Tusk Therapeutics presents data on to its anti-CD25 programme at AACR Annual Meeting 2018

On April 18, 2018 Tusk Therapeutics, an immuno-oncology company focused on developing immune-modulating therapeutics by targeting immune cells in cancer, presented pre-clinical proof-of-concept data generated in collaboration with Cancer Research UK and University College London (UCL), relating to its anti-CD25 programme at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper).

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Tusk Therapeutics presented data on its first-in-class anti-CD25 programme that has entered pre-clinical development. The antibody depletes regulatory T cells (Tregs) while preserving IL-2 binding and signalling on effector T cells (Teffs). Tusk, together with the University College London research group led by Dr. Sergio Quezada, has shown that targeting Tregs with non-IL-2 blocking anti-CD25 antibodies creates highly potent anti-tumour responses in monotherapy and combination therapy. Proof-of-concept has been established in multiple pre-clinical models.

Tregs, a subpopulation of T cells, are key players in the suppressive tumour microenvironment (TME). Tregs in the TME hinder the body’s ability to control the growth of cancerous cells and their presence is correlated with a worse prognosis in multiple cancers. Effective Treg targeting has been a topic in the cancer field for several years and Tusk’s approach demonstrates it is possible to deplete Tregs in solid tumour which leads to tumour control. Tusk’s antibody is specifically selected to preserve signalling of the IL-2 cytokine on effector cells which is a key regulator of immune-activation.

Commenting on the data, Luc Dochez, Chief Executive Officer of Tusk Therapeutics, said: "The data presented at AACR (Free AACR Whitepaper) demonstrate the unique mechanism of action of our anti-CD25 antibody. Unlike existing aCD25 antibodies our antibody has the ability to deplete Tregs without inhibiting effector cell responses. Based on the promising pre-clinical data, we believe that our anti-CD25 candidates will be an ideal combination partner for existing standard of care and immuno-oncology treatments."

​The data was presented as an oral presentation by Dr. Sergio Quezada, Group Leader and Cancer Research UK Senior Research Fellow at The UCL Cancer Institute, and Chairman of Tusk Therapeutics’ Scientific Advisory Board and in two posters, presented by the Tusk and UCL teams. Tusk Therapeutics’ first-in-class anti-CD25 antibody programme was built on novel biology discovered by Tusk Therapeutics in collaboration with Dr. Quezada and his team at UCL. Tusk Therapeutics, Cancer Research UK (via its Commercial Partnerships Team) and UCL announced in 2017, an exclusive licensing and collaboration deal to develop and commercialise antibody-based therapeutics against CD25.

Genocea Presents Data at AACR Annual Meeting Further Highlighting Advantages of ATLAS Platform in Identification of Neoantigens over in silico Methods

On April 18, 2018 Genocea Biosciences, Inc. (NASDAQ:GNCA), a biopharmaceutical company developing neoantigen cancer vaccines, reported highlights from its scientific presentations at the 2018 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR 2018), taking place April 14-18, 2018 in Chicago, IL (Press release, Genocea Biosciences, APR 18, 2018, View Source [SID1234525509]).

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Jessica Flechtner, Ph.D., Genocea’s chief scientific officer commented on the AACR (Free AACR Whitepaper) presentations: "We continue to generate data that demonstrate the versatility of our ATLAS platform. As the studies presented at AACR (Free AACR Whitepaper) indicate, ATLAS is a differentiator for Genocea – allowing us to do what in silico approaches cannot – to both identify and characterize neoantigens for use in personalized cancer vaccines. We believe that our ability to find stimulatory and inhibitory antigens during the neoantigen selection process combined with our capacity to explore mechanisms of inhibitory antigens in a murine model, may enable us to help cure cancer by pioneering next-generation cancer vaccines."

