On September 5, 2018 Checkmate Pharmaceuticals (Checkmate), reported that it has entered into a clinical trial collaboration and supply agreement with the alliance between Merck KGaA, Darmstadt, Germany, and Pfizer to evaluate CMP-001, a TLR9 agonist, in combination with avelumab*, a human anti-PD-L1 antibody (Press release, Checkmate Pharmaceuticals, SEPT 5, 2018, View Source [SID1234529297]). The collaboration will evaluate the safety and effectiveness of CMP-001 administered in combination with avelumab in patients with advanced squamous cell cancer of the head and neck (SCCHN) resistant to a prior PD-1/PD-L1 inhibitor.

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!

"This collaboration is an important next step in advancing our clinical development program for CMP-001 into indications beyond melanoma, where we already have demonstrated proof-of-concept,’’ said Art Krieg, CEO of Checkmate. "Merck KGaA, Darmstadt, Germany, and Pfizer are ideal partners for Checkmate given their commitment to developing avelumab broadly in the immuno-oncology field."

"Early data suggest CMP-001 exhibits clinically encouraging activity and we are looking forward to investigating this compound in combination with avelumab in advanced head and neck cancer," said Chris Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-oncology, Early Development and Translational Oncology, Pfizer Global Product Development. "Our collaboration with Checkmate further demonstrates the alliance’s commitment to explore novel combinations with avelumab to potentially improve patient outcomes."

"Combining avelumab with CMP-001 adds to our clinical development strategy of IO combinations in different hard-to-treat cancers," said Alise Reicin, Head of Global Clinical Development at the Biopharma business of Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono. "We look forward to working with Checkmate to explore how the combination of these agents can potentially advance care for these patients."

Avelumab has received accelerated approval** by the US Food and Drug Administration (FDA) for the treatment of patients with metastatic Merkel cell carcinoma (MCC) and previously treated patients with locally advanced or metastatic urothelial carcinoma (mUC), and is under further clinical evaluation across a range of tumor types under a global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer.

*Avelumab is under clinical investigation for treatment of SCCHN in combination with CMP-001 and has not been demonstrated to be safe and effective for this use. There is no guarantee that avelumab will be approved for SCCHN by any health authority worldwide.

About CMP-001

CMP-001 is a first-in-class CpG-A Toll-like receptor 9 (TLR9) agonist that is encapsulated in a virus-like particle (VLP). CMP-001 is designed to induce both innate and adaptive anti-tumor immune responses, thereby converting immunologically "cold" tumors into immunologically "hot" tumors, with the potential to mediate tumor regression. It is the only CpG-A class TLR9 agonist in clinical trials and differs from other CpG classes in clinical development by having a native DNA backbone that induces the highest levels of type I IFN. Based on analyses of gene expression in human tumors showing that increased IFN and related immune gene expression is associated with better response to PD-1 inhibition, it is believed that this mechanism of action may restore, enable or improve responses to anti-PD-1/PD-L1 therapeutics.

CMP-001 is being evaluated in multiple tumor types to assess its safety, activity, alternative routes of administration and combination with other immunotherapies and modalities. For information on CMP-001 trials that are currently recruiting patients, please visit www.clinicaltrials.gov.

About Avelumab

Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.1-3 Avelumab has also been shown to induce NK cell mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.3-5 In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

Avelumab is currently being evaluated in the JAVELIN clinical development program, which involves at least 30 clinical programs, including seven Phase III trials, and more than 8,600 patients across more than 15 different tumor types. For a comprehensive list of all avelumab trials, please visit clinicaltrials.gov.

Approved Indications in the US**

The US Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO) for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information from the US FDA Approved Label

The warnings and precautions for avelumab (BAVENCIO) include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions), infusion-related reactions and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO for mMCC and patients with locally advanced or metastatic UC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash.

On September 4, 2018 Santhera Pharmaceuticals (SIX: SANN) reported its first half-year results as of June 30, 2018, outlines the Company’s vision and strategy as it moves through the second half of 2018, and positions itself for future growth (Press release, Santhera Pharmaceuticals, SEP 4, 2018, View Source [SID1234529256]).

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!

