On April 8, 2019 WuXi Biologics ("WuXi Bio") (2269.HK), a leading global open-access biologics technology platform company offering end-to-end solutions for biologics discovery, development and manufacturing, and NBE-Therapeutics (NBE), a privately owned Swiss biotech company developing best-in-class, next-generation antibody-drug conjugate (ADC) products, reported a comprehensive development and manufacturing partnership for NBE’s first ADC lead product NBE-002 (anti-ROR1) (Press release, WuXi Biologics, APR 8, 2019, View Source [SID1234535055]). NBE-002 is a best-in-class immune-stimulatory ADC (iADC) treatment against the ROR1 cancer target and is planned to enter into clinical trials in mid 2020 in triple negative breast cancer and other indications.

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NBE-Therapeutics develops next-generation iADC products with the aim to improve the outcome for cancer patients, as it continues to develop iADCs based on its proprietary technology platforms. With its proprietary SMAC-TechnologyTM to generate site-specifically conjugated ADCs and its proprietary highly-potent anthracycline toxin platform, NBE has the ability to develop highly targeted treatments with long-lasting anti-tumor immunity. The partnership with WuXi Biologics will enable the supply of NBE’s product for clinical trials under Investigational New Drug (IND) applications worldwide. With the establishment of state-of-the-art integrated biologics solution center, WuXi Biologics provides comprehensive one-stop service to global partners for antibodies, ADC drug substances and drug products.

Dr. Ulf Grawunder, CEO of NBE-Therapeutics commented, "We are excited about our partnership with WuXi Biologics, which we consider one of the world-leading CDMOs for manufacturing of biologic therapeutics. WuXi Biologics will be a strong partner for our next step in the development of our highly promising cancer treatments with long-lasting anti-tumor immunity. This collaboration will accelerate the transition of our preclinical iADC development programs to clinical validation. We look forward to working with WuXi Biologics over the coming years to deliver improved treatment options for global cancer patients."

"We are glad that NBE-Therapeutics with one of the best ADC platforms in the industry selected WuXi Biologics as their long-term partner for its first highly promising anti-ROR1 ADC program. It is another testament to the premier quality and global excellence of our integrated services, which continue to drive rapid expansion of our market share in Europe. We are excited in working with 7 companies on over 10 programs in Switzerland alone," said Dr. Chris Chen, CEO of WuXi Biologics. "Through our global quality, world-class technical capabilities and unparalleled capacity, we aim to empower any global partners to discover, develop and manufacture any biologics to benefit patients worldwide."

On April 8, 2019 Kymab, a clinical-stage biopharmaceutical company developing antibody-based therapeutics, reported the appointment of Simon Sturge as its new CEO, effective May 1, 2019 (Press release, Kymab, APR 8, 2019, View Source [SID1234537017]). Simon succeeds David Chiswell, who remains a scientific adviser to the Company.

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"We are delighted that such an experienced leader as Simon will lead Kymab to its next stage of growth," said Martin Nicklasson, Non-Executive Chair. "Led by Simon, Kymab will continue to progress its innovative portfolio of products through the clinic and to market, driving our strategy to transform patients’ lives. This appointment is part of Kymab’s strategy to position itself for long-term success, building on the incredibly strong R&D foundation of the Company. We’d also like to thank David for many years of leadership at Kymab as CEO and previously as Chair – his leadership has been instrumental to the Company’s evolution."

Mr. Sturge brings to Kymab over 30 years of international leadership experience in both the biotechnology and pharmaceutical industry. He joins Kymab from Merck KGaA, where he was Executive Vice President Global Strategy, Business Development & Global Operations. Previously, he was Chief Operating Officer of Merck Healthcare, responsible for company’s global commercial and manufacturing operations. Over the past five years, he has been responsible for the continued growth in global sales at Merck KGaA, as well as the commercial launches of BAVENCIO (anti-PD-L1 avelumab) in solid tumours and MAVENCLAD (cladribine) for relapsing multiple sclerosis. Prior to joining Merck KGaA, Mr. Sturge served as Corporate Senior Vice President, Biopharmaceuticals at Boehringer Ingelheim, where he had responsibility for the research, development and commercialisation of the company’s global biosimilar portfolio. Before that, he held CEO roles at a number of healthcare companies including Celltech Biologics, and he served as founder and CEO of Ribotargets, which was acquired by British Biotech and subsequently renamed Vernalis.

"I am excited to have this opportunity to head Kymab at such a transformative time in its development," said Simon Sturge. "With its competitive antibody research platforms and evolving clinical pipeline, Kymab is well positioned as it progresses into an integrated discovery and development company."

