On April 12, 2021 C4X Discovery Holdings plc (AIM: C4XD), a pioneering Drug Discovery company, reported that its subsidiary, C4X Discovery Limited ("C4XD", "C4X Discovery" or the "Company"), has signed an exclusive worldwide licensing agreement with Sanofi (NASD: SNY, PAR: SAN – "Sanofi "), worth up to €414 million, for C4XD’s oral pre-clinical IL-17A inhibitor programme (Press release, C4X Discovery, APR 12, 2021, View Source [SID1234577886]). Under the terms of the agreement, C4XD will receive an upfront payment of €7 million and could receive up to a further €407 million in potential development, regulatory and commercialisation milestones, of which €11 million is in pre-clinical milestones, in addition to single digit royalties.

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Under the license, Sanofi will develop and commercialise an oral therapy for the treatment of inflammatory diseases, a multi-billion dollar market. The IL-17 family of cytokines are strong inducers of inflammation and are implicated in a variety of autoimmune diseases including psoriasis, psoriatic arthritis and ankylosing spondylitis. Current treatments targeting IL-17 are monoclonal antibodies administered via an injection. There is an urgent need for safe and efficacious oral small molecule therapies to increase the number of patients able to access IL-17 targeted drugs and expand availability into new inflammatory disease indications. C4XD’s small molecule IL-17A inhibitor programme can selectively block IL-17 activity in vivo whilst maintaining molecular size of the molecule in the traditional "drug-like" range suitable for oral administration. Sanofi will continue to work with the C4XD team to access its unique and proprietary 4D Conformetrix technology, as the programme advances towards clinical studies.

Clive Dix, CEO of C4X Discovery, said: "We are proud to be working with Sanofi to create much needed oral therapies in the underserved inflammatory disease space. While antibody therapies have demonstrated the potential of IL-17 inhibition in the generation of highly effective treatments, the injectable route means many patients currently do not have access to the medicines that can change their lives. We believe that our small molecule programme has the potential to create high value, efficacious and convenient oral IL-17 therapeutics for this large market. The Psoriasis market alone is estimated to be worth c.$24 billion per annum by 20271, and when combined with Sanofi’s development expertise our programme has the potential to address a number of indications.

"This is the second significant agreement for a C4XD programme and marks a major milestone for the Company, not only validating the strength of our Drug Discovery expertise, but also our strategy to drive shareholder value through early-stage revenue generating deals. With Indivior progressing our molecule for opioid addiction through a Phase I clinical trial and now our partnership with Sanofi driving potential next generation oral IL-17 therapies, we look forward with confidence to further develop our portfolio and deliver additional novel small molecule drug candidates tackling significant patient needs."

On April 12, 2021 XNK Therapeutics AB ("XNK" or the "Company"), a Swedish clinical stage immunotherapy company treating cancer by developing novel NK cell-based therapies, reported the completion of a private placement of SEK 64 million (Press release, CellProtect Nordic Pharmaceuticals, APR 12, 2021, View Source [SID1234577885]). The purpose of the issue is primarily to finance the Company’s research and development efforts.

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"XNK has made significant progress with its technology platform and this new funding will be key to continue the clinical development of our leading investigational drug candidate," said Johan Liwing, CEO of XNK.

On April 11, 2021 StoneWise, a medical technology company that accelerates novel drug discovery with artificial intelligence, reported that it has completed its series B and B+ financing to raise a total of US$100 million (Press release, Stonewise, APR 11, 2021, View Source [SID1234654561]).

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The series B financing was led by Legend Capital, while the series B+ funding was co-led by Greater Bay Area Community Development Fund and Lightspeed China. New investors include CDH VGC Fund and Eastern Bell Capital. Existing shareholders HillHouse Ventures, SIG, Long Hill Capital, and Linear Capital made additional investments.

The proceeds will be used to recruit and retain world-leading talents and upgrade the AI-enabled drug discovery platform so as to advance innovation and improve R&D efficiency.

"We will use the proceeds from these two rounds of financing to strengthenour talent team, accelerate technology iteration, and support project execution," says Zhou Jielong, founder of StoneWise. "We expect more eminent professionals to join us in the early stage of pharmaceutical development. Together, we will identify promising drug candidates faster, advance the use of AI in drug innovation, and improve life quality," he continues.

StoneWise completed four rounds of financing in 2020. Its investors include high impact players in both the pharmaceutical and the AI sectors. The latest financing will empower StoneWise to leverage its molecular design platform and knowledge graph to gear up AI-driven discovery of novel drugs.

It takes up to 15 years and around US$2.6 billion on average to develop a new drug. As one of the global pioneers to apply AI to small molecule drug R&D, StoneWise makes drug development more time-efficient and cost-effective with its drug discovery platform.