Summary of AACR (Free AACR Whitepaper) Poster #730, "Empirical neoantigen identification using the ATLAS platform across thousands of mutations and multiple tumor types highlights advantages over algorithmic prediction methods":

ATLAS enables identification of biologically relevant CD4+ and CD8+ T cell neoantigens in subjects in an unbiased manner, by using subjects’ own antigen-presenting cells (APCs) and T cells rather than predictive algorithms to identify and characterize T cell responses to all candidate neoantigens.
Neoantigen screening was performed on 23 individuals across eight tumor types with mutational burden ranging from 9 to 319 unique mutations.
Empiric identification of neoantigens derived from somatic mutations from each patient’s tumor independently of HLA type and without predictions resulted in the following observations:
ATLAS identified stimulatory neoantigens of both CD4+ and CD8+ T cells, which Genocea believes confirms the importance of including antigens of relevance for both T cell subsets in neoantigen vaccines;
There is little overlap between CD4+ and CD8+ T cell neoantigens; fewer than 2% of empirically confirmed neoantigens were shared between T cell subsets;
Prediction algorithms missed up to 69% of ATLAS-identified neoantigens, with only 2% of CD8+ neoantigens and 24% of CD4+ neoantigens accurately predicted;
The major histocompatibility complex (MHC) class I algorithm appeared to better predict CD4+, not CD8+, neoantigens;
ATLAS also identified inhibitory neoantigens of both CD4+ and CD8+ T cells
Inhibitory neoantigens outnumbered stimulatory neoantigens more than three-fold in aggregate in the screened patients;
Inhibitory antigens currently cannot be identified using in silico approaches.
Summary of Poster #5718, "ex vivo ATLASTM identification of neoantigens for personalized cancer immunotherapy in mouse melanoma":

The B16F10 mouse melanoma model was utilized to characterize neoantigens. More than 1,600 tumor-specific mutations (possible neoantigens) were interrogated using the ATLAS technology and CD8+ T cells from tumor-bearing C57BL/6 mice.
Similar to human neoantigen screens, mouse ATLAS (mATLAS) identified both stimulatory and inhibitory neoantigens:
99% of mutations identified using whole exome sequencing were screened;
68 stimulatory (4% of total mutations) and 57 inhibitory (3% of total mutations) neoantigens were identified.
NetMHCPan, a MHC-binding prediction algorithm, failed to identify the majority of mATLAS-identified neoantigens:
Only 2% of B16F10 neoantigens predicted by algorithms were empirically confirmed to be stimulatory antigens;
91% of stimulatory neoantigens empirically identified with mATLAS were not predicted;
6% of algorithm-predicted neoantigens were inhibitory.
These data demonstrate that inhibitory antigens can be identified in mouse models, allowing for future research into the mechanism of ATLAS-identified inhibitory responses and their relationship to stimulatory neoantigens in mediating tumor control.

OBI Pharma Announces FDA Clearance of OBI-3424 IND Application for A Phase I/II Study Targeting AKR1C3 Solid Tumors

On April 18, 2018 OBI Pharma, Inc., a Taiwan biopharma company (TPEx: 4174), reported that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for a Phase I/II study of OBI-3424, a first-in-class DNA alkylating agent that targets cancers that overexpress the aldo-keto reductase 1C3 (AKR1C3) enzyme (Press release, OBI Pharma, APR 18, 2018, View Source [SID1234525525]).

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OBI plans to enroll patients with local solid tumors, including hepatocellular carcinoma (HCC) and castrate-resistant prostate cancer (CRPC). OBI Pharma’s Chief Medical Advisor, Tillman Pearce, M.D., noted, "This clinical trial intends to verify the safety and preliminary activity profile of OBI-3424, a novel first-in-class prodrug of a DNA alkylating cancer therapeutic that is selectively activated by AKR1C3, an enzyme that is overexpressed in a variety of solid and liquid tumors. We are delighted to conduct this first-in-man clinical trial at the University of Texas M.D. Anderson Cancer Center and The James Cancer Hospital and Solove Research Institute of Ohio State University, two of America’s leading academic oncology research institutions".

Amy Huang, General Manager of OBI Pharma, added, "OBI Pharma is proud to further develop our unique targeted cancer pipeline, including targets like the Globo series and AKR1C3. OBI-3424 enhances OBI’s pipeline in solid and liquid tumors for cancer patients who over-express AKR1C3. OBI is taking a first-step towards testing the safety and initial efficacy of a new class of AKR1C3 targeted therapy. We are excited to develop novel targeted therapeutics in the fight against cancers of unmet need."

