On May 10, 2017 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported MedImmune, AstraZeneca’s global biologics research and development arm, will start a new clinical trial investigating the combination of MEDI0457, an immunotherapy designed to generate antigen specific killer T cell responses targeting HPV-associated tumors, and durvalumab, an investigational PD-L1 checkpoint inhibitor (Press release, Inovio, MAY 10, 2017, View Source;Neck-Cancer/default.aspx [SID1234518975]). The combination trial will enroll patients with metastatic HPV-associated squamous cell carcinoma of the head & neck (SCCHN) with persistent or recurrent disease after chemotherapy treatment.

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The open-label study is designed to evaluate the safety and efficacy of the combination therapy in approximately 50 subjects at multiple U.S. sites. Subjects will receive multiple doses of MEDI0457 (previously known as INO-3112) and durvalumab. The primary endpoints of the study are safety and objective response rate. The study will also evaluate immunological impact, progression-free survival and overall survival.

Dr. J. Joseph Kim, Inovio’s President and CEO, said, "This study marks a significant moment for Inovio as we transition into a late-stage biotechnology company. MedImmune is investigating the possibility of elevating the response rate of checkpoint inhibitors by using durvalumab in combination with a DNA plasmid vaccine originally from Inovio which has shown the ability to generate killer T cells. I’m a strong believer in this combination regimen strategy against cancer: utilize Inovio’s cancer vaccine to generate significant levels of antigen-specific killer T cells, have them infiltrate into tumors — or what is being referenced as turning a tumor from "cold" to "hot" — then suppress the cancer cells’ defensive mechanisms utilizing a checkpoint inhibitor. We think that powerful combination can be effective in treating multiple tumors going forward."

Increasing evidence suggests that response rates from checkpoint inhibitors such as MedImmune’s durvalumab can be enhanced when used in combination with cancer vaccines like MEDI0457 that generate tumor-specific T cells. Interim data from a MEDI0457 monotherapy study of head and neck cancer patients demonstrated that MEDI0457 generated robust HPV16/18 specific CD8+ T cell responses in peripheral blood and increased CD8+ T cell infiltration in resected tumor tissue samples.

In 2015, MedImmune acquired exclusive rights to Inovio’s INO-3112 immunotherapy for all HPV-associated cancers. MedImmune provided an upfront payment of $27.5 million to Inovio as well as potential future payments upon reaching development and commercial milestones totaling up to $700 million. MedImmune will fund all development costs. Inovio is entitled to receive up to double-digit tiered royalties on INO-3112 product sales.

About HPV-associated Head & Neck Cancer
Head and neck cancer is the sixth most common cancer worldwide. Human papillomavirus (HPV), the most common sexually transmitted disease in the US, is known to play a major role in the development of head and neck cancers, which include cancers of the oral cavity, oropharynx, nose/nasal passages and larynx. New cases of HPV-associated squamous cell carcinoma of the head & neck (SCCHN) are growing fastest in developed countries like the US. There are approximately 16,000 new cases of HPV-associated SCCHN per year in the US alone. In contrast, the rate of smoking and alcohol-related SCCHN has been steadily declining. Men are four times more likely than women to be diagnosed with this disease. Patients with HPV-associated SCCHN tend to be diagnosed at a younger age than those with smoking and alcohol related disease.

Head and neck cancers are currently treated by surgical removal of the cancer and lymph nodes, often followed by radiation and chemotherapy based on the extent of the disease. While patients may achieve good long-term survival, standard treatments can change their physical appearance and are associated with significant short and long-term toxicities which may interfere with salivary gland function, taste, smell, and the ability to swallow. The biology and natural history of oropharyngeal HPV infection and the best clinical management of patients with HPV-associated SCCHN are not well understood.

About MEDI0457 (INO-3112)
Inovio’s DNA-based immunotherapies help the immune system activate disease-specific killer T cells to fight a targeted disease. INO-3112 targets disease associated with the high-risk HPV types 16 and 18, which are responsible for over 70% of cervical pre-cancers and cancers and 60% of head and neck cancers. INO-3112 combines Inovio’s VGX-3100, its immunotherapy targeting HPV-associated diseases, with its DNA-based immune activator encoding IL-12.

