On February 25, 2019 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported updated data from a Phase 1 study evaluating ivosidenib (TIBSOVO; AG-120) in combination with azacitidine in newly diagnosed isocitrate dehydrogenase-1 (IDH1) mutant acute myeloid leukemia (AML) patients (Press release, Agios Pharmaceuticals, FEB 25, 2019, View Source [SID1234533625]). The data were featured at the 17th International Symposium on Acute Leukemias taking place in Munich.

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"With longer follow up from the ongoing Phase 1 study, the ivosidenib and azacitidine combination data in newly diagnosed AML patients are striking, with a 65% CR+CRh rate, 57% CR rate and the majority of CR patients achieving IDH1 mutation clearance," said Courtney DiNardo, M.D., lead investigator and assistant professor, department of leukemia at the University of Texas MD Anderson Cancer Center. "The combination regimen showed a 12-month survival rate of 82%, which is impressive given the age and comorbidities associated with patients who are not eligible for intensive chemotherapy. From a safety perspective, results from the combination were consistent with the safety profiles of each drug used alone and cytopenias were in line with those seen for azacitidine alone and favorable compared with other emerging hypomethylating agent combinations."

"As the Phase 1 data have matured, we saw an increase in patients achieving deep and durable remissions, validating our belief that the combination of azacitidine and ivosidenib has the potential to be a compelling treatment option and the cornerstone of therapy for frontline AML patients with an IDH1 mutation who are ineligible for intensive chemotherapy," said Chris Bowden, M.D., chief medical officer at Agios. "We will further evaluate the clinical benefit of ivosidenib in this treatment combination as part of the ongoing Phase 3 AGILE trial."

About the Ongoing Phase 1/2 Study
The ongoing Phase 1/2 study is evaluating an investigational use of ivosidenib or enasidenib in combination with azacitidine in patients with newly diagnosed IDH mutant AML unable to receive intensive chemotherapy. Data presented are from the ivosidenib arm of the Phase 1b portion of the study, in which 23 patients received 500 mg of ivosidenib daily plus azacitidine. Enrollment in the ivosidenib arm is complete.

As of the August 1, 2018 data cutoff, 14 (61%) patients remained on study.
The median number of treatment cycles was 8 (range 1-22).
The median age was 76 years old, and 52% of patients were age 75 or older.
74% of patients had de novo AML and 26% had secondary AML.
Ivosidenib Safety

The most common all-grade adverse events (AEs) regardless of cause occurring in ≥50% of patients were nausea (61%), diarrhea (57%), anemia (52%) and thrombocytopenia (52%).
The most common Grade 3/4 AEs were thrombocytopenia (48%), anemia (44%) and febrile neutropenia (44%).
Investigator reported IDH differentiation syndrome (DS) was reported in four patients, of which three were serious AEs. All four cases resolved, including two who achieved a complete response (CR), one stable disease and one was not evaluable for response.
Mean neutrophil and platelet counts were maintained near or above thresholds for CR with partial hematologic recovery (CRh) while on study treatment with ivosidenib and azacitidine. CRh is defined as <5% of blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts (ANC >500/microliter and platelets >50,000/microliter).
Ivosidenib Efficacy

Overall, 78% (18/23) of patients had a response.
65% (15/23) of patients had a CR+CRh
57% (13/23) of patients had a CR.
The median duration of CR (95% CI 7.7, NE) as well as CR+CRh (95% CI 7.7, NE) had not been reached.
The median time to response was 1.8 months (range 0.7-3.8 months) and the median time to CR was 3.5 months (range 0.8-6 months).
The 12-month survival rate was 82%.
The median duration of follow-up was 9.5 months (range 1.3-24 months).
For patients who achieved a CR, IDH1 mutation clearance was observed in 9 of 13 patients with available bone marrow mononuclear cells (BMMCs) and 10 of 13 patients with available peripheral blood mononuclear cells (PBMCs) as quantified by a sensitive digital PCR assay with lower limit of sensitivity for mutant IDH1 of 0.02-0.04% (or 10-4).
Ivosidenib is not approved in any country for the treatment of patients with newly diagnosed AML or approved in combination with azacitidine.

