On January 9, 2019 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported its 2019 financial guidance at the 37th annual JP Morgan Healthcare Conference (Press release, Halozyme, JAN 9, 2019, View Source [SID1234532605]).

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"Looking ahead, our ENHANZE business is gaining momentum with key product development milestones expected this year, including potential FDA approval of a subcutaneous formulation of Herceptin and regulatory submissions for the subcutaneous formulation of Darzalex each representing important near-term catalysts," said Dr. Helen Torley, president and chief executive officer. "In our oncology business, HALO-301 has completed enrollment and topline results are projected in the second half of 2019."

Halozyme provided an update on the 2019 outlook for its ENHANZE franchise. The company expects to make meaningful progress this year toward its projection of the potential for approximately $1 billion in royalty revenue in 2027. During the first quarter, FDA action is expected on the Biologics License Application (BLA) filed by ENHANZE partner Genentech, a member of the Roche Group, for the subcutaneous (SC) formulation of trastuzumab (Herceptin). In the second half of 2019, ENHANZE partner Janssen Biotech, Inc. anticipates filing for approval of the SC formulation of its multiple myeloma drug daratumumab (Darzalex). Also in the second half, Halozyme expects a phase 3 study will be initiated by a partner for an undisclosed target.

By the end of 2019, the company expects three ENHANZE programs to be in phase 3 studies and to have nine active phase 1 programs in addition to its three currently marketed products. This accelerating partner activity supports the projection of the potential for approximately $1 billion in royalty revenue in 2027. Additionally, potential lifetime milestone payments associated with existing ENHANZE partnership programs in development are projected to be $1 billion, with $225 million to $300 million in revenues projected between 2019 and 2021.

The company also provided an update on its late stage targeted oncology asset PEGPH20. Enrollment in HALO-301, the company’s phase 3 study evaluating PEGPH20 in metastatic pancreas cancer, was completed at the end of 2018 with approximately 500 subjects enrolled. The company projects the study will achieve its target of 330 OS (overall survival) events between August and November of 2019. Based on this timeline, the company projects topline results will be available in the second half of 2019.

Halozyme and its partners continue to explore the pan-tumor potential of PEGPH20. This includes ongoing phase 1b studies in pancreas cancer, gastric cancer, gall bladder cancer and cholangiocarcinoma.

2019 Financial Guidance

The company also provided financial guidance for 2019:

Net revenue of $175 million to $185 million, excluding revenue from any new ENHANZE global collaboration and licensing agreements.
Operating expenses of $265 million to $275 million, or $225 million to $235 million excluding an expected increase in cost of goods sold. Excluding the cost of goods sold the modest increase in expenses is driven by ENHANZE partner support, and support of the potential commercialization of PEGPH20.
Operating cash burn of $75 million to $85 million.
Debt repayment of approximately $90 million.
Year-end cash balance of $180 million to $190 million.
Table 1. 2019 Financial Guidance

Guidance Range

Net Revenue

$175 million to $185 million

Operating Expenses

$265 million to $275 million

Operating Expenses (excl. COGS)

$225 million to $235 million

Operating Cash Burn

$75 million to $85 million

Debt Repayment

~$90 million

Year-end Cash Balance

$180 million to $190 million

The company plans to report fourth quarter and full year 2018 financial results on February 21, 2019.

A replay of Dr. Torley’s presentation at the conference today can be accessed for the next 90 days via the "Investors" section of www.halozyme.com. Also, a copy of the presentation made today was filed with the Securities and Exchange Commission as part of a Form 8-K that can also be accessed via the "Investors" section of www.halozyme.com.

On January 9, 2019 Veracyte, Inc. (Nasdaq: VCYT) reported that Bonnie H. Anderson, chairman and chief executive officer, is scheduled to present at the 21st Annual Needham Growth Conference in New York City on Tuesday, January 15, 2019 at 8:40 a.m. EST (5:40 a.m. PST) (Press release, Veracyte, JAN 9, 2019, View Source [SID1234532601]).

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A live audio webcast of the company’s presentation will be available by visiting Veracyte’s website at View Source A replay of the webcast will be available for 90 days following the conclusion of the live presentation broadcast.

On January 9, 2019 Selexis SA, a pioneering life sciences company and a global leader in mammalian cell line generation technology, reported that it has signed additional commercial license agreements (CLAs) with Agenus Inc., (NASDAQ: AGEN), an immuno-oncology company with a pipeline of immune-modulating antibodies, cancer vaccines, and adoptive cell therapies (Press release, Selexis , JAN 9, 2019, View Source [SID1234532600]).1 Under the new CLAs, Agenus will leverage Selexis’ modular SUREtechnology Platform for the rapid, stable, and cost-effective production of its therapeutic proteins.

