On November 28, 2018 Cold Genesys, Inc. reported that it has entered into a clinical collaboration with Merck (known as MSD outside the United States and Canada) to evaluate the combination of Cold Genesys’ lead oncolytic immunotherapy candidate CG0070 with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab), in a Phase 2 clinical study (Press release, Cold Genesys, NOV 28, 2018, View Source [SID1234531682]).

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The trial is planned to evaluate the preliminary safety and efficacy of CG0070 plus KEYTRUDA in patients with Non-Muscle Invasive Bladder Cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG), an unmet medical need, as no treatment for this indication has been approved by the FDA in approximately 20 years.

CG0070, an investigational oncolytic immunotherapy based on a modified adenovirus type 5 backbone that contains a cancer-selective promoter and a GM-CSF transgene, destroys bladder tumor cells through their defective retinoblastoma (Rb) pathway, which is present in many cancers. Several CG0070 clinical studies including a completed Phase 2 study (BOND2) have demonstrated a favorable safety profile and encouraging efficacy in patients with NMIBC following BCG failure.

"We are delighted to be collaborating with Merck on this innovative combination approach," said Arthur Kuan, CEO of Cold Genesys. "CG0070, which has demonstrated clinical safety and efficacy in over 100 patients for the treatment of NMIBC, may potentially exhibit additional effect when combined with KEYTRUDA, which also has demonstrated single agent activity in the indication."

Cold Genesys will sponsor the study. Additional details of the collaboration were not disclosed.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

About CG0070

CG0070, a selectively replicative oncolytic immunotherapy based on a modified adenovirus type 5 backbone that contains a cancer-selective promoter and a GM-CSF transgene, destroys bladder tumor cells through their defective Rb pathway. CG0070 was designed to work in two complementary ways. First, it replicates inside the tumor’s cells with dysfunctional Rb pathways, causing tumor cell lysis and immunogenic cell death. Then, the rupture of the cancer cells can release tumor-derived antigens, along with GM-CSF, which can stimulate a systemic anti-tumor immune response that involves the body’s own white blood cells. In advanced clinical studies, CG0070 has been shown to be a safe and efficacious agent in NMIBC following BCG failure. The scientific rationale and clinical results to date of CG0070 make it a promising agent to be developed for a variety of solid tumor types to be used alone or in combination with immune checkpoint modulators.

On November 28, 2018 Oncorus, Inc., an oncolytic virus company focused on driving innovation to transform outcomes for cancer patients, reported the nomination of ONCR-177, a next-generation locally administered oncolytic virus clinical candidate for multiple solid tumor indications (Press release, Oncorus, NOV 28, 2018, View Source [SID1234531681]). ONCR-177 utilizes Oncorus’ proprietary, next-generation oncolytic herpes simplex virus (oHSV) platform. In addition, Oncorus has created a unique synthetic oncolytic virus platform, which will enable the company to develop multiple oncolytic viruses for repeated, systemic administration. Proprietary innovations in potency and safety engineered by Oncorus into both platforms enable best-of-class potential for the company’s portfolio programs and the opportunity to pursue multiple cancer types.

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"While we’ve seen early promise of the ability of oncolytic virus therapies to improve the response rates of checkpoint inhibitors, many patients still do not respond to these agents. Our team is committed to changing this fact," said Theodore (Ted) Ashburn, M.D., Ph.D., President and Chief Executive Officer of Oncorus. "We are driving multiple proprietary innovations across two distinct platforms that are enabling a portfolio of oncolytic virus product candidates with best-in-class potential. We intend to become the leaders in realizing the full potential of this exciting treatment modality to dramatically transform outcomes for cancer patients."

Dr. Ashburn will give an update on the company’s pipeline and business at a presentation today at 7:30 AM EST at the Piper Jaffray 30th Annual Health Care Conference in New York City, highlighting key accomplishments from 2018 to date and outlining near- and long-term value drivers for the company.

Key 2018 Accomplishments:

Nomination of lead clinical candidate, ONCR-177. Oncorus recently nominated a lead clinical candidate, ONCR-177, a locally administered oncolytic virus therapy. ONCR-177 features key innovations engineered into Oncorus’ next-generation oHSV platform, including the largest number of immunomodulatory payloads in the class. These payloads include IL-12, FLT3L, CCL4 and antagonists of the clinically proven checkpoint inhibitors, CTLA-4 and PD-1, to enable the recruitment and activation of T cells, natural killer (NK) cells and dendritic cells and increase the likelihood of productive anti-tumor responses. ONCR-177 is also a fully-replication competent virus in that it retains the ability to expresses γ34.5, which allows the virus to replicate in the presence of host antiviral immune responses, a feature unique among oHSVs that have been developed to date or are being developed currently. ONCR-177 also features Oncorus’ proprietary microRNA-attenuation strategy, which leverages the differential expression of microRNA sequences to allow robust viral replication in tumor cells, while preventing replication in healthy tissue. In addition, Oncorus has developed a complementary and orthogonal approach to protecting neurons from viral infection by engineering mutations in UL37, an HSV protein, which prevent both axonal retrograde transport and latency.
The company intends to file an investigational new drug application (IND) and start a first-in-human study by the end of 2019 in order to evaluate ONCR-177 in multiple solid tumor indications.

