SYNIMMUNE GmbH Initiates First-in-Human Study of Fc-Optimized Antibody FLYSYN for the Treatment of Acute Myeloid Leukemia

On May 30, 2017 SYNIMMUNE GmbH, a biotechnology company focusing on the development of innovative and effective anti-tumor antibodies for orphan hematopoietic malignancies, reported that the Company has recently initiated a first-in-human clinical study of FLYSYN, a novel Fc-optimized antibody, for the treatment of acute myeloid leukemia (AML) (Press release, Synimmune, MAY 30, 2017, View Source [SID1234552070]).

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The phase I study of FLYSYN is being conducted at the University Hospital Tuebingen and at the University Hospital Ulm in Germany and will enroll up to 28 AML patients with minimal residual disease. Four patient cohorts will receive increasing doses of FLYSYN, each as a single intravenous infusion. The dose escalation phase will be followed by an expansion cohort phase to assess initial efficacy.

The primary endpoints of the study are safety and tolerability. Secondary endpoints include immunogenicity, pharmacokinetics and pharmacodynamics as well as preliminary efficacy in terms of overall response rate and duration of response. Patients will be followed for up to 18 months. Preliminary results from the trial are expected in 2018, the trial is projected to complete in early 2019.

"The initiation of this phase I study with FLYSYN is a major milestone for SYNIMMUNE, as this is the first antibody from our pipeline to be tested in humans," said Dr. Martin Steiner, CEO of SYNIMMUNE GmbH. "The key goals of this study are to determine the maximum tolerated dose and to assess the preliminary therapeutic effect of FLYSYN in AML patients with minimal residual disease. Today, the majority of these patients relapse within several months. Our antibody is intended to delay or even prevent such relapse. We therefore believe that, if proven safe and effective, FLYSYN could become an attractive treatment option for many AML patients."

About FLYSYN:

The chimeric and Fc-optimized IgG1 antibody FLYSYN binds specifically and with high avidity to the human fms-like tyrosine kinase 3 (FLT3). An increased expression of this cell surface receptor is measured on leukemic blast cells in 70-100% of AML patients, while only small amounts of FLT3 are expressed on monocytes and progenitor stem cells, avoiding off-target binding and stem cell toxicity. Therefore, FLT3 is a suitable and highly selective target for therapeutic antibodies to treat leukemia patients.

FLYSYN contains a genetic optimization of its Fc-part, resulting in optimized binding to cells expressing the Fc receptor, particularly Natural Killer (NK) cells, and thus in substantially improved antibody-dependent cell-mediated cytotoxicity (ADCC). FLYSYN is a monospecific antibody for the treatment of AML patients at a stage of minimal residual disease (MRD). Most AML patients achieve complete remission (CR) with MRD after regular chemotherapy, but the majority relapses to AML within several months, requiring additional courses of chemotherapy or stem cell transplantation. FLYSYN is intended to delay or prevent such relapse in AML patients with MRD.

i2 Pharmaceuticals Acquires Antibody and Protein Engineering Technology Portfolio from Sea Lane Biotechnologies

On May 30, 2017 i2 Pharmaceuticals, Inc., a biopharmaceutical company focused on next generation discovery and development of therapeutics with a focus on personalized cancer treatment, reported the acquisition of all of the antibody and engineered protein technology of Sea Lane Biotechnologies, LLC, Redwood City, California, including several potential product candidates (Press release, i2 Pharmaceuticals, MAY 30, 2017, View Source [SID1234521986]).

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The acquisition consists of three distinct classes of protein therapeutics, including world-class human antibody libraries, human b-cell derived antibodies, and a new class of engineered protein therapeutics called Surrobodies. Surrobodies allow for the facile creation of bispecific therapeutic agents from vast arrays of monospecific agents. In addition, this new class of protein can be readily transformed by coupling small molecule drugs to Surrobodies to create Surrobody Drug Conjugates (SDC’s), the next generation in potent cancer therapeutics.

"We are thrilled with the acquisition of the product candidates and technologies so exquisitely crafted at Sea Lane. In particular, the antibodies and Surrobodies developed by Sea Lane for Immuno-Oncology (IO) complement existing programs at i2 Pharma in the development of cancer therapeutics," said Dr. Bruce Eaton, i2’s Founder, Chairman and CEO. "We are now uniquely positioned with protein, small molecule and RNA therapeutic modalities that can be mixed and matched to innovate beyond the traditional boundaries of drug discovery with a goal of developing next generation, highly efficacious, cost effective personalized therapeutics."