About TIBSOVO (ivosidenib)

TIBSOVO (ivosidenib) is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test. For more information, visit TIBSOVO.com.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.
WARNINGS AND PRECAUTIONS

Differentiation Syndrome: See Boxed WARNING. In the clinical trial, 19% (34/179) of patients with relapsed or refractory AML treated with TIBSOVO experienced differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. Symptoms of differentiation syndrome in patients treated with TIBSOVO included noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased. Of the 34 patients who experienced differentiation syndrome, 27 (79%) recovered after treatment or after dose interruption of TIBSOVO. Differentiation syndrome occurred as early as 1 day and up to 3 months after TIBSOVO initiation and has been observed with or without concomitant leukocytosis.

If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. If concomitant noninfectious leukocytosis is observed, initiate treatment with hydroxyurea or leukapheresis, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxyurea treatment. If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt TIBSOVO until signs and symptoms are no longer severe.

QTc Interval Prolongation: Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. One patient developed ventricular fibrillation attributed to TIBSOVO. Concomitant use of TIBSOVO with drugs known to prolong the QTc interval (e.g., anti-arrhythmic medicines, fluoroquinolones, triazole anti-fungals, 5-HT3 receptor antagonists) and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. Conduct monitoring of electrocardiograms (ECGs) and electrolytes. In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or in those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary.

Interrupt TIBSOVO if QTc increases to greater than 480 msec and less than 500 msec. Interrupt and reduce TIBSOVO if QTc increases to greater than 500 msec. Permanently discontinue TIBSOVO in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.

Guillain-Barré Syndrome: Guillain-Barré syndrome occurred in <1% (2/258) of patients treated with TIBSOVO in the clinical study. Monitor patients taking TIBSOVO for onset of new signs or symptoms of motor and/or sensory neuropathy such as unilateral or bilateral weakness, sensory alterations, paresthesias, or difficulty breathing. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) of any grade were fatigue (39%), leukocytosis (38%), arthralgia (36%), diarrhea (34%), dyspnea (33%), edema (32%), nausea (31%), mucositis (28%), electrocardiogram QT prolonged (26%), rash (26%), pyrexia (23%), cough (22%), and constipation (20%).
The most frequently reported ≥Grade 3 adverse reactions (≥5%) were electrocardiogram QT prolonged (10%), dyspnea (9%), leukocytosis (8%), tumor lysis syndrome (6%), and differentiation syndrome (5%).
Serious adverse reactions (≥5%) were differentiation syndrome (10%), leukocytosis (10%), and electrocardiogram QT prolonged (7%). There was one case of progressive multifocal leukoencephalopathy (PML).
DRUG INTERACTIONS

Strong or Moderate CYP3A4 Inhibitors: Reduce TIBSOVO dose with strong CYP3A4 inhibitors. Monitor patients for increased risk of QTc interval prolongation.

Strong CYP3A4 Inducers: Avoid concomitant use with TIBSOVO.

Sensitive CYP3A4 Substrates: Avoid concomitant use with TIBSOVO.

QTc Prolonging Drugs: Avoid concomitant use with TIBSOVO. If co-administration is unavoidable, monitor patients for increased risk of QTc interval prolongation.

LACTATION

Many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with TIBSOVO and for at least 1 month after the last dose.

Please see full Prescribing Information, including Boxed WARNING.

About Acute Myelogenous Leukemia (AML)
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and the median age of diagnosis is 68. The vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 27 percent. IDH1 mutations are present in about 6 to 10 percent of AML cases.

On February 25, 2019 Actinium Pharmaceuticals, Inc. (NYSE American: ATNM), reported that new data from the ongoing pivotal Phase 3 SIERRA trial for Iomab-B was reported in a late breaking oral presentation at the 2019 Transplantation & Cellular Therapy Meetings of ASBMT and CIBMTR (TCT Meetings) that was held on February 20th – 24th (Press release, Actinium Pharmaceuticals, FEB 25, 2019, View Source [SID1234533624]). Dr. Sergio Giralt, Chief, Adult Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center presented the late breaking oral presentation. It was reported that all patients who received Iomab-B, received a BMT or Bone Marrow Transplant with 100% (28/28) of patients achieving engraftment and Donor Chimerism. The new data indicated that 92% (26/28) of these patients achieved Full Donor Chimerism prior to day 100, which is defined as at least 95% of donor cells being engrafted in the recipient. Full Donor Chimerism prior to day 100 is a clinically significant outcome that indicates acceptance of donor cells and transplant success.

