On February 21, 2018 TG Therapeutics, Inc. (NASDAQ:TGTX) reported the publication of the results from the Phase 1 first-in-human study of umbralisib (TGR-1202), the Company’s novel once-daily PI3K delta inhibitor, in The Lancet Oncology (Press release, TG Therapeutics, FEB 21, 2018, View Source [SID1234524106]). The paper includes safety and efficacy information from 90 patients with relapsed or refractory b-cell malignancies, including patients with Chronic Lymphocytic Leukemia (CLL) and various forms of lymphoma treated with single agent umbralisib. In this study, umbralisib was well tolerated with a favorable safety profile distinct from prior generation PI3K delta inhibitors. Grade 3/4 immune mediated AEs commonly associated with other PI3K delta inhibitors were limited, with transaminitis occurring in 3 patients ( < 3%), and pneumonia and colitis in 2 patients each ( < 2% for each). Notably, both events of colitis occurred at doses exceeding the current Phase 3 dose. Umbralisib was also clinically active with 85% of relapsed or refractory CLL patients achieving an objective response (50% per IWCLL criteria; 35% a partial response with lymphocytosis) and 53% of patients with relapsed or refractory Follicular Lymphoma (FL) achieving an objective response, including 2 patients with a Complete Response (CR).

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These data, in addition to the unique structural attributes and enhanced selectivity profile of umbralisib, are described further in the manuscript entitled, "Umbralisib, a novel PI3K and casein kinase-1 epsilon inhibitor, in relapsed or refractory chronic lymphocytic leukaemia and lymphoma: an open-label, phase 1, dose-escalation, first-in-human study," which was published yesterday in The Lancet Oncology. The online version of the article can be accessed at http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30082-2/fulltext.

Dr. Howard A. Burris, the Chief Medical Officer and Executive Director of the Drug Development Program at the Sarah Cannon Research Institute in Nashville, TN, and lead author stated, "We are pleased to have treated the first patient ever with umbralisib over 5 years ago and believe it has an important place in the treatment landscape for patients with hematologic malignancies. Several patients from this Phase 1 study are still on study today, approaching 5 years of continuous daily therapy, speaking to both the safety and efficacy profile of this unique agent."

Dr. Owen A. O’Connor, Professor of Medicine and Experimental Therapeutics, Director Lymphoid Malignancies at Columbia Presbyterian Medical Center, stated, "Pre-clinically umbralisib has a very unique profile, selectively inhibiting both PI3K delta and CK1 epsilon, as previously described in our Blood paper. The clinical results in this paper support our thesis that the differentiated preclinical profile explains the differences seen in the clinic between umbralisib and the other PI3K delta inhibitors."

"We want to thank Dr. Burris, Dr. O’Connor and all the investigators who participated in this first-in-human Phase 1 trial for umbralisib, which has set the stage for our ongoing pivotal UNITY-CLL and UNITY-NHL trials. With over 1,000 patients treated with umbralisib to date, we and the investigators believe umbralisib is a differentiated, active and more selective PI3K delta inhibitor that exhibits a favorable safety profile as compared to prior generation molecules," stated Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer.

On February 21, 2018 Genmab A/S (Nasdaq Copenhagen: GEN) reported its Annual Report for 2017 (Press release, Genmab, FEB 21, 2018, View Source [SID1234524098]). Below is a summary of business progress and financial performance for the year, and financial outlook for 2018 from the report. The full report is attached as a PDF file and can be found on the investor section of the company’s website, www.genmab.com. An online summary of the report is available at View Source

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2017 ACHIEVEMENTS

Business Progress

Maximize daratumumab progress

EMA decision & launch in 2nd line + multiple myeloma (MM) relapsed / refractory setting – Achieved
FDA decision 3rd line MM setting (daratumumab + pomalidomide) – Achieved
Phase III MM interim efficacy analysis in frontline (ALCYONE trial) – Achieved
Start Phase III subcutaneous trial – Achieved
Start trials in solid tumors and non-MM blood cancers – Achieved
Report non-MM clinical data — Expected in 2018
Optimize ofatumumab value

Phase III refractory FL headline results — Expected in 2018
Strengthen differentiated product pipeline

Phase I/II tisotumab vedotin data – Achieved
Progress HuMax-AXL-ADC Phase I/II clinical trial – Achieved
IND/CTA submission HexaBody-DR5/DR5 – Achieved
IND/CTA submission DuoBody-CD3xCD20 – Achieved
Progress pre-clinical pipeline — Achieved
Strengthen partnership portfolio with next generation technologies

Enter new technology collaborations — Not achieved
Progress partnered programs — Achieved
Disciplined financial management

Execute controlled company growth with selective investments in product pipeline — Achieved
Financial Performance

