On February 16, 2022 Milestone Pharmaceuticals Inc. (Nasdaq: MIST), a biopharmaceutical company focused on the development and commercialization of innovative cardiovascular medicines, reported the appointment of David Bharucha, M.D., Ph.D., as Chief Medical Officer, effective February 15, 2022 (Press release, Milestone Pharmaceuticals, FEB 16, 2022, View Source [SID1234608190]). Dr. Bharucha is a cardiac electrophysiologist who brings to Milestone over thirty years of global drug development and clinical experience across a range of therapeutic areas, with a focus on cardiovascular medicine. He will replace Francis Plat, M.D., who will transition to Chief Scientific Officer of the Company and, following the completion of the Phase 3 RAPID trial in the second half of 2022, will serve in an advisory capacity.

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"It is a pleasure to welcome David to the Milestone team," said Joseph Oliveto, President and Chief Executive Officer of Milestone Pharmaceuticals. "His specialized training in cardiovascular rhythm disorders combined with his extensive drug development and medical experience will be invaluable as we continue to advance etripamil in patients with paroxysmal supraventricular tachycardia and atrial fibrillation with rapid ventricular rate. On behalf of the entire Milestone team, I would also like to thank Francis, who has played a foundational role in advancing the etripamil program to where it is today, for his steadfast dedication to the Company over the years and for his continued contribution as we work to gain market approval of etripamil to help patients in need."

"As we approach topline data readout of the RAPID trial expected in the second half of 2022, I firmly believe that etripamil has the potential to change the treatment paradigm for patients with episodic cardiovascular conditions," said Dr. Bharucha. "I look forward to working alongside the talented Milestone team to bring this promising therapy to as many appropriate patients as possible."

Dr. Bharucha most recently served as Vice President, Research and Development, Clinical Development at Allergan, a division of AbbVie. Prior to that, Dr. Bharucha held positions of increasing responsibility in Research and Development at Allergan, Actavis, PLC, and Forest Laboratories, where he led multiple U.S. and global programs, including in therapeutic areas of cardiovascular, internal medicine, anti-infectives, women’s health and urology, encompassing both new drug application (NDA) and label-expansion approvals. He has served on faculty at Mt. Sinai School of Medicine (NY) and Jefferson Medical University (Philadelphia). Dr. Bharucha’s training included fellowships in cardiology and electrophysiology at the Massachusetts General Hospital, Harvard Medical School. Dr. Bharucha received his M.D. (Honors) and Ph.D. (Biochemistry and Molecular Biology) from The University of Chicago, and his B.A. in Biology from Haverford College.

On February 16, 2022 Charles River Laboratories International, Inc. (NYSE: CRL) reported its results for the fourth-quarter and full-year 2021 and reaffirmed guidance for 2022 (Press release, Charles River Laboratories, FEB 16, 2022, View Source [SID1234608189]). For the quarter, revenue was $905.1 million, an increase of 14.4% from $791.0 million in the fourth quarter of 2020.

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Acquisitions contributed 5.9% to consolidated fourth-quarter revenue growth. The divestiture of the Research Models and Services operations in Japan (RMS Japan) in October 2021 reduced reported revenue growth by 1.4%. The impact of foreign currency translation reduced reported revenue growth by 0.6%. Excluding the effect of these items, organic revenue growth was 10.5%, driven by contributions from all three business segments, led by the Manufacturing segment. The comparison to the COVID-19-related impact in 2020 increased both the reported and organic revenue growth rates by 0.5% in the fourth quarter of 2021.

On a GAAP basis, fourth-quarter net income attributable to common shareholders was $137.6 million, a decrease of 3.9% from $143.2 million for the same period in 2020. Fourth quarter diluted earnings per share on a GAAP basis were $2.67, a decrease of 5.0% from $2.81 for the fourth quarter of 2020. The decreases in GAAP net income and earnings per share primarily reflected a loss from the Company’s venture capital and other strategic investments of $0.19 per share in the fourth quarter of 2021, compared to a gain of $1.01 per share for the same period in 2020. The decreases were partially offset by acquisition-related adjustments associated with contingent consideration and a gain on the sale of RMS Japan.

On a non-GAAP basis, net income was $128.4 million for the fourth quarter of 2021, an increase of 5.2% from $122.1 million for the same period in 2020. Fourth-quarter diluted earnings per share on a non-GAAP basis were $2.49, an increase of 4.2% from $2.39 per share for the fourth quarter of 2020. The increases in non-GAAP net income and earnings per share were primarily driven by higher revenue and operating income, partially offset by a higher tax rate and net interest expense.

