On July 20, 2018 PureTech Health plc (LSE: PRTC) ("PureTech Health"), a clinical-stage biopharmaceutical company developing novel medicines focused on the Brain-Immune-Gut (BIG) Axis, reported that it has entered into a multiyear collaboration with F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc., to advance PureTech’s milk-derived exosome platform technology for the oral administration of Roche’s antisense oligonucleotide platform (Press release, PureTech Health, JUL 20, 2018, View Source [SID1234536199]). Under the terms of the agreement, PureTech Health will receive up to $36 million, including upfront payments, research support, and early preclinical milestones. PureTech Health will be eligible to potentially receive development milestone payments of over $1 billion and additional sales milestones and royalties for an undisclosed number of products.

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PureTech’s milk exosome-based technology is uniquely designed to facilitate the oral administration of complex payloads such as nucleic acids, peptides, and small molecules. These exosomes are believed to traffic via lymphatic circulation and could potentially enable the targeting of immune cells in novel ways.

Daphne Zohar, Co-founder and Chief Executive Officer of PureTech Health, said: "We are excited to accelerate the development of this promising technology from our internal lymphatic and immune cell trafficking programmes. The expertise and resources that Roche is bringing to the collaboration will help us to potentially address one of the biggest challenges in oligonucleotide-based therapeutic development: oral administration of nucleic acids."

PureTech Health has been advancing internal research and development projects that focus on the Brain-Immune-Gut (BIG) Axis, with an emphasis on lymphatics and immune cell trafficking to modulate immunity in a tissue-specific manner. These internal pipeline programmes are being consolidated into a separate division of PureTech Health called Ariya. PureTech’s Internal division, which includes the milk-derived exosome technology, has generated compelling pre-clinical data and secured key intellectual property for its lymphatic and immune cell trafficking programmes.

About PureTech’s Milk Exosomes Technology

Milk exosomes represent a significant opportunity to potentially resolve the long-standing challenge of oral bioavailability of macromolecules and complex small molecules. Exosomes, which contain mixtures of lipids, proteins and nucleic acids, play a critical physiologic role in intercellular communication and the transport of macromolecules between cells and tissues. Mammalian-derived exosomes have attractive potential as vehicles for the administration of a variety of drug payloads, especially nucleic acids, since their natural composition will likely provide superior tolerability over the variety of synthetic polymers currently in use. Most sources of mammalian exosomes are not suitable or viable as vehicles for oral administration of drugs due to their lack of stability under the harsh physiologic conditions associated with transit through the stomach and small intestine; however, the milk-derived exosomes that form the basis for PureTech’s internally-developed technology have evolved naturally and specifically to accomplish the task of oral transport of complex biological molecules. The technology is based on research conducted by PureTech Health and its academic collaborators, including Ramesh Gupta, PhD, Agnes Brown Duggan Chair in Oncological Research at the James Graham Brown Cancer Center, and Professor in the Department of Pharmacology and Toxicology at University of Louisville, and exclusively licensed to PureTech Health.

Targeting the CD47-SIRPα axis is emerging as one of the most promising new cancer immunotherapy approaches seeking to target the innate immune response. A recent analysis reveals just how intense the global interest is and a growing list of stakeholders operating in this field.

Highest Stage Breakdown of CD47/SIRPα Molecules

Most of the identified molecules are either anti-CD47 antibodies or SIRPα-Fc recombinant proteins. In healthy cells, CD47 serves as a “don’t eat me” signal by binding to the transmembrane SIRPα protein on phagocytic cells, preventing the engulfment of “self” by macrophages. In several cancer types, tumor cells overexpress CD47 to elude the immune system. Exploration of this property has been the driving force to attract hundreds of million of dollars in investments to companies like Tioma Therapeutics (now Arch Oncology), Surface Oncology and Forty Seven, the latter of which has just recently completed a $100M+ IPO. Deals in this area include the early adopter move in 2012 by Celgene securing Inhibrx’ anti-CD47 antibody in a $500 million dollar deal to the recent billion dollar plus agreement between OSE Immunotherapeutics and Boehringer Ingelheim.

