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LEO Pharma and PellePharm Announce Collaboration to Develop Innovative Therapies for Rare Skin Diseases of $ 760 Million

On November 20, 2018 LEO Pharma, a Danish company specializing in dermatology, and PellePharm, California’s forerunner of rare diseases, reported a strategic development and commercialization collaboration to address unmet medical needs various skin diseases without approved drugs and to promote innovation and access to potential therapies for patients with life-changing diseases such as Gorlin-Goltz syndrome and high-frequency basal cell carcinoma (BCC), two distinct and rare skin cancers (Press release, Leo, NOV 20, 2018, View Source [SID1234531516]).

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" We are very pleased to partner with PellePharm, the pioneers of Gorlin-Goltz Syndrome and experts in rare skin diseases. It supports our ambitious strategy for 2025 and marks the entry of LEO Pharma into the field of rare skin diseases. It also provides a unique opportunity to further develop the first compound to treat people with very severe skin conditions who are currently not receiving any therapies, "said Thorsten Thormann, Vice President of Research at LEO Pharma.

Under the terms of the agreement, LEO Pharma has initially committed $ 70 million of equity and research and development R & D to support the global Phase 3 study for the topical gel, patidegib, 2% To finance the prevention and treatment of Gorlin-Goltz syndrome, with LEO Pharma securing an option to acquire all of its shares in PellePharm. In addition, PellePharm and its shareholders could receive up to $ 690 million including a merger payment and milestone payments for approval and commercialization. In addition, after achieving certain commercial milestones, PellePharm shareholders are entitled to a double-digit royalty payment.

" Our company is committed to fighting rare dermatological diseases at the source and providing patients with new breakthrough treatments as efficiently and effectively as possible. As the world leader in the field of medical dermatology, LEO Pharma is the ideal development and marketing partner. This collaboration paves the way for our pivotal Phase 3 Gorlin-Goltz syndrome study in early 2019. Following the potential merger, we look forward to working with LEO Pharma on other rare skin diseases with unmet needs, "said Sanuj Ravindran, President and Chief Executive Officer of PellePharm.

Under the terms of the agreement, a Joint Development Committee will be set up, where PellePharm will be responsible for global development and LEO Pharma will have an advisory role. Both companies will jointly push ahead with marketing planning and LEON Pharma’s Chief Financial Officer Anders Kronborg will join PellePharm’s Board of Directors.

"The Gorlin Syndrome Group welcomes the news about the collaboration between PellePharm and LEO Pharma in developing patidegib with topical application for BCC treatment. Data from the PellePharm Phase 2 study suggest that patidegib is an effective BZK treatment with minimal side effects. We hope that by working with LEO these benefits will be confirmed in a Phase 3 study. An effective topical treatment for the prevention or treatment of BCC could prevent the painful, disruptive and disfiguring surgical procedures that we are currently undergoing, "said Sally Webster, chairperson, and Matthew Helbert, trustee of the Gorlin Syndrome Group UK

There are currently no FDA-approved therapies for Gorlin-Goltz syndrome and surgery is the treatment standard for this rare disease. Sometimes patients with this lifelong, serious illness have to undergo up to 30 surgeries per year from the middle age of teens.

PellePharm’s topical formulation (2%) is expected to be the first approved therapy for the prevention of Gorlin-Goltz syndrome, also known as nevoid cell basal cell carcinoma nevus syndrome (BCCNS), and has entered Phase 2 clinical trials has shown promise in treating patients with Gorlin-Goltz syndrome and sporadic BCC in the US and the UK.

" For more than 18 years, our organization has been dedicated to helping, educating, and finding much-needed preparations for people with Gorlin-Goltz Syndrome (BCCNS), and yet there are still no FDA-approved therapies for this serious disease," said Jean Pickford, executive director of the BCCNS Alliance. " Especially against the background of the Patidegib Phase 3 trial, which will begin recruitment in early 2019, PellePharm’s commitment – now in partnership with LEO Pharma – is very encouraging to our community."

PellePharm was advised by Rothschild & Co. on this transaction.

