On February 16, 2022) CASI Pharmaceuticals, Inc. (Nasdaq: CASI), a U.S. biopharmaceutical company focused on developing and commercializing innovative therapeutics and pharmaceutical products, reported preliminary and unaudited revenues for the fourth quarter and full-year 2021 and provided an update on key highlights for 2022 (Press release, CASI Pharmaceuticals, FEB 16, 2022, View Source [SID1234608186]).

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Wei-Wu He, Ph.D., CASI’s Chairman and Chief Executive Officer, commented "In March 2021, we in licensed CB-5339, a first-in-class VCP/p97 inhibitor for the greater China market. In June 2021, we dosed our first patient in our CID-103 program, a fully human IgG1 anti-CD38 monoclonal antibody’s Phase 1 study; and in December 2021, we received CTA approval from CDE for BI-1206, a first-in-class novel anti-FcγRIIB antibody. Thanks to the efforts of the global CASI team, we have been able to successfully advance our pipeline initiatives during 2021 and position ourselves for continued progress during 2022."

"With EVOMELA as our primary commercial product, we have built a commercial group of more than 100 hematology sales and medical marketing specialists in China. We believe that we have significantly increased the value of our commercial franchise and that our commercial franchise brings us closer to the key opinion leaders in the Chinese hematology-oncology space. We believe that the value of our commercial franchise is also is a key reason many global innovators choose to partner with us due to our access to the market and local clinical development resources. In 2021, our commercial franchise has thoroughly prepared for the anticipated China NDA filing of CD19 CAR-T program, which we currently expect to be in late 2022 or early 2023" Dr. He commented.

Dr. He continued, "Our achievements in 2021 form a great foundation from which we plan to build upon throughout 2022 and beyond. We continue preparations for the commercialization of CNCT-19. During 2022, we anticipate that EVOMELA will continue to be the core of our commercial operation, while we further progress our other pipeline assets. During 2022, we anticipate the start of the BI-1206 phase I trial in China; CB-5339 is expected to receive CTA approval from NMPA during 2022; and CID-103’s Phase I study will continue. We are excited by our momentum and will continue to execute on several key milestones across our broad portfolio in the quarters ahead."

Preliminary and Unaudited Fourth Quarter and Unaudited Full-Year 2021 Revenues, Cash Position, and 2022 EVOMELA (melphalan for injection) Revenue Guidance

·The Company anticipates that it will report EVOMELA revenue of approximately $9.12 million for the fourth quarter ended December 31, 2021, and approximately $30 million for the full-year ended December 31, 2021, exceeding the projected $27 million guidance, and representing a 100% percent increase over the 2020 revenue of $15 million.

·The Company is targeting full-year 2022 revenue guidance of more than 30% growth over 2021 for EVOMELA.

·CASI expects to report approximately $38.7 million of cash and cash equivalents as of December 31, 2021.

·The Company’s fourth quarter and full-year 2021 revenues are preliminary and are subject to the completion of the Company’s 2021 audit. Complete fourth quarter and full-year 2021 financial results will be reported in March 2022.

Key Highlights for 2021

CASI continues to advance pipeline products through clinical trial stages in China and globally.

·Our partner, Juventas Cell Therapy Ltd ("Juventas"), continues the development of CNCT19, an autologous CD19 CAR-T investigative product for which CASI has co-commercial and profit-sharing rights. CNCT19 is being developed as a potential treatment for patients with hematological malignancies which express CD19 including, B-cell acute lymphoblastic leukemia ("B-ALL") and B-cell non-Hodgkin lymphoma ("B-NHL"). The Phase 1 studies in B-ALL and B-NHL in China have been completed by Juventas. The Phase 2 B-ALL and B-NHL registration studies are both currently enrolling.

·Along with our partner, BioInvent, we continue to progress the development and regulatory framework for BI-1206 in China. The National Medical Products Administration (NMPA) granted BI-1206 Clinical Trial Application (CTA) approval in December 2021. EC approval from a leading investigational site was granted in January 2022. BI-1206 is BioInvent’s lead drug candidate and is currently being investigated in two Phase 1/2 trials. One is evaluating the BI-1206 combination with rituximab for the treatment of non-Hodgkin lymphoma, which includes patients with FL, MCL and marginal zone lymphoma (MZL) who have relapsed or are refractory to rituximab. A second Phase 1/2 trial is investigating BI-1206 in combination with anti-PD1 therapy Keytruda (pembrolizumab) in solid tumors.

·CB-5339 CTA application for the Multiple Myeloma indication is in preparation after receiving pre-IND feedback from NMPA in January 2022. Cleave Therapeutics is responsible for the ex-China development of CB-5339, an oral second-generation, small molecule VCP/p97 inhibitor, and is evaluating the molecule, in a Phase 1 clinical trial in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

·CID-103 is a fully human IgG1 anti-CD38 monoclonal antibody recognizing a unique epitope that has demonstrated encouraging preclinical efficacy and safety profile compared to other anti-CD38 monoclonal antibodies. CASI maintains exclusive global rights and is developing CID-103 for the treatment of patients with multiple myeloma. The Phase 1 dose escalation and expansion study of CID-103 in patients with previously treated relapsed or refractory multiple myeloma is ongoing in France and the UK.

