On March 19, 2019 Principia Biopharma Inc. (Nasdaq: PRNB), a late-stage biopharmaceutical company dedicated to bringing transformative oral therapies to patients with significant unmet medical needs in immunology and oncology, reported financial results for the fourth quarter and full year ended December 31, 2018 (Press release, Principia Biopharma, MAR 19, 2019, View Source [SID1234534515]).

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"In 2018, we made progress across all of our programs, in addition to completing a successful initial public offering. We continued the momentum into the new year with presentations at both the American Academy of Dermatology and the Americas Committee for Treatment and Research in Multiple Sclerosis," said Martin Babler, Chief Executive Officer of Principia. "In 2019, we are focusing on the continued clinical development of our assets. We will continue to expand enrollment in our Phase 3 program for PRN1008 around the world. One of our goals this year is to have top-line data from PRN1008 in both the Phase 2 clinical trial in immune thrombocytopenia and the Phase 2 extension trial in pemphigus."

Full Year 2018 and Recent Program Highlights

PRN1008 for the treatment of pemphigus (pemphigus vulgaris (PV) and pemphigus foliaceus (PF))

Announced presentation of positive Phase 2 results as late breaker at 2019 American Academy of Dermatology

Initiated global, randomized, double-blind, placebo-controlled, pivotal, Phase 3 clinical trial, the PEGASUS study, in approximately 120 patients to evaluate PRN1008, using a background treatment of tapering doses of corticosteroids

Initiated Phase 2 extension to the Believe-PV clinical trial increasing the active treatment period from 12 to 24 weeks

Potential Pemphigus Milestones

Phase 2 extension top-line data: fourth quarter of 2019

Phase 3 data: first half of 2022

PRN1008 for the treatment of Immune Thrombocytopenia (ITP)

Received orphan-drug designation from FDA for treatment of ITP

Continued conducting an open-label adaptive Phase 2 trial in up to 24 patients with relapsed primary or secondary ITP

Potential ITP Milestone

Phase 2 top-line data: fourth quarter of 2019

PRN2246/SAR442168 for the treatment of Multiple Sclerosis

Presented positive Phase 1 results at 2019 Americas Committee for Treatment and Research in Multiple Sclerosis

Received $25 million in 2018 related to numerous successful development activities

Potential PRN2246/SAR442168 Milestone

Phase 2 initiation by Sanofi

PRN1371 for the treatment of bladder cancer

Completed Phase 1 dose escalation

Initiated Phase 1 expansion cohort in patients with metastatic urothelial carcinoma

Potential PRN1371 Milestone

Phase 1 dose escalation data: first half of 2019

Immunoproteasome

Reacquired rights to oral immunoproteasome program in March 2019

General Corporate Recent Highlights

Completed initial public offering (IPO) raising approximately $122.2 million in gross proceeds

Completed Series C crossover round raising approximately $50.0 million in gross proceeds. The transaction was led by Cormorant Asset Management, HBM Healthcare Investments, RTW Investments, and Samsara BioCapital in addition to existing investors

Appointed Dolca Thomas, M.D. as Chief Medical Officer. Dr. Thomas has approximately 15 years of industry and medical experience, including most recently with Roche, Pfizer, and Bristol-Myers Squibb

Appointed industry veteran John W. Smither to the Board of Directors and Chairperson of our Audit Committee. Mr. Smither has approximately 20 years of industry and financial experience, and currently serves as CFO of Sienna Biopharmaceuticals, Inc.

Fourth Quarter and Full Year 2018 Financial Results

Cash Position: Cash, cash equivalents, and marketable securities were $180.6 million as of December 31, 2018, compared to $41.1 million as of December 31, 2017. The increase in Principia’s cash position is mainly due to net proceeds of $113.6 million from its IPO and net proceeds of $49.8 million from its Series C financing.

Revenues: Collaboration revenue was $26.1 million for the three months ended December 31, 2018, compared to $3.4 million for the same period in 2017. Collaboration revenue for the full year of 2018 was $69.1 million, compared to $5.2 million for the full year of 2017. The increase was due to the revenue recognition of an upfront payment of $40.0 million received in December 2017 from Sanofi and an upfront payment of $15.0 million received in June 2017 from AbbVie Biotechnology Limited, as well as the revenue recognition of milestone payments totaling $25.0 million received in 2018 from Sanofi, of which $10.0 million were received in the fourth quarter of 2018.

