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Aduro Biotech Receives Milestone Payment From Janssen for Acceptance of Investigational New Drug Application for ADU-214 in Lung Cancer

On October 29, 2015 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that it has received a milestone payment from Janssen Biotech, Inc. for the acceptance of Aduro’s Investigational New Drug (IND) Application by the U.S. Food and Drug Administration for ADU-214, a LADD immunotherapy product candidate for the treatment of lung cancer (Press release, Aduro BioTech, OCT 29, 2015, View Source [SID:1234507841]). Janssen, Aduro’s license partner for ADU-214, expects to initiate a multi-center Phase 1 trial to evaluate the safety and immunogenicity of intravenous administration of ADU-214 by the end of 2015.

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"The acceptance of the IND marks an important milestone for Aduro, as ADU-214 will be the first immunotherapy compound to enter clinical trials through our license agreement with Janssen," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "Lung cancer is the leading cause of cancer-related deaths worldwide and traditionally has been very difficult to treat. We believe ADU-214 may be an attractive alternative in combatting this deadly disease."

In October 2014, Aduro entered into its second agreement with Janssen Biotech, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, granting an exclusive, worldwide license to ADU-214 and other product candidates engineered for the treatment of lung cancer and certain other cancers based on Aduro’s novel LADD immunotherapy platform. Under the agreement facilitated by Johnson & Johnson Innovation center, Aduro received a $30 million up-front payment and a milestone payment associated with submission of the IND, and is eligible to receive future development, regulatory and commercialization milestone payments up to a potential total of $786 million. In addition, Aduro is eligible to receive royalties at a rate ranging from high single-digits to low teens on worldwide net sales upon successful launch and commercialization.

About LADD

LADD is Aduro’s proprietary platform of live-attenuated double-deleted Listeria monocytogenes strains that have been engineered to induce a potent innate immune response and to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity.

Seattle Genetics Initiates Phase 2 Clinical Trial of Denintuzumab Mafodotin (SGN-CD19A) Combination Therapy in Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

On October 29, 2015 Seattle Genetics, Inc. (NASDAQ:SGEN) reported the initiation of a randomized phase 2 clinical trial of denintuzumab mafodotin (SGN-CD19A) in combination with the second-line salvage regimen of rituximab (Rituxan), ifosfamide, carboplatin and etoposide (RICE), for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common type of aggressive non-Hodgkin lymphoma (Press release, Seattle Genetics, OCT 29, 2015, View Source [SID:1234507840]).

The study is intended to evaluate the activity and safety of the combination regimen compared to RICE alone. Denintuzumab mafodotin is an antibody-drug conjugate (ADC) targeting CD19, a protein expressed uniformly on almost all B-cell malignancies. The ADC is designed to be stable in the bloodstream and release its cytotoxic agent upon internalization into CD19-expressing cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects associated with traditional chemotherapy while enhancing antitumor activity.

"The only curative option for patients with diffuse large B-cell lymphoma, or DLBCL, who relapse after initial treatment is an intensive salvage regimen with the goal of achieving the best possible response prior to autologous stem cell transplant. Those who are transplanted in PET-negative complete remission have the best outcomes. Currently, only 50 percent of DLBCL patients are able to proceed to a transplant following treatment with any of the currently available salvage treatment regimens, representing a significant need to identify more effective treatment options," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "In relapsed DLBCL patients in a phase 1 clinical trial, we have observed an objective response rate over 50 percent with denintuzumab mafodotin monotherapy and a tolerability profile that is well suited to combination regimens. Our preclinical data suggest that combining denintuzumab mafodotin with RICE may result in synergistic activity, potentially leading to improved treatment outcomes in relapsed or refractory DLBCL patients."

In this phase 2 randomized, open-label, multi-center clinical trial, approximately 150 relapsed/refractory DLBCL or grade 3B follicular lymphoma patients who are eligible for an autologous stem cell transplant (ASCT) will be randomized to receive RICE either with or without denintuzumab mafodotin every three weeks for three cycles. The primary endpoint is to compare the complete remission rates between the two study arms. Secondary endpoints include safety of the combination regimen, progression-free survival, overall survival and the number of patients who are able to undergo autologous transplant.

At the 2014 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, data were presented from an ongoing phase 1 trial of relapsed/refractory aggressive non-Hodgkin lymphoma patients who received single-agent denintuzumab mafodotin every three weeks. Of the 51 evaluable patients, including 45 DLBCL patients, the objective response rate across all dose levels was 35 percent, including 20 percent complete remissions and 16 percent partial remissions. In the subset of patients who had relapsed disease, the objective response rate was 55 percent, including 32 percent complete remissions and 23 percent partial remissions. The most common adverse events of any grade occurring in more than 25 percent of patients were blurred vision (60 percent), dry eye (46 percent), fatigue (38 percent), constipation (33 percent) and keratopathy (31 percent). Ocular symptoms and corneal findings were superficial, generally reversible, and were managed with steroid eye drop treatment and dose modifications. The majority of affected patients experienced improvement and/or resolution at last follow up. Furthermore, no significant myelosuppression or peripheral neuropathy were observed, suggesting that denintuzumab mafodotin may be well tolerated in combination with multi-agent chemotherapy.