On February 16, 2022 Oasmia Pharmaceutical reported that it will publish its year-end report for 2021 on February 24, 2022, at 08.00 am CET (Press release, Oasmia, FEB 16, 2022, View Source [SID1234608169]). The company will hold a conference call and an online presentation on the same day at 10.00 am CET. The call will be hosted by CEO Francois Martelet and CFO Fredrik Järrsten. The presentation will be in English and followed by a question-and-answer session.

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On February 16, 2022 A team of researchers and doctors at Upstate Medical University, led by Leszek Kotula, MD/PhD, reported tht they have published ground-breaking findings in breast cancer research (Press release, SUNY Upstate, FEB 16, 2022, View Source [SID1234608187]).

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The translational study, titled "ABI1 based expression signature predicts breast cancer metastasis and survival" was published in the prestigious journal Molecular Oncology in December.

"The study carries significant potential to be utilized in clinical diagnosis in the future," Kotula said. "Our paper is producing a new kind of paradigm. By analyzing the primary tumor gene expression, we can predict, with very high potential to be correct, whether this tumor metastasizes in the future, in ten years, in 20 years, based on the collaboration of seven genes."

Breast cancer is the second most common cancer in women after skin cancer, and metastatic breast cancer is often incurable. While mammograms can detect tumors, there is currently no way to precisely predict metastatic potential of a tumor, or the likelihood it will spread to another part of the body such as the bones, lungs, brain and liver.

That’s where this research can have an impact.

Kotula’s research centers on the role of seven genes in the development of metastatic breast cancer, and the ABI1 is the key gene in that expression signature. It one of the proteins of the WAVE complex, which is a multi-protein unit responsible for making cells invasive.

Kotula, an associate professor of urology, biochemistry and molecular biology at Upstate, discovered the ABI1 gene in 1998. In 2001, he published the first study on the gene’s role in prostate cancer. Subsequent work from his lab delineated mechanisms of prostate tumor progression associated with ABI1. In prostate cancer, the presence of the gene inhibits cancer growth, while low levels or the absence of it leads to prostate cancer.

It’s the opposite in breast cancer. High levels of ABI1, or an overexpression, corresponds with poor survival and shorter relapse time in patients with primary breast cancer tumors.

"I started breast cancer (research) because I was puzzled by the discordant function of the protein/gene in different types of cancer," Kotula said. "It’s very interesting. We are coming to an understanding about this gene’s role, and it all makes sense now. But we need to do a lot of research. It’s a homeostatic gene. Too much is bad, too little is bad. You need to have a certain level. The homeostatic genes like ABI1 often play a critical role in drug treatment sensitivities and resistance."

In the breast cancer study, the team translated observations from a mouse model to genetic information of human breast cancer patients. Kotula’s student Angelina Regua (who is now a postdoctoral fellow at the Wake Forest Cancer Center) confirmed the observation from breast cancer patients in the novel mouse model with breast cancer metastasis.

Regua disrupted, or knocked out, the ABI1 gene in mice with breast cancer. When both copies of the gene were knocked out, there was almost no metastasis. When one copy of the gene was knocked out, tumor progression slowed. The mouse model established that ABI1 is the critical gene responsible for metastasis to the lungs.

Then they analyzed human gene information using data provided by The Cancer Genome Atlas (or TCGA) and predicted there are seven genes that predict metastatic potential. Upstate’s Vladimir Kuznetsov, PhD, a professor of urology, biochemistry and molecular biology, and his group of students in collaboration with Kotula’s lab used advanced bioinformatic and novel biostatistics approaches to develop a 7-gene prognostic ABI1-based gene signature for breast cancer metastasis.

The work was a collaborative effort between the Kotula and Kuznetsov Laboratories, Abirami Sivapiragasam, MD, from Upstate’s Department of Medicine, and Isabelle Bichindaritz, MD from SUNY Oswego.

"I love to collaborate," Kotula said. "I talk about my science to everybody, the door to my lab is open to collaborators and new ideas. Translational science requires multidisciplinary collaborations to make meaningful progress. This is possible in our Urology department, led by the surgeon-scientist Dr. Gennady Bratslavsky."

The study, which began in 2015 and has cost about $400,000 thus far, was mainly funded by the Carol M. Baldwin Breast Cancer Research Fund of CNY, the Upstate Cancer Center Pilot Grant (Connolly Fund), and the National Cancer Institute. The Upstate Foundation Dawn K. (Smith) Steber Endowment for Cancer Research also contributed to the study.

Kotula says the paper generated potential for multiple future studies, including a Phase I Clinical trial, where researchers will do gene sequencing on tumors of breast cancer patients, follow them for metastasized tumors, looking for the role of the ABI1.

The prognostic signature will help advance better drug targets and diagnosis, bringing science one step closer to a cure.

"People are treated right now with certain drugs," Kotula said. "Many of them fail to prevent or cure metastases. This is the next biggest problem to solve, why they fail. We want to understand how ABI1-signature genes behave under the treatment. The treatment that will alter the signature will be evaluated for metastatic potential with the hope to prevent it."

