On August 11, 2020 Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH / TSX:AUP) (Aurinia or the Company) reported financial results for the second quarter ended June 30, 2020 and provided an update on recent operational highlights (Press release, Aurinia Pharmaceuticals, AUG 11, 2020, View Source [SID1234563520]).

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"The acceptance of the voclosporin NDA is a significant step towards our goal of delivering the first FDA-approved therapy specifically for people living with lupus nephritis," commented Peter Greenleaf, President and Chief Executive Officer of Aurinia. "These people suffer from a debilitating, progressive condition that, if not adequately or quickly controlled, leads to life-threatening end-stage renal disease. Despite its high healthcare burden, lupus nephritis has no approved treatments in the United States which we believe has contributed to low awareness of this condition. Aurinia feels the urgency of its mission to change the course of lupus nephritis for this community in need, by combining deep engagement and advocacy efforts with truly innovative medical science."

In addition to preparing for the launch of voclosporin for use as a potential treatment for lupus nephritis (LN), Aurinia continues to explore voclosporin in other proteinuric kidney indications and expects to provide an update on a planned clinical development program later this year. The Company’s development of voclosporin ophthalmic solution (VOS) for dry eye syndrome (DES) remains on track to report topline results from its Phase 2/3 AUDREYTM dose-ranging trial during the fourth quarter of 2020.

Max Colao, Chief Commercial Officer of Aurinia, commented, "As we make progress on our regulatory submission, we’re rapidly building a world class commercial team that is fully resourced and committed to engaging the lupus nephritis community and healthcare professionals. Our strategy for a successful U.S. launch will be executed by deeply experienced Aurinia specialists and led by a proven leadership team. We are driven to make a difference in the lives of the lupus nephritis patients and our team will be launch ready in advance of our PDUFA date of January 22, 2021."

Second Quarter 2020 Highlights

New Drug Application for voclosporin granted Priority Review and January 22, 2021 PDUFA date

In July 2020 the Company announced that the U.S. Food & Drug Administration (FDA) has accepted the filing of its New Drug Application (NDA) for voclosporin, as a potential treatment for LN. The FDA has granted Priority Review for the NDA, which provides an expedited six-month review, and has assigned a Prescription Drug User Fee Act (PDUFA) target action date of January 22, 2021. The FDA has also informed the Company that they are not currently planning to hold an advisory committee meeting to discuss the application. The FDA has the option to change this decision based on review of the pending NDA. There are currently no FDA-approved treatments for LN.

Further supportive data from AURORA pivotal study presented at scientific conferences

The Company presented additional safety data and subgroup analyses from the completed AURORA pivotal trial of voclosporin at two scientific meetings during the quarter: the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) 2020 Virtual Congress and the European League Against Rheumatism (EULAR) 2020 E-Congress. The data further supported the safety profile of voclosporin on an additional measure of kidney function and its clinically meaningful benefits for trial participants across ethnicities and self-reported race. These data were notable for further adding to the evidence supporting voclosporin’s benefit over the standard-of-care with no apparent safety penalty, and its potential to deliver equal clinical benefits for patients of ethnicities or self-reported races disproportionately affected by lupus nephritis.

Phase 2/3 AUDREY Phase 2/3 Clinical Trial of VOS

In June 2020, Aurinia announced it had completed enrollment for the Phase 2/3 AUDREYTM clinical trial evaluating voclosporin ophthalmic solution (VOS) for the potential treatment of DES, a chronic disease estimated to affect more than 16 million people in the United States.

The AUDREYTM trial is a randomized, double-masked, vehicle-controlled, dose-ranging study evaluating the efficacy and safety of VOS in subjects with DES. A total of 509 subjects have been enrolled and randomized into one of four arms with a 1:1:1:1 randomization schedule, in which patients receive either VOS 0.2%, VOS 0.1%, VOS 0.05% or vehicle, dosed twice daily for 12 weeks. The primary outcome measure for the trial is the proportion of subjects with a 10mm or greater improvement in the Schirmer Tear Test (STT) at four weeks. Secondary outcome measures will include STT at other time points, Fluorescein Corneal Staining (FCS) at multiple time points, change in eye dryness, burning/stinging, itching, photophobia, eye pain and foreign body sensation at multiple time points, and additional safety endpoints. AUDREYTM builds on positive exploratory Phase 2 results demonstrating that 0.2% VOS administered twice daily was superior to cyclosporin A 0.05% (Restasis) administered twice daily across all objective endpoints. Top-line results from the AUDREYTM clinical study are anticipated during the fourth quarter of 2020.

Recent Director and Officer Appointments

Appointment of Timothy P. Walbert to the Board

On April 20, 2020, Aurinia announced the appointment of Mr. Walbert to the Board of Directors. Mr. Walbert has nearly 30 years of experience commercializing pharmaceutical products. Mr. Walbert is currently Chairman, President and Chief Executive Officer of Horizon Therapeutics plc. He also served as President, Chief Executive Officer and Director of IDM Pharma, Inc., a public biopharmaceutical company which was acquired by Takeda.

Appointment of Joe Miller as Chief Financial Officer

On April 27, Aurinia appointed Mr. Miller as Chief Financial Officer following the retirement of Mr. Dennis Bourgeault, who served in that role since 1998. Mr. Miller will be responsible for developing and leading the Company’s financial operations to effectively support the Company’s rapid growth.

