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 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage company developing highly differentiated therapeutics targeting the underlying mechanisms of cancer, reported that new preclinical data for CG-806, its first-in-class, highly potent oral small molecule pan-FLT3/pan-BTK inhibitor, and APTO-253, its MYC inhibitor, are being presented in two separate posters at the 2019 AACR (Free AACR Whitepaper) Annual Meeting in Atlanta, GA (Press release, Aptose Biosciences, APR 1, 2019, View Source [SID1234534822]).

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CG-806 Poster

The poster, CG-806, a pan-FLT3 / pan-BTK inhibitor, demonstrates superior potency against cells from IDH-1 mutant and other non-favorable risk groups of AML patients, explores the activity of CG-806 on primary patient samples with acute myeloid leukemia (AML), in studies that were conducted in collaboration with the Beat AML Initiative. CG-806 demonstrated significant potency across sub-groups of AML cells, including relapsed/refractory AML and those with genetic abnormalities related to poor prognoses in AML patients. CG-806 demonstrated superior potency when compared to other FLT3 inhibitors, including midostaurin, sorafenib, sunitinib, dovitinib, quizartinib, crenolanib and gilteritinib. While patient samples with FLT3-ITD mutations were expected to have greater sensitivity to CG-806, the sensitivity of patient cells with IDH1 R132 mutations was an unexpected finding. In 28-day GLP toxicity and toxicokinetic studies, CG-806 continued to demonstrate a favorable safety profile. The poster also highlights results of combination studies with CG-806 and venetoclax, which demonstrated enhanced killing of primary cancer cells from patients with AML and B-cell cancers.

"With our IND for CG-806 just recently allowed by the FDA, we are eager to begin Phase 1 human clinical trials," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "The Beat AML initiative has allowed us, with our research collaborators at Oregon Health & Science University (OHSU), to test the response of actual patient samples (ex vivo) to CG-806, alone and in combination, and enables us to assess its effectiveness based upon specific genetic profiles of patients. The wealth of CG-806 data continues to grow and strongly supports the clinical development of CG-806. It is our goal to improve the odds of achieving long-term disease remissions for patients."

APTO-253 Poster

The poster, Resistance to APTO-253 caused by internal deletion and alternate promoter usage of the MYC gene in Raji B cells, presents in vitro studies that further define the mechanism of action of APTO-253. A novel small molecule, APTO-253 inhibits expression of the MYC oncogene, leading to apoptosis in human-derived solid tumor and hematologic cancer cells without the myelosuppression seen with other chemotherapies. Researchers found that APTO-253 targets a G-quadruplex motif in the P1/P2 promoter region of the MYC gene and inhibits MYC gene expression to induce apoptosis, resulting in its ability to potently kill hematologic malignant cell lines and primary samples from AML and chronic lymphocytic leukemia (CLL) patients. In this study, researchers performed long-term in vitro studies to determine if and how cells might develop resistance to APTO-253. MYC driven Raji cells required three years in increasing concentrations of APTO-253 in order to adopt multiple modifications and develop high level resistance to APTO-253. These modifications include up-regulation of the ABCG2 transporter, acquisition of a more stable MYC protein lacking the conserved core sequence of MYC Box III generated by deletion of an internal region of the MYC gene exon 2, and utilization of alternate P3 promoter not inhibited by G4 binding and stabilization.

Both of the AACR (Free AACR Whitepaper) posters can be accessed here or at the publications and presentations section of Aptose’s website www.aptose.com.

About CG-806

CG-806 is an oral, first-in-class pan-FLT3/pan-BTK multi-cluster kinase inhibitor and is in a Phase 1 clinical trial for hematologic malignancies. This small molecule, in-licensed from CrystalGenomics Inc. in Seoul, South Korea, demonstrates potent inhibition of wild type and all mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), cures animals of acute myeloid leukemia (AML) tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML. Likewise, CG-806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser (C481S) mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG-806 may be developed for various B cell malignancy patients (including CLL/SLL, FL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent BTK inhibitors. Because CG-806 targets key kinases/pathways operative in malignancies derived from the bone marrow, it is in development for B-cell cancers and AML.

