On January 5, 2017 Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform, and Servier, an independent international pharmaceutical company, reported a broad collaboration in immuno-oncology (IO) (Press release, Pieris Pharmaceuticals, JAN 5, 2017, View Source [SID1234517279]). Despite the impressive clinical efficacy of checkpoint inhibitors to date, a majority of patients fail to respond to approved therapies. The collaboration seeks to address this significant unmet clinical need by advancing a series of novel molecules, including multiple dual immune checkpoint blockade approaches.

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Under the collaboration, Pieris and Servier will initially pursue five bispecific therapeutic programs, led by Pieris’ PRS-332 program, a potentially best-in-class PD-1-targeting bispecific checkpoint inhibitor. Pieris and Servier will jointly develop PRS-332 and split commercial rights geographically, with Pieris retaining all commercial rights in the United States and Servier having commercial rights in the rest of the world. The four additional committed programs have been defined, which may combine antibodies from the Servier portfolio with one or more Anticalin proteins based on Pieris’ proprietary platform to generate innovative immuno-oncology bispecific drug candidates. The collaboration may be expanded by up to three additional therapeutic programs. Pieris has the option, at a predefined time point, to co-develop and retain commercial rights in the United States for up to three programs beyond PRS-332, while Servier will be responsible for development and commercialization of the 4 other programs worldwide.

The financial terms of the collaboration include an upfront payment to Pieris of EUR30 million (approximately $31.3 million USD). Pieris may also receive FTE funding for specific projects, an option fee upon potential expansion of the collaboration as well as development-dependent and commercial milestone payments for PRS-332 and each additional program. The total development, regulatory and sales-based milestone payments to Pieris could reach EUR324 million (approximately $338 million USD) for PRS-332, and up to EUR193 million (approximately $201 million USD) for each of the other programs.Pieris and Servier will share preclinical and clinical development costs for each co-developed program. In addition, Pieris will be entitled to receive tiered royalties up to low double digits on the sales of commercialized products in the Servier territories.

Pieris’ multispecific technology allows simultaneous checkpoint inhibition on the same cell, which could have a clear advantage over monoclonal antibody cocktails against different checkpoint targets. PRS-332 is a novel PD-1-based bispecific, comprising an anti-PD-1 antibody genetically linked to an Anticalin protein targeting an undisclosed checkpoint target. Pieris has developed PRS-332, which is currently in preclinical development, with the intent to simultaneously block two immune checkpoints co-expressed on exhausted T cells to further improve on existing PD-1 therapies.

"Servier is a highly complementary partner for Pieris, with a very clear commitment to oncology and outstanding development capabilities," stated Dr. Louis Matis, Senior Vice President and Chief Development Officer of Pieris. "The synergies of building unique bispecifics from Servier’s antibodies and Pieris’ Anticalin proteins are multifold, as the versatility of our platform allows for extensive combinatorial target opportunities with the numerous IO ‘building blocks’ our team has discovered to date."

"This alliance will significantly enhance Servier’s portfolio in immuno-oncology, which already comprises 5 products in late preclinical or early development. Servier’s recognized expertise in drug development will efficiently complement Pieris’ innovative technology, allowing both companies to bring innovative solutions to cancer patients," stated Jean-Pierre Abastado, PhD, Director of Oncology R&D at Servier.

"Servier has built a diversified and innovative portfolio in oncology that includes small molecules, engineered antibodies, and cell therapies for the treatment of both hematological malignancies and solid tumors. Today’s alliance with Pieris adds another dimension to our strategy of becoming a key player in oncology, providing several next-generation bispecific IO drugs to our pipeline," added Emmanuel Canet, M.D., Ph.D., President of Servier R&D.

"Our alliance with Servier is clearly a transformative one for Pieris and is the type of partnership we deliberately set out to achieve to create significant long-term value. This collaboration provides not only an opportunity to advance multiple programs with retained rights in the number one oncology market, but also provides significant funding and flexibility for Pieris to balance financial and operational resources as we enter the next stage of corporate development," stated Stephen Yoder, President and Chief Executive Officer of Pieris. "The Servier alliance will act as a significant building block of our pipeline expansion in immuno-oncology and demonstrates the value of our proprietary Anticalin drug class."

On January 5, 2017 ARTSaVIT LTD reported that it has completed a $6.3 million Series A round of financing led by Arkin Bio Ventures and Pontifax, with participation of M Ventures, Carmel Innovation and Carmel – Haifa University Economic Corporation Ltd (Press release, ARTSaVIT, JAN 5, 2017, View Source [SID1234561841]).

