On February 25, 2022 ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported financial results for the quarter and year ended December 31, 2021 (Press release, ImmunoGen, FEB 25, 2022, View Source [SID1234609037]).

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"2021 was a productive year for ImmunoGen, highlighted by positive pivotal data for our lead program, advances across our earlier-stage portfolio, and further strengthening our balance sheet and management team," said Mark Enyedy, ImmunoGen’s President and Chief Executive Officer. "The top-line SORAYA data provide the opportunity to establish mirvetuximab soravtansine as the new standard of care for patients with FRα-positive platinum-resistant ovarian cancer, and we look forward to presenting detailed results from SORAYA during the plenary session at SGO next month."

Enyedy continued, "We also formalized our plans to expand mirvetuximab into platinum-sensitive disease as a monotherapy and in combinations to serve a broader population of ovarian cancer patients, presented promising initial data for IMGN632, now known as pivekimab sunirine, in relapsed/refractory AML and frontline BPDCN at ASH (Free ASH Whitepaper), continued dose-escalation for IMGC936, and submitted the IND for IMGN151. Together with the appointment of key leadership positions and an oversubscribed follow-on offering in the fourth quarter, this progress positions us for success in 2022 and beyond. We have an exciting year ahead, with the potential launch of our first product, top-line data for our second pivotal program, advancement of our earlier-stage portfolio, and further building our pipeline and research capabilities."

RECENT PROGRESS

●Reported positive top-line data from SORAYA, a pivotal single-arm study of mirvetuximab soravtansine (mirvetuximab) in folate receptor alpha (FRα)-high platinum-resistant ovarian cancer in patients previously treated with Avastin (bevacizumab).
●Continued patient enrollment in the confirmatory MIRASOL study.
●Initiated accrual in PICCOLO, a single-arm study of mirvetuximab monotherapy in FRα-high recurrent platinum-sensitive ovarian cancer.
●Aligned with the US Food and Drug Administration (FDA) on the design for GLORIOSA, a randomized Phase 3 study of mirvetuximab in combination with bevacizumab maintenance in FRα-high platinum-sensitive ovarian cancer.
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●Supported investigator-sponsored trials of mirvetuximab plus carboplatin in a single-arm study in the neoadjuvant setting and a randomized study in patients with recurrent platinum-sensitive ovarian cancer.
●Continued the pivotal Phase 2 CADENZA study of pivekimab sunirine (pivekimab, formerly IMGN632) in frontline and relapsed/refractory (R/R) blastic plasmacytoid dendritic cell neoplasm (BPDCN).
●Presented initial data from the Phase 1b/2 study of pivekimab in combination with Vidaza (azacitidine) and Venclexta (venetoclax) in R/R acute myeloid leukemia (AML) in an oral session, and initial frontline BPDCN data in a poster session, at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.
●Opened an expansion cohort combining pivekimab, azacitidine, and venetoclax in unfit relapsed AML.
●Advanced dose escalation in the Phase 1 study of IMGC936 in multiple solid tumor types.
●Submitted the investigational new drug (IND) application for IMGN151.
●Appointed Kristen Harrington-Smith as Chief Commercial Officer, Mimi Huizinga, MD, MPH, FACP as Head of Medical Affairs, and Tracey L. McCain, Esq. to the Board of Directors.
●Announced a global licensing agreement granting Eli Lilly and Company (Lilly) exclusive rights to research, develop, and commercialize ADCs directed to targets selected by Lilly based on ImmunoGen’s novel camptothecin technology.

