On February 25, 2022 Elthera AG, iCellate Medical AB, Targos Molecular Pathology GmbH and Prof. Dr. Susanne Sebens at the Institute of Experimental Cancer Research (IET) at the University of Kiel are proud reported that the clinical trial for their joint project ELEVATE, funded by the EUREKA Eurstars programme, has commenced (Press release, Elthera, FEB 25, 2022, View Source;utm_medium=rss&utm_campaign=1400-2 [SID1234609049]).

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We are excited to enroll the first subject into the ELEVATE clinical trial. Over the next two years, this trial aims to enroll approximately 200 subjects with colorectal or pancreatic cancer, as well as 50 healthy controls. Tumor and liquid biopsy samples will be collected at the Institute of Experimental Cancer Research at the University of Kiel and will be analysed by the project partners iCellate, Elthera, IET, and Targos. Samples will be analysed for the presence of the cancer-associated target protein L1CAM on tumors, circulating tumor cells and in plasma, with the aim of establishing an integrated diagnostic armamentarium to support patient selection and treatment monitoring for the anti-L1CAM immunotherapy developed by Elthera.

Since the project’s inception in late 2020, Elthera AG (Schlieren, Switzerland) has nominated the clinical candidate molecule for its anti-L1CAM therapy and has initiated pilot preclinical safety studies. iCellate Medical AB (Solna, Sweden) has developed a liquid biopsy-based analysis to identify patients with L1CAM+ circulating tumor cells (CTCs), and Targos Molecular Pathology GmbH (Kassel, Germany) has developed a solid tumor-based immunohistochemistry method to identify patients with L1CAM+ tumors. Prof. Dr. Susanne Sebens’ group at the IET (Kiel, Germany) has prepared for patient recruitment. IET will further evaluate the potential of the anti-L1CAM therapy to be combined with established chemo- and immunotherapies.

"I can’t describe how exiciting this is. To start this very important trial that we now have prepared for over a year is a significant milestone in this project and for iCellate’s circulating tumor cell (CTC) platform, CellMate" says Åsa Rosenquist, VP R&D at iCellate Medical.

Gunther Spohn, CSO of Elthera, comments: "This study will be instrumental in developing a powerful diagnostic toolbox for the clinical testing of our innovative anti-L1CAM immunotherapy. The integration of both solid and liquid tumor biomarkers will provide invaluable information for both patient selection and treatment monitoring in our upcoming clinical phase I/II studies."

On February 25, 2022 GlycoMimetics, Inc. (Nasdaq: GLYC) reported that it will host a conference call and webcast to report its fourth quarter and 2021 year-end financial results on Thursday, March 3, 2022, at 8:30 a.m. ET (Press release, GlycoMimetics, FEB 25, 2022, View Source [SID1234609048]).

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The dial-in number for the conference call is (844) 413-7154 for domestic participants and (216) 562-0466 for international participants, with participant code 4048456. Participants are encouraged to connect 15 minutes in advance of the call to ensure they can connect. A webcast replay will be available via the "Investors" tab on the GlycoMimetics website for 30 days following the call. A dial-in phone replay will be available for 24 hours after the close of the call by dialing (855) 859-2056 for domestic participants and (404) 537-3406 for international participants, with participant code 4048456.

On February 25, 2022 Rubius Therapeutics, Inc. (Nasdaq: RUBY), a clinical-stage biopharmaceutical company that is biologically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics for the treatment of cancer and autoimmune diseases, reported fourth quarter and full year 2021 financial results (Press release, Rubius Therapeutics, FEB 25, 2022, View Source [SID1234609047]).

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"Twenty twenty-one was a year of strong execution for Rubius Therapeutics as we advanced our clinical oncology pipeline, strengthened our in-house manufacturing capabilities and showed preclinical proof of concept of our tolerance induction approach in type 1 diabetes, which has the potential to be extended to other T cell-mediated autoimmune diseases," said Pablo J. Cagnoni, M.D., president and chief executive officer of Rubius Therapeutics. "Twenty twenty-two is set to be a catalyst rich year with several clinical data milestones, including, during the first quarter, updated results from our single-agent RTX-240 Phase 1 clinical trial in advanced solid tumors and, during the second half of 2022, initial clinical data from our RTX-240 Phase 1 arm in combination with pembrolizumab in advanced solid tumors and from our RTX-321 clinical trial in advanced HPV 16-positive cancers."

