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Upon closing, Janssen will make a cash payment of $750 million to XBiotech. In addition, XBiotech may receive up to $600 million in potential milestone payments. XBiotech expects to generate additional revenue from the manufacturing supply agreement and clinical services agreement with Janssen over the next two years.

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ASLN stock continued to rise in after-hours trading on December 17, 2019. ASLN stock continues to attract buyers after the H.C. Wainwright¡¦s price target hike back on December 10, 2019.

ASLN stock in the 15-minute time frame shows an incredible move that continued in after-hours trading (brows shaded area) on December 17, 2019.

On December 10, 2019, H.C. Wainwright analyst Yi Chen raised Aslan Pharmaceuticals¡¦ price target to $5 from $2 and reiterates a Buy rating on the shares.Low-dose ASLAN004 demonstrateed positive efficacy and safety in atopic dermatitis, Chen tells investors in a research note. These early signs of efficacy are very encouraging as 200 mg is the lowest dose cohort in the study, and the observed efficacy has yet to peak, Chen tells investors in a research note.

On December 2, 2019, Piper Jaffray analyst Edward Tenthoff upgraded Aslan Pharmaceuticals to Overweight from Neutral with a price target of $8, up from $1. The stock in premarket trading is up 85%, or $3.24, to $7.06. The company reported preliminary Phase I multiple-ascending dose data on subcutaneous ASLAN004 to treat moderate-to-severe atopic dermatitis, and in the lowest dose cohort, three evaluable patients experienced at least 60% reduction in the Eczema Area Severity Index score at one month, Tenthoff tells investors in a research note. Further, ASLAN004 was safe with no discontinuations or serious adverse events reported, the analyst adds. He also notes that Aslan is also conducting a Phase II study of ASLAN003 in acute myeloid leukemia. Both or either drug could represent partnering opportunities, says Tenthoff.

On December 1, 2019, ASLAN Pharmaceuticals announced positive preliminary data from the lowest dose cohort of its ongoing multiple ascending dose, or MAD, study of ASLAN004 for the treatment of moderate-to-severe atopic dermatitis, or AD. ASLAN004 is a first-in-class fully human monoclonal antibody that binds to the IL-13 receptor alpha1 subunit (IL-13Ralpha1), blocking signalling of two pro-inflammatory cytokines, IL-4 and IL-13, which are central to triggering symptoms of AD, such as redness and itching of the skin. The first patient was enrolled into the double blind study at Changi General Hospital in Singapore on 22 October 2019. As of November 29, 6 patients had been treated in the lowest dose cohort and 3 have completed at least one month of dosing. In a review of unclean blinded data, the Eczema Area and Severity Index, or EASI, scores of the 3 patients were reduced by 85%, 70% and 59% from baseline and the EASI score continued to fall at 4 weeks with maximal efficacy expected at 6 to 8 weeks. ASLAN004 was well-tolerated and, to date, there have been no serious adverse events or treatment discontinuations. Corresponding changes were seen in other measures of efficacy. The data monitoring committee, or DMC, will meet in late December, after which the second dose cohort is expected to open. The randomised, double-blind, placebo-controlled MAD study will evaluate 3 doses of ASLAN004 delivered subcutaneously and will be followed by an expansion cohort at the most efficacious dose. Each dose cohort will contain up to 6 patients on ASLAN004 and 2 patients on placebo, and the expansion cohort will contain 12 patients on ASLAN004 and 6 patients on placebo. Patients are dosed weekly for 8 weeks to determine safety and the maximal efficacy of ASLAN004. The study will recruit up to 50 moderate-to-severe atopic dermatitis patients and study completion is expected in the second half of 2020, with interim results expected in early 2020.

Dr Mark McHale, Head of R&D, ASLAN Pharmaceuticals, said: ¡§We are pleased to report encouraging preliminary data from this study of ASLAN004. Whilst the data remains early, we had not anticipated to observe such pronounced improvements in patients enrolled into the lowest dose cohort. We look forward to the second dose cohort opening following the DMC meeting in December and further interim data in early 2020.¡¨

Atopic dermatitis is the most common dermatological disease, affecting over 200 million patients worldwide, characterized by red inflamed skin and severe daytime and night-time itching, which can severely impact patients¡¦ quality of life. Up to one-third of adult atopic dermatitis patients are considered moderate to severe, for which currently available therapeutics are limited and management is challenging in the majority of cases.

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Upon closing, Janssen will make a cash payment of $750 million to XBiotech. In addition, XBiotech may receive up to $600 million in potential milestone payments. XBiotech expects to generate additional revenue from the manufacturing supply agreement and clinical services agreement with Janssen over the next two years.

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AUSTIN, Texas, Dec. 07, 2019 (GLOBE NEWSWIRE) -- XBiotech Inc. (XBIT) announced today that it has entered into a definitive agreement with Janssen Biotech, Inc., a Janssen Pharmaceutical Company of Johnson & Johnson, to sell XBiotech¡¦s novel antibody (bermekimab) that neutralizes interleukin-1 alpha (IL-1⍺). IL-1⍺ promotes disease-causing inflammation in a wide range of medical conditions. Janssen will acquire all rights to bermekimab under the terms of the agreement, and XBiotech will be free to use its True Human Antibody discovery program to develop new antibody therapeutics that target IL-1⍺ to treat non-dermatological diseases. XBiotech plans to re-enter clinical development expeditiously with a next generation anti-IL-1⍺ therapeutic.

Following the acquisition, XBiotech will use its proprietary manufacturing technology to produce clinical supplies of bermekimab for Janssen under a supply agreement. In addition, XBiotech will contract with Janssen to provide clinical trial operation services to complete two ongoing Phase II clinical studies evaluating bermekimab in Hidradenitis Suppurativa and Atopic Dermatitis.

Upon closing, Janssen will make a cash payment of $750 million to XBiotech. In addition, XBiotech may receive up to $600 million in potential milestone payments. XBiotech expects to generate additional revenue from the manufacturing supply agreement and clinical services agreement with Janssen over the next two years.

XBiotech plans to use a portion of the proceeds from this transaction to fund discovery and development of its next generation True Human anti-IL-1⍺ antibody program. Additionally, a portion of the revenue will be dedicated to advancing other antibody therapeutics in XBiotech¡¦s pipeline. The Company is also planning to use part of the proceeds in a capital transaction, such as a stock repurchase, subject to board review and approval.

John Simard, XBiotech¡¦s President & CEO, stated, ¡§We are proud that Janssen has chosen bermekimab as an agent it believes could have an important impact. We believe their acquisition will enable recognition and increase awareness of the full potential of this first-in-class therapeutic. This transaction also provides us the opportunity to showcase our powerful True Human antibody discovery platform, which we are now utilizing to pursue next generation anti-Il-1⍺ antibody therapeutics to treat multiple areas of unmet need outside of dermatology.¡¨

The acquisition of bermekimab provides further validation of the foundational science behind targeting IL-1a as a means to block disease-causing inflammation. Clinical and pre-clinical research suggests blocking IL-1a may be used to treat a number of chronic and acute inflammatory conditions, including skin disease, heart disease, heart attack, stroke, rheumatological disease, gastrointestinal diseases, and cancer.

Simard further stated, ¡§The cash infusion from the bermekimab transaction will enable XBiotech to accelerate our True Human antibody pipeline. The Company will also have sufficient cash to support a significant capital transaction, which could provide for a non-dilutive liquidity event for our valued shareholders who have supported XBiotech¡¦s pioneering work.¡¨

The transaction is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act, and is expected to close shortly after HSR approval.

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Sanofi and Regeneron Report Positive Proof-of-Concept Data for Dupilumab, an IL-4R alpha Antibody, in Atopic Dermatitis

Update: Dupixent (dupilumab) Now FDA Approved - March 28,2017

Phase 1b Data Presented at Late Breaking Session of 71st Annual Meeting of the American Academy of Dermatology

PARIS and TARRYTOWN, N.Y., March 02, 2013, 2013 /PRNewswire/ -- Sanofi and Regeneron Pharmaceuticals, Inc. today announced that pooled data from two Phase 1b trials with dupilumab (REGN668/SAR231893), an investigational, high-affinity, subcutaneously administered, fully-human antibody targeting the alpha subunit of the interleukin 4 receptor (IL-4R alpha), were presented at the 71st Annual Meeting of the American Academy of Dermatology (AAD) in Miami.

The primary objective of the Phase 1b studies was to assess the safety profile of dupilumab. Other exploratory endpoints included pharmacokinetic, biomarker, and efficacy parameters. The efficacy data showed that treatment with four weekly subcutaneous injections of dupilumab at either 150 milligrams (mg) or 300mg per week, significantly improved the signs and symptoms of patients with moderate-to-severe atopic dermatitis (AD) whose disease was not adequately controlled with topical medications. Specifically, patients treated with dupilumab had significant improvements in body surface area (BSA) score, Investigator Global Assessment (IGA) score, and Eczema Area Severity Index (EASI) from baseline to week 4 compared to placebo (p<0.05 vs. placebo for all measures and doses). The significant improvements in BSA, IGA, and EASI scores were maintained at week 8 in the 300mg dose group (p<0.05 vs. placebo). A responder analysis demonstrated that at week 4, 54.5% of patients treated with the 150mg dose and 71.4% of patients treated with the 300mg dose achieved a reduction in EASI score of 50% or greater compared to 18.8% with placebo (p<0.05). The most common adverse events (AEs) were nasopharyngitis (19.6% vs 12.5% for placebo) and headache (11.8% vs 6.3% for placebo).

Through blockade of IL-4R alpha, dupilumab modulates signaling of both the IL-4 and IL-13 pathway, which have been implicated in the pathophysiology of allergic disease, said George D. Yancopoulos, M.D., Ph.D., Chief Scientific Officer of Regeneron and President of Regeneron Laboratories. We look forward to presenting additional data from a 12-week, Phase 2a trial in atopic dermatitis, as well as starting a larger Phase 2b trial with dupilumab in patients with atopic dermatitis, later this year.

Presented today in a late-breaking clinical trials session at the AAD meeting, the Phase 1b trials included 67 patients randomized to three different doses of dupilumab (75mg, n=8; 150mg, n=22; 300mg, n=21) and placebo (n=16). The primary objective of the Phase 1b studies was to assess the safety profile of dupilumab. Other endpoints included pharmacokinetic, biomarker, and efficacy parameters. Following the 4-week treatment period, patients in the studies were followed for an additional 4 weeks for a total of 8 weeks.

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-----------------------------

Upon closing, Janssen will make a cash payment of $750 million to XBiotech. In addition, XBiotech may receive up to $600 million in potential milestone payments.

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XBiotech Announces Agreement to Sell True Human Antibody Bermekimab Targeting IL-1a to Janssen

GlobeNewswireDecember 7, 2019

XBiotech will continue its True Human anti IL-1⍺ antibody discovery program outside of dermatology and use its manufacturing technology to produce clinical supplies of bermekimab for Janssen

AUSTIN, Texas, Dec. 07, 2019 (GLOBE NEWSWIRE) -- XBiotech Inc. (XBIT) announced today that it has entered into a definitive agreement with Janssen Biotech, Inc., a Janssen Pharmaceutical Company of Johnson & Johnson, to sell XBiotech¡¦s novel antibody (bermekimab) that neutralizes interleukin-1 alpha (IL-1⍺). IL-1⍺ promotes disease-causing inflammation in a wide range of medical conditions. Janssen will acquire all rights to bermekimab under the terms of the agreement, and XBiotech will be free to use its True Human Antibody discovery program to develop new antibody therapeutics that target IL-1⍺ to treat non-dermatological diseases. XBiotech plans to re-enter clinical development expeditiously with a next generation anti-IL-1⍺ therapeutic.