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"We are excited that data from the SIERRA trial continue to demonstrate strong engraftment, particularly in this patient population who have limited access to BMT, which is the only curative treatment option, with current chemotherapy based conditioning approaches", said Dr. Mark Berger, Actinium’s Chief Medical Officer. "Full Donor Chimerism is an important metric in this setting that indicates patients receiving Iomab-B are having successful transplants, which is significant for the SIERRA trial. I am delighted that we were able to report these new data on strong donor chimerism to the transplant community at the TCT Meetings after reporting at ASH (Free ASH Whitepaper) in December that all patients receiving Iomab-B received a BMT and achieved engraftment. We are motivated by the positive reception that the engraftment, safety and feasibility data have received from trial investigators and referring physicians. These data from the SIERRA trial will serve us well as we work to complete enrollment of the SIERRA trial and bring this important therapy to patients with significant unmet needs."

The SIERRA trial (Study of Iomab-B in Elderly Relapsed or Refractory AML) is a 150-patient pivotal Phase 3 multi-center randomized trial that will compare outcomes of patients who receive Iomab-B and a BMT to those patients receiving physician’s choice of salvage chemotherapy, defined as conventional care, as no standard of care exists for this patient population. The primary endpoint of the SIERRA trial is dCR or durable Complete Remission of 6 months. The SIERRA trial is currently enrolling patients at 18 sites in the U.S and Canada including many of the leading BMT sites based on volume. Patients with active, relapsed or refractory AML have dismal prognoses and are typically not offered potentially curative transplant as an option, largely because salvage treatments have a limited ability to produce a complete remission, which is necessary prior to conventional BMT if conventional BMT is to be successful. However, with Iomab-B targeted conditioning, a complete remission prior to starting the Iomab-B conditioning is not necessary for a successful transplant. Iomab-B is an ARC or Antibody Radiation-Conjugate that targets CD45, an antigen expressed on leukemia, lymphoma and immune cells, and delivers Iodine-131 that kills targeted cells via linear energy transfer. Safety and feasibility data from the first 38 patients (25% of planned enrollment) in the SIERRA trial including donor chimerism data that were presented in a late breaking oral session at TCT can accessed here. Additional safety and feasibility analyses will occur when 50% and 75% of patients have been enrolled. The SIERRA trial also permits ad hoc interim analyses that may be requested at Actinium’s discretion to assess safety and efficacy when 70 and 110 patients have reached the primary endpoint of 6-month dCR. However, these interim analyses will not expend meaningful alpha and repowering of the study is not required as trial size cannot be increased after an Ad-hoc interim analysis.

Key highlights from the SIERRA Trial presented at ASH (Free ASH Whitepaper) and the TCT Meetings include:

All patients receiving a therapeutic dose of Iomab-B engrafted despite active disease with high blast count (median 30%, or median 45% for crossover patients)
15 of 19 (79%) patients in the control arm failed to achieve a complete response
67% (10/15) of patients eligible for crossover successfully transplanted after Iomab-B treatment
Patients receiving Iomab-B received a BMT more quickly post-randomization (28 days) than patients receiving conventional care (67 days)
In the conventional care arm, there was no difference in time to BMT for patients that crossed over to Iomab-B (66 days) compared to those achieving complete remission with conventional care (67 days)
No Grade 3 or 4 Iomab-B infusion related reactions with all Iomab-B infusions completed
No 100-Day non-relapse mortality in patients randomized to Iomab-B arm
All patients receiving Iomab-B and a BMT (28/28) achieved Donor Chimerism prior to day 100
94% of patients initially randomized to receive Iomab-B and a BMT (17/18) achieved Full Donor Chimerism > 95% prior to day 100 with 1 patient achieving 65% donor chimerism
90% of patients who crossed-over to receive Iomab-B and a BMT (9/10), after salvage chemotherapy in the control arm failed to produce a CR or Complete Response, also achieved Full Donor Chimerism > 95% prior to day 100 with 1 patient achieving 86% donor chimerism
Sandesh Seth, Actinium’s Chairman and CEO said, "Iomab-B has been studied extensively across multiple clinical trials and disease indications where it has consistently demonstrated the ability to condition patients for BMT in a well-tolerated manner with high engraftment rates and improved clinical outcomes including a survival benefit. As the lead candidate in our pipeline, it is heartening to see interim safety and feasibility data consistent with prior clinical evidence as the trend of strong engraftment with Iomab-B continues in the pivotal multi-center SIERRA trial. In addition, our other posters at TCT supporting the value proposition of Iomab-B from a healthcare economics perspective are also illuminative of the potential opportunity available. We are also excited to note the strong data from the Iomab-ACT program for targeted lymphodepletion prior to CART and other adoptive cell therapies supportive of clinical advancement that was presented at this TCT Meeting. We look forward to providing additional updates as we continue to build and advance our industry leading, multi-asset, multi-indication targeted conditioning portfolio."

