On June 10, 2020 Aptevo Therapeutics Inc. (Nasdaq: APVO), a biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR bispecific technology platform, and Alligator Bioscience AB (Nasdaq Stockholm: ATORX), a biotechnology company developing antibody-based pharmaceuticals for tumor-directed immunotherapy, reported that new preclinical data for ALG.APV-527 are being presented at the PEGS Virtual Interactive Global Summit, on June 10, 2020 in an oral presentation entitled, "ALG.APV-527: Tumor-directed T-cell stimulation, in vivo tumor regression, and safety studies of a 4-1BB x 5T4 ADAPTIR bispecific antibody (Press release, Alligator Bioscience, JUN 10, 2020, View Source [SID1234560960])."

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"Our latest preclinical data for ALG.APV-527 looks very encouraging and shows that ALG.APV-527 may overcome many of the limitations observed with other 4-1BB monoclonal antibody therapeutics by improving the biodistribution, efficacy and potential safety of this novel class of immunotherapies," said Jane Gross, Ph.D., Chief Scientific Officer for Aptevo. "Since ALG.APV-527 localizes at the tumor site, immune activation depends on binding with 5T4 tumor antigen to activate via 4-1BB, therefore limiting systemic activation seen with other 4-1BB agonists. Most interestingly, our latest preclinical data show the potential for a favorable safety profile for ALG.-APV-527. In a head-to-head comparison with a urelumab analogue in preclinical studies, ALG.APV-527 did not induce systemic T-cell activity at high doses, a key differentiator from other 4-1BB therapies."

ALG.APV-527 is a novel immunotherapeutic bispecific candidate intended for the treatment of multiple solid tumors expressing 5T4, a tumor-restricted antigen. 5T4 is an antigen that is highly expressed in a large percentage of solid tumors, including, non-small cell lung cancer (NSCLC), head and neck cancer and mesothelioma. ALG.APV-527 is designed to activate anti-tumor responses by inducing signaling through the co-stimulatory receptor 4-1BB (CD137), which is an immune receptor that is upregulated on activated T cells and natural killer (NK) cells.

The preclinical data presented at the PEGS Virtual Interactive Global Summit show that ALG.APV-527 may overcome many of the limitations of competitor 4-1BB antibodies as it selectively enhances the function of activated T cells and NK cells in the presence of the tumor antigen 5T4, as shown in vitro, and potently rejects tumors in an in vivo animal model.

In a high-dose toxicity human 4-1BB knock-in murine study comparing ALG.APV-527 with a urelumab analogue, ALG.APV-527 was well tolerated at high doses with no evidence of systemic T-cell activation and no impact on body or spleen weight, whereas the urelumab analogue induced weight loss, systemic activation of T cells, and signs of ulcerative dermatitis.

In summary, the data presented at PEGS demonstrate that ALG.APV-527:

Enhances CD8+ T cell and NK function and proliferation upon 5T4-mediated engagement
Accumulates at 5T4-positive tumors in preclinical models
In an in vivo human 4-1BB knock-in model:
Induces rejection of established bladder cancer cells at low doses
Induces anti-tumor immunological memory responses
Does not induce systemic T-cell activation at high doses, which were observed in a side-by side comparison with a urelumab analogue

Is well tolerated after repeated dosing in a GLP toxicology study and displays an antibody-like half-life with a mean half-life of 8 days
"Our data supports that ALG.APV-527 has the potential to induce a strong anti-tumor immune response without systemic toxicity, which is exactly what we hoped to see," commented Christina Furebring, Ph.D., Vice President Projects at Alligator.

About ALG.APV-527
ALG.APV-527 is a bispecific antibody (4-1BB x 5T4) intended for tumor-directed treatment of solid cancers. ALG.APV-527 was built using Aptevo’s ADAPTIR bispecific platform and combines binding domains sourced from the ALLIGATOR-GOLD human scFv library. The ALG.APV-527 bispecific antibody consists of two moieties, one moiety activating tumor-specific T cells through the co-stimulatory receptor 4-1BB, the other moiety binding to the 5T4 protein displayed on the surface of tumor cells. This enables the immune-activating effect of ALG.APV-527 to be directed specifically to the tumor and not against normal tissue.