About OBI-3424

OBI-3424 is a first-in-class novel small-molecule prodrug that selectively targets cancers overexpressing the enzyme aldo-keto reductase 1C3 (AKR1C3), and selectively releases a potent DNA alkylating agent in the presence of the AKR1C3 enzyme. This selective mode of activation distinguishes OBI-3424 from traditional alkylating agents, such as cyclophosphamide and ifosfamide, which are non-selective.

AKR1C3 overexpression has been documented in a number of treatment-resistant and difficult-to-treat cancers including: hepatocellular carcinomas (HCC), castrate-resistant prostate cancer (CRPC), and T-cell acute lymphoblastic leukemia (T-ALL). AKR1C3 is highly expressed in up to 15 solid and liquid tumors.

Furthermore, individualized patient selection by staining for AKR1C3 overexpression by immunohistochemistry can be performed based on tumor biopsies or circulating tumor cells to identify patients with other tumor types most likely to respond to treatment with OBI-3424, and thus offering the possibility for a streamlined clinical development strategy.

OBI Pharma holds worldwide rights for OBI-3424 with the exception of the following countries, whose rights are held by Ascenta Pharma: China, Hong Kong, Macao, Taiwan, Japan, South Korea, Singapore, Malaysia, Thailand, Turkey, and India.

Numerate to join ATOM Consortium to Rapidly Accelerate Preclinical Drug Development

On April 18, 2018 Computational drug design company Numerate reported that it has signed a letter of intent to join an open consortium of scientists staffed from two U.S. national laboratories, industry, and academia working to transform drug discovery and development into an approach that is rapid, integrated and with better patient outcomes (Press release, Numerate, APR 18, 2018, View Source [SID1234525510]).

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Accelerating Therapeutics for Opportunities in Medicine (ATOM) formed in October 2017 with the goal of reducing preclinical drug discovery from six years to just one, using cancer as the exemplar disease.

ATOM is integrating high-performance computing and biological, chemical, preclinical, and clinical data from public and industry sources to create an active learning platform that considers all aspects of drug discovery and pharmacology. ATOM will integrate emerging high-fidelity, data-rich experimental technologies, and cutting-edge software into the approach.

"This will create an ecosystem which will foster the rapid and dynamic collaboration needed to advance precision medicine and tremendously benefit patients," wrote Guido Lanza, president and CEO of Numerate, and Brandon Allgood, CTO, in the letter signed April 3, 2018.

"Our organization’s business priorities and directions are strongly aligned with the fundamental elements of ATOM … and we look forward to outlining the specific contributions we can make to the ATOM consortium as collaborators," they wrote.

John Baldoni, ATOM founder and governing board co-chair, and senior vice president for R&D at GSK, said Numerate is well-known for its innovative software approach to drug discovery.

"This collaboration provides Numerate with extensive and unique data sources and computer power with which they can optimize their drug discovery algorithms," Baldoni said. "This letter of intent signals how cutting-edge private-sector organizations can benefit in this public/private consortium."

Numerate joins the founding members of ATOM: GSK, the National Cancer Institute’s Frederick National Laboratory for Cancer Research (FNLCR), the University of California, San Francisco (UCSF), and the Department of Energy/National Nuclear Security Administration (NNSA)’s Lawrence Livermore National Laboratory (LLNL), which is contributing supercomputer resources and cognitive simulation expertise to the ATOM consortium. ATOM headquarters is located in the Mission Bay neighborhood of San Francisco.

ATOM seeks other organizations to join the consortium to bring their expertise into this new environment.

"We are excited to see the addition of industry leaders to the consortium and to the effort to bring effective new drugs to cancer patients more rapidly," said Eric Stahlberg, director of high performance computing at the Frederick National Laboratory.

The partners agree to work together to develop, test, and validate a multidisciplinary approach to drug discovery where science, technology and engineering, supercomputing simulations, data science, and artificial intelligence are integrated into a drug-discovery platform, ultimately to be shared with the drug development community at large.