About Patidegib

The topical gel patidegib has been shown to be promising in a phase 2 clinical trial for the relief of BZK tumors in Gorlin-Goltz syndrome by blocking the hedgehog signaling pathway and thereby controlling the disease at the source. The topical formulation of patidegib is expected to achieve the efficacy already demonstrated for oral patidegib in Phase 1 studies without the occurrence of negative systemic side effects. The gel formulation is stable at room temperature for at least two years, so this could be a realistic treatment option for ongoing home-based treatment of Gorlin-Goltz syndrome and high-frequency BCC.

Über das Gorlin-Goltz-Syndrom

Das Gorlin-Goltz-Syndrom ist eine seltene, genetisch bedingte Krankheit, die durch konstitutionelle, vererbbare Mutationen in einem Allel des Tumorsuppressorgens PATCHED1 (PTCH1) gekennzeichnet ist, das als primärer Inhibitor des Hedgehog-Signalwegs wirkt. Dadurch bilden sich meist im Gesicht mehrere Basalzellkarzinome.

Because there are no FDA-approved drugs for Gorlin-Goltz syndrome, surgery is the standard of care. It may happen that people with severe Gorlin-Goltz syndrome have to undergo up to 30 surgeries per year, which often have to be repeated and may be associated with scarring and disfigurement. It is estimated that around 10,000 people in the United States and one in 31,000 people are affected by Gorlin-Goltz syndrome. Gorlin-Goltz Syndrome is also referred to as Gorlin Syndrome, Basal Cell Nevus Syndrome (BCNS), and Naso-Bold Cell Carcinoma Syndrome (NBCCS).

About radiofrequency basal cell carcinoma (BCC)

High-frequency BCC, like Gorlin-Goltz syndrome, is a rare disease characterized by the development of an unusually high BCC number. In contrast to patients with Gorlin-Goltz syndrome, patients with radiofrequency BCC are not born with a germ-line mutation in the PTCH1 gene and do not suffer from the other systemic manifestations of Gorlin-Goltz syndrome. The standard of care for patients with radiofrequency BCC is surgery.

Synlogic to Webcast Presentation at the 30th Annual Piper Jaffray Healthcare Conference

On November 20, 2018 Synlogic (Nasdaq:SYBX) reported that Aoife Brennan, M.B., B.Ch., Synlogic’s president and chief executive officer, will provide a corporate update at the 30th Annual Piper Jaffray Healthcare Conference at 8:30 am ET on Wednesday, November 28, 2018, in New York City (Press release, Synlogic, NOV 20, 2018, View Source [SID1234531515]).

Exelixis Announces Webcasts of Investor Conference Presentations in November

On November 20, 2018 Exelixis, Inc. (NASDAQ: EXEL) reported that Michael M. Morrissey, Ph.D., the company’s President and Chief Executive Officer, will provide an overview of the company at the following investor conferences in November (Press release, Exelixis, NOV 20, 2018, View Source [SID1234531514]):

The 30th Annual Piper Jaffray Healthcare Conference: Exelixis is scheduled to present at 11:00 AM EST / 8:00 AM PST on Tuesday, November 27, 2018 in New York.
Evercore ISI HealthConX: Exelixis is scheduled to present at 2:00 PM EST / 11:00 AM PST on Wednesday, November 28, 2018 in Boston.
To access the webcast links, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company’s website at least 15 minutes prior to each presentation to ensure adequate time for any software download that may be required to listen to the webcasts. Replays will also be available at the same location for 14 days.

Five Prime Therapeutics to Present at 30th Annual Piper Jaffray Healthcare Conference

On November 20, 2018 Five Prime Therapeutics, Inc. (NASDAQ: FPRX), a clinical-stage biotechnology company discovering and developing innovative immuno-oncology protein therapeutics, reported that Aron Knickerbocker, Chief Executive Officer, will present at the 30th Annual Piper Jaffray Healthcare Conference, November 28, 2018 at 11:10 am ET (Press release, Five Prime Therapeutics, NOV 20, 2018, View Source [SID1234531513]).