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ARTSaVIT was co-founded by Carmel, the economic corporation of the University of Haifa, Carmel Innovations Fund and Professor Sarit Larisch from the University of Haifa, Israel. Prof. Larisch has identified and characterized ARTS, a protein which regulates the levels of several important anti-apoptotic proteins by promoting their degradation. Apoptosis is a highly regulated process of natural cell death. Faulty regulation of apoptosis is implicated in many human diseases, including cancer. Moreover, resistance to apoptosis is a hallmark of most human cancers.

The insights gathered by Prof. Larisch and the unique function of ARTS led to the establishment of the company, which is developing small molecule ARTS mimetics designed to selectively induce apoptosis in cancer cells. The company received seed investment from the Carmel Innovations Fund, which supported the research and development of the company to its current stage.

ARTSaVIT will move from its facilities at Carmel, University of Haifa, to the state-of-the-art facilities at the M Ventures Israel BioIncubator, which will support the development of the start-up with its infrastructure and a wide range of incubation facilities and services.

Dr. Rom Eliaz, Head of the M Ventures Israel BioIncubator commented: "We are excited to join forces with Arkin Bio Ventures, Pontifax and Carmel and would like to welcome ARTSaVit to our BioIncubator. Following the completion of this fundraising, the company is now well positioned to reach its next value inflection point".

Elka Nir, CEO of Carmel Ltd, the economic corporation of the Haifa University and CEO of Carmel Innovations Fund, noted: "We are proud and excited that M Ventures together with Arkin Bio Ventures and Pontifax invested in ARTSaVIT. It demonstrates the excellent quality and potential of the research and researchers at the University of Haifa. It is another great success for the Carmel Innovation Fund and its business model, which is funding seed companies, supporting them to a stage of significant value "

On January 5, 2017 Avidity Biosciences reported the completion of a $16 million Series B financing round to support the development of its Antibody-siRNA Conjugate (ASC) platform (Press release, Avidity Biosciences, JAN 5, 2017, View Source [SID1234521096]). The Series B round includes investment of $10 million in new capital and conversion of $6 million in convertible debt. Takeda Pharmaceuticals, through its venture group, led the Series B round, and both new and existing investors participated, including Alethea Capital, Alexandria Real Estate Equities, Brace Pharma, EcoR1 Capital, F-Prime Capital, Moore Venture Partners and Tavistock Life Sciences.

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"Our ASC platform unites two of the most impactful innovations over the past twenty years – monoclonal antibodies and oligonucleotides – to create a new class of precision medicines," said Troy Wilson, Ph.D., J.D., president and chief executive officer of Avidity Biosciences. "Although siRNA-based therapeutics have demonstrated significant clinical and commercial promise, conventional approaches are limited to targeting diseases of the liver. Because ASCs use antibodies to overcome barriers of delivering siRNA, they have the potential to impact a broader range of therapeutic areas. Our goal is to partner with leading pharmaceutical and biotechnology companies to deliver a pipeline of ASCs targeting genetic drivers of disease."

ASCs link a monoclonal antibody—designed against a specific molecular target—with a siRNA therapeutic payload, allowing the conjugate to have unmatched specificity and selectivity. In preclinical models, ASCs have shown potential to knockdown messenger RNA levels in multiple important cell types and tissues, including tumor, muscle, heart, lung, liver and B cells. In addition, ASCs have drug-like properties comparable to antibodies and antibody-drug conjugates.

In connection with the financing, Avidity Biosciences annouced that Michael Martin, Ph.D., global head of Takeda Ventures Inc., and Todd Brady, director of finance and investments of Brace Pharma Capital, will join its board of directors. Tony Hsu, founder and chief investment officer of Alethea Capital, will also join the board as a non-voting member.

"We believe Avidity’s ASC platform offers a compelling approach that builds on successes with antibodies, ADCs and oligonucleotide-based therapeutics," said Dr. Martin. "Avidity has recruited a top-notch team and made significant progress against its scientific and business goals. We look forward to working with the company to realize the promise of ASCs as a new class of precision medicines."

On January 5, 2017 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics, rreported its 2016 year-end cash balance and reviewed key anticipated events for 2017 (Press release, OncoMed, JAN 5, 2017, View Source [SID1234517304]).

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OncoMed ended 2016 with approximately $184.6 million in cash. OncoMed’s current cash is estimated to be sufficient to fund operations through at least the third quarter of 2018, without taking into account future potential milestone payments from partners. Full-year cash expenses for 2016 were approximately $115 million, in accordance with the company’s 2016 guidance. OncoMed expects 2017 operating cash burn to be less than $100 million, before considering potential milestones/opt-ins.

