On April 2, 2019 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported new clinical data on vopratelimab (JTX-2011) at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta, GA (Press release, Jounce Therapeutics, APR 2, 2019, View Source [SID1234535387]). The Jounce poster presentations show that patients in the ICONIC trial with emergence of ICOS hi CD4 T cells have improved progression free survival (PFS) and overall survival (OS) compared to patients with ICOS lo CD4 T cells. Data related to important immune characteristics of ICOS hi CD4 T cells were also presented.

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"We are pleased to see our initial observations of tumor reductions associated with ICOS hi CD4 T cells now extend to improved PFS and OS. All observed benefit in the study was in the group of patients that showed emergence of these cells. As vopratelimab, and not PD-1 inhibitors, is responsible for the emergence of the ICOS hi CD4 cells, we are using this key translational data to guide our next steps in development," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "We have further characterized the ICOS hi CD4 T cells as activated T effector cells by flow cytometry and gene expression profiling and demonstrated peripheral expansion of T cell receptor (TCR) clones originally found in the matched archival tumor. These characteristics provide additional scientific support for clinical study designs based on the emergence of ICOS hi CD4 T cells."

In a poster titled "Improved progression-free and overall survival (PFS/OS) in patients (pts) with emergence of JTX-2011 (vopratelimab) associated biomarker (ICOS high CD4 T cells) on the ICONIC trial," the ICONIC investigators and Jounce scientists describe the baseline characteristics and clinical outcomes of patients with emergence of ICOS hi CD4 T cells as compared to patients who did not develop this T cell population.

Three groups of ICONIC relapsed refractory solid tumor patients were compared in the new analysis: 1) 18 patients who have demonstrated ICOS hi CD4 T cells in the blood, 2) 32 patients who have demonstrated ICOS lo CD4 T cells, and 3) a group of patients enrolled in parts A through D which includes an additional 151 patients that were not tested for ICOS status due to lack of samples ("All Patients"). The analyses revealed:

The emergence and persistence of the ICOS hi CD4 T cell biomarker in the peripheral blood is associated with improved PFS and OS:
All benefit in the study, measured by tumor reductions, PFS and OS, was in the ICOS hi CD4 T cell group
PFS: median 6.2 months for patients with ICOS hi CD4 T cells vs 2 months for both patients with only ICOS lo CD4 T cells and All Patients
OS: median not yet reached for patients with ICOS hi CD4 T cells vs 9 months for patients with only ICOS lo CD4 T cells and 9.1 months for All Patients
The emergence of ICOS hi CD4 T cells is attributed to vopratelimab and not PD-1 inhibitors
There is no association of ICOS hi CD4 T cells with the common predictive biomarkers microsatellite instability-high (MSI-H), tumor mutation burden (TMB) or PD-L1 immunohistochemistry (IHC)
The ICOS hi CD4 T cell group included PD-1 naive and experienced patients across multiple solid tumor types
In a poster titled "Genetic and molecular profiling of ICOS hi CD4 T cells demonstrates clonal expansion of TH1 effector cells following vopratelimab (JTX-2011) treatment in subjects with solid tumors," Jounce researchers describe the characteristics of ICOS hi CD4 T cells associated with vopratelimab treatment, including:

Vopratelimab stimulates CD4 T cells with pre-existing high levels of ICOS
Peripheral TCR clones associated with the original matched tumor are expanded in patients with emergent ICOS hi CD4 T cells
ICOS hi CD4 T cells are not T regulatory cells and display distinct characteristics of activated T effector cells by both flow cytometry and transcriptional profiling
"We are encouraged by the improved PFS and OS data associated with the emergence of the ICOS hi CD4 T cell biomarker and are convinced that meaningful advancements in immuno-oncology will require the type of science-based translational understandings that the Jounce team and platform have enabled to advance vopratelimab thus far," said Richard Murray, Ph.D., chief executive officer and president of Jounce Therapeutics. "We have established our translational technology base for the purpose of creating a preclinical and, more importantly, clinical scientific understanding of the mechanism of action of new immunotherapies and the characteristics of responding versus non-responding patients to focus the next steps of clinical development for vopratelimab and our pipeline."

The posters are available on the "Our Approach" section of the Jounce Therapeutics website at www.jouncetx.com.

Jounce Therapeutics to Host Event and Webcast
Jounce Therapeutics will host an investor and analyst event beginning at 6:30 p.m. ET and live webcast beginning at 7:00 p.m. ET, on Tuesday, April 2, 2019. To access the live webcast, please visit the "Events & Presentations" page in the Investors and Media section of the company’s website at www.jouncetx.com. The webcast will be archived and made available for replay on the company’s website approximately two hours after the call and will be available for 30 days thereafter.

About Vopratelimab (JTX-2011)
Jounce’s lead product candidate, vopratelimab, is a monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO­Stimulator, a protein on the surface of certain T cells. The company is developing vopratelimab to treat solid tumors as a single agent and in combination with other therapies.

