On April 2, 2019 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a clinical-stage oncology-focused biopharmaceutical company pioneering a novel class of investigational antibody therapeutics based on its Probody therapeutic technology platform, reported the presentation of clinical and preclinical data for CX-2009, a CD166 targeting Probody Drug Conjugate (PDC), at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta, Georgia (Press release, CytomX Therapeutics, APR 2, 2019, View Source [SID1234534905]).

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"Collectively, these data highlight the potential opportunity for CX-2009, a novel first-in-class CD166-targeting anti-cancer agent," said Sean McCarthy, D. Phil., president, chief executive officer and chairman of CytomX. "In our first clinical dose escalation with CX-2009, we have seen clear evidence of tumor shrinkage in multiple cancers in heavily pretreated patients and an encouraging safety profile. The safety profile of CX-2009 is of particular note given the widespread expression of CD166 on normal tissues and suggests that CytomX masking technology can allow targeting of novel, broadly distributed antigens. Moreover, our preclinical and clinical research is revealing a relationship between target levels and anti-cancer activity, further validating CD166 as a potential new point of intervention in cancer treatment. In addition, our preclinical research into the combination of CX-2009 with a PD-1 Probody provides preliminary evidence for the potential of these two mechanisms to synergize with each other. Based on these integrated observations presented at AACR (Free AACR Whitepaper) 2019, we are excited to advance CX-2009 to the next phase of development."

Preliminary Results of PROCLAIM-CX-2009, a First-in-Human, Dose-Finding Study of the Probody Drug Conjugate CX-2009 in Patients with Advanced Solid Tumors

Presenter: Funda Meric-Bernstam. M.D., Chair of the Department of Investigational Cancer Therapeutics, Medical Director of the Institute for Personalized Cancer Therapy, and Professor, Divisions of Cancer Medicine and Surgery, MD Anderson Cancer Center

Preliminary safety and antitumor activity were reported from the dose-escalation phase (Part A and A2) of the ongoing PROCLAIM-CX-2009 study evaluating CX-2009 in seven selected tumor types. As of a February 26, 2019 data snapshot, 78 patients were enrolled. Of 71 patients evaluable for efficacy, for patients who received ≥4 mg/kg of CX-2009 and had at least one post-baseline on-study tumor assessment, 15/39 (38%) achieved tumor shrinkage, including seven unconfirmed partial responses (4 patients with breast cancer, 2 with ovarian cancer and one with head and neck cancer). 29/39 (74%) achieved stable disease or better at the time of the first on-treatment scan.

CX-2009 was generally well tolerated. The maximum tolerated dose (MTD) was not reached at the highest dose level tested of 10 mg/kg. The most common treatment-related adverse events (TRAE) were grade 1 and 2 and included nausea (32%), fatigue (24%) and decreased appetite (23%). The most common grade 3/4 TRAE was keratitis (8%).

A Probody Drug Conjugate Targeting CD166 (ALCAM) Enhances Preclinical Antitumor Activity of a Probody Therapeutic Targeting PD-1

Presenter: Erwan Le Scolan, Ph.D., Senior Scientist, CytomX Therapeutics

The anti-tumor activity of CX-2009 was studied in a syngeneic mouse model. Results show that the combination treatment of CX-2009 with a surrogate mouse anti-PD-1 Probody significantly inhibited tumor growth in mouse CT-26 tumors engineered to express human CD166, as compared to either agent as a monotherapy. In addition, CX-2009 was shown to induce immunogenic cell death of cancer cells in vitro while sparing T cells, an action that may enhance T cell priming. These results highlight the potential to combine the PDC CX-2009 with a Probody therapeutic targeting the PD pathway, such as the CytomX anti-PD-L1 Probody, CX-072, as well as potentially combining other antibody drug conjugates or PDCs with immune checkpoint inhibitors.

CD166-DM4 Probody Drug Conjugate (CX-2009) Treatment of 198 Patient-derived Xenograft Models (PDX) in a Mouse Clinical Trial Format

Presenter: Bob Liu, Ph.D., Senior Scientist, CytomX Therapeutics

CytomX is evaluating the anti-tumor activity of CX-2009 in 198 PDX tumor models in a mouse clinical trial format dosed with 5 mg/kg of CX-2009 every 2 weeks for 3 doses. 129 models (65%) had been dosed at the time of data cutoff. Results from the ongoing study show anti-tumor activity in 82% of the models compared to control. Tumor shrinkage relative to pre-dosing was observed in 22% of models relative to untreated controls, and 48% of CX-2009-treated tumors yielded tumor growth inhibition of greater than 50%. CD166 mRNA level was associated with antitumor activity, which may provide a strategy for prospectively identifying patients most likely to respond to CX-2009.

About CX-2009 and the PROCLAIM-CX-2009 Trial

CX-2009, a PDC that targets the cell surface protein CD166, is being developed for the treatment of solid tumors. CD166 is highly and homogeneously expressed on multiple tumor types. CX-2009 is designed to target CD166 specifically in the tumor microenvironment and deliver the tubulin-destabilizing maytansine payload, DM4, to cancer cells. In preclinical studies, CD166 has been shown to effectively internalize antibody-drug conjugates resulting in potent cell killing in-vitro. CX-2009 has shown anti-cancer activity in multiple preclinical models. CX-2009 is wholly owned by CytomX. The DM4 payload is being developed under license from ImmunoGen Inc.

CX-2009 is being studied within PROCLAIM (PRObody CLinical Assessment In Man), CytomX’s international modular umbrella clinical trial program that encompasses the Phase 1/2 development of multiple Probody therapeutics. PROCLAIM-CX-2009 is a dose-finding Phase 1/2 study evaluating CX-2009 as monotherapy in patients with select cancer types, including non-small cell lung cancer, breast cancer, ovarian cancer, endometrial cancer, cholangiocarcinoma (bile duct cancer), head and neck cancer and castration-resistant prostate cancer. The objectives of the study are to establish the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of CX-2009.

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.

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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]).

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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.

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"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]):

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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.