On June 10, 2019 Avacta Group plc (AIM: AVCT), the developer of Affimer biotherapeutics and research reagents, reported that it has selected the clinical development candidate for first-time-in-human clinical trials of the Affimer platform (Press release, Avacta, JUN 10, 2019, View Source [SID1234536979]). This important milestone means that the Group remains on track to submit an IND/CTA application for an Affimer PD-L1 inhibitor by the end of 2020.

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The Group has generated a wide range of Affimer inhibitors of PD-L1, a well known cancer immunotherapy target. This target was chosen to demonstrate safety and tolerability of the Affimer platform in human and, importantly, to provide a proprietary basis for its novel tumour microenvironment activated drug conjugate (TMAC) and bispecific cancer immunotherapies.

Avacta has selected a specific Affimer molecule (AVA004) as its clinical candidate because of its excellent in vitro and in vivo pharmacological properties. This Affimer has been shown to have equivalent tumour growth inhibition to three approved monoclonal antibody inhibitors of PD-L1 (Tecentriq, Imfinzi and Bavencio) in several in vivo animal efficacy models.

This molecule will therefore now be taken forwards into clinical manufacturing and IND/CTA enabling studies, allowing the Group to remain on track for an IND/CTA application in late 2020 and dosing of first patients shortly afterwards.

The planned phase I study will be in patients with advanced PD-L1 positive solid tumours. This study will explore both intra-venous and sub-cutaneous routes of administration to provide proof-of-concept with primary endpoints of safety, tolerability and appropriate pharmacokinetics/pharmacodynamics, and with a secondary efficacy endpoint. The study will include 20-30 patients in at least two sites in North America and Europe.

The cancer immunotherapy market is currently worth $60bn and is predicted to double by 20251. Avacta’s combinatorial approach to treatment through its TMAC and bispecific cancer immunotherapies, which build upon inhibition of PD-L1, are designed not only to compete strongly in this market through improved clinical benefit to patients, but also to expand the market to patients who do not respond to single checkpoint inhibitors.

Avacta will provide an on-line analyst briefing on the AVA004 in vitro and in vivo pharmacology data at 16:00 BST on Wednesday, 12 June 2019. To register for this analyst briefing please contact [email protected].

Dr Alastair Smith, Chief Executive Officer, Avacta Group plc, commented:

"Selection of the Affimer PD-L1 inhibitor candidate for clinical development is an important milestone in our development of the Affimer therapeutic platform. The Group remains firmly on track to submit an application to the regulators for a first-time-in-human clinical study late in 2020.

Demonstration of appropriate safety and tolerability in humans is key to de-risking the platform overall for partners and therefore key to the number and value of licensing deals in the future.

Not only will the PD-L1 programme be used to demonstrate the safety of the Affimer platform in humans, but it will provide us with a proprietary inhibitor of the PD-1/PD-L1 checkpoint pathway which will be central to our ground-breaking TMAC drug conjugates and bispecifics. These novel programmes will allow us to build a clinically differentiated pipeline to address the lack of a durable response to single immune checkpoint therapies for most patients.

It is a hugely exciting period for Avacta and I look forward to keeping the market updated on our progress."

1. View Source

On June 10, 2019 The Janssen Pharmaceutical Companies of Johnson & Johnson have reported the latest research to be presented at the 24th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress taking place in Amsterdam, The Netherlands, from 13–16 June 2019 (Press release, Johnson & Johnson, JUN 10, 2019, View Source [SID1234536978]). Janssen will present 28 company-sponsored abstracts from its leading haematological malignancy portfolio at the congress, including the latest results for DARZALEX (daratumumab) and IMBRUVICA (ibrutinib).

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"With more than 11,000 attendees, EHA (Free EHA Whitepaper) is the premier congress for the latest innovations in haematology in Europe and Janssen is proud to be presenting important data from our clinical development programmes," said Dr Patrick Laroche, Europe, Middle East and Africa (EMEA) Haematology Therapeutic Area Lead, Janssen-Cilag France. "We are committed to changing outcomes and improving options for patients diagnosed with cancer. Therefore, we are pleased to present results from the daratumumab CASSIOPEIA study, which has been selected for inclusion in the Presidential Symposium. We are also encouraged by the five-year ibrutinib RESONATETM-2 follow-up findings, which provide longer-term evidence supporting the efficacy and safety of this BTK inhibitor in the treatment of chronic lymphocytic leukaemia."

