On May 8, 2017 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported the presentation of preclinical data demonstrating that CG’806, a highly potent pan-FLT3/BTK inhibitor, exerts compelling activity against acute myeloid leukemia (AML) cells harboring mutant forms of FLT3 and eradicates AML tumors in a murine xenograft model (Press release, Aptose Biosciences, MAY 8, 2017, View Source;p=RssLanding&cat=news&id=2270752 [SID1234518895]). The data were presented in a poster on Sunday, May 7, 2017 at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Conference Hematologic Malignancies: Translating Discoveries to Novel Therapies, held May 6-9 in Boston, MA.

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The poster, entitled CG’806, a first-in-class FLT3/BTK inhibitor, exerts superior potency against AML cells harboring ITD, TKD and gatekeeper mutated FLT3 or wild-type FLT3, demonstrated the superior potency of CG’806, relative to competitive agents, against hematologic malignancy cell lines driven by various WT or mutant forms of FLT3. In addition, once daily oral dosing of CG’806 in a murine model achieved sustained micromolar plasma concentration over a 24hr period, and was accompanied by complete elimination of AML FLT3-ITD tumors in the absence of toxicity.
Results were presented by Weiguo Zhang, M.D., Ph.D., Assistant Professor of Leukemia at The University of Texas MD Anderson Cancer Center, for a research team led by Michael Andreeff, M.D., Ph.D., Professor of Leukemia.

"Given the potency of CG’806 against all of the mutant forms of FLT3 AML and the ability to eradicate AML tumors in murine xenograft models, CG’806 has demonstrated the potential to be superior to other FLT3 inhibitors and is beginning to differentiate itself as a targeted treatment for AML," commented William G. Rice, Ph.D., Chairman and Chief Executive Officer of Aptose. "We believe CG’806 has the potential to become the best-in-class FLT3 inhibitor, and our internal efforts now are focused on delivering CG’806 to AML patients as soon as practicable."

CG’806 and competitor FLT3 inhibitors were tested for potency to kill a series of isogenic cells, in which a specific form (WT or mutant) of FLT3 drove survival and proliferation of cells. Compared to second-generation FLT3 inhibitors (quizartinib, gilteritinib, or crenolanib), CG’806 showed more pronounced anti-proliferative effects in leukemia cells with the ITD mutation, D835 mutations, the ITD plus F691I/Y842D/D835 mutations, or in FLT3 wild-type cells. The IC50s were 0.17, 0.82, 9.49, 0.30, 8.26, 9.72, and 0.43 nM for human FLT3-ITD mutated AML cells MV4-11 (FLT3-ITD) and MOLM13 (FLT3-ITD), murine leukemia Ba/F3 (FLT3-WT), Ba/F3 (FLT3-ITD), Ba/F3 (FLT3-D835Y), Ba/F3 (FLT3-ITD+D835Y), and Ba/F3 (FLT3-ITD+F691L) cells, respectively. CG’806 triggered profound apoptosis in cell lines harboring FLT3-ITD mutations and suppressed FLT3 and its downstream MAPK/AKT signaling. Moreover, CG’806 demonstrated in vivo tumor eradication without toxicity when administered orally, once daily for 14 days as a single agent in the MV4-11 AML murine xenograft model, and demonstrated sustained micromolar plasma drug levels in mice after a single oral administration.

The presentation will be published in the AACR (Free AACR Whitepaper) Hematologic Malignancies Conference Proceedings. The poster can also be accessed here or at the Publications & Presentations section of the Aptose website, www.aptose.com.

About CG’806
CG ‘806 is a once daily, oral, first-in-class pan-FLT3/BTK inhibitor. This small molecule demonstrates potent inhibition of mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the Cys481Ser mutant of the BTK enzyme, as well as other oncogenic kinases operative in B cell malignancies, suggesting CG’806 may be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.

On May 8, 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, Celgene, MAY 6, 2017, View Source [SID1234518896]). 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 4, 2017 Alligator reported that it will host a live webcast for analysts, investors and media on Friday, 5 May 2017, at 13:30 CET to discuss the data (Press release, Alligator Bioscience, MAY 4, 2017, View Source [SID1234538690]).

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ADC-1013, licensed to Janssen Biotech Inc., was shown to induce synergistic anti-tumor effects in combination with PD-1 receptor blockade in a pre-clinical bladder cancer model. Moreover, ADC-1013 indicated the potential to augment the effect of cancer vaccines in a lymphoma model.

"The new data supports that ADC-1013 may act synergistically with other immunotherapies, notably PD-1 checkpoint blockade and cancer vaccines, and holds great promise for the clinical programme." says Per Norlén, CEO at Alligator Bioscience.

The ATOR-1015 mechanism of action was confirmed in vitro and in vivo, and demonstrated tumor-directed immune activation. ATOR-1015 activated effector T-cells and suppressed regulatory T-cells in tumors, but not elsewhere in the body. Additional data included demonstration of anti-tumor effects in multiple tumor models and a strong data package on critical development properties including high solubility, thermal stability and manufacturing yield.

