On April 2, 2019 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported the successful completion of the cash tender offer, through a subsidiary, for all of the outstanding shares of common stock of Immune Design (NASDAQ: IMDZ) at a purchase price of $5.85 per share (Press release, Merck & Co, APR 2, 2019, View Source [SID1234534914]). As of the tender offer expiration, 41,970,607 shares of common stock of Immune Design were validly tendered and not withdrawn from the tender offer, representing approximately 86.75 percent of the outstanding common stock of Immune Design on a fully diluted basis. All of such shares have been accepted for payment in accordance with the terms of the tender offer, and Merck expects to promptly pay for such shares.

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Merck expects to complete the acquisition of Immune Design today through a merger of Merck’s wholly-owned subsidiary with and into Immune Design in which all shares not tendered into the offer will be canceled and converted into the right to receive cash equal to the $5.85 offer price per share without interest, less any applicable withholding taxes. Upon completion of the merger, Immune Design will become a wholly-owned subsidiary of Merck and the common stock of Immune Design will cease to be traded on the NASDAQ Stock Market.

On April 2, 2019 Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, reported its new preclinical data across its franchise of selective cyclin-dependent kinase 7 (CDK7) inhibitors at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta (Press release, Syros Pharmaceuticals, APR 2, 2019, View Source [SID1234534930]). New data on SY-1365, a first-in-class selective CDK7 inhibitor currently in a Phase 1 clinical trial, suggest that RB pathway alterations are predictive of response in preclinical models of high-grade ovarian cancer (HGOC) and support the ongoing clinical investigation of SY-1365 in patient populations enriched for RB pathway alterations. New preclinical data on SY-5609, a selective oral CDK7 inhibitor, demonstrate broad anti-tumor activity in preclinical models of triple-negative breast cancer (TNBC) and ovarian cancer.

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"The new data on SY-1365 and SY-5609 further demonstrate our leadership in selective CDK7 inhibition, which we believe represents a potentially transformative targeted approach for many difficult-to-treat cancers," said Eric R. Olson, Ph.D., Syros’ Chief Scientific Officer. "The data highlight our ability to discover highly selective small molecule inhibitors of CDK7, a target that has been historically difficult to drug selectively, as well as to identify potential patient selection strategies to enable targeted and efficient clinical development. We remain focused on executing on the ongoing Phase 1 trial evaluating SY-1365 in select ovarian and breast cancer patient populations that we believe are most likely to respond. Meanwhile, we also continue to advance SY-5609, our highly selective and potent oral CDK7 inhibitor, toward a Phase 1 study. Together, we believe SY-1365 and SY-5609 could make for a powerful CDK7 franchise with the potential to provide a profound benefit for patients."

RB Alterations Predictive of Response to SY-1365 in Preclinical Models
Researchers from Syros evaluated tumor growth inhibition in a panel of HGOC patient derived xenograft (PDX) models, including both high-grade serous ovarian cancer (HGSOC) and clear cell ovarian cancer, to determine whether RB pathway alterations predict response to treatment with SY-1365. RB pathway alterations are present in 67 percent of HGSOC patients, according to The Cancer Genome Atlas analysis. In Syros’ study, RB pathway alterations were prospectively defined per The Cancer Genome Atlas criteria – including RB1 deletion or mutation, CDKN2A downregulation or deletion, CCNE1 amplification, CCND1 amplification, or CCND2 upregulation.

These data show that:

Ninety percent (9 of 10) of the PDX models with RB pathway alterations responded to treatment with SY-1365.
Forty percent (6 of 15) of the PDX models without prospectively defined RB alterations responded to treatment with SY-1365, suggesting the presence of other undetected RB pathway changes or alternative mechanisms, including transcriptional regulation, conferring sensitivity to SY-1365.
Overall, Syros believes these results support the ongoing development of SY-1365 in patient populations, including HGSOC and CDK4/6-inhibitor resistant hormone receptor-positive (HR+) breast cancer, that are enriched for RB pathway alterations, as well as the evaluation of these alterations as potential biomarkers of response to SY-1365.

Syros is currently conducting a Phase 1 clinical trial assessing the safety and efficacy of SY-1365 as a single agent and in combination with standard-of-care therapies in multiple ovarian and breast cancer patient populations. The trial includes cohorts evaluating SY-1365 as a single agent in patients with relapsed ovarian clear cell cancer; as a single agent in HGSOC patients who have had three or more prior lines of therapy; in combination with carboplatin in HGSOC patients who have had one or more prior lines of therapy; in combination with fulvestrant in HR+ breast cancer patients who are resistant to treatment with a CDK4/6 inhibitor; and as a single agent in patients with solid tumors accessible for biopsy. Syros expects to report initial clinical data from the dose expansion portion of the trial in the fourth quarter of 2019. Additional details about the trial can be found using the identifier NCT03134638 at www.clinicaltrials.gov.

