On April 8, 2020 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Zai Lab Limited (NASDAQ: ZLAB) reported a strategic collaboration for the development and commercialization of REGN1979 (CD20xCD3 bispecific antibody) in mainland China, Hong Kong, Taiwan and Macau (Press release, Zai Laboratory, APR 8, 2020, View Source [SID1234556192]). The collaboration will support global clinical development for REGN1979, starting with the ongoing potentially registrational Phase 2 program in B-cell non-Hodgkin lymphoma (B-NHL). Additionally, if REGN1979 is approved, Zai Lab will leverage its capabilities to commercialize REGN1979 in this region. REGN1979 is the most advanced investigational bispecific monoclonal antibody from Regeneron’s bispecific platform and is designed to trigger tumor killing by linking and activating a cytotoxic T-cell (binding to CD3) to a lymphoma cell (binding to CD20).

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Under the terms of the agreement, Regeneron will receive a $30 million upfront payment and is eligible to receive up to $160 million in additional regulatory and sales milestones. Zai Lab will contribute to the global development costs for REGN1979 for certain trials and will receive the rights to develop and exclusively commercialize REGN1979 in oncology in mainland China, Hong Kong, Taiwan and Macau. Additionally, Zai Lab will make payments to Regeneron based on net sales, such that Regeneron shares in a significant portion of any potential profits. Regeneron will be responsible for the manufacture and supply of REGN1979 for development and commercialization in the region.

"Zai Lab is an ideal collaborator for us, with an established and respected track record that aligns with our mission to use the power of science to repeatedly bring new medicines to patients with serious diseases," said Israel Lowy, M.D., Ph.D., Senior Vice President and Head of Clinical and Translational Sciences for Oncology at Regeneron. "Zai’s support will not only help bolster enrollment into global REGN1979 trials, but will also enable this promising investigational medicine to reach patients faster in this key region, if approved."

"Regeneron is a global leader in the research and development of innovative medicines, and we are delighted to collaborate on the investigational bispecific antibody REGN1979 as we expand our oncology franchise into hematologic cancers," said Samantha Du, Ph.D., Founder, Chairperson and Chief Executive Officer at Zai Lab. "Zai looks forward to contributing significantly to the success of REGN1979 with our regulatory and clinical expertise, and

commercial footprint in mainland China, Hong Kong, Taiwan and Macau. We are committed to collaborating with Regeneron to expand its global effort and bring innovative medicines to patients with unmet medical needs."

REGN1979 was granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for the treatment of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). REGN1979 is currently being investigated as a treatment for late stages of FL, DLBCL and other lymphomas in a Phase 1 trial as well as a potentially registrational Phase 2 trial. Positive data for REGN1979 from the Phase 1 trial were last shared at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

Conference Call and Webcast Information

Zai Lab will host a live conference call and webcast today, April 8, 2020 at 8:00 a.m. EST to discuss the strategic collaboration. Listeners may access the live webcast by visiting the Company’s website at View Source Participants must register in advance of the conference call. Details are as follows:

Registration Link: View Source

Conference ID: 4299594

All participants must use the link provided above to complete the online registration process in advance of the conference call. Upon registering, each participant will receive a dial-in number, Direct Event passcode, and a unique access PIN, which can be used to join the conference call.

A replay will be available shortly after the call and can be accessed by visiting the Company’s website at View Source

About the Regeneron Bispecific Antibody Platform

All of Regeneron’s bispecifics are designed to closely resemble natural human antibodies and bind to two different targets. They are derived from a next-generation version of Regeneron’s proprietary VelocImmune technology that utilizes a proprietary genetically-engineered mouse platform endowed with a genetically-humanized immune system to produce optimized fully-human antibodies and further created using the company’s Veloci-Bi platform. These allow for the creation of bispecifics with no linkers or artificial sequences. Additionally, Regeneron bispecifics are manufactured using similar approaches used for human antibody medicines, with similar pharmacokinetics.

VelocImmune has been used to create multiple antibodies including Dupixent (dupilumab), Praluent (alirocumab), Libtayo (cemiplimab-rwlc) and Kevzara (sarilumab), which are approved in multiple countries around the world. Regeneron previously used these technologies to rapidly develop a treatment for Ebola virus infection, which is currently under review by the FDA, and is now being used in efforts to create prophylactic and treatment medicines for COVID-19.