"The tumor-directed immune activation demonstrated by ATOR-1015 is remarkable. The predicted mechanism of action is confirmed and, based on the data, immune activation may be confined to the tumor area. The objective of adding clinical efficacy without adding significant toxicity seems to be within reach, and we are very much looking forward to initiating clinical development of ATOR-1015 in 2018," Per Norlén adds.

Webcast
The webcast can be accessed live on the link below and will be available on the company website 30 minutes after the broadcast.

View Source

Phone numbers for participants from:
UK: +442030089803
SE:+46856642696
US: +18558315946

For further information, please contact:
Per Norlén, CEO
Telephone: + 46 46 286 42 80 (switchboard)
E-mail: [email protected]

Rein Piir, VP Investor Relations at Alligator
Telephone: +46 708 537292
E-mail: [email protected]

Per-Olof Schrewelius, CFO
Telephone: +46 46 286 42 85
E-mail: [email protected]

This information is such information as Alligator Bioscience AB (publ) is obligated to disclose in accordance with EU market abuse regulation. The information was submitted, through the above contact persons, for publication on 4 May 2017 at 20:20 (CET).

Emergent BioSolutions has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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On May 4, 2017 NewLink Genetics Corporation (NASDAQ:NLNK), reported consolidated financial results for the first quarter 2017, as well as progress in its clinical development programs (Press release, NewLink Genetics, MAY 4, 2017, View Source [SID1234518856]).

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Recent Highlights:

Presented promising interim Phase 2 data of the IDO pathway inhibitor, indoximod, in combination with KEYTRUDA (pembrolizumab) for patients with advanced melanoma at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) plenary session on April 4, 2017
Presented a poster on NLG802, "A novel prodrug of indoximod with enhanced pharmacokinetic properties," at AACR (Free AACR Whitepaper) on April 4, 2017
Abstract accepted for presentation at the 2017 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) for a randomized double-blind, placebo-controlled Phase 2 study of indoximod in combination with the vaccine, PROVENGE (sipuleucel-T), for patients with metastatic castration resistant prostate cancer
Abstract accepted for presentation at the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting submitted by our partner on a Phase 1b dose-escalation study of navoximod (GDC-0919) in combination with TECENTRIQ (atezolizumab) in multiple solid tumors
"We believe that the emerging clinical data from NewLink Genetics and other companies are validating the fundamental hypothesis that the IDO pathway is central to immuno-suppression in cancer," said Charles J. Link, Jr. MD, Chairman, Chief Executive Officer and Chief Scientific Officer. "We have two distinct IDO pathway inhibitors advancing in the clinic, indoximod – which is wholly-owned by NewLink Genetics – and navoximod (GDC-0919), which is partnered to Genentech/Roche. In addition, we have a next-generation compound, a novel prodrug of indoximod, NLG802, which we expect to enter the clinic by the end of Q3 this year."

Guidance for remainder of 2017:

Metastatic castration resistant prostate cancer: Randomized, placebo-controlled Phase 2 clinical trial data to be presented at ASCO (Free ASCO Whitepaper) on Monday, June 5, 2017
Metastatic pancreatic cancer: Indoximod in combination with gemcitabine + ABRAXANE (nab-paclitaxel) Phase 2 trial to be presented at an upcoming medical meeting in the second half of 2017
Acute Myeloid Leukemia (AML): Interim data from a Phase 1b dose-escalation study of indoximod in combination with standard of care chemotherapy for patients with newly diagnosed AML to be presented second half of 2017
The Company announced that it intends to initiate a pivotal trial of indoximod plus anti-PD-1 inhibitors for patients with advanced melanoma by the end of 2017. The trial is expected to use an adaptive design that incorporates a brief dose confirmation stage followed by a definitive randomized stage.

"The clinical data for indoximod in advanced melanoma establishes the basis for this pivotal trial," said Nicholas N. Vahanian, MD, President and Chief Medical Officer.

Financial Results:

Cash Position: NewLink Genetics ended the first quarter with cash and cash equivalents totaling $118.2 million compared to $131.5 million for the year ending December 31, 2016.

We expect to end 2017 with approximately $75 million in cash and equivalents, which excludes any cash that may be received from financings or milestones.

R&D Expenses: Research and development expenses were $15.7 million in the first quarter of 2017 compared to $21.9 million in the first quarter of 2016. The decrease was due primarily to a $4.6 million decline in clinical trial and manufacturing-related spend, a decrease in personnel-related spend of $1.4 million, and a decrease in licensing and consulting fees of $1.0 million, offset by an increase in stock compensation expense of $822,000.

G&A Expenses: General and administrative expenses in the first quarter of 2017 were $8.2 million compared to $9.2 million in the first quarter of 2016. The decrease was due to a decline of $700,000 in consulting and legal fees, a decrease of $700,000 in personnel-related spend, offset by an increase in stock compensation expense of $437,000.

Net Loss: NewLink Genetics reported a net loss of $20.9 million or loss of $0.72 per diluted share for the first quarter of 2017 compared to a net loss of $23.7 million or loss of $0.82 per diluted share for the first quarter of 2016.

NewLink Genetics ended Q1 2017 with 29,219,661 shares outstanding.