Following the acquisition, XBiotech will use its proprietary manufacturing technology to produce clinical supplies of bermekimab for Janssen under a supply agreement. In addition, XBiotech will contract with Janssen to provide clinical trial operation services to complete two ongoing Phase II clinical studies evaluating bermekimab in Hidradenitis Suppurativa and Atopic Dermatitis.

Upon closing, Janssen will make a cash payment of $750 million to XBiotech. In addition, XBiotech may receive up to $600 million in potential milestone payments. XBiotech expects to generate additional revenue from the manufacturing supply agreement and clinical services agreement with Janssen over the next two years.

XBiotech plans to use a portion of the proceeds from this transaction to fund discovery and development of its next generation True Human anti-IL-1⍺ antibody program. Additionally, a portion of the revenue will be dedicated to advancing other antibody therapeutics in XBiotech¡¦s pipeline. The Company is also planning to use part of the proceeds in a capital transaction, such as a stock repurchase, subject to board review and approval.

John Simard, XBiotech¡¦s President & CEO, stated, ¡§We are proud that Janssen has chosen bermekimab as an agent it believes could have an important impact. We believe their acquisition will enable recognition and increase awareness of the full potential of this first-in-class therapeutic. This transaction also provides us the opportunity to showcase our powerful True Human antibody discovery platform, which we are now utilizing to pursue next generation anti-Il-1⍺ antibody therapeutics to treat multiple areas of unmet need outside of dermatology.¡¨

The acquisition of bermekimab provides further validation of the foundational science behind targeting IL-1a as a means to block disease-causing inflammation. Clinical and pre-clinical research suggests blocking IL-1a may be used to treat a number of chronic and acute inflammatory conditions, including skin disease, heart disease, heart attack, stroke, rheumatological disease, gastrointestinal diseases, and cancer.

Simard further stated, ¡§The cash infusion from the bermekimab transaction will enable XBiotech to accelerate our True Human antibody pipeline. The Company will also have sufficient cash to support a significant capital transaction, which could provide for a non-dilutive liquidity event for our valued shareholders who have supported XBiotech¡¦s pioneering work.¡¨

The transaction is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act, and is expected to close shortly after HSR approval.

About XBiotech

XBiotech is a fully integrated, global biopharmaceutical company dedicated to pioneering the discovery, development and commercialization of therapeutic antibodies. XBiotech currently is advancing a pipeline of therapies by harnessing naturally occurring antibodies from patients with immunity to certain diseases. Utilizing natural human immunity as a source of new medicines offers the potential to redefine the standards of care for a wide range of diseases. The discovery and manufacturing techniques which enable this were designed by and are exclusive to XBiotech. Headquartered in Austin, Texas, XBiotech also leads the development of innovative, proprietary manufacturing technology to reduce the cost and complexity of biological drug production. For more information, visit www.xbiotech.com.

Story continues

About True Human™ Therapeutic Antibodies

XBiotech¡¦s True Human™ antibodies are the only available antibodies derived without modification from humans who possess natural immunity to certain diseases. (Unlike all commercially available antibodies, which are called ¡§Humanized¡¨ or ¡§Fully Human,¡¨ XBiotech¡¦s True Human™ antibodies are directly sourced from the natural human immune response for specific diseases without modification, and thereby have not been shown to cause immunogenicity.) With discovery and clinical programs across multiple disease areas, XBiotech¡¦s True Human antibodies have the potential to harness the body¡¦s natural immunity to fight disease with unprecedented safety, efficacy, and tolerability.

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements, including declarations regarding management¡¦s beliefs and expectations, including with respect to XBiotech¡¦s strategic ambitions, regarding the expected timing of closing of the transaction with Janssen, filings and approvals relating to the transaction, the amount and timing of potential future milestone payments by Janssen, the mechanism of action and potential safety and efficacy of bermekimab, the anticipated timing of clinical studies with bermekimab, the progression and results of such studies, statements regarding the regulatory pathway for bermekimab and the timing of regulatory filings, and statements regarding any capital allocation decisions, including as to potential share repurchases. In some cases, you can identify forward-looking statements by terminology such as may, will, should, would, could, expects, plans, contemplate, anticipates, believes, estimates, predicts, projects, intend or continue or the negative of such terms or other comparable terminology, although not all forward-looking statements contain these identifying words. Forward-looking statements are subject to inherent risks and uncertainties in predicting future results and conditions that could cause the actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties are subject to the disclosures set forth in the Risk Factors section of certain of our SEC filings. Forward-looking statements are not guarantees of future performance, and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Contact

Ashley Otero

aotero@xbiotech.com

512-386-2930

finance.yahoo.com/news/xbiotech-announces-agreement-sell-true-080532684.html

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Merck & Co., Inc. MRK announced that it has entered into a definitive agreement to acquire Massachusetts-based small biopharmaceutical company ArQule, Inc. ARQL for $2.7 billion to boost its oncology portfolio. Under the terms of the deal, Merck has offered to buy all outstanding shares of ArQule for $20 per share in cash, representing a premium of almost 104% to the latter¡¦s Friday closing price of $9.66.

The acquisition of ArQule will strengthen Merck¡¦s oncology pipeline with the addition of some strategic assets including ARQ 531.

ArQule¡¦s lead pipeline candidate ARQ 531, an oral BTK inhibitor, is currently being evaluated in phase II dose expansion study for the treatment of B-cell malignancies. In early clinical studies, the candidate demonstrated a manageable safety profile and showed signs of anti-tumor activity for treating patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and Richter¡¦s Transformation.

ArQule has several other pipeline candidates in early-stage development for addressing various types of indications, mainly cancer.

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LEO Pharma reveals positive top-line Phase III results for tralokinumab

¤¦³Á¥Ö½§¬ì±M®aLEO Pharmaªí¥Ü¡A¦±§´³æ§Ü¬O¤@ºØ¬ã¨s©Êªº¡A§¹¥þ¤H·½¤Æªº³æ§J¶©§ÜÅé¡A¥i¯S²§©Ê¤¤©M¥Õ¤¶¯À13¡]IL-13¡^²Ó­M¦]¤l¡A¦b¨ä¤T¶µÃöÁ䪺III´Á¬ã¨s¡]ECZTRA 1-3¡^¤¤§¡¹F¨ì¤F©Ò¦³¥D­n©M¦¸­n²×ÂI¥Î©óªvÀø¦¨¤Hªº¤¤«×¦Ü­««×¯SÀ³©Ê¥Öª¢¡]AD¡^¡C¦b¬ã¨s´Á¶¡¡AÁ`ªº¤£¨}¨Æ¥óµo¥Í²v¦btralokinumab©M¦w¼¢¾¯¤§¶¡¬O¥i¤ñªº¡C

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LEO Pharma©ó2016¦~±qªü´µ§Q±d¡]LSE¡GAZN¡^Àò±o¤F¥Ö½§¯e¯f¤¤ªºtralokinumabªºÅv§Q¡A¸Ó¥æ©ö¯A¤Î¦V­^°ê-·ç¨å»sÃÄ¥¨ÀY¹w¥I1.15»õ¬ü¤¸¡A¥H¤Î°ª¹F10»õ¬ü¤¸ªº°Ó·~¬ÛÃö¨½µ{¸O©M²£«~¾P°âªº¯S³\Åv¨Ï¥Î¶O¤ñ¨Ò¤£¶W¹L¦Ê¤À¤§¤Q¡Cªü´µ§Q±d¦b©I§l¨t²Î¯e¯f©M¥Ö½§¯f¾Ç¥H¥~ªº¥ô¦ó¨ä¥L¾AÀ³¯g¤è­±«O¯d¹ï¦±§´¯]³æ§Üªº©Ò¦³Åv§Q¡C

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LEO Pharma¥þ²y¬ãµo°õ¦æ°ÆÁ`µôKim Kjoeller³Õ¤h»¡¡G¡§ AD³B©ó¤¤«×¦Ü­««×§Î¦¡¡A·|¾É­P±wªÌÃø¥H§Ô¨üªº¤Ï´_µo§@¯gª¬¡C¡¨ ¡§¾¨ºÞ³Ìªñ¦³¤F·sªºªvÀø¤èªk¡A¦ý§Ú­Ì¤£Â_Å¥¨ì¥@¬É¦U¦aªºÂåÀø«O°·±M·~¤H­ûªº·N¨£¡A»Ý­n§ó¦hªºªvÀø¿ï¾Ü¨Ó¸Ñ¨M¨C¦ì±wªÌªº¤£¦PÅé¼x©M¯gª¬¡C³o¨Ç¬ã¨sµ²ªG¥O§Ú­Ì·P¨ì¹ª»R¡A³o¨Çµ²ªGªí©ú¡A¹ï©ó±w¦³³oºØ¨Ï¤H°I®zªººC©Ê¥Ö½§¯fªº±wªÌ¡A¦±§´¯]³æ§Ü¥i¯à¬O¤@ºØ¦³®Ä¥B­@¨ü©Ê¨}¦nªºªø´ÁªvÀø¤è®×¡C¡¨

LEO Pharma­p¹º¦b2020¦~¦VºÊºÞ¾÷ºc´£¥æ¥Î©óªvÀø¤¤¦Ü­««×ADªº¦¨¦~±wªÌªºtralokinumabªº¤W¥«±ÂÅv¥Ó½Ð¡A¨Ö­p¹º±N³o¨Ç¬ã¨sªº¸Ô²Óµ²ªG´£¥æ¬ì¾Ç¤j·|¨Ã¦b¦P¦æµû¼f¤¤µoªí¥H¤Î2020¦~ªºÂå¾Ç´Á¥Z¡C

www.thepharmaletter.com/article/leo-pharma-reveals-positive-top-line-phase-iii-results-for-tralokinumab

Danish dermatology specialist LEO Pharma says that tralokinumab ¡V an investigational, fully-human monoclonal antibody that specifically neutralizes the interleukin-13 (IL-13) cytokine ¡V met all primary and secondary endpoints in its three pivotal Phase III studies (ECZTRA 1-3) for the treatment of moderate-to-severe atopic dermatitis (AD) in adults. During the studies, the overall adverse event rate was comparable between tralokinumab and placebo.

IL-13 is a key driver of the type 2 inflammation that plays a major role in AD, which is the most common inflammatory skin disease in the developed world, affecting up to 5% of adults across the USA, Canada, Europe and Japan. AD can have a significant, negative impact on patients¡¦ well-being, primarily due to distressing itch, sleep deprivation and social stigmatization due to visible lesions.

LEO Pharma acquired rights for tralokinumab in skin diseases in 2016 from AstraZeneca (LSE: AZN), in a deal that involved and upfront payment of $115 million to the Anglo-Swedish pharma major, as well up to $1 billion in commercially-related milestones and up to mid-teen tiered percentage royalties on product sales. AstraZeneca retains all rights to tralokinumab in respiratory disease and any other indications outside of dermatology.