James C. Foster, Chairman, President and Chief Executive Officer, said, "2021 was another exceptional year for Charles River, with robust revenue and earnings growth, significant operating margin expansion, and meaningful cash flow generation. This performance reflects the unprecedented demand that we are seeing across most of our businesses, as well as the breadth and scientific depth of our leading, non-clinical portfolio.

"We believe that Charles River is a stronger company today than it has ever been. We have built the leading safety assessment franchise in the world; established an integrated, end-to-end discovery offering for both small and large molecules; and most recently, a comprehensive, scientifically advanced solution for our clients’ complex biologics and cell and gene therapies. We believe that the strength of our portfolio, coupled with robust industry fundamentals and the investments that we are making to accommodate client demand, will fuel low-teens revenue growth in 2022 and enable us to achieve our strategic and financial goals," Mr. Foster concluded.

Fourth-Quarter Segment Results

Research Models and Services (RMS)

Revenue for the RMS segment was $165.6 million in the fourth quarter of 2021, an increase of 5.7% from $156.7 million in the fourth quarter of 2020. The impact of the RMS Japan divestiture reduced revenue by 7.2%, and the impact of foreign currency translation reduced revenue by 0.4%. Organic revenue growth of 13.3% was primarily driven by robust demand for research models, particularly in China, as well as higher revenue for research model services. Fourth quarter revenue for the cell supply business, which consists of HemaCare and Cellero, continued to be impacted by donor access and availability. The comparison to the COVID-19-related impact in 2020 increased both the reported and organic revenue growth rates by 2.3% in the fourth quarter of 2021.

In the fourth quarter of 2021, the RMS segment’s GAAP operating margin increased to 24.3% from 21.9% in the fourth quarter of 2020, and on a non-GAAP basis, the operating margin increased to 26.9% from 25.1%. The GAAP and non-GAAP operating margin increases were driven primarily by operating leverage from higher research models sales volume.

Discovery and Safety Assessment (DSA)

Revenue for the DSA segment was $534.1 million in the fourth quarter of 2021, an increase of 7.9% from $495.0 million in the fourth quarter of 2020. The impact of foreign currency translation reduced revenue by 0.4%, and acquisitions contributed 1.6% to DSA revenue growth. Organic revenue growth of 6.7% was driven principally by the Safety Assessment business, with the Discovery Services business also contributing.

In the fourth quarter of 2021, the DSA segment’s GAAP operating margin decreased to 17.8% from 18.4% in the fourth quarter of 2020. The decrease was primarily due to acquisition-related adjustments associated with contingent consideration. On a non-GAAP basis, the operating margin was essentially unchanged at 23.1%, compared to 23.2% in the fourth quarter of 2020. The impact of foreign currency translation reduced the DSA operating margin by approximately 40 basis points.

Manufacturing Solutions (Manufacturing)

Revenue for the Manufacturing segment was $205.3 million in the fourth quarter of 2021, an increase of 47.4% from $139.3 million in the fourth quarter of 2020. The acquisitions of Cognate BioServices (Cognate) and Vigene Biosciences (Vigene) contributed 27.8% to Manufacturing revenue growth, while the impact of foreign currency translation reduced revenue by 1.6%. Organic revenue growth of 21.2% was driven primarily by robust demand across the Biologics Testing Solutions, Microbial Solutions, and Avian Vaccine businesses. The comparison to the COVID-19-related impact in 2020 increased the reported and organic revenue growth rates in the fourth quarter of 2021 by 1.1% and 0.9%, respectively.

In the fourth quarter of 2021, the Manufacturing segment’s GAAP operating margin increased to 44.6% from 35.3% in the fourth quarter of 2020, primarily due to acquisition-related adjustments associated with contingent consideration. The non-GAAP operating margin decreased to 35.7% from 37.3% in the fourth quarter of 2020, driven primarily by the addition of the Cognate and Vigene CDMO businesses.

Full-Year Results

For 2021, revenue increased by 21.1% to $3.54 billion from $2.92 billion in 2020. Organic revenue growth was 15.1%. The comparison to the COVID-19-related impact in 2020 increased the reported and organic revenue growth rates in 2021 by 2.9% and 2.8%, respectively.

On a GAAP basis, net income attributable to common shareholders was $391.0 million in 2021, an increase of 7.3% from $364.3 million in 2020. Diluted earnings per share on a GAAP basis in 2021 were $7.60, an increase of 5.6% from $7.20 in 2020. On a GAAP basis, the Company recorded a loss from venture capital and other strategic investments totaling $0.44 per share in 2021, compared to a gain of $1.51 in 2020.

