On September 30, 2021 Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") and JCR Pharmaceuticals Co., Ltd. (TSE:4552) ("JCR") reported a geographically-focused exclusive collaboration and license agreement to commercialize JR-141 (INN: pabinafusp alfa), an investigational, next-generation recombinant fusion protein of an antibody against the human transferrin receptor and iduronate-2-sulfatase (IDS) enzyme for the treatment of Hunter syndrome (also known as Mucopolysaccharidosis type II or MPS II) (Press release, Takeda, SEP 30, 2021, View Source [SID1234590585]). Hunter syndrome is caused by a deficiency of IDS and manifests in different forms. JR-141, applied with J-Brain Cargo, JCR’s proprietary blood-brain barrier (BBB) technology, is engineered to transport the therapeutic enzyme across the BBB to directly reach the brain and address both the somatic and neuronopathic manifestations of the disease, which can lead to progressive cognitive decline.

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Under the terms of the exclusive collaboration and license agreement, Takeda will exclusively commercialize JR-141 outside of the United States, including Canada, Europe, and other regions (excluding Japan and certain other Asia-Pacific countries). JCR will receive an upfront payment for such ex-U.S. license, and is eligible to receive additional development and commercial milestones as well as tiered royalties on potential sales. The two companies will collaborate to bring this therapy to patients as quickly as possible upon completion of the global Phase 3 program, which will be conducted by JCR.

Takeda receives an option under a separate option agreement, which allows Takeda to acquire an exclusive license to commercialize JR-141 in the U.S. upon completion of the Phase 3 program.

"Takeda is committed to continuously improving the way Hunter syndrome is treated. JR-141 introduces a new way to deliver proteins across the blood-brain barrier, overcoming our current challenges to treat the underlying neuronopathic manifestations of Hunter syndrome and help maintain or improve cognitive function in these patients," said Dan Curran, M.D., Head, Rare Genetics & Hematology Therapeutic Area Unit at Takeda. "We will work closely with JCR to apply our expertise in enzyme replacement therapies with the hope of bringing this potentially transformative therapy to patients as quickly as possible."

"JCR is pleased to have reached an agreement with Takeda who is well placed to achieve our common goal of maximizing the impact of JR-141," said Shin Ashida, President, Chairman of JCR. "Our mission is to provide transformative treatment options as soon as possible to patients with lysosomal storage disorders (LSDs) with central nervous system symptoms, such as Hunter syndrome. JR-141 is the first-ever approved biopharmaceutical in Japan that penetrates the blood-brain barrier. I expect that we will be able to achieve this mission through our partnership with Takeda to deliver a new treatment option to Hunter patients around the world as swiftly as possible."

JR-141 met its primary endpoint in an open-label Phase 2/3 clinical trial in Japan demonstrating significant reductions in heparan sulfate (HS) in the cerebrospinal fluid, a biomarker for assessing the drug’s effectiveness in reducing disease-causing substrate in the central nervous system, in all subjects for whom measurements were available after 52 weeks of treatment. Somatic disease control was maintained in patients who switched from standard enzyme replacement therapy (ERT). The study also demonstrated an improvement in somatic symptoms in participants who had not previously received standard ERT prior to the start of the trial. Additionally, a neurocognitive development assessment demonstrated maintenance or improvement of age-equivalent function in 21 of the 25 patients at one year. There were no reports of serious treatment-related adverse events in the trial.1

About JR-141

JR-141 is a recombinant fusion protein of an antibody against the human transferrin receptor and iduronate-2-sulfatase, the enzyme that is missing or malfunctioning in subjects with Hunter syndrome. It is expected to be effective against the neuronopathic manifestations of the disease by crossing the BBB through transferrin receptor mediated transcytosis using J-Brain Cargo, JCR’s proprietary BBB technology. Uptake into cells is mediated through the transferrin receptor and mannose-6-phosphate receptor. JCR has advanced development activities by establishing the necessary evidence from the molecular design stage to the nonclinical and clinical trial phases. In non-clinical trials, JCR has confirmed both high affinity binding of JR-141 to transferrin receptors, and passage across the BBB into neuronal cells as evidenced by electron microscopy.