ANTICIPATED UPCOMING EVENTS

●Present full SORAYA data during the plenary session at the Society of Gynecologic Oncology (SGO) Annual Meeting in March.
●Submit the biologics license application (BLA) to the FDA for mirvetuximab in FRα-high platinum-resistant ovarian cancer in the first quarter of 2022 to support potential accelerated approval and launch.
●Generate top-line data for the confirmatory MIRASOL study in the third quarter of 2022.
●Initiate GLORIOSA, a randomized Phase 3 trial of mirvetuximab in combination with bevacizumab maintenance in FRα-high platinum-sensitive ovarian cancer, in the second quarter of 2022.
●Initiate Trial 0420, a single-arm Phase 2 trial of mirvetuximab in combination with carboplatin followed by mirvetuximab continuation in FRα-low, medium, and high patients with platinum-sensitive ovarian cancer, in the second quarter of 2022.
●Report top-line data from the pivotal CADENZA study of pivekimab in BPDCN in the second half of 2022.
●Initiate expansion cohort combining pivekimab, azacitidine, and venetoclax in frontline AML.
●Complete dose-escalation in the Phase 1 study evaluating IMGC936, with initial data anticipated in 2022.
●Begin enrollment in the Phase 1 study of IMGN151 following submission of chemistry, manufacturing, and controls (CMC) information to the FDA.

FINANCIAL RESULTS

Total revenues were $28.0 million for the quarter ended December 31, 2021 compared to $85.8 million for the quarter ended December 31, 2020, and $69.9 million for the year ended December 31, 2021 compared to $132.3 million for the year ended December 31, 2020. The decrease in both periods was driven by the recognition of a $60.5 million upfront fee received under the Company’s collaboration agreement with Jazz Pharmaceuticals during the quarter and year ended December 31, 2020 and a reduction in non-cash royalty revenue in 2021 due to the completion of the first tranche of payments under the 2015 Kadcyla royalties agreement. Partially offsetting these decreases, during the quarter and year ended December 31, 2021, the Company recognized $14.6 million of the $40.0 million upfront fee previously received pursuant to the Company’s collaboration agreement with Huadong Medicine.

Research and development expenses rose to $49.0 million for the quarter ended December 31, 2021 compared to $39.6 million for the quarter ended December 31, 2020, and $151.1 million for the year ended December 31, 2021 compared to $114.6 million for the year ended December 31, 2020. The increases in both periods were driven by greater clinical trial expenses, personnel and temporary staffing costs, external manufacturing costs, and third-party service fees in support of commercial readiness.

General and administrative expenses were $13.6 million for the quarter ended December 31, 2021 compared to $9.7 million for the quarter ended December 31, 2020, and $43.8 million for the year ended December 31, 2021 compared to $38.6 million for the year ended December 31, 2020. The increases in both periods were

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driven by higher professional fees and personnel expenses, including greater non-cash stock compensation expense.

Net loss for the fourth quarter of 2021 was $(37.2) million, or $(0.17) per diluted share, compared to net income of $31.4 million, or $0.16 per diluted share, for the fourth quarter of 2020. Net loss for the year ended December 31, 2021 was $(139.3) million, or $(0.68) per diluted share, compared to a net loss of $(44.4) million, or $(0.25) per diluted share, for the year ended December 31, 2020.

ImmunoGen had $478.8 million in cash and cash equivalents as of December 31, 2021, compared with $293.9 million as of December 31, 2020, and had $2.1 million of convertible debt outstanding as of December 31, 2020. There was no convertible debt outstanding as of December 31, 2021. Cash used in operations was $169.4 million for the year ended December 31, 2021 compared with $78.6 million for the year ended December 31, 2020, with the prior year benefitting from a $40 million upfront license payment received from Huadong Medicine and lower operating expenses for the year as discussed above. Capital expenditures were $(1.4) million for year ended December 31, 2021, compared with $0.5 million of net proceeds from the sale of equipment in the year ended December 31, 2020.

FINANCIAL GUIDANCE

For 2022, ImmunoGen expects:

●revenues between $75 million and $85 million;
●operating expenses between $285 million and $295 million; and
●cash and cash equivalents at December 31, 2022, to be between $245 million and $255 million.

Given the range in timing for potential approval, revenue guidance does not yet include potential product sales from mirvetuximab.

ImmunoGen expects that its current cash, combined with anticipated product and collaboration revenues, will fund operations into 2024.