Anticipated 2022 Catalysts and Operational Objectives

Present additional clinical results from the Phase 1 arm of the RTX-240 Phase 1/2 clinical trial in advanced solid tumors and the Phase 1 arm in relapsed/refractory acute myeloid leukemia (AML) during the first quarter of 2022
Initiate RTX-240 Phase 2 expansion cohorts in select solid tumor types during the first quarter of 2022
Report initial clinical results from the Phase 1 clinical trial of RTX-321 in patients with advanced HPV 16-positive cancers during the second half of 2022
Present initial clinical data from the Phase 1 arm of the RTX-240 clinical trial in combination with pembrolizumab in patients with advanced solid tumors during the second half of 2022
Fourth Quarter and Full Year 2021 Highlights

Broad Immune Stimulation

RTX-240

Established clinical proof of concept of RTX-240 in advanced solid tumors, based on initial results reported in March 2021, potentially increasing the likelihood of clinical success across the oncology pipeline
Patients continue to be dosed in the single-agent RTX-240 Phase 1 solid tumor clinical trial, with no dose-limiting toxicities observed to date and a clear dose response in the increase of NK cells and other pharmacodynamic effects
Additional clinical results are expected from this trial and the Phase 1 arm in relapsed/refractory AML during the first quarter of 2022
The Company plans to initiate RTX-240 Phase 2 expansion cohorts in select solid tumor types during the first quarter of 2022
Continuing dose escalation in the RTX-240 Phase 1 combination study with pembrolizumab in patients with advanced solid tumors with initial clinical data expected during the second half of 2022
RTX-224

In January 2022, the first patient was dosed in the Phase 1/2 clinical trial of RTX-224 in selected relapsed/refractory or locally advanced solid tumors that include non-small cell lung cancer, cutaneous melanoma, head and neck squamous cell carcinoma, urothelial (bladder) carcinoma and triple-negative breast cancer
Presented preclinical data at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting in November 2021, demonstrating that the mouse surrogate of RTX-224, mRBC-224, generated potent anti-tumor activity in B16F10 melanoma models, intravenously and subcutaneously, that was associated with pharmacodynamic changes in blood and tumors, including activated CD4+ and CD8+ T cells, NK cells and macrophages
Antigen-Specific Immune Stimulation

RTX-321 Artificial Antigen-Presenting Cell (aAPC) Development Program for Human Papillomavirus (HPV) 16-Positive Cancers

Continuing enrollment in the Phase 1 clinical trial of RTX-321 in patients with advanced HPV 16-positive cancers with no dose limiting toxicities observed to date
Planning to report initial clinical results during the second half of 2022
Autoimmune Diseases and Type 1 Diabetes

Demonstrated tolerance induction with bystander suppression in stringent type 1 diabetes preclinical models
Established efficacy in the BDC2.5 adoptive transfer model with data supporting that repeated dosing extended duration of disease protection, reversed established inflammation, which is important for the treatment of existing autoimmunity, and induced two types of regulatory T cells, resulting in protection against re-challenge
Showed efficacy in non-obese diabetes (NOD) preclinical model
Results at 25 weeks exhibit bystander suppression by delivering only two antigens, indicating the mouse surrogate of RTX-T1D prevented or delayed disease caused by many autoantigens
These findings are potentially translatable beyond type 1 diabetes to multiple autoimmune diseases, including other Rubius’ high priority target indications, multiple sclerosis and celiac disease
Manufacturing

Increased cells produced per batch by four times in 50L bioreactors from 2020 to 2021, enabling uninterrupted clinical supply for three Phase 1 arms of the RTX-240 clinical trial and Phase 1 RTX-321 trial
Introduced frozen drug substance for RTX-321 and RTX-224, potentially enabling inventory storage of greater than two years
In process of scaling to 200L bioreactors by mid-2022 to support potential pivotal trials and eventual commercialization
Fourth Quarter 2021 Financial Results

Net loss for the fourth quarter of 2021 was $55.0 million or $0.61 per common share, compared to $40.5 million or $0.50 per common share in the fourth quarter of 2020.

In the fourth quarter of 2021, Rubius invested $39.8 million in research and development (R&D) related to its novel RED PLATFORM and towards expanding and advancing its product pipeline, as compared to $25.6 million in the fourth quarter of 2020. This year-over-year increase was principally due to a $11.0 million increase in costs incurred for the Company’s lead cancer programs, RTX-240 and RTX-321, primarily from clinical research organization (CRO) and internal manufacturing costs incurred in connection with the three arms of its Phase 1/2 clinical trial of RTX-240, for its Phase 1 clinical trial of RTX-321 for the treatment of HPV16-positive cancers and for start-up costs related to its Phase 1 clinical trial of RTX-224. Additionally, personnel-related costs increased $1.4 million principally for additions to headcount to support the Company’s expanded operations and stock-based compensation increased by $1.5 million.

