On June 20, 2017 Merck, a leading science and technology company, reported its corporate venture arm Merck Ventures created iOnctura SA, Geneva, Switzerland (Press release, iOnctura, JUN 20, 2017, View Source [SID1234519625]). This immuno-oncology spin-out company was formed around two assets from the Healthcare R&D portfolio of Merck and three assets from Cancer Research Technology (CRT). CRT is the commercial arm of Cancer Research UK, London, UK. Merck Ventures will manage the investment and will be represented on iOnctura’s board of directors.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Our goal is to modulate key culprits of immunosuppression in the tumor microenvironment to maximize the therapeutic potential of checkpoint inhibitors for patients," said Catherine Pickering, CEO and co-founder of iOnctura. "Through our key alliances with CRT and Merck, we are optimally positioned to explore novel combination therapies and advance them quickly to cancer patients."

iOnctura aims to develop a pipeline of selected assets that target and modulate mechanisms that drive immunosuppression in the tumor microenvironment (TME). Such immunosuppression has been shown to be one of the main causes behind a significant number of patients not responding to first generation checkpoint inhibitors. iOnctura, through its alliances with Merck and CRT, has already built a pipeline of promising programs and entered a research collaboration with CRT Discovery Laboratories. In exchange for the exclusive global option to license three immuno-oncology assets from CRT, iOnctura will provide CRT with an initial equity holding in the company and will make further payments for the achievement of late development and approval milestones as well as royalties on net sales. iOnctura has also secured access to future supply of avelumab, being co-developed and co-commercialized by Merck and Pfizer, which will enable acceleration into initial clinical proof of concept studies.

Stuart Farrow, CRT’s director of biology, said: "We’re delighted that these three potential new cancer treatments, partly developed by our drug discovery laboratories alongside leading Cancer Research UK-funded scientists, have been prioritized for further development through the formation of this new company. The ongoing support by our drug discovery laboratories will hopefully help build a strong development pipeline for iOnctura."

Merck Ventures, the strategic venture investment arm of Merck, is providing the initial seed funding to iOnctura. Hakan Goker, Senior Investment Director at Merck Ventures, and Keno Guttierrez will represent Merck Ventures on iOnctura’s board of directors.

On June 19, 2017 Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a leader in the discovery and development of engineered CAR-T cell therapies, reported promising early clinical results at the 3-month follow-up of the first dose-level in the solid tumor arm of the THINK trial (THerapeutic Immunotherapy with CAR-T NKR-2) (Press release, Celyad, JUN 20, 2017, View Source [SID1234519620]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

At the first 3 x 108 cell dose-level administered to a total of three patients with metastatic cancer, the two colorectal cancer (mCRC) patients, who were progressing after at least two prior chemotherapy regimens, achieved a confirmed Stable Disease (SD) according to RECIST criteria at three months. According to recent studies conducted on similar patient populations, median progression free survival in these patients under standard of care is between 1.9 and 3.2 months. The third patient, a refractory pancreatic patient, was in progression at the same time point. No toxicity signals were observed in any of the patients.

Christian Homsy, CEO of Celyad comments: "We are pleased to have observed these encouraging preliminary results in such a late stage population. Despite being dosed only at a tenth of the expected efficacious dose based on animal experiments, the results show a stabilization of the disease. We look forward to the next stages of the trial."

Dr. Frédéric Lehmann, Vice President Clinical Development and Medical Affairs at Celyad adds: "These early results in the two heavily pre-treated mCRC patients are encouraging, considering the dismal clinical outcome of the existing standard of care for this refractory patient population. Based on these preliminary results, we look forward to progressing our clinical development plan, including higher doses and longer follow-up in the THINK study, as well at starting the SHRINK (CAR-T NKR-2 cells in combination with chemotherapy) and LINK (loco-regional administration) clinical trials shortly."

Patients in the second dose of the solid tumor arm (1 x 109) are currently being enrolled and treated. CAR-T NKR-2 cells have so far showed a safety profile that could allow an outpatient clinical approach.

