On December 21, 2020 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, and City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases, reported that a Phase 1 single-center, two-arm clinical trial has been initiated to establish the safety and feasibility of administering MB-101 (autologous IL13Rα2-CAR T cells) to patients with leptomeningeal brain tumors (e.g., glioblastoma, ependymoma or medulloblastoma) (Press release, Mustang Bio, DEC 21, 2020, View Source [SID1234573176]). The trial will enroll up to 30 patients and take place at City of Hope, where the chimeric antigen receptor T ("CAR T") cell therapy was initially developed.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

All subjects enrolled in the trial will undergo surgery for the placement of an intraventricular (ICV) Rickham catheter for CAR T cell delivery. The Phase 1 trial will establish the safety and feasibility of administering MB-101 through the ICV Rickham catheter over four weekly cycles in patients with glioblastoma (Arm 1) and ependymoma or medulloblastoma (Arm 2). The primary endpoints that will be evaluated are toxicity and survival at three months. Secondary endpoints include overall survival, CAR T and endogenous T cell levels, cytokine levels and phenotype detection in peripheral blood, tumor cyst fluid and cerebrospinal fluid.

Lisa Feldman, M.D., Ph.D., a neurosurgeon and assistant clinical professor in the Division of Neurosurgery at City of Hope and principal investigator of the clinical trial, commented, "Leptomeningeal brain tumors are a form of metastatic brain cancer, which is currently very difficult to treat. We are encouraged by the potential of administering autologous IL13Rα2-CAR T cells intraventricularly to patients with leptomeningeal brain tumors. This CAR T cell therapy has demonstrated early safety and efficacy results in a previous clinical trial conducted at City of Hope, and we believe these preliminary results warrant further evaluation of these CAR T cells. We look forward to providing updates on the trial and to continue working closely with Mustang with the goal of bringing a safe and effective treatment option to patients with this life-threatening disease."

Manuel Litchman, M.D., president and chief executive officer of Mustang, said, "We are pleased to further study MB-101 in leptomeningeal brain tumors as it has already demonstrated therapeutic potential when infused into the ventricular system, including delivering a complete response in a leptomeningeal glioblastoma patient that was published in the New England Journal of Medicine. Our ongoing work with City of Hope continues to advance the research of our CAR T portfolio to bring potential therapies to patients suffering from devastating diseases."

Additional information about the trial can be found on clinicaltrials.gov using the identifier NCT04661384.

About MB‐101 (IL13Rα2‐specific CAR T cells)
IL13Rα2 is an attractive target for CAR T therapy as it has limited expression in normal tissue but is overexpressed on the surface of the majority of malignant glioma cells, including glioblastoma multiforme, ependymoma and medulloblastoma. CAR T cells are designed to express a membrane‐tethered IL‐13 receptor ligand (IL‐13) incorporating a single‐point mutation that provides high affinity for IL13Rα2 and reduces binding to IL13Rα1 in order to reduce healthy tissue targeting. Mustang is developing MB‐101 as an optimized CAR T product incorporating enhancements in CAR design and T cell engineering to improve antitumor potency and T cell persistence. MB‐101 includes a second‐generation hinge optimized CAR containing mutations in the IgG4 linker to reduce off‐target Fc interactions, the 4-1BB (CD137) co‐stimulatory signaling domain for improved persistence of CAR T cells and the extracellular domain of CD19 as a selection/safety marker. To further improve persistence, central memory T cells are enriched and genetically engineered using a manufacturing process that limits ex vivo expansion to reduce T cell exhaustion and maintain a memory T cell phenotype.