"It has been rewarding to guide Kymab through a period of significant growth. Kymab is now a recognized leader in the antibody space, with an extensive pipeline and two lead candidates in the clinic," said Dave Chiswell, former CEO of Kymab. "I have known Simon for some years and I am pleased to hand over the reins to him. Simon is highly experienced and well positioned to lead Kymab and its exceptional staff, pipeline and partnerships, as it continues to discover and develop transformative antibody therapies for patients in need."

On April 8, 2019 4SC AG (4SC, FSE Prime Standard: VSC) reported preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 that confirm domatinostat’s mode of action in Merkel cell carcinoma (MCC) (Press release, 4SC, APR 8, 2019, View Source [SID1234535040]). The data were presented by Prof. Dr. Dr. Jürgen C. Becker, Department of Translational Skin Cancer Research at the University Hospital Essen, Germany, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. The AACR (Free AACR Whitepaper) Meeting took place at the Georgia World Congress Center in Atlanta, USA, from 29 March to 3 April 2019.

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Merkel cell carcinoma – tumor cells hide from the immune system

MCC is a rare, highly aggressive skin cancer often caused by either infection with Merkel cell polyomavirus or extensive UV exposure. Patients suffer from rapidly enlarging nodules that are between 0.5 and 5 cm in diameter, while the tumor aggressively spreads through the blood vessels to lymph nodes and many organs.

Although immune checkpoint inhibitors have shown compelling clinical activity in MCC, in some patients the tumor cells are very adept at evading the immune system. The tumor cells and its microenvironment prevent immune cells from entering the tumor and limit the presentation of tumor-signals on their surface. For these patients, refractory to or relapsing on checkpoint inhibitor therapy, currently no further treatment options are available.

Prof. Dr. Dr. Jürgen C. Becker explained: "In previous experiments we demonstrated that the immune escape mechanisms of MCC cells were epigenetically reversible1. Therefore, we were highly interested in testing the effect of 4SC’s domatinostat, an orally available, epigenetically active small molecule inhibitor targeting histone deacetylases class I, on MCC cell lines.

"Our new data demonstrate that domatinostat increased the presentation of tumor signals on the cells’ surface, stopped MCC cells from dividing and even induced cell death. All these effects were specific for MCC cell lines and did not occur in healthy control cells."

Frank Hermann, M.D., Chief Development Officer of 4SC, said: "We thank our collaborators for the dedication and energy devoted to their research with domatinostat. The fact that domatinostat counteracts the immune escape of MCC at different levels suggests that the combination of domatinostat with checkpoint inhibitors is potentially a promising therapeutic strategy in MCC and we plan to initiate a potentially pivotal clinical trial later this year."

Abstract ID 2368: Domatinostat increases apoptosis, G2M cell-cycle arrest and immunogenicity of Merkel cell carcinoma

The poster is available on 4SC’s website.

Reference:

1 Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma. C. Ritter, K. Fan, A. Paschen, S. Reker Hardrup, S. Ferrone, P. Nghiem, S. Ugurel, D. Schrama, and J. C. Becker. Sci Rep. 2017 May 23;7(1):2290. doi: 10.1038/s41598-017-02608-0

On April 8, 2019 LSK BioPharma (or "LSKB"), a US-based biopharmaceutical firm and Jiangsu Hengrui Medicine, Co., Ltd. (SHA:600276, or "Hengrui"), one of the largest and most innovative fully-integrated biopharmaceutical companies based in China, reported that the Companies have received FDA clearance to initiate a clinical trial in the United States in first-line patients with advanced hepatocellular carcinoma (HCC), evaluating the safety and efficacy of LSKB’s rivoceranib, a selective VEGFR-2 inhibitor commonly known as apatinib, in combination with Hengrui’s camrelizumab (SHR-1210), a humanized anti-PD-1 monoclonal antibody currently under NDA review in China for classic Hodgkin’s Lymphoma (cHL) (Press release, LSK BioPharma, APR 8, 2019, View Source [SID1234535056]).

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"We are happy with this important regulatory milestone in our global clinical collaboration," said Dr. Sung Chul Kim, LSKB’s President. "We are enthusiastic to work with Hengrui to hopefully help more HCC patients through development of this combination therapy."

"As one of the leading biopharmaceutical companies in China, Hengrui is committed to developing breakthrough medicines for patients worldwide. This milestone is another step towards our mission. We look forward to working with LSKB to jointly make a difference for HCC patients around the world," said Dr. Piaoyang Sun, Chairman of Hengrui.

Currently, Hengrui is conducting an open-label, single arm multicenter phase 2 study (NCT03463876) to evaluate the efficacy and safety of the combination of camrelizumab and apatinib in patients with advanced HCC in China, where Hengrui has received approval of apatinib monotherapy for advanced gastric cancer. At ASCO (Free ASCO Whitepaper) 2018, it was reported that the objective response rate (ORR) and disease control rate (DCR) were 50.0% and 85.7%, respectively, among 14 evaluated advanced HCC patients treated by camrelizumab in combination with apatinib in an open-label, phase 1 study in China (Xu et al., NCT02942329). In addition, camrelizumab and apatinib combination therapy is also being evaluated by Hengrui for multiple indications including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and gastric cancer (GC) in China.

