PureTech Health Announces Collaboration with Boehringer Ingelheim to Advance Immuno-oncology Product Candidates using its Lymphatic Targeting Platform

On April 17, 2019 PureTech Health plc (LSE: PRTC) ("PureTech Health"), an advanced biopharmaceutical company developing novel medicines for dysfunctions of the Brain-Immune-Gut (BIG) axis, reported that it has entered into a research collaboration with Boehringer Ingelheim to develop novel product candidates for an undisclosed number of targets by leveraging PureTech’s proprietary lymphatic targeting technology for immune modulation (Press release, PureTech Health, APR 17, 2019, View Source [SID1234535154]). Under terms of the agreement, PureTech Health will receive up to $26 million, including upfront payments, research support, and preclinical milestones, and is eligible to receive more than $200 million in development and sales milestones, in addition to royalties on product sales. The collaboration will initially focus on applying PureTech’s lymphatic targeting technology to an immuno-oncology product candidate designated by Boehringer Ingelheim.

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"We see great promise in leveraging PureTech’s platform to target the lymphatic system and deliver therapeutic candidates directly to the lymph nodes responsible for priming, educating and proliferating immune cells," said Clive Wood, PhD, global head of discovery research at Boehringer Ingelheim. "The approach is a potentially powerful tool for modulating the immune system and may allow us to improve efficacy and reduce systematic toxicities through precise targeting."

The partnership leverages the potential of the proprietary lymphatic targeting platform that PureTech Health is developing through its internal R&D division. The approach harnesses the gut’s lipid transport mechanisms to enable oral administration and transport of drug candidates directly through the gut-draining lymphatic vasculature, also bypassing first pass metabolism in the liver. More specifically, the therapeutic candidates are directed to the mesenteric lymph nodes, which program as many as 70 percent of circulating adaptive immune cells. By targeting the lymphatic system directly, the technology has the potential to achieve more effective and precise immunomodulation of local tissues, while sparing the patient from the risks of extensive systemic exposure to the drug. PureTech’s lymphatic targeting approach, which is based on the research of Chris Porter, PhD, Director of the Monash Institute of Pharmaceutical Sciences (MIPS) at Monash University, can potentially be applied to therapeutic molecules across a range of physiochemical properties and holds promise for the development of novel therapeutics for gastrointestinal, central nervous system, and autoimmune diseases as well as cancer.

"This collaboration signals the exciting potential of another proprietary platform from our internal R&D to enable novel immunotherapy approaches by harnessing the lymphatic system’s capacity for immune cell trafficking and immunomodulation," said Daphne Zohar, co-founder and chief executive officer of PureTech Health. "We look forward to working with the excellent scientific teams at Boehringer Ingelheim to advance this important program, which has the potential to greatly expand therapeutic options for patients with cancer."

The research collaboration with Boehringer Ingelheim will focus first on using this approach to administer an immuno-oncology candidate for gastrointestinal (GI) cancers directly to the gut lymphatics. About 70 percent of immune cells reside in lymphatic tissues associated with the GI tract, so targeting immunomodulatory agents with this approach could potentially tune both systemic and local immunity. Once the product candidates enter the development stage, Boehringer Ingelheim will assume full responsibility for development and PureTech Health will be eligible for various developmental and sales milestones in addition to royalties on product sales.

About PureTech’s Lymphatic Targeting Platform
PureTech’s proprietary lymphatic targeting platform is designed to the body’s natural lipid transport mechanisms to enable the transport of drug molecules directly into the lymphatic system when administered orally. This pathway facilitates entry into the mesenteric lymph nodes, which are crucial centers for immune cell priming, education and proliferation in the GI tract. Targeting the lymphatic vasculature enables rational design of therapeutics to modulate immunity in a tissue-specific manner and minimize systemic toxicity due to global immunosuppression. Preclinical data suggest PureTech’s lymphatic targeting platform could potentially enable more efficacious and less toxic therapeutics addressing cancer and inflammatory and autoimmune diseases. This technology is based on the pioneering research of Professor Chris Porter and his team at the Monash Institute of Pharmaceutical Sciences, Monash University, who continue to collaborate with PureTech Health on the program. All the relevant intellectual property associated with his work on this technology is exclusively licensed to PureTech and is supported by additional PureTech Health patents.

