On January 4, 2023 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported positive top-line results from its IMerge Phase 3 clinical trial evaluating the Company’s first-in-class telomerase inhibitor, imetelstat, in lower risk myelodysplastic syndromes (MDS) patients who are relapsed, refractory or ineligible for erythropoiesis stimulating agents (ESAs) (Press release, Geron, JAN 4, 2023, View Source [SID1234625801]). The trial met its primary efficacy endpoint of 8-week TI and a key secondary endpoint of 24-week TI, demonstrating highly statistically significant and clinically meaningful benefit of imetelstat versus placebo with no new safety signals and safety results consistent with prior imetelstat clinical trials.

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"Today is a great day for lower risk MDS patients who are living with the burden of transfusions. The results from the IMerge Phase 3 study were resoundingly positive, presenting compelling durability of transfusion independence, delivering on the promise of imetelstat and telomerase inhibition for these patients," said John A. Scarlett, M.D., Geron’s Chairman and Chief Executive Officer. "This milestone is the first of many upcoming catalysts for Geron, with planned U.S. and EU regulatory submissions in 2023, as well as preparations for a potential U.S. commercial launch. In addition, in 2024, we expect an interim analysis of the IMpactMF Phase 3 trial of imetelstat in relapsed/refractory myelofibrosis."

Summary of Top-Line Results: Primary 8-Week TI Endpoint and Key 24-Week TI Secondary Endpoint Met with Statistical Significance and Meaningful Clinical Improvements

Significant and durable transfusion independence achieved with imetelstat versus placebo

IMerge Phase 3 is a double-blind, 2:1 randomized, placebo-controlled clinical trial to evaluate imetelstat in patients with IPSS Low or Intermediate-1 risk (lower risk) transfusion dependent MDS who were relapsed after, refractory to, or ineligible for, ESA treatment, had not received prior treatment with either a hypomethylating agent (HMA) or lenalidomide and were non-del(5q).

The table below summarizes the top-line efficacy results from the primary analysis of data from IMerge Phase 3, which showed a highly statistically significant and clinically meaningful difference between imetelstat and the placebo comparator arm for the primary endpoint of 8-week TI and key secondary endpoint of 24-week TI. With a clinical data cut-off occurring in October 2022, median time on study and median time on treatment for patients on imetelstat was approximately 20 months and 8 months, respectively, and approximately 18 months and 7 months for placebo, respectively.

Imetelstat
(n=118)

Placebo
(n=60)

P-value*

8-week TI, n (%)

47 (39.8)

9 (15.0)

<0.001

95% confidence interval

(30.9, 49.3)

(7.1, 26.6)

24-week TI, n (%)

33 (28.0)

2 (3.3)

<0.001

95% confidence interval

(20.1, 37.0)

(0.4, 11.5)

* Cochran Mantel Haenszel test stratified for prior RBC transfusion burden (≤6 units or >6 units of RBCs/8 weeks) and baseline IPSS risk score (Low or Intermediate-1)

Highly statistically significant (p<0.001; hazard ratio 0.23) durable transfusion independence for 8-week TI responders was achieved with a median TI duration approaching one year for imetelstat, compared to approximately 13 weeks for placebo, using Kaplan-Meier estimates. The median TI duration was approximately 1.5 years (80 weeks) for imetelstat 24-week TI responders.

Transfusion independence achieved broadly across lower risk MDS subtypes

As shown in the table below, statistically significant (p<0.05) 8-week TI was demonstrated with imetelstat versus placebo across lower risk MDS subtypes, including RS+ and RS- status, high and very high transfusion burden and IPSS Low and Intermediate-1 risk status, with similar 8-week TI responses seen for imetelstat within each subtype category.

