On April 18, 2023 Mythic Therapeutics, a clinical-stage biotechnology company focused on the development of next-generation antibody-drug conjugate therapies for the treatment of a wide range of cancers, reported preclinical data highlighting the potential of MYTX-011, its investigational cMET-targeting ADC, for treating a broader range of cMET+ cancers than other cMET-targeting ADCs in development (Press release, Mythic Therapeutics, APR 18, 2023, View Source;utm_medium=rss&utm_campaign=mythic-therapeutics-presents-preclinical-data-on-investigational-cmet-targeting-antibody-drug-conjugate-adc-mytx-011-at-american-association-for-cancer-research-aacr-annual-meeting [SID1234630247]). These data were presented today as a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

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"We are excited by the findings of this study, which demonstrate the potential of MYTX-011 to not only expand the use of ADCs to patients who have not been eligible for treatment due to their level of target expression or tumor type, but also increase ADC efficacy as compared to current cMET-targeting ADCs in development," said Gilles Gallant, BPharm, PhD, FOPQ, Chief Development Officer at Mythic Therapeutics. "These data reinforce the continued evaluation of MYTX-011, not only through our ongoing Phase 1 KisMET-01 clinical trial in NSCLC, where cMET overexpression occurs in up to 70% of cases,[1],[2] but also for patients with other cMET-expressing cancers who are still in need of targeted treatment options."

Details of the poster presentation are as follows:

Title: MYTX-011: A novel cMET-targeting antibody-drug conjugate (ADC) engineered to increase on-target uptake in and efficacy against cMET expressing tumors
Presenter: Nimish Gera, Ph.D., Vice President, Biologics at Mythic Therapeutics
Session Title: Targeting Protein Kinases and Phosphatases for Therapy 1
Session Date and Time: Today, April 18, 2023, from 1:30 PM – 5:00 PM
Location: Poster Section 17
Poster Board Number: 13

Published Abstract Number: 5000

MYTX-011 was designed using Mythic’s FateControl platform by introducing an optimized set of mutations into an anti-cMET antibody. This engineering is designed to allow MYTX-011 to bind cMET on the surface of cancer cells and be selectively freed once inside of cancer cells, increasing the delivery of a potent chemotherapy, MMAE, inside of cancer cells.

In this study, the efficacy of MYTX-011 was evaluated on 62 different cancer cell lines grown in vitro, including NSCLC, head and neck, gastric, pancreatic and other cancer types which are known to express cMET. The efficacy of MYTX-011 was also evaluated in mouse models of NSCLC that expressed moderate and high levels of cMET, as measured by an immunohistochemistry (IHC) test.

MYTX-011 demonstrated higher internalization in cMET+ tumor cells and broader, more potent efficacy, including a greater than 3-fold increase in efficacy in mouse models of NSCLC, as compared to other cMET-targeting ADCs. MYTX-011 also exhibited favorable pharmacokinetics in monkeys including increased half-life, reduced target-mediated drug disposition, and reduced release of free MMAE payload, as compared to other cMET-targeting ADCs. The toxicity profile of MYTX-011 in monkeys was consistent with other vcMMAE-based ADCs. No MYTX-011-related clinical toxicities were found, and the only findings included MMAE-related neutropenia and mild bone marrow toxicity, both of which were reversible.

Mythic recently announced that the first subject was dosed with MYTX-011 in its Phase 1 KisMET-01 multi-center, dose escalation and dose expansion clinical trial in subjects with NSCLC. More information about the clinical trial is available at clinicaltrials.gov (identifier: NCT05652868).

About MYTX-011

MYTX-011, a cMET-targeting ADC, leverages Mythic’s innovative FateControl technology, which allows ADCs to actively navigate inside of cells to potentially increase delivery of anti-cancer agents to tumor cells with less impact on healthy cells. This breakthrough approach takes the next step beyond linker-payload technologies and is designed to improve ADC efficacy against a broad set of molecular targets and patient profiles.

On April 18, 2023 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported its participation in Stifel 2023 Targeted Oncology Days (Press release, Kura Oncology, APR 18, 2023, View Source [SID1234630246]). Troy Wilson, Ph.D., J.D., President and Chief Executive Officer, is scheduled to participate in a virtual fireside chat at 1:00 p.m. ET / 10:00 a.m. PT on April 25, 2023.