Competitive sector

According to analytics firm GlobalData, the atopic dermatitis market will grow from $6.4 billion in 2017 to $18.3 billion in 2027 across the seven major markets (7MM = USA, France, Germany, Italy, Spain, the UK, and Japan), expanding at a compound annual growth rate (CAGR) of 11.1%.

The sector has a significant heavyweight on the market in the form of Sanofi (Euronext: SAN) and Regeneron¡¦s (Nasdaq: EGN) Dupixent (dupilumab), which is already generating blockbuster revenues and peak sales of $11 billion are projected.

A late-stage IL-13 is Dermira¡¦s (Nasdaq: DERM) lebrikizumab, which was acquired from Roche (ROG: SIX) after the latter failed in its effort in asthma.

Also, Janssen Biotech, part of US healthcare giant Johnson & Johnson (NYSE: JNJ), just a few days ago acquired XBiotech¡¦s (Nasdaq: XBIT) novel antibody, bermekimab, that neutralizes interleukin-1 alpha (IL-1⍺).

¡§In its moderate-to-severe form, AD can cause unbearable recurring symptoms for patients,¡¨ said Dr Kim Kjoeller, executive vice president, global R&D at LEO Pharma. ¡§Despite recent treatment advances, we consistently hear from healthcare professionals around the world that additional treatment options are needed to address the different signs and symptoms for each patient. We are encouraged by these study results, which show that tralokinumab could be an efficacious and well-tolerated long-term treatment solution for patients living with this debilitating chronic skin disease,¡¨ he added.

LEO Pharma is planning to submit marketing authorization applications for tralokinumab for the treatment of adult patients with moderate-to-severe AD to regulatory agencies in 2020 and plans to submit the detailed results of these studies for presentation at scientific congresses and publication in peer-reviewed medical journals in 2020 as well.

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www.globenewswire.com/news-release/2019/03/18/1756186/0/en/Dermira-Announces-Positive-Topline-Results-from-Phase-2b-Study-of-Lebrikizumab-in-Patients-with-Atopic-Dermatitis.html

Dermira Announces Positive Topline Results from Phase 2b Study of Lebrikizumab in Patients with Atopic Dermatitis

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March 18, 2019 07:00 ET | Source: Dermira, Inc.

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125 mg lebrikizumabµ¹ÃÄÁuªº¦¸­n²×ÂI¥¼¹F¨ì²Î­p¾Ç·N¸q¡C

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About Lebrikizumab Phase 2b Study

Across all of the doses evaluated, lebrikizumab showed a dose-dependent and statistically significant improvement in the primary endpoint, the mean percent change in EASI score from baseline to week 16. The improvement in EASI score was 62.3% for patients receiving lebrikizumab, 125 milligrams (mg), every four weeks (p=0.0165), 69.2% for patients receiving lebrikizumab, 250 mg, every four weeks (p=0.0022) and 72.1% for patients receiving lebrikizumab, 250 mg, every two weeks (p=0.0005) compared to 41.1% for patients receiving placebo.

Patients treated with lebrikizumab at the 250 mg dose every two or four weeks achieved statistically significant improvements in other key efficacy measures compared to placebo after 16 weeks of treatment, including:

Lebrikizumab 250 mg every four weeks:

•33.7% of lebrikizumab-treated patients achieved clearing or near-clearing of skin lesions, as measured by an investigator¡¦s global assessment (IGA) score of 0 or 1, and a reduction of at least 2 points from baseline, compared to 15.3% with placebo (p=0.0392).

•56.1% of lebrikizumab treated patients achieved a reduction of at least 75% from baseline in EASI score (EASI-75), compared to 24.3% on placebo (p=0.0021).

•36.1% of lebrikizumab treated patients achieved a reduction of at least 90% from baseline in EASI score (EASI-90), compared to 11.4% on placebo (p=0.0062).

Lebrikizumab 250 mg every two weeks:

•44.6% of lebrikizumab-treated patients achieved clearing or near-clearing of skin lesions, as measured by an IGA score of 0 or 1, and a reduction of at least 2 points from baseline, compared to 15.3% with placebo (p=0.0023).

•60.6% of lebrikizumab treated patients achieved a reduction of at least 75% from baseline in EASI-75, compared to 24.3% on placebo (p=0.0005).

•44.0% of lebrikizumab treated patients achieved a reduction of at least 90% from baseline in EASI-90, compared to 11.4% on placebo (p=0.0006).

The secondary endpoints for the 125 mg lebrikizumab dosing arm did not meet statistical significance.

The most common adverse events reported across all three lebrikizumab dosing arms were upper respiratory tract infection (7.5% vs. 5.8% for placebo), nasopharyngitis (6.6% vs. 3.8% for placebo), headache (3.1% vs. 5.8% for placebo) and injection site pain (3.1% vs. 1.9% for placebo). Rates of conjunctivitis (2.6% compared to no reports for placebo) and herpes infections (2.2% compared to no reports for placebo) were low. Overall, adverse events observed in lebrikizumab-treated patients were primarily mild to moderate in severity and infrequently led to treatment discontinuation.

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And Regeneron Announce That Dupilumab Has Received FDA Breakthrough Therapy Designation In Atopic Dermatitis

Paris and Tarrytown, New York - November 20, 2014 - Sanofi and Regeneron Pharmaceuticals, Inc. today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to dupilumab for the treatment of adults with moderate-to-severe atopic dermatitis (AD) that are not adequately controlled with topical prescription therapy and/or for whom these treatments are not appropriate. Dupilumab is an investigational therapy blocking IL-4 and IL-13, two cytokines required for the Th2 immune response. The designation is based on previously announced positive results from Phase 1 and 2 clinical trials.

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About Dupilumab and IL-4/IL-13 Signaling

Dupilumab, a fully-human monoclonal antibody, is directed against the IL-4 receptor alpha subunit, which blocks signaling from both IL-4 and IL-13. IL-4 and IL-13 are key cytokines that are required for the initiation and maintenance of the Th2 (Type 2 helper T-cell) immune response, which is believed to be a critical pathway in allergic inflammation.

Dupilumab was created using Regeneron¡¦s pioneering VelocImmuneR technology and is being co-developed with Sanofi in atopic dermatitis, asthma and chronic sinusitis with nasal polyposis. Dupilumab is an investigational agent under clinical development and its safety and efficacy have not been fully evaluated by any regulatory authority

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Dermira Receives Fast Track Designation from FDA for Lebrikizumab for the Treatment of Atopic Dermatitis

Business Wire Business Wire¡EDecember 10, 2019

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¡§§Ú­Ì«Ü°ª¿³FDA±Â¤©lebrikizumab§Ö³t³q¹D¦WºÙ¡A¨Ã·NÃѨ줤«×¦Ü­««×¯SÀ³©Ê¥Öª¢±wªÌªº»Ý¨D¥¼±o¨ìº¡¨¬¡Alebrikizumab¥i¥H¬°³oºØÄY­«¯e¯f´£¨ÑªvÀøªº¼ç¤O¡A¡¨ Tomm Wiggansªí¥ÜDermira°õ¦æ©x¡C ¡§¦pªG¦b¥¿¦b¶i¦æªºµû¦ô¬ã¨sªvÀøªº¦w¥þ©Ê¡A¦³®Ä©Ê©M­@¨ü©Êªº²Ä¤T¶¥¬q¬ã¨s¤¤ÃÒ¹ê¤F¦­´Áªº²Ä¤G¶¥¬q¬ã¨sµ²ªG¡A¨º»ò³oºØ§Ö³t³q¹DªººÙ¸¹¨Ï§Ú­Ì§ó¥i¯à§ó§Ö¦a¬°±wªÌ´£¨Ñ·sªºªvÀø¿ï¾Ü¡C¡¨

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finance.yahoo.com/news/dermira-receives-fast-track-designation-133000115.html

Dermira, Inc. (NASDAQ: DERM), a biopharmaceutical company dedicated to bringing biotech ingenuity to medical dermatology by delivering differentiated, new therapies to the millions of patients living with chronic skin conditions, today announced that the

U.S. Food and Drug Administration (FDA) has granted Fast Track designation for lebrikizumab, its novel, investigational treatment being evaluated for patients with moderate-to-severe atopic dermatitis.

Fast Track is a designation granted by the FDA intended to facilitate the drug development process and expedite the review of therapies to treat serious conditions and fill an unmet medical need, including by demonstrating an advantage over currently available therapy. The goal of the Fast Track process is to ensure important new treatments reach patients as quickly as possible.

We are pleased that the FDA granted lebrikizumab its Fast Track designation and recognizes the unmet need for patients living with moderate-to severe atopic dermatitis and the potential for lebrikizumab to offer a treatment for this serious condition, said Tom Wiggans, chairman and chief executive officer of Dermira. This Fast Track designation puts us one step closer to potentially delivering a new therapeutic option more quickly to patients should the results from earlier Phase 2 studies be confirmed in the ongoing Phase 3 studies assessing the safety, efficacy and tolerability of the investigational therapy.

Lebrikizumab is currently being evaluated in two Phase 3 studies, ADvocate 1 and ADvocate 2, to confirm its safety and efficacy in adolescent and adult patients, ages 12 years and older, with moderate-to-severe atopic dermatitis.

About Atopic Dermatitis

Atopic dermatitis is the most common and severe form of eczema, a chronic inflammatory condition that can present as early as childhood and continue into adulthood. A moderate-to-severe form of the disease is characterized by a range of signs and symptoms, including rashes on the skin that often cover much of the body, as well as intense, persistent itching. The condition can have a negative impact on patients¡¦ mental and physical functioning, limiting their daily activities and health-related quality of life. Patients with moderate-to-severe atopic dermatitis have reported a larger impact on quality of life than patients with psoriasis.

About Lebrikizumab

Lebrikizumab is a novel, investigational, monoclonal antibody designed to bind IL-13 with very high affinity, specifically preventing the formation of the IL-13R£\1/IL-4R£\ heterodimer complex and subsequent signaling, thereby inhibiting the biological effects of IL-13 in a targeted and efficient fashion. IL-13 is believed to be a central pathogenic mediator that drives multiple aspects of the pathophysiology underlying the range of signs and symptoms of atopic dermatitis by promoting type 2 inflammation and mediating its effects on tissue, resulting in skin barrier dysfunction, itch, skin thickening and infection.