8-Week TI

Imetelstat, n (%)

Placebo, n (%)

Difference (95% CI)

P-value*

Overall

47/118 (39.8)

9/60 (15.0)

24.8 (9.9, 36.9)

<0.001

WHO category

RS+

33/73 (45.2)

7/37 (18.9)

26.3 (5.9, 42.2)

0.016

RS-

14/44 (31.8)

2/23 (8.7)

23.1 (-1.3, 40.6)

0.038

Transfusion burden

4-6 units

28/62 (45.2)

7/33 (21.2)

23.9 (1.9, 41.4)

0.027

>6 units

19/56 (33.9)

2/27 (7.4)

26.5 (4.7, 41.8)

0.023

IPSS risk category

Low

32/80 (40.0)

8/39 (20.5)

19.5 (-0.1, 35.2)

0.034

Intermediate-1

15/38 (39.5)

1/21 (4.8)

34.7 (8.8, 52.4)

0.004

* Cochran Mantel Haenszel test stratified for prior RBC transfusion burden (≤6 units or >6 units of RBCs/8 weeks) and baseline IPSS risk score (Low or Intermediate-1)

Increase in hemoglobin levels, reduction in RBC transfusions and hematologic improvement-erythroid (HI-E)

Mean hemoglobin levels in imetelstat patients increased significantly (p<0.001) over time compared to placebo patients. For patients achieving 8-week TI, median increases in hemoglobin were 3.6 g/dL for imetelstat and 0.8 g/dL for placebo. Imetelstat patients also experienced a statistically significant (p=0.042) and clinically meaningful mean reduction in RBC transfusion units compared to placebo.

A highly statistically significant (p<0.001) HI-E rate was achieved for imetelstat (42.4%) versus placebo (13.3%) using the IWG 2018 criteria for HI-E. The original IMerge protocol was finalized in 2015, and applying the IWG 2006 HI-E criteria in use at that time, the difference between the imetelstat and placebo patients was not statistically significant (p=0.112). The current IWG 2018 HI-E criteria places greater emphasis on durability by measuring response for >16 weeks, rather than >8 weeks as specified by the IWG 2006 criteria.

Clinical and molecular evidence supporting the potential for MDS disease modification with imetelstat

Clinical and molecular evidence supporting the potential for MDS disease modification with imetelstat included a one-year median TI duration for imetelstat 8-week TI responders, a median rise of 3.6 g/dL in hemoglobin levels in those same patients and >50% variant allele frequency decreases in SF3B1, TET2, DNMT3A and ASXL1 mutations.

"The notable results from IMerge Phase 3 underscore our belief that, with the unique mechanism of action of imetelstat as a telomerase inhibitor, the drug has the potential to become a first-in-class therapy for lower risk MDS patients. The meaningful clinical results observed in the trial, including duration of TI, increases in hemoglobin levels, decreases in transfusions and reductions in mutation burdens, suggest imetelstat treatment may be altering the course of the disease. We look forward to presenting additional data from the trial at medical meetings later this year to further develop the evidence for potential disease modification previously observed in Phase 2 trials in both lower risk MDS and relapsed/refractory MF," said Faye Feller, M.D., Chief Medical Officer of Geron. "I would also like to express my deep appreciation to the Geron employees, past and present, as well as all of the patients and their families, the clinicians, study coordinators and site personnel, whose participation in this trial was integral to obtaining the results we are presenting today."

Safety results consistent with prior clinical experience with imetelstat

The treatment emergent adverse events (TEAEs) observed in IMerge Phase 3 were consistent with the known safety profile of imetelstat from prior clinical trials and no new safety signals were found. Overall treatment discontinuation rates were consistent between the imetelstat and placebo groups (77.1% vs. 76.3%, respectively). Treatment discontinuation rates related to lack of efficacy were higher for the placebo group (42.4%) versus imetelstat (23.7%), and lower for adverse events between the placebo and imetelstat groups (0.0% vs. 16.1%, respectively).

The most common non-hematologic TEAEs (≥10%) in the imetelstat group included asthenia, COVID-19, peripheral edema, headache, diarrhea and alanine aminotransferase increase. Grade 3 liver function test (LFT) elevations reported in the trial were transient and reversible to Grade 2 or lower, with no cases of liver test elevations consistent with Hy’s Law or Drug-Induced Liver Injury observed.

