On January 10, 2022 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported the appointment of Jathin Bandari, M.D., as Chief Medical Officer (Press release, Protara Therapeutics, JAN 10, 2022, View Source [SID1234598465]). Dr. Bandari is a practicing urologic oncologist, recently serving at the University of Rochester where he specialized in both minimally invasive urologic oncology and advanced open pelvic retroperitoneal cancer surgery, and where he maintains a faculty appointment. Dr. Bandari joined Protara in April 2020 as Vice President, Head of Clinical Development, and most recently was Interim Chief Medical Officer.

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"We are thrilled for Dr. Bandari to expand his role with Protara," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "His deep experience working with urologic cancer patients is invaluable as we continue to advance our lead product candidate, TARA-002, for the treatment of non-muscle invasive bladder cancer (NMIBC)."

"Since joining Protara in April 2020, I have been fortunate to work with a talented and innovative team, progressing TARA-002 as a potential therapy for NMIBC, lymphatic malformations, and possibly other cancers," said Dr. Bandari. "I am thrilled to join this exemplary team as Chief Medical Officer and work to advance transformative therapies for people with cancer and rare diseases."

Dr. Bandari received his M.D. from Johns Hopkins University and completed his urology residency at University of Pittsburgh Medical Center. Following residency, he completed a Society of Urologic Oncology fellowship at the University of Pittsburgh Medical Center. He is an active member of the American Urological Association, Society of Urologic Oncology, American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), and Southwest Oncology Group. He has over 50 publications, national speakerships, textbooks, and grants.

On January 10, 2022 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application for FT536, an off-the-shelf, multiplexed-engineered, iPSC-derived, chimeric antigen receptor (CAR) NK cell product candidate (Press release, Fate Therapeutics, JAN 10, 2022, View Source [SID1234598464]). FT536 is derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with four functional elements, including a novel CAR that uniquely targets the α3 domain of the major histocompatibility complex (MHC) class I related proteins A (MICA) and B (MICB). MICA and MICB are stress proteins that are expressed at high levels on many solid tumors. The Company plans to initiate clinical investigation of FT536 as a monotherapy and in combination with tumor-targeting monoclonal antibody therapy for the treatment of multiple solid tumor indications.

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"We are very pleased with our progress in bringing first-in-class, multiplexed-engineered NK cell product candidates to patients for the treatment of solid tumors. MICA and MICB are emerging as exciting pan-cancer immunotherapy targets across a wide range of solid tumors, and FT536 represents a novel therapeutic strategy designed to target these stress-induced ligands," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "With the proteolytic shedding of the α1 and α2 domains of MICA/B being recognized as a common tumor escape mechanism, we are encouraged that our novel CAR design, which uniquely targets the α3 domain of MICA/B, has shown the potential to overcome shedding and restore NK and T cell-mediated tumor immunity. We look forward to treating patients with FT536 as monotherapy and in combination with monoclonal antibody therapy to promote a multi-pronged attack against solid tumors."

FT536 also incorporates a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments such as the suppressive tumor microenvironment. The multi-center Phase 1 clinical trial of FT536 is designed to determine the maximum tolerated dose of FT536 and assess its safety and clinical activity as monotherapy and in combination with one of an array of five monoclonal antibodies for the treatment of advanced solid tumors. Eligible tumor types include advanced non-small cell lung cancer, colorectal cancer, head and neck cancer, gastric cancer, breast cancer, ovarian cancer, and pancreatic cancer.

The Phase 1 clinical protocol allows for administration of FT536 initially in up to two, 30-day cycles, with each cycle consisting of three days of conditioning chemotherapy and three weekly doses of FT536. Patients with clinical benefit may be re-treated with up to two additional cycles. Furthermore, for those patients that achieve initial clinical response, additional treatment with FT536 may be administered following disease progression. The off-the-shelf treatment regimen is designed to be administered in the outpatient setting.