Highlights of the data to be presented by Janssen include:

First-Time Daratumumab Data in the Treatment of Newly Diagnosed Patients with Relapsed/Refractory Multiple Myeloma, and its Investigational Subcutaneous Formulation1,2
Fourteen daratumumab abstracts have been selected for presentation at the EHA (Free EHA Whitepaper) Annual Congress this year, four of which will be featured in oral sessions. Notably, results from the Phase 3 CASSIOPEIA study evaluating daratumumab in combination with bortezomib, thalidomide and dexamethasone for newly diagnosed patients with multiple myeloma who are transplant eligible have been selected for presentation as part of the Presidential Symposium (Abstract #S145).1 The Presidential Symposium includes the six best abstracts of the Congress, reflecting ground-breaking research as chosen by the Scientific Program Committee. These data recently supported regulatory filings in both the European Union and the U.S., seeking to expand the current indication for daratumumab in the frontline setting.

Findings from the Phase 3 COLUMBA study will be presented (Abstract #S823) evaluating a daratumumab subcutaneous formulation in the treatment of patients with relapsed or refractory multiple myeloma.2

Ibrutinib Long-Term Data in Chronic Lymphocytic Leukaemia3
Results from the final analysis of the Phase 3 RESONATETM-2 study (PCYC-1115/1116) study evaluating ibrutinib monotherapy in previously untreated patients with chronic lymphocytic leukaemia (CLL) will be presented in an oral session (Abstract #S107).3 Ibrutinib, a once daily oral BTK inhibitor, is jointly developed and commercialised by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.3

Select company-sponsored abstracts follow below. Abstracts for additional Janssen therapies will also be presented and can be found through the EHA (Free EHA Whitepaper) abstract database here.

Abstract No. Title Date/Time
Daratumumab
Oral Presentations
Abstract #S1451

Phase 3 Randomized Study of Daratumumab + Bortezomib/Thalidomide/Dexamethasone (D-VTd) Versus VTd in Transplant-eligible Newly Diagnosed Multiple Myeloma: Part 1 CASSIOPEIA Results Presidential Symposium,
Friday, June 14 3:45 – 4:00 PM CEST

Abstract #S8744

Efficacy of Daratumumab, Bortezomib, Thalidomide, and Dexamethasone in Transplant-eligible Newly Diagnosed Multiple Myeloma Based Minimal Residual Disease Status: Analysis of CASSIOPEIA Saturday, June 15
4:45 – 5:00 PM CEST

Abstract #S8232

Randomized, Open-label, Non-inferiority, Phase 3 Study of Subcutaneous Versus Intravenous Daratumumab Administration in Patients with Relapsed or Refractory Multiple Myeloma: COLUMBA Saturday, June 15
11:30 – 11:45 AM CEST

Abstract #S8755

Subcutaneous Daratumumab, Cyclophosphamide, Bortezomib, and Dexamethasone in Patients with Newly Diagnosed Amyloid Light Chain Amyloidosis: Updated Safety Run-in Results of ANDROMEDA Saturday, June 15
5:00 – 5:15 PM CEST

Poster Presentations
Abstract #PF5986

Stem Cell Yield and Transplantation in Transplant-eligible Newly Diagnosed Multiple Myeloma Patients Receiving Daratumumab, Bortezomib, Thalidomide, and Dexamethasone: Phase 3 CASSIOPEIA Study Friday, June 14
5:30 – 7:00 PM CEST

Abstract #PF5927

Impact of Age on Efficacy and Safety of Daratumumab in Combination with Lenalidomide and Dexamethasone in Patients with Transplant-ineligible Newly Diagnosed Multiple Myeloma: MAIA Friday, June 14
5:30 – 7:00 PM CEST

Abstract #PF6038

Faster and Sustained Improvement in Health-related Quality of Life in Transplant-ineligible Newly Diagnosed Multiple Myeloma Patients Treated with Daratumumab, Lenalidomide, and Dexamethasone (D-Rd) Versus Rd: MAIA Friday, June 14
5:30 – 7:00 PM CEST

Abstract #PF5919

Efficacy and Safety of Daratumumab, Lenalidomide, and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Subgroup Analysis of POLLUX Based on Cytogenetic Risk Friday, June 14
5:30 – 7:00 PM CEST

Abstract #PF59610

Efficacy and Safety of Daratumumab, Bortezomib, and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Subgroup Analysis of CASTOR Based on Cytogenetic Risk Friday, June 14
5:30 – 7:00 PM CEST

Abstract #PF64111

Characterization of Treatments and Real-life Outcomes in Patients with Newly Diagnosed Multiple Myeloma Who Received Frontline Autologous Stem Cell Transplantation in Sweden Friday, June 14
5:30 – 7:00 PM CEST