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The trial will recruit up to 50

moderate-to-severe

atopic dermatitis patients and study completion is expected in the second half of 2020, with interim results expected in early 2020. After completion of the MAD trial, we plan to initiate a phase 2b dose-range finding trial in atopic dermatitis patients.

sec.report/Document/0001193125-19-306309/

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Out-License and Other Agreements

Almirall Agreement

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¥H¤Î¦b¼Ú¬w±N¥Î©óªvÀø©Î¹w¨¾©Ò¦³¾AÀ³¯gªº¨Ó¥¬¦C³æ§Ü°Ó·~¤Æ¡]¡§ Lebrikizumab¼Ú·ù³\¥i¡¨¡^¡C

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¦b¹F¦¨¬Y¨Ç¶}µo¡AºÊºÞ©M¾P°â¨½µ{¸O«áÃB¥~¤ä¥Iªº´Ú¶µ¡A¥]¬A»P§Ú­Ìµo°_ªº3,000¸U¬ü¤¸¬ÛÃöªº

¬Y¨Ç3´ÁÁ{§É¬ã¨s¥H¤Î¯S³\Åv¨Ï¥Î¶O¥Nªí¤F¼Ú¬wlebrikizumab²b¾P°âÃBªº¦Ê¤À¤ñ¡C

2019¦~10¤ë¡A§Ú­Ì±Ò°Ê¤F²Ä¤@­Ó

lebrikizumab 3´ÁÁ{§É¬ã¨sIJµo¤FAlmirall 750¸U¬ü¤¸ªº¨½µ{¸O¥I´Ú¡C

750¸U¬ü¤¸ªº¨½µ{¸O¥I´Ú¬OAlmirall¦³¸q°È´N¬Y¨Ç¬Y¨Ç3´ÁÁ{§É¬ã¨sªº±Ò°Ê¦V§Ú­Ì¤ä¥IÁ`­p3000¸U¬ü¤¸¡C

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¥æ¥ILebrikizumab¼Ú·ù³\¥i¡A¥H¤Î¡]ii¡^¶i¦ælebrikizumab²Ä¤T¶¥¬q¶}µo­p¹º¡C§Ú­Ì½T©wºI¦Ü6¤ëªº¥æ©ö»ù®æ

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We entered into an option and license agreement with Almirall in February 2019 (¡§Almirall Agreement¡¨), under which Almirall acquired an option to

exclusively license rights to develop lebrikizumab for the treatment or prevention of dermatology indications, including, but not limited to atopic dermatitis, and

commercialize lebrikizumab for the treatment or prevention of all indications in Europe (¡§Lebrikizumab EU License¡¨). In exchange, we received a non-refundable

upfront option fee of $30.0 million in March 2019. In June 2019, Almirall exercised its option pursuant to the Almirall Agreement. In connection with this exercise,

Almirall paid us an option exercise fee of $50.0 million, which we received in July 2019. Under the terms of the Almirall Agreement, we are entitled to receive

additional payments upon the achievement of certain development, regulatory and sales milestones, including $30.0 million in connection with the initiation by us of

certain Phase 3 clinical studies, as well as royalty payments representing percentages of net sales of lebrikizumab in Europe. In October 2019, we initiated the first

lebrikizumab Phase 3 clinical study, which triggered a $7.5 million milestone payment by Almirall to us. The $7.5 million milestone payment is part of the

$30.0 million in aggregate that Almirall is obligated to pay us in connection with the initiation of certain Phase 3 clinical studies.

Upon Almirall¡¦s election to exercise its option pursuant to the Almirall Agreement, we identified the following distinct performance obligations: (i) the

delivery of the Lebrikizumab EU License and (ii) the conduct of the lebrikizumab Phase 3 development program. We determined that the transaction price as of June

30, 2019 was $110.0 million, consisting of: (i) the $30.0 million upfront option fee; (ii) the $50.0 million option exercise fee; and (iii) the $30.0 million in milestones

in connection with the initiation of certain Phase 3 clinical studies, which were determined to not be constrained. Other future potential regulatory milestones were

considered to be fully constrained, as we determined that the achievement of such milestones is contingent upon success in future clinical trials and regulatory

approvals, which are not within our control and are uncertain at this stage. We expect that the sales-based milestone and royalty payments will be recognized when the

sales occur or the milestone is achieved. We will re-evaluate the transaction price each reporting period.

§Ú­Ì®Ú¾Ú¨â¶µ¼i¬ù¸q°È¤¤¨C¤@¶µªº¦ô­p¿W¥ß°â»ù¨Ó¤À°t¥æ©ö»ù®æ¡C§Ú­Ì½T©w¤F¿W¥ß

°ò©ó²{ª÷¬y¶q§é²{ªkªºLebrikizumab¼Ú·ù³\¥iªº¾P°â»ù®æ¡A¨Ã¦Ò¼{¤F¥H¤U´X­Ó¦]¯À¡A¥]¬A¦ý¤£­­©ó¡G¦ô­p¥«³õ

»Ý¨D¡A»s³y©M¨ÑÀ³¦¨¥»¡A¶}µo©M°Ó·~¤Æ¦¨¥»¡A§é²{²v¡A¶}µo©M§å­ã®É¶¡ªí¥H¤Î§Þ³N¥i¯à©Ê

©MºÊºÞ¤è­±ªº¦¨¥\¡C¤À°tµ¹§Ú­ÌªºLebrikizumab¼Ú·ù³\¥i¼i¬ù¸q°Èªº¥æ©ö»ù®æ³¡¤À·|¦b¥ß§Y°O¿ý

Almirall©ó2019¦~²Ä¤G©u«×¦æ¨Ï¨ä¿ï¾ÜÅv¡A¦]¬°Lebrikizumab¼Ú·ù³\¥i¥Nªí¤F¦Û2005¦~°_ÂàÅýªº¥\¯à©Êª¾ÃѲ£Åv

Almirallªº´ÁÅv¦æÅv¤é´Á¬°2019¦~6¤ë¡C§Ú­Ì®Ú¾Ú¥H¤U±¡ªp½T©w¤Flebrikizumab 3´Á¶}µo­p¹ºªº¿W¥ß°â»ù¡G

­n°õ¦æªºªA°Èªº©Ê½è¡A¬ÛÃö¶O¥Îªº¦ôºâ¥H¤ÎÃþ¦üªA°Èªº²Ä¤T¤è¶O²v¡C

¥æ©ö»ù®æ¤¤¤À°tµ¹§Ú­Ìªº³¡¤À

lebrikizumab²Ä¤T¶¥¬q¶}µo­p¹ºªº¼i¬ù¸q°È¨Ï¥Î¿é¤Jªk§@¬°lebrikizumab²Ä¤T¶¥¬q¶}µo½T»{¬°¦¬¤J

¸Ó­p¹º¥¿¦b§¹¦¨¡A¨ãÅéµøLebrikizumab¶}µo­p¹ºÁ`¶O¥Î©M¨C­Ó®É´Áªº¹ê»Ú¶O¥Î¦Ó©w¡C

¦b¦¹´Á¶¡

ºI¦Ü2019¦~9¤ë30¤éªº¤T­Ó¤ë¡A§Ú­Ì¶}©l´£¨Ñ¬ãµoªA°È¨Ã¶}©l½T»{»Plebrikizumab²Ä¤T¶¥¬q¬ÛÃöªº¦¬¤J

¶}µo­p¹º¼i¦æ¸q°È¡C

ºI¦Ü2019¦~9¤ë30¤éªº¤T­Ó¤ë©M¤E­Ó¤ë¡A§Ú­Ì¤À§O½T»{¤F130¸U¬ü¤¸©M5990¸U¬ü¤¸ªº¨ó§@©M³\¥i¦¬¤J

¦b§Ú­ÌªºÂ²©ú¦X¨Ö¹BÀç³øªí¤¤»P¡m Almirall¨óij¡n¬ÛÃö¡CºI¦Ü2019¦~9¤ë30¤é¡A¤w±N2,010¸U¬ü¤¸°O¬°»¼©µ¦¬¤J

¦b²©úªº¦X¨Ö¸ê²£­t¶Åªí¤W¡A¹w­p±N¦b³Ñ¾lªº²Ä3¶¥¬q¶}µo´Á¤º½T»{¬°¨ó§@©M³\¥i¦¬¤J¡C

We allocated the transaction price based on the estimated stand-alone selling prices of each of the two performance obligations. We determined the stand-alone

selling price for the Lebrikizumab EU License based on a discounted cash flow approach and considered several factors including, but not limited to: estimated market

demand, manufacturing and supply costs, development and commercialization costs, discount rate, development and approval timelines and probabilities of technical

and regulatory success. The portion of the transaction price allocated to our Lebrikizumab EU License performance obligation was recorded immediately upon

Almirall¡¦s exercise of its option in the second quarter of 2019, as the Lebrikizumab EU License represents functional intellectual property that was transferred as of

the date of Almirall¡¦s option exercise in June 2019. We determined the stand-alone selling price for our lebrikizumab Phase 3 development program based on the

nature of the services to be performed, estimates of the associated costs and third-party rates for similar services. The portion of the transaction price allocated to our

lebrikizumab Phase 3 development program performance obligation is being recognized as revenue using the input method as the lebrikizumab Phase 3 development

program is being completed, subject to changes in estimated total lebrikizumab development program costs and actual costs incurred during each period. During the

three months ended September 30, 2019, we began performing research and development services and started recognizing revenue related to the lebrikizumab Phase 3

development program performance obligation.

For the three and nine months ended September 30, 2019, we recognized $1.3 million and $59.9 million, respectively, as collaboration and license revenue

related to the Almirall Agreement in our condensed consolidated statements of operations. As of September 30, 2019, $20.1 million was recorded as deferred revenue

on the condensed consolidated balance sheets and is expected to be recognized as collaboration and license revenue over the remaining Phase 3 development period.

s23.q4cdn.com/229915008/files/doc_financials/2019/q3/eed4f82f-3329-4341-9c3f-3b2ff6647f9c.pdf

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Atopic Dermatitis: Global Drug Market | Forecast to 2027

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Thanks

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Prevalence of Childhood & Adult Atopic Dermatitis (AD)

Approximately 9.6 million U.S. children under the age of 18 have AD, and one-third have moderate to severe disease. 5, 7, 8

The prevalence of childhood AD has steadily increased from 8% to ~12% since 1997. 4

An estimated 16.5 million U.S. adults (7.3%) have AD that initially began at >2 years of age, with nearly 40% affected by moderate or severe disease. 9

Atopic dermatitis is not solely a disease of childhood onset; 1 in 4 adults report adult-onset of initial symptoms. 10, 11

Atopic dermatitis affects a similar number of male and female children, however, studies have shown it is more common in adult females than males. 2, 5, 6, 8, 9, 12, 13

In the U.S., AD affects more African-American/black children and European-American children compared to Hispanic children. 5, 7, 12

Although study percentages vary, adults that are multiracial or white tend to have the highest prevalence of atopic dermatitis. 2, 9, 14

African-American/black and Hispanic children tend to have more severe AD compared to white children. 8, 14

Children born outside the U.S. have a 50% lower risk of developing AD that increases after living in the U.S. for 10 years. 15

80% of individuals affected with AD experience disease onset prior to 6 years of age, and current data suggests at least 80% will ¡§outgrow¡¨ their AD by adolescence or adulthood. 16, 17

Children with more severe, persistent AD have a higher risk for prolonged disease, although AD may persist regardless of severity. 17, 18

nationaleczema.org/research/eczema-facts/

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Driven by the advent of new, systemic therapies addressing unmet needs in moderate-to-severe patients, major- marketsalesofbranded,systemic therapies for AD are projected to exceed $21B by 2027

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ASLAN PHARMACEU/ADR (NASDAQ:ASLN) Upgraded to ¡§Overweight¡¨ by Piper Jaffray Companies

Piper Jaffray Companies upgraded shares of ASLAN PHARMACEU/ADR (NASDAQ:ASLN) from a neutral rating to an overweight rating in a research note issued to investors on Monday, The Fly reports. The brokerage currently has $8.00 price target on the stock.

