On April 1, 2019 Dynavax Technologies Corporation (NASDAQ: DVAX) and 4SC AG (FSE Prime Standard: VSC) reported the combination of 4SC’s orally available class I selective HDAC inhibitor domatinostat (4SC-202) with Dynavax’s intratumoral TLR9 agonist SD-101 induced a systemic anti-tumoral immune response in tumor mouse models, resulting in the significant decrease in tumor size of both target tumors and distant site metastases (Press release, Dynavax Technologies, APR 1, 2019, View Source [SID1234534838]).

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Combination of SD-101 with domatinostat showed better results than combinations of SD-101 with competing HDAC inhibitors. The triple combination of both compounds with PD-1 blockade (checkpoint inhibition) demonstrated even higher efficacy.

Émilie Degagné, PhD, scientist at Dynavax will present the data in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting, which takes place from 29 March to 3 April 2019 in Atlanta, USA.

Combined mode of actions of SD-101 plus checkpoint inhibitor plus domatinostat

SD-101 is a TLR9 agonist, which was specifically developed for cancer based upon its ability to stimulate both IFN-α production and the maturation of plasmacytoid dendritic cells into tumor antigen presenting cells. This results in increased activation and proliferation of tumor-specific CD8+ T cells which attack distant site non-injected tumors. Domatinostat, acting via epigenetic regulation, renders tumor cells more visible to the immune system and promotes a general immune response against tumor tissue as well as infiltration of T cells into the tumor tissue.

Preclinical data demonstrate that the combination of intra-tumoral SD-101 and systemic domatinostat strongly synergize to induce substantial regression of the primary (injected) tumor, as well as distant site non-injected tumors, including lung metastases. Checkpoint inhibitors, such as anti-PD-1 antibodies further boost the anti-tumor T-cell response, leading to rejection in mice with high metastatic burden. These data indicate that the combination of these three different treatment classes result in induction of a more potent tumor-specific immune response and better recognition and elimination of tumors by immune cells, especially in cancer patients refractory to anti-PD-1 treatment.

"We believe the induction of innate immunity will be instrumental in the future treatment of cancer and are pleased to work with 4SC as they develop differentiated drug candidates to modulate the immune system," said Eddie Gray, CEO of Dynavax. "SD-101 has demonstrated significant antitumor effects by direct enhancement of innate immunity and adds meaningful clinical benefit to anti-PD-1 therapy. The addition of domatinostat to this combination shows encouraging results and we look forward to continuing to assess the potential of this combination."

Jason Loveridge, Ph.D., CEO of 4SC, added: "We thank Eddie Gray and his team at Dynavax for performing these highly promising experiments. We are very impressed by the data on the triple-combination of SD-101, domatinostat and PD-1 blockade and believe there is significant potential for novel combinations based on immunotherapeutics such as these to fight cancer, especially in patients who are resistant to or progressing on treatment with prior immunotherapies. Of particular importance to us was the clear demonstration of domatinostat’s superiority as compared to competing HDAC inhibitors."

Abstract ID 2259: Tumor abscopal responses induced by the TLR9 agonist, SD-101, are strongly potentiated by a HDAC class I inhibitor, domatinostat.

Date: 1 April 2019
Time: 1:00 PM – 5:00 PM EDT
Session: PO.CL06.05 – Combination Immunotherapies 1
Location: Exhibit Hall B, Section 19, Poster Board Number 18

Further information

About SD-101

SD-101, the Company’s lead clinical candidate, is a proprietary, second-generation, Toll-like receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide. Dynavax is evaluating this intratumoral TLR9 agonist in several clinical studies to assess its safety and activity, including a Phase 2 study in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy, in patients with advanced melanoma and in patients with head and neck squamous cell cancer, in a clinical collaboration with Merck. Dynavax maintains all commercial rights to SD-101.

