On January 8, 2018 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported initial safety data from its two ongoing pilot studies of SPEAR T-cells targeting MAGE-A10, one in non-small cell lung cancer (NSCLC) and a triple tumor study in bladder, melanoma, and head & neck cancers (Press release, Adaptimmune, JAN 8, 2018, View Source;p=RssLanding&cat=news&id=2325398 [SID1234522943]).

To date, 8 patients have each received 100 million transduced MAGE‑A10 SPEAR T-cells in the first dose cohorts of both studies. No evidence of toxicity related to off-target binding or alloreactivity has been observed. There have been no reports of neurotoxicity safety events similar to CAR‑T cell-related encephalopathy syndrome (CRES)1. In the NSCLC study, there has been one serious adverse event of cytokine release syndrome (CRS), a Grade 4 event that resolved with treatment. This event led to cohort 1 expansion from 3 to 6 patients. No dose limiting toxicities were observed in cohort 1 of the triple tumor study.

Following review by the independent safety review committee (SRC), the decision has been made to escalate to the next dose of 1 billion transduced MAGE-A10 SPEAR T-cells in the triple tumor study. This was the therapeutic threshold dose observed with SPEAR T‑cells targeting NY-ESO in the synovial sarcoma pilot study. The decision to escalate in the NSCLC cohort will be reviewed by the SRC following dosing of the 6th patient.

"These safety results, with one of our wholly-owned SPEAR T-cell treatments, and the upcoming escalation to the next dose in the triple tumor study are significant as they allow us to progress treating patients in these studies at a potentially active cell dose," said Rafael Amado, Adaptimmune’s Chief Medical Officer. "As data accumulate throughout 2018, we will continue to share meaningful safety and efficacy data from the MAGE-A10 and MAGE-A4 programs at relevant scientific venues."

Details about Ongoing Trials with SPEAR T-cells Targeting MAGE-A10
There are two ongoing clinical trials with SPEAR T-cells targeting MAGE-A10; one in non-small cell lung cancer (NSCLC), and a triple tumor study in bladder, melanoma, and head & neck cancers. Both studies are dose escalation trials that evaluate three doses of transduced SPEAR T-cells, administered after a lymphodepleting chemotherapy regimen. The three doses being evaluated are 100 million, 1 billion and 1 to 5 billion transduced SPEAR T-cells.

NSCLC study: In this study, five patients have received SPEAR T-cells in the first group of Cohort 1 (1a without fludarabine) 2, and there was one report of Grade 4 CRS that resolved with treatment.

Triple Tumor Study: Three patients have been dosed in the first cohort. There were no reports of CRS greater or equal to Grade 3, and all cases resolved with supportive treatment.

On January 8, 2018 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported that it has successfully manufactured the first SPEAR T-cells for a patient at its Navy Yard facility in Philadelphia (Press release, Adaptimmune, JAN 8, 2018, View Source;p=RssLanding&cat=news&id=2325396 [SID1234522941]). In addition, Adaptimmune announced an agreement with Cell and Gene Therapy Catapult for vector production in the UK, which will ensure vector supply for its ongoing and future clinical studies.

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"We are making great strides to becoming a fully integrated cell therapy company. Our Navy Yard facility is now fully operational producing SPEAR T-cells for patients. In addition, we have vector supply into 2019, and the initiation of our own vector manufacturing capability at the Catapult facility will extend vector supply further," said James Noble, Adaptimmune’s Chief Executive Officer. "We will continue to work with our cell manufacturing partner PCT, now part of Hitachi, where we have dedicated space and personnel for production of our SPEAR T-cells, as well as our other vector suppliers. Having these dedicated resources both in-house and through external partnerships is essential to ensure our future success as a fully integrated cell therapy company."

First SPEAR T-cells manufactured at the Navy Yard
The first SPEAR T-cells have been successfully manufactured by the Adaptimmune team at our own Navy Yard headquarters for a patient in the first dose cohort of the ongoing MAGE-A4 multiple tumor study in bladder, melanoma, head & neck, ovarian, non-small cell lung, esophageal, and gastric cancers.