About Durvalumab
Durvalumab, previously known as MEDI4736, a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumour’s immune-evading tactics and inducing an immune response. Additional clinical trials are ongoing to investigate durvalumab as monotherapy or in combination with tremelimumab in non-small cell lung cancer, head and neck squamous cell carcinoma, bladder, hepatocellular carcinoma and blood cancers.

On May 10, 2017 Endocyte, Inc. (NASDAQ:ECYT), a leader in developing targeted small molecule drug conjugates (SMDCs) and companion imaging agents for personalized therapy, reported financial results for the first quarter ending March 31, 2017, and provided a clinical and pipeline update (Press release, Endocyte, MAY 10, 2017, View Source [SID1234518974]).

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"We look forward to providing safety and efficacy updates for our clinical trials of both EC1169 and EC1456 at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) next month," said Mike Sherman, president and CEO at Endocyte. "In addition, we continue to discover compelling applications of the SMDC platform and are working to more rapidly bring assets toward clinical development in several exciting areas, to drive more value from our pipeline. These include our dual-targeted DNA crosslinker drug that can attack both tumor associated macrophages (TAMs) and cancer cells, EC2629, and our chimeric antigen receptor T-cell (CAR T-cell) SMDC adaptor platform."

"Enrollment in the expansion phase of the EC1169 trial in prostate cancer continues to progress well, and we recently completed our work with EC1456 exploring multiple dosing schedules," added Dr. Alison Armour, Endocyte’s chief medical officer. "We also enrolled the first patient in the study of EC1456 in ovarian cancer patients undergoing surgery to provide tissue-based characterization following drug administration."

Lead SMDC Programs

EC1169 (PSMA-targeted tubulysin): Enrolling patients in the expansion phase of the EC1169 trial in up to 50 taxane-exposed metastatic castration-resistant prostate cancer (mCRPC) patients and up to 50 taxane-naïve mCRPC patients at a maximum clinical dose of 6.5 mg/m2 once per week. The primary endpoint of this expansion phase is radiographic progression-free survival (rPFS), with a target of 5 months for taxane-naïve mCRPC patients and 3 months for taxane-exposed mCRPC patients. Secondary endpoints, which will provide earlier insight into drug activity, include overall response rates as measured by response evaluation criteria in solid tumors (RECIST) 1.1 and prostate-specific antigen (PSA). Enrollment is not limited based on the results of the scan with EC0652, but primary endpoints of the trial are to be assessed on PSMA positive patients.

EC1456 (folate receptor-targeted tubulysin): Enrolling expansion cohort of up to 40 folate receptor-positive (FR-positive) non-small cell lung cancer (NSCLC) patients, as determined by an etarfolatide scan, to receive the maximum clinical dose of 6.0 mg/m2 twice per week. Patients included in this expansion phase of the trial will have received first-line chemotherapy and may have also been treated with anti-programmed death-1 (anti-PD-1) therapy. Endocyte is also conducting an ovarian cancer surgical study to characterize EC1456 at the tumor level through a multifaceted analysis of collected tissue samples after administration of the drug.

Immuno-oncology Pipeline

EC2629: Pre-clinical development currently underway with a potential Investigational New Drug (IND) filing in mid-2017. EC2629 leverages a proprietary warhead with a dual mechanism of action: targeting both TAMs and FR-positive cancer cells.

CAR T-Cell Development Program: Continued progress with next-generation CAR T-cell therapeutic platform, in collaboration with leading experts in the field at Seattle Children’s Research Institute. Endocyte announced new research in a late-breaking poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2017, on the application of Endocyte’s SMDC technology. Data demonstrated that Endocyte’s bi-specific adaptor molecules can mitigate or eliminate cytokine storms in animal models and could meaningfully improve the safety and tolerability of CAR T-cell therapies. Pre-clinical evaluations for the CAR T-cell program by Dr. Michael Jensen are expected to be completed in the second half of 2017, in anticipation of a potential IND filing in 2018.