About domatinostat (4SC-202)

Domatinostat is an orally administered small molecule Class I selective HDAC inhibitor with a unique mode of action that was designed to strengthen the body’s own anti-tumor immune response. Domatinostat also influences the tumor microenvironment facilitating infiltration of immune cells into the tumor and making it more visible to the immune system.

Domatinostat has been investigated in a Phase I study with 24 heavily pretreated patients with several types of advanced hematologic cancers and was well tolerated. Positive signs of anti-tumor efficacy were also observed; with one complete remission (28 months) and one partial responder (8 months).

In addition to its therapeutic potential in cancer monotherapy, 4SC is evaluating domatinostat’s capacity as a partner in combination therapies, specifically in the immuno-oncology area. In this respect, 4SC initiated a Phase Ib/II study of domatinostat in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab in patients with advanced-stage melanoma. A second Phase II study of domatinostat in combination with the anti-PD-L1 checkpoint inhibitor avelumab in patients with advanced-stage microsatellite-stable gastrointestinal cancer is conducted by Prof. David Cunningham of The Royal Marsden NHS Foundation Trust (London, UK).

As soon as results from the aforementioned trials will be available, 4SC plans to advance domatinostat into a potentially pivotal study in combination with a checkpoint inhibitor in PD-(L)1 refractory patients with advanced Merkel-cell carcinoma (MCC).

On April 1, 2019 Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer, autoimmune disease, asthma and allergic diseases, reported that company management will participate in two upcoming conferences (Press release, Xencor, APR 1, 2019, View Source [SID1234534854]):

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Jefferies 6th Annual IO Cell Therapy Summit
Date: Friday, April 5, 2019
Location: Boston, MA
18th Annual Needham Healthcare Conference
Date: Tuesday, April 9, 2019
Presentation Time: 2:10 p.m. ET
Location: New York, NY
A live webcast of the Needham Healthcare Conference presentation will be available under "Events & Presentations" in the Investors section of the Company’s website located at View Source A replay of the event will be posted on the Xencor website approximately one hour after the live event and will be available for 90 days following the event.

On April 1, 2019 Bolt Biotherapeutics, Inc., a biotechnology company focused on unleashing the power of the immune system to achieve anti-tumor immunity, reported its positive preclinical proof of concept data on its promising Immune-Stimulating Antibody Conjugate (ISAC) platform (Press release, Bolt Biotherapeutics, APR 1, 2019, View Source [SID1234534874]). The data showed the potential of ISACs to eradicate tumors in animal models, which led to immunological memory of tumor-antigen positive and tumor-antigen negative tumors, suggestive of epitope spreading. These data were presented today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Conference in Atlanta, Georgia in a poster presentation titled "TLR7/8 immune-stimulating antibody conjugates elicit robust myeloid activation and durable anti-tumor immunity."

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In contrast to traditional TLR agonists that require intratumoral administration, Bolt presented a series of in vivo studies demonstrating that its novel Boltbody ISACs can be delivered systemically and generate antitumor immunity in several different cancer models. In human tumor models ranging in HER2 expression level, Boltbody ISAC treatment demonstrated significant anti-tumor efficacy against tumors that could not be controlled by the clinically-validated parental antibody, trastuzumab. Furthermore, in a syngeneic tumor model, animals previously cleared of HER2 positive tumors by Boltbody ISAC treatment were challenged with a second tumor lacking expression of the HER2 tumor-antigen and were resistant to tumor growth. In summary, the key preclinical achievements presented are:

 Anti-tumor efficacy in trastuzumab refractory models
 Immunological memory
 Epitope spreading against tumors without HER2 antigen expression

"This is an exciting opportunity for Bolt to be able to share our novel technology for the first time. We believe our Boltbody ISACs offer many unique benefits including the ability to achieve potent localized antitumor activity following systemic administration given the encouraging results observed by others with intratumoral delivery of TLR agonists in patients," stated David Dornan, Ph.D., senior vice president of research at Bolt Biotherapeutics. "We are advancing toward clinical assessment of our lead candidate as rapidly as possible."