The expression of MICA and MICB proteins, which is induced by cellular stress, damage or transformation, has been reported for many solid tumor types. Cytotoxic lymphocytes, such as NK cells and CD8+ T cells, can recognize and bind the membrane-distal α1 and α2 domains of MICA/B, activating a potent cytotoxic response. However, cancer cells frequently evade immune cell recognition by proteolytic shedding of the α1 and α2 domains of MICA/B. A recent publication in Science (DOI:10.1126/science.aao0505) by Kai W. Wucherpfennig, M.D., Ph.D., Chair of the Department of Cancer Immunology and Virology at the Dana-Farber Cancer Institute and co-leader of the Cancer Immunology Program at Dana-Farber / Harvard Cancer Center, demonstrated that antibody targeting of the MICA/B α3 domains specifically prevents MICA/B shedding and restores NK cell-mediated immunity. Additionally, in a more recent publication in Cancer Immunology Research (DOI: 10.1158/2326-6066.CIR-19-0483), Dr. Wucherpfennig also demonstrated that cancers with B2M and JAK1 inactivating mutations resulting in loss of MHC Class I expression can be effectively targeted with MICA/B α3 domain-specific antibodies to restore NK cell-mediated immunity against solid tumors resistant to cytotoxic T cells. The Company’s FT536 program is supported by an exclusive license from the Dana-Farber Cancer Institute to intellectual property covering novel antibody fragments binding MICA/B for iPSC-derived cellular therapeutics.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

On January 10, 2022 Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines designed to bring the curative power of stem cell transplant to more patients, reported that progress across its portfolio of targeted conditioning and stem cell mobilization programs and set out its milestone expectations for both clinical and preclinical data in 2022 (Press release, Magenta Therapeutics, JAN 10, 2022, View Source [SID1234598463]). These updates will also be discussed during a webcast presentation at the 40th Annual J.P. Morgan Healthcare Conference on Thursday, January 13 at 9:45 a.m. EST.

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"2022 will be an important year for the Magenta portfolio" said Jason Gardner, D. Phil., President and Chief Executive Officer, Magenta Therapeutics. "We believe we will clinically demonstrate that MGTA-117 targets and binds selectively to CD117-expressing cells, potently depletes those cells and the product profile will be well-tolerated in our Phase 1/2 clinical study. We have developed biomarker assays that we believe will provide early insights into the biologic activity of MGTA-117. We are also thrilled to introduce our second targeted conditioning program in the development pipeline, an antibody drug conjugate targeting CD45 which has the potential to deplete both stem cells and immune cells without chemotherapy. Finally, with our MGTA-145 program, we are focused on optimizing the collection yield of mobilized stem cells. We believe MGTA-145 can offer a faster and more reliable mobilization regimen for stem cell transplantation as well as ex vivo and in vivo gene therapies."

Targeted Conditioning

MGTA-117 Program:

2022 Clinical Data from Phase 1/2 Clinical Trial: Evaluating Target Selectivity, Potency and Tolerability. The MGTA-117 Phase 1/2 clinical trial is open for enrollment. This dose escalation clinical trial will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of MGTA-117 as a single dose in patients with relapsed/refractory Acute Myeloid Leukemia (AML) and Myelodysplasia-Excess Blasts (MDS-EB).

Specifically, dosing cohorts expected to enroll in 2022 will allow for evaluation of MGTA-117’s ability to:

selectively target CD117 as measured by receptor occupancy;
potently deplete CD117-expressing cells such as stem cells, progenitors, and tumor cells; and
rapidly clear from the body with a well-tolerated profile as determined by pharmacokinetic analysis and clinical chemistry tests, respectively.
Magenta’s preclinical evidence supports the MGTA-117 target selectivity, potency and tolerability profile. In GLP toxicology studies, MGTA-117 potently depleted stem cells at a dose level where there were no drug-related findings in hepatic, reproductive, neurologic, cardiovascular, or respiratory organs.

Phase 1/2 Clinical Trial Design for MGTA-117. MGTA-117 will be assessed in patients with relapsed/refractory AML and MDS-EB in a multi-center, open-label, single-ascending-dose trial. Patients in the first cohort will receive 0.02 mg/kg administered intravenously (IV), and subsequent cohort doses will be determined in accordance with a modified Fibonacci sequence.

Magenta will assess data from each cohort and, after collection of adequate safety, pharmacokinetic and pharmacodynamic data, Magenta intends to engage with the U.S. Food and Drug Administration (FDA) to transition to the primary target population of patients eligible for stem cell transplantation. In addition, Magenta plans to explore MGTA-117 as a targeted conditioning agent for stem cell gene therapies.

CD45-Antibody Drug Conjugate Program:

Magenta has initiated investigational new drug application-enabling studies on its second targeted conditioning program, an antibody drug conjugate (ADC) targeting CD45. Due to the expression of CD45 on stem cells and immune cells, Magenta’s CD45-ADC is designed to selectively target and deplete stem cells and lymphocytes, which could allow patients with blood cancers and autoimmune diseases to avoid use of chemotherapy prior to stem cell transplant. Magenta expects to have preclinical data from a dose ranging toxicology study in the second half of 2022.