On June 10, 2020 AbbVie (NYSE: ABBV) and Genmab A/S (Nasdaq: GMAB) reported that AbbVie and Genmab have signed a broad collaboration agreement to jointly develop and commercialize three of Genmab’s early-stage investigational bispecific antibody product candidates and enter into a discovery research collaboration for future differentiated antibody therapeutics for cancer (Press release, AbbVie, JUN 10, 2020, View Source [SID1234560959]). The companies will partner to develop Genmab’s next-generation bispecific antibody programs, epcoritamab (DuoBody-CD3xCD20), DuoHexaBody-CD37 and DuoBody-CD3x5T4. The collaboration combines Genmab’s world-class discovery and development engine and next-generation bispecific antibody therapeutic candidates with AbbVie’s deep clinical expertise, innovative antibody-drug conjugate (ADC) platform and global commercial leadership in hematological cancers.

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The discovery research collaboration will combine proprietary antibodies from both companies along with Genmab’s DuoBody technology and AbbVie’s payload and ADC technology to select and develop up to four additional differentiated next-generation antibody-based product candidates, potentially across both solid tumors and hematological malignancies. Genmab’s DuoBody-CD3 technology engages and directs cytotoxic T cells selectively to tumors to elicit an immune response towards malignant tumor cells. AbbVie’s ADC technology allows the delivery of a therapeutic toxin directly to cancer cells while sparing normal, healthy cells, providing for a more targeted, less toxic treatment approach.

"This transformative collaboration will allow us to accelerate, broaden and maximize the development of some of our promising early-stage bispecific antibodies, including epcoritamab, with the ultimate goal of bringing these potential therapies much faster to cancer patients," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "Today’s announcement marks the beginning of a new journey for Genmab that combines our world-class knowledge in antibody biology and deep expertise in truly innovative next-generation antibody technology platforms, with AbbVie’s R&D prowess and their leadership position in hematological cancers."

"Epcoritamab is a strong fit for our robust hematological oncology franchise", said Michael Severino, M.D., Vice Chairman and President, AbbVie. "By combining the strengths of our two organizations, we can advance the treatment landscape for patients battling cancer."

Collaboration Details
This collaboration will provide for the joint development and commercialization of the three bispecific antibody therapeutic candidates. For epcoritamab, the companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. Genmab will book net sales in the U.S. and Japan and receive tiered royalties on remaining global sales. For DuoHexaBody-CD37, DuoBody-CD3x5T4 and any product candidates developed as a result of the companies’ discovery research collaboration, Genmab and AbbVie will share responsibilities for global development and commercialization in the U.S. and Japan. Genmab retains the right to co-commercialize these products, along with AbbVie, outside of the U.S. and Japan. For the discovery research partnership, Genmab will conduct Phase 1 studies for these programs. AbbVie retains the right to opt-in to program development.

Financial Terms
Under the terms of the agreement, AbbVie will pay Genmab USD 750 million in upfront payment with the potential for Genmab to receive up to USD 3.15 billion in additional development, regulatory and sales milestone payments for all programs as well as tiered royalties between 22% and 26% on net sales for epcoritamab outside the U.S. and Japan. Except for these royalty-bearing sales, the parties share in pre-tax profits from the sale of products on a 50:50 basis. Included in these potential milestones are up to USD 1.15 billion in payments related to clinical development and commercial success across the three existing bispecific antibody programs. In addition, if all four next-generation antibody product candidates developed as a result of the discovery research collaboration are successful, Genmab is eligible to receive up to USD 2.0 billion in option exercise and success-based milestone payments.

Conference Call
Genmab will hold a conference call in English to discuss this news today, Wednesday, June 10, 2020, at 6:00 AM CDT / 7:00 AM EDT / 1:00 PM CEST. The dial in numbers are:

+1 855 857 0686 (US participants)
+44 3333000804 (international participants)

Confirmation code: 48035919

A live and archived webcast of the call and relevant slides will be available at www.genmab.com.