Thomas Meier, PhD, Chief Executive Officer of Santhera, said: "Our vision is to be a leader in the development and commercialization of rare disease therapies for neuro-ophthalmology, neuromuscular and pulmonary indications. Our strategy to achieve this vision focuses on three distinct pillars: One, we continue to expand our commercial reach and grow sales of our revenue generating product Raxone for the treatment of LHON. Turnover during the first half-year has been above expectation and we are on track to exceed our 2018 guidance. Two, we are progressing our pipeline assets towards regulatory approval in the EU and the U.S. and, with the inclusion of new data, intend to submit marketing authorization applications for idebenone in DMD in 2019. Three, we are pursuing an active in-licensing strategy for high quality, late-stage rare disease assets with a short time to market."

"We see multiple business development opportunities to leverage our existing development, regulatory and commercial capabilities and our recent in-licensing for POL6014 to treat cystic fibrosis is the first example of Santhera advancing this strategy. With this vision and strategy in mind, we believe Santhera is optimally positioned to create value with its existing and future product portfolio opportunities."

Financial highlights:

1H 2018 sales of CHF 16.0 million, increase of 48% compared to 1H 2017
Operating expenses of CHF 39.9 million (1H 2017: CHF 30.5 million)
Operating result of CHF -26.3 million (1H 2017: CHF -21.4 million) leading to a net result of
CHF -27.4 million (1H 2017: CHF -22.7 million)
Cash, cash equivalents and short-term financial assets of CHF 34.8 million (June 30, 2018)
Full year sales guidance raised to CHF 30-32 million
Operational highlights:

Acquisition of worldwide exclusive license to develop and commercialize clinical stage candidate POL6014 for cystic fibrosis (CF) and other pulmonary diseases
Renewal of the Early Access to Medicines Scheme (EAMS) Scientific Opinion by UK’s Medicines and Healthcare products Regulatory Agency (MHRA) for idebenone for patients with Duchenne muscular dystrophy (DMD) in the UK
Launch of Expanded Access Program with idebenone for patients with DMD in the U.S.
Submissions of regulatory dossiers for Raxone in Leber’s hereditary optic neuropathy (LHON) in South Korea and Serbia
Analysis of new data linking study findings with idebenone in DMD to clinically relevant patient benefits for inclusion in regulatory submissions in Europe and the U.S. (planned for 2019)
Progress with clinical development candidates having successfully completed first clinical trial with omigapil in patients with congenital muscular dystrophy (CMD) and advanced preparations for multiple-ascending dose trial for POL6014 in CF
First half-year overview