mitchellmessenger.com/2019/12/06/aslan-pharmaceu-adr-nasdaqasln-upgraded-to-overweight-by-piper-jaffray-companies.html

¾Ú¡m The Fly¡n³ø¾É¡A¶g¤@¦b¤@¥÷¬ã¨s³ø§i¤¤¡APiper Jaffray Companies±NASLAN PHARMACEU / ADR¡]NASDAQ¡GASLN¡^ªºªÑ²¼µû¯Å±q¤¤©Êµû¯Å¤W½Õ¦Ü¶W­«¡C ¸Ó¨é°Ó¥Ø«e¹ï¸ÓªÑªº¥Ø¼ÐªÑ»ù¬°8.00¬ü¤¸¡C

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sec.report/Document/0001193125-19-306309/

Form 424B5 Aslan Pharmaceuticals Ltd

Prospectus [Rule 424(b)(5)]

SEC.report

/ ASLAN Pharmaceuticals Ltd

/ Form 424B5

/ (Filer)

Published: 2019-12-04 17:18:12

ASLAN004 ¡V Multiple Ascending Dose Clinical Trial in

Moderate-to-Severe

Atopic Dermatitis

In October 2019, we announced the enrolment of the first patient in our MAD clinical trial testing the

first-in-class

therapeutic antibody ASLAN004 in

moderate-to-severe

atopic dermatitis patients. The randomised, double-blind, placebo-controlled clinical trial will evaluate three doses of ASLAN004 delivered subcutaneously and will be followed by an expansion cohort at the most efficacious dose. Each dose cohort will contain up to six patients on ASLAN004 and two patients on placebo, and the expansion cohort will contain 12 patients on ASLAN004 and six patients on placebo. Patients are dosed weekly for eight weeks to determine safety and the maximum efficacy of ASLAN004. The trial will recruit up to 50

moderate-to-severe

atopic dermatitis patients and study completion is expected in the second half of 2020, with interim results expected in early 2020. After completion of the MAD trial, we plan to initiate a phase 2b dose-range finding trial in atopic dermatitis patients.

On December 2, 2019, we reported preliminary unclean blinded data from the first three patients treated with the lowest dose of ASLAN004, 200mg, that had completed at least one month of dosing. ASLAN004 was well-tolerated and, to date, there have been no serious adverse events or treatment discontinuations. The EASI scores of the three patients were reduced by 85%, 70% and 59% and the EASI score continued to fall at four weeks with maximal efficacy expected at six to eight weeks. Corresponding changes were seen in other measures of efficacy. The data monitoring committee is scheduled for late December, after which the second dose cohort is expected to open.

Atopic dermatitis is the most common dermatological disease, affecting over 200 million patients worldwide, characterized by red inflamed skin and severe daytime and night-time itching, which can severely impact patients¡¦ quality of life. Up to

one-third

of adult atopic dermatitis patients are considered moderate to severe, for which currently available therapeutics are limited and management is challenging in the majority of cases.

page s-3

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August 8, 2017

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ù¤ó¡]Roche¡^¥h¦~¹Á¸Õ¨ÏLebrikizumabªvÀø­ý³Ý¨Ã¥H¥¢±Ñ§i²×¡A¥L©Ó»{2016¦~2¤ëªº¨â¶µ¤T´Á¸ÕÅç¥O¤H¥¢±æªºµ²ªG¡CLAVOLTAII¸ÕÅç¿ù¹L¤F¥D­n²×ÂI¡A¦]¬°¸Ó¸ÕÅçÅã¥Ü¤F¦å²M°©½¤³J¥Õ©Î¦å²G¶Ý»Ä©Ê²É²Ó­M¤ô¥­¸û°ªªº¤Hªº­ý³Ý«æ©Êµo§@²v¨S¦³²Î­p¾Ç·N¸q¡C

¦ý¬O¡ALAVOLTA I¸ÕÅç¹F¨ì¤F¨ä¥D­n²×ÂI¡A³oªí©ú¦å²Mperiostin©Î¦å²G¶Ý»Ä©Ê²É²Ó­M¤ô¥­¸û°ªªº¤Hªº­ý³Ý«æ©Êµo§@²vÅãµÛ­°§C¡A¨Ã¥B³q¹L¤@¬íÄÁªº±j¨î©I®ð¶q´ú¶q¡AªÍ¥\¯àÅãµÛ§ïµ½¡]FEV1¡^-¾¨ºÞÆ[¹î¨ìªº®ÄªG¤p©óII´Á¬ã¨s¤¤¬Ý¨ìªº®ÄªG¡C

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www.genengnews.com/topics/drug-discovery/dermira-gains-rights-to-roche-il-13-inhibitor-lebrikizumab-in-up-to-1-4b-partnership/

Dermira said today it has agreed to obtain exclusive, worldwide rights from Roche and its Genentech subsidiary to develop and commercialize lebrikizumab, a monoclonal antibody targeting interleukin-13 (IL-13), for most indications, in a deal that could generate up to $1.4 billion for the pharma giant.

Under the companies¡¦ licensing agreement, Dermira will gain rights to lebrikizumab in atopic dermatitis and all other indications except interstitial lung diseases, such as idiopathic pulmonary fibrosis¡Xindications to which Roche will retain rights.

Roche tried and failed last year to advance lebrikizumab in asthma, acknowledging disappointing results from two Phase III trials in February 2016. The LAVOLTA II trial missed its primary endpoint by showing rates of asthma exacerbations in people with higher levels of serum periostin or blood eosinophils that were not statistically significant.

However, the LAVOLTA I trial met its primary endpoint, showing a significant reduction in the rate of asthma exacerbations in people with higher levels of serum periostin or blood eosinophils, as well as significant improvement in lung function as measured by forced expiratory volume in one second (FEV1)¡Xthough observed effects were less than seen in Phase II studies.

Today, Dermira said it planned to launch a Phase IIb dose-ranging study assessing lebrikizumab in adults with moderate-to-severe atopic dermatitis in the first quarter of 2018. The goal of the study will be to optimize the dose of lebrikizumab for an eventual Phase III clinical program.

Preliminary design elements of the Phase IIb dose-ranging study include evaluating a loading dose and higher dose regimens of lebrikizumab than were explored in previous atopic dermatitis studies, according to Dermira.

¡§The addition of this program to our development portfolio represents an important step toward our goal of building a leading medical dermatology company dedicated to delivering differentiated, new therapies to the millions of patients living with chronic skin conditions,¡¨ Dermira chairman and CEO Tom Wiggans said in a statement.

Promising Preclinical, Early Clinical Results

Dermira CMO Eugene Bauer, M.D., added that lebrikizumab has generated promising preclinical and early clinical data that have suggested that higher doses of lebrikizumab could lead to greater efficacy in atopic dermatitis¡Xwhile potentially offering a less frequent and therefore more convenient dosing regimen relative to existing therapies.

Dermira has agreed to pay Roche an initial $80 million this year and $55 million in 2018¡Xas well as payments tied to achieving milestones.

The milestone payments include $40 million upon the initiation of Dermira¡¦s first Phase III clinical study, up to $210 million upon achieving regulatory and first commercial sale milestones in certain territories, and up to $1.025 billion upon achieving net sales thresholds for lebrikizumab in indications other than interstitial lung disease.

Under their collaboration, Roche retains exclusive rights to develop and promote lebrikizumab for interstitial lung diseases, such as idiopathic pulmonary fibrosis.

Dermira added that it also agreed to pay Roche royalties totaling percentages of net sales ranging from the high single-digits to the high teens.

The deal is expected to close in the third quarter, subject to expiration or termination of the waiting period under the Hart¡VScott¡VRodino Antitrust Improvements Act, as amended.

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en.wikipedia.org/wiki/Interleukin_13

Interleukin 13 (IL-13) is a protein that in humans is encoded by the IL13 gene.[4][5][6] IL-13 was first cloned in 1993 and is located on chromosome 5q31 with a length of 1.4kb.[4] It has a mass of 13 kDa and folds into 4 alpha helical bundles.[7] The secondary structural features of IL-13 are similar to that of Interleukin 4 (IL-4); however it only has 25% sequence homology to IL-4 and is capable of IL-4 independent signaling.[7][4][8] IL-13 is a cytokine secreted by T helper type 2 (Th2) cells, CD4 cells, Natural killer T cell, Mast cell, Basophil cells, Eosinophil cells and Nuocyte cells.[7] Interleukin-13 is a central regulator in IgE synthesis, goblet cell hyperplasia, mucus hypersecretion, airway hyperresponsiveness, fibrosis and chitinase up-regulation.[7] It is a mediator of allergic inflammation and different diseases including asthma.[7]

Functions

IL-13 has effects on immune cells that are similar to those of the closely related cytokine IL-4.[4] However, IL-13 is suspected to be central mediator of the physiologic changes induced by allergic inflammation in many tissues.[4]

Although IL-13 is associated primarily with the induction of airway disease, it also has anti-inflammatory properties.[4] IL-13 induces a class of protein-degrading enzymes, known as matrix metalloproteinases (MMPs), in the airways.[4] These enzymes are required to induce aggression of parenchymal inflammatory cells into the airway lumen, where they are then cleared.[4] Among other factors, IL-13 induces these MMPs as part of a mechanism that protects against excessive allergic inflammation that predisposes to asphyxiation.[4]

IL-13 is known to induce changes in hematopoietic cells, but these effects are probably less important than that of IL-4.[4] Furthermore, IL-13 can induce immunoglobulin E (IgE) secretion from activated human B cells.[4][7] Deletion of IL-13 from mice does not markedly affect either Th2 cell development or antigen-specific IgE responses induced by potent allergens.[4] In comparison, deletion of IL-4 deactivates these responses. Thus, rather than a lymphoid cytokine, IL-13 acts more prominently as a molecular bridge linking allergic inflammatory cell to the non-immune cells in contact with them, thereby altering physiological function.[4]

The signaling of IL-13 begins through a shared multi-subunit receptor with IL-4.[7] This receptor is a heterodimer receptor complex consisting of alpha IL-4 receptor (IL-4R£\) and alpha Interleukin-13 receptor (IL-13R1).[7] The high affinity of IL-13 to the IL-13R1 leads to their bond formation which further increase the probability of a heterodimer formation to IL-4R1 and the production of the type 2 IL-4 receptor. Heterodimerization activates both the STAT6 and the IRS.[7] STAT6 signaling is important in initiation of the allergic response.[7] Most of the biological effects of IL-13, like those of IL-4, are linked to a single transcription factor, signal transducer and activator of transcription 6 (STAT6).[7] Interleukin-13 and its associated receptors with £\ subunit of the IL-4 receptor (IL-4R£\) allows for the downstream activation of STAT6.[9] The JAK Janus kinase proteins on the cytoplasmic end of the receptors allows for the phosphorylation of STAT6, which then forms an activated homodimer and are transported to the nucleus.[9] Once, in the nucleus, STAT6 heterodimer molecule regulates gene expression of cell types critical to the balance between host immune defense and allergic inflammatory responses such as the development of Th2.[9] This can be resulted from an allergic reaction brought about when facing an Ala gene. IL-13 also binds to another receptor known as IL-13R£\2.[10] IL-13R£\2 (which is labelled as a decoy receptor) is derived from Th2 cells and is a pleotropic immune regulatory cytokine.[10] IL-13 has greater affinity (50-times) to IL-13R£\2 than to IL-13Ra1.[10] The IL-13R£\2 subunit binds only to IL-13 and it exists in both membrane-bound and soluble forms in mice.[10] A soluble form of IL-13R£\2 has not been detected in human subjects.[10] Studies of IL-13 transgenic mice lungs with IL-13R£\2 null loci indicated that IL-13R£\2 deficiency significantly augmented IL-13 or ovalbumin-induced pulmonary inflammation and remodeling.[10] Most normal cells, such as immune cells or endothelial cells, express very low or undetectable levels of IL-13 receptors.[10] Research has shown that cell-surface expression of IL-13R£\2 on human asthmatic airway fibroblasts was reduced compared with expression on normal control airway fibroblasts.[10] This supported the hypothesis that IL-13R£\2 is a negative regulator of IL-13¡Vinduced response and illustrated significantly reduced production of TGF-£]1 and deposition of collagen in the lungs of mice.[10]