R&D Expenses: Total research and development expenses were $13.7 million for the three months ended December 31, 2018, including stock-based compensation expense of $0.8 million, compared to $7.5 million for the same period in 2017, including stock-based compensation expense of $0.1 million. For the full year of 2018, total research and development expenses were $40.5 million, including stock-based compensation expense of $1.4 million, compared to $25.4 million for full year of 2017, including stock-based compensation expense of $0.5 million. The increase in total research and development expenses was mainly driven by an increase in PRN1008 program costs, attributable to various manufacturing campaigns and the initiation of a global Phase 3 trial in pemphigus in November 2018 and the initiation of an ITP clinical trial in December 2017, as well as an increase in employee related expenses.

G&A Expenses: General and administrative expenses were $4.2 million for the three months ended December 31, 2018, including stock-based compensation expense of $0.6 million, compared to $2.0 million for the same period in 2017, including stock-based compensation

expense of $0.2 million. For the full year of 2018, general and administrative expenses were $11.5 million, including stock-based compensation expense of $1.4 million, compared to $6.4 million for the full year of 2017, including stock-based compensation expense of $0.6 million. The increase in total general and administrative expenses was primarily driven by increased employee related expenses and facility costs.

Net Income (Loss): For the three months ended December 31, 2018, net income was $9.4 million compared to a net loss of $2.8 million for the same period in 2017. For the full year of 2018, net income was $18.2 million, compared to a net loss of $28.7 million for the full year of 2017.

Financial Guidance

The Company anticipates its cash, cash equivalents, and marketable securities will fund operations toward the end of 2020, based on existing planned expenditures.

On March 19, 2019 Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH / TSX: AUP) ("Aurinia" or the "Company") reported its financial results for the fourth quarter and year ended December 31, 2018 (Press release, Aurinia Pharmaceuticals, MAR 19, 2019, View Source [SID1234534506]). Amounts, unless specified otherwise, are expressed in U.S. dollars.

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2018 and Recent Highlights

Notice of Allowance from the United States Patent and Trademark Office ("USPTO") for claims which have the potential to cover voclosporin’s method of use and dosing protocol for lupus nephritis ("LN’) until December 2037.
Phase 2a Dry Eye Study results released in January 2019 demonstrating statistically superior efficacy of voclosporin ophthalmic solution ("VOS") versus Restasis.
AURORA Phase 3 trial in LN completed patient enrollment, ahead of schedule, in September 2018 – on track for top-line data in late 2019.
Phase 2 FSGS study with voclosporin initiated in June 2018 with patient recruitment ongoing.
Cash, cash equivalents, and short-term investments of $125.9 million as of December 31, 2018.
Balance sheet strengthened with additional $30 million raised through ATM facility during Q1 2019.
"The team at Aurinia has made extraordinary progress throughout 2018 by achieving a number of significant clinical milestones with voclosporin, and we are excited for what lies ahead in 2019. In addition to completing enrollment in the AURORA Phase 3 trial ahead of schedule last September, we also released Phase 2a dry eye study results with VOS that we believe further demonstrate the potential of voclosporin", commented Richard M. Glickman, Chief Executive Officer and Chairman of the Board of Aurinia Pharmaceuticals."

Dr. Glickman further commented, "With the recent Notice of Allowance we received from the USPTO for claims covering voclosporin’s method of use and dosing protocol for the treatment of proteinuric kidney diseases including LN, we are very pleased with the additional exclusivity that could extend to December 2037 which I believe provides additional value creating opportunities for our shareholders.

Highlights

USPTO Notice of Allowance

On February 25, 2019, Aurinia announced that it received a Notice of Allowance from the USPTO for claims directed at its novel voclosporin dosing protocol for LN (U.S. patent application 15/835,219, entitled "PROTOCOL FOR TREATMENT OF LUPUS NEPHRITIS").

The allowed claims broadly cover the novel voclosporin individualized flat-dosed pharmacodynamic treatment protocol adhered to and required in both the previously reported Phase 2 AURA-LV trial and the Company’s ongoing Phase 3 confirmatory AURORA trial. Notably, the allowed claims cover a method of modifying the dose of voclosporin in patients with LN based on patient specific pharmacodynamic parameters.