The platform provides pharmaceutical companies an integrated solution, featuring a vast range of tools such as a wide range of AI models, interactive medical knowledge graph, deep learning-driven scaffold hopping/derivatization, and generative molecular creation and design.

Richard Li, President of Legend Capital says, "Drug innovation is at the core of pharmaceutical development, and it is also a major entry point for AI application. StoneWise is an industry leader in terms of new technology development, strategic planning and project execution. We are confident that via integrating AI with computational chemistry, pharmacology, molecule dynamics, quantum mechanics, and other cutting-edge technologies, StoneWise will strive to lead AI-driven drug innovation."

"Drug discovery industry faces challenges such as long R&D cycles, low success rates, and sky-rocketing costs, which can be more effectively addressed by AI technologies. Up to now, multiple drugs developed with the support of AI entered into clinical development stages," says Mingyu Wang, senior partner of CDH VGC. "StoneWise’s AI platform has been well received by many pharmaceutical companies. We are confident on its growth potential and expect a continuous output of high-quality drug candidates., and a significantly improved drug discovery R&D system."

On April 11, 2021 Checkmate Pharmaceuticals, Inc. (NASDAQ: CMPI) ("Checkmate"), a clinical stage biopharmaceutical company focused on developing its proprietary technology to harness the power of the immune system to combat cancer, reported the presentation of new translational data from Checkmate’s Phase 1b trial of vidutolimod (CMP-001) in combination with pembrolizumab in patients with advanced anti-PD-1 refractory melanoma (Press release, Checkmate Pharmaceuticals, APR 11, 2021, View Source [SID1234577914]).

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Vidutolimod (CMP-001) demonstrates improved response in noninflamed anti–PD-1 refractory melanoma and response is associated with serum CXCL10 (Abstract #: 5231: NCT02680184)

During the 2021 AACR (Free AACR Whitepaper) Virtual Clinical Trials with Novel Immuno-oncology Strategies Session on April 11 from 4:00 – 5:45pm ET, Jason Luke, MD, Director, Cancer Immunotherapeutics Center, UPMC Hillman Cancer Center, and Associate Professor of Medicine, University of Pittsburgh School of Medicine, presents new translational data from an ongoing Phase 1b study of vidutolimod in combination with pembrolizumab in patients with PD-1 blockade refractory advanced melanoma.

Key highlights from these clinical data include:

93% of patients had progressive disease as their last response assessment on prior PD-1 blockade therapy, 42% had an elevated LDH, and the median sum of the target lesions longest diameter was 6.7 cm, indicating advanced disease
Response rates to vidutolimod in combination with pembrolizumab were similar across baseline patient characteristics including BRAF mutation, LDH level, number of prior systemic cancer treatments, best response to prior PD-1 blockade therapy, and prior ipilimumab
Responders and non-responders were not distinguished by baseline tumor characteristics including PD-L1 CPS, IFNg transcriptional signature, CD8+ T cells, or nonsynonymous mutations
All patients showed the expected rapid induction of anti-Qb antibodies to the virus-like particle (VLP), which facilitate the pharmacodynamic response to vidutolimod, and the antibody titers were not associated with clinical response
Clinical activity of vidutolimod in combination with pembrolizumab was associated with serum CXCL10 induction magnitude, induction of an inflammatory gene expression profile, and CD8+ T cells in injected and noninjected tumors
"These translational data provide new insights into the rapid pharmacodynamic responses to vidutolimod and support the conclusion that clinical responses to treatment are not associated with the previously-described predictive markers for response to PD-1 blockade such as inflamed tumors," said Dr. Jason Luke.

On April 11, 2021 Taiho Oncology, Inc. reported efficacy and safety results from the Phase 2 FOENIX-CCA2 trial, a single-arm multicenter Phase 2 study evaluating futibatinib (TAS-120) in patients with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene rearrangements including gene fusions who have failed at least one line of therapy (Press release, Taiho, APR 11, 2021, View Source [SID1234577871]). The data were presented online as an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 Week 1 Clinical Trials Plenary from 2:00 – 3:45 PM ET on April 11, 2021.

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In the FOENIX-CCA2 trial, 103 patients with locally advanced or metastatic unresectable iCCA harboring FGFR2 gene rearrangements including fusions who had received one or more prior lines of systemic therapy received futibatinib 20 mg once daily until disease progression or unacceptable toxicity. The study met its primary endpoint of a greater than 20% objective response rate (ORR) assessed by independent central review with an ORR of 41.7%. Secondary endpoints of duration of response (DOR) and disease control rate (DCR) were also reported; responses were durable, with a median DOR of 9.7 months and 72% of responses ≥6 months, and a DCR of 82.5%. Median progression-free survival (PFS) was 9.0 months and median overall survival (OS) was 21.7 months, with 72% of patients alive at 12 months.