On December 21, 2020 Exelixis, Inc. (NASDAQ: EXEL) reported that COSMIC-311, the phase 3 pivotal trial evaluating cabozantinib (CABOMETYX) versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after up to two prior vascular endothelial growth factor receptor (VEGFR)-targeted therapies, met the co-primary endpoint of demonstrating significant improvement in progression-free survival. Cabozantinib reduced the risk of disease progression or death by 78% with a hazard ratio of 0.22 (96% CI 0.13 – 0.36; p<0.0001) at this planned interim analysis (Press release, Exelixis, DEC 21, 2020, View Source [SID1234573175]). The safety profile was consistent with that previously observed for cabozantinib.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Considering the poor prognosis and lack of progress in the treatment of differentiated thyroid cancer following anti-VEGFR therapy, a significant improvement in progression-free survival is a long-awaited clinical advance," said Marcia S. Brose, M.D., Ph.D., Full Professor of Otorhinolaryngology: Head and Neck Surgery and Director of the Center for Rare Cancers and Personalized Therapy at the Abramson Cancer Center of the University of Pennsylvania, and principal investigator of the trial. "These encouraging results from COSMIC-311 suggest cabozantinib has the potential to become an important new option for these patients. We look forward to sharing the detailed data from the trial at an upcoming medical meeting."

Given these results, the independent data monitoring committee for the study recommended to stop enrollment and unblind sites and patients. Exelixis intends to discuss the study results, proposed changes to the study conduct, as well as plans for a regulatory filing with the U.S. FDA in the near term.

"We are very pleased that at this early interim analysis of COSMIC-311, cabozantinib has demonstrated a clinically meaningful and statistically significant improvement in progression-free survival for patients with differentiated thyroid cancer who are in need of additional treatment options after prior therapy," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "We are thankful to the patients, physicians and site staff who are participating in this trial during the COVID-19 pandemic. We intend to discuss the findings with regulatory authorities and look forward to sharing the detailed final COSMIC-311 results when they become available."

COSMIC-311 is a multicenter, randomized, double-blind, placebo-controlled phase 3 pivotal trial that aimed to enroll approximately 300 patients at 150 sites globally. Patients were randomized in a 2:1 ratio to receive either cabozantinib 60 mg or placebo once daily. Detailed results will be submitted for presentation at a future medical conference. More information about this trial is available at ClinicalTrials.gov.

About Differentiated Thyroid Cancer
Approximately 53,000 new cases of thyroid cancer will be diagnosed in the U.S. in 2020.1 Nearly three out of four of these cases will be in women, and the disease is more commonly diagnosed at a younger age compared to most other adult cancers.1 While cancerous thyroid tumors include differentiated, medullary and anaplastic forms, differentiated thyroid tumors make up about 90 percent of cases.1 These include papillary, follicular and Hürthle cell cancer.1 Differentiated thyroid cancer is typically treated with surgery followed by ablation of the remaining thyroid tissue with radioiodine, but approximately 5% to 15% of cases are resistant to radioiodine treatment. 2,3 For these patients, life expectancy is only three to six years from the time metastatic lesions are detected.4,5,6

About CABOMETYX (cabozantinib)
In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC and for the treatment of patients with HCC who have been previously treated with sorafenib. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

CABOMETYX is not indicated for radioiodine-refractory differentiated thyroid cancer.

Important Safety Information

Warnings and Precautions

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of perforations and fistulas, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic event requiring medical intervention.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension occurred in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Proteinuria: Proteinuria occurred in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, and vomiting.

Drug Interactions

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

On December 21, 2020 ImmunityBio, a privately-held immunotherapy company, and NantKwest, Inc. (NASDAQ: NK), a clinical-stage, natural killer cell-based therapeutics company, reported they have entered into an agreement to merge in a stock-for-stock transaction (Press release, ImmunityBio, DEC 21, 2020, https://ir.nantkwest.com/news-releases/news-release-details/immunitybio-and-nantkwest-merge-creating-leading-immunotherapy?field_nir_news_date_value[min]= [SID1234573174]). The combination will create a leading immunotherapy and cell therapy company focused on oncology and infectious disease.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Together, ImmunityBio and NantKwest will have a broad, clinical-stage pipeline – including 13 assets in clinical trials and 11 in Phase II to III – as well as a robust early stage pipeline to address other difficult to treat cancers. The combination of NantKwest’s Natural Killer (NK) cell platform and ImmunityBio’s immunotherapy fusion protein, immunomodulator, and adenovirus platforms have already resulted in complete responses in late stage, difficult to treat metastatic cancers. To date complete responses have been noted in patients with second line or greater metastatic pancreatic cancer, triple-negative breast cancer, head and neck cancer, and Merkel Cell Carcinoma. This strong track record of combination immunotherapies across the two companies’ platforms supports the potential of the combined assets to transform the future of immunotherapy beyond checkpoints by synergizing NantKwest’s cell-based therapies with ImmunityBio’s immunotherapy platforms.