Richard Lerner, the Lita Annenberg Hazen Professor of Immunochemistry and former President of The Scripps Research Institute, believes strongly in the capabilities of the Surrobody technology. "The Surrobody technology was created as an alternative to conventional antibody based approaches, with the potential for a wide range of protein engineering advantages. The Sea Lane Biotechnologies team and their commercial and academic partners clearly demonstrated the power of the Surrobody technology for many applications including multi-specific and drug conjugate formats. With this acquisition, i2 Pharmaceuticals now has a compelling portfolio of Surrobody and antibody product candidates and technologies to add to its other exciting capabilities," Lerner stated.

"We are excited about the combination of the Sea Lane technologies and product candidates with i2 Pharma’s existing portfolio of transformative technologies for drug discovery," said Lawrence Horowitz, CEO of Sea Lane Biotechnologies.

"We share the vision at i2 Pharmaceuticals and their highly competent team. Our shared goal is efficacious, cost effective personalized therapeutics with a positive impact on patient lives. The combination of Sea Lane and i2 Pharma technologies can make that happen," said Michael Horowitz, Chief Operating Office of Sea Lane Biotechnologies.

Inspyr Therapeutics and Lewis and Clark Pharmaceuticals to Merge

On Inspyr Therapeutics (OTCQB:NSPXD), a clinical-stage biotechnology company, and Lewis and Clark Pharmaceuticals, a privately-held biotechnology company, reported that they have entered into an agreement to create an integrated company with a proprietary platform driving a pipeline of novel therapeutics (Press release, Inspyr Therapeutics, MAY 30, 2017, View Source [SID1234520533]).

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Under this agreement, Inspyr will purchase Lewis and Clark in an all-stock transaction and will execute plans to leverage a team with significant experience to advance a broader pipeline of novel therapeutics. The boards of directors of both Inspyr and Lewis and Clark have unanimously approved the proposed agreement, which is subject to customary closing conditions as well as reaching a definitive agreement on all of the terms.

“By combining the strengths of each organization, we are creating an integrated biopharmaceutical company with a unique ability to potentially improve outcomes for patients in a variety of therapeutic areas. Our capabilities will span from the discovery of new molecules through clinical development and regulatory filings,” said Peter Grebow Ph.D., Chairman of Inspyr. “Over the last 12 months, we embarked on a path to unlock the potential of our lead therapy Mipsagargin, strengthen the management team and broaden the pipeline. We will now have proprietary platform technology, additional expertise and laboratory facilities, while also broadening the pipeline. We believe this transaction immediately creates a stronger company and longer term allows us to explore new options to generate additional value from this proprietary platform and pipeline of novel therapies.”

“Our proprietary platform has been validated with multiple therapies and we are eager to advance into IND-enabling studies,” said Robert Thompson, Ph.D., Founder and Chief Executive Officer of Lewis and Clark Pharmaceuticals. “We are excited to leverage the Inspyr team’s expertise in translational medicine and clinical development, in particular for oncology therapeutics, to accelerate our pipeline toward the clinic and unlock additional value from this technology.”

Inspyr will become an integrated biopharmaceutical company focused on advancing a broad pipeline of novel therapies to treat cancer, inflammation, and other serious diseases. Inspyr’s lead product candidate Mipsagargin, a novel prodrug therapeutic for cancer, is being developed initially for hepatocellular carcinoma (HCC), or liver cancer. Lewis and Clark’s pipeline of novel proprietary and potentially first-in-class adenosine receptor modulator based compounds are currently in advanced preclinical development as oncology or anti-inflammatory agents. For more information on the pipeline, please visit View Source

Key strategic benefits from creating an integrated company include:
• Novel proprietary technology platform. Lewis and Clark’s industry-leading proprietary technology platform is based on adenosine chemistry and biology. From this platform, Lewis and Clark has developed multiple adenosine receptor modulator based compounds that are advancing into studies to support planned Investigational New Drug (IND) applications. Inspyr intends to leverage this platform to explore future potential license opportunities.
• Broad pipeline of novel therapies for oncology and inflammation.

