On April 4, 2018 Molecular Partners AG (ticker: MOLN), a clinical-stage biopharmaceutical company developing a new class of drugs known as DARPin therapies*, reported that new pre-clinical data from two of its pipeline candidates, MP0310 and its lead proprietary oncology drug MP0250, as well as the DARPin toolbox will be presented at the Annual Meeting 2018 of the American Association of Cancer Research (AACR) (Free AACR Whitepaper) in Chicago (Press release, Molecular Partners, APR 4, 2018, View Source [SID1234525191]).

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MP0310 targets simultaneously 4-1BB and FAP and is the first of a series of tumor-restricted agonists that only activate immune cells in the tumor and not in the rest of the body thereby allowing full activation and potentially opening the therapeutic window for combinations.

MP0250 is a phase 2 multi-DARPin candidate targeting simultaneously VEGF and HGF, two prominent escape pathways, and has the potential to reverse resistance that has built to standard of care cancer therapies.

The four abstracts to be presented include the most recent pre-clinical data of MP0310 as well as the rationale of MP0250 in EGFR mutated NSCLC (Non-small Cell Lung Cancer).

"We are very pleased with the progress of our portfolio showcasing the innovation power of the DARPin technology in the multi-specific biologics space," commented Michael T. Stumpp, Chief Scientific Officer. "With MP0250 and MP0310, we are moving forward with two candidates that have the potential to add significant patient benefit and support existing therapies."

The data will be presented in the following sessions under the following titles:

MP0310:
Tuesday, 17 April 2018, 8.00 am: PO.IM02.07 – Immunomodulatory Agents and Interventions 1: 3752 / 2 – Preclinical pharmacology of MP0310: A 4-1BB/FAP bispecific DARPin drug candidate promoting tumor-restricted T-cell co-stimulation (Link et al.)
Tuesday, 17 April 2018, 8.00 am: PO.TB07.01 – Cancer Imaging: Immunology and Systems Analysis in Vivo: 3029 / 2 – FAP-mediated tumor accumulation of a T-cell agonistic FAP/4-1BB DARPin drug candidate analyzed by SPECT/CT and quantitative biodistribution
(Reichen et al.)
Portfolio:
Tuesday, 17 April 2018, 1.00 pm: PO.CL06.05 – Immune Checkpoints 4: 4552 / 7 – Tumor-restricted immune modulation by multispecific molecules from the DARPin toolbox (Fiedler et al.)
MP0250:
Tuesday, 17 April 2018, 1.00 pm: PO.CT05 – Phase I/II, II, and III Trials in Progress: CT149 / 1 – MP0250, a VEGF- and HGF-blocking multi-DARPin drug candidate, in combination with tyrosine-kinase-inhibitors targeting EGFR-mutated NSCLC: Preclinical rationale and phase Ib/II study outline (Kiemle-Kallee et al.)
Full details on the Molecular Partners’ sessions at AACR (Free AACR Whitepaper) 2018 as well as all presentations can be found here. Following their presentation at the AACR (Free AACR Whitepaper), the posters will also be available one the Molecular Partners website.

About the DARPin Difference
DARPin therapeutics are a new class of protein therapeutics opening an extra dimension of multi-specificity and multi-functionality. DARPin candidates are potent, specific, safe and very versatile. They can engage in more than 5 targets at once, offering potential benefits over those offered 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 Phase 1 clinical development for the treatment of solid tumors and in Phase 2 development for hematological tumors. In addition, Molecular Partners intends to further evaluate MP0250 for solid tumors in a phase 1b/2 trial for EGFR-mutated NSCLC. MP0274, the second-most advanced DARPin drug candidate in oncology, has broad anti-HER activity; it inhibits HER1, HER2 and HER3-mediated downstream signaling via Her2, leading to induction of apoptosis. MP0274 has moved into Phase 1. 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 April 4, 2018 Moleculin Biotech, Inc., (NASDAQ: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company focused on the development of oncology drug candidates, all of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported that patients have successfully begun treatment in its U.S. Phase I/II clinical trial of Annamycin for the treatment of relapsed or refractory acute myeloid leukemia ("AML") (Press release, Moleculin, APR 4, 2018, View Source [SID1234525177]).

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The first patient enrolled in Moleculin’s Annamycin clinical trial was treated at The University Hospitals Cleveland Medical Center Seidman Cancer Center on March 28, 2018.

"It is exciting to now have this trial fully under way," commented Walter Klemp, Chairman and CEO of Moleculin. "We are also pleased that the same Cancer Center has begun treatment of the second patient as well, so we are hopeful that the pace of recruitment will also meet our expectations. We continue to work toward opening additional U.S. sites to increase patients’ access to this clinical trial."