SY-5609 Demonstrates Selectivity, Potency and Anti-Tumor Activity Preclinically
Researchers from Syros conducted a series of preclinical studies to characterize the in vitro and in vivo profile of SY-5609. The data show that SY-5609:

Demonstrated 13,000- to 49,000-fold greater selectivity for CDK7 over other CDK family members, including CDK2, CDK9 and CDK12.
Induced robust tumor growth inhibition effects and cell cycle arrest in TNBC and ovarian cancer cell lines at low nanomolar drug concentrations, with apoptosis demonstrated only in the TNBC and ovarian cancer models, but not in non-cancerous cells.
Significantly impacted tumor growth in vivo, with complete regressions observed with SY-5609 as a monotherapy in multiple TNBC and ovarian cancer cell line xenograft models at doses below the maximum tolerated dose.
Demonstrated substantial tumor growth inhibition in multiple TNBC and ovarian cancer PDX models, with minimum weight loss observed.
Led to decreases in CDK7 downstream protein markers, including MCL1, in treated tumor tissue, confirming CDK7 inhibition in vivo.
Syros is currently advancing SY-5609 through investigational new drug application enabling studies, with a Phase 1 oncology trial expected to begin in early 2020.

The posters presented at AACR (Free AACR Whitepaper) are now available on the Publications and Abstracts section of the Syros website at www.syros.com.

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:
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On April 2, 2019 Massive Bio, Inc., a leader in providing simplified and affordable access to clinical trials and precision oncology to cancer patients treated at community-based oncology practices, reported that its Trials-in-Progress poster titled "SYNERGY-AI: Artificial intelligence based precision oncology clinical trial matching and registry" will be presented by Dr. Selin Kurnaz, a lead investigator, at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 in Atlanta, GA, USA, during the Phase I-III Trials in Progress session on April 2nd, 2019 (Press release, Admera Health, APR 2, 2019, View Source [SID1234537386]).

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The poster (Abstract #CT218), View Source!/6812/presentation/10031 discusses the ongoing, pivotal global registry for cancer patients evaluating the feasibility and clinical utility of an Artificial Intelligence-based precision oncology clinical trial matching tool powered by a virtual tumor board (VTB) program. The SYNERGY-AI registry is the first of its kind to combine artificial intelligence, genomic biomarkers and multi-variate analysis to accelerate clinical trial matching and promote access to promising cancer therapies.

"We continue active enrollment in this innovative precision oncology and artificial intelligence project, and we are honored and excited to be among the highly selected group of clinical trials to be presented at AACR (Free AACR Whitepaper). Moreover, we are the only company in the market that operationalizes technology – we not only pre-screen patients, we find sites to the patients, eliminate insurance barriers and truly close the last mile in oncology clinical trial enrollment. We clean massive operational inefficiencies and we are making a leap frog in clinical research," said Selin Kurnaz, PhD., CEO and Co-Founder of Massive Bio.

In addition, today, Massive Bio and Admera Health announced a non-exclusive collaborative agreement as active participants in SYNERGY-AI registry. Under the terms of the agreement, Massive Bio and Admera Health will focus on real world evidence, biomarker data and clinical trial matching in precision oncology studies. In addition, Admera Health also provides genomics and bioinformatics services to customers wishing to conduct research in a CLIA environment.

"By combining the expansive technology and precision oncology capabilities of Massive Bio with Admera Health’s specialization in genomics and bioinformatics, we hope to develop and provide the next wave of molecular-based portfolio of technology innovations and services," stated Jeffrey R. Mitchell, Associate Director of Strategy and Marketing of Admera Health. Mitchell continued, "In addition, given the geographic strengths of our respective companies, there will also be opportunities to expand clinical trials using each other’s proprietary technology around the globe."

Commenting on the announcement, Chief Medical Advisor and Co-Founder of Massive Bio Inc., Dr. Arturo Loaiza-Bonilla, MD, MSEd, stated, "Massive Bio’s Artificial Intelligence technology platform is extremely well positioned to enable just-in-time clinical trial matching and enrollment, with a targeted therapy and immunotherapy focus, and is proven to accelerate access to innovative therapies, sponsor and CRO efficiency, as well as time to market. We certainly welcome collaborations with all stakeholders in the diagnostics and research space, aiming to close existing gaps in cancer research." Chief Business Officer of Massive Bio Inc, Harry Buchman also stated, "With a growing number of successful development applications, it is our goal to continue to promote precision oncology approaches at the point-of-care, and to ease access to clinical trials, while reducing patient and provider burden and overall cancer care costs."