This Notice of Allowance concludes a substantive examination of the patent application at the USPTO, and after administrative processes are completed and fees are paid, is expected to result in the issuance of a U.S. patent with a term extending to December 2037. If the FDA approves the use of voclosporin for LN and the label for such use follows the dosing protocol under the Notice of Allowance, the issuance of this patent will expand the scope of intellectual property protection for voclosporin, which already includes robust manufacturing, formulation, synthesis and composition of matter patents.

AURORA LN Clinical Trials

Aurinia’s Phase 3 clinical trial ("AURORA") is evaluating voclosporin for the treatment of LN, which was initiated in May of 2017, completed enrollment in September 2018. The target enrolment of 324 patients was surpassed due to high patient and investigator demand with 358 LN patients randomized in sites across 27 countries. Top-line data is expected to be available in Q4 2019.

A significant percentage of patients who have completed the AURORA trial are rolling over into the AURORA blinded extension trial ("AURORA 2"). The purpose of AURORA 2 is to assess the long-term benefit/risk of voclosporin in patients with LN; this trial is not a requirement for potential regulatory approval of voclosporin.

Dry Eye Syndrome ("DES")

In July 2018, Aurinia initiated a Phase 2a head-to-head study of voclosporin ophthalmic solution ("VOS") versus Restasis (cyclosporine ophthalmic emulsion) 0.05% for the treatment of moderate to severe DES. This four-week study enrolled a total of 100 patients.

In January 2019 the Company announced results from this study. The study evaluated efficacy, safety and tolerability head to head with Restasis.

VOS showed statistical superiority to Restasis on FDA-accepted objective signs of DES
42.9% of VOS subjects vs 18.4% of Restasis subjects (p=0.0055) demonstrated ≥ 10mm improvement in Schirmer Tear Test ("STT") at Week 4
VOS showed statistical superiority to Restasis in Fluorescein Corneal Staining ("FCS") (p=0.0003)
The primary endpoint of drop discomfort at 1-minute on the first day of therapy showed no statistical difference between the treatment groups, as both groups exhibited low drop discomfort scores
With respect to the primary endpoint of drop discomfort, VOS did not meet the primary endpoint as both drugs were well tolerated and demonstrated less than anticipated drop discomfort. However, secondary outcome measures on efficacy, namely the STT and FCS, demonstrated statistically superior results over Restasis.

Focal Segmental Glomerulosclerosis ("FSGS")

Aurinia initiated a Phase 2 proof-of-concept study for FSGS in June 2018 and is currently in the process of enrolling patients with this disease. This proof-of-concept Phase 2 open-label study aims to enroll approximately 20 treatment-naïve patients diagnosed with primary FSGS.

Financial Liquidity at December 31, 2018

At December 31, 2018, Aurinia had cash, cash equivalents and short-term investments of $125.9 million compared to $173.5 million of cash and short-term investments at December 31, 2017. Net cash used in operating activities was $51.6 million for the year ended December 31, 2018, compared to $41.2 million for the year ended December 31, 2017.

At-The-Market ("ATM") Facility

On November 30, 2018, Aurinia entered into an open market sale agreement with Jefferies LLC pursuant to which the Company could from time to time sell, through ATM offerings, common shares that would have an aggregate offering amount of up to $30 million. Subsequent to year-end, the ATM was fully utilized. Aurinia received gross proceeds of $30 million and issued 4.6 million common shares. The Company incurred share issue costs of $1.2 million including a 3% commission and professional and filing fees related to the ATM offering.

February 14, 2014 Warrant Exercises

The derivative warrants outstanding related to the February 14, 2014 private placement offering were exercised subsequent to December 31, 2018. Certain holders of these warrants elected the cashless exercise option and the Company issued 687,000 common shares on the cashless exercise of 1.3 million warrants. Three holders of 464,000 warrants exercised these warrants for cash, at a price of $3.2204. We received cash proceeds of $1.5 million and issued 464,000 common shares.

The Company believes, based on its current plans that Aurinia has sufficient financial resources to fund the existing LN program, including the AURORA trial and the AURORA 2 extension trial, complete the NDA submission to the FDA, conduct the ongoing Phase 2 study for FSGS, commence additional DES studies and fund operations into mid-2020.

Financial Results for the Fourth Quarter Ended December 31, 2018

The Company reported a consolidated net loss of $14.6 million or $0.17 per common share for the fourth quarter ended December 31, 2018, as compared to a consolidated net loss of $3.3 million or $0.04 per common share for the fourth quarter ended December 31, 2017.