Stem Cell Mobilization and Collection

MGTA-145 Dosing and Administration Optimization Clinical Trial. As previously disclosed, Magenta intends to initiate a dosing and administration optimization clinical trial with MGTA-145 in combination with plerixafor. Clinical data from a Phase 2 investigator-initiated clinical trial with 25 multiple myeloma patients showed that MGTA-145, in combination with plerixafor, mobilized a sufficient number of stem cells for transplantation in 88% of patients (22/25). In addition, all patients transplanted with cells mobilized by MGTA-145 plus plerixafor as of the data cut-off date had successful engraftment (18/18 patients) with prolonged durability through the 100-day follow-up period (13/13 patients). The regimen was generally well-tolerated. Magenta believes there are specific opportunities to further improve cell collection yield by adjustments to the regimen dosing, and administration timing. Magenta expects to generate data from this healthy subjects clinical trial in the second half of 2022.

Sickle Cell Disease (SCD) – Stem Cell Mobilization Phase 2 Clinical Trial. Magenta is advancing trial initiation activities. The trial is designed to evaluate mobilization and collection of stem cells in adults and adolescents with SCD. Magenta and its clinical collaboration partner, bluebird bio, will each characterize the collected cells. Magenta plans to gene-modify the cells and transplant them into established preclinical models to evaluate graft quality and engraftment. Data from this clinical trial could provide proof-of-concept for MGTA-145, in combination with plerixafor, as a first-line mobilization regimen for patients with SCD and, more broadly, across other gene therapy applications. Magenta expects to generate data from this clinical trial in the second half of 2022.

Cash Guidance

With focused allocation of capital and resources on both clinical stage programs and CD45-ADC, Magenta now expects its cash reserves to fund its operating plan into the fourth quarter of 2023. Magenta ended 2021 with approximately $162 million of cash, cash equivalents, and marketable securities (unaudited).

On January 10, 2022 Replimune Group, Inc. (Nasdaq: REPL), a clinical stage biotechnology company pioneering the development of a novel class of tumor-directed oncolytic immunotherapies, reported that Provide a corporate update, highlighting the progress of key programs (Press release, Replimune, JAN 10, 2022, View Source [SID1234598456]).

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"Data with RP1 in various high-value skin cancer indications has continued to mature in 2021," said Philip Astley-Sparke, Chief Executive Officer of Replimune. "We have been thrilled to see the clear trends in safety and efficacy persist, with durability data that suggests RP1 has the profile to provide many patients with transformative long-term benefit. With our objective of establishing a broad skin cancer franchise with RP1, which has progressed to commercial planning, we have begun to validate the potential of our RP2 and RP3 oncolytic immunotherapies beyond skin cancers, including in tumor types that commonly metastasize to the liver. Replimune continues to build towards an exciting, data rich 2022, beginning later this quarter with a number of clinical updates, and visibility into the RP2/RP3 Phase 2 clinical development strategy."

Anticipated Key Milestones for 2022

CERPASS – Registration-directed Phase 2 clinical trial in cutaneous squamous cell carcinoma (CSCC)

RP1 in combination with Libtayo (cemiplimab-rwlc) in CSCC: The Company is actively enrolling patients in a registration-directed, global, randomized, controlled, 180-patient Phase 2 clinical trial (CERPASS) evaluating RP1 in combination with Libtayo vs. Libtayo alone in patients with advanced CSCC. The Company expects to complete enrollment such that the trigger for the primary data analysis is expected in late 2022.
IGNYTE – Multi-cohort Phase 2 clinical trial of RP1 combined with Opdivo (nivolumab)

Anti-PD-1 failed melanoma cohort: The Company continues to enroll patients in the 125-patient cohort of the IGNYTE Phase 2 clinical trial in patients with anti-PD1 failed melanoma. The company expects to release interim data from this cohort in late 2022.

Non-melanoma skin cancer (NMSC) cohort: The Company has completed enrollment of 30-patients with anti-PD-1 naïve NMSC and continues to enroll patients with anti-PD-1 failed NMSC. The Company remains on track to provide updated data from the anti-PD1 naïve patients and initial data from the anti-PD-1 failed patients in the first quarter of 2022.

