On March 29, 2019 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address cancer, liver and inflammatory diseases, reported that it has filed its annual report on Form 20-F for the fiscal year ended December 31, 2018 with the U.S. Securities and Exchange Commission (the "SEC") (Press release, Can-Fite BioPharma, MAR 29, 2019, View Source [SID1234534769]).

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The annual report, which contains the Company’s audited consolidated financial statements, can be accessed on the SEC’s website at View Source as well as via the Company’s investor relations website at View Source

The Company will deliver a hard copy of its annual report, including its complete audited consolidated financial statements, free of charge, to its shareholders upon request to Can-Fite Investor Relations at 10 Bareket Street, Kiryat Matalon, Petah-Tikva 4951778, Israel or by phone at +972-3-9241114.

On March 29, 2019 Forbius, a clinical-stage company that develops novel biologics for the treatment of fibrosis and cancer, reported that it will report the results from its Phase 1 dose-finding trial with novel, tumor selective, anti-epidermal growth factor receptor (EGFR) antibody-drug conjugate (ADC) AVID100 at the AACR (Free AACR Whitepaper) Annual Meeting 2019 (Press release, Forbius, MAR 29, 2019, View Source [SID1234534768]). An additional AACR (Free AACR Whitepaper) poster presentation will feature preclinical data confirming AVID100’s novel mechanism of action, which potently targets tumor cells while sparing EGFR-expressing non-tumor cells.

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Details and highlights of the presentations are as follows:

CT056 / 13 – A Phase Ia/IIa trial of AVID100, an anti-EGFR antibody-drug conjugate

Poster presentation: April 1, 8:00 AM – 12:00 PM EDT, Section 17
Author: N. Lakhani
(Abstract available here)

AVID100 was well-tolerated in a Phase 1 dose-escalation study in patients with advanced solid tumors of epithelial origin (any EGFR status)
Most common treatment-related adverse events (TRAEs, in > 25% patients) were rash (66.7%; grade 1 or 2), nausea (41.7%; grade 1 or 2), and fatigue (29.2%; grade 1 or 2)
Recommended Phase 2 dose (RP2D) of 220 mg/m2 (~6 mg/kg) confirmed, one of the highest RP2Ds reported for maytansinoid payload ADCs (Deslandes, 2014)
Phase 2 (AVID100-01; NCT03094169) enrollment ongoing to evaluate AVID100 efficacy, safety, and tolerability in patients with EGFR-overexpressing (IHC 3+) SCCHN and sqNSCLC
218 / 9 – AVID100 is an anti-EGFR ADC that promotes DM1-meditated cytotoxicity on cancer cells but not on normal cells

Poster presentation: March 31, 1:00 PM – 5:00 PM EDT, Section 9
Author: M. Thwaites
(Abstract available here)

AVID100 is highly potent and selectively cytotoxic against EGFR-expressing cancer cells, while sparing normal EGFR-positive keratinocytes
Protection of EGFR-expressing normal cells is shown to be a function of AVID100’s antibody moiety, which inhibits EGFR signaling and proliferation in normal cells
About AVID100 and the AVID100-01 Trial

AVID100 is a highly potent EGFR-targeting antibody-drug conjugate (ADC) that was engineered to achieve enhanced anti-tumor efficacy without a corresponding increase in toxicity against skin and other EGFR-expressing normal tissues. In preclinical studies, AVID100 demonstrated significant anti-cancer activity, including in EGFR-overexpressing tumor models that are resistant to marketed EGFR inhibitors. AVID100 is the only anti-EGFR ADC in clinical development that targets both wild-type and mutant forms of EGFR.

In a successfully completed Phase 1 study, AVID100 reported a recommended Phase 2 dose (RP2D) of 220 mg/m2 (~6mg/kg), which is expected to be in the therapeutically active range based on preclinical efficacy studies. Treatment was generally well-tolerated, with the majority of treatment-related adverse events in the Phase 1 trial at RP2D being grade 1 or 2 in severity.

AVID100-01 (NCT03094169) is an open label, multicenter, dose-escalation study to evaluate the safety and efficacy of AVID100 in patients with confirmed EGFR-overexpressing tumors.

On March 29, 2019 Celularity, Inc. ("Celularity" or the "Company"), a clinical-stage cell therapeutics company developing allogeneic cellular therapies harnessed from human placentas, reported results from two Phase 1 studies of PNK-007, an investigational allogeneic off-the-shelf natural killer (NK) cell therapy, in patients with acute myeloid leukemia (AML) and in patients with multiple myeloma (MM) (Press release, Celularity, MAR 29, 2019, View Source [SID1234534767]).

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Translational immunotherapy study results from the Company’s late-breaking presentation in AML showed that PNK-007 persisted in the blood and marrow for up to one month, providing evidence of expansion and further maturation of the PNK-007 in HLA (Human Leukocyte Antigen) unmatched patients.

