On September 4, 2018 Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, reported the achievement of a development milestone in its collaboration with Eli Lilly and Company (Press release, Zymeworks, SEPT 4, 2018, View Source [SID1234529269]). In accordance with Zymeworks’ 2013 licensing and collaboration agreement with Lilly, Zymeworks will receive a milestone payment of US$2.0 million for Lilly’s submission of an IND application for a bispecific antibody enabled by Zymeworks’ proprietary Azymetric platform. Previously, Zymeworks announced Lilly’s nomination of two bispecific immuno-oncology drug candidates for late-stage preclinical development.

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"The team at Lilly has done an impressive job advancing a novel bispecific therapeutic built on our Azymetric platform to the IND stage in a relatively short period of time," said Ali Tehrani, Ph.D., President and Chief Executive Officer of Zymeworks. "Moving a compound into the clinic is an important step in drug development and we look forward to future progress with Lilly as well as our five other partners."

Under its two licensing and collaboration agreements with Lilly, Zymeworks has granted Lilly worldwide licenses to research, develop and commercialize multiple bispecific therapeutics directed towards Lilly’s targets. To date, Zymeworks has received an upfront licensing payment and multiple research milestone payments under these agreements, in addition to historical equity investments made by Lilly in Zymeworks. Zymeworks is also eligible to receive further development and commercial milestone payments and tiered royalties on global product sales.

About the Azymetric Platform

The Azymetric platform enables the transformation of monospecific antibodies into bispecific antibodies, giving the antibodies the ability to simultaneously bind two different targets. Azymetric bispecific technology enables the development of multifunctional biotherapeutics that can block multiple signaling pathways, recruit immune cells to tumors, enhance receptor clustering degradation, and increase tumor-specific targeting. These features are intended to enhance efficacy while reducing toxicities and the potential for drug-resistance. Azymetric bispecifics have been engineered to retain the desirable drug-like qualities of naturally occurring antibodies, including low immunogenicity, long half-life and high stability. In addition, they are compatible with standard manufacturing processes with high yields and purity, potentially significantly reducing drug development costs and timelines.

On September 4, 2018 Helix BioPharma Corp. (TSX: HBP), (FSE: HBP) ("Helix" or the "Company"), an immuno-oncology company developing innovative drug candidates for the prevention and treatment of cancer, reported that its collaborator ProMab Biotechnologies, Inc. ("ProMab") will present at the CAR-TCR Summit 2018 being held from September 4th – 7th, 2018 in Boston, Massachusetts (Press release, Helix BioPharma, SEP 4, 2018, View Source [SID1234530406]).

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Dr. Vita Golubovskaya, Director, R&D, BD of Promab Biotechnologies will present on September 5th at 12:25pm. The title of the presentation is "Novel CAR-T Cells Against Solid and Hematological Cancers". Dr. Golubovskaya’s presentation will include certain preclinical data from the multiple myeloma project currently in collaboration with Helix.

Helix continues to aim for a possible first-in-human CAR-T study in 2019. To achieve this goal, Helix’s wholly-owned Polish subsidiary Helix Immuno-Oncology ("HIO") will be leading the preclinical and clinical development program in Poland prioritizing a possible European clinical submission. Helix and HIO are engaging experts to advise on the program and are currently securing the necessary financial resources to meet the project timelines.

On September 4, 2018 OncoSec Medical Incorporated (OncoSec) (NASDAQ: ONCS), a company developing intratumoral cancer immunotherapies, reported that it has secured a $15 million investment from Alpha Holdings, Inc. (KOSDAQ: 117670) as part of a value focused, fundamental strategic investment centered on the clinical development of OncoSec’s lead immunotherapy product candidate, TAVO (tavokinogene telseplasmid) (Press release, OncoSec Medical, SEP 4, 2018, View Source [SID1234529254]). TAVO enables the intratumoral delivery of DNA-based interleukin-12 (IL-12), a naturally occurring protein with powerful immune-stimulating functions.

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"This investment from Alpha Holdings is a testament to the growth of OncoSec and the momentum building behind our rapidly advancing TAVO programs, which are designed to enable the intratumoral delivery of IL-12 to stimulate the body’s immune system to target and attack cancer," said Daniel J. O’Connor, President and Chief Executive Officer of OncoSec. "In addition to increasing our current capital, aligning with Alpha Holdings provides an opportunity to strengthen our presence in South Korea and Asia, while developing a long-term relationship with a company that, like OncoSec, recognizes the potential of our TAVO platform to expand the larger, multibillion-dollar checkpoint market, which has yet to be fully unlocked across multiple cancer types."

Alpha Holdings is a leading Korean company engaged in the design, development, service and manufacture of system semiconductors, as well as the development of biotechnologies and thermal compound materials. Since 2002, Alpha Holdings has successfully carried out many projects as a major partner of Samsung Advanced Foundry Eco-system (SAFE) of Samsung Electronics. Alpha Holdings, a listed company in the KOSDAQ Market, was founded in 2002 and is headquartered in Seongnam, South Korea.

"In targeting opportunities for growth, we believe the biotechnology sector and the immunotherapy space in particular, offer significant potential," said Hee Do Koo, President and Chief Executive Officer of Alpha Holdings. "Our investment in OncoSec is a prime example of this vision and our mission to align ourselves with biotechnology companies developing innovative technologies to treat large patient populations in need of new, more efficacious treatment modalities."

