Adaptate Biotherapeutics formed to develop antibody-based therapies that modulate gamma delta T-cells

On October 16, 2019 GammaDelta Therapeutics, a company focussed on harnessing the unique properties of gamma delta (γδ) T-cells to develop transformational immunotherapies, reported the formation of a spin-out company (Press release, GammaDelta Therapeutics, OCT 16, 2019, View Source [SID1234551806]): Adaptate Biotherapeutics. While GammaDelta Therapeutics’ primary goal is to develop γδ T-cell based cell therapy products, the new spin-out will build on GammaDelta’s knowledge to modulate γδ T-cell activity using therapeutic antibodies, with the potential to trigger an immune response against cancer.

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γδ T-cells are a distinct T-cell sub-type that respond to molecular patterns of distress and have been shown to have tremendous potential in treating cancer and other immunological disorders. GammaDelta Therapeutics was formed in 2016 to harness these properties, and since then has gained extensive knowledge of γδ T-cell biology developing a portfolio of investigational cell therapies poised to enter clinical development. In addition to gaining insight into cell growth and isolation, the company’s scientists have also discovered a number of potential drug targets and antibodies that have potential to modulate the activity of γδ T-cells in situ.

Adaptate Biotherapeutics has been formed to further develop these targets and antibodies for therapeutic purposes and advance them into clinical studies. Dr. Natalie Mount, currently Chief Scientific Officer of GammaDelta will move to Adaptate Biotherapeutics as Chief Executive Officer. The two companies will continue sharing their insights into γδ T-cell biology as they work towards developing different therapeutic modalities.

The founding of Adaptate Biotherapeutics has been made possible by investment from Abingworth and Takeda Pharmaceutical Company Limited. Takeda has a time-limited option to acquire Adaptate Biotherapeutics in the future. Both Adaptate Biotherapeutics and GammaDelta Therapeutics have also benefited from the support of King’s College London, the Francis Crick Institute and Cancer Research Technology.

Dr. Paolo Paoletti, CEO of GammaDelta Therapeutics, said: "γδ T-cells have tremendous therapeutic potential that is yet to be fully realised, and our fascinating journey has afforded additional opportunities beyond our main focus on cell therapy. Spinning out these activities to create Adaptate Biotherapeutics now enables the deployment of a focussed effort on non-cell therapy. Natalie has managed this effort as part of her role at GammaDelta Therapeutics, and she is the natural CEO to lead the efforts of Adaptate. I’m extremely pleased for this opportunity for Natalie and want to thank Raj Mehta, Director of BD, IP and Alliance Management at GammaDelta Therapeutics, for his work on the spin-out and Abingworth and Takeda for their continued support."

Dr. Natalie Mount, CEO of Adaptate Biotherapeutics, said: "I’m proud to be leading this new company, and excited by the potential we have to expand the therapeutic opportunities of γδ T-cells. Both companies continue to share the same ultimate goal of harnessing the power of these cells to improve the lives of patients and I look forward to driving Adaptate Biotherapeutics to achieve this goal."

Adaptate Biotherapeutics formed to develop antibody-based therapies that modulate gamma delta T-cells

On October 16, 2019 GammaDelta Therapeutics, a company focussed on harnessing the unique properties of gamma delta (γδ) T-cells to develop transformational immunotherapies, reported the formation of a spin-out company: Adaptate Biotherapeutics. While GammaDelta Therapeutics’ primary goal is to develop γδ T-cell based cell therapy products, the new spin-out will build on GammaDelta’s knowledge to modulate γδ T-cell activity using therapeutic antibodies, with the potential to trigger an immune response against cancer (Press release, GammaDelta Therapeutics, OCT 16, 2019, View Source [SID1234542309]).

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γδ T-cells are a distinct T-cell sub-type that respond to molecular patterns of distress and have been shown to have tremendous potential in treating cancer and other immunological disorders. GammaDelta Therapeutics was formed in 2016 to harness these properties, and since then has gained extensive knowledge of γδ T-cell biology developing a portfolio of investigational cell therapies poised to enter clinical development. In addition to gaining insight into cell growth and isolation, the company’s scientists have also discovered a number of potential drug targets and antibodies that have potential to modulate the activity of γδ T-cells in situ.

Adaptate Biotherapeutics has been formed to further develop these targets and antibodies for therapeutic purposes and advance them into clinical studies. Dr. Natalie Mount, currently Chief Scientific Officer of GammaDelta will move to Adaptate Biotherapeutics as Chief Executive Officer. The two companies will continue sharing their insights into γδ T-cell biology as they work towards developing different therapeutic modalities.

