On October 1, 2019 Refuge Biotechnologies, Inc. ("Refuge"), a synthetic biology company developing intelligent cell therapeutics for cancer immunotherapy, reported that Bing Wang, Ph.D., Co-Founder and Chief Executive Officer of Refuge, is scheduled to present at the 2019 Cantor Fitzgerald Global Healthcare Conference on Friday, October 4, 2019 at 8:55 AM ET (Press release, Refuge Biotechnologies, OCT 1, 2019, View Source [SID1234539995]).

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A live audio webcast will be accessible in the media section of the company’s website at www.refugebiotech.com. A replay of the webcast will be archived on the company’s website for 40 days.

On October 1, 2019 ORPHELIA Pharma, a French biopharmaceutical company dedicated to the development and marketing of paediatric drugs in the fields of oncology and neurology, reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the issuance of a marketing authorization for Ivozall (Press release, ORPHELIA Pharma, OCT 1, 2019, View Source [SID1234539964]).

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Ivozall is a solution for infusion containing 1 mg/ml clofarabine and supplied in 20 ml-vials. Clofarabine is an essential medicine for the treatment of relapsed or refractory Acute Lymphoblastic Leukaemia (ALL) in children. Ivozall will be the first generic form of clofarabine to be authorised under the European centralized procedure.

« We are particularly pleased with this decision which comes after continuous efforts of our company together with our partners », comments Jeremy Bastid, Chief Development Officer of ORPHELIA Pharma. « This positive opinion is a key milestone in the process of making Ivozall, our first medicinal product in oncology, available to the paediatric community ».

« The CHMP has acknowledged the interest of Ivozall in improving health of children with ALL. We are eagerly awaiting the marketing authorisation expected for November 2019 », highlights Hugues Bienaymé, General Manager of ORPHELIA Pharma. « We anticipate to make Ivozall available to the hospital centres treating ALL patients in some countries from February 2020 », added Gilles Alberici, Chairman of ORPHELIA Pharma. « Other countries will be handled by ORPHELIA distributors, to be selected in the course of 2020 ».

About Acute Lymphoblastic Leukaemia

Acute Lymphoblastic Leukaemia is a cancer associated with the uncontrolled proliferation of lymphoblasts that invade the bone marrow. The disease progresses rapidly and aggressively and requires immediate treatment. ALL is a rare disease, with around 7,000 people diagnosed each year in Europe. The majority of ALL cases occurs in children. Although rare, ALL is the most common type of childhood cancer. Clofarabine is indicated for the treatment of ALL in paediatric patients who have relapsed or are refractory after receiving at least two prior regimens and where there is no other treatment option anticipated to result in a durable response.

On October 1, 2019 Navrogen, Inc. reported that it has entered into a Cooperative Research and Development Agreement (CRADA) with researchers at the U.S. National Cancer Institute (NCI) (Press release, Navrogen, OCT 1, 2019, View Source [SID1234539980]). The CRADA is focused on advancing antibody-based experimental medicines to targets associated with tumor-mediated immuno-suppression. Researchers at the NCI, led by Dr. Ira Pastan, NIH Distinguished Investigator and co-chief of NCI Center for Cancer Research’s Laboratory of Molecular Biology, have developed compounds that can uniquely target molecules on inflammatory cells and unlock their immuno-suppressed state within the tumor microenvironment. Under this CRADA, Navrogen is responsible for validating and advancing the preclinical development of these compounds towards clinical trials.

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"We have been fortunate to work with some of the leading researchers focused on immune-mediated anti-cancer therapies" stated Luigi Grasso, Ph.D., Chief Scientific Officer of Navrogen. The agents focused within this program have been previously shown in early clinical studies to unlock the immune response within tumors, and we hope to leverage their use with new approaches in tumors that exhibit immune suppression of this pathway."

The CRADA program complements Navrogen’s focus on developing novel agents that can overcome humoral immune suppression which is mediated by tumor-produced humoral immuno-oncology (HIO) factors.

On October 1, 2019 ElevateBio, a Cambridge-based biotechnology holding company, reported it has established and launched HighPassBio, a company dedicated to advancing novel targeted T cell immunotherapies (Press release, ElevateBio, OCT 1, 2019, View Source [SID1234539996]). The company’s lead product is an engineered T cell receptor (TCR) T cell therapy for HA-1 expressing tumors, which is designed to treat and potentially prevent relapse of leukemia following hematopoietic stem cell transplant (HSCT). The product and approach were developed by researchers at Fred Hutchinson Cancer Research Center.

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"At ElevateBio we are committed to building therapeutics companies with the world’s leading innovators in cell and gene therapy to advance novel treatments that have strong potential to dramatically improve patient lives," said David Hallal, Chairman and CEO of ElevateBio. "We look forward to leveraging our centralized industry-leading cell and gene therapy process development and manufacturing capabilities while working closely with Dr. Marie Bleakley and her team, to accelerate their impressive work through clinical development with the goal of serving patients who have no other treatment options. Additionally, we will explore this approach as a potential treatment for other diseases that are treated by stem cell transplants."