Lewis and Clark’s pipeline of novel proprietary therapies includes four lead programs: a dual A2A/A2B antagonist, an A2A antagonist, an A2B antagonist, and an A2A agonist. These therapies are highly potent and selective, with important molecular properties that enable enhanced distribution in tissue and penetration of human skin. These therapies are in advanced preclinical development.
The dual A2A/A2B antagonist has both immune function modulation and anti-angiogenic properties and thus has potential as an immuno-oncology and anti-angiogenic agent to treat multiple types of solid and hematological malignancies.
The A2A agonists offers the potential to treat inflammatory and autoimmune diseases as arthritis, Crohn’s disease, diabetic nephropathy, and psoriasis.
The A2B antagonist offers the potential to treat asthma, type 2 diabetes, atherosclerosis, and nonalcoholic fatty liver disease.
Inspyr’s lead therapy, Mipsagargin, currently is in development for the treatment of solid tumors.
– For liver cancer, Mipsagargin in combination with Nexavar is being evaluated in a preclinical study in liver tumor models that express different levels of PSMA, the target of Mipsagargin. Inspyr is finalizing the design of a clinical study to examine the potential benefits of Mipsagargin in combination with Nexavar in patients with advanced hepatocellular carcinoma (HCC), or liver cancer.
– For gastric cancer, Inspyr has initiated a preclinical study in gastric cancer tumor models that express different levels of PSMA. In this initial study, Mipsagargin will be evaluated first in combination with paclitaxel and in a subsequent study will be evaluated in combination with DC101 (Cyramza surrogate antibody).
– Utilizing Lewis and Clark’s wet laboratory facilities, Inspyr has the potential to internally develop additional pro-drugs targeting PSMA with different toxic payloads.

• Experienced leadership. Inspyr’s team has significant clinical development, translational medicine, and business operations experience in the biopharmaceutical industry. Lewis and Clark, which was founded by Robert Thompson, Ph.D, an industry-recognized leader in adenosine chemistry, has a team with significant expertise in preclinical development, toxicology, regulatory filings, adenosine receptor pharmacology, physiology, and molecular biology.

Pursuant to the terms of the transaction, Lewis and Clark Pharmaceuticals will become a wholly-owned subsidiary of Inspyr. Upon the closing of the transaction, existing Lewis and Clark stockholders are expected to own 50% of Inspyr’s common shares, on an as converted basis.

About Inspyr Therapeutics
Inspyr Therapeutics, Inc. develops therapies for cancer using a novel technology platform that combines a powerful therapeutic (thapsigargin) with a patented prodrug delivery system that targets the release of drugs within solid tumors. Mipsagargin, its lead drug candidate, has been studied in a Phase 2 clinical trial in patients with Nexavar-refractory hepatocellular carcinoma (HCC) and has been granted Orphan Drug designation by the U.S. Food and Drug Administration (FDA) in this indication. For additional information on Inspyr Therapeutics, visit www.inspyrtx.com.

About Lewis and Clark Pharmaceuticals
Lewis and Clark Pharmaceuticals is a privately-held biotechnology company developing novel proprietary compounds from an industry-leading technology platform based on adenosine chemistry and biology. In addition, Lewis and Clark maintains fully-equipped, state-of-the-art organic and analytical chemistry laboratories located in Charlottesville, Virginia. The Company’s chemists and toxicologist have expertise in chemical synthesis and analysis, non-clinical dose formulation and plasma concentration analysis, assay development, and toxicology.

Intensity Therapeutics, Inc. Successfully Administers INT230-6 to First Patient in a Phase 1/2 Trial

On May 30, 2017 Intensity Therapeutics, Inc., a privately held biotechnology company developing proprietary cancer immunotherapy products, reported that the first patient successfully received treatment with the Company’s lead product, INT230-6, as part of a Phase 1/2 international clinical study (Press release, Intensity Therapeutics, MAY 30, 2017, View Source [SID1234519325]). Initiation of the study followed acceptance of an investigational new drug (IND) submission by the US Food and Drug Administration’s Division of Oncology Products 1 (DOP1) and receipt from Health Canada of a No Objection Letter following submission of a clinical trial application (CTA). The clinical trial, IT-01 (NCT#03058289), entitled A Phase 1/2 Safety Study of Intratumorally Administered INT230-6 in Adult Subjects with Advanced Refractory Cancers, aims to enroll approximately 60 patients with several different types of advanced solid tumors.

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"Bringing our novel product, INT230-6, into human testing is a major milestone for Intensity Therapeutics," commented President and CEO Lewis H. Bender. "Over the past few years our Company has demonstrated impressive tumor shrinkage in several murine models of cancers. INT230-6 eradicated large tumors, activated a systemic immune response and improved survival. Animals having a complete response acquired the capability to spontaneous clear re-challenges of the same cancer throughout the remainder of their lives, suggesting a protective effect similar to that of a vaccine. We are therefore excited to have initiated human testing. Our staff, investigators and clinical centers are enthusiastic about bringing patients our potentially lifesaving product."

This unique Phase 1/2 study will first assess the safety of INT230-6 in tumors treated at the skin surface (e.g. breast, melanoma, head-and-neck and lymphoma). Subsequent patients receiving INT230-6 will include those with deep tumors (e.g. liver, pancreatic, colon, lung and others). Investigators will utilize image guidance to inject the tumors. Additionally, a cohort is planned to explore INT230-6 in combination with anti-PD1 agents. The study’s primary goal is to demonstrate the safety of INT230-6. Secondary analyses will examine the efficacy of INT230-6 treatment via multiple parameters. The trial includes several adaptive components that will allow for adjustments in patient groups, dosing schedule and dose volumes administered.