The manufacturing facility at the Navy Yard can deliver cells for up to 300 patients per year, with the possibility of expansion that would enable manufacture for up to 1000 patients per year. In addition to production at its wholly-owned manufacturing facility at the Navy Yard, Adaptimmune will continue working with the PCT team to manufacture SPEAR T-cells.

Vector supply extended to beyond 2020
The agreement, which was executed on January 5, 2018 with Cell and Gene Therapy (CGT) Catapult, will enable Adaptimmune to have its own dedicated vector manufacturing space in the UK. It will ensure vector supply production beyond 2020 for ongoing studies with all three SPEAR T-cell therapies, MAGE-A4, MAGE-A10 and AFP.

The module, in which Adaptimmune will use its own novel vector manufacturing process and be responsible for operation of the manufacturing process, is located in the UK-based CGT Manufacturing Centre. The CGT manufacturing Centre is a Good Manufacturing Practice (GMP) facility designed to enable the development of commercial scale manufacturing systems in cell and gene therapy by offering a full suite of GMP facilities, support and expertise.

On January 8, 2018 Molecular Partners AG (ticker: MOLN), a clinical-stage biopharmaceutical company developing a new class of drugs known as DARPin therapies*, reported initial safety and efficacy data from its ongoing phase 2 study of MP0250 in multiple myeloma (MM) (Press release, Molecular Partners, AUG 8, 2018, View Source [SID1234522938]).

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Eight patients have been treated in the first cohort of 8 mg/kg MP0250 and were included in the safety analysis set. No dose-limiting toxicities (DLTs) have been reported to date. Most frequent adverse events were Grade 1 and 2, except two Grade 3 adverse events (thrombocytopenia and transitory liver enzyme elevation) observed in two patients.

Of seven response evaluable patients receiving MP0250 in combination with bortezomib and dexamethasone, three patients showed partial response (PR) and one patient minimal response (MR). Responses were analyzed according to the International Myeloma Working Group (IMWG) criteria.

"We are very pleased with the good initial safety and tolerability data we observed in the first eight patients treated with MP0250 in combination with bortezomib and dexamethasone. Furthermore, we see promising responses within this first dose cohort. We look forward to evaluating additional patients at higher doses of MP0250 with bortezomib and dexamethasone to treat resistant multiple myeloma patients," commented Dr. Andreas Harstrick, Chief Medical Officer at Molecular Partners.

MP0250 is a proprietary DARPin drug candidate neutralizing VEGF and HGF and thus blocking key escape pathways and resistance. Increases in VEGF and HGF are associated with disease progression in multiple myeloma and have been linked to poor prognosis: they are known to be able to stimulate neovascularization, bone destruction, and myeloma proliferation, migration, and adhesion in the bone marrow. MP0250 shows activity in many preclinical tumor models including in multiple myeloma models in which it enhances the effects of bortezomib on inhibition of M protein production and bone lysis and reduces invasion of tumor cells. MP0250 has shown a favorable safety profile in a phase 1 clinical study in 45 patients in advanced solid tumors.

In the phase 2 MM study, the safety and efficacy of MP0250 is examined in combination with bortezomib (Velcade) and dexamethasone in patients with relapsed and refractory multiple myeloma (RRMM) who have failed standard therapies. The study is performed in Germany, Poland and Italy. A total of 40 patients are planned to be treated, 12 patients in the dose-escalation phase (Part 1) to establish a safe dose, and an additional 28 patients in the dose-expansion phase (Part 2) resulting in a total of 34 patients at the target dose. Additional safety and efficacy data are expected by the end of 2018.

About the DARPin Difference
DARPin therapeutics are a new class of protein therapeutics that open an extra dimension of multi-specificity and multi-functionality. DARPin candidates are potent, specific, safe and very versatile. They can engage more than five targets at once, offering potential benefits over those provided by conventional monoclonal antibodies or other currently available protein therapeutics.