On April 4, 2018 Pfizer Inc. reported that the U.S. Food and Drug Administration (FDA) accepted the company’s New Drug Application and granted priority review for dacomitinib, a pan-human epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-activating mutations (Press release, Pfizer, APR 4, 2018, View Source [SID1234525178]). The European Medicines Agency has also accepted the Marketing Authorization Application for dacomitinib for the same indication.

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The FDA grants Priority Review to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in September 2018.

"While significant progress has been made in the treatment of patients with non-small cell lung cancers harboring EGFR-activating mutations, it remains a challenging disease and new treatment options are needed," said Mace Rothenberg, M.D., chief development officer, Oncology, Pfizer Global Product Development. "In the pivotal clinical trial that supports these applications, dacomitinib showed clinically meaningful improvement in progression-free survival over gefitinib, one of the first EGFR-targeted therapies to demonstrate activity in this disease. These filing acceptances are an important step toward increasing treatment options for patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer."

Dacomitinib is the second investigational Pfizer lung cancer medicine to receive regulatory acceptance within two months, reinforcing Pfizer’s commitment to patients with NSCLC where there continues to be a significant unmet need.

The submissions are based on results from the Phase 3 ARCHER 1050 study, a global head-to-head trial investigating dacomitinib (n=227) compared to gefitinib (n=225) that showed dacomitinib may offer a clinically meaningful improvement over gefitinib. Patients that received dacomitinib in the study experienced a median progression-free survival (PFS) of 14.7 months compared with 9.2 months in patients treated with gefitinib, as measured by Blinded Independent Central Review (BICR). This difference represented a 41 percent reduction in the risk of disease progression or death for patients treated with dacomitinib compared with gefitinib (HR = 0.59 [95% CI: 0.47,0.74], p <0.0001) as a first-line treatment in locally advanced or metastatic NSCLC with EGFR-activating mutations.

The adverse events (AEs) observed with dacomitinib in the study were consistent with findings from previous trials. The most common AEs were diarrhea (87%), nail changes (62%), rash/dermatitis acneiform (49%), and mouth sores (44%). The most common Grade 3 AEs with dacomitinib were rash (14%) and diarrhea (8%). Grade 4 AEs occurred in 2 percent of dacomitinib-treated patients. There was one case of Grade 5 diarrhea and one case of Grade 5 liver disease. The discontinuation rate due to treatment-related AEs for dacomitinib was 10 percent compared to 7 percent for gefitinib.

The ARCHER 1050 results were published in Lancet Oncology, shared as an oral late-breaker presentation at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and featured in the ASCO (Free ASCO Whitepaper) press program. A final assessment of overall survival from ARCHER 1050 will be presented at a medical meeting later this year.

About Dacomitinib

Dacomitinib is an investigational, oral, once-daily, irreversible pan-human epidermal growth factor receptor tyrosine kinase inhibitor (TKI). It has not received regulatory approval in any country.

In 2012, Pfizer and SFJ Pharmaceuticals Group entered into a collaborative development agreement to conduct ARCHER 1050 across multiple sites.

About Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer deaths worldwide.1 NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting.2 Approximately 75 percent of NSCLC patients are diagnosed late with metastatic or advanced disease where the five-year survival rate is only five percent.2,3,4

EGFR is a protein that helps cells grow and divide. When the EGFR protein is mutated it can cause cancer cells to form. EGFR mutations occur in 10 to 35 percent of NSCLC tumors globally, yet the disease is associated with low survival rates and disease progression remains a challenge. 5,6

About Pfizer in Lung Cancer

Pfizer Oncology is committed to addressing the unmet needs of patients with lung cancer, the leading cause of cancer-related deaths worldwide and a particularly difficult-to-treat disease. Pfizer strives to address the diverse and evolving needs of patients with non-small cell lung cancer (NSCLC) by developing efficacious and tolerable therapies, including biomarker-driven therapies and immuno-oncology (IO) agents and combinations. By combining leading scientific insights with a patient-centric approach, Pfizer is continually advancing its work to match the right patient with the right medicine at the right time. Through our growing research pipeline and collaboration efforts, we are committed to delivering renewed hope to patients living with NSCLC.

On April 4, 2018 Siamab Therapeutics, Inc., a biopharmaceutical company developing novel glycan-targeted cancer therapeutics, reported that it will present new research findings for its ST1 monoclonal antibody (mAb) therapeutic program during a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018, being held April 14-18, 2018, at McCormick Place in Chicago (Press release, Siamab Therapeutics, APR 4, 2018, View Source [SID1234525179]). Myeloid derived suppressor cells (MDSCs) are shown to express Sialyl-Tn (STn) across a wide range of patient tumor samples and may therefore represent an optimal therapeutic target for the ST1 program. MDSCs are major regulators of the tumor anti-immune response that act by suppressing T cells. Ovarian xenograft model data will be presented that further demonstrates the potential for targeting STn+ MDSCs with ST1 in a clinical setting. ST1, Siamab’s lead program, is in late stage preclinical development formatted as an antibody drug conjugate (ADC) for the treatment of STn-expressing solid tumors.