In a separate press release issued today, ImmunityBio announced that ImmunityBio’s IL-15 fusion protein, Anktiva, with FDA Breakthrough Therapy status for non-muscle invasive bladder cancer CIS, has achieved primary endpoint with 72% complete response.

ImmunityBio was founded by Dr. Patrick Soon-Shiong, MD, a physician and scientist who invented Abraxane for the treatment of metastatic breast cancer, lung cancer and advanced pancreatic cancer. The companies, including their operations, are aligned given their long-standing collaboration programs with opportunity for advancing clinical development of the late stage Phase II and III trials.

Dr. Soon-Shiong said, "We are developing next-generation immunotherapies to defeat cancer and infectious disease. By combining ImmunityBio’s immunotherapy platform, which includes the Anktiva IL-15 superagonist, with NantKwest’s natural killer cell platform, the merged entity will have a powerful and broad product portfolio that can activate both the innate (natural killer cell and macrophage) and adaptive (T cell) immune systems to create long-term immunological memory. What distinguishes the merged entity is the late stage immunotherapy product pipeline that is designed to eliminate the need for high-dose chemotherapy, improve the outcomes of current CAR T cell therapies, and extend beyond checkpoint inhibitors. With 13 clinical trials across multiple tumor types at Phase I to III and with the combined talent in research, clinical development and manufacturing, the merged entity is poised to be a leader in the immunotherapy space."

"We are excited to join forces with ImmunityBio, a company and team we have collaborated with for many years across our platforms," said Rich Adcock, NantKwest Chief Executive Officer. "With the integration of ImmunityBio’s pipeline, cutting-edge R&D capabilities, talented employees and clinical expertise, we expect to accelerate the delivery of new treatments for patients with unmet needs. Together we can unlock the combined potential of our assets, and look forward to building on our continued success as one company."

Michael Blaszyk, an independent director of NantKwest and member of the Special Committee stated, "This transaction is a compelling opportunity to drive value creation for shareholders. Our Special Committee carefully evaluated the ImmunityBio proposal and determined it is in the best interests of shareholders and also benefits other stakeholders, including our employees, partners and patients."

ImmunityBio is a leading late stage immunotherapy company activating both the innate (natural killer cell and macrophage) and adaptive (T cell) immune system to treat serious unmet needs within oncology and infectious diseases. Founded in 2014 and headquartered in Culver City, ImmunityBio’s platform is designed to overcome limitations of the current standards of T cell-based immunotherapies, including checkpoint inhibitors and CAR-T cells. The company has established a robust next generation immunotherapy clinical pipeline with a strategy toward registrational intent in various indications, beyond checkpoint therapy treatment alone.

Strategic and Financial Rationale

Key attributes of the combined company will include:

Expansive clinical-stage pipeline and intellectual property portfolio. 13 assets in clinical trials, including 11 in Phase II to III clinical trials, as well as a strong global intellectual property portfolio of issued and pending worldwide patent applications with patent life extending to 2035 and beyond.
Differentiated technology and assets. Best-in-class combined discovery and development platforms for novel therapies and next-generation early-stage candidates across immunotherapy, neoepitopes and molecules enhancing allogeneic and autologous NK and T-cell therapies.
Significant market opportunity. Well positioned to combine expertise, platforms and resources to address patients across oncology and infectious disease.
Cutting-edge cell manufacturing expertise and ready-to-scale facilities. Extensive and seasoned R&D, clinical trial, and regulatory operations and development teams, which together will occupy over 200,000 square feet of manufacturing and R&D facilities.
Improved ability to combine platforms and therapies. The transaction improves the ability to more seamlessly combine programs and leverage resources and expertise across both companies’ platforms, ultimately strengthening the efforts of both companies on behalf of patients to drive better outcomes in the fight against oncology and infectious disease.
Significant potential for strategic and financial synergies. This opportunity will come from meaningful streamlining of clinical operations, therapeutic discovery and development, and manufacturing.
Transaction Details