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A live audio webcast of the fireside chat will be available in the Investors section of Kura’s website at www.kuraoncology.com, with an archived replay following the event.

On April 18, 2023 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported updated results from the Phase 1 study evaluating the safety and efficacy of once-weekly selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis (NCT04562389) (Press release, Karyopharm, APR 18, 2023, View Source [SID1234630245]). The data, featured in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, show that rapid, deep and sustained spleen responses and robust symptom improvement were achieved at both weeks 12 and 24, in patients treated with selinexor 60mg in combination with ruxolitinib.

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As of the February 24, 2023 data cut-off date, 24 patients had been assigned to either a 40mg or 60mg once weekly dose of selinexor, combined with ruxolitinib. All patients initiated treatment > 24 weeks prior to the data cut-off date.

Key Findings

Efficacy
SVR35 (≥35% reduction in spleen volume) and TSS50 (≥50% reduction in total symptom score)

60mg of selinexor
Week 12
Efficacy evaluable population: 83.3% SVR35 and 80.0% TSS50
Intent to treat population: 71.4% SVR35 and 66.7% TSS50
Week 24
Efficacy evaluable population: 91.7% SVR35 and 77.8% TSS50
Intent to treat population: 78.6% SVR35 and 58.3% TSS50
SVR35 responses were observed in 100% of evaluable patients at any time and rates were consistent regardless of subgroups, including males and patients treated with low dose ruxolitinib.
Improvement in major spleen and cytokine-related symptoms were observed across all MFSAF (Myelofibrosis Symptom Assessment Form) domains.
40mg of selinexor
Week 12
Efficacy evaluable population: 30.0% SVR35 and 66.7% TSS50
Intent to treat population: 30.0% SVR35 and 60.0% TSS50
Week 24
Efficacy evaluable population: 50.0% SVR35 and 57.1% TSS50
Intent to treat population: 40.0% SVR35 and 40.0% TSS50
Safety

Both the 40mg and 60mg dose levels of selinexor were generally well tolerated and manageable, allowing most patients to remain on therapy, up to 68 weeks, as of the data cut-off date.
The most common treatment emergent adverse events (TEAEs), regardless of grade, experienced with the 40mg and 60mg selinexor doses, respectively, in combination with ruxolitinib were nausea (70.0%; 78.6%), anemia (40.0%; 64.3%) and fatigue (60.0%; 57.1%), most of which were grades 1-2.
The most common treatment emergent grade ≥3 adverse events experienced with the 40mg and 60mg selinexor doses, respectively, in combination with ruxolitinib were anemia (30.0%; 42.9%), thrombocytopenia (10.0%, 28.6%) and neutropenia (20.0%; 7.1%).
There were two treatment-related discontinuations, one due to thrombocytopenia and one due to peripheral neuropathy.
75% of nausea events were grade 1, were mostly transient and did not lead to treatment-related discontinuations. Nausea rates and grades were reduced for patients who received prophylactic antiemetics. Meaningful weight gain was observed at week 24 despite the incidence of nausea.
"We are enthusiastic about the impressive spleen volume reductions and robust symptom improvement observed with the 60mg dose of selinexor and ruxolitinib combination at week 24, which represent very meaningful improvements relative to the current standard of care of ruxolitinib alone. These data suggest that the combination of selinexor and ruxolitinib has the potential to be a transformative therapy for first line myelofibrosis patients," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. "We are also very encouraged by the preliminary data showing rapid normalization in platelets and stability of hemoglobin levels, as potential evidence of disease modification for these patients. We look forward to building upon these findings as we plan the initiation of a pivotal Phase 3 study in front-line myelofibrosis later this quarter."

"There remains significant unmet need in the treatment of myelofibrosis, with less than half of patients achieving an SVR35 with the current standard of care therapy," said Dr. Haris Ali, City of Hope Comprehensive Cancer Center. "The spleen responses and symptom improvements seen across all patients with the 60mg selinexor dose is very compelling. These data suggest this tolerable and unique combination of XPO1 and JAK inhibition has the potential to significantly improve these key efficacy measures for first line myelofibrosis patients."