In addition, JCR has confirmed that using J-Brain Cargo technology, enzymes are taken up into various brain tissues. A decrease in substrate accumulation has also been confirmed in an animal model of Hunter syndrome.2,3,4 In several clinical trials with JR-141, JCR obtained evidence of reduction of heparan sulfate concentrations in the CSF, a biomarker for assessing the drug’s effectiveness in reducing disease-causing substrate in the central nervous system, consistent with the results obtained from non-clinical studies. JCR also obtained clinical results that demonstrate positive effects of JR-141 on neurocognition.5,6,7,8

JR-141 was approved by the Ministry of Health, Labour and Welfare and marketed since May 2021 under the brand name "IZCARGO I.V. Infusion 10mg."

About Hunter Syndrome

Hunter syndrome is a severely debilitating, rare lysosomal disease caused by a deficiency of iduronate-2-sulfatase, an enzyme that is needed to break down substances in the body called glycosaminoglycans (GAGs).9 Without this enzyme, GAGs can build up, causing a range of disease-related signs and symptoms.9,10 Roughly two of every three patients with Hunter syndrome are also affected with progressive cognitive decline.11 Hunter syndrome affects 1 in 162,000 total live births, and almost exclusively males.12

On September 30, 2021 Exscientia plc (Nasdaq: EXAI), an AI-driven pharmatech company committed to discovering, designing and developing the best possible drugs in the fastest and most effective manner, reported the pricing of its upsized initial public offering in the United States of 13,850,000 American Depositary Shares ("ADSs") representing 13,850,000 ordinary shares at an initial public offering price of $22.00 per ADS, for total gross proceeds of approximately $304.7 million (Press release, Exscientia, SEP 30, 2021, View Source [SID1234590601]). All ADSs sold in the offering were offered by Exscientia. The ADSs are expected to begin trading on the Nasdaq Global Select Market on October 1, 2021 under the ticker symbol "EXAI." In addition, Exscientia has granted the underwriters a 30-day option to purchase up to an additional 2,077,500 ADSs at the initial public offering price, less underwriting discounts and commissions. The offering is expected to close on or about October 5, 2021, subject to customary closing conditions.

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In addition to the ADSs sold in the public offering, the Company announced the concurrent sale of an additional 7,272,727 ADSs at the initial offering price of $22.00 per ADS, for gross proceeds of $160.0 million, in private placements to SVF II Excel (DE) LLC, or Softbank, and the Bill & Melinda Gates Foundation. The sale of these ADSs will not be registered under the Securities Act of 1933, as amended, and will be subject to a 180-day lock-up agreement.

Goldman Sachs & Co. LLC, Morgan Stanley & Co. LLC, BofA Securities and Barclays Capital Inc. are acting as joint book-running managers for the offering.

A registration statement relating to these securities became effective on September 30, 2021. The offering will be made only by means of a prospectus. When available, copies of the final prospectus related to the offering can be obtained from any of the joint book-running managers for the offering: Goldman Sachs & Co. LLC, Attn: Prospectus Department, 200 West Street, New York, New York 10282, telephone: 866-471-2526, facsimile: 212-902-9316, e-mail: [email protected]; Morgan Stanley & Co. LLC, Attn: Prospectus Department, 180 Varick Street, 2nd Floor, New York, New York 10014, by telephone at 866-718-1649 or by email at [email protected]; BofA Securities, NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, NC 28255-0001, Attention: Prospectus Department, or email: [email protected]; or Barclays Capital Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, by telephone at 1-888-603-5847 or by email at [email protected]. For the avoidance of doubt, such prospectus will not constitute a "prospectus" for the purposes of the Regulation (EU) 2017/1129 and has not been reviewed by any competent authority in any member state in the European Economic Area or the United Kingdom.

A registration statement relating to these securities has been filed with, and declared effective by, the U.S. Securities and Exchange Commission (the "SEC"). Copies of the registration statement can be accessed through the SEC’s website at www.sec.gov. This press release does not constitute an offer to sell or the solicitation of an offer to buy securities, and shall not constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of that jurisdiction.

In any member state of the European Economic Area (the "EEA") this announcement and any offering are only addressed to and directed at persons who are "qualified investors" ("Qualified Investors") within the meaning of the Prospectus Regulation (Regulation (EU) 2017/1129). In the United Kingdom, this announcement and any offering are only addressed to and directed at persons who are "qualified investors" within the meaning of the UK Prospectus Regulation (Regulation (EU) 2017/1129 as if forms part of domestic law by virtue of the European Union (Withdrawal) Act 2018) (i) who have professional experience in matters relating to investments falling within Article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005, as amended (the "Order"), (ii) high net worth entities who fall within Article 49(2)(a) to (d) of the Order, or (iii) to whom it may otherwise lawfully be communicated (all such persons being referred to as "relevant persons").