"The promise of oncolytic viruses as a therapeutic tool in the fight against cancer has been clear for some time. However, a fundamental challenge to date has been the need to sacrifice potency to ensure safety," said Christophe Quéva, Ph.D., Oncorus’ Chief Scientific Officer. "Our team has been working diligently to enhance our oHSV platform in a number of innovative ways to successfully overcome this ‘potency versus safety’ tradeoff. We are very encouraged by our progress to date and look forward to seeing how our innovations improve outcomes in clinical studies involving ONCR-177."

Achieved in vivo proof-of-concept for synthetic virus program for repeat, systemic administration. Oncorus has made notable progress advancing its research programs for systemic intravenous delivery for its breakthrough synthetic virus platform. Systemic delivery of oncolytic viruses offers the promise of targeting indications not amenable to locally administered oncolytic virus therapy such as cancers of the lung. The company recently achieved in vivo proof-of-concept for its systemic virus platform and aims to nominate a lead clinical candidate synthetic virus by the end of 2019.
Solidified leadership with key hires. Oncorus made key management hires in 2018 that helped expand the company’s expertise, solidify its leadership team, and position it for rapid growth. In September, the company announced that Theodore (Ted) T. Ashburn, M.D., Ph.D., was appointed President and CEO. Dr. Ashburn brings a wealth of experience in immuno-oncology drug development and commercialization to Oncorus. Mitchell H. Finer, Ph.D., Oncorus’ co-founder, founding CEO and MPM Capital Managing Director, assumed the role of Executive Chairman. Other key hires include John Goldberg, M.D., Senior Vice President, Clinical Development; Brett Belongia, Ph.D., Senior Director of CMC; Brian Haines, Ph.D., Senior Director Pharmacology, Toxicology; and Tooba Cheema, Ph.D., Director of Biomarkers and Translational Medicine.
Closed the third and final tranche of Series A round of financing. Oncorus closed a third and final tranche of its Series A financing, which raised a total of $61.4 million. The company’s blue-chip investor syndicate includes founding investor MPM Capital, as well as MPM’s UBS Oncology Impact Fund (OIM), Deerfield Management, Arkin Bio Ventures, Long March, Astellas and Celgene.
Continued to build a robust intellectual property (IP) estate. Oncorus continued to pursue a broad IP strategy and augment its current patent estate surrounding its proprietary innovations for both its oHSV and synthetic virus platforms and respective applications.
2019 Goals:

Oncorus’ key goals and upcoming value drivers include:

Filing an IND and initiating a first-in-human Phase 1 study involving ONCR-177
Nominating a lead synthetic virus clinical candidate for repeat systemic administration, and
Continuing to expand its team with the recruitment of key talent across multiple disciplines
"It’s an exciting time to be in the oncolytic virus therapy space, given the continued progress of this modality and its potential to become an important addition to the arsenal of immuno-oncology therapies available to cancer patients," said Dr. Finer. "2018 has been a year of important growth for Oncorus on both the scientific and business fronts. We have clear momentum as we approach 2019 and look forward to transitioning into a clinical stage company, progressing our portfolio of best-in-class products and, above all, realizing the promise of oncolytic virus therapy for cancer patients."

On November 28, 2018 HOOKIPA Pharma Inc. ("HOOKIPA"), a clinical stage biopharmaceutical company developing a new class of immuno-therapeutics targeting infectious diseases and cancers based on its proprietary technology platform, reported that it entered into a research collaboration and license agreement with DarwinHealth to develop novel immunotherapies based on the systematic discovery and prioritization of the next generation of immunogenic, tumor-specific cryptic antigens (Press release, Hookipa Biotech, NOV 28, 2018, View Source [SID1234531680]). DarwinHealth is a precision-focused cancer medicine company, utilizing systems-biology derived algorithms to identify appropriate therapies for cancer patients and to systematically discover and prioritize the next generation of immunogenic, tumor-specific antigens.