On February 23, 2019 Xynomic Pharma, a clinical stage US-China oncology drug development company, and Bison Capital Acquisition Corp. (Nasdaq: BCAC), reported that jointly announced the dosing of the first South Korean patient at the Asan Medical Center in South Korea in the on-going global pivotal Phase 3 trial of Xynomic’s abexinostat combined with pazopanib as a first- or second-line therapy against renal cell carcinoma (RCC) (Press release, Xynomic Pharmaceuticals, FEB 23, 2019, View Source [SID1234533611]). According to US International Trade Administration, South Korea is the third largest pharmaceutical market in Asia and the 13th largest globally. Furthermore, Xynomic plans to roll out this multi-national trial, currently ongoing in the United States, in Europe and China in the first half of 2019.

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In addition, to support its on-going Phase 3 trial and potential submissions for new drug approval of its lead drug candidate abexinostat, Xynomic has appointed Dr. Sophia Paspal as the Vice President, Regulatory Affairs and Quality Assurance. Dr. Paspal assumes overall responsibility to strengthen Xynomic’s regulatory compliance and quality assurance functions. Dr. Paspal brings 20 years of relevant global industry experience. From 2017 to January 2019, Dr. Paspal worked at Capricor Therapeutics, Inc. and Cellics Therapeutics, Inc., holding the same title. From 2015 to 2017 Dr. Paspal worked as the Director of Regulatory Affairs, Oncology, at Halozyme Therapeutics Inc. From 2014 to 2015 Dr. Paspal worked as Associate Director of Regulatory Affairs, Neurology, for Dart NeuroScience LLC. Prior to 2014, Dr. Paspal worked for companies such as Shire PLC, Allergan, Inc., and Pfizer in developing and implementing regulatory strategies and obtaining and maintaining regulatory approvals. Dr. Paspal holds Regulatory Affairs Certification (RAC) and Drug Development Certification from Temple University RA and QA Program. Dr. Paspal holds a Bachelor of Science in Chemistry and Ph.D. in Pharmaceutics from the University of Minnesota, Twin Cities in Minnesota.

On February 23, 2019 Gamida Cell Ltd. (Nasdaq: GMDA), a leading cellular and immune therapeutics company, reported that translational data from the completed Phase 1/2 clinical study of NiCord were reported in an oral presentation at the 2019 Transplantation & Cellular Therapy (TCT) Meetings of American Society for Blood and Marrow Transplantation (ASBMT) and Center for International Blood and Marrow Transplant Research (CIBMTR) in Houston, Texas (Press release, Gamida Cell, FEB 23, 2019, View Source [SID1234533609]). The data demonstrated that treatment with NiCord, an investigational advanced cell therapy designed to enhance and expand the life-saving benefits of bone marrow transplant for patients with hematologic malignancies, resulted in rapid and robust immune reconstitution. NiCord is currently being evaluated in an international, randomized Phase 3 study in patients with hematologic malignancies.1

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"Reconstitution of a patient’s bone marrow and immune system is a crucial factor in recovery following allogeneic hematopoietic stem cell transplant," said Jaap-Jan Boelens, M.D., Ph.D., Chief, Pediatric Stem Cell Transplantation and Cellular Therapies Service, Memorial Sloan Kettering Cancer Center. "We were particularly encouraged by the finding that reconstitution of CD4+ T cells with NiCord treatment was at least as fast as transplant with unmanipulated cord blood and unrelated bone marrow in adolescents and young adults, who typically achieve more rapid recovery than adults."