HighPassBio’s scientific founder is Marie Bleakley, M.D., Ph.D., M.ClinEpi, pediatric oncologist and stem cell transplant physician at Fred Hutchinson Cancer Research Center and chair of the scientific advisory board (SAB) of HighPassBio. As the chair of HighPassBio’s SAB, Dr. Bleakley will continue working with ElevateBio to advance and accelerate this innovative program through clinical development toward patients.

A Phase 1 clinical trial has treated initial patients and is recruiting adult and pediatric patients who have relapsed with leukemia or related conditions following blood and marrow transplantation (also known as stem cell transplantation). More details on www.clinicaltrials.gov under the study ID number NCT03326921.

About TCR-Engineered T Cell Therapy

A key role of the immune system is to detect tumor antigens, engage T cells and eradicate the tumor. However, the immune response to tumor antigens varies and is often insufficient to prevent tumor growth and relapse. An approach known as adoptive T cell therapy, using T cell receptors, or TCRs, can overcome some of the obstacles to establishing an effective immune response to fight off the target tumor. TCRs are molecules found on surface of T cells that can recognize tumor antigens that are degraded to small protein fragments inside tumor cells. Unlike CAR T cells that recognize only surface antigens, TCRs can recognize small protein fragments derived from intracellular and surface antigens offering a more diverse way to attack tumors. These small protein fragments show up on the tumor cell surface with another protein called major histocompatibility complex (MHC), get recognized by the TCRs and consequently signal the body’s immune system to respond to fight off and kill the tumor cells.

Tumor-specific TCRs can be identified and then engineered into T cells that recognize and attack various types of cancers, representing a novel approach to treating and potentially preventing disease.

Adoptive T cell therapy can be applied to tackling relapse of leukemia post hematopoietic stem cell transplant (HSCT) by targeting the antigens expressed only by the patient and not by the stem cell transplant donor, known as minor histocompatibility antigens, or HA1. HA1 is expressed predominantly or exclusively on hematopoietic cells and leukemic cells. There is evidence that T cells specific for HA1 can induce a potent and selective antileukemic effect. HA1 TCR T cell therapy is a new investigational immunotherapy for the management of post transplantation leukemia relapse.

About Leukemia post HSCT Treatment and the Risk of Relapse

Leukemia, a cancer of the blood or bone marrow characterized by an abnormal proliferation of blood cells, is the tenth most common type of cancer in the U.S. with an estimated 60,140 new cases and 24,400 deaths in 2016. Leukemia arises from uncontrolled proliferation of a specific type of hematopoietic (blood) cell that is critical for a functional immune system. As a result, when patients are given very high doses of chemotherapy to eradicate leukemic cells most normal cells are killed as well, necessitating a transplant of hematopoietic stem cells from a donor to reconstitute the patient’s bone marrow and circulating hematopoietic cells. In some cases, the transplanted T cells from the donor can also recognize and eliminate the hematopoietic cells, including leukemia, from the recipient, thus preventing relapse.

While the majority of HSCT recipients are cured, 25-50 percent of HSCT recipients’ relapse, leukemia relapse remains the major cause of allogeneic HSCT failure, and the prognosis for patients with post-HCT relapse is poor. Relapse occurs following allogeneic HSCT in approximately one-third of patients with acute leukemia who undergo the procedure, and most patients subsequently die of their disease.

About HighPassBio

HighPassBio, an ElevateBio portfolio company, is working to advance a novel approach to treating hematological malignancies by leveraging T cell receptor (TCR)-engineered T cells, known as TCR T cells. The company’s lead program is designed to treat or potentially prevent relapse of leukemia in patients who have undergone hematopoietic stem cell transplant (HSCT). The technology was born out of Fred Hutchinson Cancer Research Center by world renowned expert, Dr. Marie Bleakley.

On October 1, 2019 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported that new data on IPH5401 and monalizumab were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress in Barcelona, Spain (Press release, Innate Pharma, OCT 1, 2019, View Source [SID1234539965]).

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Poster presentations highlighted:

Preliminary results of STELLAR-001, a Phase I dose-escalation study of IPH5401, an anti-C5aR antibody, in combination with durvalumab in advanced solid tumors;
One-year survival data of the first expansion cohort of the Phase II trial evaluating monalizumab in combination with cetuximab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)

"We are pleased with the continued progress of monalizumab and IPH5401. We believe that by targeting C5a receptors, IPH5401 is a potentially first-in-class therapeutic antibody for cancer treatment. The preliminary clinical data set from the STELLAR-001 dose-escalation trial prompted us to start and broaden the expansion cohorts in three different settings where anti-PD-(L)1 have shown no or limited activity," said Pierre Dodion, Chief Medical Officer of Innate Pharma. "In addition, the survival data set for the combination of monalizumab and cetuximab in head and neck cancer support further development in IO-pretreated and IO-naïve patients, populations with high unmet medical need."