The founding of Adaptate Biotherapeutics has been made possible by investment from Abingworth and Takeda Pharmaceutical Company Limited. Takeda has a time-limited option to acquire Adaptate Biotherapeutics in the future. Both Adaptate Biotherapeutics and GammaDelta Therapeutics have also benefited from the support of King’s College London, the Francis Crick Institute and Cancer Research Technology.

Dr. Paolo Paoletti, CEO of GammaDelta Therapeutics, said: "γδ T-cells have tremendous therapeutic potential that is yet to be fully realised, and our fascinating journey has afforded additional opportunities beyond our main focus on cell therapy. Spinning out these activities to create Adaptate Biotherapeutics now enables the deployment of a focussed effort on non-cell therapy. Natalie has managed this effort as part of her role at GammaDelta Therapeutics, and she is the natural CEO to lead the efforts of Adaptate. I’m extremely pleased for this opportunity for Natalie and want to thank Raj Mehta, Director of BD, IP and Alliance Management at GammaDelta Therapeutics, for his work on the spin-out and Abingworth and Takeda for their continued support."

Dr. Natalie Mount, CEO of Adaptate Biotherapeutics, said: "I’m proud to be leading this new company, and excited by the potential we have to expand the therapeutic opportunities of γδ T-cells. Both companies continue to share the same ultimate goal of harnessing the power of these cells to improve the lives of patients and I look forward to driving Adaptate Biotherapeutics to achieve this goal."

Nicox: Third Quarter 2019 Business Update and Financial Highlights

On October 16, 2019 Nicox S.A. (Euronext Paris: FR0013018124, COX), an international ophthalmology company, reported a Q3 2019 business update and financial highlights, revenue and cash position for Nicox and its subsidiaries (the "Nicox Group"), as well as key upcoming milestones (Press release, NicOx, OCT 16, 2019, View Source [SID1234542293]).

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Michele Garufi, Chairman and Chief Executive Officer of Nicox, said, "The encouraging topline results from the Dolomites Phase 2 clinical trial of NCX 470 confirm the potential of both this product candidate and of our research platform, and set the stage for the next phase of Nicox’s development. Together with the NCX 4251 blepharitis trial, results of which we expect later in the fourth quarter, Nicox would have two advanced clinical programs in 2020."

Key Upcoming Milestone
NCX 4251 Phase 2 results: Clinical trial in patients with acute exacerbations of blepharitis continuing on track for topline data in Q4 of this year.
NCX 470 Phase 3: End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) expected in early 2020.
Third Quarter 2019 Business update
Nicox announced positive topline results of the Dolomites trial, its multicenter, U.S. Phase 2 safety and efficacy clinical study evaluating NCX 470, a novel second generation nitric oxide (NO)-donating bimatoprost analog, in patients with open-angle glaucoma or ocular hypertension. The 0.065% dose of NCX 470 demonstrated non-inferiority and statistical superiority to latanoprost 0.005%, the U.S. market leader in prostaglandin analog prescriptions.
The total number of prescriptions1 for VYZULTA in the U.S. exceeded 3,000 per week for the first time, with scripts in the third quarter of 2019 increasing by 10% compared to second quarter 2019 and by 127% compared to third quarter 2018.
Nicox amended its bond financing agreement with Kreos Capital and drew down €4 million in additional debt. Under the amended agreement, Nicox may draw down a further €3 million or €8 million on December 31, 2019 subject to notice to Kreos prior to December 16, 2019. Apart from the amended notice dates, payment dates and amounts mentioned here, all other contractual terms remain unchanged.
Nicox entered into an exclusive license agreement with Ocumension Therapeutics for the development and commercialization of NCX 4251, a novel, patented ophthalmic suspension of fluticasone propionate nanocrystals, in the Chinese market and received a €2.0 million upfront payment in July 2019.
In July 2019 we received a $3.0 million milestone payment from U.S. partner Eyevance Pharmaceuticals linked to completion by Nicox of regulatory and manufacturing responsibilities concerning ZERVIATE (cetirizine ophthalmic solution), 0.24% in the U.S. From now on, all manufacturing and regulatory responsibilities, together with decisions on launch timing, lie with Eyevance. Eyevance has informed Nicox that the commercial launch of ZERVIATE in the U.S. is currently projected in the first half of 2020.
We strengthened our Management in CMC Development by appointing Dr. Ramesh Krishnamoorthy, Ph.D., to the newly-created position of Senior Director and Head, Late Stage CMC and Quality Control, effective September 1, 2019. Dr. Krishnamoorthy brings to Nicox over 24 years of experience in CMC, pharmaceutical development, and quality control aspects of sterile ophthalmic products. Dr. Krishnamoorthy holds an M.S. degree in pharmaceutics and Ph.D. in industrial and physical pharmacy.
Third Quarter 2019 Financial Highlights
As of September 30, 2019, the Nicox Group had cash and cash equivalents of €17.4 million, as compared with €17.3 million at June 30, 2019 and €22.1 million at end December 31, 2018. Including the cash from the recent bond financing and the research tax credit payments related to years 2017 and 2018 received in October, the cash available is €22.6 million. Net revenue2 for the third quarter of 2019 was €0.5 million versus €0.4 million in the third quarter of 2018.