CONFERENCE CALL INFORMATION

ImmunoGen will hold a conference call today at 8:00 a.m. ET to discuss these results. To access the live call by phone, dial (877) 621-5803; the conference ID is 5566069. The call may also be accessed through the Investors and Media section of the Company’s website, www.immunogen.com. Following the call, a replay will be available at the same location.

On February 25, 2022 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, autoimmune and infectious diseases reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the approval of KIMMTRAK (tebentafusp) for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM) (Press release, Immunocore, FEB 25, 2022, View Source [SID1234609036]).

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The CHMP positive opinion is one of the final steps before marketing authorization is granted by the EMA, which has the authority to approve medicines for use throughout the European Union. If approved, KIMMTRAK would be the first T cell receptor therapy commercially available in Europe. Immunocore’s Marketing Authorisation Application was reviewed under EMA’s accelerated assessment procedure, which is given if the CHMP determines the treatment is of major interest from a public health perspective and represents a therapeutic innovation.

"The CHMP’s recommendation of KIMMTRAK brings us closer to providing a much-needed treatment option to patients in Europe," said Bahija Jallal, Chief Executive Officer of Immunocore. "This year, hundreds of people across the EU will be diagnosed with metastatic uveal melanoma. Left with minimal-to-no options, these patients have a devastating prognosis. KIMMTRAK is the first therapy to demonstrate a survival benefit in patients with this disease, providing new hope to these individuals and to the doctors treating them."

The recommendation comes just one month after regulatory approval of KIMMTRAK by the United States Food and Drug Administration (FDA) last month (January 25), making it the first and now only therapy for the treatment of unresectable or metastatic uveal melanoma to be approved by the FDA.
The CHMP recommendation of KIMMTRAK is based on the results of Immunocore’s Phase 3 IMCgp100-202 clinical trial, which were published in the September 23, 2021 issue of the New England Journal of Medicine. The randomized pivotal trial evaluated overall survival (OS) of KIMMTRAK compared to investigator’s choice (either pembrolizumab, ipilimumab, or dacarbazine) in patients with previously untreated mUM. 378 patients were randomized in a 2:1 ratio to either KIMMTRAK or investigator’s choice. Data from the trial, the largest Phase 3 trial undertaken in mUM, showed that KIMMTRAK demonstrated unprecedented median OS benefit as a first-line treatment. The OS Hazard Ratio (HR) in the intent-to-treat population favored KIMMTRAK, HR=0.51 (95% CI: 0.37, 0.71); p< 0.0001, over investigator’s choice (82% pembrolizumab; 13% ipilimumab; 6% dacarbazine). In the clinical trials, across both arms, patients stopped treatment for disease progression, unless the patient was otherwise deriving benefit, or for unacceptable toxicity.1
Dr. Paul Nathan, uveal melanoma lead for the European Organisation for Research and Treatment of Cancer, said: "Metastatic uveal melanoma has historically been associated with a particularly poor prognosis and, up until now, has been refractory to most treatments. KIMMTRAK represents a significant new form of treatment, offering the chance at a longer life for patients with the disease, and with it, hope."

In the randomised Phase 3 trial of KIMMTRAK (tebentafusp), treatment-related adverse reactions were manageable and consistent with the proposed mechanism of action. Among the patients treated with KIMMTRAK, the most common Grade 3 or higher adverse events were rash (18%), pyrexia (4%), and pruritus (5%). In the 245 patients treated with KIMMTRAK, Grade 3 cytokine release syndrome (CRS) occurred in <1% of patients and were generally well-managed. There were no Grade 4 CRS events observed in the Phase 3 clinical trial.

The United Kingdom’s Medicines and Healthcare Regulatory Agency (MHRA), Health Canada, and the Australian Government Department of Health Therapeutic Goods Administration (TGA) have each accepted the submission of the Company’s Marketing Authorisation Application. In April of 2021, Immunocore launched a global early access program to make KIMMTRAK readily available to mUM patients. The Company is focused on continuing to treat these patients with KIMMTRAK as regulatory approval is sought in the EU and the individual EU Member States. There are currently over 200 patients in the early access program.