Anti-PD(L)-1 failed non-small cell lung cancer (NSCLC) cohort: Enrollment is open in a 30-patient cohort of RP1 in combination with Opdivo in anti-PD(L)-1 failed NSCLC patients, with initial data is expected to be released in late 2022.
ARTACUS – Phase 1b/2 clinical trial of RP1 as monotherapy in solid organ transplant recipients with CSCC

Enrollment continues in this 65-patient clinical trial with potential registrational intent, assessing the safety and efficacy of RP1 in organ transplant recipients with skin cancer. The Company remains on track to present initial data from this clinical trial in the first quarter of 2022.
RP2 and RP3

RP2 alone and in combination with Opdivo in difficult-to-treat cancers: The Company presented Phase 1 clinical data demonstrating deep and durable responses in difficult-to-treat cancers both as monotherapy and in combination with Opdivo in November 2021. The Company also initiated its expansion of the Phase 1 clinical trial of RP2 in combination with Opdivo, with a focus on patients with liver metastases from various prevalent tumor types including patients with lung, breast and gastrointestinal cancers. The company expects to present initial data from the expansion patients in late 2022.

RP3 alone and in combination with Opdivo: The Company is enrolling patients in a Phase 1 clinical trial for RP3, with initial data expected to be presented in the first quarter of 2022. The Company expects to start enrolling patients to be treated with RP3 in combination with Opdivo early in 2022, including patients with liver metastases from various prevalent tumor types such as lung, breast, head and neck cancer and gastrointestinal cancers. The company expects to present initial data from the expansion patients in late 2022.

RP2 and/or RP3 next stage development including in patients with liver metastases from a range of tumor types: The Company remains on track to initiate a broad clinical development program with RP2 and/or RP3, intended to include a range of prevalent tumor types, including in patients with liver metastases, around mid-year 2022. Details of this plan remain on track to be presented in the first quarter of 2022.
J.P. Morgan Conference Presentation and Webcast

As previously announced, the Company will be present at the virtual meeting of the 40th Annual J.P. Morgan Healthcare Conference on Monday, Jan. 10 at 7:30 a.m. PT. A simultaneous webcast of the presentation will be available in the Investors section of Replimune’s website at www.replimune.com. A replay will be available for 30 days following the conference.

About CERPASS
CERPASS is Replimune’s registration-directed randomized, global Phase 2 clinical study to compare the effects of Libtayo alone versus a combination of Libtayo and Replimune’s investigational oncolytic immunotherapy RP1. The clinical trial is enrolling enroll 180 patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who are naïve to anti-PD-1 therapy. The clinical trial will evaluate complete response (CR) rate and overall response rate (ORR) as its two primary efficacy endpoints as assessed by independent review, as well as duration of response, progression-free survival (PFS), and overall survival (OS) as secondary endpoints. The study is being conducted under a clinical trial collaboration agreement with Regeneron in which the costs of the trial are shared and full commercial rights retained by Replimune. Libtayo is being jointly developed by Regeneron and Sanofi.
Libtayo is a registered trademark of Regeneron.

About IGNYTE
IGNYTE is Replimune’s multi-cohort Phase 1/2 trial of RP1 plus Opdivo. There are 4 tumor specific cohorts currently enrolling in this clinical trial including a 125-patient cohort in anti-PD-1 failed cutaneous melanoma. This cohort was initiated after completing enrollment in a prior Phase 2 cohort in the same clinical trial of approximately 30 patients with melanoma. The additional cohorts are in non-melanoma skin cancers which includes both naïve and anti-PD-1 failed CSCC, in anti-PD1 failed microsatellite instability high, or MSI-H/dMMR tumors and anti-PD(L)-1 failed non-small cell lung cancer, or NSCLC. This trial is being conducted under a collaboration and supply agreement with Bristol-Myers Squibb Company. Opdivo is a registered trademark of Bristol-Myers Squibb Company.

About RP1
RP1 is Replimune’s lead product candidate and is based on a proprietary new strain of herpes simplex virus engineered and genetically armed to maximize tumor killing potency, the immunogenicity of tumor cell death, and the activation of a systemic anti-tumor immune response.

About RP2 & RP3
RP2 and RP3 are derivatives of RP1 that express additional immune-activating proteins. RP2 expresses an anti-CTLA-4 antibody-like molecule and RP3 additionally expresses the immune co-stimulatory pathway activating proteins CD40L and 4-1BBL. RP2 and RP3 are intended to provide targeted and potent delivery of these proteins to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic immune-based efficacy on tumors and limiting off-target toxicity

On January 10, 2022 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that program updates and upcoming key milestones that are expected to substantially broaden and advance the company’s clinical pipeline (Press release, ORIC Pharmaceuticals, JAN 10, 2022, View Source [SID1234598455]).