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"It’s gratifying to have the opportunity to play a part in Agenus’ mission to redefine cancer treatment by advancing promising new biologics for individuals living with cancer," said Yemi Onakunle, PhD, MBA, Selexis vice president, licensing and business development. "The Selexis team has a notable track record of success in helping our partners overcome protein-expression challenges and advance products rapidly and safely through the clinic to the market where they can be made available to patients in need."

The Selexis SUREtechnology Platform improves the way mammalian cells are used in the discovery, development and manufacturing of recombinant proteins and drugs. The platform provides key significant advantages over traditional approaches, enabling: speed, high-yield, stability and flexibility.

"Our fully integrated capabilities, from early discovery of protein therapeutics to GMP manufacturing, allows us to rapidly produce and clinically test promising new drug candidates thereby delivering innovation with speed. A critical step in this process is the in-house development of commercially viable cell-lines expressing novel and complex proteins," said Alex Duncan, PhD, chief technology officer at Agenus. "We have successfully used the Selexis’ platform to drive our lead anti-CTLA4 (AGEN1884) and anti-PD1 (AGEN2034) programs, and are excited to partner with them to advance our novel single agent and multi-specific antibody programs."

On January 9, 2019 Adimab, LLC, the global leader in the discovery and optimization of fully human monoclonal and bispecific antibodies, reported that 12 new partner programs entered clinical development in 2018 (Press release, Adimab, JAN 9, 2019, View Source [SID1234532599]). This brings the total number of Adimab partner programs that have entered the clinic to 21.

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"We carefully track the progression of our partners’ programs and try to benchmark their success against established industry metrics. At this point we are seeing more than half of our funded discovery programs proceed into product development, which is well above industry average," said Guy Van Meter, Senior Vice President of Business Development.

"It’s one thing to show fancy slides with fantasy data; it’s a very different thing to get actual molecules into clinical development. This year we more than doubled the number of Adimab antibodies in clinical development and saw the approval of our first antibody," said Tillman Gerngross, Chief Executive Officer and Co-Founder of Adimab.

Resulting from a 2013 discovery collaboration, Innovent Biologics received BLA approval for its PD1 program in 2018, making it the most advanced partner program coming from the Adimab Platform. Notably, Innovent was able to go from discovery to BLA approval in five years.

Partners that have initiated clinical development in 2018 include Alector, Five Prime Therapeutics, Innovent Biologics, Merck, Novartis, Potenza Therapeutics (an Astellas Pharma company), Tizona Therapeutics, and others. In 2018, Adimab partners exercised options to 16 commercial licenses to advance programs into product development, bringing the total number of optioned programs to over 50. Partners exercising commercial options in 2018 include Alector, DragonFly Therapeutics, iTeos Therapeutics, Innovent Biologics, Regeneron, Takeda, Tusk Therapeutics, and others.

On January 9, 2019 NantKwest Inc. (Nasdaq:NK), a leading, clinical-stage, natural killer cell based therapeutics company, reported the launch of a novel triple combination, phase II clinical trial in Merkel cell carcinoma (MCC) (Press release, NantKwest, JAN 9, 2019, https://ir.nantkwest.com/news-releases/news-release-details/nantkwest-announces-launch-merkel-cell-carcinoma-phase-ii-trial?field_nir_news_date_value[min]=2019 [SID1234532598]).

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NantKwest’s phase II immunotherapy trial builds upon the company’s earlier phase II single-combination study using its proprietary, off-the-shelf aNKTM natural killer cell therapy and IL-15/Fc superagonist (N-803), which produced an objective responses in 3 of 7 patients.

In this new clinical trial, patients will be dosed with: (i) the novel chemotherapy-free combination of our haNK cell therapy, which are aNK cells that are genetically engineered to express the high-affinity variant of the CD16 receptor (V158 FcγRIIIa), (ii) avelumab, a PD-L1 targeting checkpoint inhibitor, and (iii) N-803, a superagonist IL-15/Fc cytokine therapy, in a regimen designed to synergistically optimize the therapeutic potential of each agent.