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"We are pleased to present new patient tumor data and ovarian carcinoma xenograft data for our ST1 antibody drug conjugate targeting STn at the AACR (Free AACR Whitepaper) 2018 annual meeting," said Jeff Behrens, president and chief executive officer of Siamab. "These research findings are exciting as they continue to show that STn provides a uniquely glycan-specific target for the treatment of solid tumors. Importantly, the findings demonstrate that our antibody therapeutic targeting STn offers the potential to go beyond tumor targeting to also directly target and deplete immune-suppressive MDSCs, enabling immune system re-engagement and increasing the potential for better patient outcomes."

The poster presentation will highlight new data showing the presence of STn on the surface of MDSCs in a growing body of patient tumor samples, as well as data in patients and xenograft models linking STn expression on MDSCs to tumor cell STn expression. In addition, the poster will highlight data that demonstrates depletion of STn+ MDSCs after treatment with an anti-STn ADC in an ovarian carcinoma xenograft model.

Details for the poster presentation are as follows:

Abstract Title and Number: Myeloid derived suppressor cells (MDSCs) express Sialyl Tn (STn) and are a therapeutic target for anti-STn antibody drug conjugates (#6892)
Date: Wednesday, April 18, 2018
Time: 8:00 a.m.-12:00 p.m. CT
Session Title: Therapeutic Antibodies, including Engineered Antibodies 4
Location: McCormick Place, Poster Section 28
Poster Board Number: 20

Siamab’s proprietary technology platform enables the development of highly specific mAb therapeutics, including ADCs, targeting cancer cell surface glycans called tumor-associated carbohydrate antigens (TACAs). TACAs are an emerging set of tumor specific antigens implicated in immune suppression, chemoresistance and a cancer stem cell (CSC) phenotype. STn, the sialylated version of the carbohydrate Tn antigen, is broadly expressed in human cancers including ovarian, gastric, colon, prostate, pancreatic and lung. The presence of STn in tumors is associated with metastatic disease, poor prognosis, and reduced overall survival. Tumor STn expression is well-established and can be leveraged for targeted cancer therapy; however, its expression on immuno-suppressive tumor infiltrating lymphocytes, such as MDSCs, is a new finding. Siamab has identified and utilized the presence of STn on MDSCs to target and deplete MDSCs in vivo, providing a potential novel therapeutic approach for the treatment of solid tumors.

A copy of the poster will be made available on the company’s website after the presentation.

On April 4, 2018 Vaccibody AS, a clinical stage immunotherapy company focused on developing personalized neoantigen cancer vaccines to target solid tumors, reported that informed consent signed by the first patient and enrolment process initiated in the clinical trial. (Press release, Vaccibody, APR 4, 2018, View Source [SID1234525180]) The patient will be enrolled in Heidelberg, Germany at the National Center for Tumor Diseases by principal investigator, Prof. Dr. med. Jürgen Krauss, Head of Section for Clinical Immunotherapy.

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Prof. Dr. med. Jürgen Krauss, said, "We are very pleased to have initiated this clinical phase I/IIa for Vaccibody’s neoantigen vaccine. The neoantigen vaccine holds the potential to assist the patient’s immune system to generate specific T-cell responses to its individual cancer neoantigens and in this way may help the patient to more effectively fight the cancer. We hope this clinical trial will help pave the way for a novel class of new efficacious and safe treatment for cancer patients."

Mads Axelsen, MD, Chief Medical Officer in Vaccibody, said "We are proud and very pleased to work with so experienced cancer experts in this trial as Prof. Jürgen Krauss from Heidelberg, Prof. Angela Krackhardt from Munich and Prof. Elke Jäger from Frankfurt. This first-in-man trial is planned to enroll up to 40 patients with locally advanced or metastatic non-small cell lung cancer, melanoma, renal, bladder or head and neck cancer. The VB10.NEO vaccine will be given in combination with standard of care checkpoint inhibitors as a new treatment modality to help patients with cancer."

Dr. Agnete Fredriksen, President and Chief Scientific Officer in Vaccibody, commented "The first patient marks an important new phase in Vaccibody and we are very excited to start to tailor-make one vaccine per patient using our proprietary vaccination technology. The unique ability to induce strong CD8 T cell responses to multiple neoepitopes that we have observed in preclinical models, in addition to the manufacturing advantages essential for individualized vaccines, are basis for our enthusiasm moving this concept into clinical trials."