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Under the terms of the agreement, DarwinHealth will utilize a combined single-cell transcriptome analysis and bioinformatics-based approach using both mouse and human cancerous and non-cancerous tissues to identify the next generation of shared "off-the-shelf" tumor-specific antigens. HOOKIPA will perform the validation experiments and be granted exclusive rights to the development, manufacturing and commercialization of products arising from the collaboration.

"Immunotherapy is one of the areas of greatest potential for future cancer treatment. Arguably, all antigen-specific immunotherapy is limited by the scarcity of known antigens. The current group of shared tumor self-antigens has been established for many years, and while more recent efforts have been aimed at identifying patient-specific neo-antigens, systematic attempts to identify the next generation of tumor self-antigens have not been pursued as aggressively," said Dr. Igor Matushansky, Chief Medical Officer and Global Head of Research and Development of HOOKIPA. "This is why the primary objective of our next generation, antigen discovery program – entitled HIDE [Human Immunotranscript Discovery initiativE]" – with DarwinHealth is to identify a novel constellation of shared self-antigens for multiple tumor subtypes. Our goal is that following a successful completion of the two-year program, antigens with validated immunogenicity will be deployed clinically as antigen-specific, vector-mediated immunotherapy using our TheraT* vector."

"DarwinHealth utilizes proprietary, systems biology-generated algorithms to match cancer patients with the drugs and drug combinations that are most likely to produce a successful treatment outcome. These same algorithms can also be used to prioritize investigational drugs and compound combinations of unknown potential against a full spectrum of human malignancies, as well as novel cancer targets," explained Andrea Califano, Dr. co-founder of DarwinHealth and Clyde and Helen Wu Professor of Chemical Systems Biology and Chair, Department of Systems Biology at Columbia University, "and importantly, for immuno-oncology applications, DarwinHealth can apply proprietary bioinformatics- and experimentally-based methodologies to identify human, cryptic immunogenic transcripts (crypto-antigens) that can be optimally delivered using HOOKIPA’s highly innovative vector."

Commenting on this immuno-oncology-focused collaboration, Gideon Bosker, CEO and co-founder of DarwinHealth said: "Combining HOOKIPA´s proprietary viral vector technology with DarwinHealth´s novel, systems-based approach to identifying next generation, shared antigens shows immense promise, potentially enabling cancer research to leap forward and transform patients´ lives."

On November 28, 2018 Vor Biopharma, an immuno-oncology company pioneering hematopoietic stem cell (HSC) therapies for the treatment of hematological malignancies and affiliate of PureTech Health plc (LSE: PRTC), reported that the United States Patent and Trademark Office (USPTO) issued U.S. Patent No. 10,137,155 related to the Company’s technology platform (Press release, Vor BioPharma, NOV 28, 2018, View Source [SID1234531678]). This foundational patent is the first of its kind in the immuno-oncology field and broadly covers compositions and therapeutic methods related to using novel modified HSCs to enable targeted immunotherapies. The platform technology underlies Vor’s pipeline of immuno-oncology candidates, including lead candidate VOR33.

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The now patented technology is designed to address the fundamental limitations of traditional targeted therapies, including antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor (CAR) T cells, for the treatment of hematologic malignancies. These existing therapies target antigens on malignant cells that also appear on healthy cells, which can result in mass depletion of critical life-sustaining cells. Vor’s approach employs the use of antigen-modified hematopoietic stem cells (amHSCs), which are designed to repopulate a patient’s blood with cells that have a benign genetic modification to a specific surface antigen that escapes targeting and protects the cells from depletion by targeted immunotherapies. By sparing healthy blood cells, this approach may potentially improve patient safety, enable maximal dosing of cancer-targeted therapies, increase the number of potential patient populations that could benefit from these therapies, and expand the reach of targeted immunotherapies beyond B-cell cancers to a broad range of hematological malignancies, including acute myeloid leukemia (AML).

"The USPTO’s allowance of these broad claims provides validation that our approach and intellectual property are novel and first-in-class," said Aleks Radovic-Moreno, Ph.D., PureTech Health Vice President and Vor program lead. "The compositions and methods covered in the patent protect our lead product candidate as we continue development of our technology towards the clinic. This technology has the potential to provide a novel therapeutic approach for patients with aggressive blood cancers that otherwise have very few treatment options and poor prognoses."

The relevant intellectual property is exclusively licensed to Vor Biopharma and is based on technology developed by Siddhartha Mukherjee, M.D., D. Phil, Associate Professor of Medicine at Columbia University and a Staff Physician at Columbia University Medical Center, and his colleagues.