Financial Liquidity at June 30, 2020 and July Public Offering of Common Shares

All amounts in this press release, unless specified otherwise, are expressed in U.S. dollars.

As of June 30, 2020, Aurinia had cash, cash equivalents and short-term investments of $264.4 million compared to $286.1 million at March 31, 2020 and $306 million at December 31, 2019. Net cash used in operating activities was $22.6 million for the second quarter ended June 30, 2020 compared to $13.3 million for the second quarter ended June 30, 2019.

Following the recently completed $200 million public offering, which closed on July 27, 2020, the Company’s cash, cash equivalents and short term investments totaled approximately $442.06 million at July 31, 2020. The Company believes that it has sufficient financial resources to fund its current plans, which include conducting its ongoing research and development (R&D) programs, completing the NDA submission to the FDA, conducting pre-commercial and launch activities, manufacturing and packaging commercial drug supply required for launch, and fund its supporting corporate and working capital needs through the end of 2022.

Financial Results for Three Months Ended June 30, 2020

The Company reported a consolidated net loss of $29.5 million or $0.26 per Common Share for the second quarter ended June 30, 2020, as compared to a consolidated net loss of $15.9 million or $0.17 per Common Share for the second quarter ended June 30, 2019.

The loss for the second quarter ended June 30, 2020 reflected an increase of $3.0 million in the estimated fair value of derivative warrant liabilities compared to a reduction of $625,000 in the estimated fair value of derivative warrant liabilities for the second quarter ended June 30, 2019. 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 the Company. The outstanding warrants expire on December 28, 2021.

The loss before the change in estimated fair value of derivative warrant liabilities and income taxes was $26.6 million for the second quarter ended June 30, 2020 compared to $16.5 million for the same period in 2019.

R&D expenses decreased to $11.1 million for the second quarter ended June 30, 2020 compared to $11.2 million for the second quarter ended June 30, 2019. The decrease in these expenses primarily reflected higher costs related to the preparation of the NDA submission and related supporting activities, the ongoing VOS Phase 2/3 AUDREYTM trial, the AURORA 2 extension trial and the expansion of the medical affairs team to support the launch of voclosporin partially offset by lower AURORA trial costs as this trial is now complete. Non-cash stock compensation expense charged to R&D also increased to $1.1 million for the second quarter ended June 30, 2020 compared to $749,000 for the comparable period in 2019 reflecting the hiring of a significant number of personnel in 2020 and an increase in the fair value of the stock options granted due to the increase in the Company’s share price.

Corporate, administration and business development expenses increased to $15.5 million for the second quarter of 2020 compared to $4.9 million for the second quarter of 2019. These expenses included the expansion of the commercial team, higher consulting and professional fees, insurance costs, and personnel compensation costs as the corporate organization buildout continued in the second quarter of 2020. Non-cash stock compensation expense charged to corporate, administration and business development also increased to $3.1 million for the second quarter ended June 30, 2020 compared to $1.2 million for the comparable period in 2019 reflecting the hiring of a significant number of personnel in 2020 and an increase in the fair value of the stock options granted due to the increase in the Company’s share price.

Financial Results for Six Months Ended June 30, 2020

For the six months ended June 30, 2020, Aurinia reported a consolidated net loss of $46.1 million or $0.41 per Common Share compared to a consolidated net loss of $28.3 million or $0.31 per common share for the comparable period in 2019.

R&D expenses were $24.9 million for the six months ended June 30, 2020 compared to $21.8 million for the same period in 2019. The increase in these expenses reflected higher costs incurred for the AURORA 2 extension trial, and preparation costs associated with the LN NDA submission partially offset by lower AURORA trial costs as this trial is now complete.

Corporate, administration and business development expenses were $26.6 million for the six months ended June 30, 2020 compared to $8.8 million for the same period in 2019. The increase reflects the same items as noted in the second quarter corporate, administration and business development expenses.

Non-cash stock compensation expense totaled $7.7 million for the six months ended June 30, 2020 as compared with $3.6 million for the same period in 2019 and is included in both research and development and corporate, general and business development expenses.

For the six months ended June 30, 2020 Aurinia recorded a decrease of $6.9 million in the estimated fair value of derivative warrant liabilities compared to a decrease of $2.4 million for the comparable period in 2019.

This press release should be read in conjunction with our unaudited interim condensed consolidated financial statements and the Management’s Discussion and Analysis for the second quarter ended June 30, 2020 which 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 second quarter ended June 30, 2020 financial results today, Tuesday, August 11, 2020 at 4:30 p.m. ET. The webcast can be accessed on the investor section of the Aurinia website at www.auriniapharma.com. To participate in the teleconference please dial +1-877-407-9170 (Toll-free U.S. & Canada).

About Voclosporin

Voclosporin, an investigational drug, is a novel and potentially best-in-class calcineurin inhibitor (CNI) with clinical data in over 2,600 patients across indications. Voclosporin is an immunosuppressant, with a synergistic and dual mechanism of action. By inhibiting calcineurin, voclosporin blocks IL-2 expression and T-cell mediated immune responses and stabilizes the podocyte in the kidney. Voclosporin may result in a more predictable pharmacokinetic and pharmacodynamic relationship (potentially requires no therapeutic drug monitoring), an increase in potency (versus cyclosporine A), and an improved metabolic profile compared to legacy CNIs. Aurinia anticipates that upon regulatory approval, patent protection for voclosporin will be extended in the United States and certain other major markets, including Europe and Japan, until at least October 2027 under the Hatch-Waxman Act and comparable patent extension laws in other countries with anticipated pediatric extension. Further, a U.S. patent has also been issued covering the voclosporin dosing protocol with a term extending to December 2037, if the FDA incorporates the dosing protocol used in both the AURA and AURORA trials into the product label.