On the patent front, it is evident that that the Synthon/Sanquin Blood Supply intellectual property rights hold some clout in the CD47 world following Forty Seven’s $47 million settlement and license agreement with Synthon. The license agreement also includes some far reaching concessions by Forty Seven in order for them to obtain freedom to operate. Moreover a recent patent analysis accessible in this product shows several new CD47/SIRPA bispecific/fusion-proteins, CD47 mimetics and additional, previously unknown, combination therapy strategies set forth along with methods for determining responsiveness to anti-cd47 agent

CD47/SIRPα Molecules Are In Development in Thirty Five Different Tumor Types

On the clinical development front, this report identifies fewer than ten molecules targeting the CD47-SIRPα axis which have made it into the clinic. So far with encouraging results, following the early termination of a Phase I/II trial of Tioma’s Ti-061 in late 2017.

Several of these trials also shed light on biomarker- and combination therapies of interest. On the horizon, this field will soon have another injection of candidate therapies with bispecific CD47 antibodies entering the clinic in late 2018 or early 2019.

The CD47/SIRPα Molecules Are Also Targeting Thirteen Other Targets, Including Bispecific Antibodies

Moreover, targeting the CD47-SIRPα axis also has the potential to become the combination therapy of choice as has already been demonstrated via mediating longer survival in mice together with oncolytic virotherapy and enhancing phagocytic capacity when used together with Carisma Therapeutics’ CAR macrophages. Carisma Therapeutics themselves have just announced a $53 million series A round of financing in order to develop its novel CAR macrophage cellular immunotherapy and is estimating that their project(s) will enter into the clinic in 2019.

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On July 19, 2018 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a Fortress Biotech (NASDAQ: FBIO)
Company focused on the development of novel immunotherapies based on proprietary chimeric antigen receptor
engineered T cell (CAR T) technology, reported that it has completed a pre-Investigational New Drug (pre-IND) meeting with the U.S. Food and Drug Administration (FDA) for MB-102 (CD123 CAR T) (Press release, Mustang Bio, JUL 19, 2018, View Source [SID1234527786]). MB-102 is a CAR T therapy in development for the treatment of acute myeloid leukemia (AML), blastic plasmacytoid dendritic cell neoplasm (BPDCN) and high-risk myelodysplastic syndrome (MDS). Mustang will continue its efforts on its IND filing to the FDA for MB-102.

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Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "We are pleased with the FDA’s feedback on our development plan and expect to submit an IND filing for MB-102 in the fourth quarter as planned. We anticipate that our manufacturing facility will be ready to process patient cells in the next few months, which will help enable initiation of our Phase 1/2 clinical trial of MB-102 in AML, BPDCN and MDS to begin in 2019, after approval of Mustang’s first IND."

About MB-102 (CD123 CAR T)
MB-102 (CD123 CAR T) is a CAR T cell therapy that is produced by engineering patient T cells to recognize and eliminate CD123-expressing tumors. CD123 is widely expressed on bone marrow cells of patients with MDS, as well as in hematologic malignancies including AML, B cell acute lymphoblastic leukemia, hairy cell leukemia, BPDCN, chronic myeloid leukemia and Hodgkin’s lymphoma.

In the first-in-human clinical trial at City of Hope (NCT02159495), MB-102 has demonstrated complete responses at low doses in AML and BPDCN without dose-limiting toxicities, as reported at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2017. Dose escalation continues at City of Hope in both indications.

On July 19, 2018 Alligator Bioscience (Nasdaq Stockholm: ATORX), a biotechnology company developing antibody-based pharmaceuticals for tumor-directed immunotherapy, reported that the company has submitted a clinical trial authorization (CTA) application to the relevant regulatory authorities to start a phase I study of its wholly-owned bispecific drug candidate ATOR-1015 (Press release, Alligator Bioscience, JUL 19, 2018, View Source [SID1234527787]).