"As a physician who has spent decades developing and understanding cancer immunotherapies, I was pleased to see that the Boltbody ISACs not only cleared tumors, but also generated immunological memory. This indicates the potential for a patient’s immune system to keep cancer from returning," stated Ed Engleman, M.D., Bolt founder and co-director of the Immunology and Immunotherapy Research Program at the Stanford Cancer Institute. "Boltbody ISACs demonstrate the potential to treat patients who are refractory to standard of care therapies and have not yet generated a robust anti-tumor immune response."

About Bolt Biotherapeutics’ Immune-Stimulating Antibody Conjugate (ISAC) Platform Technology
The Boltbody platform consists of Immune-Stimulating Antibody Conjugates (ISAC) that harness the ability of TLR agonists to convert cold tumors into immunologically hot tumors (illuminating tumors to the immune system allowing them to be invaded by tumor killing cells). Boltbody ISACs have demonstrated the ability to eliminate tumors following systemic administration in preclinical models and have also led to the development of immunological memory.

On April 1, 2019 Altimmune, Inc. (Nasdaq: ALT), a clinical-stage immunotherapeutics company, reported financial results for the year ended December 31, 2018, and provided a corporate update (Press release, Altimmune, APR 1, 2019, View Source [SID1234534891]).

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"We made great progress in 2018, starting with encouraging data from our NasoVAX and HepTcell trials, re-capitalizing the Company, and bolstering the leadership team," said Vipin K. Garg, Ph.D., President and Chief Executive Officer.

Dr. Garg continued, "2019 is shaping up to be just as transformative as we advance HepTcell toward Phase 2 clinical development, perform proof-of-concept studies for ALT-702, pursue acquisitions of complementary immunotherapeutic assets, and seek a partner to advance NasoVAX. We are optimistic that focusing on the development of early to mid-stage product candidates that address significant unmet needs will lead to long-term success for Altimmune."

Corporate Update

Leadership team highlights

The Board of Directors appointed Vipin K. Garg, Ph.D. as President and Chief Executive Officer. Vipin is a seasoned executive with over three decades of experience in the biotechnology and pharmaceutical industries and possesses a proven track record of building and managing both private and publicly traded companies.
The Company engaged Will Brown as Acting Chief Financial Officer. He is responsible for all accounting and finance matters including equity offerings, SEC reporting, and investor relations. Will is a CPA with significant public accounting experience at PwC and was formerly a controller at Rheem, a multi-national manufacturing company.
The Company hired José Ochoa as Chief Business Officer. Jose is leading all business development activities including acquisitions, in-licensing, partnerships and out-licensing. José comes to the Company with a wealth of experience including senior business development positions at IDT Biologika Corporation and Emergent BioSolutions.
Corporate development highlights

The Company fully retired its 2017 preferred shares and related warrants, and raised gross proceeds of $56 million, including from a registered direct offering in March 2019.
The Company completed a comprehensive review of its clinical development pipeline with a strategic decision to focus its resources on immunotherapeutic programs in early to mid-stage development. Accordingly, the Company is seeking a partner for its NasoVAX program and is reviewing in-licensing and acquisition candidates to broaden its development pipeline.
Program highlights
HepTcell
In December 2018, the Company reported final results of a pre-planned analysis of its first-in-human evaluation of HepTcell in patients with chronic hepatitis B infection, which met the primary safety endpoint and demonstrated encouraging results where two adjuvanted HepTcell arms had markedly greater increases in T-cell immunity over baseline than the placebo group. HBV-specific immune activation is widely recognized as being a key requirement of HBV functional cure, and the Company plans to advance the HepTcell program into Phase 2 development. The Phase 1 results will be presented on April 12, 2019 at The International Liver Congress sponsored by The European Association for the Study of the Liver (EASL) being held in Vienna, AustriaApril 10-14, 2019.

