On March 16, 2016 Cellectis (Alternext: ALCLS – Nasdaq: CLLS), a biopharmaceutical company focused on developing immunotherapies based on gene edited CAR T-cells (UCART), and MabQuest SA, a biotech company focused on the development of antibody-based therapeutic interventions, reported that they have entered into a research collaboration and license agreement pertaining to the development of a new class of monoclonal antibodies targeting PD-1 (Press release, Cellectis, MAR 16, 2016, View Source [SID1234645116]).

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The action of these PD-1 antibodies is to promote the recovery of T-cells from exhaustion through a new mechanism of action. This new class of antibodies differs from currently approved anti-PD-1 mAbs in that they do not block the PD-1-PD-L1 interaction. These anti-PD-1 mAbs have potential uses for multiple indications in immunotherapy, including notably treatments for a variety of cancers. Cellectis plans to use this new class of anti-PD-1 antibodies either in combination therapy with its gene-edited UCART product candidates or single-agent or in combination with other already approved immunotherapy drugs.

In vitro studies have shown that the combination of these novel PD-1 mAbs with currently approved anti-PD-1 mAbs enhances the recovery of T-cells from exhaustion. Due to their new mechanism of action, these anti-PD-1 mAbs may be used in combination with other PD-1/PD-L1 inhibitors, such as Nivolumab and Pembrolizumab, or other checkpoints inhibitors and immunotherapy approaches for boosting the therapeutic effects of single therapy. Furthermore, this novel class of anti-PD-1 mAbs may represent an alternative and effective therapeutic intervention in those cancer patients with tumors expressing low levels of PD-L1, with respect to the currently approved anti-PD-1 mAbs. In addition, Cellectis intend to combine these PD-1 mAbs with its gene-edited UCART product candidates to enhance their activity and increase their half-life.

The agreement includes a collaboration phase funded by Cellectis whereby Cellectis and MabQuest will jointly pursue preclinical research on several candidate antibodies; and a clinical development and commercialization phase of the best selected antibodies which will be led by Cellectis.

Under the agreement, MabQuest has granted an exclusive option to Cellectis. Upon exercise of the option, Cellectis would be granted worldwide exclusive rights over the family of PD-1 antagonist antibodies developed under the collaboration for all fields, and further potential derivatives of these antibodies.

"We are very pleased to have signed this agreement with MabQuest, with founders and lead scientists who have great expertise in the field of immunology and monoclonal antibodies," said André Choulika, Chairman and Chief Executive Officer of Cellectis. "This collaboration is an important building block for our gene-edited UCART product candidates and for our immunotherapy franchise. This new partnership fits perfectly into Cellectis’ strategy of expanding our focus in the cancer immunotherapy space with our CAR T-cell based approaches."

"The collaboration agreement with Cellectis is a tremendous opportunity for MabQuest to move into clinical development with this new class of anti-PD-1 mAbs. This collaboration will also boost MabQuest’s discovery program to develop additional antibody-based strategies to modulate the host immune system," said Dr. Giuseppe Pantaleo, President of MabQuest and Professor of Medicine and Chief of the Service of Immunology and Allergy at the Lausanne University Hospital, Lausanne, Switzerland.

On March 16, 2016 Amrita Therapeutics ("the Company"), a biopharmaceutical company developing innovative technologies from the microbiome, reported that it is pleased to announce its submission to the FDA of a pre-INDType B Meeting request for discussion of development plans for the Company’s lead oncology peptide AT-01C (Press release, Amrita Therapeutics, MAR 16, 2016, View Source [SID:1234512730]).

Amrita Therapeutics’ AT-01C peptide demonstrates p53 ("guardian of the genome") tumor suppression and binds to the SMAR1* protein for down-regulation of oncogenes with little or no toxicity to healthy tissues, with effectiveness against solid tumors including genitourinary, gastrointestinal (GI), liver and CNS cancers. In parallel to clinical development of AT-01C, the Company is focusing on the ‘master regulator’ SMAR1 biomarker as a companion diagnostic test to identify patients most likely to benefit from AT-01C therapy.

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Susan K. Finston, Amrita Therapeutics’ Chief Executive Officer notes, "we continue to gain insights into the extraordinary therapeutic potential of peptides from the microbiome and look forward to clinical development of AT-01C to address unmet needs of cancer patients."

With less toxicity and fewer side effects, naturally occurring peptide drugs have a greater likelihood of regulatory approval double that of small molecule new chemical entities (NCEs) for a range of indications including infectious diseases, metabolic disorders and advanced cancer therapies. Amrita’s first peptide drug has the potential to reach sales in excess of $ 1 billion within the first years of launch.

On March 16, 2016 GSK and Miltenyi Biotec reported a strategic collaboration that will bring together GSK’s expertise in developing cell and gene therapy based treatments with Miltenyi Biotec’s global leadership in cell processing and related technologies in cell therapy (Press release, GlaxoSmithKline, MAR 16, 2016, View Source [SID:1234509747]). The collaboration seeks to optimise the manufacture and delivery of these personalised therapies using increased automation and leading edge processing technology.

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GSK is building a cell and gene therapy R&D platform to underpin development of novel therapies in oncology and rare diseases – two of its core research areas. This reflects the company’s belief in cell and gene therapy’s potential as an important treatment approach for tackling the underlying cause of serious disease.

Through the collaboration, Miltenyi Biotec will engage with GSK to integrate greater automation and high-tech processing technology into GSK’s current cell and gene therapy R&D manufacturing capabilities. The goal is to use this increased automation to further industrialise cell and gene therapy, overcoming the manufacturing and scale-up constraints associated with current, more manual cell and gene therapy processes. This could reduce the costs and geographical barriers associated with this treatment approach, speed development of therapies and support their potential beyond rare diseases and limited populations.