On August 11, 2020 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune disease, reported the grant of a new patent (number 10,736,940) entitled "Combined Preparations for the Treatment of Cancer" by the United States Patent Office (Press release, Immutep, AUG 11, 2020, View Source [SID1234563477]).

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This United States patent follows the grant of the corresponding European, Australian and Japanese patents (announced 23 May 2019, 21 June 2019 and 7 May 2020, respectively) and protects Immutep’s intellectual property relating to combined therapeutic preparations comprising its lead active immunotherapy candidate eftilagimod alpha ("efti" or "IMP321") and a chemotherapy agent. The chemotherapy agent is either a platinum-based anti-neoplastic agent, such as oxaliplatin or carboplatin, or a topoisomerase I inhibitor, such as topotecan.

This new patent highlights the ongoing and important steps being taken by the Company to protect its lead product candidate in a range of novel and highly relevant combination formats, in both chemo-immunotherapy and other immunotherapy settings.

The patent expiry date is 25 January 2035 (including 37 days of patent term adjustment).

On August 11, 2020 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) reported its financial results for the first half-year of 2020 (Press release, Evotec, AUG 11, 2020, View Source;announcements/press-releases/p/evotec-se-reports-first-half-year-2020-results-and-corporate-updates-5965 [SID1234563470]).

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OVERALL POSITIVE FINANCIAL PERFORMANCE REFLECTING GROWTH ACROSS ALL BUSINESS LINES
Significant Group revenue growth of 12% to € 231.0 m (H1 2019: € 207.1 m)
Revenue growth in both business segments: EVT Execute revenues up 16% to € 228.2 m (H1 2019: € 196.8 m); EVT Innovate revenues up 8% to € 44.6 m (H1 2019: € 41.2 m)
Adjusted Group EBITDA amounting to € 47.3 m (H1 2019: € 58.2 m)
Increased investments in unpartnered R&D of € 21.6 m (H1 2019: € 18.7 m)
Robust liquidity positon of € 275.7 m (31 December 2019: € 320 m)
No material impact by COVID-19 pandemic on overall financial and strategic development so far; slight delays in conclusion of contracts and milestone achievements

CONVINCING OPERATIONAL PROGRESS
Multiple new and extended drug discovery and development agreements
New 5-year contract with the US Environmental Protection Agency
Just – Evotec Biologics strengthens its position: contract with U.S. Department of Defense to develop and manufacture monoclonal antibodies for treatment and/or prevention of COVID-19 (after period-end)
Construction of first J.POD biologics manufacturing facility in Seattle, WA, USA progressing well
Evotec partner Zogenix received marketing approval from FDA for FINTEPLA; Evotec as supporting long-term partner will supply commercial API (Active Pharmaceutical Ingredients)
Continued progress in co-owned pipeline, despite certain COVID-19 related delays
New QRbeta initiative based on Evotec’s iPSC-based beta cell replacement therapy regained from Sanofi
New BRIDGE ("Autobahn Labs") and equity participations as well as successful follow-on financings

INCREASING EXPANSION OF INFRASTRUCTURE IN MULTIMODALITY
Establishment of new site Evotec GT in Austria, dedicated to gene therapy-based projects; multi-year gene therapy research alliance between Evotec GT and Takeda
Further expansion of Evotec’s multimodality platform into Antisense Therapy through cooperation with Secarna Pharmaceuticals

CORPORATE
Virtual Annual General Meeting 2020 approved all proposed agenda items
Election of new Supervisory Board Member Mr Kasim Kutay
Acquisition of "Biopark By Sanofi SAS" in Toulouse making Evotec the full owner of the Toulouse site; rebranding of the site into "Campus Curie Toulouse" (after period-end)

GUIDANCE FOR FULL-YEAR 2020 CONFIRMED WITH REGARD TO REVENUES AND ADJUSTED EBITDA, HIGHER INVESTMENTS IN R&D PLANNED
Unchanged business outlook in terms of revenue and adjusted EBITDA, taking into account currently visible COVID-19 effects
Group Revenues from contracts with customers expected to range from € 440 – 480 m (2019: € 446.4 m)
Adjusted Group EBITDA expected to be in the range of € 100 – 120 m (2019: € 123.1 m)
Due to promising investments in EVT Innovate, increase of guidance for "unpartnered R&D" to approx. € 45 m (before approx. € 40 m)

STRONG FINANCIAL POSITION
In the first six months of 2020 Evotec continued on its growth path: Group revenues from contracts with customers increased by 12% to € 231.0 m (H1 2019: € 207.1 m) due to a positive performance across all business lines, for the first time added revenues from Just – Evotec Biologics (€ 16.3 m) and despite the anticipated loss of payments of Sanofi for the Toulouse site (€ 7.5 m) from April 2020. Also, favourable exchange rate effects had a positive impact of € 2.4 m.

Thereof, base revenues accounted for € 223.2 m, an increase of 19% over the same period of the previous year (H1 2019: € 188.0 m), while revenues from upfront, milestone and licence payments decreased to € 7.8 m (H1 2019: € 19.1 m).