"Our studies with INT230-6 have shown the ability to stimulate a strong T-cell response as a monotherapy. There is considerably enhanced activity using INT230-6 in combination with checkpoint inhibitors such as anti-PD-1 antibodies, while maintaining a favorable safety profile," said Chief Medical Officer Ian B. Walters, MD. "We are optimistic that our novel trial design can quickly detect evidence of direct tumor killing and immune system activation. Physicians
desperately need improved treatments for patients with advanced cancers that are not responding to approved immunotherapies. Intensity Therapeutics is grateful to the volunteers participating in our study and looks forward to collecting data on INT230-6 in different cancer types."

About INT230-6

INT230-6 is a novel, anti-cancer drug for direct intratumoral injection. The product contains potent anti-cancer agents that disperse throughout tumors and diffuse into cancer cells. INT230-6 was identified from Intensity’s DfuseRxSM platform and is being evaluated in a clinical trial; IT- 01. In preclinical studies INT230-6 administration eradicated tumors by a combination of direct tumor kill coupled with recruitment of dendritic cells to the tumor micro-environment that stimulated anti-cancer T-cell activation. Treatment with INT230-6 in in vivo models of severe cancer resulted in substantial improvement in overall survival compared to standard therapies. Further, INT230-6 provided complete responder animals with long-term, durable protection from multiple re-inoculations of the initial cancer and resistance to other cancers.

About Study IT-01

IT-01 is entitled A Phase 1/2 Safety Study of Intratumorally Administered INT230-6 in Adult Subjects with Advanced Refractory Cancers. The trial aims to enroll approximately 60 patients with different types advanced solid tumor malignancies in a multicycle dosing regimen. The study will be conducted in multiple countries and includes a cohort combining INT230-6 with an anti-PD-1 antibody. Currently the study is recruiting in the U.S. at two hospitals associated with the University of Southern California (USC) and in Canada at the University Health Network (UHN) in Toronto. The principal investigator at USC is Dr. Anthony El-Khoueiry; the principal investigator at UHN is Dr. Lillian Siu. The study’s primary objective is to assess the safety and tolerability of multiple intratumoral doses of INT230-6. Secondary assessments are to understand preliminary efficacy of INT230-6 by measuring the injected and bystander tumor responses. The study will characterize the systemic pharmacokinetic profile of multiple doses of INT230-6’s drug substances after single and then multiple intratumoral injections. Exploratory analysis will characterize patient outcome, as well as evaluate various tumor and anti-tumor immune response biomarkers that may correlate with response. Data will be used to assess the progression free and overall survival in subjects receiving INT230-6. Further information can be found at www.clinicaltrials.gov (NCT#03058289).

Merck KGaA, Darmstadt, Germany Licenses Selexis SUREtechnology Platform for Immuno-Oncology Antibody Program

On May 30, 2017 Selexis SA, a pioneering life sciences company and a global leader in mammalian cell line generation technology, reported that it has entered an agreement with an affiliate of Merck KGaA, Darmstadt, Germany, which operates its biopharmaceutical business as EMD Serono in the U.S. and Canada, to leverage the Selexis SUREtechnology Platform and SURE CHO-M (suspension-adapted CHO-K1) cell line to advance a Merck KGaA, Darmstadt, Germany immuno-oncology antibody program (Press release, Selexis, MAY 30, 2017, View Source [SID1234519324]).

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"It’s a testament to the value of our technologies that another major multinational pharmaceutical company has selected Selexis as a development partner. We are proud to enter an agreement with Merck KGaA, Darmstadt, Germany, a respected leader in the fields of oncology and immunology," said Igor Fisch, PhD, Selexis chairman and chief executive officer. "Our talented team offers a unique and innovative technology solution to our partners; a model that continues to be validated by the expansion of our collaborations across many biologics and vaccine development programs."
Selexis’ proprietary and high performance SUREtechnology Platform facilitates the rapid, stable, and cost-effective production of virtually any recombinant protein including those that are difficult to express in other systems. It also provides seamless integration of the biologics and vaccine development continuum, spanning discovery to commercialization.

"Our SUREtechnology Platform is a one of the most viable options that biopharmaceutical companies like Merck KGaA, Darmstadt, Germany choose for developing cell lines for production of antibodies that address unmet needs in immuno-oncology," said Marco Bocci, PhD, DPharm, Selexis vice president, licensing and business development. "We’re proud to offer this platform and other tools that can assist in bringing drugs to patients that otherwise may not have been possible to develop."