Strong Raxone sales in 1H 2018
Net sales of Raxone in Europe amounted to CHF 16.0 million (1H 2017: CHF 10.9 million) which corresponds to a strong 48% increase year-on-year. Turnover was mainly driven by increased number of patients receiving the drug in existing markets and new launches in additional EU countries. Santhera’s goal is to provide treatment to LHON patients worldwide and the Company has submitted a new drug application for LHON in South Korea, one of the major markets in Asia. A decision from the South Korean drug regulatory authorities who granted orphan drug designation for Raxone in LHON can be expected by summer 2019. At the end of the first half of 2018, Santhera was marketing Raxone in more than 20 countries.
Broadened product pipeline with licensing agreement
In February, Santhera completed the first step in its strategy to in-license pipeline strengthening, clinical stage product candidates in neuro-ophthalmology, neuromuscular and pulmonary diseases by entering into a license agreement with Polyphor for POL6014. Under the agreement, Santhera obtained the worldwide, exclusive rights to develop and commercialize POL6014, a clinical stage selective inhibitor of human neutrophil elastase with the potential to treat cystic fibrosis and other pulmonary diseases.
UK’s MHRA renewed EAMS positive scientific opinion for Raxone in DMD
In June, the UK’s MHRA renewed the EAMS scientific opinion for Raxone for a further year for patients with DMD in respiratory function decline who are not taking glucocorticoids. Inclusion in EAMS allows eligible patients with DMD, who meet criteria defined under this scheme, to gain free of charge access to Raxone in the UK.
Launch of U.S. Expanded Access Program with idebenone for patients with DMD
Santhera has successfully launched and enrolled the first patients in a U.S. Expanded Access Program (EAP), called BreatheDMD, with idebenone. Through the BreatheDMD program, eligible patients in the U.S. with DMD who are 10 years and older and in respiratory function decline can obtain access to investigational idebenone, at no cost, through a growing network of research centers across the U.S.
New supporting data to be included in submissions for marketing authorization applications for DMD in 2019
In July, Santhera announced results of a comparative analysis of the Phase III DELOS trial outcome with new data from natural history studies. This analysis showed that the treatment effect with idebenone observed in the DELOS trial can be linked to a delay in the initiation of assisted ventilation by three years, which is of high clinical relevance. In coming months, Santhera and its academic partners will prepare for the publication of additional clinical data that demonstrate long-term efficacy of idebenone on respiratory function outcomes in patients with DMD, thereby supporting the positive data from the successful Phase III DELOS trial. The findings will be discussed with regulators in the coming months and will be included in the regulatory dossier in preparation of marketing authorization applications for idebenone in DMD in Europe and the U.S. in 2019.
Omigapil safe and well tolerated in patients with congenital muscular dystrophy (CMD)
The single-center interventional trial to establish the pharmacokinetic profile and to evaluate the safety and tolerability of omigapil in pediatric and adolescent patients with CMD was successfully completed. Santhera plans to seek advice on the clinical development program of omigapil by the TREAT-NMD Advisory Committee for Therapeutics (TACT).
Liquidity base allows for the continuation of the strategy as planned
As of the end of June 2018, Santhera had cash, cash equivalents and short-term financial assets of CHF 34.8 million (December 31, 2017: CHF 58.2 million). These funds will allow the Company to proceed with its clinical trial program and regulatory filings as foreseen.
Revenue Guidance

Santhera will continue to grow its international business, advance its pipeline programs and proceed business development initiatives to expand its late stage product portfolio. Based on its sales performance in the first six months of the current year and the positive outlook, the Company expects to exceed its guidance of CHF 28-30 million and anticipates reaching a higher turnover of CHF 30-32 million in 2018.

Conference Call
Santhera will host a conference call on September 4, 2018 at 13:00 CEST / 12:00 BST / 07:00 EDT. Thomas Meier, PhD, CEO of Santhera, and Christoph Rentsch, CFO of Santhera, will discuss the half-year 2018 financial results and will provide an update on corporate developments.
Participants are invited to call one of the following numbers 10-15 minutes before the conference call starts (no dial-in code is required):
Europe: +41 58 310 50 00
UK: +44 207 107 0613
USA: +1 631 570 5613

On September 4, 2018 BioInvent International AB (OMXS: BINV) reported that it has started dosing of the first patient in a dose escalation, consecutive-cohort, open-label phase I/IIa study of BI-1206 after recently obtaining approval from the Swedish Medical Product Agency and the U.S. Food and Drug Administration to initiate patient inclusion (Press release, BioInvent, SEP 4, 2018, http://www.bioinvent.com/media/press-releases/releases?id=69B6C3003DD16AD1 [SID1234529257]). The study will recruit approximately 30 patients across sites in the EU and the U.S. The trial will evaluate BioInvent’s proprietary antibody BI-1206 in combination with rituximab in patients with indolent relapsed or refractory B-cell non-Hodgkin’s lymphoma. The targeted sub-indications are mantle cell lymphoma, follicular lymphoma, and marginal zone lymphoma. The study will explore BI-1206’s safety and tolerability, and seek to determine a recommended phase ll dose when given in combination with rituximab.

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!

Andres McAllister, Chief Medical Officer of BioInvent, said: "With its unique ability to recover and enhance the activity and efficacy of rituximab – a major component of the current standard treatment of NHL and clinically one of the best validated antibodies in cancer therapy, BI-1206 has the potential to become a mainstay in the cancer drug arsenal, and substantially improve outcomes."