First Quarter 2017 Financial Results

Endocyte reported a net loss of $11.5 million, or $0.27 per basic and diluted share, for the first quarter of 2017, compared to a net loss of $10.2 million, or $0.24 per basic and diluted share for the same period in 2016.

Research and development expenses were $8.0 million for the first quarter of 2017, compared to $6.5 million for the same period in 2016. The increase was primarily attributable to increases in expenses related to the EC1169 phase 1 trial, including drug manufacturing expenses, expenses related to the development of EC2629 and other pre-clinical work and general research, and expenses related to the EC1456 phase 1 trial, which were partially offset by a decrease related to non-cash stock-based compensation expenses.

General and administrative expenses were $3.7 million for the first quarter of 2017, compared to $3.8 million for the same period in 2016. The slight decrease was primarily attributable to a decrease in compensation expense, which was partially offset by an increase in expenses related to professional fees.

Cash, cash equivalents and investments were $127.6 million at March 31, 2017, compared to
$163.3 million at March 31, 2016, and $138.2 million at December 31, 2016.

Financial Expectations

The company anticipates its cash balance at the end of 2017 to be approximately $100 million.

About EC1169 and EC0652

EC1169 is an investigational therapeutic SMDC constructed of a high affinity prostate specific membrane antigen (PSMA)-targeting ligand conjugated through a bioreleasable linker system to a potent microtubule inhibitor, tubulysin B hydrazide (TubBH). Patient PSMA-status is determined using the investigational companion imaging agent, EC0652.

About EC1456 and etarfolatide

EC1456 is an investigational therapeutic SMDC constructed of a high affinity FR-targeting ligand conjugated through a spacer and bioreleasable linker system to a potent cytotoxic microtubule inhibitor, TubBH. Patient FR-status is determined using the investigational companion imaging agent, etarfolatide.

On May 10, 2017 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported that the first patient has been enrolled in the Phase 1 clinical trial of LOXO-292, an investigational, highly potent and selective RET inhibitor (Press release, Loxo Oncology, MAY 10, 2017, View Source [SID1234518973]). RET gene alterations are thought to play a key role in the development of certain cases of lung, thyroid, colon and other cancers.

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"We are excited to put a second, purpose-built precision medicine into clinical development," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "We believe that patients with RET-altered lung, thyroid and other cancers have highly actionable genetic events that are not well addressed by existing therapies. LOXO-292 was designed to deliver potent RET inhibition, while avoiding off-target activities that can compromise dose intensity and contribute to toxicity. If our hypothesis is correct, LOXO-292 could have meaningful single agent anti-tumor activity in RET-altered cancers, and the ability to address key resistance mutations that could otherwise limit the clinical potential of RET inhibition in affected patients. In advancing our larotrectinib program, we have worked closely and creatively with patients and their doctors to deliver on the promise of precision medicine. We hope that LOXO-292 opens a new and exciting chapter in this story."

This first-in-human, global, multi-center Phase 1 trial will evaluate LOXO-292 as a single agent in patients with advanced solid tumors. The primary objective of the trial is to determine the maximum tolerated dose or recommended dose for further study. Key secondary objectives include measures of safety, pharmacokinetics, and anti-tumor activity (i.e. Objective Response Rate and Duration of Response, as determined by RECIST v1.1). The trial includes a dose escalation phase and dose expansion phase. During the dose escalation phase, up to 30 patients with advanced solid tumors may be enrolled to inform the selection of a dose and schedule for the expansion phase. In the expansion phase, five cohorts are planned to allow for the characterization of preliminary activity of LOXO-292 in the following genetically-defined populations: 1) RET-fusion lung cancer patients with prior RET inhibitor experience; 2) RET-fusion lung cancer patients with no prior RET inhibitor experience; 3) RET-mutant medullary thyroid cancer patients with prior RET inhibitor experience; 4) RET-mutant medullary thyroid cancer patients with no prior RET inhibitor experience; and 5) other RET-altered solid tumors. Loxo Oncology anticipates that approximately 15 patients will be enrolled to each of the expansion cohorts.