Interleukin-13 has a critical role in the Goblet cell metaplasia.[11] Goblet cells are filled with mucin (MUC).[11] MUC5AC Mucin 5AC is a gel-like mucin product of goblet cells.[11] Interleukin-13 induces goblet cell differentiation and allows for the production of MUC5AC in tracheal epithelium.[11] 15-Lipoxygenase-1 (15LO1) which is an enzyme in the fatty acid metabolism and its metabolite, 15-HETE, are highly expressed in asthma (which lead to the overexpression of MUC5AC) and are induced by IL-13 in human airway epithelial cells. With the increasing number of goblet cells, there is the production of excessive mucus within the bronchi.[11] The functional consequences of the changes in MUC storation and secretion contributes to the pathophysiologic mechanisms for various clinical abnormalities in asthmatic patients including sputum production, airway narrowing, exacerbation and accelerated loss in lung function.[11]

Additionally, IL-13 has been shown to induce a potent fibrogenic program during the course of diverse diseases marked by elevated Type 2 cytokines such as chronic schistosomiasis and atopic dermatitis among others. It has been suggested that this fibrogenic program is critically dependent on direct IL-13 signaling through IL-4R£\ on PDGFR£]+ fibroblasts.[12]

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finance.yahoo.com/news/dermira-presents-scientific-research-findings-210500974.html

Dermira Presents New Scientific Research Findings from the Lebrikizumab Program at Leading International Itch Conference

Business Wire Business Wire¡ENovember 15, 2019

MENLO PARK, Calif.--(BUSINESS WIRE)--

New findings in human sensory neurons highlight role of IL-13 in amplifying itch and lebrikizumab¡¦s role in inhibiting itch signals in atopic dermatitis

- Lebrikizumab Phase 3 program is currently enrolling adult and adolescent patients with moderate-to-severe atopic dermatitis

Dermira, Inc. (DERM), a biopharmaceutical company dedicated to bringing biotech ingenuity to medical dermatology by delivering differentiated, new therapies to the millions of patients living with chronic skin conditions, today announced that new scientific findings highlighting the role of interleukin-13 (IL-13) in amplifying itch and the role lebrikizumab plays in reducing itch, will be presented at the 10th World Congress on Itch taking place November 17-19 in Sydney, Australia.

Itch is defined as an unpleasant sensation causing the desire to scratch the surface of the skin. Chronic itch affects approximately one-fifth of the global population and can have a significant impact on a person¡¦s quality of life. Itch is often associated with sleep disorders, depression and anxiety and is cited as one of the most burdensome aspects of atopic dermatitis, as underscored during a recent Patient-Focused Drug Development meeting.

IL-13 is believed to be a central pathogenic mediator that drives multiple aspects of the pathophysiology underlying the range of signs and symptoms of atopic dermatitis by promoting type 2 inflammation and mediating its effects on tissue, resulting in skin barrier dysfunction, itch, skin thickening and infection.

Key Research Findings

In laboratory experiments, cultured human sensory neurons were stimulated with IL-13 and subsequently introduced to several common itch-inducing agents (pruritogens), including histamine, serotonin and BAM8-22. The experiments demonstrated that IL-13 directly interacts with human sensory neurons, enhancing the itch induced by these itch-inducing agents.

When lebrikizumab was introduced, it significantly inhibited these potentiated itch signals to known pruritogens, demonstrating that lebrikizumab has the potential to block enhanced itch signals in inflammatory skin conditions such as atopic dermatitis. This finding supports the results observed in Dermira¡¦s Phase 2b dose-ranging study evaluating lebrikizumab in patients with moderate-to-severe atopic dermatitis, who reported improvements in itch symptoms as early as day two of treatment.

The findings will be submitted for publication in a peer-reviewed journal.

¡§People suffering from chronic itch associated with a host of dermatologic diseases often cite it as the most debilitating symptom,¡¨ said Luis Pena, chief development officer of Dermira. ¡§We believe these findings support our understanding of the role of lebrikizumab in reducing itch, helping to explain the improvement in itch observed in atopic dermatitis patients treated with the investigational therapy in our Phase 2b study.¡¨

Lebrikizumab is a novel, investigational, monoclonal antibody designed to bind IL-13 with very high affinity, specifically preventing the formation of the IL-13R£\1/IL-4R£\ heterodimer complex and subsequent signaling, thereby inhibiting the biological effects of IL-13 in a targeted and efficient fashion.

The findings on itch will be presented by Ferda Cevikbas, Ph.D., director of research at Dermira, on November 19, 2019 during a session titled, Concurrent Session 2: New receptors, channels and pathways for itch. Dr. Cevikbas is also serving as co-chair of the session.

Dr. Cevikbas is a noted expert in the pathophysiology of itch, having spent much of her career at the University of California, San Francisco, where she studied the differences and similarities between itch and pain. Prior to joining Dermira, she worked with a team of researchers at a biotechnology company exploring the mechanism of action for research compounds in inflammation and itch. Dr. Cevikbas is trained in dermatology and neuroscience.

¡§IL-13 has long been viewed as an important target in atopic dermatitis,¡¨ said Dr. Cevikbas. ¡§For the first time, IL-13 has been investigated in translational neuroscience studies in human sensory neurons to understand its role in chronic itch and the ability of lebrikizumab to block the effects of neuroactive IL-13. This translational work will inform future research and enhance our understanding of chronic itch in atopic dermatitis.¡¨

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www.wealth.com.tw/home/articles/22543

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·|­û¡G¤Ñ©R10141925  µoªí®É¶¡:2019/12/5 ¤U¤È 03:14:54²Ä 1872 ½g¦^À³
Dupilumab ªvÀø ¤¤-­««×COPD¤T´ÁÁ{§É

Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate-to-severe COPD With Type 2 Inflammation (BOREAS)

clinicaltrials.gov/ct2/show/NCT03930732?term=Dupixent+%28dupilumab%29&draw=1&rank=20

Estimated Enrollment ƒÊ : 924 participants

Allocation: Randomized

Intervention Model: Parallel Assignment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose: Treatment

Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, 52-week Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD) With Type 2 Inflammation

Actual Study Start Date ƒÊ : April 15, 2019

Estimated Primary Completion Date ƒÊ : January 2022

Estimated Study Completion Date ƒÊ : April 2022

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·|­û¡G¤Ñ©R10141925  µoªí®É¶¡:2019/12/4 ¤U¤È 04:45:47²Ä 1861 ½g¦^À³
Lebrikizumab AD ªº¤G­Ó¤T´ÁÁ{§É,¦@800¤H¦Ó¤w,¦Ó¥B

Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)

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1.

clinicaltrials.gov/ct2/show/NCT04146363?term=Lebrikizumab++AD&draw=1&rank=5

Evaluation of the Efficacy and Safety of Lebrikizumab in Moderate to Severe Atopic Dermatitis (ADvocate1)

Study Design

Go to sections

Study Type ƒÊ : Interventional (Clinical Trial)

Estimated Enrollment ƒÊ : 400 participants

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: Randomized, double-blind, parallel group, placebo controlled

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description: Double-blind

Primary Purpose: Treatment

Official Title: A Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Lebrikizumab in Patients With Moderate to Severe Atopic Dermatitis

Actual Study Start Date ƒÊ : October 8, 2019

Estimated Primary Completion Date ƒÊ : June 2021

Estimated Study Completion Date ƒÊ : December 2021

2.Evaluation of the Efficacy and Safety of Lebrikizumab in Moderate to Severe Atopic Dermatitis (ADvocate2)

clinicaltrials.gov/ct2/show/NCT04178967?term=Lebrikizumab++AD&draw=1&rank=4

Study Design

Study Type ƒÊ : Interventional (Clinical Trial)

Estimated Enrollment ƒÊ : 400 participants

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: Randomized, double-blind, parallel group, placebo controlled

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description: Double-blind

Primary Purpose: Treatment

Official Title: A Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Lebrikizumab in Patients With Moderate to Severe Atopic Dermatitis.

Actual Study Start Date ƒÊ : November 8, 2019

Estimated Primary Completion Date ƒÊ : June 2021

Estimated Study Completion Date ƒÊ : December 2021

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°ò¥»¤WDuplimab , AD, FDA ®Ö·Ç , ¤T¦~ªvÀøµL®Äªº±wªÌ,¤~¥ÎDuplimab¥Íª«»s¾¯, ¦~ÃĶO36,000¬ü¤¸,

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©Û¦¬ >=1 ¦~ AD

A Study of Lebrikizumab in Patients With Moderate-to-Severe Atopic Dermatitis

Study Design

Study Type ƒÊ : Interventional (Clinical Trial)

Actual Enrollment ƒÊ : 280 participants

Allocation: Randomized

Intervention Model: Parallel Assignment

Masking: Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose: Treatment

Official Title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial to Evaluate the Efficacy and Safety of Lebrikizumab in Patients With Moderate-to-Severe Atopic Dermatitis

Actual Study Start Date ƒÊ : January 30, 2018

Actual Primary Completion Date ƒÊ : February 7, 2019

Actual Study Completion Date ƒÊ : May 23, 2019

Criteria

Inclusion Criteria:

•Male or female, 18 years or older.

•Chronic AD as defined by Hanifin and Rajka (1980) that has been present for ≥1 year before the screening visit .

•Eczema Area and Severity Index (EASI) score ≥16 at the screening and the baseline visit.

•Investigator Global Assessment (IGA) score ≥3 (scale of 0 to 4) at the screening and the baseline visit.

•≥10% body surface area (BSA) of AD involvement at the screening and the baseline visit.

clinicaltrials.gov/ct2/show/NCT03443024

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Dermira Announces Initiation of Phase 3 Program Evaluating Lebrikizumab in

Patients with Moderate-to-Severe Atopic Dermatitis

- Two identical Phase 3 monotherapy studies expected to enroll a total of

approximately 800 adult and adolescent patients ages 12 and older

- Topline results from the 16-week induction period expected in the first half

of 2021

Business Wire

MENLO PARK, Calif. -- October 9, 2019

Dermira, Inc. (NASDAQ: DERM), a biopharmaceutical company dedicated to

bringing biotech ingenuity to medical dermatology by delivering

differentiated, new therapies to the millions of patients living with chronic

skin conditions, today announced dosing of the first patient in a Phase 3

study evaluating the safety and efficacy of lebrikizumab in adult and

adolescent patients ages 12 and older with moderate-to-severe atopic

dermatitis, the most common form of eczema.