"2017 represents a potentially transformational year for our company," said Paul J. Hastings, OncoMed’s Chairman and Chief Executive Officer. "Phase 2 clinical trial results for demcizumab and tarextumab are anticipated in the first half of the year, and together those investigational drugs will be eligible for potential partner opt-ins totaling close to $100 million. Three additional programs, vantictumab, ipafricept and anti-RSPO3, are also eligible for potential partner opt-ins this year, and OncoMed could receive more than $170 million in total 2017 partner opt-in payments. At the same time, our earlier-stage programs are making progress in the clinic, we will be reporting on that progress, our two novel immuno-oncology candidates, anti-TIGIT and GITRL-Fc trimer are advancing into the clinic, and we continue to discover and develop additional novel agents directed at new immuno-oncology targets."

End-of-Year Accomplishments

In December 2016, OncoMed achieved the following:

Filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for anti-TIGIT (previously "I/O#2"). TIGIT (T cell immunoglobulin and ITIM domain protein) is an inhibitory receptor that stops T-cells from attacking tumor cells. Anti-TIGIT is part of OncoMed’s collaboration with Celgene Corporation.

Enrolled the first patient in a Phase 1b clinical trial of anti-DLL4/VEGF bispecific antibody (OMP-305B83) plus FOLFIRI (folinic acid, fluorouracil and irinotecan) chemotherapy for the treatment of second-line metastatic colorectal cancer. The anti-DLL4/VEGF bispecific antibody is part of OncoMed’s collaboration with Celgene.
2017: Anticipated Key Financial Milestones and Pipeline Progress by Program

Demcizumab (anti-DLL4, OMP-21M18)

Report top-line results in the first half of 2017 from the Phase 2 YOSEMITE clinical trial of demcizumab in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine for the treatment of first-line metastatic pancreatic cancer.
OncoMed anticipates that the top-line data will include response rate, progression-free survival (PFS), interim overall survival (OS) and safety results. Subsequent analyses of event-driven OS data will be conducted mid-year and at year-end.

Submit demcizumab Phase 2 data package in the first half of 2017 to Celgene for opt-in consideration.
The Phase 2 YOSEMITE PFS, interim OS, response rate, and exploratory biomarker data are expected to form the basis of a demcizumab data package. In the first half of 2017, OncoMed will also provide Celgene with response, PFS and safety data from the Phase 2 DENALI clinical trial of demcizumab plus carboplatin and pemetrexed in first-line non-small cell lung cancer (NSCLC), as well as interim safety and efficacy data from the ongoing Phase 1b clinical trial of demcizumab plus pembrolizumab (anti-PD1, Keytruda). Additional data analyses for each of these studies will be conducted as each trial matures, with planned and final analysis of OS from the DENALI trial at year-end.
OncoMed will be entitled to a $70 million opt-in payment if Celgene exercises its option on demcizumab. Following option exercise, OncoMed and Celgene will co-develop and co-commercialize demcizumab in the U.S., sharing profits 50/50, while Celgene will lead development and commercialization outside the U.S.

Complete enrollment in the Phase 1b demcizumab plus pembrolizumab clinical trial.

Present interim data from the Phase 2 YOSEMITE and the Phase 1b demcizumab plus pembrolizumab dose-escalating trial and expansion arms at medical oncology meetings during the second half of 2017, pending abstract acceptance.
Tarextumab (anti-Notch 2/3, OMP-59R5)

Report top-line progression-free survival, overall survival, and biomarker-driven efficacy data in the first half of 2017 from the Phase 2 PINNACLE clinical trial of tarextumab in combination with cisplatin/carboplatin and etoposide for the treatment of first-line small cell lung cancer (SCLC).

Submit a tarextumab data package in the first half of 2017 to GlaxoSmithKline (GSK). GSK then has the opportunity to review the data package and consider exercising its option.
If GSK exercises its option on tarextumab, OncoMed would be entitled to receive a $25 million payment. GSK would then lead and fully fund further development and commercialization.

Present data from the Phase 2 PINNACLE clinical trial at a medical oncology meeting during the second half of 2017, pending abstract acceptance.
Wnt programs — Vantictumab (anti-Fzd7, OMP-18R5) and Ipafricept (Fzd8-Fc, OMP-54F28)

Submit data package for both programs in the first half of 2017 to Bayer for opt-in consideration.
Data package will include Phase 1b clinical trial data from the ongoing studies of both vantictumab and ipafricept.
OncoMed will be entitled to receive a $25 million payment for vantictumab and a $15 million payment for ipafricept if Bayer exercises its options on the investigational drugs. Upon option exercise, Bayer will lead and fully fund further development and commercialization.