The most frequent hematologic TEAEs were Grade 3/4 thrombocytopenia (61.9% imetelstat vs. 8.5% placebo) and neutropenia (67.8% imetelstat vs. 3.4% placebo). Clinical consequences from cytopenias, such as >Grade 3 bleeding events, infections and febrile neutropenia, were similar between the imetelstat and placebo groups. Furthermore, the median duration was shorter for imetelstat for thrombocytopenia (1.4 weeks for imetelstat vs. 2.0 weeks for placebo) and for neutropenia (1.9 weeks for imetelstat vs. 2.2 weeks for placebo). In addition, resolution of Grade 3/4 cytopenias to Grade 2 or lower by laboratory assessment within four weeks was higher for imetelstat, both for thrombocytopenia (86.3% for imetelstat vs. 44.4% for placebo) and neutropenia (81.0% for imetelstat vs. 50.0% for placebo).

"The IMerge Phase 3 efficacy results illustrate the depth, breadth and durability of transfusion independence potentially achievable with imetelstat treatment, which could be practice changing, if approved. These results are especially encouraging, because today we have limited treatment options for lower risk MDS patients that provide broad and durable transfusion independence," said Uwe Platzbecker, M.D., a principal investigator of IMerge Phase 3. "With regards to the safety results, cytopenias were manageable and reversible. Importantly for hematologists, who are accustomed to managing cytopenias, clinical consequences were limited and similar to placebo treated patients. As a once per month out-patient IV therapy, imetelstat will hopefully become a novel treatment option for lower risk MDS patients in the near future."

Planned Next Steps

In light of the positive top-line results from IMerge Phase 3, combined with data from earlier clinical trials, the Company plans to submit an NDA in the U.S. in mid-2023 and a Marketing Authorization Application (MAA) in the EU in the second half of 2023. With Fast Track designation for imetelstat from the U.S. Food and Drug Administration for the treatment of adult patients with transfusion dependent anemia due to Low or Intermediate-1 risk MDS that is not associated with del(5q) who are refractory or resistant to an ESA, a request for rolling submission of the NDA was submitted and has been granted.

Geron also plans to present additional data from IMerge Phase 3 at medical meetings later this year, including data relating to potential correlations of decreases in mutation burden and abnormal cytogenetic clones with clinical responses, patient reported outcomes, hTERT and telomerase activity biomarker data and continued follow-up of durability of transfusion independence, that may be indicative of the potential for disease modification with imetelstat.

Geron is preparing for an anticipated commercial launch of imetelstat in lower risk MDS in the first half of 2024 in the U.S. and by the end of 2024 in the EU, assuming regulatory approvals are granted.

Conference Call Details

A presentation of the data described in this press release is available on the Events and Presentations section (View Source) of Geron’s website. A conference call with Geron management to review the IMerge Phase 3 top-line results is scheduled at 8 a.m. Eastern Time this morning and may be accessed on Geron’s website.

About IMerge Phase 3

The Phase 3 portion of the IMerge Phase 2/3 study is a double-blind, 2:1 randomized, placebo-controlled clinical trial to evaluate imetelstat in patients with IPSS Low or Intermediate-1 risk (lower risk) transfusion dependent MDS who were relapsed after, refractory to, or ineligible for, erythropoiesis stimulating agent (ESA) treatment, had not received prior treatment with either a HMA or lenalidomide and were non-del(5q). To be eligible for IMerge Phase 3, patients were required to be transfusion dependent, defined as requiring at least four units of packed red blood cells (RBCs), over an eight-week period during the 16 weeks prior to entry into the trial. The primary efficacy endpoint of IMerge Phase 3 is the rate of RBC-TI lasting at least eight weeks, defined as the proportion of patients without any RBC transfusion for at least eight consecutive weeks since entry to the trial (8-week TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week TI), the duration of TI and the rate of hematologic improvement erythroid (HI-E), which defined as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least eight weeks or a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden. A total of 178 patients were enrolled in IMerge Phase 3 across North America, Europe, Middle East and Asia.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from non-clinical studies and clinical trials of imetelstat provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the U.S. Food and Drug Administration for both the treatment of adult patients with transfusion dependent anemia due to Low or Intermediate-1 risk MDS that is not associated with del(5q) who are refractory or resistant to an erythropoiesis stimulating agent, and for adult patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment.