On a non-GAAP basis, net income was $530.5 million in 2021, an increase of 28.9% from $411.5 million in 2020. Diluted earnings per share on a non-GAAP basis in 2021 were $10.32, an increase of 26.9% from $8.13 in 2020.

Research Models and Services (RMS)

For 2021, RMS revenue was $690.4 million, an increase of 20.9% from $571.2 million in 2020. Organic revenue growth increased 19.5%. The comparison to the COVID-19-related impact in 2020 increased the reported and organic revenue growth rates in 2021 by 10.1% and 9.8%, respectively.

On a GAAP basis, the RMS segment operating margin increased to 24.2% in 2021 from 18.0% in 2020. On a non-GAAP basis, the operating margin increased to 27.3% in 2021 from 22.0% in 2020.

Discovery and Safety Assessment (DSA)

For 2021, DSA revenue was $2.11 billion, an increase of 14.7% from $1.84 billion in 2020. Organic revenue growth was 12.2%. The comparison to the COVID-19-related impact in 2020 increased both the reported and organic revenue growth rates by 0.8% in 2021.

On a GAAP basis, the DSA segment operating margin increased to 19.3% in 2021 from 17.7% in 2020. On a non-GAAP basis, the operating margin increased to 23.7% in 2021 from 23.4% in 2020.

Manufacturing Solutions (Manufacturing)

For 2021, Manufacturing revenue was $742.5 million, an increase of 44.1% from $515.4 million in 2020. Organic revenue growth was 20.6%. The comparison to the COVID-19-related impact in 2020 increased the reported and organic revenue growth rates in 2021 by 2.5% and 2.1%, respectively.

On a GAAP basis, the Manufacturing segment operating margin decreased to 33.2% in 2021 from 35.2% in 2020. On a non-GAAP basis, the operating margin decreased to 34.2% in 2021 from 37.4% in 2020.

Reaffirms 2022 Guidance

The Company is reaffirming its 2022 financial guidance, which was originally provided on January 11, 2022. As previously mentioned, the Company expects to benefit from a continuation of the robust client demand that it experienced last year and price increases, which is expected to drive low-teens revenue growth in 2022. On a non-GAAP basis, earnings per share growth in 2022 is expected to be similar to revenue growth, as modest operating margin improvement will be largely offset by less favorable below-the-line items, including a higher tax rate.

The Company’s 2022 guidance for revenue growth, earnings per share, and cash flow is as follows:

2022 GUIDANCE

Footnotes to Guidance Table:

(1) The contribution from acquisitions/divestitures (net) reflects only those transactions that were completed in 2021. The partial-year revenue impact from acquisitions, principally Cognate BioServices, Retrogenix, and Vigene Biosciences, is expected to be offset by the impact from the divestitures of RMS Japan and CDMO Sweden.

(2) Organic revenue growth is defined as reported revenue growth adjusted for acquisitions, divestitures, the 53rd week in 2022, and foreign currency translation.

(3) These adjustments are related to the evaluation and integration of acquisitions and divestitures, and primarily include transaction, advisory, and certain third-party integration costs, as well as certain costs associated with acquisition-related efficiency initiatives.

(4) These items primarily relate to charges of approximately $0.10 associated with U.S. and international tax legislation that necessitated changes to the Company’s international financing structure.

Webcast

Charles River has scheduled a live webcast on Wednesday, February 16, at 8:30 a.m. ET to discuss matters relating to this press release. To participate, please go to ir.criver.com and select the webcast link. You can also find the associated slide presentation and reconciliations of GAAP financial measures to non-GAAP financial measures on the website.

Citi’s 2022 Virtual Healthcare Conference Presentation

Charles River will virtually present at Citi’s 2022 Virtual Healthcare Conference, on Wednesday, February 23rd, at 9:30 a.m. ET. Management will provide an overview of Charles River’s strategic focus and business developments.

A live webcast of the presentation will be available through a link that will be posted on ir.criver.com. A webcast replay will be accessible through the same website shortly after the presentation and will remain available for approximately two weeks.

Non-GAAP Reconciliations

The Company reports non-GAAP results in this press release, which exclude often-one-time charges and other items that are outside of normal operations. A reconciliation of GAAP to non-GAAP results is provided in the schedules at the end of this press release.