About Epcoritamab (DuoBody-CD3xCD20)
Epcoritamab (DuoBody-CD3xCD20) is a bispecific antibody created using Genmab’s proprietary DuoBody technology. Epcoritamab is designed to target CD3, which is expressed on T cells and is part of the T cell receptor signaling complex, and CD20, a clinically well validated therapeutic target. CD20 is expressed on a majority of B cell malignancies, including chronic lymphocytic leukemia (CLL), diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) and mantle cell lymphoma (MCL). In a number of laboratory models, epcoritamab has shown highly effective killing of CD20+ tumors and induced potent tumor cell lysis across a panel of B cell tumor lines. Epcoritamab is currently evaluated in a Phase 1/2 study for multiple hematological B cell malignancies.

Complete dose escalation data for epcoritamab was presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 (ASCO20) Virtual Scientific Program. The data and preliminary activity from the Phase 1/2 study of subcutaneous epcoritamab in patients with relapsed / refractory B-cell non-Hodgkin lymphoma (B-NHL) are highly encouraging showing substantial single-agent activity for epcoritamab with a manageable safety profile. In the study, epcoritamab induced rapid and deep responses in heavily pretreated patients with B-NHL across different subtypes and no dose-limiting toxicities were observed.

On June 9, 2020 JW Therapeutics, reported the completion of a US$100 million Series B round financing, the investment was co-led by CPE and Mirae Asset, jointed by CR-CP Life Science Fund and Oriza Holdings, as well as existing investors including Loyal Valley Capital, Temasek, Sequoia Capital China, ARCH Venture Partners, Juno Therapeutics, a Bristol Myers Squibb company, and WuXi AppTec (Press release, JW Therapeutics, JUN 9, 2020, View Source [SID1234560971]). This round of financing brings the total capital raised to over US$200 million.

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JW Therapeutics plans to use the proceeds to further advance its lead product JWCAR029 (a CAR-T cell product targeting CD19 in clinical phase II), further build-out a pipeline, and gear up to establish commercialization capabilities to support product launch.

James Li, Co-Founder and CEO of JW Therapeutics, commented: "We are very pleased to welcome our new investors and, by working together, we hope to accelerate our product development and serve Chinese Patients."

On June 9, 2020 Voltron Therapeutics, Inc. reported that it has entered into a Sponsored Research Agreement (SRA) with the Vaccine and Immunotherapy Center (VIC) of the Massachusetts General Hospital (MGH). Leveraging VaxCelerate, a self-assembling vaccine (SAV) platform licensed exclusively to Voltron Therapeutics by Partners HealthCare, the goal of the collaboration is to optimize the dosing and development of potent compounds that inhibit tumor growth in mice in the treatment of Human Papilloma Virus (HPV) induced malignancy and Ovarian cancer (Press release, Voltron Therapeutics, JUN 9, 2020, View Source;immunotherapy-center-at-the-massachusetts-general-hospital-to-advance-the-development-of-a-personalized-cancer-vaccine-301073035.html [SID1234560957]).

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In prior research, the SAV, when combined with a checkpoint inhibitor in a model of HPV-induced cancer, demonstrated a significant improvement in survival over either agent alone or combined. Based on these preliminary findings, several aspects of the protein core of the vaccine construct were re-engineered to optimize its ability to bind targets on cancer cells. These new Voltron Therapeutics sponsored preclinical studies set out to underscore the SAV’s safety and efficacy track record and position it for human trials.

Dr. Mark Poznansky, Director, Vaccine and Immunotherapy Center, MGH stated, "The self-assembling vaccine, co-invented with my colleague Dr. Jeffrey Gelfand, has been designed to be highly adaptable, designed for safety and allows for seamless modifications in order to target specific proteins found in tumor cells. Leveraging the protein HSP70, we are able to determine the quantity and timing of vaccination that best induces T-cell responses and explore the maximized benefit from vaccine induced anti-tumor immunity."

The SAV program has intellectual property surrounding composition of matter. The vaccine incorporates a heat shock protein that activates the immune system, bound to targeting peptides. The base core technology relies on synthesizing the heat shock protein with Avidin. Biotinylated immunogenic peptides are then bound to the HSP to customize the vaccine.