BioAtla Subsidiary, Himalaya Therapeutics, Will Develop And Commercialize CAB Products In Greater China Market

On April 16, 2019 BioAtla , LLC, a global clinical-stage biotechnology company focused on the development of Conditionally Active Biologic (CAB) protein therapeutics for the oncology market, reported that Himalaya Therapeutics SEZC, a Cayman Island corporation and majority owned subsidiary of BioAtla, has the exclusive license from BioAtla to develop and commercialize several specific, differentiated product candidates for the Greater China market of the PRC, Hong Kong, Macau and Taiwan (Press release, BioAtla, APR 16, 2019, View Source [SID1234621324]). The Himalaya Therapeutics portfolio includes two CAB candidates, CAB-AXL-ADC and CAB-ROR2-ADC, each currently in Phase 1/2 clinical trials conducted by BioAtla at sites in the United States. In addition, Himalaya Therapeutics will participate in BioAtla’s potential Greater China derived returns from the recently announced BioAtla and BeiGene, Ltd. global co-development and collaboration agreement for the development, manufacture and commercialization of CAB-CTLA-4 (BA3071). Himalaya will also support BioAtla’s global clinical trials effort in Greater China.

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"We believe that Himalaya’s product development and business related activities directly addressing Greater China will maximize the strategic opportunities for both BioAtla and Himalaya in the world’s second largest pharmaceutical market," stated Carolyn Short, General Manager of Himalaya Therapeutics. "The access to clinical development capabilities in China can accelerate the global development and potential commercialization of the BioAtla product portfolio and effectively address markets with strong growth potential and high unmet medical need," added Scott Smith, President of BioAtla.

Recent sweeping changes to the China regulatory processes for the development of pharmaceutical products now closely align them with those in the United States and broadens the use of clinical data for regulatory purposes between the two nations. Consequently, close coordination of clinical development in the U.S. and China of a pharmaceutical candidate is highly desireable and more efficient. Furthermore, the access to capital markets for early-stage biotechnology companies in China has recently been greatly enhanced especially with the revision to the stock listing requirements on the Hong Kong Stock Exchange. Himalaya Therapeutics is expected to fund its operations independent from BioAtla. These were primary motivating factors for Beijing Sinobioway Group Company and its related investor groups to contribute all of their rights to certain and any future CAB candidates that were part of their 2015 collaboration agreement with BioAtla in exchange for a minority equity position in Himalaya Therapeutics.

About Conditionally Active Biologics (CABs)

Conditionally Active Biologics are proteins generated using BioAtla’s proprietary protein discovery, evolution and expression technologies. These proteins can be monoclonal antibodies, enzymes and other proteins designed with functions dependent on changes in micro physiological conditions (e.g., pH level, oxidation, temperature, pressure, presence of certain ions, hydrophobicity and combinations thereof) both outside and inside cells.

Studies have shown that cancerous tumors create highly specific conditions at their site that are not present in normal tissue. These cancerous microenvironments are primarily a result of the well understood unique glycolytic metabolism associated with cancer cells, referred to as the Warburg Effect in aerobic cancer cells. CAB proteins are designed to deliver their therapeutic payload and/or recruit the immune response in specific and selected locations and conditions within the body and to be active only in the presence of a particular cellular microenvironment. In addition, the activation is designed to be reversible to repeatedly switch ‘on and off’ should the CAB move from a diseased to a normal cellular microenvironment and vice versa. CABs can be developed in a variety of formats, including antibodies, antibody drug conjugates (ADCs), bispecifics, chimeric antigen receptor T-cells (CAR-Ts) and combination therapies.

Nordic Nanovector: Safety Review Committee Approves Advancing to Final Dosing Regimen in Phase 1 Trial of Betalutin® in DLBCL

On April 16, 2019 Nordic Nanovector ASA (OSE: NANO) reported that the Safety Review Committee (SRC) for the ongoing LYMRIT 37-05 clinical trial of single-administration Betalutin (177Lu-satetraxetan-lilotomab) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not eligible for stem cell transplantation (SCT) has now reviewed safety data from the first three cohorts of patients (Press release, Nordic Nanovector, APR 16, 2019, View Source [SID1234553452]). Based on the data, the SRC approved advancing the trial to the next and final cohort with the dose regimen 20 MBq/kg Betalutin and a lilotomab pre-dose of 100 mg/m2.

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The LYMRIT 37-05 study is a Phase 1 open-label, single-arm, dose-escalation study designed to assess the safety, tolerability, pharmacokinetic profile and preliminary anti-tumour activity of Betalutin. Up to 24 patients are planned to be enrolled in the US and Europe in total. More information on this study can be found at www.clinicaltrials.gov (NCT02658968). Preliminary results are expected in the second half of 2019.

