On March 29, 2019 CASI Pharmaceuticals, Inc. (Nasdaq: CASI), a U.S. pharmaceutical company with a platform to develop and accelerate the launch of pharmaceutical products and innovative therapeutics in China, U.S., and throughout the world, reported financial results for the fourth quarter and year ended December 31, 2018 and provided a review of recent accomplishments and anticipated upcoming milestones (Press release, CASI Pharmaceuticals, MAR 29, 2019, View Source [SID1234534779]).

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Wei-Wu He, Ph.D., Executive Chairman of CASI Pharmaceuticals, commented, "The fourth quarter of 2018 capped a successful year for CASI with the NMPA marketing approval of EVOMELA, which is used as a conditioning treatment prior to stem cell transplantation and offers palliative treatment for multiple myeloma patients for whom oral therapy is not appropriate. Our commercialization team is laying the ground work to prepare for its launch in China which we anticipate will commence in mid-2019."

Dr. He continued, "We kicked off the first quarter of 2019 with the NMPA’s Clinical Trial Application (CTA) approval of confirmatory registration trials for both ZEVALIN, a CD20-directed radiotherapeutic antibody primarily indicated for patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin’s lymphoma, and MARQIBO, a formulation of vincristine sulfate for the treatment of patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia.

CASI Pharmaceuticals, Inc. / 9620 Medical Center Drive / Suite 300 / Rockville, MD 20850

Phone 240.864.2600 / Fax 301.315.2437

Chinese patients suffering from these three distinct hematology oncology malignancies currently have limited therapeutic alternatives available to them; we aim to make each of these products broadly accessible for patients and will continue strategically evaluating additional U.S. FDA-approved products that potentially complement our burgeoning hematology oncology portfolio in China. To further that end, we established CASI Pharmaceuticals (Wuxi) Co. Ltd. in order to build a GMP manufacturing plant in Wuxi, China which is scheduled to break ground in 2019. We look forward to advancing our pipeline, including the selected products in our ANDA portfolio, and expect to further expand our pipeline through in-licensing and acquisitions."

Full Year and Recent Business Highlights

·Announced exclusive distribution partnership for the distribution of melphalan hydrochloride for injection (EVOMELA) in China – In March 2019, efforts to ramp up EVOMELA’s launch in China prompted the announcement that China Resources Guokang Pharmaceuticals Co., Ltd. (CRGK) will be the Company’s sole distributor in China. The Company will maintain responsibility for direct marketing and sales. EVOMELA will be used in the treatment of multiple myeloma patients in China where there is currently no form of melphalan available to patients. The distribution agreement comes on the heels of the NMPA’s marketing approval for EVOMELA previously announced in December 2018.
· Announced NPMA marketing approval of EVOMELA – In December 2018, the Company announced the NMPA’s marketing approval of EVOMELA. This is the first of CASI’s pipeline assets to be approved under the NMPA’s priority review guidelines which accelerates approval for medicines that meet certain requirements identified by the Agency. The Company will conduct a post-marketing trial. In the case of EVOMELA, NMPA’s priority review and approval was granted to CASI because there is currently no form of melphalan available in China to treat multiple myeloma patients.
Announced NMPA approval of CTAs to conduct confirmatory registration trials for ibritumomab tiuxetan (ZEVALIN) and vincristine sulfate LIPOSOME injection (MARQIBO) – In February and March 2019, the Company announced NMPA approvals of CASI’s clinical trial applications (CTA) to conduct confirmatory registration trials for ZEVALIN and MARQIBO, respectively. ZEVALIN is indicated for relapsed or refractory, low-grade or follicular B-cell non-Hodgkin’s lymphoma and MARQIBO is indicated for Philadelphia chromosome-negative (Ph‒) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following two or more anti-leukemia therapies.
·Announced plans to build GMP manufacturing site in Wuxi, China – In November 2018, the Company announced that it established CASI Pharmaceuticals (Wuxi) Co., Ltd. to build its own GMP manufacturing site in Wuxi, China. The site is strategically located in The Wuxi Huishan Economic Development Zone which is a leading science and technology innovation center in the region. The Company plans to break ground this year.
·Announced acquisition of an additional HBV ANDA from Laurus Labs to build HBV therapeutic specialty – In October 2018, CASI announced that it acquired tenofovir disoproxil fumarate (TDF) which is indicated for the treatment of hepatitis B virus (HBV).