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"2021 was a transformational year for ORIC during which we presented initial data from both ongoing ORIC-101 combination trials, advanced our differentiated pipeline with three IND/CTA submissions, progressed two discovery pipeline programs into lead optimization, and further strengthened the balance sheet," said Jacob M. Chacko, M.D., president and chief executive officer. "These efforts have significantly broadened our pipeline, with expected updates from our two ongoing trials of ORIC-101 in the first half of 2022 and initial Phase 1b clinical data from our other three product candidates in the first half of 2023, for a total of five clinical updates across four programs over the next 18 months."

Program Updates and Milestones

ORIC-101: Glucocorticoid Receptor (GR) Antagonist
ORIC-101 is a potent and selective GR antagonist with two distinct mechanisms of action being evaluated in two Phase 1b trials in combination with: (1) Xtandi (enzalutamide) in metastatic prostate cancer and (2) Abraxane (nab-paclitaxel) in advanced or metastatic solid tumors. The company reported initial data from the Phase 1b study of ORIC-101 in combination with nab-paclitaxel in the second quarter of 2021 and initial data from the Phase 1b trial of ORIC-101 in combination with enzalutamide in the fourth quarter of 2021. The company expects to provide an update on both trials in the first half of 2022.

ORIC-533: CD73 Inhibitor
ORIC-533 is a highly potent, orally bioavailable CD73 inhibitor and has demonstrated more potent adenosine inhibition in preclinical studies compared to an antibody approach and other small molecule CD73 inhibitors. The FDA cleared the company’s Investigational New Drug Application (IND) for ORIC-533 in the third quarter of 2021. Based on strong mechanistic rationale and compelling preclinical single agent activity in bone marrow cells from patients with multiple myeloma, the company has initiated a Phase 1b trial as a single agent in multiple myeloma and expects to report initial data in the first half of 2023.

ORIC-114: EGFR/HER2 Inhibitor
ORIC-114 is a brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations. ORIC-114 has demonstrated systemic tumor regressions and strong intracranial antitumor activity in various EGFR exon 20 insertion NSCLC and HER2-positive breast cancer models. ORIC-114 also compares favorably in head to head in vivo studies versus multiple approved and clinical stage EGFR exon 20 and HER2 inhibitors. The company filed a Clinical Trial Application (CTA) in the fourth quarter of 2021. The Phase 1b single agent study will enroll patients with advanced solid tumors with EGFR or HER2 exon 20 alterations or HER2 amplification and will allow patients with CNS metastases that are either treated or untreated but asymptomatic. The company expects to report initial Phase 1b data from this trial in the first half of 2023.

ORIC-944: PRC2 Inhibitor
ORIC-944, is a potent and selective allosteric inhibitor of polycomb repressive complex 2 (PRC2), that targets its regulatory embryonic ectoderm development (EED) subunit and has demonstrated single agent efficacy in multiple enzalutamide-resistant prostate cancer models in preclinical studies. The IND for ORIC-944 was filed and cleared by the FDA in the fourth quarter of 2021. The company plans to pursue a single agent clinical development plan in metastatic prostate cancer and expects to report initial Phase 1b data in the first half of 2023.

Discovery Pipeline
In addition to the four product candidates, the company is leveraging its resistance platform in pursuit of multiple discovery research programs that focus on its expertise in precision oncology and hormone-dependent cancers. These programs highlight the company’s medicinal chemistry and structure-based drug design proficiency to target drivers of resistance in solid tumors like prostate, breast, and lung cancer that relapse with innate, acquired or bypass mechanisms of resistance. The company recently advanced two of these programs into lead optimization.

Anticipated Program Milestones

ORIC anticipates the following upcoming milestones:

ORIC-101: Updates from two Phase 1b combination trials in 1H 2022
ORIC-533: Initial Phase 1b data in 1H 2023
ORIC-114: Initial Phase 1b data in 1H 2023
ORIC-944: Initial Phase 1b data in 1H 2023
New program and/or indication to be announced in 2022
Financial Guidance

As of December 31, 2021, cash, cash equivalents and investments totaled $280.8 million, which the company expects will be sufficient to fund its operating plan into the first half of 2024.

Presentation and Webcast

Jacob M. Chacko, M.D., president and chief executive officer, will present a corporate overview at the 40th Annual J.P. Morgan Healthcare Conference on Tuesday, January 11, 2022, at 3:00 p.m. ET. A live webcast will be available through the investor section of the company’s website at View Source A replay of the webcast will be available for 30 days following the event.