The transaction is structured as a tax-free 100% stock-for-stock merger, with ImmunityBio to reverse merge with NantKwest. Under the terms of the agreement, ImmunityBio shareholders will receive a fixed exchange ratio of 0.8190 shares of NantKwest for each share of ImmunityBio owned. Upon completion of the transaction, on a fully diluted basis, ImmunityBio shareholders will own approximately 72% of the combined company and NantKwest shareholders will own approximately 28% of the combined company, on a fully diluted basis.

A Special Committee of the NantKwest Board of Directors, consisting of independent Directors, undertook a thorough review of the transaction and unanimously recommended that the company proceed with the transaction.

The transaction, which is expected to close in the first half of 2021, is subject to shareholder approval by a majority of unaffiliated shareholders of NantKwest, in addition to other customary closing conditions. There is no filing requirement under the Hart-Scott-Rodino Antitrust Improvements Act for this transaction.

Following the closing of the transaction, the combined company will assume the ImmunityBio name and continue to be listed on the NASDAQ exchange. However, the combined company ticker symbol is expected to be changed to IBRX.

Leadership

Richard Adcock will become the CEO of the combined company, and Dr. Soon-Shiong will serve as Executive Chairman of the Board. The combined company will be headquartered at ImmunityBio’s offices in Culver City, California.

Advisors

Goldman Sachs & Co. LLC and Lazard Frères & Co. LLC are serving as financial advisors to ImmunityBio. Fried, Frank, Harris, Shriver & Jacobson LLP is serving as legal counsel for ImmunityBio.

Barclays is serving as financial advisor to NantKwest’s Special Committee. Goodwin Procter LLP acted as legal counsel for NantKwest’s Special Committee.

Conference Call and Additional Materials

ImmunityBio and NantKwest will host a conference call today at 5:30 a.m. Pacific Time (8:30 a.m. Eastern Time) to discuss this morning’s announcement. The conference call can be accessed by dialing (866) 610-1072 within the U.S. and (973) 935-2840 for all other locations. The confirmation code is 6753467. Participants should dial in 15 minutes prior to the scheduled start time.

A live webcast of the conference call and associated presentation materials will be available on the ImmunityBio website at View Source and on the NantKwest website at https://ir.nantkwest.com/. A replay of the conference call will be available after completion of the conference call and can be accessed by dialing (855) 859-2056 or (404) 537-3406. The replay confirmation code is 6753467.

On December 21, 2020 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported that it will move forward with a singular focus on accelerating and expanding its genetically defined disease portfolio, including the mitapivat clinical programs and a robust pipeline of therapeutic candidates, and has entered into a definitive agreement to sell its commercial, clinical and research-stage oncology portfolio to Servier, an independent global pharmaceutical company (Press release, Agios Pharmaceuticals, DEC 21, 2020, View Source [SID1234573170]). Agios will receive a cash consideration of up to $2.0 billion, including $1.8 billion in upfront cash and $200 million in a potential future milestone payment for vorasidenib, as well as 5% royalties on U.S. net sales of TIBSOVO (ivosidenib tablets) from transaction close through loss of exclusivity and 15% royalties on U.S. net sales of vorasidenib from first commercial sale through loss of exclusivity.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Our decision to accelerate the next chapter of Agios’ success with a singular focus on genetically defined diseases and sell our oncology portfolio to Servier is a transformational milestone for Agios. The result of a deliberative strategic review, this decision reflects the progress we have made understanding and harnessing the science and promise of PK activation and captures the full value of our oncology assets," said Jackie Fouse, Ph.D., chief executive officer of Agios. "With mitapivat poised to become a new potential treatment option for patients with pyruvate kinase (PK) deficiency, thalassemia and sickle cell disease and with a rich pipeline based on our pioneering leadership in PK activation and cellular metabolism, Agios’ near- and long-term future is filled with significant value-generating catalysts. The proceeds from the transaction will allow us to focus on rapidly advancing our genetically defined disease portfolio for patients in need, strengthen our capital structure and return at least $1.2 billion to shareholders post-closing, achieve capital markets independence and participate in the future success of TIBSOVO and vorasidenib."