The loss for the fourth quarter ended December 31, 2018 reflected an increase of $593,000 in the estimated fair value of derivative warrant liabilities compared to a reduction of $9.0 million in the estimated fair value of derivative warrant liabilities for the fourth quarter ended December 31, 2017.

The net loss before this non-cash change in estimated fair value of derivative warrant liabilities was $13.9 million for the fourth quarter ended December 31, 2018 compared to $12.3 million for the same period in 2017.

Research and development ("R&D") expenses increased to $10.8 million in the fourth quarter of 2018, compared to $8.7 million in the fourth quarter of 2017. The increase in these expenses primarily reflected costs incurred for the AURORA 2 extension trial, the DDI study and the FSGS and DES Phase 2 studies which were newly enrolled studies in 2018.

Corporate, administration and business development expenses increased to $3.5 million for the fourth quarter of 2018, compared to $3.1 million for the fourth quarter of 2017, reflecting higher professional fees incurred during the fourth quarter of 2018.

Financial Results for the Year Ended December 31, 2018

For the year ended December 31, 2018, Aurinia recorded a consolidated net loss of $64.1 million or $0.76 per common share, which included a non-cash increase of $10.0 million related to the estimated fair value annual adjustment of derivative warrant liabilities at December 31, 2018. After adjusting for this non-cash impact, the net loss before this change in estimated fair value of derivative warrant liabilities was $54.1 million.

This compared to a consolidated net loss of $70.8 million or $0.92 per common share in 2017, which included a non-cash increase of $23.9 million in the estimated fair value of derivative warrant liabilities for the year ended December 31, 2017. After adjusting for this non-cash impact for 2017, the net loss before this change in estimated fair value of derivative warrant liabilities was $46.9 million.

The change in the revaluation of the derivative warrant liabilities is primarily driven by the change in our share price. Our share price of $6.82 was significantly higher at December 31, 2018, compared to our share price of $4.53 at December 31, 2017. This increase in our share price resulted in large increases in the estimated fair value of derivative warrant liabilities for each of 2018 and 2017. The derivative warrant liabilities will ultimately be eliminated on the exercise or forfeiture of the warrants and will not result in any cash outlay by Aurinia.

We incurred R&D expenses of $41.4 million for the year ended December 31, 2018, as compared to $33.9 million for the year ended December 31, 2017. The increase in R&D expenses in 2018 primarily reflected costs related to the AURORA 2 extension trial, the DDI study and the FSGS and DES Phase 2 studies.

We incurred corporate, administration and business development expenses of $13.7 million for the year ended December 31, 2018, as compared with $12.1 million for the same period in fiscal 2017. The increase in these expenses reflected higher corporate activity levels overall, and higher personnel compensation costs which included a non-cash stock compensation expense of $4.2 million for the year ended December 31, 2018, compared to $3.2 million for the year ended December 31, 2017.

The audited financial statements and the Management’s Discussion and Analysis for the year ended December 31, 2018, are accessible on Aurinia’s website at www.auriniapharma.com, on SEDAR at www.sedar.com or on EDGAR at www.sec.gov/edgar.

Aurinia will host a conference call and webcast to discuss the fourth quarter and year ended December 31, 2018 financial results today, Tuesday, March 19, 2019 at 4:30 p.m. ET. This event can be accessed on the investor section of the Aurinia website at www.auriniapharma.com.

On March 19, 2019 Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of stem cell transplant to more patients, reported financial results and business highlights for the fourth quarter and full year ended December 31, 2018 (Press release, Magenta Therapeutics, MAR 19, 2019, View Source [SID1234534504]).

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"2018 was a transformative year for Magenta, as we progressed our first-in-class programs and achieved multiple clinical and preclinical milestones," said Jason Gardner, D.Phil., Chief Executive Officer and President, Magenta Therapeutics. "As we begin 2019, Magenta is the only company addressing the major barriers to stem cell transplant and gene therapy, with the goal of changing the lives of patients with autoimmune diseases, blood cancers and genetic diseases through curative therapies. We are looking forward to building on this progress as we advance our conditioning, mobilization and cell therapy programs."