Lebrikizumab is a novel, investigational, monoclonal antibody designed to bind

IL-13 with very high affinity, specifically preventing the formation of the

IL-13R£\1/IL-4R£\ heterodimer complex and subsequent signaling, thereby

inhibiting the biological effects of IL-13 in a targeted and efficient

fashion. IL-13 is believed to be a central pathogenic mediator that drives

multiple aspects of the pathophysiology of atopic dermatitis by promoting type

2 inflammation and mediating its effects on tissue, resulting in skin barrier

dysfunction, itch, skin thickening and infection.

¡§The positive results of our Phase 2b dose-ranging study suggest specifically

targeting IL-13 with lebrikizumab has the potential to deliver a

best-in-disease therapy for people living with moderate-to-severe atopic

dermatitis,¡¨ said Tom Wiggans, chairman and chief executive officer of

Dermira. ¡§Our Phase 3 clinical program is designed to confirm those findings

and hopefully bring an important new treatment option to the millions of

people living with this chronic and often debilitating disease. We expect to

report findings from the 16-week induction period of the monotherapy studies

in the first half of 2021.¡¨

¡§The initiation of the Phase 3 study combined with the positive results of the

Phase 2b study underscore our confidence and excitement around the potential

of lebrikizumab for patients with moderate-to-severe atopic dermatitis,¡¨ said

Peter Guenter, chief executive officer of Almirall, Dermira¡¦s collaboration

partner in Europe. ¡§Almirall is fully committed to this partnership and to

offering breakthrough treatments, like lebrikizumab, that have the potential

to make a meaningful difference for patients living with severe skin

conditions.¡¨

Lebrikizumab Phase 3 Program

The lebrikizumab Phase 3 program includes two identical, randomized,

double-blind, placebo-controlled, parallel-group Phase 3 studies designed to

confirm the safety and efficacy of lebrikizumab as monotherapy in patients

with moderate-to-severe atopic dermatitis. The studies are expected to enroll

a total of approximately 800 adult and adolescent patients ages 12 years and

older with moderate-to-severe atopic dermatitis at approximately 200 sites in

the United States, Europe and Asia.

Key patient inclusion criteria for the monotherapy studies include the

presence of chronic atopic dermatitis for at least one year, an Investigator¡¦s

Global Assessment (IGA) score of 3 or 4 (on a 5-point scale ranging from 0 to

4), an Eczema Area Severity Index (EASI) score of 16 or greater and body

surface area (BSA) involvement of at least 10 percent at screening and

baseline.

The studies will evaluate a 250 mg dose of lebrikizumab administered by

subcutaneous injection every two weeks, following a loading dose of 500 mg

administered at baseline (day 0) and week 2, compared to placebo for 16 weeks

(the induction period). Following the end of the 16-week induction period,

study patients who respond during the induction period (as evidenced by

achievement of an IGA 0/1 response, representing a reduction of 2 or more

points in IGA score from baseline to a final score of 0 (clear) or 1 (almost

clear), or an EASI-75 response, representing an improvement in EASI score of

at least 75 percent from baseline) will be re-randomized to one of the

following treatment groups for an additional 36-week maintenance period:

* Group A: Lebrikizumab 250 mg given every two weeks;

* Group B: Lebrikizumab 250 mg given every four weeks; or

* Group C: Placebo given every two weeks.

Patients who do not achieve an IGA of 0/1 response or an EASI-75 response at

week 16 and patients who do not maintain an EASI-50 response during the

maintenance period will be assigned to receive lebrikizumab 250 mg as

open-label treatment every two weeks through week 52.

The primary efficacy endpoint of the studies is the percentage of patients

with an IGA 0/1 response from baseline to week 16.

Key secondary efficacy endpoints that will be evaluated during the 16-week

induction period include: the percentage of patients achieving EASI-75; the

percentage of patients achieving EASI-90; the percentage of patients with a

pruritus (itch) numerical rating (NRS) score of at least 4 at baseline who

achieve a reduction of at least 4 points; percentage changes in pruritus and

sleep-loss scores; and change in BSA.

The company expects to report topline findings from the 16-week induction

period in the first half of 2021. In addition to the two monotherapy studies,

the company plans to include a study in the Phase 3 program that evaluates

lebrikizumab when used in combination with topical corticosteroids. The impact

of lebrikizumab treatment on quality of life will also be assessed across a

number of additional measures.

www.bloomberg.com/press-releases/2019-10-09/dermira-announces-initiation-of-phase-3-program-evaluating-lebrikizumab-in-patients-with-moderate-to-severe-atopic-dermatitis

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¤é«e¡A¨È·à±d-KY¡]Aslam Pharmaceuticals¡^¤½¥q«Å¥¬¡A¸Ó¤½¥q¶}µoªº¹v¦VIL-13¨üÅé£\1¨È°ò¡]IL-13£\1¡^³æ§J¶©§ÜÅéASLAN004¡A¦bªvÀø¯SÀ³©Ê¥Öª¢¡]atopic dermatitis¡^ªº·§©ÀÅçÃÒ¸ÕÅ礤Àò±o¿n·¥µ²ªG

¯SÀ³©Ê¥Öª¢¬O³Ì¬°±`¨£ªº¥Ö½§¯e¯f¤§¤@¡A¥þ²y¦³¶W¹L¨â»õ¦W±wªÌ¨ü¨ì³o¤@¯e¯fªº§xÂZ¡C¯SÀ³©Ê¥Öª¢ªº¯gª¬¬°¥Ö½§¬õ¸~¡A¨Ã¦ñ¦³«ùÄòæ±Äo¡A¥i¯àÄY­«¼vÅT±wªÌªº¥Í¬¡½è¶q¡C°ª¹F¤T¤À¤§¤@ªº¦¨¤H±wªÌªº¯f±¡¹F¨ì¤¤«×¦Ü­««×¡C¹ï©ó¤j¦h¼Æ±wªÌ¨Ó»¡¡A±±¨î¯e¯f¯gª¬¤´µM¬O¤@­Ó¬D¾Ô¡C

ºI¦Ü¤µ¦~11¤ë29¤é¡A¦³6¦W±wªÌ±µ¨ü¤F³Ì§C¾¯¶qASLAN004ªºªvÀø¡C¸ÕÅçµ²ªGªí©ú¡A¦b3¦W¦Ü¤Ö±µ¨üªvÀø¤@­Ó¤ëªº±wªÌ¤¤¡A±wªÌÀã¯l­±¿n©MÄY­«µ{«×«ü¼Æ¡]Eczema Area and Severity Index, EASI¡^µû¤À»P°ò½u¬Û¤ñ¡A¤À§O­°§C¤F85%¡A70%¡A©M59% ¡CEASI¦b±µ¨üªvÀø«á²Ä4¶g¤´µM¦b«ùÄò¤U­°¡A¹w­p¦b±µ¨üªvÀø6-8¶g«á¹F¨ì³Ì¤jÀø®Ä¡C

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....IL-13 receptor (R) £\1 and are key pharmacological targets in fibrotic diseases. However, the roles of IL-13R£\1 in mediating lung injury/repair are unclear........ These data highlight underappreciated protective roles for IL-13R£\1 in lung injury and homeostasis...]

[·|­û¡GROGER588910148151 µoªí®É¶¡:2019/8/16 ¤U¤È 11:37:50²Ä 1217 ½g¦^À³

....DupilumabÂê©wIL-4R£\µ²¦X,ASLAN004Âê©wIL-13R£\1,³£¯àªýÂ_ IL-4 ¤Î IL-13, ¥u¬Oµ²ºc¾÷¨îªº±µ¦X¦¸§Ç¬Û¤Ï)

....These findings demonstrate that the IL-13R£\1 chain is required for signaling by IL-4 in fibroblasts but not in macrophages; however, in the case of IL-13, the IL-13R£\1 chain is essential for signaling by both macrophages and fibroblasts.

Interestingly, we observed that the magnitude of STAT6 activation and gene expression induced by IL-4 in wild-type macrophages is generally greater than that induced by IL-13. These results are consistent with related findings by others [19, 20]

¡K.IL-4 receptor structural studies have shown that IL-4 and IL-13 catalyze differential assembly of IL-4 receptor complexes [40, 41]. IL-4 binds initially to the IL-4R£\ chain to generate a binary complex which then recruits either £^c or the IL-13R£\1 chain to form ternary type I or type II IL-4 receptor complexes respectively. In contrast, the primary ligand-binding chain for IL-13 is IL-13R£\1, not IL-4R£\. Consequently, IL-13 binds initially to the IL-13R£\1 chain to generate IL-13/IL-13R£\1 binary complexes which then recruit the IL-4R£\ chain to complete assembly of ternary type II IL-4 receptor complexes. Therefore, IL-4 and IL-13 induce rapid assembly of type II IL-4 receptor complexes by catalyzing physical association of the same receptor chains (i.e., IL-4R£\ and IL-13R£\1), but the order of assembly is reversed. Although the receptor assembly sequences are distinct for IL-4 and IL-13, the intracellular signal transduction pathway and repertoire of genes induced by these two cytokines are largely the same.

¡K.IL-13R£\1 was essential for signaling by both IL-4 and IL-13 in fibroblasts.

¡K¡KIL-13 is a primary regulator of airway hyper-reactivity and mucus production in allergic lung inflammation, and it has been shown to play a more dominant role than IL-4 as an effector cytokine of Th2-mediated pathogenesis in several animal models

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www.transparencymarketresearch.com/asthma-treatment-market.html

Asthma Treatment Market: Increasing Penetration of Generic Drugs to Drive Sluggish Growth

The global asthma treatment market will rise from a value of ~US$ 25.6 Bn in 2019 to ~US$ 30.5 Bn by 2027, and it is anticipated that an increase in the number of FDA-approved products in parallel to the increasing awareness among asthma patients regarding quality care will drive the steady odyssey of the market.

Analysts at Transparency Market Research (TMR) anticipate that, among the strategic approaches taken towards consolidation, partnerships and collaborations will remain integral to maximize profitability from new markets. Having witnessed product recalls, manufacturers in the asthma treatment market are dedicating ample efforts to develop high-quality products, which are likely to receive easy approvals from the FDA and similar regulatory bodies.

On the demand side, as awareness regarding quality care for the treatment of asthma increases among patients, the adoption of inhalers and oral drugs is likely to increase. However, in recent times, the cost-benefits of generic drugs have been appealing to patients, which could pose as a challenge for manufacturers in the asthma treatment market.

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Atopic Dermatitis: Global Drug Market | Forecast to 2027

adminmarketby adminmarketƒeMarch 6, 2019

Summary:

Atopic Dermatitis is a widespread chronic inflammatory skin condition that can affect patients of all ages and is the result of a complex interplay of environmental, immunological, genetic, and pharmacologic factors. The atopic dermatitis market has historically remained stagnant and the pipeline for drugs in late-stage development was lacking, but recent developments have reignited interest in the treatment of the disease, especially as the estimated drug-treated population may grow to 24,000,000 people over the next decade.