There are six Regeneron investigational bispecific antibodies currently in ongoing clinical trials for multiple blood cancers and solid tumors. These bispecifics fall into three categories:

CD3 bispecifics are designed to bridge T-cells and tumor cells. At the tumor site, they activate T-cells via their CD3 receptors and promote T-cell killing of the cancer cells. Investigational candidates include:

CD20xCD3 (REGN1979) for non-Hodgkin B-cell lymphomas;

Two distinct BCMAxCD3s (REGN5458 and REGN5459) for multiple myeloma;

MUC16xCD3 (REGN4018) for ovarian cancer.

CD28 costimulatory bispecifics are also designed to bridge T-cells and tumor cells. At the tumor site, they costimulate T-cells via their CD28 receptors and may synergize with PD-1 inhibitors and/or CD3 bispecifics. Investigational candidates include:

PSMAxCD28 (REGN5678) in combination with Libtayo for prostate cancer.

Tumor-targeted bispecifics are designed to target proteins only on the cancer cell. In this way, they may affect various signaling pathways to hamper the cancer cell’s ability to survive and proliferate. Investigational candidates include:

METxMET (REGN5093) for non-small cell lung cancer that is driven by MET mutations and/or amplifications. REGN5093 targets two different parts of the MET receptor on cancer cells to degrade the receptor and block its ability to trigger cell proliferation.

Regulatory Status of Regeneron Oncology Programs

The bispecifics mentioned in this press release are currently under clinical development, and their safety and efficacy have not been fully evaluated by any regulatory authority.

Libtayo in combination with REGN5678 is currently under clinical development for prostate cancer, and its safety and efficacy have not been evaluated by any regulatory authority for this use. Libtayo is currently approved in the U.S. for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation, and in other countries for similar indications. In the U.S., the generic name for Libtayo is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration.

As part of a global collaboration agreement, Regeneron and Sanofi are jointly developing Libtayo, as well as Regeneron’s BCMAxCD3 and MUC16xCD3 bispecific programs.

About B-cell non-Hodgkin lymphoma (B-NHL) in China

Non-Hodgkin lymphomas (NHL) represent a diverse group of cancers that originate from B-, T- or natural killer-cells, with annual incidence and death rates in China of more than 88,000 and 48,000, respectively, as of 2018. NHL originating in B-cells (B-NHL) make up 85% of all NHL cases, with the two most common subtypes being DLBCL and FL.

DLBCL is an aggressive form of B-NHL with up to 50% of patients with advanced stage disease progressing after first-line treatment (e.g., relapsing or becoming refractory to treatment). For patients with R/R DLBCL, treatment options are limited and the prognosis is poor.

FL is a slow-growing (indolent) form of B-NHL with most cases diagnosed in advanced stages. Although median survival ranges from 8 to 15 years in advanced FL, current therapeutic options are not curative, and most patients relapse within 5 years regardless of the regimen. In some cases, FL can transform into DLBCL, at which point it is often treated in the same way as DLBCL.

On April 8, 2020 AIVITA Biomedical, Inc., a biotechnology company specializing in innovative cell therapy applications, reported updated survival data from a year-end analysis of its ongoing Phase 2 clinical trial of AV-GBM-1 in patients with newly diagnosed glioblastoma (GBM) (Press release, AIVITA Biomedical, APR 8, 2020, View Source [SID1234556190]).

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In the analysis, the overall survival rate at both 12 and 15 months is 76% in AV-GBM-1-treated patients (n=50), compared to overall survival of 61% at 12 months and 48% at 15 months in control patients (n=287) receiving standard of care. Patient recruitment is complete in the study, with 55 patients enrolled across eight trial sites. Additional details are available through ClinicalTrials.gov.

"Although treatment and monitoring of patients is ongoing, we are very encouraged by these interim results," said Dr. Robert O. Dillman, AIVITA Chief Medical Officer. "We completed accrual to the trial ahead of schedule, thanks to the engagement of our clinical site principal investigators and a truly outstanding manufacturing success rate at AIVITA."

AV-GBM-1 is a novel immunotherapy consisting of autologous dendritic cells loaded with autologous tumor antigens derived from self-renewing tumor-initiating cells. The treatment is administered in a series of subcutaneous injections as an adjunctive therapy. The treatment is uniquely pan-antigenic, targeting multiple antigens on autologous tumor-initiating cells responsible for the rapid growth of the disease and resistance to standard therapy.

AIVITA is currently conducting three clinical studies in the United States investigating its platform immunotherapy in patients with ovarian cancer, glioblastoma and melanoma. In a past clinical trial in metastatic melanoma, AIVITA’s autologous dendritic cells has demonstrated 72% 2-year survival and 54% 5-year survival in patients (n=92). Based on data, AIVITA is currently seeking conditional commercial approval of its melanoma treatment in Japan. The clinical trial in advanced ovarian cancer is a Phase 2 randomized study currently enrolling patients at the time of initial diagnosis.

