On April 2, 2019 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company focused on the development of precision medicines for oncology, reported new findings regarding the mechanism of action of the Company’s lead drug candidate tipifarnib and its potential clinical applications (Press release, Kura Oncology, APR 2, 2019, View Source [SID1234534892]). These findings are being presented today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 in Atlanta. A copy of the poster is available on Kura’s website at www.kuraoncology.com.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Tipifarnib is a potent and selective farnesyl transferase inhibitor currently in a registration-directed clinical trial in patients with head and neck squamous cell carcinoma (HNSCC) that carry mutations in HRAS, an exclusively farnesylated oncogene. Tipifarnib has also been shown to downregulate production of the chemokine CXCL12 in tumor models and cancer patients. New findings, presented today, suggest that gene expression of the exclusively farnesylated proteins RHOE (RND3) and PRICKLE2 is strongly associated with CXCL12 expression in bone marrow stroma, which may provide a mechanistic rationale for why the CXCL12 pathway is a therapeutic target of tipifarnib and other farnesyl transferase inhibitors.

In addition, an analysis of a subset of patients from a previously conducted Phase 2 trial of tipifarnib in patients with relapsed and refractory lymphomas identified pre-treatment tumor CXCL12 expression as a potential biomarker of clinical benefit in patients with diffuse large B-cell lymphoma (DLBCL) and mycosis fungoides, the most common form of cutaneous T-cell lymphoma (CTCL). This observation is consistent with similar findings from Kura in other indications such as peripheral T-cell lymphoma (PTCL), acute myeloid leukemia (AML) and pancreatic cancer. CXCL12 and its receptors, CXCR4 and CXCR7, have been implicated in cancer progression and poor prognosis across a large spectrum of solid tumor and hematologic indications.

"The target of farnesyl transferase inhibitors has been elusive for several decades. These findings provide key evidence supporting the inhibition of the CXCL12 pathway as a mechanism of action mediating the activity of tipifarnib in the clinic," said Antonio Gualberto, M.D., Ph.D., Head of Development and Chief Medical Officer of Kura Oncology. "CXCL12-expressing cancers represent a major unmet medical need, and we believe that CXCL12 pathway biomarkers could enable registrational strategies for tipifarnib in multiple hematologic and solid tumor indications."

In December 2018, Kura reported activity from an ongoing Phase 2 trial of tipifarnib in patients with relapsed or refractory PTCL, including a significant association between CXCL12 expression and clinical benefit, as well as proof-of-concept in angioimmunoblastic T-cell lymphoma (AITL), an aggressive form of PTCL often characterized by high levels of CXCL12 expression. The Company anticipates providing an update on this trial, including duration of response data from the AITL cohort and additional data from the CXCL12-high PTCL cohort, in mid-2019.

About Tipifarnib

Kura Oncology’s lead drug candidate, tipifarnib, is a potent and highly selective inhibitor of farnesylation, a key cell signaling process implicated in cancer initiation and development. Tipifarnib was previously studied in more than 5,000 cancer patients and showed compelling and durable anti-cancer activity in certain patient subsets, however no molecular mechanism of action had previously been determined that could explain its activity across a range of diverse clinical indications, including squamous tumors that carry mutant HRAS, as well as in lymphoid, myeloid and solid tumors that do not carry HRAS mutations. Leveraging advances in next-generation sequencing as well as emerging information about cancer genetics and tumor biology, Kura is seeking to identify those patients most likely to benefit from tipifarnib

On April 2, 2019 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus, reported a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 which is taking place March 30 through April 3 in Atlanta, Georgia (Press release, Oncolytics Biotech, APR 2, 2019, View Source [SID1234534909]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The poster, entitled, "Exploratory analysis of T cell repertoire dynamics upon systemic treatment with the oncolytic virus pelareorep in combination with pembrolizumab and chemotherapy in patients with advanced pancreatic adenocarcinoma," describes analysis of patient samples from REO 024; a study of pelareorep and Keytruda in combination with chemotherapy in patients with advanced (second-line) pancreatic cancer.