Present Phase 1b data from the ongoing clinical trials at medical oncology meetings during 2017, pending abstract acceptance.
Anti-RSPO3 (OMP-131R10)

Continue enrollment in the Phase 1a biomarker-selected expansion cohort of the Phase 1a clinical trial and the Phase 1b trial of anti-RSPO3 in combination with FOLFIRI chemotherapy in patients with colorectal cancer, including biomarker-positive subjects.

Submit a data package upon the achievement of certain enrollment objectives to Celgene for opt-in consideration.
OncoMed will be entitled to receive a $37.75 million payment if Celgene exercises its option on anti-RSPO3. Upon option exercise, OncoMed and Celgene would co-develop and co-commercialize anti-RSPO3 in the U.S., sharing profits 50/50, while Celgene would lead development and commercialization outside the U.S.
Anti-DLL4/VEGF bispecific (OMP-305B83)

Initiate second Phase 1b clinical trial of the anti-DLL4/VEGF bispecific antibody in combination with paclitaxel for the treatment of platinum-resistant ovarian cancer.
Brontictuzumab (anti-Notch1, OMP-52M51)

Begin patient enrollment in the first half of 2017 of planned Phase 1b clinical trial of brontictuzumab combined with trifluridine and tipiracil tablets (Lonsurf) in third-line colorectal cancer. The trial includes enrollment of biomarker-positive patients whose tumors express the activated form of Notch1.
Immuno-oncology Pipeline

Initiate Phase 1 clinical trial in the first half of 2017 of anti-TIGIT (OMP-313M32).
Celgene will have an option to license anti-TIGIT at the end of the Phase 1a clinical trial.

File an IND in the first half of 2017 for OncoMed’s wholly owned GITRL-Fc (OMP-336B11) trimer program.

Present preclinical data related to anti-TIGIT, pending abstract acceptance.
In future years, OncoMed is eligible for more than $4 billion in total potential milestone and option payments from its partners under its collaboration agreements with Celgene, Bayer, and GSK. To date, OncoMed has received over $465 million from its existing partners.

On January 5, 2017 Dynavax Technologies Corporation (NASDAQ: DVAX), a clinical-stage biopharmaceutical company, reported that it is reshaping its strategy and operations to prioritize its emerging clinical and preclinical immuno-oncology portfolio (Press release, Dynavax Technologies, JAN 5, 2017, View Source [SID1234517380]). The company has implemented significant organizational restructuring and cost reductions to align around its immuno-oncology business, while allowing it to advance HEPLISAV-B [Hepatitis B Vaccine, Recombinant (Adjuvanted)], its investigational hepatitis B vaccine candidate, through the U.S. Food and Drug Administration (FDA) review process and an approval decision. Dynavax continues to believe that HEPLISAV-B is an approvable product and plans to submit its response to the FDA’s outstanding questions shortly.

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To achieve these savings, Dynavax has suspended manufacturing for HEPLISAV-B and reduced its global workforce by 38 percent. The company will incur restructuring costs, currently estimated to be $3.0 million, primarily in the first quarter of 2017. The company estimates that its cash, cash equivalents and marketable securities were approximately $81.4 million as of December 31, 2016. Going forward, it expects HEPLISAV-B costs prior to any FDA decision to be less than $1 million per month, and all other operating costs to be less than $60 million per year to support continued development of its oncology program. This restructuring is currently estimated to result in approximately a 40 percent reduction in cash burn. The company will continue to evaluate the possibility of a partnership to support HEPLISAV-B as it increasingly concentrates its own strategic focus on oncology.

"We value all of our colleagues, so reducing our workforce is a sad and difficult decision. But it is one we believe is necessary to align our organization to reflect that of a clinical R&D-stage company with a promising immuno-oncology pipeline, which has become a strategically important area of our business and one we believe can potentially benefit thousands of people with cancer," said Eddie Gray, chief executive officer of Dynavax. "These measures will increase our financial strength and position us well to create significant long-term clinical and financial value. They also will allow us to advance HEPLISAV-B toward approval while we continue to evaluate the possibility of a partnership to support its approval and launch. We are grateful to all affected employees for their dedication to bringing us this far."

Prioritizing Diversified Immuno-Oncology Pipeline
Dynavax has made notable progress in the rapidly advancing area of immuno-oncology, and is focusing on two promising compounds that have shown potential to enhance the immune response against cancer.