The hematological cancer dose escalation arm, including relapsing/refractory Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM) patients, is progressing. The first dose patients have been registered and are being treated with no toxicity signals to date.

The THINK trial, conducted in the US and in Europe, includes two stages: a dose escalation and an extension stage.
The dose escalation is being conducted in parallel in solid cancers (colorectal, pancreatic, ovarian, triple negative breast and bladder) and in hematologic (AML and MM) cancer groups, while the extension phase will evaluate in parallel each tumor type independently. The dose escalation design includes three dose levels adjusted to body weight: up to 3×108, 1×109 and 3×109 NKR-2 CAR T-cells. At each dose, the patients receive three successive administrations, two weeks apart, of NKR-2 CAR T-cells at the specified dose.

NKR-2 CAR T-cell therapy was designed to act as a targeted therapy with short term persistence and multiple injections in order to provide a better controlled and more predictable safety profile. The primary objective is to avoid uncontrolled in vivo cell expansion and long-term persistence thereby replacing this paradigm with well controlled pharmacokinetics.

On June 20, 2017 The Cell and Gene Therapy Catapult (CGT Catapult) reported the sale of its subsidiary, Catapult Therapy TCR Ltd, to Cell Medica (Press release, UCLB, JUN 20, 2017, View Source [SID1234519619]). The CGT Catapult, through Catapult Therapy TCR Ltd, has been developing and conducting phase I/II clinical trials of a gene-modified T cell therapy that actively targets several blood cancers and multiple solid tumours. Financial terms were not disclosed.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Catapult Therapy TCR Ltd is a joint venture company set up by the CGT Catapult, UCL Business (UCLB) and Imperial Innovations which focused on the development of a gene-modified WT1 TCR T cell therapy for acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) that are known to overexpress the antigen WT1. It represents a promising novel treatment approach in a therapeutic area where prognosis is often poor and therapeutic options limited. Early development work on this therapy conducted at UCL and Imperial was funded by the UK charity Bloodwise. The WT1 antigen is also present on a large variety of solid tumours, giving this treatment very broad therapeutic potential.

The acquisition of Catapult Therapy TCR Ltd by Cell Medica will enable and accelerate the further development and commercialisation of this innovative treatment in one of the most promising areas of cancer immunotherapy. The optimisation and development of next-generation T cells will be conducted by Cell Medica and CGT Catapult and manufacturing will take place at CGT Catapult’s large-scale cell and gene therapy manufacturing centre located at the Stevenage BioScience Catalyst in Hertfordshire, following a grant awarded earlier this year by Innovate UK.

"We are pleased that Cell Medica has acquired the WT1 T-cell immunotherapy," said Keith Thompson, Chief Executive Officer, Cell and Gene Therapy Catapult. "With their complementary technologies, they will take over the development of this exciting new therapy. The next generation product developed in our manufacturing centre underlines our ability to support the localisation of cell manufacturing processes in the UK. It reflects the CGT Catapult’s mission to work with academia and industry in bringing forward important new technologies that can be industrialised and turned into the advanced medicines of the future, building new industries."

"Immuno-oncology is an expanding discipline representing the next generation of cancer treatments, and WT1 has shown excellent results so far. We are delighted to have created this opportunity with our academic partners UCLB and Imperial Innovations."

Gregg Sando, Chief Executive Officer, Cell Medica, said: "The acquisition of the WT1-TCR cell therapy leverages the investment we made in 2016 for exclusive rights to the Dominant TCR technology. Our objective is to show how we can enhance any existing TCR cell therapy with the Dominant TCR technology to create a more effective treatment for patients with solid tumours who otherwise have a very poor prognosis. We are also looking forward to an important collaboration with CGT Catapult to initiate manufacturing at the Stevenage GMP facility where we will work together on scale-up strategies for commercial production."

Catapult Therapy TCR Ltd academic partners highlighted the relevance of T-cell immunotherapy to future cancer therapy options.