Abstract #PF64312

Characterization of Frontline Treatment Patterns and the Proportion of Patients Reaching Subsequent Lines of Therapy in Transplant-eligible Patients with Newly Diagnosed Multiple Myeloma Friday, June 14
5:30 – 7:00 PM CEST

Abstract #PS137713

Improvement in Health-related Quality of Life for Newly Diagnosed Multiple Myeloma Transplant-eligible Patients Treated with Daratumumab, Bortezomib, Thalidomide, and Dexamethasone: CASSIOPEIA Saturday, June 15
5:30 – 7:00 PM CEST

Abstract #PS142514

Results of the Daratumumab Monotherapy Early Access Treatment Protocol in Patients from Europe and Russia with Relapsed or Refractory Multiple Myeloma Saturday, June 15
5:30 – 7:00 PM CEST

Abstract #PS139515

Comparative Effectiveness of Frontline Treatments for Patients with Newly Diagnosed Multiple Myeloma Who are Transplant-ineligible Saturday, June 15
5:30 – 7:00 PM CEST

Ibrutinib
Oral Presentation
Abstract #S1073

Five Year Follow-Up of Patients Receiving Ibrutinib For First-Line Treatment of Chronic Lymphocytic Leukemia Friday, June 14
12:00 – 12:15 PM CEST

Poster Presentations
Abstract #PF38416

Effectiveness and Safety of Ibrutinib for Chronic Lymphocytic Leukemia (CLL) in Routine Clinical Practice: Interim Analysis (IA) of the Belgian Ibrutinib Real-World Data (BIRD) Study Friday, June 14
5:30 – 7:00 PM CEST

Abstract #PF38717

French Ibrutinib Observational Study (FIRE): Real-World Study of Ibrutinib Treatment for Chronic Lymphocytic Leukemia (CLL) in France Friday, June 14
5:30 – 7:00 PM CEST

Abstract #PF38318

Prognostic Testing and Treatment Approaches Based on Real-World Clinical Experience from An Interim Analysis of the INFORMCLL Registry of Patients With Chronic Lymphocytic Leukemia [ASH encore] Friday, June 14
5:30 – 7:00 PM CEST

Abstract #PF49419

Clinical Outcomes with Single-Agent Ibrutinib for Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL): Interim Analysis (IA) of the Belgian Ibrutinib Real-World Data (BIRD) Study Friday, June 14
5:30 – 7:00 PM CEST

Abstract #PF38920

Progression-Free Survival Predicts Overall Survival in Frontline CLL Friday, June 14
5:30 – 7:00 PM CEST

Abstract #PS126421

French Ibrutinib Observational Study (FIRE): Real-World Study of Ibrutinib Treatment for Mantle Cell Lymphoma (MCL) in France Saturday, June 15
5:30 – 7:00 PM CEST

#ENDS#

About daratumumab
Daratumumab is a first-in-class22 biologic targeting CD38, a surface protein that is highly expressed across multiple myeloma cells, regardless of disease stage.23 Daratumumab is believed to induce tumour cell death through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), as well as through apoptosis, in which a series of molecular steps in a cell lead to its death.24 A subset of myeloid-derived suppressor cells (CD38+ MDSCs), CD38+ regulatory T cells (Tregs) and CD38+ B cells (Bregs) were decreased by daratumumab.26 Daratumumab is being evaluated in a comprehensive clinical development programme across a range of treatment settings in multiple myeloma, such as in frontline and relapsed settings.25,26,27,28,29,30,31,32 Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant haematologic diseases in which CD38 is expressed, such as smouldering myeloma.33,34 For more information, please see www.clinicaltrials.gov.

For further information on daratumumab, please see the Summary of Product Characteristics at View Source

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive licence to develop, manufacture and commercialise daratumumab.35

About ibrutinib
Ibrutinib is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, which works by forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B-cells.36 By blocking this BTK protein, ibrutinib decreases survival and migration of B lymphocytes, thereby delaying the progression of the cancer.37

Ibrutinib is currently approved in Europe for:38

Chronic lymphocytic leukaemia (CLL): As a single agent for the treatment of adult patients with previously untreated CLL, and as a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy.
Mantle cell lymphoma (MCL): Adult patients with relapsed or refractory mantle cell lymphoma.
Waldenström’s macroglobulinemia (WM): Adult patients who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemoimmunotherapy.
Ibrutinib is approved in more than 90 countries, and, to date, has been used to treat more than 140,000 patients worldwide across its approved indications.