About APTO-253

APTO-253 is a clinical-stage, small molecule, targeted therapeutic agent that inhibits expression of the MYC oncogene, leading to cell cycle arrest and programmed cell death (apoptosis) in human-derived solid tumor and hematologic cancer cells. Indeed, the first AML patient treated with APTO-253 at the lowest dose level demonstrated significant reductions of MYC expression in peripheral blood mononuclear cells after one 28-day cycle of drug therapy. The MYC oncogene is overexpressed in hematologic cancers, including acute myeloid leukemia (AML). Aptose researchers have reported the ability of APTO-253 to induce cell death, or apoptosis, in multiple blood cancer cell lines including AML, as well as in vitro synergy with various classes of conventional approved and investigational therapies for AML or myelodysplastic syndromes (MDS). New findings reveal that APTO-253 might also serve certain solid tumor patients with BRCA1/2 mutations, but without causing toxicity to the normal bone marrow functions.

On April 1, 2019 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported promising data from the Company’s growing bispecific and TAM (Tyro3, Axl, MerTK) receptor programs during poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 (Press release, Celldex Therapeutics, APR 1, 2019, View Source [SID1234534839]).

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"Our research and discovery efforts have yielded multiple promising candidates that address important needs in cancer immunotherapy and complement our pipeline," said Tibor Keler, Ph.D., Executive Vice President and Chief Scientific Officer of Celldex Therapeutics. "CDX-527 joins two powerful pathways in the immune system, PD-1 blockade and CD27 costimulation. The data we presented at AACR (Free AACR Whitepaper) demonstrate that this bispecific antibody candidate has greater activity than the combination of the two individual antibodies and support advancing the program into IND-enabling studies. In addition, we also presented data on our lead candidate antibodies targeting the TAM receptors, which act as checkpoints on myeloid cells. We have uncovered a unique mechanism for antibody-mediated activation of dendritic cells and macrophages and demonstrated that a surrogate MerTK mAb promotes anti-tumor immunity alone and enhances the activity of PD-1 blockade. We look forward to continuing to progress both CDX-527 and our TAM program over the course of the year," concluded Keler.

Presentation Highlights:

Poster #2392: CDX-527: A novel bispecific immune-modulating antibody targeting CD27 and PD-L1 (Vitale, et. al)

The use of bispecific antibodies provides opportunities to engage two independent pathways involved in controlling immune responses to tumors. Preclinical and clinical studies support the safety and benefit of combining PD-1 blockade with a CD27 agonist.
The bispecific CDX-527 combines a novel and potent PD-L1 antibody for blocking the PD-1 checkpoint pathway with the binding domains of a CD27 agonist antibody for CD27-mediated costimulation of T cells.
CDX-527 demonstrated potent inhibition of PD-1 signaling and T cell activation using in vitro models with reporter cell lines and human primary cell cultures.
Anti-tumor activity was tested with a surrogate bispecific molecule that binds mouse PD-L1 and human CD27 in human CD27-expressing transgenic mice. The bispecific demonstrated potent anti-tumor activity in a BCL1 lymphoma model and was significantly more effective than the combination of the CD27 and PD-L1 monoclonal antibodies (mAbs).
A pilot study in non-human primates suggests that CDX-527 demonstrates good pharmacokinetic properties and no toxicities were observed.
Based on the promising data observed to date and the PK/PD profiles, Celldex has initiated manufacturing activities and investigational new drug (IND) enabling studies to support clinical studies of CDX-527.
Poster #1555: Monoclonal antibodies targeting the TAM family of receptor tyrosine kinases (Alvarado, et al)

TAM receptors (Tyro3, Axl, MerTK) are receptor tyrosine kinases (RTKs) expressed in innate immune cells. These receptors have been gaining importance in the immunotherapy field due to their role as checkpoint molecules on macrophages, dendritic cells, and other immune cells, where they can negatively regulate anti-tumor immunity.
Celldex presented data showing that lead candidate mAbs targeting MerTK, Axl or Tyro-3 activate myeloid cells, including monocytes, macrophages and dendritic cells, enhancing pro-inflammatory cytokine release, increasing expression of costimulatory molecules and enhancing T cell activation in mixed lymphocyte reaction (MLR) assays.
Celldex demonstrated that the potent activity of the TAM-specific antibodies are dependent on a unique coupling of the TAM receptors with Fc receptors.
Celldex’s most advanced program targets MerTK, where the Company has demonstrated that antibody targeting of MerTK in mice elicits an inflammatory cytokine response similar to that observed in the human cells and in MerTK deficient mice and has anti-tumor activity when dosed alone or in combination with a PD-1 inhibitor in a colon cancer model.
These data support development of anti-TAM mAbs as therapies to activate innate immune responses with a potential for systemic dosing. The Company intends to advance potential candidates into development activities this year.