Revenue was DKK 2,365 million in 2017 compared to DKK 1,816 million in 2016. The increase of DKK 549 million, or 30%, was mainly driven by higher DARZALEX royalties under our daratumumab collaboration with Janssen.
Operating expenses increased by DKK 258 million, or 34%, from DKK 763 million in 2016 to DKK 1,021 million in 2017 driven by the advancement of tisotumab vedotin, the addi­tional investment in our product pipeline, and the increase in employees to support the expansion of our pipeline.
Operating income was DKK 1,344 million in 2017 compared to DKK 1,053 million in 2016. The improvement of DKK 291 million, or 28%, was driven by higher revenue, which was partly offset by increased operating expenses.
2017 year end cash position of DKK 5,423 million, an increase of DKK 1,501 million, or 38%, from DKK 3,922 million as of December 31, 2016.
2018 OUTLOOK

MDKK 2018 Guidance 2017 Actual Result
Revenue 2,700 — 3,100 2,365
Operating expenses (1,400) — (1,600) (1,021)
Operating income 1,300 — 1,500 1,344

Revenue
We expect our 2018 revenue to be in the range of DKK 2,700 — 3,100 million, compared to DKK 2,365 million in 2017. Our projected revenue for 2018 consists primarily of DARZALEX royalties of approximately DKK 1,750 million that are based on an estimated USD 2.0 — 2.3 billion of DARZALEX net sales in 2018. We project DARZALEX milestones of approximately DKK 550 million in 2018, consisting primarily of a commercial net sales-based milestone, compared to DKK 1,109 million in 2017. In addition, the 2018 guidance includes the one-time payment from Novartis of approximately DKK 300 million related to the transition of Arzerra from commercial availability to compassionate use programs in non-US markets. The remainder of the revenue consists of cost reimbursement income, Arzerra royalties, and DuoBody milestones.

The overall increase in revenue compared to 2017 is primarily due to a one-time payment from Novartis combined with higher DARZALEX royalties which were partly offset by a decrease in DARZALEX milestones.

Operating Result
We anticipate that our 2018 operating expenses will be in the range of DKK 1,400 — 1,600 million, compared to 2017 operating expenses of DKK 1,021 million. The increase is driven by the advancement of tisotumab vedotin, HuMax-AXL-ADC, HexaBody-DR5/DR5, DuoBody-CD3xCD20, and an increase in employees to support the expansion of our product pipeline.

We expect the operating income for 2018 to be approximately DKK 1,300 — 1,500 million compared to DKK 1,344 million reported for 2017.

More information on the Risks and Assumptions for the 2018 Financial Guidance can be found in the 2017 Annual Report available on our website www.genmab.com.

Conference Call
Genmab will hold a conference call in English to discuss the results for the full year 2017 today, February 21, 2018 at 6.00 pm CET, 5.00 pm GMT or noon EST. To join the call by phone, dial one of the following numbers and ask for the Genmab conference call:

US: + 1 646 828 8156
UK: + 44 330 336 9411
DK: + 45 35 15 81 21

A live and archived webcast of the call and relevant slides will be available at www.genmab.com.

On February 21, 2018 Integra LifeSciences Holdings Corporation (NASDAQ:IART), a leading global medical technology company, reported that it will present at the following healthcare conferences in March (Press release, IsoTis, FEB 21, 2018, View Source [SID1234524099]):

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On Monday, March 5, 2018 at 4:35 p.m. ET, Glenn Coleman, chief financial officer and corporate vice president of International, will present at the Raymond James 39th Annual Institutional Investors Conference in Orlando, FL. The session will be available through live audio webcast and can be accessed from the Investor section of www.integralife.com.

On Tuesday, March 13, 2018 at 8:30 a.m. ET, Glenn Coleman, chief financial officer and corporate vice president of International, will present at the Barclays Global Healthcare Conference in Miami Beach, FL. The session will be available through live audio webcast and can be accessed from the Investor section of www.integralife.com.

On Wednesday, March 21, 2018 at 10:20 a.m. ET, Dan Reuvers, corporate vice president and president of Codman Specialty Surgical, will present at the Oppenheimer 28th Annual Healthcare Conference in New York City.

On February 20, 2018 Sangamo Therapeutics, Inc. (Nasdaq: SGMO) reported that the company will release its fourth quarter and full year 2017 financial results before the market opens on Thursday, February 22, 2018 (Press release, Sangamo Therapeutics, FEB 20, 2018, View Source [SID1234524078]). The press release will be followed by a conference call at 8:00 a.m. ET, which will be open to the public via telephone and webcast. During the conference call, the company will review its financial results and provide a business update.

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The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 4392918. Participants may access the live webcast via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. A conference call replay will be available for one week following the conference call. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 4392918.