On December 30, 2022, GT Biopharma, Inc. (the "Company") signed a purchase agreement (the "Purchase Agreement") with an institutional investor (the "Purchaser") for the issuance and sale, in a registered direct offering (the "Offering"), of 3,600,000 shares of the Company’s common stock, par value $0.001 per share (the "Shares"), pre-funded warrants to purchase up to 2,900,000 shares of the Company’s common stock (the "Pre-Funded Warrants"), and warrants to purchase up to an aggregate of 6,500,000 shares of the Company’s common stock (the "Common Warrants") (Filing, 8-K, GT Biopharma, JAN 4, 2023, View Source [SID1234625802]). The Common Warrants have an exercise price equal to $1.00, will be exercisable commencing six months following issuance, and will have a term of exercise equal to five years following the initial exercise date. The Pre-Funded Warrants have an exercise price of $0.0001 per Share, are immediately exercisable and can be exercised at any time after their original issuance until such Pre-Funded Warrants are exercised in full. The Shares and Common Warrants were sold at an offering price of $1.00 per Share and accompanying Common Warrant and the Pre-Funded Warrants and Common Warrants were sold at an offering price of $0.9999 per Pre-Funded Warrant and accompanying Common Warrant.

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The offering of the Shares, the Common Warrants, the Pre-Funded Warrants, the Shares that are issuable from time to time upon exercise of the Common Warrants and the Shares that are issuable from time to time upon exercise of the Pre-Funded Warrants (the "Offering") was made pursuant to the Company’s shelf registration statement on Form S-3 (File No. 333-267870) (the "Form S-3") initially filed with the Securities and Exchange Commission (the "Commission") on October 13, 2022, and declared effective by the Commission on October 20, 2022.

H.C. Wainwright & Co., LLC ("Wainwright") acted as the Company’s exclusive placement agent in connection with the Offering. In connection with the Offering, the Company agreed to pay Wainwright a cash fee equal to $390,000, $35,000 for legal fees and expenses and up to $15,950 for clearing expenses. In addition, the Company has agreed to grant placement agent warrants to Wainwright to purchase up to 390,000 shares of Common Stock (the "Placement Agent Warrants"). The terms of the Placement Agent Warrants are substantially the same as the terms of the Common Warrants, except the Placement Agent Warrants will have an exercise price of $1.25 per share and will expire five years from the commencement of sales of the Offering.

Wainwright did not purchase or sell any of the Shares, the Common Warrants or the Pre-Funded Warrants and was not required to arrange the purchase or sale of any specific number of securities or dollar amount. The gross proceeds to the Company from the Offering were $6.5 million, before deducting placement agent fees and other offering expenses. The Company anticipates using the net proceeds from the Offering for general corporate purposes.

Pursuant to the Purchase Agreement, the Company agreed for a period of 60 days following the closing of the Offering not to issue, enter into an agreement to issue or announce the issuance or proposed issuance of the shares or any other securities convertible into, or exercisable or exchangeable for, shares. Such restriction does not apply to, in addition to certain customary exceptions, certain securities issuances, the issuance by the Company of equity or debt securities pursuant to acquisitions or strategic transactions approved by a majority of the Company’s disinterested directors, where not for the purpose of raising capital, or certain other compensatory issuances. The Company has also agreed for a period of one year following the closing date of the Offering not to (i) issue or agree to issue equity or debt securities convertible into, or exercisable or exchangeable for, shares at a conversion price, exercise price or exchange price which floats with the trading price of the shares or which may be adjusted after issuance upon the occurrence of certain events or (ii) enter into any agreement, including an equity line of credit, whereby the Company may issue securities at a future-determined price, subject to certain exceptions.

The Purchase Agreement contains customary representations and warranties, agreements and obligations, conditions to closing and termination provisions.

The foregoing descriptions of the Common Warrants, the Pre-Funded Warrants, the Placement Agent Warrants and the Purchase Agreement are qualified in their entirety by reference to the full text of the forms thereof, which are attached as Exhibits 4.1, 4.2, 4.3 and 10.1 hereto and incorporated by reference herein. A copy of the legal opinion and consent of Baker & McKenzie LLP, New York counsel to the Company, relating to the validity of the issuance and sale of the Shares, the Pre-Funded Warrants and Common Warrants is attached as Exhibit 5.1 hereto. A copy of the press release announcing the Offering and the Company’s entry into the Purchase Agreement is attached as Exhibit 99.1 hereto.