The DARPin technology is a fast and cost-effective drug discovery engine, producing drug candidates with ideal properties for development and very high production yields. With their good safety profile, low immunogenicity and long half-life in the bloodstream and the eye, DARPin therapies have the potential to advance modern medicine and significantly improve the treatment of serious diseases, including cancer and sight-threatening disorders. Molecular Partners is partnering with Allergan to advance clinical programs in ophthalmology and is advancing a proprietary pipeline of DARPin drug candidates in oncology. The most advanced global product candidate is abicipar, a molecule currently in phase 3, in partnership with Allergan. Several DARPin molecules for various ophthalmic indications are also in development. The most advanced systemic DARPin molecule, MP0250, is in a clinical POC study in multiple myeloma. In addition, Molecular Partners will evaluate MP0250 for the treatment of solid tumors in a phase 1b/2 trial in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). MP0274, the company’s second-most advanced DARPin drug candidate in oncology, has entered into phase 1 clinical development. With its broad anti-HER activity, MP0274 inhibits HER1-, HER2-, and HER3-mediated downstream signaling via Her2, leading to induction of apoptosis. Molecular Partners is also advancing a growing preclinical pipeline that features several immuno-oncological development programs. DARPin is a registered trademark owned by Molecular Partners AG.

On January 8, 2018 Evotec AG (Frankfurt Stock Exchange: EVT, TecDAX, ISIN: DE0005664809) and APEIRON Biologics AG, a company focused on cancer immunotherapy, reported that the companies received the first milestone payment from Sanofi under a 3-party alliance signed in August 2015 (Press release, Evotec, JAN 8, 2018, View Source [SID1234522936]). The milestone payment of EUR 3 m will be split equally between the two biotech companies. The success payment was triggered when the partners successfully advanced an undisclosed, novel immuno-oncology small molecule into late-stage pre-clinical development. Under the alliance, the three companies work together to identify small molecule leads and targets for next-generation therapies in immuno-oncology, which may complement the pre-clinical and clinical profiles of leading checkpoint inhibitors.

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Dr Cord Dohrmann, Chief Scientific Officer of Evotec, commented: "The Evotec and APEIRON teams are proud to have achieved our first milestone with Sanofi to discover and develop novel immuno-oncology small molecules therapies. It is a first-in-class approach with tremendous potential in combination with marketed checkpoint inhibitors but also as standalone therapy. The field of immuno-oncology will continue to evolve and at Evotec we will continue to invest in this area."

Dr Hans Loibner, Chief Executive Officer of APEIRON Biologics, said: "We are delighted by the progress made in our collaboration with Evotec and Sanofi. Based on our scientific findings and the mode of action, we jointly agreed to accelerate the research and pre-clinical development of this very promising molecule. The successful achievement of this milestone further demonstrates our abilities to drive innovation in the field of immuno-oncology."

ABOUT THE EVOTEC-APEIRON-SANOFI-ALLIANCE
The strategic collaboration was set up in 2015 to support the long-term pipeline building for Evotec, APEIRON Biologics and Sanofi and has a potential value of over EUR 200 m in milestone payments and significant royalties. The collaboration includes major research and development efforts to advance a first-in-class orally available small molecule approach based on a novel target to treat solid and hematopoietic cancers by enhancing the anti-tumor activity of human immune cells. All three companies are making significant contributions to this collaboration in terms of scientific expertise, technological platforms and resources. The collaboration will further enhance and complement Sanofi’s extensive oncology portfolio and enables Evotec to address the drug discovery area of immuno-oncology. Furthermore, the agreement will substantially support APEIRON’s strategy of focusing on novel and innovative checkpoint inhibiting approaches.

On January 8, 2018 Sangamo Therapeutics presented Corporate Presentation J.P. Morgan 36th Annual Healthcare Conference (Presentation, Sangamo Therapeutics, JAN 8, 2018, View Source [SID1234522999]).

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