Due to the significant lower upfront, milestone and license payments as well as the anticipated expiring payments from Sanofi for the Toulouse site from April 2020 onwards, gross margin decreased to 23.0% (H1 2019: 30.8%).

In the first half-year of 2020, Evotec continued to strongly invest into its unpartnered R&D. Thus, the expenses for unpartnered R&D increased to € 21.6 m (H1 2019: € 18.7 m), mainly due to intensified research investments into oncology and platforms such as PanOmics and cell therapy. The lower partnered R&D expenses of € 8.2 m (H1 2019: € 10.6 m) were primarily related to the infectious disease portfolio. Whereas costs of the partnership with Sanofi in this area are predominantly reported as R&D expenses the full reimbursement by Sanofi is recognised under other operating income. Total R&D expenses of € 29.8 m nearly remained stable compared to 2019 (H1 2019: € 29.3 m).

The Group’s selling, general and administrative ("SG&A") expenses for the first half-year of 2020 increased by 22% to € 36.5 m (H1 2019: € 29.9 m), which mainly resulted from the overall staff increase and the related costs as well as from transaction and integration cost from equity engagements, the consolidation of Just – Evotec Biologics and the founding of Evotec GT.

Other operating result in the first six months of 2020 amounted to € 32.2 m (H1 2019: € 31.3 m) and was mainly influenced by R&D tax credits as well as recharges of Sanofi for ID Lyon. Due to a change in the tax regulations in Italian legislation, total R&D tax credits grew less as expected compared to prior period.

The operating income decreased to € 18.9 m (H1 2019: € 24.0 m), mainly due to the significantly lower upfront, milestone and licence revenues. Most of the half-year milestones are expected to be only slightly delayed, but not lost.

The lower upfront, milestone and licence revenues also affected the adjusted Group EBITDA which decreased by 19% to € 47.3 m (H1 2019: € 58.2 m). Favourable exchange rate developments had a positive impact of approx. € 1.7 m on the adjusted Group EBITDA.

The net result in the first half-year of 2020 amounted to € 7.3 m (H1 2019: € 10.7 m).

Evotec’s liquidity position in the first six months of 2020 continued to remain robust amounting to € 275.7 m (31 December 2019: € 320.0 m). The cash-outflow resulted mainly from the high investments in capex and equity investments.

CONVINCING OPERATIONAL PERFORMANCE IN BOTH BUSINESS SEGMENTS
In the first half of 2020, the EVT Execute segment continued its strong progress of the previous quarters.

Evotec signed multiple new drug discovery and development agreements, e.g. with Boston Pharmaceuticals and Ildong, as well as multiple undisclosed partners and extended or expanded existing long-term agreements (e.g. with Amgen, Takeda). Evotec’s wholly-owned US subsidiary Cyprotex was again selected by the US Environmental Protection Agency (EPA) as its preferred service partner for the next five years. The contract is worth up to $ 13 m.

Evotec’s fully-owned subsidiary Just – Evotec Biologics had a successful start with the J.POD construction, progressing well, and its first J.POD collaboration with MSD for the development of innovative technologies for the production of biologics of the highest quality. Further multiple new agreements were concluded (e.g. with ABL, Ology). After period-end, Just – Evotec Biologics entered into a partnership with the U.S. Department of Defense to develop and manufacture monoclonal antibodies (mAbs) for treatment and/or prevention of COVID-19. The contract with the DOD values up to $ 18.2 m.

Also, the Evotec Development Business showed very good performance and started strategic initiatives in the first half-year 2020, despite the extraordinary difficult circumstances especially at the Evotec site in Verona. In June 2020, Evotec’s long-term partner Zogenix received its marketing approval from FDA for the company’s drug FINTEPLA for Dravet & LGS syndromes, securing 7-year orphan drug exclusivity for commercial exploitation in the US. Evotec will continue to be the commercial manufacturing partner of Zogenix.

In its second segment, EVT Innovate, Evotec was also very successful within the first half-year 2020.

Evotec expanded its leading position in iPSC (Induced pluripotent stem cells). After having regained the global development and commercialisation rights of the iPSC-based diabetes cell therapy programme from Sanofi, Evotec intends to move this programme forward within its QRbeta initiative. Multiple other unpartnered iPSC based initiatives showed very good progress in the first half-year 2020 (e.g. Retinal Diseases).

Evotec’s long-term partner, Bayer AG, continues to advance its P2X3 antagonist BAY1817080, an asset originating from Evotec. The Phase IIa-PoC study had a positive outcome in patients with refractory chronic cough. Preparations for a Phase-IIb study in patients with refractory chronic cough are ongoing, as are preparations for further studies in additional indications.

Together with Samsara, Biocapital and KCK Evotec initiated "Autobahn Labs", a novel virtual early stage drug discovery incubator (BRIDGE) to design and execute an accelerated path to deliver transformational new therapies. Autobahn Labs already entered into a first-of-a-kind strategic collaboration with UCLA Technology Development Group to identify and advance the most promising areas of research.

Over the first half of 2020, Evotec continued to expand its strategy of generating upside through equity investments, e.g. in leon-nanodrugs, QUANTRO Therapeutics and Exscientia. Other equity participations were made as follow-on investments (e.g. Carrick) or small seed commitments (e.g. Cajal Neuroscience).