Both the efficacy and safety data support the 60 mg dose of selinexor as the recommended dose in combination with ruxolitinib. A double-blind, randomized, Phase 3 trial of selinexor 60 mg in combination with ruxolitinib versus placebo in combination with ruxolitinib in JAKi treatment-naïve patients with myelofibrosis is expected to initiate in the first half of 2023.

Investor Webcast on Selinexor Data in Patients with Treatment-Naïve Myelofibrosis at AACR (Free AACR Whitepaper) 2023
Karyopharm will host a webcast today, April 18, 2023, at 4:30 p.m. Eastern Time, with key opinion leader Dr. John Mascarenhas, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders. Dr. Mascarenhas will discuss the relevance of the updated data with selinexor in combination with ruxolitinib to the current treatment landscape and unmet medical need in treating patients with myelofibrosis. He will also describe the design of the Company’s selinexor and ruxolitinib Phase 3 study as the study’s primary investigator.

To access the event, please dial (888) 349-0102 (local) or (412) 902-4299 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with accompanying slides, will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will be available on the Company’s website following the event.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, China, South Korea, Canada, Israel and Taiwan. XPOVIO and NEXPOVIO is marketed by Karyopharm’s partners, Antengene, Menarini, Neopharm and FORUS, in China, South Korea, Singapore, Australia, Hong Kong, Germany, Austria, Israel and Canada.

Please refer to the local Prescribing Information for full details.

Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.

Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.

Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.

Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.

Serious Infection: Monitor for infection and treat promptly.

Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.

Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.

Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.

The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to breastfeed.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1–888–209–9326 or FDA at 1–800–FDA–1088 or www.fda.gov/medwatch.

On April 18, 2023 Johnson & Johnson (NYSE: JNJ) reported results for first-quarter 2023 (Press release, Johnson & Johnson, APR 18, 2023, View Source [SID1234630244]). "Our first quarter results demonstrate strong performance across all three segments of our business and reflect the dedication of Johnson & Johnson colleagues around the world," said Joaquin Duato, Chairman of the Board and Chief Executive Officer. "With this momentum, I look forward to the remainder of the year, one filled with exciting catalysts that will create both near- and long-term value for patients and all of our stakeholders."

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OVERALL FINANCIAL RESULTS:
overallresultsupdatedformat.jpg
1 Non-GAAP financial measure; refer to reconciliations of non-GAAP financial measures included in accompanying schedules
2 Excludes the impact of translational currency
3 Excludes the net impact of acquisitions and divestitures and translational currency
4 Excludes intangible amortization expense and special items
5 Basic shares are used to calculate loss per share as use of diluted shares when in a loss position would be anti-dilutive
Note: values may have been rounded

REGIONAL SALES RESULTS:
updatedregionalsales.jpg
1 Non-GAAP financial measure; refer to reconciliations of non-GAAP financial measures included in accompanying schedules
2 Excludes the impact of translational currency
3 Excludes the net impact of acquisitions and divestitures and translational currency
Note: values may have been rounded

SEGMENT SALES RESULTS:
updatedsegmentsales.jpg
1 Non-GAAP financial measure; refer to reconciliations of non-GAAP financial measures included in accompanying schedules
2 Excludes the impact of translational currency
3 Excludes the net impact of acquisitions and divestitures and translational currency
Note: Values may have been rounded

FIRST QUARTER 2023 SEGMENT COMMENTARY:
Adjusted operational sales* reflected below excludes the net impact of acquisitions and divestitures and translational currency.

Consumer Health
Consumer Health worldwide adjusted operational sales increased 11.3%* largely driven by over-the-counter (OTC) products. Major contributors to growth in OTC were TYLENOL and MOTRIN analgesics, upper respiratory products, IMODIUM in digestive health products and international smoking cessation products. Additional contributors to growth were NEUTROGENA and AVEENO in Skin Health/Beauty products and JOHNSON’s in Baby Care products.