"We are thrilled with the rates of disease control observed in this study evaluating pelareorep and Keytruda in combination with chemotherapy in patients with advanced second-line pancreatic cancer," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics Biotech. "The data presented at AACR (Free AACR Whitepaper) now demonstrate that the degree of T cell clonality, examined in patients from REO 024, has the potential to serve as a predictive and prognostic biomarker of pelareorep therapy. Providing physicians with a simple blood test to understand which patients are likely to respond to treatment is invaluable, allowing the medical community to target the right treatment to the right patient. We look forward to utilizing this new biomarker as we move forward with all of our current clinical programs with checkpoint inhibitors including trials for multiple myeloma, our ongoing phase 2 second-line pancreatic cancer study, and of course, our breast cancer program."

Dr. Rita Laeufle, Chief Medical Officer of Oncolytics Biotech, said, "These data provide additional insight into the underlying biology that drives the efficacy of pelareorep therapy when combined with a checkpoint inhibitor and chemotherapy. We see that treatment with pelareorep can educate or prime the immune system early on during treatment. This priming occurs after pelareorep but before Keytruda, highlighting the synergy of these agents given that checkpoint inhibitors need a primed immune system that recognizes cancer cells in order to work. Importantly, the extent of early priming measured before the addition of Keytruda, is what most strongly correlates to overall survival. We believe these biological changes are intimately tied to pelareorep’s mechanism of action and serve as a biomarker with utility across multiple cancer types."

Key data and conclusions:

Patients treated with pelareorep in combination with chemotherapy and pembrolizumab showed changes in their T cell repertories with high turnover and significant expansion during treatment
These post-treatment expanded T cell populations, are "new" clones not present at baseline, suggesting effective priming of the immune system
Higher T cell clonality at baseline correlates with longer progression free survival (HR=0.05, p=0.01) and overall survival (HR=0.12, p=0.01) demonstrating the predictive value of the assay
Enhanced T cell clonality after the first cycle of treatment correlates with improved overall survival (HR=0.08, p=0.01) and serves as an on-treatment prognostic biomarker
Early expanded T cell clones, detected at day 8 of treatment (prior to pembrolizumab), most strongly correlate with survival time which suggests that early versus late clonal expansion may be elicited by pelareorep treatment
T cell clonality has significant potential as a predictive and prognostic on-treatment biomarker to pelareorep therapy
The poster was authored by Dr. Grey Wilkinson, a translational scientist at Oncolytics Biotech, and his colleagues, in collaboration with Northwestern University, UT Health San Antonio and Adaptive Biotechnologies. The poster can be found on the Posters & Publications page of Oncolytics’ website, View Source

About Pelareorep
Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.

On April 2, 2019 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer, autoimmune disease, asthma and allergic diseases, reported it has entered into a research and license agreement in which Astellas Pharma Inc. will access Xencor’s bispecific technology to advance a novel bispecific antibody program in oncology (Press release, Xencor, APR 2, 2019, Xencor and Astellas Enter Collaboration for Novel Bispecific Antibody Program [SID1234534925]). Xencor and Astellas will collaborate to generate bispecific antibodies directed toward a selected anti-tumor target for the potential treatment of patients with cancer, and Astellas will have an exclusive worldwide license to develop and commercialize novel drug candidates.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Xencor’s modular antibody engineering platform enables the rapid generation of proprietary programs for our broad pipeline of drug candidates and for our partners, as well. Our XmAb bispecific Fc domains enable antibodies and other protein structures that bind two or more different targets simultaneously, which inherently provides a wide range of potential drug candidates," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "Our partnership with Astellas further expands the potential of XmAb bispecifics to create new therapies for patients with cancer."

Under the terms of the agreement, Xencor will apply its bispecific technology to create multiple bispecific antibody candidates against the target specified by Astellas and will perform initial characterization of the molecules. Astellas will conduct all preclinical and clinical development and regulatory and commercial activities. Xencor will receive an upfront payment and will be eligible to receive development, regulatory and sales milestone payments and high-single digit to low-double digit percentage royalties on net sales.