In March 2017, Regeneron/Sanofi gained approval for Dupixent (dupilumab), the first-in-class interleukin (IL)-4 receptor inhibitor that has set a new gold standard in the treatment of atopic dermatitis. Moreover, a highly competitive and genericized topical market has pushed other pharmaceutical companies to develop their own systemic treatments, with a new class of therapies in development, Janus kinase (JAK) inhibitors, two of which have already been granted Breakthrough Therapy designation by the FDA. As a result, the atopic dermatitis market is set to become much more dynamic, with widening appreciation that atopic dermatitis is a highly variable disease and that not every patient will react in the same way to the same therapy. With existing unmet needs in the topical landscape for treatments that do not have side effects and for better understanding the pathophysiology and etiology of the disease, atopic dermatitis represents an attractive dermatology sector for drug developers. In turn, this will fuel commercial interest in this market.

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According to research the sales of drugs in the atopic dermatitis market were approximately $6.4B in 2017 in the 7MM. The US was the largest market, with approximately $5.1B in drug sales, which represented 80% of the total atopic dermatitis market. The 5EU market contributed $1.1B in sales and Japan contributed sales of $202M in 2017.

Global sales in the atopic dermatitis market are expected to grow to $18.3B by 2027, at a Compound Annual Growth Rate (CAGR) of 11.1% from 2017-2027. Research report forecasts the US to grow to $13.6B (74.5% of global sales), the 5EU to grow to $4B (21.7% of global sales), and Japan to grow to $693M (3.8% of global sales) over the next 10 years.

marketresearchdistributor.com/2019/03/06/atopic-dermatitis-drug-market-analysis-and-forecast-to-2027/

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-------Overall, this growing body of evidence suggests that AD is an IL-13-, rather than IL-4-, driven disease...

CONCLUSION

There is currently strong evidence that in AD, IL-13 is significantly

more expressed than IL-4 in lesional skin and is therefore one of

the key drivers in this condition. IL-13 has a large impact on the epidermal barrier function and the local immune response............]

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Dermira Announces Positive Topline Results from Phase 2b Study of Lebrikizumab in Patients with Atopic Dermatitis

March 18, 2019 07:00 ET | Source: Dermira, Inc.

- All three doses of lebrikizumab met primary endpoint with statistical significance

- Lebrikizumab was well-tolerated; safety profile consistent with prior studies

- Efficacy and safety profile support advancement into Phase 3; planned by end of 2019

- Conference call and webcast today at 8:30 a.m. ET / 5:30 a.m. PT

MENLO PARK, Calif., March 18, 2019 (GLOBE NEWSWIRE) -- Dermira, Inc. (NASDAQ: DERM), a biopharmaceutical company dedicated to bringing biotech ingenuity to medical dermatology by delivering differentiated, new therapies to the millions of people living with chronic skin conditions, today announced positive results from a Phase 2b dose-ranging study of lebrikizumab, an investigational therapy, in adult patients with moderate-to-severe atopic dermatitis. All three doses of lebrikizumab met the primary endpoint, demonstrating greater improvements in the Eczema Area and Severity Index (EASI) score compared to placebo. The safety profile for lebrikizumab observed in the study was consistent with prior studies evaluating this investigational therapy.

Lebrikizumab is a novel, injectable, humanized monoclonal antibody designed to bind interleukin-13 (IL-13) with high affinity, specifically preventing the formation of the IL-13R£\1/IL-4R£\ heterodimer complex, which inhibits downstream signaling. IL-13 is believed to be a central pathogenic mediator that drives multiple aspects of the pathophysiology of atopic dermatitis by promoting type 2 inflammation and mediating its effects on tissue, resulting in skin barrier dysfunction, itch, skin thickening and infection.

¡§These data are compelling and further demonstrate clinically that IL-13 is a key mediator in atopic dermatitis,¡¨ said Emma Guttman-Yassky, M.D., Ph.D., The Sol and Clara Kest Professor, Vice Chair for Research in the Department of Dermatology, Director of the Center of Excellence in Eczema at Icahn School of Medicine at Mount Sinai and a leading study investigator. ¡§I have many patients for whom current therapies do not adequately address their needs. These data show that lebrikizumab may offer a targeted, effective and well-tolerated therapeutic approach.¡¨

About Lebrikizumab Phase 2b Study

Across all of the doses evaluated, lebrikizumab showed a dose-dependent and statistically significant improvement in the primary endpoint, the mean percent change in EASI score from baseline to week 16. The improvement in EASI score was 62.3% for patients receiving lebrikizumab, 125 milligrams (mg), every four weeks (p=0.0165), 69.2% for patients receiving lebrikizumab, 250 mg, every four weeks (p=0.0022) and 72.1% for patients receiving lebrikizumab, 250 mg, every two weeks (p=0.0005) compared to 41.1% for patients receiving placebo.

Patients treated with lebrikizumab at the 250 mg dose every two or four weeks achieved statistically significant improvements in other key efficacy measures compared to placebo after 16 weeks of treatment, including:

Lebrikizumab 250 mg every four weeks:

33.7% of lebrikizumab-treated patients achieved clearing or near-clearing of skin lesions, as measured by an investigator¡¦s global assessment (IGA) score of 0 or 1, and a reduction of at least 2 points from baseline, compared to 15.3% with placebo (p=0.0392).

56.1% of lebrikizumab treated patients achieved a reduction of at least 75% from baseline in EASI score (EASI-75), compared to 24.3% on placebo (p=0.0021).

36.1% of lebrikizumab treated patients achieved a reduction of at least 90% from baseline in EASI score (EASI-90), compared to 11.4% on placebo (p=0.0062).

Lebrikizumab 250 mg every two weeks:

44.6% of lebrikizumab-treated patients achieved clearing or near-clearing of skin lesions, as measured by an IGA score of 0 or 1, and a reduction of at least 2 points from baseline, compared to 15.3% with placebo (p=0.0023).

60.6% of lebrikizumab treated patients achieved a reduction of at least 75% from baseline in EASI-75, compared to 24.3% on placebo (p=0.0005).

44.0% of lebrikizumab treated patients achieved a reduction of at least 90% from baseline in EASI-90, compared to 11.4% on placebo (p=0.0006).

The secondary endpoints for the 125 mg lebrikizumab dosing arm did not meet statistical significance.

The most common adverse events reported across all three lebrikizumab dosing arms were upper respiratory tract infection (7.5% vs. 5.8% for placebo), nasopharyngitis (6.6% vs. 3.8% for placebo), headache (3.1% vs. 5.8% for placebo) and injection site pain (3.1% vs. 1.9% for placebo). Rates of conjunctivitis (2.6% compared to no reports for placebo) and herpes infections (2.2% compared to no reports for placebo) were low. Overall, adverse events observed in lebrikizumab-treated patients were primarily mild to moderate in severity and infrequently led to treatment discontinuation.

¡§Based on the clinical profile observed in this study, we believe lebrikizumab has the potential to be a best-in-disease therapy for atopic dermatitis,¡¨ said Tom Wiggans, chairman and chief executive officer of Dermira. ¡§We intend to move quickly into a Phase 3 program following discussions with U.S. regulators. I want to thank the patients and investigators who participated in this trial and hope these contributions will support our ability to offer a new and differentiated treatment option to the millions of people struggling to effectively manage their atopic dermatitis.¡¨

Following an end-of-Phase 2 meeting with the U.S. Food and Drug Administration, Dermira plans to initiate a Phase 3 clinical development program for lebrikizumab by the end of 2019.

About the Lebrikizumab Phase 2b Study

The randomized, double-blind, placebo-controlled, parallel-group Phase 2b study was designed to evaluate the safety and efficacy of lebrikizumab as monotherapy compared with placebo and to establish the dosing regimen for a potential Phase 3 program in patients with moderate-to-severe atopic dermatitis. The study enrolled 280 patients ages 18 years and older with moderate-to-severe atopic dermatitis at 57 sites in the United States. The study evaluated three different lebrikizumab treatment dosing arms compared to a placebo arm, with patients randomized in a 3:3:3:2 fashion:

Group 1: A loading dose of 250 mg of lebrikizumab at week 0, followed by 125 mg of lebrikizumab every four weeks.

Group 2: A loading dose of 500 mg of lebrikizumab at week 0, followed by 250 mg of lebrikizumab every four weeks.

Group 3: A loading dose of 500 mg of lebrikizumab at weeks 0 and 2, followed by 250 mg of lebrikizumab every two weeks.

Group 4: Placebo at week 0 and every two weeks thereafter.

The inclusion criteria for patients enrolled in this study included chronic atopic dermatitis for at least one year, an EASI score of 16 or greater, an IGA score of 3 or 4 and a body surface area involving at least 10% at screening and baseline. Following the end of the 16-week assessment period, patients are followed for an additional 16 weeks.

About Atopic Dermatitis

Atopic dermatitis is the most common and severe form of eczema, a chronic inflammatory condition that can present as early as childhood and continue into adulthood. A moderate-to-severe form of the disease is characterized by rashes on the skin that often cover much of the body and also includes redness, cracking, dryness and intense, persistent itching. The skin condition can have a negative impact on patients¡¦ mental and physical functioning, limiting their daily activities and health-related quality of life. Patients with moderate-to-severe atopic dermatitis have reported a larger impact on quality of life than patients with psoriasis.

About Lebrikizumab

Lebrikizumab is a novel, injectable, humanized monoclonal antibody designed to bind IL-13 with very high affinity, specifically preventing the formation of the IL-13R£\1/IL-4R£\ heterodimer complex and subsequent signaling, thereby inhibiting the biological effects of IL-13 in a targeted and efficient fashion. IL-13 is believed to be a central pathogenic mediator that drives multiple aspects of the pathophysiology of atopic dermatitis by promoting type 2 inflammation and mediating its effects on tissue, resulting in skin barrier dysfunction, itch, skin thickening and infection

www.globenewswire.com/news-release/2019/03/18/1756186/0/en/Dermira-Announces-Positive-Topline-Results-from-Phase-2b-Study-of-Lebrikizumab-in-Patients-with-Atopic-Dermatitis.html

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Dupilmab ¡A¤W¥««eÉ]³õ¤ÀªR®v¦ô°ª峯¥i¾P°â50»õ¬ü¤¸¡]¥h¦~©³¤w¤W½Õ¬°80»õ¬ü¤¸¡^¡A2017¦~3¤ëFDA®Ö­ã¡A2017¦~3~7¤ë¡AªÑ»ù¥«­È¼W¥[140»õ¬ü¤¸¡C

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·§©À©ÊÁ{§É§C¾¯¶q¦p¦¹¦pªº®ÄªG¡AÁÙ¦³400mg/600mg ¥¼°µ¡A°Æ§@¥Î¤ñdupilmab ,§Æ±æÀø®Ä¤]¯à¦p Thomas Bieber , ©Ò¬ã¨s.

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Thomas Bieber

TB has been a speaker and consultant for LEO Pharmaceuticals,

Regeneron, and Sanofi

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....onlinelibrary.wiley.com/doi/pdf/10.1111/all.13954

-------Overall, this growing body of evidence suggests that AD is an IL-13-, rather than IL-4-, driven disease...

CONCLUSION

There is currently strong evidence that in AD, IL-13 is significantly

more expressed than IL-4 in lesional skin and is therefore one of

the key drivers in this condition. IL-13 has a large impact on the epidermal barrier function and the local immune response............]

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