The collaboration will also bring together the technology and expertise of both companies to advance the discovery of new CAR (chimeric antigen-receptor) T-cell based therapeutics – cells that have been engineered to target and destroy cancer cells by strengthening a patient’s natural T-cell response. GSK and Miltenyi Biotec will collaborate on defined CAR-T oncology targets and on the development of advancements in technologies in this space that may be further applied by both companies. This collaboration supplements GSK’s existing CAR-T preclinical portfolio.

Patrick Vallance, President of Pharmaceuticals R&D at GSK, said: "Cell based gene therapies are living treatments, unique to individual patients and complex to manufacture. We see tremendous potential for the cell and gene therapy platform we are building within GSK, however the complexity of current manufacturing processes limits their use to local treatment of small patient populations. Working with Miltenyi Biotec, our vision is to transform current technology so that we can expand the possibilities for cell and gene therapy treatment to wider patient populations with broader geographical reach."

Stefan Miltenyi, President and CEO at Miltenyi Biotec, said: "For more than 20 years we have been developing and providing cell therapy solutions to patients worldwide. Working together with the global experts at GSK, we will accelerate innovation to broaden patient access to future personalised cell and gene therapy."

About Cell and Gene therapies
Cell and gene therapies are potentially powerful disease modifying experimental treatments that focus on genetically engineering living cells to either repair the direct cause of a genetic defect or equip them with genes that enhance their functions.

To make cell and gene therapy treatments, selected populations of cells are extracted from the body and genetically-engineered to produce the desired therapeutic effect. This can mean replacing a faulty gene in a stem cell or changing immune cells so they can recognise tumours. The transformed cells are then re-introduced into a patient’s body where they exert their effect by replacing faulty genes or educating the immune system to recognise and kill cancer cells

On March 16, 2016 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that it will feature new preclinical data on FPA144 in a poster presentation during the 2016 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held April 16-20 in New Orleans (Press release, Five Prime Therapeutics, MAR 16, 2016, View Source [SID:1234509614]).

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Abstract #1407 titled, "FPA144, a Therapeutic Monoclonal Antibody Targeting the FGFR2b Receptor, Promotes Antibody Dependent Cell-Mediated Cytotoxicity and Stimulates Sensitivity to PD-1 the 4T1 Breast Tumor Model in Mice," is now accessible on the meeting website. The poster presentation will take place from Monday, April 18, 2016, from 8:00 AM – 12:00 PM in Section 22. The poster will be made available on the publications page of the Five Prime website following the presentation.

FPA144 is an FGFR2b-specific humanized monoclonal antibody designed to treat patients with cancers that overexpress the FGFR2b receptor. FPA144 is a targeted immunotherapy that has been engineered to recruit NK cells into the tumor microenvironment and kill cancer cells by antibody-dependent cell-mediated cytotoxicity (ADCC). At the 2014 AACR (Free AACR Whitepaper) Annual Meeting, Five Prime presented data showing that FPA144 can produce complete and durable tumor growth inhibition in FGFR2b-overexpressing and FGFR2 gene-amplified gastric cancer xenografts in immune-compromised mice. The ongoing Phase 1 monotherapy trial is enrolling patients with gastric cancer, a disease in which FGFR2b protein overexpression and FGFR2 gene amplification have been associated with poor prognosis.

In recent months, Five Prime evaluated the anti-tumor effects and immune cell recruitment of FPA144 in the 4T1 model of breast cancer in immune-competent mice. Although the tumor cells in this model express FGFR2b, the FGFR2 gene is not amplified. Therapeutic treatment with FPA144 alone in the orthotopic 4T1 model resulted in a reduction in tumor burden (33%, P<0.001) and within 24 hours, the recruitment of NK cells to the site of tumor implantation, while a modified antibody lacking Fc effector function neither inhibited tumor growth nor led to the recruitment of NK cells. Together these data indicate that enhanced ADCC activity of FPA144 may have the potential to play an important mechanistic role in anti-tumor efficacy in cancers that have modest expression of FGFR2b.

In addition, four days after treatment with FPA144, there was an influx of T cells into the tumor as well as increased expression of PD-L1, providing a strong rationale that FPA144 may combine effectively with PD-1 blockade. Although PD-1 blockade by the RPM1-14 antibody did not inhibit tumor growth as a single agent in the 4T1 model, treatment with RPM1-14 in combination with FPA144, inhibited tumor growth by 49% (P<0.001), demonstrating an additive benefit of combination therapy. These results suggest that FPA144 alters the immune cell composition of the tumor microenvironment in a way that primes the tumor for additional anti-tumor activity when combined with PD-1 blockade.

About FPA144

FPA144 is an anti-FGF receptor 2b (FGFR2b) humanized monoclonal antibody in clinical development as a targeted immune therapy for tumors that over-express FGFR2b, as determined by a proprietary immunohistochemistry (IHC) diagnostic assay. FPA144 is designed to block tumor growth through two distinct mechanisms. First, it binds specifically to FGFR2b and prevents the binding of certain fibroblast growth factors that promote tumor growth. Second, it has been engineered to drive immune-based killing of tumor cells by antibody-dependent cell-mediated cytotoxicity (ADCC) and the recruitment of natural killer (NK) cells. FGFR2 gene amplification (as identified by FISH) is found in a number of tumors, including in approximately 5% of gastric cancer patients, and is associated with poor prognosis.