Abbott Reports First-Quarter 2018 Results

On April 18, 2018 Abbott (NYSE: ABT) reported financial results for the first quarter ended March 31, 2018 (Press release, Abbott, APR 18, 2018, View Source [SID1234525493]).

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First-quarter worldwide sales of $7.4 billion increased 16.7 percent on a reported basis and 6.9 percent on an organic* basis.
Reported diluted EPS from continuing operations under GAAP was $0.23 in the first quarter.
Adjusted diluted EPS from continuing operations, which excludes specified items, was $0.59, at the upper end of Abbott’s previous guidance range.
Abbott projects full-year 2018 diluted EPS from continuing operations of $1.23 to $1.33 on a GAAP basis1. Projected full-year adjusted diluted EPS from continuing operations remains $2.80 to $2.90, reflecting 14.0 percent growth at the midpoint.
In January, Abbott announced U.S. FDA approval for magnetic resonance (MR)-conditional labeling for its Quadra AssuraTM and Quadra Assura MPTM cardiac resynchronization therapy defibrillator (CRT-D) devices and its Fortify AssuraTM implantable cardioverter defibrillator (ICD). With these approvals, Abbott has MR-conditional labeling for its suite of pacemaker, ICD and CRT-D devices.
In January, Abbott announced that FreeStyle Libre, Abbott’s revolutionary sensor-based continuous glucose monitoring system, is now available and approved for coverage by the U.S. Center for Medicare and Medicaid Services.
In March, Abbott announced clinical trial data from the MOMENTUM 3 study, which demonstrated that its HeartMate 3TM left ventricular assist device (LVAD) improved survival and clinical outcomes at two years for patients with advanced heart failure. The trial data will be submitted to the U.S. FDA to support consideration to expand the current HeartMate 3 indication to include long-term use.
"We’re off to a strong start to the year as we forecasted," said Miles D. White, chairman and chief executive officer, Abbott. "We’re particularly pleased with the continued strong growth in Medical Devices and improving performance in our Nutrition business."

* See note on organic growth below.

FIRST-QUARTER BUSINESS OVERVIEW
Note: Management believes that measuring sales growth rates on an organic basis is an appropriate way for investors to best understand the underlying performance of the business.

Organic sales growth:

Excludes prior year results for the Abbott Medical Optics (AMO) and St. Jude Medical vascular closure businesses, which were divested during the first quarter 2017;
Excludes the current and prior year results for Rapid Diagnostics, which reflect results for Alere Inc., which was acquired on Oct. 3, 2017; and
Excludes the impact of foreign exchange.
Following are sales by business segment and commentary for the first quarter:

Total Company

($ in millions)

% Change vs. 1Q17

Sales 1Q18

Reported

Organic

U.S.

Int’l

Total

U.S.

Int’l

Total

U.S.

Int’l

Total

Total *

2,675

4,715

7,390

15.1

17.6

16.7

5.0

8.0

6.9

Nutrition

758

998

1,756

3.8

9.5

7.0

3.8

5.5

4.7

Diagnostics

700

1,137

1,837

89.2

44.3

58.7

1.8

7.3

5.5

Established Pharmaceuticals

1,044

1,044

n/a

9.9

9.9

n/a

6.8

6.8

Medical Devices

1,209

1,535

2,744

6.4

22.0

14.6

6.9

11.7

9.4

* Total 2018 Abbott sales from continuing operations include Other Sales of $9 million.

n/a = Not Applicable.

Note: In order to compute results excluding the impact of exchange rates, current year U.S. dollar sales are multiplied or divided, as appropriate, by the current year average foreign exchange rates and then those amounts are multiplied or divided, as appropriate, by the prior year average foreign exchange rates.

First-quarter 2018 worldwide sales of $7.4 billion increased 16.7 percent on a reported basis. On an organic basis, worldwide sales increased 6.9 percent. Refer to tables titled "Non-GAAP Reconciliation of Adjusted Historical Revenue" for a reconciliation of adjusted historical revenue.

Nutrition

($ in millions)

% Change vs. 1Q17

Sales 1Q18

Reported

Organic

U.S.