Key Highlights from IPH5401’s STELLAR-001 Study
In the STELLAR-001 dose-escalation study, 14 patients were included across four doses. Six patients had NSCLC, five had HCC, two had urothelial carcinoma (UCC), and one had renal cell carcinoma (RCC).

The combination of IPH5401 and durvalumab was reported to be well tolerated. No dose limiting toxicity was reported and no dose relationship was observed regarding safety. Pharmacodynamic analyses confirmed full receptor saturation at all dose levels and provided the basis for dose selection for the expansion cohorts.

Twelve patients were evaluated for efficacy. Early activity signals were observed in HCC and NSCLC patients, which included:

One confirmed partial response was reported in a HCC patient with prior progression after nivolumab
One prolonged stable disease (40 weeks) was reported in a NSCLC patient with prior progression after nivolumab

The Company will initiate the planned expansion cohorts in NSCLC patients with secondary resistance to prior IO treatment and in IO-naïve HCC patients to generate additional safety and efficacy data as well as additional translational analyses on tumor biopsies. In addition, based on the data generated in the dose escalation, the Company plans to add an additional cohort testing IPH5401 in combination with durvalumab in IO-pretreated HCC patients, subject to regulatory approval.

Key highlights from the Phase II study of monalizumab in combination with cetuximab in patients with R/M SCCHN, one-year survival data
In a cohort of 40 SCCHN patients previously treated with chemotherapy alone or chemotherapy followed by PD-1/L1 checkpoint inhibitors, the combination of monalizumab and cetuximab demonstrated a manageable safety profile and a response rate of 27.5% (36% and 17% in IO-naïve and IO-pretreated patients, respectively). Responses were observed in platinum-resistant patients and human papillomavirus (HPV) positive and negative patients.

Additional efficacy highlights included:

Median overall survival of 8.5 months with median follow-up time of 17 months;
Trend for improved survival in IO-pretreated patients (14.1 months in IO-pretreated patients and 7.8 months in IO naïve patients); and
12-month overall survival rate of 44% (60% in IO-pretreated and 32% in IO naïve patients)
These data suggest that the combination of monalizumab and cetuximab may provide promising response rates and favorable trends in overall survival. The Company is moving forward with the planned expansion cohorts in IO-pretreated and IO-naïve R/M SCCHN patients.

About IPH5401:
IPH5401 is a potentially first-in-class therapeutic antibody that specifically binds and blocks C5a receptors (C5aR) expressed on subsets of myeloid-derived suppressor cells (MDSC) and neutrophils. Part of the innate immune system, these types of cells promote tumor growth by secreting inflammatory and angiogenic factors, potently suppress anti-tumor T and NK cells and hamper the activities of PD-1 checkpoint inhibitors.

C5a, a factor in the complement cascade, is often overexpressed in tumors, where it attracts and activates MDSCs and neutrophils in the tumor microenvironment. Preliminary evidence suggests high expression of the C5a receptor in both NSCLC and HCC.

About Monalizumab:
Monalizumab is a potentially first-in-class dual checkpoint inhibitor targeting NKG2A receptors expressed on tumor infiltrating cytotoxic CD8+ T cells and NK cells.

NKG2A is an inhibitory checkpoint receptor for HLA-E. By expressing HLA-E, cancer cells can protect themselves from killing by NKG2A+ immune cells. HLA-E is frequently overexpressed in the cancer cells of many solid tumors and hematological malignancies. Hence, monalizumab may re-establish a broad anti-tumor response mediated by NK and T cells. Monalizumab may also enhance the cytotoxic potential of other therapeutic antibodies.

AstraZeneca (LSE/STO/NYSE: AZN) obtained full oncology rights to monalizumab in October 2018 through a co-development and commercialization agreement initiated in 2015. The ongoing clinical development for monalizumab is focused on investigating monalizumab in combination strategies.

About Durvalumab:
Durvalumab, a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumor’s immune-evading tactics and inducing an immune response.

As part of a broad development program, durvalumab is being investigated as monotherapy and in combination with IO, small molecules, and chemotherapies across a range of tumors and stages of disease.

About Cetuximab:
Cetuximab is an anti-EGFR monoclonal antibody blocking oncogenic signaling and inducing Fcγ receptor-mediated antibody dependent cellular cytotoxicity (ADCC). NK cells mediate cetuximab-induced ADCC against SCCHN. Genetic and preclinical experiments suggest that ADCC can be enhanced by NK-stimulators.

The activity of cetuximab single agent in R/M SCCHN is limited with a 12.6% ORR, a median PFS of 2.3 months and a median OS of 5.8 months (Vermorken et al, JCO 2007).