Under the terms of the agreement, Alpha Holdings has committed to purchase a total of $15 million worth of shares of common stock from OncoSec at $1.50 per share. The purchase is to be made in two tranches, each subject to a six-month holding requirement. Further details of the transaction can be found in the Form 8-K filed by the Company describing the agreement

On September 4, 2018 Dynavax Technologies Corporation (NASDAQ: DVAX) reported publication of a preclinical study demonstrating that inhalation of a TLR9 agonist can stimulate effective immunity against lung tumors and complement the actions of PD-1 blockade to generate durable, systemic anti-tumor immunity (Press release, Dynavax Technologies, SEP 4, 2018, View Source [SID1234530120]). The paper titled Inhaled TLR9 Agonist Renders Lung Tumors Permissive to PD-1 Blockade by Promoting Optimal CD4+ and CD8+ T cell Interplay, by Dynavax scientists M.Gallotta, H. Assi, E. Degagné, S. Kannan, R.Coffman and C. Guiducci was published in the journal Cancer Research. The study demonstrated that combining an inhaled TLR9 agonist with systemic anti-PD-1 led to long-term survival in two different mouse lung tumor models, mediated by systemic immunity that eradicated tumors both in the lung and in distal organs. The study further delineated the distinctive mechanisms of action of these agents in the lung environment.

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Administration of the TLR9 agonist SD-101 into the lungs of mice with metastatic tumors generated anti-tumor responses that controlled or eliminated tumor growth in the lungs as well as in non-treated organs, including liver. Treatment with SD-101 resulted in ~90% decrease in tumor burden in both the lung and liver. This led to a significant increase in survival time, with a majority of mice surviving beyond 90-100 days. Treatment with SD-101 and anti-PD-1 resulted in a large increase of tumor-reactive T cells, which were required for anti-tumor activity. The durable control of liver metastases shows that local administration of SD-101 to the lung generates an anti-tumor T cell response capable of controlling tumor growth beyond the lung itself.

The TLR9 agonist used in these studies was SD-101, Dynavax’s lead clinical candidate currently being developed as an intratumoral agent in combination with anti-PD-1 therapy in patients with advanced melanoma and head and neck squamous cell carcinoma. Unpublished data demonstrates that another TLR9 agonist, DV281 – optimized for delivery to primary lung tumors and lung metastases – has equivalent activity in these models. These studies provide the preclinical rationale for the Phase 1b dose escalation study of inhaled DV281 currently being conducted by Dynavax in advanced non-small lung cancer patients (NCT03326752). DV281 and SD-101 stimulate potent Type 1 interferon induction along with maturation of dendritic cells into effective antigen-presenting cells. These combined actions lead to the increased numbers of cytotoxic T cells that are critical for the induction of effective systemic anti-tumor immunity.

On September 4, 2018 TESARO, Inc. (NASDAQ: TSRO), an oncology-focused biopharmaceutical company, reported it has initiated the second stage of the JASPER study that is designed to assess clinical benefit of ZEJULA in combination with an anti-PD-1 antibody in first-line non-small cell lung cancer (NSCLC) patients (Press release, TESARO, SEP 4, 2018, View Source [SID1234529255]). The decision to advance the trial was based on achieving the protocol defined response criteria in the initial cohort of 16 treated patients with high PD-L1 expression, of which 14 were evaluable for a response. Nine of the 14 patients had objective responses by RECIST criteria at the time of the analysis1; with all 14 patients experiencing tumor shrinkage.

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"These JASPER data provide preliminary evidence that the combination of ZEJULA and an anti-PD-1 antibody could be active as a first-line treatment for patients with non-small cell lung cancer and high levels of PD-L1 expression," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "In the second stage of the trial, 36 additional patients will be enrolled and treated with ZEJULA in combination with TSR-042, our anti-PD-1 antibody. TSR-042 is the foundation of our lung cancer strategy, and is also being studied as a monotherapy in our GARNET trial in anti-PD-(L)1 naïve patients who have progressed on chemotherapy, and in combination with TSR-022, our anti-TIM-3 antibody, in AMBER, a study in late-line NSCLC patients that have progressed after anti-PD-(L)1 therapy. We look forward to sharing lung cancer data from both GARNET and AMBER at the Society for the Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November."

About the JASPER Clinical Trial
JASPER is a Phase 2, open-label, single arm trial designed to evaluate the safety and efficacy of ZEJULA in combination with an anti-PD-1 antibody for the treatment of first-line NSCLC. Patients were enrolled in stage 1 of the study and received a starting dose of 200 milligrams of niraparib once per day and 200 milligrams Q3 weeks of an anti-PD-1 antibody. The primary endpoint of stage 1 of the study was objective response rate (ORR) per RECIST. Other endpoints include durability of response, disease control rate, progression free survival (PFS), overall survival (OS) and safety and tolerability.

About ZEJULA (Niraparib)
Niraparib is marketed in the United States and Europe under trade name ZEJULA. ZEJULA (niraparib) is a poly(ADP-ribose) polymerase (PARP) inhibitor indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. In preclinical studies, ZEJULA concentrates in the tumor relative to plasma, delivering greater than 90% durable inhibition of PARP 1/2 and a persistent antitumor effect.

ZEJULA (niraparib) Select Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in patients treated with ZEJULA in some clinical studies. Discontinue ZEJULA if MDS/AML is confirmed.

Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients treated with ZEJULA. Do not start ZEJULA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically after this time.

Hypertension and hypertensive crisis have been reported in patients treated with ZEJULA. Monitor blood pressure and heart rate monthly for the first year and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for six months after receiving the final dose. Because of the potential for serious adverse reactions in breastfed infants from ZEJULA, advise a lactating woman not to breastfeed during treatment with ZEJULA and for one month after receiving the final dose.