IMPORTANT STRATEGIC BUSINESS EXPANSION INTO NEW MODALITIES AND MARKETS
A very important step towards Evotec’s long-term vision of becoming a fully modality-agnostic drug discovery and development partnership company was the establishment of the new site Evotec GT in Austria, dedicated to research and development of gene therapy-based projects. In April, Evotec GT signed a long-term research alliance with Takeda covering selected Takeda gene therapy projects for core therapeutic areas like oncology, rare diseases, neuroscience and gastroenterology.

In June 2020, Evotec signed a strategic partnership with Secarna Pharmaceuticals in the field of Antisense Therapy and already initiated a first project with the aim to establish a pipeline of co-owned antisense oligonucleotide therapies.

Already in the first quarter of 2020, Evotec entered into the field of formulation nanotechnology by signing a strategic partnership with the Munich-based company leon-nanodrugs.

CORPORATE
Evotec’s shareholders at the virtual Annual General Meeting 2020 approved all proposals the Company’s Management put to vote with the required majority. The shareholders elected a new Supervisory Board member: Mr Kasim Kutay, CEO of Novo Holdings A/S, succeeds Dr Michael Shalmi, who resigned from the Board.

In May, Kara Carter, Executive Vice President Infectious Disease of Evotec, was appointed as President of the International Society of the Antiviral Research (ISAR).

Shortly after period-end, on 01 July 2020 Evotec acquired the "Biopark By Sanofi SAS" in Toulouse including all land and buildings of the Sanofi site. The acquisition will allow Evotec to significantly expand its existing capacities at its Toulouse site and to secure further, long-term growth of its Toulouse-based operations. The site will be rebranded into "Campus Curie Toulouse".

 

FINANCIAL GUIDANCE 2020
At present, the management of Evotec confirms the financial guidance published in the 2019 Annual Report on 26 March 2020 and confirmed in the Q1 Quarterly Statement on 14 May 2020 with regard to revenues and adjusted EBITDA.

Due to additional very promising investments in innovative technology platforms and development candidates in EVT Innovate, Evotec plans to invest even more in research and development. For this reason, the forecast for "unpartnered R&D" has been raised from previously approx. € 40 m to now approx. € 45 m.

Webcast/Conference Call
The Company is going to hold a conference call to discuss the results as well as to provide an update on its performance. Furthermore, the Management Board will present an outlook for the fiscal year 2020. The conference call will be held in English.

Conference call details

Date: Wednesday, 12 August 2020

Time: 02.00 pm CEST (08.00 am EDT, 01.00 pm BST)

A simultaneous slide presentation for participants dialling in via phone is available at View Source

Webcast details

To join the audio webcast and to access the presentation slides you will find a link on our home page shortly before the event.

A replay of the conference call will be available for seven days after the conference and can be accessed in Europe by dialling +49 69 20 17 44 222 (Germany) or +44 20 3364 5150 (UK) and in the USA by dialling +1 844 307 9362. The access code is 315597273#. The on-demand version of the webcast will be available on our website: View Source

On August 11, 2020 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biotechnology company specializing in the development of novel treatments for brain tumors, reported that CEO, John M. Climaco, will be issuing a shareholder webinar on August 13th, 2020 at 4:30pm ET to discuss business developments and the progress of the Company’s lead candidate Berubicin, novel DNA-binding agent WP1244 and development agreement with WPD Pharmaceuticals for WP1122 (Press release, CNS Pharmaceuticals, AUG 11, 2020, View Source [SID1234563463]).

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Details of the webinar are below:

Date:

August 13th, 2020

Time:

4:30-5:00pm ET

Link:

View Source

On August 11, 2020 Eisai Inc. reported the topline results from Study 211, a Phase 2 trial evaluating the efficacy and safety of LENVIMA, an orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, comparing two starting doses (18 mg versus 24 mg daily) in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) (Press release, Eisai, AUG 11, 2020, View Source [SID1234563462]). Results indicate that the lower starting dose (18 mg) of LENVIMA did not meet the non-inferiority requirement compared to the approved starting dose (24 mg) in patients with RAI-refractory DTC as measured by objective response rate (ORR) at week 24. The data from this study support the selection of 24 mg as an appropriate starting dose for patients with RAI-refractory DTC.

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Study 211 was conducted as a post-marketing commitment to the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA) and other regions following priority review designation and approval of LENVIMA for the treatment of patients with locally recurrent or metastatic, progressive, RAI-refractory DTC.

The primary objective of the Phase 2, multicenter, randomized, double-blind study was to determine whether a starting dose of LENVIMA at 18 mg once daily would provide comparable efficacy based on ORR at 24 weeks with an improved safety profile compared to 24 mg starting dose based on treatment-emergent adverse events (TEAEs) of Grade 3 or higher. The 18 mg dose did not show non-inferiority in efficacy to the 24 mg dose as measured by ORR at week 24. The primary safety endpoint demonstrated that the incidences of Grade 3 or higher TEAEs through week 24 were similar between the 24 mg and 18 mg treatment arms.

"These findings help reinforce the efficacy and safety of LENVIMA for patients living with RAI-refractory differentiated thyroid cancer while supporting the appropriate starting dose for these patients," said Dr. Takashi Owa, Chief Medicine Creation and Chief Discovery Officer, Oncology Business Group at Eisai. "Studies like this post-marketing trial represent Eisai’s continued commitment to prioritizing patients’ needs and safety through the ongoing examination of our medicines. We would like to thank the patients, their families and clinical investigators for their participation in Study 211, and we look forward to presenting the full results of this study at an upcoming medical meeting."

