On February 23, 2017 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported new positive clinical data from a Phase II Investigator Sponsored Trial assessing the combination of OncoSec’s investigational intratumoral therapy, ImmunoPulse IL-12, and the approved anti-PD- 1 therapy (pembrolizumab), in patients with unresectable metastatic melanoma (Press release, OncoSec Medical, FEB 23, 2017, View Source [SID1234517814]). The results of this single-arm, open-label trial, which was led by the University of California, San Francisco (UCSF), indicated that ImmunoPulse IL-12 can increase response rates in patients who are not expected to respond to anti-PD-1 therapy alone.

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The trial is evaluating the following key endpoints: best overall response rate (BORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune-related Response Criteria; safety and tolerability; duration of response; 24-week landmark progression-free survival (PFS); median PFS; and overall survival (OS). The study results showed an overall response rate (ORR) at 24 weeks of 43% (9/21), and BORR of 48% by RECIST v1.1. There were 24% (5/21) complete responders (CR), 19% (4/22) partial responders (PR), and 9% (2/21) stable disease (SD) for a total disease control rate of 52% (11/21). These data are consistent with, and expand upon, previously reported preclinical and clinical data that provide a strong rationale for combining ImmunoPulse IL-12 with anti-PD-1 blockade.

"Collectively, these data suggest that intratumoral IL-12 DNA with electroporation in combination with pembrolizumab can effectively alter the tumor microenvironment by triggering adaptive resistance," said Alain Algazi, M.D., the study’s lead investigator, and skin cancer specialist in the Melanoma Center at the UCSF Helen Diller Family Comprehensive Cancer Center. "This increases the substrate for a therapeutic PD-1/PD-L1 blockade while driving systemic anti-tumor immunity and concordant clinical responses in patients unlikely to benefit from anti-PD-1 monotherapy."

Dr. Algazi presented the study findings today in an oral presentation titled, "Immune monitoring outcomes of patients with stage III/IV melanoma treated with a combination of pembrolizumab and intratumoral plasmid interleukin 12 (pIL-12)" (Abstract #78), at the ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium in Orlando, FL.

In this trial, a biomarker that has previously been shown to be predictive of response to checkpoint inhibitor therapy was used to enroll 22 patients who have a low likelihood of responding to an anti-PD-1 therapy. These patients were treated with the combination of intravenous pembrolizumab and ImmunoPulse IL-12 for more than 24 weeks.

The combination therapy continued to demonstrate a favorable safety profile and was well tolerated. Importantly, of the 22 patients enrolled, nine had previous checkpoint inhibitor therapy; ORR for this subset of patients was 33% (3/9).

Comprehensive immune monitoring of blood and tissue samples showed that the combination of ImmunoPulse IL-12 with pembrolizumab produces a safe and powerful systemic immune response. This response leads to an increase in tumor-specific CD8+ T-cells and an "adaptive immune resistance" that broadly supports an immune-directed mechanism that is differentiated between responders and non-responders. Analysis of the biomarker data suggests that the combination of ImmunoPulse IL-12 with pembrolizumab is transforming "cold" tumors, which would be predicted to not respond to anti-PD-1 therapy, into "hot" tumors, thus increasing the potential for a meaningful clinical response to the checkpoint inhibitor therapy. Moreover, an analysis of pre-treatment samples using various analytical methods that have also been demonstrated to predict response to anti-PD-1 therapy, including immunohistochemistry (IHC) and RNA expression of critical immune-related genes by NanoString, correlate with the predictive biomarker used to enroll patients for this study.

"OncoSec’s vision to bring intratumoral gene therapies to the oncology market continues to advance with these positive, impactful data, which hold immense promise for cancer patients who are unlikely to benefit from immunotherapy," said Punit Dhillon, OncoSec President and CEO. "These results provide a strong foundation for our planned Phase II registration trial, which will evaluate the combination of ImmunoPulse IL-12 and an anti-PD-1 therapy in melanoma patients who have previously failed an approved anti-PD-1 therapy alone. We expect to initiate this study later in 2017."