As of September 30, 2019, the Nicox Group had financial debt of €7.4 million in the form of a bond financing agreement with Kreos Capital signed in January 2019.

Only figures at 31 December 2018 are audited. All figures of this press release are non-audited.
Notes
1. Bloomberg data, comparing the period of the weeks ending 5 July 2019 to 27 September 2019 with the periods of the weeks ending 5 April 2019 to 28 June 2019 and 6 July 2018 to 28 September 2018
2. Net revenue consists of revenue from collaborations less royalty payments which corresponds to Net profit in the consolidated statements of profit or loss

Amphivena Initiates Solid Tumor Clinical Trial

On October 16, 2019 Amphivena Therapeutics, Inc., a private clinical stage immuno-oncology company developing T cell engager therapeutics for cancer, reported dosing of the first patient in a Phase 1 clinical trial in solid tumors evaluating AMV564, a CD33/CD3 T cell engager that selectively eliminates myeloid derived suppressor cells (MDSC), sparing normal neutrophils and monocytes (Press release, Amphivena Therapeutics, OCT 16, 2019, View Source [SID1234542310]).

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"Our lead candidate, AMV564, originating from our platform technology, is a bivalent T cell engager that binds with high avidity and specificity to CD33. AMV564 has been shown to eliminate subsets of activated myeloid cells, including granulocytic, monocytic and immature MDSC, in acute myeloid leukemia patients," said Jeanmarie Guenot, Ph.D., Amphivena Chief Executive Officer and President. "This creates a unique opportunity for Amphivena to evaluate the effect of AMV564 on these immune suppressive cells and the potential therapeutic benefit of relieving this important source of T cell suppression in patients with solid tumors."

The multi-center Phase 1 study is currently open for enrollment at NEXT Oncology (PI: Raghad Karim) in San Antonio, TX, MD Anderson Cancer Center (PI: Sarina Piha-Paul) and Peninsula Cancer Institute (PI: Alexander Starodub) in Newport News, VA. The study will be a multicenter, all-comers solid tumor dose-finding trial with expansion cohorts planned in 2020. AMV564 is being administered to solid tumor patients by subcutaneous injection.

About AMV564

AMV564 is a bivalent, bispecific (2:2) T cell engager that binds CD33 and CD3. To date, over 50 patients have received AMV564 in two Phase 1 clinical trials for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). It is currently being evaluated in a First-in-Human Phase 1 trial in patients with relapsed/refractory AML at Washington University School of Medicine, MD Anderson Cancer Center, New York-Presbyterian/Weill Cornell Medical Center and Weill Cornell Medicine, Fred Hutchinson Cancer Research Center, The Ohio State University Wexner Medical Center, University of Pennsylvania Medical Center, Northwestern Memorial Hospital, and The Johns Hopkins Hospital.

The safety, efficacy and selectivity of AMV564 was highlighted most recently at both the 24th European Hematology Association (EHA) (Free EHA Whitepaper) meeting in Amsterdam (Abstract S877) and at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, CA last December. Amphivena believes that AMV564 has demonstrated novel clinical activity by rapidly and selectively eliminating leukemic blasts and rare immature, granulocytic and monocytic MDSCs while sparing normal CD33-expressing cells, including neutrophils and monocytes.

AMV564 is also being evaluated in a Phase 1 solid tumor study which is currently open to enrollment.

Abbott Reports Third-Quarter 2019 Results

On October 16, 2019 Abbott (NYSE: ABT) reported financial results for the third quarter ended Sept. 30, 2019 (Press release, Abbott, OCT 16, 2019, View Source [SID1234542295]).