About Uveal Melanoma
Uveal melanoma is a rare and aggressive form of melanoma, which affects the eye. Although it is the most common primary intraocular malignancy in adults, the diagnosis is rare, and up to 50% of people with uveal melanoma will eventually develop metastatic disease. Unresectable or metastatic uveal melanoma typically has a poor prognosis and had no approved treatment until KIMMTRAK.

About KIMMTRAK
KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect and activate T cells to recognize and kill tumor cells. KIMMTRAK has been granted Breakthrough Therapy Designation, Fast Track designation and orphan drug designation by the FDA in the United States, Accelerated Assessment by the EMA, and Promising Innovative Medicine (PIM) designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma.

About Phase 3 IMCgp100-202 Trial
The IMCgp100-202 (NCT03070392) is a randomized pivotal trial that evaluated overall survival (OS) of KIMMTRAK (tebentafusp-tebn) compared to investigator’s choice (either pembrolizumab, ipilimumab, or dacarbazine) in HLA-A*02:01-positive adult patients with previously untreated mUM. KIMMTRAK demonstrated an unprecedented OS benefit with a Hazard Ratio (HR) in the intent-to-treat population favoring KIMMTRAK, HR=0.51 (95% CI: 0.37, 0.71); p< 0.0001, over investigator’s choice (82% pembrolizumab; 13% ipilimumab; 6% dacarbazine).

IMPORTANT U.S. SAFETY INFORMATION Regarding FDA Approval

Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS occurred in 89% of patients who received KIMMTRAK with 0.8% being grade 3 or 4. Ensure immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS.

Skin Reactions

Skin reactions, including rash, pruritus, and cutaneous edema occurred in 91% of patients treated with KIMMTRAK. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions.

Elevated Liver Enzymes

Elevations in liver enzymes occurred in 65% of patients treated with KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.

Embryo-Fetal Toxicity

KIMMTRAK may cause fetal harm. Advise pregnant patients of potential risk to the fetus and patients of reproductive potential to use effective contraception during treatment with KIMMTRAK and 1 week after the last dose.

The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate.

Please see full Prescribing Information, including BOXED WARNING for CRS.

About ImmTAC Molecules
Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilising monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognise and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognise intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumours, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumours, regardless of mutational burden or immune infiltration, including immune "cold" low mutation rate tumours.

On February 25, 2022 Eisai (Headquarters: Tokyo, CEO: Haruo Naito) and Merck & Co., Inc., Kenilworth, N.J., U.S.A. (known as MSD outside the United States and Canada) reported that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved the combination of LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, plus KEYTRUDA, the anti-PD-1 therapy from Merck & Co., Inc., Kenilworth, N.J., U.S.A., for radically unresectable or metastatic renal cell carcinoma (RCC) (Press release, Eisai, FEB 25, 2022, View Source [SID1234609035]). LENVIMA plus KEYTRUDA is also approved in the U.S. and Europe for the first-line treatment of adult patients with advanced RCC. This marks the second approval of this combination in Japan; in December 2021, LENVIMA plus KEYTRUDA was approved for unresectable, advanced or recurrent endometrial carcinoma that progressed after chemotherapy.

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The approval is based on results from the pivotal Phase 3 CLEAR (Study 307)/KEYNOTE-581 trial, in which LENVIMA plus KEYTRUDA demonstrated statistically significant improvements versus sunitinib in the primary efficacy outcome measure of progression-free survival (PFS). Results showed LENVIMA plus KEYTRUDA (n=355) reduced the risk of disease progression or death by 61% (HR=0.39 [95% CI, 0.32-0.49]; p<0.0001), with a median PFS of 23.9 months versus 9.2 months for sunitinib (n=357).