The full-text abstract is available and can be viewed on ASCO (Free ASCO Whitepaper)-SITC’s website at www.immunosym.org. The presentation is available in the Publications section of OncoSec’s website.

About the ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium
The ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium is a three-day meeting focused on clinical and translational research in immuno-oncology and the implications for clinical care. This is a new meeting, one that will address the high level of need for clinical education in a field where all aspects of care are fundamentally different from traditional therapies. For more information, please visit www.immunosym.org.

On February 9, 2017 Atreca, Inc., a biotechnology company focused on developing novel therapeutics based on a deep understanding of the human immune response, reported the presentation of positive preclinical findings in its immuno-oncology program, generated via the Company’s Immune Repertoire Capture (IRC) technology platform (Press release, Atreca, FEB 22, 2017, View Source [SID1234522956]). Atreca’s IRC technology identifies and generates sequences of native antibodies and T cell receptors (TCRs) from active human immune responses, including natively paired and complete variable regions of receptors expressed by specifically selected B- and T-cells. New findings from Atreca’s lead program are being highlighted at the 24th annual Molecular Medicine TriConference, taking place at the Moscone North Convention Center in San Francisco, CA, February 19-24, 2017.

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In a presentation, titled "The Immune Repertoire Capture (IRC) Technology Platform," Daniel Emerling, Ph.D., Atreca’s Senior Vice President, Research, is presenting key preclinical findings today at 12:10 p.m. Pacific Time, including:

Atreca’s researchers have used IRC technology to generate functional antibodies from the active immune response of individuals with metastatic disease who experienced a response to therapy.
Several patient-derived antibodies have been shown to bind tumor tissue but not normal tissue, and some antibodies bind multiple tumor types, including lung and breast adenocarcinoma, and renal cell carcinoma.
In a preclinical syngeneic in vivo tumor model, administration of the human variable regions derived from a particular patient antibody (linked to a mouse constant region) resulted in clearance of tumor in a majority of the animals, with concomitant infiltration of immune system cells into tumor tissue. Potential synergy with a checkpoint inhibitor was also observed.
"We are thrilled with the continued momentum of our programs based on successful anti-tumor immune responses in cancer patients undergoing treatment," stated N. Michael Greenberg, PhD, Atreca’s Chief Scientific Officer. "Our most recent data validate our next-generation approach in monotherapy as well as combination therapy, potentially addressing the substantial need to enhance patient responses to checkpoint inhibition. The unique features and capabilities of our platform allow us to pursue diverse applications outside of cancer as well, and we look forward to our progress as we advance toward IND-enabling studies in our lead program."

Atreca applies IRC to generate sequences of native antibodies and TCRs from cancer patients who have responded well to immunotherapy and other treatments, patients with autoimmune disease, vaccinated subjects, and patients who resolve infections. Analyses of the resulting essentially unbiased and error-free repertoires yield insights into immunology, as well as potent antibodies targeting tumors, pathogens, and autoimmune epitopes.

On February 22, 2017 Argos Therapeutics Inc. (Nasdaq:ARGS), an immuno-oncology company focused on the development and commercialization of individualized immunotherapies based on the Arcelis precision immunotherapy technology platform, reported that the Independent Data Monitoring Committee (IDMC) for the company’s pivotal Phase 3 ADAPT clinical trial of rocapuldencel-T in combination with sunitinib/standard-of-care for the treatment of metastatic renal cell carcinoma (mRCC) has recommended that the study be discontinued for futility based on its planned interim data analysis (Press release, Argos Therapeutics, FEB 22, 2017, View Source [SID1234517784]). The IDMC concluded that the study was unlikely to demonstrate a statistically significant improvement in overall survival in the combination treatment arm, utilizing the intent-to-treat population, the primary endpoint of the study. The IDMC noted that rocapuldencel-T was generally well-tolerated in the trial.

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In conjunction with its clinical and scientific advisors, the company is analyzing the preliminary ADAPT trial data set and plans to discuss the data with the U.S. Food and Drug Administration (FDA). The company plans to leave the ADAPT trial open while the company conducts its ongoing data review and discussions with FDA. Based on these analyses and discussions, the company will make a determination as to the next steps for the rocapuldencel-T clinical program.