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Third-quarter worldwide sales of $8.1 billion increased 5.5 percent on a reported basis and 7.6 percent on an organic* basis.
Reported diluted EPS from continuing operations under GAAP was $0.53 in the third quarter. Adjusted diluted EPS from continuing operations, which excludes specified items, was $0.84, an increase of 12.0 percent versus prior year1.
Abbott narrowed its full-year 2019 outlook for diluted EPS from continuing operations on a GAAP basis to $2.06 to $2.08, and full-year adjusted diluted EPS from continuing operations to $3.23 to $3.25, reflecting 12.5 percent growth versus the prior year at the midpoint of the range2.
FreeStyle Libre achieved worldwide sales of $496 million in the quarter, an increase of 63.1 percent on a reported basis and 67.6 percent on an organic basis versus the prior year.
During the third quarter, FreeStyle Libre obtained public reimbursement coverage in Ontario and Quebec, becoming the first and only sensor-based glucose monitoring system to be listed by any provincial health plan in Canada.
Worldwide sales of MitraClip were $176 million in the quarter, an increase of 30.4 percent on a reported basis and 31.9 percent on an organic basis, including U.S. growth of 45.7 percent versus the prior year. During the third quarter, Abbott announced U.S. FDA approval of its next-generation MitraClip device, which offers enhancements and more sizes to offer doctors further options.
In September, Abbott announced data from its COAPT Trial that shows that MitraClip is projected to increase life-expectancy and quality of life compared to guideline-directed medical therapy alone in heart failure patients with secondary mitral regurgitation, or a leaky mitral heart valve.
During the third quarter, Abbott received U.S. FDA approval for its Alinity-S diagnostics system, the latest technology for screening and protecting the U.S. blood and plasma supply.
"We’re performing exceptionally well across several areas," said Miles D. White, chairman and chief executive officer, Abbott. "We’re right on track to achieve ongoing EPS and organic sales growth at the upper-end of our initial guidance ranges for the year."

* See note on organic growth below.

THIRD-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.

Organicsales growth:

Excludes the prior year first, second and third-quarter results for a non-core business within U.S. Adult Nutrition, which was discontinued during the third quarter 2018; and
Excludes the impact of foreign exchange.

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.

Third-quarter 2019 worldwide sales of $8.1 billion increased 5.5 percent on a reported basis. On an organic basis, worldwide sales increased 7.6 percent. Refer to tables titled "Non-GAAP Reconciliation of Adjusted Historical Revenue" for a reconciliation of adjusted historical revenue.

Worldwide Nutrition sales increased 2.0 percent on a reported basis in the third quarter. On an organic basis, sales increased 3.8 percent. Refer to tables titled "Non-GAAP Reconciliation of Adjusted Historical Revenue" for a reconciliation of adjusted historical revenue.

Worldwide Pediatric Nutrition sales increased 0.5 percent on a reported basis in the third quarter, including an unfavorable 0.9 percent effect of foreign exchange, and increased 1.4 percent on an organic basis. In the U.S., sales growth was led by Abbott’s market-leading toddler brands, PediaSure and Pedialyte. International sales declined 2.4 percent on a reported basis and 0.7 percent on an organic basis, driven by challenging market dynamics in Greater China, partially offset by growth across several countries in Southeast Asia and Latin America.

Worldwide Adult Nutrition sales increased 3.9 percent on a reported basis in the third quarter and increased 6.9 percent on an organic basis. International Adult Nutrition sales increased 7.5 percent on a reported basis and 10.4 percent on an organic basis in the third quarter. Sales performance in the quarter was led by strong growth of Ensure, Abbott’s market-leading complete and balanced nutrition brand, and Glucerna, Abbott’s market-leading diabetes-specific nutrition brand.

Worldwide Diagnostics sales increased 4.7 percent on a reported basis in the third quarter, including an unfavorable 1.9 percent effect of foreign exchange, and increased 6.6 percent on an organic basis.

Core Laboratory Diagnostics sales increased 8.3 percent on a reported basis and 10.6 percent on an organic basis in the third quarter. Sales performance was led by above-market growth in the U.S. and internationally, where Abbott is achieving continued strong adoption of its Alinity family of innovative and highly differentiated diagnostic instruments. During the third quarter, Abbott received U.S. FDA approval for its Alinity-S blood and plasma screening diagnostics instrument and several testing assays.

Molecular Diagnostics sales decreased 7.8 percent on a reported basis in the third quarter, including an unfavorable 1.4 percent effect of foreign exchange, and decreased 6.4 percent on an organic basis. Internationally, sales growth in the quarter was negatively impacted by lower non-governmental organization purchases in Africa.