"Our first Phase 1 studies of PNK-007 in AML and MM demonstrated an encouraging safety profile, and in MM specifically, we monitored minimal residual disease (MRD) status in patients as an exploratory efficacy endpoint," said Xiaokui Zhang, Ph.D., Executive Vice President and Chief Scientific Officer. "Based on these studies, we believe PNK-007 offers a novel modality to improve the treatment outcome for patients, and further validates Celularity’s proprietary IMPACT platform in a clinical setting," added Nassir Habboubi, M.D., Executive Vice President and Chief Medical Officer.

The Company plans to initiate a Phase 1b/2a study in AML patients and a Phase 2 study in MM patients during the second half of 2019. These studies will investigate the safety and efficacy of CYNK-001, the cryopreserved successor product to PNK-007.

"The positive results from these first-in-human studies of PNK-007 confirm our unique approach of deriving cell therapy from placental cells, and suggest this investigational immunotherapy has the potential to become an important new immuno-oncology option for patients with serious blood cancers, including those who were heavily pretreated and failed previous lines of therapy, or who have undergone autologous stem cell transplant," said Robert J. Hariri, M.D., Ph.D., Celularity’s Founder, Chairman and CEO. "Given the challenges associated with currently available patient-sourced and adult donor cell therapies, we believe there is an important need for next-generation, allogeneic, off-the-shelf immunotherapies that are more tolerable, accessible, and affordable to patients and the healthcare system."

In addition to results from the PNK-007 studies, Celularity will also present pre-clinical data in an oral session evaluating its proprietary genetically-modified allogeneic NK cells (GM-NK) derived from human placental CD34+ progenitors for the treatment of a broad spectrum of blood cancers and solid tumor cancers. Results from early pre-clinical studies showed that this genetic modification of PNK led to a two to four-fold increase in anti-tumor activity against a range of hematologic and solid cancer cell lines as well as primary tumor cells.

"We look forward to advancing this important program, as it will pave the way for genetically modified NK cell therapy as another option for cancer patients," Dr. Hariri continued.

About PNK-007
PNK‐007 is the only allogeneic, off-the-shelf NK cell therapy being developed from placental hematopoietic stem cells as a potential treatment option for various hematologic cancers and solid tumors. NK cells are a unique class of immune cells, innately capable of targeting cancer cells and interacting with adaptive immunity. When derived from the placenta, these cells offer intrinsic safety and versatility, allowing potential use across a range of organs and tissues. PNK cells are currently being investigated as a treatment for acute myeloid leukemia (AML) and multiple myeloma (MM).

About CYNK-001
CYNK-001 is the only cryopreserved, off-the-shelf NK cell therapy being developed from placental hematopoietic stem cells as a potential treatment option for various hematologic cancers and solid tumors.

On March 29, 2019 Northern Biologics Inc., a company focused on developing first-in-class immuno-oncology products, reported the presentation of initial results from the Phase I trial of their lead antibody, MSC-1, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting in Atlanta, Georgia (Press release, Northern Biologics, MAR 29, 2019, View Source [SID1234534766]).

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Session Title: Phase I Clinical Trials: Part 1
Session Date and Time: Sunday Mar 31, 2019 1:00 PM – 5:00 PM
Session Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 16 Poster Board Number: 9

MSC-1 is a humanized antibody against a soluble cytokine called LIF (see "About LIF" below). LIF plays a multi-faceted role in cancer, and as a result of inhibiting the target opens-up two therapeutic avenues: reversal of tumor immunosuppression and modulation of cancer initiating cells (CICs) to promote tumor cell differentiation and sensitivity to chemotherapy.

The open-label, dose-escalation, dose-expansion Phase I trial in the U.S., Europe and Canada is testing MSC-1 as monotherapy in patients with relapsed or refractory advanced solid tumors. The primary objectives of the dose escalation part of the study are to evaluate the safety and tolerability of MSC-1 and determine the recommended dose for MSC-1 monotherapy in dose expansion. Secondary and exploratory objectives include assessing progression-free survival and characterizing the pharmacodynamic effects of MSC-1 in peripheral blood through stabilization of LIF levels and in tumor biopsies as measured by changes in the tumor microenvironment and cell signaling.

The dose escalation portion of the study completed enrollment in early March, with 41 patients enrolled in 9 months, in dose cohorts ranging from 75 mg to 1,500 mg. This includes expanded escalation cohorts being evaluated for additional safety, PK/PD and biomarker analyses, including studying the tumor microenvironment in matched pre- and post-treatment tumor biopsies. There have been no dose-limiting toxicities or tolerability issues observed at any dose.

Six patients have been treated for 16 weeks or longer. Moreover, some patients displayed decreases in tumor biomarkers CA19-9 and CA125. MSC-1 has shown a favorable PK profile, typical of an antibody, and evidence of durable peripheral LIF stabilization.