Despite the curative potential of bone marrow transplants, it is estimated that more than 40 percent of eligible patients in the U.S. do not receive one for various reasons, including finding a matched donor.2 Even for patients who do receive a transplant, treatment is not always effective and can lead to serious complications that can dramatically affect quality of life.3 NiCord is intended to address the current limitations of bone marrow transplant by providing a therapeutic dose of cells while preserving the cells’ functional therapeutic characteristics.

Data Presented at TCT Annual Meeting

The oral presentation, "Rapid and Robust CD4+ and CD8+ T-, NK-, B-Cell, Dendritic Cell, and Monocyte Reconstitution after Nicotinamide-Expanded Cord Blood Transplantation" (Abstract 69), described in-depth immune reconstitution data from the completed Phase 1/2, multi-center clinical study of NiCord as a stand-alone graft after myeloablative therapy in patients with high-risk hematologic malignancies.4 Immune reconstitution for 27 patients receiving NiCord was compared to retrospective cohorts of adolescent and young adults with hematologic malignancies receiving unmanipulated cord blood transplantation (unCBT, n=27) or unrelated bone marrow transplantation (BMT, n=20). The primary endpoint was the probability of achieving CD4+ immune reconstitution (>50×106/L) within the first 100 days. Secondary endpoints included the recovery of B cells, CD4+ T cells and natural killer (NK) cells during the first year after transplantation. Analyses were performed at the University Medical Centre Utrecht, Laboratory of Translational Immunology.

The analysis showed that 91 percent of patients receiving NiCord achieved successful immune reconstitution of CD4+ T cells at 100 days after transplantation. Reconstitution of T cells in the NiCord group (median age 41.5 years) was similar to the unCBT and BMT cohorts (median age 15.4 and 14.3 years, respectively), despite the younger age of the cohorts, who would be expected to reconstitute faster. In addition, reconstitution of a number of cell types, including B cells (p = 0.02) and NK cells (p < 0.001), was significantly faster after transplantation with NiCord compared to the cohorts, and suggests that NiCord reconstitutes diverse functions of the immune system. These findings may be explained by the higher stem cell dose and proliferative capacity of NiCord.

"Our goal is to bring a potentially transformative new treatment option to patients in need of bone marrow transplant, and these data further reinforce our belief in the clinical potential of NiCord," stated Ronit Simantov, M.D., chief medical officer at Gamida Cell. "We are continuing to enroll patients in our ongoing Phase 3 study and expect to complete patient enrollment in the second half of 2019, followed by an anticipated topline data readout in the first half of 2020."

During the TCT Annual Meeting, new data were also presented from Gamida Cell’s NAM-NK clinical program, as well as initial data from a Phase 1/2 study of NiCord in patients with severe aplastic anemia. More information on those presentations can be found here.

About NiCord

NiCord, the company’s lead clinical program, is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant solution for patients with hematologic malignancies (blood cancers). NiCord is the first bone marrow transplant product to receive Breakthrough Therapy Designation from the U.S. Food and Drug Administration and has also received Orphan Drug Designation in the U.S. and EU. In a Phase 1/2 clinical study, NiCord demonstrated rapid and durable time to engraftment and was generally well-tolerated.5 A Phase 3 study evaluating NiCord in patients with leukemia and lymphoma is ongoing in the U.S., Europe and Asia.1 NiCord is also being evaluated in a Phase 1/2 clinical study in patients with severe aplastic anemia.6 The aplastic anemia investigational new drug application is currently filed with the FDA under the brand name CordIn, which is the same investigational development candidate as NiCord. For more information on clinical trials of NiCord, please visit www.clinicaltrials.gov.

NAM-NK and NiCord are investigational therapies, and their safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.