On February 16, 2022 The Life Raft Group reported A recent paper published in Cancers, was the result of a global roundtable sponsored by CTOS and SPAEN (Press release, The Life Raft Group, FEB 16, 2022, View Source [SID1234608205]).

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Held on November 9, 2021, patients and advocates from Sarcoma Patients EuroNet (SPAEN) and medical experts from the Connective Tissue Oncology Society (CTOS) met as an ancillary part of the CTOS 2021 Annual meeting. Representatives from both organizations discussed the challenges and roadblocks to effective global sarcoma care and management. This paper highlights the major findings and proposes potential future steps.

Both the LRG’s Sara Rothschild, Vice President of Program Services, and Piga Fernández, LRG Global Consultant, who was also representing Fundación GIST Chile, were invited to this roundtable, as patient advocates, with the goal in mind of publishing a paper on sarcoma care and the challenges globally. Their role was to give their opinion, as patients and patient advocates on the topics that were discussed.
According to Piga, "As patient advocates, participating in this Round Table was very important. It was a great opportunity to make visible the difficult journey sarcoma patients must travel before reaching the final correct diagnosis and correct treatment. The main difficulties identified were the lack of specialists, difficult access to treatments and the long time that patients have to wait until they reach a center of excellence where they can be treated effectively. We were able to highlight the need to educate primary care professionals, to shorten the time of diagnosis, and the importance of global collaborative efforts to address the multiple problems sarcoma patients have."

According to SPAEN, "It’s a remarkable first step of a truly global initiative of Sarcoma Experts and Patient Advocates with the aim to address and overcome challenges in sarcoma care together. We brought experience and expertise from all stakeholders, from many parts of the world, from different areas of expertise together and hope to continue to do so! With hard work, enthusiasm, dedication, collaboration, and time, we aim to ultimately improve sarcoma management for patients around the globe."

On February 16, 2022 Cambrian BioPharma, a multi-asset longevity biotech, reported a licensing agreement with Novartis to advance novel, selective compounds designed and characterized by Novartis to target the mechanistic target of rapamycin (mTOR) pathway (Press release, Cambrian Biopharma, FEB 16, 2022, View Source [SID1234649843]). The licensed assets are structural analogs of the FDA-approved drug rapamycin, which has been shown to prevent or reverse multiple age-related health deficits in mice1 and extend their average lifespan by up to 31%2.

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The assets will be developed by new Cambrian subsidiary Tornado Therapeutics led by industry and Novartis veteran Joan Mannick, M.D., as CEO. The most advanced asset is now moving into IND-enabling studies, while a second asset is undergoing preclinical efficacy testing.

Under the terms of the agreement, Cambrian acquired exclusive, worldwide rights to the assets, while Novartis received an upfront payment and is entitled to royalties and milestone payments for successfully commercialized medicines. Financial terms of the agreement were not disclosed.

"Pioneers in longevity therapeutics have seen the potential of next-generation mTOR inhibitors for years," said James Peyer, CEO of Cambrian BioPharma. "This partnership, led by Dr. Mannick and combining Cambrian’s development capabilities with the foundational work done at Novartis, creates a fantastic opportunity to bring a new class of potentially safer, more effective mTOR inhibitors to patients."

"Although mTOR inhibitors are the best validated therapeutic targeting aging biology, their potential benefits for human aging are just beginning to be explored," said Dr. Mannick, CEO of Tornado Therapeutics. "The assets we have in-licensed from Novartis will allow us to do a thorough assessment of the safety and efficacy of mTOR inhibitors in aging-related conditions in humans with the ultimate goal of extending healthy lifespan."

Dr. Mannick joins Tornado Therapeutics from Life Biosciences, where she served as Head of Research and Development. Prior to joining Life Biosciences, she was the Co-Founder and Chief Medical Officer of resTORbio, now Adicet Bio. Previously, she served as Executive Director of the New Indications Discovery Unit at the Novartis Institutes for BioMedical Research, where she led clinical studies of mTOR inhibitors to improve immune function in older adults. Prior to Novartis, Dr. Mannick served as Medical Director at Genzyme working in multiple therapeutic areas and was faculty member at Harvard Medical School and University of Massachusetts Medical School. She received an A.B. from Harvard College and an M.D. from Harvard Medical School and completed her residency at Brigham and Women’s Hospital, followed by an infectious diseases fellowship as part of the Harvard Combined Infectious Diseases Program.

About mTOR Inhibitors

The FDA-approved drug rapamycin and its analogues (rapalogs) are inhibitors of the mechanistic target of rapamycin (mTOR). mTOR inhibitors are an exceptionally well-explored therapeutic class, encompassing three FDA-approved medications evaluated in more than 3,000 clinical trials. Recent studies have demonstrated that mTOR inhibitors extend health and lifespan in multiple organisms, including yeast, worms, flies and mice, establishing them as the best validated class of longevity therapeutics1. The next generation mTOR inhibitors in-licensed by Cambrian are predicted to have improved safety and efficacy as compared to currently approved rapalogs.