"We are proud of our heritage in oncology and the novel therapies we have advanced for patients with hematologic malignancies and solid tumors, and we are pleased to have found an excellent home for our oncology portfolio in Servier, a successful, patient-focused, global pharmaceutical company," continued Dr. Fouse. "Servier is committed to the oncology patient community and to investing in our assets and our people. This transaction will allow the oncology portfolio to grow and thrive with Servier and will provide Agios with the resources required to optimize the development of our promising genetically defined disease therapies, ultimately enabling the greatest overall positive impact for patients."

"The strategic acquisition of Agios’ oncology business, including its precision medicine portfolio and pipeline, is aligned with our ambition to become a recognized player in oncology and further supports our commitment to provide innovative treatments to cancer patients with unmet medical needs. It is a key step for the Servier Group as it will significantly strengthen our position in the U.S. and reinforce our R&D capabilities in oncology," stated Olivier Laureau, president of Servier. "We look forward to welcoming the experienced Agios oncology teams to Servier following the closing."

"Agios is a leader in the cellular metabolism space with a proven track record of discovering, developing and commercializing precision medicines," said David K. Lee, CEO, Servier Pharmaceuticals, the U.S. subsidiary of Servier. "The acquisition of Agios’ oncology business, including highly experienced talent from research, development, technical operations and commercial functions, allows for an immediate expansion of our U.S. business into other hematologic malignances and provides the potential for longer-term growth into the solid tumor space, thus ensuring that we can serve more patients living with unmet cancer needs than ever before."

Transaction Details
The transaction includes the transfer of Agios’ oncology portfolio and associated employees, including its marketed medicine TIBSOVO which is approved in the U.S. as monotherapy for the treatment of adults with IDH1-mutant relapsed or refractory acute myeloid leukemia (AML) and for adults with newly diagnosed IDH1-mutant AML who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy. TIBSOVO is also under investigation in two Phase 3 combination trials in newly diagnosed AML, and as a potential treatment for previously treated IDH1-mutant cholangiocarcinoma and IDH1-mutant myelodysplastic syndrome (MDS). Servier will also acquire Agios’ co-commercialization responsibilities for Bristol Myers Squibb’s IDHIFA (enasidenib) and conduct certain clinical development activities within the IDHIFA development program.

In addition, the transaction includes Agios’ oncology pipeline and clinical programs, including vorasidenib, an investigational, brain-penetrant, dual inhibitor of mutant IDH1 and IDH2 which is currently being studied in the registration-enabling Phase 3 INDIGO study in patients with IDH-mutant low-grade glioma; AG-270, an investigational first-in-class methionine adenosyltransferase 2a (MAT2A) inhibitor being evaluated in combination with taxanes in patients with methylthioadenosine phosphorylase (MTAP)-deleted non-small cell lung cancer and pancreatic cancer; AG-636, a novel inhibitor of dihydroorotate dehydrogenase (DHODH); and Agios’ oncology research programs.

All of Agios’ U.S.-based employees who primarily support the oncology business will receive a comparable offer at Servier.

The transaction has been approved by the Board of Directors and is subject to approval by Agios shareholders and satisfaction of regulatory conditions. It is currently expected that the transaction will close in the second quarter of 2021.

Goldman Sachs & Co. LLC and Morgan Stanley & Co. LLC are serving as financial advisers to Agios, and Wachtell, Lipton, Rosen & Katz is serving as its legal adviser.