Thyroid cancer is the most common endocrine malignancy and global figures show that its incidence is on the rise. In 2020, it is estimated that there will be 52,890 new cases of thyroid cancer in the U.S. and that women are three times more likely to develop thyroid cancer than men. The most common types of thyroid cancer, papillary and follicular (including Hürthle cell), are classified as DTC and account for approximately 90% of all cases. While most patients with DTC are curable with surgery and radioactive iodine treatment, the prognosis for those patients whose cancers persist or recur is poor.

About LENVIMA (lenvatinib)

LENVIMA (lenvatinib) is a kinase inhibitor that is indicated:

For the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC)
In combination with everolimus, for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy
For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)
In combination with pembrolizumab, for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy, and are not candidates for curative surgery or radiation. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial
LENVIMA, discovered and developed by Eisai, is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. In syngeneic mouse tumor models, lenvatinib decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone.

Important Safety Information

Warnings and Precautions

Hypertension. In DTC, hypertension occurred in 73% of patients on LENVIMA (44% grade 3-4). In RCC, hypertension occurred in 42% of patients on LENVIMA + everolimus (13% grade 3). Systolic blood pressure ≥160 mmHg occurred in 29% of patients, and 21% had diastolic blood pressure ≥100 mmHg. In HCC, hypertension occurred in 45% of LENVIMA-treated patients (24% grade 3). Grade 4 hypertension was not reported in HCC.

Serious complications of poorly controlled hypertension have been reported. Control blood pressure prior to initiation. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at reduced dose when hypertension is controlled or permanently discontinue based on severity.

Cardiac Dysfunction. Serious and fatal cardiac dysfunction can occur with LENVIMA. Across clinical trials in 799 patients with DTC, RCC, and HCC, grade 3 or higher cardiac dysfunction occurred in 3% of LENVIMA treated patients. Monitor for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Arterial Thromboembolic Events. Among patients receiving LENVIMA or LENVIMA + everolimus, arterial thromboembolic events of any severity occurred in 2% of patients in RCC and HCC and 5% in DTC. Grade 3-5 arterial thromboembolic events ranged from 2% to 3% across all clinical trials. Permanently discontinue following an arterial thrombotic event. The safety of resuming after an arterial thromboembolic event has not been established and LENVIMA has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.

Hepatotoxicity. Across clinical studies enrolling 1,327 LENVIMA-treated patients with malignancies other than HCC, serious hepatic adverse reactions occurred in 1.4% of patients. Fatal events, including hepatic failure, acute hepatitis and hepatorenal syndrome, occurred in 0.5% of patients. In HCC, hepatic encephalopathy occurred in 8% of LENVIMA-treated patients (5% grade 3-5). Grade 3-5 hepatic failure occurred in 3% of LENVIMA-treated patients. 2% of patients discontinued LENVIMA due to hepatic encephalopathy and 1% discontinued due to hepatic failure.

Monitor liver function prior to initiation, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Renal Failure or Impairment. Serious including fatal renal failure or impairment can occur with LENVIMA. Renal impairment was reported in 14% and 7% of LENVIMA-treated patients in DTC and HCC, respectively. Grade 3-5 renal failure or impairment occurred in 3% of patients with DTC and 2% of patients with HCC, including 1 fatal event in each study. In RCC, renal impairment or renal failure was reported in 18% of LENVIMA + everolimus–treated patients (10% grade 3).

Initiate prompt management of diarrhea or dehydration/hypovolemia. Withhold and resume at reduced dose upon recovery or permanently discontinue for renal failure or impairment based on severity.

Proteinuria. In DTC and HCC, proteinuria was reported in 34% and 26% of LENVIMA-treated patients, respectively. Grade 3 proteinuria occurred in 11% and 6% in DTC and HCC, respectively. In RCC, proteinuria occurred in 31% of patients receiving LENVIMA + everolimus (8% grade 3). Monitor for proteinuria prior to initiation and periodically during treatment. If urine dipstick proteinuria ≥2+ is detected, obtain a 24-hour urine protein. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Diarrhea. Of the 737 LENVIMA-treated patients in DTC and HCC, diarrhea occurred in 49% (6% grade 3). In RCC, diarrhea occurred in 81% of LENVIMA + everolimus–treated patients (19% grade 3). Diarrhea was the most frequent cause of dose interruption/reduction, and diarrhea recurred despite dose reduction. Promptly initiate management of diarrhea. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Fistula Formation and Gastrointestinal Perforation. Of the 799 patients treated with LENVIMA or LENVIMA + everolimus in DTC, RCC, and HCC, fistula or gastrointestinal perforation occurred in 2%. Permanently discontinue in patients who develop gastrointestinal perforation of any severity or grade 3-4 fistula.

QT Interval Prolongation. In DTC, QT/QTc interval prolongation occurred in 9% of LENVIMA-treated patients and QT interval prolongation of >500 ms occurred in 2%. In RCC, QTc interval increases of >60 ms occurred in 11% of patients receiving LENVIMA + everolimus and QTc interval >500 ms occurred in 6%. In HCC, QTc interval increases of >60 ms occurred in 8% of LENVIMA-treated patients and QTc interval >500 ms occurred in 2%.