On January 4, 2023 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported an initial update on PRESERVE 3, an ongoing Phase 2, randomized, open-label study of first-line platinum-based chemotherapy and maintenance therapy with the immune checkpoint inhibitor, avelumab, administered alone, or in combination with trilaciclib, in patients with untreated, locally advanced or metastatic urothelial carcinoma (mUC) (Press release, G1 Therapeutics, JAN 4, 2023, View Source [SID1234625800]). Additional safety and efficacy data, including the primary endpoint of progression free survival (PFS), are anticipated in the middle of 2023.

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Initial Phase 2 Results

The confirmed objective response rate (ORR) per RECIST v1.1 was comparable between arms; ORR was 40.0% (n=18/45) and 46.7% (n=21/45) among evaluable patients in the trilaciclib and control arms, respectively. Longer-term follow-up is required to characterize additional anti-tumor endpoints including median duration of confirmed objective response and PFS, which is the primary endpoint of the study.

Safety is reviewed by the data monitoring committee (DMC) on an ongoing basis, and it has recommended that the study continue as planned. Though early, the safety and tolerability profile of trilaciclib administered prior to chemotherapy is generally consistent with that expected in patients treated with gemcitabine plus cisplatin/carboplatin and avelumab maintenance for previously untreated advanced or metastatic urothelial carcinoma.

"The immunomodulatory mechanism of action of trilaciclib lends itself to longer term anti-tumor efficacy endpoints like PFS, as opposed to shorter term response rate endpoints, as was noted in the Phase 2 trial in triple negative breast cancer (TNBC)," said Raj Malik, M.D., Chief Medical Officer at G1 Therapeutics. "We look forward to the results of the maintenance portion of this trial, particularly given the preclinical work that we have conducted showing the potential synergy of trilaciclib with checkpoint inhibitors – which we seek to validate clinically in this study with longer term duration of response and PFS data. We would expect to present these results at a medical meeting in 2023."

Trilaciclib, an IV-administered transient CDK4/6 inhibitor, is a first-in-class therapy designed to preserve bone marrow and immune system function during chemotherapy to improve patient outcomes. Depending on the tumor type and the chemotherapy backbone, this mechanistic profile can drive patient benefits of myeloprotection and/or anti-tumor efficacy. Its mechanism of action of improving overall immune response by improving long term immune surveillance lends itself to longer term endpoints, such as progression free survival.

Phase 2 Trial Design

In this Phase 2 randomized, open-label study, 94 patients with mUC were randomized (1:1) to receive either gemcitabine/platinum chemotherapy (induction phase) followed by avelumab (checkpoint inhibitor) maintenance therapy (maintenance phase) or trilaciclib prior to gemcitabine/platinum chemotherapy followed by trilaciclib plus avelumab maintenance therapy.

The primary endpoint is to evaluate the anti-tumor efficacy of trilaciclib when combined with platinum-based chemotherapy and the checkpoint inhibitor avelumab maintenance therapy as measured by PFS during the overall study. Key secondary endpoints include evaluation of the anti-tumor efficacy of trilaciclib as measured by ORR, duration of objective response, PFS in the maintenance period, overall survival, and probability of survival at Month 16, and evaluation of the myeloprotective effects of trilaciclib on chemotherapy-induced myelosuppression.

About Bladder Cancer

Bladder cancer is the most common malignancy involving the urinary system and is the sixth most common cancer in the United States. The American Cancer Society estimates that approximately 84,000 new cases of bladder cancer will be diagnosed in the U.S. in 2021. Approximately 2.4% of the US population will be diagnosed with bladder cancer at some point during their lifetime; the average age at diagnosis is 73 years and it is rarely diagnosed in people less than 40 years of age. Urothelial carcinoma, also known as transitional cell carcinoma (TCC), urothelial bladder cancer, or urothelial cell carcinoma (UCC) of the urinary tract, is the most common type of bladder cancer in the U.S. and Europe, where it accounts for 90% of all bladder cancers. It also accounts for up to 15% of kidney cancers diagnosed in adults. The overall 5-year survival rate for metastatic urothelial carcinoma is approximately 5.5%, which has remained unchanged over the past 25 years.