Common treatment-related adverse events (TRAEs) were hyperphosphatemia (85%), alopecia (33%) and dry mouth (30%). The most frequent grade 3 TRAE was hyperphosphatemia (30%), which resolved in patients with adequate management. One grade 4 TRAE of increased ALT was reported and there were no treatment related deaths.

"The results of FOENIX-CCA2 are significant for patients living with refractory intrahepatic cholangiocarcinoma with FGFR2 gene fusions or other rearrangements as futibatinib showed a meaningful ORR of 41.7% and good durability of responses," said medical oncologist Lipika Goyal, MD, MPhil, Massachusetts General Hospital Cancer Center, and lead investigator on the study. "These results represent another example of the promise of precision medicine in cholangiocarcinoma and indicate that futibatinib could be an option for patients with refractory CCA if approved."

The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) for futibatinib for the treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring FGFR2 gene rearrangements, including gene fusions in February 2021 based on efficacy and safety results from the FOENIX-CCA2 study. The FDA Office of Orphan Drug Development granted futibatinib orphan drug status for the treatment of cholangiocarcinoma in May 2018.

Additional Data on Futibatinib (TAS-120) in iCCA Presented

Taiho Oncology also presented preclinical and Phase 1 clinical data for futibatinib at AACR (Free AACR Whitepaper) as poster presentations. Presentations include:

Acquired resistance to ATP-competitive and irreversible FGFR inhibitors (FGFRi’s): A library-based approach: Hiroshi Sootome, MS, Manager, Translational Research Planning & Management group, Taiho Pharmaceutical Co., Ltd. (1117). Results were shared online as a poster presentation from 8:30 AM – 11:59 PM ET on April 10, 2021.
Effect of futibatinib on QT/QTc interval: a randomized, controlled, double-blind study: Ikuo Yamamiya, PhD, Associate Director, Bioanalytics & DMPK, Taiho Oncology, Inc. (CT128). Results were shared online as a poster presentation from 8:30 AM – 11:59 PM ET on April 10, 2021.
Evaluation of potential drug-drug interactions (DDIs) between futibatinib and CYP3A inhibitors/inducers, CYP3A substrates, or proton pump inhibitors (PPIs): Ikuo Yamamiya, PhD, Associate Director, Bioanalytics & DMPK, Taiho Oncology, Inc. (CT125). Results were shared online as a poster presentation from 8:30 AM – 11:59 PM ET on April 10, 2021.
Please visit Taiho Oncology’s virtual Medical Booth for more information.

"With the low survival rates typically seen in patients with intrahepatic cholangiocarcinoma, the possibility of a new treatment option with demonstrated efficacy and safety is an important development for the oncology community," said Martin J. Birkhofer, MD, Senior Vice President and Chief Medical Officer, Taiho Oncology, Inc. "Taiho Oncology looks forward to sharing these data with regulatory authorities, with the hope of supporting approval for this important investigational therapy."

About Futibatinib (TAS-120)
Futibatinib (TAS-120) is an investigational, oral, potent, selective, and irreversible small-molecule inhibitor of FGFR1, 2, 3 and 4 being studied as a potential treatment for patients with advanced solid tumors with FGFR1-4 genetic aberrations, including cholangiocarcinoma, who were previously treated with chemotherapy or other therapies. Futibatinib selectively and irreversibly binds to the ATP binding pocket of FGFR1-4 resulting in the inhibition of FGFR-mediated signal transduction pathways, reduced tumor cell proliferation and increased tumor cell death in tumors with FGFR1-4 genetic aberrations.

About Cholangiocarcinoma
Cholangiocarcinoma (CCA), also known as bile duct cancer, is not common. About 8,000 people in the U.S. are diagnosed with CCA each year.1 This includes both intrahepatic (inside the liver) and extrahepatic (outside the liver) cancers. CCA can occur at younger ages, but it is seen mainly in older people. The average age of people in the U.S. diagnosed with cancer of the intrahepatic bile ducts is 70, and for cancer of the extrahepatic bile ducts it is 72.1 The five-year survival rate of intrahepatic CCA (all SEER stages combined) is 9%.2

The main treatment for CCA is surgery. Radiation therapy and chemotherapy may be used if the cancer cannot be entirely removed with surgery and in cases where the edges of the tissues removed at the operation show cancer cells (also called a positive margin). Both stage III and stage IV cancers cannot be completely removed surgically. Currently, standard treatment options are limited to radiation, palliative therapy, liver transplantation, surgery, chemotherapy and interventional radiology.3