On February 23. 2019 Bausch Health Companies Inc. (NYSE/TSX: BHC) ("Bausch Health," the "Company" or the "Offeror") reported that it has increased the maximum aggregate purchase amount of its outstanding notes listed in the table below (collectively, the "Notes") that it may purchase pursuant to the previously announced cash tender offers (collectively, the "Tender Offers," and each offer to purchase a series of notes individually, a "Tender Offer") upon terms and subject to the conditions set forth in the Offers to Purchase and Consent Solicitation Statement dated Feb. 22, 2019 (the "Statement"), as supplemented by this release, and the related Letter of Transmittal and Consent (Press release, Valeant, FEB 23, 2019, View Source [SID1234533596]). The Company announced that it has increased the maximum aggregate purchase price of the Notes that may be purchased pursuant to the Tender Offers from $1,250,000,000 to $1,500,000,000 (the "Aggregate Maximum Purchase Amount") and it has increased the maximum aggregate purchase price of the 5.50% Senior Notes due 2023 (the "5.50% Notes") and 5.875% Senior Notes due 2023 (the "5.875% Notes" and, together with the 5.50% Notes, the "2023 Notes") that may be purchased pursuant to the Tender Offers from $550,000,000 to $800,000,000 (the "Tender Cap"). The Company also announced that the Tender Offers and the Solicitation are subject to, among other conditions, the completion of concurrent private offerings by Bausch Health and/or its subsidiaries of at least $1,500 million aggregate principal amount of senior notes, an increase from $1,250 million.

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The Company is also soliciting consents (the "Solicitation," and, together with the Tender Offers, the "Tender Offers and Solicitation") to certain proposed amendments to the indenture governing its 5.625% Senior Notes due 2021 (the "2021 Notes") to eliminate substantially all of the restrictive covenants and events of default and related provisions contained in the indenture under which the 2021 Notes were issued (the "Proposed Amendments"). No amendments to the indenture governing the 2023 Notes are being sought. All other terms and conditions of the Tender Offers and Solicitation will remain the same.

A $800,000,000 Tender Cap applies to the aggregate purchase price of the 5.50% Notes and the 5.875% Notes.

Per $1,000 principal amount of Notes validly tendered and accepted for purchase in the applicable Tender Offer (exclusive of any Accrued Interest, which will be paid by the Offeror in addition to the Tender Offer Consideration or the Total Consideration, as applicable, to, but not including, the applicable Settlement Date). References to aggregate purchase price herein exclude Accrued Interest, if any.

Includes the Applicable Premium, if any.

The Tender Offers and Solicitation will expire at 11:59 p.m., New York City time, on March 21, 2019 (such date and time with respect to a Tender Offer and the Solicitation, as it may be extended for such Tender Offer and the Solicitation, the "Expiration Date"). No tenders will be valid if submitted after the Expiration Date. Tendered Notes may be withdrawn from the applicable Tender Offer and, with respect to the 2021 Notes, the related consents may be revoked at or prior to, but not after, 5:00 p.m., New York City time, on March 7, 2019 (such date and time with respect to a Tender Offer and the Solicitation, as it may be extended for such Tender Offer and the Solicitation, the "Withdrawal Deadline"). Holders of Notes who tender their Notes after the Withdrawal Deadline, but prior to the Expiration Date, may not withdraw their tendered Notes or, with respect to the 2021 Notes, revoke their delivered consents, except for certain limited circumstances where additional withdrawal rights are required by law. Holders may not tender their 2021 Notes without delivering their consents to the Proposed Amendments to the indenture under which the 2021 Notes were issued and may not deliver their consents to the Proposed Amendments without tendering their 2021 Notes pursuant to the applicable Tender Offer.

Subject to the terms and conditions of the Tender Offers, the consideration for each $1,000 principal amount of Notes validly tendered (and not validly withdrawn) and accepted for purchase pursuant to the Tender Offers and the Solicitation will be the tender offer consideration for the applicable series of Notes set forth in the table above (with respect to each series of Notes, the "Tender Offer Consideration"). Holders of Notes that are validly tendered (and not validly withdrawn) at or prior to 5:00 p.m., New York City time, on March 7, 2019 (such date and time with respect to a Tender Offer, as it may be extended for such Tender Offer, the "Early Tender Date") and accepted for purchase pursuant to the Tender Offers and the Solicitation will receive the applicable Tender Offer Consideration plus the early tender premium, if any, for the applicable series of Notes as set forth in the table above (with respect to each series of Notes, the "Applicable Premium" and, together with the applicable Tender Offer Consideration, the "Total Consideration"). Holders of Notes validly tendered after the Early Tender Date, but at or prior to the Expiration Date, and accepted for purchase pursuant to the Tender Offers and the Solicitation will receive the applicable Tender Offer Consideration, but not the Applicable Premium for the applicable series of Notes. No tenders will be valid if submitted after the Expiration Date.