This announcement must not be acted on or relied on (i) in the United Kingdom, by persons who are not relevant persons, and (ii) in any member state of the EEA, by persons who are not Qualified Investors. Any investment or investment activity to which this announcement relates is available only to and will only be engaged with (i) in the United Kingdom, relevant persons, and (ii) in any member state of the EEA, Qualified Investors.

On September 30, 2021 BYOMass, Inc., a biotech company developing selective TGF-β superfamily therapeutics, reported that it will be participating in the BIO-Europe Digital 2021 Conference, taking place virtually October 25 to 28 (Press release, BYOMass, SEP 30, 2021, View Source [SID1234592175]). Members of the BYOMass business development team will participate in partnering activities at this conference.

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To schedule a meeting, please use the BIO-Europe partnering portal or contact us.

The international BIO-Europe 2021 gathering will be held digitally to bring the global biopharma and investment leaders together to build partnerships that facilitate innovation and medical breakthroughs with four days of presentations and productive one-on-one partnering meetings.

On September 30, 2021 United Therapeutics Corporation (Nasdaq: UTHR) reported it has officially converted to a public benefit corporation (PBC) (Press release, United Therapeutics, SEP 30, 2021, View Source [SID1234590565]). The conversion follows shareholder approval of the company’s proposal to amend its charter at today’s Special Meeting of Shareholders. This is the first PBC conversion of a public biotech or pharmaceutical company.

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United Therapeutics’ conversion to a PBC aligns its legal charter with its longstanding practices of improving patients’ health, enhancing employee engagement, attracting top talent, promoting healthy communities, and addressing important sustainability priorities through its use of green-building technologies, while simultaneously delivering strong shareholder returns. The company has a proven track record of value creation, along with six years of experience operating its Lung Biotechnology PBC subsidiary (the first ever PBC subsidiary of a publicly-traded biopharmaceutical company), so it understands this corporate form well. This PBC conversion initiative was led by the Nominating and Governance Committee of United Therapeutics’ Board of Directors.

"We are inspired by our shareholders who recognize that caring for our patients, planet, employees, communities, and other stakeholders enhances our ability to generate strong shareholder returns," said Martine Rothblatt, Ph.D., Chairperson and Chief Executive Officer of United Therapeutics. "Becoming a PBC aligns United Therapeutics’ corporate structure with our foundational DNA and gives us a strong platform to advance our objectives of developing novel pharmaceutical therapies and finding a cure for end-stage organ diseases by creating an unlimited supply of transplantable organs."

United Therapeutics has been proud to receive support from key partners and employees throughout this process, and our stakeholders have shared the following statements as the company operates in its new form as a PBC:

"My interest in United Therapeutics stems from its clear, passionate care for the patients and communities it serves and an unrelenting mission to find a cure for pulmonary arterial hypertension (PAH). A close relative of mine was diagnosed with PAH, and Martine’s deep interest in the mission was inspiring both personally and professionally," said Manju Lal, a Senior Cardiopulmonary Specialist at United Therapeutics. "United Therapeutics values its people and I am proud to be a part of the family, for the past 14 years and counting!"

Robert C. Bourge, M.D., Professor of Medicine, Radiology, and Surgery and Senior Vice Chair, Department of Medicine at The University of Alabama at Birmingham, said, "Having worked with United Therapeutics since its inception, I am not surprised by this evolution. United Therapeutics has always prioritized patients’ wellbeing, and its commitment to expanding the therapies available to patients living with pulmonary hypertension and advancing the future of organ transplants will continue to drive its success. I am honored to have been part of the growth and development of United Therapeutics."

John Hoeppner, Head of U.S. Stewardship and Sustainable Investing for Legal & General Investment Management America, added, "As a manager that values responsible financial sustainability as well as leadership and creativity, we applaud UT being willing to explore the potential that becoming a PBC may hold."

A PBC is a for-profit corporation that, while creating value for shareholders, must also consider the best interests of those materially affected by the company’s conduct and the specific public benefit that it chooses to adopt in its charter. PBCs are intended to produce public benefits and to operate in a responsible and sustainable manner.