Monitor and correct electrolyte abnormalities at baseline and periodically during treatment. Monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Withhold and resume at reduced dose upon recovery based on severity.

Hypocalcemia. In DTC, grade 3-4 hypocalcemia occurred in 9% of LENVIMA-treated patients. In 65% of cases, hypocalcemia improved or resolved following calcium supplementation with or without dose interruption or dose reduction. In RCC, grade 3-4 hypocalcemia occurred in 6% of LENVIMA + everolimus– treated patients. In HCC, grade 3 hypocalcemia occurred in 0.8% of LENVIMA-treated patients. Monitor blood calcium levels at least monthly and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity.

Reversible Posterior Leukoencephalopathy Syndrome. Across clinical studies of 1,823 patients who received LENVIMA as a single agent, RPLS occurred in 0.3%. Confirm diagnosis of RPLS with MRI. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity and persistence of neurologic symptoms.

Hemorrhagic Events. Serious including fatal hemorrhagic events can occur with LENVIMA. In DTC, RCC, and HCC clinical trials, hemorrhagic events, of any grade, occurred in 29% of the 799 patients treated with LENVIMA as a single agent or in combination with everolimus. The most frequently reported hemorrhagic events (all grades and occurring in at least 5% of patients) were epistaxis and hematuria. In DTC, grade 3-5 hemorrhage occurred in 2% of LENVIMA-treated patients, including 1 fatal intracranial hemorrhage among 16 patients who received LENVIMA and had CNS metastases at baseline. In RCC, grade 3-5 hemorrhage occurred in 8% of LENVIMA + everolimus–treated patients, including 1 fatal cerebral hemorrhage. In HCC, grade 3-5 hemorrhage occurred in 5% of LENVIMA-treated patients, including 7 fatal hemorrhagic events. Serious tumor-related bleeds, including fatal hemorrhagic events, occurred in LENVIMA-treated patients in clinical trials and in the postmarketing setting. In postmarketing surveillance, serious and fatal carotid artery hemorrhages were seen more frequently in patients with anaplastic thyroid carcinoma (ATC) than other tumors. Safety and effectiveness of LENVIMA in patients with ATC have not been demonstrated in clinical trials.

Consider the risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (eg, carotid artery). Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction. LENVIMA impairs exogenous thyroid suppression. In DTC, 88% of patients had baseline thyroid stimulating hormone (TSH) level ≤0.5 mU/L. In patients with normal TSH at baseline, elevation of TSH level >0.5 mU/L was observed post baseline in 57% of LENVIMA-treated patients. In RCC and HCC, grade 1 or 2 hypothyroidism occurred in 24% of LENVIMA + everolimus–treated patients and 21% of LENVIMA-treated patients, respectively. In patients with normal or low TSH at baseline, elevation of TSH was observed post baseline in 70% of LENVIMA-treated patients in HCC and 60% of LENVIMA + everolimus–treated patients in RCC.

Monitor thyroid function prior to initiation and at least monthly during treatment. Treat hypothyroidism according to standard medical practice.

Impaired Wound Healing. Impaired wound healing has been reported in patients who received LENVIMA. Withhold LENVIMA for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of LENVIMA after resolution of wound healing complications has not been established.

Embryo-fetal Toxicity. Based on its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to pregnant women. In animal reproduction studies, oral administration of lenvatinib during organogenesis at doses below the recommended clinical doses resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits. Advise pregnant women of the potential risk to a fetus; and advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for at least 30 days after the last dose.

Adverse Reactions

In DTC, the most common adverse reactions (≥30%) observed in LENVIMA-treated patients were hypertension (73%), fatigue (67%), diarrhea (67%), arthralgia/myalgia (62%), decreased appetite (54%), decreased weight (51%), nausea (47%), stomatitis (41%), headache (38%), vomiting (36%), proteinuria (34%), palmar-plantar erythrodysesthesia syndrome (32%), abdominal pain (31%), and dysphonia (31%). The most common serious adverse reactions (≥2%) were pneumonia (4%), hypertension (3%), and dehydration (3%). Adverse reactions led to dose reductions in 68% of LENVIMA-treated patients; 18% discontinued LENVIMA. The most common adverse reactions (≥10%) resulting in dose reductions were hypertension (13%), proteinuria (11%), decreased appetite (10%), and diarrhea (10%); the most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were hypertension (1%) and asthenia (1%).

In RCC, the most common adverse reactions (≥30%) observed in LENVIMA + everolimus–treated patients were diarrhea (81%), fatigue (73%), arthralgia/myalgia (55%), decreased appetite (53%), vomiting (48%), nausea (45%), stomatitis (44%), hypertension (42%), peripheral edema (42%), cough (37%), abdominal pain (37%), dyspnea (35%), rash (35%), decreased weight (34%), hemorrhagic events (32%), and proteinuria (31%). The most common serious adverse reactions (≥5%) were renal failure (11%), dehydration (10%), anemia (6%), thrombocytopenia (5%), diarrhea (5%), vomiting (5%), and dyspnea (5%). Adverse reactions led to dose reductions or interruption in 89% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and proteinuria (5%). Treatment discontinuation due to an adverse reaction occurred in 29% of patients.