About LOXO-292
LOXO-292 is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. RET fusions have been identified in approximately 2% of non-small cell lung cancer, 10-20% of papillary thyroid cancer, and a subset of colon and other cancers. RET point mutations account for approximately 60% of medullary thyroid cancer. Both RET fusion and select RET mutated cancers are primarily dependent on this single activated kinase for their proliferation and survival. This dependency, often referred to as "oncogene addiction," renders such tumors highly susceptible to small molecule inhibitors targeting RET. LOXO-292 was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms that could otherwise limit the activity of this therapeutic approach. LOXO-292 is currently being studied in a Phase 1 trial. Interested patients and physicians can contact the Loxo Oncology Physician and Patient RET Clinical Trial Hotline at 1-855-RET-4-292 or email [email protected].

On May 10, 2017 Actinium Pharmaceuticals, Inc. (NYSE MKT:ATNM) ("Actinium" or "the Company"), a biopharmaceutical Company developing innovative targeted payload immunotherapeutics for the treatment of advanced cancers, reported that the Company received clearance from Health Canada to initiate the pivotal Phase 3 SIERRA Trial of Iomab-B at Canadian based clinical trial sites (Press release, Actinium Pharmaceuticals, MAY 10, 2017, View Source [SID1234518969]). Iomab-B is Actinium’s lead asset that upon approval, is intended to prepare and condition patients for a bone marrow transplant (BMT), also referred to as a hematopoietic stem cell transplant (HSCT), which is often considered the only potential cure for patients with certain blood-borne cancers and blood disorders. The SIERRA trial is a 150-patient, randomized, multicenter pivotal study evaluating Iomab-B followed by an HSCT in patients with relapsed or refractory acute myeloid leukemia (AML) who are age 55 and above compared to physician’s choice of chemotherapy that patient’s in the control arm will receive.

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According to the Canadian Blood and Marrow Transplant Group (CBMTG), there are approximately 15 centers in Canada that perform blood and marrow transplants who participate in the CBMTG’s registry. In CBMTG’s 2015/2016 annual report, it reported that there were 7,693 allogeneic transplants performed in Canada including 2,417 for patients with AML.

Dr. Mark Berger, Chief Medical Officer of Actinium said, "The clearance to initiate the SIERRA trial in Canada is an exciting milestone for Iomab-B as it offers us the opportunity to make Iomab-B available to more patients in need. We are expecting to open 15-20 clinical trial sites in the SIERRA trial and we are excited to begin to have participation from sites in Canada. The promise of Iomab-B is that it will enable a bone marrow transplant and long term survival for these patients that have few options for treatment."

About Iomab-B

Iomab-B is Actinium’s lead product candidate that is currently being studied in a 150-patient, multicenter pivotal Phase 3 clinical trial in patients with relapsed or refractory acute myeloid leukemia who are age 55 and above. Upon approval, Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant, which is often considered the only potential cure for patients with certain blood-borne cancers and blood disorders. Iomab-B targets cells that express CD45, a pan-leukocytic antigen widely expressed on white blood cells with the monoclonal antibody, BC8, labeled with the radioisotope, iodine-131. By carrying iodine-131 directly to the bone marrow in a targeted manner, Actinium believes Iomab-B will avoid the side effects of radiation on most healthy tissues while effectively killing the patient’s cancer and marrow cells. In a Phase 2 clinical study in 68 patients with advanced AML or high-risk myelodysplastic syndrome (MDS) age 50 and older, Iomab-B produced complete remissions in 100% of patients and patients experienced transplant engraftment at day 28. Iomab-B was developed at the Fred Hutchinson Cancer Research Center where it has been studied in almost 300 patients in a number of blood cancer indications, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), Hodgkin’s disease (HD), Non-Hodgkin lymphomas (NHL) and multiple myeloma (MM). Iomab-B has been granted Orphan Drug Designation for relapsed or refractory AML in patients 55 and above by the U.S. Food and Drug Administration and the European Medicines Agency.