On January 4, 2023 Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS), reported that senior management will present at the upcoming 41st Annual J.P. Morgan Healthcare Conference on Tuesday, January 10, 2023, at 8:15 a.m. Pacific Time (Press release, Coherus Biosciences, JAN 4, 2023, View Source [SID1234625797]). The presentation and Q&A session will be accessible via Webcast through a link posted on the Investor Events Calendar section of the Coherus website: View Source This webcast will be available for replay until February 10, 2023.

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On January 4, 2023 Checkpoint Therapeutics, Inc. ("Checkpoint") (Nasdaq: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported the submission of a Biologics License Application ("BLA") to the U.S. Food and Drug Administration ("FDA") for the approval of cosibelimab, its investigational anti-PD-L1 antibody, as a treatment for patients with metastatic cutaneous squamous cell carcinoma ("cSCC") or locally advanced cSCC who are not candidates for curative surgery or radiation (Press release, Checkpoint Therapeutics, JAN 4, 2023, View Source [SID1234625796]).

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"This is a major milestone for Checkpoint Therapeutics, representing our first submission of a marketing application for one of our investigational medications and furthering our evolution from a development-stage company to a fully integrated commercial organization to support the potential launch of cosibelimab," said James Oliviero, President and Chief Executive Officer of Checkpoint. "cSCC is the second most common type of skin cancer in the United States. While most cases involve localized tumors amenable to curative resection, approximately 40,000 cases will become advanced, and an estimated 15,000 people will die from their disease each year. Based on its compelling and differentiated product profile and the positive data generated to date, we believe cosibelimab has the potential to be an important treatment option for patients. Importantly, we continue to plan for cosibelimab to be positioned, upon regulatory approval, as potentially the first and only price disruptive PD-1/PD-L1 inhibitor in the U.S. market." Mr. Oliviero continued, "We want to thank the patients and their families, as well as the physicians and their research teams, who participated in our trial and contributed immensely to the advancement of cosibelimab."

The BLA submission is based on positive efficacy and safety results from Checkpoint’s ongoing registration-enabling, multi-regional, multicohort clinical trial evaluating cosibelimab administered as fixed doses of either 800 mg every two weeks or 1200 mg every three weeks in patients with selected recurrent or metastatic cancers, including pivotal cohorts in metastatic and locally advanced cSCC.

In January 2022, Checkpoint announced that the metastatic cSCC cohort met its primary endpoint, with cosibelimab demonstrating a confirmed objective response rate ("ORR") of 47.4% (95% CI: 36.0, 59.1) based on independent central review of 78 patients enrolled in the cohort using Response Evaluation Criteria in Solid Tumors version 1.1 ("RECIST 1.1") criteria. In June 2022, Checkpoint announced positive interim results from its locally advanced cSCC cohort, with cosibelimab demonstrating a confirmed ORR of 54.8% (95% CI: 36.0, 72.7) based on independent central review of 31 patients enrolled in the cohort, exceeding a clinically meaningful lower bound of the 95% two-sided confidence interval of 25%. Based upon interactions with the FDA, the BLA submission includes both the metastatic and locally advanced cSCC indications.

About Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma is the second most common type of skin cancer in the United States, with an estimated annual incidence of approximately 1 million cases according to the Skin Cancer Foundation. While most cases are localized tumors amenable to curative resection, approximately 40,000 cases will become advanced, and an estimated 15,000 people will die from their disease each year. In addition to being a life-threatening disease, cSCC causes significant functional morbidities and cosmetic deformities based on tumors commonly arising in the head and neck region and invading blood vessels, nerves and vital organs such as the eye or ear.

About Cosibelimab

Cosibelimab is a potential best-in-class, high affinity, fully-human monoclonal antibody of IgG1 subtype that directly binds to programmed death ligand-1 ("PD-L1") and blocks the PD-L1 interaction with the programmed death receptor-1 ("PD-1") and B7.1 receptors. Cosibelimab’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response. Cosibelimab is potentially differentiated from the currently marketed PD-1 and PD-L1 antibodies through sustained >99% target tumor occupancy to reactivate an antitumor immune response and the additional benefit of a functional Fc domain capable of inducing antibody-dependent cell-mediated cytotoxicity ("ADCC") for potential enhanced efficacy in certain tumor types.