"We are pleased with the preliminary safety profile of MSC-1 in this trial that has enrolled patients at a very rapid pace," said Joan Seoane, Ph.D., ICREA Professor and Director of Translational Research at Vall d’Hebron University Hospital’s Institute of Oncology (VHIO). "We are excited to report on the effect of this first-in-class molecule on multiple measures in hopes of bringing benefit to patients with advanced cancers."

"These clinical results, coupled with exciting preclinical data, increase our conviction that targeting LIF can bring therapeutic benefit to defined populations of cancer patients," said Philip Vickers, Ph.D., CEO of Northern Biologics. "We now have a deep understanding of the biology underlying our first-in-class antibody."

About LIF

LIF, or leukemia inhibitory factor, is an exciting emerging target in the immuno-oncology space. Northern Co-Founder Joan Seoane first elucidated a role for the cytokine in cancer in a seminal 2009 publication in Cancer Cell. Since that time, several independent labs have demonstrated the role of LIF in many cancers. LIF is hypothesized to contribute to tumor growth and progression by acting on multiple aspects of cancer biology, including immunosuppression within the tumor microenvironment (TME), and regulation of cancer initiating cells (CICs), which are thought to underpin tumor growth, metastasis and resistance to therapy.

On March 29, 2019 Advaxis, Inc. (NASDAQ: ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported the presentation of ADXS-NEO data in a poster discussion entitled "Safety and Immunogenicity of a Personalized Neoantigen-Listeria Vaccine in Cancer Patients" at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting underway in Atlanta (Press release, Advaxis, MAR 29, 2019, View Source [SID1234534765]). The discussion will be held on Sunday, March 31, 2019 from 1:00-5:00 p.m. ET and will be led by J. Randolph Hecht, M.D., Professor of Clinical Medicine, David Geffen School of Medicine at UCLA and Director of the UCLA Gastrointestinal Oncology Program.

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ADXS-NEO is a live, attenuated Listeria monocytogenes (Lm) immunotherapy, using personalized antigen delivery based on whole-exome sequencing of a patient’s tumor to identify personal neoantigens. The ongoing Phase 1 trial is designed to evaluate the safety, tolerability and preliminary clinical immunological activity of ADXS-NEO alone (Part A) and in combination with anti-PD-1 antibody therapy (Part B) in subjects with certain types of advanced or metastatic solid tumors. Part C of the trial will be an expansion of the combination therapy arm and will be initiated based on emerging data from the first two parts of the trial.

Preliminary findings from the ADXS-NEO Phase 1 study include the following:

Substantial anti-tumor immunity, including T cell responses to neoantigens and antigen spreading, was observed within one week of first dose at both dose levels
Dosing of ADXS-NEO at 1×108 colony forming units (CFU) has been well-tolerated in two patients
ADXS-NEO dosed at 1×109 CFU was beyond the maximum tolerated dose (MTD)
Reversible Grade 3 hypoxia (n=2) and Grade 3 hypotension (n=1) were dose-limiting toxicities (DLTs)
Manufacturing of ADXS-NEO, comprised of 40 personal neoantigens, was successfully completed within seven to eight weeks for each subject
"Advaxis’ ADXS-NEO is a novel, personalized vaccine encoding mutations specific to an individual patient’s tumor designed to induce anti-cancer immunity. Four patients have been evaluated across two dose levels thus far in this ongoing clinical trial. While dose level 1 (1×109 CFU) was determined to be above the MTD, dose level -1a (1×108 CFU) has been safe and well tolerated in two patients treated to date, with primarily Grade 1 and Grade 2 chills, fever and tachycardia. Substantial immunological activity was observed across both dose levels, including rapid neoantigen-specific CD8+ T cell generation, which is essential for potential clinical benefit. We look forward to the planned combination therapy arm with checkpoint inhibitors," said Dr. Hecht.

"The patients being evaluated for safety and tolerability in Part A all have late-stage disease and have been treated with numerous prior therapies. As a result, we did not expect to observe significant clinical activity in this cohort," said Andres Gutierrez, M.D. Ph.D., Chief Medical Officer of Advaxis. "Nevertheless, we have seen some encouraging clinical signals to date, including one patient at dose level 1 with non-small cell lung cancer who achieved stable disease after only two doses of ADXS-NEO, which is consistent with rapid immune activation." He concluded, "This is the first presentation of clinical data from our ADXS-NEO program at a major medical conference. We are continuing to enroll subjects and gather additional clinical and immune correlative data, and plan to share updated data from this study throughout this year."

The full abstract is available at www.advaxis.com and the poster will be available on the Company’s website on Sunday, March 31, 2019 at 1:00 p.m. ET.

About ADXS-NEO

ADXS-NEO is an investigational personalized Lm-based immunotherapy designed to generate immune response against mutation-derived tumor-specific neoantigens identified through DNA sequencing of a patient’s own tumor. The program focuses on creating a customized treatment for each patient targeting multiple neoantigens found in a biopsy of the patient’s tumor.