Pharmaceutical
Pharmaceutical worldwide adjusted operational sales grew 7.2%*, driven by DARZALEX (daratumumab), a biologic for the treatment of multiple myeloma, STELARA (ustekinumab), a biologic for the treatment of a number of immune-mediated inflammatory diseases, ERLEADA (apalutamide), a next-generation androgen receptor inhibitor for the treatment of patients with prostate cancer, CARVYKTI (ciltacabtagene autoleucel), a BCMA-directed CAR-T immunotherapy for the treatment of patients with relapsed or refractory multiple myeloma, and XARELTO (rivaroxaban), a direct oral anticoagulant. Also contributing to growth were sales of the Janssen COVID-19 Vaccine (Ad26.COV2.S) for the prevention of the SARS-CoV-2 Virus. This growth was partially offset by declines in sales of REMICADE (infliximab), a biologic approved for the treatment of several immune-mediated inflammatory diseases, IMBRUVICA (ibrutinib), an oral, once daily therapy approved for use in treating certain B-cell malignancies, a type of blood or lymph node cancer, and ZYTIGA (abiraterone acetate), an oral, once daily medication for use in combination with prednisone for the treatment of metastatic castration-resistant prostate cancer.

MedTech
MedTech worldwide adjusted operational sales grew 6.4%*, driven primarily by electrophysiology products in Interventional Solutions, contact lenses in Vision, wound closure products in General Surgery, and knees in Orthopaedics. MedTech worldwide operational sales grew 11.0%*, with the acquisition of Abiomed contributing 4.6%.

NOTABLE NEW ANNOUNCEMENTS IN THE QUARTER:
The information contained in this section should be read in conjunction with Johnson & Johnson’s other disclosures filed with the Securities and Exchange Commission, including its Current Reports on Form 8-K, Quarterly Reports on Form 10-Q and Annual Reports on Form 10-K. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. The reader is also encouraged to review all other news releases and information available in the Investors section of the company’s website at news releases, as well as www.factsabouttalc.com, www.factsaboutourprescriptionopioids.com, and www.LTLManagementInformation.com.

Regulatory
Janssen Receives Positive CHMP Opinion for AKEEGA (Niraparib and Abiraterone Acetate Dual Action Tablet) Plus Prednisone or Prednisolone for the Treatment of Adult Patients with BRCA1/2 Gene-Mutated Metastatic Castration Resistant Prostate Cancer
Press Release
Janssen Submits New Drug Application to the U.S. Food and Drug Administration Seeking Approval of Niraparib and Abiraterone Acetate Dual-Action Tablet, Plus Prednisone, as a First-Line Targeted Treatment for Patients with Metastatic Castration-Resistant Prostate Cancer with BRCA Gene Mutations
Press Release
Data Release
Janssen Announces Unblinding of Phase 3 CARTITUDE-4 Study of CARVYKTI (cilta-cel) as Primary Endpoint Met in Treatment of Patients with Relapsed and Refractory Multiple Myeloma
Press Release
Late Breaking Data on Pulmonary Vein Isolation with HELIOSTAR Balloon Ablation Catheter Presented at AF Symposium 2023
Press Release
First Look at Data on Biosense Webster’s Investigational Pulsed Field Ablation Platform Presented at AF Symposium 2023
Press Release
Janssen Reports Positive Topline Phase 2 Results for Nipocalimab in Pregnant Individuals at High Risk for Severe Hemolytic Disease of the Fetus and Newborn (HDFN)
Press Release
Janssen Data at ASCO (Free ASCO Whitepaper) GU Support Ambition to Transform Treatment of Prostate and Bladder Cancer Through Precision Medicine and Early Intervention
Press Release
TREMFYA (guselkumab) Demonstrates a Differentiated Binding Mechanism from Risankizumab in In Vitro Studies
Press Release
New STELARA (ustekinumab) Long-Term Data Support its Established Safety Profile in Inflammatory Bowel Disease and Durable Efficacy in Ulcerative Colitis
Press Release
Late-Breaking Phase 3 A DUE Data Show Investigational Single Tablet Combination Therapy of Macitentan and Tadalafil Significantly Improves Pulmonary Hemodynamics versus Monotherapy in Patients with Pulmonary Arterial Hypertension (PAH)
Press Release
TREMFYA (guselkumab) Real-World Data Analyses Show Greater Treatment Persistence Than IL-17s in Both Bio-naïve and Bio-experienced Patients Living With Moderate to Severe Plaque Psoriasis
Press Release
New RYBREVANT (amivantamab-vmjw) Data Showed Long-Term Clinical Response and Safety in Patients with Advanced Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations Who Have Failed Prior Platinum-Based Chemotherapy
Press Release
Other
Johnson & Johnson Subsidiary LTL Management LLC ("LTL") Re-Files for Voluntary Chapter 11 to Equitably Resolve All Current and Future Talc Claims1
Press Release
Johnson & Johnson Appoints Dr. John Reed as Executive Vice President, Pharmaceuticals, R&D
Press Release
Johnson & Johnson Names Dr. Paula A. Johnson, President of Wellesley College, to its Board of Directors
Press Release
Johnson & Johnson Announces Pricing of $7.75 Billion of Senior Notes Issued by Kenvue Inc.
Press Release
Janssen Provides Portfolio Update
Press Release
ERLEADA (apalutamide), First-and-Only Next-Generation Androgen Receptor Inhibitor with Once-Daily, Single-Tablet Option, Now Available in the U.S.1
Press Release