"We are extremely disappointed with these results, which included seventy-five percent of the targeted events needed to permit the primary analysis and assessment of overall survival in the study," said Jeff Abbey, president and chief executive officer of Argos Therapeutics. "We sincerely appreciate the patients and investigators who have participated in the ADAPT Phase 3 trial, and remain convinced in the ability of precision immunotherapy to improve the lives of patients."

Rocapuldencel-T is an individualized immunotherapy that is designed to capture mutated and variant antigens that are specific to each patient’s tumor and induce an immune response targeting that patient’s tumor antigens. The randomized Phase 3 ADAPT trial evaluating rocapuldencel-T plus sunitinib/standard-of-care therapy versus standard-of-care therapy alone in newly diagnosed mRCC patients was opened in January 2013 and completed enrollment in July 2015. A total of 462 mRCC patients were randomized to the trial. The primary endpoint of the trial is a statistically significant improvement in overall survival.

On February 22, 2017 Celltrion Healthcare reported that the European Commission has approved TruximaTM (biosimilar rituximab) for all indications of reference rituximab in the European Union (EU) (Press release, Celltrion, FEB 22, 2017, View Source;division=R [SID1234531693]). Truxima is the first biosimilar monoclonal antibody (mAb) approved in an oncology indication worldwide.[1] The approval of Truxima builds on Celltrion Healthcare’s strong global clinical biosimilar programme.

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"We are excited to offer the first biosimilar mAb in oncology. With our partners across Europe, we will work together to ensure that Truxima is available to the many patients who can benefit from this treatment", said Jung-Jin Seo, Chairman of Celltrion Group, speaking at a meeting of their European partners in Paris. "For healthcare systems burdened with high cost oncology treatments, we are pleased to provide an option that has the potential to offer significant savings whilst ensuring patients retain access to high-quality and effective treatments."

Truxima is approved in the EU for the treatment of people with non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukaemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis and microscopic polyangiitis.[1] This approval is based on the totality of evidence submitted to the European Medicines Agency showing compelling similarity between Truxima and reference rituximab in terms of efficacy, safety, immunogenicity, pharmacodynamics (PD) and pharmacokinetics (PK) in patients with RA and advanced follicular lymphoma, a type of NHL.[2] These trials were conducted in over 600 patients and include data up to 104 weeks.[2]

Dr Bertrand Coiffier, the global principle investigator of the advanced follicular lymphoma study, Head of the Department of Hematology at Hospices Civils de Lyon and Professor at the University Claude Bernard, Lyon, France said, "Biosimilar rituximab has been shown to have comparable efficacy and safety to reference rituximab in a large program of trials providing convincing evidence for the similarity of the two products. This has been recognised by the regulatory authorities, and hopefully this will pave the way for further innovation in this area".

Budget saving impact

Biosimilars have the potential to offer cost savings for healthcare systems and therefore the potential to increase patient access to biological therapies.[3],[4]

"Assuming the price of biosimilar rituximab is 70% compared to reference rituximab, and the market share of biosimilar rituximab is 30% (first year), 40% (second year) and 50% (third year), over this three-year time period the budget savings across the 28 countries of the EU would be around €570 million", said Prof. László Gulácsi, Head of Department of Health Economics, Corvinus University of Budapest; HTA Consulting Budapest, Hungary. "This equates to 49,000 new RA, NHL and CLL patients who could be receiving life-changing treatment which is clearly a huge aggregate health-gain at both a national and EU level."

— Ends—

Notes to editors:

About hematological cancers

Hematological cancers begin in blood-forming tissue or cells of the immune system. There are three common types of hematological cancers: lymphoma, leukaemia and myeloma. There are many types of NHL, the most common group is B cell lymphomas, of which follicular lymphoma and diffuse large B cell lymphoma are the most common. CLL is a type of leukaemia and is characterised by accumulation of monoclonal B cells (a type of white blood cell).