"Voltron Therapeutics is excited to continue our groundbreaking work with the VIC by supporting ongoing research dedicated to our Oncology program and the advancement of the VaxCelerate platform to develop vaccines to fight a range of cancers," said Pat Gallagher, Chief Executive Officer, Voltron Therapeutics. "The resources at the VIC and MGH to support vaccine development and innovation are instrumental in helping us advance this important work. We are hopeful that further development, pre-clinical testing and additional proof of concept results could lead to first in human trials in 2021 and ultimately make a significant and lasting difference in the treatment of cancer patients."

Additionally, Voltron Therapeutics has closed on $3.5 million in a Series-A Preferred funding round. The funds raised will be used to accelerate the development of SAV technology and expansion of the Company’s vaccine portfolio.

"This funding for Voltron Therapeutics will allow the company to conclude preclinical work as it moves toward human trials with the self-assembling vaccine," added James Ahern, Founder of Laidlaw Venture Partners, and member of the Voltron Therapeutics Board of Directors. "We at LVP are committed to continuing to support Voltron as it progresses the SAV portfolio into clinical development, with financial sponsorship and leverage of our expert network."

Voltron Therapeutics and MGH have a longstanding relationship for the development of vaccines to fight infectious diseases and cancer. Recently, Voltron Therapeutics announced a separate joint agreement to advance an application of the VaxCelerate platform to develop a vaccine designed to protect patients at risk of Coronavirus (COVID-19) infection. This vaccine will be entering animal testing this quarter. Currently, preclinical data exists in two different infectious disease settings with encouraging results. The COVID-19 vaccine could be in humans by late 2020/early 2021.

On June 9, 2020 NFlection Therapeutics, Inc., a biopharma therapeutics developer dedicated to targeting disease pathways to uncover new approaches to fighting rare disease, reported the closing of a $20 million Series A financing round with investment from venBio Partners and F-Prime Capital (Press release, NFlection Therapeutics, JUN 9, 2020, View Source [SID1234560956]). The company also announced the initiation of the first clinical trial of its lead product, NFX-179 Gel, a topically applied therapy.

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The Phase 2a study, on the heels of the successful submission of their Investigational New Drug Application with the U.S. Food and Drug Administration, will be a safety, tolerability and pharmacokinetic/pharmacodynamic study of NFX-179 Gel in adult patients with cutaneous neurofibromatosis type-1 (NF-1). This study will evaluate three concentrations of NFX-179 Gel compared with its vehicle (placebo) in a randomized, double-blind, placebo-controlled, clinical trial of 48 patients with cutaneous neurofibromatosis type-1. The study will be conducted at five investigational centers across the United States.

"This study allows us to determine the drug’s ability to suppress key biomarkers involved in the progression of neurofibromas and will aid in the selection of doses for a larger Phase 2b study," said Christopher Powala, president & chief executive officer of NFlection. "There are no FDA-approved products for this condition, and NFX-179 Gel has the potential to address this unmet medical need."

"Almost all adults with neurofibromatosis type-1 develop cutaneous nerve tumors during their lifetime. The tumors form under the skin and manifest as nodules that can be stigmatizing and even painful," said Annette Bakker, Ph.D., President, Children’s Tumor Foundation. "We are pleased that NFlection has recognized the unmet need posed by cutaneous neurofibromas, and we are encouraged that topical NFX-179 may hopefully soon provide a life-changing solution for thousands of NF-1 patients."

About Cutaneous Neurofibromatosis Type-1
Cutaneous neurofibromas are tumors that grow from small nerves in the skin or just under the skin and appear as small or larger bumps, typically beginning around the time of puberty. It is less common to see this type of neurofibroma in young children with NF1. Individuals with NF1 commonly develop more cutaneous neurofibromas as they get older. They do not become malignant, but they may be disfiguring, itchy or painful when bumped. Despite their benign nature, cutaneous neurofibromas may cause significant problems, such as depression and a sense of isolation, and may require surgical removal.