufacturing costs for TG-1101 and TGR-1202.

G&A Expenses: General and administrative (G&A) expense was $5.0 million for the three months ended March 31, 2017 as compared to $2.4 million for the three months ended March 31, 2016. The period-over-period increase in G&A expenses for the three months ended March 31, 2017 relates primarily to non-cash compensation expenses related to equity incentive grants recognized during 2017. Other G&A expenses for the three months ended March 31, 2017 remained relatively flat compared to the first quarter of 2016, and we expect G&A expenses to remain relatively constant through the remainder of 2017.

Net Loss: Net loss was $27.7 million for the three months ended March 31, 2017 compared to a net loss of $13.8 million for the three months ended March 31, 2016.

Financial Guidance: The Company believes its cash, cash equivalents, investment securities, and interest receivable of $109.5 million as of March 31, 2017 will be sufficient to fund the Company’s planned operations through 2018.