"Gene-modified T cells targeting WT1 have enormous potential to transform the lives of cancer patients, and the expertise of UCL Professors Hans Stauss and Emma Morris have enabled this innovative treatment to evolve," said Cengiz Tarhan, Managing Director, UCL Business. "Cell Medica is excellently placed to further develop this novel treatment approach."

Tony Hickson, Managing Director, Imperial Innovations Limited, said: "This project provides a case study of two leading UK universities working together alongside a Catapult to translate their high quality research outputs into clinical stage advanced therapeutics."

On June 20, 2017 Seattle Genetics, Inc. (Nasdaq: SGEN) reported that it has submitted a supplemental Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) based on data from the phase 3 ALCANZA trial and two phase 2 investigator-sponsored trials of ADCETRIS (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL) (Press release, Seattle Genetics, JUN 20, 2017, View Source [SID1234519618]). ADCETRIS is currently not approved for the treatment of CTCL.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The submission of the supplemental BLA requesting label expansion for ADCETRIS as a treatment in CTCL patients who require systemic therapy is an important milestone. CTCL is an incurable and disfiguring disease in need of new therapeutic options, particularly those that achieve durable responses," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development of Seattle Genetics. "Results from the phase 3 ALCANZA trial demonstrated that CTCL patients treated with ADCETRIS had superior outcomes across all primary and secondary endpoints compared to patients in the control arm who were treated with either methotrexate or bexarotene standard of care agents. In addition to the ALCANZA results, data from two investigator-sponsored trials also support ADCETRIS use in this disease setting. We believe these data are clinically meaningful and support a label expansion for ADCETRIS in CTCL, which would be the fourth indication for this program."

In November 2016, based on preliminary analysis of ALCANZA, the FDA granted ADCETRIS Breakthrough Therapy Designation (BTD) for the treatment of patients with CD30-expressing mycosis fungoides and primary cutaneous anaplastic large cell lymphoma who require systemic therapy and have received one prior systemic therapy. These represent the most common subtypes of CTCL. Based on discussions with the FDA following the BTD, additional data from investigator-sponsored phase 2 trials have been incorporated into the supplemental BLA to support the potential for a broader label in CTCL.

The supplemental BLA is primarily based on positive results from a phase 3 trial called ALCANZA that were presented at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2016 and published in the Lancet in June 2017. Results from the ALCANZA trial in 128 CTCL patients requiring systemic therapy included:

The trial achieved its primary endpoint with the ADCETRIS treatment arm demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4) versus the control arm as assessed by an independent review facility. ORR4, as assessed by Global Response Score, was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm (p-value <0.0001).
Key secondary endpoints specified in the protocol, including complete response rate, progression-free survival and reduction in the burden of symptoms during treatment (Skindex-29), were all highly statistically significant in favor of the ADCETRIS arm.
The safety profile associated with ADCETRIS from the ALCANZA trial was generally consistent with the existing prescribing information. The most common adverse events of any grade include: peripheral neuropathy, nausea, diarrhea, fatigue, vomiting, alopecia, pruritis, pyrexia, decreased appetite and hypertriglyceridemia.
About CTCL

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Cutaneous lymphomas are a category of non-Hodgkin lymphoma that primarily involve the skin. According to the Cutaneous Lymphoma Foundation, CTCL is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. Progression from limited skin involvement may be accompanied by skin tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs.

The standard treatment for systemically pretreated CTCL includes skin-directed therapies, radiation and systemic therapies. The systemic therapies currently approved for treatment have demonstrated 30 to 45 percent objective response rates, with low complete response rates.

About ADCETRIS

ADCETRIS is being evaluated broadly in more than 70 ongoing clinical trials, including three Phase 3 studies, the ongoing ECHELON-1 trial in frontline classical Hodgkin lymphoma and the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, as well as the completed ALCANZA trial in cutaneous T-cell lymphoma, from which data were submitted in a supplemental BLA.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.

ADCETRIS for intravenous injection has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. The European Commission extended the current conditional marketing authorization of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT.

ADCETRIS has received marketing authorization by regulatory authorities in 67 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.