The presentation will be webcast and may be accessed at the "Events & Presentations" section of the Company’s website at View Source Five Prime will maintain an archived replay of the webcast on its website for 30 days after the conference.

Takeda Receives Clearance from the European Commission for the Proposed Acquisition of Shire plc

On November 20, 2018 Takeda Pharmaceutical Company Limited ("Takeda") reported that it has received clearance from the European Commission (the "EC") for the proposed acquisition of Shire plc ("Shire") announced on May 8, 2018 (the "Acquisition") (Press release, Takeda, NOV 20, 2018, View Source [SID1234531512]).

The EC’s approval is conditional on Takeda and Shire fulfilling commitments given to the EC in connection with the clearance. Specifically, in relation to the future potential overlap in the area of inflammatory bowel diseases between Takeda’s marketed product Entyvio (vedolizumab) and Shire’s pipeline compound SHP647, Takeda and Shire have committed to divest the pipeline compound SHP647 and certain associated rights. The divestment of SHP647 and certain associated rights is not a condition to the completion of the Acquisition.

SHP647 is an exciting pipeline compound and Takeda expects the asset to attract interest from a number of potential buyers. Takeda remains committed to Entyvio, which has been granted marketing authorization in more than 60 countries and is the cornerstone of Takeda’s diverse specialty gastrointestinal portfolio.

"We are very pleased to have secured clearance from the European Commission, the final regulatory approval required to proceed with our acquisition of Shire," said Christophe Weber, President and Chief Executive Officer of Takeda. "We are another step closer to creating a global, values-based, R&D-driven biopharmaceutical leader, and after several months of constructive dialogue, we are optimistic that our shareholders recognize the significant long-term value creation potential of this powerful combination."

The Acquisition has now received clearances from the European Commission, the United States Federal Trade Commission, the Japan Fair Trade Commission, the State Administration for Market Regulation in China and the Brazilian Administrative Council for Economic Defense, among other regulatory authorities.

As announced on November 12, 2018, Takeda has published a circular containing a notice of its decision to hold an Extraordinary General Meeting of Shareholders (the "EGM") to vote on the necessary matters relating to the proposed Acquisition. The EGM is to be convened at 10:00 a.m. (Tokyo time) on December 5, 2018 at INTEX Osaka, Hall 6B Zone.

Takeda also confirms its previously announced expectation that, subject to receiving the necessary shareholder approvals and sanction of the scheme of arrangement by the Jersey court, completion of the Acquisition will take place on January 8, 2019. Further announcements will be made as appropriate.

About Entyvio (vedolizumab)
Vedolizumab is a gut-selective biologic and is approved as an intravenous (IV) formulation.1 It is a humanized monoclonal antibody designed to specifically antagonize the alpha4beta7 integrin, inhibiting the binding of alpha4beta7 integrin to intestinal mucosal addressin cell adhesion molecule 1 (MAdCAM-1), but not vascular cell adhesion molecule 1 (VCAM-1).2 MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract.3 The alpha4beta7 integrin is expressed on a subset of circulating white blood cells. These cells have been shown to play a role in mediating the inflammatory process in ulcerative colitis (UC) and Crohn’s disease (CD).4 5 By inhibiting alpha4beta7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.

Vedolizumab IV is approved for the treatment of adult patients with moderately to severely active UC and CD, who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNFα) antagonist. Vedolizumab IV has been granted marketing authorization in over 60 countries, including the United States and European Union, with over 200,000 patient years of exposure to date. 6

Therapeutic Indications

Ulcerative colitis
Vedolizumab is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNFα) antagonist.

Crohn’s disease
Vedolizumab is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNFα) antagonist.

Important Safety Information

Contraindications
Hypersensitivity to the active substance or to any of the excipients.

Special warnings and special precautions for use
Vedolizumab should be administered by a healthcare professional equipped to manage hypersensitivity reactions, including anaphylaxis, if they occur. Appropriate monitoring and medical support measures should be available for immediate use when administering vedolizumab. Observe all patients during infusion and until the infusion is complete.