·Announced key new hires for China and U.S. operations – In 2018, the Company announced key new hires to both CASI locations in Beijing, China and Rockville, MD, U.S.A. in order to support the Company as it continues to grow and commercialize. In September the Company appointed George Chi, CPA, CFA, as CASI’s Chief Financial Officer, and in October, the Company appointed Larry Zhang as President of CASI (Beijing) Pharmaceuticals Co., Ltd., the Company’s operating subsidiary in China.

Fourth Quarter and Full Year 2018 Financial Highlights

R&D Expenses:

Research and development (R&D) expenses for the year ended December 31, 2018 were $8.5 million compared to $7.6 million in 2017, an increase of $0.9 million. The increase in 2018 reflects a $1.1 million increase in regulatory related services, primarily associated with our acquired ANDAs in 2018; a $1.3 million increase in amortization expense due to ANDAs acquired in 2018; and a $1.0 million increase in personnel costs due to new employees hired in 2018, offset by $2.7 million in higher costs associated with the quality testing phase of the NMPA regulatory review of ZEVALIN and EVOMELA in 2017.

R&D expenses for the quarter ended December 31, 2018 were $3.3 million compared to $3.8 million in 2017, a decrease of $0.5 million. The decrease in R&D expenses primarily reflects $2.3 million in higher costs associated with the quality testing phase of the NMPA regulatory review of ZEVALIN and EVOMELA in 2017, offset by $0.8 million higher regulatory services associated with our acquired ANDAs in 2018, $0.5 million more of personnel costs, and $0.4 million amortization expense associated with our ANDAs acquired in 2018.

G&A Expenses:

General and administrative (G&A) expenses for the year ended December 31, 2018 were $18.0 million compared to $3.2 million in 2017. The increase of $14.8 million in G&A over the prior year primarily reflects an increase of $5.0 million in non-cash stock compensation expense largely attributed to stock options issued to the Company’s Executive Chairman, an increase in salary, benefits and recruitment expense in China, primarily related to sales and marketing efforts to prepare for the anticipated launch of the Company’s first commercial product in China, as well as other G&A functions. There were also increased costs associated with business development related to exploratory acquisition activities, investor and public relations activities, and an increase in legal and other professional services fees during 2018.

G&A expenses for the quarter ended December 31, 2018 were $5.8 million compared to $1.2 million in 2017. The increase in G&A over the prior period primarily reflects the increase in non-cash stock compensation expense of $2.0 million, an increase in personnel costs, primarily in China, and increases in consulting and professional services fees during the 2018 period.

Net Loss:

The net loss for the year ended December 31, 2018 was ($27.5 million), or ($0.32) per share, compared with a net loss of ($10.8 million) or ($0.18) per share in 2017. The larger net loss for both periods is primarily due to the non-cash stock-based compensation expense for stock options issued during 2018, costs associated with the technology transfer activities and regulatory support for our ANDA portfolio, the write-off of approximately $0.7 million in January 2018 due to acquired in-process R&D primarily related to ANDAs not approved by the FDA, and increased costs associated with G&A functions, including employment costs for sales and marketing efforts, increased business development related to exploratory acquisition efforts and investor relations activities, higher professional service fees, and administrative fees associated with the Company’s September 2018 financing.

The Company reported a net loss of ($9.3 million), or ($0.1) per share, for the quarter ended December 31, 2018. This compares with a net loss of ($5.0 million), or ($0.08) per share for the fourth quarter of 2017. The increase in net loss is primarily due to increases in non-cash stock compensation expense, personnel costs, and consulting and professional fees during the 2018 period compared to the 2017 period.

As of December 31, 2018, CASI had cash and cash equivalents of approximately $84.2 million.

Further information regarding the Company, including its Annual Report on Form 10-K for the year ended December 31, 2018, can be found at www.casipharmaceuticals.com.

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.