On February 16, 2022 InflaRx N.V. (Nasdaq: IFRX), a clinical-stage biopharmaceutical company developing anti-inflammatory therapeutics by targeting the complement system, reported the start of the second dosing cohort of the vilobelimab and PD-1 checkpoint inhibitor, pembrolizumab, combination arm of the Phase II clinical trial in cutaneous squamous cell carcinoma (cSCC) (Press release, InflaRx, FEB 16, 2022, View Source [SID1234608188]).

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The open label, non-comparative, two-stage, Phase II trial (NCT04812535) is ongoing at sites in Europe, the U.S. and elsewhere. The study is investigating two independent arms: vilobelimab alone (Arm A) and vilobelimab in combination with pembrolizumab (Arm B). The main objectives of the trial are to assess the safety and antitumor activity of vilobelimab monotherapy and to determine the maximum tolerated or recommended dose, safety and antitumor activity in the combination arm. The trial is expected to enroll a total of approximately 70 patients.

"We are pleased to see the progress in our first oncology study with vilobelimab and that there are to date no safety concerns in either arm," said Dr. Korinna Pilz, Global Head of Clinical Research and Development at InflaRx. "Scientific data suggest C5a involvement in tumor formation and progression, as well as in immunosuppression, and there is pre-clinical evidence of synergies between PD-1 and C5a/C5aR inhibitors in inducing anti-tumor responses. While there are PD-1 checkpoint inhibitors approved for the treatment of advanced cSCC, there currently are no treatment options for patients who are PD-1 checkpoint inhibitor resistant or refractory. We look forward to continuing to advance the development of vilobelimab with the hope of bringing a new therapy to treat the advanced stages of this potentially deadly skin cancer."

In the combination Arm B, three patients have been treated for at least 36 days in the first dosing cohort of the study, receiving intravenous infusions of 400 mg of vilobelimab on Days 1, 4, 8, and 15 and from Day 22 onwards, 800 mg every two weeks. Patients are also receiving 400 mg of pembrolizumab starting on Day 8 of the first cycle and every six weeks thereafter. The data from the first 36 days of treatment have been reviewed by the Steering Committee and no safety concerns were raised. The Steering Committee recommended to continue the study as planned and to open enrollment for the second dosing cohort with 1200 mg vilobelimab every two weeks after administration of 600 mg vilobelimab on Days 1,4, 8 and 15. The interim analysis in Arm B required to move to the second stage of the Phase II trial is expected after ten patients have been treated and are evaluable for response assessment at the recommended Phase II dose level, which will be selected based on data from the safety run-in phase of the study. These data are expected to be available in the first quarter of 2023.

In parallel, enrollment continues in the monotherapy Arm A. In this arm, patients are receiving a dose of 800 mg vilobelimab on Days 1, 4, 8, and 15 of the first cycle, followed by a dose of 1600 mg vilobelimab every two weeks starting on Day 22. Six patients are now enrolled in this arm. The interim analysis in Arm A required to proceed to the second stage is expected to be available after ten patients are evaluable for response assessment. These data are expected to be available in the third quarter of 2022.

About Cutaneous Squamous Cell Carcinoma (cSCC)
cSCC is the second most common form of skin cancer and, if caught early, it is generally curable. In the U.S. alone, according to the Skin Cancer Foundation, an estimated 1.8 million cases are diagnosed each year, which translates to about 205 cases diagnosed every hour. The incidence of cSCC has increased up to 200% in the past three decades. Approximately 5% of patients with cSCC develop locally advanced or metastatic disease. These forms of cSCC have a poor prognosis with low survival rates. Over 15,000 people in the U.S. die each year from this disease.

About Vilobelimab (IFX-1)
Vilobelimab is a first-in-class monoclonal anti-human complement factor C5a antibody, which highly and effectively blocks the biological activity of C5a and demonstrates high selectivity towards its target in human blood. Thus, vilobelimab leaves the formation of the membrane attack complex (C5b-9) intact as an important defense mechanism, which is not the case for molecules blocking the cleavage of C5. Vilobelimab has been demonstrated in pre-clinical studies to control the inflammatory response driven tissue and organ damage by specifically blocking C5a as a key "amplifier" of this response. Vilobelimab is believed to be the first monoclonal anti-C5a antibody introduced into clinical development. Over 300 people have been treated with vilobelimab in completed clinical trials, and the antibody has been shown to be well tolerated. Vilobelimab is currently being developed for various indications, including hidradenitis suppurativa, ANCA-associated vasculitis and pyoderma gangraenosum, as well as other areas, such as critical COVID-19 and cutaneous squamous cell carcinoma (cSCC).

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) 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.