The most common adverse reactions seen with ibrutinib include diarrhoea, neutropenia, haemorrhage (e.g. bruising), musculoskeletal pain, nausea, rash, and pyrexia.38

For a full list of side effects and information on dosage and administration, contraindications and other precautions when using ibrutinib please refer to the Summary of Product Characteristics for further information.

On June 10, 2019 Seattle Genetics, Inc. (Nasdaq:SGEN) reported U.S. Food and Drug Administration (FDA) approval of Polivy (polatuzumab vedotin-piiq), which is an antibody-drug conjugate (ADC) targeting CD79b that utilizes Seattle Genetics’ technology. Polivy was developed and will be commercialized by Genentech, a member of the Roche Group (Press release, Seattle Genetics, JUN 10, 2019, View Source [SID1234536977]). It was approved in combination with bendamustine plus Rituxan (rituximab) (BR) for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), who have received at least two prior therapies. Polivy previously received FDA Breakthrough Therapy Designation, and was approved more than two months ahead of the Prescription Drug User Fee Act (PDUFA) action date of August 19, 2019.

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"The approval of Polivy under our collaboration with Genentech is an important milestone for Seattle Genetics as it extends the reach of our technology to more patients with significant unmet medical needs," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "This approval, along with our own internal ADCs in development and those of other collaborators, such as GlaxoSmithKline, highlights that ADCs continue to grow as an important therapeutic approach to treating both hematologic malignancies and solid tumors."

Polivy was granted PRIME (PRIority MEdicines) designation by the European Medicines Agency (EMA) for the treatment of patients with R/R DLBCL. PRIME is a designation implemented by the EMA to support data generation and development plans for promising medicines, providing a pathway for accelerated evaluation by the agency. Polivy is also being investigated by Genentech in several ongoing clinical trials for the treatment of non-Hodgkin lymphoma (NHL), including frontline DLBCL.

Seattle Genetics’ ADC technology combines the specificity of monoclonal antibodies, innovative linker systems and potent cell-killing agents to treat cancer. The technology has been licensed to several companies, including Genentech and GlaxoSmithKline. Under the terms of these agreements, each company has rights to use the technology with antibodies against selected targets. The licensee is responsible for research, product development, manufacturing and commercialization. Seattle Genetics is entitled to receive fees, progress-dependent milestone payments and royalties on worldwide net sales of any resulting ADC products.

On June 10, 2019 FibroGen, Inc. (NASDAQ: FGEN), a leading biopharmaceutical company discovering and developing a pipeline of first-in-class therapeutics, reported that Chief Executive Officer Thomas B. Neff will participate in a Fireside Chat at the Goldman Sachs 40th Annual Global Healthcare Conference in Rancho Palos Verdes, California, on Wednesday, June 12, at 10:00 a.m. Pacific Time (Press release, FibroGen, JUN 10, 2019, View Source;p=irol-newsArticle&ID=2401014 [SID1234536975]). A live audio webcast of the presentation will be available under the Investors section of the FibroGen website at www.fibrogen.com. The replay of the webcast will be available for at least 14 days following the webcast.

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On June 10, 2019 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, with an initial focus on myelodysplastic syndromes (MDS), reported two presentations at the 24th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) being held June 13-16, 2019 in Amsterdam, Netherlands (Press release, Onconova, JUN 10, 2019, View Source [SID1234536974]). Dr. Steven Fruchtman, President & CEO, Dr. Ric Woodman, CMO, and Dr. Ronnee Adesanya, VP Medical Affairs, will be attending the conference.

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DETAILS OF THE PRESENTATIONS:

Title: PHASE II STUDY OF ORAL RIGOSERTIB COMBINED WITH AZACITIDINE IN PATIENTS WITH HIGHER-RISK MYELODYSPLASTIC SYNDROMES (MDS)

Format: ORAL PRESENTATION: Abstract S839
Location – Elicium 1

Date/Time: Saturday, June 15 / 12:00 – 12:15

Presenter: Shyamala C. Navada, MD
Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, NY

Title: RIGOSERTIB MODULATES HEMATOPOIESIS GENE SIGNALING PATHWAYS ALONE OR IN SEQUENCES
COMBINATION WITH AZACITIDINE ON MDS CELLS IN VITRO

Format: POSTER PRESENTATION: Abstract PS1332
Location – Poster area

Date/Time: Saturday, June 15 / 17:30 – 19:00

Presenter: Lewis R. Silverman, MD
Tisch Cancer Institute, Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, NY
A copy of the poster and oral presentation slides will be available immediately following the event by visiting the Scientific Presentations section of Onconova’s website: View Source