Commenting on the initiation of this novel triple combination trial in MCC, Patrick Soon-Shiong, MD, Chairman and CEO of NantKwest said, "Even in a heavily pretreated patient population, including patients who have failed checkpoint inhibitor therapy, we were encouraged to see our combination of aNK cell and N-803 therapy exhibit preliminary clinically meaningful antitumor activity, including objective response in this resistant setting."

Dr. Soon-Shiong continued, "Building upon this human clinical trial data, we are pleased to announce the transition of this earlier study to include haNK cell therapy in combination with the IL-15 superagonist N-803 and the PD-L1 checkpoint inhibitor avelumab, which we believe, when used together, will offer synergies and the potential to improve response rates for patients with MCC that may also potentially translate to a number of additional solid tumor indications."

In preclinical and human clinical studies conducted by NantKwest, the combination of haNK cells with a number of different therapeutic antibodies, including avelumab, led to enhanced tumor cell killing when compared to the use of the antibody alone. The IL-15/Fc superagonist N-803, developed by NantCell, Inc., an affiliate company, has been shown to synergistically activate NK and T cells and enhance cancer cell killing in both single agent and combination therapy. The PD-L1 checkpoint inhibitor avelumab, a monoclonal antibody developed by Merck KGaA and approved in 2017 by the FDA, targets the programmed death-ligand 1 protein (PD-L1), commonly expressed on a wide range of cancer cells. Avelumab works by blocking PD-L1 from binding PD-1 receptors on T-cells, resulting in an increase in CD8+ T-cell immune responses. This effect is amplified with the addition of N-803 and haNK cells.

With encouraging preclinical and clinical responses already demonstrated for aNK as a single agent therapy or in combination, we believe this existing dataset provides validation for our novel, triple combination clinical trial design.

MCC is a rare and aggressive skin cancer that arises from uncontrolled growth of cells in the skin. Increasing in incidence, approximately 2,500 new cases are reported in the U.S. each year. Patients with metastatic or locally advanced MCC have an extremely poor prognosis, with less than 20% of patients surviving longer than five years. Typically these patients are treated with a range of drugs, including chemotherapy, which can result in significant side effects. Although new immune therapies have the potential to improve survival, MCC is still fatal for a majority patients who have progressed on or after treatment with a checkpoint inhibitor and represents an unmet medical need.

Study Design

The Phase II clinical study will evaluate a combination therapy with our off-the-shelf CD16-targeted natural killer cells (haNK), the IL-15 superagonist (N-803), and avelumab, without the use of cytotoxic chemotherapy, in subjects with MCC that have progressed on or after treatment with a checkpoint inhibitor. The combination of these agents have been safely studied in our previous clinical trials for other solid cancer indications. The goal of combining these therapies is to synergistically maximize the killing of cancer cells while attempting to spare patients from chemotherapy and its associated adverse side effects.

haNK Cell Therapy Platform

NantKwest’s haNK cell therapy platform is a natural killer cell therapy that was developed to optimize the key role of natural killer cells in mediating innate immunity, enhancing adaptive immune responses, and, specifically in the case of haNK, improve anti-tumor responses via antibody-dependent cell-mediated cytotoxicity (ADCC). ADCC is an important component of the human immune system associated with the synergistic interaction of natural killer cells with antibodies to directly kill a target cell that has been identified by an antigen-specific antibody. ADCC represents one of the key mechanisms that antibodies utilize to target and kill cancer cells. Engineered to express the high-affinity variant of the CD16, high affinity Fc receptor (V158 FcγRIIIa), in preclinical studies, the combination of haNK cells with a number of different therapeutic antibodies led to enhanced tumor cell killing when compared to the use of the antibody as a single therapeutic agent, providing strong support for this novel combination immunotherapeutic approach.

N-803 Superagonist IL-15 Cytokine Therapy

Interleukin-15 (IL-15) is a critical factor controlling the development, proliferation and activation of effector natural killer (NK) cells and CD8+ memory T cells. In preclinical and clinical studies, this cytokine has exhibited potent antitumor activities against well-established tumors. N-803, developed by NantCell, an affiliate company, is a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. In preclinical and clinical studies, N-803 has shown improved biological activity, longer persistence in lymphoid tissues and enhanced anti-tumor activity by simultaneously mobilizing both the innate and adaptive arms of the immune system. This robust immunostimulatory capacity is believe to elicit rapid and durable responses against cancer cells compared to native, non-complexed IL-15 in vivo.

For additional information regarding this MCC clinical trial please visit, www.clinicaltrials.gov and for additional information on NantKwest, please visit www.nantkwest.com