In addition to the Tender Offer Consideration or the Total Consideration, as applicable, all Holders of Notes accepted for purchase pursuant to the Tender Offers and the Solicitation will, on the Early Settlement Date (as defined below) or the Final Settlement Date (as defined below), as applicable, also receive accrued and unpaid interest on those Notes from the last interest payment date with respect to those Notes to, but not including, the Early Settlement Date or the Final Settlement Date, as applicable (the "Accrued Interest").

If the Company receives valid consents of the holders of a majority in aggregate principal amount of the outstanding 2021 Notes (the "Requisite Consents"), the Company will execute a supplemental indenture effecting the Proposed Amendments. The Proposed Amendments will not become operative, however, unless and until the Company accepts for purchase and pays the Total Consideration with respect to validly tendered 2021 Notes and validly delivered consents representing a majority in aggregate principal amount of the outstanding 2021 Notes.

The Offeror reserves the right, in its sole discretion, to increase or decrease the amount of Notes purchased in any Tender Offer at any time such that the Aggregate Maximum Purchase Amount and the Tender Cap may be increased or decreased without extending the Early Tender Date or the Withdrawal Deadline or otherwise reinstating withdrawal rights for any Tender Offer, subject to compliance with applicable law, which could result in the Offeror purchasing a greater or lesser amount of Notes in the Tender Offers. If the Aggregate Maximum Purchase Amount or the Tender Cap changes, the Offeror does not expect to extend the Withdrawal Deadline, subject to applicable law.

The Offeror reserves the right, in its sole discretion, at any point following the Early Tender Date and prior to the Expiration Date, to accept for purchase any Notes validly tendered (and not validly withdrawn) at or prior to the Early Tender Date (the date of such acceptance and purchase, the "Early Settlement Date"), subject to the Aggregate Maximum Purchase Amount, the Tender Cap, the Acceptance Priority Levels and proration as described in the Statement. The Early Settlement Date will be determined at the Offeror’s option, assuming the conditions to the Tender Offers and the Solicitation have been either satisfied or waived by the Offeror at or prior to the Early Settlement Date. If the Offeror elects to have an Early Settlement Date, it will accept Notes validly tendered at or prior to the Early Tender Date, subject to the Aggregate Maximum Purchase Amount, the Tender Cap, the Acceptance Priority Levels and proration as described in the Statement. Irrespective of whether the Offeror chooses to exercise its option to have an Early Settlement Date, it will purchase any remaining Notes that have been validly tendered at or prior to the Expiration Date and accepted for purchase, subject to all conditions to the Tender Offers and the Solicitation having been either satisfied or waived by the Offeror, promptly following the Expiration Date (the date of such acceptance and purchase, the "Final Settlement Date"; the Final Settlement Date and the Early Settlement Date each being a "Settlement Date"), subject to the Aggregate Maximum Purchase Amount, the Tender Cap, the Acceptance Priority Levels and proration as described in the Statement. The Final Settlement Date is expected to occur on the second business day following the Expiration Date, assuming the conditions to the Tender Offers and the Solicitation have been either satisfied or waived by the Offeror at or prior to the Expiration Date and Notes having an aggregate purchase price (exclusive of Accrued Interest) equal to the Aggregate Maximum Purchase Amount are not purchased on the Early Settlement Date.

Subject to the Aggregate Maximum Purchase Amount, the Tender Cap, the Acceptance Priority Levels and proration as described in the Statement, all Notes validly tendered at or prior to the Early Tender Date having the highest Acceptance Priority Level will be accepted for purchase before any Notes validly tendered at or prior to the Early Tender Date having the lowest Acceptance Priority Level are accepted for purchase, and all Notes validly tendered after the Early Tender Date having the highest Acceptance Priority Level will be accepted for purchase before any Notes validly tendered after the Early Tender Date having the lowest Acceptance Priority Level are accepted for purchase. However, even if the Tender Offers are not fully subscribed as of the Early Tender Date, subject to the Aggregate Maximum Purchase Amount and the Tender Cap, Notes validly tendered at or prior to the Early Tender Date will be accepted for purchase before any Notes validly tendered after the Early Tender Date are accepted for purchase, even if such Notes validly tendered after the Early Tender Date have the highest Acceptance Priority Level than Notes validly tendered at or prior to the Early Tender Date. Therefore, if the aggregate purchase price of Notes validly tendered at or prior to the Early Tender Date equals or exceeds the Aggregate Maximum Purchase Amount, the Offeror will not accept for purchase any Notes tendered after the Early Tender Date, and if the aggregate purchase price of 2023 Notes validly tendered at or prior to the Early Tender Date equals or exceeds the Tender Cap, the Offeror will not accept for purchase 2023 Notes tendered after the Early Tender Date, in each case unless the Offeror increases the Tender Cap and/or Aggregate Maximum Purchase Amount. Additional information about the application of the Aggregate Maximum Purchase Amount, Acceptance Priority Levels, Tender Cap and proration is set forth in the Statement.