Point of Care Diagnostics sales increased 6.3 percent on a reported basis in the third quarter, including an unfavorable 0.4 percent effect of foreign exchange, and increased 6.7 percent on an organic basis. Sales growth was led by Abbott’s market-leading i-STAT handheld system in the U.S. and internationally.

Rapid Diagnostics sales decreased 0.7 percent on a reported basis in the third quarter, including an unfavorable 1.5 percent effect of foreign exchange, and increased 0.8 percent on an organic basis. Organic sales growth was led by infectious disease testing in developed markets and cardio-metabolic testing globally, partially offset by lower than expected infectious disease testing sales in Africa.

Established Pharmaceuticals sales increased 4.4 percent on a reported basis in the third quarter, including an unfavorable 3.5 percent effect of foreign exchange, and increased 7.9 percent on an organic basis.

Key Emerging Markets include India, Brazil, Russia and China along with several additional emerging countries that represent the most attractive long-term growth opportunities for Abbott’s branded generics product portfolio. Sales in these geographies increased 2.8 percent on a reported basis in the third quarter and increased 6.8 percent on an organic basis, which excludes an unfavorable 4.0 percent effect of foreign exchange. Organic sales growth was led by strong growth across several geographies, including India, China and Brazil.

Other sales increased 9.2 percent on a reported basis in the third quarter, including an unfavorable 1.7 percent effect of foreign exchange, and increased 10.9 percent on an organic basis.

Includes drug-eluting stents, balloon catheters, guidewires, vascular imaging/diagnostics products, vessel closure,

carotid and other coronary and peripheral products.

Note: Insertable Cardiac Monitor (ICM) sales, which had previously been reported in Electrophysiology, are now included in Rhythm Management. Historical periods have been adjusted to reflect this change.

Worldwide Medical Devices sales increased 8.9 percent on a reported basis in the third quarter and increased 10.6 percent on an organic basis, led by double-digit growth in Electrophysiology, Heart Failure, Structural Heart and Diabetes Care.

In Electrophysiology, growth was led by strong performance in cardiac diagnostic and ablation catheters, which are used to help physicians accurately and effectively treat atrial fibrillation, a form of irregular heartbeat.

In Heart Failure, strong double-digit growth was driven by market adoption of Abbott’s HeartMate 3 left ventricular assist device, which has been shown to improve survival and clinical outcomes in patients with advanced heart failure.

Growth in Structural Heart was led by MitraClip, Abbott’s market-leading device for the minimally invasive treatment of mitral regurgitation, or a leaky mitral heart valve. In the third quarter, Abbott announced U.S. FDA approval of its next-generation MitraClip device, MitraClip G4, which offers an expanded range of clip sizes, an alternative leaflet grasping feature and facilitation of procedure assessment in real time to offer doctors further options when treating mitral valve disease.

In Diabetes Care, sales increased 29.6 percent on a reported basis and 33.1 percent on an organic basis in the third quarter. Sales growth in the quarter was led by FreeStyle Libre, Abbott’s revolutionary continuous glucose monitoring system, with worldwide sales of $496 million, an increase of 63.1 percent on a reported basis and 67.6 percent on an organic basis versus the prior year. During the third quarter, FreeStyle Libre obtained public reimbursement coverage in Ontario and Quebec, becoming the first and only sensor-based glucose monitoring system to be listed by any provincial health plan in Canada.

ABBOTT’S GUIDANCE FOR 2019
Abbott is narrowing its guidance for 2019 diluted earnings per share from continuing operations under Generally Accepted Accounting Principles (GAAP) to $2.06 to $2.08. Abbott forecasts net specified items for the full year 2019 of $1.17 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 $3.23 to $3.25 for the full year 2019.

Abbott is issuing fourth-quarter 2019 guidance for diluted earnings per share from continuing operations under GAAP of $0.59 to $0.61. Abbott forecasts specified items for the fourth quarter 2019 of $0.35 per share 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 $0.94 to $0.96 for the fourth quarter.

ABBOTT DECLARES 383RD CONSECUTIVE QUARTERLY DIVIDEND
On Sept. 12, 2019, the board of directors of Abbott declared the company’s quarterly dividend of $0.32 per share. Abbott’s cash dividend is payable Nov. 15, 2019, to shareholders of record at the close of business on Oct. 15, 2019.

Abbott has increased its dividend payout for 47 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.