On February 20, 2018 H3 Biomedicine Inc., a clinical stage biopharmaceutical company specializing in the discovery and development of next generation cancer therapies using its data molecular science and precision chemistry product engine, reported publication of the discovery and preclinical characterization of H3B-8800, its oral, first-in-class modulator of the SF3b spliceosome complex (Press release, H3 Biomedicine, FEB 20, 2018, View Source [SID1234524068]). The publication highlights the significant anti-tumor activity of H3B-8800 in several in vivo models, including patient-derived xenografts (PDX) of hematological malignancies with recurrent mutations in RNA splicing factor genes that comprise the spliceosome. The H3B-8800 data generated by H3 Biomedicine scientists and collaborators appear in the most recent issue of Nature Medicine and can be accessed online at nature.com/nm. (Seiler M. et al, "H3B-8800, a novel oral splicing modulator, induces lethality in spliceosome-mutant cancers").

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RNA splicing is the biological process by which pre-cursor messenger RNA (pre-mRNA) is edited into a mature mRNA. Splicing factors are proteins that carry out the editing process which is catalyzed by the core spliceosome complex. Mutations in genes encoding for certain of these RNA splicing factors that form the spliceosome are among the most common mutations found in patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) and Chronic Lymphocytic Leukemia (CLL), and occur in subsets of patients with solid tumors.

Despite the high prevalence of these mutations in cancer, no known spliceosome mutation-targeting cancer therapies are approved currently. Based on these promising preclinical data, H3 Biomedicine is a leader in this emerging area of drug discovery, and is currently evaluating H3B-8800 in a Phase 1 clinical trial for patients with AML, MDS and CMML identified by certain splicing factor mutations, and expects to present initial clinical data from this ongoing study in 2018. In 2017, H3B-8800 was granted orphan drug designation for AML and CMML.

"The significant anti-tumor activity shown in this publication demonstrates preclinical proof-of-concept of H3B-8800 in several hematological cancers of high unmet medical need," said Peter Smith, Ph.D., Chief Scientific Officer of H3 Biomedicine, Inc. "No therapies currently exist to affect mutations in the spliceosome in cancers, and H3B-8800 is the first known investigational therapy to modulate and target cancer cells with mutated genes in this complex. The discovery of H3B-8800 highlights the power of the H3 Biomedicine product engine to create highly differentiated investigational therapies to address molecular traits driving cancers in subsets of patients."

The Nature Medicine publication outlines the discovery process led by H3 Biomedicine scientists to create and characterize a highly potent and selective, oral, first-in-class modulator of the SF3b complex to target cancer cells with mutations in RNA splicing factor genes. Data highlights of the publication include:

Dose-dependent anti-leukemic efficacy and splicing modulation of H3B-8800 in a cell line xenograft model of SF3B1-mutant leukemia and significant anti-tumor activity in an SF3B1-mutant AML PDX model;
Anti-leukemic efficacy of H3B-8800 in mice with SRSF2-mutant CMML in which ten-day treatment with H3B-8800 substantially reduced leukemic burden in peripheral blood, spleen and liver;
Differential anti-tumor efficacy in in vitro and in vivo models with mutant genes in the spliceosome compared to wild-type or normal genes in the complex; and
In mechanism of action studies, H3B-8800 was shown to exploit a synthetic lethality imposed by aberrant splicing leading to differential cell killing in tumor cells harboring spliceosome mutations whereas normal cells were substantially less affected. This phenomenon is not shared by other small molecule spliceosome modulators.
H3B-8800 is one of three investigational therapies of H3 Biomedicine in clinical trials. The two additional investigational therapies include:

H3B-6545, an oral, first-in-class ESR1 covalent antagonist targeting wild-type and mutant estrogen receptor in endocrine-therapy resistant metastatic breast cancer patients; and
H3B-6527, an oral, potent and highly selective small molecule covalent inhibitor of FGFR4 for treatment of hepatocellular carcinoma (HCC) patients with overexpression of FGF19.
Portions of the work described in the Nature Medicine publication were originally presented at the 2016 American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting by lead author Silvia Buonamici, Ph. D., Executive Director, Target Biology and Translational Research, H3 Biomedicine.

About H3B-8800
H3B-8800 is a potent, selective, and orally bioavailable small molecule modulator of wild-type and mutant SF3b complex, a key component of the spliceosome. Recurrent heterozygous mutations in several core members (SF3B1, U2AF1, SRSF2, ZRSR2) of the spliceosome have been identified in both hematological malignancies, including myelodysplastic syndrome, acute myelogenous leukemia and chronic lymphocytic leukemia, as well as solid tumors such as skin, lung, breast and pancreatic cancers. Preclinical data indicates that H3B-8800 modulates RNA splicing and shows preferential antitumor activity in a range of spliceosome mutant cancer models. H3 is conducting initial clinical development in patients with hematological malignancies (including MDS, AML, and CMML) that may carry mutations in the core spliceosome genes to assess the safety and preliminary efficacy of H3B-8800.