The company’s lead clinical candidate, SD-101, an investigational cancer immunotherapeutic, is currently being studied in several Phase 1/2 studies evaluating its potential to be broadly effective against multiple solid tumors and hematologic malignancies. SD-101, an intratumoral TLR9 agonist, has shown encouraging early clinical data in metastatic melanoma.

At the Society for Melanoma Research conference in November 2016, Dynavax announced the first findings from an ongoing Phase 1/2 study of SD-101 in combination with Keytruda (pembrolizumab), Merck’s anti-PD-1 treatment. Early results evaluating 13 patients with metastatic melanoma for efficacy and 19 patients for safety were reported. In patients naïve to anti-PD-1 treatment, objective responses were observed in four of five patients (80 percent), including one complete response and three partial responses. In a small number of patients with progressive disease stable disease was observed while receiving Keytruda and SD-101 in combination. The combination of the two drugs was well-tolerated with no dose-limiting toxicities. These encouraging clinical data will be enhanced by a dose-expansion phase to further explore the efficacy of this combination.

Dynavax is also developing a second TLR9 agonist, DV281, which has completed preclinical testing in models for lung cancer. Lung cancer remains an area of high unmet need, with fewer than 20 percent of patients responding to the most recently-approved immunotherapies. DV281 will be administered as an inhaled therapeutic. Dynavax intends to begin Phase 1 studies of DV281 in the second quarter of 2017.

The company expects to present additional data from its immuno-oncology portfolio at medical conferences throughout 2017, including at the American Association for Cancer Research (AACR) (Free AACR Whitepaper), the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper).

Continuing to Advance HEPLISAV-B while Maintaining Manufacturing Capacity at Reduced Cost
Dynavax plans to respond this month to the November 2016 Complete Response Letter (CRL) from the FDA regarding its Biologics License Application (BLA) for HEPLISAV-B, and will advance the vaccine through an expected six-month FDA review period. The company remains confident that the existing clinical data package meets the requirements for approval. During the regulatory review period, Dynavax will retain, but furlough, the majority of the workforce supporting its manufacturing facility in Germany. This approach will enable the company to leverage the existing stockpiled inventory of HEPLISAV-B, while providing it with the ability to re-activate and scale for commercial launch activities.

Conference Call Details
The Dynavax management team will host a conference call and webcast today, Thursday, January 5, 2017, at 4:30 p.m. Eastern Time, to provide more information about the restructuring. The live call can be accessed by phone by dialing (877) 479-1857 (domestic) or +1 (503) 343-6309 (international) and specifying conference call code 47911578. A link to the live webcast may be accessed by visiting the "Investors" section of the Dynavax website or directly at www.dynavax.com. A replay of the conference call may be accessed for one week following the call by dialing (855) 859-2056 (domestic) or +1 (404) 537-3406, and using the passcode 47911578.

About SD-101
SD-101 is Dynavax’s proprietary CpG-C class oligodeoxynucleotide. SD-101 is a potent activator of dendritic cells, activating them to mature and produce Type 1 interferons through specific binding to TLR9, a key recognition receptor in the innate immune system. SD-101 is delivered directly to the tumor, where it can stimulate highly effective immune responses to tumor antigens. SD-101 is being evaluated in several Phase 1/2 oncology studies to assess its safety and activity.

About DV281
DV281, a newly developed TLR9 agonist, is a CpG-C class oligodeoxynucleotide developed specifically for inhaled delivery to lung tumors that are not easily accessible for intratumoral injection. Inhaled DV281 induces dendritic cell activation and tumor microenvironment changes comparable to intratumoral injection of SD-101. Studies in animal models of lung tumors show that DV281 dramatically reduces lung tumor burden and leads to immune-mediated control of tumor metastases outside the lung. Dynavax intends to initiate a Phase 1 study in the second quarter of 2017.

About HEPLISAV-B
HEPLISAV-B is an investigational adult hepatitis B vaccine that combines hepatitis B surface antigen with Dynavax’s proprietary TLR 9 agonist to enhance the immune response. HEPLISAV-B is administered in two doses over one month. In Phase 3 trials, HEPLISAV-B demonstrated higher and earlier protection with fewer doses than a currently licensed hepatitis B vaccine. The investigational vaccine’s safety profile is based on clinical trials that generated safety data from more than 14,000 participants. The most frequently reported local reaction was injection site pain. The most common systemic reactions were fatigue, headache and malaise, all of which were similar to an existing vaccine.

Dynavax has worldwide commercial rights to HEPLISAV-B.