For more information about the denintuzumab mafodotin phase 2 DLBCL clinical trial, including enrolling centers, visit www.clinicaltrials.gov.

About Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphoma represents a diverse group of cancers that develop in the lymphatic system and are characterized by uncontrolled growth and accumulation of abnormal lymphocytes. Lymphocytes are a type of blood cells that are responsible for defending the body against infection. The most common forms of non-Hodgkin lymphoma are diffuse large B-cell lymphoma (an aggressive subtype) and follicular lymphoma (an indolent subtype).

Nymox Reports Results of Prospective Cross-Over Study of Fexapotide Treatment for Prostate Cancer

On October 29, 2015 Nymox Pharmaceutical Corporation (NASDAQ:NYMX) reported that long-term randomized cross-over data from the Company’s trial of fexapotide triflutate for low grade localized prostate cancer has shown statistical significance in efficacy compared to controls (Press release, Nymox, OCT 29, 2015, View Source [SID:1234507839]).

The study results indicate that randomized control subjects who subsequently switched to fexapotide had long-term outcomes significantly superior to control patients who did not change (cross-over) to fexapotide treatment.

These results are the initial 18 month follow-up results for the fexapotide trial for prostate cancer to be reported. The cross-over study arm of NX03-0040 consisted of 35 subjects. Based on biopsy progression the proportion of patients who progressed on biopsy and required biopsy progression-related surgery or radiotherapy in the cross-over group (0%) at 18 months was significantly less than in the control group (p<.03).

The cross-over group patients received randomized fexapotide 15 mg or 2.5 mg in a single treatment targeted toward the positive baseline cancer focus identified in initial positive biopsies. There were no cases in either of the 2 fexapotide dosage level treatment groups with biopsy progression at 18 months (p<.03).

In addition to the positive clinical progression results, the primary endpoint of the study (re-biopsy absence of tumor in the initially positive biopsy baseline area of the prostate) also reached statistical significance (p<.03) in the cross-over study. At the 18 month assessments, the post-treatment biopsy taken from the treated area of the prostate which was initially positive at baseline, showed absence of tumor (tumor presence in re-biopsy of baseline positive focus n=0) in the cross-over treated patients, which was statistically significant compared to controls (p<.03).

The Company expects to report results from its long-term NX03-0040 low grade localized prostate cancer study in the fourth quarter.

One of the major problems with current prostate treatments for localized prostate cancer (radical prostatectomy, external beam radiation, or brachytherapy) is the relatively high incidence of reported sexual dysfunction post-treatment. In 9 studies, NX-1207 treatment has been shown to have no significant adverse effect post-treatment on sexual function or testosterone levels.

– See more at: View Source#sthash.3ka4h1Wh.dpuf

OncoSec Enrolls First Patient in Biomarker-Focused Pilot Study in Triple Negative Breast Cancer

On October 29, 2015 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported that the Company has enrolled the first patient into a pilot biomarker trial of ImmunoPulse IL-12 in patients with triple negative breast cancer (TNBC) (Press release, OncoSec Medical, OCT 29, 2015, View Source [SID:1234507833]). ImmunoPulse IL-12, which employs intratumoral electroporation to enhance delivery of DNA-based interleukin-12 (IL-12), is designed to enhance tumor immunogenicity, leading to increased tumor infiltrating lymphocytes (TILs) and pro-inflammatory cytokines.

Previous studies have demonstrated that breast cancer patients whose tumors are associated with markers of inflammation, such as the presence of TILs, have better clinical outcomes. These data have initiated an effort by an international consortium to develop guidelines and recommendations for the routine evaluation of TILs for breast cancer. Further, preliminary data reported at the 2014 San Antonio Breast Cancer Symposium indicate that TNBC is responsive to cancer immunotherapies, such as anti-PD-1/PD-L1 checkpoint therapies. However, response rates in these TNBC patients, who were selected for study participation based upon TIL status, were only 18 to 33 percent.

"There is increasing evidence that breast cancer patients with tumors characterized by a ‘pro-inflammatory phenotype,’ including those with TNBC, have better responses to chemotherapy and experience longer disease-free and overall survival rates," said Mai H. Le, MD, Chief Medical Officer at OncoSec. "We anticipate that ImmunoPulse IL-12 will drive a tumor-specific inflammatory response in TNBC patients. The goal with ImmunoPulse IL-12 is to increase the number of patients who will benefit from anti-PD-1 therapy. We are very excited to be working closely with our colleagues at Stanford University to evaluate the role of ImmunoPulse IL-12 in promoting tumor immunogenicity."