Upcoming Anticipated Milestones:

The Company plans to achieve the following key milestones in 2019:

Present preclinical data on C100 anti-CD45 targeted conditioning program in autoimmune diseases and declare development candidate

Present preclinical data on C200 anti-CD117 targeted conditioning in gene therapy, and advance development candidate

Begin Phase 1 study of MGTA-145 first-line mobilization agent in healthy volunteers in the first half of 2019, and present clinical data in the second half of 2019

Present additional clinical data from the Phase 2 study of MGTA-456 in IMDs

Recent Business Highlights:

Updated preclinical data for C100 conditioning program showed potent depletion of hematopoietic stem cells and immune cells: At the Transplant and Cellular Therapy (TCT) meeting in February 2019, Magenta presented data from its C100 targeted conditioning program, showing potent stem and immune cell depletion with an anti-CD45 amanitin antibody-drug conjugate (ADC) that was well tolerated at efficacious doses in non-human primates. The Company expects to declare a development candidate for this program in 2019 and intends to develop C100 in both autoimmune diseases and blood cancers.

Declared development candidate in C200 targeted conditioning program and presented preclinical data: At the end of 2018, Magenta declared a development candidate in its C200 targeted conditioning program, which is designed to deplete stem cells in the bone marrow. The Company presented data at the TCT meeting in February 2019 on the development candidate, an anti-CD117 amanitin ADC, showing that it potently and selectively depleted hematopoietic stem cells in non-human primates while preserving the immune system. The ADC was well tolerated at the efficacious doses. Magenta has begun investigational new drug (IND)-enabling studies with this ADC and plans to develop it as a conditioning agent for stem cell gene therapy, in patients with genetic disorders such as sickle cell disease, where current conditioning regimens are toxic.

Updated preclinical data for MGTA-145 first-line mobilization therapy showed differentiated efficacy from standard of care: In data presented at the TCT meeting in February 2019, Magenta showed that a single dose of MGTA-145 plus plerixafor mobilized two to three times more stem cells in non-human primates than a multi-day regimen of current standard of care, G-CSF. The cells mobilized with MGTA-145 plus plerixafor rapidly engrafted in non-human primates following autologous transplant. A subset of the MGTA-145-mobilized cells from non-human primates was also shown to suppress graft-vs.-host-disease and extend survival in preclinical models. The company expects to initiate a Phase 1 study of MGTA-145 in the first half of 2019 and share clinical results in the second half of 2019.

Updated clinical data for MGTA-456 cell therapy showed early signs of clinical benefit in IMDs: Magenta presented updated data from the Phase 2 clinical study of MGTA-456 in patients with IMDs at the TCT meeting in February 2019. Patients with cerebral adrenoleukodystrophy (cALD) treated with MGTA-456 in the study showed persistent resolution of brain inflammation and stable disease scores. Patients with Hurler syndrome treated with MGTA-456 showed correction of enzyme deficiency and decrease in toxic metabolites. These early clinical benefits are associated with improved long-term disease outcomes in patients undergoing stem cell transplant for IMDs. The Company will next present data from this study at the American Academy of Neurology (AAN) annual meeting in May. A Phase 2 investigator-initiated study of MGTA-456 in blood cancers began in December 2018. After careful review of comprehensive transplant outcomes data in sickle cell disease, the Company will evaluate development of MGTA-456 in sickle cell disease as less toxic conditioning becomes available.

Fourth Quarter Financial Results:

Cash Position: Cash, cash equivalents and marketable securities as of December 31, 2018, were $142.6 million compared to $51.4 million on December 31, 2017. The increase is primarily driven by net proceeds from the $52.2 million Series C preferred stock financing completed in April 2018, and net proceeds of $89.9 million from Magenta’s IPO completed in June 2018, offset by $57.6 million in net loss during 2018. Magenta anticipates that its cash, cash equivalents and marketable securities will be sufficient to fund operations and capital expenditures through 2020 on the Company’s current business plan.

Research and Development Expenses: Research and development (R&D) expenses were $12.4 million in the fourth quarter of 2018, compared to $5.6 million for the same period in 2017. The increase was primarily due to increased costs related to drug discovery efforts in our conditioning programs, preclinical costs, toxicology studies and manufacturing to support our mobilization program, the advancement of the MGTA-456 Phase 2 clinical trial, continued progression of the Company’s pipeline and increased costs associated with the growth of the Company.

General and Administrative Expenses: General and administrative (G&A) expenses were $5.5 million for the fourth quarter of 2018, compared to $2.6 million for the same period in 2017. The increase was primarily due to increased G&A personnel and facility costs associated with the growth of the Company.

Net Loss: Net loss was $16.7 million for the fourth quarter of 2018, compared to net loss of $8.0 million for the same period in 2017.