The Tender Offers are not conditioned upon a minimum amount of Notes of any series, or a minimum amount of Notes of all series, being tendered. However, the Tender Offers and the Solicitation are subject to, and conditioned upon, the satisfaction or waiver of certain conditions described in the Statement, including completion of concurrent private offerings by Bausch Health and/or its subsidiaries of at least $1,500 million aggregate principal amount of senior notes to finance the payment of the Tender Offer Consideration and the Total Consideration. While none of the Tender Offers are subject to receipt of the Requisite Consents, the Solicitation is conditioned on receipt of the Requisite Consents.

If, following the consummation of the Tender Offers and the Solicitation, any 2021 Notes remain outstanding, the Offeror intends to promptly redeem such 2021 Notes in accordance with terms of the 2021 Notes and the indenture under which the 2021 Notes were issued. In addition, if the aggregate purchase price of 2023 Notes validly tendered by the Expiration Date and accepted for purchase does not exceed the Tender Cap, the Offeror intends to retire or repay existing debt in a purchase price equal to the excess of the Tender Cap over the aggregate purchase price of 2023 Notes validly tendered and accepted for purchase in the Tender Offers.

J.P. Morgan is acting as the dealer manager and solicitation agent in the Tender Offers and Solicitation. Global Bondholder Services Corporation has been retained to serve as both the depositary and the information agent for the Tender Offers and Solicitation. Persons with questions regarding the Tender Offers and Solicitation should contact J.P. Morgan Securities LLC at (collect) (212) 834-3260 or (toll free) (866) 834-4666. Requests for copies of the Statement, the related Letter of Transmittal and Consent and other related materials should be directed to Global Bondholder Services Corporation at (toll-free) (866) 470-4200 or (collect) (212) 430-3774.

None of the Offeror, its board of directors or officers, the dealer managers and solicitation agents, the depositary, the information agent or the trustee with respect to the Notes, or any of their respective affiliates, makes any recommendation that holders tender or refrain from tendering all or any portion of the principal amount of their Notes, and no one has been authorized by any of them to make such a recommendation. Holders must make their own decision as to whether to tender their Notes and, if so, the principal amount of Notes to tender. The Tender Offers and Solicitation are made only by the Statement and related Letter of Transmittal and Consent. This news release is neither an offer to purchase nor a solicitation of an offer to sell any notes in the Tender Offers nor a solicitation of consents with respect to the Notes or any other securities. The Tender Offers and the Solicitation are not being made to holders of Notes in any jurisdiction in which the making or acceptance thereof would not be in compliance with the securities, blue sky or other laws of such jurisdiction. In any jurisdiction in which the Tender Offers and the Solicitation are required to be made by a licensed broker or dealer, the Tender Offers and the Solicitation will be deemed to be made on behalf of the Offeror by the dealer manager and solicitation agent or one or more registered brokers or dealers that are licensed under the laws of such jurisdiction.

Any securities issued pursuant to the financing transactions described above will not be registered under the Securities Act of 1933, as amended (the "Securities Act"), or any state securities law and may not be offered or sold in the United States absent registration or an applicable exemption from registration under the Securities Act and applicable state securities laws. Such securities have not been and will not be qualified for sale to the public by prospectus under applicable Canadian securities laws and, accordingly, any offer and sale of the securities in Canada will be made on a basis which is exempt from the prospectus requirements of such securities laws.

This news release is being issued pursuant to Rule 135c under the Securities Act and shall not constitute an offer to sell or the solicitation of an offer to sell or the solicitation of an offer to buy any securities that may be issued pursuant to the financing transactions described above. Further, nothing contained herein shall constitute a notice of redemption of the Notes.