Melinda L. Telli, MD, Assistant Professor of Medicine (Oncology) and Irene Wapnir, MD, Professor of Surgery (General Surgery), are leading this clinical trial at Stanford University Medical Center. Approximately 10 patients are planned for enrollment into this trial. The primary objective of the study is to evaluate the potential of ImmunoPulse IL-12 to promote a pro-inflammatory molecular and histological signature in tumor samples obtained from study participants. Secondary objectives include: evaluation of safety and tolerability; evaluation of local ablative effect (% necrosis); and description of other evidence of anti-tumor activity.

To learn more about the trial, visit www.oncosec.com. Additional details can also be found at www.clinicaltrials.gov.

About Triple Negative Breast Cancer (TNBC)
Breast cancer cells that test negative for estrogen receptors (ER-), progesterone receptors (PR-), and HER2 (HER2-) means the cancer is triple negative.1 Approximately 15-20 percent of US breast cancer cases are triple negative breast cancer (TNBC),2 which disproportionately affects younger women as well as African-American women, followed by Hispanic women.3

TNBC remains a poor-prognosis breast cancer subtype, with limited treatment options for patients with advanced, recurrent disease. In the recurrent disease setting, chemotherapy remains the standard of care, and median survival is approximately 13 months from the time of disease recurrence.4

Emerging evidence shows immunotherapy options may play an important role in the treatment paradigm for TNBC. Preliminary data demonstrated the anti-PD-1 antibody, pembrolizumab, led to an objective response in approximately 18 percent of TNBC patients;5 the anti-PD-L1 antibody, MPDL3280A, achieved an objective response in 33 percent of patients.6 There is increasing evidence that tumors need TILs for anti-PD-1/PD-L1 therapies to be most effective. Data also show TILs promote better responses to chemotherapy and improve clinical outcomes in breast cancer, including TNBC.7-12

Igenica Biotherapeutics Enters Into a Strategic Oncology Research Agreement with MedImmune

On October 28, 2015 – Igenica Biotherapeutics, Inc., a company focused on the discovery and development of innovative antibody-based therapies for the treatment of cancer, reported that it has entered into an oncology research agreement with MedImmune, the global biologics research and development arm of AstraZeneca (NYSE: AZN) (Press release, Igenica, OCT 28, 2015, View Source [SID1234519302]). Igenica and MedImmune will evaluate the potential of antibody-drug conjugates (ADCs) targeting Surface Antigen in Leukemia (SAIL), a novel cell surface protein with high prevalence of expression in a variety of hematologic malignancies and several solid tumors. Preclinical data have supported the selective targeting of tumors expressing SAIL with ADCs.

Under the agreement, Igenica will contribute its proprietary anti-SAIL antibodies, including IGN786, and its proprietary SNAP ADC drug linker, and MedImmune will provide its proprietary anti-tumor payload. Igenica and MedImmune will then jointly investigate the resulting novel ADC in preclinical studies.

MedImmune will receive an option to an exclusive worldwide license to anti-SAIL antibodies and antibody-drug conjugates resulting from the collaboration. Igenica will receive an exclusive option fee and, if MedImmune exercises its option, is also eligible to receive an upfront license fee, clinical, regulatory and commercialization milestones, and royalties on net sales. MedImmune will fund all development and commercialization costs under a license agreement.

"We are pleased to collaborate with MedImmune, a leading biotechnology company, to build on our pioneering research," commented John Celebi, Chief Business Officer, Igenica. "This agreement provides a strong opportunity to realize the potential value of IGN786 and complements our strategy focused on targeting drugs to block the immunosuppressive activities of immune cells in the tumor microenvironment to reinvigorate or activate de novo anti-tumor responses."

"We look forward to working with Igenica Biotherapeutics on developing a novel antibody-drug conjugate in hematology," said Ronald Herbst, Vice President, Oncology Research & Development, MedImmune. "Developing next generation antibody-drug conjugates is a key strategic area for us, and we are committed to advancing our pipeline in this area both externally and internally."

About IGN786 and SAIL
IGN786 is a humanized monoclonal antibody that binds to SAIL, a cell surface protein with high prevalence of expression in a variety of hematologic malignancies and several solid tumors. Igenica was the first to describe the biological properties of human SAIL and elucidate its potential as an antibody-drug conjugate approach (Blood Cancer Journal (2015) 5, e316). Preclinical data with IGN786 have supported the selective targeting of tumors expressing SAIL with antibody-drug conjugates.