Int’l

Total

U.S.

Int’l

Total

U.S.

Int’l

Total

Total

758

998

1,756

3.8

9.5

7.0

3.8

5.5

4.7

Pediatric

448

546

994

3.7

10.5

7.3

3.7

6.3

5.1

Adult

310

452

762

4.0

8.4

6.6

4.0

4.4

4.3

Worldwide Nutrition sales increased 7.0 percent on a reported basis in the first quarter, including a favorable 2.3 percent effect of foreign exchange, and increased 4.7 percent on an organic basis.

Worldwide Pediatric Nutrition sales increased 7.3 percent on a reported basis in the first quarter, including a favorable 2.2 percent effect of foreign exchange, and increased 5.1 percent on an organic basis. International sales increased 10.5 percent on a reported basis, including a favorable 4.2 percent effect of foreign exchange, and increased 6.3 percent on an organic basis, which was led by strong growth across several countries in Asia, including Greater China. In the U.S., continued above-market growth was led by market share gains in the infant nutrition category.

Worldwide Adult Nutrition sales increased 6.6 percent on a reported basis in the first quarter, including a favorable 2.3 percent effect of foreign exchange, and increased 4.3 percent on an organic basis. Worldwide sales growth was led by Ensure, Abbott’s market-leading complete and balanced nutrition brand, and Glucerna, Abbott’s market-leading diabetes-specific nutrition brand.

Diagnostics

($ in millions)

% Change vs. 1Q17

Sales 1Q18

Reported

Organic

U.S.

Int’l

Total

U.S.

Int’l

Total

U.S.

Int’l

Total

Total *

700

1,137

1,837

89.2

44.3

58.7

1.8

7.3

5.5

Core Laboratory

228

791

1,019

5.6

13.8

11.9

5.6

6.5

6.3

Molecular

39

79

118

(13.8)

17.5

5.0

(13.8)

11.4

1.3

Point of Care

110

31

141

0.6

23.0

4.8

0.6

18.6

4.0

Rapid Diagnostics *

323

236

559

n/m

n/m

n/m

n/m

n/m

n/m

* Rapid Diagnostics reflects sales from Alere Inc., which was acquired on Oct. 3, 2017. Organic growth rates above exclude results from the Rapid Diagnostics business.

n/m = Percent change is not meaningful.

Worldwide Diagnostics sales increased 58.7 percent on a reported basis in the first quarter. On an organic basis, sales increased 5.5 percent. Refer to tables titled "Non-GAAP Reconciliation of Adjusted Historical Revenue" for a reconciliation of adjusted historical revenue.

Core Laboratory Diagnostics sales increased 11.9 percent on a reported basis in the first quarter, including a favorable 5.6 percent effect of foreign exchange, and increased 6.3 percent on an organic basis, reflecting continued above-market growth driven by share gains in the U.S. and internationally.

Molecular Diagnostics sales increased 5.0 percent on a reported basis in the first quarter, including a favorable 3.7 percent effect of foreign exchange, and increased 1.3 percent on an organic basis. As expected, strong growth in infectious disease testing, Abbott’s core area of focus in the molecular diagnostics market, was partially offset by a planned scale down in other testing areas, primarily in the U.S.

Point of Care Diagnostics sales increased 4.8 percent on a reported basis in the first quarter, including a favorable 0.8 percent effect of foreign exchange, and increased 4.0 percent on an organic basis, led by strong international growth of Abbott’s i-STAT handheld system.

Rapid Diagnostics worldwide sales of $559 million were led by infectious disease testing, including strong flu and strep testing volumes in the U.S.

Established Pharmaceuticals

($ in millions)

% Change vs. 1Q17

Sales 1Q18

Reported

Organic

U.S.

Int’l

Total

U.S.

Int’l

Total

U.S.

Int’l

Total

Total

1,044

1,044

n/a

9.9

9.9

n/a

6.8

6.8

Key Emerging Markets

793

793

n/a

8.7

8.7

n/a

6.8

6.8

Other

251

251

n/a

13.9

13.9

n/a

6.6

6.6

Established Pharmaceuticals sales increased 9.9 percent on a reported basis in the first quarter, including a favorable 3.1 percent effect of foreign exchange, and increased 6.8 percent on an organic basis.

