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Xenetic Biosciences Reports 2016 Year End Financial Results and Provides Business Update

On April 3, 2017 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a clinical-stage biopharmaceutical company focused on the discovery, research and development of next-generation biologic drugs and novel orphan oncology therapeutics, reported its financial results for the year ended December 31, 2016 (Press release, Xenetic Biosciences, APR 3, 2017, View Source [SID1234537802]). The Company’s management team will host a quarterly update conference call with a live webcast on Tuesday, April 4, 2017 at 8:30 AM ET for investors, analysts and other interested parties (details below).

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Xenetic also provided an update on its license deal with Shire plc (LSE: SHP, NASDAQ: SHPG), a significant stockholder of the Company, along with the clinical status of the product candidate SHP656, or PSA-Recombinant Factor VIII ("rFVIII") being developed as a long-acting therapeutic for the treatment of hemophilia utilizing Xenetic’s proprietary PolyXen platform technology. The stated goal of Shire is to introduce an innovative, modified FVIII protein with a significantly prolonged circulating half-life, with the objective of providing a once weekly treatment or reaching higher trough activity levels for greater efficacy. SHP656 is currently in a Phase 1/2 clinical study. Shire expects to report topline data from this Phase 1/2 study in the second quarter of 2017 and, if the outcome of the trial is successful, Xenetic expects Shire to launch a Phase 3 trial in 2017. Xenetic has the potential to receive from Shire up to $100 million in cash milestones plus royalties linked to sales.

Additionally, Xenetic provided an update to its corporate progress as well as clinical and regulatory status and anticipated milestones for the Company’s lead product candidate, XBIO-101 (sodium cridanimod), a small-molecule immunomodulator and interferon inducer which, in preliminary studies, has been shown to increase progesterone receptor ("PrR") expression in endometrial tumor tissue. The Company is currently preparing to commence patient recruitment in the second quarter of 2017 for a Phase 2 clinical study of XBIO-101 in conjunction with progestin therapy for the treatment of progestin resistant endometrial cancer. Xenetic also recently filed a protocol under its existing investigational new drug application ("IND") for a biomarker study of XBIO-101 in triple negative breast cancer ("TNBC").

Recent Corporate Highlights

Uplisted to the Nasdaq Capital Market;
Received a $3 million milestone payment from Shire plc related to Shire’s advancing the Phase 1/2 clinical study for SHP656 being developed as a long-acting therapeutic for the treatment of hemophilia;
Filed a protocol under its existing IND for a biomarker study of XBIO-101 for the treatment of TNBC;
Expanded its patent portfolio geographically into key markets including areas of Europe, Asia and North America and strengthened the patent portfolio in the US providing robust protection of its platform technology;
Appointed Jeffrey Eisenberg as Chief Operating Officer;
Appointed Curtis A. Lockshin, Ph.D. as Chief Scientific Officer; and
Appointed Edward J. Benz, Jr., M.D., former CEO of the Dana-Farber Cancer Institute, to its Board of Directors.
"Over the course of 2016 and the beginning of 2017, we have worked diligently to lay a solid foundation for the Company and as such, have positioned ourselves for what we believe will be a transformational year. The corporate achievements we’ve made, including our uplist to Nasdaq, the bolstering of both our management team with two C-level appointments as well as our board of directors and notable progress with our clinical and regulatory strategies, have enabled us to build momentum which we believe has the potential to propel Xenetic to its next stage of growth," stated M. Scott Maguire, Xenetic’s CEO.

Expected Near-Term Milestones

Commence patient recruitment in Q2 2017 for a Phase 2 clinical study of XBIO-101 in conjunction with progestin therapy for the treatment of endometrial cancer in women with recurrent or persistent disease who have failed progestin monotherapy;
Announce topline data from the Shire Phase 1/2 study of SHP656 in Q2 2017;
Receive milestone payment from Shire if endpoints are achieved in Phase 1/2 study of SHP656; and
Leverage Shire SHP656 program to enter into more industry collaborations involving the PolyXen technology.
"Moving forward, we are excited for the year ahead and remain committed to executing our strategy. We believe that our expected near term corporate and clinical advancements will unlock significant shareholder value, in both the short-term and long-term," concluded Mr. Maguire.

Summary of Financial Results for Fiscal Year 2016

Net loss for the three months ended December 31, 2016, was $0.4 million, or a net loss applicable to common stockholders of $4.4 million after accretion of beneficial conversion feature on convertible preferred stock of $4.0 million, compared to a net loss of approximately $3.6 million for the same period in 2015. The decrease in net loss was primarily related to $3.0 million of milestone revenue earned in December 2016.