"Nearly one in three cases of renal cell carcinoma are diagnosed at an advanced stage,1 and patients are in need of new treatment options that may improve survival outcomes, 2" said Dr. Gregory Lubiniecki, Vice President, Oncology Clinical Research, Merck & Co., Inc., Kenilworth, N.J., U.S.A. Research Laboratories. "In the CLEAR/KEYNOTE-581 trial, KEYTRUDA plus LENVIMA reduced the risk of disease progression or death by 61% versus sunitinib, a current standard of care. We are encouraged that patients with certain types of advanced renal cell carcinoma may have the opportunity to benefit from this combination."

"Today’s milestone for LENVIMA plus KEYTRUDA as a treatment for radically unresectable or metastatic renal cell carcinoma is particularly exciting as it marks the second approval for the combination in Japan," said Terushige Iike, President of Eisai Japan, Senior Vice President, Eisai. "We are thrilled to be able to provide Japanese patients with a new treatment option, illustrating our shared commitment with Merck & Co., Inc., Kenilworth, N.J., U.S.A. to develop therapies with the aim of addressing the unmet needs of those living with difficult-to-treat cancers. We would like to thank the patients, families and healthcare providers who made this approval possible."

The Japanese package inserts for LENVIMA and KEYTRUDA note that in the CLEAR /KEYNOTE-581 trial, adverse reactions were observed in 341 (96.9%) of 352 patients (including 42 of 42 Japanese patients) in the safety analysis set. The most common adverse reactions included diarrhea in 192 patients (54.5%), hypertension in 184 patients (52.3%), hypothyroidism in 150 patients (42.6%), decreased appetite in 123 patients (34.9%), fatigue in 113 patients (32.1%), stomatitis in 113 patients (32.1%), palmar-plantar erythrodysesthesia syndrome in 99 patients (28.1%), proteinuria in 97 patients (27.6%), nausea in 94 patients (26.7%), dysphonia in 87 patients (24.7%), rash in 77 patients (21.9%), and asthenia in 71 patients (20.2%).

Renal cell carcinoma is the most common type of kidney cancer worldwide; about nine out of 10 kidney cancer diagnoses are RCC.3 In Japan, there were more than 25,000 new cases of kidney cancer diagnosed and more than 8,000 deaths from the disease in 2020.4　Approximately 30% of patients with RCC will have metastatic disease at diagnosis.5 Survival is highly dependent on the stage at diagnosis, and with a five-year survival rate of 14% for patients diagnosed with metastatic disease, the prognosis for these patients is poor.6

Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A. continue to study the LENVIMA plus KEYTRUDA combination across several types of cancer with more than 20 clinical trials.

The approval is based on data from CLEAR (Study 307)/KEYNOTE-581 (ClinicalTrials.gov, NCT02811861(New Window)), a Phase 3, multicenter, open-label, randomized trial conducted in 1,069 patients with advanced RCC in the first-line setting. The primary efficacy outcome was PFS as assessed by blinded independent central review (BICR) according to RECIST v1.1. Key secondary efficacy outcome measures were overall survival and objective response rate.

Patients were randomized 1:1:1 to receive LENVIMA (20 mg orally once daily) plus KEYTRUDA (200 mg intravenously every three weeks for up to 24 months), or LENVIMA (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily for four weeks on treatment, followed by two weeks off treatment). Treatment continued until unacceptable toxicity or disease progression as determined by investigator and confirmed by BICR using RECIST v1.1. If disease progression was observed by imaging evaluation, clinically stable patients with no symptoms indicating disease progression were allowed to continue on study treatment until disease progression was observed in a subsequent imaging evaluation.

About LENVIMA (lenvatinib) Capsules

LENVIMA, discovered and developed by Eisai, is an orally available kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. In syngeneic mouse tumor models, LENVIMA decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone.