About the ICONIC Trial
The ICONIC trial is an adaptive, open label, dose escalation and expansion clinical study of vopratelimab alone and in combination with nivolumab, ipilimumab and pembrolizumab in patients with advanced solid tumors.

On April 2, 2019 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical stage biotechnology company focused on discovering and developing novel small molecule drugs for the treatment of cancer and other life-threatening diseases, reported new preclinical data for the company’s CD73 inhibitor CB-708 (Press release, Calithera Biosciences, APR 2, 2019, View Source [SID1234535224]). The data will be presented today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 in Atlanta, Georgia.

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CB-708 is a selective, oral inhibitor of CD73, an enzyme that synthesizes the immunosuppressive agent adenosine and is over-expressed in multiple tumor types. By blocking adenosine production in the tumor, CB-708 is designed to enhance T-cell activation leading to anti-tumor activity. Calithera plans to initiate clinical development of the compound in the second half of 2019.

"We are excited to share these new preclinical data on CB-708, our small-molecule CD73 inhibitor designed to be dosed orally in patients, and to demonstrate our progress in advancing this compound into the clinic," said Susan Molineaux, PhD, president and chief executive officer of Calithera. "CB-708 has the potential to be combined with immunotherapy or chemotherapy to activate the immune system and improve outcomes for patients with a variety of cancers."

The preclinical data being presented today by Clarissa Lee, Ph.D. (Abstract #4134, Section 25, Board 8), demonstrate that CB-708 is a potent and selective inhibitor of CD73 that has immune-mediated, single agent activity in syngeneic mouse tumor models. In addition, in pre-clinical studies CB-708 is well-tolerated and shows enhanced anti-tumor activity when combined with either an anti-PD-L1 immunotherapy or with chemotherapeutic agents such as oxaliplatin or doxorubicin.

Additional meeting information can be found at the AACR (Free AACR Whitepaper) website www.aacr.org. The CB-708 poster presentation will be available at www.calithera.com on the Publications page.

About CB-708 and CD73

CB-708 is an orally bioavailable small molecule inhibitor of CD73, an enzyme in the tumor microenvironment that produces adenosine, a powerful inhibitor of immune function in tumors. CD73 is expressed across a wide range of tumor types and tumor-infiltrating leukocytes. Expression of CD73 often correlates with poor prognosis in patients with cancer. Blockade of adenosine production by CD73 inhibition is expected to reverse immunosuppression in the tumor microenvironment and enhance the immune system’s ability to fight the cancer.

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 ImaginAb Inc., a clinical stage immuno-oncology imaging company, reported its Founder and Chief Scientific Officer Dr. Anna Wu, Ph.D. is scheduled to present at this year’s American Association of Cancer Research Annual Meeting (AACR) (Free AACR Whitepaper) (Press release, ImaginAb, APR 2, 2019, View Source [SID1234534986]). Dr. Wu will speak on Tuesday, April 2, 2019, during the session on Molecular Imaging for Cancer Immunotherapy.

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American Association of Cancer Research (AACR) (Free AACR Whitepaper)

March 29 – April 2, 2019, Georgia World Conference Center, Atlanta, Georgia

Founder and Chief Scientific Advisor of ImaginAb, Dr. Anna Wu, Ph.D., will speak on ‘ImmunoPET for visualization of T cell responses in immunotherapy’ during the following session:

ADT01. Molecular Imaging for Cancer Immunotherapy

Tuesday, April 2, 2019, 1:00 pm – 2:45 pm EDT, Room A411

Modulation of immune responses has now become a routine treatment option in cancer therapy. In spite of the huge success, a significant fraction of patients does not respond or develop resistance to therapy. To improve therapy outcomes, extensive efforts are focused on the development of tissue- and blood-based biomarkers that could enable patient selection. In addition to tumor and immune cell heterogeneity, activity of therapeutic agents at the disease site is critical for the success of therapy. Few studies have defined the pharmacokinetics (PK) and pharmacodynamics (PD) of immune checkpoint therapeutics at the disease site, and fewer have studied those parameters in real time and noninvasively. This session will focus on the novel tools and technologies, including Novel PET Tracers that enable real-time assessment of PK/PD of immune checkpoint therapeutics at the tumor that can be used in preclinical and clinical studies.

Anna M. Wu, Ph.D., is professor and chair of the Department of Molecular Imaging and Therapy, and co-director, Center for Theranostics within the Diabetes Metabolism Research Institute and professor in the Department of Radiation Oncology at City of Hope in Duarte, CA.

Media Inquiries:
ImaginAb
Salli Walker
Email: [email protected]
Phone: +1 310 645 1211

Optimum Strategic Communications
Mary Clark, Supriya Mathur
Email: [email protected]
Phone: +44 20 3950 9144

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.