1 Subsequent to the quarter

FULL-YEAR 2023 GUIDANCE:

Johnson & Johnson does not provide GAAP financial measures on a forward-looking basis because the company is unable to predict with reasonable certainty the ultimate outcome of legal proceedings, unusual gains and losses, acquisition-related expenses and purchase accounting fair value adjustments without unreasonable effort. These items are uncertain, depend on various factors, and could be material to Johnson & Johnson’s results computed in accordance with GAAP.

($ in Billions, except EPS)
April 2023
January 2023
Adjusted Operational Sales1,2,5
Change vs. Prior Year / Mid-point
4.5% – 5.5% / 5.0%
3.5% – 4.5% / 4.0%
Operational Sales2,5/ Mid-point2,5
Change vs. Prior Year / Mid-point
$97.9B – $98.9B / $98.4B
5.5% – 6.5% / 6.0%
$96.9B – $97.9B / $97.4B
4.5% – 5.5% / 5.0%
Estimated Reported Sales3,5/ Mid-point3,5
Change vs. Prior Year / Mid-point
$97.9B – $98.9B / $98.4B
5.5% – 6.5% / 6.0%
$96.9B – $97.9B / $97.4B
4.5% – 5.5% / 5.0%
Adjusted Operational EPS (Diluted)2,4/ Mid-point2,4
Change vs. Prior Year / Mid-point
$10.50 – $10.60 / $10.55
3.5% – 4.5% / 4.0%
$10.40 – $10.60 / $10.50
2.5% – 4.5% / 3.5%
Adjusted EPS (Diluted)3,4 / Mid-point3,4
Change vs. Prior Year / Mid-point
$10.60 – $10.70 / $10.65
4.5% – 5.5% / 5.0%
$10.45 – $10.65 / $10.55
3.0% – 5.0% / 4.0%

1 Non-GAAP financial measure; excludes the net impact of acquisitions and divestitures
2 Non-GAAP financial measure; excludes the impact of translational currency
3 Calculated using Euro Average Rate: January 2023 = $1.08 and April 2023 = $1.10 (Illustrative purposes only)
4 Non-GAAP financial measure; excludes intangible amortization expense and special items
5 Excludes COVID-19 Vaccine
Note: percentages may have been rounded

Other modeling considerations will be provided on the webcast.

WEBCAST INFORMATION:
Johnson & Johnson will conduct a conference call with investors to discuss this earnings release today at 8:30 a.m., Eastern Time. A simultaneous webcast of the call for investors and other interested parties may be accessed by visiting the Johnson & Johnson website. A replay and podcast will be available approximately two hours after the live webcast in the Investors section of the Company’s website at events-and-presentations.

On April 18, 2023 Immunocore Holdings plc (Nasdaq: IMCR), 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, infectious diseases and autoimmune conditions, reported four posters with KIMMTRAK (tebentafusp-tebn) data in HLA-A*02:01 patients with metastatic uveal melanoma (mUM), at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 (Press release, Immunocore, APR 18, 2023, View Source [SID1234630241]).