"This approach has the potential to broaden the use of targeted immunotherapies beyond B-cell cancers, and to help patients who have very limited treatment options," said Dr. Mukherjee.

About VOR33
Vor’s lead product candidate, VOR33, is designed to enable maximal CD33-targeted immunotherapy. CD33, a target that is present in the vast majority of acute myeloid leukemia (AML) patients, is also expressed in normal myeloid progenitor cells. Depletion of normal myeloid progenitor cells prevents the beneficial use of several CD33-targeted therapies at important stages throughout the treatment process, at higher doses, and for longer periods of time. By enabling new CD33-targeted therapies, VOR33 has the potential to overcome these challenges and improve treatment for AML. Vor anticipates initiating IND-enabling studies for VOR33 in early 2019.

On November 28, 2018 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported an update on its late-stage clinical development program for the Company’s proprietary galinpepimut-S (GPS) in patients with acute myeloid leukemia (AML) (Press release, Sellas Life Sciences, NOV 28, 2018, View Source [SID1234531677]).

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Following a clinical and regulatory strategy defining Type C dialogue with the U.S. Food and Drug Administration (FDA), the Company plans to proceed with a clinical study design and biostatistical plan to support a Phase 3 registrational study for maintenance therapy for AML patients who have achieved complete remission after second line (salvage) antileukemic therapy, or CR2. This study will be used as the basis for a Biologics License Application (BLA) submission, subject to results that are both statistically significant and reflective of an effect of sufficient magnitude to be clinically meaningful.

"Following discussion with the FDA, we are embarking upon a revised Phase 3 study for GPS in the monotherapy maintenance setting for AML patients who have achieved CR2. The new design is expected to streamline sample size, time to accrual completion, primary endpoint readout and potential time to market, as well as costs. We believe this new study design provides SELLAS with a quicker path to approval, provided the study is positive," said Dr. Angelos M. Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "In addition to a statistical analysis plan which we believe accords a viable pathway for meeting the primary endpoint, we have built in an adaptive design, thus further enhancing the probability of a positive study."

GPS was previously given fast track and orphan drug designations in AML by the FDA.

The planned Phase 3 registrational study will be a 1:1 randomized, open-label study comparing GPS monotherapy in the maintenance setting to investigators’ choice best available treatment (BAT) in AML patients who have achieved hematologic complete remission, with or without thrombocytopenia (CR2/CR2p), after second-line antileukemic therapy and who are deemed ineligible for or unable to undergo allogeneic stem-cell transplantation.

The study is expected to enroll approximately 116 patients at around 50 clinical sites in the United States and Europe. It is powered at 90% to show a statistically significant difference in the primary endpoint of overall survival (OS) from the time of study entry. Secondary endpoints to be measured include leukemia-free survival, antigen-specific T-cell immune response dynamics, measurable residual disease by multigene array, and assessments of AML clonal evolution and inflammasome molecular signatures in the tumor microenvironment in bone marrow biopsy samples. The study will have a planned interim analysis for safety and futility after 80 events.

This streamlined CR2 study design, as compared to the previously planned study in AML patients who achieved complete remission following first-line antileukemic therapy (CR1), substantially reduces the study size (116 patients in CR2 vs. 390 patients in CR1) and time until topline data (up to 2.5 years in CR2 vs. 4.5 years in CR1) which will result in corresponding significant cost savings. A Phase 2a study of GPS in the AML CR2 setting conducted at the Moffitt Cancer Center previously demonstrated a clinically meaningful and statistically significant three-fold OS prolongation in patients receiving GPS when compared to a comparable group of contemporaneously assessed unvaccinated patients with a median OS of 16.3 months vs 5.4 months and a p-value of 0.0175, respectively, with treatment-related adverse events primarily comprised of grade 1 or 2 local injection site reactions and only one grade 3 (transient leukopenia) adverse event. A prior Phase 2 study of GPS in AML patients who achieved CR1 also met its primary endpoint with an OS rate at 3 years from first vaccination of 47%.

"We are excited to begin this late-stage Phase 3 program with GPS in AML. Earlier studies have positioned this agent to be a potentially effective approach in prolonging survival by delaying or preventing recurrence in patients in complete remission, most of whom harbor measurable residual disease and have a poor prognosis if they are unable to undergo allotransplant. We are hopeful that this new immunotherapeutic vaccine approach will improve outcomes in this patient population, which is at a very high risk of leukemic relapse," said Hagop M. Kantarjian, MD, Professor and Chair of the Department of Leukemia at the University of Texas MD Anderson Cancer Center, and principal investigator of the upcoming Phase 3 AML clinical development program.