Net loss for the year ended December 31, 2016, was $54.2 million, or a net loss applicable to common stockholders of $58.2 million after accretion of beneficial conversion feature on convertible preferred stock of $4.0 million, resulting in a loss per share applicable to common stockholders of $7.84, compared to a net loss of $12.5 million resulting in a loss per share applicable to common stockholders of $2.96 for the year ended December 31, 2015. The increase in net loss was primarily related to the immediate expensing of in-process research and development acquired in 2016.

The Company ended the year with approximately $4.0 million of cash.

Conference Call and Webcast Information

Xenetic management will host a conference call for investors, analysts and other interested parties on Tuesday, April 4, 2017 at 8:30 a.m. ET. The conference call and live webcast will be accompanied by presentation slides.

To participate in the call, please dial (877) 407-6914 (domestic) or (201) 493-6709 (international). The live webcast and accompanying slides will be available by accessing the IR Calendar in the Investors section of Xenetic’s website (www.xeneticbio.com). A replay of the webcast will be available for 90 days, starting approximately two hours after the presentation ends.

Intrexon, ZIOPHARM and Merck KGaA, Darmstadt, Germany Advancing Next-Generation Non-Viral CAR-T Platform Empowered by Membrane-Bound IL-15 Under RheoSwitch Therapeutic System® Control

On April 3, 2017 Intrexon Corporation (NYSE:XON), a leader in the engineering and industrialization of biology to improve the quality of life and health of the planet, ZIOPHARM Oncology (NASDAQ:ZIOP), a biopharmaceutical company focused on new immunotherapies, and Merck KGaA, Darmstadt, Germany, a leading science and technology company, reported an update on the development of next-generation chimeric antigen receptor T cell (CAR-T) therapy for cancer as part of their strategic collaboration and license agreement (Press release, Ziopharm, APR 3, 2017, View Source [SID1234518449]).

Intrexon and ZIOPHARM Oncology, in an exclusive partnership with Merck KGaA, Darmstadt, Germany, are advancing a unique approach to develop therapeutic candidates for two CAR-T targets expressed on a wide range of tumor types, including hematologic malignancies and solid tumors.

The distinctive methodology centers on two technologies: the proprietary RheoSwitch Therapeutic System (RTS) platform to regulate expression of membrane-bound interleukin-15 (mbIL15) co-expressed with CARs and Sleeping Beauty non-viral gene integration.

"Sleeping Beauty and the RTS approach are a powerful combination to improve the manufacturing process and instill control over CAR-modified T cells co-expressing cytokines such as membrane-bound IL-15. The collaboration with Intrexon and Merck KGaA, Darmstadt, Germany, has been a catalyst to progress these next-generation gene therapy technologies. We are excited by the progress and look forward to advancing this innovative approach toward the clinic in mid-2018," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM.

The interleukin-15 (IL-15) cytokine is increasingly recognized as a key driver of therapeutic effect in CAR-T therapy, including in a recent Journal of Clinical Oncology publication which correlated lymphoma remissions with elevated IL-15 levels. Through the RTS gene switch, the expression of mbIL15 can be regulated to help CARs target cancers in a controlled manner, thus providing a new paradigm in T-cell therapy.

Additionally, the non-viral Sleeping Beauty transposon-transposase is an exceptional system for introducing genes encoding CARs and TCRs into T cells that holds multiple advantages over viral-based delivery systems. It simplifies genetic modification, and when coupled with reduced ex vivo processing, offers a pathway to shortened manufacturing and personalized T-cell therapies.

SignalRx to Present at the AACR Annual Meeting on its First-In-Class Triple PI3K/CDK4-6/BRD4 Inhibitor SRX3177 for Treating Cancer

On April 3, 2017 SignalRx Pharmaceuticals Inc., focused on developing novel small-molecule cancer therapeutics targeting key orthogonal and synergistic oncotargets, reported the upcoming presentation of scientific data on the company’s triple PI3K/CDK4-6/BRD4 inhibitor program and first-in-class triple inhibitor SRX3177 (Press release, SignalRx, APR 3, 2017, http://www.ireachcontent.com/news-releases/signalrx-to-present-at-the-aacr-annual-meeting-on-its-first-in-class-triple-pi3kcdk4-6brd4-inhibitor-srx3177-for-treating-cancer-617971313.html [SID1234527324]). The poster presentation by Dr. Donald L. Durden, MD, PhD, senior scientific advisor for SignalRx, will be poster #LB-298 at the April 5th late breaking poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Washington, DC.