Currently, LENVIMA has been approved for monotherapy as a treatment for thyroid cancer in over 75 countries including Japan, in Europe, China and elsewhere in Asia, and in the United States for locally recurrent or metastatic, progressive, radioiodine-refractory differentiated thyroid cancer. In addition, LENVIMA has been approved for monotherapy as a treatment for unresectable hepatocellular carcinoma in over 70 countries including Japan, in Europe, China and in Asia, and in the United States for first-line unresectable hepatocellular carcinoma. LENVIMA has been approved for monotherapy as a treatment for unresectable thymic carcinoma in Japan. It is also approved in combination with everolimus as a treatment for renal cell carcinoma following prior antiangiogenic therapy in over 60 countries, including in Europe and Asia, and in the United States the treatment of adult patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy. In Europe, the agent was launched under the brand name Kisplyx for renal cell carcinoma. LENVIMA has been approved in combination with KEYTRUDA (generic name: pembrolizumab), for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC) in United States and in Europe. LENVIMA has been approved in combination with KEYTRUDA as a treatment for advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation in the United States, and has been approved for the similar indication (including conditional approval) in over 10 countries such as Canada and Australia. In some regions, continued approval for this indication is contingent upon verification and description of clinical benefit in the confirmatory trials. In Europe, it has been approved in combination with KEYTRUDA (generic name: pembrolizumab) as the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation. In Japan, it has been approved in combination with KEYTRUDA (generic name: pembrolizumab) for the treatment of patients with unresectable advanced or recurrent endometrial carcinoma that progressed after cancer chemotherapy and with radically unresectable or metastatic renal cell carcinoma.

About KEYTRUDA (pembrolizumab) Injection, 100mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck & Co., Inc., Kenilworth, N.J., U.S.A. has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

About the Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A. Strategic Collaboration

In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A., known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies will jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with KEYTRUDA, the anti-PD-1 therapy from Merck & Co., Inc., Kenilworth, N.J., U.S.A.

In addition to ongoing clinical studies evaluating the LENVIMA plus KEYTRUDA combination across several different tumor types, the companies have jointly initiated new clinical studies through the LEAP (LEnvatinib And Pembrolizumab) clinical program and are evaluating the combination in more than 10 different tumor types across more than 20 clinical trials.

Eisai’s Focus on Cancer

Eisai focuses on the development of anticancer drugs, targeting the tumor microenvironment (with experience and knowledge from existing in-house discovered compounds) and the driver gene mutation and aberrant splicing (leveraging RNA Splicing Platform) as areas (Ricchi) where real patient needs are still unmet, and where Eisai can aim to become a frontrunner in oncology. Eisai aspires to discover innovative new drugs with new targets and mechanisms of action from these Ricchi, with the aim of contributing to the cure of cancers.

On February 25, 2022 Chimeric Therapeutics (ASX:CHM, "Chimeric"), a clinical-stage cell therapy company and an Australian leader in cell therapy, reported that the first patient in dose level 3 of the phase 1 CHM 1101 (CLTX CAR T) clinical trial in recurrent/ progressive glioblastoma has now initiated therapy at City of Hope, one of the largest cancer research and treatment organizations in the United States (Press release, Chimeric Therapeutics, FEB 25, 2022, View Source [SID1234609034]).

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Patients in this dose level will receive a total dose of 240 X 106 CHM 1101 (CLTX CAR T) cells through dual routes of intratumoral and intraventricular administration. Advancement to this dose level has come about rapidly following on the completion of the 2nd dose cohort without any dose limiting toxicities in December 2021.

"We are very pleased with the continued progress of the trial," said Jennifer Chow, Chimeric Therapeutics Chief Executive Officer. "With the encouraging safety and activity signs shown in the lower two dose levels we are excited to be advancing to the higher dose levels that may provide more therapeutic benefit to patients with progressive or recurrent glioblastoma."

Authorised on behalf of the Chimeric Therapeutics board of directors by Chairman Paul Hopper.

ABOUT CHLOROTOXIN CAR T
Chlorotoxin CAR T (CLTX CAR T) cell therapy is a first and best in class CAR T cell therapy that has the potential to address the high unmet medical need of patients with recurrent/ progressive glioblastoma. Research to develop the intellectual property covering this CAR T cell therapy took place at City of Hope.