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The upcoming phase I study with ATOR-1015 is a first-in-human dose escalation study in patients with advanced solid cancer. The study will be conducted at five sites in Sweden and Denmark and will enroll up to 50 patients. The primary aim of the study is to investigate the safety and tolerability of ATOR-1015 and establish the recommended dose for the subsequent phase II studies. ATOR-1015 is intended to be the first CTLA-4 and OX40-binding bispecific antibody to achieve a strong anti-tumor effect, either as a monotherapy or in combination with currently established immunotherapies such as PD-1 and PD-L1 blockers. It is expected to be suitable for treating a large number of different forms of cancer.

"We are very pleased to announce the CTA submission and look forward to starting patient recruitment as fast as possible after regulatory approval. Based on a strong preclinical data package demonstrating that ATOR-1015 localizes to the tumor and selectively activates the immune system in the tumor area, we have high expectations of this first-in-class drug candidate," said Per Norlén CEO of Alligator Bioscience.

As previously communicated, Alligator has appointed Theradex Oncology, a global contract research organization with extensive expertise in oncology clinical development, to conduct the phase I study.

For further information, please contact:

Cecilia Hofvander, Director Investor Relations & Communications

Phone +46 46 286 44 95

E-mail: [email protected]

This information is such information as Alligator Bioscience AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 4:10 p.m. CEST on July 19, 2018.

About ATOR-1015

ATOR-1015 is a next generation CTLA-4 bispecific antibody developed for tumor-directed immunotherapy with increased capability of regulatory T-cell depletion. It is wholly-owned by Alligator. ATOR-1015 binds to two different immune receptors: the checkpoint receptor CTLA-4 and the co-stimulatory receptor OX40. The immune activation is increased in areas where both target molecules are expressed at high levels, notably in the tumor microenvironment, which is believed to reduce adverse immune reactions.

On July 19, 2018 Yisheng Biopharma Co., Ltd. ("Yisheng Biopharma"), a biopharmaceutical company focusing on research, development, manufacturing, sales and marketing of immunological biologics and vaccines, reported the grand opening of Anderson Biotech Company Limited and Royal OncoCare Hospitality as two wholly owned subsidiaries of Yisheng Biopharma in Cambodia (Press release, Yisheng US Biopharma, JUL 19, 2018, View Source [SID1234528627]). The two divisions represent the first expansion of Yisheng Biopharma business and product sales operations into an ASEAN member country.

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"The opening of these two divisions is an important milestone in company history," commented Zhang Yi, Founder and Chairman of Yisheng Biopharma. "Our product YivykaTM is approved in Cambodia for the treatment of advanced solid tumors, including lung, breast, liver, colorectal and stomach cancers. We are pleased to be in a position to expand access to the benefits that this product will bring to cancer patients and are grateful for the support we have received from the Ministry of Health of the Kingdom of Cambodia."

"ASEAN countries have witnessed a significant economic boom over the last decade and represent one of the fastest growing markets for the biopharmaceutical industry," added David Shao, Ph.D., President and CEO of Yisheng Biopharma. "With a population of over 600 million under-served individuals in these countries, we are committed to expanding and deepening our presence in this region of southeast Asia. We are conducting drug development in this region, with programs in immuno-oncology, rabies and hepatitis B infection, and are well positioned to introduce a series of innovative products into this region."

YivykaTM is an innovative immuno-oncology drug recently granted a drug registration license by the Ministry of Health of the Kingdom of Cambodia. YivykaTM is the first biological product introduced into the Cambodia market by Yisheng Biopharma.

About Yisheng Biopharma Co., Ltd.

Yisheng Biopharma is a global biopharmaceutical company discovering, developing and commercializing innovative immunological biologics. With approximately 700 employees worldwide and operations in China, the United States, Singapore and certain Southeast Asian countries.