SRX3177 is developed on the rationale that concurrent PI3K inhibition can prevent resistance to CDK4/6 inhibition, and combined CDK4/6 and PI3K inhibition leads to synthetic lethality reported in a number of cancer types, including breast cancer and mantle cell lymphoma, and blocking the chromatin reader protein BRD4 downregulates MYC and cyclin D1 transcription, further promoting cell cycle arrest in G1.

The presentation will describe the discovery and early development of the molecularly designed small-molecule triple inhibitor SRX3177. Key highlights to be presented include:

SRX3177’s potent in vitro enzymatic inhibition profile (IC50: CDK4 = 2.54 nM, CDK6 = 3.26 nM; PI3Kα = 79.3 nM, PI3Kδ = 83.4 nM; BRD4-BD1 = 32.9 nM, BRD4-BD2 = 88.8 nM).
SRX3177 rational design based on thieno-pyranone scaffold and target modeling.
Up to 82-fold more potent than palbociclib in a panel of mantle cell lymphoma, neuroblastoma, and hepatocellular carcinoma cell lines.
5-Fold more potent in cancer cells than combination of BKM120 (PI3K inhibitor) + palbociclib (CDK4/6 inhibitor) + JQ1 (BRD4 inhibitor).
40-Fold less toxic to normal epithelial cells than combination of BKM120 + palbociclib + JQ1.
Cell cycle arrest and apoptosis induction with proven mode of action (p-AKT, p-Rb, chromatin release).
SignalRx is also announcing that it is seeking partnering opportunities to accelerate the development of this program and its PI3K-BRD4 program to advance novel small molecules into first-in-man clinical trials based on the promising profile of its inhibitors shown so far. Since these are single molecules with a single PK/PD and toxicity profile, there is a great opportunity to develop them as single therapeutics and streamline their development in combination therapies focused on companion diagnostics built around synthetic lethality discoveries in human cancers.

Checkpoint Therapeutics Reports Preclinical Data for Two Oncology Programs

On April 4, 2017 Checkpoint Therapeutics, Inc. ("Checkpoint") (OTCQX: CKPT), a Fortress Biotech (NASDAQ: FBIO) company, reported that preclinical data on its third-generation epidermal growth factor receptor ("EGFR") inhibitor, CK-101, and anti-programmed cell death ligand-1 ("PD-L1") antibody, CK-301, were presented this week in poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Fortress Biotech, APR 3, 2017, View Source [SID1234518456]). The data presented strongly support the clinical development of these therapies.

James F. Oliviero, President and Chief Executive Officer of Checkpoint, said, "These encouraging preclinical data demonstrate the potential of our EGFR inhibitor and anti-PD-L1 checkpoint antibody to be effective new treatment options for patients suffering from cancer. We look forward to advancing these drug candidates through the stages of clinical development, both as monotherapies as well as in combination with each other."

Key conclusions from the posters are as follows:

CK-101 (RX518), a Mutant-Selective Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in Non-Small Cell Lung Cancer (NSCLC)

CK-101 (also known as RX518) is a novel, irreversible, orally administered EGFR kinase inhibitor that specifically targets the mutant forms of EGFR, including T790M, while exhibiting minimal activity toward the wild-type EGFR. Cell proliferation assays in human cancer cell lines in vitro, and xenograft studies conducted in mouse models of NSCLC demonstrated:

CK-101 is a potent, mutant-selective inhibitor of both the activating (exon 19 deletion) and resistance mutations (L858R / T790M double mutation).

CK-101 inhibited tumor growth as a single agent in a NSCLC model with a single activating mutation (exon 19 deletion).

CK-101 showed dose-dependent inhibition of tumor growth as a single agent in a L858R / T790M double mutant NSCLC model.

CK-101 has little inhibitory potency toward wild-type EGFR (i.e., CK-101 was more than 100-fold less potent against wild-type EGFR than against L858R / T790M double mutation).

These data supported the initiation of a Phase 1/2 clinical trial in September 2016 (ClinicalTrials.gov: NCT02926768). The Phase 1 dose-escalation portion is ongoing, and Checkpoint expects to initiate the Phase 2 portion in patients with EGFR T790M mutation‐positive NSCLC cancer in the second half of 2017.