ALT-702
ALT-702 is a tumor immunostimulant product candidate that has the potential to safely elicit or improve immune responses in a variety of cancers. It is a conjugated TLR-7/8 agonist designed to reverse immune-suppressive effects in the tumor microenvironment and promote antitumoral responses without the systemic side effects associated with other injected TLR-7 and TLR-7/8 agonists. This localized immune stimulation is anticipated to turn "cold" tumors to "hot" and to synergize with immune checkpoint inhibitors. The Company is currently developing a full preclinical dataset in murine tumor models with the intention of advancing this program into the clinic.

NasoVAX
The Company completed a Phase 2 study for NasoVAX in 2018 and presented the data at the October 2018 IDWeek in San Francisco. NasoVAX was well-tolerated and immunogenic demonstrating 100% seroprotection at two of the three dose levels studied, in addition to mucosal and cellular immune responses. Subjects from the highest dose cohort were followed for an additional twelve to fourteen months after vaccination to assess durability of the antibody response. The data showed that all eight of the subjects that returned for follow-up retained their seroprotected status more than one year after vaccination. Durable responses on the order of one year are not expected from currently approved injected influenza vaccines and suggest that the immune response induced by NasoVAX could be protective for the duration of a long flu season.

NasoShield
NasoShield is an anthrax vaccine designed to provide rapid and stable protection after a single intranasal administration. The Company developed the product candidate and launched a Phase 1 study of NasoShield with the support of the Biomedical Advanced Research and Development Authority ("BARDA"). Based on initial data, NasoShield was well-tolerated but did not produce an appreciable toxin neutralizing antibody (TNA) response. Given the compelling nonclinical data obtained previously in two well-established animal models for anthrax, the Company is investigating all potential causes that may have contributed to the disparate results. Results of these investigations are expected in the first half of 2019.

Financial Results for the Year Ended December 31, 2018

The Company received net proceeds of approximately $37.4 million from a follow-on public offering and two registered direct offerings during 2018. Subsequent to year end, the Company received net proceeds of approximately $12.7 million from its March 2019 registered direct offering.

At December 31, 2018, the Company had $34.4 million in cash, cash equivalents, and restricted cash.

Revenue was $10.3 million for the year ended December 31, 2018 compared to $10.7 million in the prior year . The decrease was primarily the result of a decrease of $0.6 million in BARDA revenue due directly to changes in spending on the NasoShield research and development, and an increase of $0.3 million in NIAID revenue due directly to changes in spending on the SparVax-L research and development.

Research and development expenses were $18.5 million for the year ended December 31, 2018 compared to $18.4 million in the prior year. The increased expense was primarily due to:
an increase of $0.8 million in non-project specific research and development costs driven by employee compensation and additional allocated facility costs;
a decrease of $0.6 million due to timing of manufacturing development activities for NasoShield; and,
a decrease of $0.1 million in direct costs related to NasoVAX, SparVax-L and HepTcell.

General and administrative expenses were $9.8 million for the year ended December 31, 2018 compared to $8.5 million in the prior year. The increased expenses were primarily due to increases in severance, professional services, insurance and board of director fees; offset by a decrease in reorganization expenses related to the 2017 merger with Pharmathene which were incurred in 2017.

Impairment charges were $24.9 million for the year ended December 31, 2018 compared to $35.9 million for the prior year. Impairment charges in 2018 are related primarily to a write-down of IPR&D assets related to SparVax-L and Oncosyn. Impairment charges in 2017 are due to fully impairing the carrying value of goodwill.

Other income (expense) was $(2.5) million for the year ended December 31, 2018 compared to ($18.5) thousand in the prior year. The increased expense was primarily due to changes in the fair value of the Company’s warrant liability.

Net loss attributed to common stockholders for the year ended December 31, 2018 was $42.5 million compared to $51.4 million in the prior year.
Conference Call Details
Date: Tuesday, April 2, 2019
Time: 8:30am Eastern Time
Domestic: 877-423-9813
International: 201-689-8573
Conference ID: 13687672
Webcast: View Source

On April 1, 2019 MaxCyte presented the corporate presentation (Press release, MaxCyte, APR 1, 2019, View Source [SID1234537621]).

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