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"KIMMTRAK is now approved in over 30 countries and delivering benefit to hundreds of patients. The Phase 3 trial data presented at AACR (Free AACR Whitepaper) confirms that ctDNA reduction from tebentafusp is strongly associated with survival benefit," said David Berman, Head of Research and Development of Immunocore. "We are also proud to share the almost 4-year follow-up from the Phase 2 trial, which now represents the largest and longest follow-up on survival and safety from any TCR therapy to date."

Circulating tumor DNA (ctDNA) reduction by week 9 was observed in 88% of mUM patients treated as first-line (Phase 3 trial) and 71% in previously treated patients (Phase 2 trial); in both trials, this reduction was associated with longer overall survival (OS). ctDNA clearance was also higher in first-line patients (37%) compared to second-line patients (13%). ctDNA clearance in the Phase 3 trial was associated with 84% 1-year OS. In both trials, the association between ctDNA reduction and longer OS was also observed in patients with best RECIST response of progressive disease (PD), indicating that RECIST responses underestimate tebentafusp’s clinical benefits, and that ctDNA may be a better predictor of long OS than radiographic response.

The final analysis from the Phase 2 trial in previously treated mUM, after 46 months of follow-up, showed a median OS of 16.8 months – consistent with previous data updates. The landmark OS rates from the trial were approximately double historical rates in this patient population, as reported in two meta-analyses1,2. Later in 2023, the Company intends to provide an OS update from the Phase 3 trial. At the time of primary analysis in 2020, the median OS was 21.7 months for patients treated with KIMMTRAK, versus 16.0 months for those treated with investigator’s choice.

1 Rantala ES, Hernberg M, Kivela TT. Overall survival after treatment for metastatic uveal melanoma: a systematic review and meta-analysis. Melanoma Res. 2019; 29:561-568.
2 Khoja L, Atenafu EG, Suciu S, et al. Meta-analysis in metastatic uveal melanoma to determine progression free and overall survival benchmarks: an international rare cancers initiative (IRCI) ocular melanoma study. Ann Oncol. 2019; 30:1370-1380

The third poster provides a pooled analysis from 3 clinical trials in 12 mUM patients with orbital disease. Tebentafusp demonstrated preliminary signals of activity in intra-ocular lesions, supporting KIMMTRAK’s use in patients with unresectable uveal melanoma.

The fourth poster shares in vitro data potentially explaining how tebentafusp may lead to OS benefit even in tumors with heterogenous gp100 expression.

Poster details

Title: Early ctDNA reduction is associated with better overall survival in the Ph 3 trial of tebentafusp in previously untreated metastatic uveal melanoma
Presenting author: Ryan Sullivan
Session: Liquid Biopsies: Circulating Nucleic Acid and Circulating Tumor Cells 1

Title: Long-term survival follow-up of tebentafusp in previously treated metastatic uveal melanoma
Presenting author: Joe Sacco
Session: Phase II Clinical Trials 2

Title: Evidence of tumor response in orbital lesions treated with tebentafusp in metastatic uveal melanoma patients
Presenting author: Marcus Butler
Session: Late breaking research: clinical research 1/ Endocrinology

Title: Melanoma patients with high and low target-expression can benefit from TCR-CD3 bispecifics through direct and indirect mechanisms of tumor control
Presenting author: Esra Güç
Session: Combination Immunotherapies 2

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 approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom.

About Phase 2 IMCgp100-102 Trial
IMCgp100-102 (NCT02570308) was an open-label, multi-center, single-arm trial of the safety and efficacy of tebentafusp in patients with previously treated mUM. The trial included 127 HLA-A*02:01+ 2L+ mUM patients, treated with tebentafusp at the recommended Phase 2 dose of 68mcg following intra-patient dose escalation of 20 mcg (week 1) and 30 mcg (week 2). The primary endpoint was overall response rate (ORR), with secondary objectives being overall survival (OS) and safety in 127 patients who had enrolled after progressing on one or more prior therapies.

About Phase 3 IMCgp100-202 Trial
IMCgp100-202 (NCT03070392) is a randomized pivotal trial that evaluated overall survival (OS) of KIMMTRAK 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 SAFETY INFORMATION

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.

For more information, please see full Summary of Product Characteristics (SmPC) or full U.S. Prescribing Information (including BOXED WARNING for CRS).