On March 19, 2019 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that six abstracts highlighting progress in the Rubraca clinical development and lucitanib preclinical research programs will be presented at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place March 29 – April 3 in Atlanta (Press release, Clovis Oncology, MAR 19, 2019, View Source [SID1234534502]).

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The accepted abstracts summarize multiple clinical trials and nonclinical research in which Rubraca is being studied as single agent and combination therapy in a variety of solid tumor types including pancreatic, ovarian, bladder and prostate. In addition, one abstract summarizes ongoing nonclinical research for lucitanib.

"We are actively evaluating the potential utility of Rubraca and lucitanib in a wide range of solid tumors," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We know that many healthcare professionals and patients are hopeful about the role that these therapies may play in treating these cancers, and we are pleased to share our latest updates at this year’s AACR (Free AACR Whitepaper) meeting."

The five Clovis Oncology-sponsored presentations and one presentation of an investigator-initiated trial comprise:

Abstract CT234 – A Phase II, single arm study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic mutation in BRCA1, BRCA2 or PALB2

Presenter: Kim A. Reiss Binder
Session: CTMS03 Developmental Therapeutics: Clinical Results of Novel Agents
Date/Time: April 2, 2019, 3:35 – 3:50 PM EDT
Location: Marcus Auditorium- Bldg. A-GWCC
Abstract 727 (Poster 1) – Comprehensive genomic profiling of >1000 plasma and tumor tissue samples from metastatic castration-resistant prostate cancer (mCRPC) patients gives insight into targeted treatment strategies

Presenter: Foad Green
Session: Molecular and Cellular Biology/Genetics; Cancer Genomics 1
Date/Time: Sunday, March 31, 2019 from 1:00 – 5:00 PM EDT
Location: Exhibit Hall B, Section 33
Abstract 1214 (Poster 11) – Enhancement of anti-PD-1 antitumor efficacy in syngeneic preclinical models by the angiogenesis inhibitor lucitanib

Presenter: Rachel L. Dusek
Session: Experimental and Molecular Therapeutics; Cancer Immunotherapy
Date/Time: Monday, Apr 1, 2019 8:00 AM – 12:00 PM EDT
Location: Exhibit Hall B, Section 10
Abstract 3888 (Poster 8) – Intracranial evaluation of the in vivo pharmacokinetics, brain distribution, and efficacy of rucaparib in BRCA-mutant, triple-negative breast cancer

Presenter: Minh Nguyen
Session: Experimental and Molecular Therapeutics; Pharmacokinetics and Pharmacodynamics / Preclinical Toxicology
Date/Time: Tuesday, Apr 2, 2019 1:00 – 5:00 PM
Location: Exhibit Hall B, Section 13
Abstract CT158 (Poster 2) – ATHENA (GOG-3020/ENGOT-ov45): a randomized, double-blind, placebo-controlled, Phase III study of rucaparib + nivolumab following front-line platinum-based chemotherapy in ovarian cancer

Presenter: Shannon N. Westin
Session: Phase I-III Trials in Progress: Part 2
Date/Time: Tuesday, Apr 2, 2019 8:00 AM – 12:00 PM EDT
Location: Exhibit Hall B, Poster Section 17
Abstract CT179 (Poster 23) – ATLAS: A Phase II, open-label study of rucaparib in patients with locally advanced or metastatic urothelial carcinoma

Presenter: Petros Grivas
Session: Phase I-III Trials in Progress: Part 2
Date/Time: Tuesday Apr 2, 2019 8:00 AM – 12:00 PM EDT
Location: Exhibit Hall B, Poster Section 17
The five Clovis-sponsored posters will be available online at View Source at once they are presented at the meeting.

About Rubraca (rucaparib)

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian, metastatic castration-resistant prostate, and bladder cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Rubraca U.S. FDA Approved Indications

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Rubraca is indicated as monotherapy for the treatment of adult patients with deleterious BRCA mutations (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies and selected for therapy based on an FDA-approved companion diagnostic for Rubraca.

Select Important Safety Information

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) occur uncommonly in patients treated with Rubraca, and are potentially fatal adverse reactions. In approximately 1100 treated patients, MDS/AML occurred in 12 patients (1.1%), including those in long-term follow-up. Of these, five occurred during treatment or during the 28-day safety follow-up (0.5%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 28 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA-damaging agents. Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1).

Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose (see Dosage and Administration [2.2] in full Prescribing Information) and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks, or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample cytogenetic analysis. If MDS/AML is confirmed, discontinue Rubraca.

Based on its mechanism of action and findings from animal studies, Rubraca can cause fetal harm when administered to a pregnant woman. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca.

Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1–4) were nausea (76%), fatigue/asthenia (73%), abdominal pain/distention (46%), rash (43%), dysgeusia (40%), anemia (39%), AST/ALT elevation (38%), constipation (37%), vomiting (37%), diarrhea (32%), thrombocytopenia (29%), nasopharyngitis/upper respiratory tract infection (29%), stomatitis (28%), decreased appetite (23%) and neutropenia (20%).

Most common laboratory abnormalities in ARIEL3 (≥ 25%; Grade 1–4) were increase in creatinine (98%), decrease in hemoglobin (88%), increase in cholesterol (84%), increase in alanine aminotransferase (ALT) (73%), increase in aspartate aminotransferase (AST) (61%), decrease in platelets (44%), decrease in leukocytes (44%), decrease in neutrophils (38%), increase in alkaline phosphatase (37%) and decrease in lymphocytes (29%).

Most common adverse reactions in Study 10 and ARIEL2 (≥ 20%; Grade 1–4) were nausea (77%), asthenia/fatigue (77%), vomiting (46%), anemia (44%), constipation (40%), dysgeusia (39%), decreased appetite (39%), diarrhea (34%), abdominal pain (32%), dyspnea (21%) and thrombocytopenia (21%).

Most common laboratory abnormalities in Study 10 and ARIEL2 (≥ 35%; Grade 1–4) were increase in creatinine (92%), increase in alanine aminotransferase (ALT) (74%), increase in aspartate aminotransferase (AST) (73%), decrease in hemoglobin (67%), decrease in lymphocytes (45%), increase in cholesterol (40%), decrease in platelets (39%) and decrease in absolute neutrophil count (35%).

Co-administration of Rubraca can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring. Because of the potential for serious adverse reactions in breast-fed children from Rubraca, advise lactating women not to breastfeed during treatment with Rubraca and for 2 weeks after the last dose. You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Clovis Oncology, Inc. at 1-844-258-7662.

Click here or full Prescribing Information and additional Important Safety Information.

Rubraca ▼ (rucaparib) EU Authorized Use and Important Safety Information

Rucaparib is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Rucaparib is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Summary warnings and precautions: Haematological toxicity: Patients should not start Rubraca until they have recovered from haematological toxicities caused by previous chemotherapy (≤ CTCAE Grade 1). Complete blood count testing prior to starting treatment with Rubraca and monthly thereafter is advised. Rubraca should be interrupted or dose reduced and blood counts monitored weekly until recovery for the management of low blood counts. Myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML): If MDS/AML is suspected, the patient should be referred to a haematologist for further investigation. If MDS/AML is confirmed, Rubraca should be discontinued. Photosensitivity: Patients should avoid spending time in direct sunlight as they may burn more easily. When outdoors, patients should wear protective clothing and sunscreen with SPF of 50 or greater. Gastrointestinal toxicities: Low grade (CTCAE Grade 1 or 2) nausea and vomiting may be managed with dose reduction or interruption. Additionally, antiemetics may be considered for treatment or prophylaxis.

Click here to access the current Summary of Product Characteristics. Healthcare professionals should report any suspected adverse reactions via their national reporting systems.

About Lucitanib

Lucitanib is an oral, potent inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDFGRα/β) and fibroblast growth factor receptors 1 through 3 (FGFR1-3).

Emerging clinical data support the combination of angiogenesis inhibitors and immunotherapy to increase effectiveness in multiple cancer indications. Angiogenic factors, such as vascular endothelial growth factor (VEGF), are frequently up-regulated in tumors and create an immunosuppressive tumor microenvironment. Use of antiangiogenic drugs reverses this immunosuppression and can augment response to immunotherapy.

Lucitanib is an unlicensed medical product.