On September 30, 2021 Isarna Therapeutics reported the appointment of Claus Schalper as Chief Executive Officer. Mr. Schalper joins Isarna with over 20 years of experience as an executive and serial entrepreneur in the life science and biotech industries (Press release, Isarna Therapeutics, SEP 30, 2021, View Source [SID1234590586]). His appointment expands Isarna’s management team, which includes Prof. Marion R. Munk as Chief Medical Officer, Dr. René Rückert as Chief Operating Officer and Chris Huiskamp as Chief Financial Officer. The leadership team will be focused on developing Isarna’s lead product ISTH0036 as a promising therapeutic candidate for diseases of the eye.

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"Isarna has reached an exciting stage of development for its lead program, ISTH0036, which has broad applicability in a range of ophthalmology indications," said Claus Schalper, CEO of Isarna Therapeutics. "I value the opportunity to work together with Marion, René and Chris as we move ISTH0036 toward the next clinical trial to further evaluate its potential to benefit patients with retinal diseases that continue to have a high level of unmet medical need."

Claus Schalper, MBA, joins Isarna from Pieris Pharmaceuticals, a company that he co-founded in 2001 and where he held the position of Chief Financial Officer among other roles, playing an important part in the company’s evolution into a US-NASDAQ listed biotechnology company. Mr. Schalper also co-founded XL-protein GmbH and led the company to profitability by executing a series of collaborations with pharma and biotech companies. Mr. Schalper began his career with Arthur Andersen and subsequently served as CEO for several companies in the technology industry. He holds a Master of Business Administration from the University of Bamberg, Germany.

"Claus brings a broad range of leadership and corporate development experience to Isarna. With the management team now in place, the company is well-positioned to implement its product development strategy and reach the next value inflection points for ISTH0036 in ophthalmology," said Matthias Kromayer, Managing Partner and member of the Executive Board at MIG Capital, Isarna’s lead investor.

Prof. Marion R. Munk, MD, PhD, FEBO, joined Isarna as Chief Medical Officer in 2019. She brings over 10 years of clinical expertise in retina, uveitis and age-related macular degeneration research and is a board-certified ophthalmologist currently serving as attending retina specialist and Managing Director of the Bern Photographic Reading Center at the University Hospital Bern, Switzerland. She previously worked at the Feinberg School of Medicine, Chicago, Illinois and the AKH Vienna, Austria, and serves as a consultant for many key players in the ophthalmology drug and device development space. Prof. Munk holds a bachelor’s degree in theoretical physics as well as a MD and PhD in ophthalmology and clinical neuroscience from the Medical University, Vienna.

René Rückert, MD, MBA, joined Isarna in 2018 as interim CMO and in 2019 took the role of the Chief Operating Officer. He brings extensive experience in ophthalmology drug development including many years as a leader and global manager at Bayer and Novartis where he led the global development of the current gold standard therapies in AMD and DME, Eylea and Lucentis. Dr. Rückert previously served as Clinical Vice President, Chief Medical Officer and Chief Operating Officer at a number of innovative biotech and Medtech Companies. In his role at Isarna, Dr. Rückert oversees the company’s operations and clinical development programs and supports the company with his business acumen and his global network. Dr. Rückert is a trained immunologist and board-certified for biochemistry; he received his medical degree from the Charité Berlin, Germany and an MBA from the Warwick Business School, UK.

Isarna Therapeutics has extensive expertise in antisense therapies targeting the messenger RNA (mRNA) transcript for transforming growth factor (TGF)-β, a protein that is chronically elevated in ophthalmic and fibrotic diseases and is used as escape mechanisms by tumors during immune therapy. In ophthalmic indications, fibrosis is a key driver of reduced vision and lack of long-term efficacy of current therapies, TGF-β is a key driver of fibrosis, so ISTH0036 could be the first therapy to prevent the fibrotic changes in patients with retinal pathologies. The company’s Phase 2 candidate, ISTH0036, blocks TGF-β 2, which is a major driver of severe retinal diseases such as, wet (neovascular) age-related macular degeneration (AMD) and diabetic macular edema (DME). Preclinical evidence supports a key role of TGF-β 2 in macular edema and neovascularization, supporting the development in AMD and DME as an intravitreal injection. Animal data support target engagement and therefore suppression of TGF-β 2 beyond four months after a single intravitreal injection. The company previously presented data from its Phase 1 dose-escalation trial with ISTH0036 in which the compound showed excellent safety and was well-tolerated at all dose levels.