About AIVITA’S Clinical Trials

OVARIAN CANCER

AIVITA’s ovarian Phase 2 double-blind study is active and enrolling approximately 99 patients who are being randomized in a 2:1 ratio to receive either the autologous tumor-initiating cell-targeting immunotherapy or autologous monocytes as a comparator.

Patients eligible for randomization and treatment will be those (1) who have undergone debulking surgery, (2) for whom a cell line has been established, (3) who have undergone leukapheresis from which sufficient monocytes were obtained, (4) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), and (5) who have completed primary therapy. The trial is not open to patients with recurrent ovarian cancer.

For additional information about AIVITA’s AVOVA-1 trial patients can visit: www.clinicaltrials.gov/ct2/show/NCT02033616

GLIOBLASTOMA

AIVITA’s glioblastoma Phase 2 single-arm study is active and is enrolling approximately 55 patients to receive the tumor-initiating cell-targeting immunotherapy.

Patients eligible for treatment will be those (1) who have recovered from surgery such that they are about to begin concurrent chemotherapy and radiation therapy (CT/RT), (2) for whom an autologous tumor cell line has been established, (3) have a Karnofsky Performance Status of > 70 and (4) have undergone successful leukapheresis from which peripheral blood mononuclear cells (PBMC) were obtained that can be used to generate dendritic cells (DC). The trial is not open to patients with recurrent glioblastoma.

For additional information about AIVITA’s AV-GBM-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03400917

MELANOMA

AIVITA’s melanoma Phase 1B open-label, single-arm study will establish the safety of administering anti-PD1 monoclonal antibodies in combination with AIVITA’s tumor-initiating cell-targeting immunotherapy in patients with measurable metastatic melanoma. The study will also track efficacy of the treatment for the estimated 14 to 20 patients. This trial is not yet open for enrollment.

Patients eligible for treatment will be those (1) for whom a cell line has been established, (2) who have undergone leukapheresis from which sufficient monocytes were obtained, (3) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), (4) who have either never received treatment for metastatic melanoma or were previously treated with enzymatic inhibitors of the BRAF/MEK pathway because of BRAF600E/K mutations and (5) are about to initiate anti-PD1 monotherapy.

For additional information about AIVITA’s AV-MEL-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03743298

On April 7, 2020 Amphista Therapeutics, a biopharmaceutical company creating first-in-class cancer therapeutics that harness the body’s natural processes to selectively and efficiently degrade and remove disease causing proteins, reported the closing of a USD $7.5m Series A round, led by Advent Life Sciences (Press release, Amphista Therapeutics, APR 7, 2020, View Source [SID1234557642]). Seed round funders the Scottish Investment Bank, with backing from the Scottish Growth Scheme, and the European Investment Fund joined the round, along with new investor, US-based life sciences BioMotiv.

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Amphista’s CEO Nicola Thompson said, "This international financing provides Amphista with a firm foundation to underpin a Series B round to progress our oncology pipeline to the clinic. Our vision is to create a leading protein degradation company on the global stage that delivers ground-breaking new medicines to patients in areas of high unmet need."

Raj Parekh, General Partner at lead investor Advent Life Sciences said, "We are excited to support Amphista in its next stage of development. The Company has a potentially unique approach to targeted protein degradation when compared with traditional proteolysis targeting chimera (PROTAC) platforms. We believe that Amphista has great potential with its differentiated proprietary technology to address traditionally undruggable targets."

Satish Jindal, CEO of BioMotiv, and newly appointed Amphista Chairman, commented, "We are a mission-driven accelerator, and we are excited by Amphista’s focus to rapidly produce potent bifunctional small molecules to augment the body’s own processes to remove disease-associated proteins. We see huge potential to accelerate Amphista’s breakthrough technology platform into medicines."

Amphista’s scientific founder, Professor Alessio Ciulli, based at the University of Dundee, is an internationally renowned expert in the field of targeted protein degradation (TPD). "Highly specific TPD is a transformative new modality for tackling previously undruggable targets with high therapeutic value." said Ciulli.

Amphista’s TPD small molecules instruct the cell to degrade the target directly rather than activating or inhibiting the target protein function. As protein-protein interactions are involved in disease progression, removing the target protein provides a clear therapeutic advantage over simple inhibition. Specifically, Amphista’s platform is independent of traditional E3 ubiquitin ligases used by the field, potentially expanding the available target scope of TPD approaches and should overcome recently identified PROTAC resistance mechanisms.