About rheumatoid arthritis

In Europe more than 2.9 million people have RA, many of whom are of working age. On average, every third person with RA becomes work disabled and up to 40 per cent leave work completely within 5 years of diagnosis.[5] Although there is no cure for RA, there are many treatments that can reduce inflammation and ease pain. As with all rheumatic diseases early diagnosis and intervention is key.

About Truxima (biosimilar rituximab)

Truxima is a mAb that targets CD20, a protein found on the surface of most B cells. Overactive B cells can stimulate attack of healthy cells in immune-related diseases such as RA. B cells are also implicated in some types of hematological cancer including NHL and CLL. B cells express CD20 at many stages of their development making the protein a good target for treatments.

Truxima is approved in the EU for the treatment of people with NHL, CLL, RA, granulomatosis with polyangiitis and microscopic polyangiitis. Further details of the approved indications and safety information for Truxima are available in the summary of product characteristics (SmPC).[1]

Overview of Truxima studies

Phase 1 clinical data demonstrated the PK of Truxima and reference rituximab were statistically equivalent over 24 weeks after a single course of treatment, and that their efficacy, PD, immunogenicity and safety were similar up to 2 courses of treatments (up to 72 weeks).[2]

A phase 1 open label extension study showed that switching to Truxima from reference rituximab was similarly effective with comparable safety to continuing Truxima for two years.[2]

Three phase 3 studies in patients with RA, advanced follicular lymphoma and low-tumor-burden follicular lymphoma (LTBFL) are ongoing:

· Truxima showed highly similar efficacy, PK, PD, immunogenicity and safety profiles to reference rituximab in people with RA up to 48 weeks[2]

· Truxima showed equivalent PK to reference rituximab with similar efficacy, PD, immunogenicity and safety profiles up to 8 cycles of treatment (every 3 weeks) in people with advanced follicular lymphoma[2]

On February 22, 2017 PMV Pharmaceuticals, Inc., a leader in the discovery and development of p53-targeted small molecule drugs for the treatment of cancer, reported the completion of a $74 million Series B financing round (Press release, PMV Pharma, FEB 22, 2017, View Source [SID1234520736]). This financing was led by Topspin Biotech Fund and a group of investors with Euclidean Capital, with participation from existing investors InterWest Partners, OrbiMed Advisors, and Osage University Partners.

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The proceeds will be used to develop and advance into the clinic the Company’s pipeline of mutant p53 restoration drug candidates.

p53 is the most commonly mutated protein in human cancers, with more than half of all tumors containing mutant p53. The protein plays a pivotal role in the body’s natural defense mechanism against cancer and induces a highly-organized program of cellular death to prevent the proliferation of potentially cancerous cells.

Cancer cells often have mutations in p53 that enable them to escape death. PMV Pharma’s unique mechanism of action promises to restore p53 to its normal function, eliminating this escape route and selectively killing the mutant cancer cells without affecting normal tissues.

"PMV Pharmaceutical’s world-class founders, scientific advisors, and leadership team, together with its transformative chemistry and biology platform position PMV Pharma to be a leader in next-generation cancer therapies to improve patients’ lives," said Steve Winick of Topspin. In conjunction with the Series B financing, Mr. Winick will be joining PMV’s Board of Directors.

"This financing provides PMV Pharma with the resources to broadly expand our pipeline and to bring p53 therapies to the clinic," said David Mack, Ph.D., President and CEO of PMV Pharmaceuticals. "We are excited to have Topspin join us in our pursuit of developing meaningful new medicines for large segments of the cancer population. The enthusiasm and confidence from our new and existing investors underscore the important advances we have made."
About PMV Pharma

PMV Pharma was co-founded by Dr. Arnold Levine, one of the discoverers of the p53 protein and a professor emeritus at the Simons Center for Systems Biology at the Institute for Advanced Study. p53 is the most commonly mutated gene in cancer, with over 50 percent of all human tumors containing a p53 mutant protein. PMV Pharma is developing first-in-class p53 and p53 pathway modulators for the treatment of cancer. Bringing together leaders in the field to utilize over three decades of p53 biology, PMV Pharma combines unique biological understanding with pharmaceutical development focus. PMV Pharma is headquartered in Cranbury, New Jersey.