Infusion-related reactions
In clinical studies, infusion-related reactions (IRR) and hypersensitivity reactions have been reported, with the majority being mild to moderate in severity. If a severe IRR, anaphylactic reaction, or other severe reaction occurs, administration of vedolizumab must be discontinued immediately and appropriate treatment initiated (e.g., epinephrine and antihistamines). If a mild to moderate IRR occurs, the infusion rate can be slowed or interrupted and appropriate treatment initiated (e.g., epinephrine and antihistamines). Once the mild or moderate IRR subsides, continue the infusion. Physicians should consider pre-treatment (e.g., with antihistamine, hydrocortisone and/or paracetamol) prior to the next infusion for patients with a history of mild to moderate IRR to vedolizumab, in order to minimize their risks.

Infections
Vedolizumab is a gut-selective integrin antagonist with no identified systemic immunosuppressive activity. Physicians should be aware of the potential increased risk of opportunistic infections or infections for which the gut is a defensive barrier. Vedolizumab treatment is not to be initiated in patients with active, severe infections such as tuberculosis, sepsis, cytomegalovirus, listeriosis, and opportunistic infections until the infections are controlled, and physicians should consider withholding treatment in patients who develop a severe infection while on chronic treatment with vedolizumab. Caution should be exercised when considering the use of vedolizumab in patients with a controlled chronic severe infection or a history of recurring severe infections. Patients should be monitored closely for infections before, during and after treatment. Before starting treatment with vedolizumab, screening for tuberculosis may be considered according to local practice. Some integrin antagonists and some systemic immunosuppressive agents have been associated with progressive multifocal leukoencephalopathy (PML), which is a rare and often fatal opportunistic infection caused by the John Cunningham (JC) virus. By binding to the α4β7 integrin expressed on gut-homing lymphocytes, vedolizumab exerts an immunosuppressive effect on the gut. Although no systemic immunosuppressive effect was noted in healthy subjects, the effects on systemic immune system function in patients with inflammatory bowel disease are not known. Healthcare professionals should monitor patients on vedolizumab for any new onset or worsening of neurological signs and symptoms, and consider neurological referral if they occur. If PML is suspected, treatment with vedolizumab must be withheld; if confirmed, treatment must be permanently discontinued. Typical signs and symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body, clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. The progression of deficits usually leads to death or severe disability over weeks or months.

Malignancies
The risk of malignancy is increased in patients with ulcerative colitis and Crohn’s disease. Immunomodulatory medicinal products may increase the risk of malignancy.

Prior and concurrent use of biological products
No vedolizumab clinical trial data are available for patients previously treated with natalizumab. Caution should be exercised when considering the use of vedolizumab in these patients. No clinical trial data for concomitant use of vedolizumab with biologic immunosuppressants are available. Therefore, the use of vedolizumab in such patients is not recommended.

Vaccinations
Prior to initiating treatment with vedolizumab all patients should be brought up to date with all recommended immunizations. Patients receiving vedolizumab may receive non-live vaccines (e.g., subunit or inactivated vaccines) and may receive live vaccines only if the benefits outweigh the risks.

Adverse reactions include: nasopharyngitis, headache, arthralgia, upper respiratory tract infection, bronchitis, influenza, sinusitis, cough, oropharyngeal pain, nausea, rash, pruritus, back pain, pain in extremities, pyrexia, and fatigue.

Please consult with your local regulatory agency for approved labeling in your country.

For U.S. audiences, please see the full Prescribing Information including Medication Guide for ENTYVIO.7

For EU audiences, please see the Summary of Product Characteristics (SmPC) for ENTYVIO.

Takeda’s Commitment to Gastroenterology
Gastrointestinal (GI) diseases can be complex, debilitating and life-changing. Recognizing this unmet need, Takeda and our collaboration partners have focused on improving the lives of patients through the delivery of innovative medicines and dedicated patient disease support programs for over 25 years. Takeda aspires to advance how patients manage their disease. Additionally, Takeda is leading in areas of gastroenterology associated with high unmet need, such as inflammatory bowel disease, acid-related diseases and motility disorders. Our GI Research & Development team is also exploring solutions in celiac disease and liver diseases, as well as scientific advancements through microbiome therapies.