On April 7, 2020 Abbisko Therapeutics Co., Ltd. reported the completion of the cohort 1 study for ABSK-021 phase I clinical trial in the US and the enrollment of the first patient for ABSK-011 phase I trial in Taiwan, China (Press release, Abbisko Therapeutics, APR 7, 2020, View Source;article_id=142&brd=1 [SID1234556284]). ABSK-021 has demonstrated excellent PK properties in the first cohort of patients with strong target engagement. Both innovative drug candidates, independently discovered and developed by Abbisko Therapeutics, have officially entered into clinical stage development.

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ABSK-021 is a highly potent and selective small molecule inhibitor of CSF-1R with oral availability. Blocking CSF-1R signaling pathway can modulate tumor microenvironment, release tumor immunosuppression, and synergize with a variety of anticancer therapies such as tumor immune-checkpoint antibodies to achieve better tumor inhibition. Clinical studies have demonstrated that inhibition of CSF-1R activity can be used to treat tenosynovial giant cell tumor (TGCT) and many other human malignancies.

ABSK-011 is an oral, potent, and highly selective small molecule inhibitor of FGFR4 that exhibited strong anti-tumor effects in preclinical models with excessive activation of FGFR4 signaling. In December of 2019, ABSK-011 was first approved by the FDA of Taiwan (China) to enter into Phase I clinical study. In February, ABSK-011 was also approved for entering clinical studies by the national medical products administration of China (NMPA).

On April 7, 2020 A new study published in Cancer Discovery shows a possible alternative to chemotherapy for infants with high-grade glioma tumors (Press release, The Institute of Cancer Research, APR 7, 2020, View Source [SID1234556253]). The study reveals that high-grade glioma brain tumors in babies are molecularly unique and could be candidates for targeted treatments.

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High-grade gliomas, tumors of the glial cells, are a rapidly growing type of brain tumor that 150-180 children in North America are diagnosed with each year. More than half of all brain tumors in children are gliomas. Children who are diagnosed as infants, less than 12 months, have a better chance at survival, with only 20% of older children living past five years.

"It’s especially cruel when cancer affects such small children, so it is encouraging that this study offers some hope for very young patients and their families," said Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London. "The research offers a better understanding of the biology of brain tumors in infants and finds that they might potentially be treated with new targeted drugs. That’s vitally important because infants are particularly vulnerable to the side effects from standard treatments such as chemotherapy, and we need much better, kinder options."

This new research has found that when cancer is looked at in infants, the tumors are biologically different than those in older children. Scientists discovered that infant tumors could be targeted with precision medicines because of the genetic make-up of the tumors, which can have devastating side effects and be harmful while their brain is still developing.

"Our study offers the biological evidence to pick out those infants who are likely to have a better outcome from their disease, so these very small children and their families can be spared the harmful effects of chemotherapy," said Professor Chris Jones, Professor of Pediatric Brain Tumour Biology at The Institute of Cancer Research, London.

Scientists at The Institute of Cancer Research in London, working with colleagues at the Hopp Children’s Cancer Center Heidelberg in Germany, the UCL Great Ormond Street Institute of Child Health, and St. Jude Children’s Research Hospital in the U.S., looked at 241 infants diagnosed with glioma brain tumors. This was the largest and most comprehensive study of infant gliomas to date. Research showed a genetic difference from the samples of infant and children’s tumor samples, though they look similar under a microscope. Of the 241 samples, 130 of them had entirely different genetic make-up from other forms of childhood brain tumors. Around 65 of the 130 unique types of tumors had specific molecular weaknesses like ALK and NTRK gene fusions that can be targeted with non-chemo medicines.

In research with mice, they found mice treated with Lorlatinib had a significant shrink in tumor size, compared to those treated with chemotherapy, who’s tumors kept growing, although at a slower rate.

In ‘mini tumors’ grown from patient samples, tumors with NTRK and other genes were sensitive to targeted treatments.

A small number of patients from the study were able to be successfully treated with ALK or NTRK targeted drugs.

These results could mean new hope for families affected and are set to change the World Health Organization’s diagnostic guidelines with brain tumors in infants to be classed separately from other childhood brain tumors.

"Chemotherapy is currently a good treatment option for babies with brain tumors – but our study has found that some children could be spared this treatment," said Dr. Matthew Clarke, Clinical Research Fellow in the Glioma Team at The Institute of Cancer Research, London. "With further testing, I’m hopeful that existing targeted drugs could expand our arsenal of options to treat these smallest of patients."