Agios’ Genetically Defined Disease Portfolio
Agios’ genetically defined disease portfolio is anchored by its lead clinical candidate, mitapivat, which the company believes is a potential blockbuster across three distinct hemolytic anemias. Agios is conducting two global, pivotal Phase 3 studies to evaluate mitapivat as a potential treatment for adults with pyruvate kinase (PK) deficiency; the company recently announced positive topline results from the ACTIVATE study and expects to report data from the ACTIVATE-T study in the first quarter of 2021. Agios anticipates filing for U.S. and EU regulatory approval in adults with PK deficiency in 2021, with a potential 2022 commercial launch in both geographies. Mitapivat is also being evaluated in a fully enrolled Phase 2 study in adults with non-transfusion-dependent α- or β-thalassemia, and as a potential treatment for sickle cell disease under a Cooperative Research and Development Agreement (CRADA) with the U.S. National Institutes of Health. In 2021, Agios expects to initiate global, pivotal Phase 3 studies in thalassemia, including both α-and β-thalassemia, as well as transfusion dependent and non-transfusion dependent patient populations, and in sickle cell disease. In addition, Agios intends to evaluate mitapivat in pediatric patients across all three diseases.

Beyond mitapivat, Agios is advancing a growing genetically defined disease pipeline based on its core expertise in cellular metabolism and pioneering leadership in PK activation. AG-946, a clinical-stage, next-generation oral activator of both wild-type and mutated pyruvate kinase R (PKR) enzymes, entered a first-in-human clinical study in the third quarter of 2020. Agios’ late-stage research pipeline is evolving to include a rich and sustainable portfolio of genetically defined disease targets with clear disease area applications. These include hereditary and acquired anemias, myopathies, retinal diseases and diseases of inborn errors of metabolism such as aminoacidurias, aminoacidemias and others. As the company’s research efforts continue to develop, Agios may pursue value-adding partnerships that may bring complementary expertise for certain disease areas.

Investor Webcast Information
Agios will host an investor webcast today at 8:00 a.m. ET to discuss today’s announcement. The event will be webcast live and can be accessed under "Events & Presentations" in the Investors section of Agios’ website at www.agios.com. The archived webcast will be available on Agios’ website beginning approximately two hours after the event.
bout Agios

On December 21, 2020 Servier, a global pharmaceutical Group, and Celsius Therapeutics, a company focused on bringing precision medicine to patients with cancer and autoimmunity, reported a strategic collaboration focused on the identification and validation of novel colorectal cancer (CRC) drug targets (Press release, Celsius Therapeutics, DEC 21, 2020, View Source [SID1234573168]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"As colorectal cancer remains a leading contributor to cancer deaths worldwide, we see an urgent need to bring forward new therapeutic options for patients. Through this collaboration, we will leverage Celsius’ single-cell genomics platform, machine learning capabilities, and target validation expertise to refine our understanding of the different subtypes of CRC and discover new drug targets with the goal of developing novel precision therapies for specific patient subsets. Servier will discover and develop candidate drugs leveraging our end-to-end small molecule and large molecule capabilities," said Hugues Dolgos, Global Head of Oncology R&D at Servier.

Under the terms of collaboration, Celsius will analyze hundreds of samples from defined CRC patient populations using its proprietary single-cell genomics platform and will work to identify and validate new drug targets during the three-year research period. Servier will receive an exclusive option to research, develop, and commercialize products directed to up to three of the targets. Celsius would receive an upfront payment and research funding, and would be eligible to receive over $700 million in potential discovery, development, and commercialization milestone payments, along with tiered royalties.

"Celsius’ mission is to understand how different cell populations and cellular programs drive disease, and to translate those insights into precision therapies for patients with difficult-to-treat diseases," said Tariq Kassum, M.D., chief executive officer of Celsius. "Servier is a complementary partner with a like-minded commitment to cancer patients in need of new therapeutic options. This collaboration, along with our growing network of academic and industry partnerships, validates Celsius as a partner of choice for target discovery in oncology and autoimmune diseases."