About the Study

The SYNERGY-AI Registry is an international prospective, observational cohort study of adult and pediatric patients with advanced solid and hematological malignancies. Using a proprietary application programming interface (API) linked to existing electronic health records (EHR) platforms, individual clinical data is extracted, analyzed and matched to a parametric database of existing institutional and non-institutional CT. Machine learning algorithms allow for optimized matching based on CT allocation and availability. Enrollment is ongoing, with a target of ?1,500 patients. Please refer to View Source for details.

On April 2, 2019 OncoSec Medical Incorporated (OncoSec) (NASDAQ: ONCS), a company developing novel cancer immunotherapies, reported its pre-clinical data highlighting its novel anti-tumor product candidate, SPARK, and its improved electroporation generator, "APOLLO," during a poster presentation at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta, Georgia (Press release, OncoSec Medical, APR 2, 2019, View Source [SID1234534898]).

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The poster, entitled, "Intratumoral electroporation of plasmid IL-12 and CXCL9 with membrane-bound anti-CD3 elicits robust anti-tumor immunity," provides new preclinical data demonstrating robust anti-tumor responses driven by significant enhancements made to OncoSec’s proprietary cancer immunotherapy platform.

"The data presented at AACR (Free AACR Whitepaper) highlight OncoSec’s potentially game-changing approach to drug development. With this data, we show the ability to not only identify the right genes to have anti-cancer effect, but, importantly, that we can deliver those genes directly into tumor cells. We are able to do this with any gene that is identified as having an anti-cancer effect, without having to expose the patient to a systemic therapy, in an expeditious and cost-effective manner. In doing so, these cells convert immunologically cold tumors into inflamed immunogenic lesions, which is fundamental to generating objective responses in both treated and untreated distant tumors," said Daniel J. O’Connor, President and CEO of OncoSec. "Many immunotherapies are stalled for serious toxicity issues associated with treatment, including cytokine release syndrome. In contrast, our clinical studies, in more than 180 patients with several different tumor types, have demonstrated that TAVO has broad clinical activity without the toxicity commonly associated with IL-12. The foundation of our DNA-based immunotherapy relies on electroporation, which bypasses the pitfalls associated with viral vectors or systemic cytokines."

The Company’s research laboratory discovered complimentary anti-tumor immunological pathways related to IL-12 derived from samples of previously treated TAVO patients. These discoveries resulted in the selection of two new genes, CXCL9 and aCD3 (expressing membrane-bound anti-CD3), to further drive a now enhanced version of IL-12, utilizing P2A in place IRES (TAVOPLUS). In parallel, OncoSec’s researchers reengineered the Company’s existing electroporation generator. The new generator, APOLLO, greatly increases DNA-plasmid cellular transfection rates in order to deliver more anti-cancer fighting genes directly into tumor cells. These independent evolutions of both components of OncoSec’s proprietary cancer immunotherapy platform converged in the design of its new product candidate, SPARK.

Highlights of the data presented at AACR (Free AACR Whitepaper) regarding SPARK and APOLLO demonstrate that:

APOLLO, using lower voltage and a longer pulse width, greatly increased DNA-plasmid cellular transfection rates to deliver more anti-cancer fighting genes directory into tumor cells;
TAVOPLUS, OncoSec’s new proprietary IL-12 enhanced DNA-plasmid, which expresses full-length IL-12 via bicistronic expression of both the p35 and p40 subunits, coupled with APOLLO, meaningfully improves anti-cancer responses;
SPARK, OncoSec’s new proprietary product candidate, drives strong anti-tumor immune responses by combining two novel anti-cancer genes, CXCL9 and aCD3, with TAVOPLUS
CXCL9 with TAVOPLUS
Productively modulates immune/tumor microenvironment
Significantly increases antigen-specific CD8+ CTL
Augments abscopal response of TAVOPLUS
aCD3, expressing membrane bound anti-CD3, with TAVOPLUS
Drives polyclonal T cell expansion and antigen-specific killing in vivo
Augments abscopal response when combined with TAVOPLUS
aCD3 complements CXC by strongly increasing cytotoxic anti-cancer tumor inflammation; and
SPARK, when delivered via APOLLO, significantly improves regression of untreated (distant) tumors in a difficult to treat preclinical melanoma model
"The encouraging data presented at AACR (Free AACR Whitepaper) demonstrate the potential of SPARK to integrate three key immunotherapeutic elements, IL-12, CXCL9 and anti-CD3 complimentary, into a single novel, multi-gene expression platform that we believe will have broad applicability across numerous tumor types," said Christopher G. Twitty, Chief Scientific Officer of OncoSec. "Importantly, SPARK builds upon our plasmid-based cancer immunotherapy platform by amplifying the power of intratumoral IL-12 through the sequenced addition of both CXCL9, a critical T cell chemokine and anti-CD3, a membrane-bound strong pan T cell stimulator. We look forward to filing an Investigational New Drug (IND) application for SPARK."