Based upon earlier studies, it is hypothesized that the combination of rivoceranib and camrelizumab may enhance the immune system, aiding the fight against cancer. In addition to the known anti-angiogenic effects of rivoceranib, it may also enhance camrelizumab’s anti-tumor activity by normalizing tumor vasculature and reversing the tumor suppressive immune microenvironment.

About Rivoceranib (Apatinib)

Rivoceranib, also known as apatinib or Aitan (brand name) in China, is the first successful small-molecule angiogenesis inhibitor in gastric cancer. Rivoceranib is investigational outside of China including in the United States; and safety and efficacy have not been established. It acts by inhibiting angiogenesis, a critical process in cancer growth and proliferation. Specifically, rivoceranib selectively inhibits VEGFR-2 which mediates the primary pathway for tumor-mediated angiogenesis.

Hengrui, who owns the China rights to rivoceranib, received the approval from China National Medical Products Administration (NMPA, formerly known as CFDA) in 2014 to market the drug under the brand name Aitan in China for advanced gastric cancer. LSKB, which holds the global rights (ex-China), has completed enrollment of a global (12 countries including US, Japan, Korea, Italy, Germany, and Russia) phase 3 clinical trial of rivoceranib in advanced or metastatic gastric cancer patients. Rivoceranib (apatinib) is currently listed in 220 clinical studies on www.clinicaltrials.gov with over 20,000 patients enrolled or planned to be enrolled in trials targeting numerous cancers including GC, colorectal cancer (CRC), HCC, NSCLC, esophageal cancer, thyroid cancer, mesothelioma, and neuroendocrine tumors. It has also shown potential to improve outcomes in combination with chemotherapeutics and immunotherapy, as well as for maintenance therapy. LSKB has received notification designating rivoceranib as an orphan medicinal product for the treatment of gastric cancer from the European Commission in the European Union, the US FDA, as well as the MFDS in South Korea.

Rivoceranib was developed by Advenchen Laboratories in Southern California under the designation YN968D1. The compound was exclusively licensed to Hengrui in China (2005) and LSKB (2007) for rest of the world.

About Camrelizumab (SHR-1210)

Camrelizumab (SHR-1210) is an investigational humanized monoclonal antibody recognizing the programmed death-1 (PD-1) receptor. Camrelizumab functions as an immune checkpoint inhibitor by specifically blocking the interaction between PD-1 and PD-L1 and reversing the immunosuppressive signal of PD-1 on the T cell. Approximately 20 clinical trials on camrelizumab in multiple indications including lung cancer, liver cancer, gastric cancer, esophageal cancer, nasopharyngeal carcinoma, lymphoma, melanoma and other advanced solid tumors are being conducted in China and Australia as monotherapy or in combination with other therapeutic agents. A marketing application for camrelizumab for relapsed/refractory classic Hodgkin’s Lymphoma was submitted by Hengrui to China NMPA, which was accepted in April 2018, and is currently under review.

On April 7, 2019 Celltrion (KRX:068270) and the Canada-based iProgen Biotech Inc. reported to agree to partner for the development of novel ADCs against validated antibody targets, including HER21 and CD202 (Press release, Celltrion, APR 7, 2019, View Source [SID1234535030]).

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The terms of the partnership agreement include: (1) Celltrion manufactures and supplies four recombinant antibodies to iProgen, among which two are HER2 and CD20 targeting, selected by Celltrion, and two additional targets to be selected by iProgen, (2) Celltrion provides supports for the Chemistry, Manufacturing, and Control (CMC) activities for the IND application and the Phase-1 clinical trial, (3) iProgen conducts the Phase-1 clinical trial using these drug candidates, and (4) upon completion of Phase 1, Celltrion has the right of first negotiation on these drug candidates for global in-licensing.

The antibodies encompassing iProgen’s proprietary delivery technology, Antibody Delivery Enhancing Domain (ADED) is expected to increase anti-tumor efficacy by enhancing the drug delivery and internalization to cancer cells. The ADED technology is applied to anti-HER2 ADCs to potentially treat not only the breast cancer patients with high levels of HER2 expression more effectively but also those with low levels with no approved targeted therapies. In addition to HER2, other tumor antigens may be therapeutically targeted by ADCs that embody this technology.

The representative of Celltrion said, "Celltrion has been searching for novel technologies that could expand the use of existing antibody therapeutics and produce biobetters and next-generation biotherapeutics, in order to bolster its pipeline outside biosimilars and small molecules," adding that "We will keep on enriching our pipeline to include a panel of oncology drugs, as part of the effort to improve patients’ lives worldwide."