On March 19, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) approved Tecentriq (atezolizumab), in combination with carboplatin and etoposide (chemotherapy), for the initial (first-line) treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) (Press release, Hoffmann-La Roche, MAR 19, 2019, View Source [SID1234534499]). This approval is based on results from the Phase III IMpower133 study, which showed that Tecentriq in combination with chemotherapy helped people live significantly longer compared to chemotherapy alone (median overall survival [OS]=12.3 vs. 10.3 months; hazard ratio [HR]=0.70, 95% CI: 0.54–0.91; p=0.0069) in the intention-to-treat (ITT) population.[1] The Tecentriq-based combination also significantly reduced the risk of disease worsening or death (progression-free survival, PFS) compared to chemotherapy alone (PFS=5.2 versus 4.3 months; HR=0.77, 95% CI: 0.62-0.96; p=0.017). Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of Tecentriq.

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"Tecentriq is the first cancer immunotherapy approved for the initial treatment of extensive-stage small cell lung cancer, which is especially difficult to treat," said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head of Global Product Development. "Until now, there have been limited treatment advances for this disease, and we are excited to bring a potential new standard of care to patients that has been shown to improve survival compared to chemotherapy.

Results from the Phase III IMpower133 study were simultaneously presented at the 2018 World Conference on Lung Cancer (WCLC) and published in The New England Journal of Medicine.

In the US, Tecentriq is approved in combination with Avastin (bevacizumab), paclitaxel and carboplatin (chemotherapy), for the initial (first-line) treatment of adults with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumour aberrations. In Europe, the Tecentriq and Avastin combination is approved for the initial treatment of people with metastatic non-squamous NSCLC, including people with EGFR mutant or ALK genomic tumour aberrations after failure of appropriate targeted therapies. Tecentriq is also approved by the FDA to treat adults with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumour aberrations should have disease progression on FDA approved therapy for NSCLC harbouring these aberrations prior to receiving Tecentriq.

About the IMpower133 study
IMpower133 is a Phase III, multicentre, double-blinded, randomised placebo-controlled study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (carboplatin and etoposide) vs. chemotherapy (carboplatin and etoposide) alone in chemotherapy-naïve adults with ES-SCLC.

The study enrolled 403 people who were randomised equally (1:1) to receive:

Tecentriq in combination with carboplatin and etoposide (Arm A), or
Placebo in combination with carboplatin and etoposide (Arm B, control arm)
During the treatment-induction phase, people received treatment on 21-day cycles for four cycles, followed by maintenance with Tecentriq or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). Treatment could be continued until persistent radiographic PD or symptomatic deterioration was observed.

The co-primary endpoints were progression-free survival (PFS) as determined by the investigator using RECIST v1.1 and OS in the ITT population.

A summary of the ITT data from the IMpower133 study that support this approval is included below.[1]

Tecentriq in combination with chemotherapy helped people live significantly longer compared to chemotherapy alone (OS=12.3 vs. 10.3 months; HR=0.70, 95% CI: 0.54-0.91; p=0.0069) in the ITT population.
The Tecentriq-based combination also significantly reduced the risk of disease worsening or death compared to chemotherapy alone (PFS=5.2 vs. 4.3 months; HR=0.77; 95% CI: 0.62-0.96; p=0.017).
Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of Tecentriq. Serious adverse reactions occurred in 37% of people receiving Tecentriq plus chemotherapy compared to 35% of people receiving chemotherapy alone. The most common adverse reactions (≥20%) in people receiving Tecentriq plus chemotherapy were feeling tired or weak (fatigue/asthenia; 39%), nausea (38%), hair loss (alopecia; 37%), decreased appetite (27%) and constipation (26%) and vomiting (20%).
About SCLC
Lung cancer is the leading cause of cancer death globally.[2] Each year 1.76 million people die as a result of the disease; this translates into more than 4,800 deaths worldwide every day.[2] Lung cancer can be broadly divided into two major types: NSCLC and SCLC, with SCLC accounting for approximately 15% of all lung cancer cases.[3]

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. Currently, Roche has nine Phase III lung cancer studies evaluating Tecentriq alone or in combination with other medicines.

In the United States Tecentriq in combination with nab-paclitaxel is approved for treatment of PD-L1-positive metastatic triple-negative breast cancer; and in combination with Avastin and chemotherapy for the initial treatment of people with metastatic non-squamous NSCLC. In the Europe Union, the non-squamous NSCLC indication includes people with EGFR mutant or ALK genomic tumour aberrations after failure of appropriate targeted therapies. Tecentriq is also approved in the European Union, United States and more than 85 countries for people with previously treated metastatic non-small cell lung cancer (NSCLC) and for certain types of untreated or previously treated metastatic urothelial carcinoma who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer. By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.

To learn more about the Roche approach to cancer immunotherapy please follow this link: View Source