On April 2, 2019 Unum Therapeutics Inc. (NASDAQ: UMRX), a clinical-stage biopharmaceutical company focused on the development of cellular immunotherapies to treat cancer based on its novel T cell technology platforms, reported that Charles Wilson, Chief Executive Officer, will present a corporate overview at two upcoming investor conferences in April (Press release, Unum Therapeutics, APR 2, 2019, View Source [SID1234534980]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Jefferies 6th Annual IO Cell Therapy Summit on Friday, April 5, 2019, at 4:25 p.m. ET in Boston, MA

H.C. Wainwright Global Life Sciences Conference on Tuesday, April 9, 2019, at 1:50 p.m. BST / 9:50 a.m. EDT in London, United Kingdom. This presentation will be webcast live, and available for replay on the "Events" section of Unum’s investor relations webpage (investors.unumrx.com/events), where it will be archived for approximately 90 days.

On April 2, 2019 Aura Biosciences, a leader in the development of novel targeted therapies in ocular oncology, reported that it closed a $40 million Series D financing (Press release, Aura Biosciences, APR 2, 2019, View Source [SID1234534856]). New investor Medicxi led the round, with current investors also participating.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Company plans to use the proceeds from the Series D financing to support the late stage clinical development of their lead asset, light-activated AU-011, for the treatment of primary choroidal melanoma.

"The additional funding provided by this Series D financing enables Aura to continue to execute on our goals of developing the first targeted treatment for patients with primary choroidal melanoma, a life and vision threatening rare disease with no drugs approved," said Elisabet de los Pinos, Ph.D., Chief Executive Officer of Aura. "We are delighted to have the support from lead investor Medicxi, along with our existing investors, as we enter this next stage of the company’s growth."

In conjunction with the closing of the financing, Giovanni Mariggi, Ph.D., a Partner at Medicxi, will join Aura’s Board of Directors.

About Choroidal Melanoma

Choroidal melanoma is a rare and aggressive type of eye cancer. Choroidal melanoma is the most common primary intraocular tumor in adults and develops in the uveal tract of the eye. No targeted therapies are commercially available at present. The most common current treatment for choroidal melanoma is plaque radiotherapy, which involves surgical placement of a radiation device on the exterior of the eye over the tumor and is associated with severe visual loss and other long-term sequelae such as dry eye, glaucoma, cataracts and radiation retinopathy. The only other alternative is enucleation, or total surgical removal of the eye. Choroidal melanoma metastasizes in approximately 50 percent of cases with liver involvement in 80-90% of cases and, unfortunately, metastatic disease is universally fatal (source: OMF). There is a very high unmet need for a new vision-sparing targeted therapy that could enable early treatment intervention for this life-threatening rare disease given the lack of approved therapies, and the comorbidities of radioactive treatment options.

About Light-Activated AU-011

AU-011 is a first-in-class targeted therapy in development for the primary treatment of choroidal melanoma. The therapy consists of proprietary viral-like particle bioconjugates (VPB) that are activated with an ophthalmic laser. The VPBs bind selectively to unique receptors on cancer cells in the eye and are derived from technology originally pioneered by Dr. John Schiller of the Center for Cancer Research at the National Cancer Institute (NCI), recipient of the 2017 Lasker-DeBakey Award. Upon activation with an ophthalmic laser, the VPB rapidly and specifically disrupts the cell membrane of tumor cells while sparing key eye structures, which may allow for the potential of preserving patients’ vision and reducing other long-term complications of radiation treatment. AU-011 can be delivered using equipment commonly found in an ophthalmologist’s office and does not require a surgical procedure, pointing to a potentially less invasive, more convenient therapy for patients and physicians. AU-011 for the treatment of choroidal melanoma has been granted orphan drug and fast track designations by the U.S. Food and Drug Administration and is currently in clinical development.