Lisa Rojkjaer, Chief Medical Officer of Nordic Nanovector, commented: "We are pleased to be moving ahead with the final cohort of patients in the study, which will enable the selection of a recommended dose for further evaluation of safety and preliminary efficacy in additional patients."

DLBCL is an aggressive form of non-Hodgkin’s Lymphoma (NHL) that accounts for up to 43% of all NHL cases, making it the most common form of the disease. Approximately 40% of DLBCL patients relapse after first-line combination treatment with rituximab and chemotherapy and only 30-40% of relapsed patients respond with subsequent high-dose chemotherapy followed by SCT (ref. 1). There are currently very few therapeutic options for patients not eligible for SCT, which makes relapsed DLBCL a serious unmet medical need. The number of diagnosed cases of DLBCL in the US and Europe in 2016 was 26,500 and 17,200, respectively. These numbers are expected to reach 31,500 (US) and 19,000 (Europe) by 2024 (ref. 2).

The National Centre for Research and Development Awards Orion Biotechnology With a Grant to Progress Development of a Treatment for Advanced Colorectal Cancer

On April 16 2019 Orion Biotechnology Canada Ltd., a developer of novel medical treatments, reported that its European subsidiary Orion Biotechnology Polska Sp. z.o.o. was awarded a grant of just under two million U.S. dollars by the Polish National Centre for Research and Development (NCBR) (Press release, Orion Biotechnology, APR 16, 2019, View Source [SID1234535183]). The grant will help co-fund a project to advance development of the company’s innovative oncological drug candidate (OB-002O). Pre-clinical evaluation and a Phase 1 clinical trial are planned as part of the project.

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OB-002O is a first-in-class chemokine analog drug candidate being testing by Orion Biotechnology for use in the treatment of solid tumors including colorectal cancer (CRC). The active agent in OB-002O is 5P12-RANTES, a CCR5 receptor antagonist, or chemokine analog, being developed by Orion Biotechnology for a range of clinical indications including cancer, neuroinflammation and HIV prevention.

"Our goal for OB-002O is to block the CCL5/CCR5 pathway which plays a critical role in cancer biology in order to inhibit tumor growth and metastasis," explained Ian McGowan, chief medical officer for Orion Biotechnology. "NCBR’s financial support will help us to investigate the potential for OB-002O to treat late-stage cancers, including CRC, for which there is no effective treatment available today."

"OB-002O represents an exciting new class of drugs – chemokine analogues – that falls under the broad and promising category of immunotherapy," said Mark Groper, CEO of Orion Biotechnology. "We are very pleased that the National Centre for Research and Development has demonstrated confidence in our technology and company by providing this sizable investment."

Results of Single Center Prospective Study on Delcath’s PHP Therapy Presented at ECIO 2019

On April 16, 2019 Delcath Systems, Inc. (OTCQB: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported that results from a prospective phase 2 study conducted by Leiden University Medical Center (LUMC) in the Netherlands on the use of the Delcath Hepatic CHEMOSAT Delivery System to treat patients with metastatic ocular melanoma with liver metastases were presented at the European Conference on Interventional Oncology (ECIO) annual meeting (Press release, Delcath Systems, APR 16, 2019, View Source [SID1234535164]).

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The LUMC study, Percutaneous hepatic perfusion with melphalan in patients with unresectable liver metastases from ocular melanoma using the Delcath System’s second-generation hemofiltration system: a prospective phase II study, was conducted by a team led and presented by Dr. Mark Burgmans. The study evaluated 35 patients with unresectable liver metastases from ocular melanoma treated with CHEMOSAT between February 2014 and June 2017. The 35 patients underwent a total of 72 PHP treatments, and tumor response was evaluable in 32 patients. Primary endpoints were overall response, overall survival, and progression free survival. Secondary measures included safety measures and hematologic toxicity.

Results of the study showed that one patient had a complete response and 22 had partial response, for a combined overall response rate of 74.1%. Overall survival was 20.3 months and mean progression free survival was 8.1 months.

Safety analysis showed a total of 14 serious adverse events were recorded. The hematologic toxicities were in a majority of the cases self-limiting and manageable. Investigators concluded that "PHP Therapy with the Generation Two version of CHEMOSAT is an effective and safe treatment for patients with hepatic metastases from ocular melanoma."

The ECIO 2019 conference was held April 8-11 in Amsterdam, the Netherlands.