On June 10, 2020 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for CI-8993, the first-in-class monoclonal anti-VISTA antibody (Press release, Curis, JUN 10, 2020, View Source [SID1234560962]). Curis plans to initiate a Phase 1a/1b study of CI-8993 in the second half of 2020.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The clearance of our IND is an important step for the advancement of VISTA therapies, as CI-8993 becomes the first anti-VISTA antibody in development to enter clinical testing," said James Dentzer, President and Chief Executive Officer of Curis. "When activated, VISTA plays a critical role in suppressing T cell activity. Conversely, it has been shown in preclinical studies that blocking VISTA reduces the suppression of T cells and reactivates anti-tumor immune function. We are eager to leverage our extensive experience with VISTA and pioneer this first-in-class anti-VISTA antibody program."

Certain cancers, such as mesothelioma, triple negative breast cancer, non-small cell lung cancer, and gynecologic malignancies, are known to be highly driven by VISTA. These cancers may be amenable to monotherapy treatment with anti-VISTA therapy.

In other cancers, anti-VISTA therapy may be more effective as part of a combination approach. VISTA is independent of, and complementary to, other immune checkpoints, including PD1 and CTLA4. Published studies have shown that VISTA expression increases up to 5-fold as a compensatory mechanism following anti-CTLA4 or anti-PD1 treatment. Further preclinical studies have explored this relationship more deeply and support the potential of combining anti-VISTA therapy with anti-PD1 or anti-CTLA4 therapies.

The multi-center, open-label Phase 1a/1b dose escalation study of CI-8993 in patients with relapsed / refractory solid tumors will evaluate approximately 50 patients, with the goal of identifying a recommended dose and schedule. Curis expects to initiate this study in the second half of 2020.

About VISTA

VISTA is a novel negative checkpoint ligand that is homologous to PD-1/PD-L1 and suppresses T cell activation. VISTA relieves negative regulation by hematopoietic cells and enhances protective anti-tumor immunity, and is highly expressed on myeloid cells and T cells. Preclinically, VISTA monoclonal antibody treatment increased the number of tumor-specific T cells in the periphery, and enhanced the infiltration, proliferation and effector function of tumor-reactive T cells within the tumor microenvironment (TME). VISTA blockade alters the suppressive feature of the TME by decreasing the presence of monocytic myeloid-derived suppressor cells and increasing the presence of activated dendritic cells (DCs) within the TME leading to enhanced T cell mediated immunity. VISTA monoclonal antibody administration as a monotherapy has been shown to suppress the growth of both transplantable and inducible melanoma in preclinical models. Previous studies have demonstrated that VISTA blockade may be synergistic with peptide-based cancer vaccines to impair the growth of established tumors.

On June 10, 2020 Celyad SA (Euronext & Nasdaq: CYAD), clinical-stage biotechnology company focused on the discovery and development of chimeric antigen receptor T cell (CAR T) therapies for cancer, reported the launch of its corporate rebranding, including changing its name to Celyad Oncology (Press release, Celyad, JUN 10, 2020, View Source [SID1234560961]). The new name highlights the Company’s significant progress with its next-generation CAR T programs and emphasizes its commitment to cancer patients.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

As part of the rebranding, the Company also introduced a new logo and launched a new corporate website, www.celyad.com. The Company’s common stock will continue trading on the Euronext and Nasdaq Global Market exchanges under the ticker symbol "CYAD".

"Our rebranding under Celyad Oncology more accurately reflects our team’s expertise in developing innovative cell therapies against cancer," said Filippo Petti, CEO of Celyad Oncology. "As we embark on this next chapter, we look forward to our continued evolution as we strive to shape the future of our off-the-shelf and personalized CAR T cell therapies for cancer patients with unmet medical needs. In addition, today’s announcement offers us the opportunity to reiterate our strong position in the field of oncology and increased strategic focus in our allogeneic CAR T franchise on the heels of our recent update at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) conference, which featured our non-gene edited allogeneic candidates and technology platforms."

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])."

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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."