About BI-1206 in combination with rituximab
BI-1206 is a monoclonal antibody that recognizes with high affinity and selectivity FcγRIIB (CD32B), the only inhibitory member of the FcγR family. CD32B is highly overexpressed by a number of NHL tumors, and overexpression has been shown to be associated with poor prognosis in difficult-to-treat forms of NHL, such as mantle cell lymphoma or follicular lymphoma. By blocking FcγRIIB, BI-1206 is expected to recover and enhance the activity of rituximab or other anti-CD20 monoclonal antibodies. The combination of the two drugs could provide a new and important option for patients suffering from NHL.

On September 4, 2018 Aduro Biotech, Inc. (NASDAQ: ADRO) reported the publication of a peer reviewed paper in Leukemia authored by scientists from the Dana Farber Cancer Institute and Aduro as part of their ongoing collaboration to study the role of APRIL (A PRoliferation Inducing Ligand) in multiple myeloma (MM) (Press release, Aduro Biotech, SEP 4, 2018, View Source;p=RssLanding&cat=news&id=2366001 [SID1234529283]). The authors profile the impact that APRIL, acting through its receptor TACI (transmembrane activator and cyclophilin ligand interactor), has on immune regulatory T cells (Tregs) in MM. The paper further reports that APRIL binding to TACI contributes to the immunosuppressive and treatment resistant MM bone marrow microenvironment, an effect that could potentially be mitigated by anti-APRIL antibody, BION-1301. Aduro is currently advancing BION-1301 in a Phase 1/2 dose escalation trial for the treatment of MM.

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!

Key findings from the study include the observation that TACI expression is significantly higher in Tregs than conventional T cells from the same patient. APRIL significantly stimulates proliferation and survival of these Tregs, whereas a neutralizing anti-APRIL antibody (BION-1301) may inhibit these effects. Furthermore, the paper explained how APRIL specifically augments Tregs to enhance MM cell survival.

"It is now well-known that APRIL acts through its two receptors TACI and BCMA (B cell maturation antigen), the most specific MM antigen expressed at high levels in malignant plasma cells/B cells of all MM patients. Our newest findings from this study indicate that an anti-APRIL antibody such as BION-1301 may have the potential to treat MM through a differentiated mechanism of action, not only by inhibiting APRIL binding to BCMA, but also stimulating immunity to cancer by blocking APRIL binding to TACI," commented Dr. Yu-Tzu Tai, lead author and Principal Scientist in Medical Oncology at the Dana-Farber Cancer Institute.

The paper entitled "APRIL signaling via TACI mediates immunosuppression by T regulatory cells in multiple myeloma: therapeutic implications," can be accessed at View Source

About APRIL
APRIL is a member of the tumor necrosis factor superfamily and is primarily secreted by bone marrow and/or myeloid cells. APRIL is overproduced in patients with multiple myeloma and binds to BCMA and TACI to stimulate a wide variety of responses that promote MM growth and survival and suppress the immune system so that the tumor cells are protected and sustained in the bone marrow.

About BION-1301
Aduro is currently evaluating BION-1301, its most advanced proprietary B-select monoclonal antibody, as a novel therapy for MM. Despite new treatments recently approved in MM, this disease remains incurable as patients relapse, or become resistant to, currently-available therapies. In preclinical studies, Aduro has established that APRIL plays a crucial part in the protective bone marrow tumor microenvironment. In these studies, APRIL, through BCMA, was shown to be critically involved in the survival, proliferation and chemoresistance of MM, and upregulates mechanisms of immunoresistance, including PD-L1 upregulation. BION-1301, a humanized antibody that blocks APRIL from binding to its receptors, has been shown in preclinical studies to halt tumor growth and overcome drug resistance. In addition, BION-1301 also demonstrated the ability to inhibit immune suppressive effects of regulatory T cells via TACI but not BCMA in MM blood and bone marrow. BION-1301 is currently being evaluated in a Phase 1/2 clinical study in patients with relapsed or refractory MM.

On September 4, 2018 BeiGene, Ltd. (NASDAQ: BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that the company will present at the Morgan Stanley 16th Annual Global Healthcare Conference in New York, NY (Press release, BeiGene, SEP 4, 2018, View Source;p=irol-newsArticle&ID=2365780 [SID1234529258]). The presentation is scheduled for 11:40 AM ET on Wednesday, September 12, 2018.

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!