Key Emerging Markets comprise several countries that represent the most attractive long-term growth opportunities for Abbott’s branded generics product portfolio. Sales in these geographies increased 8.7 percent on a reported basis in the first quarter, including a favorable 1.9 percent effect of foreign exchange, and increased 6.8 percent on an organic basis. Sales growth was led by double-digit growth across several geographies, including India, China and Brazil.

Medical Device
Worldwide Medical Devices sales increased 14.6 percent on a reported basis in the first quarter. On an organic basis, sales increased 9.4 percent. Refer to tables titled "Non-GAAP Reconciliation of Adjusted Historical Revenue" for a reconciliation of adjusted historical revenue.

In Cardiovascular and Neuromodulation, worldwide sales growth in the first quarter was led by double-digit growth in Electrophysiology and Neuromodulation. Growth in Electrophysiology includes share gains from the recent U.S. launch of Abbott’s Confirm RxTM Insertable Cardiac Monitor (ICM), the world’s first and only smartphone-compatible ICM designed to help physicians remotely identify cardiac arrhythmias. In Heart Failure, sales growth was led by market uptake of Abbott’s HeartMate 3 system. In the quarter, Abbott announced clinical trial data from the MOMENTUM 3 study demonstrating that its HeartMate 3 LVAD improved survival and clinical outcomes at 2 years for patients with advanced heart failure. The trial data will be submitted to the U.S. FDA to support consideration to expand the current HeartMate 3 indication to include long-term use. Growth in Structural Heart was driven by MitraClip, Abbott’s market-leading device for the minimally-invasive treatment of mitral regurgitation. In March, Abbott announced MitraClip was granted national reimbursement in Japan, which enables greater access for patients to this life-altering therapy. In Neuromodulation, strong double-digit growth was led by a portfolio of recently launched products for the treatment of chronic pain and movement disorders.

In Diabetes Care, worldwide sales increased 44.2 percent on a reported basis in the first quarter, including a favorable 11.3 percent effect of foreign exchange, and increased 32.9 percent on an organic basis. Strong double-digit growth was led by FreeStyle Libre, Abbott’s revolutionary sensor-based continuous glucose monitoring (CGM) system, which removes the need for routine fingersticks2 for people with diabetes. During the quarter, Abbott announced that the FreeStyle LibreLink3,4 app is available in Europe for use with compatible smartphones, which allows people to access glucose data directly from their phones and eliminates the need to carry a separate scanning device.

ABBOTT’S FULL-YEAR EARNINGS-PER-SHARE GUIDANCE

Abbott projects 2018 diluted earnings per share from continuing operations under Generally Accepted Accounting Principles (GAAP) of $1.23 to $1.33.

Abbott forecasts net specified items for the full year 2018 of approximately $1.57 per share. Specified items include intangible amortization expense, acquisition-related expenses, charges associated with cost reduction initiatives and other expenses.

Excluding specified items, projected adjusted diluted earnings per share from continuing operations would be $2.80 to $2.90 for the full year 2018.

Abbott is issuing second-quarter 2018 guidance for diluted earnings per share from continuing operations under GAAP of $0.33 to $0.35. Abbott forecasts specified items for the second quarter 2018 of $0.37 primarily related to intangible amortization, acquisition-related expenses, cost reduction initiatives and other expenses. Excluding specified items, projected adjusted diluted earnings per share from continuing operations would be $0.70 to $0.72 for the second quarter.

ABBOTT DECLARES 377TH CONSECUTIVE QUARTERLY DIVIDEND

On Feb. 16, 2018, the board of directors of Abbott declared the company’s quarterly dividend of $0.28 per share. Abbott’s cash dividend is payable May 15, 2018, to shareholders of record at the close of business on April 13, 2018.

Abbott has increased its dividend payout for 46 consecutive years and is a member of the S&P 500 Dividend Aristocrats Index, which tracks companies that have annually increased their dividend for at least 25 consecutive years.