Preclinical Characterization of a Novel Fully Human IgG1 Anti-PD-L1 mAb CK-301

Based on the various assays performed, the poster concluded:
CK-301 is a high affinity PD-L1 specific fully humanized lgG1 antibody which blocks binding of PD-L1 to PD-1.

Activity of CK-301 in all assays tested was similar to anti-PD-L1’s used as active controls (surrogates of avelumab, atezolizumab or durvalumab).

Similar to the approved anti-PD-L1, avelumab, CK-301 has the potential to induce ADCC (antibody-dependent cell-mediated cytotoxicity).

A first-in-human Phase 1 study of CK-301 is planned to commence this year.

The posters are available on the Publications page within the Pipeline section of Checkpoint’s website,
www.checkpointtx.com.

TRILLIUM THERAPEUTICS PRESENTS TTI-621 PRECLINICAL DATA AT AACR ANNUAL MEETING AND PROVIDES CLINICAL UPDATE

On April 3, 2017 Trillium Therapeutics Inc. (Nasdaq/TSX: TRIL) a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported the following preclinical and clinical updates on its TTI-621 program (Filing, 6-K, Trillium Therapeutics, APR 3, 2017, View Source [SID1234518448]).

AACR presentations:
Today the company presents two preclinical posters at the 110th American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Washington, DC:

The first presentation (Abstract #2646), entitled "Intratumoral Delivery of TTI-621 (SIRPaFc), a CD47-Blocking Immunotherapeutic, Inhibits Tumor Growth and Prolongs Animal Survival in a Subcutaneous B Cell Lymphoma Model," demonstrated that TTI-621 was efficacious when injected directly into tumors in a xenograft model. In addition, intratumoral TTI-621 increased the phagocytosis of tumor cells by both M1 and M2 tumor-associated macrophages. These data support the clinical evaluation of direct tumor injections of TTI-621. A Phase 1 study of intratumorally delivered TTI-621 in patients with percutaneously accessible solid tumors and mycosis fungoides is ongoing (NCT02890368).

The second presentation (Abstract #2653), entitled "The Anti-Myeloma Activity of TTI-621 (SIRPαFc), a CD47-Blocking Immunotherapeutic, is Enhanced When Combined With a Proteasome Inhibitor," showed that TTI-621 exhibits anti-myeloma activity on its own that is further enhanced by combination with FDA-approved proteasome inhibitors, such as bortezomib and carfilzomib. These data provide a rationale to evaluate a combination cohort of TTI-621 and a proteasome inhibitor in multiple myeloma patients.

Clinical update:
The company is currently enrolling patients in the expansion phase of its ongoing Phase 1 trial of TTI-621, in patients with multiple hematologic malignancies (NCT02663518). Trillium is providing this clinical update in conjunction with the AACR (Free AACR Whitepaper) presentations.

To date, 33 evaluable patients have been enrolled into the expansion phase of the trial, with several patients demonstrating preliminary evidence of anti-tumor activity. In the AML cohort, one patient with minimal residual disease (consisting of 0.7% abnormal blasts at baseline) obtained a complete molecular remission after 4 infusions of TTI-621. A second marrow analysis at week 8 confirmed a complete molecular remission, the patient continues to tolerate weekly infusions of TTI-621 and remains in continued remission for 15+ weeks.

In the TTI-621/rituximab combination cohort, 3 of 6 patients who have had at least one interval PET/CT restaging obtained partial metabolic responses, as demonstrated by decreased tumor activity on PET/CT scans. These patients with CD20-positive, B-cell lymphoma received weekly IV infusions of TTI-621 and rituximab. Manageable infusion reactions occurred in most patients after the first infusion of TTI-621 and the combination therapy has been associated with acceptable outpatient tolerability. These responding patients remain on treatment and progression-free for 19+ (DLBCL), 18+ (transformed lymphoma), and 8+ weeks (follicular lymphoma) in continuing follow-up.

"Patients with treatment-refractory lymphoma and acute myeloid leukemia continue to represent a pronounced unmet clinical need," said Trillium’s Chief Medical Officer, Eric Sievers, MD. "We and the clinical investigators are encouraged that several of the patients treated with the TTI-621/rituximab combination obtained robust lymphoma regressions. Moreover, while anecdotal, the achievement of complete molecular remission in a patient with relapsed AML is intriguing. Taken together, we believe that the multiple clinical responses observed across varied hematologic malignancies to date is promising."

Details of these clinical responses with further follow-up will be reported at scientific symposia later this year.