CLTX CAR T cell therapy uniquely utilizes chlorotoxin (CLTX), a peptide derived from scorpion toxin, as the tumour-targeting component of the chimeric antigen receptor (CAR). CLTX and CLTX CAR T cells have been shown in preclinical models to bind more broadly and specifically to GBM cells than other targeting domains like EGFR, HER-2 or IL-13.

In preclinical models, CLTX CAR T cells also demonstrated potent antitumor activity against glioblastoma while not exhibiting any off-tumor recognition of normal human cells and tissues, indicating a potentially optimal safety and efficacy profile.

On February 25, 2022 Clarity Pharmaceuticals (ASX: CU6) ("Clarity"), a clinical-stage radiopharmaceutical company developing next-generation products to address the growing needs in oncology, reported that it has successfully treated its first participant in cohort 2 of the 64Cu/67Cu SARTATE neuroblastoma therapy trial (CL04) at the increased dose level of 175MBq/kg body weight (Press release, Clarity Pharmaceuticals, FEB 25, 2022, https://www.claritypharmaceuticals.com/news/1patient_cohort2/ [SID1234608956]).

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Clarity has recently progressed to cohort 2 of the CL04 trial following the completion of cohort 1 where three participants received therapy with 67Cu SARTATE at a dose of 75MBq/kg body weight. The Safety Review Committee assessed the data from cohort 1 where no dose limiting toxicities have occurred and recommended to progress the trial to cohort 2, without modification, increasing the dose to 175MBq/kg body weight.

Clarity’s Executive Chairman, Dr Alan Taylor, commented, "We are very excited to dose the first patient in cohort 2 in our neuroblastoma therapy trial in the US, having successfully completed cohort 1 in January 2022. The increase in administered activity between cohorts 1 and 2 is significant in radiation-sensitive disease, such as neuroblastoma, and cohort 2 will see administered activities more than double in comparison to cohort 1. We look forward to continuing recruitment in cohort 2 at all five clinical sites in the US, building upon the encouraging initial data from cohort 1 and further gathering evidence of diagnostic and therapeutic benefits of the SARTATE product for the treatment of children with neuroblastoma."

The CL04 trial is a theranostic (diagnosis and therapy) trial in paediatric patients with high-risk neuroblastoma (NCT04023331)1. It is a multi-centre, dose-escalation, open label, non-randomised, Phase 1/2a clinical trial with up to 34 participants conducted at five clinical sites in the US.

Neuroblastoma most often occurs in children younger than 5 years of age and presents when the tumour grows and causes symptoms. It is the most common type of cancer to be diagnosed in the first year of life and accounts for around 15% of paediatric cancer mortality.2 High-risk neuroblastoma accounts for approximately 45% of all neuroblastoma cases. Patients with high-risk neuroblastoma have the lowest 5-year survival rates at 40%-50%.3

In 2020, the US Food and Drug Administration (FDA) awarded Clarity two Orphan Drug Designations (ODDs), one for 64Cu SARTATE as a diagnostic agent for the clinical management of neuroblastoma and one for 67Cu SARTATE as a therapy of neuroblastoma, as well as two Rare Paediatric Disease Designations (RPDDs) for these products. Should Clarity be successful in achieving US FDA New Drug Applications for these two products, RPDDs may potentially allow the Company to access a total of two tradeable Priority Review Vouchers (PRVs) which most recently traded at USD110M per voucher.4

Dr Taylor said, "Our team, clinicians and collaborators have all shown strong dedication to progressing the neuroblastoma trial at some of the best cancer centres in the US, driven by our mutual goal of improving the treatment paradigm for children with this insidious disease. In the times when the pandemic was having a significant impact on clinical site operations and recruitment, this support is indicative of the importance and urgency of improving the prognosis of children with high-risk neuroblastoma, where current treatment strategies are limited. We continue working closely with the clinical sites and the US FDA to progress this trial swiftly, building upon the mounting evidence of the advantages of the SARTATE treatment paradigm over current treatment regiments, in pursuit of Clarity’s ultimate goal of improving treatment outcomes for children and adults with cancer."

This announcement has been authorised for release by the Executive Chairman.