General and administrative (G&A) expenses were $13.9 million during the fourth quarter of 2021, as compared to $14.1 million for the fourth quarter of 2020. While there were increases totaling $1.0 million across professional fees, facility and personnel costs, they were offset by a decline in stock-based compensation expense of $1.2 million following the full vesting of large awards early in the third quarter of 2021.

Full Year 2021 Financial Results

Net loss for the full year 2021 was $196.5 million or $2.23 per common share, compared to $167.7 million or $2.08 per common share for the full year 2020.

For the full year 2021, Rubius invested $141.6 million in R&D related to its novel RED PLATFORM and towards expanding and advancing its product pipeline, as compared to $116.1 million for the full year 2020. The year-over-year increase was driven by $28.7 million of incremental costs to advance the Company’s lead cancer programs, including CRO and internal manufacturing costs. These costs were associated with the three arms of its Phase 1/2 clinical trial of RTX-240, for its Phase 1 clinical trial of RTX-321 in patients with advanced HPV 16-positive cancers, and for start-up costs related to its Phase 1 clinical trial of RTX-224. The increase in cancer program costs was partially offset by a $5.0 million reduction in rare disease program costs following the deprioritization of the Company’s rare disease pipeline in March 2020. Additionally, platform development, early-stage research and other unallocated expenses increased by $1.8 million. This consisted of $4.3 million in additional stock-based compensation and a $3.1 million increase in personnel and facility related costs, which were partially offset by reductions in contract R&D, laboratory supplies and research materials as research activities shifted to support clinical programs.

G&A expenses were $53.0 million during full year of 2021, as compared to $50.3 million for the same period in 2020. The higher costs were driven by a $3.4 million increase in personnel and facility related costs, as well as a $1.6 million increase in professional and consultant fees. These increases were offset by a decrease in stock-based compensation expense following the vesting of large awards early in the second half of 2021.

Cash Position

As of December 31, 2021, cash and cash equivalents were $225.8 million as compared to $176.3 million in cash, cash equivalents and investments as of December 31, 2020, providing Rubius with a cash runway into the second quarter of 2023 and the ability to extend the runway into the middle of 2023. In connection with its underwritten public offering completed in March 2021, the Company received net proceeds of $187.2 million, after deducting underwriting discounts and commission and other offering costs. In addition, in June 2021, the Company amended its debt facility, postponing principal payments by two and a half years, until mid-2024.
About RTX-240
RTX-240, Rubius Therapeutics’ lead oncology program, is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to simultaneously present hundreds of thousands of copies of the costimulatory molecule 4-1BB ligand (4-1BBL) and IL-15TP (trans-presentation of IL-15 on IL-15Rα) in their native forms. RTX-240 is designed to broadly stimulate the immune system by activating and expanding both NK and memory T cells to generate a potent anti-tumor response.

About RTX-321
RTX-321, the Company’s second oncology program, is an allogeneic, off-the-shelf aAPC therapy product candidate that is engineered to induce a tumor-specific immune response by expanding antigen-specific T cells. RTX-321 expresses hundreds of thousands of copies of an HPV peptide antigen bound to major histocompatibility complex class I proteins, the costimulatory molecule 4-1BBL and the cytokine IL-12 on the cell surface to mimic human T cell-APC interactions.

About RTX-224
RTX-224 is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to express hundreds of thousands of copies of 4-1BBL and IL-12 on the cell surface. In contrast to RTX-240, RTX-224 is designed as a broad immune agonist of both adaptive and innate responses, activating CD8+ and CD4+ T cells, promoting antigen presentation and activating and expanding NK cells. It is expected to produce a broad and potent anti-tumor T cell response, an innate immune response and have anti-tumor activity in those tumor types with known sensitivity to T cell killing, including tumor types with high mutational burden, PD-L1 expression and prior activity of checkpoint inhibitors.

About Red Cell Therapeutics in Autoimmune Diseases
Red Cell Therapeutics for the treatment of autoimmune disease are biologically engineered to express proteins and peptides inside the cell and are designed to be phagocytized, or ingested, by dendritic cells or macrophages to induce tolerance, retraining the immune system to no longer recognize these self-antigens as foreign.

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

Graphic

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.