In HCC, the most common adverse reactions (≥20%) observed in LENVIMA-treated patients were hypertension (45%), fatigue (44%), diarrhea (39%), decreased appetite (34%), arthralgia/myalgia (31%), decreased weight (31%), abdominal pain (30%), palmar-plantar erythrodysesthesia syndrome (27%), proteinuria (26%), dysphonia (24%), hemorrhagic events (23%), hypothyroidism (21%), and nausea (20%). The most common serious adverse reactions (≥2%) were hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%), and decreased appetite (2%). Adverse reactions led to dose reductions or interruption in 62% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were fatigue (9%), decreased appetite (8%), diarrhea (8%), proteinuria (7%), hypertension (6%), and palmar-plantar erythrodysesthesia syndrome (5%). Treatment discontinuation due to an adverse reaction occurred in 20% of patients. The most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were fatigue (1%), hepatic encephalopathy (2%), hyperbilirubinemia (1%), and hepatic failure (1%).

In EC, the most common adverse reactions (≥20%) observed in LENVIMA + pembrolizumab – treated patients were fatigue (65%), hypertension (65%), musculoskeletal pain (65%), diarrhea (64%), decreased appetite (52%), hypothyroidism (51%), nausea (48%), stomatitis (43%), vomiting (39%), decreased weight (36%), abdominal pain (33%), headache (33%), constipation (32%), urinary tract infection (31%), dysphonia (29%), hemorrhagic events (28%), hypomagnesemia (27%), palmar-plantar erythrodysesthesia (26%), dyspnea (24%), cough (21%) and rash (21%).

Adverse reactions led to dose reduction or interruption in 88% of patients receiving LENVIMA. The most common adverse reactions (≥5%) resulting in dose reduction or interruption of LENVIMA were fatigue (32%), hypertension (26%), diarrhea (18%), nausea (13%), palmar-plantar erythrodysesthesia (13%), vomiting (13%), decreased appetite (12%), musculoskeletal pain (11%), stomatitis (9%), abdominal pain (7%), hemorrhages (7%), renal impairment (6%), decreased weight (6%), rash (5%), headache (5%), increased lipase (5%) and proteinuria (5%).

Fatal adverse reactions occurred in 3% of patients receiving LENVIMA + pembrolizumab, including gastrointestinal perforation, RPLS with intraventricular hemorrhage, and intracranial hemorrhage.

Serious adverse reactions occurred in 52% of patients receiving LENVIMA + pembrolizumab. Serious adverse reactions in ≥3% of patients were hypertension (9%), abdominal pain (6%), musculoskeletal pain (5%), hemorrhage (4%), fatigue (4%), nausea (4%), confusional state (4%), pleural effusion (4%), adrenal insufficiency (3%), colitis (3%), dyspnea (3%), and pyrexia (3%).

Permanent discontinuation due to adverse reaction (Grade 1-4) occurred in 21% of patients who received LENVIMA + pembrolizumab. The most common adverse reactions (>2%) resulting in discontinuation of LENVIMA were gastrointestinal perforation or fistula (2%), muscular weakness (2%), and pancreatitis (2%).

Use in Specific Populations

Because of the potential for serious adverse reactions in breastfed infants, advise women to discontinue breastfeeding during treatment and for at least 1 week after last dose. LENVIMA may impair fertility in males and females of reproductive potential.

No dose adjustment is recommended for patients with mild (CLcr 60-89 mL/min) or moderate (CLcr 30-59 mL/min) renal impairment. LENVIMA concentrations may increase in patients with DTC, RCC or EC and severe (CLcr 15-29 mL/min) renal impairment. Reduce the dose for patients with DTC, RCC, or EC and severe renal impairment. There is no recommended dose for patients with HCC and severe renal impairment. LENVIMA has not been studied in patients with end stage renal disease. No dose adjustment is recommended for patients with HCC and mild hepatic impairment (Child-Pugh A). There is no recommended dose for patients with HCC with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment.

No dose adjustment is recommended for patients with DTC, RCC, or EC and mild or moderate hepatic impairment. LENVIMA concentrations may increase in patients with DTC, RCC, or EC and severe hepatic impairment. Reduce the dose for patients with DTC, RCC, or EC and severe hepatic impairment.

LENVIMA (lenvatinib) is available as 10 mg and 4 mg capsules.

Please see Prescribing Information for LENVIMA (lenvatinib) at View Source

About the Eisai and Merck Strategic Collaboration
In March 2018, Eisai and Merck, known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies will jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with Merck’s anti-PD-1 therapy pembrolizumab.

In addition to ongoing clinical studies evaluating the pembrolizumab plus LENVIMA combination across several different tumor types, the companies have jointly initiated new clinical studies through the LEAP (LEnvatinib And Pembrolizumab) clinical program and are evaluating the combination in 13 different tumor types (endometrial carcinoma, hepatocellular carcinoma, melanoma, non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, urothelial cancer, biliary tract cancer, colorectal cancer, gastric cancer, glioblastoma, ovarian cancer and triple-negative breast cancer) across 18 clinical trials.

Eisai’s Focus on Cancer
Eisai focuses on the development of anticancer drugs, targeting the tumor microenvironment (with experience and knowledge from Halaven and Lenvima) and the driver gene mutation and aberrant splicing (leveraging RNA Splicing Platform) as areas (Ricchi) where real patient needs are still unmet, and where Eisai can become a frontrunner in oncology. Eisai will discover innovative new drugs with new targets and mechanisms of action from these Ricchi, with the aim of contributing to the cure of cancers.